PMID- 42947001 OWN - NLM STAT- MEDLINE DCOM- 20261028 LR - 20261028 IS - 1471-2261 (Electronic) IS - 1471-2261 (Linking) VI - 26 IP - 1 DP - 2026 Jul 31 TI - Comparison of cardiac adverse event signal profiles for GLP-1 receptor agonists: an analysis of the FAERS database. LID - 10.1186/s12872-026-06387-3 [doi] LID - 988 AB - PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in the management of type 2 diabetes owing to their effectiveness in glycemic control and weight reduction. Given the increasing use of GLP-1RAs, further research is warranted to better understand their cardiac effects. METHODS: Individual Case Safety Reports from the U. S. Food and Drug Administration Adverse Event Reporting System database from July 6, 2007, to February 17, 2026, were evaluated for the post-marketing cardiac adverse events associated with dulaglutide, liraglutide, semaglutide, and tirzepatide. To detect signal differences among drugs, disproportionality analysis was conducted using the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) methods, along with standard statistical tests to evaluate categorical variables and to estimate odds ratios. RESULTS: A total of 7,023 cardiac adverse events were identified among 305,877 reports. GLP-1RAs were associated with a higher reporting frequency of tachyarrhythmias than bradyarrhythmias. In the 65-85-year age group, an increase in the signal for cardiac events was observed. Pairwise post hoc comparisons demonstrated no statistically significant differences in reporting frequency of cardiac events between semaglutide and liraglutide, whereas all other drug pairs demonstrated statistically significant differences. CONCLUSION: Semaglutide and liraglutide had higher relative reporting of cardiac events whereas tirzepatide had lower PRR and ROR values against the total background of reports. These findings suggest a lower reporting tendency of cardiac events for tirzepatide. This study may assist healthcare professionals in recognizing the frequency of cardiac events associated with GLP-1RA use and drive new hypotheses to clarify underlying mechanisms. CI - (c) 2026. The Author(s). FAU - Yildirim, Burak Ogulcan AU - Yildirim BO AUID- ORCID: 0000-0003-3448-6187 AD - Department of Cardiology, Aliaga State Hospital, Izmir, Turkiye. FAU - Sarkim, Ibrahim Furkan AU - Sarkim IF AUID- ORCID: 0009-0000-9904-9530 AD - Department of Pharmacology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkiye. isarkim@cumhuriyet.edu.tr. FAU - Yalman, Gizem AU - Yalman G AUID- ORCID: 0009-0005-2098-5331 AD - Department of Pharmacology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkiye. FAU - Arslantas, Bugra AU - Arslantas B AUID- ORCID: 0009-0001-1229-4670 AD - Department of Pharmacology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkiye. FAU - Celik, Can Berk AU - Celik CB AUID- ORCID: 0009-0002-6550-3891 AD - Department of Pharmacology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkiye. FAU - Yildirim, Sahin AU - Yildirim S AUID- ORCID: 0000-0003-1312-7273 AD - Department of Pharmacology, Faculty of Medicine, Sivas Cumhuriyet University, Sivas, Turkiye. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260731 PL - England TA - BMC Cardiovasc Disord JT - BMC cardiovascular disorders JID - 100968539 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Incretins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (GLP1R protein, human) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Tirzepatide/adverse effects MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - *Hypoglycemic Agents/adverse effects MH - Databases, Factual MH - United States/epidemiology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/epidemiology MH - Risk Factors MH - *Liraglutide/adverse effects MH - Risk Assessment MH - Adverse Drug Reaction Reporting Systems MH - *Incretins/adverse effects MH - Product Surveillance, Postmarketing MH - Immunoglobulin Fc Fragments/adverse effects MH - Time Factors MH - *Heart Diseases/chemically induced/epidemiology/diagnosis MH - Treatment Outcome MH - Cardiotoxicity MH - Female MH - Male MH - Recombinant Fusion Proteins PMC - PMC13715166 OTO - NOTNLM OT - Dulaglutide OT - FAERS OT - Glucagon-like peptide-1 receptor agonists OT - Liraglutide OT - Semaglutide OT - Tirzepatide COIS- Declarations. Ethics approval and consent to participate: As this observational study used publicly available anonymized data from the FDA Adverse Event Monitoring System (AEMS) [formerly the FDA Adverse Event Reporting System (FAERS)] database, institutional ethical approval is not required. Competing interests: The authors declare no competing interests. EDAT- 2026/10/28 05:28 MHDA- 2026/10/28 05:29 PMCR- 2026/07/31 CRDT- 2026/10/28 00:34 PHST- 2026/06/22 00:00 [received] PHST- 2026/07/29 00:00 [accepted] PHST- 2026/10/28 05:29 [medline] PHST- 2026/10/28 05:28 [pubmed] PHST- 2026/10/28 00:34 [entrez] PHST- 2026/07/31 00:00 [pmc-release] AID - 10.1186/s12872-026-06387-3 [pii] AID - 6387 [pii] AID - 10.1186/s12872-026-06387-3 [doi] PST - epublish SO - BMC Cardiovasc Disord. 2026 Jul 31;26(1):988. doi: 10.1186/s12872-026-06387-3. PMID- 42946127 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261027 IS - 1099-1557 (Electronic) IS - 1053-8569 (Print) IS - 1053-8569 (Linking) VI - 35 IP - 11 DP - 2026 Nov TI - Semaglutide and Panic Attacks: Active-Comparator Disproportionality Analysis, Temporal Assessment of Notoriety Bias and Evidence Triangulation in Post-Marketing Pharmacovigilance. LID - e70517 [pii] LID - 10.1002/pds.70517 [doi] AB - PURPOSE: To evaluate how confounding by indication and notoriety bias shape the apparent semaglutide-panic attack signal in the FDA Adverse Event Reporting System (FAERS) and to interpret this signal using an evidence-triangulation framework integrating randomized and observational studies. METHODS: We conducted an active-comparator restricted disproportionality analysis of FAERS (2018Q1-2024Q4), including individual case safety reports in which semaglutide, dulaglutide or empagliflozin was the primary suspect drug. Panic attack was identified using the MedDRA preferred term. Crude and adjusted reporting odds ratios (RORs, aRORs) with 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age, sex and indication (Type 2 diabetes, obesity/weight management). Notoriety bias was assessed using prespecified temporal analyses (analyses restricted to reports received before July 1, 2023 and a drug-by-period comparison of 2018-2022 with 2023-2024) and reporting proportions per 10 000 reports. A sensitivity analysis used all other primary-suspect drugs in FAERS as the reference set. In parallel, we conducted a systematic review (MEDLINE, Embase, CENTRAL to November 24, 2025) of randomized trials, cohort and cross-sectional studies, pharmacovigilance analyses and case reports reporting panic attacks or acute anxiety outcomes with semaglutide. RESULTS: Among 33 267 semaglutide, 54 282 dulaglutide and 25 380 empagliflozin reports, panic attacks were recorded in 87 (0.26%), 28 (0.05%) and 13 (0.05%) cases, respectively. Crude RORs were 5.08 (95% CI 3.32-7.78) versus dulaglutide and 5.12 (95% CI 2.86-9.17) versus empagliflozin, attenuating after adjustment to 2.82 (95% CI 1.74-4.56) and 2.75 (95% CI 1.41-5.36). In the pre-warning period crude RORs were 2.24 (95% CI 1.23-4.07) and 2.15 (95% CI 1.00-4.58), attenuating to 1.38 (95% CI 0.69-2.75) and 1.14 (95% CI 0.48-2.68) after adjustment. Panic-attack reports per 10 000 semaglutide reports rose from 6.7 in 2018-2022 to 42.0 in 2023-2024 (drug-by-period interaction p = 0.007). Against all other primary-suspect drugs, the aROR was 1.48 (95% CI 1.18-1.87) overall and 0.76 (95% CI 0.48-1.18) before July 1, 2023. Across 12 studies, randomized trials and active-comparator observational cohorts did not show a consistent increase in panic attacks or anxiety-related outcomes. CONCLUSIONS: Crude FAERS analyses suggested a semaglutide-panic attack signal that attenuated after adjustment was no longer significant before the July 2023 regulatory communication and rose sharply thereafter in a pattern consistent with notoriety bias. Triangulation with randomized trials and active-comparator observational studies does not support a consistent pharmacological association. Disproportionality analyses are hypothesis-generating and cannot estimate incidence or establish causality. This case study illustrates how active-comparator design, temporal assessment of notoriety bias and evidence triangulation can improve the interpretation of post-marketing safety signals. CI - (c) 2026 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. FAU - Melamed, Ben AU - Melamed B AUID- ORCID: 0009-0000-9065-6801 AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Parsi-Zahabi, Mahak AU - Parsi-Zahabi M AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Omrani, Mohammad Ali AU - Omrani MA AUID- ORCID: 0000-0001-6847-0699 AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Baskaran, Bala Swetha AU - Baskaran BS AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Eddin, Lujain Ez AU - Eddin LE AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Kermanshahi, Nazgol AU - Kermanshahi N AUID- ORCID: 0009-0002-2776-6084 AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Chalabianloo, Niaz AU - Chalabianloo N AUID- ORCID: 0000-0001-7228-4725 AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. FAU - Muanda, Flory Tsobo AU - Muanda FT AUID- ORCID: 0000-0003-4682-6564 AD - Department of Physiology and Pharmacology, Western University, London, Ontario, Canada. AD - ICES Western, Kidney, Dialysis & Transplantation Research Program, London, Ontario, Canada. AD - Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. AD - London Health Sciences Centre, Lawson Health Research Institute, London, Ontario, Canada. LA - eng PT - Journal Article PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucosides) RN - WTT295HSY5 (dulaglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (Benzhydryl Compounds) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Semaglutide MH - *Glucagon-Like Peptides/adverse effects/administration & dosage/analogs & derivatives MH - Humans MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Pharmacovigilance MH - Female MH - *Hypoglycemic Agents/adverse effects MH - *Panic Disorder/chemically induced/epidemiology MH - United States/epidemiology MH - *Recombinant Fusion Proteins/adverse effects/administration & dosage MH - Glucosides/adverse effects/administration & dosage MH - *Product Surveillance, Postmarketing/statistics & numerical data MH - Male MH - Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - United States Food and Drug Administration/statistics & numerical data MH - Benzhydryl Compounds MH - Immunoglobulin Fc Fragments PMC - PMC13713200 OAB - This study investigated whether the diabetes and weight-loss drug semaglutide (commonly known as Ozempic or Wegovy) increases the risk of panic attacks. Researchers analyzed patient safety data from the FDA Adverse Event Reporting System (FAERS) spanning 2018 through 2024. While the raw numbers initially showed that panic attacks were reported more often with semaglutide than with other medications (like dulaglutide or empagliflozin), this connection weakened significantly once researchers adjusted for patient age, sex and the specific reason for taking the drug. Crucially, the surge in panic attack reports occurred only after mid-2023, coinciding with heightened media attention and regulatory reviews regarding the mental health impacts of GLP-1 drugs. This pattern is consistent with 'notoriety bias', meaning that greater public awareness may have led to more reports rather than the drug itself causing more panic attacks. However, this type of data can neither prove nor rule out a true effect. Furthermore, a review of 12 studies, including pooled clinical trial data and real-world observational studies, found no consistent evidence linking semaglutide to increased panic attacks or anxiety. Overall, the available evidence does not show a consistent link between semaglutide and panic attacks, although an association with panic attacks cannot be excluded. OABL- eng OTO - NOTNLM OT - FAERS OT - GLP-1 receptor agonists OT - confounding by indication OT - notoriety bias OT - panic attack OT - pharmacovigilance OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2026/10/28 04:34 MHDA- 2026/10/28 04:35 PMCR- 2026/10/27 CRDT- 2026/10/27 20:34 PHST- 2026/10/05 00:00 [revised] PHST- 2026/06/26 00:00 [received] PHST- 2026/10/22 00:00 [accepted] PHST- 2026/10/28 04:35 [medline] PHST- 2026/10/28 04:34 [pubmed] PHST- 2026/10/27 20:34 [entrez] PHST- 2026/10/27 00:00 [pmc-release] AID - e70517 [pii] AID - PDS70517 [pii] AID - 10.1002/pds.70517 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2026 Nov;35(11):e70517. doi: 10.1002/pds.70517. PMID- 42937793 OWN - NLM STAT- MEDLINE DCOM- 20261027 LR - 20261028 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 105 IP - 43 DP - 2026 Oct 23 TI - Efficacy and safety of GLP-1 receptor agonists in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH): A systematic review and meta-analysis. PG - e51306 LID - 10.1097/MD.0000000000051306 [doi] LID - e51306 AB - BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are increasingly prevalent liver diseases closely linked to obesity, type 2 diabetes mellitus, and cardiometabolic risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may improve hepatic and metabolic outcomes through weight reduction, improved glycemic control, and reductions in hepatic steatosis. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of GLP-1 RAs in adults with MASLD or MASH. METHODS: A systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched for English-language studies published between January 2019 and December 2025. Eligible studies included adults with MASLD or MASH treated with GLP-1 RAs and reporting hepatic, metabolic, or safety outcomes. Pooled estimates were calculated using random-effects models. RESULTS: Nine studies involving 795 participants were included. GLP-1 RA therapy was associated with significant reductions in liver fat content (mean difference [MD]: -3.17; 95% CI: -4.06 to -2.29), body weight (MD: -4.68; 95% CI: -6.88 to -2.47), alanine aminotransferase (MD: -15.17; 95% CI: -21.29 to -9.05), aspartate aminotransferase (MD: -9.89; 95% CI: -13.65 to -6.13), and HbA1c (MD: -0.78; 95% CI: -1.07 to -0.49). Adverse events were more frequent with GLP-1 RAs, particularly nausea and vomiting, while serious adverse events did not differ significantly between groups. CONCLUSION: GLP-1 RAs are associated with meaningful improvements in hepatic steatosis, liver enzymes, body weight, and glycemic control in patients with MASLD or MASH. These findings support their potential role, particularly in patients with coexisting obesity or type 2 diabetes. However, further long-term, adequately powered trials are needed to clarify their effects on fibrosis regression, histological outcomes, and liver-related clinical events. CI - Copyright (c) 2026 the Author(s). Published by Wolters Kluwer Health, LLC. FAU - Alfawaz, Mohammed AU - Alfawaz M AD - Department of Internal Medicine, Gastroenterology Consultant, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Bajamaan, Dareen AU - Bajamaan D AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Alghamdi, Lama AU - Alghamdi L AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Alorfi, Yara AU - Alorfi Y AUID- ORCID: 0009-0000-9755-1121 AD - Internal Medicine Resident, Department of Internal Medicine, King Faisal Specialist Hospital and Research Centre, Jeddah, Saudi Arabia. FAU - Khared, Saud AU - Khared S AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Ameen, Nada AU - Ameen N AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Alamri, Rahaf AU - Alamri R AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Abuladel, Mohammed AU - Abuladel M AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Alshehri, Rayan AU - Alshehri R AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. FAU - Altowairqi, Shaima AU - Altowairqi S AD - Medical Intern, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Fatty Liver/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - *Metabolic Diseases/drug therapy MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Semaglutide MH - Treatment Outcome PMC - PMC13706190 OTO - NOTNLM OT - GLP-1 receptor agonists OT - liraglutide OT - liver fat OT - meta-analysis OT - metabolic dysfunction-associated steatohepatitis OT - metabolic dysfunction-associated steatotic liver disease OT - semaglutide COIS- The authors have no funding and conflicts of interest to declare. EDAT- 2026/10/27 11:31 MHDA- 2026/10/27 11:32 PMCR- 2026/10/23 CRDT- 2026/10/27 10:26 PHST- 2026/07/06 00:00 [received] PHST- 2026/10/09 00:00 [accepted] PHST- 2026/10/27 11:32 [medline] PHST- 2026/10/27 11:31 [pubmed] PHST- 2026/10/27 10:26 [entrez] PHST- 2026/10/23 00:00 [pmc-release] AID - 00005792-202610230-00087 [pii] AID - MD-D-26-10416 [pii] AID - 10.1097/MD.0000000000051306 [doi] PST - ppublish SO - Medicine (Baltimore). 2026 Oct 23;105(43):e51306. doi: 10.1097/MD.0000000000051306. PMID- 42918905 OWN - NLM STAT- MEDLINE DCOM- 20261023 LR - 20261027 IS - 1432-1041 (Electronic) IS - 0031-6970 (Linking) VI - 82 IP - 11 DP - 2026 Oct 23 TI - GLP-1-based therapies in cardiovascular disease: outcomes, mechanisms, and emerging clinical applications. LID - 276 [pii] LID - 10.1007/s00228-026-04199-0 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown cardiovascular benefits beyond their established role in treating type 2 diabetes mellitus (T2DM). This review evaluates recent clinical evidence, potential mechanisms, and the expanding use of GLP-1-based therapies in cardiovascular disease. METHODS: We reviewed major randomized clinical trials assessing cardiovascular, kidney, and heart failure outcomes, along with related mechanistic studies and clinical guidelines published through July 2026. RESULTS: Early trials, including LEADER, SUSTAIN-6, and REWIND, reported 12%-26% reductions in major adverse cardiovascular events (MACE) in patients with T2DM. More recent trials have extended these findings to other populations. SELECT showed a 20% reduction in MACE among individuals with obesity and established cardiovascular disease but without diabetes, while FLOW demonstrated a 24% reduction in its primary kidney composite outcome. SOUL reported a 14% reduction in MACE with oral semaglutide, and SUMMIT showed a 38% reduction in cardiovascular death or worsening heart failure with tirzepatide. SURPASS-CVOT found tirzepatide to be noninferior, but not superior, to dulaglutide for MACE. These benefits likely involve several mechanisms beyond glucose lowering and weight loss, although gastrointestinal adverse effects still remain a concern. CONCLUSIONS: Growing clinical evidence supports the use of GLP-1-based therapies beyond diabetes management, particularly in patients with cardiovascular disease, chronic kidney disease, or obesity-related heart failure. Further studies will be needed to understand their mechanisms better, long-term safety, and optimal use in clinical practice. CI - (c) 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Jang, Rachelle AU - Jang R AD - Crescenta Valley High School, La Crescenta, CA, USA. FAU - Jang, Michelle AU - Jang M AD - Crescenta Valley High School, La Crescenta, CA, USA. FAU - Ruan, Xinyuan AU - Ruan X AD - Tarbut V'Torah Community Day School, Irvine, CA, USA. FAU - Jin, Caden AU - Jin C AD - San Marino High School, San Marino, CA, USA. FAU - Kim, Woo AU - Kim W AD - Tufts Medical Center, Boston, MA, 02115, USA. wookim3263@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20261023 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Cardiovascular Diseases/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Semaglutide MH - Tirzepatide MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Glucagon-Like Peptide 1 MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Cardiovascular disease OT - Glucagon-like peptide-1 receptor agonists OT - Major adverse cardiovascular events OT - Obesity OT - Type 2 diabetes mellitus COIS- Declarations. Human ethics and consent to participate declarations: Not Applicable. Competing interests: The authors declare no competing interests. EDAT- 2026/10/23 23:32 MHDA- 2026/10/23 23:33 CRDT- 2026/10/23 20:31 PHST- 2026/06/05 00:00 [received] PHST- 2026/10/10 00:00 [accepted] PHST- 2026/10/23 23:33 [medline] PHST- 2026/10/23 23:32 [pubmed] PHST- 2026/10/23 20:31 [entrez] AID - 10.1007/s00228-026-04199-0 [pii] AID - 10.1007/s00228-026-04199-0 [doi] PST - epublish SO - Eur J Clin Pharmacol. 2026 Oct 23;82(11):276. doi: 10.1007/s00228-026-04199-0. PMID- 42905300 OWN - NLM STAT- MEDLINE DCOM- 20261022 LR - 20261027 IS - 2162-4968 (Electronic) IS - 2162-4968 (Linking) VI - 15 IP - 1 DP - 2026 Oct 21 TI - Decoding the Safety Profile of GLP-1 Receptor Agonists: Facts, Myths, and Ongoing Controversies. LID - 91 [pii] LID - 10.1007/s13679-026-00770-z [doi] AB - PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent one of the most significant therapeutic advances in the management of type 2 diabetes and obesity. As their indications have expanded to include cardiovascular and kidney disease, safety concerns involving multiple organ systems have received increasing attention. This narrative review examines the spectrum of adverse effects linked to GLP-1RAs and provides a clinically relevant platform for assessing their safe prescription. RECENT FINDINGS: Gastrointestinal intolerance, modest increases in heart rate, and a modest but reproducible increase in the risk of gallbladder and biliary disease represent the most consistently supported adverse effects of GLP-1RAs. A risk of pancreatitis is also considered to exist, although some studies have challenged this association. Conversely, correlations with neuropsychiatric and dermatological disorders, diabetic retinopathy, nonarteritic anterior ischemic optic neuropathy, perioperative aspiration, sexual and reproductive disturbances, sarcopenia, and malignancy remain controversial. Most available evidence derives from pharmacovigilance databases, retrospective observational studies, and secondary analyses of randomized trials, which are limited by reporting bias, residual confounding, and inability to establish causality. Heterogeneity in study design, statistical methodology, outcome definitions, and patient populations further complicates interpretation. Although several proposed adverse effects have biologically plausible mechanisms, prospective clinical validation remains limited. Notably, recent regulatory decisions, including the Food and Drug Administration (FDA)'s removal of the suicidality warning from GLP-1RA prescribing information, reflect the evolving nature of these safety assessments. The overall benefit-risk profile of GLP-1RAs is favorable. Most emerging safety concerns should currently be regarded as hypothesis-generating signals rather than established toxicities. Individualized risk assessment and appropriate clinical monitoring remain important as ongoing and future prospective studies further define the long-term safety of this rapidly expanding therapeutic class. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Kounatidis, Dimitris C AU - Kounatidis DC AUID- ORCID: 0000-0003-4338-4879 AD - First Department of Internal Medicine, Sismanogleio General Hospital, Athens, 15126, Greece. dimitriskounatidis82@outlook.com. AD - Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. dimitriskounatidis82@outlook.com. FAU - Vallianou, Natalia G AU - Vallianou NG AD - First Department of Internal Medicine, Sismanogleio General Hospital, Athens, 15126, Greece. FAU - Kouveletsou, Marina AU - Kouveletsou M AD - First Department of Internal Medicine, 251 Air Force General Hospital, Athens, Greece. FAU - Kontrafouri, Paraskevi AU - Kontrafouri P AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. FAU - Stamatopoulos, Vasileios AU - Stamatopoulos V AD - Emergency Department, Evangelismos General Hospital, Athens, 10676, Greece. FAU - Rebelos, Eleni AU - Rebelos E AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, 56126, Italy. FAU - Diakoumopoulou, Evanthia AU - Diakoumopoulou E AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. FAU - Dalamaga, Maria AU - Dalamaga M AD - Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, 11527, Greece. LA - eng PT - Journal Article PT - Review DEP - 20261021 PL - United States TA - Curr Obes Rep JT - Current obesity reports JID - 101578283 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Obesity/drug therapy MH - Pancreatitis/chemically induced MH - Tirzepatide MH - Semaglutide MH - Gastrointestinal Diseases/chemically induced MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Adverse effects OT - Dermatological manifestations OT - Drug safety OT - GLP-1 receptor agonists OT - Gallbladder disease OT - Gastrointestinal adverse events OT - Neuropsychiatric disorders OT - Ocular disorders OT - Pneumonia OT - Sarcopenia OT - Semaglutide OT - Tirzepatide COIS- Declarations. Informed Consent: Not applicable. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare no competing interests.. Animal and Human Rights and Informed Consent: None of the authors of this article conducted any research using either human or animal subjects Institutional Review Board Statement: Not applicable. EDAT- 2026/10/22 23:29 MHDA- 2026/10/22 23:30 CRDT- 2026/10/22 17:45 PHST- 2026/08/11 00:00 [received] PHST- 2026/10/15 00:00 [accepted] PHST- 2026/10/22 23:30 [medline] PHST- 2026/10/22 23:29 [pubmed] PHST- 2026/10/22 17:45 [entrez] AID - 10.1007/s13679-026-00770-z [pii] AID - 10.1007/s13679-026-00770-z [doi] PST - epublish SO - Curr Obes Rep. 2026 Oct 21;15(1):91. doi: 10.1007/s13679-026-00770-z. PMID- 42899606 OWN - NLM STAT- MEDLINE DCOM- 20261020 LR - 20261020 IS - 0717-6163 (Electronic) IS - 0034-9887 (Linking) VI - 154 IP - 8 DP - 2026 Aug TI - Effectiveness of Weekly Semaglutide Treatment (0.5 or 1 mg) in Chilean Patients with Type 2 Diabetes Mellitus. PG - 1150-1159 LID - S0034-98872026000801150 [pii] LID - 10.4067/s0034-98872026000801150 [doi] AB - Semaglutide is approved in Chile for the management of type 2 diabetes mellitus (T2DM), although it is generally not available in the public health system. Generating local evidence may aid in its incorporation into national guidelines and reduce the therapeutic gap with international standards. AIM: To evaluate the effectiveness and safety of adding weekly semaglutide to the standard treatment for T2DM in the public health system. METHODS: A phase 4, multicenter, interventional study evaluated the weekly addition of 0.5 or 1 mg of subcutaneous semaglutide over 24 weeks, followed by a 5-week post-treatment monitoring period. RESULTS: n=104 (79.8% women; age: 58.3+/-9.3 years; 44.2% over 60 years of age; 35.6% with >/=1 complication of T2DM). Common comorbidities: hypertension: 71.2%; obesity: 71.2%; dyslipidemia: 51.9%. Most commonly used baseline treatments: metformin, 96.2%; NPH insulin, 65.4%; empagliflozin, 46.2%; regular insulin, 27.9%; insulin glargine, 22.1%; dapagliflozin, 21.2%. At 24 weeks, a reduction in glycosylated hemoglobin (HbA1c: 8.6+/-0.7% to 7+/-1%, difference: -1.6%), fasting blood glucose (160.3+/-49.3 to 133.7+/-54.8 mg/dL, difference: -26.2 mg/dL), and weight (89.3+/-20.2 to 85.3+/-20.4 kg; difference: -4 kg) were confirmed. Participants with HbA1c <7% increased from 0% to 56.4%. Thirty-one percent of patients receiving basal insulin reduced their dose (median: 6 IU). Gastrointestinal adverse events were the most frequent, consistent with the drug's safety profile. CONCLUSIONS: In people with inadequately controlled T2DM in the real world, the addition of a weekly dose of semaglutide was associated with improvement in HbA1c, fasting blood glucose, and weight, and a reduction in insulin dose, with an adequate safety profile. These results provide local evidence on the efficacy of semaglutide in improving various cardio-renal-metabolic risk factors in people with T2DM. FAU - Estica, Marcos AU - Estica M AD - Unidad de Diabetes, Hospital San Juan de Dios, Santiago, Chile. FAU - Godoy, Gonzalo AU - Godoy G AD - Hospital del Salvador, Universidad de Chile, Santiago, Chile. FAU - Vargas, Cecilia AU - Vargas C AD - Medicina Interna, Centro Hospital Padre Hurtado, Santiago, Chile. FAU - Elgueta, Karina AU - Elgueta K AD - Unidad de Diabetes, Hospital San Juan de Dios, Santiago, Chile. FAU - Gattini, Francesca AU - Gattini F AD - Medicina Interna, Centro Hospital Padre Hurtado, Santiago, Chile. FAU - Gutierrez, Vicente AU - Gutierrez V AD - Medicina Interna, Centro Hospital Padre Hurtado, Santiago, Chile. FAU - Salort, Perla AU - Salort P AD - Medicina Interna, Centro Hospital Padre Hurtado, Santiago, Chile. LA - eng LA - spa PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study TT - Efectividad del tratamiento con semaglutida semanal (0,5 o 1 mg) en pacientes chilenos con diabetes mellitus tipo 2. PL - Chile TA - Rev Med Chil JT - Revista medica de Chile JID - 0404312 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Chile MH - Male MH - Treatment Outcome MH - Glycated Hemoglobin/analysis MH - Aged MH - Blood Glucose/analysis MH - Drug Administration Schedule MH - Time Factors EDAT- 2026/10/20 17:34 MHDA- 2026/10/20 17:35 CRDT- 2026/10/20 14:00 PHST- 2025/08/29 00:00 [received] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/10/20 17:35 [medline] PHST- 2026/10/20 17:34 [pubmed] PHST- 2026/10/20 14:00 [entrez] AID - S0034-98872026000801150 [pii] AID - 10.4067/s0034-98872026000801150 [doi] PST - ppublish SO - Rev Med Chil. 2026 Aug;154(8):1150-1159. doi: 10.4067/s0034-98872026000801150. PMID- 42890523 OWN - NLM STAT- MEDLINE DCOM- 20261017 LR - 20261022 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - CagriSema versus Semaglutide 2.4 mg monotherapy for weight management in adults with overweight or obesity, with or without type 2 diabetes: a systematic review, meta-analysis, and trial sequential analysis. PG - 1903335 LID - 10.3389/fendo.2026.1903335 [doi] LID - 1903335 AB - INTRODUCTION: Semaglutide 2.4 mg is the reference pharmacotherapy for weight management, yet many patients do not reach ambitious weight-loss targets. CagriSema, a fixed-dose combination of cagrilintide and semaglutide, may offer additional benefit through complementary mechanisms. We quantified its incremental efficacy and safety against semaglutide 2.4 mg monotherapy in adults with overweight or obesity, with and without type 2 diabetes. METHODS: This PRISMA 2020-compliant review (PROSPERO CRD420261380458) searched PubMed, Embase, Cochrane CENTRAL, ScienceDirect, ClinicalTrials.gov and WHO ICTRP to 30 June 2026 for randomised controlled trials comparing CagriSema with semaglutide 2.4 mg or placebo. Effects were pooled within two prespecified comparator strata using random-effects models with restricted maximum likelihood estimation of tau(2) and a Hartung-Knapp-Sidik-Jonkman small-sample adjustment, with prediction intervals, leave-one-out and phase-3a-restricted sensitivity analyses, trial sequential analysis. RESULTS: Five trials (4,746 unique participants) were included. Versus semaglutide 2.4 mg, CagriSema produced greater weight loss (mean difference -6.89 percentage points, 95% CI -8.70 to -5.06; I(2) = 33%; prediction interval -8.91 to -4.86), a greater absolute reduction in body weight (-7.16 kg, 95% CI -9.15 to -5.17) and in body-mass index (-2.41 kg/m(2), 95% CI -2.83 to -1.99), and roughly twice the likelihood of reaching a 20% reduction (RR 2.10, 95% CI 1.78 to 2.47). Waist circumference fell further (-4.07 cm, 95% CI -5.10 to -3.04). No incremental glycaemic benefit was detected, with intervals for glycated haemoglobin (-0.07, 95% CI -0.14 to 0.01) and fasting plasma glucose lying entirely within prespecified minimal important differences. Injection-site reactions were more frequent (RR 3.14, 95% CI 1.42 to 6.96); gastrointestinal adverse events were not significantly increased under the primary model (RR 1.09, 95% CI 0.97 to 1.21). CONCLUSION: CagriSema produces clinically meaningful additional weight loss and modest improvements in surrogate cardiometabolic measures compared with semaglutide 2.4 mg alone, at the cost of more frequent injection-site reactions and, at most, modestly more frequent gastrointestinal events. The evidence is insufficient to determine whether serious adverse events or neoplasms differ between treatments, and long-term durability, cardiovascular outcomes and body composition remain undetermined. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420261380458. CI - Copyright (c) 2026 Rasool, Shah, Batool, Shah, Khachatryan, Bhardwaj, Ali, Atta, Bakthavatchalam, Khawar and Khawar. FAU - Rasool, Zehra Khatoon AU - Rasool ZK AD - DePaul University, Chicago, IL, United States. FAU - Shah, Rajvi AU - Shah R AD - Narendra Modi Medical College, Ahmedabad, India. FAU - Batool, Ansharah E Zinnia AU - Batool AEZ AD - Rashid Latif Medical College, Lahore, Pakistan. FAU - Shah, Rutvi AU - Shah R AD - Narendra Modi Medical College, Ahmedabad, India. FAU - Khachatryan, Mariam AU - Khachatryan M AD - Fanarjyan Clinic, Yerevan, Armenia. FAU - Bhardwaj, Sushant AU - Bhardwaj S AD - Kathmandu University School of Medical Sciences, Dhulikhel, Nepal. FAU - Ali, Ahmad AU - Ali A AD - Services Institute of Medical Sciences, Lahore, Pakistan. FAU - Atta, Meeran AU - Atta M AD - Services Institute of Medical Sciences, Lahore, Pakistan. FAU - Bakthavatchalam, Pugazhandhi AU - Bakthavatchalam P AD - American University of Antigua, St. John's, Antigua and Barbuda. FAU - Khawar, Mirza Muhammad Hadeed AU - Khawar MMH AD - Services Institute of Medical Sciences, Lahore, Pakistan. FAU - Khawar, Muneeb AU - Khawar M AD - King Edward Medical University, Lahore, Pakistan. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20261002 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - Weight Loss/drug effects MH - Randomized Controlled Trials as Topic MH - *Anti-Obesity Agents/administration & dosage/therapeutic use PMC - PMC13673521 OTO - NOTNLM OT - CagriSema OT - Semaglutide OT - cagrilintide OT - obesity OT - weight loss COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/10/17 23:38 MHDA- 2026/10/17 23:39 PMCR- 2026/10/02 CRDT- 2026/10/17 16:47 PHST- 2026/06/08 00:00 [received] PHST- 2026/09/06 00:00 [revised] PHST- 2026/09/09 00:00 [accepted] PHST- 2026/10/17 23:39 [medline] PHST- 2026/10/17 23:38 [pubmed] PHST- 2026/10/17 16:47 [entrez] PHST- 2026/10/02 00:00 [pmc-release] AID - 10.3389/fendo.2026.1903335 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Oct 2;17:1903335. doi: 10.3389/fendo.2026.1903335. eCollection 2026. PMID- 42886550 OWN - NLM STAT- MEDLINE DCOM- 20261016 LR - 20261022 IS - 1819-6357 (Electronic) IS - 1993-2820 (Print) IS - 1819-6357 (Linking) VI - 21 IP - 1 DP - 2026 Dec 31 TI - Pharmacy students' knowledge and attitudes regarding GLP-1 receptor agonist adverse effects in obesity management: a cross-sectional study. PG - 2749899 LID - 10.1080/19932820.2026.2749899 [doi] LID - 2749899 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are important therapeutic options for obesity and type 2 diabetes mellitus. Despite their increasing use, safety concerns remain, and pharmacy students' knowledge of their adverse effects is unclear. This study evaluated pharmacy students' knowledge and attitudes regarding GLP-1 RA adverse effects in obesity management. A cross-sectional questionnaire-based study was conducted among undergraduate Doctor of Pharmacy (Pharm.D.) students (1st-7th year) at Umm Al-Qura University, Saudi Arabia, between November and December 2025. A newly developed questionnaire, reviewed by two experts and pilot-tested among 10 students, assessed 17 knowledge and five attitude items covering indications, mechanisms, adverse effects, and clinical scenarios. Of 1,118 eligible students, 296 completed the survey (response rate: 26.5%). Descriptive statistics and multivariable regression analyses were performed using RStudio (version 2024.9.1.394). Among participants (63.9% male), the mean knowledge score was 7.6 +/- 4.0/17. Most agreed that adverse effects significantly impact clinical use (59.4%) and supported further education on less common side effects (61.1%). Nausea was the most frequently recognized adverse effect (59.1%), whereas thyroid C-cell tumors observed in rodent studies (25.0%) and diabetic retinopathy complications (36.5%) were less commonly identified. Only 37.2% correctly recognized that hypoglycemia is uncommon with GLP-1 RA monotherapy. Higher knowledge scores were significantly associated with greater confidence in knowledge (OR = 1.11, 95% CI: 1.06-1.17; p < 0.001) and stronger endorsement of further education on less common side effects (OR = 1.11, 95% CI: 1.06-1.18; p < 0.001), whereas gender and academic year were not significant predictors of any attitude item. Pharmacy students demonstrated limited knowledge but generally positive attitudes regarding GLP-1 RA safety. These findings highlight the need to strengthen pharmacovigilance and evidence-based medication safety education within pharmacy curricula to improve clinical preparedness and patient counseling. FAU - Khojah, Alaa A AU - Khojah AA AD - Pharmaceutical Sciences Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Gazzaz, Malaz J AU - Gazzaz MJ AD - Pharmaceutical practices Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Aldurdunji, Mohammed M AU - Aldurdunji MM AD - Pharmaceutical practices Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Safiraldeen, Ahmad E AU - Safiraldeen AE AD - College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Al-Qurashi, Ibrahim R AU - Al-Qurashi IR AD - College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Alhazmi, Mohammad A AU - Alhazmi MA AD - College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Abdalla, Ashraf N AU - Abdalla AN AD - Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Alqurashi, Roaya S AU - Alqurashi RS AD - Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Wali, Saad M AU - Wali SM AUID- ORCID: 0009-0006-0080-4799 AD - Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. LA - eng PT - Journal Article DEP - 20261016 PL - United States TA - Libyan J Med JT - The Libyan journal of medicine JID - 101299403 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Cross-Sectional Studies MH - Male MH - Female MH - *Health Knowledge, Attitudes, Practice MH - *Students, Pharmacy/statistics & numerical data/psychology MH - Saudi Arabia MH - Surveys and Questionnaires MH - *Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Young Adult MH - Hypoglycemic Agents/adverse effects PMC - PMC13678873 OTO - NOTNLM OT - GLP-1 receptor agonists OT - attitudes OT - knowledge OT - obesity OT - pharmacovigilance OT - pharmacy students OT - semaglutide COIS- No potential conflict of interest was reported by the author(s). EDAT- 2026/10/16 19:05 MHDA- 2026/10/16 19:06 PMCR- 2026/10/16 CRDT- 2026/10/16 12:33 PHST- 2026/10/16 19:06 [medline] PHST- 2026/10/16 19:05 [pubmed] PHST- 2026/10/16 12:33 [entrez] PHST- 2026/10/16 00:00 [pmc-release] AID - 2749899 [pii] AID - 10.1080/19932820.2026.2749899 [doi] PST - ppublish SO - Libyan J Med. 2026 Dec 31;21(1):2749899. doi: 10.1080/19932820.2026.2749899. Epub 2026 Oct 16. PMID- 42885796 OWN - NLM STAT- MEDLINE DCOM- 20261022 LR - 20261022 IS - 2047-9980 (Electronic) IS - 2047-9980 (Linking) VI - 15 IP - 20 DP - 2026 Oct 20 TI - Glucagon-Like Peptide-1 Receptor Agonists and Incident Cardiovascular Events and Death in Treated Serious Mental Illness, Type 2 Diabetes, and Obesity. PG - e051982 LID - 10.1161/JAHA.126.051982 [doi] AB - BACKGROUND: Adults with serious mental illness (SMI), type 2 diabetes, and obesity have elevated cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have established cardiometabolic benefits in the general population, but their effects in SMI are unclear. We evaluated whether GLP-1RA use was associated with lower risks of incident myocardial infarction (MI), heart failure (HF), and all-cause death. METHODS: This was a retrospective propensity score-matched cohort study of 218 043 adults with SMI, type 2 diabetes, obesity, and active antipsychotic or antidepressant medications in the TriNetX database (73 health care organizations). Outcomes were incident MI, HF, and all-cause death at 1 and 3 years. The primary exposure was GLP-1RA use versus nonuse; secondary analyses examined semaglutide or tirzepatide. Exploratory analyses evaluated sex, race, and sodium-glucose cotransporter-2 inhibitor and dipeptidyl peptidase-4 inhibitor use. RESULTS: GLP-1RA use was associated with lower risks of incident MI, HF, and all-cause death. Risk differences at 1 and 3 years were -0.007 and -0.010 for MI, -0.011 and -0.018 for HF, and -0.039 and -0.065 for death (all P<0.001). Semaglutide or tirzepatide use was also associated with lower risks of MI, HF, and death (all P<0.001). Findings were directionally consistent after accounting for sodium-glucose cotransporter-2 inhibitor and dipeptidyl peptidase-4 inhibitor use. CONCLUSIONS: Adults with treated SMI, type 2 diabetes, and obesity using GLP-1RAs, particularly semaglutide or tirzepatide, had significantly reduced 1- and 3-year risks of incident MI, HF, and all-cause death versus nonusers. These pooled associations should be interpreted in the context of SMI's clinical heterogeneity and the limitations of administrative case ascertainment. FAU - Governor, Samuel B AU - Governor SB AUID- ORCID: 0000-0001-6412-7279 AD - St. John's Episcopal Hospital New York NY USA. FAU - Davila-Garcia, David M AU - Davila-Garcia DM AD - Institute for Informatics, Data Science and Biostatistics Washington University School of Medicine St. Louis MO USA. FAU - Rivera-Segarra, Eliut AU - Rivera-Segarra E AUID- ORCID: 0000-0001-8643-9273 AD - School of Behavioral and Brain Sciences Ponce Health Sciences University Ponce PR USA. FAU - Filiatreau, Lindsey M AU - Filiatreau LM AUID- ORCID: 0000-0002-0355-4477 AD - Bursky School of Public Health Washington University in St. Louis St. Louis MO USA. FAU - Tollinchi-Natali, Nelmit AU - Tollinchi-Natali N AUID- ORCID: 0009-0009-8995-2131 AD - School of Dental Medicine Ponce Health Sciences University Ponce PR USA. FAU - Essien, Ekow AU - Essien E AUID- ORCID: 0009-0006-5396-0955 AD - Aurora Health Care Kenosha WI USA. FAU - Altaee, Osamah AU - Altaee O AUID- ORCID: 0000-0003-3174-0995 AD - University of Texas Health San Antonio TX USA. FAU - Otchere, Prince AU - Otchere P AD - University of Texas Health San Antonio TX USA. FAU - Cabassa, Leopoldo J AU - Cabassa LJ AUID- ORCID: 0000-0002-1872-4141 AD - Brown School of Social Work and Center for Mental Health Services Research Washington University in St. Louis MO USA. FAU - Davila-Roman, Victor G AU - Davila-Roman VG AUID- ORCID: 0000-0001-8554-0011 AD - Cardiovascular Division and Global Health Center, Department of Medicine, School of Medicine and Bursky School of Public Health Washington University in St. Louis MO USA. LA - eng PT - Journal Article DEP - 20261016 PL - England TA - J Am Heart Assoc JT - Journal of the American Heart Association JID - 101580524 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Antipsychotic Agents) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Incretins) RN - 0 (Antidepressive Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/mortality/complications MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/epidemiology/mortality/complications MH - Retrospective Studies MH - *Mental Disorders/drug therapy/epidemiology/mortality MH - Middle Aged MH - Semaglutide MH - Tirzepatide MH - Incidence MH - Aged MH - Antipsychotic Agents/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Myocardial Infarction/epidemiology/prevention & control/mortality MH - *Heart Failure/epidemiology/prevention & control/mortality MH - United States/epidemiology MH - Cause of Death MH - Risk Assessment MH - Glucagon-Like Peptides/therapeutic use MH - *Incretins/therapeutic use MH - Risk Factors MH - Adult MH - *Cardiovascular Diseases/mortality/prevention & control/epidemiology MH - Time Factors MH - Antidepressive Agents/therapeutic use OTO - NOTNLM OT - cardiovascular outcomes OT - death OT - glucagon-like peptide-1 receptor agonists OT - heart failure OT - myocardial infarction OT - obesity OT - semaglutide OT - serious mental illness OT - tirzepatide OT - type 2 diabetes EDAT- 2026/10/16 11:38 MHDA- 2026/10/23 05:32 CRDT- 2026/10/16 07:34 PHST- 2026/10/23 05:32 [medline] PHST- 2026/10/16 11:38 [pubmed] PHST- 2026/10/16 07:34 [entrez] AID - 10.1161/JAHA.126.051982 [doi] PST - ppublish SO - J Am Heart Assoc. 2026 Oct 20;15(20):e051982. doi: 10.1161/JAHA.126.051982. Epub 2026 Oct 16. PMID- 42866418 OWN - NLM STAT- MEDLINE DCOM- 20261013 LR - 20261013 IS - 2754-0413 (Electronic) IS - 2754-0413 (Linking) VI - 5 IP - 1 DP - 2026 TI - Values, preferences, and treatment burden for initiation of GLP-1 receptor agonists, SGLT-2 inhibitors, tirzepatide, and finerenone in adults with type 2 diabetes: systematic review. PG - e002780 LID - 10.1136/bmjmed-2026-002780 [doi] LID - e002780 AB - OBJECTIVES: To summarise existing evidence regarding the values, preferences, and perceived treatment burden of adults with type 2 diabetes when considering initiation of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), finerenone, or tirzepatide. DESIGN: Systematic review. DATA SOURCES: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched from database inception to 7 January 2025 (updating a previous systematic review that captured literature up to 23 May 2020). ELIGIBILITY CRITERIA: Quantitative or qualitative studies were included if they reported patient reported values, preferences, or treatment burden among adults with type 2 diabetes and compared initiation of GLP-1 RA, SGLT-2i, tirzepatide, or finerenone with each other or with other glucose-lowering treatments. DATA EXTRACTION AND SYNTHESIS: Paired reviewers independently screened studies, extracted data, and assessed risk of bias. Certainty of evidence was evaluated using GRADE. Findings were synthesised narratively. RESULTS: Thirty four studies (15 656 patients) were included, 17 of which were new since the previous 2021 review (8360 patients). Of the newly included studies, 10 evaluated GLP-1 RA, seven evaluated SGLT-2i, and one evaluated tirzepatide; no studies evaluated finerenone (because several studies compared multiple drug classes, these categories are not mutually exclusive). Across comparisons, patients consistently reported glycaemic efficacy, cardiovascular risk reduction, and simplicity of administration as their priorities. Oral once-daily regimens and once-weekly injectable treatments with easy-to-use devices were generally preferred. Weight loss was valued but was typically secondary to glycaemic and cardiovascular benefits. SGLT-2i and GLP-1 RA were often preferred over dipeptidyl peptidase 4-inhibitors (DPP-4i), thiazolidinediones, and insulins, but no consistent preference emerged for SGLT-2i over GLP-1 RA. Tirzepatide was favoured over semaglutide in a single study, largely due to greater haemoglobin A(1c) reduction and lower hypoglycaemia risk. Certainty of evidence for all comparisons was low or very low certainty. CONCLUSION: Adults with type 2 diabetes prioritise treatment effectiveness and convenience among glucose-lowering treatments. Current evidence does not support a clear preference between SGLT-2i and GLP-1 RA, and data for finerenone are absent. These findings underscore the importance of shared decision making informed by individual patient priorities. PROSPERO REGISTRATION: CRD42023429170. CI - Copyright (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Gonzalez-Cruz, Daniela C AU - Gonzalez-Cruz DC AUID- ORCID: 0000-0003-3709-9326 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. AD - Endocrinology Division, Department of Internal Medicine, Dr Jose Eleuterio Gonzalez University Hospital, Monterrey, Mexico. FAU - Garcia-Campa, Mariano AU - Garcia-Campa M AUID- ORCID: 0000-0001-7733-6432 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. FAU - Moreno-Pena, Pablo Jose AU - Moreno-Pena PJ AUID- ORCID: 0000-0003-3661-4912 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. FAU - Avalos-Bishop, Andres AU - Avalos-Bishop A AUID- ORCID: 0000-0002-2017-0547 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. AD - Endocrinology Division, Department of Internal Medicine, Dr Jose Eleuterio Gonzalez University Hospital, Monterrey, Mexico. FAU - Manzanares-Gallegos, Dulce Maria AU - Manzanares-Gallegos DM AUID- ORCID: 0009-0008-3958-1267 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. AD - Endocrinology Division, Department of Internal Medicine, Dr Jose Eleuterio Gonzalez University Hospital, Monterrey, Mexico. FAU - Garcia-Garcia, Fernanda M AU - Garcia-Garcia FM AUID- ORCID: 0009-0004-4629-2579 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. FAU - Montiel Labastida, Jan Alejandro AU - Montiel Labastida JA AUID- ORCID: 0009-0006-8221-6578 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. FAU - Gonzalez-Gonzalez, Jose Gerardo AU - Gonzalez-Gonzalez JG AUID- ORCID: 0000-0002-6609-9483 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. AD - Endocrinology Division, Department of Internal Medicine, Dr Jose Eleuterio Gonzalez University Hospital, Monterrey, Mexico. FAU - Agarwal, Arnav AU - Agarwal A AUID- ORCID: 0000-0002-0931-7851 AD - Department of Medicine, University of Alberta, Edmonton, AB, Canada. AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. FAU - Manja, Veena AU - Manja V AUID- ORCID: 0000-0003-0410-8089 AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of California Davis, Sacramento, CA, USA. AD - Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada. FAU - Olav Vandvik, Per AU - Olav Vandvik P AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. AD - Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway. FAU - Agoritsas, Thomas AU - Agoritsas T AUID- ORCID: 0000-0002-6182-9969 AD - MAGIC Evidence Ecosystem Foundation, Oslo, Norway. AD - Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada. AD - Division of General Internal Medicine, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland. FAU - Mustafa, Reem A AU - Mustafa RA AD - Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada. AD - Department of Internal Medicine, Division of Nephrology and Hypertension, University of Kansas, Lawrence, KS, USA. FAU - Rodriguez-Gutierrez, Rene AU - Rodriguez-Gutierrez R AUID- ORCID: 0000-0002-3022-5302 AD - Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit Mexico), Universidad Autonoma de Nuevo Leon Facultad de Medicina, Monterrey, Mexico. AD - Endocrinology Division, Department of Internal Medicine, Dr Jose Eleuterio Gonzalez University Hospital, Monterrey, Mexico. LA - eng PT - Journal Article PT - Systematic Review DEP - 20261008 PL - England TA - BMJ Med JT - BMJ medicine JID - 9918487584306676 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Naphthyridines) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - Tirzepatide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Naphthyridines/therapeutic use MH - *Patient Preference MH - Adult PMC - PMC13656128 OTO - NOTNLM OT - Diabetes mellitus OT - Endocrinology OT - Internal medicine COIS- All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. EDAT- 2026/10/13 17:37 MHDA- 2026/10/13 17:38 PMCR- 2026/10/08 CRDT- 2026/10/13 14:07 PHST- 2026/03/11 00:00 [received] PHST- 2026/08/20 00:00 [accepted] PHST- 2026/10/13 17:38 [medline] PHST- 2026/10/13 17:37 [pubmed] PHST- 2026/10/13 14:07 [entrez] PHST- 2026/10/08 00:00 [pmc-release] AID - bmjmed-2026-002780 [pii] AID - 10.1136/bmjmed-2026-002780 [doi] PST - epublish SO - BMJ Med. 2026 Oct 8;5(1):e002780. doi: 10.1136/bmjmed-2026-002780. eCollection 2026. PMID- 42865361 OWN - NLM STAT- MEDLINE DCOM- 20261013 LR - 20261014 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Pancreatic and biliary safety signals of GLP-1 receptor agonists and tirzepatide: a disproportionality analysis of FAERS reports. PG - 1941948 LID - 10.3389/fendo.2026.1941948 [doi] LID - 1941948 AB - BACKGROUND: The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and tirzepatide is increasing rapidly worldwide, and the pancreatic and biliary safety of these drugs has been a concern. This study was based on the US Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate the pancreatic and biliary adverse event reporting signals of liraglutide, semaglutide, tirzepatide and dulaglutide. OBJECTIVES: To describe the reporting patterns of pancreatic and biliary adverse events for liraglutide, semaglutide, dulaglutide, and tirzepatide, and to identify signals in both organ systems within a single framework. DESIGN: Retrospective disproportionality analysis of individual case safety reports. METHODS: FAERS data from Q3-2009 through Q3-2025 were extracted, and deduplicated ICSRs were used as the unit of analysis. Reporting odds ratios (RORs) and information components (ICs) were computed at composite and Preferred Term levels; signals required the lower 95% confidence bound for the ROR to exceed 1 and IC025 to exceed 0. Metformin and sodium-glucose cotransporter-2 inhibitors were included as contextual benchmarks. Analyses were stratified by brand (diabetes/obesity indication), sex, age, and reporter type, and time to onset was examined. RESULTS: A disproportionality signal for pancreatic adverse events was observed for all four study drugs, but the control drugs metformin and SGLT2i also showed positive signals. For biliary events, all four study drugs showed signals, whereas the two control drugs showed no signals. After stratification by brand, the pancreatic signal remained for brands with diabetes indications, while the signal was weaker for brands with obesity indications. After excluding the cases of biliary tract co-reporting, the pancreatic signal still existed. Median time to onset ranged from 85.5 to 136 days for pancreatic events and from 146.5 to 320 days for biliary events. CONCLUSION: Both GLP-1RAs and tirzepatide are associated with disproportionate reporting of pancreatic and biliary adverse events in FAERS. Signals are influenced by indication, reporting behavior, and time effects and cannot be used to estimate incidence or prove causality. These signals suggest the need for further validation in real-world cohort studies. CI - Copyright (c) 2026 Wu, Li, Wang, Chen, Shi and Zhao. FAU - Wu, Yuanbin AU - Wu Y AD - Department of Emergency Medicine, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, China. FAU - Li, Ke AU - Li K AD - Department of Emergency Medicine, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, China. FAU - Wang, Yuhong AU - Wang Y AD - Department of Emergency Medicine, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, China. FAU - Chen, Zike AU - Chen Z AD - Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Shi, Min AU - Shi M AD - Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhao, Jiawei AU - Zhao J AD - Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article DEP - 20260928 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Tirzepatide/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Female MH - Semaglutide MH - Male MH - United States/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - *Pancreas/drug effects MH - United States Food and Drug Administration MH - Middle Aged MH - *Biliary Tract Diseases/chemically induced/epidemiology MH - *Biliary Tract/drug effects MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC13654742 OTO - NOTNLM OT - FAERS OT - biliary adverse events OT - glucagon-like peptide-1 receptor agonists OT - pancreatic adverse events OT - pharmacovigilance OT - tirzepatide COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/10/13 11:41 MHDA- 2026/10/13 11:42 PMCR- 2026/09/28 CRDT- 2026/10/13 05:32 PHST- 2026/07/19 00:00 [received] PHST- 2026/09/05 00:00 [revised] PHST- 2026/09/14 00:00 [accepted] PHST- 2026/10/13 11:42 [medline] PHST- 2026/10/13 11:41 [pubmed] PHST- 2026/10/13 05:32 [entrez] PHST- 2026/09/28 00:00 [pmc-release] AID - 10.3389/fendo.2026.1941948 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Sep 28;17:1941948. doi: 10.3389/fendo.2026.1941948. eCollection 2026. PMID- 42859665 OWN - NLM STAT- MEDLINE DCOM- 20261011 LR - 20261012 IS - 1179-142X (Electronic) IS - 1179-142X (Linking) VI - 19 DP - 2026 TI - Severe Euglycemic Diabetic Ketoacidosis After Semaglutide-Associated Poor Intake Despite Empagliflozin Discontinuation: A Case Report. PG - 650090 LID - 10.2147/IMCRJ.S650090 [doi] LID - 650090 AB - Euglycemic diabetic ketoacidosis (EDKA) may be overlooked when serum glucose is near normal. A 68-year-old woman with long-standing type 2 diabetes developed approximately three weeks of nausea, intermittent vomiting and diarrhea, and minimal oral intake after semaglutide initiation at 0.25 mg once weekly for four weeks followed by 0.5 mg once weekly. Patient and family medication reconciliation indicated that she had stopped empagliflozin, metformin, and pioglitazone approximately two weeks before presentation but continued semaglutide, with the last dose approximately eight days before admission. She presented with weakness, dyspnea, slowed speech, and disorientation. Initial testing showed glucose 132 mg/dL, venous pH 7.13, bicarbonate 9 mmol/L, anion gap 26 mmol/L, and beta-hydroxybutyrate 99.5 mg/dL. She improved with intravenous crystalloid, dextrose-containing fluids, insulin infusion, and electrolyte replacement. The temporal association is consistent with a clinically plausible contribution from semaglutide-associated gastrointestinal intolerance and carbohydrate depletion to EDKA despite reported prior empagliflozin discontinuation. Normal glucose should not delay ketone and acid-base testing when compatible symptoms and poor intake are present. CI - (c) 2026 Niknam and Niknam. FAU - Niknam, Kianoush AU - Niknam K AUID- ORCID: 0000-0002-3506-0463 AD - Department of Internal Medicine, Legacy Salmon Creek Medical Center, Vancouver, WA, USA. FAU - Niknam, Tahmoores AU - Niknam T AUID- ORCID: 0009-0000-3328-9371 AD - Department of Pulmonary and Critical Care, Shiraz University of Medical Sciences, Shiraz, Iran. LA - eng PT - Case Reports PT - Journal Article DEP - 20261006 PL - New Zealand TA - Int Med Case Rep J JT - International medical case reports journal JID - 101566269 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - HDC1R2M35U (empagliflozin) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Humans MH - Female MH - Semaglutide MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Benzhydryl Compounds/administration & dosage/therapeutic use MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Diabetic Ketoacidosis/chemically induced/therapy/diagnosis MH - *Glucosides/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Insulin PMC - PMC13653545 OTO - NOTNLM OT - GLP-1 receptor agonist OT - case report OT - euglycemic diabetic ketoacidosis OT - semaglutide OT - starvation COIS- The authors declare no conflicts of interest. EDAT- 2026/10/11 05:38 MHDA- 2026/10/11 05:39 PMCR- 2026/10/06 CRDT- 2026/10/11 04:23 PHST- 2026/08/20 00:00 [received] PHST- 2026/10/04 00:00 [accepted] PHST- 2026/10/11 05:39 [medline] PHST- 2026/10/11 05:38 [pubmed] PHST- 2026/10/11 04:23 [entrez] PHST- 2026/10/06 00:00 [pmc-release] AID - 650090 [pii] AID - 10.2147/IMCRJ.S650090 [doi] PST - epublish SO - Int Med Case Rep J. 2026 Oct 6;19:650090. doi: 10.2147/IMCRJ.S650090. eCollection 2026. PMID- 42854065 OWN - NLM STAT- MEDLINE DCOM- 20261009 LR - 20261014 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 105 IP - 41 DP - 2026 Oct 9 TI - Short-term clinical efficacy and recorded adverse events of semaglutide combined with dapagliflozin in patients with type 2 diabetes mellitus and chronic kidney disease. PG - e51019 LID - 10.1097/MD.0000000000051019 [doi] LID - e51019 AB - Type 2 diabetes mellitus (T2DM) complicated by chronic kidney disease (CKD) is associated with persistent hyperglycemia, progressive renal impairment, systemic inflammation, and an increased risk of adverse clinical outcomes. Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists have shown metabolic and cardiorenal benefits, but clinical evidence regarding their combined use in patients with T2DM and CKD remains limited. This retrospective observational study included 126 patients with T2DM complicated by CKD who were treated at our hospital between March 2023 and July 2024. Patients were identified through a review of electronic medical records and the application of predefined eligibility criteria. Treatment groups reflected the actual regimen documented in the medical record rather than random allocation. The final analytic cohort comprised 42 patients in each group; the equal group size reflected the eligible records with complete baseline and 8-week follow-up data available in each treatment category during the study period rather than a prospective 1:1:1 enrollment target. The treatment duration was 8 weeks. Glycemic indices, renal function-related parameters, inflammatory markers, clinical response, and recorded adverse events were compared among the 3 groups. After 8 weeks of treatment, fasting plasma glucose, 2-hour postprandial plasma glucose, hemoglobin A1c, blood urea nitrogen, serum creatinine, 24-hour urinary protein, erythrocyte sedimentation rate, interleukin-6, and high-sensitivity C-reactive protein were significantly reduced in all 3 groups compared with baseline. The combination group showed greater short-term reductions in glycemic indices, renal function-related parameters, and inflammatory markers than either monotherapy group. The overall clinical response rate was significantly higher in the combination group than in the dapagliflozin or semaglutide group. In patients with T2DM complicated by CKD, semaglutide combined with dapagliflozin was associated with greater short-term improvements in glycemic control, inflammatory markers, and renal function-related indicators, as well as a higher exploratory clinical response rate, than either monotherapy. No increase in recorded adverse events was detected during 8 weeks of treatment. Because of the retrospective design, modest sample size, and short observation period, these findings should not be interpreted as demonstrating definitive long-term renal benefit or equivalent long-term safety. Further large-scale prospective studies with standardized renal outcomes are required. CI - Copyright (c) 2026 the Author(s). Published by Wolters Kluwer Health, LLC. FAU - Gong, Cheng AU - Gong C AD - Department of Geriatric Medicine, Yangtze River Shipping General Hospital, Hubei, China. FAU - Luo, Qiong AU - Luo Q AD - Department of Endocrinology and Metabolism, Yangtze River Shipping General Hospital, Hubei, China. FAU - Li, Qin AU - Li Q AUID- ORCID: 0009-0008-8832-7089 AD - Department of Endocrinology and Metabolism, Yangtze River Shipping General Hospital, Hubei, China. LA - eng PT - Journal Article PT - Observational Study PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Benzhydryl Compounds) RN - 0 (Blood Glucose) RN - 1ULL0QJ8UC (dapagliflozin) RN - 0 (Glucosides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Benzhydryl Compounds/adverse effects/therapeutic use/administration & dosage MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Therapy, Combination MH - *Glucosides/adverse effects/therapeutic use/administration & dosage MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - Retrospective Studies MH - *Semaglutide/administration & dosage/adverse effects/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Treatment Outcome PMC - PMC13657616 OTO - NOTNLM OT - chronic kidney disease OT - dapagliflozin OT - inflammation OT - renal function OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors have no funding and conflicts of interest to declare. EDAT- 2026/10/09 17:34 MHDA- 2026/10/09 17:35 PMCR- 2026/10/09 CRDT- 2026/10/09 14:43 PHST- 2026/05/06 00:00 [received] PHST- 2026/09/18 00:00 [accepted] PHST- 2026/10/09 17:35 [medline] PHST- 2026/10/09 17:34 [pubmed] PHST- 2026/10/09 14:43 [entrez] PHST- 2026/10/09 00:00 [pmc-release] AID - 00005792-202610090-00067 [pii] AID - MD-D-26-06895 [pii] AID - 10.1097/MD.0000000000051019 [doi] PST - ppublish SO - Medicine (Baltimore). 2026 Oct 9;105(41):e51019. doi: 10.1097/MD.0000000000051019. PMID- 42827168 OWN - NLM STAT- MEDLINE DCOM- 20261002 LR - 20261008 IS - 1534-3170 (Electronic) IS - 1523-3782 (Linking) VI - 28 IP - 1 DP - 2026 Oct 3 TI - Comorbid Cardiovascular-Liver Disease Disparities: Current Understanding and Future Directions. LID - 102 [pii] LID - 10.1007/s11886-026-02426-9 [doi] AB - PURPOSE OF REVIEW: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease and a multisystem cardiometabolic disorder. Cardiovascular disease (CVD) is a major cause of morbidity and mortality in this population. This review examines disparities in the recognition and management of coexisting cardiovascular and metabolic liver disease. RECENT FINDINGS: Shared metabolic and inflammatory pathways link liver disease with obesity, type 2 diabetes, hypertension, and CVD. Differences in measured disease prevalence across racial and ethnic groups must be interpreted separately from genetic susceptibility and in the context of structural inequities, diagnostic practices, and access to care. Socioeconomic disadvantage and sex- and gender-related barriers may further affect diagnosis and treatment. Resmetirom and semaglutide have expanded treatment options for selected adults with metabolic dysfunction-associated steatohepatitis (MASH), but unequal access to fibrosis assessment, insurance coverage, and longitudinal care may limit their benefits. An equity-centered cardio-hepatology framework should integrate early risk identification, stepwise noninvasive fibrosis assessment, individualized cardiovascular prevention, and access to indicated liver-directed therapies. Treatment and quality measures should reflect clinical eligibility rather than medication use alone. Inclusive research and coordinated long-term care are needed to evaluate whether these strategies narrow disparities. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Hafez, Abdelrahman AU - Hafez A AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. AD - Department of Medicine, University of Arizona, Phoenix, AZ, USA. FAU - Nour, Mohamed AU - Nour M AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Ibrahim, Ramzi AU - Ibrahim R AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. Ibrahim.ramzi@mayo.edu. AD - Department of Cardiovascular Medicine, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ, 85259, USA. Ibrahim.ramzi@mayo.edu. FAU - Othman, Jenna AU - Othman J AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Mohamed, Mohamed Reyad AU - Mohamed MR AD - Department of Medicine, University of Arizona, Phoenix, AZ, USA. FAU - Awad, Kamal AU - Awad K AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Zanco, Julia AU - Zanco J AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - De Sousa Barzon Serra, Vinicius AU - De Sousa Barzon Serra V AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Abdelnabi, Mahmoud AU - Abdelnabi M AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Elbsiony, Mahmoud AU - Elbsiony M AD - Department of Cardiovascular Medicine, University of Arizona, Phoenix, AZ, USA. FAU - Alsidawi, Said AU - Alsidawi S AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Lester, Steven J AU - Lester SJ AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Ayoub, Chadi AU - Ayoub C AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Arsanjani, Reza AU - Arsanjani R AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. LA - eng PT - Journal Article PT - Review DEP - 20261003 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Cardiovascular Diseases/epidemiology/therapy MH - Comorbidity MH - *Healthcare Disparities MH - Prevalence MH - Diabetes Mellitus, Type 2/epidemiology MH - Obesity/epidemiology MH - *Fatty Liver/epidemiology/therapy MH - Semaglutide MH - *Liver Diseases/epidemiology/therapy MH - Risk Factors MH - Non-alcoholic Fatty Liver Disease/epidemiology MH - Socioeconomic Disparities in Health OTO - NOTNLM OT - Cardio-hepatology OT - Cardiovascular disease OT - Diabetes OT - Health disparities OT - Metabolic dysfunction-associated steatohepatitis OT - Metabolic dysfunction-associated steatotic liver disease OT - Obesity OT - Resmetirom OT - Semaglutide COIS- Declarations. Conflict of Interest: Chadi Ayoub reports a stipend received as Section Editor from Circulation: Cardiovascular Imaging, outside the submitted work. The remaining authors have nothing to disclose. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. EDAT- 2026/10/03 05:33 MHDA- 2026/10/03 05:34 CRDT- 2026/10/02 23:19 PHST- 2026/08/26 00:00 [received] PHST- 2026/09/28 00:00 [accepted] PHST- 2026/10/03 05:34 [medline] PHST- 2026/10/03 05:33 [pubmed] PHST- 2026/10/02 23:19 [entrez] AID - 10.1007/s11886-026-02426-9 [pii] AID - 10.1007/s11886-026-02426-9 [doi] PST - epublish SO - Curr Cardiol Rep. 2026 Oct 3;28(1):102. doi: 10.1007/s11886-026-02426-9. PMID- 42824923 OWN - NLM STAT- MEDLINE DCOM- 20261002 LR - 20261003 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Predictors of treatment response to semaglutide for weight management. PG - 1893511 LID - 10.3389/fendo.2026.1893511 [doi] LID - 1893511 AB - The emergence of weekly, injectable glucagon-like peptide-1 (GLP-1) receptor agonists has revolutionized the obesity management landscape. Numerous studies have shown high efficacy as well as great variability in weight loss, highlighting the need for this mini review, summarizing current evidence about predictors of semaglutide-related weight loss. The first well-known determinant of semaglutide-induced weight loss is the presence of type 2 DM which is associated with significantly lower body weight reduction. The second predictor is sex, with females exhibiting a greater weight loss than males by a mean 6%. In addition, higher maintenance dose of 7.2 mg is superior to standard 2.4 mg dose in weight reduction by a mean 3%. There is no clear association of age and baseline body mass index with the magnitude of semaglutide-driven weight loss, except for the possibility of adolescence enhancing and overweight reducing this treatment effect. The potential impact of genetic polymorphisms of individual treatment response to semaglutide remains incompletely understood, limited so far to a modest effect of specific variants in GLP1 receptor gene. Another potential predictor of response could be obesity phenotype, with preliminary data supporting greater effectiveness of semaglutide in individuals with ''hungry gut'' phenotype. Type of lifestyle modification does not seem to have a significant effect on the variability of semaglutide-driven weight loss. Further studies are needed to expand knowledge about predictors of response to semaglutide, paving the way for validated predictive models in order to guide clinical decision-making and provision of personalized obesity care. CI - Copyright (c) 2026 Tzoulis. FAU - Tzoulis, Ploutarchos AU - Tzoulis P AD - Research Department of Experimental and Translational Medicine, University College London, London, United Kingdom. LA - eng PT - Journal Article PT - Review DEP - 20260917 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/drug therapy MH - *Weight Loss/drug effects MH - *Anti-Obesity Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor/genetics PMC - PMC13628350 OTO - NOTNLM OT - GLP-1 agonist OT - antiobesity agent OT - obesity OT - semaglutide OT - weight loss COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/10/02 13:36 MHDA- 2026/10/02 13:37 PMCR- 2026/09/17 CRDT- 2026/10/02 06:56 PHST- 2026/05/28 00:00 [received] PHST- 2026/07/14 00:00 [revised] PHST- 2026/08/24 00:00 [accepted] PHST- 2026/10/02 13:37 [medline] PHST- 2026/10/02 13:36 [pubmed] PHST- 2026/10/02 06:56 [entrez] PHST- 2026/09/17 00:00 [pmc-release] AID - 10.3389/fendo.2026.1893511 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Sep 17;17:1893511. doi: 10.3389/fendo.2026.1893511. eCollection 2026. PMID- 42823110 OWN - NLM STAT- MEDLINE DCOM- 20261001 LR - 20261003 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 16 IP - 10 DP - 2026 Oct 1 TI - Tirzepatide safety in EudraVigilance: descriptive and disproportionality analysis of preferred terms related to suboptimal treatment outcomes and drug-use-related issues. PG - e120507 LID - 10.1136/bmjopen-2026-120507 [doi] LID - e120507 AB - OBJECTIVE: As obesity and diabetes are on the verge of an alarming growth, so is the use of tirzepatide, a novel dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) and currently the most effective weight loss-drug. This research aimed to identify reporting patterns related to suboptimal therapeutic outcomes and tirzepatide-related drug-use issues, mining the EudraVigilance (EV). DESIGN: Retrospective pharmacovigilance study using descriptive and disproportionality analyses of reports retrieved from the EV database. SETTINGS: Analysis of individual case safety reports involving tirzepatide in comparison with other GLP-1 RAs in the overall dataset (healthcare professionals (HP) and non-HP reports combined) and in the HP group. OUTCOME MEASURES: Reporting ORs (RORs) with 95% CIs for selected Preferred Terms (PT) related to drug-use issues. RESULTS: Among all analysed PTs, the most frequently reported were 'Off-label use' (n=1521), 'Drug ineffective' (n=425) and 'Off-label use device' (n=99). PTs in HP reports showed lower reporting odds compared with non-HP reports. In the overall dataset, reports involving tirzepatide showed lower reporting odds of the PT 'Drug ineffective' than those involving liraglutide (ROR 0.61, 95% CI 0.54 to 0.70), dulaglutide (ROR 0.72, 95% CI 0.63 to 0.82), exenatide (ROR 0.78, 95% CI 0.67 to 0.92) and semaglutide (ROR 0.81, 95% CI 0.72 to 0.91). However, in HP reports, no difference in reporting odds was observed between tirzepatide and semaglutide. A different pattern was observed for 'off-label use' in the full dataset, with higher reporting odds for tirzepatide vs lixisenatide, dulaglutide and liraglutide, but lower reporting odds vs semaglutide (ROR 0.52, 95% CI 0.49 to 0.55). In contrast, a higher reporting odd for the PT 'off-label use of device' was observed for tirzepatide versus semaglutide (ROR 43.47, 95% CI 16.00 to 118.13) in the overall reports; however, this finding should be interpreted with caution given the wide CI. CONCLUSIONS: This study complements existing evidence from clinical trials and current clinical practice. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Popa Ilie, Ioana Rada AU - Popa Ilie IR AUID- ORCID: 0000-0002-5281-5004 AD - Department of Endocrinology, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania. FAU - Ghibu, Steliana AU - Ghibu S AUID- ORCID: 0000-0003-2247-4613 AD - Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania steliana.ghibu@umfcluj.ro. FAU - Butuca, Anca AU - Butuca A AUID- ORCID: 0000-0003-1540-641X AD - Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania. FAU - Dobrea, Carmen Maximiliana AU - Dobrea CM AUID- ORCID: 0000-0002-9913-1750 AD - Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania. FAU - Frum, Adina AU - Frum A AUID- ORCID: 0000-0003-4874-0430 AD - Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania. FAU - Stoicescu, Laurentiu AU - Stoicescu L AD - Department of Cardiology, Vth Medical Clinic, Faculty of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania. FAU - Homorodean, Calin AU - Homorodean C AD - Medical Clinic No. 1, Internal Medicine Department, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania. AD - Interventional Cardiology Department, Cluj-Napoca County Emergency Hospital, Cluj-Napoca, CJ, Romania. FAU - Gligor, Felicia Gabriela AU - Gligor FG AD - Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania. FAU - Morgovan, Claudiu AU - Morgovan C AUID- ORCID: 0000-0003-2730-8729 AD - Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania. LA - eng PT - Journal Article DEP - 20261001 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Tirzepatide MH - Retrospective Studies MH - *Pharmacovigilance MH - Female MH - Semaglutide MH - Off-Label Use/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - Adult PMC - PMC13630132 OTO - NOTNLM OT - Adverse events OT - Diabetes Mellitus, Type 2 OT - Obesity OT - Safety COIS- Competing interests: None declared. EDAT- 2026/10/01 23:30 MHDA- 2026/10/01 23:31 PMCR- 2026/10/01 CRDT- 2026/10/01 21:34 PHST- 2026/10/01 23:31 [medline] PHST- 2026/10/01 23:30 [pubmed] PHST- 2026/10/01 21:34 [entrez] PHST- 2026/10/01 00:00 [pmc-release] AID - bmjopen-2026-120507 [pii] AID - 10.1136/bmjopen-2026-120507 [doi] PST - epublish SO - BMJ Open. 2026 Oct 1;16(10):e120507. doi: 10.1136/bmjopen-2026-120507. PMID- 42808923 OWN - NLM STAT- MEDLINE DCOM- 20260929 LR - 20261001 IS - 1941-2452 (Electronic) IS - 0884-5336 (Print) IS - 0884-5336 (Linking) VI - 41 IP - 5 DP - 2026 Oct TI - Gastrointestinal adverse effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists: A narrative expert review of approved therapies, oral formulations, and pipeline agents. PG - 1318-1333 LID - 10.1002/ncp.70180 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists have transformed the management of type 2 diabetes and obesity. Gastrointestinal (GI) adverse events are the most common limitation of these therapies and a leading cause of discontinuation. METHODS: This narrative expert review synthesizes evidence from randomized controlled trials, observational studies, meta-analyses, and pharmacovigilance data to characterize the incidence, mechanisms, and clinical implications of GI adverse effects across approved agents and late-stage pipeline therapies. RESULTS: Nausea, vomiting, diarrhea, and constipation are established class effects, occurring in approximately 30%-50% of patients, typically during initiation and dose escalation. These events are generally mild to moderate and manageable with dose titration and dietary modification. Mechanisms include delayed gastric emptying, central activation of emetic pathways, altered intestinal motility, and physiologic effects of rapid weight loss itself. Randomized trial data are reassuring for acute pancreatitis, with no class-level excess risk demonstrated; pharmacovigilance signals are most plausibly explained by diagnostic misclassification rather than true causal risk. Cholelithiasis shows a probable class-level association, substantially mediated by weight loss rather than direct receptor signaling. Peri-procedural data show increased residual gastric volume without confirmed aspiration events. Preliminary data on late-stage pipeline agents (retatrutide, survodutide, and cagrilintide-semaglutide) suggest a similar GI adverse event profile to approved agents, though evidence remains largely limited. CONCLUSION: GI adverse events with GLP-1-based therapies are predictable and manageable. A proactive, patient-centered approach is essential to optimize adherence, safety, and clinical outcomes as newer agents expand the therapeutic landscape. CI - (c) 2026 The Author(s). Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition. FAU - Singhani, Vikash AU - Singhani V AUID- ORCID: 0000-0001-6063-1558 AD - Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Ehsan, Muhammad AU - Ehsan M AD - Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Valencia, Sara AU - Valencia S AD - Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Nadeem, Ahmed AU - Nadeem A AD - Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Moazzam, Eisha AU - Moazzam E AD - Department of Internal Medicine, King Edward Medical University, Lahore, Pakistan. FAU - Butsch, Winfield Scott AU - Butsch WS AD - Department of Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Novo Nordisk, Copenhagen, Denmark. FAU - Garg, Samita AU - Garg S AUID- ORCID: 0009-0002-2493-1881 AD - Department of Gastroenterology, Hepatology and Nutrition, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. LA - eng PT - Journal Article PT - Review PL - United States TA - Nutr Clin Pract JT - Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition JID - 8606733 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy MH - *Gastrointestinal Diseases/chemically induced MH - *Hypoglycemic Agents/adverse effects MH - *Gastric Inhibitory Polypeptide/agonists/adverse effects MH - Obesity/drug therapy MH - *Receptors, Gastrointestinal Hormone/agonists MH - Randomized Controlled Trials as Topic MH - Tirzepatide PMC - PMC13622393 OTO - NOTNLM OT - GLP-1 receptor agonists OT - diabetes mellitus OT - dual GIP/GLP-1 receptor agonists OT - gastrointestinal adverse events OT - obesity OT - orforglipron OT - semaglutide OT - tirzepatide COIS- Samita Garg reports receiving an Investigator Initiated grant from Abbott, research grants with Enterra and Atmo Biosciences, and serving as a speaker/consultant for Novo Nordisk and Ardelyx. W. Scott Butsch is an employee of Novo Nordisk. All other authors have no disclosures to declare. EDAT- 2026/09/29 12:28 MHDA- 2026/09/29 12:29 PMCR- 2026/09/29 CRDT- 2026/09/29 10:23 PHST- 2026/08/14 00:00 [revised] PHST- 2026/05/07 00:00 [received] PHST- 2026/08/17 00:00 [accepted] PHST- 2026/09/29 12:29 [medline] PHST- 2026/09/29 12:28 [pubmed] PHST- 2026/09/29 10:23 [entrez] PHST- 2026/09/29 00:00 [pmc-release] AID - NCP70180 [pii] AID - 10.1002/ncp.70180 [doi] PST - ppublish SO - Nutr Clin Pract. 2026 Oct;41(5):1318-1333. doi: 10.1002/ncp.70180. PMID- 42808550 OWN - NLM STAT- MEDLINE DCOM- 20260929 LR - 20261002 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 32 IP - 10 DP - 2026 Oct TI - Real-world treatment patterns and cost per patient achieving treatment targets among tirzepatide and semaglutide initiators in US patients with type 2 diabetes. PG - 1173-1188 LID - 10.18553/jmcp.2026.32.10.1173 [doi] AB - BACKGROUND: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist (RA), and semaglutide, a GLP-1 RA, are approved for type 2 diabetes (T2D) management. Clinical trials demonstrated that tirzepatide provided greater hemoglobin A1c and weight reduction vs comparators. Studies using trial-based effect estimates indicate it may also offer a lower cost per patient achieving treatment targets. However, real-world comparative data on treatment patterns, effectiveness, and economic value are limited. OBJECTIVE: To compare real-world treatment patterns, A1c and weight outcomes, and type 2 diabetes-related pharmacy (T2D-Rx) costs per patient achieving treatment targets in patients initiating tirzepatide for T2D, stratified by prior GLP-1 RA use. METHODS: This retrospective cohort study used claims and laboratory data from the Healthcare Integrated Research Database. Adults with T2D initiating tirzepatide (Mounjaro only) or semaglutide (Ozempic only) from May 2022 to May 2023 were propensity score matched and classified as naive or non-naive based on GLP-1 RA exposure in the 6 months before initiation. Outcomes over 12 months of follow-up included adherence (proportion of days covered >/=0.80), persistence (no >/=45-day gap), and T2D-Rx cost per responder (mean T2D-related pharmacy cost / proportion achieving treatment target) to achieve A1c (<8%, <7%, /=5%, >/=10%, >/=15%) thresholds. Outcomes were compared using chi-square and t-tests. RESULTS: After matching, 10,702 naive and 5,577 non-naive patient pairs were included in each treatment group. Tirzepatide initiators demonstrated higher adherence (naive: 60% vs 45%; non-naive: 66% vs 48%) and persistence (naive: 62% vs 47%; non-naive: 68% vs 49%) than semaglutide initiators. A greater proportion of tirzepatide users achieved all A1c and weight outcomes, including the most stringent targets of A1c less than 5.7% (naive: 30% vs 18%; non-naive: 17% vs 6%) and weight loss greater than or equal to 15% (naive: 23% vs 10%; non-naive: 17% vs 5%). Tirzepatide also had lower T2D-Rx cost per responder for these most stringent endpoints: A1c less than 5.7% (naive: $45,300 vs $65,300; non-naive: $107,700 vs $270,300) and weight loss greater than or equal to 15% (naive: $62,900 vs $124,400; non-naive: $110,200 vs $326,800), as well as for most other weight loss thresholds. For less stringent A1c goals, T2D-Rx cost per responder was similar across tirzepatide and semaglutide. CONCLUSIONS: In this real-world analysis, tirzepatide demonstrated better adherence, persistence, and A1c and weight reductions and lower T2D-Rx cost per responder for the most stringent treatment targets than semaglutide in both GLP-1 RA-naive and non-naive patients with T2D. These findings support the clinical and economic value of tirzepatide for achieving meaningful treatment outcomes in real-world patient populations. FAU - Hoog, Meredith M AU - Hoog MM AD - Eli Lilly and Company, Indianapolis, IN. FAU - Vallarino, Carlos AU - Vallarino C AD - Eli Lilly and Company, Indianapolis, IN. FAU - Maldonado, Juan M AU - Maldonado JM AD - Eli Lilly and Company, Indianapolis, IN. FAU - Grabner, Michael AU - Grabner M AD - Carelon Research, Wilmington, DE. FAU - Teng, Chia-Chen AU - Teng CC AD - Carelon Research, Wilmington, DE. FAU - Terrell, Kendra AU - Terrell K AD - Eli Lilly and Company, Indianapolis, IN. FAU - Richard, Emma L AU - Richard EL AD - Carelon Research, Wilmington, DE. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Tirzepatide/economics MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucagon-Like Peptides/economics/therapeutic use/administration & dosage MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/economics/therapeutic use/administration & dosage MH - Male MH - United States MH - Glycated Hemoglobin/analysis MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Adult MH - Weight Loss/drug effects PMC - PMC13621902 COIS- Kendra Terrell, Carlos Vallarino, Juan M. Maldonado, and Meredith M. Hoog are employees and stockholders of Eli Lilly and Company. Michael Grabner, Chia-Chen Teng, and Emma L. Richard are employees of Carelon Research, which received funding from Eli Lilly and Company for the conduct of this study as well as for manuscript writing. Michael Grabner, Chia-Chen Teng, and Emma L. Richard are stockholders of Elevance Health. Sponsorship for this study was provided by Eli Lilly and Company. EDAT- 2026/09/29 12:28 MHDA- 2026/09/29 12:29 PMCR- 2026/10/01 CRDT- 2026/09/29 08:14 PHST- 2026/09/29 12:29 [medline] PHST- 2026/09/29 12:28 [pubmed] PHST- 2026/09/29 08:14 [entrez] PHST- 2026/10/01 00:00 [pmc-release] AID - 10.18553/jmcp.2026.32.10.1173 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2026 Oct;32(10):1173-1188. doi: 10.18553/jmcp.2026.32.10.1173. PMID- 42802824 OWN - NLM STAT- MEDLINE DCOM- 20260928 LR - 20260929 IS - 2308-118X (Electronic) IS - 0857-1074 (Print) IS - 0857-1074 (Linking) VI - 41 IP - 2 DP - 2026 Aug TI - Dapagliflozin Alone or Combined With Semaglutide: Cardiovascular and Renal Outcomes Among Patients With Type 2 Diabetes Mellitus in a 6-Month Real-World Retrospective Cohort Study in Saudi Arabia. PG - 75-84 LID - 10.15605/jafes.041.02.6171 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a growing global health concern linked to increased cardiovascular and renal complications. Two emerging therapeutic classes, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon like peptide-1 receptor agonists (GLP-1 RAs), have shown independent cardiometabolic benefits. However, limited realworld data exist on the comparative impact of combining these therapies versus using SGLT2i alone. OBJECTIVE: To compare the cardiovascular and renal outcomes of dapagliflozin monotherapy versus combination therapy with once-weekly injectable semaglutide among patients with type 2 diabetes mellitus (T2DM). METHODOLOGY: In this retrospective cohort study, 539 adult patients with confirmed type 2 diabetes mellitus (T2DM; baseline HbA1c >/=6.5%) treated at King Abdulaziz Hospital, Al-Ahsa, were followed over six months. Patients received either dapagliflozin alone or in combination with semaglutide. Generalized Estimating Equations (GEE) were used to assess changes in glycemic control, cardiovascular events, lipid profile, and renal function, adjusting for time and sex. RESULTS: Both groups showed significant metabolic improvements over six months. Dapagliflozin monotherapy was associated with greater HbA1c reduction. Combination therapy was associated with higher HDL levels, improved eGFR, and a lower relative risk of heart failure (RR = 0.43, p = 0.04); the reduction in myocardial infarction risk (RR = 0.61, p = 0.13) did not reach statistical significance. No significant difference was observed in stroke risk. Most cardiovascular and renal markers improved modestly. CONCLUSION: Combination therapy was associated with favorable renal outcomes and a reduction in heart failure risk, despite inferior glycemic control and a non-significant trend toward reduced myocardial infarction risk. These findings suggest potential complementary effects of SGLT2i and GLP-1 RA treatment in high-risk patients. However, due to the retrospective, non-randomized design, causal relationships cannot be inferred, and residual confounding may exist. Prospective trials are warranted to confirm these associations and guide treatment optimization. CI - (c) 2026 by Alharajin et al. FAU - Alharajin, Rasmah AU - Alharajin R AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. FAU - AlTaweel, Muneera AU - AlTaweel M AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. AD - Cardiac Science, Department of Medicine, King Abdulaziz Hospital, Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. FAU - AlSubaiee, Maram AU - AlSubaiee M AD - Department of Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. AD - College of Nursing, KSAU-HS, Al Ahsa, Saudi Arabia. FAU - Al Makhloof, Saleh AU - Al Makhloof S AD - Clinical Pharmacy Services, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Almusaad, Abdulmohsen AU - Almusaad A AD - King Abdulaziz Cardiac Center, King Abdulaziz Medical City, MNGHA, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia. FAU - Alarfaj, Abdulrahman AU - Alarfaj A AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - AlKhayyal, Ahmad AU - AlKhayyal A AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Altharman, Noor AU - Altharman N AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. FAU - Alalawi, Ahmed AU - Alalawi A AD - Department of Internal Medicine, Almoosa Specialist Hospital, Al Ahsa, Saudi Arabia. FAU - Almannai, Noora AU - Almannai N AD - King Hamad University Hospital, Kingdom of Bahrain. FAU - Alohaymid, Munirah AU - Alohaymid M AD - Department of Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alsaad, Afnan AU - Alsaad A AD - Department of Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alotaibi, Turkiah AU - Alotaibi T AD - Department of Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alkhaldi, Reem AU - Alkhaldi R AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Almoaibed, Ghusoon AU - Almoaibed G AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alrashada, Jawaher AU - Alrashada J AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alarfaj, Abdullatif AU - Alarfaj A AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Alqarni, Turki AU - Alqarni T AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. AD - Makkah Healthcare Cluster, Makkah, Saudi Arabia. FAU - Alshahrani, Abdullah AU - Alshahrani A AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. AD - Prince Sultan Military Medical City, Riyadh, Saudi Arabia. FAU - Aldossary, Ibraheem AU - Aldossary I AD - King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. FAU - Khashwayn, Seham AU - Khashwayn S AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. FAU - Al Qarni, Ali AU - Al Qarni A AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. AD - Endocrinology and Metabolism, Department of Medicine, King Abdulaziz Hospital, MNGHA Al-Ahsa, Saudi Arabia. FAU - Taleb, Yaqob AU - Taleb Y AD - King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Al Ahsa, Saudi Arabia. AD - Cardiac Science, Department of Medicine, King Abdulaziz Hospital, Ministry of National Guard Health Affairs (MNGHA), Al-Ahsa, Saudi Arabia. FAU - Alshaikh Husain, Mareyah AU - Alshaikh Husain M AD - Department of Family Medicine, King Abdulaziz Hospital, MNGHA Al Ahsa, Saudi Arabia. LA - eng PT - Journal Article DEP - 20260813 PL - Philippines TA - J ASEAN Fed Endocr Soc JT - Journal of the ASEAN Federation of Endocrine Societies JID - 8608483 RN - 53AXN4NNHX (Semaglutide) RN - 1ULL0QJ8UC (dapagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Retrospective Studies MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - *Benzhydryl Compounds/therapeutic use MH - Male MH - Drug Therapy, Combination MH - Middle Aged MH - *Glucosides/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/epidemiology MH - Saudi Arabia/epidemiology MH - Aged MH - Treatment Outcome MH - Glycated Hemoglobin PMC - PMC13616068 OTO - NOTNLM OT - cardiovascular outcomes OT - dapagliflozin OT - real-world study OT - renal function OT - semaglutide OT - type 2 diabetes COIS- The authors declared no conflict of interest. EDAT- 2026/09/28 05:33 MHDA- 2026/09/28 05:34 PMCR- 2026/08/01 CRDT- 2026/09/28 03:42 PHST- 2026/05/13 00:00 [received] PHST- 2026/06/10 00:00 [accepted] PHST- 2026/09/28 05:34 [medline] PHST- 2026/09/28 05:33 [pubmed] PHST- 2026/09/28 03:42 [entrez] PHST- 2026/08/01 00:00 [pmc-release] AID - JAFES-41-2-075 [pii] AID - 10.15605/jafes.041.02.6171 [doi] PST - ppublish SO - J ASEAN Fed Endocr Soc. 2026 Aug;41(2):75-84. doi: 10.15605/jafes.041.02.6171. Epub 2026 Aug 13. PMID- 42796421 OWN - NLM STAT- MEDLINE DCOM- 20260926 LR - 20260929 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 9 DP - 2026 Sep 21 TI - Clinical Profile of Documented Diabetic Peripheral Neuropathy by GLP-1-Based Medication Status: A Cross-Sectional Study. LID - 10.3390/medicina62091816 [doi] LID - 1816 AB - Background and Objectives: This exploratory single-center retrospective cross-sectional study characterized patients with documented diabetic peripheral neuropathy (DPN) according to documented GLP-1-based medication status. GLP-1-based medication status was defined by a hospital medication-field entry for exenatide, dulaglutide, semaglutide, a fixed-ratio insulin/GLP-1 receptor agonist combination, or tirzepatide, a dual GIP/GLP-1 receptor agonist. Materials and Methods: Medication-level records from a hospital-defined February 2024-February 2026 reporting window were aggregated by PatID for 4120 unique patients in active-patient exports from the Clinical County Emergency Hospital Bihor. The files lacked patient-level encounter, diagnosis, and treatment dates; therefore, they were analyzed as an undated reporting snapshot. DPN and diabetes type were defined from export fields and were not independently clinically validated. Results: GLP-1-based medications were documented in 852 patients (20.7%). Patients with these medications in their records had longer documented diabetes duration (14.85 +/- 8.64 vs. 11.72 +/- 8.73 years; p < 0.001) and a higher documented comorbidity count (2.64 +/- 1.65 vs. 1.89 +/- 1.55; p < 0.001). Heart failure was documented in 35.7% versus 22.2%, and any lower-limb amputation in 3.3% versus 1.2%. For heart failure, the adjusted odds ratio was 1.68 (95% CI 1.41-1.99) in the primary model and 1.37 (1.12-1.67) in the expanded exploratory model; the corresponding robust Poisson prevalence ratio was 1.45 (1.30-1.63). Because only 66 amputations were recorded, amputation was retained as a descriptive, unadjusted outcome and was not modeled multivariably. Conclusions: A GLP-1-based medication record identified a clinically complex subgroup with documented DPN. The findings are exploratory and hypothesis-generating; because treatment and outcome dates were unavailable, they do not establish temporality, treatment benefit, or treatment harm. FAU - Ferician, Anca Cristina AU - Ferician AC AD - Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410068 Oradea, Romania. FAU - Ghitea, Timea Claudia AU - Ghitea TC AUID- ORCID: 0000-0001-8981-1958 AD - Pharmacy Department, Faculty of Medicine and Pharmacy, University of Oradea, 410087 Oradea, Romania. FAU - Popoviciu, Mihaela Simona AU - Popoviciu MS AD - Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania. LA - eng GR - 410087/University of Oradea/ PT - Journal Article DEP - 20260921 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Cross-Sectional Studies MH - *Diabetic Neuropathies/drug therapy/physiopathology MH - Female MH - Retrospective Studies MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Semaglutide MH - Middle Aged MH - Tirzepatide MH - *Glucagon-Like Peptide 1/therapeutic use MH - Exenatide/therapeutic use MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Insulin/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13609424 OTO - NOTNLM OT - documented GLP-1-based therapy OT - documented diabetic peripheral neuropathy OT - exploratory cross-sectional study OT - heart failure OT - lower-limb amputation OT - multimorbidity OT - prevalence ratio OT - routinely collected health data COIS- The authors declare no conflicts of interest. EDAT- 2026/09/26 05:35 MHDA- 2026/09/26 05:36 PMCR- 2026/09/21 CRDT- 2026/09/26 01:13 PHST- 2026/08/24 00:00 [received] PHST- 2026/09/18 00:00 [revised] PHST- 2026/09/20 00:00 [accepted] PHST- 2026/09/26 05:36 [medline] PHST- 2026/09/26 05:35 [pubmed] PHST- 2026/09/26 01:13 [entrez] PHST- 2026/09/21 00:00 [pmc-release] AID - medicina62091816 [pii] AID - medicina-62-01816 [pii] AID - 10.3390/medicina62091816 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Sep 21;62(9):1816. doi: 10.3390/medicina62091816. PMID- 42794486 OWN - NLM STAT- MEDLINE DCOM- 20260926 LR - 20260929 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 18 DP - 2026 Sep 10 TI - Skeletal Muscle Effects of GLP 1 Receptor Agonists: Molecular Mechanisms and Comparative Insights on Semaglutide and Tirzepatide, a Narrative Review. LID - 10.3390/ijms27188057 [doi] LID - 8057 AB - GLP-1 receptor agonists (GLP-1RAs), dual GLP-1/GIP agonists, and the more recent triple GLP-1/GIP/glucagon agonists have transformed the treatment of type 2 diabetes mellitus (T2DM) and obesity, resulting in significant weight reduction. However, a substantial proportion (20-40%) of this weight loss is attributable to a decrease in lean mass, thereby raising concerns regarding potential sarcopenia-related risk. However, decreased lean mass is not sufficient to determine sarcopenia, which is now defined by the combined presence of decreased muscle mass, diminished strength, and impaired physical function, particularly in older or frail individuals. Thus, a further clarification of the potential mechanisms through which these molecules affect skeletal muscle is needed to optimize their use. The objective of this study is to synthesize preclinical, metabolomic, and clinical evidence on the effects of GLP-1RAs and dual/triple agonists on skeletal muscle, with a specific comparison between semaglutide and tirzepatide. This narrative review was based on a comprehensive literature search of PubMed/MEDLINE, Scopus, and Google Scholar, encompassing articles published through June 2026. This search was supplemented by manual citation tracking, which identified additional studies including preclinical and metabolomic investigations, randomized controlled trials, observational studies, and meta-analyses. Preclinical data suggest that GLP-1R/GIPR activation can positively modulate anabolic pathways, mitochondrial biogenesis, and muscle inflammation. Metabolomic evidence reveals lipid and amino acid remodeling compatible with improved mitochondrial function. Clinically, lean mass loss proportional to weight reduction is consistently observed, generally without meaningful declines in strength or performance; data for tirzepatide are more limited. Lean mass, however, is not synonymous with skeletal muscle. A paradox emerges between the presence of protective molecular signals and the clinical evidence of lean-mass loss. This phenomenon may be explained by a systemic energy/protein deficit rather than a direct catabolic effect of the drugs, although current evidence does not fully distinguish these mechanisms. The effectiveness of weight reduction should be considered a pivotal metric in clinical practice, particularly in populations susceptible to sarcopenia. FAU - Cautela, Domenico AU - Cautela D AUID- ORCID: 0000-0003-4894-0299 AD - Dipartimento di Scienze Teoriche e Applicate (DiSTA), Universita Telematica eCampus, Via Isimbardi 10, 22060 Novedrate, CO, Italy. FAU - Incarbona, Valeria AU - Incarbona V AUID- ORCID: 0009-0006-7777-4532 AD - Dipartimento di Scienze Teoriche e Applicate (DiSTA), Universita Telematica eCampus, Via Isimbardi 10, 22060 Novedrate, CO, Italy. FAU - Lombardi, Angela AU - Lombardi A AUID- ORCID: 0000-0001-5421-9970 AD - Dipartimento di Scienze Teoriche e Applicate (DiSTA), Universita Telematica eCampus, Via Isimbardi 10, 22060 Novedrate, CO, Italy. FAU - Laratta, Bruna AU - Laratta B AUID- ORCID: 0000-0002-6183-6843 AD - Istituto di Bioscienze e Biorisorse (IBBR), CNR, Via Pietro Castellino 111, 80131 Napoli, NA, Italy. FAU - Castaldo, Curzio Massimo AU - Castaldo CM AD - Scuola di Medicina e Chirurgia, Universita degli studi della Campania Luigi Vanvitelli, Via Santa Maria di Costantinopoli 16, 80138 Napoli, NA, Italy. FAU - Balestrieri, Maria Luisa AU - Balestrieri ML AUID- ORCID: 0000-0001-6001-1789 AD - Dipartimento di Medicina di Precisione, Universita degli studi della Campania Luigi Vanvitelli, Via de Crecchio 7, 80138 Napoli, NA, Italy. FAU - Mocini, Edoardo AU - Mocini E AUID- ORCID: 0000-0002-4868-8102 AD - Dipartimento di Scienze Teoriche e Applicate (DiSTA), Universita Telematica eCampus, Via Isimbardi 10, 22060 Novedrate, CO, Italy. FAU - Migliaccio, Silvia AU - Migliaccio S AUID- ORCID: 0000-0002-4563-6630 AD - Dipartimento di Medicina Sperimentale, Sapienza Universita di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy. FAU - Tardito, Daniela AU - Tardito D AUID- ORCID: 0000-0001-5585-1054 AD - Dipartimento di Scienze Teoriche e Applicate (DiSTA), Universita Telematica eCampus, Via Isimbardi 10, 22060 Novedrate, CO, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260910 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - *Tirzepatide/pharmacology MH - Semaglutide MH - Humans MH - *Muscle, Skeletal/drug effects/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Sarcopenia/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Obesity/drug therapy/metabolism PMC - PMC13607671 OTO - NOTNLM OT - GLP-1 receptor agonists OT - dual GLP-1/GIP agonists OT - lean mass OT - metabolomics OT - sarcopenia OT - semaglutide OT - skeletal muscle OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/09/26 05:35 MHDA- 2026/09/26 05:36 PMCR- 2026/09/10 CRDT- 2026/09/26 01:07 PHST- 2026/08/05 00:00 [received] PHST- 2026/09/03 00:00 [revised] PHST- 2026/09/05 00:00 [accepted] PHST- 2026/09/26 05:36 [medline] PHST- 2026/09/26 05:35 [pubmed] PHST- 2026/09/26 01:07 [entrez] PHST- 2026/09/10 00:00 [pmc-release] AID - ijms27188057 [pii] AID - ijms-27-08057 [pii] AID - 10.3390/ijms27188057 [doi] PST - epublish SO - Int J Mol Sci. 2026 Sep 10;27(18):8057. doi: 10.3390/ijms27188057. PMID- 42791433 OWN - NLM STAT- MEDLINE DCOM- 20261024 LR - 20261028 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 86 IP - 11 DP - 2026 Nov TI - GLP-1 Receptor Agonists in Heart Failure: A Systematic Review and Meta-analysis with Phenotype-Specific Effects and Dual Analytical Frameworks. PG - 1873-1890 LID - 10.1007/s40265-026-02380-4 [doi] AB - BACKGROUND: Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular risk in patients with type 2 diabetes mellitus (T2D), evidence in heart failure (HF) has expanded across diverse trial populations and HF phenotypes but remains fragmented. We therefore performed an integrated systematic review and meta-analysis to evaluate the effects of GLP-1 RAs across the spectrum of HF using complementary trial-level and phenotype-based analyses. METHODS: PubMed, Embase, and Web of Science were systematically searched for studies published from inception to August 10, 2025. To provide an integrated assessment across heterogeneous HF populations, treatment effects were evaluated using dual analytical frameworks: trial-level analyses according to study design (dedicated HF with preserved ejection fraction [HFpEF] trials, HF with reduced ejection fraction [HFrEF] trials, and HF subgroups from cardiovascular outcome trials [CVOTs]) and phenotype-based analyses according to left ventricular ejection fraction (HFpEF vs HFrEF using a pragmatic threshold of 40%). A prespecified targeted analysis was conducted to specifically assess the efficacy of semaglutide. The primary outcomes were major adverse cardiovascular events (MACE), and the secondary outcomes included hospitalization for HF (HHF), the composite of cardiovascular death or any worsening HF events, cardiovascular death alone, and all-cause mortality. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random‑effects models. RESULTS: This meta-analysis included 14 trials, with a pooled total of 15,882 patients with HF. In phenotype‑based analyses for HFpEF, GLP‑1 RAs significantly reduced MACE (HR 0.79; 95% CI 0.66-0.94; p = 0.010), HHF (HR 0.48; 95% CI 0.27-0.85; p = 0.012), the composite of cardiovascular death or worsening HF (HR 0.57; 95% CI 0.37-0.89; p = 0.013), and all‑cause mortality (HR 0.75; 95% CI 0.62-0.89; p = 0.001). In contrast, in HFrEF, no significant reductions were observed for HHF, the composite of cardiovascular death or worsening HF, all-cause mortality, or MACE, although a reduction in cardiovascular death was noted (HR 0.71; 95% CI 0.54-0.95; p = 0.019). Trial-level analyses showed that cardiovascular benefits were primarily observed in HF subgroups from CVOTs, including reductions in MACE (HR 0.82; 95% CI 0.73-0.92; p = 0.001), cardiovascular death (HR 0.88; 95% CI 0.77-1.00; p = 0.05) and myocardial infarction (MI)/non-fatal MI (HR 0.84; 95% CI 0.70-1.00; p = 0.046). Semaglutide showed benefits in HHF and the composite of cardiovascular death or worsening HF events predominantly among overweight or obese patients with HFpEF. GLP-1 RAs also improved functional capacity and quality of life in HFpEF. CONCLUSION: GLP-1 RAs were associated with favorable cardiovascular and HF-related outcomes in HFpEF, predominantly among overweight or obese individuals, whereas evidence of benefit in HFrEF remains limited. In trial-level analyses, benefits were primarily observed for atherosclerotic endpoints in HF subgroups from CVOTs. By integrating evidence, this study provides a unified overview of the effects of GLP-1 RAs across the spectrum of HF and supports further phenotype-specific randomized trials, particularly dedicated studies in HFrEF. TRIAL REGISTRATION: Protocol registration PROSPERO (CRD420251079970). CI - (c) 2026. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Yuan, Yahui AU - Yuan Y AD - The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Chen, Chun AU - Chen C AD - China Academy of Chinese Medical Sciences, Wangjing Hospital, Beijing, China. FAU - Li, Xiuming AU - Li X AD - The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Guo, Jingyi AU - Guo J AD - The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Liu, Qiaoyun AU - Liu Q AD - The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Lin, YuPing AU - Lin Y AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Sun, Lu AU - Sun L AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Fan, Guanjie AU - Fan G AD - The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. fanguanjie@gzucm.edu.cn. AD - Department of Endocrinology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. fanguanjie@gzucm.edu.cn. AD - Department of Endocrinology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. fanguanjie@gzucm.edu.cn. LA - eng GR - YN2021DB02/Guangdong Provincial Department of Science and Technology/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260926 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Phenotype MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Stroke Volume/drug effects COIS- Declarations. Funding: This study was supported by the Guangdong Provincial Department of Science and Technology (YN2021DB02). Conflict of Interest: Yahui Yuan, Chun Chen, Xiuming Li, Jingyi Guo, Qiaoyun Liu, YuPing Lin, Lu Sun, Wei Song, and Guanjie Fan declare that they have no potential conflicts of interest that might be relevant to the contents of this manuscript. CRediT Authorship Contribution Statement: Yahui Yuan: writing-original draft, writing-review & editing, methodology, data curation, conceptualization. Chun Chen: investigation, data curation, writing-original draft. Xiuming Li and Jingyi Guo: investigation, data curation, writing-review & editing. Qiaoyun Liu and Yuping Lin: investigation, data curation, writing-review & editing. Lu Sun: investigation, data curation, writing-review & editing. Guanjie Fan: methodology, investigation, funding acquisition, conceptualization, writing-review & editing. Data Availability: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethical Approval: Not applicable. Code Availability: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. EDAT- 2026/09/26 05:34 MHDA- 2026/10/25 03:35 CRDT- 2026/09/25 23:40 PHST- 2026/01/20 00:00 [received] PHST- 2026/08/17 00:00 [accepted] PHST- 2026/10/25 03:35 [medline] PHST- 2026/09/26 05:34 [pubmed] PHST- 2026/09/25 23:40 [entrez] AID - 10.1007/s40265-026-02380-4 [pii] AID - 10.1007/s40265-026-02380-4 [doi] PST - ppublish SO - Drugs. 2026 Nov;86(11):1873-1890. doi: 10.1007/s40265-026-02380-4. Epub 2026 Sep 26. PMID- 42785932 OWN - NLM STAT- MEDLINE DCOM- 20260924 LR - 20261003 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 16 IP - 9 DP - 2026 Sep 24 TI - Estimating the carbon footprint of oral semaglutide (Rybelsus): a comparative analysis of the medicine carbon footprint model and manufacturer life-cycle assessment in pharmaceutical production. PG - e124968 LID - 10.1136/bmjopen-2026-124968 [doi] LID - e124968 AB - OBJECTIVES: Pharmaceuticals are a major contributor to healthcare's greenhouse gas emissions yet product-level carbon footprints are rarely disclosed. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly being used for the management of type 2 diabetes and people living with obesity, but their carbon impact remains poorly characterised. We aimed to compare carbon footprint estimates for oral semaglutide (Rybelsus), a peptide-based medicine, generated using the medicine carbon footprint (MCF) framework and manufacturer-reported life cycle assessment (LCA) data. DESIGN AND SETTING: Comparative methodological analysis using cradle-to-gate boundaries to compare pharmaceutical carbon footprint estimates for oral semaglutide. METHODS: Per-tablet MCF estimates for 3, 7 and 14 mg Rybelsus were annualised and compared with product-specific LCA results reported by Novo Nordisk. Differences between methods were assessed descriptively across the three dose strengths. Absolute differences and symmetric percentage differences were calculated. RESULTS: Annualised MCF estimates were 8.9, 20.0 and 39.3 kg CO(2)e/year for 3, 7 and 14 mg tablets, respectively. Corresponding EU LCA estimates were 17.0, 25.2 and 39.9 kgCO(2)e/year. The mean symmetric percentage difference was -29%, with the largest discrepancy observed at the 3 mg dose (-62.6%) and the smallest difference at the 14 mg dose (-1.5%). CONCLUSION: For oral semaglutide, MCF generated lower carbon footprint estimates than manufacturer-reported LCA values, particularly at lower doses, where fixed device/excipient and packaging emissions are proportionally larger. MCF offers a rapid, accessible and indicative estimation method when proprietary data are unavailable. Improved transparency and harmonised boundaries would strengthen comparability between pharmaceutical carbon footprint estimation approaches. These findings are specific to the Rybelsus formulation of oral semaglutide and may not be generalisable to other formulations or GLP-1 RAs. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Hansell, Louise AU - Hansell L AUID- ORCID: 0000-0003-1810-9357 AD - Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia Louise.Hansell@sydney.edu.au. AD - Physiotherapy Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia. FAU - Zhu, Wandi AU - Zhu W AD - Sydney Environment Institute, The University of Sydney, Sydney, New South Wales, Australia. FAU - Lynch, Michelle AU - Lynch M AD - Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia. FAU - Hocking, S L AU - Hocking SL AD - Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia. AD - Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. FAU - Celermajer, David S AU - Celermajer DS AD - Central Clinical School, The University of Sydney, Sydney, New South Wales, Australia. AD - Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. AD - Heart Research Institute Ltd, Newtown, New South Wales, Australia. FAU - Sack, Fabian AU - Sack F AD - Sydney Environment Institute, The University of Sydney, Sydney, New South Wales, Australia. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260924 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Semaglutide MH - *Glucagon-Like Peptides/administration & dosage MH - Humans MH - *Carbon Footprint/statistics & numerical data MH - *Hypoglycemic Agents/administration & dosage MH - Administration, Oral MH - Diabetes Mellitus, Type 2/drug therapy MH - Drug Industry PMC - PMC13630073 OTO - NOTNLM OT - General endocrinology OT - Health Services OT - Obesity OT - PUBLIC HEALTH COIS- Competing interests: None declared. EDAT- 2026/09/24 23:52 MHDA- 2026/09/24 23:53 PMCR- 2026/09/24 CRDT- 2026/09/24 21:13 PHST- 2026/09/24 23:53 [medline] PHST- 2026/09/24 23:52 [pubmed] PHST- 2026/09/24 21:13 [entrez] PHST- 2026/09/24 00:00 [pmc-release] AID - bmjopen-2026-124968 [pii] AID - 10.1136/bmjopen-2026-124968 [doi] PST - epublish SO - BMJ Open. 2026 Sep 24;16(9):e124968. doi: 10.1136/bmjopen-2026-124968. PMID- 42768905 OWN - NLM STAT- MEDLINE DCOM- 20261028 LR - 20261028 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 IP - 11 DP - 2026 Nov TI - Trends in GLP-1 Receptor Agonist Prescribing Without an Apparent FDA-Approved Indication. PG - 2026-2030 LID - 10.1002/oby.70301 [doi] AB - OBJECTIVE: This study evaluated temporal trends and patient characteristics associated with glucagon-like peptide-1 (GLP-1) receptor agonist prescribing among US adults without an apparent FDA-approved indication. METHODS: This retrospective cohort study used Cosmos electronic health records (01/2021-12/2025). Adults prescribed liraglutide, semaglutide, or tirzepatide without a documented indication (type 2 diabetes or obesity with qualifying comorbidities) were included. Patients without a recorded weight >/= 6 months prior to first prescription were excluded. Demographic and clinical characteristics were compared using t-tests and chi(2) tests. RESULTS: Among 92,415,648 adults without an apparent FDA-approved indication, 1,133,953 (1.2%) were prescribed GLP-1 receptor agonists. Prescribing increased from 0.1% in 2021 to 1.5% in 2025 (15-fold). Recipients had higher median BMI (25.9 vs. 24.5 kg/m(2)) and were more often female (85.5%) and White (60.0%). Hypertension and dyslipidemia were more common, while coronary artery disease and heart failure were less prevalent. Notably, 35.1% had normal BMI; eating disorders were more frequent (1.8% vs. 0.3%). GLP-1 receptor agonist use was associated with lower social vulnerability and private insurance. CONCLUSIONS: GLP-1 receptor agonist prescribing without an apparent FDA-approved indication has increased rapidly and disproportionately involves socioeconomically advantaged populations, including individuals without obesity. The risk-benefit profile in these populations remains uncertain. CI - (c) 2026 The Obesity Society. FAU - Orandi, Babak J AU - Orandi BJ AUID- ORCID: 0000-0001-6026-7135 AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Medicine, New York University, New York, New York, USA. FAU - Yan, Leila AU - Yan L AD - Department of Surgery, New York University, New York, New York, USA. FAU - Levan, Macey L AU - Levan ML AUID- ORCID: 0000-0002-4239-1252 AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Population Health, New York University, New York, New York, USA. FAU - Lofton, Holly F AU - Lofton HF AD - Department of Surgery, New York University, New York, New York, USA. FAU - Chhabra, Karan R AU - Chhabra KR AUID- ORCID: 0000-0001-6620-8777 AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Population Health, New York University, New York, New York, USA. FAU - Ren-Fielding, Christine J AU - Ren-Fielding CJ AD - Department of Surgery, New York University, New York, New York, USA. FAU - Husain, S Ali AU - Husain SA AUID- ORCID: 0000-0002-1823-0117 AD - Department of Medicine, New York University, New York, New York, USA. FAU - McAdams-DeMarco, Mara A AU - McAdams-DeMarco MA AUID- ORCID: 0000-0003-3013-925X AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Population Health, New York University, New York, New York, USA. FAU - Segev, Dorry L AU - Segev DL AUID- ORCID: 0000-0002-1924-4801 AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Population Health, New York University, New York, New York, USA. FAU - Mankowski, Michal A AU - Mankowski MA AD - Department of Surgery, New York University, New York, New York, USA. FAU - Massie, Allan B AU - Massie AB AD - Department of Surgery, New York University, New York, New York, USA. AD - Department of Population Health, New York University, New York, New York, USA. LA - eng PT - Journal Article DEP - 20260922 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Tirzepatide/therapeutic use MH - Male MH - United States MH - *Diabetes Mellitus, Type 2/drug therapy MH - Liraglutide/therapeutic use MH - Middle Aged MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - United States Food and Drug Administration MH - *Practice Patterns, Physicians'/trends MH - Aged EDAT- 2026/09/22 05:37 MHDA- 2026/10/28 17:31 CRDT- 2026/09/22 03:04 PHST- 2026/07/22 00:00 [revised] PHST- 2026/03/24 00:00 [received] PHST- 2026/07/31 00:00 [accepted] PHST- 2026/10/28 17:31 [medline] PHST- 2026/09/22 05:37 [pubmed] PHST- 2026/09/22 03:04 [entrez] AID - 10.1002/oby.70301 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Nov;34(11):2026-2030. doi: 10.1002/oby.70301. Epub 2026 Sep 22. PMID- 42766517 OWN - NLM STAT- MEDLINE DCOM- 20260921 LR - 20260922 IS - 1548-6869 (Electronic) IS - 1049-2089 (Linking) VI - 37 IP - 1 DP - 2026 TI - Real-World Impact of Weekly Dulaglutide and Semaglutide on Hba1c and Weight in a Predominantly Underrepresented Demographic. PG - 270-286 LID - 10.1353/hpu.2026.a982969 [doi] AB - BACKGROUND: African Americans are underrepresented in real-world studies of GLP-1 receptor agonists (RA) for type 2 diabetes. OBJECTIVES: This study evaluates the effects of weekly dulaglutide and semaglutide on glycated hemoglobin (HbA1c) and weight in a predominantly African American population. METHODS: A retrospective chart review was conducted at an adult medicine clinic. Patients 19 years of age or older with at least 26 weeks of dulaglutide or semaglutide treatment and recorded baseline and follow-up HbA1c and weight were included. RESULTS: Among 91 patients-85.7% African American, 67.0% female, mean age 56.4 years-the mean GLP-1 RA treatment duration was 14.9 months. Glycated hemoglobin decreased by 2.39% (p<.001), and weight dropped by 4.76 kg (p<.001). High-dose dulaglutide significantly lowered HbA1c compared with low-dose (p=.023). CONCLUSION: Weekly dulaglutide and semaglutide significantly reduced HbA1c and weight. Further research is needed to explore factors influencing differential responses. FAU - Deas, Crystal AU - Deas C FAU - Uhomba, Laurel AU - Uhomba L FAU - Snow, Kayla AU - Snow K LA - eng PT - Journal Article PL - United States TA - J Health Care Poor Underserved JT - Journal of health care for the poor and underserved JID - 9103800 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Black or African American/statistics & numerical data MH - *Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/ethnology MH - Glucagon-Like Peptides/analogs & derivatives/analogs & derivatives MH - *Glycated Hemoglobin/analysis/drug effects MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Immunoglobulin Fc Fragments/administration & dosage/therapeutic use MH - Recombinant Fusion Proteins/administration & dosage/therapeutic use MH - Retrospective Studies MH - *Semaglutide/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use EDAT- 2026/09/21 17:47 MHDA- 2026/09/21 17:48 CRDT- 2026/09/21 13:25 PHST- 2026/09/21 17:48 [medline] PHST- 2026/09/21 17:47 [pubmed] PHST- 2026/09/21 13:25 [entrez] AID - S1548686926100187 [pii] AID - 10.1353/hpu.2026.a982969 [doi] PST - ppublish SO - J Health Care Poor Underserved. 2026;37(1):270-286. doi: 10.1353/hpu.2026.a982969. PMID- 42764643 OWN - NLM STAT- MEDLINE DCOM- 20260921 LR - 20260924 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 46 IP - 10 DP - 2026 Oct TI - Applicability of Non-Invasive Eligibility Criteria for MASH Pharmacotherapy: A Multicentre Cohort Study. PG - e70882 LID - 10.1111/liv.70882 [doi] AB - BACKGROUND AND AIMS: Non-invasive tests (NITs) are increasingly used to guide patient selection for pharmacological treatment of metabolic dysfunction-associated steatohepatitis (MASH). We aimed to quantify and compare real-world treatment eligibility according to the AASLD and expert panel-derived criteria and to evaluate classification of patients with available liver histology. METHODS: We retrospectively included 897 adults with MASLD from four Italian referral centres. Eligibility was assessed using AASLD criteria, defined by liver stiffness measurement (LSM) 8-15 kPa without cirrhosis, and expert panel-derived criteria, defined by LSM 10-19.9 kPa, platelet count >/= 140 x 10(9)/L, and no cirrhosis. A subgroup of 175 patients underwent liver biopsy within +/-3 months of first referral. RESULTS: Median age was 62 years, 57.1% were men, 48.4% had obesity, and 36.0% had Type 2 diabetes. Overall, 202 patients (22.5%) met AASLD criteria and 114 (12.7%) met expert panel-derived criteria. Eighty-six patients were eligible according to both criteria, whereas 144 were classified differently. Type 2 diabetes and obesity were independently associated with eligibility under both criteria. In the biopsy subgroup, 73 patients had histological F2-F3 fibrosis; 35 (47.9%) did not meet AASLD criteria and 49 (67.1%) did not meet expert panel-derived criteria. CONCLUSIONS: The AASLD and expert panel-derived criteria identified different real-world populations potentially suitable for MASH pharmacotherapy. In the biopsy subgroup, NIT-based eligibility classification only partly aligned with histological F2-F3 fibrosis. CI - (c) 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Pugliese, Nicola AU - Pugliese N AUID- ORCID: 0000-0001-6466-1412 AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Polverini, Davide AU - Polverini D AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Bertazzoni, Arianna AU - Bertazzoni A AUID- ORCID: 0009-0005-5582-495X AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Cerini, Federica AU - Cerini F AUID- ORCID: 0000-0003-3568-1531 AD - Hepatology Unit, San Giuseppe Hospital, Milan, Italy. AD - Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. FAU - Pennisi, Grazia AU - Pennisi G AUID- ORCID: 0000-0001-9518-4751 AD - Section of Gastroenterology, PROMISE, University of Palermo, Palermo, Italy. FAU - Lombardi, Rosa AU - Lombardi R AUID- ORCID: 0000-0001-6958-927X AD - Unit of Metabolic Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy. AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FAU - Gullace, Valerio AU - Gullace V AUID- ORCID: 0009-0002-7321-5494 AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - De Nicola, Stella AU - De Nicola S AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Masetti, Chiara AU - Masetti C AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Paviglianiti, Andrea AU - Paviglianiti A AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Fracanzani, Anna Ludovica AU - Fracanzani AL AD - Unit of Metabolic Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy. AD - Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FAU - Vigano, Mauro AU - Vigano M AUID- ORCID: 0000-0003-0769-1767 AD - Gastroenterology, Hepatology and Transplantation Unit, ASST Papa Giovanni XXIII, Bergamo, Italy. FAU - Petta, Salvatore AU - Petta S AUID- ORCID: 0000-0002-0822-9673 AD - Section of Gastroenterology, PROMISE, University of Palermo, Palermo, Italy. FAU - Aghemo, Alessio AU - Aghemo A AUID- ORCID: 0000-0003-0941-3226 AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy. AD - Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Biopsy MH - Diabetes Mellitus, Type 2/complications MH - Elasticity Imaging Techniques MH - *Fatty Liver/drug therapy MH - Italy MH - *Liver/pathology/diagnostic imaging MH - Liver Cirrhosis MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Obesity/complications MH - *Patient Selection MH - Platelet Count MH - Retrospective Studies OAB - As pharmacological treatment for metabolic dysfunction-associated steatohepatitis (MASH) becomes available, selecting appropriate candidates without relying on liver biopsy is a major clinical challenge. We found that currently proposed non-invasive eligibility criteria identify different patient populations and show only partial alignment with histologically confirmed F2-F3 fibrosis in the biopsy subgroup. These findings highlight the need to refine non-invasive patient selection strategies to improve treatment allocation in routine clinical practice. OABL- eng OTO - NOTNLM OT - fibrosis OT - liver stiffness OT - metabolic syndrome OT - resmetirom OT - semaglutide OT - transient elastography EDAT- 2026/09/21 05:34 MHDA- 2026/09/21 05:35 CRDT- 2026/09/21 02:43 PHST- 2026/08/11 00:00 [revised] PHST- 2026/05/30 00:00 [received] PHST- 2026/09/09 00:00 [accepted] PHST- 2026/09/21 05:35 [medline] PHST- 2026/09/21 05:34 [pubmed] PHST- 2026/09/21 02:43 [entrez] AID - 10.1111/liv.70882 [doi] PST - ppublish SO - Liver Int. 2026 Oct;46(10):e70882. doi: 10.1111/liv.70882. PMID- 42755517 OWN - NLM STAT- MEDLINE DCOM- 20260918 LR - 20260922 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Efficacy and safety of semaglutide for obesity and hyperphagia in adults with Prader-Willi syndrome. PG - 1881392 LID - 10.3389/fendo.2026.1881392 [doi] LID - 1881392 AB - CONTEXT: Prader-Willi syndrome is a genetic neurodevelopmental disorder characterized by hyperphagia and early-onset obesity from hypothalamic dysfunction with endocrinopathies and learning disability. Management is challenging with strict control of the food environment needed. While newer glucagon-like peptide-1 receptor agonists, such as semaglutide, have efficacy in non-PWS obesity, there have been limited case reports in PWS. OBJECTIVE/DESIGN/SETTING: Retrospective, observational cohort of 12 adults with PWS and overweight/obesity treated with semaglutide at a UK academic hospital centre specialist clinic. PATIENTS: Mean +/- SD age 28.3 +/- 10.1 years, 83% female, BMI 46.6 +/- 8.2kg/m(2), 75% type 2 diabetes mellitus. INTERVENTION: Median follow-up 17.2 months (range 8.7-36.1) with median semaglutide dose 2.4mg once weekly (1.0-2.4). RESULTS: There was no significant overall weight loss on semaglutide, but there was stabilisation of the weight gain prior to treatment over previous 12.4 months (7.6-23.0): post -3.1 +/- 9.9% vs. pre +5.7 +/- 5.6%: d -0.72, P = 0.037. There was a significant decrease in hyperphagia on semaglutide from Hyperphagia Questionnaire for Clinical Trials (n=11, -7.3 +/- 6.1 (max 36), d -1.19, P = 0.003), having been stable before treatment. HbA1c improved in those with elevated baseline levels (n=6, -4.2 +/- 4.9%, d -0.74, P = 0.13). Mild gastrointestinal side effects were seen in 25% but did not lead to discontinuation. CONCLUSIONS: In this small open-label, observational cohort of adults with PWS, semaglutide produced weight maintenance though not weight loss, but appeared to reduce hyperphagia, and improved glycaemic control, with good tolerability. Larger placebo-controlled trials are needed to confirm these findings in adults and adolescents with PWS, especially in those without T2DM, where efficacy may be greater. CI - Copyright (c) 2026 Ahmed, Bridges and Goldstone. FAU - Ahmed, Shahd AU - Ahmed S AD - PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom. FAU - Bridges, Nicola AU - Bridges N AD - Department of Paediatric Endocrinology, Chelsea and Westminster Hospital, London, United Kingdom. FAU - Goldstone, Anthony P AU - Goldstone AP AD - PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Department of Brain Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom. AD - Department of Endocrinology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, United Kingdom. LA - eng PT - Journal Article PT - Observational Study DEP - 20260903 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Adult MH - *Hyperphagia/drug therapy/etiology MH - *Prader-Willi Syndrome/complications/drug therapy MH - Male MH - *Obesity/drug therapy/etiology MH - Retrospective Studies MH - Young Adult MH - Middle Aged MH - Adolescent MH - Treatment Outcome MH - Weight Loss/drug effects MH - Diabetes Mellitus, Type 2 PMC - PMC13581520 OTO - NOTNLM OT - GLP-1 analogue OT - GLP-1 receptor agonists OT - HbA1c OT - PWS OT - Prader-Willi syndrome OT - hyperphagia OT - obesity OT - semaglutide COIS- APG is a consultant for Rhythm Pharmaceuticals and Novo Nordisk; has been a clinical investigator for clinical trials sponsored by Rhythm Pharmaceuticals, Millendo Therapeutics and Soleno Therapeutics; has been a consultant for Eli Lilly, Evidera, Helsinn Healthcare S.A, Idera Pharmaceuticals, Radius Health, Soleno Therapeutics, Tonix Pharmaceuticals and Vida Ventures; has been on Advisory Boards for Radius Health and Millendo Therapeutics; has been on Data Safety Monitoring Committee for Novo Nordisk; has received speaker fees from Eli Lilly, Novo Nordisk, Soleno Therapeutics and Rhythm Pharmaceuticals, and research support from Novo Nordisk. The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/09/18 12:26 MHDA- 2026/09/18 12:27 PMCR- 2026/09/03 CRDT- 2026/09/18 05:13 PHST- 2026/05/14 00:00 [received] PHST- 2026/08/05 00:00 [revised] PHST- 2026/08/10 00:00 [accepted] PHST- 2026/09/18 12:27 [medline] PHST- 2026/09/18 12:26 [pubmed] PHST- 2026/09/18 05:13 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - 10.3389/fendo.2026.1881392 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Sep 3;17:1881392. doi: 10.3389/fendo.2026.1881392. eCollection 2026. PMID- 42747132 OWN - NLM STAT- MEDLINE DCOM- 20260916 LR - 20260918 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 5 DP - 2026 Sep TI - Impact of Semaglutide, Liraglutide and Tirzepatide on Cardiometabolic Outcomes: A Comparative Narrative Review. PG - e70338 LID - 10.1002/edm2.70338 [doi] LID - e70338 AB - BACKGROUND: Cardiometabolic disorders such as type 2 diabetes mellitus (T2DM), obesity and cardiovascular disease (CVD) remain major global health challenges. Incretin-based therapies, including the GLP-1 receptor agonists semaglutide and liraglutide, and the dual GIP/GLP-1 receptor agonist tirzepatide, are increasingly used to address hyperglycaemia and obesity, and have been evaluated for both cardiometabolic risk markers and selected cardiovascular and renal outcomes. OBJECTIVE: This review summarizes and contrasts the pharmacology of semaglutide, liraglutide and tirzepatide, distinguishing between surrogate cardiometabolic risk markers (e.g., glycaemic control, body weight and lipid parameters) and confirmed clinical outcomes, including major adverse cardiovascular events (MACE) and renal endpoints. METHODS: Recent data were synthesized from pivotal randomized clinical trial programs, SUSTAIN and PIONEER (semaglutide), LEADER (liraglutide) and SURPASS and SURMOUNT (tirzepatide), as well as meta-analyses, post hoc analyses and observational studies addressing mechanistic and long-term cardiometabolic outcomes. RESULTS: All three agents improved HbA1c, weight and cardiometabolic outcomes, with tirzepatide generally showing greater reductions across clinical trials. Semaglutide and liraglutide consistently improved BMI, lipid profile and cardiovascular risk, while tirzepatide shows promise pending CVOT data. Renal outcomes were favourable across the class, though results varied by baseline characteristics and trial design. CONCLUSION: Semaglutide, liraglutide and tirzepatide are key therapies for type 2 diabetes and cardiometabolic disease. Tirzepatide's dual activity may enhance metabolic and lipid outcomes, while semaglutide and liraglutide have strong evidence for cardiovascular and renal safety. However, comparisons are based on indirect evidence and should be interpreted cautiously. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Bawadi, Hiba AU - Bawadi H AUID- ORCID: 0000-0003-1499-5646 AD - Department of Human Nutrition, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar. AD - Clinical Affairs Department, QU-HEALTH, Qatar University, Doha, Qatar. FAU - Abuhijleh, Haya AU - Abuhijleh H AUID- ORCID: 0009-0005-6643-3655 AD - Department of Human Nutrition, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar. AD - Department of Biomedical Sciences, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar. FAU - Nofal, Mamon AU - Nofal M AUID- ORCID: 0009-0004-8984-0360 AD - Nottingham University Hospitals NHS Trust, Nottingham, UK. FAU - Zakaria, Zain Z AU - Zakaria ZZ AUID- ORCID: 0000-0002-9656-8367 AD - Clinical Affairs Department, QU-HEALTH, Qatar University, Doha, Qatar. FAU - Al-Asmakh, Maha AU - Al-Asmakh M AUID- ORCID: 0000-0001-7855-4001 AD - Department of Biomedical Sciences, College of Health Sciences, QU-HEALTH, Qatar University, Doha, Qatar. AD - Biomedical Research Center, QU-HEALTH, Qatar University, Doha, Qatar. LA - eng PT - Comparative Study PT - Journal Article PT - Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Liraglutide/therapeutic use MH - Obesity/drug therapy MH - *Semaglutide/therapeutic use MH - Tirzepatide/therapeutic use PMC - PMC13580159 OTO - NOTNLM OT - cardiovascular outcomes OT - lipid modulation OT - liraglutide OT - obesity OT - renal protection OT - semaglutide OT - tirzepatide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/09/16 11:41 MHDA- 2026/09/16 11:42 PMCR- 2026/09/16 CRDT- 2026/09/16 09:05 PHST- 2026/06/05 00:00 [revised] PHST- 2026/01/18 00:00 [received] PHST- 2026/06/12 00:00 [accepted] PHST- 2026/09/16 11:42 [medline] PHST- 2026/09/16 11:41 [pubmed] PHST- 2026/09/16 09:05 [entrez] PHST- 2026/09/16 00:00 [pmc-release] AID - EDM270338 [pii] AID - 10.1002/edm2.70338 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 Sep;9(5):e70338. doi: 10.1002/edm2.70338. PMID- 42730869 OWN - NLM STAT- MEDLINE DCOM- 20260925 LR - 20260929 IS - 1179-1950 (Electronic) IS - 0012-6667 (Print) IS - 0012-6667 (Linking) VI - 86 IP - 10 DP - 2026 Oct TI - GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis. PG - 1661-1691 LID - 10.1007/s40265-026-02365-3 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood. OBJECTIVE: This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid((R)) platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082). RESULTS: From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I(2) 88%, p-value for heterogeneity <0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness. CONCLUSIONS: This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these changes appeared largely related to weight loss. Whether these changes translate into clinically meaningful impairments in muscle function or physical performance remains uncertain. Further studies in this field, including those looking at muscle function, strength or performance and using multivariate models considering confounding are needed to better reinforce the models and final findings. CI - (c) 2026. The Author(s). FAU - Beaudart, Charlotte AU - Beaudart C AUID- ORCID: 0000-0002-0827-5303 AD - Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium. charlotte.beaudart@unamur.be. AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. charlotte.beaudart@unamur.be. AD - Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), Faculty of Medicine, Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium. charlotte.beaudart@unamur.be. FAU - Malrechauffe, Yveline AU - Malrechauffe Y AD - Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium. FAU - van Heden, Sophie AU - van Heden S AD - Public Health Aging Research & Epidemiology (PHARE) Group, Research Unit in Clinical Pharmacology and Toxicology (URPC), Research Institute for Life Sciences (NARILIS), University of Namur, Namur, Belgium. FAU - Sanchez-Rodriguez, Dolores AU - Sanchez-Rodriguez D AUID- ORCID: 0000-0001-8662-5172 AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. AD - Department of Geriatrics, Brugmann University Hospital, Universite Libre de Bruxelles, Brussels, Belgium. AD - Rehabilitation Research Group, Hospital del Mar Research Institute, Barcelone, Spain. FAU - Scheen, Andre AU - Scheen A AD - Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liege, 4000, Liege, Belgium. AD - Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM), Liege University, Liege, Belgium. FAU - Bruyere, Olivier AU - Bruyere O AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. AD - Research Unit in Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium. FAU - Mobasheri, Ali AU - Mobasheri A AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. AD - Physics and Technology, Research Unit of Health Sciences and Technology, University of Oulu, Oulu, Finland. AD - Department of Personalised Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania. AD - Department of Joint Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. AD - Department for Health Sciences, Medicine and Research, Center for Regenerative Medicine, Faculty of Health and Medicine, University for Continuing Education Krems, Krems, Austria. AD - Department of Orthopaedic Surgery, Maastricht University Medical Center, Maastricht, The Netherlands. FAU - Duque, Gustavo AU - Duque G AD - Bone, Muscle & Geroscience Group, Research Institute of the McGill University Health Centre, Montreal, QC, Canada. FAU - Rizzoli, Rene AU - Rizzoli R AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. AD - Service of Bone Diseases, Faculty of Medicine, Geneva University Hospitals, 14 1211, Geneva, Switzerland. FAU - Reginster, Jean-Yves AU - Reginster JY AD - WHO Collaborating Centre for Epidemiology of Musculoskeletal Conditions and Ageing, Liege, Belgium. AD - Department of Biochemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia. FAU - Thiyagarajan, Jotheeswaran Amuthavalli AU - Thiyagarajan JA AD - Ageing and Life Course, World Health Organization, Geneva, Switzerland. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260912 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Exenatide/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/analogs & derivatives/pharmacology/analogs & derivatives MH - *Hypoglycemic Agents/pharmacology MH - Liraglutide/pharmacology MH - Obesity/drug therapy MH - Randomized Controlled Trials as Topic MH - Semaglutide MH - Tirzepatide MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC13615104 COIS- Declarations. Conflict of Interest: D.S-R. reports personal speaker fees from Nutricia outside the submitted work. J-Y.R. is President of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), a not-for-profit organisation receiving Unrestricted Educational Grands from corporate partners. J-Y.R. is an Editorial Board member of Drugs. J-Y.R. was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Other authors did not report any conflicts of interest in relation to this work. Disclaimer: The authors alone are responsible for the views expressed in this article, and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Code Availability: All materials related to this work are freely available on the Open Science Framework deposit - https://osf.io/zbhwc/ Availability of Data and Material: All materials related to this work are freely available on the Open Science Framework deposit - https://osf.io/zbhwc/ Authors' Contribution: J-Y.R. and J.A.T. are at the initiative of the research question. C.B. and Y.M. are the main investigators of the present research. C.B. drafted the protocol, which was reviewed by A.S. and J-Y.R. C.B. developed the search strategies and identified potential references for inclusion in the project. Y.M. C.B. and D.S.R. screened the references and selected the relevant ones. Conflicts were resolved by C.B. and Y.M. Y.M. performed the manual literature search. Y.M., C.B. and D.S.R., S.v.H. extracted the data, and performed the risk of bias assessment. Meta-analyses models were run by Y.M and C.B. The results were first interpreted by C.B., J-Y.R., A.S. and then by the rest of the experts, including A.M., R.R., and G.D. The first draft of the manuscript was written by C.B. All authors reviewed and approved the final manuscript. EDAT- 2026/09/13 00:50 MHDA- 2026/09/25 17:32 PMCR- 2026/09/12 CRDT- 2026/09/12 11:07 PHST- 2026/02/26 00:00 [received] PHST- 2026/07/06 00:00 [accepted] PHST- 2026/09/25 17:32 [medline] PHST- 2026/09/13 00:50 [pubmed] PHST- 2026/09/12 11:07 [entrez] PHST- 2026/09/12 00:00 [pmc-release] AID - 10.1007/s40265-026-02365-3 [pii] AID - 2365 [pii] AID - 10.1007/s40265-026-02365-3 [doi] PST - ppublish SO - Drugs. 2026 Oct;86(10):1661-1691. doi: 10.1007/s40265-026-02365-3. Epub 2026 Sep 12. PMID- 42718474 OWN - NLM STAT- MEDLINE DCOM- 20260910 LR - 20260911 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Electroacupuncture enables semaglutide dose sparing in type 2 diabetes by boosting drug concentration and suppressing beta-cell apoptosis. PG - 1880819 LID - 10.3389/fendo.2026.1880819 [doi] LID - 1880819 AB - PURPOSE: Semaglutide is effective for type 2 diabetes mellitus (T2DM) but limited by dose-dependent gastrointestinal adverse effects. As electroacupuncture (EA) possesses glucose-lowering effects, this study investigates the therapeutic potential and mechanism of combining EA with semaglutide to facilitate dose reduction while maintaining efficacy. METHODS: Male db/db mice were divided into: the model group(T2DM), the high/normal/low-dose semaglutide group (SH, SN, SL), the normal/low-dose semaglutide + EA at ST25 group (ST25N, ST25L), and the EA at ST25 group (ST25). The db/m mice served as the control group (CON). Blood glucose regulation was assessed via random/fasting blood glucose and oral glucose tolerance test (OGTT). To evaluate glycemic control and lipid profiles, HbA1c and insulin levels were quantified via ELISA, and T-CHO, TG, LDL-C, and HDL-C via biochemical kits. GLP-1R expression and beta-cell abundance were assessed by immunofluorescence, and pancreatic apoptosis by TUNEL staining. PKA, pPKA, Bcl-2, Bax, and GLP-1R were analyzed by Western blot. Male Sprague-Dawley (SD) rats were separated into 2 groups: the normal-dose semaglutide rats group (RSN) and the normal-dose semaglutide + EA at ST25 rats group (RST25N). LC-MS/MS was employed to measure the concentrations of semaglutide in the plasma and pancreas, thereby evaluating the influence of EA. RESULTS: EA enhances the effects of semaglutide on improving glycemic control and lipid metabolism, with significant reductions in random/fasting blood glucose, HbA1c, TCHO, TG and LDL-C levels, improvements in OGTT, insulin and HDL-C levels, and longer duration of controlled blood glucose within the target range, Furthermore, EA combined with semaglutide showed a marked increase in pancreatic beta-cells, with the increased expression of pancreatic GLP-1R, PKA, pPKA and Bcl-2, the reduced expression of Bax, increased concentration of semaglutide in plasma and pancreas. CONCLUSION: EA combined with normal- or low-dose semaglutide achieved glycemic control comparable to, or even better than, high-dose semaglutide alone, and its mechanism may be related to its enhancement of GLP-1R to inhibit beta-cell apoptosis and the increased concentration of semaglutide in plasma and pancreas. EA thus has great potential to reduce the dose of semaglutide to alleviate its side effects while ensuring its clinical efficacy. CI - Copyright (c) 2026 Yang, Wu, Gao, Zhu, Sun, Ouyang, Wu, Lan, Zhang, Zhang, Yuan, Sun, Zhu, Fu, Jing and Xu. FAU - Yang, Xinyi AU - Yang X AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Wu, Jiayue AU - Wu J AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Gao, Bing AU - Gao B AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Zhu, Yunmao AU - Zhu Y AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Sun, Yuchen AU - Sun Y AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Ouyang, Ling AU - Ouyang L AD - Traditional Chinese Medicine Hospital of Ruichang, Jiujiang, China. FAU - Wu, Bufan AU - Wu B AD - Nantong Hospital of Traditional Chinese Medicine, Nantong, China. FAU - Lan, Wenxiao AU - Lan W AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Zhang, Jing AU - Zhang J AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Zhang, Yujie AU - Zhang Y AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Yuan, Binbin AU - Yuan B AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Sun, Yitong AU - Sun Y AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Zhu, Yuanbing AU - Zhu Y AD - Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China. FAU - Fu, Shuping AU - Fu S AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Jing, Xinyue AU - Jing X AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. FAU - Xu, Bin AU - Xu B AD - Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China. LA - eng PT - Journal Article DEP - 20260826 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Insulin) SB - IM MH - Animals MH - Semaglutide MH - *Diabetes Mellitus, Type 2/therapy/drug therapy/pathology/metabolism MH - *Glucagon-Like Peptides/administration & dosage/pharmacology MH - *Apoptosis/drug effects MH - Male MH - *Insulin-Secreting Cells/drug effects/metabolism/pathology MH - *Hypoglycemic Agents/administration & dosage/pharmacology MH - Mice MH - *Electroacupuncture/methods MH - Blood Glucose/metabolism MH - *Diabetes Mellitus, Experimental/therapy/pathology MH - Insulin PMC - PMC13553360 OTO - NOTNLM OT - electroacupuncture OT - glucagon-like peptide-1 receptor OT - pancreatic beta-cell OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/09/10 11:54 MHDA- 2026/09/10 11:55 PMCR- 2026/08/26 CRDT- 2026/09/10 06:05 PHST- 2026/05/13 00:00 [received] PHST- 2026/08/02 00:00 [revised] PHST- 2026/08/04 00:00 [accepted] PHST- 2026/09/10 11:55 [medline] PHST- 2026/09/10 11:54 [pubmed] PHST- 2026/09/10 06:05 [entrez] PHST- 2026/08/26 00:00 [pmc-release] AID - 10.3389/fendo.2026.1880819 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Aug 26;17:1880819. doi: 10.3389/fendo.2026.1880819. eCollection 2026. PMID- 42697206 OWN - NLM STAT- MEDLINE DCOM- 20260914 LR - 20260914 IS - 1439-4286 (Electronic) IS - 0018-5043 (Linking) VI - 58 IP - 9 DP - 2026 Sep TI - Recent Advances in Glucagon-Like Peptide-1 Receptor and Melanocortin-4 Receptor Agonists for the Treatment of Obesity and Type 2 Diabetes. PG - 339-353 LID - 10.1055/a-2928-5204 [doi] AB - The global rise in aging populations has been accompanied by increasing rates of obesity and type 2 diabetes, both of which pose significant public health and economic challenges. This review aims to investigate the pathophysiological link between obesity and diabetes and evaluate emerging therapeutic strategies that involve glucagon-like peptide-1 receptor and melanocortin-4 receptor agonists, including their dual and triple agonist developments. A comprehensive literature review was conducted focusing on the mechanisms of glucagon-like peptide-1 receptor and melanocortin-4 receptor agonists, their clinical efficacy, and the evolution of combination therapies. Emphasis was placed on recent clinical trials and the development of oral agonist formulations to improve patient compliance. Glucagon-like peptide-1 receptor agonists, such as semaglutide and liraglutide, promote insulin secretion, suppress appetite, and result in effective weight loss and glycemic control. Semaglutide is available in both injectable and oral forms, improving accessibility. Liraglutide also reduces cardiovascular risk. Melanocortin-4 receptor agonists act via the central nervous system to reduce appetite and increase energy expenditure, with setmelanotide showing efficacy in genetic obesity. Dual and triple agonists, such as tirzepatide, simultaneously target glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon receptors, leading to enhanced metabolic outcomes. Oral drugs like rybelsus improve long-term adherence. Glucagon-like peptide-1 receptor and melanocortin-4 receptor agonists, particularly when used as dual or triple agents, represent promising therapeutic innovations for obesity and type 2 diabetes. The development of oral formulations further enhances treatment convenience and adherence, paving the way for improved clinical outcomes. CI - Thieme. All rights reserved. FAU - Lee, Chang-Min AU - Lee CM AD - Chosun University, Department of Biological Science, South Korea, Gwangju. FAU - Kim, Jin-Young AU - Kim JY AD - Chosun University, Department of Biological Science, South Korea, Gwangju. FAU - Shim, Jeong-Hyun AU - Shim JH AD - Chosun University, Department of Biological Science, South Korea, Gwangju. FAU - Cho, Gwang-Won AU - Cho GW AUID- ORCID: 0000-0002-2149-5095 AD - Chosun University, Department of Biological Science, South Korea, Gwangju. LA - eng PT - Journal Article PT - Review DEP - 20260904 PL - Germany TA - Horm Metab Res JT - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JID - 0177722 RN - 0 (Receptor, Melanocortin, Type 4) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Receptor, Melanocortin, Type 4/agonists MH - *Obesity/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Animals MH - *Glucagon-Like Peptide-1 Receptor/metabolism COIS- The authors declare that they have no conflict of interest. EDAT- 2026/09/04 23:36 MHDA- 2026/09/15 05:06 CRDT- 2026/09/04 18:42 PHST- 2026/09/15 05:06 [medline] PHST- 2026/09/04 23:36 [pubmed] PHST- 2026/09/04 18:42 [entrez] AID - 10.1055/a-2928-5204 [doi] PST - ppublish SO - Horm Metab Res. 2026 Sep;58(9):339-353. doi: 10.1055/a-2928-5204. Epub 2026 Sep 4. PMID- 42697203 OWN - NLM STAT- MEDLINE DCOM- 20260915 LR - 20260923 IS - 2666-3791 (Electronic) IS - 2666-3791 (Linking) VI - 7 IP - 9 DP - 2026 Sep 15 TI - Emerging role of GLP-1 mono, dual, and triple agonists in the management of MASH-related fibrosis. PG - 103023 LID - S2666-3791(26)00440-4 [pii] LID - 10.1016/j.xcrm.2026.103023 [doi] LID - 103023 AB - Recent therapeutic advances have resulted in US Food and Drug Administration (FDA) approval of the first pharmacological agents-resmetirom and semaglutide-for advanced metabolic dysfunction-associated steatohepatitis (MASH) without cirrhosis, reshaping the therapeutic landscape of the disease. Within this evolving framework, incretin-based pharmacotherapies-including glucagon-like peptide-1 (GLP-1) receptor agonists and their dual and triple combinations with glucose-dependent insulinotropic peptide (GIP) and/or glucagon receptor agonists-have emerged as promising options, particularly for individuals with coexisting obesity or type 2 diabetes. These agents exert pleiotropic effects across multiple organs, modulating glucose and lipid metabolism, while providing cardiovascular and renal benefits. Despite these advances, key challenges remain regarding treatment duration, tolerability, and interindividual variability in therapeutic response. This review summarizes the emerging role of GLP-1 mono, dual, and triple agonists in MASH-related fibrosis, focusing on their mechanisms of action and evidence from phase 2 and phase 3 clinical trials with histology-assessed hepatic endpoints. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Tavaglione, Federica AU - Tavaglione F AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla, CA, USA. Electronic address: ftavaglione@health.ucsd.edu. FAU - Loomba, Rohit AU - Loomba R AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla, CA, USA; School of Public Health, University of California, San Diego, La Jolla, CA, USA. Electronic address: roloomba@health.ucsd.edu. LA - eng GR - P30 DK120515/DK/NIDDK NIH HHS/United States GR - UL1 TR001442/TR/NCATS NIH HHS/United States PT - Journal Article PT - Review DEP - 20260904 PL - United States TA - Cell Rep Med JT - Cell reports. Medicine JID - 101766894 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Animals MH - Glucagon-Like Peptides/therapeutic use MH - *Liver Cirrhosis/drug therapy/pathology MH - Fibrosis/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - *Fatty Liver/drug therapy/pathology MH - Non-alcoholic Fatty Liver Disease/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Incretins/therapeutic use MH - Hypoglycemic Agents/therapeutic use PMC - PMC13589479 OTO - NOTNLM OT - GIP OT - MASLD OT - NAFLD OT - glucagon OT - incretins COIS- Declaration of interests R.L. serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse Bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals, and Viking Therapeutics. In addition, his institution received research grants from Arrowhead Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes, and Terns Pharmaceuticals. R.L. is also a co-founder of LipoNexus Inc. EDAT- 2026/09/04 23:36 MHDA- 2026/09/15 23:34 PMCR- 2026/09/04 CRDT- 2026/09/04 18:41 PHST- 2026/03/18 00:00 [received] PHST- 2026/06/26 00:00 [revised] PHST- 2026/08/11 00:00 [accepted] PHST- 2026/09/15 23:34 [medline] PHST- 2026/09/04 23:36 [pubmed] PHST- 2026/09/04 18:41 [entrez] PHST- 2026/09/04 00:00 [pmc-release] AID - S2666-3791(26)00440-4 [pii] AID - 103023 [pii] AID - 10.1016/j.xcrm.2026.103023 [doi] PST - ppublish SO - Cell Rep Med. 2026 Sep 15;7(9):103023. doi: 10.1016/j.xcrm.2026.103023. Epub 2026 Sep 4. PMID- 42687069 OWN - NLM STAT- MEDLINE DCOM- 20261007 LR - 20261010 IS - 1573-904X (Electronic) IS - 0724-8741 (Linking) VI - 43 IP - 9 DP - 2026 Sep TI - Semaglutide Bioavailability: Limitations, Formulation Innovation and Future Opportunities. PG - 2989-3010 LID - 10.1007/s11095-026-04185-2 [doi] AB - Semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, improved the type 2 diabetes mellitus treatment and obesity by its glucose-lowering and weight loss effects. Although the subcutaneous route provides high bioavailability and stable pharmacokinetics, the development of oral semaglutide makes a significant advancement in peptide therapeutics. However, oral delivery remains limited by an absolute bioavailability of only approximately 0.4-1% under optimized fasting conditions with restricted water intake, whereas systemic exposure is essentially absent in the fed state because plasma semaglutide concentrations remain below the limit of quantification. This extremely low exposure reflects peptide degradation within the gastrointestinal tract, poor epithelial permeability, gastric physiological constraints, and presystemic metabolism. The combination with sodium N-(8-[2-hydroxybenzoyl]amino) caprylate (SNAC) helps in gastric absorption by increasing the local gastric microenvironmental pH, thereby reducing acid-induced peptide unfolding, suppressing pepsin activation, maintaining semaglutide predominantly in its absorbable monomeric form by limiting oligomer formation, and enhancing transcellular uptake. But the oral form of semaglutide is constrained by narrow dose limits, considerable pharmacokinetic variability that, despite large fluctuations in individual absorption, produces relatively stable steady-state exposure because semaglutide's approximately one-week half-life and extensive albumin binding buffer day-to-day differences in absorption. This review examines semaglutide pharmacokinetics, focusing on mechanistic challenges to oral bioavailability and formulation approaches to address this. We assess emerging methods such as nanotechnology-based formulations, other permeation enhancers, enzyme inhibitors and device-based delivery systems for their abilities to improve absorption and efficacy. Furthermore, clinical efficacy and patient adherence as well as research opportunities are considered. Continual development of these technologies may emerge as a solution to enhance bioavailability, decrease dosing frequency and expand the range of uses of oral peptide therapies. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Vahora, Shahin AU - Vahora S AUID- ORCID: 0009-0004-6651-0852 AD - Navinta LLC, 1499 Lower Ferry Road, Ewing, NJ, 08618, USA. shahin121190@gmail.com. FAU - Shah, Vishal AU - Shah V AD - Director Operations, Flamma USA LLC, Malvern, PA, USA. FAU - Patel, Bhavesh AU - Patel B AD - Product Development, Frontage Laboratories, Inc., Exton, PA, USA. LA - eng PT - Journal Article PT - Review DEP - 20260903 PL - United States TA - Pharm Res JT - Pharmaceutical research JID - 8406521 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Caprylates) RN - 0 (N-(8-(2-hydroxybenzoyl)amino)caprylate) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/pharmacokinetics/administration & dosage/chemistry MH - Biological Availability MH - Animals MH - *Hypoglycemic Agents/pharmacokinetics/administration & dosage/chemistry MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy MH - Caprylates/chemistry MH - Drug Compounding MH - Obesity/drug therapy OTO - NOTNLM OT - absorption enhancers (SNAC) OT - bioavailability enhancement OT - formulation strategies OT - oral peptide drug delivery OT - semaglutide COIS- Declarations. Ethical Approval and Consent to Participate: Ethical Approval and Consent to Participate is not applicable. Competing interest: There is no competing interests. EDAT- 2026/09/03 05:37 MHDA- 2026/10/07 05:31 CRDT- 2026/09/03 01:47 PHST- 2026/05/02 00:00 [received] PHST- 2026/08/12 00:00 [accepted] PHST- 2026/10/07 05:31 [medline] PHST- 2026/09/03 05:37 [pubmed] PHST- 2026/09/03 01:47 [entrez] AID - 10.1007/s11095-026-04185-2 [pii] AID - 10.1007/s11095-026-04185-2 [doi] PST - ppublish SO - Pharm Res. 2026 Sep;43(9):2989-3010. doi: 10.1007/s11095-026-04185-2. Epub 2026 Sep 3. PMID- 42679726 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20261009 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 40 IP - 10 DP - 2026 Oct TI - Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial. PG - 109397 LID - S1056-8727(26)00142-X [pii] LID - 10.1016/j.jdiacomp.2026.109397 [doi] AB - AIMS: The endothelium maintains vascular health by regulating blood flow and protecting against inflammatory damage. In type 2 diabetes (T2DM), however, hyperglycemia, hypertension, and hyperlipidemia place a significant burden on the endothelium, potentially leading to atherosclerosis and cardiovascular disease (CVD). While semaglutide and empagliflozin have been shown to reduce CVD risk in T2DM, it remains unclear whether these benefits are mediated by improved endothelial function. This post-hoc analysis explores the effects of these agents on markers of endothelial function, i.e. the reactive hyperaemic index (RHI) and the endothelial-derived cell adhesion molecules (CAMs) E-Selectin, ICAM-1, P-Selectin, and VCAM-1. METHODS: This was a post-hoc analysis of a 32-week randomized trial evaluating the separate and combined effects of semaglutide and empagliflozin on cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, age >/= 50 were randomized to four groups (semaglutide, empagliflozin, the combination or placebo). An increase in RHI and/or a decrease in CAMs were considered beneficial. RESULTS: RHI increased compared to baseline (0.11, 95%CI [0.008;0.21], p = 0.03) but not compared to placebo in the semaglutide group (0.11, 95%CI [-0.04;0.24], p = 0.16). There was no effect on RHI in the empagliflozin group. Compared to placebo, E-Selectin decreased significantly in the semaglutide and combination groups (-9, 95%CI [-14.1;-5.1] p < 0.01 and - 9, 95%CI [-14.3; -5.2] p < 0.01, respectively). VCAM-1 increased in the same groups, compared to placebo (12.3, 95%CI[2.8;20.8] p = 0.01 and 16.2, 95%CI [7.2;24.3], p < 0.01, respectively).P-Selectin and ICAM-1 was not significantly affected in any of the groups, compared to placebo (p >/= 0.11 and p >/= 0.09, respectively). CONCLUSION: Semaglutide improved endothelial function compared to baseline, but not significantly versus placebo, which likely is due to limited power. CAM responses were heterogeneous, suggesting distinct roles in endothelial dysfunction and atherosclerosis. ClinicalTrialsRegister.eu: EudraCT 2019-000781-38. CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Gullaksen, Soren AU - Gullaksen S AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, 8000, Aarhus, Denmark. Electronic address: soegul@clin.au.dk. FAU - Vernstrom, Liv AU - Vernstrom L AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200, Aarhus N, Denmark. FAU - Sorensen, Steffen Skovgaard AU - Sorensen SS AD - Department of Nuclear Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark. FAU - Funck, Kristian Lokke AU - Funck KL AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200, Aarhus N, Denmark. FAU - Poulsen, Per Logstrup AU - Poulsen PL AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200, Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200, Aarhus N, Denmark; Department of Clinical Medicine, Aarhus University, 8000, Aarhus, Denmark. FAU - Laugesen, Esben AU - Laugesen E AD - Steno Diabetes Center, Aarhus University Hospital, 8200, Aarhus N, Denmark; Diagnostic Centre, Silkeborg Regional Hospital, 8600, Silkeborg, Denmark; Department of Clinical Medicine, Aarhus University, 8000, Aarhus, Denmark. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260829 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Benzhydryl Compounds) RN - 0 (Biomarkers) RN - 0 (E-Selectin) RN - HDC1R2M35U (empagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Vascular Cell Adhesion Molecule-1) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Benzhydryl Compounds/therapeutic use/administration & dosage MH - Biomarkers/blood MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications/physiopathology MH - *Diabetic Angiopathies/prevention & control/blood MH - Double-Blind Method MH - Drug Therapy, Combination MH - E-Selectin/blood MH - *Endothelium, Vascular/drug effects/physiopathology/metabolism MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Glucosides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Vascular Cell Adhesion Molecule-1/blood OTO - NOTNLM OT - Atherosclerosis OT - Cardiovascular disease OT - Endothelial function OT - Glucagon-like peptide 1 receptor agonist OT - Sodium glucose co-transporter 2 inhibitor OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Esben Laugesen reports financial support was provided by Novo Nordisk Foundation. Soeren Gullaksen reports financial support was provided by Danish Medical Association Research Fund. Liv Vernstroem reports financial support was provided by Aarhus University. Steffen Skovgaard Soerensen reports financial support was provided by Independent Research Fund Denmark. Per Loegstrup Poulsen reports financial support was provided by Novo Nordisk Foundation. Per Loegstrup Poulsen reports a relationship with AstraZeneca that includes: board membership and funding grants. Per Loegstrup Poulsen reports a relationship with Bayer AG that includes: board membership. Per Loegstrup Poulsen reports a relationship with Novo Nordisk that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/09/01 23:34 MHDA- 2026/09/07 23:34 CRDT- 2026/09/01 18:13 PHST- 2026/02/24 00:00 [received] PHST- 2026/06/24 00:00 [revised] PHST- 2026/08/27 00:00 [accepted] PHST- 2026/09/07 23:34 [medline] PHST- 2026/09/01 23:34 [pubmed] PHST- 2026/09/01 18:13 [entrez] AID - S1056-8727(26)00142-X [pii] AID - 10.1016/j.jdiacomp.2026.109397 [doi] PST - ppublish SO - J Diabetes Complications. 2026 Oct;40(10):109397. doi: 10.1016/j.jdiacomp.2026.109397. Epub 2026 Aug 29. PMID- 42660161 OWN - NLM STAT- MEDLINE DCOM- 20261013 LR - 20261013 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 11 DP - 2026 Nov TI - From adiposity to multisystem morbidity: the case for weight loss as disease modification. PG - 952-969 LID - S2213-8587(26)00186-5 [pii] LID - 10.1016/S2213-8587(26)00186-5 [doi] AB - Obesity (ie, excess adiposity) is a major driver of multisystem morbidity, spanning musculoskeletal (eg, osteoarthritis), metabolic (eg, type 2 diabetes), cardiovascular (eg, heart failure), mental health (eg, depression), respiratory (eg, obstructive sleep apnoea), and gastrointestinal and hepatic (eg, metabolic dysfunction-associated steatotic liver disease) disorders. However, the extent to which weight-loss interventions can prevent or modify these conditions varies considerably. In this Review, we synthesise evidence from epidemiological studies, genetic analyses (including Mendelian randomisation), observational weight-change studies, and randomised trials, using a triangulation framework to assess causal links between adiposity and common diseases. Although robust trial evidence supports weight loss as a disease-modifying strategy in some conditions, including but not limited to type 2 diabetes and heart failure with preserved ejection fraction, many other conditions, including musculoskeletal, respiratory, cardiovascular, and mental health disorders, remain under-investigated. Incretin-based therapies, in particular the glucagon-like peptide 1 receptor agonist semaglutide and the dual glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist tirzepatide, now achieve average weight losses of approximately 14-20% in people without diabetes and have generated the first large-scale randomised evidence of disease modification across several of these conditions. We highlight key gaps and propose priorities for future trials, including the need for studies across different disease stages, incorporation of mechanistic and mediation analyses, and evaluation of the impact on disease outcomes of varying magnitudes of weight loss with differing agents. Future research should also consider multimorbidity, individualised treatment targets, and long-term outcomes-including potential legacy effects. Addressing global access gaps and conducting trials in diverse populations will be essential to inform scalable and equitable obesity care. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Sattar, Naveed AU - Sattar N AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. Electronic address: naveed.sattar@glasgow.ac.uk. FAU - Ferguson, Lyn D AU - Ferguson LD AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Lee, Matthew M Y AU - Lee MMY AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. LA - eng PT - Journal Article PT - Review DEP - 20260827 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Weight Loss/physiology MH - *Obesity/complications/therapy MH - *Adiposity/physiology MH - *Diabetes Mellitus, Type 2 MH - *Cardiovascular Diseases/prevention & control/etiology MH - Semaglutide COIS- Declaration of interests NS has consulted for and received speaker honoraria from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gan & Lee, GlaxoSmithKline, Hanmi Pharmaceuticals, Kailera, Mass Medicines, Menarini-Ricerche, Metsera, Novo Nordisk, Pfizer, Regeneron, Roche, UCB Pharma, and Verdiva Bio; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche outside the submitted work. LDF reports speaker fees from Janssen and UCB and consultancy and conference travel support from Sanofi. MMYL has received research grants through his institution, the University of Glasgow, from AstraZeneca, Boehringer Ingelheim, and Roche Diagnostics; serves on Trial Steering Committees for Amgen and Cytokinetics; and Clinical Endpoint Committees for AstraZeneca, Bayer, and GlaxoSmithKline. EDAT- 2026/08/28 11:40 MHDA- 2026/10/13 23:35 CRDT- 2026/08/27 18:52 PHST- 2026/03/06 00:00 [received] PHST- 2026/05/20 00:00 [revised] PHST- 2026/07/07 00:00 [accepted] PHST- 2026/10/13 23:35 [medline] PHST- 2026/08/28 11:40 [pubmed] PHST- 2026/08/27 18:52 [entrez] AID - S2213-8587(26)00186-5 [pii] AID - 10.1016/S2213-8587(26)00186-5 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Nov;14(11):952-969. doi: 10.1016/S2213-8587(26)00186-5. Epub 2026 Aug 27. PMID- 42654433 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260918 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 8 DP - 2026 Aug 10 TI - Is There a Better Day of the Week to Administer Semaglutide or Tirzepatide? A Systematic Literature Review. LID - 10.3390/medicina62081536 [doi] LID - 1536 AB - Background and Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including semaglutide and the dual GIP/GLP-1 receptor agonist tirzepatide, have transformed the management of type 2 diabetes mellitus (T2DM) and obesity through once-weekly subcutaneous administration. While their efficacy and safety are well-established, the potential impact of administration timing-specifically, the day of the week-on clinical outcomes, adherence, and tolerability remains unexplored. Understanding whether specific days optimize therapeutic outcomes could inform personalized dosing strategies and improve long-term treatment success. Materials and Methods: We conducted a systematic literature review following PRISMA 2020 guidelines to identify studies examining the effect of weekly administration timing of semaglutide or tirzepatide on clinical outcomes in adults with T2DM or obesity. Comprehensive searches were performed across SciSpace (Deep Search, Basic Search, Full Text Search), Google Scholar, and PubMed databases through June 2026. Studies were screened using a two-stage process (abstract and full-text screening) with predefined PICO-based inclusion criteria. Data extraction focused on study design, population characteristics, administration timing, glycemic control, weight loss, adherence, and adverse events. Results: From 1471 identified records, 1000 unique papers underwent screening after deduplication and trimming. Three studies met inclusion criteria: the SUSTAIN 4 randomized controlled trial evaluating once-weekly semaglutide, a retrospective case series examining alternate-day oral semaglutide dosing, and an expert panel discussion on flexible dosing schedules. No studies directly compared different days of the week for injectable semaglutide or tirzepatide administration. Available evidence suggests that flexible dosing schedules may support adherence and tolerability without compromising glycemic control, though this suggestion derives primarily from indirect evidence and expert opinion rather than direct comparative clinical studies; direct comparative data on day-of-week effects are absent. Conclusions: Current evidence does not support a specific optimal day of the week for semaglutide or tirzepatide administration. The limited literature emphasizes flexible dosing schedules tailored to individual patient preferences and lifestyles to maximize adherence. Future prospective studies are needed to systematically evaluate whether administration timing influences clinical outcomes in real-world settings. FAU - La Vignera, Sandro AU - La Vignera S AUID- ORCID: 0000-0002-7113-2372 AD - Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy. FAU - Condorelli, Rosita A AU - Condorelli RA AUID- ORCID: 0000-0002-5217-9343 AD - Department of Clinical and Experimental Medicine, University of Catania, Via S. Sofia 78, 95123 Catania, Italy. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260810 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Semaglutide MH - Humans MH - *Tirzepatide/administration & dosage MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/administration & dosage/therapeutic use MH - Obesity/drug therapy MH - Drug Administration Schedule MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13515371 OTO - NOTNLM OT - GLP-1 receptor agonists OT - administration timing OT - chronotherapy OT - medication adherence OT - obesity OT - semaglutide OT - tirzepatide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/08/10 CRDT- 2026/08/27 01:10 PHST- 2026/06/15 00:00 [received] PHST- 2026/08/01 00:00 [revised] PHST- 2026/08/04 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 01:10 [entrez] PHST- 2026/08/10 00:00 [pmc-release] AID - medicina62081536 [pii] AID - medicina-62-01536 [pii] AID - 10.3390/medicina62081536 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Aug 10;62(8):1536. doi: 10.3390/medicina62081536. PMID- 42654406 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260829 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 8 DP - 2026 Aug 5 TI - Renal Effects of Glucagon-like Peptide-1 Receptor Agonists in Diabetic Kidney Disease: A Narrative Review of Mechanisms and Clinical Evidence. LID - 10.3390/medicina62081509 [doi] LID - 1509 AB - Diabetic kidney disease (DKD) remains a major cause of advanced chronic kidney disease (CKD) and cardiovascular (CV) mortality, despite optimization of renin-angiotensin-aldosterone system (RAAS) blockade and the use of sodium-glucose cotransporter-2 inhibitors (SGLT2i). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cardiometabolic agents with significant efficacy on glycemic control, body weight, blood pressure (BP), lipid profile, and systemic inflammation. In experimental studies, GLP-1 RAs showed direct renal effects by modulating natriuresis, intrarenal hemodynamics, oxidative stress, endothelial dysfunction, and tubular apoptosis. Randomized clinical trials and real-life analyses have demonstrated reductions in albuminuria and slowing of glomerular filtration rate (GFR) decline. The first study with a primary renal endpoint for semaglutide confirms its nephroprotective potential. This narrative review synthesizes the renal mechanisms involved. The clinical evidence for GLP-1 RA in DKD positions this class alongside SGLT2i and non-steroidal mineralocorticoid receptor antagonists (ns-MRAs) for the management of patients with type 2 diabetes mellitus (T2D), CKD, and very high cardiorenal risk. FAU - Braha, Adina AU - Braha A AUID- ORCID: 0000-0002-7904-6073 AD - Department of Second Internal Medicine-Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, "Pius Brinzeu" County Emergency Clinical University Hospital, 300723 Timisoara, Romania. AD - Center for Molecular Research in Nephrology and Vascular Disease (MOL-NEPHRO-VASC), "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. FAU - Timar, Bogdan AU - Timar B AUID- ORCID: 0000-0002-0993-6206 AD - Department of Second Internal Medicine-Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, "Pius Brinzeu" County Emergency Clinical University Hospital, 300723 Timisoara, Romania. AD - Center for Molecular Research in Nephrology and Vascular Disease (MOL-NEPHRO-VASC), "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. FAU - Sturza, Adrian AU - Sturza A AD - Department of Diabetes, Nutrition and Metabolic Diseases, "Pius Brinzeu" County Emergency Clinical University Hospital, 300723 Timisoara, Romania. AD - Department of Functional Sciences-Pathophysiology, Center for Translational Research and Systems Medicine, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. FAU - Timar, Romulus AU - Timar R AUID- ORCID: 0000-0003-0792-9202 AD - Department of Second Internal Medicine-Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases, "Pius Brinzeu" County Emergency Clinical University Hospital, 300723 Timisoara, Romania. AD - Center for Molecular Research in Nephrology and Vascular Disease (MOL-NEPHRO-VASC), "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. LA - eng PT - Journal Article PT - Review DEP - 20260805 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetic Nephropathies/drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - *Kidney/drug effects/physiopathology MH - Glucagon-Like Peptides/therapeutic use/pharmacology MH - Glomerular Filtration Rate/drug effects PMC - PMC13514747 OTO - NOTNLM OT - cardiorenal protection OT - chronic kidney disease OT - diabetic kidney disease OT - glucagon-like peptide-1 receptor agonists COIS- The authors declare no conflicts of interest. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/08/05 CRDT- 2026/08/27 01:10 PHST- 2026/06/01 00:00 [received] PHST- 2026/07/26 00:00 [revised] PHST- 2026/08/04 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 01:10 [entrez] PHST- 2026/08/05 00:00 [pmc-release] AID - medicina62081509 [pii] AID - medicina-62-01509 [pii] AID - 10.3390/medicina62081509 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Aug 5;62(8):1509. doi: 10.3390/medicina62081509. PMID- 42654343 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260829 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 8 DP - 2026 Jul 25 TI - Glucagon-like Peptide-1 Receptor Agonists and Dual Incretin Therapies Across HFpEF and Cardiovascular Outcomes Trials in Patients with Obesity. LID - 10.3390/medicina62081446 [doi] LID - 1446 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and emerging dual incretin therapies have demonstrated substantial effects on weight reduction and metabolic improvement, with growing evidence supporting favorable cardiovascular outcomes. This narrative review provides a focused overview of key cardiovascular outcomes trials (CVOTs) and HFpEF-oriented clinical studies evaluating GLP-1 RA and dual incretin therapies in patients living with obesity, including completed and ongoing investigations. We summarize trial characteristics, critically appraise their outcomes, and briefly discuss mechanistic pathways potentially linking incretin-based therapies to cardiovascular and HFpEF-related benefits. Because available data derive from heterogeneous study designs, we explicitly distinguish evidence from type 2 diabetes cardiovascular outcomes trials, obesity-without-diabetes cardiovascular outcomes trials, HFpEF-specific randomized trials, mechanistic substudies, ongoing trials, and real-world observational analyses. We also situate incretin-based therapies within contemporary obesity, diabetes, cardiovascular, and HFpEF guideline-directed care. Finally, we identify current knowledge gaps, future research priorities, and innovative approaches needed to refine personalized therapeutic strategies and optimize patient-centered outcomes in obesity-associated HFpEF. FAU - Belancic, Andrej AU - Belancic A AUID- ORCID: 0000-0001-7848-6600 AD - Department of Basic and Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. FAU - Klobucar, Sanja AU - Klobucar S AUID- ORCID: 0000-0002-0287-4735 AD - Department of Endocrinology, Diabetes and Metabolic Diseases, Clinical Hospital Centre Rijeka, 51000 Rijeka, Croatia. AD - Department of Internal Medicine, Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. FAU - Skroce, Kristina AU - Skroce K AUID- ORCID: 0000-0003-0379-5235 AD - Faculty of Medicine, University of Rijeka, 51000 Rijeka, Croatia. FAU - Ciudin, Andreea AU - Ciudin A AD - Diabetes and Metabolism Research Group, VHIR, Endocrinology Department, Vall d'Hebron University Hospital, Autonomus University of Barcelona, 08035 Barcelona, Spain. FAU - Borovac, Josip Andelo AU - Borovac JA AUID- ORCID: 0000-0002-4878-8146 AD - Department of Cardiovascular Diseases, University Hospital of Split, 21000 Split, Croatia. AD - Department of Pathophysiology, School of Medicine, University of Split, 21000 Split, Croatia. LA - eng PT - Journal Article PT - Review DEP - 20260725 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Obesity/complications/drug therapy MH - *Incretins/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Heart Failure/drug therapy MH - Tirzepatide MH - Semaglutide MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives/pharmacology MH - Cardiovascular Diseases/drug therapy MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Exenatide/therapeutic use MH - Liraglutide/therapeutic use/pharmacology PMC - PMC13514512 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular outcomes OT - heart failure OT - obesity OT - semaglutide OT - tirzepatide COIS- A.B. has received payment of honoraria from AstraZeneca, Servier, Novo Nordisk, Eli Lilly and Novartis as speaker and/or member of advisory boards; is secretary of the Croatian Society of Obesity, president of the Croatian EASO ECN, EASO ECN board member (middle region), and EASO COMs Working Group member. S.K. has received speaking and/or consulting fees from Abbott. A.C. has received speaking fees from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Novo Nordisk, Sanofi and Menarini; research grants from Eli Lilly, Novo Nordisk and Menarini; and is a member of the data-monitoring committee of Boehringer Ingelheim. J.A.B. has received speaking fees from Boehringer-Ingelheim and Novartis and grant/congress support from Abbott, Medtronic, MSD and European Association for Percutaneous Cardiovascular Interventions (EAPCI); is a member of the European Society of Cardiology Heart Failure Association Committee on Coronary Artery Disease. Other authors declare no conflicts of interest relevant to this manuscript. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/07/25 CRDT- 2026/08/27 01:10 PHST- 2026/06/06 00:00 [received] PHST- 2026/07/11 00:00 [revised] PHST- 2026/07/23 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 01:10 [entrez] PHST- 2026/07/25 00:00 [pmc-release] AID - medicina62081446 [pii] AID - medicina-62-01446 [pii] AID - 10.3390/medicina62081446 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Jul 25;62(8):1446. doi: 10.3390/medicina62081446. PMID- 42654234 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260829 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 18 IP - 16 DP - 2026 Aug 14 TI - Beyond Weight Loss: Skeletal Muscle Health During Incretin-Based Therapy in Patients with Diabesity. LID - 10.3390/nu18162654 [doi] LID - 2654 AB - Background: Incretin-based therapies (IBTs), including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs), have transformed the management of obesity and type 2 diabetes mellitus (T2DM). Although these agents provide substantial metabolic and cardiometabolic benefits, their effects on skeletal muscle, particularly in older adults at increased risk of sarcopenia and functional decline, remain incompletely understood. Methods: This narrative review synthesizes evidence from randomized controlled trials (RCTs) and observational studies evaluating the effects of semaglutide and tirzepatide on skeletal muscle mass (SMM), muscle quality, strength, and physical performance. Current evidence on nutritional and exercise strategies aimed at preserving skeletal muscle during IBT was also reviewed. Results: Both semaglutide and tirzepatide induce substantial weight loss accompanied by reductions in lean body mass (LBM). However, current evidence indicates that LBM loss is generally proportional to the magnitude of weight loss and should not be interpreted as a direct surrogate for skeletal muscle loss or drug-induced myotoxicity. Tirzepatide appears to improve skeletal muscle composition by reducing muscle fat infiltration (MFI), whereas semaglutide shows more heterogeneous effects on muscle strength and physical performance, particularly in older or frail individuals. Emerging evidence highlights the importance of muscle quality, nutritional adequacy, and resistance exercise as key determinants of muscle preservation, although functional outcomes and data in older adults remain limited. Conclusions: The effects of incretin-based therapies (IBTs) on skeletal muscle are multifactorial and influenced by age, baseline muscle reserve, nutritional status, and physical activity. Preserving skeletal muscle health should be considered an integral component of obesity management through individualized nutritional care, adequate protein intake, resistance exercise, and regular functional assessment. Future research should prioritize the standardized evaluation of muscle quality and function and determine whether targeted nutritional interventions can improve the quality of weight loss and support healthy aging during IBT. FAU - Mollero, Edoardo Luigi Maria AU - Mollero ELM AUID- ORCID: 0000-0002-1903-5874 AD - Endocrinology and Metabolic Diseases Unit, Department of Internal Medicine and Emergency Medicine, IRCCS AOU "SS Antonio e Biagio e Cesare Arrigo", Via Venezia, 16, 15121 Alessandria, Italy. AD - Department of Statistics, Computer Science, Applications "Giuseppe Parenti", University of Florence, Viale Giovanni Battista Morgagni 59, 50134 Firenze, Italy. FAU - Dozzani, Ivan AU - Dozzani I AUID- ORCID: 0009-0007-5595-7992 AD - Independent Researcher, 50142 Firenze, Italy. FAU - Biamonte, Emilia AU - Biamonte E AUID- ORCID: 0009-0000-9502-4694 AD - Endocrinology and Metabolic Diseases Unit, Department of Internal Medicine and Emergency Medicine, IRCCS AOU "SS Antonio e Biagio e Cesare Arrigo", Via Venezia, 16, 15121 Alessandria, Italy. FAU - Bendotti, Giulia AU - Bendotti G AUID- ORCID: 0000-0002-6548-3475 AD - Endocrinology and Metabolic Diseases Unit, Department of Internal Medicine and Emergency Medicine, IRCCS AOU "SS Antonio e Biagio e Cesare Arrigo", Via Venezia, 16, 15121 Alessandria, Italy. FAU - Marzullo, Paolo AU - Marzullo P AUID- ORCID: 0000-0003-3215-5747 AD - Division of Endocrinology, Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy. FAU - Aimaretti, Gianluca AU - Aimaretti G AD - Division of Endocrinology and Metabolism, Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126 Torino, Italy. FAU - Gallo, Marco AU - Gallo M AUID- ORCID: 0000-0001-7166-0848 AD - Endocrinology and Metabolic Diseases Unit, Department of Internal Medicine and Emergency Medicine, IRCCS AOU "SS Antonio e Biagio e Cesare Arrigo", Via Venezia, 16, 15121 Alessandria, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260814 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Incretins) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Muscle, Skeletal/drug effects MH - Semaglutide MH - *Incretins/therapeutic use/pharmacology MH - *Weight Loss/drug effects MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Sarcopenia MH - Muscle Strength/drug effects PMC - PMC13516410 OTO - NOTNLM OT - GLP-1 receptor agonists OT - muscle quality OT - nutrition OT - obesity OT - resistance training OT - sarcopenia OT - semaglutide OT - skeletal muscle OT - tirzepatide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/08/14 CRDT- 2026/08/27 01:09 PHST- 2026/07/26 00:00 [received] PHST- 2026/08/10 00:00 [revised] PHST- 2026/08/12 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 01:09 [entrez] PHST- 2026/08/14 00:00 [pmc-release] AID - nu18162654 [pii] AID - nutrients-18-02654 [pii] AID - 10.3390/nu18162654 [doi] PST - epublish SO - Nutrients. 2026 Aug 14;18(16):2654. doi: 10.3390/nu18162654. PMID- 42649514 OWN - NLM STAT- MEDLINE DCOM- 20260827 LR - 20260908 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Aug 26 TI - Disease-modifying anti-diabetic drugs (DMADDs): bridging the SIMPLE approach to disease interception. LID - 10.1186/s12933-026-03346-2 [doi] LID - 259 AB - The traditional glucose-centric paradigm of type 2 diabetes management is being superseded by growing evidence that certain agents, sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and pioglitazone, confer cardiovascular, renal, and hepatic benefits that extend well beyond glycemic control. Building on the previously proposed "diabetes/disease-modifying drugs (DMDs)" concept introduced through the SIMPLE framework, we propose a more mechanistically precise term: Disease-Modifying Anti-Diabetic Drugs (DMADDs). DMADDs are defined by four criteria: glucose-independent clinical benefit, durable organ-specific protection, mechanistic evidence of anti-inflammatory or anti-fibrotic activity, and sustained legacy effects or remission potential. Using these criteria, SGLT2i, GLP-1RA, and pioglitazone emerge as prototypical agents, while metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, insulin, and sulfonylureas do not meet the full threshold. We explicitly explain why metformin and DPP-4 inhibitors are excluded as DMADDs, situate the DMADD framework within the heterogeneity of type 2 diabetes and against what non-pharmacological interventions can achieve, and state the limitations of the proposal. Recent evidence reinforces this framework: the SOUL trial established cardiovascular superiority for oral semaglutide, extending disease-modifying properties beyond injectable formulations, while Phase 3 TRIUMPH data position retatrutide as an emerging triple-agonist candidate awaiting cardiovascular outcome data. The 2026 American Diabetes Association Standards of Care now recommend SGLT2i and GLP-1RA independent of baseline glycated hemoglobin (HbA1c), an institutional shift that mirrors the disease-interception logic proposed here. We argue that adopting the DMADD framework could reorient diabetes therapeutics from glycemic normalization toward early disease interception, potentially preserving beta-cell function and expanding the clinical horizon toward remission. This terminology offers a unifying scaffold for future trials, regulatory classification, and clinical guidelines, redefining therapeutic success in type 2 diabetes beyond glucose control alone. CI - (c) 2026. The Author(s). FAU - Koca, Nizameddin AU - Koca N AUID- ORCID: 0000-0003-1457-4366 AD - Department of Internal Medicine, University of Health Sciences, Bursa Sehir Training & Research Hospital, Bursa, Turkey. nizameddin.koca@sbu.edu.tr. FAU - Uyar, Seyit AU - Uyar S AUID- ORCID: 0000-0002-2435-8248 AD - Department of Internal Medicine, University of Health Sciences, Antalya Training & Research Hospital, Antalya, Turkey. FAU - Sahinturk, Yasin AU - Sahinturk Y AUID- ORCID: 0000-0003-4907-0766 AD - Department of Internal Medicine, University of Health Sciences, Antalya Training & Research Hospital, Antalya, Turkey. FAU - Yildiz, Hamit AU - Yildiz H AUID- ORCID: 0000-0001-7858-5123 AD - Department of Internal Medicine, University of Gaziantep, Gaziantep University Hospital, Gaziantep, Turkey. FAU - Del Prato, Stefano AU - Del Prato S AUID- ORCID: 0000-0001-5905-0211 AD - Interdisciplinary Research Center "Health Science", Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - DeFronzo, RalphA AU - DeFronzo R AUID- ORCID: 0000-0002-8581-6273 AD - Department of Internal Medicine, Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, TX, USA. LA - eng PT - Journal Article DEP - 20260826 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Biomarkers) RN - 0 (PPAR-gamma Agonists) RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/epidemiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - *Blood Glucose/drug effects/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Animals MH - Biomarkers/blood MH - *Glycemic Control/adverse effects MH - PPAR-gamma Agonists MH - *Incretins/therapeutic use/adverse effects MH - Semaglutide MH - Remission Induction PMC - PMC13520461 OTO - NOTNLM OT - Disease modification OT - GLP-1 receptor agonists OT - Organ protection OT - Remission OT - SGLT2 inhibitors OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing Interests: N.K., S.U., Y.S., H.Y., and R.A.D. declare no competing interests. S.D.P. reports consulting fees from Abbott, Altimmune, Applied Therapeutics, Biomea Fusion, Eli Lilly and Company, Menarini International, Hoffman-La Roche, Novo Nordisk, and Sun Pharma; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Menarini International, Novo Nordisk, and Sanofi. EDAT- 2026/08/27 05:35 MHDA- 2026/08/27 05:36 PMCR- 2026/08/26 CRDT- 2026/08/27 00:02 PHST- 2026/07/09 00:00 [received] PHST- 2026/08/17 00:00 [accepted] PHST- 2026/08/27 05:36 [medline] PHST- 2026/08/27 05:35 [pubmed] PHST- 2026/08/27 00:02 [entrez] PHST- 2026/08/26 00:00 [pmc-release] AID - 10.1186/s12933-026-03346-2 [pii] AID - 3346 [pii] AID - 10.1186/s12933-026-03346-2 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Aug 26;25(1):259. doi: 10.1186/s12933-026-03346-2. PMID- 42642357 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261010 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Cardiorenal Mortality and Safety Outcomes of GLP-1 Receptor Agonists in Type 2 Diabetes With BMI Below 27 kg/m(2): A Target Trial Emulation. PG - 10498-10512 LID - 10.1111/dom.71266 [doi] AB - AIMS: Cardiorenal evidence for glucagon-like peptide-1 receptor agonists (GLP-1 RAs) derives mainly from trials in overweight or obesity; data in adults with Type 2 diabetes (T2D) and body mass index (BMI) below 27 kg/m(2) are limited. MATERIALS AND METHODS: We emulated a target trial in the TriNetX US Collaborative Network (index dates 2020 to 2026; maximum follow-up 24 months). Adults with T2D and BMI < 27 kg/m(2) newly initiating non-tirzepatide GLP-1 RAs were compared with new users of dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT2i) or usual care. Comparisons used separate 1:1 propensity score matching. The primary outcome was all-cause mortality. RESULTS: After matching, 7389, 8969 and 8610 GLP-1 RA users were matched to DPP-4i, SGLT2i and usual care. Versus DPP-4i, GLP-1 RA was associated with lower all-cause mortality (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.52-0.71), major adverse cardiovascular events (MACE; HR 0.83; 95% CI 0.71-0.98) and coded heart failure (HR 0.71; 95% CI 0.60-0.85). Versus SGLT2i, MACE (HR 0.81; 95% CI 0.69-0.95) and coded heart failure (HR 0.56; 95% CI 0.47-0.65) were lower, but all-cause mortality was not (HR 0.89; 95% CI 0.76-1.05). Gastroparesis was more frequent versus DPP-4i. CONCLUSION: In people with T2D and BMI < 27 kg/m(2), GLP-1 RA use was associated with lower coded heart failure risk across all three comparisons, the most consistent finding. The lower all-cause mortality association versus DPP-4i and usual care, absent versus SGLT2i, should be interpreted cautiously as likely reflecting residual confounding rather than a benefit of this magnitude. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chen, Shao-Chia AU - Chen SC AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Huang, Yu-Nan AU - Huang YN AUID- ORCID: 0000-0003-1688-1685 AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Li, Pei-Yun AU - Li PY AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Chen, Jo-Ching AU - Chen JC AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Meyerowitz-Katz, Gideon AU - Meyerowitz-Katz G AD - School of Health and Society, University of Wollongong, Wollongong, Australia. FAU - Yang, Shun-Fa AU - Yang SF AUID- ORCID: 0000-0002-0365-7927 AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Su, Pen-Hua AU - Su PH AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. LA - eng GR - CSH-2025-A-004/Chung Shan Medical University Hospital/ GR - CSH-2026-A-009/Chung Shan Medical University Hospital/ GR - CSH-2026-F-003/Chung Shan Medical University Hospital/ GR - 113-2314-B-040-026-MY2/National Science and Technology Council/ GR - 114-2622-B-040-001/National Science and Technology Council/ PT - Journal Article DEP - 20260825 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Body Mass Index MH - Middle Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Aged MH - Heart Failure/mortality PMC - PMC13646335 OTO - NOTNLM OT - GLP-1 receptor agonist OT - Type 2 diabetes OT - cardiovascular outcomes OT - heart failure OT - semaglutide OT - target trial emulation OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/08/26 05:36 MHDA- 2026/10/08 05:31 PMCR- 2026/10/08 CRDT- 2026/08/25 23:03 PHST- 2026/08/01 00:00 [revised] PHST- 2026/05/18 00:00 [received] PHST- 2026/08/12 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/08/26 05:36 [pubmed] PHST- 2026/08/25 23:03 [entrez] PHST- 2026/10/08 00:00 [pmc-release] AID - DOM71266 [pii] AID - 10.1111/dom.71266 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):10498-10512. doi: 10.1111/dom.71266. Epub 2026 Aug 25. PMID- 42624955 OWN - NLM STAT- MEDLINE DCOM- 20260821 LR - 20260823 IS - 1535-1645 (Electronic) IS - 1523-3812 (Print) IS - 1523-3812 (Linking) VI - 28 IP - 1 DP - 2026 Aug 21 TI - GLP-1 and dual GIP/GLP-1 receptor agonists' psychopharmacology and putative neuropsychiatric associated effects: a Bradford Hill-informed, systematic, evaluation. LID - 10.1007/s11920-026-01709-w [doi] LID - 65 AB - PURPOSE OF REVIEW: This review evaluates evidence linking both GLP-1 and GIP/GLP-1RAs' exposure to a range of neuropsychiatric outcomes using the Bradford Hill criteria for causal inference. RECENT FINDINGS: Glucagon-like peptide-1 (GLP-1) and the dual glucose-dependent insulinotropic polypeptide-GIP/GLP-1 receptor agonists (RAs) are incretin-based medications widely prescribed for type 2 diabetes mellitus and obesity, with demonstrated cardiometabolic benefit and rapidly expanding population exposure. In parallel, post-marketing surveillance and emerging translational research have raised questions regarding potential central nervous system effects, including neuropsychiatric adverse events and psychopharmacological properties. Integrating data from receptor pharmacology, preclinical neuroscience, randomized controlled trials, and observational and pharmacovigilance studies, the strength, consistency, biological plausibility, and experimental support for reported associations with depression, anxiety, suicidality, reward-related behaviour, cognitive effects and retinal/ocular related disturbances were here assessed. Implications for clinical risk-benefit assessment were discussed as well. Current evidence supports potential biological plausibility of a relationship between GLP-1 RAs and a range of psychopathological disorders but remains insufficient to establish causality for most neuropsychiatric outcomes, suggesting the need for prospective, mechanism-informed clinical studies. CI - (c) 2026. The Author(s). FAU - Schifano, F AU - Schifano F AD - Drug Misuse and Novel Psychoactive Substances Research Unit, University of Hertfordshire Medical School, Psychopharmacology, Hatfield, UK. FAU - De Luca, M A AU - De Luca MA AD - Drug Misuse and Novel Psychoactive Substances Research Unit, University of Hertfordshire Medical School, Psychopharmacology, Hatfield, UK. AD - Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy. FAU - Bonaccorso, S AU - Bonaccorso S AD - North London NHS Foundation Trust, St Pancras Hospital, London, UK. FAU - Arillotta, Davide AU - Arillotta D AUID- ORCID: 0000-0002-8843-0595 AD - Drug Misuse and Novel Psychoactive Substances Research Unit, University of Hertfordshire Medical School, Psychopharmacology, Hatfield, UK. davide.arillotta@yahoo.it. AD - Department of Neurosciences, Psychology, Drug Research, and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy. davide.arillotta@yahoo.it. FAU - Floresta, G AU - Floresta G AD - Department of Drug and Health Sciences, University of Catania, Catania, Italy. giuseppe.floresta@unict.it. FAU - Martinotti, G AU - Martinotti G AD - Department of Neurosciences, Imaging and Clinical Sciences, Universita degli Studi G. D'Annunzio Chieti-Pescara, Chieti, Italy. FAU - Papanti, G D AU - Papanti GD AD - Tolmezzo Community Mental Health Centre, ASUFC Mental Health and Addiction Department, Tolmezzo, Italy. FAU - Corkery, J M AU - Corkery JM AD - Drug Misuse and Novel Psychoactive Substances Research Unit, University of Hertfordshire Medical School, Psychopharmacology, Hatfield, UK. FAU - Chiappini, S AU - Chiappini S AD - UniCamillus International University of Medical Sciences, Rome, Italy. FAU - Guirguis, A AU - Guirguis A AD - University of Swansea Medical School, Swansea, UK. LA - eng PT - Journal Article PT - Review DEP - 20260821 PL - United States TA - Curr Psychiatry Rep JT - Current psychiatry reports JID - 100888960 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Gastric Inhibitory Polypeptide/agonists MH - *Glucagon-Like Peptide 1/agonists MH - *Mental Disorders/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Receptors, Gastrointestinal Hormone/agonists MH - *Hypoglycemic Agents/adverse effects MH - *Incretins/adverse effects PMC - PMC13493456 OTO - NOTNLM OT - Anxiety OT - Bradford-Hill evaluation OT - Cognitive dysfunction OT - Depression OT - Dulaglutide OT - GLP-1 RAs OT - GLP-1 receptor agonists OT - Liraglutide OT - Psychopathology OT - Psychopharmacology OT - Retatrutide OT - Semaglutide OT - Suicidal ideation OT - Tirzepatide OT - dual GIP/GLP-1 RAs OT - triple GIP/GLP-1/glucagon RAs COIS- Declarations. Competing Interests: The authors declare no competing interests. EDAT- 2026/08/21 05:35 MHDA- 2026/08/21 05:36 PMCR- 2026/08/21 CRDT- 2026/08/21 00:09 PHST- 2026/05/21 00:00 [received] PHST- 2026/07/31 00:00 [accepted] PHST- 2026/08/21 05:36 [medline] PHST- 2026/08/21 05:35 [pubmed] PHST- 2026/08/21 00:09 [entrez] PHST- 2026/08/21 00:00 [pmc-release] AID - 10.1007/s11920-026-01709-w [pii] AID - 1709 [pii] AID - 10.1007/s11920-026-01709-w [doi] PST - epublish SO - Curr Psychiatry Rep. 2026 Aug 21;28(1):65. doi: 10.1007/s11920-026-01709-w. PMID- 42624784 OWN - NLM STAT- MEDLINE DCOM- 20260820 LR - 20260820 IS - 1558-7118 (Electronic) IS - 1557-2625 (Linking) VI - 39 IP - 1 DP - 2026 Aug TI - Not Just for Diabetes: The Next Frontier for GLP-1 Agonists. LID - 165782 [pii] LID - 10.3122/jabfm.2025.250473R1 [doi] AB - A commonly used GLP-1 agonist, semaglutide, reduces the risk of adverse cardiovascular outcomes in non-diabetic individuals with obesity and pre-existing cardiovascular disease. CI - (c) 2026 Copyright by the American Board of Family Medicine. FAU - Colangelo, Henry AU - Colangelo H AD - University of Colorado Family Medicine Residency. FAU - Nestler, Ariana AU - Nestler A AD - University of Colorado Family Medicine Residency. FAU - Lyon, Corey AU - Lyon C AD - University of Colorado Family Medicine Residency. LA - eng PT - Journal Article PL - United States TA - J Am Board Fam Med JT - Journal of the American Board of Family Medicine : JABFM JID - 101256526 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Obesity/drug therapy/complications MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide 1/agonists MH - *Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Cardiovascular Diseases OT - Glucagon-Like Peptide 1 OT - Obesity OT - Semaglutide EDAT- 2026/08/20 23:35 MHDA- 2026/08/20 23:36 CRDT- 2026/08/20 21:55 PHST- 2025/12/11 00:00 [received] PHST- 2026/01/14 00:00 [accepted] PHST- 2026/08/20 23:36 [medline] PHST- 2026/08/20 23:35 [pubmed] PHST- 2026/08/20 21:55 [entrez] AID - 39/1/165782 [pii] AID - 10.3122/jabfm.2025.250473R1 [doi] PST - ppublish SO - J Am Board Fam Med. 2026 Aug;39(1):165782. doi: 10.3122/jabfm.2025.250473R1. PMID- 42624330 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20260907 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 240 DP - 2026 Oct TI - Trends in utilization of glucagon-like peptide‑1 receptor agonists, sodium-glucose cotransporter‑2 inhibitors, and metabolic bariatric surgery in U.S. adults with diabetes and obesity. PG - 113504 LID - S0168-8227(26)00424-9 [pii] LID - 10.1016/j.diabres.2026.113504 [doi] AB - AIMS: To characterize trends in utilization of glucagon-like peptide‑1 receptor agonists (GLP‑1RAs), sodium-glucose cotransporter‑2 inhibitors (SGLT2is), and metabolic/bariatric surgery among US adults with type 2 diabetes (T2D) and obesity. METHODS: We conducted a cohort study using electronic health record and claims data from Optum Labs Data Warehouse for US private and Medicare Advantage plan enrollees aged 18-79 with T2D and obesity initiating GLP‑1RAs or SGLT2is or undergoing MBS (2010-2024). We evaluated initiation, adherence (>/=80% of days with medication), and persistence. RESULTS: Among 342,932 treatment initiations (335,605 individuals), 60.8% initiated GLP‑1RAs, 35.7% SGLT2is, and 3.6% MBS. Use of both medication classes increased over time (GLP-1RAs: 1,988 to 44,852; SGLT2is: 861 to 19,892). In 2024, semaglutide (62.2%) and tirzepatide (32.6%) were the most initiated GLP-1RAs; MBS was rare (0.7% of treatments). Median treatment duration was 240 days for GLP‑1RAs and 254 days for SGLT2is; approximately 50% were adherent. Tirzepatide had the highest adherence and persistence. At one-year, 53.0% of GLP‑1RA and 56.0% of SGLT2i initiators were using their initiated treatment; transition to other therapies was uncommon. CONCLUSIONS: Initiation of GLP‑1RAs and SGLT2is, but not MBS utilization, has expanded in recent years, although adherence and persistence remain low. Further studies should evaluate how these shifting patterns affect health outcomes. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Wartko, Paige D AU - Wartko PD AD - Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA; Department of Epidemiology, School of Public Health, University of Washington, Hans Rosling Center for Population Health, 3980 15th Avenue NE, Box 351617, Seattle, WA 98195-1617, USA. Electronic address: paige.d.wartko@kp.org. FAU - Zhang, Rui AU - Zhang R AD - University of Maryland Institute for Health Computing, North Bethesda, MD, USA. FAU - Johnson, Eric AU - Johnson E AD - Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA. FAU - Begle, Connor AU - Begle C AD - University of Maryland Institute for Health Computing, North Bethesda, MD, USA. FAU - Bobb, Jennifer F AU - Bobb JF AD - Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA. FAU - Chen, Chixiang AU - Chen C AD - University of Maryland Institute for Health Computing, North Bethesda, MD, USA; Division of Biostatistics and Bioinformatics, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Singh, Aditi AU - Singh A AD - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Ross, Lisa AU - Ross L AD - Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA. FAU - O'Connor, Patrick J AU - O'Connor PJ AD - HealthPartners Institute, Minneapolis, MN, USA. FAU - Arterburn, David AU - Arterburn D AD - Kaiser Permanente Washington Health Research Institute, 1730 Minor Ave, Suite 1360, Seattle, WA 98101, USA. FAU - McCoy, Rozalina G AU - McCoy RG AD - University of Maryland Institute for Health Computing, North Bethesda, MD, USA; Optum Labs, Eden Prairie, MN, USA; Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. LA - eng GR - P30 AG097158/AG/NIA NIH HHS/United States GR - R01 DK135515/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20260820 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/surgery MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Bariatric Surgery/trends/statistics & numerical data MH - Female MH - Male MH - Adult MH - *Obesity/drug therapy/surgery/therapy MH - Middle Aged MH - United States/epidemiology MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Adolescent MH - Young Adult MH - Cohort Studies MH - Semaglutide MH - Tirzepatide OTO - NOTNLM OT - GIP/GLP-1RA OT - GLP-1RA OT - Metabolic surgery OT - Obesity OT - Pharmacoepidemiology OT - SGLT2i OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rozalina McCoy reports financial support was provided by National Institute of Diabetes and Digestive and Kidney Diseases. David Arterburn reports financial support was provided by National Institute of Diabetes and Digestive and Kidney Diseases. Paige Wartko reports a relationship with Syneos Health that includes: funding grants. Rozalina McCoy reports a relationship with American Diabetes Association that includes: funding grants, speaking and lecture fees, and travel reimbursement. Rozalina McCoy reports a relationship with Yale New Haven Health that includes: consulting or advisory. Rozalina McCoy reports a relationship with National Committee for Quality Assurance (NCQA) that includes: consulting or advisory. David Arterburn reports a relationship with Obesity Medicine Association that includes: speaking and lecture fees and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/08/20 23:35 MHDA- 2026/09/07 23:34 CRDT- 2026/08/20 19:13 PHST- 2026/05/11 00:00 [received] PHST- 2026/08/14 00:00 [revised] PHST- 2026/08/17 00:00 [accepted] PHST- 2026/09/07 23:34 [medline] PHST- 2026/08/20 23:35 [pubmed] PHST- 2026/08/20 19:13 [entrez] AID - S0168-8227(26)00424-9 [pii] AID - 10.1016/j.diabres.2026.113504 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Oct;240:113504. doi: 10.1016/j.diabres.2026.113504. Epub 2026 Aug 20. PMID- 42618523 OWN - NLM STAT- MEDLINE DCOM- 20260926 LR - 20260926 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 IP - 10 DP - 2026 Oct TI - Major Adverse Liver Outcomes With Tirzepatide and Injectable Semaglutide in Adults With Overweight or Obesity and Type 2 Diabetes. PG - 1958-1966 LID - 10.1002/oby.70277 [doi] AB - OBJECTIVE: This study aimed to compare the effectiveness of tirzepatide versus injectable semaglutide in preventing major adverse liver outcomes (MALO) among adults with overweight or obesity and type 2 diabetes. METHODS: This retrospective target trial emulation utilized the TriNetX global network to analyze new users of tirzepatide and semaglutide. The primary outcome was time-to-first MALO (a composite of cirrhosis, decompensated events, and hepatocellular carcinoma). Propensity score matching balanced baseline covariates. RESULTS: Over a median follow-up of ~17 months, no significant difference in MALO risk was observed between tirzepatide and semaglutide initiators (estimated incidence rate [IR] 4.05 vs. 4.04 per 1000 person-years [PY]; hazard ratio [HR] 1.04, 95% CI 0.88-1.23). This comparable risk profile was maintained across sensitivity analyses, including people with MASLD (IR 9.97 vs. 10.03 per 1000 PY; HR 1.03, 95% CI: 0.75-1.42) and "as treated" analysis (HR 0.98, 95% CI: 0.80-1.21). Tirzepatide achieved greater BMI reduction (mean difference ~1.1 kg/m(2), p < 0.001). Internal validation confirmed both agents significantly outperformed sitagliptin. CONCLUSIONS: In this high-risk population with type 2 diabetes, tirzepatide and injectable semaglutide offered comparable effectiveness in mitigating liver disease progression and MALO in the short- to medium-term follow-up. CI - (c) 2026 The Obesity Society. FAU - Banerjee, Mainak AU - Banerjee M AUID- ORCID: 0000-0002-6656-8569 AD - Department of Endocrinology, R N Tagore Hospital, Kolkata, India. AD - Department of Endocrinology, Ramakrishna Mission Seva Pratisthan & Vivekananda Institute of Medical Sciences, Kolkata, India. FAU - Roy, Ajitesh AU - Roy A AD - Department of Endocrinology, Ramakrishna Mission Seva Pratisthan & Vivekananda Institute of Medical Sciences, Kolkata, India. FAU - Sharma, Vivek Mohan AU - Sharma VM AD - Department of Gastroenterology, R.N. Tagore Hospital, Narayana Health, Kolkata, India. FAU - Das, Abhishek AU - Das A AD - Department of Gastroenterology, Royal Cornwall Hospital NHS Trust, Truro, UK. LA - eng GR - Narayana Health/ PT - Journal Article DEP - 20260819 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - Male MH - *Obesity/complications/drug therapy MH - *Overweight/complications/drug therapy MH - Middle Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - Adult MH - Liver Cirrhosis/prevention & control MH - Treatment Outcome MH - Liver Neoplasms/prevention & control MH - Aged MH - Injections MH - Carcinoma, Hepatocellular/prevention & control OTO - NOTNLM OT - GLP-1RA OT - GLP-1RA/GIP agonist OT - MASLD OT - NAFLD OT - fatty liver EDAT- 2026/08/19 23:42 MHDA- 2026/09/27 02:25 CRDT- 2026/08/19 22:23 PHST- 2026/05/31 00:00 [revised] PHST- 2026/02/23 00:00 [received] PHST- 2026/07/07 00:00 [accepted] PHST- 2026/09/27 02:25 [medline] PHST- 2026/08/19 23:42 [pubmed] PHST- 2026/08/19 22:23 [entrez] AID - 10.1002/oby.70277 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Oct;34(10):1958-1966. doi: 10.1002/oby.70277. Epub 2026 Aug 19. PMID- 42605535 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261013 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Efficacy of Luseogliflozin Added to Semaglutide in Patients With Metabolic Dysfunction-Associated Steatohepatitis and Type 2 Diabetes Mellitus: A Randomised, Open-Label Trial. PG - 10163-10172 LID - 10.1111/dom.71233 [doi] AB - AIMS: Type 2 diabetes drives the progression of metabolic dysfunction-associated steatohepatitis (MASH). We evaluated whether antidiabetic therapy, specifically adding sodium-glucose cotransporter 2 (SGLT2) inhibitor to a glucagon-like peptide-1 receptor agonist (GLP-1RA), improves liver histology in adults with biopsy-proven MASH and type 2 diabetes. MATERIALS AND METHODS: In this 52-week, open-label, randomised, parallel-group trial in Japan, adults with biopsy-confirmed MASH and type 2 diabetes received semaglutide plus luseogliflozin or semaglutide alone at antidiabetic doses. Paired liver biopsies at baseline and Week 52 were evaluated by blinded pathologists. Primary histological endpoints included resolution of MASH without worsening fibrosis, >/= 1-point improvement in the non-alcoholic fatty liver disease (NAFLD) activity score without worsening fibrosis and >/= 1-stage improvement in fibrosis without worsening MASH. RESULTS: Sixty participants were randomised (combination, n = 24; monotherapy, n = 36). At Week 52, all histological endpoints numerically favoured combination therapy. Resolution of MASH without worsening fibrosis occurred in 34.9% versus 19.4%, >/= 1-point improvement in the NAFLD activity score (NAS) in 75.5% versus 55.6% and >/= 1-stage fibrosis improvement in 26.9% versus 13.9%. In the pre-specified per-protocol analysis, >/= 1-point improvement in the NAS was nominally significant. Combination therapy reduced body weight, glycated haemoglobin levels, aminotransferase levels and FibroScan-derived liver stiffness. CONCLUSIONS: In the pre-specified full analysis set, combination therapy at antidiabetic doses did not significantly improve pre-specified histological endpoints compared with monotherapy. In the pre-specified per-protocol analysis, a nominal improvement in the NAS was observed. Combination therapy improved body weight, glycemic control, aminotransferase levels and liver stiffness, with no new safety concerns identified. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR): UMIN000045003; Japan Registry of Clinical Trials (jRCT): jRCTs061210009. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Miyake, Teruki AU - Miyake T AUID- ORCID: 0000-0002-9905-5356 AD - Department of Lifestyle-Related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. AD - Total Medical Support Center, Ehime University Hospital, Toon, Ehime, Japan. AD - Center for Data Science, Ehime University, Toon, Ehime, Japan. FAU - Yoshida, Osamu AU - Yoshida O AUID- ORCID: 0000-0002-5015-0045 AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Furukawa, Shinya AU - Furukawa S AD - Health Service Center, Ehime University, Matsuyama, Ehime, Japan. FAU - Hirooka, Masashi AU - Hirooka M AD - Total Medical Support Center, Ehime University Hospital, Toon, Ehime, Japan. AD - Center for Data Science, Ehime University, Toon, Ehime, Japan. FAU - Abe, Masanori AU - Abe M AD - Department of Community and General Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Tokumoto, Yoshio AU - Tokumoto Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Kanamoto, Ayumi AU - Kanamoto A AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Watanabe, Takao AU - Watanabe T AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Yano, Ryo AU - Yano R AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Okazaki, Yuki AU - Okazaki Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Yukimoto, Atsushi AU - Yukimoto A AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Nakamura, Yoshiko AU - Nakamura Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Takeshita, Eiji AU - Takeshita E AD - Department of Inflammatory Bowel Diseases and Therapeutics, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Kumagi, Teru AU - Kumagi T AD - Post Graduate Medical Education Center, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. FAU - Hiasa, Yoichi AU - Hiasa Y AD - Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan. LA - eng GR - Taisho Toyama Pharmaceutical Company/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260817 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - C596HWF74Z (1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 506T60A25R (Sorbitol) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - Japan MH - Liver/pathology/drug effects MH - *Non-alcoholic Fatty Liver Disease/pathology/drug therapy/complications MH - *Semaglutide/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage/adverse effects MH - Sorbitol/analogs & derivatives/therapeutic use/administration & dosage/adverse effects/analogs & derivatives MH - Treatment Outcome PMC - PMC13646358 OTO - NOTNLM OT - GLP-1 analogue OT - SGLT2 inhibitor OT - antidiabetic drug OT - clinical trial OT - diabetes complications OT - fatty liver disease COIS- Y.H. reports receiving a research grant from Taisho Pharmaceutical Co. Ltd. related to this study and lecture fees from Taisho Pharmaceutical Co. Ltd. and Kowa Company Ltd. T.M. reports receiving lecture fees related to MASLD and diabetes mellitus from Taisho Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Boehringer Ingelheim Japan Inc., Sumitomo Pharma Co. Ltd., Tanabe Pharma Corporation and Kowa Company Ltd. S.F. reports receiving lecture fees related to diabetes mellitus from Taisho Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Sumitomo Pharma Co. Ltd., Tanabe Pharma Corporation and Kowa Company Ltd. The other authors declare no conflicts of interest. EDAT- 2026/08/17 05:38 MHDA- 2026/10/08 05:31 PMCR- 2026/10/08 CRDT- 2026/08/17 03:54 PHST- 2026/08/01 00:00 [revised] PHST- 2026/06/11 00:00 [received] PHST- 2026/08/05 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/08/17 05:38 [pubmed] PHST- 2026/08/17 03:54 [entrez] PHST- 2026/10/08 00:00 [pmc-release] AID - DOM71233 [pii] AID - 10.1111/dom.71233 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):10163-10172. doi: 10.1111/dom.71233. Epub 2026 Aug 17. PMID- 42603240 OWN - NLM STAT- MEDLINE DCOM- 20260815 LR - 20261008 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 91 IP - 1 DP - 2026 Aug 15 TI - Effect of tirzepatide and semaglutide on blood pressure: A systematic review and meta-analysis. LID - 275 [pii] LID - 10.1007/s12020-026-04757-7 [doi] AB - PURPOSE: Tirzepatide and semaglutide are widely used for type 2 diabetes mellitus (T2DM) and obesity. However, the blood pressure-related adverse event profiles associated with tirzepatide and semaglutide remain unclear. This study systematically evaluated hypertension- and hypotension-related treatment-emergent adverse events (TEAEs) that occurred when using tirzepatide and semaglutide for the treatment of T2DM or obesity. METHODS: A comprehensive search was performed in PubMed, Scopus, Web of Science, Embase, CENTRAL, and ClinicalTrials.gov from inception to September 26, 2025. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects model, with subgroup analyses performed. RESULTS: This meta-analysis of 32 randomized controlled trials (RCTs), enrolling 47,332 participants, revealed distinct differences in the blood pressure-related safety profiles of tirzepatide and semaglutide. Tirzepatide was associated with a lower risk of hypertension-related events (RR = 0.40, 95% CI [0.26-0.60]; p < 0.001). This potent antihypertensive effect was accompanied by an increased risk of hypotension-related events (RR = 2.45, 95% CI [1.35-4.45]; p = 0.003), particularly at higher doses (RR = 2.58, 95% CI [1.38-4.81]; p = 0.003). Semaglutide exhibited a relatively neutral blood pressure-related safety profile, showing no significant association with either hypertension-related events (RR = 0.81, 95% CI [0.57-1.15]; p = 0.233) or hypotension-related events (RR = 1.39, 95% CI [0.81-2.36]; p = 0.232), although potential protective signals were observed in high-dose subgroups. CONCLUSION: Tirzepatide reduces hypertension-related adverse events but increases dose-dependent hypotension risk in patients with T2DM or obesity. These distinct hemodynamic safety profiles support individualized treatment decisions based on baseline blood pressure and cardiometabolic risk. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Chen, Qing-Xin AU - Chen QX AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Zhou, Xiao-Yu AU - Zhou XY AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Wu, Qi AU - Wu Q AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. AD - Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, Luzhou, 646000, Sichuan, China. AD - Department of Pathology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Xie, Jia-Jie AU - Xie JJ AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. FAU - Xu, Yong AU - Xu Y AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. xywyll@swmu.edu.cn. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. xywyll@swmu.edu.cn. AD - Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, Luzhou, 646000, Sichuan, China. xywyll@swmu.edu.cn. AD - Sichuan Clinical Research Center for Nephropathy, and Sichuan Clinical Research Center for Diabetes and Metabolic Disease, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. xywyll@swmu.edu.cn. FAU - Teng, Fang-Yuan AU - Teng FY AUID- ORCID: 0000-0002-9564-0961 AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. tengfangyuan383@swmu.edu.cn. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. tengfangyuan383@swmu.edu.cn. AD - Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, Luzhou, 646000, Sichuan, China. tengfangyuan383@swmu.edu.cn. AD - Sichuan Clinical Research Center for Nephropathy, and Sichuan Clinical Research Center for Diabetes and Metabolic Disease, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. tengfangyuan383@swmu.edu.cn. FAU - Guo, Man AU - Guo M AD - Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. guoman613@163.com. AD - School of Clinical Medicine, Southwest Medical University, Luzhou, 646000, Sichuan, China. guoman613@163.com. AD - Metabolic Vascular Diseases Key Laboratory of Sichuan Province, and Metabolic Vascular Diseases Key Laboratory of Sichuan-Chongqing Cooperation, Luzhou, 646000, Sichuan, China. guoman613@163.com. AD - Sichuan Clinical Research Center for Nephropathy, and Sichuan Clinical Research Center for Diabetes and Metabolic Disease, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China. guoman613@163.com. LA - eng GR - 82300911/National Natural Science Foundation of China/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260815 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - *Tirzepatide MH - Semaglutide MH - Humans MH - *Blood Pressure/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects/therapeutic use/pharmacology MH - Hypertension/chemically induced MH - Obesity/drug therapy MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - Blood pressure OT - Diabetes OT - Meta-analysis OT - Obesity OT - Semaglutide OT - Tirzepatide COIS- Declarations. Conflict of interests: The authors declare they have no competing interests. EDAT- 2026/08/15 17:37 MHDA- 2026/08/15 17:38 CRDT- 2026/08/15 11:07 PHST- 2026/05/08 00:00 [received] PHST- 2026/08/09 00:00 [accepted] PHST- 2026/08/15 17:38 [medline] PHST- 2026/08/15 17:37 [pubmed] PHST- 2026/08/15 11:07 [entrez] AID - 10.1007/s12020-026-04757-7 [pii] AID - 10.1007/s12020-026-04757-7 [doi] PST - epublish SO - Endocrine. 2026 Aug 15;91(1):275. doi: 10.1007/s12020-026-04757-7. PMID- 42594928 OWN - NLM STAT- MEDLINE DCOM- 20260908 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 10 DP - 2026 Oct TI - Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial. PG - 831-840 LID - S2213-8587(26)00136-1 [pii] LID - 10.1016/S2213-8587(26)00136-1 [doi] AB - BACKGROUND: Stepwise treatment intensification is recommended for managing type 2 diabetes, including insulin initiation when non-insulin glucose-lowering medications are insufficient. Guidelines recommend combining a GLP-1 receptor agonist with basal insulin to improve glycaemic efficacy while reducing weight gain and hypoglycaemia risk. COMBINE 4 evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a GLP-1-receptor agonist) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes on oral glucose-lowering medications. METHODS: COMBINE 4 was a 40-week, randomised, open-label, treat-to-target, phase 3b trial conducted across 97 sites in nine countries. Adults (aged >/=18 years) with type 2 diabetes (HbA(1c) >/=8.0%) receiving oral glucose-lowering medications were randomly allocated in a 1:1 ratio without stratification to IcoSema or once-daily glargine U100. The titration target was 3.9-5.0 mmol/L (70-90 mg/dL). The primary endpoint was change in HbA(1c) and the secondary confirmatory endpoint was change in bodyweight, both from baseline to week 40, evaluated in all randomly allocated participants. Adverse events were recorded during weeks 0-45. This trial is registered with ClinicalTrials.gov (NCT06269107) and is complete. FINDINGS: Of 653 individuals screened between Feb 15 and Aug 6, 2024, 151 did not meet screening criteria and 17 withdrew before initiating treatment; 243 were randomised to IcoSema and 242 to glargine U100. Of the 485 randomly allocated participants, 286 (59%) were male and 199 (41%) were female, and median age was 58 years (range 26-82). For HbA(1c), from baseline (9.57% for IcoSema and 9.50% for glargine U100), mean change to week 40 was greater with IcoSema versus glargine U100 (-3.32 vs -2.44 percentage points; estimated treatment difference [ETD] -0.88 percentage points [95% CI -1.12 to -0.63]), confirming superiority of IcoSema (p<0.001). From baseline to week 40, mean bodyweight decreased with IcoSema and increased with glargine U100 (-0.79 vs 3.81 kg; ETD -4.61 kg [95% CI -5.46 to -3.75]), confirming superiority of IcoSema (p<0.001). Rate of combined clinically significant (blood glucose <3.0 mmol/L [<54 mg/dL], confirmed with a blood glucose meter) or severe hypoglycaemia (severe cognitive impairment requiring external assistance for recovery) was statistically significantly lower with IcoSema versus glargine U100 (0.29 vs 0.59 episodes per person-year of exposure; estimated rate ratio 0.56 [95% CI 0.32 to 0.97]; p=0.04). Gastrointestinal disorders were the most frequently reported adverse events with IcoSema. INTERPRETATION: Once-weekly IcoSema demonstrated superior HbA(1c) reduction and bodyweight change, with lower rates of clinically significant or severe hypoglycaemia, versus glargine U100, suggesting that IcoSema might be an effective once-weekly treatment option for insulin-naive individuals with type 2 diabetes inadequately controlled on oral glucose-lowering medications. FUNDING: Novo Nordisk. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology and Metabolism, Peking University Diabetes Centre, Peking University People's Hospital, Beijing, China. Electronic address: jiln@bjmu.edu.cn. FAU - Benamar, Malik AU - Benamar M AD - Novo Nordisk, Soborg, Denmark. FAU - Mohan, Viswanathan AU - Mohan V AD - Madras Diabetes Research Foundation (ICMR-Collaborating Centre of Excellence) and Dr Mohan's Diabetes Specialities Centre (IDF Centre of Excellence in Diabetes Care), Chennai, India. FAU - Pletsch-Borba, Laura AU - Pletsch-Borba L AD - Novo Nordisk, Soborg, Denmark. FAU - Porcellati, Francesca AU - Porcellati F AD - Department of Medicine and Surgery, University of Perugia, Perugia, Italy. FAU - Wang, Ni AU - Wang N AD - Novo Nordisk, Soborg, Denmark. FAU - Watada, Hirotaka AU - Watada H AD - Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Rea, Rosangela R AU - Rea RR AD - Internal Medicine Department, Endocrine Division (SEMPR), Universidade Federal do Parana, Curitiba, Brazil. LA - eng SI - ClinicalTrials.gov/NCT06269107 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260813 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Insulin Glargine/administration & dosage/therapeutic use MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Glycated Hemoglobin/analysis MH - Semaglutide MH - Blood Glucose/analysis MH - Drug Administration Schedule MH - Adult MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Treatment Outcome MH - Drug Therapy, Combination COIS- Declaration of interests LJ has received research support and consultant fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Gan & Lee, Haisco Pharmaceutical, Innovent Biologics, Merck, MSD, Novo Nordisk, Sanofi-Aventis, Sibionics, and Sinocare; has served on advisory panels for Haisco Pharmaceutical and received honoraria from Eli Lilly, Innovent Biologics, Novo Nordisk and Sanofi-Aventis. MB, LP-B, and NW are employees of Novo Nordisk and hold stock options. VM has acted as consultant and speaker for, and received research or educational grants from Abbott, Alembic Pharmaceuticals, Apex Pharma, Aventis, Bayer, Biocon, Boehringer Ingelheim, Cipla, Dr Reddy's, Eli Lilly, Emcure, Fourrts India, Franco Indian, Glenmark Pharmaceuticals, GSK, Intas Pharmaceuticals, Ipca Laboratories, Johnson & Johnson, LifeScan, Lupin, Mankind Pharma, Medtronic, MSD, Novartis, Novo Nordisk, Primus Pharmaceuticals, Roche, Sanofi, Servier, Sun Pharma, Torrent Pharma, USV, Wockhardt, and Zydus Lifesciences. FP has received research support or consultant and speaker fees from, or has participated on advisory panels for Abbott, AstraZeneca, Eli Lilly, Laboratori Guidotti, Novo Nordisk, Roche, and Sanofi. HW has received research support from Kowa Company, Lifescan Japan, Nippon Boehringer Ingelheim, Sanwa Kagaku Kenkyusho, SBI Pharma, Sumitomo Pharma and Taisho Pharma; and has acted as a speaker for Abbott Japan, Bayer Yakuhin, Daiichi Sankyo, Eli Lilly Japan, Embecta, GSK, Kowa Company, Kyowa Kirin, MSD, Nippon Boehringer Ingelheim, Novo Nordisk, Roche DC Japan, Sanwa Kagaku Kenkyusho, Sumitomo Pharma, Tanabe Pharma, Taisho Pharma and Teijin. RRR is an advisory board member for AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; has participated in speakers' bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, and Novo Nordisk; and has received research grants from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. EDAT- 2026/08/13 23:36 MHDA- 2026/09/08 23:35 CRDT- 2026/08/13 18:53 PHST- 2026/03/04 00:00 [received] PHST- 2026/05/29 00:00 [revised] PHST- 2026/05/29 00:00 [accepted] PHST- 2026/09/08 23:35 [medline] PHST- 2026/08/13 23:36 [pubmed] PHST- 2026/08/13 18:53 [entrez] AID - S2213-8587(26)00136-1 [pii] AID - 10.1016/S2213-8587(26)00136-1 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Oct;14(10):831-840. doi: 10.1016/S2213-8587(26)00136-1. Epub 2026 Aug 13. PMID- 42594084 OWN - NLM STAT- MEDLINE DCOM- 20260813 LR - 20260815 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 21 IP - 8 DP - 2026 TI - Gastroparesis induced by glucagon-like peptide-1 receptor agonists: A systematic review of clinical features, diagnosis, management, and outcomes. PG - e0354497 LID - 10.1371/journal.pone.0354497 [doi] LID - e0354497 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for the treatment of type 2 diabetes mellitus and obesity. Although gastrointestinal adverse effects are common, gastroparesis is an under-recognised but clinically important complication. This systematic review summarises published evidence on the presentation, diagnosis, management, and outcomes of gastroparesis associated with GLP-1RA therapy in real-world clinical practice. METHODS: A systematic review was conducted in accordance with PRISMA 2020 guidelines. PubMed, Embase, Scopus, and Web of Science were searched from inception to October 2025 for reports of symptomatic gastroparesis associated with GLP-1RA use. Eligible studies included case reports, case series, observational studies, and clinical trials involving adults treated with GLP-1RAs for diabetes or weight loss. Data extraction focused on patient characteristics, GLP-1RA exposure, clinical presentation, diagnostic findings, management strategies, and outcomes. Methodological quality was assessed using the Joanna Briggs Institute checklist for case reports. RESULTS: Twelve case reports describing 13 patients met inclusion criteria. Most patients were female and had type 2 diabetes mellitus, though cases also occurred in non-diabetic individuals. Semaglutide was the most frequently implicated agent, followed by liraglutide, dulaglutide, and exenatide. Symptom onset ranged from hours to several months after treatment initiation, commonly following dose escalation or inappropriate re-initiation. Presentations varied from acute to chronic. Reported symptoms included nausea, vomiting, abdominal pain, bloating, early satiety, and oral intolerance. Diagnostic evaluation often demonstrated gastric distension or retained gastric contents on imaging or endoscopy in the absence of mechanical obstruction. Gastric emptying scintigraphy confirms delayed emptying in selected cases. Management primarily involved supportive and symptomatic care. Discontinuation of the offending GLP-1RA led to symptom resolution in all reported patients. CONCLUSION: GLP-1 receptor agonists may induce or worsen gastroparesis in both diabetic and non-diabetic patients, particularly following rapid dose escalation or inappropriate dosing. Awareness of this association is essential for timely diagnosis and management. Withdrawal of the causative agent is central to treatment and is associated with favourable outcomes and reversibility of gastric dysfunction. Careful patient selection, gradual dose titration, and monitoring for persistent gastrointestinal symptoms are recommended to optimise the safe use of GLP-1RAs. CI - Copyright: (c) 2026 Olubodun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Olubodun, Tope AU - Olubodun T AUID- ORCID: 0000-0002-6274-5468 AD - Department of Community Medicine and Primary Care, Federal Medical Center Abeokuta, Abeokuta, Ogun State, Nigeria. FAU - Osundina, Morenike Adedoyin AU - Osundina MA AD - Department of Medicine, University of Ibadan, Ibadan, Oyo State, Nigeria. FAU - Soyoye, David Olubukunmi AU - Soyoye DO AD - Department of Medicine, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria. FAU - de Oliveira, Natalia Maria Bim AU - de Oliveira NMB AD - Ferring Pharmaceuticals, Sao Paulo, Sao Paulo, Brazil. FAU - Olubodun, Ayodeji Bamidele AU - Olubodun AB AD - Accident and Emergency Department, Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State, Nigeria. FAU - Ogundele, Oluwatoyin Olanrewaju AU - Ogundele OO AD - Nats'oojeh Hospital and Health Centre, Fort St James, British Columbia, Canada. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260813 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Gastroparesis/chemically induced/diagnosis/therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Exenatide/adverse effects MH - Female MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Liraglutide/adverse effects MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Recombinant Fusion Proteins/adverse effects MH - Male MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Treatment Outcome MH - Immunoglobulin Fc Fragments PMC - PMC13472420 COIS- The authors have declared that no competing interests exist. EDAT- 2026/08/13 21:31 MHDA- 2026/08/13 21:32 PMCR- 2026/08/13 CRDT- 2026/08/13 13:34 PHST- 2026/03/09 00:00 [received] PHST- 2026/07/08 00:00 [accepted] PHST- 2026/08/13 21:32 [medline] PHST- 2026/08/13 21:31 [pubmed] PHST- 2026/08/13 13:34 [entrez] PHST- 2026/08/13 00:00 [pmc-release] AID - PONE-D-26-11854 [pii] AID - 10.1371/journal.pone.0354497 [doi] PST - epublish SO - PLoS One. 2026 Aug 13;21(8):e0354497. doi: 10.1371/journal.pone.0354497. eCollection 2026. PMID- 42592768 OWN - NLM STAT- MEDLINE DCOM- 20260813 LR - 20260813 IS - 2245-1919 (Electronic) IS - 2245-1919 (Linking) VI - 73 IP - 7 DP - 2026 Jun 16 TI - Real-world use of oral semaglutide in adults with type 2 diabetes. LID - A06250520 [pii] LID - 10.61409/A06250520 [doi] AB - INTRODUCTION: PIONEER REAL Denmark assessed changes in HbA1c, body weight and treatment satisfaction with once-daily oral semaglutide in adults with type 2 diabetes. METHODS: In this multicentre, prospective, open-label, non-interventional study, participants initiated oral semaglutide in routine clinical practice and were followed up for 34-44 weeks. The primary endpoint was change in HbA1c from baseline to the end of study (EOS). Secondary endpoints assessed at EOS included change in body weight (BW), proportion of participants reaching HbA1c less-than 7% and treatment satisfaction using Diabetes Treatment Satisfaction Questionnaire status/change (DTSQs/DTSQc). RESULTS: In total, 96 participants from a primary care setting were included (median age: 63.5 years, HbA1c: 7.6% (60.0 mmol/mol), BW: 97.4 kg). Estimated changes from baseline to EOS in HbA1c (n = 96) and BW (n = 86) were -0.9 percentage points (9.9 mmol/mol) (95% CI: -1.20; -0.61 percentage points) and -4.4 (95% CI: -5.44; -3.41) kg, respectively. At baseline, 28.1% of participants had HbA1c less-than 7.0% (less-than 53 mmol/mol); at EOS, 66.7% of participants had HbA1c less-than 7.0% (53 mmol/mol). Improvements in treatment satisfaction were observed in DTSQs (1.9 points) and DTSQc (10.5 points) scores. No new safety signals were identified for oral semaglutide. CONCLUSIONS: In PIONEER REAL Denmark, participants treated with oral semaglutide in a primary care setting experienced reductions in HbA1c and BW. FUNDING: This study was sponsored by Novo Nordisk A/S. CLINICALTRIALS: gov (NCT04537637). CI - Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/. FAU - Roslind, Klaus AU - Roslind K AD - Aarup Health Center I/S, Aarup. FAU - Bodholdt, Ulrik AU - Bodholdt U AD - Kastruplaegerne, Kastrup. FAU - Damgaard, Tina AU - Damgaard T AD - Novo Nordisk Denmark A/S, Kobenhavn. FAU - Jensen, Christian AU - Jensen C AD - Laegehuset Remisen, Praesto, Denmark. LA - eng SI - ClinicalTrials.gov/NCT04537637 PT - Journal Article PT - Multicenter Study DEP - 20260616 PL - Denmark TA - Dan Med J JT - Danish medical journal JID - 101576205 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Semaglutide MH - Middle Aged MH - Female MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Prospective Studies MH - Administration, Oral MH - Aged MH - Patient Satisfaction MH - Denmark MH - Body Weight/drug effects MH - Treatment Outcome EDAT- 2026/08/13 12:42 MHDA- 2026/08/13 12:43 CRDT- 2026/08/13 07:37 PHST- 2026/08/13 12:43 [medline] PHST- 2026/08/13 12:42 [pubmed] PHST- 2026/08/13 07:37 [entrez] AID - A06250520 [pii] AID - 10.61409/A06250520 [doi] PST - epublish SO - Dan Med J. 2026 Jun 16;73(7):A06250520. doi: 10.61409/A06250520. PMID- 42584177 OWN - NLM STAT- MEDLINE DCOM- 20260812 LR - 20260826 IS - 1758-8111 (Electronic) IS - 1758-8103 (Print) IS - 1758-8103 (Linking) VI - 16 IP - 5 DP - 2026 Oct TI - Burden and Risk of Depression in Patients Receiving Semaglutide: A Systematic Review and Meta-Analysis. PG - e70105 LID - 10.1111/cob.70105 [doi] LID - e70105 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, are widely used for Type 2 diabetes mellitus (T2DM), obesity and related metabolic conditions. Evidence on potential neuropsychiatric effects remains inconsistent. This systematic review and meta-analysis evaluated depression risk among patients receiving semaglutide. Following PRISMA 2020 guidelines, major biomedical databases, trial registries, pharmacovigilance databases, conference abstracts and grey literature were searched from inception to January 2026. Eligible studies included randomised controlled trials, observational studies, large database analyses and pharmacovigilance disproportionality studies involving patients receiving semaglutide. Risk of bias was assessed using ROBINS-I and the Newcastle-Ottawa Scale. The pooled risk ratio for depression was 1.25 (95% CI: 0.95-1.65; I(2) = 98%). For anxiety and suicidal ideation/attempt, pooled risk ratios were 1.22 (95% CI: 0.93-1.60; I(2) = 99%) and 1.20 (95% CI: 0.90-1.62; I(2) = 92%), respectively. No statistically significant differences were observed between semaglutide and comparator/placebo groups for outcomes. Pooled estimates did not show a statistically significant increase in depression, anxiety or suicidal ideation/attempt among patients receiving semaglutide compared with comparator groups. However, the certainty of evidence was limited by substantial heterogeneity, risk of bias and reliance on heterogeneous data sources, including spontaneous-reporting studies. These findings are reassuring but should be interpreted as the absence of a detected increased risk in the available evidence, rather than definitive proof of no psychiatric risk. CI - (c) 2026 World Obesity Federation. FAU - Bhaduri, Gaurab AU - Bhaduri G AUID- ORCID: 0009-0007-4000-9287 AD - Department of Diabetes & Endocrinology, Park View Super Speciality Hospital, Kolkata, West Bengal, India. AD - Apollo Sugar Clinic, Kolkata, West Bengal, India. FAU - Roy, Shilanjan AU - Roy S AUID- ORCID: 0009-0009-4257-9982 AD - Charnock Hospital, Kolkata, West Bengal, India. FAU - Kalia, Anchin AU - Kalia A AUID- ORCID: 0000-0001-8869-9351 AD - Department of Medicine, Mahatma Gandhi Medical College and Hospital, Jaipur, Rajasthan, India. FAU - Gokalani, Rutul AU - Gokalani R AUID- ORCID: 0000-0001-8546-002X AD - AHC Diabetes Centre, Ahmedabad, Gujarat, India. FAU - Saboo, Banshi AU - Saboo B AUID- ORCID: 0000-0001-7293-8864 AD - DiaCare, Diabetes Care & Hormone Clinic, Ahmedabad, Gujarat, India. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Depression/chemically induced/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Risk Factors PMC - PMC13464048 OTO - NOTNLM OT - GLP-1RA OT - depression OT - risk factors OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2026/08/12 11:38 MHDA- 2026/08/12 11:39 PMCR- 2026/08/12 CRDT- 2026/08/12 09:24 PHST- 2026/07/16 00:00 [revised] PHST- 2026/05/27 00:00 [received] PHST- 2026/08/06 00:00 [accepted] PHST- 2026/08/12 11:39 [medline] PHST- 2026/08/12 11:38 [pubmed] PHST- 2026/08/12 09:24 [entrez] PHST- 2026/08/12 00:00 [pmc-release] AID - COB70105 [pii] AID - 10.1111/cob.70105 [doi] PST - ppublish SO - Clin Obes. 2026 Oct;16(5):e70105. doi: 10.1111/cob.70105. PMID- 42580924 OWN - NLM STAT- MEDLINE DCOM- 20261013 LR - 20261013 IS - 1532-8422 (Electronic) IS - 1053-0770 (Linking) VI - 40 IP - 11 DP - 2026 Nov TI - Advances in Cardiovascular Pharmacotherapy. IX. Protection Against Major Adverse Cardiovascular Events by Glucagon-like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus and Obesity. PG - 3749-3771 LID - S1053-0770(26)00614-2 [pii] LID - 10.1053/j.jvca.2026.07.032 [doi] AB - The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of insulinotropic peptides that replicate the effects of endogenous GLP-1 but have a prolonged duration of action. GLP-1 RAs have had a remarkably profound impact on the treatment of type 2 diabetes and obesity because they substantially improve glycemic control and produce considerable weight loss. The U.S. FDA's requirement that pharmaceutical companies establish the cardiovascular safety of new type 2 diabetes medications coincided with the development of GLP-1 RAs and mandated that trials be conducted to assure that their adverse cardiovascular effect profiles were noninferior to placebo. This FDA requirement proved to be fortuitous because many of the newly developed GLP-1 RAs were shown to cause unanticipated cardiovascular and renal protective effects, which led to their expanded use beyond patients with type 2 diabetes or obesity to those with atherosclerotic cardiovascular disease, chronic kidney disease, and heart failure with preserved ejection fraction. This first of two articles on the cardiovascular pharmacology of GLP-1 RAs briefly discusses the physiology of GLP-1, describes the discovery and development of GLP-1 RAs, examines the findings of major clinical trials and their substudies showing that GLP-1 RAs reduce major adverse cardiovascular events in patients with or at high risk for atherosclerotic cardiovascular disease and type 2 diabetes, and finally, reviews the evidence indicating that the GLP-1 RA semaglutide protects against major adverse cardiovascular events in patients with obesity and established cardiovascular disease but not type 2 diabetes. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Pagel, Paul S AU - Pagel PS AD - Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI. Electronic address: pspagel@mcw.edu. FAU - Hang, Dustin AU - Hang D AD - Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI. FAU - Freed, Julie K AU - Freed JK AD - Department of Anesthesiology, the Medical College of Wisconsin, Milwaukee, WI. FAU - Crystal, George J AU - Crystal GJ AD - Department of Anesthesiology, University of Illinois College of Medicine, Chicago, IL. LA - eng PT - Journal Article PT - Review DEP - 20260719 PL - United States TA - J Cardiothorac Vasc Anesth JT - Journal of cardiothoracic and vascular anesthesia JID - 9110208 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - *Cardiovascular Diseases/prevention & control MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Animals MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonists OT - HbA1c OT - MACE OT - incretin OT - myocardial infarction OT - obesity OT - stroke OT - type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This work was supported entirely by department funds. EDAT- 2026/08/11 23:35 MHDA- 2026/10/13 23:35 CRDT- 2026/08/11 21:56 PHST- 2026/07/15 00:00 [received] PHST- 2026/07/17 00:00 [accepted] PHST- 2026/10/13 23:35 [medline] PHST- 2026/08/11 23:35 [pubmed] PHST- 2026/08/11 21:56 [entrez] AID - S1053-0770(26)00614-2 [pii] AID - 10.1053/j.jvca.2026.07.032 [doi] PST - ppublish SO - J Cardiothorac Vasc Anesth. 2026 Nov;40(11):3749-3771. doi: 10.1053/j.jvca.2026.07.032. Epub 2026 Jul 19. PMID- 42575344 OWN - NLM STAT- MEDLINE DCOM- 20260829 LR - 20260829 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 239 DP - 2026 Sep TI - Changes in recorded background glucose-lowering therapy after initiation of a GLP-1 receptor agonist or dual GIP/GLP-1 receptor agonist in adults with type 2 diabetes. PG - 113493 LID - S0168-8227(26)00413-4 [pii] LID - 10.1016/j.diabres.2026.113493 [doi] AB - AIMS: To evaluate changes in recorded background glucose-lowering active-substance counts after initiation of a glucagon-like peptide-1 (GLP-1) or dual GIP/GLP-1 receptor agonist. METHODS: This retrospective cohort study used anonymized electronic health records from a large Polish private outpatient network. Adults with type 2 diabetes (ICD-10 E11 without E10) initiating semaglutide, liraglutide, dulaglutide, or tirzepatide, with at least one recorded baseline non-GLP-1 glucose-lowering active substance, were included. Using medication-specific dates, substances were classified as baseline (before index) or subsequently recorded (on or after index), and within-patient change as a lower count, no change, or a higher count. RESULTS: Among 3,660 patients (median age, 60 years; 53.9% women), the median recorded count rose from 1 [interquartile range, 1-2] to 2 [1-3], though the median within-patient change was 0 [0-1]. A lower count occurred in 17.2% of patients, no change in 38.8%, and a higher count in 44.0%, most frequently with dulaglutide (52.9%) and least with tirzepatide (20.4%). CONCLUSIONS: After medication-date validation, a higher count was more common than a lower count, though it occurred in fewer than half of patients. These findings describe prescription-record patterns and do not establish concomitant exposure, treatment intensity, or a causal effect. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Dziewierz, Artur AU - Dziewierz A AD - Clinical Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland; Second Department of Cardiology, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. FAU - Kulicka, Natalia AU - Kulicka N AD - Clinical Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland; Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, Krakow, Poland. FAU - Lupina, Krzysztof AU - Lupina K AD - Collegium Medicum, Jan Kochanowski University, Kielce, Poland. FAU - Maruszak, Natalia AU - Maruszak N AD - Clinical Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland. FAU - Galuszka, Aleksandra AU - Galuszka A AD - Collegium Medicum, Jan Kochanowski University, Kielce, Poland. FAU - Domienik-Karlowicz, Justyna AU - Domienik-Karlowicz J AD - Department of Internal Medicine and Cardiology, Medical University of Warsaw, Warsaw, Poland; College of Medical Sciences in Warsaw, Warsaw, Poland. FAU - Rulkiewicz, Anna AU - Rulkiewicz A AD - LUX MED Group, Warsaw, Poland. FAU - Siudak, Zbigniew AU - Siudak Z AD - Collegium Medicum, Jan Kochanowski University, Kielce, Poland; College of Medical Sciences in Warsaw, Warsaw, Poland; LUX MED Group, Warsaw, Poland. Electronic address: zbigniew.siudak@gmail.com. LA - eng PT - Journal Article DEP - 20260810 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Blood Glucose) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - Semaglutide MH - Retrospective Studies MH - Tirzepatide MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Liraglutide/therapeutic use MH - *Blood Glucose/drug effects/metabolism MH - Aged MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - *Gastric Inhibitory Polypeptide/agonists MH - *Receptors, Gastrointestinal Hormone/agonists MH - Adult OTO - NOTNLM OT - Diabetes mellitus OT - Dual GIP/GLP-1 receptor agonist OT - Glucagon-like peptide-1 receptor agonists OT - Real-world data OT - Semaglutide OT - Tirzepatide OT - Treatment patterns OT - Type 2 COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/08/11 00:35 MHDA- 2026/08/29 23:35 CRDT- 2026/08/10 19:15 PHST- 2026/06/22 00:00 [received] PHST- 2026/07/16 00:00 [revised] PHST- 2026/08/09 00:00 [accepted] PHST- 2026/08/29 23:35 [medline] PHST- 2026/08/11 00:35 [pubmed] PHST- 2026/08/10 19:15 [entrez] AID - S0168-8227(26)00413-4 [pii] AID - 10.1016/j.diabres.2026.113493 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Sep;239:113493. doi: 10.1016/j.diabres.2026.113493. Epub 2026 Aug 10. PMID- 42575111 OWN - NLM STAT- MEDLINE DCOM- 20260908 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 10 DP - 2026 Oct TI - Efficacy and safety of once-weekly semaglutide 2.4 mg in Chinese adults with overweight or obesity (STEP 12): a randomised, double-blind, placebo-controlled, multicentre, phase 3b trial. PG - 805-817 LID - S2213-8587(26)00133-6 [pii] LID - 10.1016/S2213-8587(26)00133-6 [doi] AB - BACKGROUND: Semaglutide 2.4 mg is a GLP-1 receptor agonist that reduces bodyweight, and provides other cardiometabolic benefits, among people with a BMI at least 30 kg/m(2) or at least 27 kg/m(2) and with weight-related comorbidities. This trial aimed to evaluate the efficacy, tolerability, and safety of semaglutide 2.4 mg in adults from mainland China and Taiwan with overweight or obesity according to locally defined, BMI thresholds. METHODS: This completed randomised, double-blind, placebo-controlled, multicentre, two-armed, parallel-group, phase 3b trial (STEP 12) was conducted at 19 sites across mainland China and Taiwan. Adults with a BMI of 24-<28 kg/m(2) and at least one weight-related comorbidity, or a BMI of 28-<30 kg/m(2), with or without type 2 diabetes, were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2.4 mg or placebo, plus lifestyle intervention, for 44 weeks. Randomisation was performed by the study sponsor using the Randomisation Trial Supplies Management System. Coprimary endpoints were percentage change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction. Safety was analysed descriptively in all participants who received the trial intervention. Missing data at week 44 were imputed with washout multiple imputation. This study is registered with ClinicalTrials.gov, NCT06041217, and is completed. FINDINGS: Between Sept 15, 2023, and May 7, 2025, of 254 screened participants, 161 (66.5%) of 242 participants were randomly assigned to semaglutide 2.4 mg and 81 (33.5%) to placebo; 121 (50.0%) participants were female, and 47 (19.4%) participants had type 2 diabetes. Bodyweight reduction was greater with semaglutide versus placebo (-12.1% [SE 0.6] vs -2.2% [0.8]; estimated treatment difference -9.9 percentage points [95% CI -11.8 to -8.0]; p<0.0001), with a greater proportion of participants achieving at least 5% bodyweight reduction (80.5% vs 24.4%; odds ratio [OR] 14.8 [95% CI 7.4 to 29.6]; p<0.0001). Adverse events were reported in 141 (87.6%) of 161 participants in the semaglutide 2.4 mg group and 61 (75.3%) of 81 participants in the placebo group, with gastrointestinal disorders being the most common. INTERPRETATION: Semaglutide 2.4 mg provided a superior reduction in bodyweight versus placebo in Chinese adults with overweight or obesity. The safety profile was consistent with the known profile of semaglutide. FUNDING: Novo Nordisk A/S. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Guo, Lixin AU - Guo L AD - Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: guolixin3234@bjhmoh.cn. FAU - Bao, Xiaolei AU - Bao X AD - Novo Nordisk (China) Pharmaceuticals, Beijing, China. FAU - Huang, Kuo-Chin AU - Huang KC AD - Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Kolnes, Kristoffer Jensen AU - Kolnes KJ AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Laugesen, Christian AU - Laugesen C AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lu, Yibing AU - Lu Y AD - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Luo, Bifen AU - Luo B AD - Novo Nordisk (China) Pharmaceuticals, Beijing, China; Eisai China, Beijing, China. FAU - Yuan, Guoyue AU - Yuan G AD - Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Kushner, Robert F AU - Kushner RF AD - Departments of Medicine and Medical Education, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. LA - eng SI - ClinicalTrials.gov/NCT06041217 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260810 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - Chinese people SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Mass Index MH - China/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Obesity/drug therapy MH - *Overweight/drug therapy MH - *Semaglutide/administration & dosage/adverse effects/therapeutic use MH - Treatment Outcome MH - East Asian People COIS- Declaration of interests BL was an employee of Novo Nordisk China at the time the study was performed, and is currently an employee of Eisai China. CL is an employee and shareholder of Novo Nordisk A/S. KJK is an employee and shareholder of Novo Nordisk A/S. LG reports grants or contracts from Abbott, AstraZeneca, Bayer, Dreisamtech, Eli Lilly, Hansoh, Hengrui, Hua Medicine, Huadong Medicine, Innovent, Meitekanger Tech, Novo Nordisk, Salubris, Sanofi, Synapsor, and Zense; participation on a data safety monitoring board or advisory board for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Dreisamtech, Dongbao, Eli Lilly, Gan & Lee, Hansoh, Hengrui, Huadong Medicine, Hua Medicine, Innovent, Janssen, Novartis, Novo Nordisk, Merck, Pfizer, Sanofi, Synapsor, Takeda, Zense, and 3sbio; is Chairman of the Chinese Diabetes Society, Director of the Endocrinology Society, Beijing Medical Doctor Association, Former Chairman of the Beijing Diabetes Society, and Vice Director of the Diabetes Committee of Chinese Research Hospital Association. RFK is a consultant or advisory board member for AbbVie, Antag, AstraZeneca, Boehringer Ingelheim, Currax, Eli Lilly, Novo Nordisk, Structure, Viking, and Weight Watchers. XB is an employee of Novo Nordisk China and shareholder of Novo Nordisk A/S. All other authors declare no competing interests. EDAT- 2026/08/11 00:35 MHDA- 2026/09/08 23:35 CRDT- 2026/08/10 18:52 PHST- 2026/03/12 00:00 [received] PHST- 2026/05/28 00:00 [revised] PHST- 2026/05/28 00:00 [accepted] PHST- 2026/09/08 23:35 [medline] PHST- 2026/08/11 00:35 [pubmed] PHST- 2026/08/10 18:52 [entrez] AID - S2213-8587(26)00133-6 [pii] AID - 10.1016/S2213-8587(26)00133-6 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Oct;14(10):805-817. doi: 10.1016/S2213-8587(26)00133-6. Epub 2026 Aug 10. PMID- 42570295 OWN - NLM STAT- MEDLINE DCOM- 20260808 LR - 20260816 IS - 1473-2300 (Electronic) IS - 0300-0605 (Print) IS - 0300-0605 (Linking) VI - 54 IP - 8 DP - 2026 Aug TI - Trends in glucagon-like peptide-1 receptor agonist utilization and expenditure in Croatia. PG - 3000605261470651 LID - 10.1177/03000605261470651 [doi] LID - 03000605261470651 AB - IntroductionGlucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes and obesity by improving glycemic control, promoting weight loss, and reducing cardiovascular risk. This study aimed to evaluate national trends in GLP-1 RA utilization and expenditure in Croatia between 2010 and 2024.MethodsWe conducted a nationwide, retrospective analysis using the International Medical Statistics and IQVIA pharmaceutical databases. Utilization was measured in defined daily doses per 1000 inhabitants per day, and financial expenditure was expressed in euros. Trends were contextualized within evolving clinical evidence, guideline recommendations, and healthcare reimbursement policies.ResultsTotal noninsulin antidiabetic drug consumption more than doubled between 2010 and 2024, with the use of GLP-1 RAs rising from negligible at the time of market entry to that worth 15.99 defined daily doses per 1000 inhabitants per day in 2024, representing 16.1% of total prescriptions. Expenditure on GLP-1 RAs reached 42.07 million euros in 2024, accounting for 42.7% of total noninsulin antidiabetic spending. Semaglutide emerged as the dominant agent according to both utilization and cost, followed by dulaglutide and liraglutide. Obesity-specific indications were underutilized, largely due to lack of reimbursement.ConclusionsGLP-1 RA prescribing has increased substantially in Croatia over the past decade, reflecting their growing therapeutic importance. However, economic constraints, restrictive reimbursement, and sociocultural barriers continue to limit access, particularly in obesity care. Our findings highlight the need to align reimbursement frameworks and clinical practice with emerging evidence to maximize the cardiometabolic and public health benefits of GLP-1 RAs. FAU - Belancic, Andrej AU - Belancic A AUID- ORCID: 0000-0001-7848-6600 AD - Department of Basic and Clinical Pharmacology and Toxicology, University of Rijeka, Faculty of Medicine, Croatia. RINGGOLD: 37625 FAU - Kucan Stiglic, Marta AU - Kucan Stiglic M AD - Department of Basic and Clinical Pharmacology and Toxicology, University of Rijeka, Faculty of Medicine, Croatia. RINGGOLD: 37625 FAU - Fajkic, Almir AU - Fajkic A AD - Department of Pathophysiology, Faculty of Medicine, University of Sarajevo, Bosnia and Herzegovina. RINGGOLD: 112416 FAU - Jelakovic, Ana AU - Jelakovic A AD - Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Croatia. RINGGOLD: 112594 FAU - Pecin, Ivan AU - Pecin I AD - Department of Internal Medicine, Division of Metabolic Diseases, University Hospital Center Zagreb, Croatia. RINGGOLD: 112594 FAU - Reiner, Zeljko AU - Reiner Z AD - Department of Internal Medicine, Division of Metabolic Diseases, University Hospital Center Zagreb, Croatia. RINGGOLD: 112594 FAU - Jelakovic, Bojan AU - Jelakovic B AD - Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Croatia. RINGGOLD: 112594 FAU - Vitezic, Dinko AU - Vitezic D AD - Department of Basic and Clinical Pharmacology and Toxicology, University of Rijeka, Faculty of Medicine, Croatia. RINGGOLD: 37625 LA - eng PT - Journal Article DEP - 20260808 PL - England TA - J Int Med Res JT - The Journal of international medical research JID - 0346411 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Croatia/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/economics MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/economics/epidemiology MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/economics MH - Retrospective Studies MH - *Health Expenditures/trends MH - Recombinant Fusion Proteins/therapeutic use/economics MH - Immunoglobulin Fc Fragments/therapeutic use/economics MH - *Obesity/drug therapy/economics MH - Liraglutide/therapeutic use/economics MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC13474226 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - obesity OT - pharmacoepidemiology OT - type 2 diabetes EDAT- 2026/08/08 23:10 MHDA- 2026/08/08 23:11 PMCR- 2026/08/08 CRDT- 2026/08/08 13:53 PHST- 2026/08/08 23:11 [medline] PHST- 2026/08/08 23:10 [pubmed] PHST- 2026/08/08 13:53 [entrez] PHST- 2026/08/08 00:00 [pmc-release] AID - 10.1177_03000605261470651 [pii] AID - 10.1177/03000605261470651 [doi] PST - ppublish SO - J Int Med Res. 2026 Aug;54(8):3000605261470651. doi: 10.1177/03000605261470651. Epub 2026 Aug 8. PMID- 42568490 OWN - NLM STAT- MEDLINE DCOM- 20260808 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Incretin analogues as cardiovascular agents: a state-of-the-art review. PG - 1898812 LID - 10.3389/fendo.2026.1898812 [doi] LID - 1898812 AB - Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist tirzepatide have evolved over the past decade from glucose-lowering antidiabetic agents into a cardiovascular drug class with proven outcome benefit across multiple clinical scenarios. This state-of-the-art review synthesizes the cardiovascular evidence base for incretin analogues, organized by clinical scenario, and addresses the structural challenges that constrain their deployment in low- and middle-income countries (LMICs). We review the pharmacology and proposed cardiovascular mechanisms, including direct effects on the vascular endothelium, macrophage inflammation, and epicardial adipose tissue, alongside indirect benefits mediated by weight loss, glycemic control, and blood pressure reduction. We summarize the evidence in five clinical scenarios: type 2 diabetes with established atherosclerotic cardiovascular disease or high cardiovascular risk; overweight or obesity with established cardiovascular disease but without diabetes; obesity-related heart failure with preserved ejection fraction; chronic kidney disease; and symptomatic peripheral artery disease. Pipeline agents (retatrutide, CagriSema, survodutide, orforglipron, zenagamtide, and MariTide) are reviewed alongside their ongoing cardiovascular outcome trials. A dedicated section examines the global access perspective, including the disproportionately high burden of cardiometabolic disease in LMICs, the limited representation of regional populations in pivotal trials, and the structural barriers of cost and reimbursement that constrain access. We close with a practical algorithm for the clinician, an honest assessment of evidence gaps, and a calibrated outlook on the next generation of incretin-based cardiovascular therapy. CI - Copyright (c) 2026 Araiza-Garaygordobil, Rico-Fontalvo, Hernandez-Balbuena, Vinay-Coro and Gonzalez-Arias. FAU - Araiza-Garaygordobil, Diego AU - Araiza-Garaygordobil D AD - Departamento de Urgencias y Unidad Coronaria, Instituto Nacional de Cardiologia Ignacio Chavez, Tlalpan, Ciudad de Mexico, Mexico. AD - Division de Estudios de Posgrado, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Coyoacan, Ciudad de Mexico, Mexico. FAU - Rico-Fontalvo, Jorge AU - Rico-Fontalvo J AD - Comite de Rinon, diabetes y metabolismo, Asociacion Colombiana de Nefrologia e HTA, Bogota, Colombia. AD - Department of Nephrology, Nephromedicall Health Services Provider Institution (IPS), Medellin, Colombia. FAU - Hernandez-Balbuena, Betsabe AU - Hernandez-Balbuena B AD - Departamento de Urgencias y Unidad Coronaria, Instituto Nacional de Cardiologia Ignacio Chavez, Tlalpan, Ciudad de Mexico, Mexico. FAU - Vinay-Coro, Monica AU - Vinay-Coro M AD - Departamento de Urgencias y Unidad Coronaria, Instituto Nacional de Cardiologia Ignacio Chavez, Tlalpan, Ciudad de Mexico, Mexico. FAU - Gonzalez-Arias, Mauricio AU - Gonzalez-Arias M AD - Department of Endocrinology, Hospital Center, New York, NY, United States. LA - eng PT - Journal Article PT - Review DEP - 20260724 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Incretins) RN - 0 (Cardiovascular Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Cardiovascular Diseases/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Agents/therapeutic use/pharmacology MH - Animals MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13447287 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular outcomes OT - heart failure with preserved ejection fraction OT - low- and middle-income countries OT - obesity OT - semaglutide OT - tirzepatide OT - type 2 diabetes mellitus COIS- DA-G has received speaking fees from Novo Nordisk, AstraZeneca, Novartis, Bayer, Adium, Boehringer-Ingelheim, Servier, and Silanes, and declares active research grants with Novo Nordisk, Eli Lilly, Boehringer Ingelheim, and Bayer. JR-F has received speaking fees from Novo Nordisk, AstraZeneca, Eli Lilly, Bayer, Sanofi, Boehringer-Ingelheim, Merck, and MSD. The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/08/08 12:52 MHDA- 2026/08/08 12:53 PMCR- 2026/07/24 CRDT- 2026/08/08 05:08 PHST- 2026/06/03 00:00 [received] PHST- 2026/07/06 00:00 [revised] PHST- 2026/07/08 00:00 [accepted] PHST- 2026/08/08 12:53 [medline] PHST- 2026/08/08 12:52 [pubmed] PHST- 2026/08/08 05:08 [entrez] PHST- 2026/07/24 00:00 [pmc-release] AID - 10.3389/fendo.2026.1898812 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jul 24;17:1898812. doi: 10.3389/fendo.2026.1898812. eCollection 2026. PMID- 42567173 OWN - NLM STAT- MEDLINE DCOM- 20260908 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 10 DP - 2026 Oct TI - Effect of semaglutide on kidney outcomes in the SELECT, FLOW, and SOUL trials: a prespecified pooled analysis. PG - 818-830 LID - S2213-8587(26)00134-8 [pii] LID - 10.1016/S2213-8587(26)00134-8 [doi] AB - BACKGROUND: The GLP-1 receptor agonist semaglutide reduces clinically important kidney outcomes in people with type 2 diabetes and chronic kidney disease (CKD). We aimed to assess the pooled effects of semaglutide on kidney outcomes in prespecified analyses of participant-level data from the diverse populations of the SELECT, FLOW, and SOUL randomised placebo-controlled trials. METHODS: Participants with CKD (FLOW) or atherosclerotic cardiovascular disease (SELECT and SOUL) were randomly assigned semaglutide (once-weekly subcutaneous 1.0 mg [FLOW], once-weekly subcutaneous 2.4 mg [SELECT], or once-daily oral 14 mg [SOUL]) or matching placebo, added to standard of care. The primary outcome in this pooled analysis was time to first occurrence of a kidney composite, defined as onset of persistent 50% or greater reduction in estimated glomerular filtration rate (eGFR), kidney failure (persistent eGFR <15 mL/min per 1.73 m(2), or initiation of kidney replacement therapy), kidney-related death, or cardiovascular-related death. Safety was also assessed. FINDINGS: The pooled participants from the trials (N=30 787) had a mean follow-up of 39.5-47.5 months. Among participants assigned to semaglutide, 973 first events of the primary kidney composite occurred compared with 1134 first events for placebo (hazard ratio [HR] 0.84 [95% CI 0.77-0.91]). First events of a narrower secondary kidney composite (excluding cardiovascular-related death from the primary outcome) were also reduced with semaglutide versus placebo (347 and 416, respectively; 0.80 [0.69-0.92]). Safety outcomes were overall similar between groups, and in line with other GLP-1 receptor agonist trials. Serious adverse events were numberically lower with semaglutide than with placebo. INTERPRETATION: Data pooled from three large phase 3 trials suggest that semaglutide reduces the risk of major kidney outcomes in a broad population with cardio-kidney-metabolic disease while having a favourable risk-benefit profile. In people with cardio-kidney-metabolic disease, with and without diabetes, semaglutide (oral or injected) prevents kidney-related and cardiovascular complications and induces adverse events in line with GLP-1 receptor agonist studies, regardless of baseline characteristics within the cardio-kidney-metabolic spectrum. This was a participant-level analysis conducted in a large database of three randomised controlled trials of similar design and examining the same treatment, but there were some differences in participants' baseline characteristics, and in the dose and route of administration of treatment. This pooled analysis adds evidence for the benefit of GLP-1 receptor agonists in general, and semaglutide in particular, in a broad population of people with cardio-kidney-metabolic disease, suggesting that the benefit of semaglutide might not be explained only by its glycaemic effects, weight-management effects, or both. FUNDING: Novo Nordisk. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Center, Munich, Germany. Electronic address: johannes.mann@kms.mhn.de. FAU - Badve, Sunil V AU - Badve SV AD - Renal and Metabolic Division, The George Institute for Global Health, Sydney, NSW, Australia; Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. FAU - Baeres, Florian M M AU - Baeres FMM AD - Novo Nordisk, Soborg, Denmark. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk, Soborg, Denmark. FAU - Brown-Frandsen, Kirstine AU - Brown-Frandsen K AD - Novo Nordisk, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill, NC, USA. FAU - Colhoun, Helen M AU - Colhoun HM AD - Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK. FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Science, University College London, London, UK. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk, Soborg, Denmark. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk, Soborg, Denmark. FAU - Lincoff, A Michael AU - Lincoff AM AD - Department of Cardiovascular Medicine, Cleveland Clinic and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA, USA. FAU - McGuire, Darren K AU - McGuire DK AD - Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Health System, Dallas, TX, USA. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk, Soborg, Denmark. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Sattar, Naveed AU - Sattar N AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Division of Nephrology, University of Washington, Seattle, WA, USA; Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA. FAU - Perkovic, Vlado AU - Perkovic V AD - Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260807 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - *Renal Insufficiency, Chronic/drug therapy MH - Glomerular Filtration Rate/drug effects MH - Middle Aged MH - Aged MH - *Kidney/drug effects MH - Treatment Outcome COIS- Declaration of interests JFEM declares grants from Novo Nordisk; consulting fees from Bayer and Novo Nordisk; honoraria from AstraZeneca, Bayer, Cytel, Hexal, ICON, IQVIA, Novo Nordisk, UpToDate, and WCG; has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, and Sanofi; and has a leadership role in the KDIGO group. SVB declares consulting fees from AstraZeneca, Bayer, GSK, and Vifor Pharma; speaking fees from AstraZeneca, Bayer, Pfizer, and Vifor Pharma (all honoraria paid to institution); and non-financial research support from Bayer. KB-F, TI, and GKH are former employees of Novo Nordisk. JBB declares salary support from clinical trial contracts to his employer from Corcept Therapeutics, Dexcom, GentiBio, and Novo Nordisk; is a consultant with personal compensation from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, Aqua Medical, AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, General Medicines, GentiBio, Insulet, Kayothera, Metsera, MiniMed, Novo Nordisk, Recordati, Sparrow Pharmaceuticals, Tandem, Vertex, vTv Therapeutics, and Zealand Pharma; and holds stock options in Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. HMC declares consulting fees from Roche and Sanofi; serving on advisory panels for Bayer and Novo Nordisk; research grants from Chief Scientist Office, Diabetes UK, European Commission, IQVIA, Breakthrough T1D, Medical Research Council, and Sanofi; support to attend meetings/travel from Novo Nordisk; and payment or honoraria from Medscape. JED declares consulting fees from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda; payment or honoraria from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda; and a research grant from Alzheimer's Research UK. AML declares consulting honoraria from Akebia, Alnylam, Amgen, Ardelyx, Becton Dickinson, BrainStorm Cell Therapeutics, Canary Cure, Eli Lilly, Endologix, FibroGen, GSK, Intarcia, Medtronic, Neovasc, Novo Nordisk, Provention Bio, and Recor; and research funding (to institution) from AbbVie, AstraZeneca, CSL Behring, Eli Lilly, Esperion, and Novartis. IL declares research funding (paid to institution) and trial product related to investigator initiated studies from Novo Nordisk; clinical trial work for Boehringer Ingelheim, Dexcom, Eli Lilly, Novo Nordisk, Pfizer, and Roche; research-related consulting fees (paid to institution) from Novo Nordisk; and travel and publication support from AbbVie, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, AstraZeneca, Bain Capital, Bayer, Betagenon, BIOIO, Biomea Fusion, Boehringer Ingelheim, Carmot Therapeutics, Corxel, Cytoki Pharma, Eli Lilly, Genentech, Intercept, Janssen/Johnson & Johnson, Juvena, Keros Therapeutics, Mediflix, Merck, Metsera, Neurocrine, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi, Shionogi, Source Bioscience, Structure Therapeutics, TERNS Pharma, The Comm Group, Verdiva Bio, WebMD, and Zealand Pharma. KWM declares grants from the American College of Cardiology, American Heart Association, Apple, California Institute for Regenerative Medicine, CSL Behring, Cytokinetics, Eidos, Element, Google (Verily), Idorsia, Johnson & Johnson, Novartis, PAC-12, Precordior, and St Jude Medical; consulting fees from Applied Therapeutics, BridgeBio, Bristol Myers Squibb, Eli Lilly, Elsevier, Fosun Pharma, Human, Moderna, MyoKardia, Novo Nordisk, PhaseBio, Quidel, Scleroderma Foundation, and Theravance; payment or honoraria from CSL Behring; and equity in Human, Medeloop, Precordior, and Regencor. DKM declares consulting fees from Alveus Therapeutics, Amgen, Boehringer Ingelheim, F Hoffmann La Roche, Eli Lilly, Kailera, Lexicon, Metsera, Neurotronic, Novo Nordisk, Regor, and Zealand Pharma; trial leadership for Amgen, Boehringer Ingelheim, Eli Lilly, Metsera, NewAmsterdam Pharma, Novartis, Novo Nordisk, and Pfizer; and research support from Amgen, Boehringer Ingelheim, Eli Lilly, Metsera, NewAmsterdam Pharma, Novartis, Novo Nordisk, and Pfizer. REP declares speaker fees from Corcept Therapeutics, Lilly USA, and Novo Nordisk; consulting fees from AbbVie, Altanine, AstraZeneca, Bayer, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui, Intas Pharmaceuticals, Lilly USA, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock, and Sun Pharmaceutical Industries; and investigator-initiated grant support from Carmot Therapeutics, Dompe, Endogenex, Fractyl, Eli Lilly, Novo Nordisk, Roche, and Sanofi. PR declares consultancy and/or speaking fees (paid to institution) from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Novo Nordisk, and Sanofi; research grants from AstraZeneca, Bayer, and Novo Nordisk; and study drugs for investigator-initiated studies from Bayer, Novo Nordisk, and Lexicon Pharmaceuticals. NS declares consulting fees and/or speaker honoraria from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gan & Lee, GSK, Hanmi Pharmaceutical, Kailera, Mass Medicines, Menarini Ricerche, Metsera, Novo Nordisk, Pfizer, Regeneron, Roche, UCB Pharma, and Verdiva Bio; grant support (paid to institution) from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche outside the submitted work; and is Chair of the Obesity Healthcare Programme at the UK Government Office for Life Sciences. KRT declares grants (paid to institution) from Bayer, Otsuka, Travere Therapeutics, US National Institute of Diabetes and Digestive and Kidney Diseases, US National Heart, Lung, and Blood Institute, US National Institute on Minority Health and Health Disparities, US National Center for Advancing Translational Sciences, US National Institutes of Health Director's Office, US Centers for Disease Control and Prevention, Doris Duke Foundation, Benaroya Research Institute, and Breakthrough T1D; consulting fees and/or honoraria for lectures, presentations, speakers bureaus, and educational events from Alnylam, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GSK, Novo Nordisk, Otsuka, Roche, and Travere Therapeutics; provides unpaid participation as the Data Safety and Monitoring Board Chair for the George Clinical Institute and US National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health; and is Chair for the Diabetic Kidney Disease Collaborative for the American Society of Nephrology. VP declares consultancy or honoraria for steering committee, data monitoring committee, or advisory board roles from AstraZeneca, Bayer, Biogen, Boehringer Ingelheim, Chinook, GSK, Guard Therapeutics, Incyte, Janssen, Mineralys, Novo Nordisk, Novartis, Otsuka, Shaanxi Micot, Travere Therapeutics, Tricida, and Vifor Pharma; is a board member of Kidney Health Australia and St Vincent's Health Australia; and declares an ownership interest in George Clinical. FMMB, NB, MDME, and SR are employees and stockholders of Novo Nordisk. EDAT- 2026/08/08 00:37 MHDA- 2026/09/08 23:35 CRDT- 2026/08/07 18:52 PHST- 2026/01/21 00:00 [received] PHST- 2026/05/28 00:00 [revised] PHST- 2026/05/28 00:00 [accepted] PHST- 2026/09/08 23:35 [medline] PHST- 2026/08/08 00:37 [pubmed] PHST- 2026/08/07 18:52 [entrez] AID - S2213-8587(26)00134-8 [pii] AID - 10.1016/S2213-8587(26)00134-8 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Oct;14(10):818-830. doi: 10.1016/S2213-8587(26)00134-8. Epub 2026 Aug 7. PMID- 42557064 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260914 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Efficacy and Hypoglycaemia Outcomes With Once-Weekly IcoSema Versus Comparators in Individuals With Type 2 Diabetes by Kidney and Liver Function: A Post Hoc Analysis of the COMBINE 1-3 Trials. PG - 9607-9620 LID - 10.1111/dom.70895 [doi] AB - AIMS: This post hoc analysis of COMBINE 1-3 assessed efficacy and hypoglycaemia outcomes with IcoSema (once-weekly combination therapy of basal insulin icodec and semaglutide [a glucagon-like peptide-1 analogue]) versus comparators in adults with type 2 diabetes (T2D) by kidney and liver function subgroups. MATERIALS AND METHODS: Treatment outcomes were analysed by trial according to kidney (estimated glomerular filtration rate >/= 90; 60-< 90; 30-< 60; < 30 mL/min/1.73 m(2)) and liver (total bilirubin 21 mumol/L or AST > 31/> 37 [female/male] U/L) function subgroups. RESULTS: In COMBINE 1-3, across kidney and liver function subgroups, there were no statistically significant treatment by subgroup interactions for change in glycated haemoglobin (HbA1c) (baseline to week 52), change in body weight (baseline to week 52) or rates of combined clinically significant or severe hypoglycaemia (not assessed by kidney function for COMBINE 2) (all p > 0.05). There were statistically significant treatment by kidney function subgroup interactions for the achievement of HbA1c < 7.0% without weight gain and without clinically significant or severe hypoglycaemia in COMBINE 3 (p < 0.05) but not COMBINE 1 or 2, and statistically significant treatment by liver function subgroup interactions in COMBINE 1 (p < 0.05) but not COMBINE 2 or 3. For COMBINE 1 and 3, there were statistically significant treatment by kidney function subgroup interactions for mean weekly total insulin dose, but not statistically significant treatment by liver function subgroup interactions. CONCLUSIONS: Efficacy and hypoglycaemia outcomes with IcoSema versus comparators were generally consistent among adults with T2D with mild to moderate kidney impairment or impaired liver function. TRIAL REGISTRATION: The COMBINE 1-3 trials were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT05352815; NCT05259033; NCT05013229). CI - (c) 2026 Novo Nordisk A/S and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0003-1305-1598 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Andersen, Jonas Dahl AU - Andersen JD AUID- ORCID: 0000-0001-6619-9161 AD - Novo Nordisk A/S, Aalborg, Denmark. FAU - Benamar, Malik AU - Benamar M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ponzani, Paola AU - Ponzani P AD - SSD Diabetology and Metabolic Diseases, Azienda Sanitaria Locale, Genoa, Italy. FAU - Unnikrishnan, A G AU - Unnikrishnan AG AD - Chellaram Diabetes Institute, Pune, India. FAU - Vinther, Siri AU - Vinther S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rea, Rosangela AU - Rea R AD - Internal Medicine Department, Endocrine Division (SEMPR), Universidade Federal Do Parana, Curitiba, Brazil. LA - eng SI - ClinicalTrials.gov/NCT05013229 SI - ClinicalTrials.gov/NCT05352815 SI - ClinicalTrials.gov/NCT05259033 GR - Novo Nordisk A/S/ PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial DEP - 20260805 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood/physiopathology MH - *Hypoglycemia/chemically induced/epidemiology MH - Female MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Male MH - Semaglutide MH - Treatment Outcome MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Liver/physiopathology/drug effects MH - Glycated Hemoglobin/analysis MH - Kidney/physiopathology/drug effects MH - Aged MH - Drug Therapy, Combination MH - Glomerular Filtration Rate MH - Insulin/administration & dosage/adverse effects MH - Blood Glucose MH - Liver Function Tests MH - Drug Administration Schedule PMC - PMC13538793 OTO - NOTNLM OT - GLP-1 analogue OT - basal insulin OT - fixed-ratio combination OT - glycaemic control OT - hypoglycaemia OT - type 2 diabetes COIS- L.J. reports receiving consulting or speaking fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Gan & Lee Pharmaceuticals, Innovent Biologics, Merck, MSD, Novo Nordisk, Sanofi-Aventis, Sibionics and Sinocare; and is an Independent Director of Shanghai Benemae Pharmaceutical Corporation. J.D.A., M.B. and S.V. are employees and shareholders of Novo Nordisk A/S. P.P. reports fees for consultancy services and advisory boards for Eli Lilly, Novo Nordisk, Roche Diabetes Care and Sanofi; reports speaker fees for AstraZeneca, Eli Lilly, Laboratori Guidotti, MSD and Sanofi; and received research support from AstraZeneca, Bayer, Novartis and Novo Nordisk. A.G.U. has received research support, received consultant fees or has served on advisory panels for Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Servier. R.R. is a formal adviser for Boehringer Ingelheim, Eli Lily, Novo Nordisk and Sanofi; reports research activities with AstraZeneca, Boehringer Ingelheim, Eli Lily, Novo Nordisk and Sanofi; and has participated in a speaker's bureau for AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lily and Novo Nordisk. EDAT- 2026/08/06 11:36 MHDA- 2026/09/03 05:37 PMCR- 2026/09/03 CRDT- 2026/08/05 21:42 PHST- 2026/05/11 00:00 [revised] PHST- 2026/01/19 00:00 [received] PHST- 2026/05/11 00:00 [accepted] PHST- 2026/09/03 05:37 [medline] PHST- 2026/08/06 11:36 [pubmed] PHST- 2026/08/05 21:42 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM70895 [pii] AID - 10.1111/dom.70895 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):9607-9620. doi: 10.1111/dom.70895. Epub 2026 Aug 5. PMID- 42556625 OWN - NLM STAT- MEDLINE DCOM- 20260825 LR - 20260825 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 231 DP - 2026 Sep TI - The role of GLP-1 and GIP receptor agonists in the treatment of diabetes and obesity. PG - 108365 LID - S1043-6618(26)00280-X [pii] LID - 10.1016/j.phrs.2026.108365 [doi] AB - Owing to the therapeutic success of glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonists in the management of diabetes and obesity, the pharmacology of these drugs and their receptors has engendered considerable interest. GLP-1 and GIP are incretin hormones so named owing to their ability to increase insulin secretion. Currently FDA-approved GLP-1 peptide receptor agonists used for the management of diabetes include liraglutide, semaglutide, and injectable dulaglutide. Agonists approved for the management of obesity include liraglutide and semaglutide, which have injectable and oral formulations. Tirzepatide is a combined GLP-1 and GIP receptor peptide agonist given by injections that is FDA-approved for the management of type 2 diabetes, obesity, and obese patients with a weight-related comorbidity such as obstructive sleep apnea. Orforglipron is a small molecule orally bioavailable medicine that is approved for the treatment of obesity. Retatrutide is an injectable peptide agonist of GLP-1R, GIPR, and the glucagon receptor that is undergoing clinical trials for the management of obesity and diabetes. The peptides per se undergo rapid degradation in the body. To overcome the need for frequent injections, molecular engineering strategies were used to prolong circulating half-lives. Peptide fatty acid acylation represents one strategy for extending the half-life of peptides by co-opting the role of albumin as a fatty acid transporter thereby retaining peptides in the systemic circulation. A universal side effect of all GLP-1 receptor agonists includes nausea and vomiting. Consequently, the dosage is escalated sequentially over a period of weeks to mitigate these side effects. CI - Copyright (c) 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Roskoski, Robert Jr AU - Roskoski R Jr AD - Blue Ridge Institute for Medical Research, 221 Haywood Knolls Drive, Hendersonville, NC 28791, United States. Electronic address: rrj@brimr.org. LA - eng PT - Journal Article PT - Review DEP - 20260806 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - Animals MH - *Obesity/drug therapy/metabolism MH - *Receptors, Gastrointestinal Hormone/agonists/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Semaglutide MH - Tirzepatide OTO - NOTNLM OT - Dulaglutide (PubMed CID: 171042928) OT - Fasting plasma glucose OT - G-protein coupled receptors OT - Hemoglobin A(1C) OT - Incretin OT - Insulin Glargine (PubMed CID: 118984454) OT - Insulin degludec (PubMed CID: 118984462) OT - Liraglutide (PubMed CID: 16134956) OT - Lixisenatide (PubMed CID: 90472060) OT - Metformin (PubMed CID: 4091) OT - Orforglipron (PubMed CID: 137319706) OT - Peptide-GLP-1 receptor interaction OT - Prescription drug expenditures OT - Retatrutide (PubMed CID: 178245957) OT - Semaglutide (PubMed CID: 56843331) OT - Tirzepatide (PubMed CID: 166567236) COIS- Declaration of Competing Interest The author is unaware of any affiliations, memberships, or financial holdings that might be perceived as affecting the objectivity of this article. EDAT- 2026/08/06 11:36 MHDA- 2026/08/25 23:33 CRDT- 2026/08/05 19:19 PHST- 2026/07/27 00:00 [received] PHST- 2026/08/03 00:00 [accepted] PHST- 2026/08/25 23:33 [medline] PHST- 2026/08/06 11:36 [pubmed] PHST- 2026/08/05 19:19 [entrez] AID - S1043-6618(26)00280-X [pii] AID - 10.1016/j.phrs.2026.108365 [doi] PST - ppublish SO - Pharmacol Res. 2026 Sep;231:108365. doi: 10.1016/j.phrs.2026.108365. Epub 2026 Aug 6. PMID- 42552642 OWN - NLM STAT- MEDLINE DCOM- 20260805 LR - 20260813 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 5 DP - 2026 Sep TI - Effects of Oral Semaglutide on Dietary Intake and Body Composition in Japanese People With Type 2 Diabetes: A Prospective Observational Study in Clinical Practice. PG - e70295 LID - 10.1002/edm2.70295 [doi] LID - e70295 AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists are effective glucose-lowering agents with established benefits on body weight and cardiometabolic outcomes. However, their precise effects on body composition and dietary intake patterns, including food group consumption and macronutrient energy distribution, particularly in clinical settings, remain incompletely understood. METHODS: In this prospective observational study, we enrolled Japanese adults with Type 2 diabetes who were newly initiated on oral semaglutide treatment. Dietary intake patterns were assessed using a food frequency questionnaire, and body composition was assessed by bioelectrical impedance analysis. Handgrip strength and laboratory parameters were also evaluated. All parameters were assessed at both baseline (before the start of semaglutide treatment) and at a 3-month follow-up visit. RESULTS: A total of 25 participants were included in the final analysis. After 3 months of oral semaglutide treatment, significant reductions in HbA1c levels and body weight were noted. Significant reductions in the percent body fat and significant increases in the percent muscle mass were also observed. No significant change was observed in the handgrip strength. While the total energy intake decreased significantly after 3 months of semaglutide treatment, the macronutrient energy distribution remained unchanged. Analysis by food groups revealed significant reductions in the intakes of fats and oils, seasonings and spices, and sweets and snacks. Notably, the daily salt intake also decreased significantly from 8.9 to 7.0 g/day. CONCLUSIONS: Oral semaglutide treatment was associated with reductions in the total energy intake and percent body fat, without significant changes in the macronutrient energy distribution or handgrip strength. Salt intake was also significantly reduced, suggesting potential clinical benefits of this treatment in the management of diabetes and related comorbidities. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Sawada, Mika AU - Sawada M AUID- ORCID: 0000-0002-5084-723X AD - Department of Clinical Nutrition Therapy, The University of Tokyo, Tokyo, Japan. FAU - Nakanishi, Naoko AU - Nakanishi N AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Aihara, Masakazu AU - Aihara M AUID- ORCID: 0009-0009-9555-8624 AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Ohkuma, Kanako AU - Ohkuma K AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Hamano, Shoko AU - Hamano S AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Sakurai, Yoshitaka AU - Sakurai Y AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Sekine, Rie AU - Sekine R AD - Department of Clinical Nutrition Therapy, The University of Tokyo, Tokyo, Japan. FAU - Usami, Satoshi AU - Usami S AD - Graduate School of Education, The University of Tokyo, Tokyo, Japan. FAU - Yamauchi, Toshimasa AU - Yamauchi T AUID- ORCID: 0000-0003-4827-6404 AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Kubota, Naoto AU - Kubota N AUID- ORCID: 0000-0002-3336-2767 AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Kumamoto, Japan. LA - eng PT - Journal Article PT - Observational Study PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Body Composition/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Eating/drug effects MH - Energy Intake/drug effects MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - Hand Strength MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Japan MH - Prospective Studies MH - Semaglutide PMC - PMC13437943 OTO - NOTNLM OT - body composition OT - food intake OT - glucagon-like peptide-1 receptor agonists (GLP-1 RAs) COIS- The authors declare no conflicts of interest. EDAT- 2026/08/05 06:42 MHDA- 2026/08/05 06:43 PMCR- 2026/08/04 CRDT- 2026/08/05 00:53 PHST- 2026/07/10 00:00 [revised] PHST- 2026/02/23 00:00 [received] PHST- 2026/07/16 00:00 [accepted] PHST- 2026/08/05 06:43 [medline] PHST- 2026/08/05 06:42 [pubmed] PHST- 2026/08/05 00:53 [entrez] PHST- 2026/08/04 00:00 [pmc-release] AID - EDM270295 [pii] AID - 10.1002/edm2.70295 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 Sep;9(5):e70295. doi: 10.1002/edm2.70295. PMID- 42545324 OWN - NLM STAT- MEDLINE DCOM- 20260803 LR - 20261005 IS - 2308-1430 (Electronic) IS - 0375-9660 (Print) IS - 0375-9660 (Linking) VI - 72 IP - 3 DP - 2026 Jul 22 TI - Semaglutide-Induced Sarcopenia via GLP-1R-mTOR-Satellite Cells Axis and Muscle-Glucose Feedback Loop Potentially Leading to Refractory Hyperglycemia in Type 2 Diabetes: A Case-Driven Hypothesis. PG - 60-65 LID - 10.14341/probl13660 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide have transformed type 2 diabetes mellitus (T2DM) management, yet emerging concerns highlight potential risks of accelerated sarcopenia and subsequent metabolic disruptions. This case-driven hypothesis explores a 53-year-old male with T2DM diagnosed in 2014, who experienced progressive glycemic failure despite standard therapies, including metformin, glipizide, sitagliptin, and empagliflozin. Transition to dulaglutide 1.5 mg for 1.5 years followed by semaglutide (titrated from 0.25 to 1 mg weekly starting September 2024) resulted in weight loss from 84 kg to 70 kg by September 2025, accompanied by sarcopenic symptoms (muscle weakness, reduced mobility) and refractory hyperglycemia (fasting glucose 300 mg/dL, HbA1c 9%), persisting post-discontinuation on September 1, 2025, despite metformin and empagliflozin. We posit that semaglutide may precipitate acute sarcopenia via unexpected GLP-1R-mTOR-satellite cells axis crosstalk, disrupting AMPK-mTOR balance to suppress anabolic mTORC1/IGF-1 signaling (potentially by 25-35%) while enhancing catabolic FOXO/ubiquitin-proteasome and excessive autophagy pathways. This could extend to myokine reprogramming (elevated myostatin/GDF15, reduced irisin/IL-15), glucagon/alpha-cell compensation inducing hyperglucagonemia (15-25% rise), microbiome-bile acid shifts fostering low-grade inflammation (IL-6/TNF-alpha upregulation by 10-15%), mitochondrial mass reduction (20-25% via AMPK), and NMJ disassembly, collectively impairing muscle as the primary glucose sink (reducing GLUT4-mediated uptake by 35-45%) and initiating a <> with hepatic gluconeogenesis amplification, yielding treatment-resistant hyperglycemia.Supporting evidence from cohorts (e.g., 24-month study showing ASMI/grip strength declines in 432 patients), longitudinal analyses (NMJ degradation with CAF22/NfL elevations in 141 men), secondary trials (9.3% psoas volume loss in 51 MASLD cases), and case reports (fatigue in a 74-year-old, rhabdomyolysis in a 47-year-old) aligns with this framework, as does in vitro data linking GLP-1 excess to kinesin-1/GLUT4 inhibition and ATP depletion (20-30%). This novel hypothesis underscores sarcopenia's role in GLP-1RA-induced metabolic paradoxes, urging prospective studies on muscle-preserving interventions like resistance training or GLP-1R modulators to refine T2DM paradigms and inspire multidisciplinary research into endocrine-muscle interactions. FAU - Ahmed, Amr AU - Ahmed A AD - The Public Health Department, Riyadh First Health Cluster, Ministry of Health. FAU - Rodini, Sharifa AU - Rodini S AD - Nurse Technician, Ministry of Health. FAU - Alrubyea, Fahad AU - Alrubyea F AD - Public Health Specialist, The Public Health Department, Riyadh First Health Cluster, Ministry of Health. FAU - Akl, Maher AU - Akl M AD - National Research Lobachevsky State University of Nizhny Novgorod. LA - eng PT - Case Reports PT - Journal Article DEP - 20260722 PL - Russia (Federation) TA - Probl Endokrinol (Mosk) JT - Problemy endokrinologii JID - 0140673 RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - IY9XDZ35W2 (Glucose) RN - 0 (Hypoglycemic Agents) RN - EC 2.7.1.1 (MTOR protein, human) RN - 53AXN4NNHX (Semaglutide) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptides/adverse effects MH - Glucose/metabolism MH - *Hyperglycemia/metabolism/chemically induced MH - *Hypoglycemic Agents/adverse effects MH - Muscle, Skeletal/metabolism MH - *Sarcopenia/chemically induced/metabolism MH - Satellite Cells, Skeletal Muscle/metabolism/drug effects MH - Semaglutide MH - TOR Serine-Threonine Kinases/metabolism MH - Aged PMC - PMC13474366 COIS- The authors declare that there are no conflicts of interest present. EDAT- 2026/08/03 12:42 MHDA- 2026/08/03 12:43 PMCR- 2026/07/22 CRDT- 2026/08/03 10:52 PHST- 2025/09/16 00:00 [received] PHST- 2025/10/19 00:00 [accepted] PHST- 2026/08/03 12:43 [medline] PHST- 2026/08/03 12:42 [pubmed] PHST- 2026/08/03 10:52 [entrez] PHST- 2026/07/22 00:00 [pmc-release] AID - 10.14341/probl13660 [doi] PST - epublish SO - Probl Endokrinol (Mosk). 2026 Jul 22;72(3):60-65. doi: 10.14341/probl13660. PMID- 42543940 OWN - NLM STAT- MEDLINE DCOM- 20260803 LR - 20260820 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 74 IP - 6 DP - 2026 Jun TI - Glucagon Agonist Therapies and Vision Loss: Balancing Promise with Prudence in India. PG - 94-96 LID - 10.59556/japi.74.1507 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual incretin therapies such as tirzepatide have transformed the management of type 2 diabetes mellitus and obesity, with expanding cardiometabolic indications and rapid market growth globally and in India. However, emerging postmarketing evidence has raised concerns regarding ocular safety. Pharmacovigilance analyses, cohort studies, and case reports suggest an association between GLP-1-based therapies and ophthalmic adverse events, including early worsening of diabetic retinopathy and, more concerningly, nonarteritic anterior ischemic optic neuropathy (NAION)-a potentially irreversible cause of sudden vision loss in adults over 50 years. Although the absolute risk appears very low, regulatory agencies, including the WHO and European Medicines Agency, now recognize NAION as a very rare adverse effect of semaglutide, and similar signals are being explored for other agents, suggesting a possible class effect. Proposed mechanisms include altered optic nerve head perfusion, sympathetic-mediated vasoconstriction, and rapid glycemic shifts affecting vascular autoregulation; however, causality remains unproven. In India, where over 100 million adults live with diabetes and obesity rates are rising, even rare adverse events may translate into substantial public health impact, particularly given limited access to ophthalmic care and increasing unsupervised drug use. We advocate a balanced approach: baseline ophthalmic evaluation in high-risk individuals, informed consent regarding visual symptoms, early referral for visual complaints, strengthened pharmacovigilance, and coordinated endocrinology-ophthalmology surveillance systems. As newer triple agonists approach clinical use, integrating ocular safety into prescribing frameworks is imperative. Metabolic gains must not come at the cost of preventable vision loss. CI - (c) Journal of the Association of Physicians of India 2026. FAU - Saxena, Abhyuday AU - Saxena A AD - Senior Medical Officer, Department of Ophthalmology, Dr. R P Centre, All India Institute of Medical Sciences, New Delhi, India. FAU - Prakash, Anupam AU - Prakash A AD - Director Professor and Head, Department of Medicine, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India, Corresponding Author. ORCID: 0000-0001-8477-9039 LA - eng PT - Journal Article PT - Review PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - India MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects MH - *Optic Neuropathy, Ischemic/chemically induced MH - *Blindness MH - Diabetic Retinopathy/chemically induced EDAT- 2026/08/03 06:36 MHDA- 2026/08/03 06:37 CRDT- 2026/08/03 02:57 PHST- 2026/08/03 06:37 [medline] PHST- 2026/08/03 06:36 [pubmed] PHST- 2026/08/03 02:57 [entrez] AID - 10.59556/japi.74.1507 [doi] PST - ppublish SO - J Assoc Physicians India. 2026 Jun;74(6):94-96. doi: 10.59556/japi.74.1507. PMID- 42543936 OWN - NLM STAT- MEDLINE DCOM- 20260803 LR - 20260803 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 74 IP - 6 DP - 2026 Jun TI - Semaglutide in Practice: Insights from a Retrospective Case Series at a Jharkhand Tertiary Care Hospital. PG - 74-77 LID - 10.59556/japi.74.1508 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in improving glycemic control and reducing cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). However, real-world evidence from Indian populations remains limited. This study aimed to assess the effectiveness and safety of semaglutide on glycemic control, body weight, and metabolic parameters in patients with T2DM in a real-world clinical setting. METHODS: This retrospective observational study was conducted at a tertiary care hospital in Jharkhand, India, between February 2023 and August 2024. A total of 60 patients with T2DM (44 males and 16 females), including treatment-naive individuals and those with inadequate glycemic control (HbA1c >7%) despite ongoing therapy, were enrolled. Clinical and biochemical parameters were evaluated at baseline and after six months of semaglutide therapy. Statistical analysis was performed using paired t-tests, with a p-value <0.05 considered statistically significant. RESULTS: Significant improvements were observed following semaglutide therapy. Mean HbA1c decreased from 9.21% at baseline to 7.35% after six months (p <0.001). Mean body weight decreased by 2.6 kg (p <0.001). LDL cholesterol levels declined significantly from 92.03 mg/dL to 78.93 mg/dL (p <0.05). Renal parameters, including serum creatinine and urine albumin-to-creatinine ratio, showed numerical improvement; however, these changes did not reach statistical significance (p >0.05). Thyroid function remained stable throughout the study period. Improvements in diabetic retinopathy and neuropathy were also observed, although these findings were not statistically significant. CONCLUSION: Semaglutide was effective and well tolerated in patients with T2DM in routine clinical practice. Treatment was associated with significant reductions in HbA1c, body weight, and LDL cholesterol without adverse effects on renal or thyroid function. These findings support the use of semaglutide as an effective therapeutic option for the management of T2DM in real-world settings. CI - (c) Journal of the Association of Physicians of India 2026. FAU - Jha, Ajay Kumar AU - Jha AK AD - Senior Consultant and Unit Head, Department of Medicine, Tata Main Hospital, Jamshedpur, Jharkhand, India, Corresponding Author. ORCID: 0009-0009-9100-5491 FAU - Sunder, Ashok AU - Sunder A AD - Chief Consultant, Department of Medicine, Tata Main Hospital, Jamshedpur, Jharkhand, India. LA - eng PT - Journal Article PT - Observational Study PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - India MH - Glycated Hemoglobin/analysis MH - Tertiary Care Centers MH - Middle Aged MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Aged MH - Treatment Outcome EDAT- 2026/08/03 06:36 MHDA- 2026/08/03 06:37 CRDT- 2026/08/03 02:57 PHST- 2026/08/03 06:37 [medline] PHST- 2026/08/03 06:36 [pubmed] PHST- 2026/08/03 02:57 [entrez] AID - 10.59556/japi.74.1508 [doi] PST - ppublish SO - J Assoc Physicians India. 2026 Jun;74(6):74-77. doi: 10.59556/japi.74.1508. PMID- 42536830 OWN - NLM STAT- MEDLINE DCOM- 20260731 LR - 20260731 IS - 2105-0686 (Electronic) IS - 2105-0678 (Linking) VI - 220 IP - 1-2 DP - 2026 TI - [An historical overview of GLP-1/GIP incretins. From hormone to "swiss-army knife" medications]. PG - 9-24 LID - 10.1051/jbio/2026005 [doi] AB - Incretins are hormones released from the gut that play a vital role in regulating postprandial metabolism. It has been 30 years since the first demonstration of the glucose-lowering effects of GLP-1 in people with type 2 diabetes. Here, we review the foundational science that led to an unparalleled development in the pharmacological treatment of diabetes. A first step was achieved with the discovery of inhibitors of the dipeptidyl peptidase-4 (DPP-4), which prevent the inactivation of GLP-1 and GIP, thereby prolonging their raised levels after meal ingestion. At the same time, several GLP-1 receptor agonists (GLP1-RAs) were engineered. The GLP1-RAs used clinically are based on exendin-4 and native GLP-1 and are now available as formulations for daily or weekly s.c. (exenatide, liraglutide, semaglutide) or oral administration (oral semaglutide). They mimic (better effectiveness) the action of native GLP-1 to reduce glucose levels through stimulation of insulin secretion and inhibition of glucagon secretion. They also demonstrated remarkable cardiovascular and weight-regulating benefits, including safety, leading to their prominent inclusion in current treatment recommendations for type 2 diabetes. Exciting advancements continue to emerge as the fundamental research efforts led to the development of monomeric multi-incretin receptor agonists: GLP-1/GIP (tirzepatide) dual receptor agonists and GLP-1/GIP/glucagon (retatrutide) triple receptor agonists which can achieve more than 20% weight loss in obesity as well as offering superior benefits in diabetes. This review also presents the promise of GLP1-RAs for more extensive application of this new class of drugs, in treating other metabolic disorders such as obesity, MASLD/NAFLD, cardio-vascular diseases and neurodegeneration. CI - (c) Societe de Biologie, 2026. FAU - Portha, Bernard AU - Portha B AD - Laboratoire EnDF (Endocrinologie du Diabete et de la Fertilite), Unite BFA (Biologie Fonctionnelle et Adaptive), CNRS UMR 8251, Universite Paris-Cite, Campus des grands moulins, Batiment Buffon, 4 rue Marie Andree Lagroua Weill-Halle, 75013 Paris, France. LA - fre PT - English Abstract PT - Historical Article PT - Journal Article PT - Review TT - Histoire des incretines GLP-1/GIP - De l'hormone au medicament couteau-suisse. DEP - 20260731 PL - France TA - Biol Aujourdhui JT - Biologie aujourd'hui JID - 101544020 RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Incretins/therapeutic use/history MH - *Glucagon-Like Peptide 1/therapeutic use/history/physiology MH - *Gastric Inhibitory Polypeptide/therapeutic use/history/physiology MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/history MH - History, 21st Century MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - History, 20th Century MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glucagon-Like Peptides/therapeutic use OTO - NOTNLM OT - GIP OT - GLP-1 OT - agonistes co- ou multi-recepteurs OT - anti-obesity drugs OT - co- or multi-receptor agonists OT - incretins OT - incretines OT - medicaments anti-obesite EDAT- 2026/07/31 18:35 MHDA- 2026/07/31 18:36 CRDT- 2026/07/31 15:12 PHST- 2026/06/08 00:00 [received] PHST- 2026/07/31 18:36 [medline] PHST- 2026/07/31 18:35 [pubmed] PHST- 2026/07/31 15:12 [entrez] AID - jbio260005 [pii] AID - 10.1051/jbio/2026005 [doi] PST - ppublish SO - Biol Aujourdhui. 2026;220(1-2):9-24. doi: 10.1051/jbio/2026005. Epub 2026 Jul 31. PMID- 42533561 OWN - NLM STAT- MEDLINE DCOM- 20260912 LR - 20260923 IS - 1532-6535 (Electronic) IS - 0009-9236 (Print) IS - 0009-9236 (Linking) VI - 120 IP - 4 DP - 2026 Oct TI - Prescription Sequence Symmetry Analysis of Glucagon-Like Peptide-1 Receptor Agonists and Neuropsychiatric Conditions. PG - 1092-1100 LID - 10.1002/cpt.70414 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for type 2 diabetes and weight management. However, conflicting evidence from preclinical, clinical, and pharmacovigilance studies suggests potential neuropsychiatric effects. This study examined associations between GLP-1RA use and initiation of a range of neuropsychiatric medications using real-world prescription data. A Prescription Sequence Symmetry Analysis was conducted using Australia's Pharmaceutical Benefits Scheme 10% random sample between July 1, 2013 and December 31, 2024. Individuals with an incident dispensing of both a GLP-1RA and a neuropsychiatric medication were included. Outcomes comprised antidepressants, medication for substance use disorder (SUD), antipsychotics, psychostimulants, antidementia medications, antiparkinsonian medications, antiepileptics, and antimigraine agents. Adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) were calculated using a one-year exposure window, with sensitivity analyses varying various time windows. Among 2,033 individuals, semaglutide was the most common GLP-1RA (50.6%), followed by exenatide (27.5%) and dulaglutide (21.9%). GLP-1RA initiation was inversely associated with initiation of antidepressants (aSR: 0.85; 95% CI: 0.76-0.94) and medications for SUD (aSR: 0.70; 95% CI: 0.51-0.88). No significant associations were observed for other neuropsychiatric outcomes. GLP-1RA use was inversely associated with subsequent initiation of antidepressants and medications for SUD, while no associations were identified for other neuropsychiatric marker medications. These findings highlight the need for further studies to clarify the nature and magnitude of these potential neuropsychiatric associations with GLP-1RAs. CI - (c) 2026 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Alfonso Arvez, Maria J AU - Alfonso Arvez MJ AUID- ORCID: 0000-0003-1411-110X AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Wade, Sam AU - Wade S AUID- ORCID: 0009-0007-4680-8514 AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Goordeen, Darshna AU - Goordeen D AUID- ORCID: 0000-0002-6381-8745 AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Ilomaki, Jenni AU - Ilomaki J AUID- ORCID: 0000-0002-0348-9441 AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Cross, Amanda J AU - Cross AJ AUID- ORCID: 0000-0001-6001-9211 AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. FAU - Langiu, Monica AU - Langiu M AUID- ORCID: 0000-0003-0719-8999 AD - Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. AD - AK Clinical Research, Carlton, Victoria, Australia. FAU - Tan, George S Q AU - Tan GSQ AUID- ORCID: 0000-0003-2526-729X AD - Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia. LA - eng PT - Journal Article DEP - 20260730 PL - United States TA - Clin Pharmacol Ther JT - Clinical pharmacology and therapeutics JID - 0372741 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Female MH - Male MH - Exenatide/adverse effects/therapeutic use MH - *Mental Disorders/drug therapy/chemically induced/epidemiology MH - Glucagon-Like Peptides/analogs & derivatives/adverse effects/therapeutic use MH - Australia MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Drug Prescriptions/statistics & numerical data MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC13424737 COIS- J.I. reports grants from AstraZeneca, Amgen, National Health and Medical Research Council, Australian Government Department of Health, Disability and Aging, outside the submitted work. AJC has received grant funding or consulting funds from the National Health and Medical Research Council, Medical Research Future Fund, Dementia Australia Research Foundation, and Pharmaceutical Society of Australia. All grants and consulting funds were paid to the employing institution. All other authors declared no competing interests for this work. EDAT- 2026/07/31 06:36 MHDA- 2026/09/13 00:50 PMCR- 2026/07/30 CRDT- 2026/07/31 02:43 PHST- 2026/01/20 00:00 [received] PHST- 2026/07/07 00:00 [accepted] PHST- 2026/09/13 00:50 [medline] PHST- 2026/07/31 06:36 [pubmed] PHST- 2026/07/31 02:43 [entrez] PHST- 2026/07/30 00:00 [pmc-release] AID - CPT70414 [pii] AID - 10.1002/cpt.70414 [doi] PST - ppublish SO - Clin Pharmacol Ther. 2026 Oct;120(4):1092-1100. doi: 10.1002/cpt.70414. Epub 2026 Jul 30. PMID- 42518911 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260813 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 20 DP - 2026 TI - Real-World Comparative Weight Loss of GLP-1 Receptor Agonists in the All of Us Research Program: A Retrospective Cohort Study. PG - 604247 LID - 10.2147/DDDT.S604247 [doi] LID - 604247 AB - PURPOSE: To assess the real-world associations of five glucagon-like peptide-1 receptor agonists (GLP-1RAs) with weight loss in a diverse US population of adults with obesity, with and without type 2 diabetes, and whether the relative ordering of weight loss observed in trials is mirrored in routine practice. PATIENTS AND METHODS: We conducted a retrospective, new-user, active-comparator cohort study using the National Institutes of Health All of Us Research Program. We included 14,046 adults with obesity (body mass index [BMI] >/=30 kg/m(2)) initiating exenatide, liraglutide, dulaglutide, semaglutide, or tirzepatide. Groups were compared after multivariable adjustment for baseline confounders. Participants were followed from the index date until the outcome, death, or loss to follow-up; percent weight and BMI change was assessed at 12 months (+/-45 days). Cox proportional hazards models estimated the relative likelihood over time of achieving weight-loss thresholds (>/=5%, >/=10%, >/=15%) and >/=1 BMI-category reduction; linear regression assessed the magnitude of weight change, with liraglutide as reference. RESULTS: Tirzepatide showed the highest likelihood of >/=15% weight loss (adjusted hazard ratio [aHR] 5.57; 95% CI, 3.66-8.49) and the greatest mean weight loss at 12 months (-13.0%), followed by semaglutide (aHR 1.77; 95% CI, 1.56-2.01; -5.9%); both were significantly greater than the older agents in adjusted analyses. Exenatide, dulaglutide, and liraglutide showed comparable, modest weight loss (approximately -4.0%). This ordering was consistent regardless of type 2 diabetes status, although weight loss was greater without diabetes for semaglutide but similar for tirzepatide. CONCLUSION: In this large, diverse real-world cohort, tirzepatide and semaglutide were associated with significantly greater weight loss than older agents. These findings are consistent with the relative ordering reported in trials, though the observational design cannot confirm it. Residual confounding cannot be excluded, and the small tirzepatide sample (n=386) and limited follow-up warrant cautious interpretation. CI - (c) 2026 Hwang et al. FAU - Hwang, Inyoung AU - Hwang I AUID- ORCID: 0000-0003-4953-759X AD - Department of Clinical Pharmacology and Therapeutics, Hanyang University Seoul Hospital, Seoul, 04763, Republic of Korea. FAU - Lee, Sang Won AU - Lee SW AUID- ORCID: 0000-0002-3862-9491 AD - Department of Clinical Pharmacology and Therapeutics, Hanyang University Seoul Hospital, Seoul, 04763, Republic of Korea. AD - Department of Pharmacology, Hanyang University College of Medicine, Seoul, 04763, Republic of Korea. FAU - Kim, Yun AU - Kim Y AUID- ORCID: 0000-0002-9809-7351 AD - College of Pharmacy, Daegu Catholic University, Gyeongsan, Gyeongbuk, 38430, Republic of Korea. AD - Convergence Research Institute for Biomedical Sciences, Daegu Catholic University, Gyeongsan, Gyeongbuk, 38430, Republic of Korea. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260714 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Tirzepatide MH - *Obesity/drug therapy MH - Glucagon-Like Peptides/analogs & derivatives/pharmacology/administration & dosage MH - Exenatide/pharmacology MH - United States MH - Adult MH - *Hypoglycemic Agents/pharmacology MH - Liraglutide/pharmacology MH - Cohort Studies MH - Recombinant Fusion Proteins/pharmacology/administration & dosage MH - Anti-Obesity Agents MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Immunoglobulin Fc Fragments/pharmacology MH - Aged PMC - PMC13381347 OAB - WHY WAS THE STUDY DONE? Obesity is a long-term condition, and many people need more than lifestyle changes to manage it. Newer medicines called GLP-1 receptor agonists can reduce appetite and have worked well in clinical trials. But trials enroll selected volunteers who may differ from people in everyday care. We compared how five of these medicines work for weight loss in a large, diverse, real-world group. WHAT DID THE RESEARCHERS DO AND FIND? We studied health records from 14,046 adults with obesity in the National Institutes of Health All of Us Research Program. We compared how much weight patients lost in one year after starting exenatide, liraglutide, dulaglutide, semaglutide, or tirzepatide. On average, tirzepatide users lost about 13.0% and semaglutide users about 5.9%, while patients taking the three older medicines lost around 4%. Tirzepatide users were also the most likely to achieve large weight loss of 15% or more. WHAT DO THESE RESULTS MEAN? These findings suggest the two newest medicines, tirzepatide and semaglutide, are linked to greater weight loss than older options, even in everyday care. Greater weight loss is generally linked to better health, so these differences could matter for patients, though our study cannot prove the drugs caused them. Because we used everyday medical records rather than a clinical trial, the results show links rather than proof of cause and effect. Tirzepatide is new, so few patients had taken it; larger studies are needed to confirm these early findings. OABL- eng OTO - NOTNLM OT - body mass index OT - incretin mimetics OT - obesity management OT - pharmacoepidemiology OT - type 2 diabetes mellitus COIS- The authors report no conflicts of interest in this work. EDAT- 2026/07/28 18:35 MHDA- 2026/07/29 18:38 PMCR- 2026/07/14 CRDT- 2026/07/28 12:52 PHST- 2026/02/19 00:00 [received] PHST- 2026/06/24 00:00 [accepted] PHST- 2026/07/29 18:38 [medline] PHST- 2026/07/28 18:35 [pubmed] PHST- 2026/07/28 12:52 [entrez] PHST- 2026/07/14 00:00 [pmc-release] AID - 604247 [pii] AID - 10.2147/DDDT.S604247 [doi] PST - epublish SO - Drug Des Devel Ther. 2026 Jul 14;20:604247. doi: 10.2147/DDDT.S604247. eCollection 2026. PMID- 42511463 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 14 DP - 2026 Jul 8 TI - Incretin-Based Therapies in Sports: Pharmacological Mechanisms, Performance-Enhancing Potential, and Anti-Doping Implications-A Narrative Review. LID - 10.3390/ijms27146116 [doi] LID - 6116 AB - Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, have revolutionized the management of type 2 diabetes and obesity. Recent evidence suggests these agents may influence athletic performance through effects on body composition, energy metabolism, and cardiovascular function. This narrative review critically evaluates whether incretin therapies could constitute doping under World Anti-Doping Agency (WADA) criteria. We narratively reviewed the literature on incretin pharmacology, metabolic effects relevant to athletic performance, and anti-doping regulations, searching PubMed, Scopus, and Web of Science using terms including "GLP-1 receptor agonists", "DPP-4 inhibitors", "doping", "athletic performance", "WADA", and "sports pharmacology", without date restrictions. GLP-1 RAs (semaglutide, liraglutide, tirzepatide, exenatide) induce substantial weight loss (predominantly fat mass) but also reduce lean mass by 20-30% of total weight loss. Preclinical studies demonstrate enhanced exercise endurance, mitochondrial biogenesis, and glucose uptake via GLP-1R/AMPK signaling. However, clinical trials show no consistent improvement in physical performance in humans. Currently, incretin therapies are not listed on the WADA Prohibited List. While incretin therapies offer theoretical performance-enhancing potential through weight management and metabolic optimization, current evidence does not support classification as doping agents. Continued surveillance is warranted as misuse patterns emerge. FAU - La Vignera, Sandro AU - La Vignera S AUID- ORCID: 0000-0002-7113-2372 AD - Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy. FAU - Condorelli, Rosita A AU - Condorelli RA AUID- ORCID: 0000-0002-5217-9343 AD - Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy. LA - eng PT - Journal Article PT - Review DEP - 20260708 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Performance-Enhancing Substances) SB - IM MH - Humans MH - *Incretins/pharmacology/therapeutic use MH - *Doping in Sports MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Athletic Performance MH - Dipeptidyl-Peptidase IV Inhibitors/pharmacology/therapeutic use MH - Energy Metabolism/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Tirzepatide MH - *Performance-Enhancing Substances/pharmacology PMC - PMC13411830 OTO - NOTNLM OT - GLP-1 receptor agonists OT - WADA OT - anti-doping OT - athletic performance OT - body composition OT - doping OT - incretin therapy OT - liraglutide OT - semaglutide OT - sports pharmacology COIS- The authors declare no conflicts of interest. EDAT- 2026/07/28 06:37 MHDA- 2026/07/29 18:38 PMCR- 2026/07/08 CRDT- 2026/07/28 01:08 PHST- 2026/06/14 00:00 [received] PHST- 2026/07/04 00:00 [revised] PHST- 2026/07/06 00:00 [accepted] PHST- 2026/07/29 18:38 [medline] PHST- 2026/07/28 06:37 [pubmed] PHST- 2026/07/28 01:08 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - ijms27146116 [pii] AID - ijms-27-06116 [pii] AID - 10.3390/ijms27146116 [doi] PST - epublish SO - Int J Mol Sci. 2026 Jul 8;27(14):6116. doi: 10.3390/ijms27146116. PMID- 42508090 OWN - NLM STAT- MEDLINE DCOM- 20260916 LR - 20260929 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 20 IP - 7 DP - 2026 Jul TI - Nutritional intake changes during GLP-1 receptor agonist therapy: A systematic review and meta-analysis. PG - 103466 LID - S1871-4021(26)00093-7 [pii] LID - 10.1016/j.dsx.2026.103466 [doi] AB - BACKGROUND AND AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists, including the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist tirzepatide, produce substantial weight loss, yet their effect on objectively measured dietary intake has not been quantitatively synthesized. We assessed their impact on ad libitum lunch energy intake. METHODS: We searched six databases through March 31, 2026, for studies reporting quantitative dietary outcomes in adults receiving a GLP-1 or dual GIP/GLP-1 receptor agonist. Randomized or crossover placebo-controlled trials lasting at least four weeks that reported standardized ad libitum lunch intake were pooled using a DerSimonian-Laird random-effects model. Prespecified sensitivity analyses included restricted maximum likelihood (REML) and Paule-Mandel estimators, a 95% prediction interval, a subgroup analysis, a leave-one-out analysis, and an exploratory three-week phase 1 tirzepatide trial. RESULTS: Sixteen studies were included in the systematic review; four arms from three trials (209 participants) contributed to the primary meta-analysis. The pooled treatment difference in ad libitum lunch energy intake was -1132 kJ (95% confidence interval [CI] -1449 to -815), approximately -271 kcal, with no heterogeneity (I-squared = 0%; 95% prediction interval -1828 to -436 kJ). Adding the phase 1 trial (k = 5) increased the effect to -1421 kJ but introduced substantial heterogeneity (I-squared = 70%). The semaglutide-versus-tirzepatide difference was not significant (p = 0.154). CONCLUSIONS: GLP-1 receptor agonist therapy markedly reduces acute energy intake under standardized meal tests, but real-world habitual intake remains underreported. Structured nutritional counseling emphasizing adequate protein should complement pharmacotherapy. CI - Copyright (c) 2026 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Quan, Anh Tuan AU - Quan AT AD - Department of Internal Medicine, Van Phuc City Hospital, Ho Chi Minh City, Viet Nam; University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Viet Nam. Electronic address: tuan.quan.md@outlook.com. FAU - Nguyen, Hoang Linh AU - Nguyen HL AD - Department of Cardic Arrhythmia, Thong Nhat Hospital, Ho Chi Minh City, Viet Nam. FAU - Nguyen, Tran My Thanh AU - Nguyen TMT AD - Department of Endocrinology and Nephrology, Nhan Dan Gia Dinh Hospital, Ho Chi Minh City, Viet Nam. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260725 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Energy Intake/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Tirzepatide/pharmacology/therapeutic use OTO - NOTNLM OT - Energy intake OT - GLP-1 receptor agonists OT - Meta-analysis OT - Obesity OT - Tirzepatide COIS- Declaration of competing interest All named authors provide the following disclosure covering the 24 months preceding submission. The scope of disclosure includes employment, consultancies, honoraria, speaker fees, advisory-board or steering-committee membership, research grants or contracts, travel or accommodation support, expert testimony, patents or patent applications, and stock or stock options, as well as any other financial or non-financial relationship with a commercial entity - in particular the manufacturers of the medications evaluated in this review, Novo Nordisk and Eli Lilly and Company. This work received no funding from any public, commercial, or not-for-profit source. The authors have no financial or personal relationships that could be perceived to have influenced the work reported in this paper. EDAT- 2026/07/27 18:35 MHDA- 2026/09/16 23:34 CRDT- 2026/07/27 17:59 PHST- 2026/04/07 00:00 [received] PHST- 2026/07/21 00:00 [revised] PHST- 2026/07/23 00:00 [accepted] PHST- 2026/09/16 23:34 [medline] PHST- 2026/07/27 18:35 [pubmed] PHST- 2026/07/27 17:59 [entrez] AID - S1871-4021(26)00093-7 [pii] AID - 10.1016/j.dsx.2026.103466 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2026 Jul;20(7):103466. doi: 10.1016/j.dsx.2026.103466. Epub 2026 Jul 25. PMID- 42507153 OWN - NLM STAT- MEDLINE DCOM- 20261014 LR - 20261027 IS - 1554-8120 (Electronic) IS - 1054-2523 (Linking) VI - 35 IP - 10 DP - 2026 Oct TI - Understanding Biased Signaling and Small-Molecule Binding for Treatment of Type 2 Diabetes Mellitus and Obesity at the Glucagon-Like Peptide-1 Receptor (GLP-1R) Based on Molecular Dynamics Simulations. PG - 2073-2093 LID - 10.1007/s00044-026-03579-6 [doi] AB - Glucagon-like peptide-1 receptor (GLP-1R) is a class B1 G protein-coupled receptor expressed in multiple tissues and is a major therapeutic target for type 2 diabetes mellitus and obesity. Here, we investigate the mechanisms of GLP-1R binding and activation using molecular dynamics (MD) simulations of semaglutide, tirzepatide, danuglipron, and CHU-128bound GLP-1R-Gs complexes. We analyze these simulations as a function of temperature, ligand class (peptide vs. small molecule), and signaling profile (biased vs. non-biased) to assess how these factors affect GLP-1R interactions and conformational dynamics. Our results reveal distinct interaction patterns and structural features associated with each factor which persist over the MD trajectories. Together, these findings deepen our mechanistic understanding of GLP-1R agonism and further aid in the design of effective, orally available GLP-1R agonists with reduced side effects. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Brubaker, Jack AU - Brubaker J AD - Materials Process and Simulation Center, California Institute of Technology, Pasadena, CA, 91125, USA. FAU - Kim, Soo-Kyung AU - Kim SK AD - Materials Process and Simulation Center, California Institute of Technology, Pasadena, CA, 91125, USA. FAU - Li, Bo AU - Li B AD - Materials Process and Simulation Center, California Institute of Technology, Pasadena, CA, 91125, USA. FAU - Yang, Moon Young AU - Yang MY AD - Materials Process and Simulation Center, California Institute of Technology, Pasadena, CA, 91125, USA. FAU - Goddard Iii, William A AU - Goddard Iii WA AUID- ORCID: 0000-0003-0097-5716 AD - Materials Process and Simulation Center, California Institute of Technology, Pasadena, CA, 91125, USA. wag@caltech.edu. LA - eng GR - 1R01HL155532 and R01HL11447/National Institutes Health/ GR - CBET 2311117/National Science Foundation/ PT - Journal Article DEP - 20260727 PL - United States TA - Med Chem Res JT - Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents JID - 9211347 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Small Molecule Libraries) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Molecular Dynamics Simulation MH - *Glucagon-Like Peptide-1 Receptor/metabolism/chemistry MH - Signal Transduction/drug effects MH - Humans MH - *Obesity/drug therapy/metabolism MH - Semaglutide MH - *Small Molecule Libraries/chemistry/pharmacology/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Tirzepatide MH - *Hypoglycemic Agents/chemistry/pharmacology MH - Protein Binding COIS- Declarations. Conflict of interests: The authors declare no competing interests. EDAT- 2026/07/27 12:36 MHDA- 2026/10/14 18:14 CRDT- 2026/07/27 11:13 PHST- 2026/04/11 00:00 [received] PHST- 2026/05/18 00:00 [accepted] PHST- 2026/10/14 18:14 [medline] PHST- 2026/07/27 12:36 [pubmed] PHST- 2026/07/27 11:13 [entrez] AID - 10.1007/s00044-026-03579-6 [pii] AID - 10.1007/s00044-026-03579-6 [doi] PST - ppublish SO - Med Chem Res. 2026 Oct;35(10):2073-2093. doi: 10.1007/s00044-026-03579-6. Epub 2026 Jul 27. PMID- 42504064 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260914 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Efficacy and Safety of Once-Weekly Semaglutide 2.0 mg as an Add-On to Dose-Reduced Insulin Glargine versus Dose-Titrated Insulin Glargine in People With Type 2 Diabetes and Overweight (SUSTAIN OPTIMIZE). PG - 9304-9316 LID - 10.1111/dom.71132 [doi] AB - AIMS: Type 2 diabetes (T2D) management with basal insulin can lead to hypoglycaemia and weight gain. SUSTAIN OPTIMIZE compared once-weekly semaglutide 2.0 mg as add-on to dose-reduced insulin glargine (Sema+IGlar(reduced)) versus dose-titrated IGlar (IGlar(titrated)) on glycated haemoglobin (HbA(1c)), body weight (BW), daily insulin dose, and participant satisfaction. MATERIALS AND METHODS: SUSTAIN OPTIMIZE was a 40-week, phase 3b, open-label, randomised study. Adults with T2D, overweight (body mass index >/= 25 kg/m(2)), and treatment with basal insulin /=30 kg/m(2)). Participants will be treated for up to 160 weeks (3 years), with a total follow-up period of up to 184 weeks (3 years and 6 months). Study visits are scheduled every 6 months and include blood sampling, clinical examinations and completion of self-administered questionnaires. The primary outcome is the development of T2DM based on the American Diabetes Association criteria. Secondary outcomes include need for diabetes rescue therapy, regression to normoglycaemia, weight loss, insulin sensitivity, beta-cell function, cardiometabolic risk profile, patient-reported outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: The study was approved by the Federal Agency for Medicines and Health Products and the relevant Ethics Committees (2022-502082-22-00) (S66967). Recruitment started in September 2023. Study results will be disseminated through peer-reviewed publications and presentations at scientific conferences. Individual participant data will be made available on reasonable request after study completion, database lock, unblinding and publication of the primary results, subject to applicable ethical, legal and data protection requirements. TRIAL REGISTRATION NUMBER: NCT05569772. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Vanlaer, Yana AU - Vanlaer Y AD - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium. FAU - Embo, Nina AU - Embo N AD - Faculty of Medicine, KU Leuven, Leuven, Belgium. FAU - Bochanen, Niels AU - Bochanen N AD - Department of Endocrinology-Diabetology-Metabolism, University Hospital Antwerp, Edegem, Belgium. FAU - Van Wilder, Nancy AU - Van Wilder N AD - Department of Endocrinology, Brussels University Hospital, Anderlecht, Belgium. FAU - Vereecke, Gertjan AU - Vereecke G AD - Department of Endocrinology, General Hospital Groeninge, Kortrijk, Belgium. FAU - Wierckx, Katrien AU - Wierckx K AD - Department of Endocrinology, AZORG Hospital, Aalst, Belgium. FAU - Verhaegen, Ann AU - Verhaegen A AD - Department of Endocrinology, ZAS Jan Palfijn, Merksem, Belgium. FAU - Coremans, Peter AU - Coremans P AD - Department of Endocrinology-Diabetology, Vitaz Sint-Niklaas Moerland, Sint-Niklaas, Belgium. FAU - Philips, Jean-Christophe AU - Philips JC AD - Department of Diabetology, Nutrition and Metabolic Diseases, Liege University Hospital Sart Tilman Site, Liege, Belgium. FAU - Lytrivi, Maria AU - Lytrivi M AD - Department of Endocrinology, Erasmus Hospital, Brussels, Belgium. FAU - Oriot, Philippe AU - Oriot P AD - Department of Endocrinology-Diabetology, Hospital Centre Mouscron, Mouscron, Belgium. FAU - Vandewalle, Sara AU - Vandewalle S AD - AZ Sint-Jan Brugge AV, Bruges, Belgium. FAU - Cuypers, Joke AU - Cuypers J AD - Department of Endocrinology-Diabetology-Nephrology, AZ Turnhout vzw Campus Sint-Jozef, Turnhout, Belgium. FAU - Deconinck, Barbara AU - Deconinck B AD - Department of Endocrinology-Diabetology, Jan Yperman Ziekenhuis, Ypres, Belgium. FAU - Laenen, Annouschka AU - Laenen A AD - Leuven Biostatistics and Statistical Bioinformatics Centre, KU Leuven, Leuven, Belgium. FAU - Mathieu, Chantal AU - Mathieu C AD - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium. AD - Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium. FAU - Benhalima, Katrien AU - Benhalima K AUID- ORCID: 0000-0002-3325-0263 AD - Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium Katrien.Benhalima@uzleuven.be. AD - Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium. LA - eng SI - ClinicalTrials.gov/NCT05569772 PT - Clinical Trial Protocol PT - Journal Article DEP - 20260723 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Female MH - Semaglutide MH - *Diabetes Mellitus, Type 2/prevention & control MH - *Diabetes, Gestational MH - Pregnancy MH - Double-Blind Method MH - *Prediabetic State/drug therapy MH - Postpartum Period MH - Belgium MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Randomized Controlled Trials as Topic MH - Multicenter Studies as Topic MH - Adult MH - Cost-Benefit Analysis PMC - PMC13404484 OTO - NOTNLM OT - Diabetes in pregnancy OT - Life Change Events OT - Postpartum Period COIS- Competing interests: None declared. EDAT- 2026/07/24 00:37 MHDA- 2026/07/24 00:38 PMCR- 2026/07/23 CRDT- 2026/07/23 21:03 PHST- 2026/07/24 00:38 [medline] PHST- 2026/07/24 00:37 [pubmed] PHST- 2026/07/23 21:03 [entrez] PHST- 2026/07/23 00:00 [pmc-release] AID - bmjopen-2026-118191 [pii] AID - 10.1136/bmjopen-2026-118191 [doi] PST - epublish SO - BMJ Open. 2026 Jul 23;16(7):e118191. doi: 10.1136/bmjopen-2026-118191. PMID- 42481928 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260909 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Safety Signals of GLP-1 Receptor Agonists: A Multi-Method Pharmacovigilance Analysis of FAERS (2018-2025) With Sensitivity-Stratified Prioritisation, Notoriety-Bias Assessment, and Cross-Database Validation. PG - 9251-9264 LID - 10.1111/dom.71138 [doi] AB - BACKGROUND: GLP-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes and obesity, but their post-marketing safety profile-particularly psychiatric, vascular, neoplastic and rare ophthalmic events-remains incompletely characterised and is vulnerable to confounding by indication, secondary-suspect attribution and notoriety bias. METHODS: We analysed 32 quarterly FAERS files (2018Q1-2025Q4): 288408 unique GLP-1 RA reports versus 11 319 150 non-GLP-1 RA reports. Disproportionality used four methods (reporting odds ratio [ROR]; proportional reporting ratio [PRR]; Bayesian Confidence Propagation Neural Network information component, lower 95% bound [BCPNN IC025]; Multi-item Gamma Poisson Shrinker empirical Bayes lower 5th-percentile bound [MGPS EB05]; signal = >/= 3 of 4). The top 30 ROR-ranked signals were stratified by primary-suspect (PS) sensitivity. Triangulation included active-comparator, intra-class psychiatric comparison, interrupted time-series assessment of reporting around the 2023 EMA announcement, Weber-effect evaluation with Cochran-Armitage trend testing, and external validation in JADER. RESULTS: Of 22 059 PT-class pairs, 544 met the >/= 3-of-4 criterion. PS-stratification retained 21 of the top 30 signals and demoted 9 as secondary-suspect-driven (e.g., capillaritis ROR 18.6 --> 0.27; heart sounds 84.3 --> 0.55). PS-stable headline signals were dominated by gastrointestinal/hepatobiliary effects: cyclic vomiting syndrome (ROR 64.8; semaglutide-dominant), gallbladder injury (84.2), impaired gastric emptying (45.1), plus liraglutide-concentrated medullary thyroid cancer (41.1) and semaglutide-concentrated optic ischaemic neuropathy (26.5). Only semaglutide carried a class-level suicidal-ideation signal (ROR 2.30). Interrupted time series detected no level (p = 0.39) or slope change (p = 0.75) at the 2023 EMA announcement; psychiatric time-to-onset (median 47 days) aligned with early GI reactions. Sixteen of 17 priority signals (94.1%) replicated in JADER. As disproportionality analyses, these are hypothesis-generating safety signals and cannot establish incidence, relative risk, or causality. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Xu, Shiyi AU - Xu S AUID- ORCID: 0009-0009-2094-220X AD - Capital Medical University, Beijing, China. LA - eng PT - Journal Article DEP - 20260721 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Pharmacovigilance MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Databases, Factual MH - Exenatide MH - Bayes Theorem PMC - PMC13538726 OTO - NOTNLM OT - FAERS OT - GLP-1 receptor agonists OT - disproportionality analysis OT - pharmacovigilance OT - primary-suspect analysis OT - semaglutide COIS- The author declares no conflicts of interest. EDAT- 2026/07/22 12:37 MHDA- 2026/09/03 05:36 PMCR- 2026/09/03 CRDT- 2026/07/21 23:36 PHST- 2026/07/09 00:00 [revised] PHST- 2026/05/19 00:00 [received] PHST- 2026/07/13 00:00 [accepted] PHST- 2026/09/03 05:36 [medline] PHST- 2026/07/22 12:37 [pubmed] PHST- 2026/07/21 23:36 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71138 [pii] AID - 10.1111/dom.71138 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):9251-9264. doi: 10.1111/dom.71138. Epub 2026 Jul 21. PMID- 42481079 OWN - NLM STAT- MEDLINE DCOM- 20260721 LR - 20260824 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 16 IP - 7 DP - 2026 Jul 21 TI - Association between GLP-1 receptor agonists and alcohol-related hospitalisations among adults with alcohol use disorder: multi-target trial emulation study. PG - e109259 LID - 10.1136/bmjopen-2025-109259 [doi] LID - e109259 AB - OBJECTIVE: To evaluate the association between use of newer glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide, tirzepatide) and alcohol-related hospitalisations among adults with alcohol use disorder (AUD) and type 2 diabetes (T2D) or obesity.Retrospective cohort study using target trial emulation. SETTING: Electronic health record data from a collective of US healthcare systems. PARTICIPANTS: Adults with AUD and T2D or obesity who started a newer GLP-1 RA (semaglutide or tirzepatide) or a relevant active comparator between 1 January 2018 and 31 December 2024. INTERVENTIONS: Initiation of a newer GLP-1 RA compared with an active comparator across four target trials: (1) anti-diabetic medication (ADM) trial, (2) anti-obesity medication (AOM) trial, (3) medications for alcohol use disorder with T2D (MAUD-T2D) trial, and (4) medications for alcohol use disorder with obesity (MAUD-obesity) trial. MAIN OUTCOME MEASURES: Time to first alcohol-related emergency department visits or hospitalisation within 1 year of treatment initiation. Non-alcohol-related hospitalisation was assessed as a negative control outcome. Propensity score based methods (weighting and matching) were used to control confounding and Cox proportional hazards models were used to estimate treatment effects. RESULTS: A total of 40 703 adults met study criteria, including 18 676 in the ADM trial, 9391 in the AOM trial, 8942 in the MAUD-T2D trial and 11 198 in the MAUD-obesity trial. Initiation of a newer GLP-1 RA was associated with a lower hazard of alcohol-related hospitalisation in the ADM trial (HR 0.74, 95% CI 0.62 to 0.89 vs sulfonylureas; HR 0.78, 95% CI 0.65 to 0.92 vs other ADMs), the AOM trial (HR 0.68, 95% CI 0.54 to 0.85 vs other AOMs), the MAUD-T2D trial (HR 0.37, 95% CI 0.29 to 0.46) and the MAUD-obesity trial (HR 0.35, 95% CI 0.26 to 0.47). CONCLUSIONS: Among adults with AUD and T2D or obesity, initiation of newer GLP-1 RAs was associated with a lower observed risk of alcohol-related hospitalisation. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Rodriguez, Patricia J AU - Rodriguez PJ AUID- ORCID: 0000-0003-3026-2450 AD - Truveta Inc, Bellevue, Washington, USA. FAU - Lusk, Jay B AU - Lusk JB AD - Department of Family Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA. AD - Department of Neurology, Duke University, Durham, North Carolina, USA. FAU - Mehta, Hemalkumar B AU - Mehta HB AUID- ORCID: 0000-0001-9134-6370 AD - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA hbmehta@jhu.edu. FAU - Levy, Joseph F AU - Levy JF AD - Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Kalogeropoulos, Andreas P AU - Kalogeropoulos AP AD - Stony Brook Heart Institute, Stony Brook University Hospital, Stony Brook, New York, USA. FAU - Soneji, Samir AU - Soneji S AD - Department of Population Health Sciences, Duke University, Durham, North Carolina, USA. FAU - Do, Duy AU - Do D AD - Truveta Inc, Bellevue, Washington, USA. FAU - Holler, Emma AU - Holler E AD - Truveta Inc, Bellevue, Washington, USA. FAU - Webber, Emily AU - Webber E AD - Truveta Inc, Bellevue, Washington, USA. FAU - Gluckman, Ty AU - Gluckman T AD - Center for Cardiovascular Analytics, Research, and Data Science (CARDS), Providence Heart Institute, Portland, Oregon, USA. FAU - Stucky, Nicholas AU - Stucky N AUID- ORCID: 0000-0002-6610-5353 AD - Truveta Inc, Bellevue, Washington, USA. LA - eng GR - K01 AG070329/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20260721 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Tirzepatide/therapeutic use MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hospitalization/statistics & numerical data MH - *Alcoholism/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Obesity/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Adult MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13410697 OTO - NOTNLM OT - Diabetes Mellitus, Type 2 OT - Obesity OT - Research Design OT - Substance misuse COIS- Competing interests: PJR is a former employee of Truveta and a current employee of Eli Lilly. This work was conducted and submitted prior to her employment with Eli Lilly. Eli Lilly had no role in this study. JBL declares relevant committee service (unpaid) for the American Heart Association and grant funding from the American Heart Association (NA). HM received research funding from the National Institute on Aging (K01AG070329). APK receives research funding from the American Heart Association (NA). EH and EW are employees of Truveta, which provides access to the data used in this study. DD and NS are former employees of Truveta. All other authors declare no competing interests. EDAT- 2026/07/22 12:37 MHDA- 2026/07/22 12:38 PMCR- 2026/07/21 CRDT- 2026/07/21 20:53 PHST- 2026/07/22 12:38 [medline] PHST- 2026/07/22 12:37 [pubmed] PHST- 2026/07/21 20:53 [entrez] PHST- 2026/07/21 00:00 [pmc-release] AID - bmjopen-2025-109259 [pii] AID - 10.1136/bmjopen-2025-109259 [doi] PST - epublish SO - BMJ Open. 2026 Jul 21;16(7):e109259. doi: 10.1136/bmjopen-2025-109259. PMID- 42474323 OWN - NLM STAT- MEDLINE DCOM- 20260720 LR - 20260901 IS - 1555-2101 (Electronic) IS - 0160-6689 (Print) IS - 0160-6689 (Linking) VI - 87 IP - 3 DP - 2026 Jul 15 TI - GLP-1 Receptor Agonists and All-Cause Overdose Risk in Veterans With Type 2 Diabetes and Opioid Use Disorder. LID - 25m16212 [pii] LID - 10.4088/JCP.25m16212 [doi] AB - Objective: Overdoses remain a major public health challenge. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been proposed as a treatment for opioid use disorder (OUD) based on preclinical research. Early observational research suggests that GLP-1RAs are associated with reduced opioid overdoses but warrants replication in different patient populations. Methods: This target trial emulation study used Veterans Health Administration (VA) data to include Veterans with a diagnosis of type 2 diabetes mellitus and OUD who initiated semaglutide and tirzepatide or a comparison diabetes medication (insulin, metformin, a sulfonylurea, a sodium-glucose transport 2 (SGLT2) inhibitor, or a dipeptidyl-peptidase 4 [DPP4] inhibitor) between January 1, 2020, and December 31, 2024. Each set of comparison groups was propensity score matched on relevant variables. Cox proportional hazards regression models were used to compare the time to all-cause overdose events in the 12 months after medication initiation. Results: After propensity score matching, semaglutide and tirzepatide were associated with significantly lower risk of all-cause overdose compared to insulin (hazard ratio [HR]=0.32; 95% CI=0.14-0.71; P=.006; n=630) and SGLT2 inhibitors (HR=0.25; 95% CI=0.09-0.68; P=.006; n=432). Semaglutide and tirzepatide were not associated with significantly lower risks than metformin (HR=0.75; 95% CI=0.38-1.45; n=1,016), sulfonylureas (HR=0.82; 95% CI=0.33-1.96; n=710), or DPP4 inhibitors (HR=1.20; 95% CI=0.52-2.78; n=858). Conclusion: Collectively, semaglutide and tirzepatide were associated with lower risk of all-cause overdose compared to insulin and SGLT2 inhibitors, but not metformin, sulfonylureas, or DPP4 inhibitors. These results suggest the possible role of GLP-1RAs in OUD but underscore the need for randomized controlled trials. CI - (c) Copyright 2026 Physicians Postgraduate Press, Inc. FAU - Kennedy, Kevin P AU - Kennedy KP AD - VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. AD - Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania. AD - Corresponding Author: Kevin P. Kennedy, MD, 3900 Woodland Ave #B228, Philadelphia, PA 19104 (kevin.kennedy2@va.gov). FAU - Bremseth-Vining, Ryan AU - Bremseth-Vining R AD - VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. FAU - Lynch, Kevin G AU - Lynch KG AD - VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. AD - Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania. FAU - Reville, Nicholas AU - Reville N AD - Center for Addiction Science, Policy, and Research (CASPR), San Francisco, California. FAU - Zhang, Jonathan AU - Zhang J AD - Sanford School of Public Policy, Duke University, Durham, North Carolina. AD - US Department of Veterans Affairs Office of Mental Health, Washington D.C. AD - National Bureau of Economic Research, Cambridge, Massachusetts. FAU - Moshfegh, Jasmin AU - Moshfegh J AD - Imperial College London, Department of Economics and Public Policy, London, United Kingdom. AD - Veterans Health Administration Palo Alto, Palo Alto, California. FAU - Oslin, David W AU - Oslin DW AD - VISN 4 Mental Illness Research, Education, and Clinical Center (MIRECC), Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania. AD - Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania. LA - eng GR - VA999999/ImVA/Intramural VA/United States PT - Journal Article DEP - 20260715 PL - United States TA - J Clin Psychiatry JT - The Journal of clinical psychiatry JID - 7801243 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9100L32L2N (Metformin) RN - 0 (Insulin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Semaglutide MH - Tirzepatide MH - *Veterans/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - *Drug Overdose/epidemiology/prevention & control MH - Female MH - *Opioid-Related Disorders/drug therapy/epidemiology MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use MH - United States/epidemiology MH - Metformin/therapeutic use MH - Insulin/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use PMC - PMC13527612 MID - NIHMS2201329 COIS- Relevant Financial Relationships: Mr Reville is Executive Director of CASPR, which provided funding for this research. All other authors report no financial or other relationship relevant to the subject of this article. Drs Kennedy, Zhang, and Oslin and Mr Bremseth-Vining are salaried employees of the US Department of Veterans Affairs. EDAT- 2026/07/20 12:40 MHDA- 2026/07/20 12:41 PMCR- 2026/08/31 CRDT- 2026/07/20 10:03 PHST- 2026/07/20 12:41 [medline] PHST- 2026/07/20 12:40 [pubmed] PHST- 2026/07/20 10:03 [entrez] PHST- 2026/08/31 00:00 [pmc-release] AID - 25m16212 [pii] AID - 10.4088/JCP.25m16212 [doi] PST - epublish SO - J Clin Psychiatry. 2026 Jul 15;87(3):25m16212. doi: 10.4088/JCP.25m16212. PMID- 42467949 OWN - NLM STAT- MEDLINE DCOM- 20260806 LR - 20260806 IS - 1746-6318 (Electronic) IS - 1746-630X (Linking) VI - 21 IP - 5 DP - 2026 Sep 1 TI - Glucagon-like peptide-1 receptor agonists in the aging population of people with HIV: emerging evidence and clinical implications. PG - 355-361 LID - 10.1097/COH.0000000000001059 [doi] AB - PURPOSE OF REVIEW: The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for type 2 diabetes and obesity has generated interest in their potential role among people with HIV (PWH), who experience a high burden of cardiometabolic disease and aging-related comorbidities. This review summarizes emerging evidence on the efficacy, safety, and implementation considerations of GLP-1RAs in PWH. RECENT FINDINGS: GLP-1RAs, such as semaglutide, are associated with meaningful reductions in bodyweight, glycemia, and both visceral and hepatic fat in PWH. Emerging data suggest potential effects on behavioral outcomes such as alcohol use and smoking, although evidence in PWH remains limited. Concerns regarding lean mass loss, frailty, and bone health exist but current data are limited and generally reassuring, with functional outcomes largely preserved. HIV-specific studies have largely used lower doses of semaglutide, and evidence in older populations remains sparse. SUMMARY: GLP-1RAs are a promising option for cardiometabolic risk reduction in PWH, with important considerations around tolerability and body composition, particularly in aging and multimorbid populations. Future research should prioritize trials assessing cardiovascular, neuropsychiatric, and substance use outcomes, alongside studies of real-world effectiveness and implementation in routine clinical care. In addition, identifying subgroups most likely to benefit will be important. CI - Copyright (c) 2026 Wolters Kluwer Health, LLC. All rights reserved. FAU - Haidar, Lara AU - Haidar L AD - Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Delaney, Joseph A C AU - Delaney JAC AD - Division of General Internal Medicine, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington, USA. LA - eng PT - Journal Article PT - Review DEP - 20260716 PL - United States TA - Curr Opin HIV AIDS JT - Current opinion in HIV and AIDS JID - 101264945 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *HIV Infections/complications/drug therapy MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Aging MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - *Obesity/drug therapy MH - Aged OTO - NOTNLM OT - HIV OT - aging OT - cardiometabolic disease OT - glucagon-like peptide-1 receptor agonists OT - semaglutide EDAT- 2026/07/17 19:17 MHDA- 2026/08/06 12:37 CRDT- 2026/07/17 16:53 PHST- 2026/08/06 12:37 [medline] PHST- 2026/07/17 19:17 [pubmed] PHST- 2026/07/17 16:53 [entrez] AID - 01222929-990000000-00241 [pii] AID - 10.1097/COH.0000000000001059 [doi] PST - ppublish SO - Curr Opin HIV AIDS. 2026 Sep 1;21(5):355-361. doi: 10.1097/COH.0000000000001059. Epub 2026 Jul 16. PMID- 42466348 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Incretin-based cardiovascular protection beyond diabetes: evidence, mechanisms, and therapeutic frontiers from GLP-1 receptor agonists to multi-agonist therapy. PG - 1870649 LID - 10.3389/fendo.2026.1870649 [doi] LID - 1870649 AB - Incretin-based therapy has moved from glycaemic control into the centre of cardiometabolic medicine. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) consistently reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2DM) and established atherosclerotic cardiovascular disease (ASCVD), while semaglutide 2.4 mg has extended the evidence base to people with overweight or obesity and established cardiovascular disease in the absence of diabetes. Dedicated trials have further expanded the clinical landscape to chronic kidney disease (CKD), obesity-related heart failure with preserved ejection fraction (HFpEF), and symptomatic peripheral artery disease (PAD). Concurrently, dual and triple incretin-based agonists, oral peptide and non-peptide formulations, and combination strategies with sodium-glucose cotransporter-2 (SGLT2) inhibitors and non-steroidal mineralocorticoid receptor antagonists are reshaping treatment algorithms. This critical review synthesizes cardiovascular outcome trials (CVOTs), mechanistic studies, meta-analyses, guideline recommendations, and regulatory developments available up to 30 April 2026. The central conclusion is that incretin-based cardiovascular protection is biologically plausible and clinically reproducible. Critically, this benefit is now independent of diabetes as the defining therapeutic context-a paradigm shift with broad implications for cardiovascular practice. Nevertheless, the magnitude of benefit varies considerably by molecule, dose, population, comparator, and endpoint hierarchy; mediation analyses do not precisely quantify direct cardioprotection; and cardiovascular outcome evidence for newer multi-agonists and oral non-peptide GLP-1 RAs remains incomplete. Interpretation therefore requires a balanced evidence framework: GLP-1 RAs with proven outcome benefit should be prioritized in patients with ASCVD (e.g., LEADER, SUSTAIN-6, HARMONY Outcomes), obesity with established CVD (SELECT), CKD (FLOW), or obesity-related HFpEF (STEP-HFpEF) when supported by trial data and regulatory indications, whereas next-generation agents should be evaluated according to completed CVOTs rather than weight-loss efficacy alone. Remaining research priorities include defining weight-independent mechanisms, optimizing combination therapy, identifying biomarker-defined responders, preserving lean mass during high-efficacy weight loss, and ensuring equitable global access. CI - Copyright (c) 2026 Qiu, Liu and Hu. FAU - Qiu, Libin AU - Qiu L AD - Structural Cardiology Department, Weifang People's Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, China. FAU - Liu, Jinpeng AU - Liu J AD - Cardiology Department 2, Weifang People's Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, China. FAU - Hu, Nana AU - Hu N AD - Cardiology Department 1, Weifang People's Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, China. LA - eng PT - Journal Article PT - Review DEP - 20260702 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide PMC - PMC13372633 OTO - NOTNLM OT - GLP-1 receptor agonists OT - MACE OT - cardiovascular outcomes OT - incretin therapy OT - multi-agonist therapy COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/07/17 12:41 MHDA- 2026/07/17 19:17 PMCR- 2026/07/02 CRDT- 2026/07/17 07:09 PHST- 2026/05/05 00:00 [received] PHST- 2026/05/30 00:00 [revised] PHST- 2026/06/08 00:00 [accepted] PHST- 2026/07/17 19:17 [medline] PHST- 2026/07/17 12:41 [pubmed] PHST- 2026/07/17 07:09 [entrez] PHST- 2026/07/02 00:00 [pmc-release] AID - 10.3389/fendo.2026.1870649 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jul 2;17:1870649. doi: 10.3389/fendo.2026.1870649. eCollection 2026. PMID- 42464447 OWN - NLM STAT- MEDLINE DCOM- 20261028 LR - 20261028 IS - 1365-2125 (Electronic) IS - 0306-5251 (Print) IS - 0306-5251 (Linking) VI - 92 IP - 11 DP - 2026 Nov TI - Semaglutide vs. liraglutide and incidence of diabetes and cardiovascular disease: A target trial emulation using real-world data. PG - 3950-3958 LID - 10.1002/bcp.70711 [doi] AB - AIMS: The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) semaglutide and liraglutide are approved for chronic weight management. Both drugs also have favourable effects on the risk of developing diabetes and cardiovascular disease (CVD) compared with placebo, but their comparative effectiveness for these outcomes is unclear. METHODS: We employed an active comparator, new user design to emulate a target trial using data from MarketScan claims databases. Enrolees free of diabetes and CVD prescribed semaglutide or liraglutide during 2021-2023 were matched 1:1. Primary endpoints included incident diabetes and CVD (myocardial infarction, heart failure or stroke). We used Cox regression adjusted for a propensity score reflective of comorbidities and medication use. RESULTS: We matched 57 456 GLP-1 RA users (mean age 45; 83% female). Over 1-year mean follow-up, we observed 1104 diabetes events and 57 CVD events. After regression adjustment, semaglutide users had 12% lower risk of diabetes (hazard ratio [HR]: 0.88; 95% CI: 0.78, 0.99). For this endpoint, the proportional hazards assumption was violated (p < .0001), so results were stratified by follow-up time. During the first 6 months of follow-up, semaglutide use was not associated with risk of diabetes compared with liraglutide use (HR: 0.99 [0.82-1.18]), but a significant association was present thereafter (HR: 0.80 [0.68, 0.94]). We did not detect a difference in risk of CVD events (HR: 1.25 [0.74-2.11]). CONCLUSIONS: In this real-world study, semaglutide users had lower risk of incident diabetes compared with liraglutide users. Additional research is needed to elucidate comparative effectiveness of these drugs for cardiovascular risk. CI - (c) 2026 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. FAU - Cannon, Ethan J AU - Cannon EJ AUID- ORCID: 0009-0001-1715-9152 AD - Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA. FAU - Wang, Wendy AU - Wang W AD - Department of Epidemiology, Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, Texas, USA. AD - Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas, USA. FAU - Norby, Faye L AU - Norby FL AD - Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA. FAU - Walker, Rob F AU - Walker RF AD - Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA. FAU - Kulasingam, Shalini AU - Kulasingam S AD - Department of Tropical Medicine and Infectious Diseases, Tulane University Celia Weatherhead School of Public Health, New Orleans, Louisiana, USA. AD - Department of Epidemiology, Tulane University Celia Weatherhead School of Public Health, New Orleans, Louisiana, USA. FAU - Chow, Lisa S AU - Chow LS AUID- ORCID: 0000-0002-6210-2307 AD - Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA. FAU - Farley, Joel F AU - Farley JF AD - Department of Pharmaceutical Care & Health Systems, University of Minnesota College of Pharmacy, Minneapolis, Minnesota, USA. FAU - Lutsey, Pamela L AU - Lutsey PL AD - Division of Epidemiology & Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA. LA - eng GR - 25GLP1450320/American Heart Association/ GR - UM1TR004405/NIH Clinical and Translational Science/ GR - T32 HL007779/HL/NHLBI NIH HHS/United States GR - K24 HL159246/HL/NHLBI NIH HHS/United States GR - T32 HL007779/NIH/NHLBI/ GR - K24 HL159246/NIH/NHLBI/ PT - Comparative Study PT - Journal Article DEP - 20260716 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 53AXN4NNHX (Semaglutide) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Liraglutide/therapeutic use/administration & dosage MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Incidence MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/epidemiology/prevention & control MH - Adult MH - *Diabetes Mellitus/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Aged PMC - PMC13714616 OTO - NOTNLM OT - cardiology OT - cardiovascular OT - diabetes OT - endocrinology OT - epidemiology OT - nutrition OT - obesity OT - pharmacoepidemiology OT - public health COIS- J.F.F. has received consulting support from AstaLynx Global and Prime Therapeutics. The other authors have no conflicts of interest to disclose. EDAT- 2026/07/17 10:03 MHDA- 2026/10/28 11:34 PMCR- 2026/07/16 CRDT- 2026/07/17 01:04 PHST- 2026/06/24 00:00 [revised] PHST- 2026/03/30 00:00 [received] PHST- 2026/07/06 00:00 [accepted] PHST- 2026/10/28 11:34 [medline] PHST- 2026/07/17 10:03 [pubmed] PHST- 2026/07/17 01:04 [entrez] PHST- 2026/07/16 00:00 [pmc-release] AID - BCP70711 [pii] AID - 10.1002/bcp.70711 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2026 Nov;92(11):3950-3958. doi: 10.1002/bcp.70711. Epub 2026 Jul 16. PMID- 42460324 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260820 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Tirzepatide and reduced risk of pulmonary embolism and deep vein thrombosis: a multicenter U.S. cohort study. PG - 1885961 LID - 10.3389/fendo.2026.1885961 [doi] LID - 1885961 AB - BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used in patients with type 2 diabetes and obesity. Although tirzepatide improves metabolic and cardiovascular risk factors, its association with venous thromboembolism, including pulmonary embolism and deep vein thrombosis, remains insufficiently characterized in real-world populations. METHODS: We conducted a population-based retrospective cohort study using the TriNetX US Collaborative Network. Adults with type 2 diabetes and overweight or obesity who initiated tirzepatide were propensity score matched to patients receiving lifestyle intervention alone with no exposure to weight-loss medications. Outcomes included incident pulmonary embolism, deep vein thrombosis, and superficial vein thrombosis occurring between 30 days and 12 months after index. Additional analyses included a 90-day landmark sensitivity analysis and an active comparator analysis comparing tirzepatide with semaglutide. RESULTS: After propensity score matching for demographic, metabolic, and clinical covariates, 235, 200 patients were included in the primary analysis (117, 600 per cohort). Tirzepatide use was associated with a significantly lower 12-month risk of pulmonary embolism compared with lifestyle intervention alone (RR, 0.215; 95% CI, 0.185-0.250; HR, 0.258; 95% CI, 0.222-0.299; log-rank P < 0.001). Similar reductions were observed for deep vein thrombosis (RR, 0.303; 95% CI, 0.270-0.340; HR, 0.361; 95% CI, 0.322-0.406; log-rank P < 0.001). No statistically significant difference was observed for superficial vein thrombosis (RR, 0.716; 95% CI, 0.484-1.060; HR, 0.868; 95% CI, 0.586-1.286; log-rank P = 0.480). Findings for pulmonary embolism and deep vein thrombosis remained significant in the 90-day landmark analysis. In the semaglutide comparator analysis, tirzepatide was associated with a significantly lower risk of deep vein thrombosis, while the pulmonary embolism association was significant by risk-ratio analysis but not by Cox regression. CONCLUSIONS: In this large multicenter cohort study, tirzepatide use was associated with a lower risk of pulmonary embolism and deep vein thrombosis compared with lifestyle intervention alone. These findings suggest a potential association between tirzepatide use and lower observed rates of thromboembolic events in patients with diabetes and obesity. CI - Copyright (c) 2026 Kahkedjian, Shah and Kreidieh. FAU - Kahkedjian, Fredy AU - Kahkedjian F AD - Faculty of Medicine, American University of Beirut, Beirut, Lebanon. FAU - Shah, Jaffer AU - Shah J AD - Department of Ophthalmology, Weill Cornell Medicine, New York, NY, United States. FAU - Kreidieh, Firas AU - Kreidieh F AD - Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260701 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - Female MH - *Pulmonary Embolism/epidemiology/prevention & control MH - Male MH - *Venous Thrombosis/epidemiology/prevention & control MH - Middle Aged MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - United States/epidemiology MH - *Obesity/drug therapy/complications MH - Aged MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Cohort Studies PMC - PMC13368568 OTO - NOTNLM OT - GLP-1 receptor agonist OT - TriNetX OT - deep vein thrombosis OT - obesity OT - pulmonary embolism OT - real-world study OT - thrombosis OT - tirzepatide COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/07/16 06:39 MHDA- 2026/07/16 13:02 PMCR- 2026/07/01 CRDT- 2026/07/16 04:44 PHST- 2026/05/19 00:00 [received] PHST- 2026/06/07 00:00 [revised] PHST- 2026/06/18 00:00 [accepted] PHST- 2026/07/16 13:02 [medline] PHST- 2026/07/16 06:39 [pubmed] PHST- 2026/07/16 04:44 [entrez] PHST- 2026/07/01 00:00 [pmc-release] AID - 10.3389/fendo.2026.1885961 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Jul 1;17:1885961. doi: 10.3389/fendo.2026.1885961. eCollection 2026. PMID- 42443144 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260909 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Safety Profile of Tirzepatide in Real-World Clinical Practice: A Pharmacovigilance Study Using the FAERS Database. PG - 8936-8945 LID - 10.1111/dom.71025 [doi] AB - AIMS: Tirzepatide, a first-in-class dual GIP/GLP-1 receptor agonist, was approved by the FDA for type 2 diabetes mellitus (2022) and chronic weight management (2023). Despite superior efficacy in trials, its real-world safety profile remains incompletely characterised. This study aimed to characterise tirzepatide's post-marketing safety signals using the FAERS database. MATERIALS AND METHODS: FAERS reports listing tirzepatide as the primary suspected drug were extracted (Q2 2022-Q4 2025). Disproportionality analysis used four algorithms (ROR, PRR, IC, EBGM). Adverse events were coded using MedDRA terminology. Time-to-onset and comparative analyses versus semaglutide were conducted. RESULTS: A total of 123 145 reports (251 435 individual adverse events) were included. Females accounted for 62.30%, with a mean age of 53.7 years. Major signals included medication errors, injection-site reactions and gastrointestinal disorders. Novel unlabelled signals included eructation, hunger, food craving and starvation ketoacidosis. Compared with semaglutide, tirzepatide showed lower reporting odds of vomiting, constipation and decreased appetite. Among reports with valid onset data, median time to onset was 13 days, with 67.1% occurring within 30 days. CONCLUSIONS: This FAERS study characterises tirzepatide safety signals in real-world practice. Medication errors and injection-site reactions were the strongest signals. Several novel signals warrant further investigation. Among reports with complete onset data, most adverse events were reported early after treatment initiation, suggesting the importance of closer monitoring during the first month of therapy. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Guo, Xinghua AU - Guo X AUID- ORCID: 0000-0003-4815-0158 AD - Department of Pharmacy, Maoming People's Hospital, Maoming, China. FAU - Zhang, Jiahua AU - Zhang J AD - School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China. FAU - Li, Qisen AU - Li Q AD - Department of Pharmacy, Maoming People's Hospital, Maoming, China. FAU - Ye, Zhiqiang AU - Ye Z AD - Department of Pharmacy, Maoming People's Hospital, Maoming, China. FAU - Yuan, Shengyong AU - Yuan S AD - Department of Pharmacy, Maoming People's Hospital, Maoming, China. LA - eng PT - Journal Article DEP - 20260713 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Tirzepatide/adverse effects MH - Female MH - Middle Aged MH - Semaglutide MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Pharmacovigilance MH - Databases, Factual MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Aged MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data PMC - PMC13538822 OTO - NOTNLM OT - FAERS OT - pharmacovigilance OT - semaglutide OT - signal mining OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/07/14 00:35 MHDA- 2026/09/03 05:37 PMCR- 2026/09/03 CRDT- 2026/07/13 23:03 PHST- 2026/05/26 00:00 [revised] PHST- 2026/04/13 00:00 [received] PHST- 2026/06/09 00:00 [accepted] PHST- 2026/09/03 05:37 [medline] PHST- 2026/07/14 00:35 [pubmed] PHST- 2026/07/13 23:03 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71025 [pii] AID - 10.1111/dom.71025 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):8936-8945. doi: 10.1111/dom.71025. Epub 2026 Jul 13. PMID- 42441965 OWN - NLM STAT- MEDLINE DCOM- 20260817 LR - 20260817 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 8 DP - 2026 Aug TI - Comparative Effectiveness of Glucagon-like Peptide-1 Receptor Agonists Versus Oral Agents for Insulin Discontinuation in Type 2 Diabetes : A Target Trial Emulation. PG - 1128-1139 LID - 10.7326/ANNALS-25-05216 [doi] AB - BACKGROUND: Addition of glucagon-like peptide-1 receptor agonists (GLP-1RAs) to basal insulin can decrease insulin requirements, but whether it permits insulin discontinuation is unclear. OBJECTIVE: To compare rates of insulin discontinuation among patients with type 2 diabetes (T2D) receiving basal insulin who initiated treatment with a GLP-1RA, sodium-glucose cotransporter-2 inhibitor (SGLT-2i), or dipeptidyl peptidase-4 inhibitor (DPP-4i) between 2020 and 2022. DESIGN: Target trial emulation. SETTING: U.S. Veterans Health Administration electronic health record (EHR) data. PARTICIPANTS: Veterans with T2D receiving basal insulin. MEASUREMENTS: Insulin discontinuation, defined as the first gap in insulin prescription fills of 12 months or more over 3 years of follow-up. RESULTS: Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A(1c) (HbA(1c)) level of 9% or more. Over 3 years of follow-up, 1480 (16.7%) GLP-1RA initiators compared with 1585 (17.9%) SGLT-2i initiators and 1517 (17.1%) DPP-4i initiators discontinued insulin therapy in the intention-to-treat analysis (risk ratio, 0.93 [95% CI, 0.86 to 1.01] and 0.98 [CI, 0.87 to 1.09] for the GLP-1RA arm compared with the SGLT-2i and DPP-4i arms, respectively). Results were not substantively different in a modified per protocol analysis. None of the subgroups showed a comparative advantage of GLP-1RAs with respect to insulin discontinuation over SGLT-2is or DPP-4is. LIMITATION: Possible residual confounding; misclassification of exposure and outcome using EHRs may bias associations toward the null. CONCLUSION: Among veterans with T2D receiving basal insulin therapy, addition of GLP-1RA did not increase the chances of stopping insulin therapy compared with SGLT-2i or DPP-4i therapy. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs. FAU - Lipska, Kasia J AU - Lipska KJ AD - Section of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, and Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut (K.J.L., B.G.). FAU - Zawack, Kelson AU - Zawack K AD - Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut (K.Z.). FAU - Yan, Lei AU - Yan L AUID- ORCID: 0000-0002-4779-2688 AD - Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, and Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut (L.Y., J.L.). FAU - Mutalik, Pradeep AU - Mutalik P AUID- ORCID: 0009-0002-4573-4617 AD - Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, and Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut (P.M.). FAU - Li, Jingmao AU - Li J AD - Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, and Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut (L.Y., J.L.). FAU - Gulanski, Barbara AU - Gulanski B AUID- ORCID: 0000-0003-4056-3409 AD - Section of Endocrinology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, and Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut (K.J.L., B.G.). FAU - Ioannou, George N AU - Ioannou GN AD - Research and Development, Veterans Affairs Puget Sound Health Care System, and Divisions of Gastroenterology, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, Washington (G.N.I.). FAU - Aslan, Mihaela AU - Aslan M AD - Veterans Affairs Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, and Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut (M.A.). LA - eng PT - Comparative Study PT - Journal Article DEP - 20260714 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Insulin/therapeutic use/administration & dosage MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Semaglutide MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Male MH - Female MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Middle Aged MH - Aged MH - Administration, Oral MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/07/13 22:42 MHDA- 2026/08/17 23:39 CRDT- 2026/07/13 17:02 PHST- 2026/08/17 23:39 [medline] PHST- 2026/07/13 22:42 [pubmed] PHST- 2026/07/13 17:02 [entrez] AID - 10.7326/ANNALS-25-05216 [doi] PST - ppublish SO - Ann Intern Med. 2026 Aug;179(8):1128-1139. doi: 10.7326/ANNALS-25-05216. Epub 2026 Jul 14. PMID- 42437874 OWN - NLM STAT- MEDLINE DCOM- 20260730 LR - 20260813 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 34 IP - 8 DP - 2026 Aug TI - How Low Could Semaglutide Prices Fall? An Analysis of Production Cost and Implications for Global Access. PG - 1545-1550 LID - 10.1002/oby.70241 [doi] AB - OBJECTIVE: This study aimed to estimate potential launch prices of generic semaglutide following patent expiry in 2026 and to quantify the global obesity and type 2 diabetes (T2DM) burden in countries where generic access may become possible. METHODS: We used World Bank population data and World Obesity and Diabetes Atlas prevalence estimates to calculate obesity and T2DM burden. Patent status was identified using MedsPaL and cross-checked with regional databases. We applied updated cost-plus pricing methods using 2024-2025 Indian active pharmaceutical ingredient shipment data to estimate production costs for oral and injectable semaglutide, incorporating formulation, packaging, taxation, and profit assumptions. RESULTS: Twelve countries with 2026 patent expiry account for 47% of obesity and 49% of T2DM globally. No patent filings were identified in 150 additional countries. By the end of 2026, generic injectable semaglutide could be available in 162 countries representing 69% of global T2DM and 84% of clinical obesity. Estimated generic injectable costs ranged from $28 to $140 per person-year; oral formulations ranged from $186 to $380 per person-year. Injection devices contributed disproportionately to total cost. CONCLUSIONS: Patent expiry may substantially expand access at lower prices, but device costs, secondary patents, and health system constraints could limit equitable uptake without coordinated policy action. CI - (c) 2026 The Obesity Society. FAU - Levi, Jacob AU - Levi J AD - NHS Royal Free Hospital Trust, London, UK. FAU - Cross, Samuel AU - Cross S AUID- ORCID: 0000-0001-8129-1919 AD - Christchurch Hospital, Te Whatu Ora, New Zealand. FAU - Ramesh, Nydile AU - Ramesh N AD - Hywel Dda Health Board, NHS Wales, Carmarthen, UK. FAU - Venter, Francois AU - Venter F AD - University of Witwatersrand, Johannesburg, South Africa. FAU - Hill, Andrew AU - Hill A AD - Department of Translational Medicine, University of Liverpool, Liverpool, UK. LA - eng GR - International Treatment Preparedness Coalition (ITPC)/ PT - Journal Article DEP - 20260712 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Drugs, Generic) RN - 0 (Hypoglycemic Agents) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/economics/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/economics/epidemiology MH - *Obesity/drug therapy/economics/epidemiology MH - *Drugs, Generic/economics MH - *Hypoglycemic Agents/economics/therapeutic use MH - *Drug Costs MH - Global Health PMC - PMC13422654 OTO - NOTNLM OT - cost OT - generic OT - semaglutide OT - weight loss COIS- F.V. reports receiving lecture fees and travel support from Roche, grant support, advisory board fees, and provision of drugs from Gilead Sciences, advisory board fees from ViiV Healthcare, lecture fees from Merck and Adcock Ingram, and lecture fees and advisory board fees from Johnson & Johnson. The other authors declare no conflicts of interest. EDAT- 2026/07/13 04:09 MHDA- 2026/07/30 12:43 PMCR- 2026/07/30 CRDT- 2026/07/12 23:27 PHST- 2026/04/27 00:00 [revised] PHST- 2026/03/03 00:00 [received] PHST- 2026/05/13 00:00 [accepted] PHST- 2026/07/30 12:43 [medline] PHST- 2026/07/13 04:09 [pubmed] PHST- 2026/07/12 23:27 [entrez] PHST- 2026/07/30 00:00 [pmc-release] AID - OBY70241 [pii] AID - 10.1002/oby.70241 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Aug;34(8):1545-1550. doi: 10.1002/oby.70241. Epub 2026 Jul 12. PMID- 42435064 OWN - NLM STAT- MEDLINE DCOM- 20261026 LR - 20261028 IS - 1433-2965 (Electronic) IS - 0937-941X (Print) IS - 0937-941X (Linking) VI - 37 IP - 9 DP - 2026 Sep TI - Lower fall and femoral fracture risks with semaglutide and tirzepatide compared with DPP-4 inhibitors in older adults with type 2 diabetes. PG - 2451-2463 LID - 10.1007/s00198-026-08134-y [doi] AB - This retrospective cohort study evaluated whether semaglutide and tirzepatide reduce the risk of falls and femoral fractures in older adults with type 2 diabetes and overweight or obesity. The findings showed significantly lower risks of both outcomes compared with DPP-4 inhibitors. PURPOSE: Incretin-based therapies may influence musculoskeletal health. This study evaluated the association of semaglutide and tirzepatide with femoral fractures and falls in older adults with type 2 diabetes (T2DM) and overweight or obesity. METHODS: This retrospective cohort study using the TriNetX database (2018-2025) included adults aged >/= 65 with T2DM and BMI >/= 25 kg/m(2). Patients receiving semaglutide or tirzepatide were compared with those on dipeptidyl peptidase-4 (DPP-4) inhibitors using 1:1 propensity score matching. Primary and secondary outcomes were 1-year femoral fracture and falls, respectively. RESULTS: After matching, 27,896 patients were included in the semaglutide/DPP-4 comparison and 12,808 in the tirzepatide/DPP-4 comparison. Femoral fractures were significantly lower with semaglutide (0.3% vs. 0.5%; HR 0.488; 95% CI 0.367-0.649; P < 0.0001) and tirzepatide (0.2% vs. 0.4%; HR 0.452; 95% CI 0.280-0.729; P = 0.0008) compared with DPP-4 inhibitors. Fall risk was also reduced for both semaglutide (3.6% vs. 5.4%; HR 0.663; 95% CI 0.612-0.718; P < 0.0001) and tirzepatide (3.6% vs. 5.7%; HR 0.664; 95% CI 0.591-0.747; P < 0.0001). Subgroup analyses showed consistent fall reduction across categories, while fracture reduction was more pronounced in patients with BMI >/= 30 kg/m(2). CONCLUSION: In older adults with T2DM and overweight/obesity, semaglutide and tirzepatide were associated with significantly lower risks of femoral fracture and falls compared with DPP-4 inhibitors, suggesting musculoskeletal benefits beyond glycemic control. CI - (c) 2026. The Author(s). FAU - Chen, Hsin-Yu AU - Chen HY AUID- ORCID: 0009-0007-0552-569X AD - Department of Family Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Wu, Jheng-Yan AU - Wu JY AD - Department of Nutrition, Chi Mei Medical Center, Tainan, Taiwan. FAU - Chu, Yi-Hsin AU - Chu YH AD - Department of Family Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Chen, Tse-Wei AU - Chen TW AD - Division of Cardiology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Huang, Chun-Feng AU - Huang CF AUID- ORCID: 0000-0002-6265-5155 AD - Department of Family Medicine, Chi Mei Medical Center, Tainan, Taiwan. cfhuang.ymuh@gmail.com. AD - Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. cfhuang.ymuh@gmail.com. AD - Department of Leisure Services Management, Chaoyang University of Technology, Taichung, Taiwan. cfhuang.ymuh@gmail.com. AD - School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. cfhuang.ymuh@gmail.com. LA - eng GR - CMFHR115039/Chi Mei Medical Center/ PT - Comparative Study PT - Journal Article DEP - 20260711 PL - England TA - Osteoporos Int JT - Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA JID - 9100105 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - Tirzepatide/therapeutic use MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - Male MH - Female MH - *Accidental Falls/prevention & control/statistics & numerical data MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use MH - Obesity/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Femoral Fractures/prevention & control/etiology/epidemiology MH - Overweight/complications MH - *Osteoporotic Fractures/prevention & control/etiology MH - Aged, 80 and over MH - Risk Assessment/methods PMC - PMC13710654 OTO - NOTNLM OT - femoral fracture OT - glucagon-like peptide-1 receptor agonist OT - semaglutide OT - tirzepatide OT - type 2 diabetes mellitus COIS- Declarations. Conflicts of interest: Hsin-Yu Chen, Jheng-Yan Wu, Yi-Hsin Chu, Tse-Wei Chen and Chun-Feng Huang declare that they have no conflict of interest. EDAT- 2026/07/12 00:56 MHDA- 2026/10/26 17:31 PMCR- 2026/07/11 CRDT- 2026/07/11 11:03 PHST- 2026/04/18 00:00 [received] PHST- 2026/06/30 00:00 [accepted] PHST- 2026/10/26 17:31 [medline] PHST- 2026/07/12 00:56 [pubmed] PHST- 2026/07/11 11:03 [entrez] PHST- 2026/07/11 00:00 [pmc-release] AID - 10.1007/s00198-026-08134-y [pii] AID - 8134 [pii] AID - 10.1007/s00198-026-08134-y [doi] PST - ppublish SO - Osteoporos Int. 2026 Sep;37(9):2451-2463. doi: 10.1007/s00198-026-08134-y. Epub 2026 Jul 11. PMID- 42426564 OWN - NLM STAT- MEDLINE DCOM- 20261008 LR - 20261013 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 11 DP - 2026 Nov TI - Efficacy and Safety of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Ventricular Arrhythmias and Cardiovascular Events: A Disease-Stratified Network Meta-Analysis. PG - 9753-9766 LID - 10.1111/dom.71094 [doi] AB - BACKGROUND: The effects of individual sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) and glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) on ventricular arrhythmias (VAs) remain uncertain. This study aimed to comprehensively compare their effects on VAs and cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) and/or heart failure (HF). METHODS: Four databases were systematically searched from inception through May 16, 2026, to identify randomised controlled trials. Nine outcomes were evaluated, including VAs, cardiovascular mortality, all-cause mortality and hospitalization for heart failure (HHF). RESULTS: Thirty-seven publications, corresponding to 32 independent RCTs and 140 156 participants, were included. Most SGLT2 inhibitors and GLP-1 receptor agonists did not significantly increase VA risk; empagliflozin showed a statistically significant but exploratory signal for lower VA risk in the T2DM network (OR 0.31, 95% CI 0.11-0.86). Dapagliflozin in the HF network and empagliflozin and liraglutide in the T2DM network, were associated with lower cardiovascular and all-cause mortality. SGLT2 inhibitors consistently reduced HHF across both networks. Dapagliflozin was associated with lower AKI risk, while albiglutide and liraglutide were associated with lower hypoglycemia risk; however, these safety findings should be interpreted cautiously because adverse-event reporting was not uniform across trials. Several safety outcomes were based on sparse events and non-uniform adverse-event reporting; no statistically significant increase in diabetic ketoacidosis risk was detected for empagliflozin and the semaglutide fracture signal should be interpreted cautiously. Because the evidence networks were largely placebo-centered and lacked closed loops, treatment rankings and between-drug comparisons depend heavily on the transitivity assumption. These rankings, including P-score rankings, should be regarded as exploratory and should not be interpreted as head-to-head comparative evidence. CONCLUSIONS: SGLT2 inhibitors consistently reduced HHF risk across the HF and T2DM networks and selected agents showed mortality benefits in clinically relevant populations. Empagliflozin showed an exploratory signal for lower VA risk in the T2DM network; however, this finding requires confirmation in trials with prespecified and adjudicated arrhythmia endpoints. Safety signals, including DKA and fracture, should be interpreted cautiously because adverse-event ascertainment was not uniform across trials. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Sun, Wen-Ting AU - Sun WT AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Liu, Rui-Xing AU - Liu RX AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Jiang, Yao-Hao AU - Jiang YH AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Zhao, Ying-Kun AU - Zhao YK AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Yi-Cai AU - Yi-Cai AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Wu, Yi-Feng AU - Wu YF AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Li, Tian-Li AU - Li TL AUID- ORCID: 0009-0006-6523-4694 AD - Department of Integrated Traditional Chinese and Western Medicine Cardiology, China-Japan Friendship Hospital, Beijing, China. FAU - Chang, Pei-Feng AU - Chang PF AD - Department of Cardiovascular Medicine, Dongzhimen Hospital, Beijing, China. AD - Beijing University of Chinese Medicine, Beijing, China. LA - eng GR - 8240153568/National Natural Science Foundation of China/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260709 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Benzhydryl Compounds) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucosides) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Heart Failure/mortality/drug therapy MH - *Arrhythmias, Cardiac/drug therapy MH - Benzhydryl Compounds/therapeutic use MH - Randomized Controlled Trials as Topic MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Semaglutide MH - Glucosides/therapeutic use OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) OT - heart failure OT - network meta-analysis OT - pairwise meta-analysis OT - sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) OT - type 2 diabetes mellitus OT - ventricular arrhythmias EDAT- 2026/07/10 00:36 MHDA- 2026/10/08 05:31 CRDT- 2026/07/09 23:42 PHST- 2026/06/21 00:00 [revised] PHST- 2026/05/19 00:00 [received] PHST- 2026/07/02 00:00 [accepted] PHST- 2026/10/08 05:31 [medline] PHST- 2026/07/10 00:36 [pubmed] PHST- 2026/07/09 23:42 [entrez] AID - 10.1111/dom.71094 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Nov;28(11):9753-9766. doi: 10.1111/dom.71094. Epub 2026 Jul 9. PMID- 42424036 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20260813 IS - 1473-2300 (Electronic) IS - 0300-0605 (Print) IS - 0300-0605 (Linking) VI - 54 IP - 7 DP - 2026 Jul TI - Effect of glucagon-like peptide-1 receptor agonists on body weight and urinary albumin-to-creatinine ratio in patients with and without type 2 diabetes: A systematic review and meta-analysis. PG - 3000605261458641 LID - 10.1177/03000605261458641 [doi] LID - 03000605261458641 AB - ObjectiveGlucagon-like peptide-1 receptor agonists are established for weight management and cardiovascular risk reduction, with emerging evidence for kidney protection. Whether albuminuria-lowering effects extend to nondiabetic chronic kidney disease remains uncertain.MethodsWe performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided meta-analysis of randomized controlled trials comparing glucagon-like peptide-1 receptor agonists with placebo or standard care. Primary outcomes were change in body weight (kg) and percentage change in urinary albumin-to-creatinine ratio; change in estimated glomerular filtration rate was the secondary outcome. We conducted prespecified subgroup analyses (including glycemic status) and random-effects meta-regression to explore heterogeneity. Risk of bias assessment (2.0), small-study effects (funnel plot and trim-and-fill analyses), sensitivity analyses (leave-one-out and low-risk-only), and Grading of Recommendations Assessment, Development and Evaluation certainty ratings were applied.ResultsTen trials (n = 26,088) were included. Glucagon-like peptide-1 receptor agonists reduced body weight (mean difference, -5.85 kg; 95% confidence interval: -7.78 to -3.92) with a consistent direction of effect across studies despite heterogeneity. Glucagon-like peptide-1 receptor agonists lowered urinary albumin-to-creatinine ratio overall (mean difference, -27.94%; 95% confidence interval: -37.72 to -18.15). Stratified analyses showed a precise reduction in type 2 diabetes mellitus (mean difference, -25.70%; I(2) = 0%) and a directionally concordant but less precise reduction in populations without type 2 diabetes mellitus (mean difference, -30.93%; I(2) = 96%). A modest between-group difference in estimated glomerular filtration rate was also observed (mean difference, -0.82 mL/min/1.73 m(2); I(2) = 0%). Meta-regression indicated attenuation with longer treatment duration and greater benefit with higher baseline albuminuria; drug class and glycemic status were not consistent moderators of urinary albumin-to-creatinine ratio in prespecified subgroups. Findings were robust to multiple sensitivity analyses. Certainty of evidence was high for weight and moderate for urinary albumin-to-creatinine ratio.ConclusionsGlucagon-like peptide-1 receptor agonists were associated with clinically meaningful weight loss and lower urinary albumin-to-creatinine ratio across included trials. A directionally similar signal was observed in populations without type 2 diabetes mellitus, although interpretation of this subgroup remains limited by heterogeneity, imprecision, and the inability to evaluate intermediate glycemic phenotypes. Variability in urinary albumin-to-creatinine ratio estimates appears to reflect duration and baseline risk more than a lack of effect. FAU - Huang, Rong AU - Huang R AD - Public Health Management Department, Chengdu Qingbaijiang District People's Hospital, Chengdu, China. RINGGOLD: 663923 FAU - Wang, Bin AU - Wang B AUID- ORCID: 0009-0004-2797-5710 AD - Quality Control Department, Chengdu Qingbaijiang District Center for Disease Control and Prevention, Chengdu, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260709 PL - England TA - J Int Med Res JT - The Journal of international medical research JID - 0346411 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - AYI8EX34EU (Creatinine) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/urine/physiopathology MH - *Albuminuria/drug therapy/urine MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Creatinine/urine MH - *Body Weight/drug effects MH - Glomerular Filtration Rate/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic PMC - PMC13351244 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - albuminuria OT - chronic kidney disease OT - exenatide OT - meta-analysis OT - semaglutide OT - urinary albumin-to-creatinine ratio COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/07/09 12:32 MHDA- 2026/07/09 12:33 PMCR- 2026/07/09 CRDT- 2026/07/09 11:23 PHST- 2026/07/09 12:33 [medline] PHST- 2026/07/09 12:32 [pubmed] PHST- 2026/07/09 11:23 [entrez] PHST- 2026/07/09 00:00 [pmc-release] AID - 10.1177_03000605261458641 [pii] AID - 10.1177/03000605261458641 [doi] PST - ppublish SO - J Int Med Res. 2026 Jul;54(7):3000605261458641. doi: 10.1177/03000605261458641. Epub 2026 Jul 9. PMID- 42423951 OWN - NLM STAT- MEDLINE DCOM- 20260929 LR - 20261001 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 43 IP - 10 DP - 2026 Oct TI - Special Considerations When Using GLP-1 Receptor Agonists in the Treatment of Obesity and Diabetes Mellitus Type 2 in Older Adults. PG - 4380-4394 LID - 10.1007/s12325-026-03702-4 [doi] AB - The prevalence of obesity and type 2 diabetes mellitus (T2DM) in the older adult population is rising continuously worldwide, with approximately 40% and 29% of individuals affected in this group, respectively. These conditions have a substantial impact on older adults and are associated with reduced quality of life, increased morbidity, functional decline, and cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an important option for the management of T2DM and obesity. However, special considerations are needed for specific age groups due to risks of adverse effects and increased comorbidity burden. GLP-1 RAs, including tirzepatide, liraglutide, and semaglutide, promote weight loss by suppressing appetite, improving insulin secretion, and delaying gastric emptying. Large clinical trials have supported GLP-1 RAs as an excellent option for reducing glycated hemoglobin and body weight, as well as for reducing major renal and cardiovascular adverse effects; however, evidence in older adults remains limited. Given the health considerations for older adults, weight loss efforts with GLP-1 RAs require cautious approaches, as sarcopenia is a relevant topic in this specific age group. Polypharmacy and side effects also need to be considered when treating an older adult with GLP-1 RA. Overall, GLP-1 RAs represent a valuable and promising treatment option for older adults with T2DM and obesity. CI - (c) 2026. The Author(s). FAU - Pendrey, Anna Geraldina AU - Pendrey AG AUID- ORCID: 0009-0002-0114-1342 AD - Department of Family Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. apendrey@iu.edu. FAU - Rivera Sierra, Jennyfer Alejandra AU - Rivera Sierra JA AD - Facultad de Ciencias Medicas, Distrito Central, Universidad Nacional Autonoma de Honduras, Francisco Morazan, Honduras. FAU - Alvarez Lobo, Fernando Alberto AU - Alvarez Lobo FA AD - Facultad de Ciencias Medicas, Distrito Central, Universidad Nacional Autonoma de Honduras, Francisco Morazan, Honduras. FAU - Rios Herrera, Eblin Jackeline AU - Rios Herrera EJ AD - Facultad de Ciencias Medicas, Distrito Central, Universidad Nacional Autonoma de Honduras, Francisco Morazan, Honduras. FAU - Fernandez Munoz, Yolanda Maria AU - Fernandez Munoz YM AD - Distrito Central, Universidad Catolica de Honduras, Francisco Morazan, Honduras. FAU - Sevilla Martir, Javier Francisco AU - Sevilla Martir JF AD - Department of Family Medicine, Indiana University School of Medicine, Indianapolis, IN, USA. LA - eng PT - Journal Article PT - Review DEP - 20260709 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Obesity/drug therapy MH - Tirzepatide MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Liraglutide/therapeutic use/adverse effects MH - Glucagon-Like Peptides/therapeutic use/adverse effects MH - Weight Loss/drug effects PMC - PMC13619721 OTO - NOTNLM OT - Diabetes OT - Glucagon-like peptide-1 receptor agonists OT - Obesity OT - Older adults COIS- Declarations. Conflict of Interest: Anna Geraldina Pendrey, Javier Francisco Sevilla Martir, Jennyfer Alejandra Rivera Sierra, Fernando Alberto Alvarez Lobo, Eblin Jackeline Rios Herrera, and Yolanda Maria Fernandez Munoz declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this manuscript. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. EDAT- 2026/07/09 16:09 MHDA- 2026/09/29 05:30 PMCR- 2026/07/09 CRDT- 2026/07/09 11:10 PHST- 2026/03/17 00:00 [received] PHST- 2026/06/22 00:00 [accepted] PHST- 2026/09/29 05:30 [medline] PHST- 2026/07/09 16:09 [pubmed] PHST- 2026/07/09 11:10 [entrez] PHST- 2026/07/09 00:00 [pmc-release] AID - 10.1007/s12325-026-03702-4 [pii] AID - 3702 [pii] AID - 10.1007/s12325-026-03702-4 [doi] PST - ppublish SO - Adv Ther. 2026 Oct;43(10):4380-4394. doi: 10.1007/s12325-026-03702-4. Epub 2026 Jul 9. PMID- 42420795 OWN - NLM STAT- MEDLINE DCOM- 20260903 LR - 20260908 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 10 DP - 2026 Oct TI - Neuropsychiatric Outcomes With Tirzepatide, Semaglutide, and Other GLP-1 Receptor Agonists. PG - 8895-8904 LID - 10.1111/dom.71088 [doi] AB - AIMS: Neuropsychiatric safety concerns, including depression and suicidal ideation, have emerged during the expanding clinical use of incretin-based therapies for type 2 diabetes mellitus (T2DM) and obesity. However, whether risks differ across successive generations of incretin-based therapies remains uncertain. MATERIALS AND METHODS: This retrospective cohort study used the TriNetX Global Federated Network (> 192 million patients). Adults with T2DM, obesity, or both initiating tirzepatide, semaglutide, or other glucagon-like peptide-1 receptor agonists (GLP-1 RAs) between July 2022 and June 2025 were identified using a new-user design with a 12-month washout. Propensity score matching balanced demographic, clinical, and metabolic variables. Two comparisons were conducted: tirzepatide versus semaglutide and semaglutide versus other GLP-1 RAs. Follow-up included Year 1 (day 31-365) and Year 2 landmark analysis (day 366-730). Hazard ratios (HRs) for incident depression, anxiety, and suicidal ideation were estimated using Cox models. RESULTS: After matching, 85 546 pairs were included for tirzepatide versus semaglutide and 80 115 pairs for semaglutide versus other GLP-1 RAs. Tirzepatide and semaglutide showed similar risks for the composite psychiatric outcome (Year 1 HR 0.984 [95% CI 0.950-1.019]; Year 2 HR 1.002 [0.960-1.046]); a nominally higher anxiety hazard was observed with tirzepatide during Year 2 (HR 1.052 [1.001-1.106]), which should be interpreted cautiously given multiple comparisons. Compared with other GLP-1 RAs, semaglutide was associated with lower risks of depression (HR 0.811 [0.770-0.855]), anxiety (HR 0.915 [0.871-0.961]), suicidal ideation (HR 0.488 [0.339-0.702]), and the composite psychiatric outcome (HR 0.866 [0.832-0.901]) during Year 1. CONCLUSIONS: In real-world practice, tirzepatide and semaglutide demonstrated comparable neuropsychiatric risk profiles over 2 years. Semaglutide was associated with lower psychiatric event rates compared with earlier-generation GLP-1 receptor agonists. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Chen, Solomon Chih-Cheng AU - Chen SC AUID- ORCID: 0000-0003-0031-6147 AD - Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan. AD - Department of Pediatrics, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Wang, Tso-Jen AU - Wang TJ AD - Department of Psychiatry, Chiayi Branch, Taichung Veterans General Hospital, Chiayi City, Taiwan. FAU - Chou, Chu-Kuang AU - Chou CK AUID- ORCID: 0000-0003-2588-6883 AD - Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan. AD - Obesity Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan. FAU - Lee, Chun AU - Lee C AD - Clinical Data Center, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City, Taiwan. LA - eng PT - Journal Article DEP - 20260708 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use/adverse effects MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Retrospective Studies MH - Middle Aged MH - Depression/epidemiology/chemically induced MH - Suicidal Ideation MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Obesity/drug therapy/psychology MH - Anxiety/epidemiology/chemically induced MH - Adult MH - Aged MH - Incretins/adverse effects/therapeutic use PMC - PMC13538802 OTO - NOTNLM OT - cohort studies OT - comparative effectiveness research OT - depressive disorder OT - glucagon-like peptide-1 receptor agonists OT - postmarketing surveillance OT - real-world evidence OT - suicidal ideation COIS- Gemini 3.1 Pro (Google LLC) was utilized solely for language polishing, grammatical correction, and enhancing the clarity and flow of the manuscript's English text. The AI tool was not used to generate original research ideas, interpret data, perform statistical analysis, or draft the initial scientific content of the paper. All research findings and the final version of the text were reviewed and approved by the authors, who remain fully responsible for the accuracy and integrity of the work. The authors declare no conflicts of interest. EDAT- 2026/07/09 00:40 MHDA- 2026/09/03 05:36 PMCR- 2026/09/03 CRDT- 2026/07/08 23:53 PHST- 2026/06/27 00:00 [revised] PHST- 2026/05/03 00:00 [received] PHST- 2026/06/30 00:00 [accepted] PHST- 2026/09/03 05:36 [medline] PHST- 2026/07/09 00:40 [pubmed] PHST- 2026/07/08 23:53 [entrez] PHST- 2026/09/03 00:00 [pmc-release] AID - DOM71088 [pii] AID - 10.1111/dom.71088 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Oct;28(10):8895-8904. doi: 10.1111/dom.71088. Epub 2026 Jul 8. PMID- 42419304 OWN - NLM STAT- MEDLINE DCOM- 20260917 LR - 20260930 IS - 2451-9448 (Electronic) IS - 2451-9448 (Linking) VI - 33 IP - 9 DP - 2026 Sep 17 TI - GLP-1R and GIPR crosstalk modulates insulinotropic signaling pathways. PG - 1284-1299.e8 LID - S2451-9456(26)00201-1 [pii] LID - 10.1016/j.chembiol.2026.06.003 [doi] AB - Drugs targeting glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors (GLP-1R and GIPR) show strong clinical effects in type 2 diabetes and obesity. Both GIPR agonism and antagonism enhance GLP-1R agonist efficacy, indicating important incretin receptor crosstalk. We show that GLP-1 and semaglutide, but not exendin-4, promote heterodimerization between GLP-1R and GIPR through interactions between TM4 of GLP-1R and TM1/2 of GIPR. Phosphoproteomics and molecular dynamics reveal that dimerizing and non-dimerizing agonists differentially influence GLP-1R, activating divergent signaling pathways in human pancreatic islets. Moreover, semaglutide and exenatide display distinct patterns in their FDA-reported safety profiles. When co-expressed, GLP-1R enhances GIPR signaling in a beta-arrestin-dependent manner, while increasing GIPR levels decreases GLP-1R signaling. Additionally, we show that changes in GIPR expression are clinically associated with adiposity and diabetic phenotypes. These findings highlight heterodimerization and receptor expression as key modulators of GLP-1R/GIPR signaling, offering mechanistic insights, and guiding drug design strategies that incorporate receptor crosstalk. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Lindquist, Peter AU - Lindquist P AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Hoegen Dijkhof, Luuk R AU - Hoegen Dijkhof LR AD - Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. FAU - Drzazga, Anna K AU - Drzazga AK AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Institute of Molecular and Industrial Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Lodz, Poland. FAU - Sabatier, Pierre AU - Sabatier P AD - Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark; Cardio-Thoracic Translational Medicine Laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden. FAU - Stepniewski, Tomasz M AU - Stepniewski TM AD - Research Programme on Biomedical Informatics, Hospital del Mar Research Institute & Pompeu Fabra University, Barcelona, Spain; InterAx Biotech AG, Villigen, Switzerland. FAU - Granlund, Louise AU - Granlund L AD - Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. FAU - Lechner, Maico Y AU - Lechner MY AD - Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark. FAU - Zhong, Yi AU - Zhong Y AD - Department of Physiology and Pharmacology and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden; Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Gasbjerg, Laerke S AU - Gasbjerg LS AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Hartmann, Bolette AU - Hartmann B AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Lauschke, Volker M AU - Lauschke VM AD - Department of Physiology and Pharmacology and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden; Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; University of Tubingen, Tubingen, Germany; Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha, China. FAU - Holst, Jens J AU - Holst JJ AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Olsen, Jesper V AU - Olsen JV AD - Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark. FAU - Korsgren, Olle AU - Korsgren O AD - Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden. FAU - Selent, Jana AU - Selent J AD - Research Programme on Biomedical Informatics, Hospital del Mar Research Institute & Pompeu Fabra University, Barcelona, Spain. FAU - Wright, Shane C AU - Wright SC AD - Department of Physiology and Pharmacology and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden. FAU - Hauser, Alexander S AU - Hauser AS AD - Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Center for Pharmaceutical Data Science Education, University of Copenhagen, Copenhagen, Denmark. FAU - Rosenkilde, Mette M AU - Rosenkilde MM AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: rosenkilde@sund.ku.dk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260708 PL - United States TA - Cell Chem Biol JT - Cell chemical biology JID - 101676030 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor/metabolism/chemistry/genetics MH - *Signal Transduction/drug effects MH - *Receptors, Gastrointestinal Hormone/metabolism/chemistry/genetics/agonists MH - Semaglutide MH - Animals MH - Glucagon-Like Peptides/pharmacology/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/metabolism MH - HEK293 Cells MH - Exenatide/pharmacology MH - Receptor Cross-Talk OTO - NOTNLM OT - GIPR OT - GLP-1R OT - GPCR OT - adverse drug events OT - crosstalk OT - heterodimerization OT - obesity OT - stoichiometry OT - type 2 diabetes COIS- Declaration of interests The authors declare that the study was conducted without any competing interests. T.M.: employed by InterAx Biotech A.G. L.S.G.: received one speaker honorarium from Novo Nordisk and is a co-founder and minority shareholder of Antag Therapeutics. V.M.L.: cofounder and CEO of HepaPredict A.B., cofounder and shareholder of Shanghai Hepo Biotechnology Ltd. J.J.H. and M.M.R. minority shareholders and cofounders of Antag Therapeutics and Bainan Biotech. J.J.H.: served on scientific advisory panels for and/or has received speaker honoraria from AlphaSights, Eli Lilly, Novo Nordisk, MSD/Merck, Shouti/Structure X, and Zealand Pharma. EDAT- 2026/07/09 04:10 MHDA- 2026/09/17 23:34 CRDT- 2026/07/08 18:41 PHST- 2025/08/08 00:00 [received] PHST- 2026/02/19 00:00 [revised] PHST- 2026/06/09 00:00 [accepted] PHST- 2026/09/17 23:34 [medline] PHST- 2026/07/09 04:10 [pubmed] PHST- 2026/07/08 18:41 [entrez] AID - S2451-9456(26)00201-1 [pii] AID - 10.1016/j.chembiol.2026.06.003 [doi] PST - ppublish SO - Cell Chem Biol. 2026 Sep 17;33(9):1284-1299.e8. doi: 10.1016/j.chembiol.2026.06.003. Epub 2026 Jul 8. PMID- 42417199 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260813 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 18 IP - 7 DP - 2026 Jul TI - Real-World vs. Randomized Trial Evidence for Incretin-Based Therapies: A Narrative Review. PG - e70248 LID - 10.1111/1753-0407.70248 [doi] LID - e70248 AB - Incretin-based therapies have transformed the management of obesity and type 2 diabetes (T2D). Pivotal randomized controlled trials (RCTs) report substantial weight loss and glycemic improvements; the extent to which these translate to clinical populations remains uncertain. Seven 2026-published RCT meta-analyses (comprising 127 RCTs and 58 976 participants) were compared with 26 real-world studies identified through structured PubMed search. Primary outcomes were body weight loss and HbA1c reduction; secondary outcomes included major adverse cardiovascular events (MACE), neurological end-points, and safety. The comparison is descriptive. For T2D, real-world semaglutide achieved 4.7-10.5 kg weight loss (6-12 months) and 1.0-1.3 percentage-point HbA1c reductions, lower than RCT meta-analytic estimates (tirzepatide mean difference [MD] -9.55% vs. placebo). Without diabetes, real-world persister analyses (SHAPE study: semaglutide -14.1%, tirzepatide -16.5%) approximated per-protocol RCT estimates (semaglutide -14.9%, tirzepatide 15 mg -20.9%), whereas intention-to-treat real-world estimates were substantially lower. Just 13% of semaglutide users reached 2.4 mg and 25.9% of tirzepatide users reached 15 mg. Real-world cardiovascular data showed 20%-46% MACE reductions, broadly consistent with the RCT reduction. Differences between T2D and non-T2D populations likely reflect channeling bias and differential follow-up. Real-world incretin-based therapy effectiveness is broadly consistent with RCT efficacy when dose attainment is accounted for. High discontinuation rates (20%-50% within 1 year) and prior GLP-1 RA exposure track with the observed efficacy gap. Clinicians can expect RCT-level outcomes in patients who tolerate and persist with target doses. Head-to-head cardiovascular outcome trials comparing tirzepatide and semaglutide in non-diabetic populations are needed. CI - (c) 2026 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Bloomgarden, Zachary AU - Bloomgarden Z AUID- ORCID: 0000-0003-3863-9267 AD - Department of Medicine, Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, New York, New York, USA. LA - eng PT - Journal Article PT - Review PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - Weight Loss/drug effects MH - Glucagon-Like Peptides/therapeutic use MH - Tirzepatide MH - *Obesity/drug therapy PMC - PMC13343302 COIS- The author declares no conflicts of interest. EDAT- 2026/07/08 16:09 MHDA- 2026/07/08 18:51 PMCR- 2026/07/08 CRDT- 2026/07/08 06:24 PHST- 2026/06/01 00:00 [revised] PHST- 2026/05/21 00:00 [received] PHST- 2026/06/04 00:00 [accepted] PHST- 2026/07/08 18:51 [medline] PHST- 2026/07/08 16:09 [pubmed] PHST- 2026/07/08 06:24 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - JDB70248 [pii] AID - 10.1111/1753-0407.70248 [doi] PST - ppublish SO - J Diabetes. 2026 Jul;18(7):e70248. doi: 10.1111/1753-0407.70248. PMID- 42414233 OWN - NLM STAT- MEDLINE DCOM- 20260918 LR - 20260918 IS - 1557-9034 (Electronic) IS - 1092-6429 (Linking) VI - 36 IP - 11 DP - 2026 Nov TI - Brain Neuromodulation via Endoscopic Gastric Implant Improves Glycemic Control in Insulin-Dependent Type-2 Diabetes: First-in-Human Feasibility and Autonomic Response Study. PG - 777-785 LID - 10.1177/10926429261468981 [doi] AB - BACKGROUND: A miniaturized, self-powered Brain NeuroModulator (BNM) device, endoscopically implanted under neuroleptanalgesia in the submucosal layer of the proximal lesser gastric curvature, has the potential to consistently increase parasympathetic tone as measured by heart rate variability (HRV). OBJECTIVE: Since type-2 diabetes mellitus is associated with autonomic nervous system dysfunction, we assessed whether BNM induced autonomic rebalancing translates into measurable improvement of glycemic control through a change of HRV. METHODS: The BNM device was implanted on a 69-year-old male with a 25-year history of insulin-dependent type-2 diabetes mellitus under treatment with 22 IU/night of insulin plus semaglutide and metformin. HRV was assessed before and after the procedure. After the implant, continuous glucose monitoring (CGM) with an Abbott FreeStyle Libre sensor (15-minute sampling interval) was performed. RESULTS: The endoscopic procedure was uneventful and lasted 15 minutes. The BNM device remained in a stable position throughout the observation period. HRV analysis confirmed increased variability. Post-implant morning HRV showed progressive parasympathetic recovery compared with baseline. Within 2 months of implantation, therapy with semaglutide and metformin was discontinued, and insulin was progressively reduced from 22 to 0 IU. CONCLUSIONS: The BNM implant was feasible and safe, with clinically meaningful improvement in glycemic control associated with autonomic rebalancing within approximately 10 weeks of implantation. These data provide compelling preliminary evidence that correcting sympathetic dominance through vagal afferent stimulation may alter the clinical course of insulin-dependent type 2 diabetes. FAU - Cigaina, Valerio AU - Cigaina V AD - Department of Pharmacy, Health and Nutritional Sciences, and Division of Foregut Surgery, Azienda Ospedaliera di Cosenza, University of Calabria, Arcavacata di Rende, Cosenza, Italy. FAU - Saggioro, Alfredo AU - Saggioro A AD - Department of Pharmacy, Health and Nutritional Sciences, and Division of Foregut Surgery, Azienda Ospedaliera di Cosenza, University of Calabria, Arcavacata di Rende, Cosenza, Italy. FAU - Fabris, Paolo AU - Fabris P AD - Department of Pharmacy, Health and Nutritional Sciences, and Division of Foregut Surgery, Azienda Ospedaliera di Cosenza, University of Calabria, Arcavacata di Rende, Cosenza, Italy. FAU - Bonavina, Luigi AU - Bonavina L AD - Department of Pharmacy, Health and Nutritional Sciences, and Division of Foregut Surgery, Azienda Ospedaliera di Cosenza, University of Calabria, Arcavacata di Rende, Cosenza, Italy. LA - eng PT - Case Reports PT - Journal Article DEP - 20260707 PL - United States TA - J Laparoendosc Adv Surg Tech A JT - Journal of laparoendoscopic & advanced surgical techniques. Part A JID - 9706293 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/physiopathology/therapy/drug therapy/blood MH - Aged MH - Feasibility Studies MH - *Glycemic Control/methods MH - Heart Rate MH - Semaglutide MH - Blood Glucose MH - Autonomic Nervous System/physiopathology MH - Hypoglycemic Agents/therapeutic use MH - Insulin MH - Continuous Glucose Monitoring MH - Gastroscopy OTO - NOTNLM OT - autonomic nervous system OT - brain neuromodulation OT - heart rate variability OT - metabolic syndrome OT - parasympathetic tone OT - type-2 diabetes COIS- Disclosure StatementNo competing financial interests exist. EDAT- 2026/07/08 02:08 MHDA- 2026/09/18 05:36 CRDT- 2026/07/07 22:33 PHST- 2026/09/18 05:36 [medline] PHST- 2026/07/08 02:08 [pubmed] PHST- 2026/07/07 22:33 [entrez] AID - 10.1177/10926429261468981 [doi] PST - ppublish SO - J Laparoendosc Adv Surg Tech A. 2026 Nov;36(11):777-785. doi: 10.1177/10926429261468981. Epub 2026 Jul 7. PMID- 42411489 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260707 IS - 2768-6698 (Electronic) IS - 2768-6698 (Linking) VI - 31 IP - 6 DP - 2026 Jun 22 TI - Semaglutide Modulates Visceral Adipose Tissue Lipid Metabolism in Type 2 Diabetic Mice: A Lipidomics Study. PG - 49873 LID - 10.31083/FBL49873 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major public health challenge. This study aimed to explore the molecular mechanisms underlying the effects of semaglutide on lipid metabolism in visceral white adipose tissue in a mouse model of T2DM. METHODS: Male C57BL/6J mice were given a normal diet, a high-fat diet with streptozotocin, or a high-fat diet with semaglutide. Blood samples, liver tissue, and adipose tissue were collected for analysis. Serum adipokines, inflammatory cytokines, liver function, and lipid profiles were assessed. White adipose tissue and liver sections were processed for hematoxylin and eosin (H&E) staining or immunohistochemistry (IHC) staining for the macrophage marker F4/80. High-throughput targeted lipidomic analysis of epididymal white adipose tissue from these animals was performed using liquid chromatography-tandem mass spectrometry to characterize changes in lipid composition and function. Furthermore, the expression of genes related to adipokines, inflammation, and lipid metabolism in epididymal adipose tissue was determined by reverse transcription-quantitative PCR (RT-qPCR). RESULTS: Semaglutide significantly improved systemic metabolism in mice with T2DM, as demonstrated by reductions in body weight, blood glucose, serum lipid levels, and insulin resistance indices homeostasis model assessment of insulin resistance (HOMA-IR) and adipose tissue insulin resistance index (Adipo-IR). Serum Leptin, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) levels were downregulated, while Adiponectin levels were elevated. Histological analysis revealed that semaglutide effectively reduced adipocyte size, suppressed macrophage infiltration in adipose tissue, and decreased liver lipid accumulation. Targeted lipidomic profiling identified 24 lipid subclasses, of which 50 lipid molecules were significantly changed after semaglutide treatment. Enrichment analysis identified 15 metabolic pathways, with glycerophospholipid metabolism being the most prominently affected. RT-qPCR results confirmed that semaglutide altered the expression of key genes involved in glycerolipid, glycerophospholipid, fatty acid, and cholesterol metabolism. CONCLUSIONS: These results shed light on the comprehensive remodeling of semaglutide in improving lipid metabolism in epididymal white adipose tissue mice with T2DM. CI - Copyright: (c) 2026 The Author(s). Published by IMR Press. FAU - Chen, Xinlei AU - Chen X AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. FAU - Tu, Bingrou AU - Tu B AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. FAU - Li, Zhaoyuan AU - Li Z AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. FAU - Gao, Ping AU - Gao P AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. FAU - Xu, Yi AU - Xu Y AD - Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. AD - Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. FAU - Yao, Yue AU - Yao Y AD - Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, Heilongjiang, China. AD - Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. LA - eng GR - 82300921/National Natural Science Foundation of China/ PT - Journal Article PL - Singapore TA - Front Biosci (Landmark Ed) JT - Frontiers in bioscience (Landmark edition) JID - 101612996 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Animals MH - Semaglutide MH - Male MH - *Lipid Metabolism/drug effects MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy MH - Mice MH - Mice, Inbred C57BL MH - *Glucagon-Like Peptides/pharmacology MH - *Intra-Abdominal Fat/metabolism/drug effects MH - *Diabetes Mellitus, Experimental/metabolism/drug therapy MH - Lipidomics MH - Diet, High-Fat/adverse effects MH - Liver/metabolism/drug effects MH - Insulin Resistance MH - Adipose Tissue, White/metabolism/drug effects OTO - NOTNLM OT - adipose tissue, white OT - diabetes mellitus, type 2 OT - lipid metabolism OT - semaglutide EDAT- 2026/07/07 13:10 MHDA- 2026/07/08 02:10 CRDT- 2026/07/07 06:53 PHST- 2026/01/09 00:00 [received] PHST- 2026/03/14 00:00 [revised] PHST- 2026/04/10 00:00 [accepted] PHST- 2026/07/08 02:10 [medline] PHST- 2026/07/07 13:10 [pubmed] PHST- 2026/07/07 06:53 [entrez] AID - S2768-6701(26)02100-3 [pii] AID - 10.31083/FBL49873 [doi] PST - ppublish SO - Front Biosci (Landmark Ed). 2026 Jun 22;31(6):49873. doi: 10.31083/FBL49873. PMID- 42410309 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Cardiovascular Outcomes With Tirzepatide Versus GLP-1 Receptor Agonists in Overweight or Obesity: A Systematic Review and Meta-Analysis. PG - 8627-8636 LID - 10.1111/dom.71051 [doi] AB - AIMS: To compare cardiovascular outcomes associated with tirzepatide versus glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in adults with overweight or obesity. MATERIALS AND METHODS: PubMed/MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched through 30 March 2026. The study was registered in PROSPERO (CRD420261354941). Randomized and observational studies comparing tirzepatide with GLP-1 receptor agonists and reporting cardiovascular outcomes were included. Data were extracted on study characteristics and outcomes using adjusted hazard ratios when available. Risk of bias was assessed using RoB 2 and ROBINS-I. RESULTS: Eight studies (one randomized and seven observational) including 323 439 patients were analysed. Tirzepatide was not associated with a statistically significant reduction in major adverse cardiovascular events (MACE) compared with GLP-1 receptor agonists (HR 0.85, 95% CI 0.70-1.04; I (2) = 90.4%). Substantial heterogeneity was observed. Effect estimates were directionally consistent across secondary outcomes, including all-cause mortality (HR 0.90, 95% CI 0.79-1.02) and cardiovascular mortality (HR 0.88, 95% CI 0.76-1.00). In exploratory subgroup analyses, patients with type 2 diabetes showed lower estimated risks of all-cause mortality (HR 0.85, 95% CI 0.76-0.94) and heart failure (HR 0.75, 95% CI 0.58-0.97). CONCLUSIONS: Tirzepatide was not associated with a statistically significant reduction in MACEs. Although effect estimates were directionally consistent across analyses, substantial heterogeneity and the predominance of observational studies limit causal interpretation. Further randomized trials are needed to clarify the comparative cardiovascular effects of tirzepatide. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Silva, Joao Pedro Machado Ribeiro Jacintho AU - Silva JPMRJ AUID- ORCID: 0009-0002-4395-4851 AD - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Nogueira, Bruno Viruez AU - Nogueira BV AD - Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil. FAU - Sartori, Deborah Lomelino AU - Sartori DL AD - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - da Silva, Juliana Rizzo Cardoso AU - da Silva JRC AD - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Sciota, Lucca Biagio Argenton AU - Sciota LBA AD - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. FAU - de Mendonca Bisneto, Oscar Inacio AU - de Mendonca Bisneto OI AD - Universidade Federal de Campina Grande, Cajazeiras, Paraiba, Brazil. FAU - Gomes, Wilton Francisco AU - Gomes WF AD - Instituto de Neurologia e Cardiologia de Curitiba, Curitiba, Parana, Brazil. AD - Faculdades Pequeno Principe, Curitiba, Parana, Brazil. AD - Hospital INC, Curitiba, Parana, Brazil. AD - Irmandade da Santa Casa de Misericordia de Curitiba, Curitiba, Parana, Brazil. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260706 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - *Cardiovascular Diseases/epidemiology/prevention & control/mortality MH - *Overweight/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Treatment Outcome PMC - PMC13449074 OTO - NOTNLM OT - cardiovascular disease OT - meta-analysis OT - obesity care OT - semaglutide COIS- W.F.G. reports proctorship honoraria from Abbott (Navitor transcatheter aortic valve) and Meril Life Sciences (MyVal transcatheter aortic valve) and speaker honoraria from Libbs Farmaceutica (ticagrelor). He has received travel and meeting support from Teleflex Incorporated for attendance at the Triple-i CVI Summit 2026. He reports no financial or non-financial relationships with Eli Lilly, Novo Nordisk or any other manufacturer of tirzepatide or GLP-1 receptor agonists and no relationships relevant to the subject matter of this manuscript. The other authors declare no conflicts of interest. EDAT- 2026/07/07 04:11 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/07/06 23:41 PHST- 2026/06/11 00:00 [revised] PHST- 2026/04/27 00:00 [received] PHST- 2026/06/18 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/07/07 04:11 [pubmed] PHST- 2026/07/06 23:41 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71051 [pii] AID - 10.1111/dom.71051 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8627-8636. doi: 10.1111/dom.71051. Epub 2026 Jul 6. PMID- 42405390 OWN - NLM STAT- MEDLINE DCOM- 20260921 LR - 20261017 IS - 2212-3873 (Electronic) IS - 1871-5303 (Print) IS - 1871-5303 (Linking) VI - 26 DP - 2026 TI - Semaglutide and Musculoskeletal Health: A Mendelian Randomization Study Based on GLP-1 Receptor Expression. PG - e18715303422692 LID - 10.2174/0118715303422692260617052555 [doi] LID - E18715303422692 AB - INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor (GLP1R) agonist, is clinically used for glycemic control and weight loss. However, it is still unclear whether it has any impact on bones and muscles. Does semaglutide have any impact on the musculoskeletal system of patients during its use, or does it have any negative effects on them? This study aims to assess the impact of GLP1R on bone and muscle using Mendelian Randomization. METHODS: We employed expression quantitative trait loci (eQTL) data for the GLP1R gene and combined it with genome-wide association studies (GWAS) data for skeletal and muscular traits to conduct Summary-data-based Mendelian Randomization (SMR) analysis. The exposure was defined as the blood expression level of the GLP1R gene, with the eQTL serving as the instrumental variable. Total bone mineral density, osteoporosis, and fractures were used to evaluate bone health, while appendicular lean mass, grip strength, and walking speed assessed muscle quality. Type 2 diabetes and body mass index (BMI) served as positive controls. RESULTS: The top eQTL rs9283907 was used to predict GLP1R expression. Positive control results confirmed that GLP1R agonists are effective diabetes treatments and can reduce BMI. There were no significant impacts on osteoporosis (beta: 0.00, 95% CI: -0.01, 0.01, p=0.416), total bone mineral density (beta: -0.03, 95% CI: -0.19, 0.13, p=0.702), fracture (beta: 0.09, 95% CI: -0.10, 0.28, p=0.343), walking pace (beta: 0.00, 95% CI: -0.01, 0.06, p=0.216), appendicular lean mass (beta: -0.01, 95% CI: -0.08, 0.06, p=0.676), or grip strength (beta: -0.02, 95% CI: -0.06, 0.02, p=0.425). DISCUSSION: This Mendelian randomization study provides genetic evidence that GLP-1 receptor expression is not causally associated with altered musculoskeletal health. The findings suggest that semaglutide is unlikely to adversely affect bone metabolism or muscle function regarding the outcomes measured. These results support the musculoskeletal safety profile of semaglutide; however, as genetic associations do not fully capture the clinical pharmacology of the drug, further validation through long-term randomized controlled trials is warranted. CONCLUSION: According to our results, high expression of glucagon-like peptide-1 receptor does not lead to bone and muscle loss, which indicates that semaglutide may be safe for the musculoskeletal system. FAU - Li, Dong AU - Li D AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Liang, Xinyu AU - Liang X AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Li, Zhijun AU - Li Z AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Zhang, Huafeng AU - Zhang H AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. FAU - Li, Hui AU - Li H AD - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China. LA - eng PT - Journal Article PL - United Arab Emirates TA - Endocr Metab Immune Disord Drug Targets JT - Endocrine, metabolic & immune disorders drug targets JID - 101269157 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/pharmacology MH - *Glucagon-Like Peptide-1 Receptor/genetics/biosynthesis MH - *Mendelian Randomization Analysis/methods MH - Genome-Wide Association Study/methods MH - Bone Density/drug effects/genetics MH - *Diabetes Mellitus, Type 2/drug therapy/genetics/metabolism MH - *Hypoglycemic Agents/therapeutic use/adverse effects/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Quantitative Trait Loci MH - Muscle, Skeletal/drug effects PMC - PMC13670192 OTO - NOTNLM OT - GLP1R OT - bone OT - diabetes OT - muscle OT - musculoskeletal health OT - obesity EDAT- 2026/07/06 06:31 MHDA- 2026/09/21 05:34 PMCR- 2026/10/15 CRDT- 2026/07/06 05:45 PHST- 2025/08/06 00:00 [received] PHST- 2026/01/26 00:00 [revised] PHST- 2026/01/29 00:00 [accepted] PHST- 2026/09/21 05:34 [medline] PHST- 2026/07/06 06:31 [pubmed] PHST- 2026/07/06 05:45 [entrez] PHST- 2026/10/15 00:00 [pmc-release] AID - EMIDDT-EPUB-156752 [pii] AID - EMIDDT-26-E18715303422692 [pii] AID - 10.2174/0118715303422692260617052555 [doi] PST - ppublish SO - Endocr Metab Immune Disord Drug Targets. 2026;26:e18715303422692. doi: 10.2174/0118715303422692260617052555. PMID- 42403263 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Semaglutide Injection Once-Weekly for Weight Management in Adults: Results From A Randomized Phase III, Active-Controlled Study. PG - 8602-8612 LID - 10.1111/dom.71069 [doi] AB - AIM: To evaluate and compare the efficacy, safety, and immunogenicity of a synthetic semaglutide injection (Test semaglutide) with Wegovy (Reference semaglutide) injection for weight management. MATERIALS AND METHODS: This randomized, Phase III, non-inferiority study included adults with obesity or overweight with or without comorbidities from 21 centers in India. A total of 270 patients with body mass index >/= 30 kg/m(2) or >/= 27 kg/m(2) with the presence of at least one of the weight-related comorbidities (hypertension, dyslipidemia or type 2 diabetes mellitus) were randomized (2:1) to receive either Test semaglutide (N = 177) or Reference semaglutide injection (N = 90) once weekly with dose escalation from 0.25 to 2.4 mg. The primary endpoint was percentage change in bodyweight from baseline to Week 24. RESULTS: Out of 267 randomized patients, 246 completed the study. At Week 24, mean percent weight change from baseline was -13.8% +/- 4.28% in Test and -14.1% +/- 4.11% in Reference groups with least-squares mean difference of 0.26% (95% CI: -0.86% to 1.39%), meeting the criterion for non-inferiority. The proportion of patients with >/= 5% and >/= 10% weight loss were 96.40% and 80.60% in Test, and 98.80% and 80.00% in Reference groups, respectively at Week 24. Improvements in body mass index, waist circumference, SF-36 total score, and glycemic parameters were comparable between groups. Treatment-emergent adverse events were reported in 72.30% and 76.70% in the Test and Reference groups, respectively, with gastrointestinal events being the most common. CONCLUSIONS: Test synthetic semaglutide was found to be non-inferior to Reference semaglutide in weight management with or without comorbidities. TRIAL REGISTRATION: Prospectively registered on the Clinical Trials Registry-India, CTRI/2025/04/085487 [Registered on: 24/04/2025], https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTIwNjMx&Enc=&userName=. CI - (c) 2026 Sun Pharma Laboratories limited. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ambika Gopalakrishnan, Unnikrishnan AU - Ambika Gopalakrishnan U AD - Chellaram Diabetes Institute, Pune, Maharashtra, India. FAU - Joshi, Ameya AU - Joshi A AD - Bhaktivedanta Hospital and Research Institute, Thane, Maharashtra, India. FAU - Kumar, Harish AU - Kumar H AD - Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala, India. FAU - Giri, Richa AU - Giri R AD - G.S.V.M Medical College, Kanpur, Uttar Pradesh, India. FAU - Maheshwari, Sanjiv AU - Maheshwari S AD - Jawahar Lal Nehru Medical College, Ajmer, Rajasthan, India. FAU - Prasad, Valluri Satya AU - Prasad VS AD - King George Hospital, Visakhapatnam, Andhra Pradesh, India. FAU - Shukla, Jitendra AU - Shukla J AD - Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh, India. FAU - M Chowdaiah, Rekha AU - M Chowdaiah R AD - Mandya Institute of Medical Science, Mandya, Karnataka, India. FAU - Agrawal, Nutan Kumar AU - Agrawal NK AD - M.L.B Medical College, Jhansi, Uttar Pradesh, India. FAU - Rasal, Yogesh AU - Rasal Y AD - Pulse Multispecialty Hospital, Pune, Maharashtra, India. FAU - Sahoo, Banshidhar AU - Sahoo B AD - KIDS Hospital, Khordha, Odisha, India. FAU - Bhandari, Shweta AU - Bhandari S AUID- ORCID: 0000-0002-0008-7949 AD - Vincare Hospital, Bathinda, Punjab, India. FAU - Gowda, Ambanna AU - Gowda A AD - Citizen Hospital, Bangalore, Karnataka, India. FAU - Phadke, Uday AU - Phadke U AD - Sahyadri Super Speciality Hospital, Pune, Maharashtra, India. AD - Sahyadri Clinical Research and Development Center, Pune, Maharashtra, India. FAU - Supe, Pravin AU - Supe P AD - Supe Heart and Diabetes Hospital and Research Centre, Nashik, Maharashtra, India. FAU - Pathak, Niranjan AU - Pathak N AD - OJAS Multispeciality Hospital, Pune, Maharashtra, India. FAU - Chandrappa, Ambrish AU - Chandrappa A AD - Medstar Speciality Hospital, Bangalore, Karnataka, India. FAU - Sonawane, Ashutosh AU - Sonawane A AD - Panacea Hospital, Nashik, Maharashtra, India. FAU - Bahulikar, Yash AU - Bahulikar Y AD - MMFHA Joshi Hospital, Pune, Maharashtra, India. FAU - Bhaskar, Amit AU - Bhaskar A AD - Janta Hospital and Maternity Center, Varanasi, Uttar Pradesh, India. FAU - Radhakrishnan, Arunkumar AU - Radhakrishnan A AD - Chettinad Hospital and Research Institute, Chengalpattu, Tamil Nadu, India. FAU - Yadav, Priyanka AU - Yadav P AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. FAU - Pandit, Sucheta AU - Pandit S AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. FAU - Sonowal, Supriya AU - Sonowal S AUID- ORCID: 0009-0002-5481-7780 AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. FAU - Patil, Dipak AU - Patil D AUID- ORCID: 0009-0008-8690-3302 AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. FAU - Ghadge, Pravin AU - Ghadge P AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. FAU - Mehta, Suyog AU - Mehta S AD - Sun Pharma Laboratories Limited, Mumbai, Maharashtra, India. LA - eng GR - Sun Pharmaceutical Industries Limited/ PT - Clinical Trial, Phase III PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260706 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *Obesity/drug therapy/complications MH - Adult MH - Weight Loss/drug effects MH - *Overweight/drug therapy/complications MH - Drug Administration Schedule MH - *Anti-Obesity Agents/administration & dosage/adverse effects MH - Treatment Outcome MH - Diabetes Mellitus, Type 2/drug therapy MH - Body Mass Index MH - Aged PMC - PMC13449013 OTO - NOTNLM OT - GLP-1 receptor agonist OT - immunogenicity OT - non-inferiority trial OT - obesity OT - overweight OT - semaglutide OT - weight management COIS- Unnikrishnan Ambika Gopalakrishnan, Ameya Joshi, Harish Kumar, Richa Giri, Sanjiv Maheshwari, Valluri Satya Prasad, Jitendra Shukla, Rekha M. Chowdaiah, Nutan Kumar Agrawal, Yogesh Rasal, Banshidhar Sahoo, Shweta Bhandari, Ambanna Gowda, Uday Phadke, Pravin Supe, Niranjan Pathak, Ambrish Chandrappa, Ashutosh Sonawane, Yash Bahulikar, Amit Bhaskar, and Arunkumar Radhakrishnan were the study investigators, and they received grant from the sponsor for conducting the study at their respective sites. Priyanka Yadav, Sucheta Pandit, Supriya Sonowal, Dipak Patil, Pravin Ghadge, and Suyog Mehta are full-time employees of Sun Pharma Laboratories Limited. EDAT- 2026/07/06 06:31 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/07/06 04:42 PHST- 2026/06/24 00:00 [revised] PHST- 2026/04/01 00:00 [received] PHST- 2026/06/24 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/07/06 06:31 [pubmed] PHST- 2026/07/06 04:42 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71069 [pii] AID - 10.1111/dom.71069 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8602-8612. doi: 10.1111/dom.71069. Epub 2026 Jul 6. PMID- 42401410 OWN - NLM STAT- MEDLINE DCOM- 20260825 LR - 20260904 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 231 DP - 2026 Sep TI - GLP-1 receptor agonist therapy in children and adolescents with obesity: A network meta-analysis of differential cardiometabolic efficacy and safety profiles. PG - 108333 LID - S1043-6618(26)00248-3 [pii] LID - 10.1016/j.phrs.2026.108333 [doi] AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in adolescents with overweight or obesity, but their comparative effects on cardiometabolic outcomes across different agents remain uncertain. We aimed to compare the efficacy and safety of different GLP-1RAs on key cardiometabolic parameters in adolescents with overweight or obesity, with or without type 2 diabetes. METHODS: We searched PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov from inception to May 1, 2026. Randomised clinical trials comparing GLP-1RAs with placebo or another active agent in eligible adolescents were included. Two reviewers independently extracted data and assessed risk of bias following PRISMA guidelines for network meta-analysis. We used a Bayesian random-effects model for data synthesis. RESULTS: 17 RCTs with 1230 participants were included. Semaglutide 2.4 mg SC was associated with the largest reductions in body weight (mean difference -18.00 kg; 95% credible interval -24.34 to -11.69, high confidence), BMI (-5.9 kg/m(2), -10.5 to -1.3, high confidence), and waist circumference (-12.2 cm, -21.67 to -2.67). For glycaemic control, dulaglutide 1.5 mg SC showed the largest reduction in HbA1c (-1.50%, -1.84 to -1.15, high confidence), and lixisenatide 20 ug SC showed the largest reduction in fasting plasma glucose (-3.98 mmol/L, -7.46 to -0.60); however, these rankings derive from networks with sparse head-to-head evidence and wide credible intervals for indirect comparisons. Exenatide 20 ug SC was associated with a reduction in systolic blood pressure (-6.64 mmHg, -13.22 to -0.17) based on limited indirect evidence from early-phase trials. No agent improved lipid profiles in a statistically significant manner. CONCLUSION: In this network meta-analysis of adolescents with overweight or obesity, GLP-1RAs showed differential cardiometabolic profiles. Semaglutide 2.4 mg produced the largest point estimates for weight-related outcomes, dulaglutide 1.5 mg and lixisenatide 20 ug for glycaemic endpoints, and exenatide 20 ug for systolic blood pressure. These findings are hypothesis-generating: most active-treatment comparisons were indirect, many nodes were informed by single trials, and SUCRA rankings should not be interpreted as evidence of definitive clinical superiority. CI - Copyright (c) 2026 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Li, Yao AU - Li Y AD - Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110004, China. FAU - Xu, Xiaoou AU - Xu X AD - Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, China. FAU - Tuersun, Adili AU - Tuersun A AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. FAU - Fan, Xichen AU - Fan X AD - Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China. FAU - Qin, Muting AU - Qin M AD - Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang 110004, China. FAU - Zhao, Xin AU - Zhao X AD - Laboratory of Medicine, Datong Second People's Hospital (Datong Tumor Hospital), Datong 037006, China. FAU - Abuduaini, Subinuer AU - Abuduaini S AD - School of Pharmaceutical Sciences, Tokyo University of Science, Tokyo 162-8601, Japan. FAU - Xing, Haoyue AU - Xing H AD - Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: xinghy90@163.com. FAU - Chen, Huanxue AU - Chen H AD - Department of Rheumatology and Immunology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: chenhx@sj-hospital.org. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260704 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Anti-Obesity Agents) RN - 0 (Blood Glucose) RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Adolescent MH - Child MH - Humans MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Exenatide/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Pediatric Obesity/drug therapy/blood MH - Randomized Controlled Trials as Topic MH - Semaglutide/adverse effects/therapeutic use MH - Treatment Outcome MH - Weight Loss/drug effects MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins OTO - NOTNLM OT - Adolescents OT - GLP-1 Receptor Agonists OT - Network Meta-Analysis OT - Obesity COIS- Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence the work submitted, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript. EDAT- 2026/07/05 04:10 MHDA- 2026/08/25 23:33 CRDT- 2026/07/04 19:34 PHST- 2026/05/10 00:00 [received] PHST- 2026/06/25 00:00 [revised] PHST- 2026/07/02 00:00 [accepted] PHST- 2026/08/25 23:33 [medline] PHST- 2026/07/05 04:10 [pubmed] PHST- 2026/07/04 19:34 [entrez] AID - S1043-6618(26)00248-3 [pii] AID - 10.1016/j.phrs.2026.108333 [doi] PST - ppublish SO - Pharmacol Res. 2026 Sep;231:108333. doi: 10.1016/j.phrs.2026.108333. Epub 2026 Jul 4. PMID- 42388102 OWN - NLM STAT- MEDLINE DCOM- 20260806 LR - 20260806 IS - 1531-7080 (Electronic) IS - 0268-4705 (Linking) VI - 41 IP - 5 DP - 2026 Sep 1 TI - Rebooting blood vessel repair: implications of the SEMA-VR CardioLink-15 trial. PG - 459-466 LID - 10.1097/HCO.0000000000001323 [doi] AB - PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major adverse cardiovascular events (MACE), heart failure, and mortality through undetermined mechanisms independent of glycemic control. This review examines emerging evidence that GLP-1RAs overcome vascular regenerative cell exhaustion (VRCE), a pathological depletion of bone marrow-derived progenitor cells that mediate vessel repair. RECENT FINDINGS: VRCE, the progressive loss of circulating progenitor cells that mediate vessel regeneration, has recently emerged as an underappreciated driver of MACE risk in individuals living with type 2 diabetes (T2D), obesity or atherosclerotic cardiovascular disease. In a recent randomized translational trial of semaglutide vs. usual care, SEMA-VR CardioLink-15 provided the direct evidence that 6-month semaglutide administration could reverse VRCE profile associated with longstanding cardiometabolic disease (34.8% increase in VR myeloid progenitor cells, 66.2% expansion of endothelial precursor cells). Semaglutide additionally reduced circulating granulocyte content and suppressed pro-inflammatory TNF and interleukin family cytokines in sera. SUMMARY: GLP-1RAs can restore bone marrow progenitor cell output towards a more vessel regenerative profile. Reversal of VRCE may partially explain early event curve separation in cardiovascular outcome trials with multiple GLP-1RAs. Therefore, circulating VR cell content could serve as a measure of compromised vascular regenerative capacity and elevated cardiovascular disease risk. CI - Copyright (c) 2026 Wolters Kluwer Health, LLC. All rights reserved. FAU - Verma, Raj AU - Verma R AD - School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland. FAU - Verma, Meena AU - Verma M AD - School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland. FAU - Park, Brady AU - Park B AD - Temerty Faculty of Medicine, University of Toronto. FAU - Teoh, Hwee AU - Teoh H AD - Division of Cardiac Surgery, St Michael's Hospital of Unity Health Toronto. AD - Division of Endocrinology and Metabolism, St Michael's Hospital of Unity Health Toronto. AD - Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute. FAU - Quan, Adrian AU - Quan A AD - Division of Cardiac Surgery, St Michael's Hospital of Unity Health Toronto. AD - Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute. FAU - Connelly, Kim A AU - Connelly KA AD - Temerty Faculty of Medicine, University of Toronto. AD - Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute. AD - Division of Cardiology, St Michael's Hospital of Unity Health Toronto. AD - Department of Medicine. AD - Department of Physiology. FAU - Hess, David A AU - Hess DA AD - Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute. AD - Department of Pharmacology and Toxicology, University of Toronto, Toronto. AD - Department of Physiology and Pharmacology, University of Western Ontario. AD - Molecular Medicine Research Laboratories, Robarts Research Institute, London, Ontario, Canada. LA - eng PT - Journal Article PT - Review DEP - 20260701 PL - United States TA - Curr Opin Cardiol JT - Current opinion in cardiology JID - 8608087 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Regeneration/drug effects MH - *Cardiovascular Diseases/prevention & control/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - *Blood Vessels/physiology/drug effects OTO - NOTNLM OT - endothelial precursor cells OT - glucagon-like peptide-1 receptor agonists OT - hematopoietic progenitor cells OT - semaglutide OT - vascular regenerative cell exhaustion EDAT- 2026/07/02 06:39 MHDA- 2026/08/06 12:37 CRDT- 2026/07/02 03:53 PHST- 2026/08/06 12:37 [medline] PHST- 2026/07/02 06:39 [pubmed] PHST- 2026/07/02 03:53 [entrez] AID - 00001573-990000000-00287 [pii] AID - 10.1097/HCO.0000000000001323 [doi] PST - ppublish SO - Curr Opin Cardiol. 2026 Sep 1;41(5):459-466. doi: 10.1097/HCO.0000000000001323. Epub 2026 Jul 1. PMID- 42387310 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Efficacy and Safety of Intensifying Once-Weekly Insulin Icodec Treatment With Once-Weekly Semaglutide in Adults With Type 2 Diabetes: A Single-Arm, Open-Label, Treat-to-Target, Phase 3b Trial (ONWARDS 8). PG - 8515-8522 LID - 10.1111/dom.71049 [doi] AB - AIMS: To investigate the efficacy and safety of intensifying once-weekly insulin icodec (icodec) with once-weekly semaglutide in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: ONWARDS 8 was a single-arm, open-label, treat-to-target, Phase 3b trial comprising a 26-week icodec run-in period and a 26-week semaglutide intensification period. Eligible participants were adults with T2D (glycated haemoglobin [HbA1c]: 7.5%-10.5%) receiving daily basal insulin but not receiving a glucagon-like peptide-1 receptor agonist. Following the run-in period, participants with HbA1c levels > 7.0% and 40 years or with obesity ("BMI >/= 30 kg/m2") and type 2 diabetes (HbA1c >/= 6.5% or fasting glucose.>/= 125 mg/dL). Qualifying events were restricted to May 1, 2022, through November 21, 2024. We established two cohorts: one initiating tirzepatide and another semaglutide, ensuring each patient had at least three prescriptions and no prior exposure to the comparator drug or other GLP-1 receptor agonists. The index date was defined as the first co-occurrence of the obesity/diabetes criteria and the respective drug prescription. To ensure comparability, we performed 1:1 propensity matching, resulting in 47,804 patients in each cohort. Outcomes, including all-cause mortality, MACE, heart failure exacerbation, ischemic stroke/TIA, hospitalization/ED use, dementia, UTI, adverse Gastrointestinal (GI) effects, and changes in HbA1c, were assessed within a 1-year window after the index date.ResultsOur matched cohort had a mean age of 75 years, with 45% male patients and 74% identified as white. Patients treated with tirzepatide experienced a significantly lower incidence of MACE at "("3.7% vs 4.1% (RR 0.918, 95% CI 0.862-0.978). All-cause mortality was also lower with tirzepatide (0.2% vs. 0.4%; Risk Ratio 0.436, 95% CI 0.338-0.562). The tirzapetide group achieved better glycemic control with a lower mean HbA1c (6.565% vs. 6.848%; p < 0.001) during the follow-up. There was no significant difference in heart failure exacerbation or UTI incidence. GI side effects were slightly less frequent in the tirzepatide cohort (9.8% vs. 10.2%; Risk Ratio 0.959, 95% CI 0.924-0.997), while hospitalization or emergency visits were comparable between the two groups.ConclusionIn this propensity matched cohort of patients with obesity and type 2 diabetes, tirzepatide demonstrated improved cardiometabolic outcomes compared to semaglutide, including lower all-cause mortality and lower HbA1c. These findings support the cardiovascular safety and efficacy of tirzapetide and highlight the need for further studies to evaluate its effectiveness in broader clinical populations. FAU - Qadeer, Abdul AU - Qadeer A AUID- ORCID: 0009-0005-8478-7086 AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Khalid, Marwah Bintay AU - Khalid MB AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. RINGGOLD: 123683 FAU - Syed, Ridwan AU - Syed R AD - Department of Cardiovascular Medicine, The University of Texas Medical Branch, Galveston, TX, USA. FAU - Jain, Samiksha AU - Jain S AD - Department of Medicine, Mobile Infirmary Medical Center, Mobile, AL, USA. RINGGOLD: 76093 FAU - Zakaria, Faiza AU - Zakaria F AD - Department of Internal Medicine, Trinity Health Oakland/Wayne State University, Pontiac, Michigan, USA. FAU - Khan, Muhammad Huzaifa Ahmed AU - Khan MHA AD - Department of Internal Medicine, Prime South GME Consortium Harlingen Medical Center, TX, USA. FAU - Gohar, Najam AU - Gohar N AD - Department of Internal Medicine, Ameer-ud-Din Medical College, Lahore, Pakistan. FAU - Shoukat, Ashraf AU - Shoukat A AD - Department of Medicine, Nishtar Medical University, Multan, Pakistan. RINGGOLD: 619131 FAU - Mortada, Ibrahim AU - Mortada I AUID- ORCID: 0009-0006-9215-880X AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Hamza, Izhan AU - Hamza I AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Motiwala, Afaq AU - Motiwala A AUID- ORCID: 0000-0002-4750-7090 AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Raja, Muhammad Waheed AU - Raja MW AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Blackwell, Thomas AU - Blackwell T AD - Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Jneid, Hani AU - Jneid H AD - Department of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20260630 PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Tirzepatide/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/blood MH - Male MH - Female MH - Treatment Outcome MH - Middle Aged MH - Retrospective Studies MH - *Obesity/drug therapy/diagnosis/mortality MH - Aged MH - Time Factors MH - Blood Glucose/drug effects/metabolism MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabesity/mortality MH - Biomarkers/blood MH - *Incretins/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism MH - Risk Factors MH - Risk Assessment MH - Glycemic Control/adverse effects PMC - PMC13319829 OTO - NOTNLM OT - obesity diabetes mellitus OT - semaglutide OT - tirzepatide COIS- Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/06/30 16:10 MHDA- 2026/06/30 16:11 PMCR- 2026/06/30 CRDT- 2026/06/30 07:03 PHST- 2026/06/30 16:11 [medline] PHST- 2026/06/30 16:10 [pubmed] PHST- 2026/06/30 07:03 [entrez] PHST- 2026/06/30 00:00 [pmc-release] AID - 10.1177_14791641261465360 [pii] AID - 10.1177/14791641261465360 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2026 May-Jun;23(3):14791641261465360. doi: 10.1177/14791641261465360. Epub 2026 Jun 30. PMID- 42372276 OWN - NLM STAT- MEDLINE DCOM- 20260817 LR - 20260818 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 8 DP - 2026 Aug TI - Weekly and Biweekly Treatment With Bofanglutide Versus Semaglutide in Chinese Patients With Type 2 Diabetes : A Phase 2b Randomized Clinical Trial. PG - 1107-1116 LID - 10.7326/ANNALS-25-04623 [doi] AB - BACKGROUND: Bofanglutide is a novel glucagon-like peptide-1 receptor agonist under development for type 2 diabetes mellitus (T2DM) and overweight and obesity. OBJECTIVE: To evaluate the efficacy and safety of bofanglutide compared with semaglutide. DESIGN: Phase 2b, randomized, open-label, active-controlled trial. (ClinicalTrials.gov: NCT06256549). SETTING: Multicenter (37 sites in China). PARTICIPANTS: Adults with T2DM who were drug-naive or receiving stable oral antidiabetic drugs (glycated hemoglobin A(1c) [HbA(1c)], 7.0% to 11.0%). INTERVENTION: Participants were randomly assigned 1:1:1:1:1 to 1 of 5 treatment groups: bofanglutide titrated to targets of 12, 18, or 24 mg (biweekly [once every 2 weeks; Q2W]); bofanglutide titrated to 24 mg (once weekly [QW]); or semaglutide titrated to 1 mg QW. MEASUREMENTS: Change in HbA(1c) level from baseline to week 24 (primary end point), secondary efficacy end points, and safety. RESULTS: Overall, 272 participants were enrolled, with a mean age of 50.8 years, HbA(1c) level of 8.35%, and body mass index of 27.9 kg/m(2). At week 24, HbA(1c) level change from baseline was -1.87% (95% CI, -2.11% to -1.63%), -2.28% (CI, -2.54% to -2.03%), and -1.94% (CI, -2.19% to -1.69%) for bofanglutide 12, 18, 24 mg Q2W, respectively; -2.32% (CI, -2.57% to -2.06%) for bofanglutide 24 mg QW; and -1.60% (CI, -1.85% to -1.35%) for 1 mg of semaglutide QW. Corresponding treatment differences versus semaglutide were -0.27% (CI, -0.61% to -0.08%), -0.68% (CI, -1.04% to -0.33%), -0.34% (CI, -0.70% to 0.02%), and -0.72% (CI, -1.08% to -0.36%), respectively. Gastrointestinal adverse events (GIAEs) (mostly grade 1 or 2 in severity) occurred in 81.8% to 87.3% and 51.9% of participants in the bofanglutide and semaglutide groups, respectively. Hypoglycemia occurred in 0% to 3.8% versus 1.9%, with no severe hypoglycemia. LIMITATION: Open-label, short duration, only Chinese participants. CONCLUSION: Meaningful reductions in HbA(1c) levels were seen with bofanglutide in patients with T2DM; GIAEs were the most common and generally manageable. PRIMARY FUNDING SOURCE: Gan & Lee Pharmaceuticals. FAU - Liu, Ming AU - Liu M AUID- ORCID: 0000-0003-2665-4072 AD - Tianjin Medical University General Hospital, Tianjin, China (M.L.). FAU - Cheng, Zhifeng AU - Cheng Z AD - The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China (Z.C.). FAU - Lu, Li AU - Lu L AD - Shandong Guoxin Yiyang Group Zaozhuang Central Hospital, Zaozhuang, China (L.L.). FAU - Cai, Hanqing AU - Cai H AD - The Second Hospital of Jilin University, Changchun, China (H.C.). FAU - Liu, Jingyu AU - Liu J AD - Chengdu Seventh People's Hospital, Chengdu, China (Jingyu Liu). FAU - Liu, Jinling AU - Liu J AD - Weifang Hospital of Traditional Chinese Medicine, Weifang, China (Jinling Liu). FAU - Zheng, Yueyue AU - Zheng Y AD - The First Affiliated Hospital of Nanyang Medical College, Nanyang, China (Y.Z.). FAU - Wang, Su AU - Wang S AUID- ORCID: 0000-0003-2892-9121 AD - Tianjin Fifth Central Hospital, Tianjin, China (S.W.). FAU - Zhao, Jing AU - Zhao J AD - Gan & Lee Pharmaceuticals, Beijing, China (J.Z., W.Y., T.X., Y.L., A.H.). FAU - Yang, Wei AU - Yang W AD - Gan & Lee Pharmaceuticals, Beijing, China (J.Z., W.Y., T.X., Y.L., A.H.). FAU - Xie, Tian AU - Xie T AD - Gan & Lee Pharmaceuticals, Beijing, China (J.Z., W.Y., T.X., Y.L., A.H.). FAU - Li, Yue AU - Li Y AD - Gan & Lee Pharmaceuticals, Beijing, China (J.Z., W.Y., T.X., Y.L., A.H.). FAU - He, Anshun AU - He A AD - Gan & Lee Pharmaceuticals, Beijing, China (J.Z., W.Y., T.X., Y.L., A.H.). FAU - Rodbard, Helena W AU - Rodbard HW AD - Endocrine and Metabolic Consultants, Rockville, Maryland (H.W.R.). FAU - Chen, Wei AU - Chen W AD - Gan & Lee Pharmaceuticals, Beijing, and Gan & Lee Pharmaceuticals Shandong, Linyi, China (W.C.). LA - eng SI - ClinicalTrials.gov/NCT06256549 PT - Clinical Trial, Phase II PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260630 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - Chinese people SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose MH - China MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Administration Schedule MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - Glycated Hemoglobin/metabolism MH - *Hypoglycemic Agents/adverse effects/administration & dosage/therapeutic use MH - Semaglutide/administration & dosage/adverse effects/therapeutic use MH - East Asian People COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2026/06/29 22:36 MHDA- 2026/08/17 23:39 CRDT- 2026/06/29 17:03 PHST- 2026/08/17 23:39 [medline] PHST- 2026/06/29 22:36 [pubmed] PHST- 2026/06/29 17:03 [entrez] AID - 10.7326/ANNALS-25-04623 [doi] PST - ppublish SO - Ann Intern Med. 2026 Aug;179(8):1107-1116. doi: 10.7326/ANNALS-25-04623. Epub 2026 Jun 30. PMID- 42365987 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Real-World Evidence of the Effectiveness and Safety of Biosynthetic Semaglutide in Type 2 Diabetes: A Multicentre Study From Pakistan. PG - 8438-8451 LID - 10.1111/dom.71043 [doi] AB - AIMS: To evaluate the real-world effectiveness, safety and patient-reported outcomes of biosynthetic semaglutide in adults with type 2 diabetes mellitus (T2DM) receiving routine outpatient care in a cost-constrained setting. METHODS: This 30-week, prospective, multicentre, non-interventional study enrolled adults with T2DM initiating biosynthetic semaglutide. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to end of study (EOS). Secondary endpoints included changes in body weight, waist circumference, patient-reported outcomes (DTSQs and SF-36v2) and safety. RESULTS: Among 217 patients, mean HbA1c decreased from 9.27% to 7.41% at EOS (-1.86%; p < 0.001). At EOS, 76.6% achieved HbA1c < 8.0% and 38.7% achieved < 7.0%. Mean body weight decreased by -7.84 kg (p < 0.001), with 76.5% achieving >/= 5% weight loss. Significant reductions were also observed in body mass index and waist circumference. Treatment satisfaction and physical quality of life improved significantly. Adverse events were predominantly non-serious and gastrointestinal. No severe hypoglycaemic episodes occurred. CONCLUSIONS: In routine clinical practice, biosynthetic semaglutide was associated with clinically meaningful improvements in glycaemic control, body weight and physical quality of life. The safety profile remained consistent with established semaglutide therapy. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12625000610437. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hussain, Arshad AU - Hussain A AD - North-West General Hospital, Peshawar, Pakistan. FAU - Wahab, Muhammad Umar AU - Wahab MU AD - Umar Diabetes and Foot Care Centre and Umar Diabetes Foundation, Islamabad, Pakistan. FAU - Qureshi, Saleem AU - Qureshi S AD - Department of Medicine, Center for Diabetes and Liver Disease, Islamabad, Pakistan. FAU - Raja, Umar Yousaf AU - Raja UY AD - Shifa International Hospitals Ltd., Islamabad, Pakistan. FAU - Munir, Atif AU - Munir A AD - Omer Hospital, Lahore, Pakistan. FAU - Gardezi, Shahnawaz AU - Gardezi S AD - City Hospital, Multan, Pakistan. FAU - Iqbal, Musarrat AU - Iqbal M AD - Department of Medicine, Center for Diabetes and Liver Disease, Islamabad, Pakistan. FAU - Afzal, Bilal AU - Afzal B AD - Mukhtar A Sheikh Hospital, Multan, Pakistan. FAU - Butt, Muhammad Daoud AU - Butt MD AD - School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Penang, Malaysia. FAU - Ong, Siew Chin AU - Ong SC AUID- ORCID: 0000-0002-9750-9588 AD - School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Penang, Malaysia. LA - eng GR - P504-LR-GAL008-0000001693-0000/BF Bioscience Pvt. Ltd./ PT - Journal Article PT - Multicenter Study DEP - 20260628 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Prospective Studies MH - Pakistan/epidemiology MH - Treatment Outcome MH - Adult MH - Weight Loss/drug effects MH - Aged MH - Quality of Life MH - Body Mass Index MH - Waist Circumference/drug effects MH - Patient Reported Outcome Measures MH - Blood Glucose PMC - PMC13448986 OTO - NOTNLM OT - biosynthetic semaglutide OT - glycaemic control OT - low- and middle-income countries OT - patient-reported outcomes OT - real-world evidence OT - safety and tolerability COIS- Dr. Arshad Hussain has received honoraria for delivering educational lectures from BF BioSciences. The funding organization provided support for the conduct of this study but had no role in the study design; data collection, analysis, or interpretation; manuscript preparation; or the decision to submit the manuscript for publication. All other authors declare that they have no competing financial or non financial interests. EDAT- 2026/06/29 00:30 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/28 20:14 PHST- 2026/06/15 00:00 [revised] PHST- 2026/05/05 00:00 [received] PHST- 2026/06/17 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/29 00:30 [pubmed] PHST- 2026/06/28 20:14 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71043 [pii] AID - 10.1111/dom.71043 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8438-8451. doi: 10.1111/dom.71043. Epub 2026 Jun 28. PMID- 42365860 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260730 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 238 DP - 2026 Aug TI - GLP-1 receptor agonists in pediatric obesity and diabetes: a systematic review of efficacy, metabolic effects, and safety. PG - 113400 LID - S0168-8227(26)00320-7 [pii] LID - 10.1016/j.diabres.2026.113400 [doi] AB - Childhood obesity and youth-onset type 2 diabetes mellitus (T2DM) are increasing, highlighting the need for effective treatments beyond lifestyle intervention and metformin. This review systematically evaluated the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in children and adolescents with obesity or T2DM. PubMed-indexed studies published from 2000 to 2025 were reviewed, including seven pivotal randomized controlled trials and six meta-analyses involving 901 participants aged 6 to < 18 years. Semaglutide 2.4 mg/week produced the greatest BMI reduction in adolescents with obesity, followed by liraglutide 3.0 mg/day, which also improved BMI SDS in adolescents and younger children. In youth-onset T2DM, liraglutide 1.8 mg/day and dulaglutide significantly improved HbA1c compared with placebo. Weight-reducing agents also improved insulin resistance and modestly reduced triglycerides, while LDL-cholesterol changes were minimal. Gastrointestinal adverse events, mainly nausea and vomiting, were the most frequent and were generally transient and dose dependent. No significant adverse effects on linear growth or pubertal progression were reported. GLP-1 RAs are effective adjuncts for pediatric obesity and T2DM, but longer-term studies are needed to assess cardiovascular safety, bone health, and growth outcomes. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Soliman, Ashraf T AU - Soliman AT AD - Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. Electronic address: atsoliman56@gmail.com. FAU - Alyafei, Fawzia AU - Alyafei F AD - Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. FAU - Khalil, Ahmed AU - Khalil A AD - Department of Pharmacy, Hamad Medical Corporation, Doha, Qatar. FAU - Kardousha, Ahmed Tawfik AU - Kardousha AT AD - Department of Pharmacy, Hamad Medical Corporation, Doha, Qatar. FAU - Ahmed, Shayma AU - Ahmed S AD - Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. FAU - Alaaraj, Nada AU - Alaaraj N AD - Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. FAU - Hamed, Noor AU - Hamed N AD - Department of Pediatrics, Division of Endocrinology, Hamad Medical Corporation, Doha, Qatar. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260628 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Child MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Adolescent MH - *Pediatric Obesity/drug therapy/metabolism MH - Liraglutide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use/adverse effects MH - Immunoglobulin Fc Fragments/therapeutic use MH - Blood Glucose OTO - NOTNLM OT - Adolescents OT - Body mass index OT - Children OT - Dulaglutide OT - Exenatide OT - GLP-1 receptor agonists OT - HOMA-IR OT - HbA1c OT - Lipid profile OT - Liraglutide OT - Pediatric obesity OT - Safety OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/06/29 04:10 MHDA- 2026/07/08 18:51 CRDT- 2026/06/28 19:21 PHST- 2026/06/03 00:00 [received] PHST- 2026/06/22 00:00 [revised] PHST- 2026/06/27 00:00 [accepted] PHST- 2026/07/08 18:51 [medline] PHST- 2026/06/29 04:10 [pubmed] PHST- 2026/06/28 19:21 [entrez] AID - S0168-8227(26)00320-7 [pii] AID - 10.1016/j.diabres.2026.113400 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Aug;238:113400. doi: 10.1016/j.diabres.2026.113400. Epub 2026 Jun 28. PMID- 42361988 OWN - NLM STAT- MEDLINE DCOM- 20260729 LR - 20260729 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 461 DP - 2026 Oct 15 TI - From evidence to practice: Identifying candidates for semaglutide in chronic atherosclerotic disease. PG - 134646 LID - S0167-5273(26)00496-1 [pii] LID - 10.1016/j.ijcard.2026.134646 [doi] AB - BACKGROUND AND AIM: Randomised clinical trials (SELECT and SOUL) demonstrated that semaglutide, a GLP-1 receptor agonist, reduces the combined outcome measure of atherothrombotic events or cardiovascular mortality in patients with coronary artery disease, both with and without diabetes. Because real-world populations may differ from trial cohorts, we assessed the proportion of patients potentially eligible for semaglutide using the criteria set out by the regulatory authorities based on the SELECT and SOUL results. METHODS AND RESULTS: Patients whose clinical characteristics were comparable to those of patients enrolled in the SELECT and SOUL trials were identified within the START and BRING-UP prevention registries. Among 12,430 patients, 623 were excluded because of severe renal impairment or ongoing GLP-1 receptor agonist therapy. The final population included 11,807 patients: 8682 without diabetes and 3125 with diabetes. Among non-diabetic patients, 3689 (42.5%) were SELECT-like, defined as overweight or obese individuals with established coronary disease. Among diabetic patients, 3059 (97.9%) were SOUL-like, defined as individuals aged >/=50 years with cardiovascular disease. Overall, 6748 of 12,430 patients (54.3%) theoretically fulfilled eligibility criteria for semaglutide treatment in real-world cardiology practice. CONCLUSIONS: According to the criteria set out by the regulatory authorities based on the SELECT and SOUL trial results, a large proportion of patients with coronary artery disease managed by cardiologists may be potentially eligible for semaglutide therapy. Identifying the target population for this therapeutic strategy may help clinicians and healthcare authorities estimate unmet clinical needs and evaluate the sustainability of innovative approaches for secondary cardiovascular prevention. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Maggioni, Aldo P AU - Maggioni AP AD - ANMCO Research Center, HCF Fondazione ANMCO per il Tuo cuore ETS, Firenze, Italy. Electronic address: maggioni@heartcarefoundation.it. FAU - Orso, Francesco AU - Orso F AD - ANMCO Research Center, HCF Fondazione ANMCO per il Tuo cuore ETS, Firenze, Italy. FAU - Lucci, Donata AU - Lucci D AD - ANMCO Research Center, HCF Fondazione ANMCO per il Tuo cuore ETS, Firenze, Italy. FAU - De Luca, Leonardo AU - De Luca L AD - Division of Cardiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. FAU - Colivicchi, Furio AU - Colivicchi F AD - Clinical and Rehabilitation Cardiology Department, San Filippo Neri Hospital, ASL Roma 1, Roma, Italy. LA - eng PT - Journal Article DEP - 20260626 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - Male MH - *Atherosclerosis/drug therapy/epidemiology/diagnosis MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Chronic Disease MH - Randomized Controlled Trials as Topic/methods MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Registries MH - *Evidence-Based Medicine/methods MH - Diabetes Mellitus, Type 2/drug therapy/epidemiology OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Diabetes OT - GLP1 RA OT - Obesity OT - Semaglutide EDAT- 2026/06/27 00:59 MHDA- 2026/07/30 00:38 CRDT- 2026/06/26 19:32 PHST- 2026/03/18 00:00 [received] PHST- 2026/06/18 00:00 [revised] PHST- 2026/06/25 00:00 [accepted] PHST- 2026/07/30 00:38 [medline] PHST- 2026/06/27 00:59 [pubmed] PHST- 2026/06/26 19:32 [entrez] AID - S0167-5273(26)00496-1 [pii] AID - 10.1016/j.ijcard.2026.134646 [doi] PST - ppublish SO - Int J Cardiol. 2026 Oct 15;461:134646. doi: 10.1016/j.ijcard.2026.134646. Epub 2026 Jun 26. PMID- 42349668 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260716 IS - 1873-3441 (Electronic) IS - 0939-6411 (Linking) VI - 226 DP - 2026 Sep TI - Hydrophobic ion pairing formed semaglutide designed for oral self-microemulsifying delivery in diabetes treatment. PG - 115167 LID - S0939-6411(26)00188-8 [pii] LID - 10.1016/j.ejpb.2026.115167 [doi] AB - Semaglutide (SET) is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes. Although injectable formulations offer high bioavailability, they are associated with poor patient compliance. In contrast, oral tablets are more convenient but suffer from limited absorption due to SET's hydrophilicity and enzymatic instability in the gastrointestinal tract. To address these challenges, we developed a hydrophobic ion pair (HIP) complex of SET and sodium docusate (SET-DOC), which was further incorporated into a self-emulsifying drug delivery system (SD@SEDDS) to facilitate oral delivery. The optimized SD@SEDDS produced a clear emulsion upon dilution, with a uniform particle size of 85.55 nm, high drug loading (2.64 mg/g), and excellent stability. In vitro transport studies using a Caco-2/HT-29 co-culture model demonstrated enhanced permeability and reduced P-glycoprotein-mediated efflux. In vivo studies in a type 2 diabetic rat model showed that SD@SEDDS significantly reduced blood glucose levels, improved lipid profiles, and exhibited good biocompatibility without observable toxicity. These findings suggested that the combination of HIP technology and SEDDS represented a promising strategy for enhancing the oral delivery efficiency of peptide drugs such as SET. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Zhang, Yuhuan AU - Zhang Y AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. FAU - Cheng, Jinghan AU - Cheng J AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. FAU - Wang, Hanming AU - Wang H AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. FAU - Zong, Zhuai AU - Zong Z AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. FAU - Zhang, Wenli AU - Zhang W AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. Electronic address: zwllz@163.com. FAU - Shen, Yan AU - Shen Y AD - Department of Pharmaceutics, State Key Laboratory of Nature Medicines, School of Pharmacy, China Pharmaceutical University, 210009, China. Electronic address: shenyan@cpu.edu.cn. FAU - Tian, Yu AU - Tian Y AD - School of Medicine, Shanghai University, Shanghai 200444, China. Electronic address: shu_yutian@shu.edu.cn. LA - eng PT - Journal Article DEP - 20260625 PL - Netherlands TA - Eur J Pharm Biopharm JT - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JID - 9109778 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Emulsions) SB - IM MH - Semaglutide MH - Animals MH - Humans MH - Administration, Oral MH - Hydrophobic and Hydrophilic Interactions MH - Caco-2 Cells MH - *Hypoglycemic Agents/administration & dosage/chemistry/pharmacokinetics MH - *Glucagon-Like Peptides/administration & dosage/chemistry/pharmacokinetics MH - *Diabetes Mellitus, Type 2/drug therapy MH - Drug Delivery Systems/methods MH - Emulsions/chemistry MH - Rats MH - Male MH - *Diabetes Mellitus, Experimental/drug therapy MH - Rats, Sprague-Dawley MH - HT29 Cells MH - Biological Availability MH - Particle Size OTO - NOTNLM OT - Caco-2/HT-29 co-culture model OT - Hydrophobic ion pairing OT - Hypoglycemic effect OT - SEDDS OT - Semaglutide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/06/26 00:45 MHDA- 2026/07/16 12:40 CRDT- 2026/06/25 19:30 PHST- 2026/04/08 00:00 [received] PHST- 2026/06/02 00:00 [revised] PHST- 2026/06/24 00:00 [accepted] PHST- 2026/07/16 12:40 [medline] PHST- 2026/06/26 00:45 [pubmed] PHST- 2026/06/25 19:30 [entrez] AID - S0939-6411(26)00188-8 [pii] AID - 10.1016/j.ejpb.2026.115167 [doi] PST - ppublish SO - Eur J Pharm Biopharm. 2026 Sep;226:115167. doi: 10.1016/j.ejpb.2026.115167. Epub 2026 Jun 25. PMID- 42342489 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20260907 IS - 1878-7533 (Electronic) IS - 1550-7289 (Linking) VI - 22 IP - 10 DP - 2026 Oct TI - Glucagon-like peptide-1 receptor agonists as a metabolic optimization strategy in surgical prehabilitation: a translational perspective. PG - 1175-1180 LID - S1550-7289(26)00708-2 [pii] LID - 10.1016/j.soard.2026.05.027 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide and tirzepatide, are increasingly prescribed for obesity and type 2 diabetes and have demonstrated substantial and rapid weight loss in large randomized trials. At the same time, prehabilitation before major abdominal surgery has become an established perioperative strategy to improve postoperative outcomes. This review explores the potential role of GLP-1RAs as a pharmacological adjunct in multimodal surgical prehabilitation. We discuss the biological rationale for metabolic optimization, the relevance of sarcopenic obesity, potential implications for oncological surgery and neoadjuvant therapy, and emerging data from bariatric and metabolic surgery. We also highlight important perioperative safety considerations, particularly delayed gastric emptying and aspiration risk, and current anesthetic guidance. Although integration of GLP-1RAs into prehabilitation pathways is biologically plausible and clinically attractive, there is currently no direct evidence supporting their use in this setting. We propose that GLP-1RAs represent a promising and testable strategy for metabolic optimization in surgical patients. Prospective studies are required to evaluate feasibility, safety, and impact on clinically meaningful outcomes. This framework is hypothesis-generating and aims to inform future translational research at the interface of metabolic medicine and perioperative care. CI - Copyright (c) 2026 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved. FAU - Rouse, Michael AU - Rouse M AD - Department of Surgery, University of Melbourne, Victoria, Australia; Department of Surgery, Western Health, Victoria, Australia. Electronic address: michael.rouse@unimelb.edu.au. FAU - Kokelaar, Rory AU - Kokelaar R AD - Department of Surgery, Western Health, Victoria, Australia. FAU - Lee, I-Lynn AU - Lee IL AD - Department of Surgery, University of Melbourne, Victoria, Australia; Department of Surgery, Western Health, Victoria, Australia. FAU - Yeung, Justin M AU - Yeung JM AD - Department of Surgery, University of Melbourne, Victoria, Australia; Department of Surgery, Western Health, Victoria, Australia. LA - eng PT - Journal Article PT - Review DEP - 20260601 PL - United States TA - Surg Obes Relat Dis JT - Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery JID - 101233161 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Bariatric Surgery/methods MH - Semaglutide MH - *Preoperative Care/methods MH - Tirzepatide MH - Glucagon-Like Peptides/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Preoperative Exercise MH - Translational Research, Biomedical MH - *Obesity/surgery/drug therapy MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - GLP-1 receptor agonist OT - Obesity OT - Perioperative medicine OT - Prehabilitation OT - Sarcopenic obesity OT - Surgical outcomes COIS- Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. EDAT- 2026/06/25 00:33 MHDA- 2026/09/07 23:34 CRDT- 2026/06/24 21:55 PHST- 2026/03/27 00:00 [received] PHST- 2026/05/07 00:00 [revised] PHST- 2026/05/26 00:00 [accepted] PHST- 2026/09/07 23:34 [medline] PHST- 2026/06/25 00:33 [pubmed] PHST- 2026/06/24 21:55 [entrez] AID - S1550-7289(26)00708-2 [pii] AID - 10.1016/j.soard.2026.05.027 [doi] PST - ppublish SO - Surg Obes Relat Dis. 2026 Oct;22(10):1175-1180. doi: 10.1016/j.soard.2026.05.027. Epub 2026 Jun 1. PMID- 42339860 OWN - NLM STAT- MEDLINE DCOM- 20260730 LR - 20260730 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 19 IP - 7 DP - 2026 Jul TI - The systems medicine view of semaglutide: from clinical trials to molecular mechanisms. PG - 651-669 LID - 10.1080/17512433.2026.2695172 [doi] AB - INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is a key therapy in managing type 2 diabetes (T2D), offering significant improvements in glycemic control, weight loss, and cardiovascular protection. Beyond these clinical benefits, multi-omics research is clarifying the molecular mechanisms underlying its systemic metabolic effects. AREAS COVERED: This review synthesizes findings from major clinical trials and recent proteomic and metabolomic studies to explain how semaglutide affects inflammatory, lipid, and extracellular matrix (ECM) pathways in multiple organs. Key molecular mediators, including adiponectin, fibroblast growth factor 21 (FGF21), apolipoprotein C-III (ApoC-III), ceramides, and ECM-remodeling proteins (MMPs, CTGF, alpha-SMA), are linked to improved insulin sensitivity, reduced adipose inflammation, and restored metabolic flexibility. The review also discusses the use of artificial intelligence (AI) and machine learning (ML) to connect omics biomarkers with clinical outcomes. EXPERT OPINION: Semaglutide exemplifies a precision medicine approach for T2D by linking clinical efficacy to molecular adaptation. Longitudinal validation of omics biomarkers and their integration into AI-driven diagnostic platforms could enable personalized, mechanism-based therapy that goes beyond glucose control to deliver comprehensive cardiometabolic protection. FAU - Vitorino, Rui AU - Vitorino R AD - Department of Medical Sciences, iBiMED, University of Aveiro, Aveiro, Portugal. AD - Cardiovascular R&D Centre - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. LA - eng PT - Journal Article PT - Review DEP - 20260701 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Hypoglycemic Agents/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - Precision Medicine/methods MH - Proteomics/methods MH - Biomarkers/metabolism MH - Insulin Resistance MH - Metabolomics/methods MH - Multiomics MH - Blood Glucose/drug effects OTO - NOTNLM OT - GLP-1 receptor agonist OT - Type 2 diabetes OT - adipose tissue OT - inflammation OT - insulin resistance OT - metabolomics OT - proteomics OT - semaglutide EDAT- 2026/06/24 12:35 MHDA- 2026/07/30 06:41 CRDT- 2026/06/24 09:35 PHST- 2026/07/30 06:41 [medline] PHST- 2026/06/24 12:35 [pubmed] PHST- 2026/06/24 09:35 [entrez] AID - 10.1080/17512433.2026.2695172 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2026 Jul;19(7):651-669. doi: 10.1080/17512433.2026.2695172. Epub 2026 Jul 1. PMID- 42338042 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Hepatic Safety of Orforglipron in Adults With Obesity or Overweight and/or Type 2 Diabetes: A Pooled Analysis of the Orforglipron Phase 3 Clinical Trials. PG - 8347-8358 LID - 10.1111/dom.71032 [doi] AB - AIMS: Orforglipron is a novel small-molecule, once daily oral non-peptide GLP-1 receptor agonist. The hepatic safety profile in adults with obesity or overweight and/or type 2 diabetes (T2D) across seven orforglipron Phase 3 clinical trials was assessed. MATERIALS AND METHODS: Overall, 11 220 participants were included in this analysis (orforglipron N = 6920; pooled comparator [placebo, oral semaglutide, dapagliflozin, insulin glargine] N = 4300) for up to 104 weeks, including safety follow-up. Eligibility criteria for these Phase 3 trials included ALT/AST < 3 x ULN in the weight management programme and /= 3 x ULN and TBIL >/= 2 x ULN; however, alternative etiologies accounted for all orforglipron cases and thus did not meet criteria for drug induced liver injury/Hy's Law. The incidence of hepatic AEs was balanced between orforglipron and pooled comparators, suggesting no increased risk with orforglipron. Results were consistent in participants with normal and elevated baseline aminotransferases. CONCLUSIONS: In this pooled analysis of orforglipron Phase 3 clinical trials, orforglipron treatment was not associated with drug-induced liver injury, demonstrating a hepatic safety profile similar to placebo or active comparators. There were no cases consistent with drug-induced liver injury/Hy's Law with orforglipron. Aminotransferase trajectories showed a hepatic profile consistent with the metabolic benefits of weight loss. CI - (c) 2026 Eli Lilly and Company and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - University of Toronto, and Wharton Weight Management Clinic, Toronto, Ontario, Canada. FAU - Stefanski, Adam AU - Stefanski A AUID- ORCID: 0009-0001-7598-402X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Chen, Jiaxun AU - Chen J AUID- ORCID: 0000-0002-7046-4201 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Rao, Girish AU - Rao G AUID- ORCID: 0000-0002-3660-5488 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Twum, Elvis Asare AU - Twum EA AUID- ORCID: 0009-0006-1093-2508 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Denning, Max AU - Denning M AUID- ORCID: 0000-0001-6215-6885 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Clinical Trial, Phase III PT - Journal Article DEP - 20260623 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - EC 2.6.1.2 (Alanine Transaminase) RN - 0 (Glucosides) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 1ULL0QJ8UC (dapagliflozin) RN - 7ZW40D021M (orforglipron) RN - 0 (Benzhydryl Compounds) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Obesity/drug therapy/complications MH - Adult MH - *Overweight/drug therapy/complications MH - Semaglutide MH - Clinical Trials, Phase III as Topic MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - *Chemical and Drug Induced Liver Injury/epidemiology/etiology MH - *Liver/drug effects MH - Alanine Transaminase MH - Aged MH - Glucosides/therapeutic use MH - Insulin Glargine/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Benzhydryl Compounds MH - Oxadiazoles MH - Fluorine Compounds PMC - PMC13448879 OAB - What is the context and purpose of this research study? o Orforglipron is an oral GLP-1 receptor agonist taken as tablet that helps to reduce blood sugar and reduce body weight. We studied how orforglipron may affect the liver in adults with obesity, overweight, and/or type 2 diabetes who participated in the Phase 3 clinical trials. What was done? o Across seven trials, orforglipron up to 17.2 mg once daily was compared to placebo, oral semaglutide, dapagliflozin, or insulin glargine. We measured changes in blood liver enzymes like AST, ALT and counted how many participants developed elevated liver enzymes above a set threshold. Analysis included all participants and those with preexisting elevated liver enzymes. We also checked for Hy's law, which signals for serious medicine related liver injury. Hy's Law screening was performed, and hepatic adverse events were summarised. What were the main results? o Treatment with orforglipron was not associated with drug-induced liver injury, and no participant met the Hy's Law criteria. Additionally, ALT and AST levels improved over time with orforglipron, which coincides with the significant weight loss and metabolic improvements previously reported in these trials. Overall, the liver safety profile of orforglipron was comparable to placebo and other comparator medicines, including peptide GLP-1 receptor agonist semaglutide. What is the originality and relevance of this study? o Findings from this analysis suggest that orforglipron was safe in adults with overweight, obesity, or type 2 diabetes-even in those with mildly to moderately elevated liver enzyme levels, which is commonly seen in MASLD. These findings support the need for dedicated studies on people with MASLD or metabolic dysfunction-associated steatohepatitis (MASH). OABL- eng OTO - NOTNLM OT - ACHIEVE OT - ATTAIN OT - hepatic safety OT - obesity OT - orforglipron OT - type 2 diabetes COIS- S.W. reported receiving nonfinancial support from Eli Lilly and Company during the conduct of the study and personal fees from Abbvie, Amgen, AstraZeneca, Bausch Health Canada, Boehringer Ingelheim, Eli Lilly and Company, i2o Therapeutics, Merck, Metsera, NGX, Novo Nordisk, and Regeneron outside the submitted work, served on an advisory board for Boehringer Ingelheim, holds a leadership role for Obesity Canada and Obesity Society, and has received medical writing support from Boehringer Ingelheim, Eli Lilly and Company, and Novo Nordisk. A.S., J.C., G.R., E.A.T. and M.D. are employees and shareholders of Eli Lilly and Company. The sponsor (Eli Lilly and Company) designed and oversaw the conduct of the trials included in this analysis. The trial site investigators were responsible for data collection, with site monitoring, data collation, and data analysis and medical writing support provided by the sponsor. EDAT- 2026/06/24 06:36 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/24 02:14 PHST- 2026/06/12 00:00 [revised] PHST- 2026/05/14 00:00 [received] PHST- 2026/06/13 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/24 06:36 [pubmed] PHST- 2026/06/24 02:14 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71032 [pii] AID - 10.1111/dom.71032 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8347-8358. doi: 10.1111/dom.71032. Epub 2026 Jun 23. PMID- 42337824 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Efficacy and Safety of GLP-1 Receptor Agonists on Combined Cardiovascular and Renal Outcomes in Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis. PG - 8337-8346 LID - 10.1111/dom.71031 [doi] AB - AIMS: Chronic kidney disease (CKD) confers substantial cardiovascular and renal morbidity. GLP-1 receptor agonists (GLP-1 RAs) have demonstrated cardiorenal protection across major randomised trials, culminating in the landmark FLOW trial. No prior systematic review has simultaneously synthesised cardiorenal outcomes in a CKD-restricted population, executed a network meta-analysis for agent-level comparisons, or assessed whether SGLT2 inhibitor background therapy modifies treatment effects. MATERIALS AND METHODS: MEDLINE, Embase, Cochrane CENTRAL, and Web of Science were searched through March 2025. Eligible RCTs enrolled adults with CKD (eGFR < 60 mL/min/1.73 m(2) or UACR >/= 30 mg/g) comparing GLP-1 RAs versus placebo for >/= 26 weeks. Primary outcomes were 3-point MACE and a KDIGO-harmonised composite kidney endpoint. Random-effects pairwise meta-analyses and a frequentist NMA were performed. GRADE certainty was assigned to all outcomes. RESULTS: Thirteen RCTs (97 428 participants; 31 846 with confirmed CKD) were included. GLP-1 RAs reduced MACE by 16% (HR 0.84, 95% CI 0.79-0.89; high certainty) and the composite kidney endpoint by 21% (HR 0.79, 95% CI 0.73-0.86; high certainty). Kidney failure risk was reduced by 28% (HR 0.72); UACR decreased by 26%. Benefits were consistent irrespective of SGLT2 inhibitor background use (interaction p = 0.41). Semaglutide ranked highest in the NMA (SUCRA 78.4%). No excess acute kidney injury risk was observed. CONCLUSIONS: GLP-1 RAs provide clinically meaningful cardiorenal protection in CKD, additive to SGLT2 inhibitor benefits. In exploratory network meta-analysis, semaglutide subcutaneous achieved the highest SUCRA ranking for kidney composite outcomes; the direct semaglutide evidence is rated high certainty by GRADE. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Kaur, Rashpinder AU - Kaur R AD - General Medicine and Care of the Elderly, Aneurin Bevan University Health Board, Newport, UK. FAU - Singh, Avtar AU - Singh A AUID- ORCID: 0009-0009-4705-0818 AD - General Medicine and Care of the Elderly, Aneurin Bevan University Health Board, Newport, UK. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260623 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - Treatment Outcome MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - Kidney/drug effects PMC - PMC13448877 OTO - NOTNLM OT - GLP-1 receptor agonists OT - MACE OT - SGLT2 inhibitors OT - cardiorenal protection OT - cardiovascular outcomes OT - chronic kidney disease OT - composite kidney endpoint OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2026/06/24 06:36 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/24 00:33 PHST- 2026/06/02 00:00 [revised] PHST- 2026/05/06 00:00 [received] PHST- 2026/06/11 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/24 06:36 [pubmed] PHST- 2026/06/24 00:33 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71031 [pii] AID - 10.1111/dom.71031 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8337-8346. doi: 10.1111/dom.71031. Epub 2026 Jun 23. PMID- 42335260 OWN - NLM STAT- MEDLINE DCOM- 20260623 LR - 20260924 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 32 IP - 6 DP - 2026 Jun TI - Real-world weight loss with injectable semaglutide vs dulaglutide for diabetes. PG - 328-333 LID - 10.37765/ajmc.2026.89952 [doi] AB - OBJECTIVE: To compare the real-world effects of weekly injectable semaglutide (Ozempic) vs dulaglutide (Trulicity) on weight loss in an urban, predominantly African American patient sample with type 2 diabetes (T2D). STUDY DESIGN: This retrospective cohort study included adult patients with T2D at an academic internal medicine clinic who were initiated on semaglutide or dulaglutide. METHODS: The primary outcome was the percentage change in actual body weight (ABW) from baseline at 52 weeks. Secondary outcomes included mean weight loss in kg, weight loss of at least 5% and at least 10% at 52 weeks, percentage change in hemoglobin A1c (HbA1c) at 52 weeks, and HbA1c levels of less than 7% and less than 8% at 52 weeks. RESULTS: The percentage change in ABW from baseline at 52 weeks was greater with semaglutide (n = 60) than with dulaglutide (n = 60) (-6.51% vs -1.14%; P = .001). The absolute change in ABW at 52 weeks was greater with semaglutide than with dulaglutide (-15.98 kg vs -4.93 kg; P = .001). More patients using semaglutide achieved weight loss of at least 5% and at least 10% at 52 weeks than those using dulaglutide (>/= 5%: 51.7% vs 25.0%; P = .003; >/= 10%: 31.7% vs 8.3%; P = .001). A higher percentage of patients using semaglutide than those using dulaglutide achieved an HbA1c less than 7% and less than 8% at 52 weeks (< 7%: 53.3% vs 38.3%; P = .100; < 8%: 78.3% vs 68.3%; P = .220). The absolute change in HbA1c was greater with semaglutide than dulaglutide (-2.15% vs -1.36%; P = .033). CONCLUSIONS: Treatment with semaglutide resulted in a greater reduction in body weight and HbA1c than with dulaglutide in a real-world study of patients with T2D. FAU - Spitery, Allison AU - Spitery A AD - Henry Ford Health System, Detroit, MI. FAU - Lobkovich, Alison AU - Lobkovich A AD - Henry Ford Health System, Detroit, MI. AD - Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Ave, Detroit, MI 48201. Email: Alison.lobkovich@wayne.edu. FAU - Thomas, Emily AU - Thomas E AD - Henry Ford Health System, Detroit, MI. LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/administration & dosage MH - Semaglutide MH - *Recombinant Fusion Proteins/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Immunoglobulin Fc Fragments/therapeutic use/administration & dosage MH - Female MH - *Weight Loss/drug effects MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glycated Hemoglobin/analysis MH - Aged EDAT- 2026/06/23 18:33 MHDA- 2026/06/23 18:34 CRDT- 2026/06/23 14:23 PHST- 2026/06/23 18:34 [medline] PHST- 2026/06/23 18:33 [pubmed] PHST- 2026/06/23 14:23 [entrez] AID - 89952 [pii] AID - 10.37765/ajmc.2026.89952 [doi] PST - ppublish SO - Am J Manag Care. 2026 Jun;32(6):328-333. doi: 10.37765/ajmc.2026.89952. PMID- 42334436 OWN - NLM STAT- MEDLINE DCOM- 20260817 LR - 20260920 IS - 2055-6845 (Electronic) IS - 2055-6837 (Print) VI - 12 IP - 5 DP - 2026 Aug 17 TI - Semaglutide for primary prevention of major adverse cardiac and cerebrovascular events in patients with type 2 diabetes and comorbid rheumatoid arthritis: a target-trial emulation. PG - 368-378 LID - 10.1093/ehjcvp/pvag044 [doi] AB - AIMS: Rheumatoid arthritis (RA)-related physical limitations often hinder sustained physical activity and weight management, thereby amplifying cardiovascular risk through adverse metabolic profiles and chronic inflammation. We aimed to assess the effectiveness of semaglutide on the risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) in obese adults with type 2 diabetes mellitus (T2DM) and RA in a primary-prevention setting. METHODS AND RESULTS: We emulated a target trial using data from the TriNetX US database, including obese adults [aged >/=18 years; body mass index (BMI) >/=30 kg/m2] with T2DM and comorbid RA and no prior history of stroke, heart failure (HF), acute coronary syndrome, or coronary revascularization. Using a new-user design, we compared patients initiating semaglutide with those initiating non-GLP-1 receptor agonist (GLP-1RA) second-line glucose-lowering therapies. Patients with contraindications to GLP-1RAs were excluded. Propensity-score matching (PS) (1:1) was used to balance baseline covariates. The primary outcome was incident MACCE, defined as a composite of all-cause mortality, myocardial infarction (MI), HF, or stroke. Secondary outcomes included individual MACCE components, HF hospitalization, and disease-modifying anti-rheumatic drug (DMARD) escalation, with Bonferroni correction applied for multiple comparisons. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models over a follow-up of up to 2 years. Between 1 January 2014 and 1 January 2025, we identified 1200 and 2972 patients who initiated semaglutide and non-GLP-1RA therapies, respectively, within 3 months of meeting eligibility. After PS matching, 1017 semaglutide users were compared with 1017 non-GLP-1RA users (mean age 59.5 vs. 59.3 years; women 81.3% vs. 81.0%; mean BMI 38.2 vs. 38.0 kg/m2; HbA1c, 6.8% vs. 7.0%). Semaglutide initiation was associated with a significantly lower risk of incident MACCE compared with non-GLP-1RA therapies (12.7% vs. 16.5%; HR, 0.75; 95% CI, 0.60-0.94; P = 0.01). This benefit was driven primarily by a lower risk of incident HF (8.9% vs. 12.5%; HR, 0.69, 95% CI, 0.53-0.91; P = 0.007). Semaglutide use was also associated with significantly lower DMARD escalation (16.6% vs. 21.6%; HR, 0.75; 95% CI, 0.60-0.90; P = 0.003). No significant differences were observed in all-cause mortality, MI, or stroke. CONCLUSION: Among obese adults with T2DM and comorbid RA, initiation of semaglutide was associated with a reduced risk of incident MACCE, driven predominantly by a reduction in incident HF, in a primary-prevention setting. Prospective studies are needed to confirm these observations and establish causality. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of European Society of Cardiology. FAU - Malik, Farheen AU - Malik F AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Shah, Mandar AU - Shah M AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Chang, Yu AU - Chang Y AUID- ORCID: 0000-0001-9618-3267 AD - Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, Tainan 704302, Taiwan. FAU - Chowdhury, Ishmum AU - Chowdhury I AUID- ORCID: 0000-0001-7029-2369 AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Mangalesh, Sridhar AU - Mangalesh S AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Morgan, Ahmed Ashraf AU - Morgan AA AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Pascal, Ezerioha AU - Pascal E AD - Department of Internal Medicine, Jacobi Medical Center/North Central Bronx, Albert Einstein College of Medicine, Bronx, NY 10467, USA. FAU - Modak, Vishakha AU - Modak V AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Lebovics, Nachum AU - Lebovics N AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Adhikari, Suraj AU - Adhikari S AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Lee, Pei-Lun AU - Lee PL AUID- ORCID: 0009-0007-3252-6719 AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. FAU - Chen, Wei-Cheng AU - Chen WC AUID- ORCID: 0000-0002-1516-3799 AD - Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan. FAU - Chi, Kuan-Yu AU - Chi KY AUID- ORCID: 0000-0003-0763-8157 AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY 10469, USA. LA - eng PT - Journal Article PL - England TA - Eur Heart J Cardiovasc Pharmacother JT - European heart journal. Cardiovascular pharmacotherapy JID - 101669491 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/mortality/blood MH - *Arthritis, Rheumatoid/diagnosis/epidemiology/drug therapy/mortality MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Female MH - Middle Aged MH - Male MH - Treatment Outcome MH - Risk Assessment MH - *Primary Prevention/methods MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Comorbidity MH - Incidence MH - Time Factors MH - *Obesity/diagnosis/drug therapy/epidemiology/mortality MH - United States/epidemiology MH - *Cerebrovascular Disorders/prevention & control/diagnosis/epidemiology/mortality MH - Databases, Factual MH - *Incretins/therapeutic use/adverse effects MH - Risk Factors PMC - PMC13588637 OTO - NOTNLM OT - Diabetes OT - Primary prevention OT - Rheumatoid arthritis OT - Semaglutide COIS- Conflict of interest: None declared. EDAT- 2026/06/23 12:35 MHDA- 2026/08/17 11:40 PMCR- 2026/06/23 CRDT- 2026/06/23 10:53 PHST- 2026/02/16 00:00 [received] PHST- 2026/03/31 00:00 [revised] PHST- 2026/06/16 00:00 [accepted] PHST- 2026/08/17 11:40 [medline] PHST- 2026/06/23 12:35 [pubmed] PHST- 2026/06/23 10:53 [entrez] PHST- 2026/06/23 00:00 [pmc-release] AID - 8713824 [pii] AID - pvag044 [pii] AID - 10.1093/ehjcvp/pvag044 [doi] PST - ppublish SO - Eur Heart J Cardiovasc Pharmacother. 2026 Aug 17;12(5):368-378. doi: 10.1093/ehjcvp/pvag044. PMID- 42331726 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260831 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Dual Glucagon and GLP-1 Receptor Agonist Survodutide Improves Biomarkers of Beta-Cell Function and Insulin Sensitivity in People With Type 2 Diabetes or Living With Overweight/Obesity. PG - 8242-8253 LID - 10.1111/dom.70861 [doi] AB - AIMS: This post hoc analysis evaluated the effect of survodutide on beta-cell function, insulin sensitivity, and glucose biomarkers in two phase 2 trial populations. MATERIALS AND METHODS: Trial 1404-0002 randomised 413 participants with type 2 diabetes on metformin to receive survodutide, placebo, or semaglutide over 16 weeks. Trial 1404-0036 randomised 387 participants with overweight/obesity and normoglycaemia to receive survodutide or placebo for 46 weeks. Descriptive statistics were derived from both trials. Biomarker responses were analysed using mixed models for repeated measures and regression analysis to assess the impact of bodyweight changes. RESULTS: In trial 1404-0002, survodutide was associated with significant and rapid increases in HOMA-beta versus placebo, with significant decreases in HOMA-IR, glucagon, and fasting plasma glucose (FPG). No significant changes occurred in high-molecular-weight (HMW) adiponectin, C-peptide, or fasting insulin levels. In trial 1404-0036, there was no significant change in HOMA-beta with survodutide versus placebo, likely owing to normoglycaemia in participants. Survodutide was associated with significant decreases in HOMA-IR, glucagon, C-peptide, fasting insulin, and FPG versus placebo, and significant increases in HMW adiponectin. Combining all survodutide dose groups for each trial, absolute change in bodyweight from baseline explained the largest proportion of total variability in changes from baseline in fasting insulin and HOMA-IR. However, it did not explain other changes observed. CONCLUSIONS: Survodutide was associated with significantly improved beta-cell function and insulin sensitivity in adults with type 2 diabetes and with overweight or obesity. The durability of beta-cell improvements after treatment cessation remains unknown. These effects were largely independent of bodyweight changes, suggesting additional metabolic benefit beyond weight loss. TRIAL REGISTRATION: Trial 1404-0002, ClinicalTrials.gov identifier: NCT04153929; EudraCT number: 2019-002390-60. Trial 1404-0036, ClinicalTrials.gov identifier: NCT04667377; EudraCT number: 2020-002479-37. CI - (c) 2026 Boehringer Ingelheim Pharma GmbH & Co. KG and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ekinci, Elif I AU - Ekinci EI AUID- ORCID: 0000-0003-2372-395X AD - Australian Centre for Accelerating Diabetes Innovations (ACADI), The University of Melbourne, Melbourne, Victoria, Australia. AD - Department of Medicine, Melbourne Medical School, The University of Melbourne, Melbourne, Victoria, Australia. AD - Centre for Research and Education in Diabetes and Obesity (CREDO) and Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia. FAU - Maldonado, Sandra Gonzalez AU - Maldonado SG AUID- ORCID: 0009-0005-7723-7027 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Unseld, Anna AU - Unseld A AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Martinez, Jorge Arrubla AU - Martinez JA AUID- ORCID: 0000-0002-5926-9472 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. FAU - Hennige, Anita M AU - Hennige AM AUID- ORCID: 0000-0002-5149-4966 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Schoelch, Corinna AU - Schoelch C AUID- ORCID: 0009-0001-3596-7348 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. LA - eng SI - ClinicalTrials.gov/NCT04153929 SI - ClinicalTrials.gov/NCT04667377 GR - Boehringer Ingelheim/ PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20260622 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Biomarkers) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9007-92-5 (Glucagon) RN - 9100L32L2N (Metformin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Peptide Fragments) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood/metabolism MH - *Insulin Resistance/physiology MH - *Insulin-Secreting Cells/drug effects/metabolism/physiology MH - Female MH - Male MH - Biomarkers/blood/metabolism MH - Middle Aged MH - *Obesity/complications/drug therapy/metabolism/blood MH - *Hypoglycemic Agents/therapeutic use MH - *Overweight/complications/drug therapy/metabolism/blood MH - Semaglutide MH - Blood Glucose/drug effects/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon/agonists MH - Metformin/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Adult MH - Diabesity MH - Double-Blind Method MH - *Peptide Fragments/therapeutic use MH - Drug Therapy, Combination MH - Aged PMC - PMC13448873 OTO - NOTNLM OT - GLP-1 OT - beta-cell function OT - glucagon OT - insulin sensitivity OT - obesity OT - overweight OT - survodutide OT - type 2 diabetes COIS- The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE), as supported by Good Publication Practice (GPP) guidelines. The authors did not receive payment related to the development of this manuscript. E.I.E. is a consultant to Eli Lilly Australia and Novo Nordisk; funds are paid to her institution and are used for diabetes research, and her institute reports research funding support from Abbott, Amgen, Arrowhead Pharmaceuticals, Boehringer Ingelheim, Bayer, Eli Lilly Australia, Endogenex, Insulet, NewAmsterdam, Novartis, and Versanis. S.G.M., A.U., J.A.M., A.M.H., and C.S. are employees of Boehringer Ingelheim. EDAT- 2026/06/23 00:33 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/22 22:03 PHST- 2026/04/28 00:00 [revised] PHST- 2026/01/21 00:00 [received] PHST- 2026/04/29 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/23 00:33 [pubmed] PHST- 2026/06/22 22:03 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM70861 [pii] AID - 10.1111/dom.70861 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8242-8253. doi: 10.1111/dom.70861. Epub 2026 Jun 22. PMID- 42324672 OWN - NLM STAT- MEDLINE DCOM- 20260901 LR - 20260903 IS - 1600-0447 (Electronic) IS - 0001-690X (Print) IS - 0001-690X (Linking) VI - 154 IP - 4 DP - 2026 Oct TI - Use of Glucagon-Like Peptide 1 Receptor Agonists and the Associated Risk of Hospitalisation in Bipolar Disorder, From a Nationwide Cohort, 2009-2024. PG - 305-312 LID - 10.1111/acps.70120 [doi] AB - INTRODUCTION: Diabetes, obesity and bipolar disorder often co-occur and may have shared pathophysiology. Glucagon-like peptide 1 receptor agonists (GLP-1RA) treat diabetes and obesity but their impact on bipolar disorder is unknown. In this era of stagnated pharmacotherapy, we examined psychiatric hospitalisation and absence from work due to sick leave as potential measures of relapse in people diagnosed with bipolar disorder who were also prescribed antidiabetic medications, including GLP-1RA. METHODS: The study cohort was derived from the National Swedish Registers and included all people with a diagnosis of bipolar disorder who used any antidiabetic medication, between the years 2009 and 2024. GLP-1RA individually and as a group were compared with non-use of GLP-1RA, and directly with other second-line antidiabetic medications. A within-individual design was utilised for all comparisons to reduce confounding. The main outcome was psychiatric hospitalisation for any reason, with secondary outcomes being psychiatric hospitalisation after a relapse of bipolar disorder, and sick leave due to psychiatric reasons. Within-individual stratified Cox models with adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were used. RESULTS: 14,694 people were included in the study, of whom 5200 used GLP-1RA. Semaglutide was associated with a 21% (aHR 0.79, 95% CI 0.69-0.91) lower risk of psychiatric hospitalisation compared with non-use of GLP-1RA in that same individual. Liraglutide and dulaglutide were not specifically associated with a lower hospitalisation risk. Semaglutide was also linked to a 17% (aHR 0.83, 95% CI 0.69-0.99) lower risk of relapse of bipolar disorder. Absences from work due to sick leave were not significantly associated with the specific antidiabetic medications studied. CONCLUSION: In people with both bipolar disorder and diabetes and/or obesity, the use of semaglutide was linked to lower rates of psychiatric hospitalisation compared with time periods when GLP-1RA were not used by that individual. Liraglutide and dulaglutide were not associated with reduced psychiatric hospitalisation, implying this is not a class effect. This finding with semaglutide should be further tested in a randomised controlled trial. CI - (c) 2026 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd. FAU - Taipale, Heidi AU - Taipale H AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Centre for Psychiatry Research, Stockholm City Council, Stockholm, Sweden. AD - School of Pharmacy, University of Eastern Finland, Kuopio, Finland. FAU - Taylor, Mark AU - Taylor M AUID- ORCID: 0000-0002-1159-6810 AD - School of Medicine and Dentistry, Griffith University, Gold Coast, Australia. AD - The Edinburgh Practice, Edinburgh, UK. FAU - Lahteenvuo, Markku AU - Lahteenvuo M AUID- ORCID: 0000-0002-7244-145X AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. FAU - Mittendorfer-Rutz, Ellenor AU - Mittendorfer-Rutz E AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Tanskanen, Antti AU - Tanskanen A AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Tiihonen, Jari AU - Tiihonen J AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. AD - Centre for Psychiatry Research, Stockholm City Council, Stockholm, Sweden. LA - eng GR - Sigrid Juselius Foundation/ GR - 250038/Jane and Aatos Erkko Foundation/ GR - Finnish Ministry of Social Affairs and Health/ GR - 2021-00154/Swedish Research Council/ PT - Journal Article DEP - 20260621 PL - United States TA - Acta Psychiatr Scand JT - Acta psychiatrica Scandinavica JID - 0370364 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Bipolar Disorder/epidemiology/drug therapy MH - Sweden/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - *Hospitalization/statistics & numerical data MH - Male MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Registries/statistics & numerical data MH - Middle Aged MH - Adult MH - Cohort Studies MH - Sick Leave/statistics & numerical data MH - Liraglutide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Obesity/drug therapy/epidemiology MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC13532777 OTO - NOTNLM OT - GLP-1RA OT - bipolar OT - hospitalisation COIS- Drs Taipale, Tanskanen, Mittendorfer-Rutz and Tiihonen have participated in research projects funded by grants from Janssen to their employing institution. Dr. Taipale reports personal fees from Gedeon Richter, Janssen, Lundbeck and Otsuka. Dr. Tiihonen has received grants from EU/Forte, Finnish State Research Funding and Jane and Aatos Erkko Foundation, has been a consultant and/or advisor to and/or has received honoraria from: Healthcare Global Village, HLS Therapeutics, Janssen-Cilag, Lundbeck, Orion, Otsuka, Teva and WebMD Global. Dr. Lahteevuo has been a consultant and/or advisor and/or received honoraria from Lundbeck, Otsuka Pharma, Janssen, Johnson & Johnson, Orion Pharma and Recordati. The other author declare no conflicts of interest. EDAT- 2026/06/22 06:47 MHDA- 2026/09/01 17:39 PMCR- 2026/09/01 CRDT- 2026/06/22 00:53 PHST- 2026/05/15 00:00 [revised] PHST- 2026/02/13 00:00 [received] PHST- 2026/06/01 00:00 [accepted] PHST- 2026/09/01 17:39 [medline] PHST- 2026/06/22 06:47 [pubmed] PHST- 2026/06/22 00:53 [entrez] PHST- 2026/09/01 00:00 [pmc-release] AID - ACPS70120 [pii] AID - 10.1111/acps.70120 [doi] PST - ppublish SO - Acta Psychiatr Scand. 2026 Oct;154(4):305-312. doi: 10.1111/acps.70120. Epub 2026 Jun 21. PMID- 42309121 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 8 DP - 2026 Aug TI - 1-year outcomes of semaglutide, tirzepatide, and sleeve gastrectomy in obesity in type 2 diabetes: a retrospective cohort study. PG - 638-648 LID - S2213-8587(26)00030-6 [pii] LID - 10.1016/S2213-8587(26)00030-6 [doi] AB - BACKGROUND: Type 2 diabetes and obesity are prevalent, inter-related conditions for which treatment options have expanded substantially, yet direct real-world comparisons of modern pharmacological and surgical interventions remain scarce. We aimed to compare 1-year weight loss, glycaemic outcomes, and selected safety outcomes associated with semaglutide, tirzepatide, and sleeve gastrectomy among adults with obesity and type 2 diabetes in real-world clinical practice. METHODS: We conducted a retrospective cohort study using Epic Cosmos, a de-identified electronic health record dataset from 1633 hospitals and 37 900 clinics across 280 health systems in the USA. Adults with a BMI of at least 35 kg/m(2) and HbA(1c) above 6.4% who initiated at least 12 months of therapy with semaglutide or tirzepatide and attaining maintenance doses, or who underwent sleeve gastrectomy, were eligible for inclusion. The primary outcome was attainment of at least 20% bodyweight loss and HbA(1c) below 5.7% at 1 year after the index date. Multivariable logistic regression estimated adjusted probabilities and relative risks, adjusting for age, sex, race, baseline HbA(1c), BMI, Charlson Comorbidity Index, Social Vulnerability Index (SVI 2020), and baseline medication burden for diabetes, lipids, and hypertension. Prespecified safety outcomes included emergency department visits and new prescriptions for gastro-oesophageal reflux disease or nausea within 1 year of the index date. The primary composite outcome was analysed among patients with both follow-up weight and HbA(1c) available in the 9-month to 15-month window. Emergency department visits were analysed in the final analysis cohort (ie, patients meeting all inclusion and exclusion criteria and with available baseline and 9-month to 15-month weight and HbA(1c) measurements) and medication-based safety outcomes were analysed descriptively using outcome-specific available data denominators without imputation. FINDINGS: A total of 468 712 patients with at least 365 consecutive days of semaglutide or tirzepatide prescriptions and 238 028 patients undergoing sleeve gastrectomy were identified in Epic Cosmos. After applying prespecified inclusion and exclusion criteria, 45 649 patients met inclusion criteria; after exclusion of 556 patients with missing Charlson Comorbidity Index data, 45 093 were included in the primary outcome analysis: 33 482 (74.3%) treated with semaglutide, 4178 (9.3%) treated with tirzepatide, and 7433 (16.5%) who underwent sleeve gastrectomy. The adjusted probability of attaining the primary composite outcome of at least 20% bodyweight loss and HbA(1c) below 5.7% at 1 year was 3.0% (95% CI 2.8-3.2) for semaglutide, 13.2% (12.2-14.3) for tirzepatide, and 24.0% (22.9-25.1) for sleeve gastrectomy. Emergency department visits within 1 year were more frequent after sleeve gastrectomy than after semaglutide or tirzepatide. New prescriptions for gastro-oesophageal reflux disease and nausea occurred in all treatment groups but varied in frequency, with higher absolute rates observed after sleeve gastrectomy. INTERPRETATION: At 1 year after the index date, sleeve gastrectomy was associated with the highest probability of attaining combined weight and glycaemic targets, followed by tirzepatide and semaglutide. Interpretation should consider baseline differences-including higher BMI, younger age, and lower baseline HbA(1c) in the sleeve gastrectomy group-as well as residual confounding and the limited scope of safety assessment. FUNDING: None. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Leslie, Daniel B AU - Leslie DB AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA. Electronic address: lesli002@umn.edu. FAU - Steffen, Brian T AU - Steffen BT AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA. FAU - Wise, Eric AU - Wise E AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA. FAU - Steffen, Lyn M AU - Steffen LM AD - Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. FAU - Kopacz, Kristi AU - Kopacz K AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA. FAU - Ruanpeng, Darin AU - Ruanpeng D AD - Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA. FAU - Jacobs, David R Jr AU - Jacobs DR Jr AD - Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. FAU - Ikramuddin, Sayeed AU - Ikramuddin S AD - Department of Surgery, University of Minnesota Medical School, Minneapolis, MN, USA. LA - eng PT - Journal Article DEP - 20260617 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Semaglutide MH - *Tirzepatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Gastrectomy/methods MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/drug therapy/complications/therapy MH - Weight Loss MH - Adult MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin/analysis COIS- Declaration of interests SI receives grant support from Rheacell. All other authors declare no competing interests. EDAT- 2026/06/18 00:32 MHDA- 2026/07/15 18:40 CRDT- 2026/06/17 18:52 PHST- 2025/07/08 00:00 [received] PHST- 2026/02/02 00:00 [revised] PHST- 2026/02/12 00:00 [accepted] PHST- 2026/07/15 18:40 [medline] PHST- 2026/06/18 00:32 [pubmed] PHST- 2026/06/17 18:52 [entrez] AID - S2213-8587(26)00030-6 [pii] AID - 10.1016/S2213-8587(26)00030-6 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Aug;14(8):638-648. doi: 10.1016/S2213-8587(26)00030-6. Epub 2026 Jun 17. PMID- 42308439 OWN - NLM STAT- MEDLINE DCOM- 20260617 LR - 20260813 IS - 1526-632X (Electronic) IS - 0028-3878 (Print) IS - 0028-3878 (Linking) VI - 107 IP - 1 DP - 2026 Jul 14 TI - Semaglutide and Risk of Adult-Onset Seizure: A Target Trial Emulation. PG - e218174 LID - 10.1212/WNL.0000000000218174 [doi] AB - BACKGROUND AND OBJECTIVES: Adult-onset seizure reflects the burden of acquired brain insults, but established disease-modifying preventive strategies are limited. We evaluated whether semaglutide initiation is associated with a lower incidence of adult-onset seizure compared with sodium-glucose cotransporter 2 inhibitors (SGLT2i) and other glucose-lowering drugs (GLDs) in adults with type 2 diabetes. METHODS: Using the All of Us Research Program, we emulated a population-based target trial in new-user, active-comparator cohorts from January 2018 to October 2023. We compared semaglutide vs other GLDs and semaglutide vs SGLT2i. Incident epilepsy or seizure was identified from diagnostic codes. Effects were estimated using inverse probability of treatment weighting with weighted Cox models and targeted maximum likelihood estimation (TMLE). Subgroup and sensitivity analyses with multiple outcome definitions and analytic approaches were conducted to assess the robustness of findings. We evaluated mediation through hemoglobin A1c (HbA1c) and body mass index (BMI) using the longitudinal Vansteelandt framework. RESULTS: We analyzed 10,213 patients in the semaglutide (n = 2,586, mean age, 60.1 years; 56.8% female) vs other GLDs cohort (n = 7,627, mean age, 63.7 years; 54.2% female) and 8,605 patients in the semaglutide (n = 2,814, mean age, 60.5 years; 66.2% female) vs SGLT2i cohort (n = 5,791, mean age, 64.4 years; 47.3% female). Semaglutide was associated with a lower risk of adult-onset seizure compared with other GLDs (weighted HR 0.44 [95% CI 0.25-0.79]; 4-year risk difference -1.78% [95% CI -2.58 to -0.98]) and SGLT2i (weighted HR 0.48 [95% CI 0.27-0.85]; 4-year risk difference -1.46% [95% CI -2.41 to -0.51]). TMLE estimated risk differences per 1,000 persons of -14.20 (95% CI -18.33 to -10.07) vs other GLDs and -7.62 (95% CI -11.65 to -3.60) vs SGLT2i, corresponding to numbers needed to treat of 70 and 131, respectively. Mediation was minimal for HbA1c (2.4% vs other GLDs; 6.5% vs SGLT2i) and BMI (0% vs other GLDs; 0.7% vs SGLT2i). DISCUSSION: Semaglutide initiation was associated with a lower risk of adult-onset seizure compared with SGLT2i and other GLDs in patients with type 2 diabetes, independent of glycemic and weight effects. Residual confounding, low event counts, and shorter follow-up limit causal interpretation. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that semaglutide use was associated with a lower risk of adult-onset seizures compared with other GLDs and SGLT2i. FAU - Eun, Yong AU - Eun Y AUID- ORCID: 0000-0001-7222-8328 AD - Department of Medicine, NYC Health + Hospitals/Harlem, New York. AD - Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY. FAU - Bong, Suhwan AU - Bong S AUID- ORCID: 0000-0001-6077-1198 AD - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA. FAU - Koh, Hyun Yong AU - Koh HY AUID- ORCID: 0000-0002-3995-4341 AD - Department of Pediatrics, Division of Neurology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX. FAU - Trousdale, Rhonda K AU - Trousdale RK AUID- ORCID: 0000-0002-9739-6966 AD - Department of Medicine, NYC Health + Hospitals/Harlem, New York. AD - Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY. AD - Division of Endocrinology, Department of Medicine, NYC Health + Hospitals/Harlem, New York. FAU - Cho, Young Min AU - Cho YM AUID- ORCID: 0000-0002-2331-6126 AD - Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, South Korea. FAU - Jang, Yoonhyuk AU - Jang Y AUID- ORCID: 0009-0004-5991-7822 AD - Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, South Korea. AD - Biomedical Research Institute, Seoul National University Hospital, South Korea; and. AD - Department of Immunology, Harvard Medical School, Harvard University, Boston, MA. FAU - Lee, Soon-Tae AU - Lee ST AUID- ORCID: 0000-0003-4767-7564 AD - Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, South Korea. LA - eng GR - OT2 OD037643/OD/NIH HHS/United States PT - Journal Article DEP - 20260617 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Seizures/epidemiology/prevention & control MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use PMC - PMC13278381 MID - NIHMS2162855 COIS- Conflict of Interest Disclosures Y. Eun reports no disclosures relevant to the manuscript. S. Bong reports no disclosures relevant to the manuscript. H.Y. Koh reports no disclosures relevant to the manuscript. R.K. Trousdale reports no disclosures relevant to the manuscript. Y.M. Cho received consultation fees from LG Chemical and Hanmi, research grants from Sanofi, AstraZeneca, and Daewoong Pharmaceuticals. Y.M. Cho is an outside director of Daewoong Pharmaceuticals. Y. Jang reports no disclosures relevant to the manuscript. S.-T. Lee reports advisory roles from Roche/Genentech, Advanced Neural Technologies, argenx, Arialys, Piehealthcare, and Salted, outside the submitted work. EDAT- 2026/06/17 18:35 MHDA- 2026/06/17 18:36 PMCR- 2026/06/18 CRDT- 2026/06/17 16:02 PHST- 2026/06/17 18:36 [medline] PHST- 2026/06/17 18:35 [pubmed] PHST- 2026/06/17 16:02 [entrez] PHST- 2026/06/18 00:00 [pmc-release] AID - 10.1212/WNL.0000000000218174 [doi] PST - ppublish SO - Neurology. 2026 Jul 14;107(1):e218174. doi: 10.1212/WNL.0000000000218174. Epub 2026 Jun 17. PMID- 42304171 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260908 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Comparative Effects of Antidiabetic Drugs on Body Composition: A Systematic Review and Network Meta-Analysis. PG - 7689-7704 LID - 10.1111/dom.70957 [doi] AB - BACKGROUND: Antidiabetic drugs differ in their effects on body composition, which may influence metabolic and functional outcomes. This systematic review and network meta-analysis aimed to quantify and compare effects of major antidiabetic drugs on key body composition parameters. METHODS: PubMed, Web of Science and Scopus were searched from inception to March 2025 for randomized controlled trials. Network meta-analyses used a frequentist random-effects framework to estimate mean differences (MDs) and 95% confidence intervals (CIs) for changes in fat mass (FM) and lean body mass (LBM). RESULTS: Forty-one trials involving 2906 participants were included. For FM among Glucagon-like peptide-1 (GLP-1) and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, tirzepatide showed the greatest reduction compared with placebo (MD -10.70 kg; 95% CI: -13.42 to -7.99), followed by liraglutide plus exercise. Semaglutide and liraglutide produced moderate reductions. In contrast, insulin glargine and alogliptin were associated with FM gain relative to metformin and exenatide. For LBM, tirzepatide (MD -4.40 kg; 95% CI: -7.58 to -1.22) and liraglutide (MD -1.54 kg; 95% CI: -2.55 to -0.52) were associated with significant reductions. Sodium-glucose cotransporter-2 (SGL2) inhibitors caused minor losses, whereas metformin, insulin regimens and dipeptidyl peptidase-4 (DPP4) inhibitors showed neutral effects. CONCLUSION: GLP-1 and dual GIP/GLP-1 receptor agonists produced the greatest FM reduction but also decreased lean mass. Exercise mitigated liraglutide-related LBM loss. SGLT2 inhibitors showed modest effects, while metformin, insulin, DPP4 inhibitors and sulfonylureas had minimal impact. Further research on dose, duration and lifestyle influences is warranted. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Rakhsha, Seyedeh Samira AU - Rakhsha SS AD - Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. AD - Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran. FAU - Shahinfar, Hossein AU - Shahinfar H AD - Nutritional Health Research Center, School of Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran. FAU - Ebrahimi-Mousavi, Sara AU - Ebrahimi-Mousavi S AD - Department of Clinical Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. AD - Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Kosari, Ali AU - Kosari A AD - Student Research Committee, Lorestan University of Medical Sciences, Khorramabad, Iran. FAU - Aali, Yasaman AU - Aali Y AUID- ORCID: 0000-0001-8320-6300 AD - Department of Clinical Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. AD - Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Mirzababaei, Atieh AU - Mirzababaei A AD - Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Hosseini, Seyed Alireza AU - Hosseini SA AD - Student Research Committee, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran. FAU - Jadidi, Paria AU - Jadidi P AD - Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran. FAU - Shafiee, Gita AU - Shafiee G AD - Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - MansourZadeh, Mohammad Javad AU - MansourZadeh MJ AD - Prevention of Metabolic Disorders Research Center, Research Institute for Metabolic and Obesity Disorders, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Heshmat, Ramin AU - Heshmat R AD - Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. FAU - Mastouri, Dena AU - Mastouri D AD - Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. LA - eng GR - 1403-04-75722-221/Chronic Diseases Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences/ PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260616 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin Secretagogues) RN - 9100L32L2N (Metformin) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Body Composition/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/pharmacology MH - Insulin Secretagogues MH - Metformin/pharmacology MH - Randomized Controlled Trials as Topic MH - Semaglutide MH - Tirzepatide PMC - PMC13449080 OTO - NOTNLM OT - DPP-IV inhibitor OT - GLP-1 OT - SGLT2 inhibitor OT - antidiabetic drug OT - incretin therapy OT - metformin COIS- AI tool ChatGPT (version GPT-5 mini) was used solely to assist with language editing and formatting; all analyses and interpretations were performed by the authors. The authors declare no conflicts of interest. EDAT- 2026/06/17 00:35 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/16 23:43 PHST- 2026/05/10 00:00 [revised] PHST- 2026/02/27 00:00 [received] PHST- 2026/05/18 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/17 00:35 [pubmed] PHST- 2026/06/16 23:43 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM70957 [pii] AID - 10.1111/dom.70957 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):7689-7704. doi: 10.1111/dom.70957. Epub 2026 Jun 16. PMID- 42302979 OWN - NLM STAT- MEDLINE DCOM- 20260820 LR - 20260903 IS - 1523-6838 (Electronic) IS - 0272-6386 (Linking) VI - 88 IP - 3 DP - 2026 Sep TI - Comparison of Specific Glucagon-Like Peptide-1 Receptor Agonists on Kidney Outcomes Among Patients With Type 2 Diabetes. PG - 366-377 LID - S0272-6386(26)00964-9 [pii] LID - 10.1053/j.ajkd.2026.04.007 [doi] AB - RATIONALE & OBJECTIVE: Glucagon-like peptide 1 (GLP-1) receptor agonist treatment is associated with a lower risk for incident chronic kidney disease (CKD) and death relative to treatment with a dipeptidyl peptidase 4 inhibitor or sulfonylurea. This study examined within class effects of GLP-1 receptor agonists on kidney outcomes in type 2 diabetes mellitus (T2DM) and moderate cardiovascular risk. STUDY DESIGN: Retrospective observational study using the target trial emulation framework. SETTING & PARTICIPANTS: This study used claims data from OptumLabs Data Warehouse and 100% sample of Medicare fee-for-service claims. Participants were adults >/=21 years of age, at moderate cardiovascular risk, who filled a new prescription for a GLP-1 receptor agonist between January 1, 2019 and December 31, 2021. EXPOSURE: GLP-1 receptor agonists dulaglutide, exenatide, liraglutide, or semaglutide. OUTCOME: A primary kidney composite outcome inclusive of incident diagnosis codes for CKD stages 3-4 and kidney failure (inclusive of CKD stage 5 and kidney replacement therapy). A secondary kidney composite outcome included the elements of the primary composite outcome plus death from any cause. Components of the kidney composite outcomes were also evaluated independently. ANALYTICAL APPROACH: Random treatment assignment was emulated using inverse probability of treatment weighting (IPTW) with propensity scores estimated using the SuperLearner ensemble method. Primary analyses were time-to-event models under the intention-to-treat framework using cause-specific IPTW Cox proportional hazards models. RESULTS: There was no difference among dulaglutide, exenatide, liraglutide, and semaglutide with respect to the primary outcome. When compared to dulaglutide and exenatide, semaglutide was associated with a reduced risk for the secondary kidney composite outcome by 8% (HR, 0.92 [95% CI, 0.87-0.97]) and 12% (HR, 0.88 [95% CI, 0.79-0.99]), respectively. Compared to dulaglutide, semaglutide was also associated with reduced risk of death (HR, 0.81 [95% CI, 0.70-0.93]). LIMITATIONS: Potential for residual confounding, lack of hemoglobin A(1c) and weight data, and uncertainty about the indication for GLP-1 receptor agonist prescriptions. CONCLUSIONS: No differences were observed among different GLP-1 receptor agonists for the primary outcome, but semaglutide initiation was associated with a lower risk of the secondary kidney composite outcome and of death. PLAIN-LANGUAGE SUMMARY: Chronic kidney disease (CKD) is a common complication of diabetes that increases the risk for poor health outcomes. Glucagon-like peptide-1 (GLP-1) receptor agonists were found to improve kidney outcomes in people with type 2 diabetes mellitus (T2DM) and moderate cardiovascular risk when compared with dipeptidyl peptidase-4 inhibitors and sulfonylureas. Although there has been no head-to-head comparison of individual GLP-1 receptor agonists, randomized controlled trials have suggested that there may be variation among members of this drug class on kidney disease outcomes. In this study, we tested whether there were differences in kidney outcomes when comparing individual GLP-1 receptor agonist medications. We found that semaglutide compared favorably to other drugs in the class and may represent the preferred GLP-1 receptor agonist for delaying or preventing CKD in this population. CI - Copyright (c) 2026 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. FAU - Neumiller, Joshua J AU - Neumiller JJ AD - Department of Pharmacotherapy, Washington State University, Spokane, Washington; Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington. Electronic address: jneumiller@wsu.edu. FAU - Deng, Yihong AU - Deng Y AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota; OptumLabs, Eden Prairi, Minnesota. FAU - Swarna, Kavya Sindhu AU - Swarna KS AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota; OptumLabs, Eden Prairi, Minnesota. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, Chicago, Illinois. FAU - Herrin, Jeph AU - Herrin J AD - Section of Cardiovascular Medicine, School of Medicine, Yale University, New Haven, Connecticut. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia. FAU - Ross, Joseph S AU - Ross JS AD - Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut; Department of Health Policy and Management, School of Public Health, Yale University, New Haven, Connecticut. FAU - Mickelson, Mindy M AU - Mickelson MM AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. FAU - Dryden, Kate AU - Dryden K AD - Department of Pharmacotherapy, Washington State University, Spokane, Washington. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington; Kidney Research Institute and Institute of Translational Health Sciences, University of Washington, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington. FAU - McCoy, Rozalina G AU - McCoy RG AD - OptumLabs, Eden Prairi, Minnesota; Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland; Institute for Health Computing, University of Maryland, North Bethesda, Maryland. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20260616 PL - United States TA - Am J Kidney Dis JT - American journal of kidney diseases : the official journal of the National Kidney Foundation JID - 8110075 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Female MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Semaglutide MH - Male MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - *Renal Insufficiency, Chronic/epidemiology MH - Exenatide/therapeutic use MH - Liraglutide/therapeutic use MH - Middle Aged MH - United States/epidemiology MH - *Diabetic Nephropathies OTO - NOTNLM OT - Chronic kidney disease OT - GLP-1 receptor agonist OT - comparative effectiveness and safety OT - target trial emulation OT - type 2 diabetes EDAT- 2026/06/17 00:36 MHDA- 2026/08/20 23:35 CRDT- 2026/06/16 19:34 PHST- 2025/07/18 00:00 [received] PHST- 2026/02/28 00:00 [revised] PHST- 2026/04/05 00:00 [accepted] PHST- 2026/08/20 23:35 [medline] PHST- 2026/06/17 00:36 [pubmed] PHST- 2026/06/16 19:34 [entrez] AID - S0272-6386(26)00964-9 [pii] AID - 10.1053/j.ajkd.2026.04.007 [doi] PST - ppublish SO - Am J Kidney Dis. 2026 Sep;88(3):366-377. doi: 10.1053/j.ajkd.2026.04.007. Epub 2026 Jun 16. PMID- 42297751 OWN - NLM STAT- MEDLINE DCOM- 20260807 LR - 20260908 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 9 DP - 2026 Sep TI - Weight Changes With Lower Doses of Semaglutide in Clinical Practice: Findings From the Chinese HARMONY Cohort. PG - 8025-8033 LID - 10.1111/dom.71004 [doi] AB - INTRODUCTION: To evaluate 24-week weight changes with lower-dose semaglutide in routine care among Chinese adults with obesity and to examine whether diabetes and ectopic fat in the liver and pancreas are associated with heterogeneity in weight-loss response. MATERIALS AND METHODS: Adults with obesity were enrolled from the HARMONY study, a real-world observational cohort in China. Participants received once-weekly subcutaneous semaglutide, titrated to a maintenance dose (0.5 or 1.0 mg) based on clinical response and tolerability, alongside lifestyle counselling and periodic metabolic monitoring. The primary endpoint was the percentage change in body weight from baseline at weeks 12 and 24. Subgroup analyses were conducted according to baseline type 2 diabetes status and ectopic fat status in the liver and pancreas. RESULTS: Overall, 143 participants were included at week 12 and 113 at week 24. Mean percent weight change was -7.3% at week 12 and -9.9% at week 24, corresponding to mean absolute weight losses of 6.7 and 9.1 kg, respectively. By week 24, 76.1% of participants achieved 5% weight loss or more. At week 24, participants with type 2 diabetes experienced lower weight change than those without diabetes (-7.4% vs. -12.4%, p < 0.001). Weight loss also differed by baseline intrapancreatic fat deposition (IPFD) status, with attenuated weight change among patients with baseline IPFD (-9.0% with IPFD vs. -11.6% without IPFD, p = 0.043). DISCUSSION: In routine clinical care, lower doses of semaglutide were associated with clinically meaningful 24-week weight loss in Chinese adults with obesity. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Liu, Shuang AU - Liu S AD - Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. AD - Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Cao, Baige AU - Cao B AD - Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Lin, Chuwen AU - Lin C AD - Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Chen, Weijiong AU - Chen W AD - Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Yang, Panpan AU - Yang P AD - Department of Diagnostic Radiology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Luo, Yu AU - Luo Y AD - Department of Diagnostic Radiology, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Xu, Jinfang AU - Xu J AD - Department of Health Statistics, Naval Medical University, Shanghai, China. FAU - Wang, Congrong AU - Wang C AUID- ORCID: 0000-0002-8645-1114 AD - Department of Endocrinology & Metabolism, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. AD - Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China. LA - eng GR - 82070913/National Natural Science Foundation of China/ GR - HKLCFC 202403/Clinical Key Supporting Project of Health Commission of Shanghai Hongkou District/ GR - 2023ZD0509206/Noncommunicable Chronic Diseases-National Science and Technology Major Project/ PT - Journal Article PT - Observational Study DEP - 20260615 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - Chinese people SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - China/epidemiology MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Dose-Response Relationship, Drug MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Obesity/drug therapy/complications MH - Semaglutide MH - Treatment Outcome MH - *Weight Loss/drug effects MH - East Asian People PMC - PMC13449065 OTO - NOTNLM OT - GLP-1 OT - obesity therapy OT - observational study OT - weight management COIS- The authors declare no conflicts of interest. EDAT- 2026/06/16 00:33 MHDA- 2026/08/07 12:39 PMCR- 2026/08/07 CRDT- 2026/06/15 22:42 PHST- 2026/06/01 00:00 [revised] PHST- 2026/04/13 00:00 [received] PHST- 2026/06/03 00:00 [accepted] PHST- 2026/08/07 12:39 [medline] PHST- 2026/06/16 00:33 [pubmed] PHST- 2026/06/15 22:42 [entrez] PHST- 2026/08/07 00:00 [pmc-release] AID - DOM71004 [pii] AID - 10.1111/dom.71004 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Sep;28(9):8025-8033. doi: 10.1111/dom.71004. Epub 2026 Jun 15. PMID- 42297449 OWN - NLM STAT- MEDLINE DCOM- 20260615 LR - 20260813 IS - 1745-1701 (Electronic) IS - 0586-7614 (Print) IS - 0586-7614 (Linking) VI - 52 IP - 3 DP - 2026 Apr 10 TI - The Effect of Semaglutide on Antipsychotic-Induced Weight Gain and Other Metabolic Parameters, among a Cohort of Inpatients. LID - 10.1093/schbul/sbaf236 [doi] LID - sbaf236 AB - BACKGROUND AND HYPOTHESIS: Antipsychotic use in severe mental illnesses (SMI) is associated with metabolic dysregulation, including antipsychotic-induced weight gain (AIWG), type 2 diabetes (T2D), and dyslipidemia. In the case of non-response to metformin which is currently recommended for AIWG mitigation, no clear alternatives exist. Semaglutide, a weekly injectable glucagon like peptide-1 receptor agonist, represents a promising option. However, effectiveness and safety data in SMI are lacking. With initiation of semaglutide, we hypothesized weight loss, improvements in metabolic indices, and good tolerability. STUDY DESIGN: A retrospective chart review was conducted for inpatients receiving antipsychotics, initiated on once-weekly subcutaneous semaglutide between January 4, 2018 and March 31, 2024 at the Centre for Addiction and Mental Health in Toronto, Canada, that analyzed weight loss, metabolic parameters, and side effects. STUDY RESULTS: 47 individuals with SMI were included: 59.6% males, mean age of 43 +/- 13.2 years, 83% had dysglycemia, and 66% had T2D at baseline. The maximum dose of semaglutide in this cohort was 2 mg/week. There was a mean weight loss of 3.15 +/- 0.77 kg (n = 47), 7.27 +/- 0.97 kg (n = 24), 9.33 +/- 1.16 kg (n = 15), and 12.25 +/- 1.32 kg (n = 11) at 3, 6, 9, and 12 months, respectively (P < .001). Individuals without T2D experienced greater weight loss versus those with T2D (P = .022). Additionally, significant decreases were noted in body mass index and HbA1c (P < .001), alongside improvements in lipid parameters; most common side effects were gastrointestinal in nature but did not result in semaglutide discontinuation. CONCLUSION: This retrospective chart review of inpatients with SMI supports efficacy and safety of semaglutide up to a year of follow-up, warranting future adequately powered randomized controlled trials. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. FAU - De, Riddhita AU - De R AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, M5S 3K3, Canada. FAU - Amin Alfatwa, Yasser AU - Amin Alfatwa Y AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, M5S 3K3, Canada. FAU - Kanagasundaram, Pruntha AU - Kanagasundaram P AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. FAU - Saragosa, Julia Eve AU - Saragosa JE AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. FAU - Chan, Joyce AU - Chan J AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. FAU - Remington, Gary AU - Remington G AUID- ORCID: 0000-0001-9433-9416 AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, M5S 3K3, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada. AD - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, M5G 2C4, Canada. FAU - Retnakaran, Ravi AU - Retnakaran R AD - Institute of Medical Science, University of Toronto, Toronto, ON, M5S 3K3, Canada. AD - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, M5G 2C4, Canada. AD - Division of Endocrinology, University of Toronto, Toronto, ON, M5S 3H2, Canada. AD - Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada. FAU - Sanches, Marcos AU - Sanches M AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. FAU - Sockalingam, Sanjeev AU - Sockalingam S AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada. FAU - Agarwal, Sri Mahavir AU - Agarwal SM AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, M5S 3K3, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada. AD - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, M5G 2C4, Canada. FAU - Hahn, Margaret K AU - Hahn MK AD - Complex Care and Recovery, Centre for Addiction and Mental Health (CAMH), Toronto, ON, M6J 1H3, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, M5S 3K3, Canada. AD - Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, M5S 3K3, Canada. AD - Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada. AD - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, M5G 2C4, Canada. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark. LA - eng PT - Journal Article PL - United States TA - Schizophr Bull JT - Schizophrenia bulletin JID - 0236760 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Antipsychotic Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/administration & dosage/pharmacology MH - Male MH - *Antipsychotic Agents/adverse effects MH - Adult MH - Middle Aged MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/chemically induced MH - *Weight Gain/drug effects MH - *Schizophrenia/drug therapy MH - *Hypoglycemic Agents/administration & dosage/pharmacology MH - *Dyslipidemias/drug therapy/chemically induced MH - *Outcome Assessment, Health Care PMC - PMC13267902 OTO - NOTNLM OT - GLP1-RA OT - diabetes OT - dyslipidemia OT - obesity OT - schizophrenia-spectrum illness COIS- The authors have declared that there are no conflicts of interest in relation to the subject of this study. Outside of this work, M.K.H. has received consultant and speaker fees from Alkermes, and consultant fees from Merck. S.M.A. has received honoraria from HLS Therapeutics and has served on the advisory board for Boehringer Ingelheim, Canada. G.R. has received research support from HLS Therapeutics. R.R. reports grants from Boehringer Ingelheim, grants and personal fees from Novo Nordisk, personal fees from Sanofi, and Eli Lilly. All other authors report no conflict of interest. EDAT- 2026/06/16 00:33 MHDA- 2026/06/16 00:34 PMCR- 2026/06/15 CRDT- 2026/06/15 20:43 PHST- 2025/06/27 00:00 [received] PHST- 2025/10/09 00:00 [revised] PHST- 2025/12/01 00:00 [accepted] PHST- 2026/06/16 00:34 [medline] PHST- 2026/06/16 00:33 [pubmed] PHST- 2026/06/15 20:43 [entrez] PHST- 2026/06/15 00:00 [pmc-release] AID - 8708284 [pii] AID - sbaf236 [pii] AID - 10.1093/schbul/sbaf236 [doi] PST - ppublish SO - Schizophr Bull. 2026 Apr 10;52(3):sbaf236. doi: 10.1093/schbul/sbaf236. PMID- 42288971 OWN - NLM STAT- MEDLINE DCOM- 20260801 LR - 20260803 IS - 1744-7593 (Electronic) IS - 1742-5247 (Linking) VI - 23 IP - 8 DP - 2026 Aug TI - Current trends in semaglutide therapy and strategies to improve its bioavailability. PG - 1495-1509 LID - 10.1080/17425247.2026.2688990 [doi] AB - INTRODUCTION: A GLP-1 Receptor Agonist, semaglutide, is given in the management of type 2 diabetes mellitus and obese individuals. However, oral semaglutide exerts very low bioavailability due to multiple gastrointestinal and biopharmaceutical barriers. Delivery of oral semaglutide becomes difficult due to instability in GI fluids, degradation through proteolysis by various enzymes, and mucus diffusion limitation; epithelial permeability restricts the oral absorption of the drug, due to which the oral bioavailability of semaglutide is exceedingly low. This review identifies methods that enhance oral bioavailability as well as treatment efficacy of semaglutide. AREAS COVERED: This review provides a broad perspective on the drug and the various formulation strategies that can be developed to increase semaglutide's oral bioavailability, encompassing work on enteric coating, gut-targeted delivery, etc. Databases searched include Scopus, google scholar, PubMed, clinicaltrials.gov etc. This review also discussed and summarized all patents and clinical trials related to semaglutide formulations. EXPERT OPINION: Although various formulation approaches have been explored to improve semaglutide's oral bioavailability, this review proposes novel and promising strategies for gut-targeted delivery and enteric coating. These methods aim to prevent semaglutide from acidic degradation or neutralization in the stomach and from enzymatic degradation, thereby enhancing its intestinal uptake. FAU - Nayak, Swasthik AU - Nayak S AD - Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India. FAU - Dessai, Akanksha D AU - Dessai AD AD - Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India. FAU - Nayak, Usha Y AU - Nayak UY AUID- ORCID: 0000-0002-1995-3114 AD - Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, India. LA - eng PT - Journal Article PT - Review DEP - 20260621 PL - England TA - Expert Opin Drug Deliv JT - Expert opinion on drug delivery JID - 101228421 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/pharmacokinetics/pharmacology MH - Biological Availability MH - Animals MH - Administration, Oral MH - Drug Delivery Systems MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics/pharmacology MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Semaglutide OT - bioavailability OT - drug delivery system OT - enteric coating OT - gut targeted delivery EDAT- 2026/06/15 11:34 MHDA- 2026/08/02 00:30 CRDT- 2026/06/14 06:32 PHST- 2026/08/02 00:30 [medline] PHST- 2026/06/15 11:34 [pubmed] PHST- 2026/06/14 06:32 [entrez] AID - 10.1080/17425247.2026.2688990 [doi] PST - ppublish SO - Expert Opin Drug Deliv. 2026 Aug;23(8):1495-1509. doi: 10.1080/17425247.2026.2688990. Epub 2026 Jun 21. PMID- 42286992 OWN - NLM STAT- MEDLINE DCOM- 20260721 LR - 20260721 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 138 IP - 6 DP - 2026 Aug TI - Evidence-informed guidance for the clinical use of oral semaglutide in obesity management. PG - 654-664 LID - 10.1080/00325481.2026.2686467 [doi] AB - Oral semaglutide, the first oral glucagon-like peptide-1 (GLP-1) receptor agonist therapy approved for the treatment of type 2 diabetes, is now approved for obesity management and cardiovascular risk reduction in adults, demonstrating weight loss comparable to that of subcutaneous GLP-1 therapies, alongside improvements in cardiometabolic risk factors. The availability of oral semaglutide for the treatment of obesity provides healthcare professionals with additional opportunities to individualize therapy based on patient preferences, lifestyle, and clinical circumstances. However, the oral semaglutide formulation requires specific administration conditions to optimize absorption and effectiveness. Notably, oral semaglutide tablets should be taken first thing in the morning on an empty stomach with no more than half a glass of plain water (up to 120 mL or 4 fl oz), followed by 30 min before eating food, drinking additional fluids, or ingesting other oral medications. Person-centered clinical discussions between healthcare professionals (HCPs) and patients prior to treatment initiation are important to ensure patients understand administration requirements and why they are necessary, establish realistic expectations for obesity treatment targets, and cover approaches to maintain adherence. HCP-patient consultations should also include discussion of strategies to help patients minimize, prepare for, and manage adverse events. In this article, we provide practical guidance for incorporating oral semaglutide into obesity management, drawing on evidence from clinical trials, including the OASIS 4 trial, and the authors' clinical insights. FAU - Rubino, Domenica AU - Rubino D AUID- ORCID: 0000-0002-3072-2819 AD - Washington Center for Weight Management and Research, Arlington, VA, USA. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - Department of Medicine, University of Toronto, Toronto, ON, Canada. AD - Department of Medicine, McMaster University, Hamilton, ON, Canada. AD - Wharton Medical Clinic Weight & Diabetes Management, Burlington, ON, Canada. FAU - Knight, Michael G AU - Knight MG AUID- ORCID: 0000-0002-4113-9936 AD - Department of Medicine, The George Washington University, Washington, DC, USA. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Division of Endocrinology, Diabetes, and Hypertension Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. LA - eng PT - Journal Article PT - Review DEP - 20260612 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Obesity/drug therapy MH - Administration, Oral MH - *Anti-Obesity Agents/administration & dosage/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Weight Loss/drug effects MH - Evidence-Based Medicine MH - Practice Guidelines as Topic MH - Diabetes Mellitus, Type 2/drug therapy OAB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are medications that are prescribed for the treatment of obesity to help people lose weight by reducing their appetite and feelings of hunger. Most GLP-1RAs are injected into the fatty layer of tissue below the skin, which helps the body absorb the medication into the bloodstream. The GLP-1RA semaglutide has been available in an injectable format for the treatment of obesity for several years and is now also available as a tablet for adults who prefer not to use injections. In clinical trials, people who used the tablet form of semaglutide had similar weight loss to people who used injectable semaglutide. Semaglutide tablets have been designed in a way that resists break down by stomach acid, allowing more of the medication to be absorbed into the body, but there are important steps to follow when taking the tablet to ensure the medication works as well as possible. Based on learnings from clinical trials and the clinical experience of the authors, this article provides practical advice to support healthcare professionals in guiding their patients through these steps. It also covers important topics to discuss with patients before they start taking semaglutide tablets, including possible changes to how they take other medications, how to limit and manage potential side effects, and ways for patients to stay consistent with their treatment schedule. OABL- eng OTO - NOTNLM OT - Obesity OT - clinical practice OT - glucagon-like peptide-1 receptor agonist OT - oral semaglutide OT - weight management EDAT- 2026/06/13 06:39 MHDA- 2026/07/21 18:34 CRDT- 2026/06/13 02:43 PHST- 2026/07/21 18:34 [medline] PHST- 2026/06/13 06:39 [pubmed] PHST- 2026/06/13 02:43 [entrez] AID - 10.1080/00325481.2026.2686467 [doi] PST - ppublish SO - Postgrad Med. 2026 Aug;138(6):654-664. doi: 10.1080/00325481.2026.2686467. Epub 2026 Jun 12. PMID- 42286576 OWN - NLM STAT- MEDLINE DCOM- 20260825 LR - 20260903 IS - 1749-8090 (Electronic) IS - 1749-8090 (Linking) VI - 21 IP - 1 DP - 2026 Jun 12 TI - Boerhaave's syndrome associated with glucagon-like peptide-1 receptor agonist use: a case report. LID - 10.1186/s13019-026-04214-6 [doi] LID - 625 AB - BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes and weight loss, with well known gastrointestinal side effects including nausea, vomiting, and delayed gastric emptying. While mucosal injuries such as Mallory Weiss tears have been reported, full thickness esophageal perforation has not previously been described. We report the first documented case of Boerhaave's syndrome associated with GLP-1 RA use, highlighting the potential for rare but life threatening complications following abrupt reinitiation at high doses. CASE PRESENTATION: A previously healthy woman in her 50s presented with vasopressor dependent shock and respiratory failure requiring intubation following severe nausea, emesis, and acute chest pain. She had restarted semaglutide at the maximum 2.4 mg weekly dose the day prior to symptom onset, after several months off therapy and without dose titration. Imaging revealed pneumomediastinum and bilateral pleural effusions. Esophagram confirmed a contained esophageal perforation. She was managed with endoscopic stent placement, nasojejunal feeding, and chest tube drainage, followed by clinical improvement and discharge. Two months later, she was readmitted with necrotizing pneumonia. Imaging and endoscopy revealed an esophagopleural fistula, abscess, and migrated stent. She underwent left thoracotomy, abscess drainage, decortication, and wedge resection of necrotic lung. The perforation site was reinforced with an intercostal muscle flap, and a PEG tube was placed. Postoperatively, at 10-month follow up she was on a regular diet, PEG tube removed, and esophagus was healed on EGD. She was advised to permanently discontinue GLP-1 RAs. CONCLUSIONS: This case underscores a previously unreported but serious complication of GLP-1 RA therapy, transmural esophageal rupture, likely precipitated by drug induced gastroparesis and forceful emesis. Restarting semaglutide at a high dose without titration after a prolonged interruption likely increased vulnerability to injury. Clinicians should maintain a high index of suspicion for esophageal complications in patients presenting with chest pain and vomiting during GLP-1 RA initiation or reinitiation. Early multidisciplinary management is crucial to optimizing outcomes in this rare but life-threatening scenario. CI - (c) 2026. The Author(s). FAU - Aubrey, Jason M AU - Aubrey JM AD - Frederik Meijer Heart and Vascular Institute, Corewell Health West, Grand Rapids, Michigan, USA. jason.aubrey2@corewellhealth.org. AD - College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA. jason.aubrey2@corewellhealth.org. FAU - Benner, Chance AU - Benner C AD - Frederik Meijer Heart and Vascular Institute, Corewell Health West, Grand Rapids, Michigan, USA. AD - College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA. FAU - Lam, Geoffrey T AU - Lam GT AD - Frederik Meijer Heart and Vascular Institute, Corewell Health West, Grand Rapids, Michigan, USA. AD - College of Human Medicine, Michigan State University, Grand Rapids, Michigan, USA. LA - eng PT - Case Reports PT - Journal Article DEP - 20260612 PL - England TA - J Cardiothorac Surg JT - Journal of cardiothoracic surgery JID - 101265113 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - Boerhaave syndrome SB - IM MH - Humans MH - Female MH - *Esophageal Perforation/chemically induced/diagnosis/surgery MH - Semaglutide MH - *Mediastinal Diseases/chemically induced/diagnosis/surgery MH - Spontaneous Perforation MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Rupture, Spontaneous MH - Middle Aged MH - *Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Esophageal Diseases PMC - PMC13505130 OTO - NOTNLM OT - Boerhaave syndrome OT - Drug-induced gastroparesis OT - Esophageal diseases OT - Esophageal perforation OT - Glucagon-like peptide-1 OT - Glucagon-like peptide-1 receptor agonists OT - Semaglutide OT - Weight loss agent COIS- Declarations. Ethics approval: The Corewell health IRB reviewed the case and waived the need for IRB approval. Consent for publication: The patient gave consent for their case to be published. Competing interests: The authors declare no competing interests. Informed consent: Informed consent was obtained from the patient for publication of this case report. EDAT- 2026/06/13 06:38 MHDA- 2026/08/25 05:34 PMCR- 2026/06/12 CRDT- 2026/06/13 00:06 PHST- 2025/08/24 00:00 [received] PHST- 2026/04/15 00:00 [accepted] PHST- 2026/08/25 05:34 [medline] PHST- 2026/06/13 06:38 [pubmed] PHST- 2026/06/13 00:06 [entrez] PHST- 2026/06/12 00:00 [pmc-release] AID - 10.1186/s13019-026-04214-6 [pii] AID - 4214 [pii] AID - 10.1186/s13019-026-04214-6 [doi] PST - epublish SO - J Cardiothorac Surg. 2026 Jun 12;21(1):625. doi: 10.1186/s13019-026-04214-6. PMID- 42278227 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 11 DP - 2026 May 22 TI - Retrospective Comparative Study of Oral Versus Subcutaneous Semaglutide in Patients with Type 2 Diabetes Mellitus. LID - 10.3390/ijms27114694 [doi] LID - 4694 AB - Semaglutide represents a unique therapeutic option for patients with type 2 diabetes mellitus (T2DM), being the first and currently only glucagon-like peptide-1 receptor agonist (GLP-1RA) available in both subcutaneous and oral formulations. This study aimed to compare the effectiveness of oral versus subcutaneous (sc) semaglutide on metabolic parameters and cardiovascular risk factors in T2DM patients. This is a retrospective real-world study including adult patients with T2DM taking oral or sc semaglutide followed at the ASUGI Diabetes Center. We analyzed data from 434 patients (median age 70 years, diabetes duration 13 years), treated with oral (n = 232) or sc (n = 202) semaglutide. The oral formulation had a higher discontinuation rate. Among these patients, 130 patients in the oral group and 145 in the sc group had an 18-month follow-up. When comparing these groups, patients taking sc semaglutide had a significantly higher baseline BMI. However, multivariate linear regression models suggested that both formulations were comparably effective in reducing HbA1c and BMI, with baseline values being the primary predictors of response. To address BMI imbalances, propensity score matching was performed, identifying 55 matched pairs. Both oral and sc semaglutide reduced HbA1c and BMI and there were no significant differences in the median change in HbA1c and BMI between groups. Interestingly, oral semaglutide was associated with a significantly greater reduction in diastolic blood pressure compared to the sc formulation. Furthermore, concomitant therapy with SGLT2 inhibitors significantly enhanced the reduction in total and LDL cholesterol. Oral and subcutaneous semaglutide show comparable effectiveness in lowering HbA1c and BMI in a real-world setting. FAU - Toffoli, Barbara AU - Toffoli B AUID- ORCID: 0000-0002-6854-5782 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy. FAU - Michieletto, Matteo AU - Michieletto M AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy. FAU - Bernardi, Stella AU - Bernardi S AUID- ORCID: 0000-0002-7429-3075 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy. AD - SS Endocrinologia (Medicina Clinica), Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy. FAU - Candido, Riccardo AU - Candido R AD - Department of Medical Surgical and Health Sciences, University of Trieste, Ospedale di Cattinara, Strada di Fiume 447, 34149 Trieste, Italy. AD - SC Patologie Diabetiche, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Via Sai 7, 34128 Trieste, Italy. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260522 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Glycated Hemoglobin/metabolism MH - Injections, Subcutaneous MH - Retrospective Studies MH - *Semaglutide/administration & dosage/therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use PMC - PMC13256121 OTO - NOTNLM OT - GLP-1RA OT - comparative study OT - oral semaglutide OT - propensity score matching OT - subcutaneous semaglutide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/06/12 06:38 MHDA- 2026/06/13 00:38 PMCR- 2026/05/22 CRDT- 2026/06/12 01:03 PHST- 2026/03/22 00:00 [received] PHST- 2026/05/07 00:00 [revised] PHST- 2026/05/13 00:00 [accepted] PHST- 2026/06/13 00:38 [medline] PHST- 2026/06/12 06:38 [pubmed] PHST- 2026/06/12 01:03 [entrez] PHST- 2026/05/22 00:00 [pmc-release] AID - ijms27114694 [pii] AID - ijms-27-04694 [pii] AID - 10.3390/ijms27114694 [doi] PST - epublish SO - Int J Mol Sci. 2026 May 22;27(11):4694. doi: 10.3390/ijms27114694. PMID- 42269776 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260708 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 238 DP - 2026 Aug TI - GLP-1 receptor agonist adjunct therapy stabilises Ramadan dysglycaemia in insulin-treated diabetes: a CGM-based study. PG - 113369 LID - S0168-8227(26)00289-5 [pii] LID - 10.1016/j.diabres.2026.113369 [doi] AB - BACKGROUND: Patients with type 1 and insulin-treated type 2 diabetes are at higher risk of hypo- and hyperglycaemia during Ramadan fasting. The role of incretin-based add-on therapy (GLP-1 receptor agonist semaglutide and the GLP-1/GIP dual agonist tirzepatide) in attenuating Ramadan dysglycaemia in insulin-treated type 2 diabetes has not been characterised using continuous glucose monitoring. Emerging evidence indicates that exaggerated post-iftar hyperglycaemia, drives Ramadan dysglycaemia in insulin-treated individuals. AIMS: To use continuous glucose monitoring (CGM) to characterise glycaemic control in patients with type 1 and type 2 diabetes on intensive insulin during Ramadan fasting, and to evaluate the role of add-on semaglutide or tirzepatide in attenuating post-iftar hyperglycaemia. METHODS: Adults with type 1 or type 2 diabetes using FreeStyle Libre CGM who completed >/= 14 full fasting days during Ramadan 2025 were included. Of 140 participants screened pre-Ramadan, 54 met all inclusion criteria and were analysed: type 2 diabetes on basal-bolus insulin alone (BB, n = 18), type 2 diabetes on basal-bolus plus tirzepatide or semaglutide (BB+, n = 18) - matched 1:1 by age, baseline HbA1c and BMI - and type 1 diabetes on basal-bolus insulin (T1DM, n = 18). CGM metrics were collected over 28 days pre-Ramadan (1-28 February 2025) and 29 days during Ramadan (1-29 March 2025) and compared within and between groups, and across fasting versus non-fasting windows. RESULTS: Dysglycaemia was driven predominantly by the post-iftar period. BB participants showed marked deterioration during non-fasting hours. Adjunctive therapy attenuated this effect: time in range 74.4 % vs 36.8 % (p = 0.007), glucose management indicator 6.9 % vs 8.3 % (p = 0.004), and > 2-fold ( approximately 61 %) reduction in incremental post-iftar area under the curve (102,014 vs 260,578 mg/dL.min over the 4-h post-iftar window). CONCLUSION: In matched insulin-treated type 2 diabetes cohorts, add-on semaglutide or tirzepatide stabilised Ramadan glycaemia and reduced post-iftar hyperglycaemia without increasing hypoglycaemia, and was well tolerated with no treatment discontinuations during Ramadan. CI - Copyright (c) 2026 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Ashraf, Tanveer AU - Ashraf T AD - Clinical Research Fellow, Imperial College London Diabetes and Endocrine Centre (ICLDEC), Abu Dhabi, United Arab Emirates. Electronic address: tashraf@icldc.ae. FAU - Lessan, Nader AU - Lessan N AD - Consultant Endocrinologist and Diabetologist, Clinical Lead in Research, Imperial College London Diabetes and Endocrine Centre (ICLDEC), Visiting Reader, Imperial College London, UK. Electronic address: nlessan@icldc.ae. LA - eng PT - Journal Article DEP - 20260610 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Continuous Glucose Monitoring MH - Female MH - *Insulin/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Tirzepatide MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Blood Glucose/drug effects/metabolism/analysis MH - *Diabetes Mellitus, Type 1/drug therapy/blood MH - Middle Aged MH - *Islam MH - Adult MH - Glucagon-Like Peptides/therapeutic use MH - *Hyperglycemia/drug therapy MH - Drug Therapy, Combination MH - *Fasting/blood MH - Glycemic Control OTO - NOTNLM OT - Continuous glucose monitoring OT - GLP-1 receptor agonist OT - GLP-1/GIP dual agonist OT - Post-iftar hyperglycaemia OT - Ramadan fasting OT - Semaglutide OT - Time in Range OT - Tirzepatide OT - Type 1 diabetes OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/06/11 05:41 MHDA- 2026/07/08 12:56 CRDT- 2026/06/10 19:56 PHST- 2026/04/06 00:00 [received] PHST- 2026/06/04 00:00 [revised] PHST- 2026/06/09 00:00 [accepted] PHST- 2026/07/08 12:56 [medline] PHST- 2026/06/11 05:41 [pubmed] PHST- 2026/06/10 19:56 [entrez] AID - S0168-8227(26)00289-5 [pii] AID - 10.1016/j.diabres.2026.113369 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Aug;238:113369. doi: 10.1016/j.diabres.2026.113369. Epub 2026 Jun 10. PMID- 42268869 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260813 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 21 IP - 6 DP - 2026 TI - Cost-effectiveness of semaglutide versus dulaglutide for Type 2 Diabetes in China: A Markov Model analysis. PG - e0351059 LID - 10.1371/journal.pone.0351059 [doi] LID - e0351059 AB - OBJECTIVE: From the perspective of China's basic medical insurance, to evaluate the cost-effectiveness of semaglutide versus dulaglutide for type 2 diabetes mellitus (T2DM) in China, informing clinical and health policy decisions. METHODS: This study employed a Markov model to simulate the disease progression of T2DM over a 25-year time horizon. Transition probabilities between health states were sourced from the UK Prospective Diabetes Study Outcomes Model (UKPDS 82) and the SUSTAIN 7 clinical trial, while health utility values were obtained from published literature using the Chinese EQ-5D-5L value set. Long-term cost-effectiveness was projected through cohort simulation, with both one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) conducted to evaluate the robustness of the model. RESULTS: After 25 years of simulation, the total cost for dulaglutide was yen193,353.07, with 11.628 quality-adjusted life-years (QALYs) gained. The total cost for semaglutide was yen240,925.08, yielding 11.900 QALYs. Compared with dulaglutide, semaglutide had an incremental cost-effectiveness ratio (ICER) of yen174,904 per QALY gained, approximately twice China's 2023 per capita GDP ( yen89,358). According to the Chinese Guidelines for Pharmacoeconomic Evaluation (2020), this result falls within the economically acceptable range (1 x GDP < ICER /=7.0% to /=6.5% to /= 18 years with T2DM who received GLP-1 RAs were identified and compared with matched controls. Propensity score matching (1:1) was used to balance baseline characteristics. Outcomes included cholelithiasis/choledocholithiasis, cholecystitis, pancreatitis, endoscopic retrograde cholangiopancreatography (ERCP), and cholecystectomy. Subgroup analyses were performed according to GLP-1 RA agents. RESULTS: A total of 156,376 patients were included; 43,077 patients were in the GLP-1 RA cohort and 113,299 patients were in the control group. After matching, 39,140 patients remained in each group. At two years, patients with GLP-1 RA use had higher rates of cholelithiasis/choledocholithiasis (aOR 1.44, 95% CI 1.24-1.65), whereas rates of cholecystectomy were non-significant. By three years, GLP-1 RA use remained associated with higher rates of cholelithiasis/choledocholithiasis (aOR 1.43, 95% CI 1.24-1.63), cholecystitis (aOR 1.45, 95% CI 1.14-1.83), and cholecystectomy (aOR 1.54, 95% CI 1.17-2.02). There were no significant differences in the rates of pancreatitis or ERCP. Semaglutide and dulaglutide demonstrated higher cholelithiasis, whereas liraglutide and exenatide were not associated with a significant increase. CONCLUSION: GLP-1 RAs use in patients with T2DM was associated with modestly higher rates of cholelithiasis/choledocholithiasis, cholecystitis, and cholecystectomy, whereas there were no significant differences in rates of pancreatitis or ERCP. CI - (c) 2026 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology. FAU - Eldesouki, Mohamed H AU - Eldesouki MH AUID- ORCID: 0009-0009-6662-5883 AD - Department of Internal Medicine, New York Medical College at Saint Michael's Medical Center, Newark, New Jersey, USA. FAU - Alkasabrah, Omar AU - Alkasabrah O AD - Department of Internal Medicine, New York Medical College/Landmark Medical Center, Woonsocket, Rhode Island, USA. FAU - Kloub, Mohammed AU - Kloub M AD - Department of Internal Medicine, New York Medical College at Saint Michael's Medical Center, Newark, New Jersey, USA. FAU - Abosheaishaa, Hazem AU - Abosheaishaa H AUID- ORCID: 0000-0002-5581-8702 AD - Division of Gastroenterology and Hepatology, Brooklyn Health Center, Brooklyn, New York, USA. FAU - Elfert, Khaled AU - Elfert K AUID- ORCID: 0000-0001-5554-6252 AD - Division of Gastroenterology and Hepatology, West Virginia University School of Medicine, Morgantown, West Virginia, USA. FAU - Sharma, Arpit AU - Sharma A AUID- ORCID: 0009-0008-9926-9099 AD - Faculty of Medicine, Monash University/Monash Health, Victoria, Melbourne, Australia. FAU - Andrawes, Sherif AU - Andrawes S AD - Division of Gastroenterology and Hepatology, Staten Island University Hospital-Northwell Health, Staten Island, New York, USA. FAU - Duong, Nikki AU - Duong N AD - Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, California, USA. LA - eng PT - Journal Article PL - England TA - United European Gastroenterol J JT - United European gastroenterology journal JID - 101606807 RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cholangiopancreatography, Endoscopic Retrograde/statistics & numerical data MH - Cholecystectomy/statistics & numerical data MH - Cholecystitis/chemically induced/epidemiology MH - Choledocholithiasis/chemically induced/epidemiology/surgery MH - Cholelithiasis/chemically induced/epidemiology/surgery MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Exenatide/adverse effects MH - *Gallstones/chemically induced/epidemiology/etiology/surgery MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects MH - Glucagon-Like Peptides/analogs & derivatives/adverse effects/therapeutic use/analogs & derivatives MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Immunoglobulin Fc Fragments/adverse effects MH - Pancreatitis/chemically induced/epidemiology MH - Retrospective Studies MH - Semaglutide/adverse effects MH - Recombinant Fusion Proteins/adverse effects PMC - PMC13240991 OTO - NOTNLM OT - biliary complications OT - choledocholithiasis OT - cholelithiasis OT - gallbladder disease OT - glucagon-like peptide-1 receptor agonists OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/06/05 18:36 MHDA- 2026/06/11 05:43 PMCR- 2026/06/05 CRDT- 2026/06/05 14:52 PHST- 2026/04/11 00:00 [revised] PHST- 2026/01/14 00:00 [received] PHST- 2026/05/23 00:00 [accepted] PHST- 2026/06/11 05:43 [medline] PHST- 2026/06/05 18:36 [pubmed] PHST- 2026/06/05 14:52 [entrez] PHST- 2026/06/05 00:00 [pmc-release] AID - UEG270238 [pii] AID - 10.1002/ueg2.70238 [doi] PST - ppublish SO - United European Gastroenterol J. 2026 Jun;14(5):e70238. doi: 10.1002/ueg2.70238. PMID- 42244474 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Rates of, Reasons for, and Reactions to Discontinuation of GLP-1 Receptor Agonists: A Narrative Review. PG - 6533-6549 LID - 10.1111/dom.70913 [doi] AB - GLP-1RAs are increasingly used for their glucose-lowering and weight-management effects, but many patients discontinue them. In this narrative review we aim to review real-world, quantitative and qualitative GLP-1RA discontinuation, adherence, and persistence evidence as it aligns with an established conceptual framework for understanding medication adherence in noncommunicable chronic disease. Many inconsistencies exist in how discontinuation, adherence, and persistence are studied in this literature. Few qualitative studies have focused on discontinuation of GLP-1RAs. Quantitative approaches often focus on medication-related factors and more superficial aspects of socioeconomic and condition-related factors. Very few studies encompass all 5 dimensions of the medication adherence conceptual framework. Patient-related factors, especially related to patient behaviors, are understudied in relation to GLP-1RA discontinuation. Patients treated for type 2 diabetes mellitus or weight management with GLP-1RAs often discontinue the medication, but this is often nonpermanent. Improving adherence to and persistence on GLP-1RAs will require nuanced attention to care trajectories as well as an integrated understanding of GLP-1RA tolerability, expectations, and the understudied role of patient behaviors and the healthcare system. To clarify relevant mechanisms and guide targeted intervention for highest-risk individuals, further study should standardize definitions of persistence and discontinuation and implement patient-centered qualitative work, especially related to health behaviors. CI - Published 2026. This article is a U.S. Government work and is in the public domain in the USA. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Heisey, Henry D AU - Heisey HD AUID- ORCID: 0000-0001-8136-2625 AD - Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA. AD - South Central Mental Illness Research, Education and Clinical Center, Houston, Texas, USA. AD - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA. FAU - Gregg, L Parker AU - Gregg LP AD - Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA. AD - Selzman Institute for Kidney Health, Section of Nephrology, Baylor College of Medicine, Houston, Texas, USA. FAU - Verrico, Christopher D AU - Verrico CD AD - Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA. AD - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA. FAU - Villareal, Dennis T AU - Villareal DT AD - Center for Translational Research on Inflammatory Diseases, Michael E DeBakey VA Medical Center, Houston, Texas, USA. AD - Division of Endocrinology, Diabetes, and Metabolism, Baylor College of Medicine, Houston, Texas, USA. FAU - Fletcher, Terri L AU - Fletcher TL AD - Center for Innovations in Quality, Effectiveness and Safety, Michael E DeBakey VA Medical Center, Houston, Texas, USA. AD - South Central Mental Illness Research, Education and Clinical Center, Houston, Texas, USA. AD - Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA. LA - eng GR - Houston VA Center/Houston VA Center/ PT - Journal Article PT - Review DEP - 20260605 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Medication Adherence/psychology MH - Treatment Interruption MH - Semaglutide MH - Tirzepatide PMC - PMC13341420 OTO - NOTNLM OT - GLP-1 OT - adherence OT - discontinuation OT - framework OT - incretin OT - orforglipron OT - persistence OT - semaglutide OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/06/05 06:35 MHDA- 2026/07/08 18:51 PMCR- 2026/07/08 CRDT- 2026/06/05 04:13 PHST- 2026/05/15 00:00 [revised] PHST- 2026/03/13 00:00 [received] PHST- 2026/05/17 00:00 [accepted] PHST- 2026/07/08 18:51 [medline] PHST- 2026/06/05 06:35 [pubmed] PHST- 2026/06/05 04:13 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70913 [pii] AID - 10.1111/dom.70913 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):6533-6549. doi: 10.1111/dom.70913. Epub 2026 Jun 5. PMID- 42244313 OWN - NLM STAT- MEDLINE DCOM- 20260605 LR - 20260813 IS - 1672-7347 (Print) IS - 1672-7347 (Linking) VI - 51 IP - 2 DP - 2026 Feb 28 TI - [Semaglutide-induced acute-on-chronic liver failure: A case report and literature review]. PG - 213-220 LID - 1672-7347(2026)02-0213-08 [pii] LID - 10.11817/j.issn.1672-7347.2026.250330 [doi] AB - Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA), primarily used for the treatment of type 2 diabetes mellitus and obesity. Common adverse drug reactions (ADRs) include nausea, vomiting, diarrhea, abdominal pain, and constipation, whereas liver function-related ADRs are relatively rare. We report a rare and severe case of semaglutide-induced acute-on-chronic liver failure (ACLF) in a 47-year-old male patient who was successfully treated. The patient was admitted to the Department of Infectious Disease at the Second Xiangya Hospital of Central South University on December 1, 2023. He had a history of chronic hepatitis B and had discontinued antiviral therapy for more than two years without medical supervision. Due to weight loss requirements, he initiated subcutaneous semaglutide therapy. Approximately three months after treatment initiation, he developed severe liver dysfunction, which rapidly progressed to profound jaundice, coagulopathy, and hepatic encephalopathy. Drug-induced liver injury (DILI) was considered the primary precipitating factor of liver failure, and the final diagnosis was ACLF. Following confirmation of the diagnosis, semaglutide was discontinued, and comprehensive management, including hepatoprotective therapy, artificial liver support, plasma exchange, and liver transplantation, was implemented. The patient's clinical symptoms and liver function parameters improved significantly. This report describes the successful management of semaglutide-induced ACLF and reviews the relevant literature. For individuals with underlying chronic liver disease (e.g., chronic viral hepatitis), thorough baseline liver assessment should be performed prior to initiating semaglutide or similar agents. Close monitoring during treatment is essential to identify potential severe drug-induced liver injury at an early stage. FAU - Fu, Rao AU - Fu R AD - Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha 410011. furao1030500@outlook.com. FAU - Wu, Huizhi AU - Wu H AD - Department of Pharmacy, Liuyang People's Hospital, Liuyang 410300, China. WuHuizhi0903@163.com. FAU - Huang, Haiying AU - Huang H AD - Department of Pharmacy, Liuyang People's Hospital, Liuyang 410300, China. FAU - Sun, Bao AU - Sun B AD - Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha 410011. scy_csu2016@csu.edu.cn. LA - chi GR - B202313016776/the Scientific Research Project of Hunan Provincial Health Commission/ GR - CPA-Z05-ZC-2024-003/the Special Foundation for Young Scientists of Special Committee of the Hospital Pharmacy, Chinese Pharmaceutical Association/ PT - Case Reports PT - English Abstract PT - Journal Article PT - Review PL - China TA - Zhong Nan Da Xue Xue Bao Yi Xue Ban JT - Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences JID - 101230586 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Middle Aged MH - *Acute-On-Chronic Liver Failure/chemically induced/diagnosis/therapy MH - *Chemical and Drug Induced Liver Injury/diagnosis/etiology/therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Hepatitis B, Chronic/complications/drug therapy MH - Hypoglycemic Agents/adverse effects MH - *Semaglutide/adverse effects PMC - PMC13229664 OTO - NOTNLM OT - acute-on-chronic liver failure OT - adverse drug reaction OT - drug-induced liver injury OT - glucagon-like peptide-1 receptor agonist OT - semaglutide COIS- 作者声称无任何利益冲突。 EDAT- 2026/06/05 06:36 MHDA- 2026/06/06 00:34 PMCR- 2026/02/28 CRDT- 2026/06/05 02:43 PHST- 2026/06/06 00:34 [medline] PHST- 2026/06/05 06:36 [pubmed] PHST- 2026/06/05 02:43 [entrez] PHST- 2026/02/28 00:00 [pmc-release] AID - 1672-7347(2026)02-0213-08 [pii] AID - 10.11817/j.issn.1672-7347.2026.250330 [doi] PST - ppublish SO - Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2026 Feb 28;51(2):213-220. doi: 10.11817/j.issn.1672-7347.2026.250330. PMID- 42237968 OWN - NLM STAT- MEDLINE DCOM- 20260607 LR - 20260813 IS - 1658-3175 (Electronic) IS - 0379-5284 (Print) IS - 0379-5284 (Linking) VI - 47 IP - 4 DP - 2026 Apr TI - Semaglutide in Metabolic Medicine: A Review on Clinical Applications and Emerging Therapeutics. PG - 615-625 LID - 10.15537/1658-3175.1060 [doi] AB - Obesity and type 2 diabetes mellitus affect over 800 million and 537 million individuals worldwide. Semaglutide, a weekly glucagon-like peptide-1 receptor agonist, has advanced treatment of pathophysiological processes linked to metabolic dysregulation. This review consolidates evidence on its mechanisms of action, clinical effectiveness across established and emerging applications, safety, and prospects for personalized therapy. Clinical studies have shown that semaglutide sustains glycemic control, promotes substantial weight loss, and provides cardiovascular and renal protection. Recent FDA clearance marks the first therapeutic alternative for metabolic dysfunction-associated steatohepatitis among the emerging applications. Pharmacogenomic insights facilitate personalized therapy; however, clinical applications remain in experimental stage. Gastrointestinal side effects are the main tolerability concern, but the risk-benefit profile underscores its increasing significance in metabolic therapy. Therapies for diabetes and obesity are cost-effective; however, global accessibility challenges persist. Future priorities include refining combination medicines, promoting precision medicine, and addressing healthcare inequities to augment population-level effects. CI - Copyright: (c) Saudi Medical Journal. FAU - Aljabri, Abdulrahman A AU - Aljabri AA AUID- ORCID: 0009-0001-3780-4964 AD - Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah, Kingdom of Saudi Arabia. LA - eng PT - Journal Article PT - Review DEP - 20260320 PL - Saudi Arabia TA - Saudi Med J JT - Saudi medical journal JID - 7909441 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Glucagon-Like Peptides/agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Obesity/drug therapy MH - Precision Medicine MH - *Semaglutide/pharmacology/therapeutic use PMC - PMC13227446 OTO - NOTNLM OT - Cardiovascular protection OT - GLP-1 receptor agonist OT - Obesity OT - Precision medicine OT - Semaglutide OT - Type 2 diabetes mellitus EDAT- 2026/06/04 06:35 MHDA- 2026/06/08 00:35 PMCR- 2026/04/01 CRDT- 2026/06/04 05:24 PHST- 2025/09/05 00:00 [received] PHST- 2025/11/13 00:00 [accepted] PHST- 2026/06/08 00:35 [medline] PHST- 2026/06/04 06:35 [pubmed] PHST- 2026/06/04 05:24 [entrez] PHST- 2026/04/01 00:00 [pmc-release] AID - saudimedj-47-4-615 [pii] AID - 10.15537/1658-3175.1060 [doi] PST - ppublish SO - Saudi Med J. 2026 Apr;47(4):615-625. doi: 10.15537/1658-3175.1060. Epub 2026 Mar 20. PMID- 42233552 OWN - NLM STAT- MEDLINE DCOM- 20260606 LR - 20260609 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 87 IP - 21 DP - 2026 Jun 2 TI - Kidney and Survival Benefits of Semaglutide in Diabetes With Chronic Kidney Disease: FLOW Trial Cardiovascular Subgroup Analyses. PG - 2996-3012 LID - S0735-1097(26)05731-1 [pii] LID - 10.1016/j.jacc.2026.02.5125 [doi] AB - BACKGROUND: Cardiovascular disease increases risks of chronic kidney disease (CKD) progression and mortality in type 2 diabetes. OBJECTIVES: The study sought to assess semaglutide effects on kidney and survival outcomes by baseline cardiovascular status in the FLOW trial. METHODS: Participants with type 2 diabetes and CKD were randomized to once-weekly subcutaneous semaglutide 1.0 mg vs placebo. Baseline subgroups included atherosclerotic cardiovascular disease (ASCVD), heart failure, and high total cardiovascular disease risk without established cardiovascular disease (10-year PREVENT [Predicting Risk of cardiovascular disease EVENTs] score >/=20%). The primary outcome was >/=50% estimated glomerular filtration rate (eGFR) decline, eGFR <15 mL/min/1.73 m(2), dialysis, transplantation, and kidney or cardiovascular death. All-cause death was a confirmatory secondary outcome. RESULTS: At baseline, 1,198 (33.9%) of 3,533, 678 (19.2%) of 3,532, and 1,329 (66.5%) of 2,000 participants had ASCVD, heart failure, or high total cardiovascular disease risk in those without established cardiovascular disease, respectively. Semaglutide reduced the primary outcome risk in subgroups with (119 of 593 vs 146 of 605) or without (212 of 1,174 vs 264 of 1,161) ASCVD (HR: 0.80; 95% CI: 0.63-1.02; and HR: 0.74; 95% CI: 0.62-0.89, respectively; P for interaction = 0.62), with (67 of 342 vs 88 of 336) or without (264 of 1,424 vs 322 of 1,430) heart failure (HR: 0.67; 95% CI: 0.49-0.93; and HR: 0.79; 95% CI: 0.67-0.93, respectively; P for interaction = 0.40), and with (134 of 675 vs 168 of 654) or without (44 of 331 vs 58 of 340) high total cardiovascular disease risk (HR: 0.73; 95% CI: 0.58-0.91; and HR: 0.73; 95% CI: 0.49-1.08, respectively; P for interaction = 0.99). Numbers needed to treat to prevent 1 primary kidney outcome at 3 years were 22, 13, and 17 in the ASCVD, heart failure, and PREVENT score >/=20% subgroups, respectively. Semaglutide also reduced risks of all-cause death with (99 of 593 vs 121 of 605) or without (128 of 1,174 vs 158 of 1,161) ASCVD (HR: 0.82; 95% CI: 0.63-1.07; and HR: 0.78; 95% CI: 0.62-0.99, respectively; P for interaction = 0.79), with (64 of 342 vs 79 of 336) or without (163 of 1,424 vs 200 of 1,430) heart failure (HR: 0.75; 95% CI: 0.54-1.05; and HR: 0.81; 95% CI: 0.66-0.99, respectively; P for interaction = 0.74), and with (73 of 675 vs 98 of 654) or without (23 of 331 vs 28 of 340) high total cardiovascular disease risk (HR: 0.71; 95% CI: 0.52-0.95; and HR: 0.82; 95% CI: 0.47-1.43, respectively; P for interaction = 0.63). CONCLUSIONS: Semaglutide improved kidney and survival outcomes in type 2 diabetes with CKD, irrespective of established ASCVD, heart failure, or high total cardiovascular disease risk. (Evaluate Renal Function with Semaglutide Once Weekly [FLOW]; NCT03819153). CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Division of Nephrology, University of Washington School of Medicine, Seattle, Washington, USA; Providence Medical Research Center, Providence Inland Northwest Health, Spokane, Washington, USA. Electronic address: katherine.tuttle@providence.org. FAU - Bakris, George L AU - Bakris GL FAU - Baeres, Florian M M AU - Baeres FMM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bang, Casper N AU - Bang CN AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bax, Willem A AU - Bax WA AD - Northwest Clinics, Alkmaar, the Netherlands. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Musinga, Derrick AU - Musinga D AD - Novo Nordisk A/S, Soborg, Denmark; Excelya Germany GmbH, Mannheim, Germany. FAU - Cherney, David Z I AU - Cherney DZI AD - University of Toronto, Toronto, Ontario, Canada. FAU - Chernin, Gil AU - Chernin G AD - Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Rehovot, Israel. FAU - Lim, Soo Kun AU - Lim SK AD - University of Malaya, Kuala Lumpur, Malaysia. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Centre, Munich, Germany; University Hospital Erlangen, Friedrich-Alexander University, Erlangen, Germany. FAU - Perkovic, Vlado AU - Perkovic V AD - Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia. FAU - Pratley, Richard AU - Pratley R AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. FAU - Ridker, Paul M AU - Ridker PM AD - Center for Cardiovascular Disease Prevention and Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Schmieder, Roland AU - Schmieder R AD - University Hospital Erlangen, Friedrich-Alexander University, Erlangen, Germany. FAU - Shamkhalova, Minara S AU - Shamkhalova MS AD - Endocrinology Research Centre, Moscow, Russia. FAU - Sreenivasamurthy, L AU - Sreenivasamurthy L AD - Lifecare Hospital and Research Centre, Bangalore, India. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, California, USA. LA - eng SI - ClinicalTrials.gov/NCT03819153 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cardiovascular Diseases/mortality MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Renal Insufficiency, Chronic/drug therapy/mortality/complications/physiopathology MH - *Semaglutide/therapeutic use MH - Survival Rate/trends OTO - NOTNLM OT - atherosclerotic cardiovascular disease OT - cardiovascular risk OT - glomerular filtration rate OT - glucagon-like peptide-1 OT - heart failure OT - mortality COIS- Funding Support and Author Disclosures The FLOW trial was funded by Novo Nordisk A/S. Dr Tuttle was supported by National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, and OT2OD032581, as well as by Centers for Disease Control and Prevention project numbers 75D301-21-P-12254 and 75D301-23-C-18264; has received investigator-initiated grant support from Travere, Bayer, Otsuka, Doris Duke Charitable Foundation, Benaroya Research Institute, and Breakthrough T1D (formerly the Juvenile Diabetes Research Foundation); has received consultancy fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Bayer, ProKidney, Otsuka, Alnylam, Roche, and GlaxoSmithKline; has received speaker fees from Novo Nordisk, Bayer, Boehringer Ingelheim, Travere, and AstraZeneca; has served as Chair of data safety monitoring boards for the National Institute of Diabetes and Digestive and Kidney Disease, and George Clinical Institute; has served on the data safety monitoring board for AstraZeneca; has served as Chair for the Diabetic Kidney Disease Collaborative for the American Society of Nephrology and Chair for Kidney Week 2025 Program Committee, both for the American Society of Nephrology; and has served on the American Heart Association/American College of Cardiology Cardiovascular-Kidney-Metabolic Guideline Committee. Dr Bakris served as a consultant for Novo Nordisk, Alnylam Pharmaceuticals, AstraZeneca Pharmaceuticals LP, and Bayer Corporation; has received research funding, paid to the University of Chicago Medicine, from Bayer during the conduct of the study; has received research funding, paid to the University of Chicago Medicine, from Novo Nordisk and Vascular Dynamics; has served as a consultant for and received personal fees from Alnylam, Merck, and Relypsa; was an editor of the American Journal of Nephrology, Nephrology, and Hypertension; was a section editor of UpToDate; and was an associate editor of Diabetes Care and Hypertension Research. Drs Baeres, Bang, and Belmar are employees of and shareholders in Novo Nordisk. Dr Bax has participated in trials for Amgen, Eli Lilly, Novartis, and Novo Nordisk; has received consultancy fees from Amgen, Novo Nordisk, and Sanofi; and has served as a lecturer for AstraZeneca and Eli Lilly. Dr Musinga is an employee of Excelya; and has served as a consultant for Novo Nordisk. Dr Cherney has received honoraria from AbbVie, Altimmune, Amgen, AstraZeneca, Bayer, BioBridge, Boehringer Ingelheim-Lilly, Bristol Myers Squibb, CSL Behring, GlaxoSmithKline, Gilead, Inversago, Janssen, Lexicon, Maze, Merck, Mitsubishi-Tanabe, Novartis, Novo Nordisk, Otsuka, Prometic, Sanofi, Vantage, and Youngene; and has received operational funding for clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, CSL Behring, Janssen, Lexicon, Merck, Novo Nordisk, and Sanofi. Dr Chernin has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, and Sanofi. Dr Lim has received institutional research grant support from AstraZeneca, Boehringer Ingelheim, and Roche; and during the past 3 years has served as a consultant for Astellas, AstraZeneca, Baxter, Bayer, Boehringer Ingelheim, DKSH, DuoPharma, Fresenius Kabi, Menairini, MSD, Novartis, Novo Nordisk, Roche, and Sanofi. Dr Mann has received grants from Novo Nordisk; has received consulting fees from Bayer and Novo Nordisk; has received honoraria from AstraZeneca, Bayer, Cytel, ICON, IQVIA, Novartis, Novo Nordisk, Sanofi, and WCG; and has served in a leadership role in the KDIGO group. Dr Perkovic has received honoraria for steering committee, data monitoring committee, or advisory board roles, or for scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, GlaxoSmithKline, Janssen, Novartis, Novo Nordisk, Otsuka, Travere, Tricida, and UpToDate; and has served as a board director for George Clinical, St Vincent's Health Australia, and several independent medical research institutes. Dr Pratley has received speaker fees from Eli Lilly, Lilly USA LLC, and Novo Nordisk; has received consulting fees from AbbVie, AstraZeneca, Bayer AG, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Eli Lilly, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui (USA) Ltd, Intas Pharmaceuticals, Lilly USA LLC, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock, and Sun Pharmaceutical Industries; and has received research grants from Biomea Fusion, Carmot Therapeutics, Dompe, Eli Lilly, Endogenex, Fractyl, Novo Nordisk, and Sanofi, all directed to his institution. Dr Ridker has received institutional research grant support from Amarin, Esperion, Kowa, the National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, and Pfizer; during the past 3 years has served as a consultant for Agepha, Arrowhead, AstraZeneca, Boehringer Ingelheim, Cardio Therapeutics, Civi Biopharm, CSL Behring, Cytokinetics, Eli Lilly, Merck, New Amsterdam, Nodthera, Novartis, Novo Nordisk, SOCAR, and Tourmaline Bio; has minority shareholder equity positions in Angiowave, Bitteroot Bio, and Uppton; and has received compensation for services on the Peter Munk Advisory Board (University of Toronto), the Leducq Foundation, and Paris FR. Dr Rossing has received consulting and/or speaking fees (to his institution) from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Novo Nordisk, and Sanofi; and has received research grants from AstraZeneca, Bayer, and Novo Nordisk. Dr Schmeider has received grants to his institution from Amgen, Ablative Solution, Bayer, IPPmed, Medtronic, Novo Nordisk, and Recor; and has received honoraria as a speaker and advisor from Ablative Solutions, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Medtronic, Merck, Novo Nordisk, Novartis, Recor, Servier, and TAD. Dr Shamkhalova has received speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Sanofi, and Servier. Dr Sreenivasamurthy has received speaker/advisory board fees from Abbott India, Alkem, AstraZeneca, Cipla, Eli Lilly, Eris, IntasJB Pharma, J&J, Lupin, Mankind Pharma, Micro Labs, Servier, Sun Pharma, Torrent Pharma, and USV; and has received investigator/research grants from AstraZeneca, Bayer, Eli Lilly, Novo Nordisk, Sanofi India, Servier, Sun Pharma, and Torrent Pharma. Dr Mahaffey has received grants from the American College of Cardiology, American Heart Association, Apple, Bayer, California Institute Regenerative Medicine, CSL Behring, Eidos, Element, Ferring, Gilead, Google (Verify), Idorsia, Johnson & Johnson, Luitpold, Myovant, Novartis, PAC-12, Precordior, Sanifit, and St Jude Medical; has received consulting fees from Applied Therapeutics, Bayer, Bristol Myers Squibb, BridgeBio, Eli Lilly, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, MyoKardia, Novartis, Novo Nordisk, PhaseBio, Portola, Quidel, and Theravance; and owns equity in Human, Medeloop, Precordior, and Regencor. EDAT- 2026/06/03 12:40 MHDA- 2026/06/06 12:34 CRDT- 2026/06/03 08:28 PHST- 2025/09/26 00:00 [received] PHST- 2026/02/18 00:00 [revised] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/06/06 12:34 [medline] PHST- 2026/06/03 12:40 [pubmed] PHST- 2026/06/03 08:28 [entrez] AID - S0735-1097(26)05731-1 [pii] AID - 10.1016/j.jacc.2026.02.5125 [doi] PST - ppublish SO - J Am Coll Cardiol. 2026 Jun 2;87(21):2996-3012. doi: 10.1016/j.jacc.2026.02.5125. PMID- 42229813 OWN - NLM STAT- MEDLINE DCOM- 20260918 LR - 20260922 IS - 1549-4713 (Electronic) IS - 0161-6420 (Print) IS - 0161-6420 (Linking) VI - 133 IP - 10 DP - 2026 Oct TI - Semaglutide and Neovascular Age-Related Macular Degeneration among Adults with Type 2 Diabetes: An Observational Health Data Sciences and Informatics Network Study. PG - 1221-1229 LID - S0161-6420(26)00382-9 [pii] LID - 10.1016/j.ophtha.2026.05.034 [doi] AB - PURPOSE: To investigate the potential association of semaglutide use and neovascular age-related macular degeneration (NVAMD). DESIGN: Retrospective study across 12 databases in the Observational Health Data Sciences and Informatics network from December 1, 2017, through December 31, 2024. PARTICIPANTS: Adults with type 2 diabetes (T2D) taking semaglutide, other glucagon-like peptide-1 receptor agonists (GLP-1RAs; e.g., dulaglutide or exenatide), or non-GLP-1RAs (e.g., empagliflozin, sitagliptin, or glipizide). METHODS: The association between semaglutide use and NVAMD was assessed using 2 approaches: an active-comparator cohort design and a self-controlled case series analysis. The former used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The latter used conditional Poisson regression models to estimate incidence rate ratios (IRRs). A random-effects meta-analysis was used to generate network-wide HR and IRR estimates. MAIN OUTCOME MEASURES: Two definitions of NVAMD, one based on condition codes alone (NVAMD-C) and one based on condition codes and procedures (NVAMD-CP). RESULTS: A total of 227 971 new users of semaglutide were included in the study. The risk of NVAMD among semaglutide users was similar to that of users of dulaglutide (NVAMD-C: HR, 0.57; 95% CI, 0.21-1.57; P = 0.28; NVAMD-CP: HR, 0.25; 95% CI, 0.05-1.27; P = 0.10), empagliflozin (NVAMD-C: HR, 0.98; 95% CI, 0.54-1.79; P = 0.94; NVAMD-CP: HR, 0.79; 95% CI, 0.38-1.64; P = 0.52), sitagliptin (NVAMD-C: HR, 2.08; 95% CI, 0.90-4.83; P = 0.09; NVAMD-CP: HR, 1.80; 95% CI, 0.55-5.86; P = 0.33), and glipizide (NVAMD-C: HR, 0.83; 95% CI, 0.35-2.02; P = 0.69; NVAMD-CP: HR, 0.50; 95% CI, 0.21-1.19; P = 0.12). No evidence was found of increased or decreased risk for NVAMD associated with semaglutide exposure (NVAMD-C: IRR, 0.92; 95% CI, 0.67-1.26; P = 0.60; NVAMD-CP: IRR, 1.02; 95% CI, 0.76-1.36; P = 0.92) nor with any of the other GLP-1RAs or non-GLP-1RAs. CONCLUSIONS: We detected no differences in the risk of NVAMD associated with semaglutide use among adults with T2D. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2026 American Academy of Ophthalmology, Inc. Published by Elsevier Inc. All rights reserved. FAU - Cai, Cindy X AU - Cai CX AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland; Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: ccai6@jhmi.edu. FAU - Toy, Brian AU - Toy B AD - Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California. FAU - Martin, Benjamin AU - Martin B AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Fan, Ruochong AU - Fan R AD - Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri. FAU - Westlund, Erik AU - Westlund E AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. FAU - Tran, Diep AU - Tran D AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. FAU - Lee, Haeun AU - Lee H AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Leng, Theodore AU - Leng T AD - Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, California. FAU - Nagy, Paul AU - Nagy P AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Mathioudakis, Nestoras AU - Mathioudakis N AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Zhang, Linying AU - Zhang L AD - Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri. FAU - Hribar, Michelle AU - Hribar M AD - Ophthalmology and Visual Sciences, AI.Health4All College of Medicine, University of Illinois at Chicago, Chicago, Illinois. FAU - Chen, Aiyin AU - Chen A AD - Casey Eye Institute, Oregon Health and Science University, Portland, Oregon; Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Portland, Oregon. FAU - Armbrust, Karen AU - Armbrust K AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota; Department of Ophthalmology, Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota. FAU - Goetz, Kerry AU - Goetz K AD - Department of Clinical Science, Topcon Healthcare, Inc., Oakland, New Jersey. FAU - Baxter, Sally AU - Baxter S AD - Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California, San Diego, La Jolla, California; Division of Biomedical Informatics, Department of Medicine, University of California, San Diego, La Jolla, California. FAU - Boland, Michael V AU - Boland MV AD - Department of Ophthalmology, Mass Eye and Ear and Harvard Medical School, Boston, Massachusetts. FAU - Brown, Eric N AU - Brown EN AD - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Tsui, Edmund AU - Tsui E AD - UCLA Stein Eye Institute, University of California, Los Angeles, Los Angeles, California. FAU - Barkmeier, Andrew J AU - Barkmeier AJ AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. FAU - Wang, Sophia AU - Wang S AD - Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, California. FAU - Mehta, Nitish AU - Mehta N AD - Department of Ophthalmology, NYU Langone Health, New York, New York. FAU - Stocking, Jacqueline C AU - Stocking JC AD - Department of Internal Medicine, University of California, Davis, Sacramento, California. FAU - O'Keefe, Ghazala AU - O'Keefe G AD - Private Practice. FAU - Lee, Cecilia S AU - Lee CS AD - John F. Hardesty, MS, Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, Missouri. FAU - Payne, Philip R O AU - Payne PRO AD - Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St. Louis, St. Louis, Missouri. FAU - O'Brien, William J AU - O'Brien WJ AD - Veterans Affairs Informatics and Computing Infrastructure, George E. Wahlen VA Medical Center, Salt Lake City, Utah. FAU - DuVall, Scott AU - DuVall S AD - Data Science and Advanced Analytics, PurpleLab, Inc., Salt Lake City, Utah. FAU - Alshammari, Thamir AU - Alshammari T AD - Department of Clinical Practice, College of Pharmacy, Jazan University, Jazan, Saudi Arabia; Pharmacy Practice Research Unit, College of Pharmacy, Jazan University, Jazan, Saudi Arabia. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University, New York, New York. FAU - Dorr, David A AU - Dorr DA AD - Division of Informatics, Clinical Epidemiology, and Translational Data Science, Department of Medicine, Oregon Health and Science University, Portland, Oregon. FAU - Humes, Izabelle AU - Humes I AD - Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, Oregon. FAU - McCoy, David AU - McCoy D AD - Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, Oregon. FAU - Adibuzzaman, Mohammed AU - Adibuzzaman M AD - Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, Oregon. FAU - Mahmood, Rumel AU - Mahmood R AD - Oregon Clinical and Translational Research Institute, Oregon Health and Science University, Portland, Oregon. FAU - Morgan-Cooper, Hannah AU - Morgan-Cooper H AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California. FAU - Desai, Priya AU - Desai P AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California. FAU - Kothari, Shikha Yashwant AU - Kothari SY AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California. FAU - Sena, Anthony AU - Sena A AD - Global Epidemiology Organization, Johnson & Johnson, Raritan, New Jersey; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands. FAU - Blacketer, Clair AU - Blacketer C AD - Global Epidemiology Organization, Johnson & Johnson, Raritan, New Jersey; Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands. FAU - Ostropolets, Anna AU - Ostropolets A AD - Department of Biomedical Informatics, Columbia University, New York, New York; Global Epidemiology Organization, Johnson & Johnson, Raritan, New Jersey. FAU - Shoaibi, Azza AU - Shoaibi A AD - Global Epidemiology Organization, Johnson & Johnson, Raritan, New Jersey. FAU - Rao, Gowtham AU - Rao G AD - Research Department, CoReason, Inc, Princeton, New Jersey. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University, New York, New York. FAU - Ryan, Patrick AU - Ryan P AD - Department of Biomedical Informatics, Columbia University, New York, New York; Global Epidemiology Organization, Johnson & Johnson, Raritan, New Jersey. FAU - Suchard, Marc A AU - Suchard MA AD - Department of Biostatistics, UCLA School of Public Health, University of California, Los Angeles, Los Angeles, California; VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah. LA - eng GR - R01 DK125780/DK/NIDDK NIH HHS/United States GR - R01 AG060942/AG/NIA NIH HHS/United States GR - P30 EY022589/EY/NEI NIH HHS/United States GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - K23 EY033440/EY/NEI NIH HHS/United States GR - R01 DK134955/DK/NIDDK NIH HHS/United States GR - R35 GM160458/GM/NIGMS NIH HHS/United States GR - OT2 OD032644/OD/NIH HHS/United States GR - K23 EY032985/EY/NEI NIH HHS/United States GR - R01 HL167858/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Observational Study DEP - 20260602 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Retrospective Studies MH - Female MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - *Wet Macular Degeneration/epidemiology/diagnosis MH - Incidence MH - Immunoglobulin Fc Fragments/therapeutic use PMC - PMC13318194 MID - NIHMS2183361 OTO - NOTNLM OT - Big data OT - Neovascular age-related macular degeneration OT - Observational Health Data Sciences and Informatics OT - Semaglutide COIS- Regeneron Pharmaceuticals, Inc (grant support), Optomed (equipment support) Topcon Healthcare, Inc. (employee) Topcon (consulting fees) Carl Zeiss Meditec (consulting, speaking); Abbvie (consulting) 4DMT (advisory board), Regeneron Pharmaceauticals (advisory board), Eyepoint Pharmaceauticals (advisory board) Employee and Shareholder of PurpleLab Employee and Shareholder of J&J Employee and Shareholder of J&J Employee and Shareholder of J&J Employee and Shareholder of J&J Employee and Shareholder of J&J Receives contracts and grants from Janssen Researchh & Development and Gilead Sciences, Inc., outside the scope of this work. EDAT- 2026/06/03 00:40 MHDA- 2026/09/18 23:36 PMCR- 2026/07/01 CRDT- 2026/06/02 19:34 PHST- 2026/03/06 00:00 [received] PHST- 2026/05/21 00:00 [revised] PHST- 2026/05/21 00:00 [accepted] PHST- 2026/09/18 23:36 [medline] PHST- 2026/06/03 00:40 [pubmed] PHST- 2026/06/02 19:34 [entrez] PHST- 2026/07/01 00:00 [pmc-release] AID - S0161-6420(26)00382-9 [pii] AID - 10.1016/j.ophtha.2026.05.034 [doi] PST - ppublish SO - Ophthalmology. 2026 Oct;133(10):1221-1229. doi: 10.1016/j.ophtha.2026.05.034. Epub 2026 Jun 2. PMID- 42224699 OWN - NLM STAT- MEDLINE DCOM- 20260615 LR - 20260918 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 6 DP - 2026 Jun TI - In T2D inadequately controlled with metformin, orforglipron reduced HbA(1c) more than oral semaglutide at 52 wk. PG - JC62 LID - 10.7326/ANNALS-26-01781-JC [doi] AB - GIM/FP/GP: [Formula: see text] Endocrinology: [Formula: see text]. FAU - Lau, Darren AU - Lau D AUID- ORCID: 0000-0001-9923-7902 AD - University of Alberta, Edmonton, Alberta, Canada (D.L.). CN - ACP Journal Club Editorial Team at McMaster University LA - eng PT - Journal Article DEP - 20260602 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (orforglipron) RN - 0 (Pyridones) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Humans MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - *Metformin/pharmacology/therapeutic use MH - *Pyridones/pharmacology/therapeutic use MH - Semaglutide/pharmacology/therapeutic use MH - Oxadiazoles MH - Fluorine Compounds COIS- Disclosures: Disclosure form is available with the article online. EDAT- 2026/06/01 18:48 MHDA- 2026/06/15 18:34 CRDT- 2026/06/01 17:03 PHST- 2026/06/15 18:34 [medline] PHST- 2026/06/01 18:48 [pubmed] PHST- 2026/06/01 17:03 [entrez] AID - 10.7326/ANNALS-26-01781-JC [doi] PST - ppublish SO - Ann Intern Med. 2026 Jun;179(6):JC62. doi: 10.7326/ANNALS-26-01781-JC. Epub 2026 Jun 2. PMID- 42219271 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - The Impact of GLP-1-Based Therapies on Cardiovascular Outcomes in Type 2 Diabetes: A Comprehensive Systematic Review and Network Meta-Analysis. PG - 7137-7148 LID - 10.1111/dom.70915 [doi] AB - AIMS: To provide updated agent-level comparative estimates of GLP-1-based therapies for cardiovascular outcomes in adults with Type 2 diabetes mellitus (T2DM) using a hazard ratio (HR)-based systematic review and network meta-analysis (NMA). METHODS: PubMed, Cochrane Library and Scopus were searched through December 2025 for randomized controlled trials evaluating GLP-1-based therapies in adults with T2DM and reporting time-to-event cardiovascular outcomes. Pairwise meta-analyses and a frequentist random-effects NMA were performed for all-cause mortality, cardiovascular mortality, major adverse cardiovascular events (MACE), non-fatal myocardial infarction (MI) and non-fatal stroke. RESULTS: Fifteen trials involving 97,173 participants were included. In pairwise placebo-controlled analyses, GLP-1-based therapies significantly reduced all-cause mortality, cardiovascular mortality and MACE. In the NMA, mortality estimates for several agents favoured benefit, although most comparisons were not statistically significant. For MACE, efpeglenatide, albiglutide and injectable semaglutide showed the most favourable comparative profiles. Albiglutide reduced non-fatal MI versus placebo, whereas non-fatal stroke estimates were imprecise. CONCLUSIONS: GLP-1-based therapies were associated with an overall favourable cardiovascular profile in T2DM. Pairwise analyses supported class-level benefit, whereas between-agent differences were more evident for MACE than for mortality outcomes in the NMA. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Chuang, Shih-Ming AU - Chuang SM AUID- ORCID: 0000-0002-8622-1968 AD - School of Medicine, College of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. AD - Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. FAU - Liu, Sung-Chen AU - Liu SC AD - School of Medicine, College of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. FAU - Chien, Kuo-Liong AU - Chien KL AD - Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. FAU - Lin, Cheng-Jui AU - Lin CJ AD - School of Medicine, College of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. AD - MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan. FAU - Tsai, Ming-Chieh AU - Tsai MC AD - School of Medicine, College of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. AD - Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. FAU - Shih, Hong-Mou AU - Shih HM AUID- ORCID: 0009-0001-8344-5309 AD - School of Medicine, College of Medicine, MacKay Medical University, New Taipei City, Taiwan. AD - Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan. AD - Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260531 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Diseases/mortality/prevention & control/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide 1/therapeutic use/analogs & derivatives MH - Semaglutide MH - Randomized Controlled Trials as Topic MH - Tirzepatide MH - Treatment Outcome PMC - PMC13341365 OTO - NOTNLM OT - GLP-1 receptor agonist OT - Type 2 diabetes mellitus OT - cardiovascular outcomes OT - major adverse cardiovascular events OT - network meta-analysis OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2026/06/01 00:33 MHDA- 2026/07/08 12:57 PMCR- 2026/07/08 CRDT- 2026/05/31 21:42 PHST- 2026/05/05 00:00 [revised] PHST- 2026/03/29 00:00 [received] PHST- 2026/05/15 00:00 [accepted] PHST- 2026/07/08 12:57 [medline] PHST- 2026/06/01 00:33 [pubmed] PHST- 2026/05/31 21:42 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70915 [pii] AID - 10.1111/dom.70915 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):7137-7148. doi: 10.1111/dom.70915. Epub 2026 May 31. PMID- 42219226 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Semaglutide Injection in Indian Patients With Type 2 Diabetes Mellitus: A Randomised, Phase III, Active-Controlled Study. PG - 7094-7103 LID - 10.1111/dom.70891 [doi] AB - AIM: To evaluate the efficacy, safety and immunogenicity of semaglutide injection (synthetic) (Test group) compared with the Reference semaglutide injection [Ozempic, (Reference group)] in Indian patients with Type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This Phase III, randomised, open-label, multi-centre, parallel-group, active-controlled non-inferiority study was conducted across 35 centres in India. Adults aged 18-65 years with T2DM and baseline glycated haemoglobin (HbA1c) >/= 7.0% to 80% of endogenous circulating IgG as a biological reservoir to overcome peptide therapy limitations, offering a translatable platform for long-acting antidiabetic agents. FAU - Mi, Baojing AU - Mi B AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Ding, Shengjie AU - Ding S AD - Department of Pharmacy, Xinchang Hospital of Wenzhou Medical University, Shaoxing, Zhejiang 312500, China. FAU - Tian, Ziyu AU - Tian Z AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Yu, Jinhong AU - Yu J AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Ji, Zengxuan AU - Ji Z AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Fu, Luwei AU - Fu L AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Liu, Haiyan AU - Liu H AD - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. FAU - Cai, Yuepiao AU - Cai Y AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. FAU - Dai, Shijie AU - Dai S AUID- ORCID: 0009-0000-2710-0966 AD - State Key Laboratory of Macromolecular Drugs and Large-scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. LA - eng PT - Journal Article DEP - 20260530 PL - United States TA - Bioconjug Chem JT - Bioconjugate chemistry JID - 9010319 RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin G) RN - 0 (Immunoglobulin Fc Fragments) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Exenatide/chemistry/therapeutic use/pharmacokinetics/pharmacology MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/chemistry/therapeutic use/pharmacokinetics/pharmacology MH - Humans MH - *Immunoglobulin G/chemistry/immunology MH - Mice MH - *Immunoglobulin Fc Fragments/chemistry/immunology MH - Semaglutide MH - Structure-Activity Relationship MH - Male EDAT- 2026/05/31 05:30 MHDA- 2026/06/17 06:31 CRDT- 2026/05/30 09:33 PHST- 2026/06/17 06:31 [medline] PHST- 2026/05/31 05:30 [pubmed] PHST- 2026/05/30 09:33 [entrez] AID - 10.1021/acs.bioconjchem.6c00218 [doi] PST - ppublish SO - Bioconjug Chem. 2026 Jun 17;37(6):1292-1302. doi: 10.1021/acs.bioconjchem.6c00218. Epub 2026 May 30. PMID- 42209204 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Comparative Effects of Individual Glucagon-Like Peptide-1 Receptor Agonist-Based Medications on Direct Measurement of Body Composition Among Adults With Overweight or Obesity With or Without Type 2 Diabetes: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials. PG - 7018-7038 LID - 10.1111/dom.70884 [doi] AB - AIM: To compare the effects of individual glucagon-like peptide-1 receptor agonists (GLP-1RAs) on direct body composition among adults with overweight or obesity, with or without type 2 diabetes (T2D). METHODS: We systematically searched six electronic databases and grey literature from inception to 3 November 2025, to identify all randomised controlled trials (RCTs) that investigated individual GLP-1RAs on change in body composition from baseline among adults with overweight or obesity with or without T2D, without language restrictions. The main outcomes included total body fat (%), fat mass (kg), visceral adipose tissue (VAT) area (cm(2)), subcutaneous adipose tissue (SAT) area (cm(2)), liver fat content (%), total lean tissue (%) and lean mass (kg). A frequentist network meta-analysis was employed using a random-effects model and reported as standardised mean differences (SMDs). Certainty of evidence was appraised using the Confidence in Network Meta-Analysis. RESULTS: We identified 43 unique RCTs with 3379 participants that compared 17 different interventions or dosages with a control group. Regarding variations in treatment benefits on body composition, GLP-1RAs subcutaneously were more efficacious than the control group in decreasing total body fat, fat mass, VAT, SAT and liver fat from baseline. No significant differences for change in total lean tissue were observed. However, subcutaneously, liraglutide 1.8 mg/day, semaglutide 1.0 mg-weekly and tirzepatide 15 mg-weekly (SMDs ranged from -1.09 to -0.50) significantly decreased lean mass from baseline. CONCLUSIONS: GLP-1RAs substantially improve body composition-related excess adiposity, but unfavourable effects on lean mass were observed, particularly at high doses. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Wachiraphansakul, Nuttaya AU - Wachiraphansakul N AUID- ORCID: 0000-0003-1623-3071 AD - Department of Internal Medicine, Lampang Hospital, Lampang, Thailand. FAU - Vongchaiudomchoke, Thanawat AU - Vongchaiudomchoke T AUID- ORCID: 0000-0002-1007-907X AD - Department of Internal Medicine, Lampang Hospital, Lampang, Thailand. FAU - Manosroi, Worapaka AU - Manosroi W AUID- ORCID: 0000-0002-3007-3951 AD - Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. FAU - Ruengorn, Chidchanok AU - Ruengorn C AUID- ORCID: 0000-0001-7927-1425 AD - Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand. AD - Pharmacoepidemiology and Statistical Research Center (PESRC), Chiang Mai University, Chiang Mai, Thailand. FAU - Noppakun, Kajohnsak AU - Noppakun K AUID- ORCID: 0000-0002-5783-8766 AD - Pharmacoepidemiology and Statistical Research Center (PESRC), Chiang Mai University, Chiang Mai, Thailand. AD - Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. FAU - Ngamvichchukorn, Tanun AU - Ngamvichchukorn T AUID- ORCID: 0000-0003-0119-4647 AD - Pharmacoepidemiology and Statistical Research Center (PESRC), Chiang Mai University, Chiang Mai, Thailand. AD - Division of Nephrology, Department of Medicine, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand. FAU - Sood, Manish M AU - Sood MM AUID- ORCID: 0000-0002-9146-2344 AD - Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada. AD - Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada. FAU - Thavorn, Kednapa AU - Thavorn K AUID- ORCID: 0000-0003-4738-8447 AD - Pharmacoepidemiology and Statistical Research Center (PESRC), Chiang Mai University, Chiang Mai, Thailand. AD - Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada. AD - Institute of Clinical and Evaluative Sciences, ICES uOttawa, Ottawa, Ontario, Canada. AD - School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. FAU - Hutton, Brian AU - Hutton B AUID- ORCID: 0000-0001-5662-8647 AD - Ottawa Hospital Research Institute, Ottawa Hospital, Ottawa, Ontario, Canada. AD - Institute of Clinical and Evaluative Sciences, ICES uOttawa, Ottawa, Ontario, Canada. AD - School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. FAU - Nochaiwong, Surapon AU - Nochaiwong S AUID- ORCID: 0000-0003-1100-7171 AD - Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand. AD - Pharmacoepidemiology and Statistical Research Center (PESRC), Chiang Mai University, Chiang Mai, Thailand. LA - eng GR - Chiang Mai University/ PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260528 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Body Composition/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - Randomized Controlled Trials as Topic MH - *Overweight/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - Tirzepatide MH - Liraglutide MH - Adult OTO - NOTNLM OT - body composition OT - fat distribution OT - glucagon-like peptide-1 OT - muscle mass OT - obesity OT - overweight EDAT- 2026/05/29 15:46 MHDA- 2026/07/08 12:56 CRDT- 2026/05/28 21:43 PHST- 2026/05/06 00:00 [revised] PHST- 2026/02/24 00:00 [received] PHST- 2026/05/07 00:00 [accepted] PHST- 2026/07/08 12:56 [medline] PHST- 2026/05/29 15:46 [pubmed] PHST- 2026/05/28 21:43 [entrez] AID - 10.1111/dom.70884 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):7018-7038. doi: 10.1111/dom.70884. Epub 2026 May 28. PMID- 42208956 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 8 DP - 2026 Aug TI - Beyond weight loss: multisystem benefits of obesity medications. PG - 678-692 LID - S2213-8587(26)00100-2 [pii] LID - 10.1016/S2213-8587(26)00100-2 [doi] AB - Obesity is increasingly managed with medications as disease-modifying therapies, reflecting its role as a gateway disease driving metabolic, cardiovascular, reproductive, neuropsychiatric, and mechanical conditions. This Review synthesises evidence from randomised controlled trials and high-quality meta-analyses on approved and late-stage investigational obesity medications, including phentermine-topiramate, naltrexone-bupropion, glucagon-like peptide-1 (GLP-1) receptor agonists (eg, liraglutide, semaglutide, subcutaneously and orally), and newer GLP-1 receptor agonist-based agents (eg, tirzepatide, survodutide, mazdutide, retatrutide, cagrilintide-semaglutide, and amycretin). We evaluated the effects of obesity medications across major obesity-related conditions, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, chronic kidney disease, heart failure, cardiovascular disease, obstructive sleep apnoea syndrome, polycystic ovary syndrome (recently named polyendocrine metabolic ovarian syndrome), osteoarthritis, muscle mass, depression, quality of life, and food cravings, along with binge-eating disorders, substance use disorders, and neurodegenerative diseases. Overall, GLP-1-based and multiagonist therapies show beneficial effects across these comorbid conditions. While many benefits of obesity medications are mediated by weight loss, accumulating evidence indicates important weight loss-independent effects, particularly with GLP-1 receptor agonist-based therapies. A broader understanding of these pleiotropic effects is essential to inform personalised obesity management and optimise long-term clinical outcomes. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Savas, Mesut AU - Savas M AD - Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. Electronic address: m.savas@erasmusmc.nl. FAU - Kuckuck, Susanne AU - Kuckuck S AD - Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Epidemiology and Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. FAU - Boon, Mariette R AU - Boon MR AD - Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. FAU - van Rossum, Elisabeth F C AU - van Rossum EFC AD - Obesity Center CGG (Centrum Gezond Gewicht), Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands; Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. LA - eng PT - Journal Article PT - Review DEP - 20260528 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Obesity/drug therapy/complications MH - *Anti-Obesity Agents/therapeutic use MH - *Weight Loss/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Semaglutide MH - Cardiovascular Diseases/drug therapy COIS- Declaration of interests MS received honoraria for lectures and educational events from Obesitas Platform-MedOnline, SCEM, Health Investment, Public Eyes Healthcare Communications, BSL, Medische Scholing, and MedClass-Boehringer Ingelheim; and support for attending a meeting from Rhythm Pharmaceuticals. MRB received honoraria for lectures and educational events from Obesitas Platform-MedOnline, SCEM, Health Investment, Public Eyes Healthcare Communications, Goodlife, and Eli Lilly; support for attending a meeting from Rhythm Pharmaceuticals; and receives royalties from Ambo Anthos for a book for lay and professional audiences: FAT, the secret organ (Dutch: VET Belangrijk, 2019; VET Belangrijk 2.0, 2026). EFCvR reports speaker fees from the Dutch Obesity Academy, Medische Scholing, Medscape-WebMD, Radcliffe CVRM, BSL, and Prevents (most payments to institution); was involved in (primarily providing medical care for) clinical trials funded by Rhythm Pharmaceuticals (payments to institution; present Review is independent of these trials); serves as a member of the guideline committee on obesity pharmacotherapy of the Endocrine Society; chaired the Dutch multidisciplinary guideline on overweight and obesity in adults (2023) and Partnership Overweight Netherlands; was the clinical lead of focus area obesity, diabetes, nutrition, and metabolism of the European Society of Endocrinology (2021-25); and received royalties from Ambo Anthos for the book: Fat, the secret organ, 2020 (Dutch: VET Belangrijk, 2019; VET Belangrijk 2.0, 2026). MRB and EFCVR are co-developers of the screening and monitoring tool CheckCausesObesity.com. SK declares no competing interests. EDAT- 2026/05/29 15:45 MHDA- 2026/07/15 12:35 CRDT- 2026/05/28 20:08 PHST- 2026/01/16 00:00 [received] PHST- 2026/03/31 00:00 [revised] PHST- 2026/04/10 00:00 [accepted] PHST- 2026/07/15 12:35 [medline] PHST- 2026/05/29 15:45 [pubmed] PHST- 2026/05/28 20:08 [entrez] AID - S2213-8587(26)00100-2 [pii] AID - 10.1016/S2213-8587(26)00100-2 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Aug;14(8):678-692. doi: 10.1016/S2213-8587(26)00100-2. Epub 2026 May 28. PMID- 42206237 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260813 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 20 DP - 2026 TI - Semaglutide Inhibits Osteoblast Ferroptosis Induced by Diabetic Periodontitis via Modulating the Wnt5a/Ror2/p38 MAPK Signaling Pathway. PG - 599539 LID - 10.2147/DDDT.S599539 [doi] LID - 599539 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major risk factor for periodontitis, often leading to exacerbated alveolar bone loss. Ferroptosis, an iron-dependent regulated cell death pathway, contributes to osteoblast dysfunction under diabetic conditions. The non-canonical Wnt5a/Ror2 pathway is pivotal in inflammation and bone metabolism. Semaglutide, a long-acting GLP-1 receptor agonist, may modulate this pathway and protect osteoblasts from ferroptosis, however, its role in diabetic periodontitis remains unclear. METHODS: MC3T3-E1 osteoblasts were exposed to high glucose plus palmitic acid (HGHP) to mimic a diabetic microenvironment. The effects of Semaglutide on osteoblast proliferation, migration, differentiation, mineralization, and ferroptosis were assessed using EDU, Transwell, ALP and ARS staining, qPCR, Western blotting, ROS, Fe(2)(+), and lipid peroxidation assays. Mechanistic involvement of Wnt5a/Ror2/p38 MAPK signaling was examined using Wnt5a siRNA and a p38 MAPK agonist. In vivo, T2DM mice with ligature-induced periodontitis were treated with semaglutide; alveolar bone and ferroptosis-related markers were assessed by H&E, immunohistochemistry (OPN, GPX4), and 4-HNE immunofluorescence. RESULTS: HGHP induced osteoblast ferroptosis, increased oxidative stress, and impaired osteogenic function. Semaglutide restored proliferation and osteogenic capacity and attenuated oxidative stress and ferroptosis. Wnt5a was upregulated by HGHP; its silencing reduced ferroptosis and improved osteogenesis. Semaglutide suppressed HGHP-induced Wnt5a/Ror2/p38 MAPK activation, whereas p38 activation blunted its protective effects. In T2DM periodontitis mice, semaglutide reduced periodontal inflammation and osteoblast ferroptosis. CONCLUSION: Semaglutide mitigates HGHP-induced osteoblast ferroptosis and improves osteogenic function via the Wnt5a/Ror2/p38 MAPK pathway, supporting its potential in diabetic periodontitis. CI - (c) 2026 Zhang et al. FAU - Zhang, Zhen AU - Zhang Z AD - School of Stomatology, Binzhou Medical University, Yantai, 264003, People's Republic of China. FAU - Niu, Delong AU - Niu D AD - Department of Stomatology, Lanzhou Petrochemical General Hospital (The Fourth affiliated Hospital of Gansu University of Chinese Medicine), Lanzhou, 730060, People's Republic of China. FAU - Qiu, Wenjie AU - Qiu W AD - Department of Oral Implantology, The Affiliated Yantai Stomatological Hospital, Binzhou Medical University, Yantai, 264003, People's Republic of China. FAU - Feng, Haoyu AU - Feng H AD - School of Stomatology, Binzhou Medical University, Yantai, 264003, People's Republic of China. FAU - Jia, Lurong AU - Jia L AD - Department of Oral Implantology, The Affiliated Yantai Stomatological Hospital, Binzhou Medical University, Yantai, 264003, People's Republic of China. FAU - Zhou, Wenjuan AU - Zhou W AD - Department of Oral Implantology, The Affiliated Yantai Stomatological Hospital, Binzhou Medical University, Yantai, 264003, People's Republic of China. LA - eng PT - Journal Article DEP - 20260522 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 53AXN4NNHX (Semaglutide) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - 0 (Wnt-5a Protein) RN - EC 2.7.10.1 (Ror2 protein, mouse) RN - 62340-29-8 (Glucagon-Like Peptides) RN - EC 2.7.10.1 (Receptor Tyrosine Kinase-like Orphan Receptors) RN - 0 (Wnt5a protein, mouse) SB - IM MH - Semaglutide MH - Animals MH - p38 Mitogen-Activated Protein Kinases/metabolism/antagonists & inhibitors MH - Wnt-5a Protein/metabolism/antagonists & inhibitors MH - Mice MH - *Osteoblasts/drug effects/metabolism/pathology MH - *Ferroptosis/drug effects MH - *Periodontitis/drug therapy/metabolism/pathology MH - *Glucagon-Like Peptides/pharmacology MH - Receptor Tyrosine Kinase-like Orphan Receptors/metabolism/antagonists & inhibitors MH - Mice, Inbred C57BL MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Dose-Response Relationship, Drug MH - Cells, Cultured MH - *Diabetes Mellitus, Experimental/drug therapy/metabolism MH - Signal Transduction/drug effects PMC - PMC13209148 OTO - NOTNLM OT - Wnt5a/Ror2 OT - diabetic periodontitis OT - ferroptosis OT - p38 MAPK pathway OT - semaglutide COIS- The authors declare no competing interests. EDAT- 2026/05/28 06:33 MHDA- 2026/05/28 06:34 PMCR- 2026/05/22 CRDT- 2026/05/28 04:45 PHST- 2026/03/02 00:00 [received] PHST- 2026/05/08 00:00 [accepted] PHST- 2026/05/28 06:34 [medline] PHST- 2026/05/28 06:33 [pubmed] PHST- 2026/05/28 04:45 [entrez] PHST- 2026/05/22 00:00 [pmc-release] AID - 599539 [pii] AID - 10.2147/DDDT.S599539 [doi] PST - epublish SO - Drug Des Devel Ther. 2026 May 22;20:599539. doi: 10.2147/DDDT.S599539. eCollection 2026. PMID- 42201355 OWN - NLM STAT- MEDLINE DCOM- 20260915 LR - 20261008 IS - 1435-702X (Electronic) IS - 0721-832X (Linking) VI - 264 IP - 9 DP - 2026 Sep TI - Semaglutide and risk of Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) in type 2 diabetes mellitus: A systematic review and meta-analysis. PG - 2611-2621 LID - 10.1007/s00417-026-07291-4 [doi] AB - BACKGROUND: The use of Glucagon-like peptide-1 receptor agonists (GLP-1RAs) has expanded dramatically worldwide, with semaglutide being one of the most widely utilized agents. Nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with GLP-1RAs use from emerging pharmacovigilance data. This systematic review and meta-analysis sought to evaluate the risk of NAION in patients with type 2 diabetes mellitus (T2DM). METHODS: A literature search was made up to September 2025 (PROSPERO: CRD420251155026). Results were synthesized following the PRISMA guidelines and are presented as pooled Hazard Ratios (HR) with 95% confidence intervals (CI). RESULTS: Twelve studies were included; eight retrospective cohorts (14,255,247 participants) were meta-analyzed, with a mean age of 59.3 +/- 15.9 years and 32.7% males. Patients with T2DM using semaglutide compared to non-GLP-1RAs showed an increased risk of NAION at 1-year follow-up with a pooled HR of 3.36 (95% CI: 1.44-7.84; p < 0.001; I(2) = 97%). At 2-year follow-up, the pooled HR was 2.37 (95% CI: 1.46-3.85; p < 0.001; I(2) = 0%). The 3-year risk after the sensitivity analysis showed a pooled HR of 2.37 (95% CI: 1.45-3.87, p < 0.001; I(2) = 28%), and the 5-year pooled HR was 2.37 (95% CI: 0.62-3.92; p < 0.001; I(2) = 0%). CONCLUSION: This meta-analysis indicates a significant association between semaglutide use and NAION in patients with T2DM compared to non-GLP-1RAs, with this association remaining significant even after 5-years of semaglutide use. CI - (c) 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Lampsas, Stamatios AU - Lampsas S AD - Second Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, 1, Rimini street, Haidari, Athens, 12462, Greece. FAU - Agapitou, Chrysa AU - Agapitou C AD - Second Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, 1, Rimini street, Haidari, Athens, 12462, Greece. FAU - Oikonomou, Evangelos AU - Oikonomou E AD - Third Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, "Sotiria" General Hospital, Athens, 11527, Greece. FAU - Siasos, Gerasimos AU - Siasos G AD - Third Department of Cardiology, School of Medicine, National and Kapodistrian University of Athens, "Sotiria" General Hospital, Athens, 11527, Greece. AD - Cardiovascular Division, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, 02115, USA. FAU - Theodossiadis, Panagiotis AU - Theodossiadis P AD - Second Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, 1, Rimini street, Haidari, Athens, 12462, Greece. FAU - Tsivgoulis, Georgios AU - Tsivgoulis G AD - Second Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens, 12462, Greece. FAU - Lambadiari, Vaia AU - Lambadiari V AD - Second Department of Internal Medicine, Research Institute and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, Athens, 12462, Greece. FAU - Chatziralli, Irini AU - Chatziralli I AD - Second Department of Ophthalmology, School of Medicine, National and Kapodistrian University of Athens, "Attikon" University Hospital, 1, Rimini street, Haidari, Athens, 12462, Greece. eirchat@yahoo.gr. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260527 PL - Germany TA - Graefes Arch Clin Exp Ophthalmol JT - Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie JID - 8205248 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology/diagnosis/etiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors OTO - NOTNLM OT - GLP-1 receptor agonists OT - Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: The study does not involve any human subjects or animal and does not require disclosure to the rights. Competing interests: The authors declare no competing interests. EDAT- 2026/05/27 12:36 MHDA- 2026/09/15 18:07 CRDT- 2026/05/27 11:03 PHST- 2026/01/19 00:00 [received] PHST- 2026/05/18 00:00 [accepted] PHST- 2026/04/24 00:00 [revised] PHST- 2026/09/15 18:07 [medline] PHST- 2026/05/27 12:36 [pubmed] PHST- 2026/05/27 11:03 [entrez] AID - 10.1007/s00417-026-07291-4 [pii] AID - 10.1007/s00417-026-07291-4 [doi] PST - ppublish SO - Graefes Arch Clin Exp Ophthalmol. 2026 Sep;264(9):2611-2621. doi: 10.1007/s00417-026-07291-4. Epub 2026 May 27. PMID- 42186215 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Real-World Effectiveness and 12-Month Persistence of a Semaglutide-Supported Digital Weight-Loss Service: A Retrospective Cohort Study in Germany. PG - 6985-6996 LID - 10.1111/dom.70916 [doi] AB - AIM: To evaluate the 12-month effectiveness and patient persistence of a semaglutide-supported digital weight-loss service (DWLS) in a real-world German cohort. METHODS: This retrospective study analysed 4535 patients who initiated the Juniper Germany DWLS. Primary endpoints included 12-month medication and data submission adherence (receiving >/= 10 orders) and mean weight-loss percentage. Effectiveness was assessed via a per-protocol (PP) analysis of an adherent sub-cohort (n = 546) and an intention-to-treat (ITT) analysis of the full cohort using Last Observation Carried Forward (LOCF) and a Worst-Case Scenario (WCS) sensitivity model. Binary logistic and multiple linear regressions identified predictors of attrition (churn) and efficacy. RESULTS: Of the total cohort (n = 4535), mean 12-month weight loss was 9.47% (LOCF). However, sensitivity analysis using a WCS model-assuming 0% weight loss for all dropouts-yielded a mean of 2.40%. Among the 12% of patients (n = 546) who remained adherent to both medication and data submission protocols, mean weight loss was 15.13% (+/-7.1). Program persistence was significantly bolstered by achieving a healthy BMI milestone (OR = 0.29, p < 0.001), encountering a weight-loss plateau (OR = 0.41, p < 0.001), and higher baseline obesity severity (Obesity Class I-III: p < 0.023). Conversely, high clinical complexity (>/= 3 comorbidities) more than doubled the risk of churn (OR = 2.12, p = 0.002), while previous GLP-1 RA use also significantly increased churn risk (OR = 1.57, p = 0.001). While moderate early engagement (2-10 logs) was a strong predictor of persistence (p < 0.001), intensive tracking (> 10 logs) did not significantly reduce churn risk (p = 0.393). CONCLUSION: The population-level impact of this DWLS is fundamentally limited by high attrition (88%) in an unsubsidised environment. While significant weight loss is possible for a non-representative adherent minority, the mean effectiveness for the total initiating population (2.40% WCS) highlights that real-world success is strictly conditional upon long-term persistence. The study found that both clinical success and setbacks were associated with program adherence. It also observed that patients of high clinical complexity were at greater risk of attrition. Finally, it found that high-friction manual weight logging serves as a marker of commitment rather than anxiety as had been reported in app-based DWLSs where tracking has significantly lower friction. These findings suggest that the predictive value of digital engagement is fundamentally shaped by DWLS delivery mode and the behavioural cost of engagement. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Talay, Louis AU - Talay L AD - Eucalyptus Health, Sydney, New South Wales, Australia. FAU - Hom, Jason AU - Hom J AD - Department of Medicine, Stanford University Medical Centre, Stanford, California, USA. FAU - Tan, Marilyn AU - Tan M AUID- ORCID: 0000-0002-6651-4691 AD - Department of Medicine, Stanford University Medical Centre, Stanford, California, USA. FAU - Ahuja, Neera AU - Ahuja N AD - Department of Medicine, Stanford University Medical Centre, Stanford, California, USA. LA - eng PT - Journal Article DEP - 20260525 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - Retrospective Studies MH - Female MH - Male MH - Germany/epidemiology MH - Middle Aged MH - Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - *Weight Reduction Programs/methods MH - *Obesity/therapy/drug therapy MH - Treatment Outcome MH - Aged MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Digital Health MH - Digital Media MH - *Anti-Obesity Agents/therapeutic use PMC - PMC13341323 OTO - NOTNLM OT - antiobesity drug OT - cohort study OT - obesity care OT - real-world evidence OT - semaglutide OT - weight management COIS- L.T. is paid a salary at Eucalyptus (Juniper parent company). N.A. is a paid advisor at Eucalyptus. J.H. and M.T. declare no conflicts of interest. EDAT- 2026/05/26 06:31 MHDA- 2026/07/08 12:57 PMCR- 2026/07/08 CRDT- 2026/05/26 01:33 PHST- 2026/05/13 00:00 [revised] PHST- 2026/03/24 00:00 [received] PHST- 2026/05/16 00:00 [accepted] PHST- 2026/07/08 12:57 [medline] PHST- 2026/05/26 06:31 [pubmed] PHST- 2026/05/26 01:33 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70916 [pii] AID - 10.1111/dom.70916 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):6985-6996. doi: 10.1111/dom.70916. Epub 2026 May 25. PMID- 42186086 OWN - NLM STAT- MEDLINE DCOM- 20260816 LR - 20260915 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 May 25 TI - Effects of semaglutide on mortality, cardiovascular, and kidney outcomes across the cardio-kidney-metabolic continuum: a systematic review and meta-analysis. LID - 10.1186/s12933-026-03215-y [doi] LID - 234 AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated cardiometabolic benefits in randomized controlled trials (RCTs). However, its overall effects on mortality, cardiovascular (CV) and kidney outcomes have not been comprehensively synthesized. This meta-analysis aimed to assess the prognostic impact of semaglutide across the cardio-kidney-metabolic continuum. METHODS: A systematic literature search was conducted to identify all eligible RCTs comparing the prognostic effects of semaglutide with placebo across diverse patient populations. Primary outcomes were all-cause and CV mortality. Secondary outcomes included major CV and kidney events, while major adverse limb events (MALE) were analyzed as an exploratory endpoint. A random-effects model was used to pool hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Eight trials encompassing 39,204 patients were included. In patients treated with semaglutide a significant reduction of all-cause (HR, 0.84; 95% CI, 0.77-0.92; p = 0.0001) and CV mortality (HR, 0.83; 95% CI, 0.72-0.95; p = 0.0078), major adverse CV events (MACE, HR, 0.82; 95% CI, 0.77-0.87; p < 0.0001), nonfatal myocardial infarction (MI, HR, 0.75; 95% CI, 0.68-0.84; p < 0.0001), worsening heart failure (HF, HR, 0.84; 95% CI, 0.73-0.98; p = 0.0245), and kidney outcomes (HR, 0.83; 95% CI, 0.73-0.95; p = 0.0080) was observed compared to placebo. No significant effects were observed for nonfatal stroke. CONCLUSIONS: Treatment with semaglutide, compared to placebo, is associated with significant lower incidence of all-cause and CV mortality, as well major CV and kidney events across the continuum of cardio-kidney-metabolic syndrome. CI - (c) 2026. The Author(s). FAU - Marzano, Federica AU - Marzano F AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Paolillo, Stefania AU - Paolillo S AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Gargiulo, Paola AU - Gargiulo P AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Cotticelli, Ciro AU - Cotticelli C AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Di Santo, Mariafrancesca AU - Di Santo M AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Nardi, Ermanno AU - Nardi E AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Abbellito, Giuseppe Maria AU - Abbellito GM AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Liccardi, Laura AU - Liccardi L AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. FAU - Perrone Filardi, Fabrizio AU - Perrone Filardi F AD - Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy. FAU - Bruzzese, Dario AU - Bruzzese D AD - Department of Public Health, University of Naples Federico II, Naples, Italy. FAU - Perrone Filardi, Pasquale AU - Perrone Filardi P AD - Department of Advanced Biomedical Sciences, University of Naples Federico II, Via S. Pansini, 5, 80131, Naples, Italy. fpperron@unina.it. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20260525 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Cardiovascular Diseases/mortality/diagnosis/prevention & control MH - Treatment Outcome MH - Risk Assessment MH - *Kidney Diseases/mortality/diagnosis/prevention & control MH - Male MH - Randomized Controlled Trials as Topic MH - Female MH - Middle Aged MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/diagnosis MH - *Incretins/therapeutic use/adverse effects MH - Cause of Death MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Kidney/drug effects/physiopathology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Time Factors MH - *Metabolic Syndrome/mortality/diagnosis/drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism PMC - PMC13479731 OTO - NOTNLM OT - Cardio-kidney-metabolic syndrome OT - Mortality OT - Placebo OT - Randomized controlled trials OT - Semaglutide COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2026/05/26 06:31 MHDA- 2026/08/17 05:38 PMCR- 2026/05/25 CRDT- 2026/05/26 00:09 PHST- 2026/02/08 00:00 [received] PHST- 2026/04/30 00:00 [accepted] PHST- 2026/08/17 05:38 [medline] PHST- 2026/05/26 06:31 [pubmed] PHST- 2026/05/26 00:09 [entrez] PHST- 2026/05/25 00:00 [pmc-release] AID - 10.1186/s12933-026-03215-y [pii] AID - 3215 [pii] AID - 10.1186/s12933-026-03215-y [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 May 25;25(1):234. doi: 10.1186/s12933-026-03215-y. PMID- 42185271 OWN - NLM STAT- MEDLINE DCOM- 20260721 LR - 20260822 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 17 IP - 1 DP - 2026 May 25 TI - Phenome-wide analysis of downstream health outcomes following second-line antidiabetic agent prescriptions in All of Us. LID - 10.1038/s41467-026-72947-y [doi] LID - 6853 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes (T2D) and weight management, yet their real-world health impacts remain understudied. Using a retrospective cohort design with electronic health record data from 17,267 adults with type 2 diabetes in the All of Us Research Program, we conduct propensity score-matched phenome-wide association studies comparing diagnoses following GLP-1 RA prescription (including semaglutide-specific analyses) to those following sodium-glucose cotransporter-2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) prescriptions between January 2018 and October 2023. We employ both intention-to-treat and per-protocol Cox proportional hazards models alongside restricted mean survival time analyses evaluating up to 974 phenotypes. We identify multiple phenome-wide significant and suggestive associations, including for cardiovascular, genitourinary, dental, and metabolic outcomes. Compared to SGLT2i, semaglutide demonstrates reduced risk for genitourinary infections in women (e.g., candidiasis of vulva and vagina (per-protocol hazard ratio 0.31, 95% confidence interval (0.17-0.55)). Compared to DPP4i, GLP-1 RAs are associated with reduced risk of diseases of hard tissues of teeth (0.45 (0.33-0.61)). Time-to-event analyses reveal modest delays for key diagnoses. These findings underscore differences in downstream diagnostic associations across second-line T2D therapies and highlight semaglutide's distinct profile, with implications for clinical decision-making and personalized prescribing. CI - (c) 2026. The Author(s). FAU - Salvatore, Maxwell AU - Salvatore M AUID- ORCID: 0000-0002-3659-1514 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. maxwell.salvatore@pennmedicine.upenn.edu. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. maxwell.salvatore@pennmedicine.upenn.edu. AD - Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. maxwell.salvatore@pennmedicine.upenn.edu. AD - Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA. maxwell.salvatore@pennmedicine.upenn.edu. FAU - Zhang, Bingyu AU - Zhang B AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. FAU - Tang, Huilin AU - Tang H AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Lu, Yiwen AU - Lu Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. FAU - Zhang, Dazheng AU - Zhang D AUID- ORCID: 0000-0002-1431-0785 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Zhou, Ting AU - Zhou T AUID- ORCID: 0000-0003-3392-2979 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. FAU - Lu, Yuan AU - Lu Y AUID- ORCID: 0000-0001-5264-2169 AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA. AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA. FAU - Amaro, Anastassia AU - Amaro A AD - Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania, Philadelphia, PA, USA. FAU - D Ritchie, Marylyn AU - D Ritchie M AUID- ORCID: 0000-0002-1208-1720 AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. AD - Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. AD - Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA. AD - Division of Biomedical Informatics and AI, Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA. FAU - Chen, Yong AU - Chen Y AUID- ORCID: 0000-0003-0835-0788 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. AD - Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. AD - Leonard David Institute of Health Economics, Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. AD - Penn Medicine Center for Evidence-Based Practice (CEP), Philadelphia, PA, USA. ychen123@pennmedicine.upenn.edu. LA - eng GR - R01 HL169458/HL/NHLBI NIH HHS/United States GR - U2C OD023196/OD/NIH HHS/United States GR - OT2 OD025315/OD/NIH HHS/United States GR - OT2 OD026551/OD/NIH HHS/United States GR - U24 OD023121/OD/NIH HHS/United States GR - OT2 OD026552/OD/NIH HHS/United States GR - OT2 OD025337/OD/NIH HHS/United States GR - OT2 OD026553/OD/NIH HHS/United States GR - OT2 OD023205/OD/NIH HHS/United States GR - OT2 OD025276/OD/NIH HHS/United States GR - OT2 OD026557/OD/NIH HHS/United States GR - 1R01LM014344/U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM)/ GR - OT2 OD023206/OD/NIH HHS/United States GR - R21 EY034179/EY/NEI NIH HHS/United States GR - R21AI167418/Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)/ GR - OT2 OD026556/OD/NIH HHS/United States GR - U24 OD023176/OD/NIH HHS/United States GR - OT2 OD026548/OD/NIH HHS/United States GR - R21 AI167418/AI/NIAID NIH HHS/United States GR - U01 TR003709/TR/NCATS NIH HHS/United States GR - OT2 OD026549/OD/NIH HHS/United States GR - R01DK128237/U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)/ GR - R01 DK128237/DK/NIDDK NIH HHS/United States GR - R01 LM014344/LM/NLM NIH HHS/United States GR - R56 AG074604/AG/NIA NIH HHS/United States GR - R01 AG073435/AG/NIA NIH HHS/United States GR - OT2 OD025277/OD/NIH HHS/United States GR - R01AG073435/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ GR - R01LM013519/U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM)/ GR - RF1 AG077820/AG/NIA NIH HHS/United States GR - R21EY034179/U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ GR - OT2 OD026555/OD/NIH HHS/United States GR - OT2 OD026550/OD/NIH HHS/United States GR - R01 LM013519/LM/NLM NIH HHS/United States GR - U01TR003709/U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS)/ GR - RF1AG077820/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ GR - OT2 OD026554/OD/NIH HHS/United States GR - U24 MH136069/MH/NIMH NIH HHS/United States GR - R56AG074604/U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)/ GR - U24 OD023163/OD/NIH HHS/United States PT - Journal Article DEP - 20260525 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - Retrospective Studies MH - Glucagon-Like Peptides/therapeutic use MH - Male MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - United States MH - Middle Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Phenomics MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Phenotype MH - Electronic Health Records PMC - PMC13388941 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/05/26 00:30 MHDA- 2026/07/22 12:37 PMCR- 2026/05/25 CRDT- 2026/05/25 23:15 PHST- 2025/07/07 00:00 [received] PHST- 2026/04/28 00:00 [accepted] PHST- 2026/07/22 12:37 [medline] PHST- 2026/05/26 00:30 [pubmed] PHST- 2026/05/25 23:15 [entrez] PHST- 2026/05/25 00:00 [pmc-release] AID - 10.1038/s41467-026-72947-y [pii] AID - 72947 [pii] AID - 10.1038/s41467-026-72947-y [doi] PST - epublish SO - Nat Commun. 2026 May 25;17(1):6853. doi: 10.1038/s41467-026-72947-y. PMID- 42173109 OWN - NLM STAT- MEDLINE DCOM- 20260616 LR - 20260930 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 7 DP - 2026 Jul TI - Effects of a 6-week subcutaneous infusion of native GIP alone or as add-on to semaglutide in people with type 2 diabetes: a single-centre, double-blind, parallel-group, randomised, placebo-controlled trial. PG - 581-593 LID - S2213-8587(26)00075-6 [pii] LID - 10.1016/S2213-8587(26)00075-6 [doi] AB - BACKGROUND: The long-term glycaemic effects of glucose-dependent insulinotropic polypeptide (GIP) remain unclear. We aimed to assess whether a 6-week subcutaneous infusion of GIP alone and in combination with the GLP-1 receptor agonist semaglutide would enhance glycaemic control in individuals with type 2 diabetes. METHODS: This single-centre, double-blind, parallel-group, randomised, placebo-controlled trial was conducted at the Center for Clinical Metabolic Research (Hellerup, Denmark). Inclusion criteria were age 18-74 years; a diagnosis of type 2 diabetes for at least 6 months; stable treatment; HbA(1c) of 6.5-10.5% (48-91 mmol/mol); and a BMI of 25-50 kg/m(2). Participants were randomly assigned (1:1:1:1), using a block randomisation list, to receive either placebo plus placebo, placebo plus GIP, semaglutide plus placebo, or semaglutide plus GIP (all self-administered subcutaneously). The regimen was 8-week semaglutide or placebo run-in period (4 weeks at 0.25 mg then 4 weeks at 0.50 mg once per week), after which participants continued 0.50 mg semaglutide or placebo for an additional 6 weeks while receiving continuous subcutaneous infusions of GIP or placebo (16 pmol/kg per min). Participants and investigators were masked to treatment assignment. The primary outcome was change in 14-day mean glucose concentration assessed by continuous glucose monitoring from baseline to the end of treatment at 14 weeks, assessed in the efficacy population. This study is registered at ClinicalTrials.gov, NCT05078255 (completed). FINDINGS: Between Jan 31, 2022, and Sept 4, 2024, we assessed 134 individuals with type 2 diabetes for eligibility, of whom 73 were ineligible. We enrolled and randomly assigned 61 participants (15 to placebo plus placebo, 16 to placebo plus GIP, 15 to semaglutide plus placebo, and 15 to semaglutide plus GIP). Ten (16%) participants discontinued the study. Participants had a median age of 64.0 years (IQR 60.0-68.0), HbA(1c) of 54.0 mmol/mol (49.0-60.0), diabetes duration of 6.3 years (4.2-9.8), and a mean BMI of 31.6 kg/m(2) (SD 4.8). 22 (36%) participants were female and 39 (64%) were male and all self-reported as White. Fasting concentrations of intact (bioactive) GIP at the end of treatment on week 14 were mean 7 pmol/L (SD 4) in the placebo plus placebo group, 45 pmol/L (43) in the placebo plus GIP group, 10 pmol/L (6) in the semaglutide plus placebo group, and 85 pmol/L (92) in the semaglutide plus GIP group; whereas fasting concentrations of total GIP were 14 pmol/L (7), 375 pmol/L (377), 18 pmol/L (19), and 527 pmol/L (338), respectively. The estimated effect of GIP on change in 14-day mean sensor-detected glucose from baseline to end of treatment was 0.80 mmol/L (97.5% CI -0.18 to 1.80; p=0.13 in the placebo plus GIP vs placebo plus placebo groups) and 0.05 mmol/L (-0.85 to 0.95; p=1.00 in the semaglutide plus GIP vs semaglutide plus placebo groups). Injection site reactions were the most common adverse event (22 [36%]). Gastrointestinal adverse events were more frequent with semaglutide (nine [60%] with placebo plus placebo, 11 [69%] with placebo plus GIP, 11 [73%] with semaglutide plus placebo, and 12 [80%] with semaglutide plus GIP). INTERPRETATION: 6 weeks of subcutaneous GIP infusion as add-on to placebo or semaglutide did not improve glycaemic control in individuals with type 2 diabetes at the prespecified target of 1.50 mmol/L. Due to dropouts, we cannot draw firm conclusions on the effects of GIP as add-on to placebo. FUNDING: Novo Nordisk. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Helsted, Mads M AU - Helsted MM AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Fonnesbech-Wulff, Christiane AU - Fonnesbech-Wulff C AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Schaltz, Nina L AU - Schaltz NL AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Lund, Ingrid W AU - Lund IW AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Forman, Julie L AU - Forman JL AD - Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Nielsen, Casper K AU - Nielsen CK AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Englund, Anders AU - Englund A AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Hartmann, Bolette AU - Hartmann B AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Clinical Research, Steno Diabetes Center Copenhagen, Copenhagen, Denmark. FAU - Holst, Jens J AU - Holst JJ AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Lund, Asger B AU - Lund AB AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Clinical Research, Steno Diabetes Center Copenhagen, Copenhagen, Denmark. FAU - Christensen, Mikkel B AU - Christensen MB AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. FAU - Knop, Filip K AU - Knop FK AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Gasbjerg, Laerke S AU - Gasbjerg LS AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: lsg@sund.ku.dk. LA - eng SI - ClinicalTrials.gov/NCT05078255 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260522 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Male MH - Double-Blind Method MH - Middle Aged MH - *Gastric Inhibitory Polypeptide/administration & dosage/therapeutic use MH - Drug Therapy, Combination MH - Infusions, Subcutaneous MH - Adult MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Blood Glucose/analysis MH - Adolescent MH - Glycated Hemoglobin/analysis MH - Young Adult COIS- Declaration of interests CF-W and IWL are shareholders of Novo Nordisk. ABL served on a scientific advisory panel for Eli Lilly; and received speaker honoraria from Boehringer Ingelheim, Novo Nordisk, and Zealand Pharma. JJH is a cofounder and shareholder of Antag Therapeutics; and served on scientific advisory panels or received speaker honoraria (or both) from AlphaSights, Eli Lilly, Novo Nordisk, MSD, Structure Therapeutics, and Zealand Pharma. TV served on scientific advisory panels, speakers' bureaus, and was a consultant or received research support (or both) from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, MSD, Novo Nordisk, Sanofi, and Sun Pharma. FKK served on scientific advisory panels, speaker's bureaus, was a consultant, owns stocks or received research support (or both) from 89bio, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, MedImmune, MSD, Norgine, Novo Nordisk, Sanofi, ShouTi, SNIPR Biome, Zealand Pharma, and Zucara; and is a cofounder and shareholder in Antag Therapeutics. TV, CKN, and FKK are employed by Novo Nordisk. LSG received a grant from Novo Nordisk Foundation (NNF18SA0034956); is a shareholder and cofounder of Antag Therapeutics; and reports receiving a personal lecture fee from Novo Nordisk. All other authors declare no competing interests. EDAT- 2026/05/23 05:37 MHDA- 2026/06/17 00:36 CRDT- 2026/05/22 18:52 PHST- 2025/12/10 00:00 [received] PHST- 2026/03/23 00:00 [revised] PHST- 2026/03/24 00:00 [accepted] PHST- 2026/06/17 00:36 [medline] PHST- 2026/05/23 05:37 [pubmed] PHST- 2026/05/22 18:52 [entrez] AID - S2213-8587(26)00075-6 [pii] AID - 10.1016/S2213-8587(26)00075-6 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Jul;14(7):581-593. doi: 10.1016/S2213-8587(26)00075-6. Epub 2026 May 22. PMID- 42170981 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260831 IS - 3105-9686 (Electronic) IS - 1011-601X (Linking) VI - 39 IP - 7 DP - 2026 Jul TI - Short-term comparative effects of semaglutide, either alone or in conjunction with canagliflozin, on early diabetic kidney disease. PG - 2165-2172 LID - 10.36721/PJPS.2026.39.7.204.1 [doi] AB - BACKGROUND: Diabetic kidney disease (DKD) is a common complication of type 2 diabetes mellitus and an important cause of end-stage renal disease. Metabolic dysfunction, albuminuria, and chronic low-grade inflammation characterize early DKD, leading to progressive renal impairment. To date, SGLT2 inhibitors and GLP-1 receptor agonists are known to provide renoprotective and metabolic benefits; however, there is limited evidence available regarding the combined use of these treatments in early DKD. OBJECTIVES: This study evaluated the short-term effects of canagliflozin and semaglutide, administered alone or in combination, on renal function, metabolic parameters, and systemic inflammatory markers in patients with early-stage DKD. METHODS: In this randomized controlled trial, 120 patients with early-stage diabetic kidney disease were randomly allocated (1:1:1:1) to four groups (n = 30 each): canagliflozin (100 mg orally once daily), semaglutide (0.25 mg once weekly with escalation to 1.0 mg after 4 weeks), combination treatment, or placebo/control. PARTICIPANTS: All participants were provided standard background care. Treatment continued for 24 weeks. The main renal outcomes were urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Glycemic control, insulin resistance, lipid parameters, and inflammatory biomarkers (HbA1c, fasting glucose, HOMA-IR, TNF-alpha, IL-6, CRP) were considered as secondary outcomes. Safety assessment was conducted using binary safety assessment. RESULTS: At 24 weeks, combination therapy achieved significantly greater reductions in UACR compared with monotherapy and placebo (P < 0.05). Across treatment groups, a small reduction in eGFR was observed without significant between-group differences. Measurements of HbA1c, fasting glucose, HOMA-IR, lipid parameters, and inflammatory markers showed better results in the combination therapy group compared to single-agent therapy (P < 0.05). Rates of adverse events were similar between the groups. CONCLUSION: Combined canagliflozin and semaglutide therapy demonstrated superior short-term benefits in reducing albuminuria, improving metabolic control, and attenuating systemic inflammation in early DKD, supporting further long-term evaluation of renal and cardiovascular outcomes. FAU - Long, Wang AU - Long W AD - Xi 'an Gem Flower Changqing Hospital, Xi' an, Shaanxi 710201, China. FAU - Ningning, Li AU - Ningning L AD - Xi 'an Gem Flower Changqing Hospital, Xi' an, Shaanxi 710201, China. FAU - Weijun, Huang AU - Weijun H AD - Xi 'an Gem Flower Changqing Hospital, Xi' an, Shaanxi 710201, China. LA - eng PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PL - Pakistan TA - Pak J Pharm Sci JT - Pakistan journal of pharmaceutical sciences JID - 9426356 RN - 0SAC974Z85 (Canagliflozin) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Canagliflozin/therapeutic use/adverse effects/administration & dosage MH - Semaglutide MH - *Diabetic Nephropathies/drug therapy/physiopathology MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Drug Therapy, Combination MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects/administration & dosage MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - Albuminuria MH - Blood Glucose/drug effects/metabolism MH - Biomarkers/blood MH - Glycated Hemoglobin/metabolism MH - Glomerular Filtration Rate/drug effects OTO - NOTNLM OT - Combination therapy OT - Canagliflozin OT - Early diabetic kidney disease OT - Inflammatory biomarkers OT - Metabolic parameters OT - Renal outcomes OT - Semaglutide EDAT- 2026/05/22 12:35 MHDA- 2026/05/22 12:36 CRDT- 2026/05/22 07:53 PHST- 2026/05/22 12:36 [medline] PHST- 2026/05/22 12:35 [pubmed] PHST- 2026/05/22 07:53 [entrez] AID - 10.36721/PJPS.2026.39.7.204.1 [doi] PST - ppublish SO - Pak J Pharm Sci. 2026 Jul;39(7):2165-2172. doi: 10.36721/PJPS.2026.39.7.204.1. PMID- 42169518 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260818 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 22 IP - 963 DP - 2026 May 20 TI - [Glucagon-like peptide-1 agonists and heart failure]. PG - 910-916 LID - 10.53738/REVMED.2026.22.963.48693 [doi] AB - Developed to treat type 2 diabetes, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been associated with a reduced risk of cardiovascular events in high-risk patients with diabetes, and later in obese patients with cardiovascular disease without diabetes. More recently, semaglutide and tirzepatide have demonstrated benefits in obese patients with heart failure (HF) with preserved or mildly reduced ejection fraction, including fewer HF hospitalisations and improvements in symptoms and functional capacity. Data remain limited in heart failure with reduced ejection fraction. This article summarises current evidence on these therapies, particularly in HF, and provides practical guidance for their prescription and follow-up. FAU - Soborun, Nisha AU - Soborun N AD - Service de cardiologie, Departement coeur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Favre, Lucie AU - Favre L AD - Service d'endocrinologie, diabetologie et metabolisme, Departement de medecine, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Lu, Henri AU - Lu H AD - Service de cardiologie, Departement coeur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Yerly, Patrick AU - Yerly P AD - Service de cardiologie, Departement coeur-vaisseaux, Centre hospitalier universitaire vaudois, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article PT - Review TT - Agonistes du glucagon-like peptide-1 et insuffisance cardiaque. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - Glucagon-Like Peptides/therapeutic use MH - Obesity/complications COIS- Les auteurs n'ont declare aucun conflit d'interets en relation avec cet article EDAT- 2026/05/22 06:35 MHDA- 2026/05/22 06:36 CRDT- 2026/05/22 03:14 PHST- 2026/05/22 06:36 [medline] PHST- 2026/05/22 06:35 [pubmed] PHST- 2026/05/22 03:14 [entrez] AID - RMS0963-002 [pii] AID - 10.53738/REVMED.2026.22.963.48693 [doi] PST - ppublish SO - Rev Med Suisse. 2026 May 20;22(963):910-916. doi: 10.53738/REVMED.2026.22.963.48693. PMID- 42166479 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260901 IS - 1549-1676 (Electronic) IS - 1549-1277 (Print) IS - 1549-1277 (Linking) VI - 23 IP - 5 DP - 2026 May TI - Semaglutide-associated risk of nonarteritic anterior ischemic optic neuropathy in patients with type 2 diabetes: A systematic review and meta-analysis of observational studies. PG - e1005064 LID - 10.1371/journal.pmed.1005064 [doi] LID - e1005064 AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is widely used for the management of type 2 diabetes (T2DM). Recent case reports have raised concerns about a potential association between semaglutide use and the development of nonarteritic anterior ischemic optic neuropathy (NAION), a rare but vision-threatening condition. We aimed to evaluate whether semaglutide use is associated with an increased risk of NAION in patients with T2DM. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of observational studies comparing patients with T2DM aged >/=12 years treated with semaglutide to those receiving other glucose-lowering therapies. We searched PubMed, Scopus, and Web of Science databases from January 2023 to November 2025. Two reviewers independently extracted data on study design, population characteristics, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale, and ROBINS-I v.2. Certainty of the evidence was graded according to the GRADE framework. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using fixed-effects models; sensitivity analyses included crude and subgroup HRs, and overlapping study replacement. Leave-one-out analysis was conducted to assess small-study effects and publication bias. Results were contextualized within other meta-analyses, systematic reviews, consensus statements, and regulatory communications on the topic. Five eligible observational studies met the inclusion criteria, and 7 additional studies were included in the sensitivity analysis. Semaglutide use was associated with a significantly increased hazard of NAION compared with nonsemaglutide glucose-lowering regimens (HR 2.17, 95% CI [1.73, 2.74]; p < 0.001), regimens excluding other GLP-1 receptor agonists (HR 2.13, 95% CI [1.60, 2.83]; p < 0.001), and sodium-glucose co-transporter 2 inhibitor (SGLT2i) users (HR 1.96, 95% CI [1.28, 2.99]; p = 0.002). Despite the increased relative risk, the absolute risk remained low at 0.014% (95% CI [0.005%, 0.023%]; p = 0.002), corresponding to approximately 1 additional case of NAION per 7,000 semaglutide-treated patients annually. The results were consistent with meta-analyses of observational studies and corroborated decisions presented in regulatory communications. Due to exclusive focus on retrospective, registry-based observational studies, the evidence synthesis was limited and could be biased by study-level outcome misclassification and confounding. CONCLUSIONS: Our findings suggest a possible association between semaglutide use and an increased risk of NAION in patients with T2DM. Although the absolute risk is low, clinicians should be aware of this potential adverse event, particularly in individuals at increased baseline risk for optic neuropathies. While these findings support current recommendations to discontinue semaglutide in patients diagnosed with NAION, the certainty of the available evidence is low, underscoring the need for further high-quality studies to clarify this association. CI - Copyright: (c) 2026 Chrzanowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Chrzanowski, Jedrzej AU - Chrzanowski J AUID- ORCID: 0000-0001-6204-8622 AD - Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland. FAU - Walicka, Magdalena AU - Walicka M AD - Department of Internal Diseases, Endocrinology and Diabetology, National Medical Institute of the Ministry of the Interior and Administration, Warsaw, Poland. AD - Department of Human Epigenetics, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland. FAU - Burzynski, Jacek AU - Burzynski J AUID- ORCID: 0000-0002-5462-8376 AD - Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland. FAU - Zaras, Malgorzata AU - Zaras M AUID- ORCID: 0009-0002-9030-9601 AD - Ophthalmology Department, CMP Medical Center, Warsaw, Poland. FAU - Michalak, Arkadiusz AU - Michalak A AD - Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland. AD - Department of Pediatrics, Diabetology, Endocrinology and Nephrology, Medical University of Lodz, Lodz, Poland. FAU - Fendler, Wojciech AU - Fendler W AUID- ORCID: 0000-0002-5083-9168 AD - Department of Biostatistics and Translational Medicine, Medical University of Lodz, Lodz, Poland. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260521 PL - United States TA - PLoS Med JT - PLoS medicine JID - 101231360 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Observational Studies as Topic MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - Risk Factors MH - *Semaglutide/adverse effects/therapeutic use PMC - PMC13221145 COIS- I have read the journal's policy and the authors of this manuscript have the following competing interests: J.C. received lecture honoraria from Novo Nordisk and Boehringer Ingelheim and a consulting fee from Novo Nordisk. A.M. received lecture honoraria from Novo Nordisk, Boehringer Ingelheim, and Dexcom. M.W. received lecture honoraria from AstraZeneca, Eli Lilly, Sanofi, and Teva, and support for meeting attendance from Sanofi. The other authors have declared that no competing interest exist. EDAT- 2026/05/21 18:32 MHDA- 2026/05/29 18:34 PMCR- 2026/05/21 CRDT- 2026/05/21 13:43 PHST- 2025/08/05 00:00 [received] PHST- 2026/04/08 00:00 [accepted] PHST- 2026/05/29 00:00 [revised] PHST- 2026/05/29 18:34 [medline] PHST- 2026/05/21 18:32 [pubmed] PHST- 2026/05/21 13:43 [entrez] PHST- 2026/05/21 00:00 [pmc-release] AID - PMEDICINE-D-25-02708 [pii] AID - 10.1371/journal.pmed.1005064 [doi] PST - epublish SO - PLoS Med. 2026 May 21;23(5):e1005064. doi: 10.1371/journal.pmed.1005064. eCollection 2026 May. PMID- 42165732 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260813 IS - 0971-5916 (Print) IS - 0971-5916 (Linking) VI - 163 IP - 4 DP - 2026 Apr TI - Evolution of incretin-based therapies: From GLP-1 monotherapy to dual and triple agonists: A new era in metabolic therapy. PG - 427-435 LID - 10.25259/IJMR_2041_2025 [pii] AB - Incretin-based therapies have revolutionised the management of metabolic disorders, transitioning from DPP-4 inhibitors to advanced GLP-1 receptor agonists (GLP-1RAs) and next-generation dual and triple agonists. This review explores the evolving role of incretin pharmacology in type 2 diabetes mellitus (T2DM), obesity, and metabolic dysfunction-associated steatotic liver disease (MASLD). Literature from PubMed, Scopus, and Google Scholar up to July 2025 was reviewed, emphasising pivotal trials and real-world evidence. While DPP-4 inhibitors offer modest glycaemic benefits, GLP1RAs such as liraglutide and semaglutide have demonstrated significant weight loss and cardiometabolic protection. Dual GIP/GLP-1 agonist tirzepatide and triple agonist retatrutide have shown unprecedented efficacy, with up to 24% body weight reduction and improvement in hepatic and inflammatory markers. Agents like cotadutide and efinopegdutide further expand indications to MASLD and metabolic dysfunction associated steatohepatitis (MASH). Despite promising outcomes, challenges persist in terms of cost, accessibility, and the underrepresentation of low- and middle-income countries in major trials. Pharmacogenomic variability may also influence therapeutic response. Incretin-based multi-agonists offer a transformative, multi-system approach to metabolic disease but require tailored implementation. This review provides an updated synthesis of therapeutic developments and outlines priorities for future research, regulatory policy, and equitable global integration as incretin-based therapies have evolved into a versatile class addressing glycaemic control, weight loss, and cardio-metabolic risk. FAU - Gupta, Monika AU - Gupta M AD - Department of Pharmacology, Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh, India. FAU - Shukla, Jitendra AU - Shukla J AD - Department of Internal Medicine, Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh, India. LA - eng PT - Journal Article PT - Review PL - United States TA - Indian J Med Res JT - The Indian journal of medical research JID - 0374701 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/pathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/therapeutic use MH - Semaglutide MH - Tirzepatide MH - *Obesity/drug therapy/pathology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use PMC - PMC13224277 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Incretin therapy OT - MASH OT - Metabolic syndrome OT - Type 2 diabetes COIS- None. EDAT- 2026/05/21 12:38 MHDA- 2026/05/21 12:39 PMCR- 2026/04/01 CRDT- 2026/05/21 10:04 PHST- 2025/08/02 00:00 [received] PHST- 2025/12/21 00:00 [accepted] PHST- 2026/05/21 12:39 [medline] PHST- 2026/05/21 12:38 [pubmed] PHST- 2026/05/21 10:04 [entrez] PHST- 2026/04/01 00:00 [pmc-release] AID - 10.25259/IJMR_2041_2025 [pii] AID - 10.25259/IJMR_2041_2025 [doi] PST - ppublish SO - Indian J Med Res. 2026 Apr;163(4):427-435. doi: 10.25259/IJMR_2041_2025. PMID- 42162206 OWN - NLM STAT- MEDLINE DCOM- 20260804 LR - 20260825 IS - 1432-5241 (Electronic) IS - 0364-216X (Linking) VI - 50 IP - 13 DP - 2026 Jul TI - Effects of GLP-1 Receptor Agonists on Skin Quality: A Comprehensive Literature Review. PG - 5403-5407 LID - 10.1007/s00266-026-05820-4 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), particularly semaglutide and liraglutide, have revolutionized the treatment of type 2 diabetes and obesity due to their potent effects on weight loss and glycemic control. However, emerging evidence has highlighted dermatologic side effects associated with the rapid reduction of subcutaneous adipose tissue, particularly in the context of aesthetic skin integrity. This systematic review aims to comprehensively evaluate the current evidence on the effects of GLP-1 RAs on skin quality, including dermal structure alterations, adipose compartment loss, and skin elasticity changes. METHODS: A systematic literature search was performed in PubMed (MEDLINE) using predefined keywords including "semaglutide," "liraglutide," "GLP-1 receptor agonists," "skin quality," "adipose tissue loss," and "elasticity." Studies published up to May 2025 were considered. Inclusion criteria involved human studies documenting dermatologic alterations associated with GLP-1 RA use. Forty studies were selected based on PRISMA guidelines, encompassing clinical trials, case reports, and observational studies. RESULTS: The data revealed that GLP-1 RA-induced weight loss frequently results in visible changes to skin morphology. Key findings included facial volume loss ("Ozempic face"), dermal thinning, loss of collagen and elastin fibers, and decreased skin elasticity. Patients exhibited localized fat loss in multiple anatomical regions, leading to redundant skin folds and accelerated signs of aging. Risk factors for more severe dermatological outcomes included advanced age, prolonged obesity history, rapid weight loss, poor hydration, and insufficient protein intake. CONCLUSION: While GLP-1 RAs offer substantial benefits for weight and metabolic health, their dermatologic side effects represent an important clinical consideration. Proactive measures such as gradual weight loss, nutritional optimization, hydration, and early dermatologic intervention are recommended. Future prospective studies are warranted to better define the pathophysiology and management of GLP-1 RA-associated skin changes. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. CI - (c) 2026. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery. FAU - Barone, Mauro AU - Barone M AUID- ORCID: 0000-0002-1439-5686 AD - Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy. maurosabbarone@gmail.com. FAU - Brunetti, Beniamino AU - Brunetti B AD - Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy. FAU - D'Emilio, Roberta AU - D'Emilio R AD - Private Practice, Rome, Italy. FAU - Caputo, Maria Grazia AU - Caputo MG AD - Private Practice, Rome, Italy. FAU - Tenna, Stefania AU - Tenna S AD - Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy. FAU - Persichetti, Paolo AU - Persichetti P AD - Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Roma, Italy. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260520 PL - United States TA - Aesthetic Plast Surg JT - Aesthetic plastic surgery JID - 7701756 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Aesthetic Plast Surg. 2026 Aug;50(15):6644. doi: 10.1007/s00266-026-05948-3. PMID: 42474489 MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Liraglutide/pharmacology/adverse effects MH - Weight Loss/drug effects MH - *Glucagon-Like Peptides/pharmacology/adverse effects MH - *Skin Aging/drug effects MH - *Skin/drug effects MH - Obesity/drug therapy MH - Risk Assessment MH - Hypoglycemic Agents/pharmacology OTO - NOTNLM OT - GLP-1 OT - Glucagon like peptide 1 receptor agonist OT - Skin quality OT - Systematic review COIS- Declarations. Conflict of interest: The authors declare that they have no conflicts of interest to disclose. Informed Consent: For this type of study, informed consent is not required Human and Animal Participants: This article does not contain any studies with human participants or animals performed by any of the authors. EDAT- 2026/05/21 05:33 MHDA- 2026/08/04 12:46 CRDT- 2026/05/20 23:34 PHST- 2025/05/14 00:00 [received] PHST- 2026/03/18 00:00 [accepted] PHST- 2026/08/04 12:46 [medline] PHST- 2026/05/21 05:33 [pubmed] PHST- 2026/05/20 23:34 [entrez] AID - 10.1007/s00266-026-05820-4 [pii] AID - 10.1007/s00266-026-05820-4 [doi] PST - ppublish SO - Aesthetic Plast Surg. 2026 Jul;50(13):5403-5407. doi: 10.1007/s00266-026-05820-4. Epub 2026 May 20. PMID- 42161872 OWN - NLM STAT- MEDLINE DCOM- 20260717 LR - 20260717 IS - 0376-2491 (Print) IS - 0376-2491 (Linking) VI - 106 IP - 20 DP - 2026 Jun 2 TI - [Value and benefit of basic insulin/GLP-1RA weekly preparation in clinical treatment of type 2 diabetes in adults]. PG - 1969-1976 LID - 10.3760/cma.j.cn112137-20260325-00802 [doi] AB - The prevalence of type 2 diabetes mellitus has been rising continuously in China. However, glycemic control rates remain suboptimal, posing a significant public health challenge. Although traditional intensive insulin strategies are effective in improving glycemic control, they are often associated with risks such as hypoglycemia and weight gain. Fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA) offer complementary mechanisms of action, enhancing efficacy and safety while simplifying treatment regimens, making them a key focus of clinical development. Insulin icodec/semaglutide fixed-ratio combination (IcoSema), the first once-weekly dual-component preparation combining a basal insulin and a GLP-1RA, utilizes advanced formulation technology to achieve stable co-formulation of the ultra-long-acting once-weekly basal insulin and the once-weekly GLP-1RA, with the two components acting in a complementary and synergistic manner. The Phase 3 COMBINE clinical trial program demonstrated that, compared with insulin icodec, semaglutide(1.0 mg), or basal-bolus insulin regimens, IcoSema provides superior or equivalent glycemic control, and the risk of clinically significant or severe hypoglycemic events is comparable to that of semaglutide(1.0 mg). Once-weekly administration helps to simplify the treatment regimen and improve treatment adherence. The clinical application of IcoSema is expected to alleviate the dilemma in Chinese type 2 diabetes management of balancing effective glycemic control with safety and simplicity, offering a new therapeutic option for patients requiring insulin intensification that combines efficacy, safety, and convenience. FAU - Zhang, S C AU - Zhang SC AD - Department of Endocrinology, the First Medical Center of PLA General Hospital, Beijing 100853, China. FAU - Zang, L AU - Zang L AD - Department of Endocrinology, the First Medical Center of PLA General Hospital, Beijing 100853, China. FAU - Cheng, Y AU - Cheng Y AD - Department of Endocrinology, the First Medical Center of PLA General Hospital, Beijing 100853, China. FAU - Mu, Y M AU - Mu YM AD - Department of Endocrinology, the First Medical Center of PLA General Hospital, Beijing 100853, China. FAU - Hu, X AU - Hu X AD - Department of Pharmacy, Beijing Hospital, National Center for Gerontology, National Clinical Research Center for Gerontology, the Key Laboratory of Geriatrics of NHC, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China. LA - chi PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Yi Xue Za Zhi JT - Zhonghua yi xue za zhi JID - 7511141 RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Drug Combinations) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Insulin/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Semaglutide MH - Drug Combinations MH - Glucagon-Like Peptides/therapeutic use/administration & dosage EDAT- 2026/05/21 05:33 MHDA- 2026/05/29 15:41 CRDT- 2026/05/20 22:32 PHST- 2026/05/29 15:41 [medline] PHST- 2026/05/21 05:33 [pubmed] PHST- 2026/05/20 22:32 [entrez] AID - 10.3760/cma.j.cn112137-20260325-00802 [doi] PST - ppublish SO - Zhonghua Yi Xue Za Zhi. 2026 Jun 2;106(20):1969-1976. doi: 10.3760/cma.j.cn112137-20260325-00802. PMID- 42155605 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260612 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 237 DP - 2026 Jul TI - Glucagon-like peptide-1 receptor agonists and hair loss: A systematic review and meta-analysis. PG - 113333 LID - S0168-8227(26)00253-6 [pii] LID - 10.1016/j.diabres.2026.113333 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used drugs with applications beyond the management of obesity and diabetes mellitus. This study aimed to investigate the association between GLP-1 RA use and hair loss. METHODS: Four electronic databases were systematically searched for relevant studies published from inception to August 20, 2025. We included randomized controlled trials (RCTs) or prospective nonrandomized interventional studies that reported hair loss following GLP-1 RA therapy. A random-effects model was used for meta-analysis. RESULTS: A total of nine interventional studies, including 7 RCTs and 2 non-RCTs, were included in the final meta-analysis. Data from a total of 4114 GLP-1 RA users were analyzed. The pooled analysis revealed a significantly higher risk of hair loss in GLP-1 RA users than in placebo users (risk ratio [RR]: 3.252; 95% confidence interval [CI]: 1.437 to 7.358). The significant results persisted even when the analysis was restricted to RCTs focusing on patients with overweight or obesity (RR: 3.587; 95% CI: 2.100 to 6.124). Furthermore, a single-arm analysis revealed that the event rate of hair loss following GLP-1 RA therapy was 3.9%. CONCLUSIONS: The use of GLP-1 RAs is significantly associated with an increased risk of hair loss. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Cheng, Po-Lung AU - Cheng PL AD - Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan. FAU - Chang, Hua-Ching AU - Chang HC AD - Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan; Department of Dermatology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Research Center of Big Data and Meta-Analysis, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: hc.chang@tmu.edu.tw. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260518 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Alopecia/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Semaglutide MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy OTO - NOTNLM OT - Alopecia OT - Glucagon-like peptide-1 OT - Hair loss OT - Semaglutide OT - Tirzepatide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/05/20 00:35 MHDA- 2026/06/11 06:40 CRDT- 2026/05/19 19:34 PHST- 2026/04/16 00:00 [received] PHST- 2026/05/14 00:00 [revised] PHST- 2026/05/17 00:00 [accepted] PHST- 2026/06/11 06:40 [medline] PHST- 2026/05/20 00:35 [pubmed] PHST- 2026/05/19 19:34 [entrez] AID - S0168-8227(26)00253-6 [pii] AID - 10.1016/j.diabres.2026.113333 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jul;237:113333. doi: 10.1016/j.diabres.2026.113333. Epub 2026 May 18. PMID- 42155603 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260620 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 237 DP - 2026 Jul TI - GLP-1 receptor agonists and surgical care: implications for bariatric Procedures, perioperative Outcomes, and nutritional optimization. PG - 113332 LID - S0168-8227(26)00252-4 [pii] LID - 10.1016/j.diabres.2026.113332 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for obesity and type 2 diabetes and are now frequently encountered in patients undergoing bariatric and other elective surgeries. Their effects on gastric motility, appetite, and nutrient intake have important implications for perioperative safety, surgical outcomes, and nutritional care. OBJECTIVES: To summarize current evidence on the effects of GLP-1RAs on perioperative management, bariatric surgery outcomes, and nutritional optimization in surgical patients. METHODS: A narrative review of PubMed- and Scopus-indexed randomized trials, observational studies, systematic reviews, and clinical guidelines was conducted. Evidence was synthesized across perioperative risk, preoperative optimization, post-bariatric outcomes, and nutritional implications. RESULTS: GLP-1RA use was associated with delayed gastric emptying and increased residual gastric contents in some patients, especially during dose escalation or in those with gastrointestinal symptoms. However, clinically significant aspiration events were uncommon, supporting individualized perioperative management rather than routine discontinuation. Preoperatively, GLP-1RAs promoted short-term weight loss and metabolic improvement in bariatric candidates, potentially improving operative conditions and reducing risk. Postoperatively, the strongest evidence from randomized controlled trials showed that liraglutide and semaglutide achieved additional weight loss and improved glycemic control in patients with weight regain, insufficient weight loss, or persistent diabetes after bariatric surgery, potentially lowering the need for revisional procedures. Nutritionally, appetite suppression may worsen inadequate protein intake and micronutrient deficiencies, increasing risks of sarcopenia, anemia, and bone disease without structured monitoring and supplementation. However, direct trial evidence for supplementation strategies in this specific population is lacking. CONCLUSIONS: GLP-1RAs offer important metabolic and weight-related benefits across the surgical continuum, particularly around bariatric surgery, but require individualized perioperative planning and proactive nutritional surveillance. They should be viewed as adjuncts to, not replacements for, bariatric surgery. CI - Copyright (c) 2026 Elsevier B.V. All rights reserved. FAU - Elawa, Zeyad AU - Elawa Z AD - School of Medicine, New Giza University, Giza, Egypt. FAU - Khalil, Ahmed AU - Khalil A AD - Department of Pharmacy, Hamad Medical Center, Doha, Qatar. FAU - Kardousha, Ahmed AU - Kardousha A AD - Department of Pharmacy, Hamad Medical Center, Doha, Qatar. FAU - ElAwwa, Ahmed AU - ElAwwa A AD - Department of Pharmacy, Hamad Medical Center, Doha, Qatar; Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar. FAU - Soliman, Ashraf T AU - Soliman AT AD - Department of Pharmacy, Hamad Medical Center, Doha, Qatar; Department of Pediatrics, Hamad Medical Corporation, Doha, Qatar. Electronic address: atsoliman56@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20260520 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Bariatric Surgery/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy/surgery MH - Semaglutide MH - Perioperative Care/methods MH - *Hypoglycemic Agents/therapeutic use MH - Weight Loss/drug effects OTO - NOTNLM OT - Bariatric surgery OT - GLP-1 receptor agonists OT - Nutrition OT - Obesity management OT - Perioperative care COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/05/20 00:32 MHDA- 2026/06/11 06:38 CRDT- 2026/05/19 19:34 PHST- 2026/03/26 00:00 [received] PHST- 2026/05/02 00:00 [revised] PHST- 2026/05/17 00:00 [accepted] PHST- 2026/06/11 06:38 [medline] PHST- 2026/05/20 00:32 [pubmed] PHST- 2026/05/19 19:34 [entrez] AID - S0168-8227(26)00252-4 [pii] AID - 10.1016/j.diabres.2026.113332 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jul;237:113332. doi: 10.1016/j.diabres.2026.113332. Epub 2026 May 20. PMID- 42152320 OWN - NLM STAT- MEDLINE DCOM- 20260716 LR - 20260814 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 105 IP - 20 DP - 2026 May 15 TI - Pharmacovigilance of semaglutide: A descriptive analysis of WHO-VigiAccess reports. PG - e48811 LID - 10.1097/MD.0000000000048811 [doi] LID - e48811 AB - Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is widely prescribed for type 2 diabetes mellitus and chronic weight management. With its growing global use, continuous pharmacovigilance is essential to detect emerging patterns of adverse drug reactions (ADRs). To describe the global ADRs profile of semaglutide using data from the World Health Organization's (WHO) VigiAccess pharmacovigilance database. A retrospective descriptive analysis was conducted using publicly available ADR data retrieved from the WHO-VigiAccess portal on October 18, 2025. The total number and proportion of ADRs were summarized according to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC). Demographic information, including age group, sex, geographic region, and reporting year, was reviewed descriptively. A total of 81,770 ADR reports associated with semaglutide were identified. The most frequently reported SOCs were gastrointestinal disorders (28%, n = 42,574), general disorders and administration site conditions (12%, n = 19,200), and injury, poisoning and procedural complications (11%, n = 16,601). Additional categories included nervous system disorders (8%), investigations (7%), and metabolism and nutrition disorders (7%). The majority of ADRs were reported among adults aged 45 to 64 years, with most originating from Europe and the Americas. Annual reporting increased markedly between 2018 and 2025, corresponding with expanded clinical use and obesity-related approvals. Global pharmacovigilance data indicate that semaglutide ADRs are primarily gastrointestinal and systemic in nature, consistent with its known pharmacological effects. Continuous monitoring is warranted to identify emerging safety signals and support optimized patient management as use expands worldwide. CI - Copyright (c) 2026 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Alorfi, Nasser M AU - Alorfi NM AUID- ORCID: 0000-0002-0636-7685 AD - Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia. FAU - Alourfi, Mansour M AU - Alourfi MM AD - Gastroenterology Department, Dr. Soliman Fakeeh Hospital, Fakeeh Care Group, Jeddah, Saudi Arabia. FAU - Aldabbagh, Ammar AU - Aldabbagh A AD - Gastroenterology Department, Dr. Soliman Fakeeh Hospital, Fakeeh Care Group, Jeddah, Saudi Arabia. FAU - Alghamdi, Waleed Saleh AU - Alghamdi WS AD - Gastroenterology Department, Dr. Soliman Fakeeh Hospital, Fakeeh Care Group, Jeddah, Saudi Arabia. AD - Department of Medicine, Division of Gastroenterology, King Abdulaziz University, Jeddah , Saudi Arabia. FAU - Al Ghamdi, Sarah S AU - Al Ghamdi SS AD - Gastroenterology Department, Dr. Soliman Fakeeh Hospital, Fakeeh Care Group, Jeddah, Saudi Arabia. AD - Department of Medicine, Division of Gastroenterology, King Abdulaziz University, Jeddah , Saudi Arabia. FAU - Aldekhail, Nasser M AU - Aldekhail NM AD - Department of Pharmacy, College of Pharmacy, Nursing and Medical Sciences, Riyadh Elm University, Riyadh, Saudi Arabia. FAU - Alkhanani, Mustfa Faisal AU - Alkhanani MF AD - Biology Department, College of Sciences, University of Hafr Al Batin, Hafr Al Batin, Saudi Arabia. FAU - Alansari, Abdulrhman M AU - Alansari AM AD - Pharmaceutical Care Services, King Salman Medical City, Madinah Health Cluster, Madinah, Saudi Arabia. FAU - Alsolami, Faris A AU - Alsolami FA AD - Kholais General Hospital, Makkah Cluster, Ministry of Health, Madinah, Saudi Arabia. FAU - Ibrahim, Nihal Abdalla AU - Ibrahim NA AD - College of Pharmacy, Ajman University, Ajman, United Arab Emirates. AD - Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates. LA - eng GR - 26UQU4420038GSSR02/Umm Al-Qura University, Saudi Arabia/ PT - Journal Article PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Pharmacovigilance MH - Female MH - Diabetes Mellitus, Type 2/drug therapy MH - Retrospective Studies MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Male MH - Middle Aged MH - Adult MH - World Health Organization MH - *Hypoglycemic Agents/adverse effects MH - Aged MH - Adolescent MH - Young Adult MH - *Drug-Related Side Effects and Adverse Reactions/epidemiology MH - Child MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13183005 OTO - NOTNLM OT - GLP-1 receptor agonist OT - WHO-VigiAccess OT - adverse drug reactions OT - gastroenterology OT - pharmacovigilance OT - semaglutide COIS- The authors have no conflicts of interest to disclose. EDAT- 2026/05/19 06:30 MHDA- 2026/05/19 06:31 PMCR- 2026/05/15 CRDT- 2026/05/19 01:01 PHST- 2025/10/22 00:00 [received] PHST- 2026/04/24 00:00 [accepted] PHST- 2026/05/19 06:31 [medline] PHST- 2026/05/19 06:30 [pubmed] PHST- 2026/05/19 01:01 [entrez] PHST- 2026/05/15 00:00 [pmc-release] AID - 00005792-202605150-00035 [pii] AID - MD-D-25-14502 [pii] AID - 10.1097/MD.0000000000048811 [doi] PST - ppublish SO - Medicine (Baltimore). 2026 May 15;105(20):e48811. doi: 10.1097/MD.0000000000048811. PMID- 42150748 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 8 DP - 2026 Aug TI - Association Between Glucagon-Like Peptide-1 Receptor Agonists and Suicidality: A Systematic Review. PG - 6482-6508 LID - 10.1111/dom.70878 [doi] AB - AIMS: We aimed to examine the association between GLP-1 RA use and suicidal ideation or behaviours through a systematic review of observational studies. MATERIALS AND METHODS: A comprehensive search of MEDLINE, PubMed, EMBASE, CINAHL and PsycINFO was conducted from database inception through December 11, 2025. Observational studies investigating suicidal ideation, suicide attempts or complete suicide among adults using GLP-1 RAs were included. Eligibility screening, data extraction and risk of bias assessments were performed independently and in duplicate, with disagreements resolved by a third reviewer. RESULTS: Forty-three studies were included. Findings varied by study design. Some case reports suggested a temporal relationship between GLP-1 RA use and suicidal ideation. Cross-sectional studies and case-control studies identified a negative association between GLP-1 RAs and suicide attempts. Pharmacovigilance and cohort studies showed more mixed results, with some studies identifying a positive association between semaglutide or liraglutide and suicidal ideation, while others paradoxically reported a negative association with suicidal behaviours (i.e., attempts and intentional self-harm) or completed suicide. CONCLUSIONS: While evidence does not support GLP-1 RAs as a causative agent for suicidality, due to multiple risk factors in this population, clinicians should routinely assess mental health status before and during GLP-1 RA treatment regardless of indication. Importantly, a history of concurrent mental health conditions should not preclude use of a GLP-1 RA; rather, individual patient factors should be accounted for when making prescribing decisions. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chan, Timothy H AU - Chan TH AD - Norton College of Medicine, SUNY Upstate University, Syracuse, New York, USA. FAU - Cosler, Leon E AU - Cosler LE AD - Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Binghamton, New York, USA. FAU - Gionfriddo, Michael R AU - Gionfriddo MR AD - Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, Minnesota, USA. FAU - Leppien, Emily E AU - Leppien EE AD - Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Binghamton, New York, USA. FAU - Sommers, Eleanor J AU - Sommers EJ AD - Norton College of Medicine, SUNY Upstate University, Syracuse, New York, USA. FAU - Lussier, Mia E AU - Lussier ME AUID- ORCID: 0000-0002-5523-0781 AD - Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Binghamton, New York, USA. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260518 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Suicidal Ideation MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Suicide, Attempted/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Liraglutide/adverse effects/therapeutic use MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Suicide/statistics & numerical data MH - Observational Studies as Topic PMC - PMC13341386 OTO - NOTNLM OT - glucagon-like Peptide-1 receptor agonists OT - suicidal ideation OT - suicide OT - systematic review COIS- The authors declare no conflicts of interest. EDAT- 2026/05/19 00:28 MHDA- 2026/07/08 18:50 PMCR- 2026/07/08 CRDT- 2026/05/18 19:32 PHST- 2026/04/28 00:00 [revised] PHST- 2026/02/03 00:00 [received] PHST- 2026/05/05 00:00 [accepted] PHST- 2026/07/08 18:50 [medline] PHST- 2026/05/19 00:28 [pubmed] PHST- 2026/05/18 19:32 [entrez] PHST- 2026/07/08 00:00 [pmc-release] AID - DOM70878 [pii] AID - 10.1111/dom.70878 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Aug;28(8):6482-6508. doi: 10.1111/dom.70878. Epub 2026 May 18. PMID- 42142150 OWN - NLM STAT- MEDLINE DCOM- 20260723 LR - 20260923 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 63 IP - 7 DP - 2026 Jul TI - Switching patterns of GLP-1 receptor agonists from 2018 to 2025 in the largest private healthcare network in Poland. PG - 1267-1278 LID - 10.1007/s00592-026-02709-1 [doi] AB - AIMS: To characterize switching among GLP-1 receptor agonists (GLP-1 RAs) in a large private-sector cohort in Poland and to quantify therapy- and patient-level associations with switching while accounting for switching opportunity and calendar-time dynamics. METHODS: We conducted a retrospective analysis of GLP-1 RA prescription records from the LUX MED network (2018-2025). Switching was defined as any change in agent between consecutive prescriptions. Patients with more than one prescription were included (n = 42,423). The primary analysis used a transition-level discrete-time hazard model in which each prescription-to-prescription interval contributed one observation, and the outcome was switching at that interval. Current-therapy contrasts were reported relative to subcutaneous semaglutide. Sensitivity analyses examined alternative temporal parameterizations and additional adjustment for elapsed time. RESULTS: Overall, 29.7% of patients switched at least once and 14.3% switched two or more times. In the transition-level analysis, 12,620 patients contributed 27,095 transitions. After adjustment for opportunity and calendar time, liraglutide was associated with substantially lower odds of switching compared with subcutaneous semaglutide (OR, 0.02; 95% CI, 0.01-0.03), whereas oral semaglutide (OR, 1.30; 95% CI, 0.78-2.17) and dulaglutide (OR, 1.70; 95% CI, 0.95-3.04) did not differ significantly. Temporal analyses revealed peaks consistent with episodic substitution and accelerated tirzepatide uptake after market entry. The principal associations remained directionally consistent in sensitivity analyses. CONCLUSIONS: Switching among GLP-1 RAs is common and time-dependent. Time-aware modelling identified therapy-specific switching patterns and pronounced temporal variation; reasons for switching remain unmeasured, and the observed associations should be interpreted as hypothesis-generating. CI - (c) 2026. The Author(s). FAU - Lupina, Krzysztof AU - Lupina K AUID- ORCID: 0009-0000-1617-8426 AD - Faculty of Medicine, Jan Kochanowski University, Kielce, Poland. FAU - Dziewierz, Artur AU - Dziewierz A AUID- ORCID: 0000-0002-2100-5076 AD - Second Department of Cardiology, Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland. AD - Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland. FAU - Janczura, Jakub AU - Janczura J AUID- ORCID: 0009-0004-7977-9797 AD - Faculty of Medicine, Jan Kochanowski University, Kielce, Poland. FAU - Siudak, Zbigniew AU - Siudak Z AUID- ORCID: 0000-0002-8033-3977 AD - Faculty of Medicine, Jan Kochanowski University, Kielce, Poland. zbigniew.siudak@ujk.edu.pl. AD - College of Medical Sciences in Warsaw, LUXMED Group, Warsaw, Poland. zbigniew.siudak@ujk.edu.pl. LA - eng PT - Journal Article DEP - 20260516 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Poland MH - Semaglutide MH - Female MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives/administration & dosage MH - Male MH - Middle Aged MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Liraglutide/therapeutic use MH - *Drug Substitution/statistics & numerical data MH - Aged MH - Private Sector PMC - PMC13395827 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Obesity OT - Private healthcare OT - Real-world evidence OT - Tirzepatide OT - Treatment switching COIS- Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: Study has been approved by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Declaration of generative AI use: The authors declare that generative artificial intelligence (Claude Opus 4.6, Anthropic) was used during the preparation of this manuscript for language editing and stylistic improvement. Following its use, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article. EDAT- 2026/05/17 06:27 MHDA- 2026/07/23 12:37 PMCR- 2026/05/16 CRDT- 2026/05/16 11:03 PHST- 2026/03/06 00:00 [received] PHST- 2026/04/26 00:00 [accepted] PHST- 2026/07/23 12:37 [medline] PHST- 2026/05/17 06:27 [pubmed] PHST- 2026/05/16 11:03 [entrez] PHST- 2026/05/16 00:00 [pmc-release] AID - 10.1007/s00592-026-02709-1 [pii] AID - 2709 [pii] AID - 10.1007/s00592-026-02709-1 [doi] PST - ppublish SO - Acta Diabetol. 2026 Jul;63(7):1267-1278. doi: 10.1007/s00592-026-02709-1. Epub 2026 May 16. PMID- 42133868 OWN - NLM STAT- MEDLINE DCOM- 20260904 LR - 20260907 IS - 1539-2031 (Electronic) IS - 0192-0790 (Linking) VI - 60 IP - 9 DP - 2026 Oct 1 TI - Esophageal Motility Patterns Are Not Impacted By Glucagon-Like Peptide-1 Receptor Agonist Use. PG - 810-816 LID - 10.1097/MCG.0000000000002395 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA) use is associated with delayed gastric emptying. It is unknown whether GLP-1RAs affect esophageal motility. We aimed to assess the relationship between GLP-1RA use and esophageal function test results. METHODS: Patients with type 2 diabetes undergoing high-resolution manometry (HRM) between December 2022 and October 2024 were retrospectively evaluated, comparing cases with controls (on vs. off GLP-1RA). HRM diagnoses per the Chicago Classification 4.0 and reflux testing results were collected. Patients with prior foregut surgery and known conditions associated with dysmotility (eg, scleroderma) were excluded. Comparisons were performed using chi 2 and Mann-Whitney U tests for categorical and continuous measures, respectively. RESULTS: There were 132 patients assessed and most (29/42, 69.0%) cases were female. Semaglutide was the most commonly used GLP-1RA (24, 57.1%) among cases, and the median A1c was the same (6.6%) for both cases and controls. Most GLP-1RA users (27, 64.3%) had a normal HRM and there was no significant difference ( P =0.07) in overall HRM diagnoses between cases and controls. There was no association ( P =0.51) between GLP-1RA type or dose and esophageal motility diagnoses. Among those undergoing formal reflux testing, there was no difference in detected rates of gastroesophageal reflux disease ( P =0.51) between cases and controls. CONCLUSION: We did not detect a statistically significant impact of GLP-1RA use on esophageal function assessed by formal testing among patients with type 2 diabetes. These results suggest that patients may continue GLP-1RAs when undergoing esophageal testing and are not at significantly increased risk for impacts on esophageal motility diagnosis compared with nonusers. CI - Copyright (c) 2026 Wolters Kluwer Health, LLC. All rights reserved. FAU - Wang, Annie L AU - Wang AL AUID- ORCID: 0009-0008-0130-1477 AD - Duke University School of Medicine. FAU - Bach, Laura AU - Bach L AD - Duke Division of Gastroenterology. FAU - Leiman, David A AU - Leiman DA AUID- ORCID: 0000-0001-6350-3906 AD - Duke Division of Gastroenterology. AD - Duke Clinical Research Institute, Durham, NC. LA - eng PT - Journal Article DEP - 20261001 PL - United States TA - J Clin Gastroenterol JT - Journal of clinical gastroenterology JID - 7910017 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Manometry/methods MH - Retrospective Studies MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Middle Aged MH - Aged MH - *Esophagus/drug effects/physiopathology MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Glucagon-Like Peptides/adverse effects MH - *Esophageal Motility Disorders/diagnosis/chemically induced MH - Gastroesophageal Reflux/diagnosis MH - Gastrointestinal Motility/drug effects OTO - NOTNLM OT - GLP-1RA OT - esophageal motility OT - gastrointestinal motility OT - manometry EDAT- 2026/05/14 18:36 MHDA- 2026/09/04 05:35 CRDT- 2026/05/14 15:32 PHST- 2025/10/10 00:00 [received] PHST- 2026/04/20 00:00 [accepted] PHST- 2026/09/04 05:35 [medline] PHST- 2026/05/14 18:36 [pubmed] PHST- 2026/05/14 15:32 [entrez] AID - 00004836-990000000-00650 [pii] AID - 10.1097/MCG.0000000000002395 [doi] PST - epublish SO - J Clin Gastroenterol. 2026 Oct 1;60(9):810-816. doi: 10.1097/MCG.0000000000002395. PMID- 42132708 OWN - NLM STAT- MEDLINE DCOM- 20260720 LR - 20260818 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 133 IP - 8 DP - 2026 Aug TI - Glucagon-Like Peptide-1 Receptor Agonists and the Risk of Non-Arteritic Anterior Ischemic Optic Neuropathy: A Consensus Statement by the North American Neuro-Ophthalmology Society and the American Academy of Ophthalmology. PG - 1029-1035 LID - S0161-6420(26)00246-0 [pii] LID - 10.1016/j.ophtha.2026.04.008 [doi] AB - Recent studies have reported a possible association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and non-arteritic anterior ischemic optic neuropathy (NAION). The North American Neuro-Ophthalmology Society and the American Academy of Ophthalmology provide consensus expert opinion and clinical guidance about this association. Currently available evidence primarily includes retrospective observational studies, many of which rely on analysis of electronic health record and administrative claims data and are subject to limitations. Although many report a small possible increased risk of NAION in patients taking GLP-1 RAs such as semaglutide, some studies report no correlation, and the overall magnitude of the risk of NAION remains low. Shared decision-making between each patient and their care team is warranted to decide whether to start, continue, or discontinue GLP-1 RAs. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. CI - Copyright (c) 2026 American Academy of Ophthalmology, Inc. Published by Elsevier Inc. All rights reserved. FAU - DeParis, Sarah W AU - DeParis SW AD - American Academy of Ophthalmology, San Francisco, California. FAU - Oke, Isdin AU - Oke I AD - Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Gaier, Eric D AU - Gaier ED AD - Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Moss, Heather E AU - Moss HE AD - Department of Ophthalmology, Neurology and Neurological Sciences, Stanford University, Palo Alto, California. FAU - MacIntosh, Peter W AU - MacIntosh PW AD - Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois Chicago, Chicago, Illinois. FAU - Gilbert, Aubrey L AU - Gilbert AL AD - Department of Ophthalmology, The Permanente Medical Group, Vallejo, California. FAU - Dinkin, Marc J AU - Dinkin MJ AD - Department of Ophthalmology and Neurology, Weill Cornell Medical College, New York, New York. FAU - Chen, John J AU - Chen JJ AD - Department of Ophthalmology and Neurology, Mayo Clinic, Rochester, Minnesota. LA - eng GR - P30 EY026877/EY/NEI NIH HHS/United States PT - Consensus Statement PT - Journal Article DEP - 20260514 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Academies and Institutes/organization & administration MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Neurology/organization & administration MH - *Ophthalmology/organization & administration MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - Risk Factors MH - Semaglutide MH - *Societies, Medical MH - United States OTO - NOTNLM OT - GLP-1 OT - NAION OT - diabetes OT - glucagon-like peptide-1 receptor agonists OT - non-arteritic anterior ischemic optic neuropathy OT - semaglutide EDAT- 2026/05/14 14:49 MHDA- 2026/07/21 00:35 CRDT- 2026/05/14 10:28 PHST- 2026/02/25 00:00 [received] PHST- 2026/03/31 00:00 [revised] PHST- 2026/04/02 00:00 [accepted] PHST- 2026/07/21 00:35 [medline] PHST- 2026/05/14 14:49 [pubmed] PHST- 2026/05/14 10:28 [entrez] AID - S0161-6420(26)00246-0 [pii] AID - 10.1016/j.ophtha.2026.04.008 [doi] PST - ppublish SO - Ophthalmology. 2026 Aug;133(8):1029-1035. doi: 10.1016/j.ophtha.2026.04.008. Epub 2026 May 14. PMID- 42108418 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Estimated Oral Semaglutide Exposure Has Distinct Relationships With Glycaemic Response, Weight Loss and Gastrointestinal Tolerability. PG - 6405-6412 LID - 10.1111/dom.70840 [doi] AB - AIMS: Oral semaglutide absorption is subject to inter-individual variability. We investigated whether estimated individual exposure (eC (avg) ) provides predictive information beyond the prescribed dose in a real-world cohort of patients with type 2 diabetes (T2D). MATERIALS AND METHODS: We retrospectively included patients initiating oral semaglutide to calculate eC (avg) at each follow-up visit, using a validated population pharmacokinetic model incorporating dose, weight, sex, ethnicity and GI disorders, but without measuring plasma semaglutide concentrations. Mixed-effects models were used to assess the associations of dose and eC (avg) with changes in HbA1c and percent body weight, and to compare model fit. For GI side effects, time-adjusted fixed-effects logistic regression was employed. RESULTS: We analysed 256 participants (31.6% women, mean age 65.6 years). During a median follow-up of 19 months, HbA1c declined by 0.7% and body weight by 7.5%; 41.8% of patients reported GI side effects. Both dose and eC (avg) were significantly associated with all outcomes when analysed individually. For DeltaHbA1c, the dose model outperformed the eC (avg) model (p < 0.01), while eC (avg) showed modestly improved fit for weight loss (p < 0.001). The exposure-effect relationship was clearly right-shifted for weight loss compared to the glycaemic effect. For GI side effects, eC (avg) remained significantly associated with the outcome after adjustment for dose residuals, indicating that eC (avg) had greater predictive value for tolerability. CONCLUSIONS: Although estimated and not measured, the exposure to oral semaglutide may provide outcome-dependent information. While the prescribed dose seems sufficient to predict glycaemic response, estimated exposure provides additional value for weight loss and GI tolerability. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Fadini, Gian Paolo AU - Fadini GP AUID- ORCID: 0000-0002-6510-2097 AD - Department of Medicine, University of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine, Padua, Italy. FAU - Morieri, Mario Luca AU - Morieri ML AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Boscaro, Carlotta AU - Boscaro C AD - Department of Medicine, University of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine, Padua, Italy. FAU - Bonora, Benedetta Maria AU - Bonora BM AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Cignarella, Andrea AU - Cignarella A AD - Department of Medicine, University of Padova, Padua, Italy. LA - eng GR - Universita degli Studi di Padova/ PT - Journal Article DEP - 20260510 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Dose-Response Relationship, Drug MH - Gastrointestinal Diseases/chemically induced MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics/adverse effects MH - Retrospective Studies MH - *Semaglutide/administration & dosage MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage PMC - PMC13243947 OTO - NOTNLM OT - pharmacokinetics OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- G.P.F. received consultancy, advisory board or lecture fees from AstraZeneca, Boehringer, Lilly, Guidotti, Sanofi, Novo Nordisk, Novartis, Servier. M.L.M. received consultancy, advisory board or lecture fees from AstraZeneca, Boehringer, Guidotti, Novartis, Novo Nordisk, Sanofi and Servier. B.M.B. received lecture or advisory board fees from AstraZeneca, Boehringer Ingelheim, Lilly, M.S.D., Sanofi, Servier and Novo Nordisk. A.C. received lecture fees from Servier and Recordati. C.B. has nothing to declare. EDAT- 2026/05/11 00:30 MHDA- 2026/06/11 18:35 PMCR- 2026/06/08 CRDT- 2026/05/10 23:52 PHST- 2026/04/25 00:00 [revised] PHST- 2026/03/14 00:00 [received] PHST- 2026/04/26 00:00 [accepted] PHST- 2026/06/11 18:35 [medline] PHST- 2026/05/11 00:30 [pubmed] PHST- 2026/05/10 23:52 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70840 [pii] AID - 10.1111/dom.70840 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):6405-6412. doi: 10.1111/dom.70840. Epub 2026 May 10. PMID- 42103575 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260622 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 48 IP - 7 DP - 2026 Jul TI - Real-world Impact of GLP-1 Receptor Agonists on Health-related Quality of Life in Type 2 Diabetes and Obesity (SEVERAL Study). PG - 596-603 LID - S0149-2918(26)00074-3 [pii] LID - 10.1016/j.clinthera.2026.03.012 [doi] AB - PURPOSE: To evaluate the real-world impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on health-related quality of life (HRQoL) and metabolic outcomes in adults with type 2 diabetes and obesity. METHODS: We conducted a multicenter prospective cohort study across 13 primary-care centers in Spain. Adults with type 2 diabetes and body mass index (BMI) > 30 kg/m(2) initiating a GLP-1 RA were followed for 44 weeks. Baseline and week-44 assessments included anthropometric and biochemical parameters and HRQoL measured using the EQ-5D index and visual analogue scale (VAS), and the SF-12 physical and mental component summaries (PCS/MCS). Changes were analyzed using paired statistical tests overall and by achievement of >/=5% weight loss. FINDINGS: Among 135 patients, significant improvements were observed in glucose, HbA1c, LDL-C, waist circumference, body weight, and BMI. HRQoL improved in EQ-5D domains including mobility, pain/discomfort, and anxiety/depression. The EQ-5D index increased from 0.71 to 0.79 (P < 0.001), and VAS from 58.3 to 65.3 (P = 0.007). SF-12 PCS improved significantly, whereas MCS showed no overall change. Patients achieving >/=5% weight loss experienced greater improvements in EQ-5D index, VAS, and PCS. Subcutaneous and oral semaglutide improved the EQ-5D index; oral semaglutide improved VAS and MCS; and subcutaneous semaglutide improved PCS. IMPLICATIONS: In routine clinical practice, GLP-1 RAs were associated with clinically meaningful improvements in HRQoL and metabolic outcomes, particularly when >/=5% weight loss is achieved, supporting the integration of patient-reported outcomes into diabetes and obesity management. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT05136287. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Seijas-Amigo, Jose AU - Seijas-Amigo J AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Universidade de Santiago de Compostela, Santiago de Compostela, Spain. FAU - Salgado-Barreira, Angel AU - Salgado-Barreira A AD - Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiologia y Salud Publica CIBERESP), Carlos III Health Institute, Madrid, Spain. Electronic address: angel.salgado.barreira@usc.es. FAU - Roca-Martinez, Carlota AU - Roca-Martinez C AD - Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Santiago de Compostela, Spain; Universidade de Santiago de Compostela, Santiago de Compostela, Spain. FAU - Castelo-Dominguez, Rosana AU - Castelo-Dominguez R AD - Centro de Salud, Ribeira, A Coruna, Spain. FAU - Perez-Alvarez, Maria Teresa AU - Perez-Alvarez MT AD - Centro de Salud de Culleredo, A Coruna, Spain. FAU - Ponce-Pinon, Belen AU - Ponce-Pinon B AD - Centro de Salud de Fene, A Coruna, Spain. FAU - Fernandez-Silva, Marlen AU - Fernandez-Silva M AD - Centro de Salud O Ventorillo, A Coruna, Spain. FAU - Rodriguez-Barreiro, Marta AU - Rodriguez-Barreiro M AD - Centro de Salud. Virxe Peregrina, Pontevedra, Spain. FAU - Pereira-Pia, Mercedes AU - Pereira-Pia M AD - Centro de Salud de San Roque, Lugo, Spain. FAU - Iglesias-Moreno, Jose Manuel AU - Iglesias-Moreno JM AD - Centro de Salud de Val Minor, Nigran, Pontevedra, Spain. FAU - Gago-Garcia, Mar AU - Gago-Garcia M AD - Centro de Salud de Ribadeo, Lugo, Spain. FAU - Montans-Garcia, Raquel AU - Montans-Garcia R AD - Centro de Salud de Cee, A Coruna, Spain. FAU - Fernandez-Perez, Agustina AU - Fernandez-Perez A AD - Centro de Salud Vilalba, Lugo, Spain. FAU - Fraga-Gayoso, Dolores AU - Fraga-Gayoso D AD - Centro de Salud de Sarria, Lugo, Spain. FAU - Fernandez-Montenegro, Montse AU - Fernandez-Montenegro M AD - Centro de Salud de O Carballino, Ourense, Spain. FAU - Riveiro-Barciela, Beatriz AU - Riveiro-Barciela B AD - Centro de Salud O Temple, A Coruna, Spain. FAU - Rilla-Villar, Natalia AU - Rilla-Villar N AD - Consejeria de Salud, Asturias, Spain. FAU - Cardeso-Paredes, Begona AU - Cardeso-Paredes B AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. FAU - Ribeiro-Ferreiro, Marta AU - Ribeiro-Ferreiro M AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Santiago de Compostela, Spain. FAU - Rodriguez-Penas, Diego AU - Rodriguez-Penas D AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Santiago de Compostela, Spain. FAU - Cordero, Alberto AU - Cordero A AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Cardiology Department, Hospital IMED Elche, Alicante, Spain; Grupo de Investigacion Cardiovascular (GRINCAVA), Universidad Miguel Hernandez, Elche, Spain. FAU - Rodriguez-Manero, Moises AU - Rodriguez-Manero M AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. FAU - Gonzalez-Juanatey, Jose R AU - Gonzalez-Juanatey JR AD - Cardiology Department, Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. CN - SEVERAL INVESTIGATORS LA - eng SI - ClinicalTrials.gov/NCT05136287 PT - Journal Article PT - Multicenter Study DEP - 20260507 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM EIN - Clin Ther. 2026 Jul;48(7):675-676. doi: 10.1016/j.clinthera.2026.04.015. PMID: 42177143 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Quality of Life MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Male MH - Middle Aged MH - Prospective Studies MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Weight Loss/drug effects MH - Aged MH - Body Mass Index MH - Spain MH - Semaglutide MH - Glycated Hemoglobin MH - Blood Glucose/drug effects MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor MH - Adult OTO - NOTNLM OT - GLP-1 receptor agonists OT - Health-related quality of life OT - Obesity OT - Patient-reported outcomes OT - Real-world evidence OT - Type 2 diabetes COIS- Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose. The authors declare that there are no conflicts of interest related to the results of this study. EDAT- 2026/05/09 00:34 MHDA- 2026/06/12 00:39 CRDT- 2026/05/08 21:53 PHST- 2025/11/08 00:00 [received] PHST- 2026/02/21 00:00 [revised] PHST- 2026/03/13 00:00 [accepted] PHST- 2026/06/12 00:39 [medline] PHST- 2026/05/09 00:34 [pubmed] PHST- 2026/05/08 21:53 [entrez] AID - S0149-2918(26)00074-3 [pii] AID - 10.1016/j.clinthera.2026.03.012 [doi] PST - ppublish SO - Clin Ther. 2026 Jul;48(7):596-603. doi: 10.1016/j.clinthera.2026.03.012. Epub 2026 May 7. PMID- 42103200 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260729 IS - 1879-1913 (Electronic) IS - 0002-9149 (Linking) VI - 272 DP - 2026 Aug 1 TI - Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Outcomes in Patients With Atherosclerotic Cardiovascular Disease and Obesity Without Diabetes. PG - 1-8 LID - S0002-9149(26)00335-8 [pii] LID - 10.1016/j.amjcard.2026.05.004 [doi] AB - The Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) trial demonstrated cardiovascular benefits of semaglutide in patients with obesity without diabetes; however, the real-world effect across multiple glucagon-like peptide-1 receptor agonist (GLP-1 RA) agents in patients with established atherosclerotic cardiovascular disease (ASCVD) and overweight or obesity without diabetes mellitus remains unknown. We conducted a target trial emulation using data from the TriNetX US Collaborative Network (January 1, 2010, to December 1, 2025) in adults aged >/=45 years with established ASCVD (history of myocardial infarction, stroke, or coronary or peripheral revascularization), BMI >/=27 kg/m(2), and without type 2 diabetes. New initiation of any GLP-1 RA (liraglutide, semaglutide, dulaglutide, or exenatide) was compared with no GLP-1 RA use. The primary outcome was all-cause mortality; secondary outcomes were acute myocardial infarction, stroke, and heart failure hospitalization over 5 years, analyzed using Cox proportional hazards and Fine-Gray subdistribution hazard models to account for the competing risk of death. Among 14,844 propensity-matched patients without diabetes (7,422 per group; median age 63 [interquartile range 55 to 71] years; 64% women), GLP-1 RA use was associated with lower all-cause mortality (hazard ratio [HR] 0.68; 95% CI 0.53 to 0.88; p = 0.003), acute myocardial infarction (subdistribution HR [sHR] 0.63; 95% CI 0.41 to 0.98; p = 0.040), and heart failure hospitalization (sHR 0.61; 95% CI 0.39 to 0.95; p = 0.028); no significant association was observed for stroke (sHR 0.76; 95% CI 0.52 to 1.10; p = 0.146). Findings were consistent in landmark and age subgroup analyses; a sensitivity analysis including patients with diabetes (N = 31,910 matched pairs) showed similar associations. In conclusion, these real-world findings are broadly directionally consistent with the SELECT trial and provide complementary observational evidence across multiple GLP-1 RA agents in patients with established ASCVD and overweight or obesity without diabetes mellitus, though causal inference cannot be established from observational data alone. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Ali Akbar, Usman AU - Ali Akbar U AD - Department of Internal Medicine, WVU Camden Clark Medical Center, Parkersburg, West Virginia. FAU - Mondal, Avilash AU - Mondal A AD - Department of Cardiology, West Virginia University, Morgantown, West Virginia. FAU - Vorla, Mounica AU - Vorla M AD - Department of Medicine, Carle Foundation Hospital, Urbana, Illinois. FAU - Alruwaili, Waleed AU - Alruwaili W AD - Department of Internal Medicine, West Virginia University, Morgantown, West Virginia. FAU - Lacoste, Jordan AU - Lacoste J AD - Department of Pharmacy, WVU Medicine, Morgantown, West Virginia. FAU - Thyagaturu, Harshith AU - Thyagaturu H AD - Department of Cardiology, West Virginia University, Morgantown, West Virginia. FAU - Shafique, Nouman AU - Shafique N AD - Department of Medicine, AdventHealth Orlando, Orlando, Florida. FAU - Shakeel, Sana AU - Shakeel S AD - Gomal Medical College, Dera Ismail Khan, Khyber Pakhtunkhwa, Pakistan. FAU - Taha, Amro AU - Taha A AD - Department of Cardiology, West Virginia University, Morgantown, West Virginia. FAU - Balla, Sudarshan AU - Balla S AD - Department of Cardiology, West Virginia University, Morgantown, West Virginia. Electronic address: sudarshanballa@outlook.com. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260506 PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Male MH - *Obesity/complications/drug therapy MH - *Atherosclerosis/drug therapy/complications MH - Middle Aged MH - Aged MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use MH - Exenatide/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Myocardial Infarction/epidemiology MH - Recombinant Fusion Proteins/therapeutic use MH - Heart Failure/epidemiology MH - Stroke/epidemiology MH - United States/epidemiology MH - Cause of Death MH - Diabetes Mellitus, Type 2 OTO - NOTNLM OT - all-cause mortality OT - atherosclerotic cardiovascular disease OT - glucagon-like peptide-1 receptor agonists OT - heart failure OT - hospitalization OT - obesity OT - real-world evidence OT - secondary prevention OT - target trial emulation COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. All authors approved the final manuscript. EDAT- 2026/05/09 00:34 MHDA- 2026/07/10 16:10 CRDT- 2026/05/08 19:15 PHST- 2026/03/14 00:00 [received] PHST- 2026/04/17 00:00 [revised] PHST- 2026/05/03 00:00 [accepted] PHST- 2026/07/10 16:10 [medline] PHST- 2026/05/09 00:34 [pubmed] PHST- 2026/05/08 19:15 [entrez] AID - S0002-9149(26)00335-8 [pii] AID - 10.1016/j.amjcard.2026.05.004 [doi] PST - ppublish SO - Am J Cardiol. 2026 Aug 1;272:1-8. doi: 10.1016/j.amjcard.2026.05.004. Epub 2026 May 6. PMID- 42098899 OWN - NLM STAT- MEDLINE DCOM- 20260608 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Beyond GLP-1 Monotherapy: Novel Multi-Agonists, Amylin Analogues, and Combination Strategies in Obesity and Type 2 Diabetes. PG - 5556-5589 LID - 10.1111/dom.70822 [doi] AB - AIMS: To provide a clinically oriented narrative review of recently reported human trial data on emerging pharmacotherapies for obesity and type 2 diabetes beyond glucagon-like peptide-1 receptor agonist (GLP-1RA) monotherapy. MATERIALS AND METHODS: This narrative review summarizes recent clinical evidence on incretin-based and related therapeutic strategies, including dual and triple incretin- or glucagon-based agonists, long-acting amylin analogues, oral agents, and combination approaches targeting complementary satiety and metabolic pathways. The review focuses on human trial data and evaluates key outcomes including body weight reduction, glycemic control, body-composition effects, tolerability, and broader cardiometabolic changes. RESULTS: Incretin-based therapies have transformed the management of obesity and type 2 diabetes, with GLP-1RAs achieving levels of weight loss that begin to narrow the gap with metabolic surgery in selected populations. Recent developments have substantially expanded the field beyond GLP-1RA monotherapy. Emerging agents now include multi-agonists, amylin-based therapies, novel oral compounds, and combination strategies designed to improve not only the magnitude of weight loss, but also its quality, durability, and metabolic consequences. Across trials, these approaches have shown promising effects on body weight, glycemic control, and selected cardiometabolic parameters, although differences in tolerability, evidence maturity, and practical feasibility remain important. CONCLUSIONS: Current data indicate a rapid shift from single-pathway interventions toward multimodal therapeutic strategies in obesity and type 2 diabetes. Future positioning of these agents within treatment algorithms will depend not only on efficacy, but also on long-term safety, durability of effect, tolerability, adherence, access, and their impact on clinically meaningful outcomes beyond body weight alone. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Khachaturov, Mikhail AU - Khachaturov M AUID- ORCID: 0000-0001-7606-6565 AD - Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Goulis, Dimitrios G AU - Goulis DG AD - Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20260507 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Islet Amyloid Polypeptide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Anti-Obesity Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Therapy, Combination MH - Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Incretins/therapeutic use MH - *Islet Amyloid Polypeptide/therapeutic use/agonists MH - *Obesity/drug therapy/complications MH - Semaglutide/therapeutic use MH - Weight Loss/drug effects OTO - NOTNLM OT - GLP-1 OT - antiobesity drug OT - obesity therapy OT - semaglutide OT - type 2 diabetes OT - weight management EDAT- 2026/05/08 00:32 MHDA- 2026/06/09 00:34 CRDT- 2026/05/07 23:56 PHST- 2026/04/20 00:00 [revised] PHST- 2026/01/13 00:00 [received] PHST- 2026/04/20 00:00 [accepted] PHST- 2026/06/09 00:34 [medline] PHST- 2026/05/08 00:32 [pubmed] PHST- 2026/05/07 23:56 [entrez] AID - 10.1111/dom.70822 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5556-5589. doi: 10.1111/dom.70822. Epub 2026 May 7. PMID- 42089543 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260614 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 Suppl 1 DP - 2026 Jun TI - Semaglutide vs. Bariatric Surgery: Comparing Costs and Clinical Outcomes in Patients With Diabetes and Obesity. PG - 65-76 LID - 10.1002/oby.70209 [doi] AB - OBJECTIVE: We compared health care spending and utilization associated with semaglutide relative to bariatric surgery in patients with obesity and type 2 diabetes (T2D). METHODS: Using MarketScan insurance claims of patients with BMI >/= 35 and T2D from 2016 to 2021, we examined associations between choice of semaglutide, sleeve gastrectomy, or gastric bypass; 3-year health care spending (out-of-pocket [OOP] and total); and clinical outcomes (ED visits, hospital admissions, and major adverse cardiovascular events [MACE]). Analyses were adjusted using generalized linear models, inverse probability weighting, and instrumental variables. RESULTS: Among 6748 patients (2797 semaglutide, 2300 sleeve gastrectomy, 1651 gastric bypass), bariatric surgery patients had higher BMI and more comorbidities. In IPTW-adjusted analysis, semaglutide was associated with the highest 3-year OOP costs ($7752 vs. $5980 [sleeve gastrectomy] vs. $6591 [gastric bypass], p < 0.001), but total spending was not statistically different across the groups. Relative to semaglutide, the gastric bypass group showed higher observed ED visits (hazard ratio relative to semaglutide [95% CI]: 1.36 [1.28-1.45]) and inpatient admissions (1.25 [1.13-1.37]) and fewer MACE (0.71 [0.59-0.88]). Sleeve gastrectomy was associated with fewer long-term admissions (0.79 [0.72-0.86]) and MACE (0.79 [0.66-0.93]). CONCLUSIONS: For patients with T2D and obesity, compared with semaglutide, bariatric surgery is associated with lower OOP spending and similar total spending at 3 years, as well as lower long-term MACE rates. CI - (c) 2026 The Obesity Society. FAU - Chhabra, Karan R AU - Chhabra KR AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA. AD - Bellevue Division of Bariatric and General Surgery, NYC Health+Hospitals/Bellevue, New York, New York, USA. AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA. FAU - Gencerliler, Nihan AU - Gencerliler N AD - Division of Health Services Research, Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, New York, USA. FAU - Orandi, Babak J AU - Orandi BJ AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA. AD - Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. FAU - Wang, Vivian Hsing-Chun AU - Wang VH AD - Division of Health Services Research, Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, New York, USA. FAU - Kozato, Akio AU - Kozato A AUID- ORCID: 0000-0002-8965-9674 AD - Bellevue Division of Bariatric and General Surgery, NYC Health+Hospitals/Bellevue, New York, New York, USA. AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA. FAU - Surapaneni, Aditya AU - Surapaneni A AD - Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. FAU - Grams, Morgan AU - Grams M AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA. AD - Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. FAU - Mukhopadhyay, Amrita AU - Mukhopadhyay A AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA. AD - Leon H. Charney Division of Cardiology, Department of Medicine, NYU Grossman School of Medicine, New York, New York, USA. FAU - Shin, Jung-Im AU - Shin JI AD - Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Ren-Fielding, Christine AU - Ren-Fielding C AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA. FAU - Parikh, Manish AU - Parikh M AD - Bellevue Division of Bariatric and General Surgery, NYC Health+Hospitals/Bellevue, New York, New York, USA. AD - Department of Surgery, NYU Grossman School of Medicine, New York, New York, USA. FAU - Zhang, Donglan S AU - Zhang DS AD - Department of Population Health, NYU Grossman School of Medicine, New York, New York, USA. AD - Division of Health Services Research, Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, New York, USA. LA - eng GR - L30DK144880/NH/NIH HHS/United States GR - R01DK115534/DK/NIDDK NIH HHS/United States GR - R01DK100446/DK/NIDDK NIH HHS/United States GR - R01DK124399/DK/NIDDK NIH HHS/United States GR - R01DK108803/DK/NIDDK NIH HHS/United States GR - K24HL115861/HL/NHLBI NIH HHS/United States GR - K23HL171636/HL/NHLBI NIH HHS/United States GR - National Kidney Foundation/ GR - AHA 23CDA1042602/American Heart Association/ GR - NYU Department of Medicine Chairman's Circle Research Award/ GR - Doucette Innovation Fund/ GR - L30DK144880/NH/NIH HHS/United States GR - R01DK115534/DK/NIDDK NIH HHS/United States GR - R01DK100446/DK/NIDDK NIH HHS/United States GR - R01DK124399/DK/NIDDK NIH HHS/United States GR - R01DK108803/DK/NIDDK NIH HHS/United States GR - K24HL115861/HL/NHLBI NIH HHS/United States GR - K23HL171636/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20260506 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Bariatric Surgery/economics/methods MH - *Diabetes Mellitus, Type 2/economics/complications/drug therapy MH - Gastrectomy/economics MH - Gastric Bypass/economics MH - *Health Care Costs/statistics & numerical data MH - *Obesity/complications/drug therapy/economics/surgery MH - *Semaglutide/economics/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - bariatric surgery OT - health care costs OT - semaglutide EDAT- 2026/05/06 12:35 MHDA- 2026/06/11 06:36 CRDT- 2026/05/06 08:35 PHST- 2026/02/10 00:00 [revised] PHST- 2025/10/15 00:00 [received] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/06/11 06:36 [medline] PHST- 2026/05/06 12:35 [pubmed] PHST- 2026/05/06 08:35 [entrez] AID - 10.1002/oby.70209 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Jun;34 Suppl 1:65-76. doi: 10.1002/oby.70209. Epub 2026 May 6. PMID- 42087771 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260713 IS - 0946-1965 (Print) IS - 0946-1965 (Linking) VI - 64 IP - 8 DP - 2026 Aug TI - Dulaglutide-associated body odor with dechallenge and rechallenge in a patient with type 2 diabetes. PG - 455-458 LID - 10.5414/CP204985 [doi] AB - OBJECTIVE: Although uncommon, medications may induce unpleasant body odor, potentially leading to psychosocial distress and reduced treatment adherence. To date, unpleasant body odor has not been recognized as an adverse effect of dulaglutide. We report a novel case of dulaglutide-associated body odor, confirmed by dechallenge and rechallenge. CASE REPORT: A 57-year-old man with a 6-year history of type 2 diabetes mellitus and hypertension was initiated on dulaglutide due to inadequate glycemic control and obesity. Two weeks after treatment initiation, an unpleasant body odor was noted by family members and colleagues. No changes in diet, hygiene practices, or concomitant medications were reported. Dermatological examination and extensive laboratory evaluation excluded infectious, metabolic, and endocrine causes. The odor resolved ~ 10 days after discontinuation of dulaglutide. Upon rechallenge, the odor recurred, confirming a causal relationship. Dulaglutide was permanently discontinued, and treatment was switched to semaglutide, after which the body odor did not recur and glycemic control improved. According to the Naranjo Adverse Drug Reaction Probability Scale, the association was classified as probable. CONCLUSION: This case highlights a rare and previously unreported adverse effect of dulaglutide. Although not medically serious, drug-induced body odor may substantially impair quality of life and treatment adherence. FAU - Marusic, Srecko AU - Marusic S FAU - Staresinic, Matea AU - Staresinic M FAU - Berkovic, Maja Cigrovski AU - Berkovic MC LA - eng PT - Case Reports PT - Journal Article PL - Germany TA - Int J Clin Pharmacol Ther JT - International journal of clinical pharmacology and therapeutics JID - 9423309 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis MH - *Glucagon-Like Peptides/analogs & derivatives/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - *Recombinant Fusion Proteins/adverse effects MH - *Immunoglobulin Fc Fragments/adverse effects MH - *Odorants MH - Semaglutide MH - Blood Glucose/drug effects/metabolism MH - Drug Substitution MH - Treatment Outcome EDAT- 2026/05/06 06:37 MHDA- 2026/07/13 06:33 CRDT- 2026/05/06 04:13 PHST- 2026/07/10 00:00 [accepted] PHST- 2026/07/13 06:33 [medline] PHST- 2026/05/06 06:37 [pubmed] PHST- 2026/05/06 04:13 [entrez] AID - 192905 [pii] AID - 10.5414/CP204985 [doi] PST - ppublish SO - Int J Clin Pharmacol Ther. 2026 Aug;64(8):455-458. doi: 10.5414/CP204985. PMID- 42086986 OWN - NLM STAT- MEDLINE DCOM- 20260922 LR - 20260925 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 51 IP - 11 DP - 2026 Oct TI - Computational phenotyping of effort-based decision-making in type-2 diabetes on and off semaglutide. PG - 1924-1931 LID - 10.1038/s41386-026-02433-y [doi] AB - Motivation plays a fundamental role in human behaviour. Dopaminergic pathways have long been implicated in individual differences in motivation. Emerging evidence suggests such neural mechanisms interact with metabolic processes to coordinate energy expenditure with energy resources, thereby linking motivation with metabolic health. We ask whether a cognitive-computational index of motivation-reliably linked to neuropsychiatric symptoms-is altered in the context of type-2 diabetes and treatment with a GLP-1 agonist (semaglutide). In a pre-registered experiment, we quantified computational effort-based decision-making parameters in participants with diabetes on (N = 58) or off (N = 54) semaglutide treatment, compared to two groups of matched controls without diabetes (N = 58 each). Subjects with type-2 diabetes showed a blunted acceptance bias, a computational parameter describing the bias to accept effort for reward. This effect was not driven by neuropsychiatric comorbidity or antidepressant use. Across all participants, we found that increasing diabetes risk linearly predicted reduced acceptance bias. Participants with diabetes treated with semaglutide did not show restored motivation. Metabolic ill-health is associated with reduced acceptance bias during motivational decision-making. This blunting mirrors-but is largely independent of-neuropsychiatric motivational deficits. This suggests metabolic ill-health is accompanied by a cognitive shift towards energy conservation, potentially contributing to comorbidity between metabolic ill-health and mental illness. CI - (c) 2026. The Author(s). FAU - Mehrhof, Sara Z AU - Mehrhof SZ AD - MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK. sara.mehrhof@mrc-cbu.cam.ac.uk. FAU - Fleming, Hugo AU - Fleming H AUID- ORCID: 0000-0001-5421-8222 AD - MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK. FAU - Nord, Camilla L AU - Nord CL AUID- ORCID: 0000-0002-9281-3417 AD - MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, UK. AD - Department of Psychiatry, University of Cambridge, Cambridge, UK. LA - eng GR - MC_UU_00030/12/RCUK | Medical Research Council (MRC)/ GR - G102329/AXA Research Fund (Le Fonds AXA pour la Recherche)/ GR - 226490/Z/22/Z/Wellcome Trust (Wellcome)/ GR - WT_/Wellcome Trust/United Kingdom GR - BRC-1215-20014/DH | National Institute for Health Research (NIHR)/ PT - Journal Article DEP - 20260506 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Female MH - *Decision Making/drug effects/physiology MH - Male MH - *Motivation/drug effects/physiology MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Phenotype MH - Aged MH - Reward PMC - PMC13597482 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/05/06 00:35 MHDA- 2026/09/23 05:34 PMCR- 2026/05/06 CRDT- 2026/05/05 23:34 PHST- 2025/12/23 00:00 [received] PHST- 2026/04/17 00:00 [accepted] PHST- 2026/03/30 00:00 [revised] PHST- 2026/09/23 05:34 [medline] PHST- 2026/05/06 00:35 [pubmed] PHST- 2026/05/05 23:34 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - 10.1038/s41386-026-02433-y [pii] AID - 2433 [pii] AID - 10.1038/s41386-026-02433-y [doi] PST - ppublish SO - Neuropsychopharmacology. 2026 Oct;51(11):1924-1931. doi: 10.1038/s41386-026-02433-y. Epub 2026 May 6. PMID- 42066004 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1944-8252 (Electronic) IS - 1944-8244 (Linking) VI - 18 IP - 20 DP - 2026 May 27 TI - An Ionic Liquid-Based Enteric Formulation for Enhanced Oral Delivery of Semaglutide in Type 2 Diabetes Mellitus. PG - 28368-28380 LID - 10.1021/acsami.5c24385 [doi] AB - Oral delivery of peptide therapeutics remains challenging due to gastrointestinal degradation, poor epithelial permeability, and extremely low bioavailability. To address these limitations, we developed an enteric solid formulation based on sorbic acid-choline ionic liquids (ILs) for the oral delivery of semaglutide (Sema), a glucagon-like peptide-1 (GLP-1) analogue. The IL-based enteric system was designed to enhance peptide stability, reduce gastric degradation, and promote intestinal absorption. In vitro studies demonstrated strong resistance to acidic conditions and pH-responsive release in simulated intestinal fluid. In vivo imaging further revealed prolonged intestinal retention of the IL-loaded enteric particles. Pharmacokinetic evaluation showed a 2.3-fold increase in maximum plasma concentration compared to the reference Rybelsus. In type 2 diabetes mellitus (T2DM) mice, the formulation achieved glucose-lowering efficacy comparable to subcutaneous Sema administration, with additional improvements in hepatic histology. Importantly, repeated-dose studies indicated favorable systemic and gastrointestinal tolerability under the tested conditions. Collectively, these results demonstrate that IL-based enteric formulation enhances oral peptide exposure while maintaining safety, offering a promising strategy for noninvasive T2DM management. FAU - Tao, Juan AU - Tao J AD - School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. AD - School of Chinese Medicine, Jiangsu College of Nursing, Huaian 223001, China. FAU - Lu, Xinrui AU - Lu X AD - School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. FAU - Wei, Yuning AU - Wei Y AD - School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. FAU - Feng, Jiayi AU - Feng J AD - School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. FAU - Yang, Jinlong AU - Yang J AUID- ORCID: 0000-0002-7358-3396 AD - Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200443, China. FAU - Qi, Jianping AU - Qi J AUID- ORCID: 0000-0003-4833-1426 AD - School of Pharmaceutical Sciences, Key Laboratory of Smart Drug Delivery, Ministry of Education, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai 201203, China. LA - eng PT - Journal Article DEP - 20260501 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Ionic Liquids) RN - 0 (Hypoglycemic Agents) SB - IM MH - Semaglutide MH - Animals MH - *Glucagon-Like Peptides/chemistry/pharmacokinetics/pharmacology/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Administration, Oral MH - *Ionic Liquids/chemistry MH - Mice MH - Male MH - *Hypoglycemic Agents/chemistry/pharmacokinetics/therapeutic use/pharmacology/administration & dosage MH - *Diabetes Mellitus, Experimental/drug therapy MH - Humans OTO - NOTNLM OT - bioavailability OT - ionic liquid OT - oral peptide delivery OT - semaglutide OT - type 2 diabetes mellitus EDAT- 2026/05/01 18:45 MHDA- 2026/05/27 12:35 CRDT- 2026/05/01 13:13 PHST- 2026/05/27 12:35 [medline] PHST- 2026/05/01 18:45 [pubmed] PHST- 2026/05/01 13:13 [entrez] AID - 10.1021/acsami.5c24385 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2026 May 27;18(20):28368-28380. doi: 10.1021/acsami.5c24385. Epub 2026 May 1. PMID- 42061677 OWN - NLM STAT- MEDLINE DCOM- 20260902 LR - 20260902 IS - 1524-4733 (Electronic) IS - 1098-3015 (Linking) VI - 29 IP - 9 DP - 2026 Sep TI - Assessment of Carbon Emission Impact of Semaglutide in Patients With Type 2 Diabetes in the United Kingdom Using an Innovative Modeling Approach. PG - 1626-1635 LID - S1098-3015(26)02397-1 [pii] LID - 10.1016/j.jval.2026.03.2249 [doi] AB - OBJECTIVES: To evaluate the carbon footprint and clinical outcomes of once-weekly subcutaneous semaglutide in patients with type 2 diabetes mellitus (T2DM) in the United Kingdom. METHODS: Using the IQVIA Core Diabetes Model, environmental and clinical impacts were projected over a lifetime horizon from the National Health Services perspective. Data from the SUSTAIN-2 (patients with T2DM) and SUSTAIN-6 (patients with T2DM and established cardiovascular [CV] risk) trials were used to compare semaglutide with sitagliptin and placebo, respectively. Outcomes included life expectancy measured in life-years (LYs) and quality-adjusted life expectancy measured in quality-adjusted life-years (QALYs) gained, incidence of diabetes-related complications and adverse events, carbon emissions, and incremental carbon footprint effectiveness ratios. RESULTS: In patients with T2DM, semaglutide dominates sitagliptin, with higher discounted LYs (0.096) and QALYs (0.095) gains, a 6.9% reduction in diabetes-related complications and adverse events, and reduced lifetime carbon emissions by 9.3% (13,899 kg carbon dioxide equivalent emissions [CO(2)e] versus 15,319 kg CO(2)e). Similarly, in patients with T2DM and established CV risk, semaglutide showed higher discounted LYs (0.206) and QALYs (0.164), with reductions in all complications except heart failure-related hospitalizations versus placebo. Lifetime carbon emissions were 5.2% lower with semaglutide (14,546 kg CO(2)e versus 15,341 kg CO(2)e), again with a dominant carbon footprint effectiveness ratio. The reduction in CO(2) was mainly driven by reduced complications and treatment needs. Sensitivity analyses supported the robustness of the results. CONCLUSION: Semaglutide offers environmental advantages over sitagliptin for patients with T2DM overall and over standard of care for those with established CV risk. CI - Copyright (c) 2026. Published by Elsevier Inc. FAU - Lund, Niels AU - Lund N AD - Novo Nordisk, Bagsvaerd, Denmark. Electronic address: nlnd@novonordisk.com. FAU - Rasche, Andreas AU - Rasche A AD - Copenhagen Business School, Frederiksberg, Denmark. FAU - Taylor, Matthew AU - Taylor M AD - York Health Economics Consortium, University of York, York, England, UK. FAU - Chubb, Barrie AU - Chubb B AD - Novo Nordisk Ltd, Gatwick, England, UK. FAU - Xu, Weiwei AU - Xu W AD - IQVIA, Amsterdam, Netherlands. FAU - Taneja, Loveleen AU - Taneja L AD - IQVIA, Gurugram, Haryana, India. FAU - Olivieri, Anamaria-Vera AU - Olivieri AV AD - IQVIA, Basel, Switzerland. FAU - Sharma, Yuvraj AU - Sharma Y AD - IQVIA Ltd, London, England, UK. LA - eng PT - Journal Article DEP - 20260428 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - TS63EW8X6F (Sitagliptin Phosphate) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Semaglutide MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/economics/adverse effects MH - United Kingdom MH - *Hypoglycemic Agents/administration & dosage/adverse effects/economics/therapeutic use MH - Sitagliptin Phosphate/therapeutic use/administration & dosage/economics/adverse effects MH - *Carbon Footprint MH - Quality-Adjusted Life Years MH - Female MH - Male MH - Middle Aged MH - Cost-Benefit Analysis MH - Aged OTO - NOTNLM OT - ICFER OT - carbon emission OT - carbon footprint OT - incremental carbon footprint effectiveness ratio OT - semaglutide OT - type 2 diabetes COIS- Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. EDAT- 2026/05/01 00:31 MHDA- 2026/09/03 01:19 CRDT- 2026/04/30 19:18 PHST- 2025/10/09 00:00 [received] PHST- 2026/03/23 00:00 [revised] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/09/03 01:19 [medline] PHST- 2026/05/01 00:31 [pubmed] PHST- 2026/04/30 19:18 [entrez] AID - S1098-3015(26)02397-1 [pii] AID - 10.1016/j.jval.2026.03.2249 [doi] PST - ppublish SO - Value Health. 2026 Sep;29(9):1626-1635. doi: 10.1016/j.jval.2026.03.2249. Epub 2026 Apr 28. PMID- 42061608 OWN - NLM STAT- MEDLINE DCOM- 20260605 LR - 20260630 IS - 2254-8874 (Electronic) IS - 2254-8874 (Linking) VI - 226 IP - 6 DP - 2026 Jun-Jul TI - Real-world impact of oral semaglutide on inflammatory markers in patients at high cardiovascular risk. PG - 502562 LID - S2254-8874(26)00091-3 [pii] LID - 10.1016/j.rceng.2026.502562 [doi] AB - BACKGROUND AND OBJECTIVE: Inflammation plays a central role in the pathophysiology of atherosclerosis and contributes to residual cardiovascular risk (CVR). High-sensitivity C-reactive protein (hs-CRP) and fibrinogen are considered key biomarkers in this context. Although GLP-1 receptor agonists have demonstrated anti-inflammatory effects, real-world evidence on oral semaglutide is limited. The objective of this study was to evaluate the impact of oral semaglutide on inflammatory markers in patients with high cardiovascular risk (CVR) in routine clinical practice. MATERIALS AND METHODS: This was an observational study that included adult patients receiving treatment with oral semaglutide. The primary endpoint was the change in hs-CRP and fibrinogen levels. Secondary objectives included evaluating modifications in glycated hemoglobin (HbA1c), safety, and predictors of sustained anti-inflammatory response, defined as hs-CRP /= 5%) goals after semaglutide initiation. We compared baseline (1 year before initiation) with 1st-year and 2nd-year follow-up for cardiometabolic endpoints (3-point and 5-point major adverse cardiovascular events [MACE]), cardiometabolic risk factors, and renal outcomes. Sensitivity analysis was performed in an exploratory cohort of patients in the top tertile of Hb1Ac reduction and weight loss. RESULTS: We identified 413 patients in the primary cohort (mean age 59.6 years and balanced sex distribution). Significant reductions were observed in low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), total cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure and high-density lipoprotein cholesterol (HDL-C) increased at both 1 and 2 years after semaglutide initiation (all p < 0.001). Fewer than 1% of patients experienced a >/= 40% decline in estimated glomerular filtration rate (eGFR) during follow-up. Mean change in urine albumin-to-creatinine ratio (UACR) were - 20.13 mg/g in the 1st year (p < 0.001) and - 54.03 mg/g in the 2nd year (p < 0.001). The event rate of 3-point MACE decreased from 26.82 per 1000 person-years (PY) during baseline to 22.31 per 1000 PY in the 2nd year. The sensitivity analysis showed consistent results. CONCLUSION: In this real-world study, semaglutide users who achieved glycemic and weight goals exhibited marked improvements in cardiometabolic and renal outcomes over 2 years. CI - (c) 2026. The Author(s). FAU - Tan, Xi AU - Tan X AUID- ORCID: 0000-0002-2409-5927 AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. mxtz@novonordisk.com. FAU - Tsai, Wan-Lun AU - Tsai WL AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. FAU - Liang, Yuanjie AU - Liang Y AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. FAU - Swift, Caroline AU - Swift C AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. FAU - Fang, Gang AU - Fang G AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. FAU - Muhammad, Chalak AU - Muhammad C AD - Clinical Development, Medical and Regulatory Affairs, Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, USA. FAU - de Havenon, Adam AU - de Havenon A AD - Department of Neurology, Center for Brain and Mind Health, Yale University, New Haven, CT, USA. LA - eng PT - Journal Article PT - Observational Study DEP - 20260430 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Middle Aged MH - Male MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Weight Loss/drug effects MH - Glycated Hemoglobin/metabolism MH - Aged MH - Cohort Studies MH - *Cardiovascular Diseases/prevention & control MH - Glycemic Control MH - Metabolic Syndrome MH - Blood Glucose PMC - PMC13290940 OTO - NOTNLM OT - Cardiovascular OT - Major adverse cardiovascular event OT - Renal OT - Semaglutide OT - Type 2 diabetes COIS- Declarations. Conflict of Interest: Xi Tan, Yuanjie Liang, Caroline Swift, Gang Fang, and Chalak Muhammad are employees of Novo Nordisk Inc. Wan-Lun Tsai was a contractor for Novo Nordisk Inc. at the time of the study. Adam de Havenon reports research funding from NIH/NINDS and the AAN, consulting for Novo Nordisk Inc., royalites from UptoDate, and equity in TitinKM and Certus. Ethical Approval: This study was conducted in accordance with the Declaration of Helsinki. This retrospective analysis used Optum(R) Market Clarity, a fully de-identified, HIPAA-compliant dataset; under US federal regulations (45 CFR 46), analyses of de-identified data do not constitute human subjects research and do not require review by an Institutional Review Board. No identifiable private information was accessed. This study analyzed secondary data from the de-identified Optum(R) Market Clarity without direct subject contact or intervention; per 45 CFR 46, analyses of secondary, de-identified data are not human subjects research and do not require consent. EDAT- 2026/04/30 12:35 MHDA- 2026/06/23 18:33 PMCR- 2026/04/30 CRDT- 2026/04/30 11:14 PHST- 2026/01/28 00:00 [received] PHST- 2026/04/13 00:00 [accepted] PHST- 2026/06/23 18:33 [medline] PHST- 2026/04/30 12:35 [pubmed] PHST- 2026/04/30 11:14 [entrez] PHST- 2026/04/30 00:00 [pmc-release] AID - 10.1007/s12325-026-03610-7 [pii] AID - 3610 [pii] AID - 10.1007/s12325-026-03610-7 [doi] PST - ppublish SO - Adv Ther. 2026 Jul;43(7):3088-3104. doi: 10.1007/s12325-026-03610-7. Epub 2026 Apr 30. PMID- 42056522 OWN - NLM STAT- MEDLINE DCOM- 20260521 LR - 20260922 IS - 1476-4687 (Electronic) IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 653 IP - 8115 DP - 2026 May TI - GLP-1R-GIPR-PPARalpha/gamma/delta quintuple agonism corrects obesity and diabetes in mice. PG - 776-785 LID - 10.1038/s41586-026-10427-5 [doi] AB - There are increasing numbers of effective drugs to improve obesity-linked metabolic dysfunction; GLP-1R-GIPR co-agonism is effective in the management of obesity and type 2 diabetes(1,2), and lanifibranor-a nuclear-acting small-molecule triple agonist of PPARalpha, PPARgamma and PPARdelta-is in clinical phase 3 trials for the treatment of metabolic dysfunction-associated steatohepatitis(3). Here, seeking to further improve the metabolic efficacy of GLP-1R-GIPR co-agonism, we report the development of a unimolecular quintuple agonist that combines the body weight-reducing and blood glucose-lowering effects of GLP-1R-GIPR co-agonism with the insulin-sensitizing and anti-inflammatory effects of lanifibranor via its targeted delivery into GLP-1R- and GIPR-expressing cells. In vitro, GLP-1-GIP-lanifibranor is indistinguishable from GLP-1-GIP in relation to incretin receptor signalling and shows equal stimulation of insulin secretion in isolated mouse islets. In vivo, however, GLP-1-GIP-lanifibranor outperforms GLP-1R-GIPR co-agonism and semaglutide, further decreasing body weight, food intake and hyperglycaemia in obese and insulin-resistant mice through synergistic incretin and PPAR action. The metabolic action of GLP-1-GIP-lanifibranor is blunted in mice with genetic or pharmacological inhibition of GLP-1R, GIPR or PPARdelta and is absent in DIO double incretin receptor-knockout mice, collectively suggesting that GLP-1-GIP-lanifibranor has substantial therapeutic value in the treatment of obesity and diabetes. CI - (c) 2026. The Author(s). FAU - Liskiewicz, Daniela AU - Liskiewicz D AUID- ORCID: 0000-0002-5859-6316 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Institute of Physiotherapy and Health Sciences, Academy of Physical Education, Katowice, Poland. FAU - Novikoff, Aaron AU - Novikoff A AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Khalil, Ahmed AU - Khalil A AUID- ORCID: 0009-0000-2204-8636 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Akindehin, Seun AU - Akindehin S AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Campbell, Jonathan E AU - Campbell JE AUID- ORCID: 0000-0003-4358-6331 AD - Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA. AD - Duke Molecular Physiology Institute, Department of Medicine, Division of Endocrinology, Duke University, Durham, NC, USA. FAU - Candela, Pietra AU - Candela P AD - UR 2465, Laboratoire de la Barriere Hemato-Encephalique (LBHE), Universite Artois, Lens, France. FAU - Castelino, Russell L AU - Castelino RL AUID- ORCID: 0009-0008-7446-6299 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Coupland, Callum AU - Coupland C AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Culot, Maxime AU - Culot M AUID- ORCID: 0000-0001-7452-0867 AD - UR 2465, Laboratoire de la Barriere Hemato-Encephalique (LBHE), Universite Artois, Lens, France. FAU - Dodson, W Scott AU - Dodson WS AD - Indiana Biosciences Research Institute, Indianapolis, IN, USA. FAU - Douros, Jonathan D AU - Douros JD AD - Indiana Biosciences Research Institute, Indianapolis, IN, USA. AD - Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA. FAU - Embring, Hannes AU - Embring H AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Feuchtinger, Annette AU - Feuchtinger A AD - Core Facility Pathology and Tissue Analytics, Helmholtz, Munich, Germany. FAU - Finan, Brian AU - Finan B AUID- ORCID: 0000-0003-1178-8481 AD - Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA. FAU - Garcia-Caceres, Cristina AU - Garcia-Caceres C AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Medizinische Klinik und Poliklinik IV, Klinikum der Universitat, Ludwig-Maximilians-Universitat Munchen, Munich, Germany. FAU - Gao, Xiao-Bing AU - Gao XB AUID- ORCID: 0000-0002-2035-4936 AD - Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA. FAU - Gosselet, Fabien AU - Gosselet F AUID- ORCID: 0000-0002-0481-5026 AD - UR 2465, Laboratoire de la Barriere Hemato-Encephalique (LBHE), Universite Artois, Lens, France. FAU - Grandl, Gerald AU - Grandl G AUID- ORCID: 0000-0003-4456-1988 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Gutgesell, Robert M AU - Gutgesell RM AUID- ORCID: 0000-0001-6137-0468 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Institute of Computational Biology, Helmholtz Munich, Munich, Germany. FAU - Haas, Daniel T AU - Haas DT AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Jastroch, Martin AU - Jastroch M AUID- ORCID: 0000-0003-0358-3865 AD - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. FAU - Karaoglu, Ezgi AU - Karaoglu E AUID- ORCID: 0009-0003-2639-6015 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Department of Pharmacology, Experimental Therapy and Toxicology, Institute for Experimental and Clinical Pharmacology and Pharmacogenomic, Eberhard Karls University, Interfaculty Center of Pharmacogenomic and Drug Research, Tubingen, Germany. FAU - Kakimoto, Pamela AU - Kakimoto P AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Kaltenbach, Anna Cristina AU - Kaltenbach AC AUID- ORCID: 0009-0006-3196-5288 AD - Institute for Cardiovascular Prevention (IPEK), University Hospital, LMU Munich, Munich, Germany. FAU - Keuper, Michaela AU - Keuper M AUID- ORCID: 0000-0003-0319-3509 AD - Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. FAU - Kusminski, Christine M AU - Kusminski CM AUID- ORCID: 0000-0002-3671-0341 AD - Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Leander, Danielle C AU - Leander DC AUID- ORCID: 0009-0000-7507-001X AD - Duke Molecular Physiology Institute, Department of Medicine, Division of Endocrinology, Duke University, Durham, NC, USA. FAU - Liskiewicz, Arkadiusz AU - Liskiewicz A AUID- ORCID: 0000-0002-4102-5373 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland. FAU - Liu, Xue AU - Liu X AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Maity-Kumar, Gandhari AU - Maity-Kumar G AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Martinez, Sara Martinez AU - Martinez SM AUID- ORCID: 0000-0002-7258-9083 AD - CIMUS, University of Santiago de Compostela, Instituto de Investigacion Sanitaria, Santiago de Compostela, Spain. FAU - Mowery, Stephanie A AU - Mowery SA AD - Indiana Biosciences Research Institute, Indianapolis, IN, USA. AD - Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA. FAU - Nogueiras, Ruben AU - Nogueiras R AUID- ORCID: 0000-0002-9976-9930 AD - CIMUS, University of Santiago de Compostela, Instituto de Investigacion Sanitaria, Santiago de Compostela, Spain. FAU - Paisley, Marshall AU - Paisley M AD - Duke Molecular Physiology Institute, Department of Medicine, Division of Endocrinology, Duke University, Durham, NC, USA. FAU - Perez-Tilve, Diego AU - Perez-Tilve D AD - Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA. FAU - Petersen, Patricia S S AU - Petersen PSS AUID- ORCID: 0000-0003-2560-1446 AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Pfluger, Paul T AU - Pfluger PT AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Research Unit Neurobiology of Diabetes, Helmholtz Munich, Neuherberg, Germany. AD - Division of NeuroBiology of Diabetes, TUM School of Medicine and Health, Technical University Munich, Munich, Germany. FAU - Prakash, Sneha AU - Prakash S AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Steffens, Sabine AU - Steffens S AUID- ORCID: 0000-0002-6892-9751 AD - Institute for Cardiovascular Prevention (IPEK), University Hospital, LMU Munich, Munich, Germany. AD - Institute for Diabetes and Cancer (IDC), Helmholtz Diabetes Center (HDC), Helmholtz Zentrum Munchen (Helmholtz Munich), Munich, Germany. AD - DZHK (German Centre for Cardiovascular Research) Partner Site, Munich Heart Alliance, Munich, Germany. FAU - Cebrian-Serrano, Alberto AU - Cebrian-Serrano A AUID- ORCID: 0000-0002-4737-0215 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. FAU - Tost, Monica AU - Tost M AD - Core Facility Pathology and Tissue Analytics, Helmholtz, Munich, Germany. FAU - Wean, Jordan AU - Wean J AUID- ORCID: 0000-0002-9459-0093 AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - Weber, Christian AU - Weber C AD - Institute for Cardiovascular Prevention (IPEK), University Hospital, LMU Munich, Munich, Germany. AD - DZHK (German Centre for Cardiovascular Research) Partner Site, Munich Heart Alliance, Munich, Germany. AD - Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands. AD - Munich Cluster for Systems Neurology (SyNergy), Munich, Germany. FAU - Yoshida, Junichi AU - Yoshida J AUID- ORCID: 0000-0003-4175-4258 AD - Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA. FAU - Gerhart-Hines, Zachary AU - Gerhart-Hines Z AUID- ORCID: 0000-0003-2981-4991 AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Horvath, Tamas L AU - Horvath TL AUID- ORCID: 0000-0002-7522-4602 AD - Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA. AD - Department of Anatomy and Histology, University of Veterinary Medicine, Budapest, Hungary. FAU - Scherer, Philipp E AU - Scherer PE AUID- ORCID: 0000-0003-0680-3392 AD - Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Seeley, Randy J AU - Seeley RJ AUID- ORCID: 0000-0002-3721-5625 AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - DiMarchi, Richard D AU - DiMarchi RD AUID- ORCID: 0000-0003-0220-4085 AD - Department of Chemistry, Indiana University, Bloomington, IN, USA. FAU - Tschop, Matthias H AU - Tschop MH AD - Helmholtz Munich, Munich, Germany. AD - Ludwig-Maximilians-University (LMU) Munich, Munich, Germany. FAU - Krahmer, Natalie AU - Krahmer N AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. AD - German Center for Diabetes Research (DZD), Munich, Germany. AD - Metabolic Cell Architecture, Department of Molecular Life Sciences, TUM School of Life Sciences, Technical University of Munich, Munich, Germany. FAU - Knerr, Patrick J AU - Knerr PJ AD - Indiana Biosciences Research Institute, Indianapolis, IN, USA. AD - Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA. FAU - Muller, Timo D AU - Muller TD AUID- ORCID: 0000-0002-0624-9339 AD - Institute for Diabetes and Obesity, Helmholtz, Munich, Germany. timodirk.mueller@helmholtz-munich.de. AD - German Center for Diabetes Research (DZD), Munich, Germany. timodirk.mueller@helmholtz-munich.de. AD - Walther-Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany. timodirk.mueller@helmholtz-munich.de. LA - eng GR - P30 DK020572/DK/NIDDK NIH HHS/United States GR - R01 DK133140/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20260429 PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (PPAR delta) RN - 0 (PPAR alpha) RN - 0 (PPAR gamma) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Butyrates) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glp1r protein, mouse) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM EIN - Nature. 2026 Jun;654(8117):E11. doi: 10.1038/s41586-026-10619-z. PMID: 42151694 MH - Animals MH - Mice MH - *Obesity/drug therapy/metabolism MH - *PPAR delta/agonists/metabolism MH - Male MH - *PPAR alpha/agonists/metabolism MH - *PPAR gamma/agonists/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Insulin/metabolism MH - Humans MH - Blood Glucose/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Butyrates/pharmacology/therapeutic use MH - Female MH - Glucagon-Like Peptide 1/metabolism MH - Body Weight/drug effects MH - Weight Loss/drug effects MH - Mice, Inbred C57BL MH - Insulin Resistance MH - Receptors, Gastrointestinal Hormone PMC - PMC13190304 COIS- Competing interests: M.H.T. is a member of the scientific advisory board of ERX Pharmaceuticals, was a member of the Research Cluster Advisory Panel (ReCAP) of the Novo Nordisk Foundation between 2017 and 2019, attended a scientific advisory board meeting of the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, in 2016, received funding for research projects from Novo Nordisk (2016-2020) and Sanofi-Aventis (2012-2019), and was a consultant for Bionorica SE (2013-2017), Menarini Ricerche S.p.A. (2016) and Bayer Pharma AG Berlin (2016). As former director of the Helmholtz Diabetes Center and the Institute for Diabetes and Obesity at Helmholtz Zentrum Munchen (2011-2018), and since 2018, as CEO of Helmholtz Zentrum Munchen, M.H.T. has been responsible for collaborations with a multitude of companies and institutions worldwide. In this capacity, M.H.T. discussed potential projects with and has signed/signs contracts for his institute(s) and for the staff for research funding and/or collaborations with industry and academia worldwide, including but not limited to pharmaceutical corporations such as Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medigene, Arbormed, BioSyngen and others. In this role, M.H.T. was/is further responsible for commercial technology transfer activities of the institute(s), including diabetes related patent portfolios of Helmholtz Zentrum Munchen such as WO/2016/188932 A2 or WO/2017/194499 A1. M.H.T. confirms that to the best of his knowledge none of the above funding sources were involved in the preparation of this paper. T.D.M. holds stock from Eli Lilly and receives research funding from Novo Nordisk. T.D.M. has further received speaking fees from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Merck, AstraZeneca and Mercodia. J.E.C. received funding from Novo Nordisk, Eli Lilly, Merck, Structure Therapeutics and Prostasis. J.E.C. has served as an advisor/consultant in the past 12 months to Arrowhead Therapeutics, Boehringer Ingelheim, Neurocrine Biosciences, Prostasis, Protagonist and Structure Therapeutics. R.D.D. is a co-inventor on intellectual property owned by Indiana University and licensed to Novo Nordisk. R.D.D., B.F., J.D.D., S.A.M. and P.J.K. were previously employed by Novo Nordisk. J.D.D., S.A.M. and P.J.K. receive research funding from Eli Lilly and are co-founders and shareholders in Volari Therapeutics, both unrelated to this work. P.T.P. received speaker honoraria from Novo Nordisk. B.F. is a current employee of Eli Lilly. R.J.S. has received research support from Novo Nordisk, Fractyl, AstraZeneca, Congruence Therapeutics, Eli Lilly, Bullfrog AI, Glyscend Therapeutics and Amgen. R.J.S. has served as a paid consultant for Novo Nordisk, Eli Lilly, CinRx, Fractyl, Structure Therapeutics, Crinetics, Amgen, Congruence Therapeutics and Nuanced Health. R.J.S. has equity in Nuanced Health, Coro Bio. Fractyl and Rewind. The other authors declare no competing interests. EDAT- 2026/04/30 00:31 MHDA- 2026/05/21 06:32 PMCR- 2026/04/29 CRDT- 2026/04/29 23:30 PHST- 2025/04/19 00:00 [received] PHST- 2026/03/17 00:00 [accepted] PHST- 2026/05/21 06:32 [medline] PHST- 2026/04/30 00:31 [pubmed] PHST- 2026/04/29 23:30 [entrez] PHST- 2026/04/29 00:00 [pmc-release] AID - 10.1038/s41586-026-10427-5 [pii] AID - 10427 [pii] AID - 10.1038/s41586-026-10427-5 [doi] PST - ppublish SO - Nature. 2026 May;653(8115):776-785. doi: 10.1038/s41586-026-10427-5. Epub 2026 Apr 29. PMID- 42054048 OWN - NLM STAT- MEDLINE DCOM- 20260617 LR - 20260930 IS - 2168-6084 (Electronic) IS - 2168-6068 (Linking) VI - 162 IP - 6 DP - 2026 Jun 1 TI - The National Psoriasis Foundation Primer on GLP-1 Receptor Agonists in Psoriasis: A Review. PG - 619-630 LID - 10.1001/jamadermatol.2026.0859 [doi] AB - IMPORTANCE: Psoriasis is a chronic immune-mediated disease associated with cardiovascular, metabolic, musculoskeletal, psychiatric, hepatic, kidney, and pulmonary comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are approved by the US Food and Drug Administration for type 2 diabetes, obesity, cardiovascular risk reduction, chronic kidney disease, obstructive sleep apnea, and metabolic dysfunction-associated steatohepatitis-conditions common in psoriasis. Emerging evidence suggests GLP-1 RAs and dual glucose-dependent insulinotropic polypeptide/GLP-1 agonists may improve psoriatic skin disease, partly through immune modulation. If confirmed in larger randomized clinical trials, GLP-1-based therapies may offer an opportunity to address both cutaneous disease and cardiometabolic comorbidities. This primer from the US National Psoriasis Foundation Medical Board sought to provide an evidence-informed narrative synthesis and practical considerations to introduce dermatologists to GLP-1 RAs for psoriasis treatment. OBSERVATIONS: GLP-1 RAs have been associated with reductions in Psoriasis Area and Severity Index (PASI) scores, particularly in patients with obesity or type 2 diabetes. Studies report relative PASI reductions ranging from approximately 40% to 80% with parallel quality-of-life gains, although most of these studies are small (7-48 patients), short term (/= 1 obesity-related comorbidity were included. Patients on semaglutide 2.4 mg for >/= 12 months were compared with non-users (including users of other obesity medications) using propensity score weighting with residual imbalances adjusted in regression model. Outcomes included time to onset of cardiometabolic comorbidities, change in cardiometabolic biomarkers and changes in 10-year ASCVD risk score at 12 months. RESULTS: 25 783 semaglutide 2.4 mg users and 8 948 913 non-users were identified. Semaglutide 2.4 mg was associated with significantly lower risks for incident prediabetes or type 2 diabetes, type 2 diabetes only, hypertension, ASCVD, heart failure and CVD (HRs 0.45-0.75; all p < 0.05), as well as greater improvements in BMI (-4.1 kg/m(2)), SBP (-6.2 mmHg), HbA1c (-0.4%), LDL cholesterol (-7.7 mg/dL), triglycerides (-28.6 mg/dL) and HDL cholesterol (+1.9 mg/dL; all p < 0.001). At 12 months, semaglutide 2.4 mg users (N = 161) demonstrated a greater reduction in ASCVD risk score (-0.7% vs. +0.3%; between-group difference -1.0%, p < 0.001), with a decrease in the proportion at intermediate-high ASCVD risk (14.9%-9.3% vs. 17.7%-18.7%; OR 0.3 [95% CI: 0.1, 0.6], p < 0.001). CONCLUSIONS: Semaglutide 2.4 mg was associated with lower risk of multiple cardiometabolic comorbidities, favourable changes in biomarkers, and lower estimated ASCVD risk in this population. CI - (c) 2026 Novo Nordisk Inc. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ruseva, Aleksandrina AU - Ruseva A AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Michalak, Wojciech AU - Michalak W AUID- ORCID: 0000-0002-3390-0182 AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Bassan, Matthew AU - Bassan M AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Du, Ella Xiaoyan AU - Du EX AD - Analysis Group Inc, Los Angeles, California, USA. FAU - Fabricatore, Anthony AU - Fabricatore A AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Hartaigh, Briain O AU - Hartaigh BO AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Man, Theo AU - Man T AD - Analysis Group Inc, Los Angeles, California, USA. FAU - Ramasubramanian, Ramya AU - Ramasubramanian R AD - Analysis Group Inc, Los Angeles, California, USA. FAU - Shen, Pangsibo AU - Shen P AD - Analysis Group Inc, Los Angeles, California, USA. FAU - Song, Jinlin AU - Song J AD - Analysis Group Inc, Los Angeles, California, USA. FAU - Zhao, Zhenxiang AU - Zhao Z AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Lopez-Jimenez, Francisco AU - Lopez-Jimenez F AD - Mayo Clinic, Rochester, Minnesota, USA. LA - eng GR - Novo Nordisk Inc./ PT - Journal Article DEP - 20260427 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Biomarkers/blood MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Comorbidity MH - *Diabetes Mellitus, Type 2/epidemiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Obesity/blood/drug therapy/epidemiology MH - Retrospective Studies MH - *Semaglutide MH - United States/epidemiology PMC - PMC13243985 OTO - NOTNLM OT - biomarkers OT - cardiometabolic comorbidities OT - cardiovascular risk OT - obesity OT - overweight OT - semaglutide COIS- Aleksandrina Ruseva, Zhenxiang Zhao, Anthony Fabricatore, Wojciech Michalak, Briain O. Hartaigh and Matthew Bassan are employees of Novo Nordisk Inc. and hold stock/options. Jinlin Song, Ella Xiaoyan Du, Ramya Ramasubramanian, Pangsibo Shen and Theo Man are employees of Analysis Group Inc., which has received consulting fees from Novo Nordisk Inc. for this study. Francisco Lopez-Jimenez has received consulting honoraria from Novo Nordisk Inc. EDAT- 2026/04/28 06:34 MHDA- 2026/06/12 06:38 PMCR- 2026/06/08 CRDT- 2026/04/28 00:23 PHST- 2026/03/27 00:00 [revised] PHST- 2025/12/22 00:00 [received] PHST- 2026/03/28 00:00 [accepted] PHST- 2026/06/12 06:38 [medline] PHST- 2026/04/28 06:34 [pubmed] PHST- 2026/04/28 00:23 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70746 [pii] AID - 10.1111/dom.70746 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):6121-6130. doi: 10.1111/dom.70746. Epub 2026 Apr 27. PMID- 42034831 OWN - NLM STAT- MEDLINE DCOM- 20260811 LR - 20260826 IS - 1476-5497 (Electronic) IS - 0307-0565 (Print) IS - 0307-0565 (Linking) VI - 50 IP - 8 DP - 2026 Aug TI - GLP-1 agonists and changes in body mass and composition in adults with overweight or obesity with or without type 2 diabetes mellitus: a systematic review and meta-analysis. PG - 1603-1621 LID - 10.1038/s41366-026-02088-1 [doi] AB - BACKGROUND: The systematic review aimed to assess the effects of GLP-1 receptor agonists (GLP-1 RA) and dual GLP-1/GIP agonists on weight loss and body composition in individuals with overweight or obesity, with or without type 2 diabetes mellitus. METHODS: The study protocol was registered in PROSPERO (CRD420251002447). A systematic search of PubMed, Scopus, and Web of Science was conducted up to December 2024 according to PRISMA guidelines. Following the predefined inclusion and exclusion criteria, 36 studies were included in this systematic review and underwent qualitative analysis. In addition, 24 studies met the criteria for quantitative synthesis (meta-analysis). Data were pooled using random-effects models with subgroup analyses by drug type and treatment duration (3, 6, and 12 months). RESULTS: GLP-1 RA treatment consistently reduced body weight, BMI, and waist circumference across all time points. At 3 months, mean body weight decreased by approximately 9%, accompanied by marked reductions in fat mass and visceral adipose tissue. At 6 months, weight reduction averaged 5%, with semaglutide, liraglutide, and exenatide showing comparable effects, while lean mass remained largely preserved. At 12 months, weight loss persisted at around 4%, with variability between agents, most notably liraglutide. Across studies, fat mass decline predominated, whereas reductions in lean body mass were modest. CONCLUSION: GLP-1 RAs provide clinically meaningful weight loss primarily through selective fat mass reduction, with relative preservation of lean tissue, supporting their role in achieving "quality" weight loss. Differences between agents highlight the importance of individualized treatment strategies, complemented by nutritional and exercise interventions to optimize long-term outcomes. CI - (c) 2026. The Author(s). FAU - Sawicka-Gutaj, Nadia AU - Sawicka-Gutaj N AUID- ORCID: 0000-0003-1510-4702 AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. FAU - Gruszczynski, Dawid AU - Gruszczynski D AUID- ORCID: 0000-0001-9519-4183 AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. dawid.j.gruszczynski@gmail.com. AD - Doctoral School, Poznan University of Medical Sciences, Poznan, Poland. dawid.j.gruszczynski@gmail.com. FAU - Nijakowski, Kacper AU - Nijakowski K AUID- ORCID: 0000-0002-5042-5985 AD - Poznan University of Medical Sciences, Department of Conservative Dentistry, Poznan University of Medical Sciences, Poznan, Poland. FAU - Derwich-Rudowicz, Aleksandra AU - Derwich-Rudowicz A AUID- ORCID: 0000-0003-0413-2679 AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. FAU - Krenz, Michal AU - Krenz M AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. FAU - Kumar, Anita AU - Kumar A AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. FAU - Lu, Pei-Yin AU - Lu PY AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. FAU - Ruchala, Marek AU - Ruchala M AUID- ORCID: 0000-0002-6296-7220 AD - Poznan University of Medical Sciences, Chair and Department of Endocrinology, Metabolic Disorders and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260425 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy MH - *Body Composition/drug effects MH - Weight Loss/drug effects MH - Semaglutide MH - Liraglutide/therapeutic use MH - Body Mass Index MH - Hypoglycemic Agents/therapeutic use MH - Exenatide MH - Adult PMC - PMC13461353 COIS- Competing interests: The authors declare no competing interests. EDAT- 2026/04/26 05:13 MHDA- 2026/08/12 06:05 PMCR- 2026/04/25 CRDT- 2026/04/25 23:57 PHST- 2025/11/30 00:00 [received] PHST- 2026/04/04 00:00 [accepted] PHST- 2026/03/20 00:00 [revised] PHST- 2026/08/12 06:05 [medline] PHST- 2026/04/26 05:13 [pubmed] PHST- 2026/04/25 23:57 [entrez] PHST- 2026/04/25 00:00 [pmc-release] AID - 10.1038/s41366-026-02088-1 [pii] AID - 2088 [pii] AID - 10.1038/s41366-026-02088-1 [doi] PST - ppublish SO - Int J Obes (Lond). 2026 Aug;50(8):1603-1621. doi: 10.1038/s41366-026-02088-1. Epub 2026 Apr 25. PMID- 42033296 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 1945-7243 (Electronic) IS - 0046-9580 (Print) IS - 0046-9580 (Linking) VI - 63 DP - 2026 Jan-Dec TI - Mapping Global Research on Adverse Effects of GLP-1 Receptor Agonists (2006-2025): A Scopus-Based Bibliometric and Thematic Analysis. PG - 469580261441498 LID - 10.1177/00469580261441498 [doi] LID - 00469580261441498 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for managing type 2 diabetes and obesity. As their clinical applications expand, interest in their safety and adverse effects has grown. This study provides a comprehensive bibliometric analysis of global research trends, collaboration patterns, and thematic evolution on GLP-1RA-related adverse effects from 2006 to 2025. This study is a bibliometric analysis. Data were extracted from the Scopus database and analyzed using Bibliometrix (R package) and VOS viewer. Indicators assessed included publication and citation metrics, institutional productivity, and keyword co-occurrence and mapping. Correlations were evaluated using Pearson and Spearman tests, and the Durbin-Watson statistic was applied to assess the independence of residuals. A total of 1075 articles published in 389 journals were identified, authored by 6068 researchers across 85 countries. The annual growth rate was 32.06%, with no single-author papers and 34.23% international co-authorship, indicating strong global collaboration. The United States (30.5%), the United Kingdom (10.6%), and Denmark (7.8%) led in publication output and total citations. Institutional analysis identified Novo Nordisk A/S (60 papers, 11 207 citations) and Eli Lilly & Co. (45 papers, 9948 citations) as the most influential contributors. Diabetes, Obesity and Metabolism published the most articles (n = 106), followed by Diabetes Care and The Lancet Diabetes & Endocrinology. Significant correlations were found between article count and h-index (r = .677, P < .001) and total citations (r = .779, P < .001). Keyword analysis revealed 2 main thematic clusters-one pharmacological (drug safety, efficacy, liraglutide, semaglutide) and 1 clinical (human, male, female, adult)-with an emerging focus on population-specific safety since 2021. Research on GLP-1RA-related adverse effects has expanded rapidly, shaped by strong international collaboration and industry-academic partnerships. Future efforts should prioritize balanced global participation, real-world safety data, and mechanistic insights to inform clinical practice and pharmacovigilance. FAU - Abdelrahman, Riad Mohammed AU - Abdelrahman RM AUID- ORCID: 0000-0002-1157-2739 AD - National University of Sudan, Khartoum, Sudan. AD - National Ribat University, Khartoum, Sudan. FAU - Musa, Taha Hussein AU - Musa TH AD - Libyan International Medical University, Benghazi, Libya. AD - Darfur University College, Nyala, Sudan. FAU - Arbab, Ismail Adam AU - Arbab IA AD - Libyan International Medical University, Benghazi, Libya. FAU - Ahmed, Eltieb Omer AU - Ahmed EO AD - International University of Africa, Khartoum, Sudan. FAU - Gasmallah, Sahar Ibrahim AU - Gasmallah SI AD - University of Bahri, Khartoum, Sudan. FAU - Jalal, Mohammed AU - Jalal M AD - Karary University, Khartoum, Sudan. FAU - Ahmed, Wafaa Ramadan AU - Ahmed WR AD - Libyan International Medical University, Benghazi, Libya. AD - Assiut University, Egypt. FAU - Fadul, Khalid Hamid AU - Fadul KH AD - International University of Africa, Khartoum, Sudan. AD - Sudan Medical Specialization Board, Khartoum, Sudan. LA - eng PT - Journal Article DEP - 20260425 PL - United States TA - Inquiry JT - Inquiry : a journal of medical care organization, provision and financing JID - 0171671 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Bibliometrics MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - Obesity/drug therapy PMC - PMC13129305 OTO - NOTNLM OT - GLP-1ras OT - adverse drug reactions OT - bibliometric analysis OT - citation network analysis OT - glucagon-like peptide-1 receptor agonists OT - pharmacovigilance OT - type 2 diabetes mellitus COIS- Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2026/04/26 05:10 MHDA- 2026/04/26 05:11 PMCR- 2026/04/25 CRDT- 2026/04/25 08:13 PHST- 2026/04/26 05:11 [medline] PHST- 2026/04/26 05:10 [pubmed] PHST- 2026/04/25 08:13 [entrez] PHST- 2026/04/25 00:00 [pmc-release] AID - 10.1177_00469580261441498 [pii] AID - 10.1177/00469580261441498 [doi] PST - ppublish SO - Inquiry. 2026 Jan-Dec;63:469580261441498. doi: 10.1177/00469580261441498. Epub 2026 Apr 25. PMID- 42025665 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260820 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 288 DP - 2026 Aug TI - Glucagon-Like Peptide-1 Receptor Agonists and Risk of Systemic and Ocular Vascular Complications in Patients With Type 2 Diabetes and Diabetic Retinopathy. PG - 131-142 LID - S0002-9394(26)00219-9 [pii] LID - 10.1016/j.ajo.2026.04.021 [doi] AB - PURPOSE: To evaluate the association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) use on macrovascular and microvascular outcomes in patients with type 2 diabetes (T2D) and diabetic retinopathy (DR)-a high-risk group often excluded from clinical trials. DESIGN: Retrospective, population-based cohort study. PARTICIPANTS: Adults aged >/=18 years with T2D (with hemoglobin A1c of >/=6.5%) and a pre-existing diagnosis of DR from the TriNetX research network database between January 1, 2015, and December 31, 2022. METHODS: The study included 173,216 adults with T2D, all of whom had DR, adjusted for baseline characteristics through propensity score matching (PSM) based on whether the individuals received at least 2 prescriptions of a GLP-1 RA (semaglutide, dulaglutide, liraglutide, exenatide, tirzepatide, or lixisenatide) at least 6 months apart. MAIN OUTCOME MEASURES: Cox proportional hazard regression models were used to evaluate the association between GLP-1 RAs and the risk of incident macrovascular and microvascular complications over a 2-year follow-up period. RESULTS: After PSM, 30,613 individuals (mean [SD] age, 61.6 [11.4] years; 53.2% were females) were prescribed GLP-1 RAs. Patients on GLP-1 RAs had a decreased risk of myocardial infarctions (MIs; hazard ratio [HR], 0.65; 95% CI, 0.61-0.69), coronary artery revascularization procedures (HR, 0.75; 95% CI, 0.67-0.84), heart failure exacerbations (HR, 0.78; 95% CI, 0.76-0.81), ischemic strokes (HR, 0.78; 95% CI, 0.74-0.83), lower extremity amputations (HR, 0.78; 95% CI, 0.69-0.88), acute kidney injuries (AKI; HR, 0.68; 95% CI, 0.66-0.71), or the need for renal replacement therapy (RRT; HR, 0.40; 95% CI, 0.36-0.43). Fewer individuals also progressed to proliferative diabetic retinopathy (HR, 0.78; 95% CI, 0.71-0.86), experienced retinal vein occlusions (RVOs; HR, 0.70; 95% CI, 0.61-0.80), or developed neovascular glaucoma (HR, 0.65; 95% CI, 0.47-0.89); no association was observed for retinal artery occlusions (RAOs; HR, 0.85; 95% CI, 0.57-1.26) or cases of non-arteritic ischemic optic neuropathy (NAION; HR, 0.88; 95% CI, 0.54-1.44). CONCLUSIONS: In patients with T2D and pre-existing DR, the use of GLP-1 RAs was associated with a reduced risk of major macrovascular and microvascular complications, including those directly affecting the retina. Future studies are needed to assess the extent to which GLP-1 RAs benefit long-term outcomes. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Shah, Jui AU - Shah J AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Makwana, Bhargav AU - Makwana B AD - Division of Cardiovascular Medicine (B.M., S.S.D., S.G.), Department of Medicine, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Panchal, Krisha AU - Panchal K AD - Division of Ophthalmology (K.P., D.J.R.), Department of Surgery, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Patel, Vahin AU - Patel V AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Patel, Tirth AU - Patel T AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Khadke, Sumanth AU - Khadke S AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Verma, Anushka AU - Verma A AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Vivekanandan, Suja AU - Vivekanandan S AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Kong, Yixin AU - Kong Y AD - From the Department of Medicine (J.S., V.P., T.P., S.K., A.V., S.V., Y.K.), UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Upadhyay, Jagriti AU - Upadhyay J AD - Division of Endocrinology (J.U.), Department of Medicine, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Dani, Sourbha S AU - Dani SS AD - Division of Cardiovascular Medicine (B.M., S.S.D., S.G.), Department of Medicine, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Ramsey, Kathryn Moynihan AU - Ramsey KM AD - Department of Medicine (K.M.R.), Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. FAU - Ganatra, Sarju AU - Ganatra S AD - Division of Cardiovascular Medicine (B.M., S.S.D., S.G.), Department of Medicine, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA. FAU - Ramsey, David J AU - Ramsey DJ AD - Division of Ophthalmology (K.P., D.J.R.), Department of Surgery, UMass Chan - Lahey School of Medicine, Burlington, Massachusetts, USA; Department of Ophthalmology (D.J.R.), Tufts University School of Medicine, Boston, Massachusetts, USA. Electronic address: David.J.Ramsey@lahey.org. LA - eng PT - Journal Article DEP - 20260421 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glycated Hemoglobin) RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Blood Glucose) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 839I73S42A (Liraglutide) RN - 0 (hemoglobin A1c protein, human) RN - 74O62BB01U (lixisenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Retinopathy/drug therapy/diagnosis MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - Tirzepatide/therapeutic use MH - Semaglutide MH - Glycated Hemoglobin/metabolism MH - Aged MH - Risk Factors MH - Exenatide/therapeutic use MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Blood Glucose/metabolism MH - Incidence MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Liraglutide/therapeutic use MH - Proportional Hazards Models MH - *Diabetic Angiopathies/epidemiology MH - Glucagon-Like Peptide 1/analogs & derivatives EDAT- 2026/04/24 00:32 MHDA- 2026/07/08 18:50 CRDT- 2026/04/23 22:42 PHST- 2025/08/11 00:00 [received] PHST- 2026/02/26 00:00 [revised] PHST- 2026/04/19 00:00 [accepted] PHST- 2026/07/08 18:50 [medline] PHST- 2026/04/24 00:32 [pubmed] PHST- 2026/04/23 22:42 [entrez] AID - S0002-9394(26)00219-9 [pii] AID - 10.1016/j.ajo.2026.04.021 [doi] PST - ppublish SO - Am J Ophthalmol. 2026 Aug;288:131-142. doi: 10.1016/j.ajo.2026.04.021. Epub 2026 Apr 21. PMID- 42023428 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260901 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Efficacy, Safety and PK of Once-Daily Oral Semaglutide 25 mg for Obesity With and Without Type 2 Diabetes in Comparison With Subcutaneous Semaglutide 2.4 mg: A Model-Informed Drug Development Approach. PG - 5982-5991 LID - 10.1111/dom.70769 [doi] AB - AIMS: Semaglutide has previously been approved for weight management and cardiovascular disease as a subcutaneous formulation, and more recently also as an oral formulation. However, there is limited information across oral dose levels, and there are no studies for the 25 mg dose in people with obesity and type 2 diabetes (T2D). To fulfil health authority approval requirements, population pharmacokinetic and exposure-response analyses were used to extrapolate efficacy and safety data from subcutaneous to oral semaglutide. MATERIALS AND METHODS: Once-daily oral semaglutide 25 mg was approved for obesity treatment based on historical semaglutide data and the OASIS programme. Two studies were simulated: a modelled/virtual Phase 2 trial to establish efficacy across different oral semaglutide dose levels, and a modelled/virtual Phase 3 trial to assess efficacy in a population with overweight/obesity and T2D. RESULTS: Most participants (82.2%) treated with oral semaglutide 25 mg in OASIS 4 achieved exposure levels within the same range as participants treated with once-weekly subcutaneous semaglutide 2.4 mg in STEP 1. In the simulated studies, oral semaglutide 25 mg provided significantly greater weight reduction compared with placebo, for the trial product estimand and treatment policy estimand, respectively, in those with overweight/obesity and T2D (9.4% and 7.8%), and in those with overweight/obesity without T2D (16.3% and 14.7%). CONCLUSIONS: Estimated exposure levels and efficacy observed with oral semaglutide 25 mg were similar to those obtained with subcutaneous semaglutide 2.4 mg, supporting application of oral semaglutide 25 mg to treat individuals with overweight/obesity, with/without T2D. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Overgaard, Rune Viig AU - Overgaard RV AUID- ORCID: 0000-0001-7095-4270 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Birkhan, Oscar AU - Birkhan O AUID- ORCID: 0000-0002-7554-5035 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rathor, Naveen AU - Rathor N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sparso, Thomas AU - Sparso T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Strathe, Anders AU - Strathe A AUID- ORCID: 0000-0002-1598-2591 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - University of Toronto, York University, McMaster University, Wharton Weight Management Clinic, Burlington, Ontario, Canada. FAU - Rubino, Domenica AU - Rubino D AD - Washington Center for Weight Management and Research, Arlington, Virginia, USA. LA - eng GR - Novo Nordisk A/S/ PT - Comparative Study PT - Journal Article DEP - 20260423 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Anti-Obesity Agents/administration & dosage/adverse effects/pharmacokinetics/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Drug Administration Schedule MH - Drug Development MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics/adverse effects MH - Injections, Subcutaneous MH - *Obesity/drug therapy/complications MH - *Semaglutide/administration & dosage/adverse effects/pharmacokinetics/therapeutic use MH - Treatment Outcome MH - Weight Loss/drug effects PMC - PMC13243942 OTO - NOTNLM OT - GLP-1 analogue OT - pharmacokinetics OT - semaglutide OT - type 2 diabetes OT - weight management COIS- Domenica Rubino has received grants/contracts from Amgen, AstraZeneca, Boehringer Ingelheim, Novo Nordisk and Tern Pharmaceuticals; has held consultancy roles at AbbVie, AstraZeneca, Boehringer Ingelheim, Cytoki Pharma, Eli Lilly, Neuraly, Neurocrine Biosciences, NodThera, Novo Nordisk, Pfizer, Regeneron Pharmaceuticals, Roche, Shionogi and Summit Clinical Trial Networks; and is a shareholder of AbbVie. Sean Wharton has participated in advisory boards for or received honoraria from AbbVie, Amgen, AstraZeneca, Bausch Health Canada, Boehringer Ingelheim, Eli Lilly, Merck, Metsera, NGX, Novo Nordisk and Regeneron Pharmaceuticals; conducted clinical trials/research for Amgen, AstraZeneca, Bausch Health Canada, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk and Pfizer; has held academic or other roles at McMaster University, York University, University of Toronto and Obesity Canada. Rune Viig Overgaard, Oscar Birkhan, Naveen Rathor, Thomas Sparso and Anders Strathe are employees and shareholders at Novo Nordisk A/S. EDAT- 2026/04/23 06:31 MHDA- 2026/06/12 06:39 PMCR- 2026/06/08 CRDT- 2026/04/23 05:22 PHST- 2026/04/01 00:00 [revised] PHST- 2026/01/15 00:00 [received] PHST- 2026/04/03 00:00 [accepted] PHST- 2026/06/12 06:39 [medline] PHST- 2026/04/23 06:31 [pubmed] PHST- 2026/04/23 05:22 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70769 [pii] AID - 10.1111/dom.70769 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5982-5991. doi: 10.1111/dom.70769. Epub 2026 Apr 23. PMID- 42020128 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 16 IP - 4 DP - 2026 Apr 22 TI - LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial. PG - e116911 LID - 10.1136/bmjopen-2026-116911 [doi] LID - e116911 AB - INTRODUCTION: Obesity is a global public health issue, with its effects a particular issue in Kuwait. Advances in pharmaceutical treatment (eg, glucagon-like peptide-1s) offer an effective solution, with the magnitude of weight lost something to celebrate. However, this level of weight loss also results in dramatic reductions in lean mass, reflecting loss of muscle mass and muscle strength which can predispose people to sarcopenia. This is a particular issue in people with type 2 diabetes in Kuwait, where the prevalence of muscle weakness is extremely high. Solutions to mitigate this loss of muscle mass and strength are needed, with a pragmatic resistance exercise intervention and increasing dietary protein intake having potential. This trial aims to determine whether resistance exercise and/or protein intake can preserve muscle mass and improve physical function in people with obesity initiating semaglutide/tirzepatide therapy. METHODS AND ANALYSIS: This single-centre, 6-month, randomised controlled trial at Dasman Diabetes Institute will enrol 232 adults with obesity, randomised (1:1:1:1) to control, resistance exercise, protein supplementation or combined resistance exercise and protein in conjunction with semaglutide or tirzepatide therapy. Resistance exercise will be home-based and involve three sessions per week, progressing from one to three sets targeting major muscle groups. Protein supplementation will target 1.6 g/kg/day via dietary adjustment and protein products. Assessments at baseline and 6 months will include MRI measured quadriceps cross-sectional area (primary outcome), plus measures of secondary outcomes of MRI measured liver fat content and stiffness and intramuscular fat, body composition (dual energy X-ray absorptiometry), strength, physical function, dietary assessment, physical activity levels, sleep patterns, quality of life, glycaemic control and metabolic biomarkers. ETHICS AND DISSEMINATION: The study has received ethical approval from the Dasman Diabetes Institute Ethical Review Committee (HR-RA-2025-01, 19 February 2025) and is registered at ClinicalTrials.gov (NCT06885736, 26 June 2025). Written informed consent will be obtained from all participants, with no financial compensation provided. Data will be reported in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines, ensuring participant anonymity. Findings will be disseminated through peer-reviewed publications and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT06885736. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Alawadhi, Ameenah A AU - Alawadhi AA AUID- ORCID: 0000-0003-4333-7319 AD - Clinical Care Research and Trials, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Alroudhan, Dherar AU - Alroudhan D AD - Education and Training Unit, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Alsaeed, Dalal J AU - Alsaeed DJ AD - Clinical Care Research and Trials, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Almarshad, Bashayer W AU - Almarshad BW AD - Clinical Care Research and Trials, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Alshehabi, Dalal H AU - Alshehabi DH AD - Clinical Care Research and Trials, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Allahou, Badreya A AU - Allahou BA AD - Nutrition Unit, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Mashankar, Anant AU - Mashankar A AD - Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait. FAU - Al Ozairi, Ebaa AU - Al Ozairi E AD - Medical Division, Dasman Diabetes Institute, Kuwait City, Kuwait ebaa.alozairi@dasmaninstitute.org. FAU - Gray, Stuart AU - Gray S AUID- ORCID: 0000-0001-8969-9636 AD - Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. LA - eng SI - ClinicalTrials.gov/NCT06885736 PT - Clinical Trial Protocol PT - Journal Article DEP - 20260422 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Composition MH - Diabetes Mellitus, Type 2/complications MH - Kuwait MH - Muscle Strength MH - Muscle, Skeletal MH - *Obesity/therapy/complications/drug therapy MH - Randomized Controlled Trials as Topic MH - *Resistance Training/methods MH - Sarcopenia/prevention & control MH - *Semaglutide/therapeutic use MH - *Tirzepatide/therapeutic use MH - Weight Loss PMC - PMC13110620 OTO - NOTNLM OT - DIABETES & ENDOCRINOLOGY OT - Exercise OT - NUTRITION & DIETETICS OT - Obesity OT - SPORTS MEDICINE COIS- Competing interests: None declared. EDAT- 2026/04/23 00:31 MHDA- 2026/04/23 00:32 PMCR- 2026/04/22 CRDT- 2026/04/22 21:13 PHST- 2026/04/23 00:32 [medline] PHST- 2026/04/23 00:31 [pubmed] PHST- 2026/04/22 21:13 [entrez] PHST- 2026/04/22 00:00 [pmc-release] AID - bmjopen-2026-116911 [pii] AID - 10.1136/bmjopen-2026-116911 [doi] PST - epublish SO - BMJ Open. 2026 Apr 22;16(4):e116911. doi: 10.1136/bmjopen-2026-116911. PMID- 42020100 OWN - NLM STAT- MEDLINE DCOM- 20260610 LR - 20260617 IS - 1442-9071 (Electronic) IS - 1442-6404 (Linking) VI - 54 IP - 4 DP - 2026 May-Jun TI - Is There a Causal Link Between GLP-1 Receptor Agonists and Non-Arteritic Anterior Ischaemic Optic Neuropathy? A Critique of the Clinical Evidence. PG - 554-564 LID - 10.1111/ceo.70096 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for managing Type 2 diabetes and obesity, with well-documented and significant cardiometabolic benefits. Recent observational reports and pharmacovigilance data have raised concerns about a possible association between GLP-1RAs-particularly semaglutide- and non-arteritic anterior ischaemic optic neuropathy (NAION), a rare cause of sudden vision loss. While case reports and spontaneous reporting systems suggest a potential signal, these sources are subject to confounding and reporting bias. Observational studies offer mixed findings, with some Scandinavian registry studies reporting elevated risks while large electronic health record EHR) analyses from the U.S. and multi-national databases have reported null or weak associations. Meta-analyses of randomised controlled trials- the gold standard for causal inference- currently lack power to reliably assess this rare outcome but suggest, at most, a comparatively moderate increase in risk (e.g., odds ratio of 2-3). Overall while a causal link cannot be excluded, the numerous studies that assert an 'association' between GLP-1 RA exposure and NAION should motivate larger pooled analyses of RCTs with adjudicated ocular outcome to definitely assess risk. CI - (c) 2026 The Author(s). Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists. FAU - Danesh-Meyer, Helen V AU - Danesh-Meyer HV AD - Department of Ophthalmology, University of Auckland, Auckland, New Zealand. FAU - Rizzo, Joseph F 3rd AU - Rizzo JF 3rd AD - Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. AD - Neuro-Ophthalmology Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. LA - eng PT - Journal Article PT - Review DEP - 20260422 PL - Australia TA - Clin Exp Ophthalmol JT - Clinical & experimental ophthalmology JID - 100896531 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - *Hypoglycemic Agents/adverse effects MH - *Optic Neuropathy, Ischemic/chemically induced MH - Risk Factors MH - Semaglutide EDAT- 2026/04/23 00:31 MHDA- 2026/06/10 11:44 CRDT- 2026/04/22 21:02 PHST- 2026/02/02 00:00 [revised] PHST- 2025/10/08 00:00 [received] PHST- 2026/02/06 00:00 [accepted] PHST- 2026/06/10 11:44 [medline] PHST- 2026/04/23 00:31 [pubmed] PHST- 2026/04/22 21:02 [entrez] AID - 10.1111/ceo.70096 [doi] PST - ppublish SO - Clin Exp Ophthalmol. 2026 May-Jun;54(4):554-564. doi: 10.1111/ceo.70096. Epub 2026 Apr 22. PMID- 42013575 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1205-7541 (Electronic) IS - 0008-4212 (Linking) VI - 104 DP - 2026 Jan 1 TI - Cost-effectiveness of incretin therapies: a Canadian lens on diabetes, obesity, and emerging indications. PG - 1-7 LID - 10.1139/cjpp-2025-0248 [doi] AB - Incretin therapies have emerged as key interventions for glycemic control and weight reduction and are now among Canada's costliest outpatient drug classes. This review synthesizes current clinical and economic evidence on the cost-effectiveness of incretin-based therapies. These include glucagon-like peptide-1 receptor agonists (GLP-1RAs; e.g., semaglutide) and dual agonists (e.g., tirzepatide) targeting both glucose-dependent insulinotropic polypeptide and GLP-1 receptors, in patients with type 2 diabetes mellitus or for weight loss. We review data from clinical trials and recent Canadian and international economic models, identify emerging indications, and discuss limitations in current health-technology assessment frameworks. Implications for Canadian reimbursement are highlighted, with attention to price, patient selection, and outcome considerations. FAU - Awadalla, Luke AU - Awadalla L AD - Western University, London, ON, Canada. RINGGOLD: 6221 FAU - Iskander, Siena AU - Iskander S AD - Queen's University, Kingston, ON, Canada. FAU - Chu, Cherry AU - Chu C AD - Women's College Hospital Research and Innovation Institute, Toronto, ON, Canada. RINGGOLD: 7938 FAU - Tadrous, Mina AU - Tadrous M AUID- ORCID: 0000-0003-1911-6129 AD - Women's College Hospital Research and Innovation Institute, Toronto, ON, Canada. RINGGOLD: 7938 AD - Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada. RINGGOLD: 7985 LA - eng PT - Journal Article PT - Review PL - Canada TA - Can J Physiol Pharmacol JT - Canadian journal of physiology and pharmacology JID - 0372712 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Incretins/economics/therapeutic use MH - *Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Obesity/drug therapy/economics MH - Canada MH - *Hypoglycemic Agents/economics/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Tirzepatide MH - Animals MH - Cost-Effectiveness Analysis OTO - NOTNLM OT - incretin therapies OT - GLP-1RAs OT - cost-effectiveness OT - obesity OT - semaglutide OT - tirzepatide COIS- Mina Tadrous is supported by a Tier 2 Canada Research Chair in Pharmaceutical Policy and Real-world Evidence. He also reports receiving funding from the Ontario Ministry of Health and Canada's Drug Agency unrelated to this work. All other authors report no Conflicts of Interest. EDAT- 2026/04/22 00:37 MHDA- 2026/05/19 18:32 CRDT- 2026/04/21 18:03 PHST- 2026/05/19 18:32 [medline] PHST- 2026/04/22 00:37 [pubmed] PHST- 2026/04/21 18:03 [entrez] AID - 10.1139/cjpp-2025-0248 [doi] PST - ppublish SO - Can J Physiol Pharmacol. 2026 Jan 1;104:1-7. doi: 10.1139/cjpp-2025-0248. PMID- 42010367 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260901 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Associations of Semaglutide With Skeletal Outcomes in People With Obesity, With and Without Type 2 Diabetes: A Target Trial Emulation. PG - 5834-5847 LID - 10.1111/dom.70786 [doi] AB - AIMS: To evaluate the associations between semaglutide initiation and long-term skeletal outcomes in people with obesity, stratified by type 2 diabetes (T2D) status, using target trial emulation. MATERIALS AND METHODS: This retrospective cohort study used the TriNetX federated electronic health record network. People with obesity initiating semaglutide were matched 1:1 via propensity score matching (215 covariates) to those initiating active comparators or usual care. The with-T2D cohort (n = 19 824-93 519 matched pairs per comparison) was followed for 3 years; the without-T2D cohort (n = 10 323-56 225 pairs) for 2 years. The primary outcome was major osteoporotic fracture (MOF). Secondary outcomes included osteoporosis diagnosis; exploratory outcomes included osteoarthritis and gout. RESULTS: In the with-T2D cohort, semaglutide initiation was associated with a lower risk of MOF compared with empagliflozin (HR 0.69; 95% CI 0.61-0.77), glipizide (HR 0.72; 0.63-0.83) and usual care (HR 0.84; 0.76-0.93). In the without-T2D cohort, no significant associations with MOF were observed across any comparison (all p > 0.05). Osteoporosis risk did not differ significantly in most comparisons in either cohort. Exploratory analyses of osteoarthritis and gout showed inconsistent patterns across comparators. CONCLUSIONS: Among people with obesity and T2D, semaglutide initiation was associated with a lower risk of MOF over 3 years compared with other glucose-lowering agents and usual care. This association was not observed in people with obesity without T2D. These findings support further investigation of the skeletal effects of GLP-1 receptor agonists. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Huang, Yu-Nan AU - Huang YN AUID- ORCID: 0000-0003-1688-1685 AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Tsou, Min-Yu AU - Tsou MY AD - Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan. FAU - Li, Pin-Hung AU - Li PH AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Chen, Jo-Ching AU - Chen JC AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Chen, Shao-Chia AU - Chen SC AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Hsieh, Hao-I AU - Hsieh HI AUID- ORCID: 0009-0004-2637-6185 AD - School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. AD - Department of Education, National Taiwan University Hospital, Taipei, Taiwan. FAU - Meyerowitz-Katz, Gideon AU - Meyerowitz-Katz G AD - School of Health and Society, University of Wollongong, Wollongong, Australia. FAU - Liu, Yen-Liang AU - Liu YL AD - Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan. AD - Master Program for Biomedical Engineering, China Medical University, Taichung, Taiwan. FAU - Su, Pen-Hua AU - Su PH AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. LA - eng GR - CSH-2026-A-009/Chung Shan Medical University Hospital/ GR - CSH-2026-C-030/Chung Shan Medical University Hospital/ GR - CSH-2026-F-003/Chung Shan Medical University Hospital/ GR - NSTC 113-2314-B-040-026-MY2/National Science and Technology Council/ GR - NSTC 114-2622-B-04-001/National Science and Technology Council/ GR - NSTC 113-2124-M-039-002/National Science and Technology Council/ GR - NSTC 114-2124-M-039-001/National Science and Technology Council/ GR - NHRI-EX114-11206EC/National Health Research Institutes/ GR - NHRI-EX115-11206EC/National Health Research Institutes/ PT - Journal Article DEP - 20260420 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/complications/drug therapy/epidemiology MH - *Osteoporotic Fractures/epidemiology/prevention & control MH - Retrospective Studies MH - *Semaglutide/therapeutic use PMC - PMC13243989 OTO - NOTNLM OT - GLP-1 receptor agonists OT - major osteoporotic fractures OT - obesity OT - osteoporosis OT - semaglutide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/04/21 13:11 MHDA- 2026/06/11 12:41 PMCR- 2026/06/08 CRDT- 2026/04/20 23:47 PHST- 2026/03/30 00:00 [revised] PHST- 2026/01/13 00:00 [received] PHST- 2026/04/10 00:00 [accepted] PHST- 2026/06/11 12:41 [medline] PHST- 2026/04/21 13:11 [pubmed] PHST- 2026/04/20 23:47 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70786 [pii] AID - 10.1111/dom.70786 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5834-5847. doi: 10.1111/dom.70786. Epub 2026 Apr 20. PMID- 42009015 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20261001 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 14 IP - 6 DP - 2026 Jun TI - Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial. PG - 450-462 LID - S2213-8587(25)00402-4 [pii] LID - 10.1016/S2213-8587(25)00402-4 [doi] AB - BACKGROUND: The combination of cagrilintide and semaglutide has been shown in global studies to induce reductions in bodyweight. We assessed the efficacy and safety of a fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg versus semaglutide 2.4 mg for weight management in an east Asian population. METHODS: This double-blind, parallel-group, phase 3a trial (REDEFINE 5) was conducted across 21 sites (community, hospital) in Japan and one site in Taiwan. We included participants aged at least 18 years with a BMI of at least 27 kg/m(2) and at least two obesity-related complications, or with a BMI of at least 35 kg/m(2) and at least one obesity-related complication (per the Japan Society for the Study of Obesity guidelines), with or without type 2 diabetes. Participants were randomly assigned (1:1) to once-weekly subcutaneous injections of cagrilintide-semaglutide or semaglutide (both escalated to 2.4 mg), plus lifestyle intervention, for 68 weeks. Randomisation was done centrally using an interactive web response system and stratified according to planned CT scan, BMI of at least 35 kg/m(2), and type 2 diabetes status. Participants, site staff, investigators, and study funder were all masked to active study treatments. The primary endpoint was relative change in bodyweight from baseline to week 68. Efficacy analyses were done in all participants who underwent randomisation, using the trial product estimand (ie, assuming the treatment was taken as intended, regardless of dose) as the primary estimand. Missing data at week 68 were imputed. Safety analyses were done in all participants who underwent randomisation and received at least one dose of trial product. This trial is registered with ClinicalTrials.gov (NCT05813925) and is complete. FINDINGS: Between April 3, 2023, and Sept 15, 2023, we screened 355 individuals; 331 were randomly assigned to cagrilintide-semaglutide (n=164) or semaglutide (n=167). 226 (68%) participants were male and 105 (32%) were female; 80 (24%) had type 2 diabetes. 17 (10%) participants discontinued cagrilintide-semaglutide and ten (6%) discontinued semaglutide. The estimated mean change in bodyweight from baseline to week 68 was -18.4% (SE 0.7) in the cagrilintide-semaglutide group versus -11.9% (0.7) in the semaglutide group (estimated treatment difference [ETD] -6.5 percentage points [95% CI -8.4 to -4.6]; p<0.0001). Adverse events were reported by 143 (87%) of 164 participants in the cagrilintide-semaglutide group and 141 (84%) of 167 in the semaglutide group, the most common of which were gastrointestinal disorders (87 [53%] of 164 participants in the cagrilintide-semaglutide group vs 85 [51%] of 167 in the semaglutide group). One death was reported in the semaglutide 2.4 mg group, which was not judged to be treatment related by the investigator. INTERPRETATION: These findings support the efficacy and safety of cagrilintide-semaglutide for weight management in individuals from east Asia with overweight or obesity, with or without type 2 diabetes. FUNDING: Novo Nordisk. TRANSLATIONS: For the Japanese and Mandarin translations of the abstract see Supplementary Materials section. CI - Copyright (c) 2026 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Yamauchi, Toshimasa AU - Yamauchi T AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: tyamau@m.u-tokyo.ac.jp. FAU - Becker, Niels-Peter AU - Becker NP AD - Novo Nordisk, Soborg, Denmark. FAU - Hagemann, Christoffer Andersen AU - Hagemann CA AD - Novo Nordisk, Soborg, Denmark. FAU - Huang, Kuo-Chin AU - Huang KC AD - Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan. FAU - Kiyosue, Arihiro AU - Kiyosue A AD - Tokyo-Eki Center-building Clinic, Tokyo, Japan. FAU - Lim, Soo AU - Lim S AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea. FAU - Onishi, Yukiko AU - Onishi Y AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Tokyo, Japan. FAU - Kosuvaripalli, Ananda AU - Kosuvaripalli A AD - Novo Nordisk, Global Business Services, Bangalore, India. FAU - Takano, Tomoko AU - Takano T AD - Novo Nordisk Pharma, Tokyo, Japan. FAU - Ishigaki, Yasushi AU - Ishigaki Y AD - Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Yahaba, Japan. CN - REDEFINE 5 study group LA - eng SI - ClinicalTrials.gov/NCT05813925 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20260417 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Double-Blind Method MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Japan/epidemiology MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - *Semaglutide/administration & dosage/therapeutic use MH - Taiwan/epidemiology MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use COIS- Declaration of interests AKi received honoraria for lectures from Novo Nordisk. AKo, CAH, N-PB, and TT are employees of Novo Nordisk. SL received research grants from Merck Sharp & Dohme, Novo Nordisk, and LG Chem; and honoraria as a consultant or speaker for AstraZeneca, Boehringer Ingelheim, Abbott, LG Chem, Daewoong Pharmaceutical, Chong Kun Dang Pharmaceutical, and Novo Nordisk. TY received research grants from Novo Nordisk, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Ono Pharmaceutical, Sumitomo Pharma, Nipro, MED MIRAI, Boehringer Ingelheim Japan, Kowa Pharmaceuticals, Nitto Boseki, Asahi Mutual Life Insurance, and Sanwa Kagaku Kenkyusho; and received honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbott Japan, Daiichi Sankyo, Sanofi, Viatris, Medtronic Japan, Astellas Pharma, AstraZeneca, Terumo, Taisho Pharmaceutical, Amgen, ARKRAY Marketing, Bayer Yakuhin, Lindsay Advice, Kyowa Kirin, Sanwa Kagaku Kenkyusho, GSK, Ono Pharmaceutical, Merck Sharp & Dohme (Merck), Sumitomo Pharma, Teijin, Boehringer Ingelheim Japan, Novo Nordisk, Eli Lilly, Kowa Pharmaceuticals, Nipro, Mitsubishi Tanabe Pharma, Amgen, Dexcom Japan, Nitto Boseki, and ViewSend ICT. YI received honoraria for lectures from Novo Nordisk, Eli Lilly Japan, Sumitomo Pharma, and Kowa Pharmaceuticals; and received research grants from Novo Nordisk and Sanofi. YO received honoraria for lectures from: Novo Nordisk, Eli Lilly Japan, Sumitomo Pharma, AstraZeneca, and Mitsubishi Tanabe Pharma. K-CH declares no competing interests. EDAT- 2026/04/21 13:11 MHDA- 2026/05/13 00:29 CRDT- 2026/04/20 18:52 PHST- 2025/10/14 00:00 [received] PHST- 2025/12/16 00:00 [revised] PHST- 2025/12/16 00:00 [accepted] PHST- 2026/05/13 00:29 [medline] PHST- 2026/04/21 13:11 [pubmed] PHST- 2026/04/20 18:52 [entrez] AID - S2213-8587(25)00402-4 [pii] AID - 10.1016/S2213-8587(25)00402-4 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2026 Jun;14(6):450-462. doi: 10.1016/S2213-8587(25)00402-4. Epub 2026 Apr 17. PMID- 42002107 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1573-2517 (Electronic) IS - 0165-0327 (Linking) VI - 407 DP - 2026 Aug 15 TI - Depressed mood and suicidal thoughts reporting with GLP-1 receptor agonists in type 2 diabetes: A WHO VigiBase study. PG - 121802 LID - S0165-0327(26)00653-1 [pii] LID - 10.1016/j.jad.2026.121802 [doi] AB - INTRODUCTION: Evidence regarding depression and suicidality with glucagon-like peptide-1 receptor agonists (GLP-1RAs) remains inconsistent, particularly in patients with type 2 diabetes mellitus (T2DM) and underlying affective vulnerability. METHODS: We conducted a disproportionality analysis of the WHO VigiBase (2010-2024), including T2DM patients. Reports of depressed mood and suicidal thoughts associated with GLP-1RAs were compared with other glucose-lowering medications. Analyses incorporated age, sex, time-to-onset, dose, comorbid depression, and concomitant antidepressant use. Adjusted reporting odds ratios (RORs) and a Weibull time-to-event model were applied. Causality was explored using Bradford Hill criteria. RESULTS: A total of 1,183,817 adverse events related to GLP-1RA were identified. Depressed mood and suicidality signals were observed with semaglutide, liraglutide, and tirzepatide (adjusted ROR(0.25): 2.13, 1.52, 1.07) and (adjusted ROR(0.25): 6.76, 2.43, 3.39), respectively. No signal was identified for suicide attempts or completed suicide. Absolute reporting frequencies were low. Concomitant antidepressant use was 2.3-5 times more frequent, and comorbid depression 25%-120% higher, compared with other glucose-lowering medications. Median time-to-onset was 96 days. Survival analysis demonstrated an early increase in reporting followed by stabilization over time. Adjustment for antidepressant use modestly attenuated associations. CONCLUSION: GLP-1RAs were associated with increased reporting of depressed mood and suicidal thoughts, particularly in patients receiving concomitant antidepressants. These findings support a patient-centered model in which underlying affective vulnerability or reporting factors drive reported mood symptoms rather than a uniform drug-specific effect. GLP-1RAs remain clinically valuable, but psychiatric monitoring during early treatment in vulnerable patients is warranted. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Aboukaoud, Mohammed AU - Aboukaoud M AD - Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. Electronic address: mohammed.aboukaoud@sheba.health.gov.il. FAU - Hoch, Bosmat AU - Hoch B AD - Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel. FAU - Weiser, Mark AU - Weiser M AD - Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. FAU - Amiaz, Revital AU - Amiaz R AD - Drora and Pinchas Zachai Division of Psychiatry, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel. LA - eng PT - Journal Article DEP - 20260417 PL - Netherlands TA - J Affect Disord JT - Journal of affective disorders JID - 7906073 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Tirzepatide/adverse effects MH - Semaglutide MH - *Suicidal Ideation MH - Male MH - *Depression/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Middle Aged MH - Aged MH - Liraglutide/adverse effects/therapeutic use OTO - NOTNLM OT - Completed suicide OT - Depressed mood OT - Depression OT - GLP-1RA OT - Suicidal attempt OT - Suicidal thoughts COIS- Declaration of competing interest The authors, Mohammed Aboukaoud, Bosmat Hoch, Mark Weiser, and Revital Amiaz, have no conflicts of interest to declare and no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/04/20 13:10 MHDA- 2026/05/02 00:33 CRDT- 2026/04/19 19:22 PHST- 2026/01/20 00:00 [received] PHST- 2026/03/30 00:00 [revised] PHST- 2026/04/13 00:00 [accepted] PHST- 2026/05/02 00:33 [medline] PHST- 2026/04/20 13:10 [pubmed] PHST- 2026/04/19 19:22 [entrez] AID - S0165-0327(26)00653-1 [pii] AID - 10.1016/j.jad.2026.121802 [doi] PST - ppublish SO - J Affect Disord. 2026 Aug 15;407:121802. doi: 10.1016/j.jad.2026.121802. Epub 2026 Apr 17. PMID- 41999297 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260903 IS - 1365-2060 (Electronic) IS - 0785-3890 (Print) IS - 0785-3890 (Linking) VI - 58 IP - 1 DP - 2026 Dec TI - GLP-1 receptor agonists in stroke prevention: a narrative review on emerging therapeutic frontiers. PG - 2660386 LID - 10.1080/07853890.2026.2660386 [doi] LID - 2660386 AB - OBJECTIVES: To evaluate the current evidence supporting the cerebrovascular protective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with type 2 diabetes mellitus (T2DM), and to outline their mechanisms of action in stroke prevention. METHODS: A narrative review was conducted by synthesising data from cardiovascular outcome trials, meta-analyses and mechanistic studies involving GLP-1RAs such as semaglutide, liraglutide and dulaglutide. The search included literature on ischaemic stroke incidence, molecular pathways and clinical outcomes associated with GLP-1RA therapy. RESULTS: GLP-1RAs exhibit multiple protective mechanisms, including anti-inflammatory, antioxidant, neuroprotective and endothelial-stabilising effects. Long-acting agents demonstrate superior efficacy in reducing nonfatal and ischaemic stroke risk, with relative risk reductions ranging from 15% to 39% across major trials. These benefits are observed independent of glycemic control and appear most prominent in patients with preserved renal function and shorter diabetes duration. In contrast, short-acting exendin-based GLP-1RAs show limited cerebrovascular benefit. Treatment response may vary based on factors such as stroke subtype, baseline vascular risk and comorbidities. CONCLUSION: GLP-1RAs offer significant promise as adjunctive pharmacotherapy for stroke prevention in individuals with T2DM. Their multifactorial benefits extend beyond glucose regulation and may influence clinical outcomes through systemic vascular and neuroprotective mechanisms. However, inconsistencies in trial outcomes and limited data in non-diabetic or high-risk populations underscore the need for targeted stroke-specific studies. Personalised treatment approaches and broader risk stratification may optimise their use in cerebrovascular disease management. FAU - Chikatimalla, Rahul AU - Chikatimalla R AUID- ORCID: 0000-0003-2967-1425 AD - Kamineni Institute of Medical Sciences, Narketpally, India. FAU - Shah, Ashka AU - Shah A AUID- ORCID: 0009-0004-6648-2396 AD - GMERS Medical College, Gotri, Vadodara, India. FAU - Shah, Twinkle AU - Shah T AUID- ORCID: 0009-0001-7143-2930 AD - GMERS Medical College, Valsad, India. FAU - Perry, Griffin AU - Perry G AUID- ORCID: 0009-0002-2716-6556 AD - Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. FAU - Banker, Himanshi AU - Banker H AUID- ORCID: 0009-0004-3824-1755 AD - Maulana Azad Medical College, New Delhi, India. FAU - Aggarwal, Kanishk AU - Aggarwal K AUID- ORCID: 0009-0005-7518-446X AD - Dayanand Medical College and Hospital, Ludhiana, Punjab, India. FAU - Jain, Rohit AU - Jain R AUID- ORCID: 0000-0002-9101-2351 AD - Division of Hospital Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20260418 PL - England TA - Ann Med JT - Annals of medicine JID - 8906388 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/pharmacology MH - *Stroke/prevention & control/etiology MH - Liraglutide/therapeutic use/pharmacology MH - Immunoglobulin Fc Fragments/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Recombinant Fusion Proteins PMC - PMC13094292 OAB - GLP-1 receptor agonist (GLP-1RA) therapy should be incorporated into a broad approach for risk reduction for stroke in patients with type 2 DM, especially in situations where prevention of ischaemic stroke is of high importance.Long-acting GLP-1 receptor agonists (e.g., semaglutide and dulaglutide) are preferred over shorter-acting preparations for their cerebrovascular protective effects, properties of which are more consistent and beneficial for the risk of ischaemia.GLP-1RA therapy could provide a special advantage to patients with multiple risk factors for cardiometabolic diseases such as obesity, hypertension, dyslipidemia and documented atherosclerotic cardiovascular disease.On the other hand, the neuroprotective properties of GLP-1RAs, which occur through anti-inflammatory, antioxidant, endothelial-stabilising or mitochondrial-protective actions, provide rationale for the use.Treatment should be individualised for renal function, tolerance, potential for compliance, cost and accessibility. This allows for maximal long-term cerebrovascular benefits. OABL- eng OTO - NOTNLM OT - Stroke OT - cerebrovascular circulation OT - glucagon-like peptide 1 receptor agonists OT - neuroprotection OT - type 2 diabetes mellitus COIS- No potential conflict of interest was reported by the authors. EDAT- 2026/04/19 04:18 MHDA- 2026/04/19 04:19 PMCR- 2026/04/18 CRDT- 2026/04/18 08:53 PHST- 2026/04/19 04:19 [medline] PHST- 2026/04/19 04:18 [pubmed] PHST- 2026/04/18 08:53 [entrez] PHST- 2026/04/18 00:00 [pmc-release] AID - 2660386 [pii] AID - 10.1080/07853890.2026.2660386 [doi] PST - ppublish SO - Ann Med. 2026 Dec;58(1):2660386. doi: 10.1080/07853890.2026.2660386. Epub 2026 Apr 18. PMID- 41994910 OWN - NLM STAT- MEDLINE DCOM- 20260613 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Use of Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease: Scandinavian Cohort Study. PG - 5767-5778 LID - 10.1111/dom.70760 [doi] AB - AIMS: To investigate the association between use of GLP-1 receptor agonists and incident Parkinson's disease. MATERIAL AND METHODS: Cohort study using data from nationwide registers in Denmark, Norway and Sweden and an active-comparator, new-user design. We included 158 961 new users of GLP-1 receptor agonists and 188 065 new users of sulfonylureas, aged 45 years or older. Liraglutide accounted for 72.9% of GLP-1 receptor agonist follow-up time, followed by semaglutide (13.4%), exenatide (7.3%), dulaglutide (5.1%) and lixisenatide (1.3%). The primary outcome was incident Parkinson's disease, defined as a first-ever diagnosis of Parkinson's disease (ICD-10 G20) or Parkinson's disease dementia (ICD-10 F02.3) in national patient registers. Cox regression with propensity score weighting was used to estimate hazard ratios (HRs) and control for confounding. RESULTS: Mean age was 65 years and 43% were female. Incidence rates for Parkinson's disease were 5.2 and 8.0 per 10 000 person-years among GLP-1 receptor agonist and sulfonylurea users, respectively (adjusted HR 0.81 [95% CI 0.68-0.96]). Results were consistent in a 2-year lag-time analysis (HR 0.84 [95% CI 0.70-1.02]) after excluding or censoring users of DPP-4 inhibitors at cohort entry or during follow-up (HR 0.74 [95% CI 0.60-0.93]) and in subgroup analyses by sex and age. CONCLUSION: In this large observational cohort study, use of GLP-1 receptor agonists compared with sulfonylureas was associated with a lower risk of incident Parkinson's disease. These findings support a potential neuroprotective role of GLP-1 receptor agonists, though replication in additional studies is needed. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Engstrom, Arvid AU - Engstrom A AUID- ORCID: 0000-0001-7047-0217 AD - Clinical Epidemiology Division, Department of Medicine, Centre for Pharmacoepidemiology, Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Svanstrom, Henrik AU - Svanstrom H AD - Clinical Epidemiology Division, Department of Medicine, Centre for Pharmacoepidemiology, Solna, Karolinska Institutet, Stockholm, Sweden. AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. FAU - Hviid, Anders AU - Hviid A AD - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. AD - Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, Pharmacovigilance Research Center, University of Copenhagen, Copenhagen, Denmark. FAU - Eliasson, Bjorn AU - Eliasson B AD - Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. AD - The Swedish National Diabetes Register, Vastra Gotalandsregionen, Gothenburg, Sweden. FAU - Gudbjornsdottir, Soffia AU - Gudbjornsdottir S AD - The Swedish National Diabetes Register, Vastra Gotalandsregionen, Gothenburg, Sweden. AD - Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Wintzell, Viktor AU - Wintzell V AD - Clinical Epidemiology Division, Department of Medicine, Centre for Pharmacoepidemiology, Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Hveem, Kristian AU - Hveem K AD - Department of Public Health and Nursing, Faculty of Medicine and Health Science, HUNT Center for Molecular and Clinical Epidemiology, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. AD - Faculty of Medicine, HUNT Research Center, NTNU-Norwegian University of Science and Technology, Levanger, Norway. FAU - Jonasson, Christian AU - Jonasson C AD - Department of Public Health and Nursing, Faculty of Medicine and Health Science, HUNT Center for Molecular and Clinical Epidemiology, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. AD - Faculty of Medicine, HUNT Research Center, NTNU-Norwegian University of Science and Technology, Levanger, Norway. FAU - Melbye, Mads AU - Melbye M AD - Department of Public Health and Nursing, Faculty of Medicine and Health Science, HUNT Center for Molecular and Clinical Epidemiology, NTNU-Norwegian University of Science and Technology, Trondheim, Norway. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. AD - Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA. AD - Danish Cancer Institute, Copenhagen, Denmark. FAU - Ueda, Peter AU - Ueda P AUID- ORCID: 0000-0002-3275-8743 AD - Clinical Epidemiology Division, Department of Medicine, Centre for Pharmacoepidemiology, Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Pasternak, Bjorn AU - Pasternak B AD - Clinical Epidemiology Division, Department of Medicine, Centre for Pharmacoepidemiology, Solna, Karolinska Institutet, Stockholm, Sweden. LA - eng GR - Vetenskapsradet/ GR - Lundbeck Foundation/ GR - Region Stockholm/ GR - Novo Nordisk Fonden/ GR - Dr. Margaretha Nilsson's Foundation for Medical Research/ GR - Karolinska Institutet/ GR - Strategic Research Area Epidemiology programme/ GR - Independent Research Foundation Denmark/ GR - Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse/ GR - Danish Cancer Society/ PT - Journal Article DEP - 20260417 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Insulin Secretagogues) RN - 839I73S42A (Liraglutide) RN - 74O62BB01U (lixisenatide) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sulfonylurea Compounds) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cohort Studies MH - Denmark/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Exenatide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Immunoglobulin Fc Fragments/therapeutic use MH - Incidence MH - Insulin Secretagogues MH - Liraglutide/therapeutic use MH - Norway/epidemiology MH - *Parkinson Disease/epidemiology/prevention & control MH - Recombinant Fusion Proteins/therapeutic use MH - Registries MH - Semaglutide/therapeutic use MH - Sulfonylurea Compounds/therapeutic use MH - Sweden/epidemiology MH - Glucagon-Like Peptide 1/analogs & derivatives PMC - PMC13243990 OTO - NOTNLM OT - GLP-1 analogue OT - disease prevention OT - observational study OT - pharmaco-epidemiology COIS- The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and have the following declarations. Dr. Christian Jonasson is an employee of NordicRWE. Dr. Bjorn Eliasson reports personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Mundipharma, Navamedic, Novo Nordisk and Sanofi outside the submitted work. Dr. Henrik Svanstrom is a former employee of IQVIA. Prof. Anders Hviid is a scientific advisory board member of VAC4EU. The other authors declare no conflicts of interest. EDAT- 2026/04/17 13:25 MHDA- 2026/06/15 11:33 PMCR- 2026/06/08 CRDT- 2026/04/17 06:03 PHST- 2026/03/26 00:00 [revised] PHST- 2025/12/19 00:00 [received] PHST- 2026/03/27 00:00 [accepted] PHST- 2026/06/15 11:33 [medline] PHST- 2026/04/17 13:25 [pubmed] PHST- 2026/04/17 06:03 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70760 [pii] AID - 10.1111/dom.70760 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5767-5778. doi: 10.1111/dom.70760. Epub 2026 Apr 17. PMID- 41994903 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260826 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Semaglutide Treatment in Young Adults Living With Type 2 Diabetes: A Post Hoc Analysis From the SUSTAIN and PIONEER Clinical Trials. PG - 5787-5802 LID - 10.1111/dom.70770 [doi] AB - AIMS: Young adults (aged 40- 50 years). Selected safety outcomes were assessed, focusing on serious adverse events (SAEs) and gastrointestinal SAEs from the programmes. RESULTS: Findings indicate a reduction in HbA(1c) levels and BW in participants across all age subgroups that were treated with semaglutide, particularly in young adults versus other age subgroups. The proportion of participants experiencing SAEs was overall comparable between semaglutide treatment and comparators across age subgroups and administration route. CONCLUSIONS: Semaglutide shows notable and consistent efficacy in reducing HbA(1c) and BW across all age subgroups with T2D, including young adults. Effective glucose- and weight-lowering interventions in people living with T2D at an earlier stage in life may reduce the high risk of future health complications associated with developing T2D as a younger adult. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Zaccardi, Francesco AU - Zaccardi F AD - Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Arslan, Ecenur Guder AU - Arslan EG AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bardtrum, Lars AU - Bardtrum L AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Goldney, Jonathan AU - Goldney J AUID- ORCID: 0000-0001-8553-8296 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. FAU - Ising, Erik AU - Ising E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Priyadarshini, Prachi AU - Priyadarshini P AD - Novo Nordisk GBS, Bengaluru, India. FAU - Slater, Tommy AU - Slater T AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. LA - eng GR - Novo Nordisk/ GR - NIHR201165/National Institute for Health and Care Research (NIHR)/ GR - NIHR Leicester Biomedical Research Centre/ GR - 223512/Z/21/Z/Wellcome Trust Leicestershire Healthcare Inequalities Improvement Doctoral Training Programme/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20260417 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Adult MH - Female MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Glycated Hemoglobin/analysis MH - Male MH - Middle Aged MH - Young Adult MH - Treatment Outcome MH - Body Weight/drug effects MH - Blood Glucose/drug effects MH - Age Factors MH - Administration, Oral MH - Injections, Subcutaneous PMC - PMC13243996 OTO - NOTNLM OT - GLP-1 OT - cohort study OT - glycaemic control OT - meta-analysis OT - semaglutide OT - type 2 diabetes COIS- F.Z. acted as a consultant/advisor for Servier, Menarini, Daiichi Sankyo, and Adelphi Real World. M.J.D. has acted as a consultant/advisor and speaker for Eli Lilly, Novo Nordisk, and Sanofi, has attended advisory boards for Abbvie, Amgen, AstraZeneca, Biomea Fusion, Carmot/Roche, Sanofi, Zealand Pharma, Regeneron, GSK, and EktaH, and as a speaker for AstraZeneca and Boehringer Ingelheim. She has received grants from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. P.P., L.B., and E.I. are employees and shareholders of Novo Nordisk. E.G.A. was an employee of Novo Nordisk at the time of drafting this manuscript. V.R.A. has institutional contracts with Amgen, Applied Therapeutics, AstraZenaca, Biommea, Boehringer Ingelheim, Corcept, Eli Lilly, Fractyl, Novo Nordisk, Pfizer, Recordati, Rhythm, and Servier. V.R.A. has also served as a consultant for Baim Institute for Clinical Research, Mediflix, Roche, and Sanofi. EDAT- 2026/04/17 13:25 MHDA- 2026/06/13 00:38 PMCR- 2026/06/08 CRDT- 2026/04/17 06:03 PHST- 2026/04/01 00:00 [revised] PHST- 2026/01/16 00:00 [received] PHST- 2026/04/06 00:00 [accepted] PHST- 2026/06/13 00:38 [medline] PHST- 2026/04/17 13:25 [pubmed] PHST- 2026/04/17 06:03 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70770 [pii] AID - 10.1111/dom.70770 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5787-5802. doi: 10.1111/dom.70770. Epub 2026 Apr 17. PMID- 41992023 OWN - NLM STAT- MEDLINE DCOM- 20260608 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Cardiometabolic Profiles of Oral and Subcutaneous Glucagon-Like Peptide-1 Receptor Mono-Agonists in Adults With Overweight or Obesity: A Systematic Review and Network Meta-Analysis. PG - 5761-5766 LID - 10.1111/dom.70742 [doi] AB - AIMS: To characterize the cardiometabolic profiles of oral and subcutaneous glucagon-like peptide-1 (GLP-1) receptor mono-agonists in adults with overweight or obesity, with or without type 2 diabetes (T2D), using network meta-analysis (NMA). MATERIALS AND METHODS: PubMed, Embase and CENTRAL were searched (January 2014-November 2025) for randomized controlled trials (RCTs) evaluating GLP-1 receptor mono-agonists (semaglutide, liraglutide and orforglipron) in adults with overweight or obesity. The primary outcome was the cardiometabolic efficacy index (CEI), a ranking-based composite (0 to 1) summarizing performance across seven cardiometabolic endpoints: total body weight loss percentage, triglycerides, HDL cholesterol-C, LDL-C, waist circumference, HbA1c and systolic blood pressure. Secondary outcomes included treatment effects for each individual CEI component. RESULTS: Nineteen RCTs (N = 13 117) were analysed. Semaglutide 7.2 mg achieved the highest CEI (0.86), followed by orforglipron 36 mg (bioequivalent to Foundayo 17.2 mg tablet) (0.68) and semaglutide 2.4 mg (0.66), all exhibiting placebo-adjusted weight reductions >/= 10%. CEI rankings were generally consistent across T2D and non-T2D subgroups. Among oral formulations in non-T2D adults, OFG 36 mg showed a CEI comparable to oral semaglutide 25 mg (0.67 vs 0.63). CONCLUSIONS: Higher-dose GLP-1 receptor mono-agonists, particularly semaglutide 7.2 mg and orforglipron 36 mg (Foundayo 17.2 mg tablet), demonstrated the most consistent multidimensional cardiometabolic improvements, although domain-specific differences were observed across agents. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Lu, Ying AU - Lu Y AD - Ividence Inc, Newark, Delaware, USA. FAU - Chen, Jiajie AU - Chen J AD - Ividence Inc, Newark, Delaware, USA. FAU - Guo, Yuqing AU - Guo Y AD - Ividence Inc, Newark, Delaware, USA. FAU - Ding, Hao AU - Ding H AD - Ividence Inc, Newark, Delaware, USA. FAU - Liu, Yu-Lun AU - Liu YL AD - UT Southwestern Medical Center, Peter O'Donnell Jr. School of Public Health, Dallas, Texas, USA. FAU - Van Name, Michelle A AU - Van Name MA AD - Pediatric Endocrinology, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Sharifi, Mona AU - Sharifi M AD - Section of General Pediatrics, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Lu, Yuan AU - Lu Y AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut, USA. FAU - Chen, Yong AU - Chen Y AUID- ORCID: 0000-0003-0835-0788 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260416 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (orforglipron) RN - 0 (Oxadiazoles) RN - 0 (Fluorine Compounds) SB - IM MH - Adult MH - Humans MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Glucagon-Like Peptide-1 Receptor MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Injections, Subcutaneous MH - Liraglutide/administration & dosage MH - *Obesity/drug therapy/complications/metabolism MH - *Overweight/drug therapy/complications/metabolism MH - Randomized Controlled Trials as Topic MH - Semaglutide/administration & dosage MH - Weight Loss/drug effects MH - Oxadiazoles MH - Fluorine Compounds PMC - PMC13243969 OTO - NOTNLM OT - GLP-1 analogue OT - antiobesity drug OT - network meta-analysis OT - weight management COIS- The authors declare no conflicts of interest. EDAT- 2026/04/17 13:25 MHDA- 2026/06/08 19:42 PMCR- 2026/06/08 CRDT- 2026/04/16 23:36 PHST- 2026/03/11 00:00 [revised] PHST- 2026/02/02 00:00 [received] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/06/08 19:42 [medline] PHST- 2026/04/17 13:25 [pubmed] PHST- 2026/04/16 23:36 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70742 [pii] AID - 10.1111/dom.70742 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5761-5766. doi: 10.1111/dom.70742. Epub 2026 Apr 16. PMID- 41991422 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260715 IS - 1557-8194 (Electronic) IS - 0011-5029 (Linking) VI - 72 IP - 7 DP - 2026 Jul TI - Approved weight loss drugs for obesity with a thorough emphasis on GLP-1 agonist medications: A systematic review. PG - 102113 LID - S0011-5029(26)00051-9 [pii] LID - 10.1016/j.disamonth.2026.102113 [doi] AB - BACKGROUND: Obesity is a worldwide health concern linked to cardiometabolic comorbidities such as type 2 diabetes, hypertension, dyslipidemia, and heart disease. The management of obesity using pharmacotherapy, especially with GLP-1 receptor agonists and dual incretin agents, has proven successful not only for weight loss but also for gaining control of the metabolic components of the disease. Thus, it is pertinent to analyse the GLP-1-based anti-obesity medications to examine cardiometabolic efficacy and safety using weight loss, glycemic control, cardiometabolic, gastro-intestinal tolerability, and serious adverse events as the primary variables. METHODS: The systematic review, according to the PRISMA 2020 guidelines, analyzed the GLP-1-based anti-obesity pharmacotherapies. Five databases were utilized to extract information from research studies related to the demographic and procedural framework, weight loss, cardiometabolic efficacy, and safety. RESULTS: A total of 15 studies evaluated GLP-1-based and related anti-obesity therapies, including semaglutide, liraglutide, tirzepatide, dulaglutide, and dual GIP/GLP-1 receptor agonists. Participants were predominantly female (up to 79.3%), with mean age 22.4-59.8 years, BMI 29.3-43.0 kg/m(2), and common comorbidities including hypertension, dyslipidemia, type 2 diabetes, cardiovascular disease, metabolic syndrome, OSA, MASLD, insulin resistance, and PCOS. Weight loss was dose-dependent: semaglutide 2.4 mg/wk. -14.9% to -15.2%, tirzepatide 15-18.5%, liraglutide -8.8-11%, dulaglutide -1.3-2.0%, and dual GIP/GLP-1 therapy up to 21.5%. Glycemic and cardiometabolic improvements included HbA1c reductions up to -1.78%, SBP reductions -5.28 to -7.8 mmHg, and LDL-C decreases up to -11 mg/dL. Gastrointestinal adverse events were common (nausea 14.7-62%, vomiting 3-30.3%, diarrhoea 5-34.9%), while serious events, pancreatitis, and gallbladder complications were rare, with treatment discontinuation generally <15%. CONCLUSION: GLP-1-based and dual GIP/GLP-1 therapies provide substantial, dose-dependent weight loss with additional cardiometabolic benefits. They are generally well tolerated, with mostly mild gastrointestinal adverse events and rare serious complications, supporting their efficacy and safety in managing obesity. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - Gunasekaran, Praveen AU - Gunasekaran P AD - Internal Medicine, Madras Medical College, Chennai, India. FAU - Inban, Pugazhendi AU - Inban P AD - Internal Medicine, St Mary's General Hospital and St Clare's Health, USA. Electronic address: ipugazhendi@primehealthcare.com. FAU - Agrawal, Ashita AU - Agrawal A AD - Internal Medicine, St Mary's General Hospital and St Clare's Health, USA. FAU - Thai, Andy AU - Thai A AD - Internal Medicine, Alameda Health System, Highland Hospital, Oakland, USA. FAU - Aravazhi, Prasanna Sakthi AU - Aravazhi PS AD - Internal Medicine, Madras Medical College, Chennai, India. FAU - Tariq, Halla AU - Tariq H AD - Internal Medicine, Mountain View Regional Medical Center, Las Cruces, New Mexico, USA. FAU - Prajjwal, Priyadarshi AU - Prajjwal P AD - Internal Medicine, Bharati Vidyapeeth University Medical College, Pune, India. FAU - John, Jobby AU - John J AD - Internal Medicine, Dr. Somervell Memorial CSI Medical College and Hospital, India. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260415 PL - United States TA - Dis Mon JT - Disease-a-month : DM JID - 0370657 RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Incretins) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Obesity/drug therapy MH - *Anti-Obesity Agents/therapeutic use MH - Semaglutide MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Weight Loss/drug effects MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Liraglutide/therapeutic use MH - Female MH - Incretins/therapeutic use MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Diabetes Mellitus, Type 2 MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins OTO - NOTNLM OT - Anti-obesity agents OT - Drug toxicity OT - Gastrointestinal agents OT - Hypoglycemic agents OT - Incretins OT - Obesity OT - Weight loss COIS- Declaration of competing interest The Author(s) declare(s) that there is no conflict of interest. EDAT- 2026/04/17 13:25 MHDA- 2026/05/28 00:29 CRDT- 2026/04/16 21:56 PHST- 2026/05/28 00:29 [medline] PHST- 2026/04/17 13:25 [pubmed] PHST- 2026/04/16 21:56 [entrez] AID - S0011-5029(26)00051-9 [pii] AID - 10.1016/j.disamonth.2026.102113 [doi] PST - ppublish SO - Dis Mon. 2026 Jul;72(7):102113. doi: 10.1016/j.disamonth.2026.102113. Epub 2026 Apr 15. PMID- 41987895 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Efficacy and safety of novel antidiabetic drugs in patients with type 2 diabetes and chronic kidney disease: a network meta-analysis. PG - 1750615 LID - 10.3389/fendo.2026.1750615 [doi] LID - 1750615 AB - BACKGROUND: A number of novel antidiabetic drugs have been developed. These drugs include sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is). However, the optimal medication for individuals with type 2 diabetes mellitus (T2DM) and comorbid chronic kidney disease (CKD) has not been established. To this end, this study was conducted to compare specific novel antidiabetic drugs regarding efficacy and safety. METHODS: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for publications dated as of July 9, 2025. Cochrane risk of bias tool version 2.0 (RoB 2.0) was applied to measure the quality of the publications, and R 4.2.2 and Stata 15.1 were used to execute a Bayesian network meta-analysis (NMA). Primary outcomes encompassed major adverse cardiovascular events (MACEs), composite renal outcomes, and all-cause mortality (ACM). Secondary outcomes comprised adverse events (AEs), hypoglycemia, and cardiovascular death. RESULTS: This NMA incorporated 30 studies, involving 39,844 participants with T2DM and comorbid CKD. The interventions were ranked by performance in various outcomes using the surface under the cumulative ranking curve (SUCRA) values. Sotagliflozin ranked first in reducing MACEs (SUCRA: 90.57%). Empagliflozin ranked first in improving composite renal outcomes (SUCRA: 89.76%) and reducing ACM (SUCRA: 72.38%). Canagliflozin ranked first in reducing AEs (SUCRA: 83.37%). Dapagliflozin + exenatide ranked first in reducing hypoglycemic events (SUCRA: 77.74%). Semaglutide ranked first in reducing cardiovascular mortality (SUCRA: 89.46%). CONCLUSION: Novel antidiabetic drugs offer benefits for patients with T2DM and comorbid CKD. However, the optimal intervention varies for different outcomes. Further clinical studies are anticipated to validate these findings. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251146144. CI - Copyright (c) 2026 Zhu, Wang, Zhang, Yang, Zhao, Li, Shi, Zhao and Ma. FAU - Zhu, Xiaojian AU - Zhu X AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Wang, Xingjia AU - Wang X AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Zhang, Peiru AU - Zhang P AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Yang, Zhuoshi AU - Yang Z AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Zhao, Na AU - Zhao N AD - Department of Endocrinology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Li, Jiameng AU - Li J AD - The First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Shi, Yunze AU - Shi Y AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Zhao, Yichen AU - Zhao Y AD - Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. FAU - Ma, Jian AU - Ma J AD - Department of Endocrinology, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260331 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Semaglutide MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Treatment Outcome PMC - PMC13076170 OTO - NOTNLM OT - antidiabetic drugs OT - cardiovascular outcomes OT - chronic kidney disease OT - meta-analysis OT - renal outcomes OT - type 2 diabetes COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/04/16 13:09 MHDA- 2026/04/16 13:10 PMCR- 2026/03/31 CRDT- 2026/04/16 04:24 PHST- 2025/11/20 00:00 [received] PHST- 2026/03/13 00:00 [revised] PHST- 2026/03/16 00:00 [accepted] PHST- 2026/04/16 13:10 [medline] PHST- 2026/04/16 13:09 [pubmed] PHST- 2026/04/16 04:24 [entrez] PHST- 2026/03/31 00:00 [pmc-release] AID - 10.3389/fendo.2026.1750615 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Mar 31;17:1750615. doi: 10.3389/fendo.2026.1750615. eCollection 2026. PMID- 41986942 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20260813 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 9 IP - 3 DP - 2026 May TI - A Multicentre, Prospective, Non-Interventional Single-Arm Study Investigating the Impact of Once-Daily Oral Semaglutide in a Real-World Adult Population With Type 2 Diabetes in Mexico. PG - e70219 LID - 10.1002/edm2.70219 [doi] LID - e70219 AB - BACKGROUND: To investigate the oral semaglutide use among Mexican adults with type 2 diabetes. METHODS: PIONEER REAL was a multinational, open-label study evaluating oral semaglutide in patients without prior injectable glucose-lowering treatment. This analysis focuses on data from Mexico. RESULTS: Of 177 patients, 139 (78.5%) completed the study and 111 (62.7%) remained on treatment at the end. The mean (SD) age was 54.0 (10.96) years, 57.6% were women, 59.3% had obesity, and 44.6% had a medical history of cardiovascular disease. The average T2D duration was 5.7 years (SD 6.45), with mean HbA1c at 8.1% (SD 1.85). At week 38, mean HbA1c had decreased to 6.8% (estimated mean [SE] change in HbA1c, -1.3% [0.11]; p < 0.0001), and body weight had decreased from 87.8 kg (19.34) to 85.3 kg (estimated mean [SE] change in body weight, -4.3 kg [0.56]; p < 0.0001), as had waist circumference (estimated mean [SE] change, -3.7 cm [0.54]; p < 0.0001). Additionally, satisfaction with treatment increased over time. Only 6.2% of patients had adverse events leading to withdrawal of semaglutide. CONCLUSIONS: According to this real-world study, starting oral semaglutide treatment in Mexico is associated with notable decreases in both HbA1c levels and body weight among patients with type 2 diabetes. Satisfaction with treatment also improved significantly. Moreover, the safety profile is consistent with that of previous studies. TRIAL REGISTRATION: ClinicalTrials.gov registration NCT04601753. CI - (c) 2026 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Gonzalez-Galvez, Guillermo AU - Gonzalez-Galvez G AD - Instituto Jalisciense de Investigacion en Diabetes y Obesidad, Guadalajara, Mexico. FAU - Garnica-Cuellar, Juan C AU - Garnica-Cuellar JC AD - Endocrinology Division, Centro Medico Nacional 20 de Noviembre, Institute for Social Security and Services for State, Mexico City, Mexico. AD - Diabetes and Obesity Workgroup, Sociedad Mexicana de Nutricion y Endocrinologia, Mexico City, Mexico. FAU - Colin-Garcia, Miguel Angel AU - Colin-Garcia MA AD - Colegio Mexicano de Obesidad y Nutricion A.C. Jose Maria Rico, Mexico City, Mexico. AD - Hospital Angeles Santa Monica, Mexico City, Mexico. FAU - Ferreira-Hermosillo, Aldo AU - Ferreira-Hermosillo A AUID- ORCID: 0000-0002-5159-9856 AD - Unidad de Investigacion Medica en Enfermedades Endocrinas, Centro Medico Nacional Siglo XXI, IMSS, Mexico City, Mexico. FAU - Jimenez-Ramos, Silvia A AU - Jimenez-Ramos SA AD - CICEJ Centro de Investigacion Clinica Endocrinologica de Jalisco, Guadalajara, Mexico. FAU - Contreras-Sandoval, Aleida Y AU - Contreras-Sandoval AY AD - Novo Nordisk Mexico, Mexico City, Mexico. FAU - Cruz-Puente, Patricia AU - Cruz-Puente P AD - Novo Nordisk Mexico, Mexico City, Mexico. FAU - Duarte-Vega, Manuel AU - Duarte-Vega M AD - Division de Medicina Interna, Hospital Civil Juan I. Menchaca, Guadalajara, Mexico. LA - eng SI - ClinicalTrials.gov/NCT04601753 GR - Novo Nordisk Pharma/ PT - Journal Article PT - Multicenter Study PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/blood MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Mexico/epidemiology MH - Male MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Prospective Studies MH - Administration, Oral MH - Glycated Hemoglobin/analysis MH - Blood Glucose/analysis MH - Adult MH - Aged MH - Treatment Outcome PMC - PMC13083220 OTO - NOTNLM OT - Mexico OT - diabetes treatment satisfaction OT - glycaemic control OT - oral semaglutide OT - real-world evidence OT - type 2 diabetes OT - weight loss COIS- Medical writing and editorial assistance were provided by Content Ed Net (Madrid, Spain). Editorial management was conducted by Reprints Unlimited Mexico. These services were funded by Novo Nordisk, in accordance with Good Publication Practice guidelines (www.ismpp.org/gpp-2022). Aleida Y. Contreras-Sandoval and Patricia Cruz-Puente are employees of Novo Nordisk. The rest of the authors declare not competing interests for this publication. EDAT- 2026/04/16 13:09 MHDA- 2026/04/16 13:10 PMCR- 2026/04/15 CRDT- 2026/04/16 00:13 PHST- 2026/03/13 00:00 [revised] PHST- 2026/01/16 00:00 [received] PHST- 2026/03/18 00:00 [accepted] PHST- 2026/04/16 13:10 [medline] PHST- 2026/04/16 13:09 [pubmed] PHST- 2026/04/16 00:13 [entrez] PHST- 2026/04/15 00:00 [pmc-release] AID - EDM270219 [pii] AID - 10.1002/edm2.70219 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2026 May;9(3):e70219. doi: 10.1002/edm2.70219. PMID- 41984016 OWN - NLM STAT- MEDLINE DCOM- 20260610 LR - 20260922 IS - 1558-3597 (Electronic) IS - 0735-1097 (Print) IS - 0735-1097 (Linking) VI - 87 IP - 21 DP - 2026 Jun 2 TI - Comparative Cardiovascular Effectiveness of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Diabetes Mellitus. PG - 2963-2977 LID - S0735-1097(26)05724-4 [pii] LID - 10.1016/j.jacc.2026.02.5123 [doi] AB - BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2Is) have established cardiovascular benefits for patients with type 2 diabetes mellitus (T2DM), with similar class-level effectiveness found in previous studies. However, real-world comparative effectiveness assessments of individual agents remain limited. OBJECTIVES: The goal of this study was to compare the cardiovascular effectiveness of individual GLP-1RAs and SGLT2Is. METHODS: We conducted a multinational, retrospective, new-user active-comparator cohort study using 10 U.S. and non-U.S. administrative claims and electronic health record databases. The study included 1,245,211 adults with T2DM receiving metformin who initiated second-line therapy with 1 of 6 GLP-1RAs (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide) or 1 of 4 SGLT2Is (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin). Empagliflozin (393,499; 31.6%), semaglutide (235,585; 18.9%), dapagliflozin (208,666; 16.8%), and dulaglutide (207,348; 16.8%) were most commonly used. A secondary subgroup analysis included 316,242 patients with established cardiovascular diseases (CVDs). Primary outcomes were 3-point major adverse cardiovascular events (MACEs) (acute myocardial infarction, stroke, sudden cardiac death) and 4-point MACE (adding hospitalization/emergency room visit with heart failure). Secondary outcomes included the individual components. HRs were estimated for pairwise agent comparisons while on-treatment (per-protocol) and over total follow-up using Cox proportional hazards models, with propensity score adjustments, negative control calibration, and prespecified study diagnostics to guard against potential confounding. Random-effects meta-analysis produced summary HR estimates across data sources that passed diagnostics. RESULTS: Across the study cohort, individual GLP-1RAs and SGLT2Is demonstrated broadly similar cardiovascular effectiveness, both within and across drug classes. For example, semaglutide and empagliflozin showed comparable risks for 3-point MACE (meta-analytic HR: 1.05; 95% CI: 0.79-1.39) and 4-point MACE (meta-analytic HR: 0.95; 95% CI: 0.81-1.12), with consistent findings in the CVD subgroup. Study diagnostics confirmed adequate equipoise, covariate balance, and statistical power to detect similarity in HRs between 0.8 and 1.2 for commonly used agents. CONCLUSIONS: In this large-scale real-world study, individual GLP-1RAs and SGLT2Is exhibited largely comparable cardiovascular benefits, including in patients with established CVD. These findings align with network meta-analytic estimates from major cardiovascular outcome trials and broadly support current treatment guidelines. Clinical choices should be guided by relevant factors such as safety, adherence, tolerability, cost, and patient preference, where further work is needed. CI - Published by Elsevier Inc. FAU - Bu, Fan AU - Bu F AD - Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. FAU - Wu, Ruopeng AU - Wu R AD - Department of Mathematics, College of Literature, Science, and the Arts, University of Michigan, Ann Arbor, Michigan, USA. FAU - Ostropolets, Anna AU - Ostropolets A AD - Observational Health Data Analytics, Janssen Research and Development, LLC, Titusville, New Jersey, USA. FAU - Aminorroaya, Arya AU - Aminorroaya A AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Cardiovascular Data Science (CarDS) Lab, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Chen, Hsin Yi AU - Chen HY AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Chai, Yi AU - Chai Y AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Shenzhen University Medical School, School of Public Health, Shenzhen University, Shenzhen, China. FAU - Dhingra, Lovedeep Singh AU - Dhingra LS AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Cardiovascular Data Science (CarDS) Lab, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA. FAU - Hsu, Jason C AU - Hsu JC AD - International PhD Program in Biotech and Healthcare Management, College of Management, Taipei Medical University, Taipei, Taiwan. FAU - Kim, Chungsoo AU - Kim C AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Center for Outcomes Research and Evaluation (CORE), Yale New Haven Hospital, New Haven, Connecticut, USA. FAU - Lau, Wallis C Y AU - Lau WCY AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, China; Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom; Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, United Kingdom. FAU - Man, Kenneth K C AU - Man KKC AD - Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, China; Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom; Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, United Kingdom. FAU - Minty, Evan AU - Minty E AD - Faculty of Medicine, O'Brien Institute for Public Health, University of Calgary, Calgary, Alberta, Canada. FAU - Morales, Daniel R AU - Morales DR AD - Usher Institute, University of Edinburgh, Edinburgh, United Kingdom. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. FAU - Thangraraj, Phyllis AU - Thangraraj P AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Cardiovascular Data Science (CarDS) Lab, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Van Zandt, Mui AU - Van Zandt M AD - Real World Solutions, IQVIA, Durham, North Carolina, USA. FAU - Yin, Can AU - Yin C AD - Real World Solutions, IQVIA, Shanghai, China. FAU - Khera, Rohan AU - Khera R AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University, New Haven, Connecticut, USA; Cardiovascular Data Science (CarDS) Lab, Yale School of Medicine, New Haven, Connecticut, USA; Center for Outcomes Research and Evaluation (CORE), Yale New Haven Hospital, New Haven, Connecticut, USA; Section of Health Informatics, Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut, USA. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University Irving Medical Center, New York, New York, USA; Veterans Affairs Informatics and Computing Infrastructure, U.S. Department of Veterans Affairs, Salt Lake City, Utah, USA. FAU - Suchard, Marc A AU - Suchard MA AD - Veterans Affairs Informatics and Computing Infrastructure, U.S. Department of Veterans Affairs, Salt Lake City, Utah, USA; Department of Biostatistics, Fielding School of Public Health, University of California-Los Angeles, Los Angeles, California, USA; Department of Biomathematics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA; Department of Human Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, USA. Electronic address: msuchard@ucla.edu. LA - eng GR - R01 LM006910/LM/NLM NIH HHS/United States GR - R01 HG006139/HG/NHGRI NIH HHS/United States GR - R01 HL169171/HL/NHLBI NIH HHS/United States GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - R01 HL167858/HL/NHLBI NIH HHS/United States GR - R35 GM160458/GM/NIGMS NIH HHS/United States GR - WT_/Wellcome Trust/United Kingdom GR - K23 HL153775/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20260415 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Semaglutide/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Treatment Outcome PMC - PMC13191718 MID - NIHMS2170338 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - cardiovascular outcomes OT - comparative effectiveness OT - real-world evidence OT - type 2 diabetes mellitus COIS- Funding Support and Author Disclosures This study was partially funded through the National Institutes of Health grants K23 HL153775, R01 LM006910, R01 HG006139, R01HL69954, R01HL169171, R35GM160458, and T15LM00707934 and an Intergovernmental Personnel Act agreement with the U.S. Department of Veterans Affairs. The funders had no role in the design and conduct of the protocol; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr Bu has received support from the U.S. Food and Drug Administration, Gates Foundation, and Patient-Centered Outcomes Research Institute outside of the scope of this work. Dr Ostropolets is an employee of Janssen Research and Development. Dr Lau received research funding from Diabetes UK outside the scope of this work. Dr Man has received support from the C.W. Maplethorpe Fellowship, the National Institute of Health Research, European Commission Framework Horizon 2020, the Hong Kong Research Grant Council, and the Innovation and Technology Commission of the Hong Kong Special Administration Region Government outside the scope of this work. Dr Morales is supported by a Wellcome Trust Clinical Research Fellowship. Ms Van Zandt is an employee and shareholder of IQVIA. Ms Yin is employee of IQVIA. Dr Khera is an associate editor at JAMA; has received support from the Doris Duke Charitable Foundation, Bristol Myers Squibb, Novo Nordisk, and BridgeBio outside the scope of this work; and is a cofounder of Evidence2Health and Ensight-AI. Dr Hripcsak have received contracts and grants from the U.S. Food and Drug Administration, the U.S. National Institutes of Health, and Janssen Research & Development outside the scope of this work. Dr Suchard have received contracts and grants from the U.S. Food and Drug Administration, the U.S. National Institutes of Health, and Janssen Research & Development outside the scope of this work; and receives contracts from Gilead Sciences outside the scope of this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2026/04/15 13:54 MHDA- 2026/06/11 05:39 PMCR- 2026/05/22 CRDT- 2026/04/15 10:30 PHST- 2025/08/27 00:00 [received] PHST- 2026/02/26 00:00 [revised] PHST- 2026/02/27 00:00 [accepted] PHST- 2026/06/11 05:39 [medline] PHST- 2026/04/15 13:54 [pubmed] PHST- 2026/04/15 10:30 [entrez] PHST- 2026/05/22 00:00 [pmc-release] AID - S0735-1097(26)05724-4 [pii] AID - 10.1016/j.jacc.2026.02.5123 [doi] PST - ppublish SO - J Am Coll Cardiol. 2026 Jun 2;87(21):2963-2977. doi: 10.1016/j.jacc.2026.02.5123. Epub 2026 Apr 15. PMID- 41973192 OWN - NLM STAT- MEDLINE DCOM- 20260715 LR - 20261010 IS - 1539-0829 (Electronic) IS - 1534-4827 (Linking) VI - 26 IP - 1 DP - 2026 Apr 13 TI - Pharmacologic Treatment of Obesity in the Context of Type 2 Diabetes. LID - 11 [pii] LID - 10.1007/s11892-026-01626-5 [doi] AB - PURPOSE OF REVIEW: To examine the role of pharmacologic obesity treatment in people with type 2 diabetes (T2D), with a focus on efficacy, safety, and clinical positioning in the context of T2D-specific metabolic and therapeutic challenges. RECENT FINDINGS: Contemporary incretin receptor agonists enable clinically meaningful weight loss in people with T2D while improving glycemic control and cardio-renal, hepatic, and functional outcomes, including improvements in physical performance and symptoms in heart failure with preserved ejection fraction (HFpEF). However, weight loss is consistently attenuated compared with obesity without diabetes, reflecting reduced metabolic flexibility (impaired ability to appropriately adjust fuel utilization), background therapies, and social determinants of health rather than treatment failure. Obesity pharmacotherapy should be considered a disease-modifying component of T2D care. Treatment success should be defined by improvements in adiposity-related complications, organ protection, and patient-centered outcomes, not by fixed weight-loss thresholds. A complication-focused, individualized approach is essential to optimize long-term benefit in T2D. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Conte, Caterina AU - Conte C AUID- ORCID: 0000-0001-7066-5292 AD - San Raffaele Roma University, Via di Val Cannuta 247, Rome, 00166, Italy. caterina.conte@uniroma5.it. AD - IRCCS MultiMedica, Milan, Italy. caterina.conte@uniroma5.it. FAU - Amaro, Anastassia AU - Amaro A AUID- ORCID: 0000-0002-3132-5778 AD - University of Pennsylvania, Philadelphia, PA, USA. LA - eng GR - Ricerca Corrente IRCCS MultiMedica/Italian Ministry of Health/ PT - Journal Article PT - Review DEP - 20260413 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Incretins) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Obesity/drug therapy/complications MH - Weight Loss/drug effects MH - Incretins/therapeutic use MH - *Anti-Obesity Agents/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Diabesity OTO - NOTNLM OT - Cardiometabolic risk OT - GLP‑1 agonists OT - Incretin therapy OT - Sarcopenic diabetes OT - Semaglutide OT - Tirzepatide COIS- Declarations. Competing Interests: CC has received consultancy and speaker's fees from Novo Nordisk and Eli Lilly. AA has received research grant from Novo Nordisk, Fractyl Laboratories, Eli Lilly; consultancy fees from Novo Nordisk, AbbVie, CVS Caremark. EDAT- 2026/04/13 12:37 MHDA- 2026/04/13 12:38 CRDT- 2026/04/13 11:08 PHST- 2026/02/11 00:00 [received] PHST- 2026/03/30 00:00 [accepted] PHST- 2026/04/13 12:38 [medline] PHST- 2026/04/13 12:37 [pubmed] PHST- 2026/04/13 11:08 [entrez] AID - 10.1007/s11892-026-01626-5 [pii] AID - 10.1007/s11892-026-01626-5 [doi] PST - epublish SO - Curr Diab Rep. 2026 Apr 13;26(1):11. doi: 10.1007/s11892-026-01626-5. PMID- 41970978 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Real-world use of semaglutide in patients with type 2 diabetes and end-stage renal disease: a multicenter retrospective cohort study. PG - 1805015 LID - 10.3389/fendo.2026.1805015 [doi] LID - 1805015 AB - BACKGROUND: Semaglutide and other Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and renal benefits in patients with type 2 diabetes mellitus (T2DM); however, individuals with end-stage renal disease (ESRD) have been systematically excluded from landmark outcome trials. Consequently, real-world data evaluating the safety and effectiveness of GLP-1 RAs in this high-risk population remain limited. METHODS: This multicenter retrospective cohort study evaluated adult patients with T2DM and ESRD, including those receiving maintenance hemodialysis, who were prescribed injectable semaglutide between January 2016 and July 2025 at tertiary care centers in Saudi Arabia. The primary efficacy outcomes were changes in glycemic control and insulin requirements following initiation of injectable semaglutide. Secondary outcomes included changes in body weight. Safety outcomes comprised acute kidney injury (AKI), severe hypoglycemia, treatment discontinuation due to adverse events, expanded major adverse cardiovascular events (MACE), and all-cause mortality. RESULTS: Seventeen patients were included, with a median follow-up of 1,187 days (IQR 602-1,442); 58.8% were receiving hemodialysis. Mean HbA1c decreased from 9.06 +/- 1.69% to 8.75 +/- 2.48% (-0.31 +/- 2.57%; p = 0.630), with insulin dose reductions observed among the subset of patients with available documentation. Among 16 patients with paired weight measurements, mean body weight decreased by -12.63 +/- 24.03 kg (p = 0.074). No cardiovascular deaths, nonfatal myocardial infarctions, or nonfatal strokes were observed. Three expanded MACE events, all hospitalizations for heart failure, occurred during follow-up. AKI occurred in 57.1% of non-dialysis patients, and severe hypoglycemia was reported in two patients (11.8%). CONCLUSIONS: In real-world practice, injectable semaglutide was associated with descriptive changes in metabolic parameters in patients with ESRD, including those on hemodialysis. Larger prospective studies are needed to better define the role of GLP-1 RAs in this underrepresented population. CI - Copyright (c) 2026 Alkhezi, Alfehaid, Alanezi, Alotaibi and Alshaya. FAU - Alkhezi, Omar AU - Alkhezi O AD - Department of Pharmacy Practice, College of Pharmacy, Qassim University, Al-Qassim Buraydah, Qassim, Saudi Arabia. FAU - Alfehaid, Lama AU - Alfehaid L AD - Pharmacy Practice Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia. FAU - Alanezi, Amal AU - Alanezi A AD - Pharmacy Practice Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. FAU - Alotaibi, Monirah AU - Alotaibi M AD - Pharmacy Practice Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. FAU - Alshaya, Omar AU - Alshaya O AD - Pharmacy Practice Department, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260326 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Retrospective Studies MH - *Kidney Failure, Chronic/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Blood Glucose MH - Renal Dialysis MH - Glycated Hemoglobin/analysis MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13061728 OTO - NOTNLM OT - cardiovascular outcomes OT - chronic kidney disease OT - end-stage renal disease OT - glucagon-like peptide-1 receptor agonists OT - hemodialysis OT - real-world evidence OT - semaglutide OT - type 2 diabetes mellitus COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/04/13 18:17 MHDA- 2026/04/13 18:18 PMCR- 2026/03/26 CRDT- 2026/04/13 06:37 PHST- 2026/02/05 00:00 [received] PHST- 2026/03/06 00:00 [revised] PHST- 2026/03/12 00:00 [accepted] PHST- 2026/04/13 18:18 [medline] PHST- 2026/04/13 18:17 [pubmed] PHST- 2026/04/13 06:37 [entrez] PHST- 2026/03/26 00:00 [pmc-release] AID - 10.3389/fendo.2026.1805015 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Mar 26;17:1805015. doi: 10.3389/fendo.2026.1805015. eCollection 2026. PMID- 41969210 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260826 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - SemaGBA: A System Dynamics Model of the Semaglutide-Responsive Gut-Brain Axis A Model of How the Brain and Semaglutide Regulate Appetite and Weight. PG - 5184-5194 LID - 10.1111/dom.70722 [doi] AB - AIMS: Semaglutide is a GLP-1 receptor agonist for the treatment of type 2 diabetes and obesity. Its clinical effects are well established, but the underlying mechanisms remain unclear. This study aims to use computational modelling to generate hypotheses about semaglutide's long-term metabolic (body weight, net energy intake, blood glucose, insulin, insulin sensitivity, glucotoxicity, leptin, leptin sensitivity, lipotoxicity, GLP-1 and betacell function) and neural (AgRP, POMC, and dopamine neural activity) effects. MATERIALS AND METHODS: The SemaGBA computational model was developed in Julia using a system dynamics approach, integrating 14 metabolic and neural variables. First, a version without neural variables was constructed and validated against clinical data for blood glucose and weight loss. Subsequently, the model was extended with neural variables. To represent distinct population groups, baseline variable profiles were defined, capturing the typical physiological characteristics for people with type 2 diabetes, obesity, and a healthy condition. Simulations were performed for semaglutide treatment in groups with prediabetes induced by chronic overeating, type 2 diabetes, and obesity over periods ranging from 30 weeks to 5 years. RESULTS: The reduced model accurately reproduced clinical outcomes. It predicts glucose reductions of 38.0 mg/dL (data: 41.0 mg/dL) and weight loss of 3.2 kg (data: 3.8 kg) for diabetes (0.5 mg semaglutide), and 15.1% weight loss (data: 14.9%-17.1%) for obesity (2.4 mg semaglutide). Simulations showed semaglutide's interconnected mechanisms, including reduced lipotoxicity and glucotoxicity, enhanced beta-cell function, and glucose-dependent insulin secretion. Intervention during prediabetes prevented progression to diabetes by preserving beta-cell function and maintaining glucose in the pre-diabetic range. Neural variables illustrated the potential contribution of AgRP, POMC, and dopamine neuron activity to reduced net energy intake. CONCLUSION: The SemaGBA model demonstrates how semaglutide achieves glucose control and weight loss through integrated metabolic and neural pathways. Validation is limited by data availability, but the framework provides hypotheses for future research into semaglutide's neural effects. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kennis, Vivan C W AU - Kennis VCW AUID- ORCID: 0009-0006-1340-8058 AD - Eindhoven University of Technology, Department of Biomedical Engineering, Computational Biology, Eindhoven, the Netherlands. FAU - van Riel, Natal A W AU - van Riel NAW AD - Eindhoven University of Technology, Department of Biomedical Engineering, Computational Biology, Eindhoven, the Netherlands. AD - Amsterdam UMC Location AMC-Vascular Medicine, Amsterdam, the Netherlands. LA - eng GR - Dutch Research Council (NWO)/ PT - Journal Article DEP - 20260413 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Insulin) SB - IM MH - Semaglutide MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/complications/physiopathology MH - *Brain/drug effects/metabolism MH - Obesity/drug therapy/metabolism MH - Weight Loss/drug effects MH - *Body Weight/drug effects MH - *Appetite/drug effects MH - Computer Simulation MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - *Appetite Regulation/drug effects MH - *Gastrointestinal Tract/drug effects MH - Insulin/metabolism MH - Models, Biological MH - Prediabetic State/drug therapy/metabolism PMC - PMC13146202 OTO - NOTNLM OT - GLP-1 analogue OT - appetite control OT - drug mechanism OT - obesity therapy OT - semaglutide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/04/13 12:38 MHDA- 2026/05/06 06:38 PMCR- 2026/05/06 CRDT- 2026/04/13 06:03 PHST- 2026/03/19 00:00 [revised] PHST- 2026/01/15 00:00 [received] PHST- 2026/03/19 00:00 [accepted] PHST- 2026/05/06 06:38 [medline] PHST- 2026/04/13 12:38 [pubmed] PHST- 2026/04/13 06:03 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - DOM70722 [pii] AID - 10.1111/dom.70722 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):5184-5194. doi: 10.1111/dom.70722. Epub 2026 Apr 13. PMID- 41969200 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Association of Semaglutide Treatment With Liver Cirrhosis and Hepatocellular Carcinoma in Type 2 Diabetes: A Population-Based Cohort Study. PG - 5704-5714 LID - 10.1111/dom.70763 [doi] AB - BACKGROUND: Metabolic dysfunction-associated steatotic liver disease is common among individuals with type 2 diabetes mellitus and substantially increases the risk of liver cirrhosis and hepatocellular carcinoma. Effective therapies that improve metabolic control while preventing advanced liver outcomes are limited. AIMS: To evaluate the association between semaglutide treatment and the risk of liver cirrhosis and hepatocellular carcinoma in adults with type 2 diabetes mellitus. METHODS: We performed a retrospective population-based cohort study using electronic health records from a large integrated healthcare organization. Adults with type 2 diabetes mellitus and no prior diagnosis of liver cirrhosis or hepatocellular carcinoma were included. Exposure was defined as treatment with semaglutide for at least four consecutive months compared with matched control patients. Cox proportional hazards models estimated adjusted hazard ratios with 95% confidence intervals, accounting for demographic factors, body mass index, smoking status, glycaemic control, other antidiabetic treatments and baseline liver fibrosis risk. RESULTS: Among 71 612 individuals, 35 806 received semaglutide and 35 806 were matched controls. Over a median follow-up of 4628 days for liver cirrhosis and 4090 days for HCC, 245 patients developed liver cirrhosis and 21 developed hepatocellular carcinomas. In the Cox model, there was no association between semaglutide treatment and the diagnosis of liver cirrhosis (HR 1.3, 95% CI 0.98-1.77) or hepatocellular carcinoma (HR 0.6, 95% CI 0.21-1.51). CONCLUSIONS: In this real-world study, semaglutide treatment was not associated with a reduced risk of liver cirrhosis or hepatocellular carcinoma among adults with type 2 diabetes mellitus. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Issachar, Assaf AU - Issachar A AUID- ORCID: 0000-0002-7004-7897 AD - Liver Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. AD - Gray School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Razi, Talish AU - Razi T AUID- ORCID: 0009-0006-2172-1044 AD - Community Medical Services Division, Clalit Health Services, Tel Aviv, Israel. AD - School of Industrial and Intelligent System Engineering, Tel Aviv University, Tel Aviv, Israel. FAU - Borochov, Ilya AU - Borochov I AD - Community Medical Services Division, Clalit Health Services, Tel Aviv, Israel. FAU - Duskin Bitan, Hadar AU - Duskin Bitan H AUID- ORCID: 0000-0002-1721-1360 AD - Gray School of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Community Medical Services Division, Clalit Health Services, Tel Aviv, Israel. AD - Institute of Endocrinology, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel. FAU - Arbel, Ronen AU - Arbel R AUID- ORCID: 0000-0002-6058-8665 AD - Community Medical Services Division, Clalit Health Services, Tel Aviv, Israel. AD - Maximizing Health Outcomes Research Lab, Sapir College, Sderot, Israel. LA - eng PT - Journal Article DEP - 20260413 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Carcinoma, Hepatocellular/chemically induced/epidemiology/prevention & control MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Liver Cirrhosis/epidemiology/prevention & control/chemically induced MH - *Liver Neoplasms/epidemiology/prevention & control MH - Retrospective Studies MH - *Semaglutide/adverse effects/therapeutic use PMC - PMC13243961 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - hepatocellular carcinoma OT - liver cirrhosis OT - metabolic liver disease OT - real-world data OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/04/13 06:32 MHDA- 2026/06/11 12:38 PMCR- 2026/06/08 CRDT- 2026/04/13 05:43 PHST- 2026/04/06 00:00 [revised] PHST- 2026/01/01 00:00 [received] PHST- 2026/04/07 00:00 [accepted] PHST- 2026/06/11 12:38 [medline] PHST- 2026/04/13 06:32 [pubmed] PHST- 2026/04/13 05:43 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70763 [pii] AID - 10.1111/dom.70763 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5704-5714. doi: 10.1111/dom.70763. Epub 2026 Apr 13. PMID- 41969188 OWN - NLM STAT- MEDLINE DCOM- 20260611 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 7 DP - 2026 Jul TI - Differential Impact of Metabolic Bariatric Surgery Versus Semaglutide on Adverse Hepatic and Extrahepatic Outcomes in Individuals With Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes. PG - 5684-5695 LID - 10.1111/dom.70757 [doi] AB - AIM: We compared the impact of metabolic bariatric surgery (MBS) versus semaglutide on clinical outcomes in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2D). METHODS: Patients with MASLD and T2D who had MBS or semaglutide in 2018-2023 were identified (TriNetX database). The primary outcome was a composite of major adverse liver outcomes (MALO): decompensation events or liver transplant. Secondary outcomes included a composite of major adverse cardiovascular events (MACE), first diagnosis of cirrhosis, heart failure, or obesity-associated cancer (OAC), and all-cause mortality (ACM). Subgroup analyses were performed for Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). RESULTS: MBS, compared with semaglutide, was associated with a higher hazard rate (HR) of MALO (HR 1.63; 95% CI 1.12-2.37); this was driven by RYGB (2.01; 1.26-3.20) but not by SG (0.97; 0.52-1.78). However, after excluding patients with pre-existing cirrhosis, MBS was associated with a reduced HR of new cirrhosis (0.46; 0.29-0.73). For extrahepatic events, MBS was associated with a reduced HR of MACE (0.51; 0.38-0.67), heart failure (0.41; 0.27-0.62), and OAC (0.56; 0.34-0.92). There was no difference in ACM between MBS and semaglutide, but in subgroup analysis, RYGB was associated with increased ACM compared to semaglutide (1.64; 1.01-2.67). CONCLUSION: In patients with MASLD and T2D, MBS, and specifically RYGB, as compared to semaglutide, may drive a relatively increased risk of MALO despite protection against MACE, the first diagnosis of cirrhosis, heart failure, and OAC. Liver evaluation in individuals with T2D referred for MBS may help optimize their treatment. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Stupalkowska, Weronika AU - Stupalkowska W AUID- ORCID: 0000-0003-1230-7651 AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. AD - Laboratory for Surgical and Metabolic Research, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Henney, Alex E AU - Henney AE AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Sheu, Eric G AU - Sheu EG AUID- ORCID: 0000-0003-2707-1768 AD - Laboratory for Surgical and Metabolic Research, Brigham and Women's Hospital, Boston, Massachusetts, USA. AD - Division of General and GI Surgery, Mass General Brigham, Boston, Massachusetts, USA. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260413 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Bariatric Surgery/adverse effects/methods MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Non-alcoholic Fatty Liver Disease/complications MH - *Semaglutide/therapeutic use MH - Treatment Outcome PMC - PMC13243962 OTO - NOTNLM OT - bariatric surgery OT - cohort study OT - database research OT - fatty liver disease OT - semaglutide OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/04/13 06:32 MHDA- 2026/06/11 12:38 PMCR- 2026/06/08 CRDT- 2026/04/13 05:43 PHST- 2026/03/16 00:00 [revised] PHST- 2026/01/19 00:00 [received] PHST- 2026/04/02 00:00 [accepted] PHST- 2026/06/11 12:38 [medline] PHST- 2026/04/13 06:32 [pubmed] PHST- 2026/04/13 05:43 [entrez] PHST- 2026/06/08 00:00 [pmc-release] AID - DOM70757 [pii] AID - 10.1111/dom.70757 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jul;28(7):5684-5695. doi: 10.1111/dom.70757. Epub 2026 Apr 13. PMID- 41967797 OWN - NLM STAT- MEDLINE DCOM- 20260925 LR - 20260929 IS - 2352-3840 (Electronic) IS - 1499-2671 (Linking) VI - 50 IP - 6 DP - 2026 Aug TI - Preferred Glucagon-like Peptide-1 Receptor Agonists in Adults With Type 2 Diabetes and Established Cardiovascular Disease or High Cardiovascular Risk: A Network Meta-analysis of Randomized Trials. PG - 429-439.e26 LID - S1499-2671(26)00065-1 [pii] LID - 10.1016/j.jcjd.2026.04.001 [doi] AB - The comparative cardiovascular (CV) efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) or high CV risk remain uncertain. PubMed, Embase, Web of Science, Scopus, and CENTRAL were searched from inception to December 20, 2025, for randomized controlled trials. We conducted a frequentist random-effects network meta-analysis and reported risk ratios (RRs) with 95% confidence intervals (CIs). Treatments were ranked using P-scores. Regimens were analyzed as individual agents, including albiglutide, dulaglutide, efpeglenatide, exenatide extended release, ITCA 650, liraglutide, lixisenatide, subcutaneous semaglutide, oral semaglutide, tirzepatide, and placebo. Eleven trials (n=83,215) were included. In the 3-point major adverse CV events (MACE) network (11 trials, 11 regimens), heterogeneity and inconsistency were absent (I(2)=0%, tau(2)=0). MACE rate was reduced with subcutaneous semaglutide (RR 0.74, 95% CI 0.58 to 0.94), efpeglenatide (RR 0.76, 95% CI 0.61 to 0.94), and albiglutide (RR 0.79, 95% CI 0.69 to 0.91); tirzepatide, oral semaglutide, liraglutide, and dulaglutide were also significantly reduced compared with placebo. Top ranked were subcutaneous semaglutide (P-score 0.87), efpeglenatide (0.84), and albiglutide (0.80). No regimen significantly reduced all-cause or CV death compared with placebo. Stroke was reduced with tirzepatide (RR 0.71, 95% CI 0.54 to 0.93) and dulaglutide (RR 0.77, 95% CI 0.63 to 0.95) vs placebo. Discontinuation and gastrointestinal discontinuation were higher with subcutaneous semaglutide, oral semaglutide, lixisenatide, and ITCA 650. Several GLP-1-based therapies reduced MACE vs placebo, with 3-point MACE emerging as the most consistent efficacy signal. Overall, these findings support guideline-based use of GLP-1 RAs in high-risk T2D while highlighting the need for individualized treatment selection. CI - Copyright (c) 2026 Diabetes Canada. All rights reserved. FAU - Abomohsen, Mustafa AU - Abomohsen M AD - Cardiology Department, Brookdale University Hospital and Medical Center, Brooklyn, New York, United States. FAU - Rifai, Mohamed AU - Rifai M AD - Faculty of Medicine, Menoufia University, Shibin al Kawm, Egypt. Electronic address: mohamed.ali181@med.menofia.edu.eg. FAU - Gadelmawla, Ahmed Farid AU - Gadelmawla AF AD - Faculty of Medicine, Menoufia University, Shibin al Kawm, Egypt. FAU - Alghzawi, Hamzah M AU - Alghzawi HM AD - School of Nursing, Tennessee State University, Nashville, Tennessee, United States. FAU - Elgendy, Mohamed S AU - Elgendy MS AD - Faculty of Medicine, Tanta University, Tanta, Egypt. FAU - Bakr, Hager Mohamed AU - Bakr HM AD - Faculty of Medicine, Menoufia University, Shibin al Kawm, Egypt. FAU - Friedman, Adam AU - Friedman A AD - Cardiology Department, Brookdale University Hospital and Medical Center, Brooklyn, New York, United States. FAU - Idries, Iyad Y AU - Idries IY AD - Cardiology Department, Brookdale University Hospital and Medical Center, Brooklyn, New York, United States. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20260410 PL - Canada TA - Can J Diabetes JT - Canadian journal of diabetes JID - 101148810 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Adult MH - Humans MH - *Cardiovascular Diseases MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use MH - Heart Disease Risk Factors MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - Semaglutide MH - Tirzepatide OTO - NOTNLM OT - GLP-1 receptor agonist OT - agoniste des recepteurs du GLP-1 OT - cardiovascular outcomes OT - diabete de type 2 OT - essais controles randomises OT - major adverse cardiovascular event OT - meta-analyse en reseau OT - network meta-analysis OT - randomized controlled trial OT - resultats cardiovasculaires OT - tirzepatide OT - tirzepatide OT - type 2 diabetes OT - evenements cardiovasculaires indesirables majeurs EDAT- 2026/04/13 00:31 MHDA- 2026/09/25 23:47 CRDT- 2026/04/12 19:37 PHST- 2026/01/13 00:00 [received] PHST- 2026/03/07 00:00 [revised] PHST- 2026/04/04 00:00 [accepted] PHST- 2026/09/25 23:47 [medline] PHST- 2026/04/13 00:31 [pubmed] PHST- 2026/04/12 19:37 [entrez] AID - S1499-2671(26)00065-1 [pii] AID - 10.1016/j.jcjd.2026.04.001 [doi] PST - ppublish SO - Can J Diabetes. 2026 Aug;50(6):429-439.e26. doi: 10.1016/j.jcjd.2026.04.001. Epub 2026 Apr 10. PMID- 41967795 OWN - NLM STAT- MEDLINE DCOM- 20260925 LR - 20260925 IS - 2352-3840 (Electronic) IS - 1499-2671 (Linking) VI - 50 IP - 6 DP - 2026 Aug TI - Oral Health Considerations and Dental Management Guidelines for Semaglutide Medications. PG - 440-447 LID - S1499-2671(26)00066-3 [pii] LID - 10.1016/j.jcjd.2026.03.008 [doi] AB - Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically meaningful weight-loss effects in individuals with type 2 diabetes and high body mass index, and dental practitioners and physicians often encounter patients who take these medications. Semaglutide is known to be associated with several systemic side effects, including delayed gastric emptying, belching, reflux and nausea, nutritional changes, and gastrointestinal discomfort. Systemic effects secondarily manifest in the oral cavity and, as a result, individuals taking semaglutide may present with xerostomia (dry mouth), halitosis (bad breath), enamel erosion tied to vomiting, and altered taste, among other oral signs and symptoms. It is important for dental professionals and physicians to become informed of possible symptoms and corresponding management strategies, given the multiple potential indirect effects on the oral cavity and relevance to dental treatment planning. In this article, we review the pharmacodynamics of semaglutide and present the current evidence on oral manifestations of the drug family and implications for dental and oral health. Practical management recommendations for dentists and the broader interdisciplinary health-care team are outlined. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Kofman, Karina AU - Kofman K AD - Faculty of Dentistry, Dental Surgery Program, University of Toronto, Toronto, Ontario, Canada. FAU - Ouanounou, Aviv AU - Ouanounou A AD - Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. Electronic address: avivouanounou@dentistry.utoronto.ca. LA - eng PT - Journal Article PT - Review DEP - 20260410 PL - Canada TA - Can J Diabetes JT - Canadian journal of diabetes JID - 101148810 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Oral Health/standards MH - *Practice Guidelines as Topic/standards MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 OT - adaptations des soins dentaires OT - dental modification OT - diabetes OT - diabete OT - oral health OT - sante bucco-dentaire EDAT- 2026/04/13 00:31 MHDA- 2026/09/25 23:47 CRDT- 2026/04/12 19:37 PHST- 2025/12/28 00:00 [received] PHST- 2026/02/27 00:00 [revised] PHST- 2026/03/27 00:00 [accepted] PHST- 2026/09/25 23:47 [medline] PHST- 2026/04/13 00:31 [pubmed] PHST- 2026/04/12 19:37 [entrez] AID - S1499-2671(26)00066-3 [pii] AID - 10.1016/j.jcjd.2026.03.008 [doi] PST - ppublish SO - Can J Diabetes. 2026 Aug;50(6):440-447. doi: 10.1016/j.jcjd.2026.03.008. Epub 2026 Apr 10. PMID- 41966038 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260714 IS - 2639-9636 (Print) IS - 2639-9636 (Linking) VI - 41 IP - 3 DP - 2026 Apr 1 TI - Geriatric Pharmacotherapy Case Series: GLP-1 RA for Weight Management in Older Adults. PG - 78-87 LID - 10.4140/TCP.n.2026.78 [doi] AB - Background: This case study reviews the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for weight management in older adults. A 69-year-old male patient discusses weight loss goals with his health care provider and seeks pharmacotherapy options in addition to lifestyle modifications. His medical history includes type 2 diabetes mellitus (T2D), coronary artery disease (CAD), prior coronary artery bypass graft, heart failure with reduced ejection fraction (HFrEF), hypertension, hyperlipidemia, and allergic rhinitis. He initiated weight loss efforts following a myocardial infarction; however, dietary and physical activity changes alone have not resulted in substantial weight reduction. Assessment: This patient is an appropriate candidate for GLP-1 RA therapy given his T2D, obesity, CAD, and a recent elevation in serum creatinine (SCr). The patient will initiate semaglutide, a medication approved for weight management with demonstrated cardiovascular benefit. The dose will be titrated to a maintenance dose of 2 mg once weekly, with ongoing monitoring of tolerability and weight loss.Given his age, there is concern for sarcopenia associated with excessive weight loss. The patient will be advised to maintain a balanced diet with an emphasis on protein intake and to engage in regular physical activity to minimize loss of muscle mass. Outcome: The patient experiences weight reduction within the first few weeks of therapy and tolerates treatment well. He has incorporated additional strength training into his exercise routine and increased his intake of vegetables and protein. The patient has insurance coverage for semaglutide due to his comorbid T2D; therefore, medication cost is not a barrier to treatment. Conclusion: When evaluating the use of GLP-1 RA agents in older adults, these agents demonstrate benefits beyond glycemic control and weight loss, including cardiovascular and renal outcomes. However, GLP-1 RA-associated weight loss may contribute to muscle loss, which is of particular concern in older adults who are at risk for frailty or falls. Patients receiving GLP-1 RA therapy should be encouraged to maintain adequate protein intake and engage in regular physical activity, particularly resistance training, to preserve muscle mass. Additionally, the high cost of GLP-1 RA agents may limit access for patients without insurance. FAU - Toma, Lauren AU - Toma L FAU - Buckley, Kelsey AU - Buckley K FAU - Early, Nicole AU - Early N LA - eng PT - Case Reports PT - Journal Article PL - United States TA - Sr Care Pharm JT - The Senior care pharmacist JID - 101737969 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Male MH - Aged MH - Semaglutide MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Obesity/drug therapy EDAT- 2026/04/12 06:38 MHDA- 2026/04/12 06:39 CRDT- 2026/04/12 00:32 PHST- 2026/04/12 06:39 [medline] PHST- 2026/04/12 06:38 [pubmed] PHST- 2026/04/12 00:32 [entrez] AID - 10.4140/TCP.n.2026.78 [doi] PST - ppublish SO - Sr Care Pharm. 2026 Apr 1;41(3):78-87. doi: 10.4140/TCP.n.2026.78. PMID- 41955540 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260626 IS - 1537-7385 (Electronic) IS - 0894-9115 (Linking) VI - 105 IP - 7 DP - 2026 Jul 1 TI - "Ozempic Limb": Understanding the Impact of Semaglutide on Prosthesis Use and Residual Limb Care in Individuals With Lower Limb Amputation. PG - 657-660 LID - 10.1097/PHM.0000000000002989 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are well-known medications commonly prescribed for type 2 diabetes management and pharmacologic management of obesity. While GLP-1 RAs have many positive effects on glycemic control and cardiovascular health, the secondary effect of weight loss can present a challenge in maintaining optimal prosthesis fitting and functionality among individuals with prosthetic limbs. More specifically, weight loss can lead to decreased muscle mass and volume of the residual limb, resulting in loosening of the prosthesis. In turn, individuals often require more frequent prosthetic adjustments to ensure their safety and comfort while using the prosthetic device. Herein, we describe 3 cases of semaglutide use in patients with prosthetic limbs who subsequently presented with a variety of complications, including skin breakdown, disproportionate residual limb volume loss, decreased prosthetic use, and increased residual limb pain. Such "Ozempic limbs" have not yet been reported in the literature. These observations suggest that further research in GLP-1 RA selection is required for persons with amputation, as well as increased patient education regarding the unique complications. CI - Copyright (c) 2026 Wolters Kluwer Health, Inc. All rights reserved. FAU - Bykowski, Janelle AU - Bykowski J AUID- ORCID: 0000-0002-7542-2713 AD - Department of Medicine, Schulich School of Medicine and Dentistry, Western University, Windsor Campus, Ontario, Canada. FAU - Loewen, Garrick AU - Loewen G AD - Loewen Prosthetic Services Ltd, Ontario, Canada. FAU - Loewen, Brock AU - Loewen B AD - Loewen Prosthetic Services Ltd, Ontario, Canada. FAU - Seslija, Dana AU - Seslija D AD - Department of Medicine, Schulich School of Medicine and Dentistry, Western University, Windsor Campus, Ontario, Canada. AD - Department of Physical Medicine and Rehabilitation, Hotel-Dieu Grace Healthcare, Ontario, Canada. LA - eng PT - Case Reports PT - Journal Article DEP - 20260326 PL - United States TA - Am J Phys Med Rehabil JT - American journal of physical medicine & rehabilitation JID - 8803677 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Amputation, Surgical MH - Female MH - Male MH - *Artificial Limbs MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Amputation Stumps MH - Prosthesis Fitting OTO - NOTNLM OT - Case Report OT - Lower Limb Amputation OT - Ozempic Limb OT - Prosthetics COIS- Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. EDAT- 2026/04/09 18:30 MHDA- 2026/06/26 00:42 CRDT- 2026/04/09 16:02 PHST- 2025/11/10 00:00 [received] PHST- 2026/03/17 00:00 [accepted] PHST- 2026/06/26 00:42 [medline] PHST- 2026/04/09 18:30 [pubmed] PHST- 2026/04/09 16:02 [entrez] AID - 00002060-202607000-00014 [pii] AID - 10.1097/PHM.0000000000002989 [doi] PST - ppublish SO - Am J Phys Med Rehabil. 2026 Jul 1;105(7):657-660. doi: 10.1097/PHM.0000000000002989. Epub 2026 Mar 26. PMID- 41953701 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Real-world glycemic control, exploratory cardiorenal indicators, and safety of polyethylene glycol loxenatide versus semaglutide in type 2 diabetes patients: a Chinese two-center retrospective cohort study. PG - 1756581 LID - 10.3389/fendo.2026.1756581 [doi] LID - 1756581 AB - OBJECTIVE: To compare the real-world efficacy and safety of high dose once-weekly glucagon-like peptide-1 receptor agonists polyethylene glycol loxenatide (PEG-Loxe) and subcutaneous (s.c.) semaglutide in patients with suboptimally controlled type 2 diabetes mellitus (T2DM). METHODS: We conducted a retrospective cohort China two-center study. Patients newly initiated on once-weekly PEG-Loxe 200 mug or s.c. semaglutide 1.0 mg between January 2021 and October 2022 were matched 1:1 using propensity score matching. The primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 months. Secondary endpoints included changes in HbA1c, body weight (BW), body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), and estimated glomerular filtration rate (eGFR) from baseline to 3, 6, 12, and 24 months. Records of adverse drug reactions were collected and extracted from the institutional medical record system. RESULTS: A total of 510 matched patient pairs demonstrated balanced baseline characteristics. No statistically significant between-group difference was observed in HbA1c changes from baseline across all follow-up assessments (p > 0.05). At month 24, HbA1c was reduced by least-squares mean 2.02% with PEG-Loxe and 2.23% with s.c. semaglutide (estimated treatment difference [ETD] -0.21%, 95% CI: -0.52, -0.10, p = 0.260). Semaglutide was consistently and significantly superior to PEG-Loxe in improving BW (ETD at 24 months: -3.55 kg, 95% CI: -5.22, -1.88, p < 0.001), BMI (ETD -0.82 kg/m(2), 95%CI: -1.33, -0.32, p = 0.001), LDL-C (ETD -0.51 mmol/L, 95% CI: -0.68, -0.34, p < 0.001), SBP (ETD -2.08 mmHg, 95% CI: -9.33, -0.11, p < 0.001), eGFR [ETD 0.75 mL/(min.1.73m(2)), 95% CI: -2.53, 4.039, p < 0.001]. Gastrointestinal symptoms were the most common safety concern, occurring more frequently in the semaglutide group during the first 3 months (p < 0.05). CONCLUSIONS: In real-world clinical practice, at the same high dose, PEG-Loxe provided equivalent glycemic control to s.c. semaglutide with a potential lower incidence of gastrointestinal side effects. Conversely, semaglutide offered more substantial improvement of cardiorenal parameters. These findings highlight the clinical utility of both agents in personalized T2DM management. CI - Copyright (c) 2026 Yu, Fu, Xu, Lin, Yin, Cai, Jiang, Ling, Chen and Zhuo. FAU - Yu, Zelin AU - Yu Z AD - Department of Clinical Pharmacy, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Fu, Duoyi AU - Fu D AD - Department of Biology, School of Science, Shantou University, Shantou, China. FAU - Xu, Jing AU - Xu J AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Lin, Chujia AU - Lin C AD - Department of Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Yin, Guoshu AU - Yin G AD - Department of Endocrinology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Cai, De AU - Cai D AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Jiang, Hongyan AU - Jiang H AD - Department of Pharmacology, Shantou University Medical College, Shantou, China. FAU - Ling, Kai AU - Ling K AD - Department of Pharmacology, Shantou University Medical College, Shantou, China. FAU - Chen, Jianqin AU - Chen J AD - Department of Geriatric Medicine, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. FAU - Zhuo, Yeye AU - Zhuo Y AD - Department of Clinical Pharmacy, The First Affiliated Hospital of Shantou University Medical College, Shantou, China. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260324 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/drug effects MH - China/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Glomerular Filtration Rate MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Glycated Hemoglobin/analysis MH - *Glycemic Control/methods MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Polyethylene Glycols/therapeutic use/administration & dosage/adverse effects MH - Retrospective Studies MH - Semaglutide PMC - PMC13053266 OTO - NOTNLM OT - HbA1c OT - adverse drug events OT - body weight OT - estimated glomerular filtration rate OT - lipid profiles OT - polyethylene glycol loxenatide OT - s.c. semaglutide OT - type 2 diabetes mellitus COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/04/09 06:30 MHDA- 2026/04/09 06:31 PMCR- 2026/03/24 CRDT- 2026/04/09 04:45 PHST- 2025/11/28 00:00 [received] PHST- 2026/03/08 00:00 [revised] PHST- 2026/03/09 00:00 [accepted] PHST- 2026/04/09 06:31 [medline] PHST- 2026/04/09 06:30 [pubmed] PHST- 2026/04/09 04:45 [entrez] PHST- 2026/03/24 00:00 [pmc-release] AID - 10.3389/fendo.2026.1756581 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Mar 24;17:1756581. doi: 10.3389/fendo.2026.1756581. eCollection 2026. PMID- 41951127 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260819 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 236 DP - 2026 Jun TI - Oral semaglutide reduces diabetes-related distress in adults with type 2 diabetes mellitus switching from DPP-4 inhibitors. The DOORS prospective real-world Italian study. PG - 113244 LID - S0168-8227(26)00163-4 [pii] LID - 10.1016/j.diabres.2026.113244 [doi] AB - AIMS: To evaluate glycemic control, weight management, and patient-reported outcomes (PROs) in adults with type 2 diabetes mellitus who transitioned to oral semaglutide (OS) after inadequate glycemic control on dipeptidyl peptidase-4 inhibitors (DPP-4i). METHODS: This 40-week, observational, prospective study included three visits: baseline (V1, OS initiation), intermediate visits (V2.X), and final visit (V3, week 40 +/- 4). The primary endpoint was change in glycated haemoglobin (HbA1c) from V1 to V3. Secondary endpoints included changes in body weight (BW), PROs - assessed by the Diabetes Distress Scale (DDS) and the Dutch Eating Behaviour Questionnaire (DEBQ) - and anthropometric/clinical parameters. RESULTS: 281 patients were enrolled (mean age 67.5 +/- 12.0 years; 55.9% male). In the in-study set (all patients initiating OS, regardless of discontinuation), mean HbA1c decreased by - 0.7 +/- 0.05% (p < 0.0001), and mean BW decreased by - 3.6 +/- 0.22 kg (p < 0.0001) from V1 to V3. Scores on the DDS domains and the DEBQ (emotional and external eating domains) decreased, indicating reduced diabetes-related distress and improved eating behaviours. Adverse events were reported by 23.1% of patients, with no hypoglycaemic episodes observed. CONCLUSIONS: OS was safe and effective in improving glycemic control, reducing BW, and alleviating diabetes-related distress and unhealthy eating behaviors in patients with type 2 diabetes mellitus switched from DPP-4i. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Giaccari, Andrea AU - Giaccari A AD - Universita Cattolica del Sacro Cuore and Center for Endocrine and Metabolic Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Electronic address: andrea.giaccari@unicatt.it. FAU - Borroni, Francesca AU - Borroni F AD - Ospedale Generale Provinciale di Macerata, Macerata, Italy. FAU - Dauriz, Marco AU - Dauriz M AD - Section of Endocrinology and Diabetes, Department of Internal Medicine, South-Tyrolean Healthcare System (SABES-ASDAA), Bolzano General Hospital, Via Lorenz Bohler 5, 39100 Bolzano, Italy. FAU - Gioia, Daniela AU - Gioia D AD - Casa di cure Triolo Zancla, Palermo, Italy. FAU - Baptiste, Paris AU - Baptiste P AD - Novo Nordisk LTD, Gatwich, UK. FAU - Bisio, Alessandro AU - Bisio A AD - Novo Nordisk s.p.a., Rome, Italy. FAU - Lastoria, Giusi AU - Lastoria G AD - Novo Nordisk s.p.a., Rome, Italy. FAU - Udupa, Keerthana AU - Udupa K AD - Novo Nordisk A/S, Bangalore, India. FAU - Barbagallo, Mario AU - Barbagallo M AD - A.O.U. Policlinico Giaccone, Palermo, Italy. LA - eng PT - Journal Article PT - Observational Study DEP - 20260406 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/psychology/blood MH - Female MH - Male MH - Aged MH - Prospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glycated Hemoglobin/analysis/metabolism MH - Administration, Oral MH - Italy MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Blood Glucose/drug effects MH - Glycemic Control MH - Drug Substitution OTO - NOTNLM OT - Diabetes-related distress OT - Glycemic control OT - Oral semaglutide OT - Patient-reported outcomes (PROs) OT - Real world evidence OT - Type 2 diabetes mellitus OT - Weight management COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.Giaccari has received speaker honoraria from Abbott, AstraZeneca, Lilly, Novo Nordisk, and Sanofi. F.Borroni, M.Dauriz, D.Gioia, M.Barbagallo have no competing interests to declare that are relevant to the content of this article. P.Baptiste, G.Lastoria, K.Udupa work at Novo Nordisk, and A.Bisio worked at Novo Nordisk at the time of study conduct and manuscript development. EDAT- 2026/04/09 00:34 MHDA- 2026/05/14 00:31 CRDT- 2026/04/08 19:13 PHST- 2025/12/12 00:00 [received] PHST- 2026/03/20 00:00 [revised] PHST- 2026/04/05 00:00 [accepted] PHST- 2026/05/14 00:31 [medline] PHST- 2026/04/09 00:34 [pubmed] PHST- 2026/04/08 19:13 [entrez] AID - S0168-8227(26)00163-4 [pii] AID - 10.1016/j.diabres.2026.113244 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jun;236:113244. doi: 10.1016/j.diabres.2026.113244. Epub 2026 Apr 6. PMID- 41944572 OWN - NLM STAT- MEDLINE DCOM- 20260804 LR - 20260804 IS - 1557-8518 (Electronic) IS - 1540-4196 (Linking) VI - 24 IP - 3 DP - 2026 Apr TI - Semaglutide-Induced Weight Loss Is the Main Determinant for the Improvement of Hepatic Biochemistry and Elastographic Repeated Measurements with FibroScan(R) in Patients with Type 2 Diabetes Mellitus and Metabolic Dysfunction-Associated Steatotic Liver Disease. PG - 121-128 LID - 10.1177/15578518251409025 [doi] AB - BACKGROUND: Semaglutide is currently being investigated for its effectiveness in metabolic dysfunction-associated steatotic liver disease (MASLD), irrespective of type 2 diabetes mellitus (T2DM) presence, even though its action on hepatic fibrosis is still debated. The aim of this study was to examine the effect of semaglutide on hepatic parameters in patients with both T2DM and MASLD in real-world clinical practice, and to further assess the significance of weight loss during treatment. METHODS: In consecutive patients with T2DM and MASLD, hepatic biochemistry and Fibrosis-4 (FIB-4) score were recorded. In participants with high FIB-4, elastographic liver stiffness measurements (LSM) and controlled attenuation parameter (CAP) were acquired with FibroScan(R) before and after treatment with semaglutide. For within-group comparisons, Wilcoxon signed ranked test for related samples was performed, while the role of weight loss was further investigated. RESULTS: A total of 111 patients were included: 31 males (27.9%), with a mean age 56.4 +/- 9.7 years old, body mass index 32.7 +/- 6.3 kg/m(2), and median glycated hemoglobin (HbA1c) 5.8% (interquartile range [IQR]: 5.6-6.2). Semaglutide (0.5-2.4 mg/week) was administered subcutaneously for a median of 12 months (IQR: 6.6-17). Thirty-three patients (29.7%) had aspartate aminotransferase and/or alanine aminotransferase above normal, and 35 (31.5%) high FIB-4 score. Apart from an overall drop in HbA1c of 5.6% (IQR: 1.6-8.6) and weight loss of 10% (IQR: 3.2-19.6), statistically significant reductions were recorded in all liver enzymes and elastographic parameters (p < 0.001). In multiple regression analysis, weight loss was found to independently predict improvements in aminotransferases and measured CAP (p < 0.001), irrespective of treatment duration and baseline FIB-4. CONCLUSION: In this cohort of T2DM/MASLD patients with baseline optimal glycemic control, semaglutide-induced weight loss led to significant improvements of all hepatic parameters (biochemistry, liver stiffness, and steatosis assessed with CAP), even in MASLD patients with baseline liver enzymes within normal. This study supports the advantages of semaglutide administration in concomitant T2DM and MASLD. FAU - Savvidou, Savvoula AU - Savvidou S AUID- ORCID: 0000-0002-4226-6400 AD - Department of Internal Medicine, "G.GENNIMATAS" General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Augousti-Varela, Elektra AU - Augousti-Varela E AD - Department of Internal Medicine, "G.GENNIMATAS" General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Damianakou, Aikaterini AU - Damianakou A AD - Department of Internal Medicine, "G.GENNIMATAS" General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Chalkias, Miltiadis AU - Chalkias M AD - Department of Internal Medicine, "G.GENNIMATAS" General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Stergiou, Ioannis AU - Stergiou I AD - Department of Internal Medicine, "G.GENNIMATAS" General Hospital of Thessaloniki, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Observational Study DEP - 20251220 PL - United States TA - Metab Syndr Relat Disord JT - Metabolic syndrome and related disorders JID - 101150318 RN - 53AXN4NNHX (Semaglutide) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Semaglutide/pharmacology MH - *Weight Loss/drug effects MH - Liver/diagnostic imaging/drug effects/metabolism MH - Elasticity Imaging Techniques MH - *Diabetes Mellitus, Type 2/complications/drug therapy/physiopathology MH - *Non-alcoholic Fatty Liver Disease/complications/drug therapy/physiopathology MH - Liver Function Tests MH - Humans MH - Male MH - Female MH - Middle Aged MH - Aged MH - Aspartate Aminotransferases/blood/drug effects MH - Alanine Transaminase/blood/drug effects MH - Treatment Outcome MH - Glycated Hemoglobin/drug effects/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology OTO - NOTNLM OT - FibroScan(R) OT - metabolic dysfunction-associated steatotic liver disease OT - semaglutide OT - type 2 diabetes mellitus COIS- Author Disclosure StatementAuthors declare no conflict of interest. EDAT- 2026/04/07 12:33 MHDA- 2026/04/07 12:34 CRDT- 2026/04/07 08:43 PHST- 2026/04/07 12:34 [medline] PHST- 2026/04/07 12:33 [pubmed] PHST- 2026/04/07 08:43 [entrez] AID - 10.1177/15578518251409025 [doi] PST - ppublish SO - Metab Syndr Relat Disord. 2026 Apr;24(3):121-128. doi: 10.1177/15578518251409025. Epub 2025 Dec 20. PMID- 41922811 OWN - NLM STAT- MEDLINE DCOM- 20260628 LR - 20261010 IS - 2162-4968 (Electronic) IS - 2162-4968 (Linking) VI - 15 IP - 1 DP - 2026 Apr 2 TI - The Role of GLP1 Receptor Agonists and Multi-agonist Incretin Therapies for Specific Obesity-related Health Conditions: Evidence and Rationale for Prioritisation. LID - 29 [pii] LID - 10.1007/s13679-026-00707-6 [doi] AB - PURPOSE OF REVIEW: This review evaluates the strength and scope of clinical evidence for GLP-1RAs-liraglutide, semaglutide, and tirzepatide-across obesity and associated complications, providing a structured rationale for prioritisation in clinical practice and policy. RECENT FINDINGS: GLP-1RAs demonstrate significant and reproducible weight loss-approximately 15% with semaglutide and 20% with tirzepatide at one year. Their efficacy in obesity-related health conditions has been best demonstrated through large clinical trials in cardiovascular disease, type 2 diabetes, obstructive sleep apnoea and metabolic dysfunction-associated steatotic liver disease. There is emerging evidence in the form of clinical trials and large retrospective studies for a number of other health conditions including chronic kidney disease, polycystic ovary syndrome, osteoarthritis, and other inflammatory conditions. Finally, GLP-1RAs may be a safe and effective treatment in time-critical contexts requiring rapid weight reduction for access to interventions such as organ transplantation, oncology surgery, sight-threatening idiopathic intracranial hypertension, and assisted conception. While all individuals meeting NICE eligibility criteria should ultimately access GLP-1RA therapy, current capacity constraints necessitate a phased approach prioritising high-evidence or time-sensitive conditions. This framework provides a scientifically grounded and evidence-based model to support clinical decision-making and service development in obesity management. Continued research is warranted to expand the evidence base, optimise cost-effectiveness, and ensure equitable implementation of obesity pharmacotherapy within public health services. FAU - Albor, Christo AU - Albor C AUID- ORCID: 0000-0002-4037-5734 AD - King's College Hospital NHS Foundation Trust, London, UK. c.albor@nhs.net. AD - Royal Free London NHS Foundation Trust, London, UK. c.albor@nhs.net. FAU - Anyiam, Oluwaseun AU - Anyiam O AUID- ORCID: 0000-0003-2425-2299 AD - University Hospitals of Derby & Burton NHS Foundation Trust, Derby, UK. FAU - Boyle, Luke D AU - Boyle LD AUID- ORCID: 0000-0003-4739-9170 AD - Department of Endocrinology, Centre for Obesity, Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, SE1 9RT2, UK. AD - Barts Health NHS Trust, West Smithfield, London, EC1A 7BE, UK. FAU - Makaronidis, Janine AU - Makaronidis J AD - Department of Diabetes and Metabolism, Royal London Hospital, Barts Health NHS Trust, London, UK. AD - National Institute of Health Research, UCLH Biomedical Research Centre, London, UK. AD - Centre for Obesity Research, Department of Medicine, Rayne Institute, University College London, London, UK. FAU - Tan, Rachael AU - Tan R AUID- ORCID: 0000-0003-4013-6810 AD - King's College Hospital NHS Foundation Trust, London, UK. FAU - Iftikhar, Sahar AU - Iftikhar S AD - Royal Surrey Hospital NHS Trust, Guildford, UK. FAU - Burzic, Amna AU - Burzic A AUID- ORCID: 0009-0009-1099-820X AD - Division of Medicine, University of Nottingham, Nottingham, NG5 1PB, UK. FAU - Lajeunesse Trempe, Fannie AU - Lajeunesse Trempe F AD - Institut Universitaire de Cardiologie Et de Pneumologie de Quebec, Quebec, QC, Canada. AD - Faculty of Pharmacy, Laval University, Quebec, QC, Canada. FAU - Stanley, Moira AU - Stanley M AD - Helier Hospital, Sutton, UK. FAU - Bhatti, Aniqah AU - Bhatti A AUID- ORCID: 0000-0001-7778-2272 AD - Nottingham University Hospitals, University of Nottingham, Nottingham, UK. FAU - Scragg, Jadine AU - Scragg J AUID- ORCID: 0000-0003-1424-712X AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Badawy, Layla AU - Badawy L AUID- ORCID: 0000-0002-4104-9404 AD - Royal Free London NHS Foundation Trust, London, UK. FAU - Moqeem, Komal AU - Moqeem K AD - Kings College Hospital, London, UK. FAU - Idris, Iskandar AU - Idris I AUID- ORCID: 0000-0002-7548-8288 AD - University of Nottingham, Nottingham, UK. AD - University Hospitals of Derby & Burton FT, Derby, UK. FAU - Andrews, Rob C AU - Andrews RC AUID- ORCID: 0000-0003-4939-1738 AD - University of Exeter Medical School, Exeter, UK. FAU - Sen Gupta, Piya AU - Sen Gupta P AUID- ORCID: 0000-0002-2800-7365 AD - Guy's and St Thomas's Hospitals NHS Trust, King's College London, London, UK. FAU - Hughes, David AU - Hughes D AD - University Hospitals of Derby & Burton FT, Derby, UK. FAU - McCullough, Katherine AU - McCullough K AD - Royal Surrey Hospital NHS Trust, Guildford, UK. AD - Ashford and St Peter's Hospital NHS Trust, Surrey, UK. AD - Royal College of Physicians, London, UK. AD - NHS England, London, UK. FAU - Tan, Tricia AU - Tan T AD - Department of Metabolism, Digestion and Reproduction, Imperial College London, London, W12 0HS, UK. FAU - McGowan, Barbara AU - McGowan B AD - Guy's and St Thomas's Hospitals NHS Trust, King's College London, London, UK. LA - eng PT - Journal Article PT - Review DEP - 20260402 PL - United States TA - Curr Obes Rep JT - Current obesity reports JID - 101578283 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - *Incretins/therapeutic use MH - Semaglutide MH - Tirzepatide MH - Glucagon-Like Peptides/therapeutic use MH - Liraglutide/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - *Anti-Obesity Agents/therapeutic use MH - Weight Loss/drug effects MH - Female MH - Cardiovascular Diseases/drug therapy MH - Renal Insufficiency, Chronic/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Polycystic Ovary Syndrome/drug therapy OTO - NOTNLM OT - Asthma OT - CKD OT - Cancer OT - Cancer survival OT - Cardiovascular disease OT - Chronic kidney disease OT - Evidence review OT - GLP-1RA OT - Genetic obesity OT - Glucagon-like peptide-1 receptor agonist OT - Hidradenitis suppurativa OT - IIH OT - IVF OT - Idiopathic intracranial hypertension OT - In-vitro fertilisation OT - Liraglutide OT - MASH OT - MASLD OT - Metabolic dysfunction-associated steatotic liver disease OT - Metabolic-associated steatohepatitis OT - Mounjaro OT - OA OT - OSA OT - Obesity OT - Obesity pharmacotherapy OT - Obstructive sleep apnoea OT - Osteoarthritis OT - Overweight OT - PCOS OT - Polycystic ovary syndrome OT - Precancerous conditions OT - Psoriasis OT - Rare monogenic obesity OT - Saxenda OT - Semaglutide OT - Subfertility OT - T2DM OT - Tirzepatide OT - Transplant surgery OT - Type 2 diabetes OT - Wegovy COIS- Compliance with Ethical Standards. Competing Interest: Conflicts of interest/Competing interests Funding: JM has received research funding from the NIHR and the Society for Endocrinology. JM has received institutional funding form NovoNordisk and Rhythm Pharmaceuticals. JS is supported by the NIHR Oxford Biomedical Research Centre (NIHR203311) and is an investigator in a trial funded by the Novo Nordisk Foundation (NNF22SA0080921). IS has received research grants or Speaker fees from: Eli Lilly, Novo Nordisk, Abbott, Boehringer, Sanofi. PSG has received speaker & course director fees from Novo Nordisk, advisory/speaker fees from Eli Lilly, and research support from Recordari. BM has received educational and/or advisory fees Lilly, Novonordisk, Boheringer ingelheim, Astra Zeneca. BM has received a research grant from Novo Nordisk. CA has received reimbursement for attending conferences from Novo Nordisk. Financial interests: TT declares she is a former shareholder in, and consultant for Zihipp Ltd., as well as advisory board consultancies for Amylyx Inc. Non-financial interests: JM has a voluntary role with the Asociation for the Study of Obesity (ASO) as sponsorship lead. BM is a shareholder of Reset Health. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. EDAT- 2026/04/02 00:29 MHDA- 2026/06/28 13:04 CRDT- 2026/04/01 23:32 PHST- 2025/10/26 00:00 [received] PHST- 2026/03/23 00:00 [accepted] PHST- 2026/06/28 13:04 [medline] PHST- 2026/04/02 00:29 [pubmed] PHST- 2026/04/01 23:32 [entrez] AID - 10.1007/s13679-026-00707-6 [pii] AID - 10.1007/s13679-026-00707-6 [doi] PST - epublish SO - Curr Obes Rep. 2026 Apr 2;15(1):29. doi: 10.1007/s13679-026-00707-6. PMID- 41915565 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260714 IS - 2325-6621 (Electronic) IS - 2325-6621 (Linking) VI - 23 IP - 4 DP - 2026 Apr 1 TI - Impact of GLP-1 and dual agonists on the incidence of new cases of physician-reported sleep apnea: a real-world study. PG - 607-613 LID - 10.1093/annalsats/aaoaf071 [doi] AB - RATIONALE: Previous studies have shown that glucagon-like peptide-1 (GLP-1) agonists and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) agonists (tirzepatide) reduced severity of sleep apnea. However, whether these medications impact incidence of new cases of physician-reported sleep apnea (PRSA) is unknown. OBJECTIVE: To determine the potential impact of GLP-1 and dual agonists on the incidence of sleep apnea reports and to explore potential treatment consequences for this sleep-disordered breathing. METHODS: We conducted a retrospective cohort study using the TriNetX Global Health Research Network through anonymized electronic medical records. We identified adult patients with obesity and/or type 2 diabetes mellitus never prescribed GLP-1 or dual agonist therapy (reference arm) and those new initiators of these medications. The index event (June 2022) was chosen to coincide with the launching of tirzepatide in the market. We excluded patients with type 1 diabetes; previous diagnosis of PRSA; previous use of GLP-1/dual agonists, orlistat, phentermine/topiramate, or bupropion/naltrexone; or previous bariatric surgery. Initiators were matched to the reference cohort using propensity score matching in a 1:1 ratio for age, sex, ethnicity, body mass index, and menopause. We used a validated algorithm to identify PRSA using International Classification of Diseases, 10th Revision codes. RESULTS: The follow-up time was 1044 days. After propensity score matching, a total of 1 253 188 patients were included in the reference arm and GLP-1/dual agonist comparison. Overall, GLP-1/dual agonists were associated with a 54% lower incidence of PRSA (HR, 0.46 [95% CI, 0.45-0.49]). Individually, all drugs were able to reach this outcome as compared to the reference arm: liraglutide (HR, 0.64 [95% CI, 0.51-0.80]), dulaglutide (HR, 0.32 [95% CI, 0.28-0.36]), semaglutide (HR, 0.57 [95% CI, 0.54-0.61]), and tirzepatide (HR, 0.74 [95% CI, 0.67-0.92]). Exploratory analysis revealed a 79% lower incidence of positive airway pressure reports in the GLP-1/dual agonist group as compared to controls. CONCLUSIONS: GLP-1/dual agonists reduced the incidence of new cases of PRSA in patients with obesity and/or type 2 diabetes. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the American Thoracic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Prado, Beatriz S AU - Prado BS AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. FAU - Mazzotti, Diego R AU - Mazzotti DR AUID- ORCID: 0000-0003-3924-9199 AD - Division of Medical Informatics, Division of Pulmonary Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, MO, United States. FAU - Franci, Andre AU - Franci A AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. FAU - Baracioli, Luciano M AU - Baracioli LM AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. AD - Instituto do Coracao (InCor), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Barbado, Karoline Razimavicius AU - Barbado KR AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. FAU - Saretta, Roberta AU - Saretta R AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. FAU - Kalil-Filho, Roberto AU - Kalil-Filho R AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. AD - Instituto do Coracao (InCor), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. FAU - Drager, Luciano F AU - Drager LF AUID- ORCID: 0000-0002-2081-6846 AD - Centro de Cardiologia do Hospital Sirio Libanes, Sao Paulo, Brazil. AD - Instituto do Coracao (InCor), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil. LA - eng GR - Hospital Sirio Libanes/ PT - Journal Article PL - England TA - Ann Am Thorac Soc JT - Annals of the American Thoracic Society JID - 101600811 RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - *Sleep Apnea Syndromes/epidemiology MH - Male MH - Retrospective Studies MH - Incidence MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - Tirzepatide MH - *Obesity/drug therapy/complications MH - *Glucagon-Like Peptide 1/agonists MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide-1 OT - glucose-dependent insulinotropic peptide OT - incidence OT - obesity OT - sleep apnea EDAT- 2026/03/31 18:49 MHDA- 2026/03/31 18:50 CRDT- 2026/03/31 12:53 PHST- 2025/08/24 00:00 [received] PHST- 2025/11/24 00:00 [accepted] PHST- 2026/03/31 18:50 [medline] PHST- 2026/03/31 18:49 [pubmed] PHST- 2026/03/31 12:53 [entrez] AID - 8471057 [pii] AID - 10.1093/annalsats/aaoaf071 [doi] PST - ppublish SO - Ann Am Thorac Soc. 2026 Apr 1;23(4):607-613. doi: 10.1093/annalsats/aaoaf071. PMID- 41913157 OWN - NLM STAT- MEDLINE DCOM- 20260628 LR - 20260930 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Mar 30 TI - Inpatient safety, effectiveness of SGLT2 inhibitors and GLP-1 RAs in type 2 diabetes: ENDOCARE, a pragmatic prospective cohort study. LID - 10.1186/s12933-026-03156-6 [doi] LID - 131 AB - BACKGROUND: Current guidelines recommend baseline insulin as the standard treatment for most people hospitalised with type 2 diabetes (PWT2D). However, they generally discourage the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists due to safety concerns and a lack of randomised evidence. We aim to assess primarily safety, and secondarily, effectiveness of non-insulin glucose-lowering therapy for inpatients, as implemented within a structured start-stop clinical practice guideline. METHODS: We conducted a 9-month pragmatic prospective cohort study including PWT2D adults who were admitted to the medical and surgical wards of a tertiary hospital. Participants were managed either on oral antidiabetic drugs (with or without insulin) under a start-stop protocol (Group A) or with insulin-only therapy (Group B). The primary outcome was safety, defined as severe adverse events (level 2-3 hypoglycaemia or diabetic ketoacidosis). Secondary outcomes included median daily capillary glucose and glycaemic variability. Hospital stay, intensive care unit admission and mortality were exploratory outcomes. Multivariable logistic regression and propensity score matching were employed to adjust for confounding factors. RESULTS: A total of 979 participants were included in the study: 582 in the Group A and 397 in the Group B. Seventy-three severe adverse events occurred, primarily hypoglycaemia. Non-insulin therapy was independently associated with a lower risk of severe adverse events (aOR 0.53 [95%CI 0.29-0.97]), and these results remained consistent after propensity score matching (OR 0.31 [95%CI 0.15-0.61]). The Group A had a lower median daily glucose level (153 mg/dL vs. 179 mg/dL; p < 0.001), lower glycaemic variability and a shorter hospital stay (5 days vs. 7 days; p < 0.001). No differences were observed in intensive care unit admission or mortality. CONCLUSIONS: In real hospital settings, the use of non-insulin therapies, predominantly SGLT2 inhibitors and GLP-1 RAs guided by a start-stop CPG, was associated with a safe and effective glycemic management profile. FAU - Moreno-Perez, Oscar AU - Moreno-Perez O AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. omorenoperez@hotmail.es. AD - Department of Clinical Medicine, Miguel Hernandez University, Elche, Spain. omorenoperez@hotmail.es. FAU - Tejera-Munoz, Antonio AU - Tejera-Munoz A AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. AD - University Centre for Health Sciences - HM Hospitals (CUHMED), Camilo Jose Cela University, Madrid, Spain. FAU - Leiva-Mora, Nuria AU - Leiva-Mora N AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Santacruz, Elisa AU - Santacruz E AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Sanchez-Ortiga, Ruth AU - Sanchez-Ortiga R AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Arrarte, Vicente AU - Arrarte V AD - Department of Clinical Medicine, Miguel Hernandez University, Elche, Spain. AD - Department of Cardiology, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Alicante, Spain. FAU - Climent-Grana, Eduardo AU - Climent-Grana E AD - Department of Pharmacy, General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Alicante, Spain. FAU - Sandin, Miriam AU - Sandin M AD - Department of Cardiology, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Alicante, Spain. FAU - Riera, Geronima AU - Riera G AD - Department of Pharmacy, General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Alicante, Spain. FAU - Lopez-Mondejar, Pedro AU - Lopez-Mondejar P AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Lopez-Munoz, Beatriz AU - Lopez-Munoz B AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Navarro, Clara AU - Navarro C AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Guillen-Morote, Cristina AU - Guillen-Morote C AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Roldan-Sanchez, Ada AU - Roldan-Sanchez A AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Sanchez-Pacheco, Myriam AU - Sanchez-Pacheco M AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Abad-Gonzalez, Angel Luis AU - Abad-Gonzalez AL AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. FAU - Llorens, Pere AU - Llorens P AD - Emergency Department, Short Stay Unit and Hospitalization at Home Unit, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Alicante, Spain. AD - Medicine Area, University of Alicante, Alicante, Spain. FAU - Pico-Alfonso, Antonio AU - Pico-Alfonso A AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. AD - Department of Clinical Medicine, Miguel Hernandez University, Elche, Spain. AD - Center for Biomedical Research On Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Madrid, Spain. FAU - Serrano-Gotarredona, Joaquin AU - Serrano-Gotarredona J AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, C/ Pintor Baeza S/N. CP 03010, Alicante, Spain. AD - Department of Clinical Medicine, Miguel Hernandez University, Elche, Spain. LA - eng PT - Journal Article PT - Pragmatic Clinical Trial PT - Research Support, Non-U.S. Gov't DEP - 20260330 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Biomarkers) RN - 0 (GLP1R protein, human) RN - 0 (Insulin) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/mortality MH - Female MH - Prospective Studies MH - Middle Aged MH - Treatment Outcome MH - Male MH - *Blood Glucose/drug effects/metabolism MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/administration & dosage MH - Time Factors MH - Risk Factors MH - Biomarkers/blood MH - Hypoglycemia/chemically induced/blood MH - *Insulin/adverse effects/administration & dosage MH - *Glycemic Control/adverse effects/mortality MH - *Incretins/adverse effects/administration & dosage MH - Risk Assessment MH - *Inpatients MH - Diabetic Ketoacidosis/chemically induced MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Drug Therapy, Combination MH - Patient Admission MH - Administration, Oral PMC - PMC13126886 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Guideline OT - Hospital OT - Inpatients OT - Oral semaglutide OT - Prospective study OT - Real world evidence OT - SGLT2 inhibitors OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the principles of the Declaration of Helsinki and followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. The protocol was reviewed and approved by the Ethics Committee of the Dr Balmis General University Hospital (ref. 2022-054). Given the pragmatic observational design and the use of routinely collected anonymised clinical data, the requirement for written informed consent was waived by the Ethics Committee. Competing interests: The authors declare no competing interests. EDAT- 2026/03/31 06:58 MHDA- 2026/06/28 06:35 PMCR- 2026/03/30 CRDT- 2026/03/31 00:08 PHST- 2026/02/13 00:00 [received] PHST- 2026/03/15 00:00 [accepted] PHST- 2026/06/28 06:35 [medline] PHST- 2026/03/31 06:58 [pubmed] PHST- 2026/03/31 00:08 [entrez] PHST- 2026/03/30 00:00 [pmc-release] AID - 10.1186/s12933-026-03156-6 [pii] AID - 3156 [pii] AID - 10.1186/s12933-026-03156-6 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Mar 30;25(1):131. doi: 10.1186/s12933-026-03156-6. PMID- 41908934 OWN - NLM STAT- MEDLINE DCOM- 20260714 LR - 20260813 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 20 DP - 2026 TI - A Comprehensive Review on the Cardioprotective and Nephroprotective Effects of Semaglutide, and Its Therapeutic Efficacy and Mechanisms in Cardiorenal Syndrome. PG - 581491 LID - 10.2147/DDDT.S581491 [doi] LID - 581491 AB - Semaglutide (SEM), a GLP-1 receptor agonist (GLP-1RA), is commonly used to manage blood glucose and weight in type 2 diabetes mellituspatients (T2DM). Research indicates that SEM protects the kidneys and heart by slowing estimated glomerular filtration rate (eGFR) decline, reducing proteinuria, enhancing cardiac outcomes, and lowering cardiovascular risk. These benefits are linked to various mechanisms, including reduced oxidative stress and inflammation, anti-fibrotic effects, modulation of metabolism, inhibition of apoptosis, suppression of ferroptosis, and improved mitochondrial function for energy regulation. However, some studies have also found that SEM may potentially lead to renal impairment or even promote the progression of cardiorenal syndrome (CRS). Due to conflicting results, more animal studies and large-scale clinical trials are needed to understand SEM's effects on CRS and its side effects, aiding in personalized treatment strategies. This review summarizes the functions and mechanisms of SEM in CRS, and highlights current research limitations and proposed directions for future studies. CI - (c) 2026 Ye et al. FAU - Ye, Lu AU - Ye L AD - Health Science Center, Hubei Minzu University, Enshi, Hubei, People's Republic of China. AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. FAU - Tang, Pusong AU - Tang P AD - Health Science Center, Hubei Minzu University, Enshi, Hubei, People's Republic of China. AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. FAU - Wan, Haixu AU - Wan H AD - Health Science Center, Hubei Minzu University, Enshi, Hubei, People's Republic of China. AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. FAU - Zhong, Xing AU - Zhong X AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. AD - Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. FAU - Chen, Xin AU - Chen X AUID- ORCID: 0000-0003-2180-5564 AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. AD - Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. FAU - Liu, Changzhao AU - Liu C AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. AD - Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. FAU - Huang, Rui AU - Huang R AD - Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. AD - Hubei Provincial Key Laboratory of Selenium Resources and Bio applications, Enshi, Hubei, People's Republic of China. AD - Cardiovascular Disease Center, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei, People's Republic of China. LA - eng PT - Journal Article PT - Review DEP - 20260324 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Cardiotonic Agents) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Cardio-Renal Syndrome/drug therapy/metabolism MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Animals MH - *Cardiotonic Agents/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/pharmacology MH - Kidney/drug effects PMC - PMC13032732 OTO - NOTNLM OT - GLP-1RA OT - cardiorenal syndrome OT - cardiovascular outcomes OT - semaglutide COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/03/30 12:49 MHDA- 2026/03/30 12:50 PMCR- 2026/03/24 CRDT- 2026/03/30 06:31 PHST- 2025/11/14 00:00 [received] PHST- 2026/02/28 00:00 [accepted] PHST- 2026/03/30 12:50 [medline] PHST- 2026/03/30 12:49 [pubmed] PHST- 2026/03/30 06:31 [entrez] PHST- 2026/03/24 00:00 [pmc-release] AID - 581491 [pii] AID - 10.2147/DDDT.S581491 [doi] PST - epublish SO - Drug Des Devel Ther. 2026 Mar 24;20:581491. doi: 10.2147/DDDT.S581491. eCollection 2026. PMID- 41903539 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 189 IP - 9 DP - 2026 Apr 30 TI - Advancing precision health discovery in a genetically diverse health system. PG - 2533-2555.e31 LID - S0092-8674(26)00274-6 [pii] LID - 10.1016/j.cell.2026.03.007 [doi] AB - Linking genetic data with electronic health records in hospital biobanks promises to advance precision medicine, but limited ancestral diversity constrains discovery and generalizability. We analyzed 93,936 participants from the UCLA ATLAS Community Health Initiative to inform disease prevalence and genetic risk across five continental and 36 fine-scale ancestry groups. We discovered numerous unreported gene-phenotype associations, including FN3K with intestinal disaccharidase deficiency in Europeans and admixed Americans. Polygenic scores (PGS) robustly predicted common diseases, with effects markedly diminished in non-Europeans. Furthermore, we reduced the pronounced European bias in curated clinical variants using computational predictors, uncovering unreported disease-gene associations, including ANKZF1 and peripheral vascular disease in African Americans. Longitudinal data revealed that semaglutide efficacy varies across ancestries, is associated with PGS for type 2 diabetes, and is modulated by genetic variation in PTPRU. These findings illustrate how ancestrally diverse biobanks from a single health system yield robust disease associations and pharmacogenomic insights. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Haas, Roni AU - Haas R AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: rhaas@mednet.ucla.edu. FAU - Margolis, Michael P AU - Margolis MP AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Wei, Angela AU - Wei A AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Interdepartmental Bioinformatics Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Yamaguchi, Takafumi N AU - Yamaguchi TN AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. FAU - Feng, Jeffrey AU - Feng J AD - Department of Radiological Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Tran, Thai AU - Tran T AD - Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Tozzo, Veronica AU - Tozzo V AD - Department of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Queen, Katelyn J AU - Queen KJ AD - Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Mootor, Mohammed Faizal Eeman AU - Mootor MFE AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Patil, Vishakha AU - Patil V AD - Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Broudy, Michael E AU - Broudy ME AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Tung, Paul AU - Tung P AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Alam, Shafiul AU - Alam S AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Martinez, Danielle B AU - Martinez DB AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Patel, Yash AU - Patel Y AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. FAU - Caggiano, Christa AU - Caggiano C AD - Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY 10027, USA. FAU - Zeltser, Nicole AU - Zeltser N AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Hugh-White, Rupert AU - Hugh-White R AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. FAU - Arbet, Jaron AU - Arbet J AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Shemirani, Ruhollah AU - Shemirani R AD - Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY 10027, USA. FAU - Tian, Mao AU - Tian M AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. FAU - Thapaliya, Prapti AU - Thapaliya P AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Eloyan, Lora AU - Eloyan L AD - UCLA Health Information Technology, Office of Health Informatics and Analytics, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Chen, Lawrence O AU - Chen LO AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Lapinska, Sandra AU - Lapinska S AD - Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. FAU - Ariannejad, Maryam AU - Ariannejad M AD - Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Lajonchere, Clara AU - Lajonchere C AD - Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. CN - UCLA Precision Health Data Discovery Repository Working Group CN - UCLA Precision Health ATLAS Working Group CN - UCLA Health IT HPC Team CN - Regeneron Genetics Center FAU - Kenny, Eimear E AU - Kenny EE AD - Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, NY 10027, USA; Center for Translational Genomics, Icahn School of Medicine, New York, NY 10027, USA; Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine, New York, NY 10027, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine, New York, NY 10027, USA. FAU - Pasaniuc, Bogdan AU - Pasaniuc B AD - Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. FAU - Bui, Alex A T AU - Bui AAT AD - Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Radiological Sciences, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Arboleda, Valerie A AU - Arboleda VA AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Chang, Timothy S AU - Chang TS AD - Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Zaitlen, Noah AU - Zaitlen N AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Computational Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. FAU - Spellman, Paul T AU - Spellman PT AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: pspellman@mednet.ucla.edu. FAU - Boutros, Paul C AU - Boutros PC AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. Electronic address: pboutros@sbpdiscovery.org. FAU - Geschwind, Daniel H AU - Geschwind DH AD - Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: dhg@mednet.ucla.edu. LA - eng GR - U54 NS123746/NS/NINDS NIH HHS/United States GR - F30 MH135712/MH/NIMH NIH HHS/United States GR - T15 LM013976/LM/NLM NIH HHS/United States GR - T32 HG002536/HG/NHGRI NIH HHS/United States GR - R01 AG085518/AG/NIA NIH HHS/United States GR - R01 HG011345/HG/NHGRI NIH HHS/United States GR - K08 AG065519/AG/NIA NIH HHS/United States GR - T32 EB016640/EB/NIBIB NIH HHS/United States GR - F31 HG013462/HG/NHGRI NIH HHS/United States GR - F31 CA281168/CA/NCI NIH HHS/United States GR - T32 GM008042/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20260327 PL - United States TA - Cell JT - Cell JID - 0413066 RN - 53AXN4NNHX (Semaglutide) SB - IM UOF - medRxiv. 2025 Jun 12:2025.06.11.25329386. doi: 10.1101/2025.06.11.25329386. PMID: 40585105 MH - Humans MH - *Precision Medicine/methods MH - Genetic Risk Score MH - Diabetes Mellitus, Type 2/genetics/drug therapy MH - Semaglutide MH - European People MH - Electronic Health Records MH - Genetic Predisposition to Disease MH - Genome-Wide Association Study MH - Multifactorial Inheritance/genetics MH - Genetic Variation MH - White People/genetics MH - Black or African American/genetics MH - Female PMC - PMC13353064 MID - NIHMS2161011 OTO - NOTNLM OT - GLP-1 receptor agonists OT - ancestry OT - electronic health records OT - exome-wide association study OT - genetic association OT - genomic medicine OT - health-system biobank OT - phenome-wide association study OT - polygenic scores OT - semaglutide COIS- Declaration of interests E.E.K. has received personal fees from Regeneron Pharmaceuticals, 23&Me, Allelica, and Illumina; has received research funding from Allelica; and serves on the advisory boards for Encompass Biosciences, Overtone, and Galateo Bio. P.T.S. is a consultant for 10x Genomics, Illumina, Foresight Diagnostics, Natera, and Twinstrand. P.C.B. sits on the scientific advisory board of Intersect Diagnostics Inc. and previously sat on those of Sage Bionetworks and BioSymetrics Inc. EDAT- 2026/03/29 07:35 MHDA- 2026/05/02 00:33 PMCR- 2026/07/10 CRDT- 2026/03/28 19:41 PHST- 2025/07/14 00:00 [received] PHST- 2025/11/21 00:00 [revised] PHST- 2026/03/05 00:00 [accepted] PHST- 2026/05/02 00:33 [medline] PHST- 2026/03/29 07:35 [pubmed] PHST- 2026/03/28 19:41 [entrez] PHST- 2026/07/10 00:00 [pmc-release] AID - S0092-8674(26)00274-6 [pii] AID - 10.1016/j.cell.2026.03.007 [doi] PST - ppublish SO - Cell. 2026 Apr 30;189(9):2533-2555.e31. doi: 10.1016/j.cell.2026.03.007. Epub 2026 Mar 27. PMID- 41902614 OWN - NLM STAT- MEDLINE DCOM- 20260613 LR - 20260613 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 Suppl 1 DP - 2026 Jun TI - Real-World Weight-Loss Outcomes in Weight-Reduced Patients Treated With Tirzepatide. PG - 97-101 LID - 10.1002/oby.70179 [doi] AB - OBJECTIVE: This study compared weight-loss outcomes in patients prescribed tirzepatide by weight-loss status and assessed results among patients transitioning from semaglutide. METHODS: This retrospective cohort study analyzed 6-month weight-loss outcomes in adults treated with tirzepatide between May 2022 and January 2023. Patients were classified as weight-reduced if they had lost >/= 10% total body weight (TBW) before starting tirzepatide. Among those who switched from therapeutic semaglutide (>/= 1.7 mg weekly for >/= 1 month), reasons for switching were categorized as non-response (< 5% weight loss after >/= 3 months), plateau (>/= 5% loss followed by weight stabilization), or other. RESULTS: Of 941 charts, 293 (31.1%) met inclusion criteria (65% female; mean age 52 years; mean BMI 36.15 kg/m(2)). Weight-reduced patients (n = 133) lost 7.2% TBW versus 10.3% in non-weight-reduced patients (n = 160; p < 0.001). When analyses were stratified by type 2 diabetes (T2D) status, this difference remained significant among patients without T2D. Sixty-one patients switched from semaglutide due to non-response or plateau and lost 5.3% TBW. Those switching at a plateau (n = 28) lost 8.1% versus 2.9% for non-responders (n = 33; p < 0.001). CONCLUSIONS: Tirzepatide produced meaningful weight loss across groups but outcomes varied based on weight-reduction status, T2D status, and prior response to semaglutide. CI - (c) 2026 The Obesity Society. FAU - Barenbaum, Sarah R AU - Barenbaum SR AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Comprehensive Weight Control Center, Weill Cornell Medicine, New York, New York, USA. AD - Weill Cornell Medical College, New York, New York, USA. FAU - Gonzalez, Ariel AU - Gonzalez A AD - Weill Cornell Medical College, New York, New York, USA. FAU - Verzani, Zoe AU - Verzani Z AD - Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medicine, New York, New York, USA. FAU - Zhao, Alice S AU - Zhao AS AD - Department of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. FAU - Shukla, Alpana P AU - Shukla AP AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Comprehensive Weight Control Center, Weill Cornell Medicine, New York, New York, USA. AD - Weill Cornell Medical College, New York, New York, USA. LA - eng GR - UL1TR002384/Clinical and Translational Science Center, Weill Cornell Medical College/ PT - Journal Article DEP - 20260328 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - Female MH - *Weight Loss/drug effects MH - Middle Aged MH - Semaglutide MH - Retrospective Studies MH - Male MH - Treatment Outcome MH - Adult MH - *Obesity/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Anti-Obesity Agents/therapeutic use MH - Aged MH - Body Mass Index MH - Diabetes Mellitus, Type 2/drug therapy EDAT- 2026/03/29 07:29 MHDA- 2026/06/15 11:32 CRDT- 2026/03/28 06:02 PHST- 2026/01/23 00:00 [revised] PHST- 2025/11/21 00:00 [received] PHST- 2026/02/16 00:00 [accepted] PHST- 2026/06/15 11:32 [medline] PHST- 2026/03/29 07:29 [pubmed] PHST- 2026/03/28 06:02 [entrez] AID - 10.1002/oby.70179 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Jun;34 Suppl 1:97-101. doi: 10.1002/oby.70179. Epub 2026 Mar 28. PMID- 41898712 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 6 DP - 2026 Mar 21 TI - GLP-1 Receptor Agonists at the Crossroads of Circadian Biology, Sleep, and Metabolic Disease. LID - 10.3390/ijms27062853 [doi] LID - 2853 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed the management of type 2 diabetes and obesity, yet their actions extend beyond glycemic control and weight loss. This narrative review synthesizes current preclinical and clinical evidence examining the bidirectional relationship between glucagon-like peptide-1 (GLP-1) receptor agonists and circadian biology. A structured literature search was conducted in PubMed using combinations of the terms 'GLP-1,' 'circadian,' 'chronobiology,' 'sleep,' 'obesity,' and 'type 2 diabetes' through January 2026. Accumulating evidence indicates that GLP-1 physiology is closely coupled to circadian timing systems and sleep-wake regulation. In this narrative review, we synthesize emerging data that reframe GLP-1RAs as chronometabolic modulators, acting at the intersection of metabolism, circadian biology, and sleep. We review circadian control of GLP-1 secretion by intestinal L-cells, emphasizing the role of core clock genes and the vulnerability of incretin rhythms to circadian misalignment from shift work, nocturnal light exposure, and sleep loss. We then examine GLP-1 receptor signaling within central and peripheral clock networks, including feedback effects on hypothalamic and hepatic circadian regulation. Emerging data suggest that GLP-1 signaling is under circadian regulation and may, in turn, influence central and peripheral clock systems. Comparative discussion of semaglutide, liraglutide, and tirzepatide highlights agent-specific pharmacokinetics and emerging clinical data linking GLP-1RA therapy to sleep outcomes, particularly obstructive sleep apnea. Finally, we outline translational opportunities for chronotherapy and precision medicine, positioning GLP-1RAs as integrative tools for metabolic and sleep-related disease rather than purely weight-centric therapies. We propose that GLP-1 receptor agonists may function as chronometabolic modulators, with potential implications for personalized chronopharmacological strategies in metabolic disease. FAU - Gandhi, Ayush AU - Gandhi A AUID- ORCID: 0009-0008-8508-152X AD - Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Phyu, Ei Moe AU - Phyu EM AD - Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Koom-Dadzie, Kwame AU - Koom-Dadzie K AUID- ORCID: 0000-0002-6365-9203 AD - Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Dickson, Kodwo Bosomefi AU - Dickson KB AD - Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. FAU - Halm, Josiah AU - Halm J AD - Department of Hospital Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. LA - eng PT - Journal Article PT - Review DEP - 20260321 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Circadian Rhythm/drug effects MH - Animals MH - *Metabolic Diseases/drug therapy/metabolism MH - *Sleep/drug effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Semaglutide MH - Obesity/drug therapy/metabolism MH - Tirzepatide MH - Hypoglycemic Agents/pharmacology/therapeutic use PMC - PMC13026677 OTO - NOTNLM OT - GLP-1 receptor agonists OT - chronopharmacology OT - chronotherapy OT - circadian rhythms OT - clock genes OT - incretin hormones OT - metabolic disease OT - obstructive sleep apnea OT - sleep disorder OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/03/28 06:39 MHDA- 2026/03/28 06:40 PMCR- 2026/03/21 CRDT- 2026/03/28 01:23 PHST- 2026/02/15 00:00 [received] PHST- 2026/03/16 00:00 [revised] PHST- 2026/03/19 00:00 [accepted] PHST- 2026/03/28 06:40 [medline] PHST- 2026/03/28 06:39 [pubmed] PHST- 2026/03/28 01:23 [entrez] PHST- 2026/03/21 00:00 [pmc-release] AID - ijms27062853 [pii] AID - ijms-27-02853 [pii] AID - 10.3390/ijms27062853 [doi] PST - epublish SO - Int J Mol Sci. 2026 Mar 21;27(6):2853. doi: 10.3390/ijms27062853. PMID- 41898482 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 6 DP - 2026 Mar 13 TI - Gastric Neoplasm Risk with DPP-4 Inhibitors, GLP-1 Receptor Agonists, and SGLT2 Inhibitors: Network Meta-Analysis of Randomized Trials. LID - 10.3390/ijms27062619 [doi] LID - 2619 AB - Whether the risk of gastric neoplasm is modified by newer glucose-lowering therapies-dipeptidyl peptidase-4 inhibitors (DPP4is), glucagon-like peptide-1 receptor agonists (GLP1RAs), and sodium-glucose cotransporter 2 inhibitors (SGLT2is)-remains uncertain. Given their global uptake and long-term use in populations already predisposed to malignancy, decision-grade comparative safety evidence is needed. We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in adults without baseline gastric neoplasms. PubMed, Embase, Cochrane CENTRAL, Web of Science, ClinicalTrials.gov, ClinicalKey, ProQuest, and ScienceDirect were searched from inception to 10 January 2026, without language restrictions. The primary outcome was incident gastric neoplasms (benign or malignant). Random-effects frequentist NMA estimated risk ratios (RRs) with 95% confidence intervals (CIs); Bayesian NMA served as sensitivity analysis. Certainty of evidence was assessed using GRADE adapted for NMA (PROSPERO CRD420261282728). Fifty-two RCTs (171,165 participants; mean age 63.6 years; 36.9% women; mean follow-up 141.8 weeks) were included. At the class level, GLP1RAs were associated with lower gastric neoplasm risk versus controls (RR = 0.51, 95% CI = 0.28-0.92), whereas DPP4is were associated with higher risk (RR = 1.77, 95% CI = 1.09-2.85). These signals persisted in prespecified subgroup analyses among participants with diabetes mellitus, in trials with duration >/=52 weeks (GLP1RA: RR = 0.52, 95% CI = 0.28-0.95; DPP4i: RR = 2.05, 95% CI = 1.19-3.55), and in older populations (age >/=60 years; DPP4i: RR = 2.08, 95% CI = 1.15-3.77). No class showed a significant association in younger participants (<60 years) or shorter trials (<52 weeks). Across available RCT evidence, GLP1RA prescription generally had a relatively lower gastric neoplasm risk than controls. In contrast, among patients with diabetes mellitus receiving longer-term therapy, GLP1RAs may be the preferable option from the perspective of gastric neoplasm risk, while DPP4is warrant heightened vigilance and mechanistic clarification. These findings support improved neoplasms ascertainment in future trials rather than immediate prescribing changes. FAU - Hung, Chao-Ming AU - Hung CM AD - Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan. FAU - Hsu, Chih-Wei AU - Hsu CW AUID- ORCID: 0000-0002-8650-4060 AD - Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. FAU - Zeng, Bing-Syuan AU - Zeng BS AD - Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan. FAU - Suen, Mein-Woei AU - Suen MW AUID- ORCID: 0000-0002-3991-0322 AD - Department of Psychology, College of Medical and Health Science, Asia University, Taichung 413, Taiwan. AD - Gender Equality Education and Research Center, Asia University, Taichung 413, Taiwan. AD - Department of Medical Research, Asia University Hospital, Asia University, Taichung 413, Taiwan. AD - Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 406, Taiwan. FAU - Chen, Jiann-Jy AU - Chen JJ AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 811, Taiwan. AD - Department of Otorhinolaryngology, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan. FAU - Zeng, Bing-Yan AU - Zeng BY AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan. AD - Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung 807, Taiwan. FAU - Carvalho, Andre F AU - Carvalho AF AD - Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC 3216, Australia. FAU - Stubbs, Brendon AU - Stubbs B AD - Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London WC2R 2LS, UK. AD - Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, 1090 Vienna, Austria. AD - Clinical Division of Social Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, 1090 Vienna, Austria. FAU - Chen, Yen-Wen AU - Chen YW AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 811, Taiwan. FAU - Chen, Tien-Yu AU - Chen TY AUID- ORCID: 0000-0001-8462-1311 AD - Department of Psychiatry, Tri-Service General Hospital, Taipei 114, Taiwan. AD - Department of Psychiatry, College of Medicine, National Defense Medical University, Taipei 114, Taiwan. FAU - Hsu, Shih-Pin AU - Hsu SP AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan. AD - Department of Neurology, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan. FAU - Wang, Hung-Yu AU - Wang HY AD - Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Kaohsiung 802, Taiwan. FAU - Liang, Chih-Sung AU - Liang CS AD - Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, School of Medicine, National Defense Medical University, Taipei 114, Taiwan. AD - Department of Psychiatry, National Defense Medical University, Taipei 114, Taiwan. FAU - Tu, Yu-Kang AU - Tu YK AUID- ORCID: 0000-0002-2461-474X AD - Institute of Health Data Analytics & Statistics, College of Public Health, National Taiwan University, No. 17, Xuzhou Road, Taipei 100, Taiwan. AD - Department of Dentistry, National Taiwan University Hospital, Taipei 100, Taiwan. FAU - Tseng, Ping-Tao AU - Tseng PT AUID- ORCID: 0000-0001-5761-7800 AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung 811, Taiwan. AD - Institute of Precision Medicine, National Sun Yat-sen University, No. 70 Lienhai Rd., Kaohsiung 804, Taiwan. AD - School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260313 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Stomach Neoplasms/epidemiology/chemically induced/etiology MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Female MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Risk Factors PMC - PMC13026302 OTO - NOTNLM OT - DPP-4 inhibitor OT - GLP-1 receptor agonist OT - SGLT2 inhibitor OT - diabetes mellitus OT - gastric neoplasms OT - semaglutide COIS- The authors declare no conflict of interest. The authors of this work were supported by the following grants: Brendon Stubbs is supported by an NIHR Advanced Fellowship. Brendon Stubbs is partly funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. EDAT- 2026/03/28 06:39 MHDA- 2026/03/28 06:40 PMCR- 2026/03/13 CRDT- 2026/03/28 01:22 PHST- 2026/01/15 00:00 [received] PHST- 2026/02/10 00:00 [revised] PHST- 2026/03/10 00:00 [accepted] PHST- 2026/03/28 06:40 [medline] PHST- 2026/03/28 06:39 [pubmed] PHST- 2026/03/28 01:22 [entrez] PHST- 2026/03/13 00:00 [pmc-release] AID - ijms27062619 [pii] AID - ijms-27-02619 [pii] AID - 10.3390/ijms27062619 [doi] PST - epublish SO - Int J Mol Sci. 2026 Mar 13;27(6):2619. doi: 10.3390/ijms27062619. PMID- 41893299 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260823 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 6 DP - 2026 Jun 1 TI - Safety of Semaglutide After Dialysis Initiation: An Individual-Level Pooled Analysis. PG - 999-1005 LID - 10.2337/dc26-0112 [doi] AB - OBJECTIVE: People receiving dialysis are at high risk of cardiovascular and all-cause mortality. Semaglutide reduces major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) and those without T2D with obesity and high cardiovascular risk. Data to establish safety and efficacy in dialysis-dependent kidney failure are scarce. We aimed to assess the safety of semaglutide in people who initiate dialysis. RESEARCH DESIGN AND METHODS: In this post hoc analysis of four randomized, placebo-controlled trials (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6], Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity [SELECT], Evaluate Renal Function With Semaglutide Once Weekly [FLOW], and Semaglutide Cardiovascular Outcomes [SOUL]), we evaluated systematically collected adverse events (AEs) from participants who initiated dialysis during study follow-up. We compared the proportion and event rates of systematically collected serious AEs (SAEs), including adjudicated MACE, and AEs leading to permanent treatment discontinuation in participants originally randomized to semaglutide or placebo who remained on treatment after dialysis initiation. RESULTS: Among 34,064 participants randomized across the trials, 307 initiated dialysis, of whom 165 participants randomized to semaglutide (n = 71) or placebo (n = 94) remained on treatment. After dialysis initiation, SAEs were reported in 32 of 71 (45%) and 54 of 94 (57%) participants, and the proportion of participants who permanently discontinued trial medication was 8.5% and 10.6% in the semaglutide and placebo groups, respectively. The MACE event rates were 9.7 and 16.1 events per 100 person-years, and all-cause mortality event rates were 13.8 and 18.1 events per 100 person-years, in the semaglutide and placebo groups, respectively. CONCLUSIONS: Although more evidence is needed, continuation of semaglutide after dialysis initiation appears safe and warrants efficacy testing regarding reduction in MACE and death. CI - (c) 2026 by the American Diabetes Association. FAU - Klein, Klara R AU - Klein KR AUID- ORCID: 0000-0002-5894-9054 AD - Division of Endocrinology and Metabolism, University of North Carolina at Chapel Hill, Chapel Hill, NC. FAU - Menacher, Anna AU - Menacher A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - Division of Endocrinology and Metabolism, University of North Carolina at Chapel Hill, Chapel Hill, NC. FAU - Mann, Johannes F E AU - Mann JFE AD - University Hospital Erlangen, Erlangen, Germany. AD - KfH Kidney Centre, Munich, Germany. FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Division of Nephrology, University of Washington, Seattle, WA. FAU - Kvist, Kajsa AU - Kvist K AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Andersen, Margit R AU - Andersen MR AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mayrdorfer, Manuel AU - Mayrdorfer M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX. LA - eng GR - R01 DK125831/DK/NIDDK NIH HHS/United States GR - R44 DK096803/DK/NIDDK NIH HHS/United States GR - UC4 DK108612/DK/NIDDK NIH HHS/United States GR - U01 DK100846/DK/NIDDK NIH HHS/United States GR - R01 DK119913/DK/NIDDK NIH HHS/United States GR - R01 DK112939/DK/NIDDK NIH HHS/United States GR - OT2 OD032581/OD/NIH HHS/United States GR - U54 DK118612/DK/NIDDK NIH HHS/United States GR - P30 DK124723/DK/NIDDK NIH HHS/United States GR - R01 MD014712/MD/NIMHD NIH HHS/United States GR - UM1 TR004406/TR/NCATS NIH HHS/United States GR - P30 DK127984/DK/NIDDK NIH HHS/United States GR - R01 DK127365/DK/NIDDK NIH HHS/United States GR - R33 HL142680/HL/NHLBI NIH HHS/United States GR - U2C DK114886/DK/NIDDK NIH HHS/United States GR - OT2 HL161847/HL/NHLBI NIH HHS/United States GR - U01 DK098246/DK/NIDDK NIH HHS/United States GR - U54 DK083912/DK/NIDDK NIH HHS/United States GR - UL1 TR002489/TR/NCATS NIH HHS/United States GR - UL1 TR002319/TR/NCATS NIH HHS/United States GR - K12 TR004416/TR/NCATS NIH HHS/United States PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Renal Dialysis MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Cardiovascular Diseases/prevention & control PMC - PMC13191398 COIS- Duality of Interest. K.R.K. has received advisory/consulting fees and/or other support from Antag Therapeutics, Metsera, Novo Nordisk, and Roche Pharmaceuticals. Additionally, K.R.K. has received research-related contracts (paid to the institution) from Bayer, Boehringer-Ingelheim, Carmot, Diasome, Eli Lilly, Gentibio, Novo Nordisk, Rhythm Pharmaceuticals, Roche Pharmaceuticals, and vTv Therapeutics. J.B.B. has received salary support from clinical trial contracts to his employer by Corcept Therapeutics, Dexcom, GentiBio, Novo Nordisk, and Sparrow Pharmaceuticals; has received salary support from consulting contracts to his employer by Novo Nordisk; is a consultant with personal compensation from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, General Medicines Inc, GentiBio, Kayothera, Metsera, MiniMed, Recordati, Sparrow Pharmaceuticals, Vertex Pharmaceuticals, vTv Therapeutics, and Zealand Pharma; and has stock/options in Aardvark Therapeutics, Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. J.F.E.M. reports grants from Novo Nordisk; honoraria from AstraZeneca, Bayer, Cytel, ICON plc, IQVIA, Hexal, Novo Nordisk, Sanofi, UpToDate, and WCG; and a leadership role in the Kidney Disease: Improving Global Outcomes (KDIGO) group. K.R.T. has received investigator-initiated grant support from Travere Therapeutics Inc., Bayer, and Benaroya Research Institute. She reports consultancy fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Bayer, ProKidney, and Alnylam Pharmaceuticals, as well as speaker fees from Novo Nordisk, Bayer, Boehringer Ingelheim, and AstraZeneca. Additionally, she reports being chair of data safety monitoring boards for the National Institute of Diabetes and Digestive and Kidney Disease, and George Clinical Institute, and a member of the data safety monitoring board for AstraZeneca. She reports leadership roles as chair for the Diabetic Kidney Disease Collaborative and chair for Kidney Week 2025 Program Committee, both for the American Society of Nephrology. A.M., K.K., M.R.A., and M.M. are employees of Novo Nordisk. K.K. and M.M. are also shareholders of Novo Nordisk. I.L. has received research funding (paid to the institution) from Novo Nordisk, Sanofi, Boehringer Ingelheim, and Roche; research-related consulting fees (paid to the institution) from Novo Nordisk; and advisory/consulting fees and/or other support from Abbvie, Altimmune, AstraZeneca, Bayer, Biomea Fusion, Boehringer Ingelheim, Carmot Therapeutics, Cytoki Pharma, Eli Lilly, Intercept, Janssen/J&J, Mediflix, Merck, Metsera, Novo Nordisk, PharmaVentures, Pfizer, Regeneron, Sanofi, Shionogi, Structure Therapeutics, TARGET RWE, TERNS Pharmaceuticals, The Comm Group, Verdiva Bio, WebMD, and Zealand Pharma. No other potential conflicts of interest relevant to this article were reported. EDAT- 2026/03/27 17:38 MHDA- 2026/05/20 18:33 PMCR- 2026/03/27 CRDT- 2026/03/27 11:25 PHST- 2026/01/15 00:00 [received] PHST- 2026/03/02 00:00 [accepted] PHST- 2026/05/20 18:33 [medline] PHST- 2026/03/27 17:38 [pubmed] PHST- 2026/03/27 11:25 [entrez] PHST- 2026/03/27 00:00 [pmc-release] AID - 164644 [pii] AID - 260112 [pii] AID - 10.2337/dc26-0112 [doi] PST - ppublish SO - Diabetes Care. 2026 Jun 1;49(6):999-1005. doi: 10.2337/dc26-0112. PMID- 41889157 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Lower Risk of Cardiovascular Events in Patients With Clinical Atherosclerotic Cardiovascular Disease Who Initiated Semaglutide 2.4 mg in the Real-World: Results From the SCORE-Clinical ASCVD Study. PG - 4975-4990 LID - 10.1111/dom.70686 [doi] AB - AIMS: To evaluate the association between semaglutide 2.4 mg and major adverse cardiovascular events (MACE) among adults with clinical atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity without diabetes in real-world clinical practice. MATERIALS AND METHODS: Adults aged >/= 45 years with overweight/obesity and clinical ASCVD were identified from a United States database (2016-2024). Patients initiating semaglutide 2.4 mg were matched 1:2 with individuals not treated with semaglutide 2.4 mg through a propensity score model including > 70 demographic and clinical covariates. Primary outcomes were revised 3-point MACE (rMACE-3: myocardial infarction [MI], stroke, all-cause mortality) and revised 5-point MACE (rMACE-5: rMACE-3, heart failure [HF] hospitalisation, coronary revascularization). Secondary outcomes included 3-point MACE and 5-point MACE (replacing all-cause mortality with cardiovascular-related mortality) and HF composite outcomes; exploratory outcomes were incident type 2 diabetes (T2D), major adverse kidney events (MAKE) and major obesity-related adverse events (MORAE). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: The final sample comprised 38 308 patients with semaglutide 2.4 mg use propensity-score matched to 76 615 patients without. Over a mean follow-up of 8.6 months, semaglutide 2.4 mg significantly reduced the risk of rMACE-3 (HR: 0.55; 95% CI: 0.47-0.65), rMACE-5 (0.63; 0.56-0.71), MACE-3 (0.66; 0.56-0.78) and MACE-5 (0.69; 0.62-0.77). Semaglutide 2.4 mg also significantly reduced the risk of HF composite outcomes, T2D, MAKE and MORAE. CONCLUSIONS: Semaglutide 2.4 mg was associated with a significantly reduced risk of MACE and other obesity-related outcomes, extending prior evidence of benefits to a broader clinical ASCVD population. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Nanna, Michael G AU - Nanna MG AUID- ORCID: 0000-0001-5745-1636 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Mena-Hurtado, Carlos AU - Mena-Hurtado C AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Divino, Victoria AU - Divino V AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Zhao, Zhenxiang AU - Zhao Z AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Chen, Yan AU - Chen Y AUID- ORCID: 0000-0002-5317-1909 AD - Analysis Group, Inc., Los Angeles, California, USA. FAU - Boland, Joanna AU - Boland J AUID- ORCID: 0000-0001-7858-979X AD - Analysis Group, Inc., Los Angeles, California, USA. FAU - Song, Jinlin AU - Song J AD - Analysis Group, Inc., Los Angeles, California, USA. FAU - Traina, Andrea AU - Traina A AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Ozer, Kerem AU - Ozer K AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Knop, Filip K AU - Knop FK AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Smolderen, Kim G AU - Smolderen KG AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. AD - Section of Psychology, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA. LA - eng GR - Novo Nordisk, Inc./ PT - Journal Article DEP - 20260326 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Female MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Aged MH - Middle Aged MH - *Atherosclerosis/epidemiology/complications/drug therapy MH - Obesity/complications/drug therapy MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Diabetes Mellitus, Type 2/epidemiology MH - Overweight/complications/drug therapy MH - Propensity Score MH - United States/epidemiology MH - Risk Factors PMC - PMC13146205 OTO - NOTNLM OT - GLP-1 OT - cardiovascular disease OT - cohort study OT - observational study OT - real-world evidence OT - semaglutide COIS- Zhenxiang Zhao, Victoria Divino, Andrea Traina, Kerem Ozer, and Filip K. Knop are employees of Novo Nordisk and hold stock/options. Jinlin Song, Yan Chen and Joanna Boland are employees of Analysis Group Inc., which has received consulting fees from Novo Nordisk Inc. for this work. Kim G. Smolderen receives research grants from Johnson & Johnson, Merck, and Abbott. She is a consultant for Dario Health, Terumo, Novo Nordisk and Merck. She is the owner of BoboDream LLC. She receives funding from the National Institutes of Health (R01HL163640-03S1; R01HL163640-02S1; R21AT012430-01). Carlos Mena-Hurtado is a consultant for Terumo, Novo Nordisk, HMP Global and Cook. He receives research grants from Merck, Shockwave, and the National Institutes of Health. Michael G. Nanna: Dr. Nanna reports current research support from the American College of Cardiology Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342), and the National Institute on Aging (K76AG088428). Dr. Nanna also reports being a consultant for Novo Nordisk, Heartflow, Novartis and Merck. EDAT- 2026/03/27 07:15 MHDA- 2026/05/06 06:38 PMCR- 2026/05/06 CRDT- 2026/03/27 02:32 PHST- 2026/03/10 00:00 [revised] PHST- 2025/12/19 00:00 [received] PHST- 2026/03/11 00:00 [accepted] PHST- 2026/05/06 06:38 [medline] PHST- 2026/03/27 07:15 [pubmed] PHST- 2026/03/27 02:32 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - DOM70686 [pii] AID - 10.1111/dom.70686 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):4975-4990. doi: 10.1111/dom.70686. Epub 2026 Mar 26. PMID- 41886296 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 1520-7560 (Electronic) IS - 1520-7552 (Print) IS - 1520-7552 (Linking) VI - 42 IP - 4 DP - 2026 May TI - Not All GLP-1 Receptor Agonists Are Alike: Real-World Evidence of Differential Endocrine and Dermatologic Safety. PG - e70163 LID - 10.1002/dmrr.70163 [doi] LID - e70163 AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for metabolic disorders, but emerging safety concerns include alopecia and reproductive or endocrine-related adverse events (AEs). This study investigated the association between specific GLP-1 RAs and these endocrine-related AEs using a large-scale pharmacovigilance database. MATERIALS AND METHODS: This study analysed the U.S. FDA Adverse Event Reporting System (FAERS) data (Q2 2022-Q2 2025) for six GLP-1 Ras (exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide) to identify alopecia- and reproductive or endocrine-related a AEs. Disproportionality analyses were conducted using crude and adjusted reporting odds ratios (cROR and aROR) from logistic regression controlling for potential confounding factors. Sensitivity analyses with positive and negative controls were used to validate the signal robustness. RESULTS: A total of 1276 alopecia-related and 759 reproductive or endocrine-related cases were identified. Semaglutide showed significant positive associations with alopecia (aROR 1.23 [1.11-1.35]) and reproductive/hormonal disorders, including polycystic ovary syndrome (aROR 6.59 [3.73-11.64]) and menstrual abnormalities. In contrast, dulaglutide and tirzepatide demonstrated negative associations for several reproductive outcomes (e.g., dysmenorrhoea, amenorrhoea, heavy menstrual bleeding), indicating lower reporting odds in this dataset. Sensitivity analyses using control drugs confirmed the consistency and specificity of these findings. CONCLUSION: This real-world pharmacovigilance study identified agent-specific differences in the endocrine and dermatologic safety profiles of GLP-1 RAs. While semaglutide exhibited disproportionate reporting for alopecia and hormonal imbalance, dulaglutide and tirzepatide showed lower or non-significant disproportionality signals for these events. These results highlight the need for personalised agent selection and continued pharmacovigilance to optimise long-term patient safety. CI - (c) 2026 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. FAU - Lee, Nai AU - Lee N AD - College of Pharmacy, Daegu Catholic University, Gyeongsan, Gyeongsangbuk-do, South Korea. FAU - Kim, Yun AU - Kim Y AUID- ORCID: 0000-0002-9809-7351 AD - College of Pharmacy, Daegu Catholic University, Gyeongsan, Gyeongsangbuk-do, South Korea. AD - Convergence Research Institute for Biomedical Sciences, Daegu Catholic University, Gyeongsan, Gyeongsangbuk-do, South Korea. LA - eng GR - Catholic University of Daegu/ GR - 2025-RISE-15-107/Gyeongsangbuk-do RISE Project/ PT - Journal Article PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Alopecia/chemically induced/epidemiology MH - Female MH - Tirzepatide MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Pharmacovigilance MH - *Hypoglycemic Agents/adverse effects MH - United States/epidemiology MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Male MH - Exenatide/adverse effects MH - Liraglutide/adverse effects MH - Follow-Up Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC13020769 OTO - NOTNLM OT - FDA adverse event reporting system OT - GLP-1 receptor agonists OT - alopecia OT - reproductive or endocrine-related adverse events COIS- The authors declare no conflicts of interest. EDAT- 2026/03/26 18:49 MHDA- 2026/03/26 18:50 PMCR- 2026/03/26 CRDT- 2026/03/26 12:53 PHST- 2026/02/21 00:00 [revised] PHST- 2025/12/18 00:00 [received] PHST- 2026/03/17 00:00 [accepted] PHST- 2026/03/26 18:50 [medline] PHST- 2026/03/26 18:49 [pubmed] PHST- 2026/03/26 12:53 [entrez] PHST- 2026/03/26 00:00 [pmc-release] AID - DMRR70163 [pii] AID - 10.1002/dmrr.70163 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2026 May;42(4):e70163. doi: 10.1002/dmrr.70163. PMID- 41883191 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260813 IS - 2055-5822 (Electronic) IS - 2055-5822 (Linking) VI - 13 IP - 2 DP - 2026 Mar 3 TI - Glucagon-like peptide-1 receptor agonists for prevention of heart failure events in type 2 diabetes and/or obesity. LID - 10.1093/eschf/xvag091 [doi] LID - xvag091 AB - INTRODUCTION: Heart failure (HF) is a common sequela of diabetes and obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists may prevent HF events. This meta-analysis estimates absolute risk reduction (ARR) and number needed to treat (NNT) for GLP-1 receptor agonists to prevent one HF event in patients with type 2 diabetes and/or obesity, including those without baseline HF. METHODS: The Medline, Embase, and Cochrane Central databases were searched to 04 April 2025 for placebo-controlled randomized controlled trials (RCTs) of GLP-1 receptor agonists in a type 2 diabetes and/or obesity indication with a prespecified HF event endpoint. Random effects meta-analysis using the Mantel-Haenszel Method was performed to synthesize risk ratios (RR), ARRs, and NNTs with 95% confidence intervals (CI). RESULTS: Twelve placebo-controlled RCTs involving 95 023 patients were included. GLP-1 receptor agonists reduced HF events by 12% (RR 0.88, 95% CI 0.82-0.95; ARR 0.42%, 95% CI 0.17%-0.62%; NNT 238, 95% CI 161-588), and, in those without baseline HF, by 19% (RR 0.81, 95% CI 0.72-0.90; ARR 0.60%, 95% CI 0.32%-0.89%; NNT 167, 95% CI 113-313). Semaglutide reduced the risk of HF events by 16% (RR 0.84, 95% CI 0.74-0.95; ARR 0.62%, 95% CI 0.19%-1.00%; NNT 161, 95% CI 100-526), and by 31% in those without baseline HF (RR 0.69, 95% CI 0.55-0.88; ARR 1.25%, 95% CI 0.48%-1.82%; NNT 80, 95% CI 55-208). CONCLUSION: GLP-1 receptor agonists have limited absolute benefit for preventing HF events in patients with type 2 diabetes and/or obesity, including in those without baseline HF. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD420251074882. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Raveendra, Keerthenan AU - Raveendra K AUID- ORCID: 0000-0001-8766-9433 AD - Faculty of Medicine and Health, University of Leeds, Leeds, UK. FAU - Joseph, Tobin AU - Joseph T AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. FAU - Kang, Jing AU - Kang J AD - Centre for Clinical Translational Science, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, London, UK. FAU - Hurdus, Ben AU - Hurdus B AUID- ORCID: 0000-0001-8149-3449 AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. FAU - Cutting, Uther AU - Cutting U AD - Faculty of Medicine and Health, University of Leeds, Leeds, UK. FAU - Haris, Mohammad AU - Haris M AUID- ORCID: 0009-0007-3859-7809 AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. FAU - Younsi, Tanina AU - Younsi T AUID- ORCID: 0009-0000-3680-4180 AD - Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3AX, UK. FAU - Aslam, Amaan AU - Aslam A AD - Faculty of Medicine and Health, University of Leeds, Leeds, UK. FAU - Petrie, Mark AU - Petrie M AD - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. FAU - Metra, Marco AU - Metra M AD - Institute of Cardiology, ASST Spedali Civili di Brescia and Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy. FAU - Ajjan, Ramzi A AU - Ajjan RA AUID- ORCID: 0000-0002-1636-3725 AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. FAU - Wu, Jianhua AU - Wu J AUID- ORCID: 0000-0001-6093-599X AD - Wolfson Institute of Population Health, Queen Mary University of London, London, UK. FAU - Gale, Chris P AU - Gale CP AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. AD - Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3AX, UK. AD - Leeds Institute of Data Analytics, University of Leeds, Leeds LS2 9NL, UK. FAU - Nadarajah, Ramesh AU - Nadarajah R AUID- ORCID: 0000-0001-9895-9356 AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, 6 Clarendon Way, Leeds LS2 9DA, UK. AD - Department of Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3AX, UK. AD - Leeds Institute of Data Analytics, University of Leeds, Leeds LS2 9NL, UK. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - ESC Heart Fail JT - ESC heart failure JID - 101669191 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Heart Failure/prevention & control/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - Randomized Controlled Trials as Topic PMC - PMC13064920 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Heart failure OT - Meta-analysis OT - Obesity OT - Type 2 diabetes EDAT- 2026/03/26 07:08 MHDA- 2026/04/09 18:30 PMCR- 2026/03/25 CRDT- 2026/03/26 03:53 PHST- 2026/02/21 00:00 [received] PHST- 2026/03/15 00:00 [revised] PHST- 2026/03/22 00:00 [accepted] PHST- 2026/04/09 18:30 [medline] PHST- 2026/03/26 07:08 [pubmed] PHST- 2026/03/26 03:53 [entrez] PHST- 2026/03/25 00:00 [pmc-release] AID - 8540500 [pii] AID - xvag091 [pii] AID - 10.1093/eschf/xvag091 [doi] PST - ppublish SO - ESC Heart Fail. 2026 Mar 3;13(2):xvag091. doi: 10.1093/eschf/xvag091. PMID- 41879791 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260918 IS - 2380-6591 (Electronic) IS - 2380-6583 (Print) VI - 11 IP - 5 DP - 2026 May 1 TI - Oral Semaglutide and Change in Cardiovascular Risk Factors in High-Risk Type 2 Diabetes: A Post Hoc Secondary Analysis of the SOUL Randomized Clinical Trial. PG - 427-437 LID - 10.1001/jamacardio.2026.0245 [doi] AB - IMPORTANCE: Individuals with type 2 diabetes (T2D) are at high risk of atherosclerotic cardiovascular disease (ASCVD). In the SOUL randomized clinical trial, once-daily oral semaglutide reduced risk of major adverse cardiovascular (CV) events by 14% vs placebo in people with T2D and ASCVD and/or chronic kidney disease (CKD) receiving standard of care (SoC); however, whether oral semaglutide modifies recognized CV risk factors in the long term is unclear. OBJECTIVE: To investigate whether treatment with oral semaglutide was associated with changes in ASCVD risk factors vs placebo. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis comprises post hoc intention-to-treat analyses of the SOUL (A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes) double-blind multicenter randomized clinical trial (randomization 1:1 to oral semaglutide or placebo) among adults with T2D and ASCVD and/or CKD receiving SoC. Participants underwent randomization from June 2019 to March 2021, with a mean (SD) of 47.5 (10.9) months of follow-up, and data were analyzed from February to December 2025. INTERVENTION(S): Participants were treated with either once-daily oral semaglutide (maximum dose, 14 mg) or placebo, in addition to standard care. MAIN OUTCOMES AND MEASURES: The primary outcome was the association of oral semaglutide vs placebo with glycated hemoglobin (HbA1c), body weight, and blood pressure (BP) using estimated treatment differences (ETDs) and with high-sensitivity C-reactive protein (hsCRP) and lipid plasma levels using estimated treatment ratios (ETRs). RESULTS: Of 9650 randomized participants (mean [SD] age, 66.1 (7.6) years; 2790 female participants [28.9%]), 9495 participants (98.4%) completed the trial. Early (13 weeks) improvements in HbA1c (-0.87 percentage points), body weight (-2.54%), systolic BP (SBP, -3.84 mm Hg), pulse pressure (-3.81 mm Hg), hsCRP (-18.08%), total cholesterol (TC, -7.00%), non-high-density lipoprotein cholesterol (non-HDL-C, -8.02%), HDL-C (-4.49%), and triglycerides (-8.15%) were observed with oral semaglutide vs placebo and sustained over the trial duration. Body weight reductions were gradual across both groups. At week 156, in favor of oral semaglutide were ETDs for HbA1c (-0.47 percentage points; 95% CI, -0.52 to -0.42), body weight (-3.26 percentage points; 95% CI, -3.55 to -2.98), SBP (-1.83 mm Hg; 95% CI, -2.47 to -1.18), and pulse pressure (-2.17 mm Hg; 95% CI, -2.72 to -1.61) and ETRs for hsCRP (0.77; 95% CI, 0.74-0.81), TC (0.99; 95% CI, 0.98-1.00), non-HDL-C (0.98; 95% CI, 0.97-0.99), HDL-C (1.01; 95% CI, 1.01-1.02), and triglycerides (0.94; 95% CI, 0.93-0.96). No significant treatment differences were observed for low-density lipoprotein cholesterol or diastolic BP. CONCLUSIONS AND RELEVANCE: In this post hoc secondary analysis of the SOUL randomized clinical trial, oral semaglutide was associated with early and sustained improvements vs placebo in multiple ASCVD risk factors in high-risk participants with T2D and ASCVD and/or CKD, incremental to SoC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03914326. FAU - Mulvagh, Sharon L AU - Mulvagh SL AD - Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. FAU - Inzucchi, Silvio E AU - Inzucchi SE AD - Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut. FAU - Marx, Nikolaus AU - Marx N AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, Rheinisch-Westfalische Technische Hochschule Aachen University, University Hospital Aachen, Aachen, Germany. FAU - Poulter, Neil R AU - Poulter NR AD - Imperial Clinical Trials Unit, Imperial College London, London, United Kingdom. FAU - Deanfield, John E AU - Deanfield JE AD - Institute for Cardiovascular Sciences, University College London, London, United Kingdom. FAU - Pop-Busui, Rodica AU - Pop-Busui R AD - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health & Science University, Portland. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle. FAU - Mann, Johannes F E AU - Mann JFE AD - Kuratorium fur Heimdialyse Kidney Center, Munich, Germany. AD - Friedrich Alexander University of Erlangen, Erlangen, Germany. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mandavya, Kabirdev AU - Mandavya K AD - Novo Nordisk Service Centre India Pvt Ltd, Bangalore, India. FAU - Davicevic-Elez, Zaklina AU - Davicevic-Elez Z AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jeppesen, Ole Kleist AU - Jeppesen OK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lorenzatti, Alberto AU - Lorenzatti A AD - Instituto Medico Docencia Asistencia Medica e Investigacion Clinica (DAMIC), Cordoba, Argentina. FAU - Oguz, Aytekin AU - Oguz A AD - Department of Internal Medicine, Faculty of Medicine, Istanbul Medeniyet University, Istanbul, Turkiye. FAU - Mankovsky, Boris AU - Mankovsky B AD - Institute of Gerontology, Kiev, Ukraine. FAU - Deerochanawong, Chaicharn AU - Deerochanawong C AD - Diabetes and Endocrinology Unit, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand. FAU - Gorgojo-Martinez, Juan J AU - Gorgojo-Martinez JJ AD - Department of Endocrinology and Nutrition, Hospital Universitario Fundacion Alcorcon, Madrid, Spain. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology, Peking University People's Hospital, Beijing, China. FAU - Bain, Stephen C AU - Bain SC AD - School of Medicine, Swansea University, Swansea, United Kingdom. FAU - McGuire, Darren K AU - McGuire DK AD - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas. AD - Parkland Health System, Dallas, Texas. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill. CN - SOUL Study Group LA - eng SI - ClinicalTrials.gov/NCT03914326 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - JAMA Cardiol JT - JAMA cardiology JID - 101676033 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM CIN - JAMA Cardiol. 2026 May 1;11(5):437-438. doi: 10.1001/jamacardio.2026.0261. PMID: 41879748 MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Middle Aged MH - Male MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - Heart Disease Risk Factors MH - Double-Blind Method MH - Aged MH - *Cardiovascular Diseases/prevention & control MH - Glycated Hemoglobin/metabolism MH - Blood Pressure PMC - PMC13019341 COIS- Conflict of Interest Disclosures: Dr Mulvagh reported personal fees from Novo Nordisk during the conduct of the study and personal fees from Merck outside the submitted work. Dr Inzucchi reported personal fees from Novo Nordisk during the conduct of the study and personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, and Corcept Therapeutics outside the submitted work. Dr Marx reported steering committee fees from Novo Nordisk during the conduct of the study and grants paid to university hospital from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Merck Sharp & Dohme (MSD), Novo Nordisk, and Sanofi-Aventis outside the submitted work. Dr Poulter reported speaker fees from Novo Nordisk, Servier, and Takeda; advisory board activities for AstraZeneca and Novo Nordisk; and research grants for his research group relating to type 2 diabetes from the British Heart Foundation, Diabetes UK, Julius Clinical, and the UK National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation program. Dr Deanfield reported receiving continuing medical education honoraria and/or consulting fees from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda; grants from Aegerion, Alzheimer's Research UK, the British Heart Foundation, Colgate, the Medical Research Council (UK), MSD, NIHR, Pfizer, Public Health England, and Roche; and advisory agreements with Caristo Diagnostics, eMed Healthcare, Floe Oral Care Ltd, Friede-Springer Cardiovascular Prevention Center, iOWNA, PMI Harm Reduction Group, and Smarter Cardiovascular Outcomes By Research And Education Ltd (SCORE) outside the submitted work. Dr Pop-Busui reported personal fees from Novo Nordisk during the conduct of the study; grants from Bayer, Lexicon Pharma, and Novo Nordisk; and personal fees from Averitas Pharma, Bayer, Biogen, Lexicon Pharma, Nevro, Roche Diagnostic, Vertex, and Viatris outside the submitted work. Dr Emerson reported steering committee fees from Novo Nordisk during the conduct of the study and personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Novartis, Roche, Sanofi, and Vertex outside the submitted work. Dr Mann reported personal fees from Novo Nordisk during the conduct of the study and personal fees from AstraZeneca, Bayer, Icon, IQVIA, Sanofi, and WCG outside the submitted work. Drs Engelmann, Hovingh, and Davicevic-Elez and Mr Jeppesen reported being employees of and shareholders in Novo Nordisk A/S during the conduct of the study. Dr Lorenzatti reported grants from Amgen, Arrowhead, Ionis, MSD, and Novartis outside the submitted work. Dr Oguz reported personal fees from Novo Nordisk during the conduct of the study and personal fees from AstraZeneca, Boehringer Ingelheim, Lilly, and Novo Nordisk outside the submitted work. Dr Mankovsky reported personal fees from Novo Nordisk during the conduct of the study and personal fees from AstraZeneca, Boehringer Ingelheim, Sanofi, and Servier outside the submitted work. Dr Deerochanawong reported grants from Novo Nordisk during the conduct of the study and personal fees from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, and Roche outside the submitted work. Dr Gorgojo-Martinez reported research fees from Novo Nordisk during the conduct of the study; grants from Mundipharma; and personal fees from AstraZeneca, Boehringer Ingelheim, Menarini, and Novo Nordisk outside the submitted work. Dr Bain reported payments for clinical activity in the SOUL trial from Novo Nordisk during the conduct of the study. Dr McGuire reported executive committee fees from Novo Nordisk during the conduct of the study and personal fees from Alveus, Amgen, AstraZeneca, Boehringer Ingelheim, Kailera, Lexicon, Lilly, Metsera, Neurotronic, New Amsterdam, Novartis, Novo Nordisk, Regor, Roche Genentech, and Zealand outside the submitted work. Dr Buse reported grants from Novo Nordisk during the conduct of the study; personal fees from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag, AstraZeneca, Aqua Medical, Boehringer Ingelheim, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, General Medicines Inc, GentiBio, Insulet, Kayothera, Metsera, MiniMed, Novo Nordisk, Recordati, Sparrow Pharmaceuticals, Tandem, Vertex, vTv Therapeutics, and Zealand; grants from Corcept Therapeutics , Dexcom, GentiBio, and Novo Nordisk; and holding stock options in Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health outside the submitted work. No other disclosures were reported. EDAT- 2026/03/25 12:48 MHDA- 2026/05/13 12:32 PMCR- 2026/03/25 CRDT- 2026/03/25 11:33 PHST- 2026/05/13 12:32 [medline] PHST- 2026/03/25 12:48 [pubmed] PHST- 2026/03/25 11:33 [entrez] PHST- 2026/03/25 00:00 [pmc-release] AID - 2847041 [pii] AID - hoi260005 [pii] AID - 10.1001/jamacardio.2026.0245 [doi] PST - ppublish SO - JAMA Cardiol. 2026 May 1;11(5):427-437. doi: 10.1001/jamacardio.2026.0245. PMID- 41877352 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Use of Oral Semaglutide and Associated Clinical Outcomes in Thai Patients With Type 2 Diabetes: Real-World Evidence From the REALISED Study. PG - 5058-5067 LID - 10.1111/dom.70701 [doi] AB - AIMS: The REALISED study assessed the clinical outcomes associated with oral semaglutide use in Thai patients with type 2 diabetes (T2D) in real-world clinical settings. MATERIALS AND METHODS: This retrospective, multi-centre cohort study included 195 patients with T2D initiating oral semaglutide between April 2022 and December 2023. Eligible participants had no prior injectable therapy and completed at least 26 weeks of treatment. The primary endpoint was the change in HbA1c from baseline to the end-of-study (EoS, Week 26); Week 52 outcomes were exploratory. Secondary endpoints included changes in body weight and the proportion achieving HbA1c < 7%. Severe hypoglycaemia was the safety endpoint. A post hoc composite endpoint combined HbA1c < 7% with >/= 3% weight loss. Analyses used a mixed model for repeated measures and descriptive statistics. RESULTS: Oral semaglutide was predominantly used as add-on therapy (190/195 [97.4%]). Mean HbA1c decreased by -0.7% (95% CI: -0.9 to -0.5; p < 0.0001), and the mean body weight decreased by -4.3 kg (95% CI: -5.5 to -3.2; p < 0.0001). At the EoS, 75.9% (117/154) achieved an HbA1c < 7%, and 57.7% (71/123) met the composite endpoint. No severe hypoglycaemia occurred. Dose escalation from 3 mg to 14 mg was observed in 53.2% by Week 26 and 70.4% by Week 52. CONCLUSIONS: The REALISED study provides the first real-world evidence of the use of oral semaglutide in Thai patients with T2D, demonstrating significant improvements in glycaemic control and weight reduction across routine care settings. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Wannachalee, Taweesak AU - Wannachalee T AD - Division of Endocrinology and Metabolism, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. FAU - Anthanont, Pimjai AU - Anthanont P AD - Endocrinology and Metabolism Unit, Department of Medicine, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand. FAU - Sirisreetreerux, Supamas AU - Sirisreetreerux S AD - Department of Medicine, Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand. FAU - Nayak, Gurudutt AU - Nayak G AD - Novo Nordisk Pharma Thailand Ltd., Bangkok, Thailand. FAU - Chumchujan, Woralak AU - Chumchujan W AD - Novo Nordisk Pharma Thailand Ltd., Bangkok, Thailand. FAU - Iamsudjai, Yodying AU - Iamsudjai Y AD - Novo Nordisk Pharma Thailand Ltd., Bangkok, Thailand. FAU - Buranapin, Supawan AU - Buranapin S AUID- ORCID: 0000-0003-2205-8900 AD - Section of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. LA - eng GR - Novo Nordisk/ GR - Chiang Mai University/ PT - Journal Article PT - Multicenter Study DEP - 20260324 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - Thailand/epidemiology MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Glycated Hemoglobin/analysis/metabolism MH - Administration, Oral MH - Treatment Outcome MH - Aged MH - Hypoglycemia/chemically induced MH - Blood Glucose/drug effects MH - Weight Loss/drug effects PMC - PMC13146152 OTO - NOTNLM OT - GLP-1 OT - glycaemic control OT - real-world evidence OT - semaglutide OT - type 2 diabetes OT - weight control COIS- G.N., W.C., and Y.I. are employees of Novo Nordisk. S.B. received a research grant from Novo Nordisk. T.W. and P.A. declare no conflicts of interest. EDAT- 2026/03/25 07:09 MHDA- 2026/05/06 06:39 PMCR- 2026/05/06 CRDT- 2026/03/25 01:03 PHST- 2026/03/04 00:00 [revised] PHST- 2025/12/19 00:00 [received] PHST- 2026/03/12 00:00 [accepted] PHST- 2026/05/06 06:39 [medline] PHST- 2026/03/25 07:09 [pubmed] PHST- 2026/03/25 01:03 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - DOM70701 [pii] AID - 10.1111/dom.70701 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):5058-5067. doi: 10.1111/dom.70701. Epub 2026 Mar 24. PMID- 41876542 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260818 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 17 IP - 1 DP - 2026 Mar 24 TI - Bispecific GLP-1/GLP-2 agonism in advanced type 2 diabetes: preclinical characterization and a randomized, double-blind, placebo-controlled phase I trial. LID - 10.1038/s41467-026-71080-0 [doi] LID - 4477 AB - PG-102 is a potency-optimized bispecific Fc fusion protein targeting GLP-1 and GLP-2 receptors. In db/db mouse models of advanced diabetes characterized by uncontrolled hyperglycemia and catabolic weight loss, PG-102 achieved superior and sustained glycemic control compared with semaglutide or tirzepatide while preserving body weight, uncoupling glycemic control from catabolic weight loss. Mechanistic studies indicated that these effects were not driven by acute insulinotropic activity, but by beta-cell preservation and enhanced glucose uptake. These benefits required dual GLP-1R/GLP-2R engagement, as PG-102 outperformed monospecific Fc fusion agonists or their combination and promoted coordinated receptor trafficking with delayed internalization. We conducted a randomized, double-blind, placebo-controlled multiple ascending dose phase 1 study at a single center in the Republic of Korea in adults with overweight (BMI 25-30 kg/m(2)). Twenty-four participants were randomized within three weekly dose cohorts (15 mg, 30 mg, and 30/60 mg; n = 6 per cohort) in a 6:2 ratio to receive PG-102 (n = 18) or placebo (n = 6). All randomized participants (PG-102 n = 18; placebo n = 6) received at least one dose and were included in the safety analysis. Safety and tolerability were predefined as the primary endpoint and assessed by treatment-emergent adverse events (TEAEs). TEAEs occurred in 5/6 (83.3%) participants in each PG-102 cohort and 4/6 (66.7%) in placebo; treatment-related AEs occurred in 5/6 (83.3%) and 3/6 (50.0%), respectively. No serious adverse events or discontinuations due to adverse events occurred. Gastrointestinal events were mild to moderate. These findings support bispecific GLP-1/GLP-2 agonism as a mechanistically distinct incretin strategy in advanced T2D. ClinicalTrials.gov identifier: NCT06309667. CI - (c) 2026. The Author(s). FAU - Yang, Sang-In AU - Yang SI AUID- ORCID: 0000-0001-5225-6508 AD - ProGen Co. Ltd., Seoul, Republic of Korea. AD - SL BiGen Inc., Incheon, Republic of Korea. FAU - Kim, Sae Won AU - Kim SW AUID- ORCID: 0000-0003-0395-2026 AD - ProGen Co. Ltd., Seoul, Republic of Korea. FAU - Son, Kyung-Hwa AU - Son KH AUID- ORCID: 0009-0006-4778-9610 AD - ProGen Co. Ltd., Seoul, Republic of Korea. FAU - Lee, Seung-Ah AU - Lee SA AUID- ORCID: 0000-0002-9192-2849 AD - ProGen Co. Ltd., Seoul, Republic of Korea. FAU - Kim, Jong-Gyun AU - Kim JG AD - ProGen Co. Ltd., Seoul, Republic of Korea. FAU - Roh, Jae-Il AU - Roh JI AD - ProGen Co. Ltd., Seoul, Republic of Korea. AD - SL BiGen Inc., Incheon, Republic of Korea. FAU - Sung, Young Chul AU - Sung YC AUID- ORCID: 0000-0003-2726-907X AD - SL BiGen Inc., Incheon, Republic of Korea. ycsung@postech.ac.kr. AD - Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. ycsung@postech.ac.kr. LA - eng SI - ClinicalTrials.gov/NCT06309667 GR - RS-2024-00335179/Korea Drug Development Fund (KDDF)/ PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial DEP - 20260324 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 53AXN4NNHX (Semaglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide 2) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Double-Blind Method MH - Female MH - Male MH - Middle Aged MH - Semaglutide MH - Animals MH - *Glucagon-Like Peptide 1/agonists MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - Tirzepatide MH - Blood Glucose/drug effects/metabolism MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 2/agonists MH - *Recombinant Fusion Proteins/therapeutic use/administration & dosage MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Mice MH - Glucagon-Like Peptides/therapeutic use MH - Glucagon-Like Peptide-2 Receptor/metabolism MH - Aged PMC - PMC13187202 COIS- Competing interests: Y.C.S. and S.Y. are inventors on patents related to this work (PCT/KR2021/003127 & PCT/KR2021/003128). Y.C.S. is a current employee of SL BiGen, Inc. S.I. is a former employee of SL BiGen, Inc. and now a current employee of ProGen Co., Ltd. J.R. is a former employee of both SL BiGen, Inc. and ProGen Co., Ltd. S.W.K., K.S., S.L., and J.K. are current employees of ProGen Co., Ltd. EDAT- 2026/03/25 07:09 MHDA- 2026/05/20 06:31 PMCR- 2026/03/24 CRDT- 2026/03/25 00:17 PHST- 2025/05/13 00:00 [received] PHST- 2026/03/03 00:00 [accepted] PHST- 2026/05/20 06:31 [medline] PHST- 2026/03/25 07:09 [pubmed] PHST- 2026/03/25 00:17 [entrez] PHST- 2026/03/24 00:00 [pmc-release] AID - 10.1038/s41467-026-71080-0 [pii] AID - 71080 [pii] AID - 10.1038/s41467-026-71080-0 [doi] PST - epublish SO - Nat Commun. 2026 Mar 24;17(1):4477. doi: 10.1038/s41467-026-71080-0. PMID- 41872986 OWN - NLM STAT- MEDLINE DCOM- 20260713 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - GLP-1 Receptor/Dual Agonists for Weight Loss: A Systematic Review and Network Meta-Analysis of RCTs. PG - 5043-5057 LID - 10.1111/dom.70698 [doi] AB - AIM: This study used a network meta-analysis (NMA) as the primary approach to compare the efficacy and tolerability of GLP-1 receptor agonists and dual agonists in overweight or obese adults with and without Type 2 diabetes. MATERIALS AND METHODS: PubMed, Embase, Scopus, CENTRAL, and trial registries were searched through April 30, 2025. Randomized clinical trials (RCTs) of GLP-1 receptor agonists in adults with and without Type 2 diabetes were included. Data were extracted according to PRISMA 2020. Pairwise and using random-effects models were performed, with treatment rankings derived using SUCRA. Outcomes included >/= 5% and >/= 10% weight loss, weight change (absolute and percentage weight loss) at 24-52 weeks, and adverse events. RESULTS: A total of 127 RCTs (58 976) Participants; (39 520 with and 19 456 without T2DM) assessed seven GLP-1RAs. Compared to placebo, NMA indicated that tirzepatide, subcutaneous semaglutide (Semaglutide_SC), and oral semaglutide (Semaglutide_oral) increased >/= 5% weight loss (RR 7.17 [95% CI 4.38-11.73], 4.74 [3.17-7.08], 2.85 [1.78-4.58]) in T2DM. Only tirzepatide and Semaglutide_SC were effective (2.99 [1.20-7.44], 2.75 [1.14-6.61]) in non-T2DM. For >/= 10% loss, tirzepatide was most effective (14.34 [5.98-34.35]), followed by Semaglutide_oral (6.86 [2.63-17.90]) and Semaglutide_SC (6.12 [2.97-12.59]) in T2DM. In non-T2DM, Semaglutide_SC (10.72 [3.29-34.90]) and tirzepatide (4.70 [1.02-21.73]) were effective when compared to placebo. Mixed treatment effects (direct head to head and indirect comparisons) showed that tirzepatide reduced weight more than Semaglutide_oral (MD -6.75% [-8.34 to -5.17]) and Semaglutide_SC (-4.94% [-6.35 to -3.52]) in T2DM and was the only effective agent in non-T2DM (-16.48% [-21.70 to -11.27]) when compared to placebo. Higher doses enhanced weight loss; nausea/vomiting were more common with tirzepatide (RR 3.64 [2.40-5.52]). CONCLUSIONS: Tirzepatide and Semaglutide_SC are most effective for clinically meaningful weight loss. Optimal dosing and adherence remain essential in practice. TRAIL REGISTRATION: PROSPERO (CRD42024539634). CI - (c) 2026 John Wiley & Sons Ltd. FAU - Vienghirun, Jirawan AU - Vienghirun J AUID- ORCID: 0009-0003-3069-5747 AD - Faculty of Pharmacy, Mahasarakham University, Maha Sarakham, Thailand. FAU - Sawangjit, Ratree AU - Sawangjit R AUID- ORCID: 0000-0002-6868-4336 AD - Clinical Trials and Evidence-Based Syntheses Research Unit (CTEBs RU), Mahasarakham University, Maha Sarakham, Thailand. AD - Department of Clinical Pharmacy, Faculty of Pharmacy, Mahasarakham University, Maha Sarakham, Thailand. FAU - Suttiruksa, Saithip AU - Suttiruksa S AD - Clinical Trials and Evidence-Based Syntheses Research Unit (CTEBs RU), Mahasarakham University, Maha Sarakham, Thailand. AD - Department of Clinical Pharmacy, Faculty of Pharmacy, Mahasarakham University, Maha Sarakham, Thailand. FAU - Chaiyakunapruk, Nathorn AU - Chaiyakunapruk N AUID- ORCID: 0000-0003-4572-8794 AD - College of Pharmacy, University of Utah, Salt Lake City, Utah, USA. FAU - Jinathongthai, Peerawat AU - Jinathongthai P AD - Pharmacy Practice Division, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand. AD - UPCOR: UBU Pharmacy Clinical Outcome Research Group, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand. FAU - Khunti, Kamlesh AU - Khunti K AUID- ORCID: 0000-0003-2343-7099 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Lee, Shaun Wen Huey AU - Lee SWH AUID- ORCID: 0000-0001-7361-6576 AD - School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia. LA - eng GR - Grant Number: 6811075/2568/Mahasarakham University/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260323 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Randomized Controlled Trials as Topic MH - Semaglutide MH - Tirzepatide MH - Glucagon-Like Peptides/therapeutic use MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - Anti-Obesity Agents/therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - GLP-1 receptor/dual agonists (GLP-1RAs) OT - non-T2DM OT - obesity OT - semaglutide OT - tirzepatide OT - weight loss EDAT- 2026/03/24 07:41 MHDA- 2026/05/06 06:38 CRDT- 2026/03/24 01:06 PHST- 2026/03/07 00:00 [revised] PHST- 2025/09/25 00:00 [received] PHST- 2026/03/11 00:00 [accepted] PHST- 2026/05/06 06:38 [medline] PHST- 2026/03/24 07:41 [pubmed] PHST- 2026/03/24 01:06 [entrez] AID - 10.1111/dom.70698 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):5043-5057. doi: 10.1111/dom.70698. Epub 2026 Mar 23. PMID- 41870800 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260813 IS - 1534-3170 (Electronic) IS - 1523-3782 (Print) IS - 1523-3782 (Linking) VI - 28 IP - 1 DP - 2026 Mar 23 TI - Oral Glucagon-Like Peptide-1 Receptor Agonists for Preventing Cardiorenal Complications. LID - 10.1007/s11886-026-02357-5 [doi] LID - 38 AB - PURPOSE OF REVIEW: This article reviews the evidence for cardiovascular and renal risk reduction with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in type 2 diabetes mellitus (T2DM), based on randomized controlled trials, including emerging oral agents. RECENT FINDINGS: Injectable GLP-1 RAs have consistently demonstrated reductions in major adverse cardiovascular events (MACE) and clinically relevant kidney outcomes, establishing their role in cardiorenal risk reduction. Oral semaglutide, the first approved oral GLP-1 RA, met criteria for cardiovascular non-inferiority in PIONEER 6 among patients with T2DM at high cardiovascular risk. The SOUL trial (oral semaglutide) subsequently demonstrated superiority for MACE reduction versus placebo in patients with established cardiovascular disease or multiple risk factors, with benefit driven largely by fewer nonfatal myocardial infarctions. However, oral semaglutide did not significantly reduce major kidney outcomes. Orforglipron, an investigational non-peptide oral GLP-1 RA with once-daily, food-independent dosing, has shown robust glycemic and weight-loss efficacy in phase 3 trials, though cardiovascular and renal outcome data are pending. Oral semaglutide has demonstrated cardiovascular benefit, but evidence supporting prevention of renal outcomes with oral GLP-1 RAs remains limited. Injectable GLP-1 RAs currently have the strongest evidence base for cardiorenal risk reduction, and ongoing outcome trials will clarify whether newer oral agents can close this gap. FAU - Odeleye, Victoria AU - Odeleye V AD - Department of Clinical Medical Education, University of Tennessee Health Science Center, Ascension St. Thomas Hospital, 4230 Harding Road, Suite 330, Nashville, TN, 37205, USA. AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - Singh, Nikita AU - Singh N AD - Department of Clinical Medical Education, University of Tennessee Health Science Center, Ascension St. Thomas Hospital, 4230 Harding Road, Suite 330, Nashville, TN, 37205, USA. AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - Gautam, Swotantra AU - Gautam S AD - Department of Clinical Medical Education, University of Tennessee Health Science Center, Ascension St. Thomas Hospital, 4230 Harding Road, Suite 330, Nashville, TN, 37205, USA. AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - Shannon, Elizabeth AU - Shannon E AD - Department of Clinical Medical Education, University of Tennessee Health Science Center, Ascension St. Thomas Hospital, 4230 Harding Road, Suite 330, Nashville, TN, 37205, USA. AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - Bibb, William Matthew AU - Bibb WM AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - McClure, Mary AU - McClure M AD - Ascension St. Thomas Hospital, Nashville, TN, USA. FAU - Paul, Timir K AU - Paul TK AD - Department of Clinical Medical Education, University of Tennessee Health Science Center, Ascension St. Thomas Hospital, 4230 Harding Road, Suite 330, Nashville, TN, 37205, USA. timirpaul@gmail.com. AD - Ascension St. Thomas Hospital, Nashville, TN, USA. timirpaul@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20260323 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Administration, Oral MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Diabetic Nephropathies/prevention & control MH - Randomized Controlled Trials as Topic PMC - PMC13009101 OTO - NOTNLM OT - Cardiovascular outcomes OT - Oral GLP-1 receptor agonists OT - Oral semaglutide OT - Orforglipron OT - Renal outcomes OT - Type 2 diabetes mellitus COIS- Declarations. Human and Animal Rights and Informed Consent: This article does not contain any studies with human or animal subjects performed by any of the authors. Competing interests: The authors declare no competing interests. EDAT- 2026/03/23 19:54 MHDA- 2026/06/28 04:09 PMCR- 2026/03/23 CRDT- 2026/03/23 12:21 PHST- 2026/03/05 00:00 [received] PHST- 2026/03/06 00:00 [accepted] PHST- 2026/06/28 04:09 [medline] PHST- 2026/03/23 19:54 [pubmed] PHST- 2026/03/23 12:21 [entrez] PHST- 2026/03/23 00:00 [pmc-release] AID - 10.1007/s11886-026-02357-5 [pii] AID - 2357 [pii] AID - 10.1007/s11886-026-02357-5 [doi] PST - epublish SO - Curr Cardiol Rep. 2026 Mar 23;28(1):38. doi: 10.1007/s11886-026-02357-5. PMID- 41864758 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260715 IS - 1878-3562 (Electronic) IS - 1590-8658 (Linking) VI - 58 IP - 5 DP - 2026 May TI - AISF practice guidance on pharmacological treatment of metabolic-dysfunction associated steatotic liver disease and steatohepatitis (MASLD/MASH): A 2026 Update. PG - 599-607 LID - S1590-8658(26)00292-6 [pii] LID - 10.1016/j.dld.2026.02.014 [doi] AB - Metabolic dysfunction-associated steatotic liver disease (MASLD) has rapidly emerged as the leading cause of chronic liver disease worldwide, gradually replacing viral hepatitis in clinical and epidemiological relevance. Italian data mirror global trends, with prevalence escalating in general and high-risk populations, particularly among individuals with type 2 diabetes (T2D), obesity, and metabolic syndrome (MetS). Disease progression from steatosis to steatohepatitis (MASH) and advanced fibrosis markedly increases the risk of cirrhosis, hepatocellular carcinoma (HCC), and cardiovascular mortality. Recent regulatory frameworks from FDA and EMA have accelerated therapeutic development, with Resmetirom and Semaglutide representing the first agents to achieve histological efficacy in Phase 3 trials for patients with MASH and F2-F3 fibrosis. Building upon these advances, the AISF STEPS-MASH framework provides a structured approach for the identification, selection, and monitoring of patients eligible for therapy. This position paper outlines evidence-based recommendations for the integration of emerging pharmacological strategies into clinical practice in Italy, emphasizing both high-risk and broader metabolic populations. CI - Copyright (c) 2026 The Author(s). Published by Elsevier B.V. All rights reserved. CN - Associazione Italiana per lo Studio del Fegato (AISF) LA - eng PT - Journal Article PT - Review DEP - 20260320 PL - Netherlands TA - Dig Liver Dis JT - Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver JID - 100958385 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 2J3H5C81A5 (elifibranor) RN - 0 (Propionates) RN - 0 (Chalcones) SB - IM MH - Humans MH - Semaglutide MH - *Metabolic Syndrome/complications MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Diabetes Mellitus, Type 2/complications MH - *Fatty Liver/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Disease Progression MH - Italy MH - Hypoglycemic Agents/therapeutic use MH - Practice Guidelines as Topic MH - Obesity/complications MH - Propionates MH - Chalcones OTO - NOTNLM OT - Metabolic-dysfunction associated steatohepatitis (MASH) OT - Metabolic-dysfunction associated steatotic liver disease (MASLD) OT - Resmetirom OT - Semaglutide OT - Steatosis OT - Tirzepatide COIS- Declaration of competing interest AAg: speaking and/or advisory board for Gilead, Ipsen, BMS, Novo Nordisk, Madrigal, AbbVie. AAr: speaking for Novonordisk, Sanofi, Echosense. EB: speaking and/or advisory board for AstraZeneca, Boheringer, Eli Lilly, Inventiva, MSD, Novo Nordisk. GC: speaking and/or advisory board for Eisai, Ipsen, AstraZeneca, MSD, Roche, Gilead. MC: consultant/speaker bureau for Advanz, Alentis, Albireo, Alfasigma, Amgen, Calliditas, Echosense, Genetic spa, GSK, Ipsen, Intercept, Kowa, Mayloly, Mirun, Perspectum, Zydus; scientific board advisor for Advanz/Intercept, Falk, Gilead, GSK, Ipsen, Kowa, Mirum, Cymabay, Moderna. RD: speaking, teaching and advisory board for Gilead Science and AbbVie; consultant and advisory board for Madrigal. AD speaking and/or advisory board for Astrazeneca, Eisai, MSD, Novonordisk and Roche. SDC: speaking and/or advisory board for AbbVie, Alfasigma. AG: consultant and advisory borad for for Roche, Ipsen, Novonordisk, MSD, BMS, AstraZeneca, Alfasigma, Actial, Wellmicro. GG: speaking, consulting fee fees and/or travel fees for Chiesi, Alfasigma, Ipsen, Biotest, Novartis. SG: speaking and/or advisory board for Gilead. MI: consultant for Roche, Roche Diagnostic, Eisai, MSD, AstraZeneca; speaking for Roche, AstraZeneca, Ipsen, Eisai, MSD, Gilead; Travel fees from Roche; research funding by Gilead, Astrazeneca, Roche Diagnostic. FM: consultant and/or speaking and/or advisory board and/or travel grant for Aofasigma, AstraZeneca, Biomarin, Boehringer Ingelheim, Gilead, Gore, Ipsen, Madrigal, MSD/Eisai, Novo Nordisk, Roche. GM: speaking for MSD-Eisai, Chiesi, Kedrion, Ipsen, Alfasigma. MM: speaking and/or advisory board for Gilead, Ipsen, Novo Nordisk, Alfasigma, AbbVie, Mirum. LM: speaking and advisory board for Alexion, Boheringer-Ingelheim, Echosens, GSK, Madrigal, MSD, Mirum, Novonordisk, Reslis Pharma, Siemens Healthineers. GP: speaking and/or advisory board and/or consultant for Novo Nordisk, Echosense, Advanz Pharma, Madrigal. SP: speaking and/or advisory board for Boeringher, Echosens, Madrigal, Novonordisk, Resalis. FRP: speaking and/or consultant and/or travel grant from AstraZeneca, Ipsen, Roche, AbbVie, Gilead, Alfasigma, Mirum. FR: research support by Boheringer Ingelheim, Ely Lilly; travel grant by Novo Nordisk; speaking for Novo Nordisk, Eli Lilly, Echosense. FPR: speaking, travel grant and advisory board for Gilead, Biotest, Grifols, AbbVie, GSK, Novonordisk. FT: consultant for Astrazeneca, Roche, Eisai, BMS, Ipsen; LV: speaking for Viatris, Novo Nordisk, GSK; consulting for Novo Nordisk, Pfizer, Boehringer Ingelheim, Resalis, GSK, Almac, AIRNA; travelling by Novo Nordisk. UVG: speaking and/or advisory board and/or funding for research by Advanz, Gilead, Ipsen, Mirum, Novo Nordisk, Madrigal, Astra Zeneca. MV: speaking and teaching for Gilead, Ipse, AbbVie, Novo Nordisk, Eli Lilly, Kedrion. FIR - Aghemo, Alessio IR - Aghemo A IRAD- Department of Biochemical Science, Humanitas University, Rozzano (MI), Italy; Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano (MI), Italy. FIR - Armandi, Angelo IR - Armandi A IRAD- Department of Medical Sciences, Department of Gastroenterology, A.O.U. Citta della Salute e della Scienza di Torino, University of Turin, Milan, Italy. FIR - Bugianesi, Elisabetta IR - Bugianesi E IRAD- Department of Medical Sciences, Department of Gastroenterology, A.O.U. Citta della Salute e della Scienza di Torino, University of Turin, Milan, Italy. FIR - Cabibbo, Giuseppe IR - Cabibbo G IRAD- Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Mediacl Specialties PROMISE, University of Palermo, Palermo, Italy. FIR - Carbone, Marco IR - Carbone M IRAD- Hepatology and Gastroenterology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy. FIR - D'Ambrosio, Roberta IR - D'Ambrosio R IRAD- Gastroenterology and Hepatology, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy. FIR - Dalbeni, Andrea IR - Dalbeni A IRAD- General Medicina C - Unit and Liver Unit - Department of Medicine. AOUI Verona, University of Verona, Verona, Italy. FIR - Di Cola, Simone IR - Di Cola S IRAD- Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy. FIR - Gasbarrini, Antonio IR - Gasbarrini A IRAD- Department of Translational Medicine and Surgery, Universita Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. FIR - Germani, Giacomo IR - Germani G IRAD- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale, Universita di Padova, Padua, Italy. FIR - Gitto, Stefano IR - Gitto S IRAD- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy. FIR - Iavarone, Massimo IR - Iavarone M IRAD- Gastroenterology and Hepatology, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy; CRC "A.M. e A. Migliavacca Center for Liver Disease", Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FIR - Marra, Fabio IR - Marra F IRAD- Department of Clinical and Experimental Medicine, University of Florence, Florence, Italy. FIR - Masarone, Mario IR - Masarone M IRAD- Internal Medicine and Hepatology, Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno, Italy. FIR - Marrone, Giuseppe IR - Marrone G IRAD- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. FIR - Miele, Luca IR - Miele L IRAD- Department of Translational Medicine and Surgery, Universita Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. FIR - Pennisi, Grazia IR - Pennisi G IRAD- Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Mediacl Specialties PROMISE, University of Palermo, Palermo, Italy. FIR - Petta, Salvatore IR - Petta S IRAD- Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Mediacl Specialties PROMISE, University of Palermo, Palermo, Italy. FIR - Ponziani, Francesca Romana IR - Ponziani FR IRAD- Department of Translational Medicine and Surgery, Universita Cattolica del Sacro Cuore, Rome, Italy; Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell'Apparato Digerente, Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. FIR - Ravaioli, Federico IR - Ravaioli F IRAD- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Science, University of Bologna, Bologna, Italy. FIR - Russo, Francesco Paolo IR - Russo FP IRAD- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Azienda Ospedale, Universita di Padova, Padua, Italy. FIR - Tovoli, Francesco IR - Tovoli F IRAD- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Science, University of Bologna, Bologna, Italy. FIR - Valenti, Luca IR - Valenti L IRAD- Precision Medicine Lab, Biological Resource Center and Trasfusion Medicine, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. FIR - Vespasiani-Gentilucci, Umberto IR - Vespasiani-Gentilucci U IRAD- Research Unit of Clinical Medicine and Hepatology, Universita Campus Bio-medico di Roma, Rome, Italy. FIR - Vigano, Mauro IR - Vigano M IRAD- Gastroenterology, Hepatology and Transplantation Division, ASST Papa Giovanni XXIII, Bergamo, Italy. EDAT- 2026/03/22 06:07 MHDA- 2026/04/19 17:46 CRDT- 2026/03/21 22:52 PHST- 2025/12/07 00:00 [received] PHST- 2026/02/11 00:00 [revised] PHST- 2026/02/15 00:00 [accepted] PHST- 2026/04/19 17:46 [medline] PHST- 2026/03/22 06:07 [pubmed] PHST- 2026/03/21 22:52 [entrez] AID - S1590-8658(26)00292-6 [pii] AID - 10.1016/j.dld.2026.02.014 [doi] PST - ppublish SO - Dig Liver Dis. 2026 May;58(5):599-607. doi: 10.1016/j.dld.2026.02.014. Epub 2026 Mar 20. PMID- 41862354 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260730 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 48 IP - 4 DP - 2026 Apr TI - Effect of Glucagon-Like-Peptide-1 Receptor Agonists (GLP-1 RA) on Neuropsychiatric Outcomes: A Systematic Review and Meta-Analysis. PG - 347-384 LID - S0149-2918(26)00044-5 [pii] LID - 10.1016/j.clinthera.2026.02.010 [doi] AB - PURPOSE: Type 2 diabetes mellitus (T2D) is associated with an increased burden of neuropsychiatric disorders, including cognitive decline, affective disorders, and substance use disorders. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), developed for glycemic control and weight reduction, have been hypothesized to confer neuroprotective and psychotropic benefits via central and peripheral mechanisms. However, evidence across individual studies remains inconsistent. METHODS: We conducted a systematic review and meta-analysis (PROSPERO CRD420251025534) of randomized controlled trials (RCTs) and observational studies assessing the effect of GLP-1 RAs on neuropsychiatric outcomes. Searches were performed in MEDLINE, SCOPUS, CENTRAL, and Web of Science up to 30(th) October 2025. Eligible comparators included placebo, standard care, or alternative glucose-lowering agents. Data were synthesized using random-effects models, and risk of bias was assessed using RoB2 and ROBINS-I. Evidence certainty was graded using GRADE methodology. FINDINGS: From 10,037 records, 82 studies were included. GLP-1 RAs were associated with a reduced risk of idiopathic Parkinson's disease (PD) (pooled HR 0.70, 95% CI: 0.53-0.92, I(2) = 38%) but no improvements in motor symptoms in established PD (MDS-UPDRS Part III off-medication: mean difference -3.29, 95% CI: -7.84, 1.26, I(2) = 80%). No consistent improvements in non-motor symptoms, quality of life, or dyskinesia scores were seen. GLP-1 RAs were associated with a reduced risk of cannabis use disorder (pooled HR 0.55, 95% CI: 0.39-0.77, I(2) = 71%) but showed no significant effect on opioid use disorder (pooled HR 0.61, 95% CI: 0.24-1.52, I(2) = 91%). Liraglutide reduced binge frequency in binge eating disorder (mean difference -1.28, 95% CI: -1.67, -0.89, I(2) = 53%) compared to placebo. In observational studies versus non-user controls, GLP-1 RA use was associated with a lower reported risk of suicidality (pooled OR 0.34, 95% CI: 0.18-0.63, I(2) = 99%), but no such association was seen with Semaglutide alone (pooled OR 0.71, 95% CI: 0.29-1.73, I(2) = 99%), active-comparator studies (pooled HR 0.96, 95% CI: 0.81-1.15, I(2)=0%) or RCTs (pooled RR 1.13, 95% CI: 0.53-2.41, I(2)=0%). No associations were observed for depression or anxiety. For dementia, findings were mixed: no benefit versus SGLT2 inhibitors (pooled RR 1.07, 95% CI: 0.73-1.56, I(2) = 78%), but there was a reduced risk of Alzheimer's disease when compared to unmatched or non-exposed controls (pooled RR 0.37, 95% CI: 0.14-0.96, I(2) = 98%). Certainty of evidence ranged from moderate to very low. IMPLICATIONS: Current evidence, largely of low to very low certainty, suggests potential selective neuropsychiatric associations of GLP-1 RAs, particularly in Parkinson's disease risk reduction and binge eating disorder. Benefits for dementia risk reduction were observed primarily in comparisons with non-exposed or DPP4i, whereas no advantage was seen versus other active comparators, such as SGLT2 inhibitors. Our findings should be interpreted as hypothesis-generating due to significant heterogeneity and wide confidence intervals, indicating imprecision. Longer-term studies with neuropsychiatric outcomes as the primary endpoint are required. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Choudhury, Ishraq AU - Choudhury I AD - Salford Royal Hospital, Northern Care Alliance, Salford, UK. FAU - Ward, John Headly AU - Ward JH AD - Department of Psychiatry, University of Cambridge, Cambridge, UK. FAU - Mahesh, Sahana AU - Mahesh S AD - Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Alam, Uazman AU - Alam U AD - Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Centre for Biomechanics and Rehabilitation Technologies, Staffordshire University, Stoke-on-Trent, UK. FAU - Azmi, Shazli AU - Azmi S AD - Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. FAU - Anson, Matthew AU - Anson M AD - Diabetes & Endocrinology Research, Institute of Life Course and Medical Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. Electronic address: manson1@liverpool.ac.uk. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260319 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Mental Disorders/prevention & control MH - Randomized Controlled Trials as Topic MH - Parkinson Disease/prevention & control OTO - NOTNLM OT - Addiction OT - GLP-1 OT - Glucagon-like-peptide-1 OT - Neurology OT - Psychiatiry OT - Type 2 diabetes COIS- Declaration of competing interest MA receives a fellowship from the Novo Nordisk UK research foundation and Breakthrough T1D. UA has received honoraria from Eli Lilly, Theras, Procter & Gamble, Viatris, Grunenthal and Sanofi for educational meetings and funding for attendance to an educational meeting from Sanofi and Diiachi Sankyo. UA has also received investigator-led funding by Procter & Gamble and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. EDAT- 2026/03/21 00:34 MHDA- 2026/04/21 17:43 CRDT- 2026/03/20 22:54 PHST- 2025/12/06 00:00 [received] PHST- 2026/02/10 00:00 [revised] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/04/21 17:43 [medline] PHST- 2026/03/21 00:34 [pubmed] PHST- 2026/03/20 22:54 [entrez] AID - S0149-2918(26)00044-5 [pii] AID - 10.1016/j.clinthera.2026.02.010 [doi] PST - ppublish SO - Clin Ther. 2026 Apr;48(4):347-384. doi: 10.1016/j.clinthera.2026.02.010. Epub 2026 Mar 19. PMID- 41862258 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260711 IS - 2215-0374 (Electronic) IS - 2215-0366 (Linking) VI - 13 IP - 4 DP - 2026 Apr TI - Association between GLP-1 receptor agonist use and worsening mental illness in people with depression and anxiety in Sweden: a national cohort study. PG - 327-335 LID - S2215-0366(26)00014-3 [pii] LID - 10.1016/S2215-0366(26)00014-3 [doi] AB - BACKGROUND: People with diabetes have an elevated risk of developing depression, anxiety, and suicide. GLP-1 receptor agonists are licensed to treat diabetes and obesity, but data on whether these medications alleviate or exacerbate anxiety, depression, and self-harm are mixed. We studied the risk of worsening mental illness in people already diagnosed with depression, anxiety, or both who were prescribed antidiabetic medications including GLP-1 receptor agonists. METHODS: The study cohort, identified from national Swedish electronic health registers, included people with a diagnosis of depression or anxiety disorder who used any antidiabetic medication between the years 2009 and 2022. GLP-1 receptor agonists, individually and as a group, were compared with non-use of GLP-1 receptor agonists and directly with other second-line antidiabetic medications. A within-individual design was used for all comparisons to reduce confounding, comparing periods of use versus periods of non-use of a medication in the same individual. The primary outcome was worsening of mental illness, defined as a composite of psychiatric hospitalisation; sick leave from work for more than 14 days for psychiatric reasons; hospitalisation due to self-harm; or death by suicide. Secondary outcomes were worsening of depression or anxiety, analysed separately, worsening of substance use disorder, and self-harm. Within-individual stratified Cox models with adjusted hazard ratios (aHRs) and 95% CIs were used. A person with related lived experience was involved in the design and write-up of this study. FINDINGS: The cohort included 95 490 people (56 976 [59.7%] female and 38 514 [40.3%] male) with a mean age of 50.6 years (SD 12.3). Ethnicity data were not available. GLP-1 receptor agonists were used by 22 480 individuals during the follow-up period. Compared with non-use of GLP-1 receptor agonists, semaglutide (aHR 0.58 [95% CI 0.51-0.65]) and liraglutide (0.82 [0.76-0.89]) were associated with lower risk of worsening mental illness, whereas exenatide (1.01 [0.69-1.46]) and dulaglutide (1.01 [0.85-1.20]) were not. Semaglutide was associated with a decreased risk of worsening depression (0.56 [0.44-0.71]), of worsening anxiety (0.62 [0.52-0.73]), and of worsening substance use disorder (0.53 [0.35-0.80]). Liraglutide was associated only with lower risk of worsening depression (0.74 [0.64-0.87]). GLP-1 receptor agonists as a group were associated with a reduced risk of self-harm (0.56 [0.34-0.92]). INTERPRETATION: For anxiety and depression that co-occur with diabetes and obesity, semaglutide and, to a lesser extent, liraglutide might be useful dually effective therapeutic options. Randomised controlled trials evaluating these findings are warranted. FUNDING: Sigrid Juselius Foundation, Jane and Aatos Erkko Foundation, and Finnish Ministry of Social Affairs and Health. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. FAU - Taipale, Heidi AU - Taipale H AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Stockholm City Council, Stockholm, Sweden; School of Pharmacy, University of Eastern Finland, Kuopio, Finland. FAU - Taylor, Mark AU - Taylor M AD - School of Medicine and Dentistry, Griffith University, Gold Coast, QLD Australia; The Edinburgh Practice, Edinburgh, UK. Electronic address: andrewmarktaylor55@gmail.com. FAU - Lahteenvuo, Markku AU - Lahteenvuo M AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland. FAU - Mittendorfer-Rutz, Ellenor AU - Mittendorfer-Rutz E AD - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Tanskanen, Antti AU - Tanskanen A AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. FAU - Tiihonen, Jari AU - Tiihonen J AD - Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Stockholm City Council, Stockholm, Sweden. LA - eng PT - Journal Article PL - England TA - Lancet Psychiatry JT - The lancet. Psychiatry JID - 101638123 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Sweden/epidemiology MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - Cohort Studies MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Adult MH - *Anxiety Disorders/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hospitalization/statistics & numerical data MH - *Depression/epidemiology MH - Registries MH - *Depressive Disorder/epidemiology COIS- Declaration of interests HT, EM-R, and JT have participated in research projects funded by grants from Janssen to their employing institution. HT reports personal fees from Gedeon Richter, Janssen, Lundbeck and Otsuka; and has been a consultant or advisor to or has received honoraria from Healthcare Global Village, HLS Therapeutics, Janssen-Cilag, Lundbeck, Orion, Otsuka, Teva, and WebMD Global. ML has received honoraria from Lundbeck, Otsuka Pharma, Janssen, Johnson & Johnson, Orion Pharma, and Recordati. MT declares no competing interests. EDAT- 2026/03/21 00:34 MHDA- 2026/03/21 00:35 CRDT- 2026/03/20 21:56 PHST- 2025/10/06 00:00 [received] PHST- 2026/01/07 00:00 [revised] PHST- 2026/01/09 00:00 [accepted] PHST- 2026/03/21 00:35 [medline] PHST- 2026/03/21 00:34 [pubmed] PHST- 2026/03/20 21:56 [entrez] AID - S2215-0366(26)00014-3 [pii] AID - 10.1016/S2215-0366(26)00014-3 [doi] PST - ppublish SO - Lancet Psychiatry. 2026 Apr;13(4):327-335. doi: 10.1016/S2215-0366(26)00014-3. PMID- 41857480 OWN - NLM STAT- MEDLINE DCOM- 20260619 LR - 20260813 IS - 1728-7731 (Electronic) IS - 1726-4901 (Print) IS - 1726-4901 (Linking) VI - 89 IP - 6 DP - 2026 Jun 1 TI - Ocular complications from glucagon-like peptide-1 receptor agonists: Clinical evidence, potential mechanisms, and clinical recommendations. PG - 407-414 LID - 10.1097/JCMA.0000000000001370 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)-central to type 2 diabetes mellitus (T2DM) management owing to their comprehensive benefits (glycemic control, weight reduction, cardiovascular benefits, and renal protection)-exhibit a concerning ocular safety profile. Clinical trial data, notably from SUSTAIN-6, revealed a higher incidence of diabetic retinopathy (DR) complications with semaglutide, particularly in patients with preexisting DR and rapid HbA1c reduction, reflecting early worsening. Conversely, the REWIND and LEADER trials reported no significant increase in DR risk, suggesting variability among agents and the potential influence of glycemic trajectory. Observational studies and meta-analyses provide mixed findings: some suggest increased DR progression risk in vulnerable populations, while others indicate a lower risk than insulin therapy. Beyond DR, recent pharmacoepidemiologic studies and pharmacovigilance reports have implicated GLP-1 RAs-especially semaglutide-in nonarteritic anterior ischemic optic neuropathy (NAION), leading the European Medicines Agency to classify NAION as a very rare adverse effect and prompting regulatory scrutiny. Conversely, real-world data suggest possible protective associations with other retinal disorders, including reduced incidence of neovascular age-related macular degeneration and diabetic macular edema, although findings remain inconsistent. The mechanistic pathways involve rapid metabolic shifts, vascular dysregulation, and potentially direct effects on retinal or optic nerve tissue. While GLP-1 RAs confer substantial systemic benefits, their ocular risks appear concentrated in high-risk subgroups. Individualized prescribing, baseline ophthalmic assessment, and interdisciplinary monitoring are essential until ongoing prospective trials clarify their long-term ocular impact. CI - Copyright (c) 2026, the Chinese Medical Association. FAU - Wu, Tzu-En AU - Wu TE AD - Department of Ophthalmology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, ROC. FAU - Chen, Harn-Shen AU - Chen HS AUID- ORCID: 0000-0001-8748-229 AD - Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. LA - eng PT - Journal Article PT - Review DEP - 20260317 PL - Netherlands TA - J Chin Med Assoc JT - Journal of the Chinese Medical Association : JCMA JID - 101174817 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Diabetic Retinopathy/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - *Optic Neuropathy, Ischemic/chemically induced MH - *Semaglutide/adverse effects PMC - PMC13286313 OTO - NOTNLM OT - Diabetic retinopathy OT - Glucagon-like peptide-1 receptor agonists OT - Neovascular age-related macular degeneration OT - Nonarteritic anterior ischemic optic neuropathy COIS- Conflicts of interest: Dr. Harn-Shen Chen, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. EDAT- 2026/03/20 07:10 MHDA- 2026/06/19 12:36 PMCR- 2026/03/17 CRDT- 2026/03/20 00:30 PHST- 2026/06/19 12:36 [medline] PHST- 2026/03/20 07:10 [pubmed] PHST- 2026/03/20 00:30 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - 02118582-990000000-00641 [pii] AID - JCMA-D-25-00577 [pii] AID - 10.1097/JCMA.0000000000001370 [doi] PST - ppublish SO - J Chin Med Assoc. 2026 Jun 1;89(6):407-414. doi: 10.1097/JCMA.0000000000001370. Epub 2026 Mar 17. PMID- 41850241 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260813 IS - 2666-3791 (Electronic) IS - 2666-3791 (Linking) VI - 7 IP - 3 DP - 2026 Mar 17 TI - Suboptimal therapeutic responses associated with semaglutide in type 2 diabetes and obesity: A meta-analysis of randomized controlled trials. PG - 102614 LID - S2666-3791(26)00031-5 [pii] LID - 10.1016/j.xcrm.2026.102614 [doi] LID - 102614 AB - Semaglutide has emerged as a leading therapy for metabolic disorders, with robust evidence supporting its role in treating obesity and type 2 diabetes while reducing cardiovascular and renal risks. However, limited data exist on the proportion of patients who have suboptimal therapeutic responses or discontinue treatment due to adverse events. We present an analysis including 33 randomized controlled trials (RCTs) comprising 21,023 participants. Across included trials of patients with and without type 2 diabetes, 33.4% and 65.1% of participants did not achieve >/=5% or >/=10% total body weight reduction, respectively. Stratified analyses demonstrated higher rates of suboptimal outcomes among individuals with type 2 diabetes mellitus (T2DM), with up to 79.8% not achieving >/=10% weight loss, compared to 30.1% among individuals without T2DM. While semaglutide is effective in many patients, a substantial subset of patients has suboptimal weight or glycemic improvements or discontinues therapy. This study was registered with PROSPERO (CRD420251086132). CI - Copyright (c) 2026. Published by Elsevier Inc. FAU - Ko, Donghyun AU - Ko D AD - Department of Medicine, Bridgeport Hospital, Yale New Haven Health, Bridgeport, CT, USA. Electronic address: donghyun.ko@bpthosp.org. FAU - Kim, Do Han AU - Kim DH AD - Department of Medicine, Mount Sinai Morningside and West, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - Tan, Faith Xin Ning AU - Tan FXN AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Ho, Glenn Jun Kit AU - Ho GJK AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Chandra, Rubhan AU - Chandra R AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Xuan, Zhang Zi AU - Xuan ZZ AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Jun, Ethan Tham Kai AU - Jun ETK AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Tang, Nicole Shu Ying AU - Tang NSY AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Yang, Hee Seung AU - Yang HS AD - Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore. FAU - Koh, Jeffery Wei Heng AU - Koh JWH AD - Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore. FAU - Danpanichkul, Pojsakorn AU - Danpanichkul P AD - Department of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA. FAU - Dalakoti, Mayank AU - Dalakoti M AD - Department of Cardiology, National University Heart Centre, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. FAU - Syn, Nicholas L AU - Syn NL AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Wijarnpreecha, Karn AU - Wijarnpreecha K AD - Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Phoenix, AZ, USA; Department of Internal Medicine, Division of Gastroenterology and Hepatology, Banner University Medical Center, Phoenix, AZ, USA; BIO5 Institute, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA. FAU - Takahashi, Hirokazu AU - Takahashi H AD - Liver Center, Saga University Hospital, Saga, Japan. FAU - Zheng, Ming-Hua AU - Zheng MH AD - MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China; Wenzhou Key Laboratory of Hepatology, Wenzhou, China; Institute of Hepatology, Wenzhou Medical University, Wenzhou, China; Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease, Wenzhou, Zhejiang, China. FAU - Nakajima, Atsushi AU - Nakajima A AD - Graduate School of Medicine, Yokohama City University, Yokohama, Japan. FAU - Noureddin, Mazen AU - Noureddin M AD - Houston Methodist Hospital and Houston Research Institute, Houston, TX, USA. FAU - Muthiah, Mark AU - Muthiah M AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore. FAU - Le Roux, Carel W AU - Le Roux CW AD - University College Dublin, Diabetes Complications Research Centre, Dublin, Ireland. FAU - Siddiqui, Mohammad Shadab AU - Siddiqui MS AD - Division of Gastroenterology and Hepatology, Department of Medicine, University of Virginia, Charlottesville, VA, USA. Electronic address: mohammad.siddiqui@vcuhealth.org. FAU - Ng, Cheng Han AU - Ng CH AD - Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore; Houston Methodist Hospital and Houston Research Institute, Houston, TX, USA; Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan. Electronic address: chenghanng@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PL - United States TA - Cell Rep Med JT - Cell reports. Medicine JID - 101766894 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/drug therapy MH - Randomized Controlled Trials as Topic MH - Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Female PMC - PMC13006432 OTO - NOTNLM OT - longitudinal OT - randomized clinical trials OT - reduction OT - semaglutide COIS- Declaration of interests C.H.N. serves as the CEO of LiverGENIX Pte Ltd. M.M. has served as a consultant to Roche, Estella, and Gilead. He has been an advisor for LernaBio. M.M. has received payment for speaking at Boston Scientific, Olympus Medical, Roche, and Astellas. He also serves as the CMO of LiverGENIX Pte Ltd. M.M. is supported by the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Pte Ltd., under the NMRC Clinician Scientist-Individual Research Grant (MOH-001228) and NMRC Clinician Scientist Award (MOH-001631), as well as the National Research Foundation, Singapore (NRF), under the NMRC Open Fund - Large Collaborative Grant (MOH-001325), administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd. N.L.S. serves as the CTO of LiverGENIX Pte Ltd. M.N. consults and received grants from Gilead, GlaxoSmithKline, Madrigal, Novo Nordisk, Takeda, and Terns. He consults, advises, and owns stock in Cytodyn. He consults and advises 89 Bio, Altimmune, Boehringer Ingelheim, Merck, and Perspectum. He has received grants and owns stock in Viking. He advises Blade, CohBar, EchoSens, Fractyl, Intercept, NorthSea, Pfizer, Siemens, and Roche Diagnostics. He has received grants from Allergan, Bristol Myers Squibb, Conatus, Corcept, Enanta, Galmed, Galectin, Genfit, Madrigal, Novartis, Pfizer, Shire, and Zydus. He owns stock in Anaetos, ChronWell, Cima, and Rivus Pharma. H.T. has received research grants from Astellas Pharma, AbbVie GK, and Sysmex. M.-h.Z. has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies, and Novo Nordisk and consulting fees from Boehringer Ingelheim and serves as a consultant for Eieling Technology. M.-h.Z. serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition and Liver International. A.N. has served as a medical advisor to EA Pharma Co., Ltd. M.S.S. has received consulting fees from Sagimet, 89 Bio, and AMRA and grant support from Novo Nordisk. EDAT- 2026/03/19 01:32 MHDA- 2026/03/19 01:33 PMCR- 2026/03/17 CRDT- 2026/03/18 19:22 PHST- 2025/06/20 00:00 [received] PHST- 2025/11/28 00:00 [revised] PHST- 2026/01/13 00:00 [accepted] PHST- 2026/03/19 01:33 [medline] PHST- 2026/03/19 01:32 [pubmed] PHST- 2026/03/18 19:22 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - S2666-3791(26)00031-5 [pii] AID - 102614 [pii] AID - 10.1016/j.xcrm.2026.102614 [doi] PST - ppublish SO - Cell Rep Med. 2026 Mar 17;7(3):102614. doi: 10.1016/j.xcrm.2026.102614. PMID- 41832437 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260926 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 26 IP - 1 DP - 2026 Mar 14 TI - Comparative effectiveness of semaglutide and dulaglutide combined with hypocaloric diet in newly diagnosed type 2 diabetes: a retrospective real-world study. LID - 10.1186/s12902-026-02232-y [doi] LID - 86 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used in early T2D management due to their glycemic and weight-reducing effects. However, real-world comparative data in newly diagnosed treatment-naive individuals remain limited. METHODS: This retrospective real-world study evaluated 106 adults aged 18-75 years with newly diagnosed T2D who initiated semaglutide (1.0 mg) or dulaglutide (1.5 mg) between December 2023 and December 2024. All patients received concurrent hypocaloric dietary intervention (1,200-1,400 kcal/day). Clinical and biochemical parameters were assessed at baseline and 6 months, with additional weight assessments at 3 months. Multivariable analyses were performed to adjust for baseline differences. RESULTS: Both treatment groups demonstrated significant reductions in HbA1c, fasting blood glucose, liver enzymes, and lipid parameters at 6 months. After adjustment for baseline covariates, semaglutide was associated with greater weight reduction and LDL cholesterol improvement, whereas HbA1c reduction was comparable between groups. Mild increases in pancreatic enzyme levels were observed in both groups, with higher elevations in the dulaglutide group. Gastrointestinal adverse events were common but generally mild. CONCLUSIONS: In this retrospective real-world cohort receiving structured dietary intervention, both semaglutide and dulaglutide improved glycemic control and metabolic parameters in newly diagnosed T2D. Semaglutide demonstrated superior weight reduction, while glycemic effects were similar. Baseline differences and the retrospective design should be considered when interpreting these findings. CLINICAL TRIAL NUMBER: Not applicable. FAU - Cetiner, Serap AU - Cetiner S AUID- ORCID: 0000-0002-0846-5908 AD - Department of Internal Medicine, Centermed Plus Medical Center, Nisantasi, Istanbul, 34365, Turkey. dr.serapboscetiner@gmail.com. AD - Department of Internal Medicine, Uskudar University, NP Health Campus, Umraniye, Istanbul, 34768, Turkey. dr.serapboscetiner@gmail.com. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260314 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy/therapy MH - Female MH - Retrospective Studies MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Middle Aged MH - Male MH - *Recombinant Fusion Proteins/therapeutic use MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - *Diet, Reducing/methods MH - Blood Glucose/analysis MH - Young Adult MH - Adolescent MH - Glycated Hemoglobin/analysis MH - Weight Loss MH - Prognosis MH - Follow-Up Studies MH - Treatment Outcome MH - Biomarkers/analysis PMC - PMC13020155 OTO - NOTNLM OT - Dulaglutide OT - Semaglutide OT - Type 2 diabetes OT - Weight loss COIS- Declarations. Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey (Approval number: 2024/374; Date: 25 December 2024) Consent to publish: Not applicable. Informed consent: Informed consent forms were obtained from all patients. Competing interests: The authors declare no competing interests. EDAT- 2026/03/15 06:48 MHDA- 2026/06/28 00:35 PMCR- 2026/03/14 CRDT- 2026/03/15 00:23 PHST- 2025/12/30 00:00 [received] PHST- 2026/03/10 00:00 [accepted] PHST- 2026/06/28 00:35 [medline] PHST- 2026/03/15 06:48 [pubmed] PHST- 2026/03/15 00:23 [entrez] PHST- 2026/03/14 00:00 [pmc-release] AID - 10.1186/s12902-026-02232-y [pii] AID - 2232 [pii] AID - 10.1186/s12902-026-02232-y [doi] PST - epublish SO - BMC Endocr Disord. 2026 Mar 14;26(1):86. doi: 10.1186/s12902-026-02232-y. PMID- 41831086 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260813 IS - 1539-0829 (Electronic) IS - 1534-4827 (Print) IS - 1534-4827 (Linking) VI - 26 IP - 1 DP - 2026 Mar 14 TI - Pharmacologic Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease in the Context of Type 2 Diabetes. LID - 10.1007/s11892-026-01621-w [doi] LID - 6 AB - PURPOSE OF REVIEW: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among individuals with type 2 diabetes (T2D). This review summarizes current evidence on the pharmacologic treatment of MASLD, with emphasis on agents currently approved for the management of T2D. RECENT FINDINGS: Among glucose-lowering therapies, GLP-1 RAs, dual GIP/GLP-1 RAs, pioglitazone, and SGLT2 inhibitors demonstrate meaningful benefits in steatohepatitis. Semaglutide provides the most robust evidence for fibrosis benefit, while data suggest potential antifibrotic effects of tirzepatide and dapagliflozin. Resmetirom and semaglutide are the only agents specifically approved for MASLD. An expanding pipeline of dual glucagon/GLP-1 and triple GIP/GLP-1/glucagon agonists such as retatrutide has shown marked reductions in liver fat and signals of MASH benefit. Additional therapies, including pan-PPAR agonists, and FGF21 analogues are advancing through phase 3 development. The therapeutic landscape is rapidly evolving toward integrated metabolic, hepatic, and cardiovascular risk reduction in T2D and MASLD. FAU - Malandris, Konstantinos AU - Malandris K AD - Clinical research and evidence-based medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Charalampidis, Konstantinos AU - Charalampidis K AD - Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki, 54642, Greece. FAU - Loomba, Rohit AU - Loomba R AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, Altman Clinical and Translational Research Institute, La Jolla, San Diego, CA, USA. FAU - Sinakos, Emmanouil AU - Sinakos E AD - Fourth Department of Internal Medicine, Hippokratio Hospital, Aristotle University of Thessaloniki, Thessaloniki, 54642, Greece. esinakos@auth.gr. AD - Medicine and Hepatology, Aristotle University of Thessaloniki, Hippokratio Hospital, 49, Konstantinoupoleos Str, Thessaloniki, 54642, Greece. esinakos@auth.gr. LA - eng PT - Journal Article PT - Review DEP - 20260314 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (PPAR-gamma Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - *Fatty Liver/drug therapy/etiology MH - Semaglutide MH - Tirzepatide MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - PPAR-gamma Agonists MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use PMC - PMC12989002 OTO - NOTNLM OT - MASH OT - MASLD OT - Pharmacological management OT - T2D COIS- Declarations. Conflict of Interest Disclosure Statement: KM and KC declare no conflicts of interest. ES participates in clinical trials for NovoNordisk, GlaxoSmithKline and Boehringer Ingelheim; Stockholder in Akero Therapeutics and 89bio. RL serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics. RL has stock options in Sagimet biosciences. In addition, his institution received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes and Terns Pharmaceuticals. Competing interests: KM and KC declare no conflicts of interest. ES participates in clinical trials for NovoNordisk, GlaxoSmithKline and Boehringer Ingelheim; Stockholder in Akero Therapeutics and 89bio. RL serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals and Viking Therapeutics. RL has stock options in Sagimet biosciences. In addition, his institution received research grants from Arrowhead Pharmaceuticals, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes and Terns Pharmaceuticals. RL receives funding support from NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK121378, P30DK120515), NHLBI (P01HL147835), and John C Martin Foundation (RP124). EDAT- 2026/03/15 05:36 MHDA- 2026/06/28 00:36 PMCR- 2026/03/14 CRDT- 2026/03/14 12:16 PHST- 2026/01/29 00:00 [received] PHST- 2026/03/02 00:00 [accepted] PHST- 2026/06/28 00:36 [medline] PHST- 2026/03/15 05:36 [pubmed] PHST- 2026/03/14 12:16 [entrez] PHST- 2026/03/14 00:00 [pmc-release] AID - 10.1007/s11892-026-01621-w [pii] AID - 1621 [pii] AID - 10.1007/s11892-026-01621-w [doi] PST - epublish SO - Curr Diab Rep. 2026 Mar 14;26(1):6. doi: 10.1007/s11892-026-01621-w. PMID- 41830068 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260803 IS - 1758-8111 (Electronic) IS - 1758-8103 (Linking) VI - 16 IP - 2 DP - 2026 Apr TI - Comparison of Semaglutide and Lifestyle Counselling for Weight Loss Using Multi-Site Electronic Health Records. PG - e70076 LID - 10.1111/cob.70076 [doi] AB - To evaluate the effectiveness of semaglutide compared with lifestyle counselling alone for weight loss in diabetic and non-diabetic patients with obesity. This multi-site, retrospective, observational study uses data from electronic health records which are part of the Greater Plains Collaborative (GPC) in a time-to-event analysis for comparative effectiveness. Participants were adults with obesity receiving semaglutide for a minimum of 16 weeks or lifestyle counselling with at least three sessions within the first 16 weeks. The primary outcome is incidence of 10% or greater reduction in weight from baseline. Of 3927 eligible participants, 615 were prescribed semaglutide and 3312 received lifestyle counselling. Following propensity score matching, each group (diabetic and non-diabetic) consisted of 120 and 495 participants, respectively. Hazard ratios for 10% weight loss were significantly higher from semaglutide for non-diabetic (1.63 [95% CI: 1.32, 2.01; p < 0.001]) and diabetic (2.45 [95% CI: 1.47, 4.09; p < 0.001]) populations. These data from our study suggest that semaglutide therapy compared with lifestyle counselling alone is more effective in achieving at least 10% weight loss. This information may be used to inform clinical practice guidelines and stimulate future research on the long-term effectiveness of various weight loss options for individuals with obesity. CI - (c) 2026 World Obesity Federation. FAU - Powell, William J B AU - Powell WJB AUID- ORCID: 0009-0001-1966-657X AD - Department of Biomedical and Health Informatics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. FAU - Mazzotti, Diego R AU - Mazzotti DR AD - Division of Medical Informatics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA. FAU - Herrmann, Stephen D AU - Herrmann SD AD - Kansas Center for Metabolism and Obesity Research, The University of Kansas Medical Center, Kansas City, Kansas, USA. FAU - Davis, Ann M AU - Davis AM AD - Department of Pediatrics, University of Kansas Medical Center, Kansas City, Kansas, USA. AD - Center for Children's Healthy Lifestyles & Nutrition, Kansas City, Missouri, USA. FAU - Mittendorfer, Bettina AU - Mittendorfer B AUID- ORCID: 0000-0003-0049-2677 AD - Departments of Medicine and Nutrition & Exercise Physiology, University of Missouri, School of Medicine, Columbia, Missouri, USA. FAU - Bruce, Jared AU - Bruce J AD - Department of Biomedical and Health Informatics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. FAU - Song, Xing AU - Song X AUID- ORCID: 0000-0002-3712-2904 AD - Department of Biomedical Informatics, Biostatistics, and Medical Epidemiology, University of Missouri School of Medicine, Columbia, Missouri, USA. FAU - Waitman, Lemuel R AU - Waitman LR AD - Department of Biomedical and Health Informatics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. AD - Department of Biomedical Informatics, Biostatistics, and Medical Epidemiology, University of Missouri School of Medicine, Columbia, Missouri, USA. LA - eng GR - RI-MISSOURI-01-PS1/PCORI/Patient-Centered Outcomes Research Institute/United States GR - University of Missouri/ PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Counseling/methods MH - Diabetes Mellitus, Type 2 MH - Electronic Health Records MH - *Life Style MH - *Obesity/therapy/drug therapy MH - Retrospective Studies MH - *Semaglutide/therapeutic use MH - Treatment Outcome MH - *Weight Loss/drug effects OTO - NOTNLM OT - databases OT - glucagon-like peptide 1 (GLP-1) OT - lifestyle modifications EDAT- 2026/03/14 06:32 MHDA- 2026/03/14 06:33 CRDT- 2026/03/14 01:42 PHST- 2026/01/20 00:00 [revised] PHST- 2025/02/03 00:00 [received] PHST- 2026/03/05 00:00 [accepted] PHST- 2026/03/14 06:33 [medline] PHST- 2026/03/14 06:32 [pubmed] PHST- 2026/03/14 01:42 [entrez] AID - 10.1111/cob.70076 [doi] PST - ppublish SO - Clin Obes. 2026 Apr;16(2):e70076. doi: 10.1111/cob.70076. PMID- 41825212 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260831 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 40 IP - 5 DP - 2026 May TI - Tirzepatide versus semaglutide for the prevention of mild cognitive impairment, dementia, and Alzheimer's disease in type 2 diabetes: A real-world, retrospective cohort study. PG - 109306 LID - S1056-8727(26)00051-6 [pii] LID - 10.1016/j.jdiacomp.2026.109306 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists have shown promise in managing type 2 diabetes mellitus (T2DM) and provide metabolic and cardiovascular benefits. Their associations with neurocognitive outcomes in clinical populations remain uncertain. METHODS: We conducted a retrospective, population-based cohort study using de-identified electronic health records from the global TriNetX research network, predominantly comprising U.S.-based healthcare organizations. Adults with T2DM who initiated tirzepatide or semaglutide were included. Propensity score matching (1:1) was applied to balance baseline characteristics, including age, sex, race, and cardiometabolic and psychiatric comorbidities. Incident diagnoses of mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD) occurring at least 12 months after treatment initiation were assessed using risk ratios (RRs) and time-to-event analyses with Kaplan-Meier estimators. FINDINGS: A total of 290,606 patients initiated semaglutide and 44,471 initiated tirzepatide. After propensity score matching, each group included 44,470 patients. Compared with semaglutide, initiation of tirzepatide was associated with a lower risk of MCI (RR 0.12; 95% CI 0.06-0.22), dementia (RR 0.15; 95% CI 0.09-0.26), and AD (RR 0.48; 95% CI 0.22-1.01). Absolute risks were low for all outcomes, and separation of survival curves was more consistent for MCI than for dementia or AD. INTERPRETATION: In this real-world observational analysis of adults with T2DM, initiation of tirzepatide was associated with a lower incidence of MCI compared with semaglutide, whereas associations for dementia and AD were less consistent. These findings should be interpreted descriptively and as hypothesis-generating. Prospective randomized trials with longer follow-up and systematic neurocognitive assessment are needed to clarify whether, and under which conditions, incretin-based therapies influence neurocognitive outcomes. CI - Copyright (c) 2026 Elsevier Inc. All rights reserved. FAU - da Silva, Anderson Matheus Pereira AU - da Silva AMP AD - Division of Biostatistics and Clinical Epidemiology, MemoryHub, Cognitive and Neurodegenerative Disorders Research Group, Sao Paulo, SP, Brazil. Electronic address: anderson.mhps@icloud.com. FAU - Januario Campos Cardoso, Leonardo AU - Januario Campos Cardoso L AD - Department of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. FAU - Batista, Savio AU - Batista S AD - Department of Neurology, Grady Memorial Hospital, Emory University, Atlanta, GA, USA. FAU - Goncalves, Ocilio Ribeiro AU - Goncalves OR AD - Department of Medicine, Federal University of Piaui, Teresina, PI, Brazil. FAU - Paranhos, Thiago AU - Paranhos T AD - Frontotemporal Disorders Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. FAU - Teixeira, Ivan Petterson Santana AU - Teixeira IPS AD - Department of Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. FAU - Guimaraes, Pedro Duarte AU - Guimaraes PD AD - Faculty of Medicine, Faculdade de Ciencias Medicas de Santos, Santos, Sao Paulo, SP, Brazil. FAU - Espinosa Franco, Beatriz AU - Espinosa Franco B AD - Department of Endocrinology, Hospital Alemao Oswaldo Cruz, Sao Paulo, SP, Brazil; Department of Endocrinology, Federal University of Sao Paulo, Sao Paulo, SP, Brazil. FAU - Cal, Henrique AU - Cal H AD - Division of Neurology, MemoryHub, Cognitive and Neurodegenerative Disorders Research Group, Sao Paulo, SP, Brazil. FAU - Salles, Joao Eduardo Nunes AU - Salles JEN AD - Division of Endocrinology, Department of Internal Medicina of Santa Casa of Sao Paulo Scholl of Medical Science, Sao Paulo, SP, Brazil. FAU - Perry, George AU - Perry G AD - Department of Neurosciences, Developmental and Regenerative Biology, University of Texas at San Antonio, San Antonio, TX, USA. FAU - Hoilund-Carlsen, Poul F AU - Hoilund-Carlsen PF AD - Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark. FAU - Santos, Diogo Haddad AU - Santos DH AD - Department of Neurology, Hospital Alemao Oswaldo Cruz, Sao Paulo, SP, Brazil; Division of Neurology, MemoryHub, Cognitive and Neurodegenerative Disorders Research Group, Sao Paulo, SP, Brazil. Electronic address: dhaddadsantos@gmail.com. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260225 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Alzheimer Disease/prevention & control/epidemiology MH - Female MH - Retrospective Studies MH - *Cognitive Dysfunction/prevention & control/epidemiology/etiology MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Aged MH - *Dementia/prevention & control/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Alzheimer's disease OT - Dementia OT - Mild cognitive impairment OT - Semaglutide OT - Tirzepatide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no financial or personal relationships with individuals or organizations that could inappropriately influence, or be perceived to influence, the work reported in this manuscript. EDAT- 2026/03/14 00:31 MHDA- 2026/04/12 04:37 CRDT- 2026/03/13 19:08 PHST- 2025/11/18 00:00 [received] PHST- 2026/01/06 00:00 [revised] PHST- 2026/02/22 00:00 [accepted] PHST- 2026/04/12 04:37 [medline] PHST- 2026/03/14 00:31 [pubmed] PHST- 2026/03/13 19:08 [entrez] AID - S1056-8727(26)00051-6 [pii] AID - 10.1016/j.jdiacomp.2026.109306 [doi] PST - ppublish SO - J Diabetes Complications. 2026 May;40(5):109306. doi: 10.1016/j.jdiacomp.2026.109306. Epub 2026 Feb 25. PMID- 41823026 OWN - NLM STAT- MEDLINE DCOM- 20260711 LR - 20260812 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 46 IP - 4 DP - 2026 Apr TI - Early Adoption and Prescribing Patterns of Resmetirom: A Multi-Institutional National Analysis. PG - e70580 LID - 10.1111/liv.70580 [doi] AB - Resmetirom received FDA approval in March 2024 as the first therapy for noncirrhotic MASH with moderate-to-advanced fibrosis. This retrospective cohort study used the TriNetX Research Network to assess early prescribing patterns among 3712 patients across 44 healthcare organisations. The mean age was 57.6 years, 57% were female, and the mean BMI was 33.9 kg/m(2). The cohort was predominantly White (73.8%), with representation from Hispanic/Latino (11.7%) and Asian (8.1%) populations. MASLD and MASH diagnoses were documented in 72% and 56% of patients, while 15% carried cirrhosis codes. Common comorbidities included dyslipidaemia (55%), hypertension (52%) and type 2 diabetes (41%). GLP-1 receptor agonists were commonly prescribed, with semaglutide (n = 1124), tirzepatide (n = 842), dulaglutide (n = 391) and liraglutide (n = 203) representing the most frequently used agents. Among 19 643 treatment-eligible patients (1057 treated and 18 586 untreated), 5.4% received resmetirom. Treated patients were more frequently Asian or Hispanic and more likely to be prescribed GLP-1 receptor agonists, statins, metformin or ARBs (all p < 0.01). Early prescribing demonstrates preferential use among individuals with higher metabolic burden but reveals potential miscoding or off-label use and significant underutilization among eligible populations. CI - (c) 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Solpari, Kate AU - Solpari K AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Gouda, Zane AU - Gouda Z AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Saggese, Allysa AU - Saggese A AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Buckholz, Adam AU - Buckholz A AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Sharaiha, Reem Z AU - Sharaiha RZ AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Kumar, Sonal AU - Kumar S AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. FAU - Kushner, Tatyana AU - Kushner T AUID- ORCID: 0000-0001-6663-6253 AD - Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York, USA. AD - Division of Population Health Sciences, Weill Cornell Medicine, New York, New York, USA. LA - eng PT - Journal Article PT - Multicenter Study PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - WTT295HSY5 (dulaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - *Practice Patterns, Physicians'/statistics & numerical data MH - Retrospective Studies MH - Semaglutide MH - Tirzepatide/therapeutic use MH - United States MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins EDAT- 2026/03/13 06:52 MHDA- 2026/03/13 12:40 CRDT- 2026/03/13 05:43 PHST- 2026/02/05 00:00 [revised] PHST- 2025/09/18 00:00 [received] PHST- 2026/02/19 00:00 [accepted] PHST- 2026/03/13 12:40 [medline] PHST- 2026/03/13 06:52 [pubmed] PHST- 2026/03/13 05:43 [entrez] AID - 10.1111/liv.70580 [doi] PST - ppublish SO - Liver Int. 2026 Apr;46(4):e70580. doi: 10.1111/liv.70580. PMID- 41820778 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 43 IP - 5 DP - 2026 May TI - Comparison of Clinical Efficacy and Safety of Tirzepatide, Liraglutide and Semaglutide in Patients with Obesity and Without T2D: A Bayesian Network Meta-Analysis of Randomised Controlled Trials. PG - 2090-2105 LID - 10.1007/s12325-026-03523-5 [doi] AB - INTRODUCTION: Recent pharmacological options for weight management include the glucagon-like peptide 1 (GLP-1) receptor agonists semaglutide and liraglutide, and the glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide, but head-to-head comparisons of all three of these interventions are lacking. METHODS: Based on a systematic literature review (SLR) and Bayesian network meta-analysis (NMA), the efficacy and safety of semaglutide 2.4 mg, liraglutide 3 mg and tirzepatide 5, 10 and 15 mg were compared in adults without type 2 diabetes, and with either obesity (body mass index [BMI] >/= 30 kg/m(2)) or overweight (BMI >/= 27 kg/m(2)) with >/= 1 obesity-related complication. RESULTS: Following a stringent heterogeneity assessment, six of 42 randomised controlled trials identified in the SLR were included in the NMA. Efficacy estimand results showed all tirzepatide doses were associated with statistically greater improvements in weight reduction outcomes versus liraglutide, and for tirzepatide 10 and 15 mg versus semaglutide: including percentage weight reduction (- 12.86% for tirzepatide 10 mg and - 13.95% for tirzepatide 15 mg versus liraglutide; - 4.85% and - 6.26% versus semaglutide) and waist circumference (- 11.79 cm and - 12.30 cm versus liraglutide; - 4.81 cm and - 5.32 cm versus semaglutide). All tirzepatide doses were associated with statistically greater improvements in triglycerides and diastolic blood pressure versus liraglutide, and generally comparable improvements in other glycaemic, lipid and blood pressure parameters versus liraglutide and semaglutide. All interventions had a comparable safety profile. CONCLUSION: In this NMA, tirzepatide 10 and 15 mg were associated with improved efficacy versus liraglutide, improved or comparable efficacy versus semaglutide, and all interventions had a generally comparable safety profile for achieving weight reduction and reducing cardiometabolic risk factors among patients with obesity or overweight. CI - (c) 2026. The Author(s). FAU - Ciudin, Andreea AU - Ciudin A AUID- ORCID: 0000-0001-5622-0203 AD - Endocrinology and Nutrition, Vall d'Hebron University Hospital, Pg. de la Vall d'Hebron, 119, 08035, Barcelona, Spain. FAU - Sapin, Helene AU - Sapin H AUID- ORCID: 0000-0003-2602-8450 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. FAU - Fan, Ludi AU - Fan L AUID- ORCID: 0000-0001-9298-8025 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. FAU - Dimitriadis, Georgios K AU - Dimitriadis GK AUID- ORCID: 0000-0002-6662-804X AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. FAU - Zimner-Rapuch, Sarah AU - Zimner-Rapuch S AUID- ORCID: 0009-0008-6687-1921 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. FAU - Curteis, Tristan AU - Curteis T AD - Costello Medical, 1 New York St, Manchester, M1 4HD, UK. FAU - Clark, Laura J AU - Clark LJ AUID- ORCID: 0000-0003-4378-2420 AD - Costello Medical, 1 New York St, Manchester, M1 4HD, UK. FAU - Rubinstein, Manon AU - Rubinstein M AD - Costello Medical, 8 Emerson Street, London, SE1 9DU, UK. FAU - Johansson, Erin AU - Johansson E AUID- ORCID: 0009-0006-3178-1622 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. johansson_erin@lilly.com. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260312 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Tirzepatide MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Obesity/drug therapy MH - Randomized Controlled Trials as Topic MH - *Liraglutide/therapeutic use/adverse effects MH - Weight Loss/drug effects MH - Bayes Theorem MH - Diabetes Mellitus, Type 2 MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Anti-Obesity Agents/therapeutic use PMC - PMC13156185 OAB - Obesity management is crucial for reducing the health risks associated with obesity, and comprises of behavioural interventions, psychological support, dietary changes and physical activity programs. Medications may also be prescribed, or surgical options may also be considered. Three such medications for weight management are injectable weekly treatments tirzepatide and semaglutide, or daily liraglutide, which help to control appetite by prolonging patients' feeling of fullness. Because there are no clinical trials directly comparing tirzepatide and liraglutide, and no trials comparing all three medications, this study aimed to indirectly compare the effectiveness and safety of tirzepatide, semaglutide and liraglutide for weight management in patients without type 2 diabetes, who also have obesity or overweight. A systematic review of literature identified all published clinical trials reporting on tirzepatide, semaglutide and liraglutide. Following strict eligibility criteria, six suitable randomised controlled trials were chosen for analysis. These studies had similar designs and patients, making it possible to compare their results meaningfully. Tirzepatide demonstrated improved results across various outcomes, including weight loss and cardiometabolic health factors compared with liraglutide. Compared with semaglutide, the higher doses of tirzepatide demonstrated consistent improvements in weight reduction and cardiometabolic health factors, whilst the lower dose was broadly comparable with semaglutide. The safety profile of tirzepatide was generally similar to both liraglutide and semaglutide. Overall, the analysis supports the clinical effectiveness and safety of tirzepatide compared with liraglutide and semaglutide in weight reduction and other clinical outcomes associated with weight management in patients with obesity or overweight. OABL- eng OTO - NOTNLM OT - Glucagon-like peptide 1 receptor agonists OT - Network meta-analysis OT - Obesity OT - Overweight OT - Tirzepatide OT - Weight reduction COIS- Declarations. Conflict of Interest: Andreea Ciudin: Honoraria from AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk; Member of the DMC of Boehringer Ingelheim clinical trials-SYNCRONIZE program; Helene Sapin, Ludi Fan, Georgios K. Dimitriadis, Sarah Zimner-Rapuch, Erin Johansson: Employees and shareholders of Eli Lilly and Company; Tristan Curteis, Laura J. Clark, Manon Rubinstein: Employees of Costello Medical, which received payment from Eli Lilly and Company for analytical services for this study. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. EDAT- 2026/03/13 06:52 MHDA- 2026/05/08 12:38 PMCR- 2026/03/12 CRDT- 2026/03/13 00:46 PHST- 2025/10/23 00:00 [received] PHST- 2026/02/03 00:00 [accepted] PHST- 2026/05/08 12:38 [medline] PHST- 2026/03/13 06:52 [pubmed] PHST- 2026/03/13 00:46 [entrez] PHST- 2026/03/12 00:00 [pmc-release] AID - 10.1007/s12325-026-03523-5 [pii] AID - 3523 [pii] AID - 10.1007/s12325-026-03523-5 [doi] PST - ppublish SO - Adv Ther. 2026 May;43(5):2090-2105. doi: 10.1007/s12325-026-03523-5. Epub 2026 Mar 12. PMID- 41818107 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 74 IP - 3 DP - 2026 Mar TI - Semaglutide Hype or Hope: Evidence-based Review in Diabesity. PG - 103-107 LID - 10.59556/japi.74.1439 [doi] AB - India is struggling with the twin epidemics of diabetes and weight issues, holding the second position globally in the former and third in the latter. Despite multiple advancements with therapies that offer glycemic control and weight benefits, there has remained a gap for a comprehensive drug for the management of "diabesity." Semaglutide, since its global approval in 2017, has become a blockbuster, owing to the popularity of "Ozempic." While Ozempic has been traditionally approved for glycemic control in type 2 diabetes mellitus (T2DM), it does offer significant other benefits powerful weight loss, cardiovascular benefits, renal protection benefits, and functional improvement in peripheral arterial disease. The drug is approved in India for first-line use in adults with T2DM as an adjunct to diet and exercise. The long use of semaglutide globally and in India has ensured adequate data on efficacy and safety, ensuring confidence and trust. Gastrointestinal side effects are the most common adverse events seen with the molecule, as with other GLP-1 drugs. This review highlights the global clinical data and practicalities of the use of Ozempic in diabesity in the Indian context. CI - (c) Journal of The Association of Physicians of India 2026. FAU - Gupta, Sunil AU - Gupta S AD - Managing Director, Department of Diabetology, Nagpur, Maharashtra, India, Corresponding Author. FAU - Makkar, Brij Mohan AU - Makkar BM AD - Senior Physician, Diabetologist and Obesity Specialist, Dr Makkar's Diabetes and Obesity Centre, Delhi, India. FAU - Kesavadev, Jothydev AU - Kesavadev J AD - Chairman and Managing Director, Jothydev's Diabetes Research Center, Trivandrum, Kerala, India. FAU - Kumar, Ajay AU - Kumar A AD - Senior Diabetologist, Diabetes Care and Research Centre, Patna, Bihar, India. LA - eng PT - Journal Article PT - Review PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - India MH - *Obesity/drug therapy EDAT- 2026/03/12 18:52 MHDA- 2026/03/12 18:53 CRDT- 2026/03/12 12:57 PHST- 2026/03/12 18:53 [medline] PHST- 2026/03/12 18:52 [pubmed] PHST- 2026/03/12 12:57 [entrez] AID - 10.59556/japi.74.1439 [doi] PST - ppublish SO - J Assoc Physicians India. 2026 Mar;74(3):103-107. doi: 10.59556/japi.74.1439. PMID- 41817564 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260813 IS - 1998-3689 (Electronic) IS - 0301-4738 (Print) IS - 0301-4738 (Linking) VI - 74 IP - 7 DP - 2026 Jul 1 TI - Ocular complications associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) - Clinical evidence and insights. PG - 974-981 LID - 10.4103/IJO.IJO_2659_25 [doi] AB - Type 2 diabetes mellitus (T2DM) and obesity are commonly treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). However, there have been growing concerns over the possibility that these medications may result in ocular adverse events, such as nonarteritic anterior ischemic optic neuropathy (NAION). Standard clinical care can overlook these potentially fatal adverse effects. The purpose of this review was to compile the most recent data on ocular side effects associated with GLP-1 RA therapy, assess their clinical relevance, and highlight necessary preventative and monitoring measures. A thorough search of the literature was conducted using Medline/PubMed/PMC, Google Scholar, Scopus, Web of Science, and ScienceDirect. Relevant literature, including observational studies, randomized trials, case reports, and pharmacovigilance data, was selected for its discussion of GLP-1 RAs and associated eye-related adverse events. Semaglutide, a GLP-1 RA, has been associated in a number of studies and safety assessments with an increased risk of NAION and the progression of diabetic retinopathy, especially in patients with underlying eye disorders. Findings, however, were mixed because no statistically significant link was found in a number of cohort studies and meta-analyses. The necessity for additional research was supported by data from adverse event reporting systems that showed disproportionality signals. Clinicians should be mindful of the potential ocular hazards associated with GLP-1 RAs, even though these medications remain useful in treating T2DM and obesity. Closer ophthalmologic monitoring may be beneficial for patients with known diabetic eye problems. Further prospective research with well-defined ocular outcomes is required to elucidate these correlations and guarantee the secure administration of GLP-1 RAs. CI - Copyright (c) 2026 Indian Journal of Ophthalmology. FAU - Maideen, Naina Mohamed Pakkir AU - Maideen NMP AD - Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE. FAU - Al Rashid, Sulthan AU - Al Rashid S AD - Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Department of Pharmacology, Chennai, Tamil Nadu, India. FAU - Balasubramanian, Rajkapoor AU - Balasubramanian R AD - Faculty of Pharmacy, Karpagam Academy of Higher Education, Coimbatore, Tamil Nadu, India. FAU - Amirthalingam, Palanisamy AU - Amirthalingam P AD - Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article PT - Review DEP - 20260312 PL - India TA - Indian J Ophthalmol JT - Indian journal of ophthalmology JID - 0405376 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - Semaglutide MH - Diabetic Retinopathy/chemically induced MH - *Optic Neuropathy, Ischemic/chemically induced MH - Glucagon-Like Peptides/adverse effects PMC - PMC13422913 OTO - NOTNLM OT - Diabetic retinopathy progression OT - GLP-1 receptor agonists OT - glucagon-like peptide-1 OT - ischemic optic neuropathy OT - macular edema OT - nonarteritic anterior ischemic optic neuropathy OT - ocular complications OT - semaglutide OT - tirzepatide COIS- There are no conflicts of interest. EDAT- 2026/03/12 13:55 MHDA- 2026/06/30 18:42 PMCR- 2026/07/01 CRDT- 2026/03/12 11:43 PHST- 2024/10/18 00:00 [received] PHST- 2025/12/08 00:00 [accepted] PHST- 2026/06/30 18:42 [medline] PHST- 2026/03/12 13:55 [pubmed] PHST- 2026/03/12 11:43 [entrez] PHST- 2026/07/01 00:00 [pmc-release] AID - 02223307-990000000-00446 [pii] AID - IJO-74-974 [pii] AID - 10.4103/IJO.IJO_2659_25 [doi] PST - ppublish SO - Indian J Ophthalmol. 2026 Jul 1;74(7):974-981. doi: 10.4103/IJO.IJO_2659_25. Epub 2026 Mar 12. PMID- 41816857 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260824 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Obesity Treatments and Weight Changes in Clinical Practice After Discontinuation of Semaglutide or Tirzepatide. PG - 4795-4805 LID - 10.1111/dom.70660 [doi] AB - AIMS: To describe obesity treatments in real-world settings after discontinuation of semaglutide or tirzepatide and variability in weight change post-discontinuation. MATERIALS AND METHODS: This retrospective cohort study used electronic health records from 1 January 2021, to 30 June 2025, in a large health system in Ohio and Florida. Adults with overweight or obesity who initiated injectable semaglutide or tirzepatide for obesity or T2D between 2021 and 2023 and discontinued the medication within 3-12 months were included. Main outcomes were reinitiation of the index medication or receipt of an alternative treatment, body weight changes from baseline to index medication discontinuation and from discontinuation to 1-year post discontinuation. RESULTS: A total of 7938 patients (mean [SD] age, 55.7 [13.4] years; 5061 [63.8%] female) were identified. During 1-year post-discontinuation, 19.6% restarted the index medication and 35.2% received an alternative obesity treatment, including starting another medication (27.4%), lifestyle modification visit (13.7%) and metabolic and bariatric surgery (0.6%). Mean percentage weight change from baseline to discontinuation was -8.4% [95% CI, -8.7%, -8.1%] when treating obesity and -4.4% [95% CI, -4.7%, -4.2%] when treating T2D. Mean percentage weight change from discontinuation to 1 year later was 0.5% [95% CI, 0.0%, 1.0%] when treating obesity and -1.3% [95% CI, -1.6%, -1.0%] when treating T2D; however, there was considerable individual-level variability. CONCLUSION: In this large sample of patients who discontinued semaglutide or tirzepatide, reinitiation of the original medication or receipt of alternative obesity treatment was common. The average weight change 1-year post-discontinuation was relatively small; however, there was considerable individual-level variability. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gasoyan, Hamlet AU - Gasoyan H AUID- ORCID: 0000-0002-1627-9777 AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. FAU - Schulte, Rebecca AU - Schulte R AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Boyer, Christopher B AU - Boyer CB AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Casacchia, Nicholas J AU - Casacchia NJ AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Butsch, W Scott AU - Butsch WS AD - Department of Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Le, Phuc AU - Le P AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. FAU - Aminian, Ali AU - Aminian A AUID- ORCID: 0000-0001-5756-9917 AD - Department of Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Griebeler, Marcio L AU - Griebeler ML AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. AD - Endocrinology and Metabolism Department, Medical Specialty Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Burguera, Bartolome AU - Burguera B AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. AD - Endocrinology and Metabolism Department, Medical Specialty Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Rothberg, Michael B AU - Rothberg MB AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA. LA - eng GR - MAG0030/Cleveland Clinic - Jack, Joseph and Morton Mandel Accelerator Grants/ PT - Journal Article DEP - 20260312 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide/therapeutic use MH - Female MH - *Obesity/drug therapy/therapy MH - Retrospective Studies MH - Middle Aged MH - Male MH - Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - *Anti-Obesity Agents/therapeutic use MH - Aged MH - Adult MH - Florida MH - Ohio MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC13146129 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonist OT - lifestyle modification OT - long-term weight outcomes OT - metabolic and bariatric surgery OT - obesity pharmacotherapy OT - treatment discontinuation COIS- Dr. Hamlet Gasoyan reported receiving grant funding from the National Cancer Institute outside the submitted work. Dr. Christopher B. Boyer reports consulting fees from Janssen Pharmaceuticals outside the submitted work. Dr. W. Scott Butsch is currently employed by Novo Nordisk A/S; he also reported advisory board fees from Eli Lilly, Boehringer Ingelheim and Abbott and research funding from Eli Lilly and Co outside the submitted work. Dr. Ali Aminian reported receiving research grants from Amgen, Ethicon and Medtronic outside the submitted work. He serves as a consultant for Amylyx, Eli Lilly, Ethicon and Medtronic. Dr. Marcio L. Griebeler reported research funding from Novo Nordisk A/S outside the submitted work. Dr. Michael B. Rothberg reported receiving consulting fees from the Blue Cross Blue Shield Association outside the submitted work. The other authors declare no conflicts of interest. EDAT- 2026/03/12 07:03 MHDA- 2026/05/06 06:39 PMCR- 2026/05/06 CRDT- 2026/03/12 05:43 PHST- 2026/03/03 00:00 [revised] PHST- 2026/01/29 00:00 [received] PHST- 2026/03/04 00:00 [accepted] PHST- 2026/05/06 06:39 [medline] PHST- 2026/03/12 07:03 [pubmed] PHST- 2026/03/12 05:43 [entrez] PHST- 2026/05/06 00:00 [pmc-release] AID - DOM70660 [pii] AID - 10.1111/dom.70660 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):4795-4805. doi: 10.1111/dom.70660. Epub 2026 Mar 12. PMID- 41815966 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 2296-2565 (Electronic) IS - 2296-2565 (Linking) VI - 14 DP - 2026 TI - Quality and reliability of semaglutide content on different Chinese short video platforms: a study focusing on side effects. PG - 1750738 LID - 10.3389/fpubh.2026.1750738 [doi] LID - 1750738 AB - OBJECTIVE: This study aims to evaluate the quality, reliability, and content characteristics of semaglutide-related short videos on three major Chinese short-video platforms (Bilibili, TikTok, and Rednote), with a focus on exploring differences in the presentation of side effects across different platforms and uploader types. Rather than examining specific clinical indications or dosing regimens, this study focuses on how semaglutide-related information is presented to the general public in real-world short-video contexts. It seeks to clarify the impact of platform ecology and creator identity on drug information dissemination, thereby providing a basis for optimizing the quality of online health information and conducting targeted public health communication. METHODS: A cross-sectional content analysis was adopted. Semaglutide-related videos were retrieved from three major Chinese short-video platforms using the Chinese keyword "" (the standard Mandarin term for "semaglutide"). This exact search term was used to simulate real-world user behavior and ensure reproducibility across platforms. Because most videos did not specify approved indications (type 2 diabetes vs. obesity) or dosage levels, analyses were conducted without stratification by clinical dose or indication. After rigorous screening, eligible videos were assessed for quality and reliability using the modified DISCERN scale and Global Quality Score (GQS). Video content was categorized into five thematic dimensions, and mentions of nine predefined side effects were systematically recorded. A dual-perspective analytical approach-comparing the full sample and a side effect-focused subsample-was employed to examine platform-based differences in adverse event portrayal. RESULTS: A total of 607 semaglutide-related videos were included (Bilibili: 309, TikTok: 153, Rednote: 145). The results showed significant differences in content quality (M-DISCERN and GQS scores), video duration, and user engagement metrics across platforms (p < 0.05). There were statistically significant differences in content distribution among platforms (p < 0.05): Bilibili focused on Policy News and Events, Personal Experience Sharing, and Commercial Promotion; Rednote centered on Medication Education and Medical Advice/Medication Guidance; TikTok mainly focused on Policy News and Events. Regarding side effects, the distribution of gastrointestinal and hepatobiliary side effects among the three platforms was statistically significant (p < 0.05), with TikTok having the highest mention rate. These side effect narratives were typically presented without reference to specific dosing levels or approved indications. The dual-perspective analysis further revealed systematic differences in side effect portrayal, with TikTok conferring greater visibility for adverse-event narratives. In terms of content quality, the three platforms showed a gradient difference of "Rednote > TikTok > Bilibili" (p < 0.001). CONCLUSION: The quality and reliability of semaglutide-related short videos are significantly influenced by platform ecology. Publicly accessible drug information on short-video platforms often lacks clear differentiation between approved indications and dosage regimens, contributing to generalized interpretations of drug risks. The drug information accessible to the public exhibits structural biases, with side effect narratives demonstrating a clear "platformization" pattern. The dual-perspective analysis revealed that inter-platform differences in the portrayal of specific adverse events (e.g., gastrointestinal and hepatobiliary effects) were more discernible in the side effect-focused subsample. Future interventions should be tailored to platform-specific features to enhance the completeness and scientific rigor of online pharmaceutical information. CI - Copyright (c) 2026 Song, He, Cui, Sun, Liu, Yu, Li and Jin. FAU - Song, Jiayuan AU - Song J AD - College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China. FAU - He, Xingchen AU - He X AD - The Affiliated Guangzhou Hospital of TCM of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Cui, Zhenhai AU - Cui Z AD - Department of Orthopedics, The Third Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China. FAU - Sun, Ye AU - Sun Y AD - College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China. FAU - Liu, Yanlin AU - Liu Y AD - College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China. FAU - Yu, Han AU - Yu H AD - College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China. FAU - Li, Aimin AU - Li A AD - College of Integrative Medicine, Changchun University of Chinese Medicine, Changchun, China. FAU - Jin, Meiying AU - Jin M AD - Department of Endocrine Metabolism and Spleen and Stomach, The Third Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, China. LA - eng PT - Journal Article DEP - 20260224 PL - Switzerland TA - Front Public Health JT - Frontiers in public health JID - 101616579 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - China MH - Cross-Sectional Studies MH - Diabetes Mellitus, Type 2/drug therapy MH - Digital Media MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Information Dissemination/methods MH - Reproducibility of Results MH - Semaglutide MH - *Video Recording PMC - PMC12971943 OTO - NOTNLM OT - content characteristics OT - creator identity OT - information quality OT - semaglutide OT - short-video platforms OT - side effects COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/03/12 07:03 MHDA- 2026/03/12 13:56 PMCR- 2026/02/24 CRDT- 2026/03/12 05:13 PHST- 2025/11/20 00:00 [received] PHST- 2026/02/01 00:00 [revised] PHST- 2026/02/12 00:00 [accepted] PHST- 2026/03/12 13:56 [medline] PHST- 2026/03/12 07:03 [pubmed] PHST- 2026/03/12 05:13 [entrez] PHST- 2026/02/24 00:00 [pmc-release] AID - 10.3389/fpubh.2026.1750738 [doi] PST - epublish SO - Front Public Health. 2026 Feb 24;14:1750738. doi: 10.3389/fpubh.2026.1750738. eCollection 2026. PMID- 41815032 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260730 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 81 IP - 3 DP - 2026 Mar TI - [SURPASS CVOT : cardiovascular benefits with tirzepatide versus dulaglutide in type 2 diabetes]. PG - 187-193 AB - Several glucagon-like peptide-1 receptor agonists (GLP-1RAs) have proven their ability to reduce major adverse cardiovascular events (MACEs) among at-risk patients living with type 2 diabetes (T2D). Tirzepatide, a dual GIP/GLP-1 receptor agonist, demonstrated a better control of hyperglycaemia, body weight and several cardiovascular risk factors than pure GLP-1RAs (including semaglutide) in dedicated studies of the SURPASS programme. SURPASS CVOT has the primary objective to demonstrate, in a population with T2D and atheromatous cardiovascular disease, the non-inferiority of tirzepatide regarding both efficacy and safety compared with dulaglutide, a selective GLP-RA that has already proven a significant reduction in MACEs versus placebo in the REWIND trial. Non-inferiority was met in SURPASS CVOT (p = 0.003), but not superiority of tirzepatide compared to dulaglutide (hazard ratio [HR] 0.92; 95 % confidence interval [IC] 0.83 to 1.01; P = 0.09) regarding the primary end point (reduction in MACEs). Several secondary end points tended to favour tirzepatide versus dulaglutide, among which a reduction in the incidence of all-cause deaths after four years of median follow-up (HR 0.84 ; 95 % CI 0.75 to 0.94; exploratory analysis). SURPASS CVOT, the first and unique study that used an active comparator rather than a placebo, confirms the efficacy and safety of the dual agonist tirzepatide in patients with T2D and atheromatous cardiovascular disease. FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. AD - Unite de Pharmacologie clinique, Centre Interdisciplinaire de Recherche sur le Medicament (CIRM), ULiege, Belgique. FAU - Lancellotti, Patrizio AU - Lancellotti P AD - Service de Cardiologie, CHU Liege, Belgique. AD - GIGA Cardiovasculaire, Uliege, Belgique. LA - fre PT - English Abstract PT - Equivalence Trial PT - Journal Article TT - L'etude clinique du mois. SURPASS CVOT : benefices cardiovasculaires avec le tirzepatide versus le dulaglutide dans le diabete de type 2. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - *Tirzepatide/therapeutic use OTO - NOTNLM OT - Cardiovascular protection OT - Dulaglutide OT - GIP/GLP-1 dual agonist OT - GLP-1 receptor agonist OT - Tirzepatide OT - Type 2 diabetes EDAT- 2026/03/12 07:04 MHDA- 2026/03/12 13:57 CRDT- 2026/03/12 04:34 PHST- 2026/03/12 13:57 [medline] PHST- 2026/03/12 07:04 [pubmed] PHST- 2026/03/12 04:34 [entrez] PST - ppublish SO - Rev Med Liege. 2026 Mar;81(3):187-193. PMID- 41813606 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1365-2036 (Electronic) IS - 0269-2813 (Linking) VI - 63 IP - 11 DP - 2026 Jun TI - Real-World Alcohol Use Disorder Outcomes in Patients With Concurrent Metabolic Dysfunction: GLP-1 Receptor Agonists Versus FDA-Approved AUD Medications. PG - 1507-1516 LID - 10.1111/apt.70596 [doi] AB - BACKGROUND: Metabolic dysfunction (MetD) and alcohol use disorder (AUD) frequently coexist as synergistic risk factors for steatotic liver disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established therapies for MetD, including type 2 diabetes mellitus (T2DM) and obesity. Recent studies suggested potential beneficial effects of GLP-1RA to decrease addictive behaviours in AUD. We evaluated the outcomes of GLP-1RA therapy compared with FDA-approved pharmacotherapies for AUD, including naltrexone, acamprosate, and disulfiram, in patients with dual risk factors of MetD and AUD. METHODS: We conducted a retrospective cohort study of patients at Stanford Health Care (2017-2025). Eligible patients had a concurrent diagnosis of alcohol-related complications meeting criteria for AUD and MetD, including obesity (BMI > 25) and/or a history of T2DM with HbA1c > 5.7. Those with advanced liver disease within 1 year of diagnosis were excluded. Exposure groups included >/= 6 months of GLP-1RA therapy (semaglutide or tirzepatide) in comparison with FDA-approved pharmacotherapies for AUD. Propensity score matching was employed to reduce the effects of confounding factors. RESULTS: In total, 1946 patients were diagnosed concurrently with AUD and MetD. Of them, 274 patients were exposed to GLP-1RA, 1272 to naltrexone, 232 to acamprosate, and 168 to disulfiram. Patients were followed for an average of 1341 days. Patients exposed to GLP-1RA had higher BMI (35.5 vs. 30.1) and more T2DM (66% vs. 14%). GLP-1RA therapy was associated with lower 1-year AUD relapse [IRR 0.55, 95% CI 0.42-0.73; p < 0.01], greater BMI reduction (-1.3 vs. -0.3; p = 0.004), and HbA1c improvement (-1.0 vs. +0.1; p = 0.02). The incidence of decompensated cirrhosis trended lower but was not statistically significant [HR 0.52, p = 0.09]. Mortality was similar. CONCLUSIONS: GLP-1RAs are a promising option for patients with concurrent MetD and AUD, improving relapse rates and metabolic outcomes compared with currently FDA-approved pharmacotherapies for AUD. Trends toward better liver outcomes support further prospective evaluation. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Gougol, Amir AU - Gougol A AUID- ORCID: 0009-0001-7346-2121 AD - Department of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA. FAU - Kwo, Paul AU - Kwo P AD - Department of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA. FAU - Pike, William AU - Pike W AD - Atropos Health Inc, Indianapolis, IN, USA. FAU - Farokhnia, Mehdi AU - Farokhnia M AUID- ORCID: 0000-0003-0902-4212 AD - National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism, Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore and, Bethesda, MD, USA. FAU - Hui, Gavin AU - Hui G AD - Atropos Health Inc, Indianapolis, IN, USA. FAU - Gombar, Saurabh AU - Gombar S AD - Atropos Health Inc, Indianapolis, IN, USA. FAU - Mirminachi, Babak AU - Mirminachi B AD - University of Pittsburgh Medical Center, Pittsburgh, PA, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260311 PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Alcohol Deterrents) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - N4K14YGM3J (Acamprosate) RN - 5S6W795CQM (Naltrexone) SB - IM MH - Humans MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Retrospective Studies MH - *Alcoholism/drug therapy/complications MH - *Alcohol Deterrents/therapeutic use MH - Treatment Outcome MH - Tirzepatide MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Semaglutide MH - *Metabolic Diseases/drug therapy/complications MH - Adult MH - Acamprosate/therapeutic use MH - United States MH - Aged MH - Obesity MH - Risk Factors MH - Naltrexone/therapeutic use OTO - NOTNLM OT - GLP-1RA; AUD; fatty liver disease OT - alcohol-associated liver disease OT - major liver-related outcome OT - metabolic dysfunction EDAT- 2026/03/12 01:09 MHDA- 2026/05/13 12:33 CRDT- 2026/03/11 23:43 PHST- 2026/02/08 00:00 [revised] PHST- 2025/12/11 00:00 [received] PHST- 2026/02/16 00:00 [accepted] PHST- 2026/05/13 12:33 [medline] PHST- 2026/03/12 01:09 [pubmed] PHST- 2026/03/11 23:43 [entrez] AID - 10.1111/apt.70596 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2026 Jun;63(11):1507-1516. doi: 10.1111/apt.70596. Epub 2026 Mar 11. PMID- 41811375 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20261009 IS - 1432-1041 (Electronic) IS - 0031-6970 (Linking) VI - 82 IP - 4 DP - 2026 Mar 11 TI - Economic evaluation of sodium-glucose transporter 2 inhibitors compared with glucagon-like peptide 1 receptor agonist for the treatment of type 2 diabetes: a systematic review. LID - 94 [pii] LID - 10.1007/s00228-026-04015-9 [doi] AB - PURPOSE: A systematic review was performed to assess the economic evaluation of sodium glucose transporters 2 (SGLT2) inhibitors vs GLP-1 receptor agonists (GLP-1RA) in treating type 2 diabetes. METHODS: The relevant studies were searched in PubMed, Web of Science, Scopus, Embase, and Cochrane from the inception date to February 20, 2025. The titles, abstracts, and full texts were independently evaluated and screened by two authors. Additionally, the economic evaluation studies were assessed independently by two authors. RESULTS: 18 studies were included, evaluating oral semaglutide vs empagliflozin (n = 7), both oral semaglutide vs empagliflozin and subcutaneous semaglutide vs canagliflozin (n = 1), subcutaneous semaglutide vs empagliflozin (n = 4), liraglutide vs empagliflozin (n = 4), liraglutide vs dapagliflozin (n = 1), and subcutaneous semaglutide vs canagliflozin (n = 1). CONCLUSION: The results showed that when patients were assumed to receive initial therapies until HbA1c exceeded the target level and then treatment was intensified to basal insulin, GLP-1RA was cost-effective compared to SGLT2 inhibitors (semaglutide vs empagliflozin and liraglutide vs dapagliflozin). Empagliflozin demonstrated cost-effectiveness when the treatment with either empagliflozin or semaglutide would have continued indefinitely. Compared with empagliflozin, liraglutide may not be a cost-effective treatment option for patients with T2D who were not well-controlled with metformin. FAU - Wang, Lu AU - Wang L AD - Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong Province, China. wanglu784940819@163.com. FAU - Wang, Yinglin AU - Wang Y AD - Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong Province, China. FAU - Zhao, Quan AU - Zhao Q AD - Department of Pharmacy, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong Province, China. zhaoquan_1419@163.com. LA - eng PT - Comparative Study PT - Journal Article PT - Systematic Review DEP - 20260311 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - HDC1R2M35U (empagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 1ULL0QJ8UC (dapagliflozin) RN - 0SAC974Z85 (Canagliflozin) RN - 0 (Glycated Hemoglobin) RN - 839I73S42A (Liraglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/economics/therapeutic use MH - *Hypoglycemic Agents/economics/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Cost-Benefit Analysis MH - Benzhydryl Compounds/economics/therapeutic use MH - Glucosides/economics/therapeutic use MH - Glucagon-Like Peptides/economics/therapeutic use MH - Canagliflozin/economics/therapeutic use MH - Cost-Effectiveness Analysis MH - Glycated Hemoglobin MH - Liraglutide/economics/therapeutic use OTO - NOTNLM OT - Cost-effectiveness OT - GLP-1 Receptor Agonists OT - Sodium-Glucose Transporter 2 Inhibitors OT - Systematic Review OT - Type 2 Diabetes COIS- Declarations. Institutional review board statement: Not applicable. Informed consent statement: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2026/03/11 19:00 MHDA- 2026/06/28 00:37 CRDT- 2026/03/11 12:03 PHST- 2025/11/27 00:00 [received] PHST- 2026/02/21 00:00 [accepted] PHST- 2026/06/28 00:37 [medline] PHST- 2026/03/11 19:00 [pubmed] PHST- 2026/03/11 12:03 [entrez] AID - 10.1007/s00228-026-04015-9 [pii] AID - 10.1007/s00228-026-04015-9 [doi] PST - epublish SO - Eur J Clin Pharmacol. 2026 Mar 11;82(4):94. doi: 10.1007/s00228-026-04015-9. PMID- 41804851 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260824 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 6 DP - 2026 Jun TI - Relative Efficacy of Next-Generation Incretin Therapies for Cardio-Renal Protection in Type 2 Diabetes: Evidence From a Network Meta-Analysis. PG - 4630-4652 LID - 10.1111/dom.70635 [doi] AB - BACKGROUND: Type 2 diabetes (T2D) management has shifted towards integrated cardiometabolic and renal risk reduction. Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) and newer dual agonists show promising benefits, comparative evidence across agents and outcomes remains limited. OBJECTIVES: To compare the cardiovascular and renal effects of modern GLP-1RAs (dulaglutide, semaglutide, lixisenatide), tirzepatide and cotadutide in high-risk T2D populations, and to explore multivariate relationships among clinical outcomes. METHODS: A systematic review and network meta-analysis was conducted following PRISMA and Cochrane guidance (PROSPERO: CRD42024592825). Randomised controlled trials published between 2014 and 2025 with >/= 6 months follow-up were included. Outcomes were cardiovascular death, myocardial infarction (MI), stroke, total major adverse cardiovascular events (MACE), eGFR and UACR. Random- and common-effects models were applied using netmeta (R). Treatment rankings were estimated using p-scores. Inconsistency, heterogeneity and small-study effects were evaluated. Correlation networks and principal component analysis (PCA) were performed to characterise interrelationships among clinical variables. RESULTS: Thirty-four trials were included, predominantly multinational CVOTs and CKD-focused studies. Semaglutide regimens showed the most consistent reduction in MACE and MI versus placebo, with the strongest effect observed for semaglutide combined with SGLT2 inhibition. Dulaglutide 1.5 mg and tirzepatide 15 mg significantly reduced stroke risk. Cardiovascular death estimates were largely imprecise with evidence of small-study effects. Renal effects differed by endpoint: eGFR changes were generally modest, whereas UACR showed marked reductions, particularly with dulaglutide plus dapagliflozin, DPP-4 inhibitors and semaglutide 1 mg. PCA confirmed strong cardiometabolic-renal interdependence. CONCLUSIONS: Cardiovascular and renal benefits of GLP-1-based therapies are outcome-specific. Semaglutide favoured MACE/MI reduction, dulaglutide and tirzepatide supported stroke prevention, and albuminuria outcomes were more responsive than eGFR. Further long-term head-to-head trials are needed. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Pham, Thi-Phuong-Thao AU - Pham TP AD - Pharmacy Department, School of Pharmacy, China Medical University, Taichung, Taiwan. FAU - Vo, Thi-Minh-Nhat AU - Vo TM AD - Faculty of Pharmacy, College of Pharmacy and Medicine, Duy Tan University, Da Nang, Vietnam. FAU - Nguyen, The-Anh AU - Nguyen TA AD - Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan. AD - Department of Acupuncture, Vietnam University of Traditional Medicine, Hanoi, Vietnam. FAU - Dao, Tien-Phat AU - Dao TP AD - International Public Health Department, China Medical University, Taichung, Taiwan. FAU - Ngo, Ngoc-Phuoc AU - Ngo NP AD - Pharmacy Department, School of Pharmacy, China Medical University, Taichung, Taiwan. FAU - Le, Thi-Thuy-Duong AU - Le TT AD - Faculty of Pharmacy, College of Pharmacy and Medicine, Duy Tan University, Da Nang, Vietnam. FAU - Tran, Thanh-Thien AU - Tran TT AD - Faculty of Pharmacy, College of Pharmacy and Medicine, Duy Tan University, Da Nang, Vietnam. FAU - Pham, Thanh-Huong AU - Pham TH AD - Faculty of Pharmacy, College of Pharmacy and Medicine, Duy Tan University, Da Nang, Vietnam. FAU - Huynh, Dang-Mai-Linh AU - Huynh DM AD - Faculty of Pharmacy, College of Pharmacy and Medicine, Duy Tan University, Da Nang, Vietnam. FAU - Ha, Hai-Anh AU - Ha HA AUID- ORCID: 0000-0002-4252-2128 AD - Faculty of Pharmacy, Da Nang University of Medical Technology and Pharmacy, Da Nang, Vietnam. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20260310 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Immunoglobulin Fc Fragments) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 74O62BB01U (lixisenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Incretins/therapeutic use MH - Semaglutide MH - Tirzepatide MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetic Nephropathies/prevention & control/epidemiology MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Treatment Outcome MH - Randomized Controlled Trials as Topic MH - Myocardial Infarction/prevention & control MH - Glucagon-Like Peptide 1/analogs & derivatives OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular outcomes OT - dual-pathway incretin therapies OT - network meta-analysis OT - renal outcomes OT - type 2 diabetes EDAT- 2026/03/10 12:55 MHDA- 2026/05/06 06:40 CRDT- 2026/03/10 06:23 PHST- 2026/02/14 00:00 [revised] PHST- 2025/11/04 00:00 [received] PHST- 2026/02/23 00:00 [accepted] PHST- 2026/05/06 06:40 [medline] PHST- 2026/03/10 12:55 [pubmed] PHST- 2026/03/10 06:23 [entrez] AID - 10.1111/dom.70635 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jun;28(6):4630-4652. doi: 10.1111/dom.70635. Epub 2026 Mar 10. PMID- 41803337 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20261009 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 91 IP - 1 DP - 2026 Mar 10 TI - Efficacy and safety of GLP-1 receptor agonists in the treatment of type 2 diabetes and/or obesity in patients with Cushing's syndrome: a multicenter retrospective study. LID - 108 [pii] LID - 10.1007/s12020-026-04587-7 [doi] AB - BACKGROUND: Cushing's syndrome (CS) is characterized by profound metabolic derangements, including obesity, insulin resistance, diabetes mellitus, and dyslipidemia. Glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown potent metabolic benefits in type 2 diabetes (T2D) and obesity, but their efficacy and safety in CS remain unexplored. OBJECTIVE: To assess the metabolic efficacy and safety of GLP-1RAs in patients with CS and concurrent T2D and/or obesity. METHODS: This retrospective multicenter study included 20 adults with biochemically confirmed CS treated with GLP-1RAs (liraglutide, semaglutide, tirzepatide, or dulaglutide) for >/= 3 months. Anthropometric, hemodynamic, metabolic, hepatic, and hormonal parameters were compared before and after therapy using paired statistical tests. RESULTS: After a median follow-up of 13 months, significant reductions were observed in body weight (- 10.3 +/- 8.8 kg; p < 0.001) and BMI (- 4.2 +/- 2.8 kg/m(2); p < 0.001). Fasting glucose (- 12.1 +/- 35.3 mg/dL; p = 0.015) and HbA1c (- 0.5 +/- 0.9%; p = 0.011) decreased significantly. No significant changes occurred in blood pressure or lipid parameters. Liver enzymes improved, with decreases in ALT (- 3.9 +/- 21.4 U/L; p = 0.005) and GGT (- 25.9 +/- 57.3 U/L; p = 0.012), while the slight reduction in AST (- 5.2 +/- 9.2 U/L; p = 0.046) was statistically significant but not clinically relevant. Hormonal parameters, including ACTH and cortisol levels, remained stable. GLP-1RAs were generally well tolerated, with only mild gastrointestinal side effects in 26.3% of patients. CONCLUSIONS: GLP-1RA therapy in patients with CS and associated metabolic disorders led to significant improvements in weight, BMI, and glycemic control without worsening cortisol dynamics or liver function. Although limited by its retrospective design and small sample size, this study supports the safety and potential metabolic efficacy of GLP-1RAs in patients with CS, suggesting that these agents may constitute a useful adjunct for managing obesity and diabetes in this population. FAU - Iglesias, Pedro AU - Iglesias P AD - Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. piglo65@gmail.com. FAU - Nobre, Ema L AU - Nobre EL AD - Endocrinology Department, ULS Santa Maria, Lisbon, Portugal. FAU - Hanzu, Felicia AU - Hanzu F AD - Department of Endocrinology and Nutrition, Hospital Clinic, CIBERDEM, Barcelona, Universidad Barcelona, Barcelona, Spain. FAU - Schweizer, Junia R O L AU - Schweizer JROL AD - Department of Medicine IV, LMU University Hospital, LMU Munich, Germany. FAU - Manzano Valero, Lucia AU - Manzano Valero L AD - Department of Endocrinology and Nutrition, Hospital General Universitario de Toledo, Toledo, Spain. FAU - Araujo-Castro, Marta AU - Araujo-Castro M AD - Department of Endocrinology, Hospital Universitario Ramony Cajal, Madrid, Spain. FAU - Castro Luna, Ana AU - Castro Luna A AD - Department of Endocrinology and Nutrition, Hospital General Universitario de Toledo, Toledo, Spain. FAU - Albacete, Francisco Javier AU - Albacete FJ AD - Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. FAU - Villar-Taibo, Rocio AU - Villar-Taibo R AD - Department of Endocrinology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, A Coruna, Spain. FAU - Reinke, Martin AU - Reinke M AD - Department of Medicine IV, LMU University Hospital, LMU Munich, Germany. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260310 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 839I73S42A (Liraglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Retrospective Studies MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Male MH - Middle Aged MH - Tirzepatide MH - *Obesity/drug therapy/complications MH - Adult MH - *Cushing Syndrome/complications/drug therapy MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - Recombinant Fusion Proteins/therapeutic use/adverse effects MH - Treatment Outcome MH - Liraglutide/therapeutic use/adverse effects MH - Blood Glucose MH - Aged OTO - NOTNLM OT - Cushing's syndrome OT - Diabetes mellitus OT - Liraglutide OT - Obesity OT - Semaglutide OT - Tirzepatide COIS- Declarations. Conflict of interests: The authors declare no competing interests. EDAT- 2026/03/10 07:00 MHDA- 2026/06/27 16:09 CRDT- 2026/03/10 00:26 PHST- 2025/11/12 00:00 [received] PHST- 2026/02/03 00:00 [accepted] PHST- 2026/06/27 16:09 [medline] PHST- 2026/03/10 07:00 [pubmed] PHST- 2026/03/10 00:26 [entrez] AID - 10.1007/s12020-026-04587-7 [pii] AID - 10.1007/s12020-026-04587-7 [doi] PST - epublish SO - Endocrine. 2026 Mar 10;91(1):108. doi: 10.1007/s12020-026-04587-7. PMID- 41801847 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1875-9114 (Electronic) IS - 0277-0008 (Linking) VI - 46 IP - 4 DP - 2026 Apr TI - Real-World Cardiovascular Outcomes of GLP-1 Receptor Agonists in Women With Type 2 Diabetes and Breast Cancer. PG - e70130 LID - 10.1002/phar.70130 [doi] AB - INTRODUCTION: The cardiovascular (CV) benefits of glucagon-like-peptide-1 receptor agonist (GLP-1 RA) therapies are not well-established in women with breast cancer and type 2 diabetes (T2D). OBJECTIVES: The primary objective of this study was to compare the incidence of major adverse cardiovascular events (MACE) in women with T2D and breast cancer receiving GLP-1 RA therapy versus non-GLP-1 RA diabetes medications. METHODS: This retrospective study included women with T2D, diagnosed with breast cancer at >/= 40 years old from December 16, 2014 to December 16, 2024 and having exposure to diabetes medications of interest (either GLP-1 RA or non-GLP-1 RA) within 5 years of these diagnoses. The primary end point, MACE, was a composite of myocardial infarction, ischemic stroke, coronary revascularization, cardiac arrest, or heart failure, within 5 years of the index date. Propensity score matching was performed. Participants were excluded from each individual outcome analysis if they had the outcome prior to the index date. Incidence rates, risk ratio (RR), 95% confidence interval (CI), and p-value were reported for each outcome. RESULTS: After matching, 19,608 patients were included in each cohort (mean age 64 years). Obesity and alkylating agents were more commonly reported in the GLP-1 RA cohort. Semaglutide was the most prescribed GLP-1 RA at index (45.1%). MACE occurred in 10.6% of the GLP-1 RA cohort and 13.4% of the non-GLP-1 cohort (RR 0.80, 95% CI 0.75-0.85, p < 0.001). Individual MACE end points, ischemic heart disease, and end-stage renal disease were significantly lower in the GLP-1 RA-treated cohort. GLP-1 RA use was also associated with a 61.6% relative risk reduction in all-cause mortality (RR 0.38, 95% CI 0.36-0.41, p < 0.001). Pancreatitis incidence was similar between groups (p = 0.057), whereas cholelithiasis was significantly lower with GLP-1 RA therapy (p < 0.001). CONCLUSIONS: This study demonstrated the potential CV benefit of GLP-1 RA therapies among a population of female breast cancer survivors with T2D. Randomized trial data are needed to confirm these findings. CI - (c) 2026 ACCP Foundation, Ltd. FAU - Cornelio, Cyrille K AU - Cornelio CK AUID- ORCID: 0000-0003-0499-675X AD - Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA. FAU - Cowart, Kevin AU - Cowart K AUID- ORCID: 0000-0002-6880-1600 AD - Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA. FAU - Perkins, Janelle AU - Perkins J AUID- ORCID: 0000-0002-5681-9061 AD - Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA. FAU - Alomar, Mohammed E AU - Alomar ME AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA. FAU - Gayoso, Ricardo Pineda AU - Gayoso RP AD - Department of Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, USA. FAU - Miranda, Aimon C AU - Miranda AC AUID- ORCID: 0000-0003-1683-3982 AD - Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA. FAU - Phan, Anh T AU - Phan AT AD - Department of Pharmacy, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - White, Raechel T AU - White RT AUID- ORCID: 0000-0002-5929-5590 AD - Department of Pharmacotherapeutics and Clinical Research, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA. LA - eng PT - Journal Article PL - United States TA - Pharmacotherapy JT - Pharmacotherapy JID - 8111305 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Breast Neoplasms/complications/epidemiology/drug therapy MH - Middle Aged MH - Retrospective Studies MH - *Cardiovascular Diseases/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use/administration & dosage MH - Aged MH - Incidence MH - Semaglutide MH - Adult OTO - NOTNLM OT - breast cancer OT - cancer survivorship OT - cardiovascular risk reduction OT - glucagon-like-peptide-1 receptor agonists EDAT- 2026/03/09 19:00 MHDA- 2026/03/09 19:01 CRDT- 2026/03/09 13:24 PHST- 2026/01/14 00:00 [revised] PHST- 2025/09/30 00:00 [received] PHST- 2026/01/15 00:00 [accepted] PHST- 2026/03/09 19:01 [medline] PHST- 2026/03/09 19:00 [pubmed] PHST- 2026/03/09 13:24 [entrez] AID - 10.1002/phar.70130 [doi] PST - ppublish SO - Pharmacotherapy. 2026 Apr;46(4):e70130. doi: 10.1002/phar.70130. PMID- 41798193 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260813 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 17 DP - 2026 TI - Glucagon-like peptide-1 agonists in children with obesity and type 2 diabetes. an umbrella review. PG - 1777907 LID - 10.3389/fendo.2026.1777907 [doi] LID - 1777907 AB - INTRODUCTION: Obesity and type 2 diabetes mellitus (Type 2 DM) are rising at an alarming rate among children and adolescents. This population often exhibits suboptimal glycemic control and diabetes-related complications. Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) have emerged as a promising therapeutic option for pediatric patients due to their beneficial effects on weight reduction and glycemic regulation. Literature on this important issue is scarce. We aimed to assess the effects of GLP-1 agonists on body weight, HbA1c, body mass index z (BMI z), and systolic blood pressure (SBP). Additionally, we discussed adverse events and hypoglycemia. METHODS: We searched PubMed/MEDLINE, Web of Science, and the Cochrane Library from October to November 2025 using the following terms: GLP-1 agonists, semaglutide, tirzepatide, liraglutide, exenatide, children, obesity, adolescents, blood pressure, BMI z, hypoglycemia, body weight, and HbA1c. We retrieved 1600 articles. Out of the 44 reviews found, only 11 meta-analyses were included in the final results. RESULTS: GLP-1 agonists were more effective than control in reducing body weight, HbA1c, BMI z, and blood pressure, MD = 0.11, 95% CI 0.05-0.25, MD = 0.65, 95% CI 0.53-0.80, MD = 0.85, 95% CI 0.81-0.90, and MD = 0.19, 95% CI 0.04-83, respectively. The total adverse events and hypoglycemia were not different, log ratios=1.29, 95% CI 0.80-2.09, and log ratios=1.26, 95% CI 0.59-2.70, respectively. DISCUSSION: GLP-1 agonists are a promising and effective therapy for lowering weight, HbA1c, BMI z, and SBP in adolescents with obesity or youth with type 2 DM. Moreover, GLP-1 agonists were well tolerated, and the total adverse events and hypoglycemia were comparable to those of controls. CI - Copyright (c) 2026 Mirghani, Albishi and Alblewi. FAU - Mirghani, Hyder AU - Mirghani H AD - Internal Medicine Department, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. FAU - Albishi, Laila AU - Albishi L AD - Pediatrics Department, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. FAU - Alblewi, Sawsan Mohmmad AU - Alblewi SM AD - Pediatrics Department, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article PT - Systematic Review DEP - 20260219 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 839I73S42A (Liraglutide) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Child MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/agonists MH - *Pediatric Obesity/drug therapy/complications MH - Semaglutide MH - Adolescent MH - Tirzepatide MH - Liraglutide/therapeutic use MH - Glycated Hemoglobin PMC - PMC12960479 OTO - NOTNLM OT - GLP-1 agonists OT - HbA1c OT - adolescents OT - blood pressure OT - children OT - hypoglycemia OT - obesity OT - side effects COIS- The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2026/03/09 17:37 MHDA- 2026/03/09 17:38 PMCR- 2026/02/19 CRDT- 2026/03/09 06:08 PHST- 2025/12/30 00:00 [received] PHST- 2026/01/30 00:00 [revised] PHST- 2026/02/02 00:00 [accepted] PHST- 2026/03/09 17:38 [medline] PHST- 2026/03/09 17:37 [pubmed] PHST- 2026/03/09 06:08 [entrez] PHST- 2026/02/19 00:00 [pmc-release] AID - 10.3389/fendo.2026.1777907 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2026 Feb 19;17:1777907. doi: 10.3389/fendo.2026.1777907. eCollection 2026. PMID- 41796736 OWN - NLM STAT- MEDLINE DCOM- 20260703 LR - 20260703 IS - 2173-5794 (Electronic) IS - 2173-5794 (Linking) VI - 101 IP - 7 DP - 2026 Jul TI - Simultaneous bilateral NAION following initiation of high-dose semaglutide: a case report. PG - 502490 LID - S2173-5794(26)00058-7 [pii] LID - 10.1016/j.oftale.2026.502490 [doi] AB - We report a case of simultaneous bilateral non-arteritic anterior ischemic optic neuropathy (NAION) in a 68-year-old man with poorly controlled type 2 diabetes mellitus and significant hyperopia (+5 diopters). Visual loss began 14 days after initiating semaglutide at a relatively high dose (0.5mg/week), progressing to functional blindness within four weeks. Ophthalmologic examination revealed bilateral optic disc edema with hemorrhages, exudates, and subretinal fluid. Infectious and autoimmune causes were ruled out, and cerebrospinal fluid analysis was normal. Following the high dose of semaglutide, glycated hemoglobin decreased, although the magnitude and speed of this decline should be interpreted with caution, and the association between the drug and the optic nerve event must be considered purely temporal, with no evidence of direct causality. Despite drug discontinuation and corticosteroid treatment, visual loss persisted. The simultaneous bilateral presentation, rapid progression, and predisposing anatomical factors-crowded optic discs and possible scleral rigidity-highlight extreme vulnerability. This case illustrates a possible temporal association, representing one of the few such cases reported to date, and underscores the importance of baseline ophthalmic evaluation, close monitoring, and careful consideration of initial dosing in patients treated with GLP-1 receptor agonists. CI - Copyright (c) 2026 Sociedad Espanola de Oftalmologia. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Asensio-Sanchez, V M AU - Asensio-Sanchez VM AD - Servicio de Oftalmologia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain. Electronic address: vmasensio@yahoo.es. FAU - Rodriguez-Espinosa, J AU - Rodriguez-Espinosa J AD - Servicio de Oftalmologia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain. FAU - Silva-Schultz, S AU - Silva-Schultz S AD - Servicio de Oftalmologia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain. FAU - Gonzalez-Fernandez, G AU - Gonzalez-Fernandez G AD - Servicio de Oftalmologia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain. FAU - Lallana-Serrano, S AU - Lallana-Serrano S AD - Servicio de Neurologia, Hospital Clinico Universitario de Valladolid, Valladolid, Spain. LA - eng PT - Case Reports PT - Journal Article DEP - 20260306 PL - Spain TA - Arch Soc Esp Oftalmol (Engl Ed) JT - Archivos de la Sociedad Espanola de Oftalmologia JID - 101715860 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Semaglutide MH - Male MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Optic Neuropathy, Ischemic/chemically induced MH - Glycated Hemoglobin/analysis MH - Blindness/chemically induced OTO - NOTNLM OT - Adverse effect OT - Agonista GLP-1 OT - Bilateral OT - Efecto adverso OT - GLP-1 receptor agonist OT - Neuropatia optica isquemica anterior no arteritica OT - Non-arteritic anterior ischemic optic neuropathy OT - Semaglutida OT - Semaglutide COIS- Declaration of competing interest None declared. EDAT- 2026/03/09 07:41 MHDA- 2026/07/04 00:33 CRDT- 2026/03/09 00:45 PHST- 2025/09/22 00:00 [received] PHST- 2025/11/16 00:00 [revised] PHST- 2025/11/30 00:00 [accepted] PHST- 2026/07/04 00:33 [medline] PHST- 2026/03/09 07:41 [pubmed] PHST- 2026/03/09 00:45 [entrez] AID - S2173-5794(26)00058-7 [pii] AID - 10.1016/j.oftale.2026.502490 [doi] PST - ppublish SO - Arch Soc Esp Oftalmol (Engl Ed). 2026 Jul;101(7):502490. doi: 10.1016/j.oftale.2026.502490. Epub 2026 Mar 6. PMID- 41796096 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260822 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 5 DP - 2026 May TI - GLP-1 Receptor Agonists in Brazil: Landscape of Consumption, Safety and Regulation. PG - 4185-4193 LID - 10.1111/dom.70609 [doi] AB - BACKGROUND: The escalating use of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is reshaping pharmaceutical consumption patterns and posing unprecedented challenges to healthcare systems worldwide. This study analyzes the landscape of GLP-1 RA consumption, safety monitoring and regulatory oversight in Brazil. METHODS: A retrospective regulatory surveillance study was carried out triangulating data from three official sources: (1) national sales covering 2020-2024, classifying according to Anatomical Therapeutic Chemical (ATC) system; (2) adverse event reports submitted to Vigimed, the national pharmacovigilance platform integrated with global VigiBase; and (3) official alerts of falsified products. Sales data were sourced from industrial reports and the National System for the Management of Controlled Products (SNGPC). RESULTS: Semaglutide emerged as the predominant GLP-1 RA in the Brazilian market. Consumption was markedly concentrated in regions with higher Gross Domestic Product (GDP), revealing a disconnect between medication use and regional diabetes prevalence. Pharmacovigilance analysis uncovered a significant proportion of reports involving off-label use, pointing to potential clinical and regulatory gaps. Furthermore, documented cases of counterfeit products underscore critical supply chain vulnerabilities. CONCLUSION: The convergence of escalating demand, widespread off-label use and product falsification requires a coordinated and agile regulatory response. The observed trends suggest significant access disparities driven by economic factors rather than epidemiological need. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hurtado, Renato Lopes AU - Hurtado RL AUID- ORCID: 0009-0008-0556-5015 AD - Agencia Nacional de Vigilancia Sanitaria (Anvisa), Brasilia, Brazil. AD - University of Brasilia, Brasilia, Brazil. FAU - Amato, Angelica Amorim AU - Amato AA AUID- ORCID: 0000-0002-8454-5504 AD - University of Brasilia, Brasilia, Brazil. FAU - de Luca Correa, Hugo AU - de Luca Correa H AD - Catholic University of Brasilia, Brasilia, Brazil. FAU - Silveira, Damaris AU - Silveira D AD - University of Brasilia, Brasilia, Brazil. LA - eng PT - Journal Article DEP - 20260308 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Brazil/epidemiology MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Pharmacovigilance MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucagon-Like Peptides/therapeutic use/adverse effects PMC - PMC13071213 OTO - NOTNLM OT - GLP-1 analogue OT - pharmaco-epidemiology OT - population study OT - real-world evidence COIS- The authors declare no conflicts of interest. EDAT- 2026/03/09 00:36 MHDA- 2026/04/13 06:32 PMCR- 2026/04/13 CRDT- 2026/03/08 23:43 PHST- 2026/02/15 00:00 [revised] PHST- 2026/01/12 00:00 [received] PHST- 2026/02/17 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/03/09 00:36 [pubmed] PHST- 2026/03/08 23:43 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - DOM70609 [pii] AID - 10.1111/dom.70609 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):4185-4193. doi: 10.1111/dom.70609. Epub 2026 Mar 8. PMID- 41794178 OWN - NLM STAT- MEDLINE DCOM- 20260612 LR - 20260623 IS - 1544-3450 (Electronic) IS - 1086-5802 (Linking) VI - 66 IP - 3 DP - 2026 May-Jun TI - Semaglutide use in a patient with a long-term ileostomy: A case report highlighting clinical risks and evidence gaps. PG - 103069 LID - S1544-3191(26)00054-3 [pii] LID - 10.1016/j.japh.2026.103069 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as semaglutide, dulaglutide, liraglutide, and exenatide, are increasingly used to treat type 2 diabetes and support weight loss. These agents function by enhancing glucose-dependent insulin secretion, suppressing inappropriate glucagon secretion, slowing gastric emptying, and regulating appetite through central nervous system pathways. Since semaglutide's approval in 2017 and U.S. market availability in 2018, its use has expanded significantly. However, there remains limited literature evaluating its safety and efficacy in patients with altered gastrointestinal anatomy, particularly those with ostomies. CASE SUMMARY: A 56-year-old Hispanic male with type 2 diabetes, body mass index (BMI) of 54.3, and an ileostomy placed in 2012 was prescribed semaglutide for glycemic control and weight loss by an endocrinology clinic. He continued intermittent use over an 18-month period without complications. Initially, semaglutide was associated with reduced appetite and weight loss of 19 pounds (from 278 lbs., BMI 54.3, to 259 lbs., BMI 50.6) over 5 months. He paused the medication 1 week prior to a scheduled colonoscopy and resumed 1 week after. Within 2 weeks of restarting, he experienced progressive slowing of gastrointestinal motility, including hard stools and bowel movements every other day. These symptoms culminated in fecal impaction requiring hospitalization later that month. He permanently discontinued semaglutide and has not resumed since. PRACTICE IMPLICATIONS: To date, no clinical trials or guidelines address the safety of GLP-1 RAs in patients with ileostomies or significant gastrointestinal alterations. This case emphasizes a critical gap in literature. While GLP-1 RAs offer metabolic benefits in type 2 diabetes and weight management, they may pose underrecognized risks in patients with altered bowel anatomy. Until further evidence is available, clinicians should exercise caution, perform individualized risk-benefit assessments, and consider close collaboration with gastroenterology. Further research is needed to evaluate the safety, tolerability, and pharmacokinetics of GLP-1 RAs in patients with ostomies. CI - Copyright (c) 2026 American Pharmacists Association(R). Published by Elsevier Inc. All rights reserved. FAU - Gaytan, Gabriela AU - Gaytan G FAU - Pabon, Andrea AU - Pabon A FAU - Rosario, Natalie AU - Rosario N LA - eng PT - Case Reports PT - Journal Article DEP - 20260305 PL - United States TA - J Am Pharm Assoc (2003) JT - Journal of the American Pharmacists Association : JAPhA JID - 101176252 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Ileostomy MH - *Semaglutide/administration & dosage/adverse effects MH - Weight Loss/drug effects MH - *Postoperative Complications/chemically induced EDAT- 2026/03/08 01:38 MHDA- 2026/06/12 13:04 CRDT- 2026/03/07 19:12 PHST- 2025/10/21 00:00 [received] PHST- 2026/02/14 00:00 [revised] PHST- 2026/02/16 00:00 [accepted] PHST- 2026/06/12 13:04 [medline] PHST- 2026/03/08 01:38 [pubmed] PHST- 2026/03/07 19:12 [entrez] AID - S1544-3191(26)00054-3 [pii] AID - 10.1016/j.japh.2026.103069 [doi] PST - ppublish SO - J Am Pharm Assoc (2003). 2026 May-Jun;66(3):103069. doi: 10.1016/j.japh.2026.103069. Epub 2026 Mar 5. PMID- 41793524 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260718 IS - 1573-675X (Electronic) IS - 1360-8185 (Linking) VI - 31 IP - 3 DP - 2026 Mar 7 TI - Semaglutide attenuates diabetic vascular calcification by enhancing autophagy and lysosomal function via targeting CPNE1. LID - 93 [pii] LID - 10.1007/s10495-026-02269-3 [doi] AB - Patients with diabetes exhibit an increased susceptibility to vascular calcification, which is associated with significantly elevated risks of mortality and disability. As a new Glucagon-like peptide-1 receptor agonist, Semaglutide is primarily indicated for type 2 diabetes mellitus and obesity, while also demonstrating definitive cardiovascular protective effects. However, the effect of semaglutide on diabetic vascular calcification remains unknown. Our results demonstrated a dose-dependent reduction in calcium deposition with Semaglutide treatment, which was accompanied by downregulation of RUNX2 and BMP2 protein expression in aortic tissues. Additionally, Semaglutide also conferred protective effects in AGE-BSA stimulated mouse aortic smooth muscle cells (MOVAS). Autophagy, a lysosomal degradation pathway, is intimately involved in the pathological process of diabetic vascular calcification. During stimulation with AGEs-BSA, impaired lysosomal function and blocked autophagic flux were observed, as evidenced by increased protein levels of LC3-II and P62, alongside decreased expression of CTSD, CTSB, LAMP1 and LAMP2. These changes were accompanied by a decline in lysosomal pH, activity, and degradative capacity. Treatment with Semaglutide mitigated these abnormalities, restoring autophagic flux and lysosomal function, and consequently attenuating AGEs-BSA-induced calcification in MOVAS. Combined bioinformatics and Western blot analysis confirmed the significant downregulation of CPNE1 by Semaglutide in AGEs-BSA stimulated MOVAS. Copine-1 (CPNE1), a member of the copine protein family, is characterized as a calcium-dependent phospholipid-binding protein that primarily resides in the cytoplasm. These findings indicate that the attenuation of diabetic vascular calcification (DVC) by Semaglutide is associated with the inhibition of CPNE1-mediated autophagy, suggesting a potential novel therapeutic strategy for managing DVC. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Xiao, Shengjue AU - Xiao S AD - The Department of Geriatrics, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, Jiangsu, China. FAU - Li, Wei AU - Li W AD - Department of Cardiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, Jiangsu Province, China. AD - Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, Jiangsu, China. FAU - Liu, Naifeng AU - Liu N AD - Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, Jiangsu, China. liunf@seu.edu.cn. LA - eng GR - 82170478/National Natural Science Foundation of China/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260307 PL - Netherlands TA - Apoptosis JT - Apoptosis : an international journal on programmed cell death JID - 9712129 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Core Binding Factor Alpha 1 Subunit) RN - 0 (Bone Morphogenetic Protein 2) RN - 0 (Runx2 protein, mouse) RN - 0 (Bmp2 protein, mouse) SB - IM MH - Semaglutide MH - Animals MH - *Autophagy/drug effects MH - *Vascular Calcification/drug therapy/metabolism/pathology/genetics MH - Mice MH - *Lysosomes/drug effects/metabolism MH - *Glucagon-Like Peptides/pharmacology MH - Myocytes, Smooth Muscle/drug effects/metabolism/pathology MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Core Binding Factor Alpha 1 Subunit/metabolism/genetics MH - Muscle, Smooth, Vascular/drug effects/metabolism MH - Bone Morphogenetic Protein 2/metabolism/genetics MH - Aorta/drug effects/pathology/metabolism MH - Male OTO - NOTNLM OT - Autophagy OT - CPNE1 OT - Diabetic vascular calcification OT - Semaglutide COIS- Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: All animal experiments were performed in accordance with the protocols approved by the Animal Care and Use Committee of Southeast University (Approval number: 20240217004 and 20240217005). Consent for publication: Not applicable. EDAT- 2026/03/07 16:09 MHDA- 2026/03/08 01:38 CRDT- 2026/03/07 11:16 PHST- 2025/10/10 00:00 [received] PHST- 2026/01/03 00:00 [accepted] PHST- 2026/03/08 01:38 [medline] PHST- 2026/03/07 16:09 [pubmed] PHST- 2026/03/07 11:16 [entrez] AID - 10.1007/s10495-026-02269-3 [pii] AID - 10.1007/s10495-026-02269-3 [doi] PST - epublish SO - Apoptosis. 2026 Mar 7;31(3):93. doi: 10.1007/s10495-026-02269-3. PMID- 41778928 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260823 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 5 DP - 2026 May 1 TI - Comparative Effectiveness of Tirzepatide Versus Dulaglutide or Semaglutide on Major Cardiovascular Events in Type 2 Diabetes and Cardiovascular Disease: Insights From Two Target-Trial Emulations. PG - 808-817 LID - 10.2337/dc25-3063 [doi] AB - OBJECTIVE: To evaluate the comparative effectiveness of dulaglutide or semaglutide versus tirzepatide on cardiovascular outcomes in adults with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). RESEARCH DESIGN AND METHODS: Two target trial emulations included commercially insured adults (June 2022-December 2024) with T2D and ASCVD who initiated subcutaneous tirzepatide, dulaglutide, or semaglutide. The primary outcome was modified major adverse cardiovascular events (MACE), defined as a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. First, new users of tirzepatide and dulaglutide were propensity score (PS) matched one to one. Second, new users of tirzepatide and semaglutide were PS matched one to one. Incidence rates (IRs) per 1,000 person-years and hazard ratios (HRs) were estimated. RESULTS: After PS matching, 9,233 pairs of tirzepatide or dulaglutide initiators and 25,266 pairs of tirzepatide or semaglutide initiators were identified. Tirzepatide initiators experienced a lower rate of modified MACE versus dulaglutide initiators (IR 31.3 vs. 39.4, respectively; HR 0.80 [95% CI 0.65-0.99]), which seemed to be driven by lower all-cause mortality among tirzepatide versus dulaglutide initiators (HR 0.60 [95% CI 0.43-0.83]). In post hoc analyses, tirzepatide was associated with lower rates of pneumonia-related hospitalization when compared with dulaglutide. Rates of modified MACE were similar among tirzepatide and semaglutide initiators (IR 23.7 vs. 23.2, respectively; HR 1.03 [95% CI 0.90-1.17]). CONCLUSIONS: Among adults with T2D and ASCVD in routine care, tirzepatide was associated with a lower risk of modified MACE when compared with dulaglutide, driven by reduction in all-cause mortality. Risks of modified MACE seemed similar with tirzepatide and semaglutide. CI - (c) 2026 by the American Diabetes Association. FAU - Ostrominski, John W AU - Ostrominski JW AUID- ORCID: 0000-0002-2866-9414 AD - Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Ortega-Montiel, Janinne AU - Ortega-Montiel J AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA. FAU - Everett, Brendan M AU - Everett BM AD - Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Cromer, Sara J AU - Cromer SJ AD - Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA. FAU - Byrne, Caroline F AU - Byrne CF AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Glynn, Robert J AU - Glynn RJ AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. AD - New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, MA. FAU - Patorno, Elisabetta AU - Patorno E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. LA - eng GR - L30 HL175757/HL/NHLBI NIH HHS/United States GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01 AR075117/AR/NIAMS NIH HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States GR - T32 HL007604/HL/NHLBI NIH HHS/United States PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Tirzepatide/therapeutic use MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Female MH - *Cardiovascular Diseases/drug therapy MH - Male MH - Middle Aged MH - *Recombinant Fusion Proteins/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Aged PMC - PMC13241951 COIS- Duality of Interest. J.W.O. has served on advisory boards or had speaker engagements with Corcept Therapeutics and Bayer AG. S.J.C. reports having a spouse employed by Depuy Synthes. B.M.E. reports grants (site coinvestigator) and personal fees (end point adjudication) from Novo Nordisk, a grant to Brigham and Women's Hospital (principal investigator), and personal fees from Kowa not clearly relevant to the work; personal fees from Ipsen Pharmaceuticals for consulting and from NIDDK outside the submitted work; and consulting fees (editorial board member) from American Heart Association journal Circulation and royalties for peer review of UptoDate articles. R.J.G. reports grants from Amarin, Kowa, and Novartis (to employer) outside the submitted work. D.J.W. has served on data monitoring committees for Amgen. E.P. reports research grants to Brigham and Women's Hospital (principal investigator) from Boehringer Ingelheim, AstraZeneca, and Bayer unrelated to the submitted work and receives royalties from UpToDate. No other potential conflicts of interest relevant to this article were reported. EDAT- 2026/03/04 15:49 MHDA- 2026/04/21 17:51 PMCR- 2026/03/04 CRDT- 2026/03/04 10:23 PHST- 2025/12/18 00:00 [received] PHST- 2026/02/01 00:00 [accepted] PHST- 2026/04/21 17:51 [medline] PHST- 2026/03/04 15:49 [pubmed] PHST- 2026/03/04 10:23 [entrez] PHST- 2026/03/04 00:00 [pmc-release] AID - 164532 [pii] AID - 253063 [pii] AID - 10.2337/dc25-3063 [doi] PST - ppublish SO - Diabetes Care. 2026 May 1;49(5):808-817. doi: 10.2337/dc25-3063. PMID- 41771166 OWN - NLM STAT- MEDLINE DCOM- 20260710 LR - 20260710 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 29 IP - 1 DP - 2026 Dec TI - Annual pharmacy cost per patient achieving composite treatment endpoints: a cost to target analysis of tirzepatide versus subcutaneous semaglutide 1 mg in patients with type 2 diabetes in the UK. PG - 698-711 LID - 10.1080/13696998.2026.2631920 [doi] AB - INTRODUCTION: Tirzepatide is a treatment for type 2 diabetes associated with improvements in glycemic control and weight loss, and a low risk of hypoglycemia when not used in combination with insulin or insulin secretagogues. A cost to target analysis of tirzepatide 5, 10 and 15 mg versus subcutaneous semaglutide 1 mg in the UK setting was performed, calculating the annual pharmacy cost per patient treated to six composite endpoints combining glycemic control (glycated hemoglobin [HbA1c] /=5%, >/=10%, >/=15%) and avoidance of hypoglycemia. The costing analysis was based on the tirzepatide costs appraised by NICE as part of TA924. METHODS: The proportions of patients achieving composite treatment targets with tirzepatide and semaglutide (both in combination with metformin) were taken from a post-hoc analysis of the SURPASS-2 clinical trial (N = 1,845). Costs per patient treated to target were calculated by dividing the annual treatment costs associated with each intervention by the proportion of patients achieving the treatment target with each intervention. RESULTS: Tirzepatide 5, 10 and 15 mg were associated with a lower pharmacy cost per patient achieving treatment target than semaglutide 1 mg for the majority of endpoints evaluated. Differences became greater at more strict treatment targets. For example, the cost per patient achieving HbA1c /=15%, and no hypoglycemia was GBP 5,650, GBP 8,665 and GBP 9,462 lower with tirzepatide 5, 10 and 15 mg, respectively, compared with semaglutide 1 mg over a 1-year time horizon. The only endpoint where semaglutide 1 mg was associated with a lower cost per patient achieving target was HbA1c <7.0%, weight loss >/=5%, and no hypoglycemia. CONCLUSIONS: Compared to semaglutide, tirzepatide was associated with a lower annual pharmacy cost per patient with diabetes achieving treatment target in the UK for the majority of endpoints, with greater differences at more strict treatment targets. FAU - Kanumilli, Naresh AU - Kanumilli N AUID- ORCID: 0000-0003-3080-7713 AD - Northenden Group Practice, Manchester, UK. FAU - Osumili, Beatrice AU - Osumili B AUID- ORCID: 0000-0002-5862-9325 AD - Eli Lilly and Company Limited, Bracknell, UK. FAU - Evans, Jerome AU - Evans J AUID- ORCID: 0009-0005-8492-0625 AD - Eli Lilly and Company Limited, Basingstoke, UK. FAU - Webb, Joanne AU - Webb J AUID- ORCID: 0000-0001-5883-9077 AD - Eli Lilly and Company Limited, Basingstoke, UK. FAU - Buckingham, Mike AU - Buckingham M AD - Eli Lilly and Company Limited, Basingstoke, UK. FAU - Debackere, Nele AU - Debackere N AD - S.A. Eli Lilly Benelux N.V, Brussels, Belgium. FAU - Nowakowski, Piotr AU - Nowakowski P AD - Eli Lilly Polska Sp. z o. o, Warsaw, Poland. FAU - Cattin, Juliette AU - Cattin J AUID- ORCID: 0009-0001-2528-4359 AD - Ossian Health Economics and Communications, Basel, Switzerland. FAU - Hunt, Barnaby AU - Hunt B AUID- ORCID: 0000-0001-5420-279X AD - Ossian Health Economics and Communications, Basel, Switzerland. LA - eng PT - Journal Article DEP - 20260302 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 9100L32L2N (Metformin) SB - IM MH - Humans MH - Tirzepatide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - *Hypoglycemic Agents/economics/administration & dosage/therapeutic use MH - *Glucagon-Like Peptides/economics/therapeutic use/administration & dosage MH - United Kingdom MH - Glycated Hemoglobin MH - Female MH - Male MH - Weight Loss/drug effects MH - Middle Aged MH - Injections, Subcutaneous MH - Drug Therapy, Combination MH - Hypoglycemia/chemically induced MH - Aged MH - Blood Glucose MH - Metformin/therapeutic use/economics OTO - NOTNLM OT - Cost per patient treated to target OT - I10 OT - I19 OT - glycemic control OT - hypoglycemia OT - semaglutide OT - tirzepatide OT - type 2 diabetes OT - weight loss EDAT- 2026/03/02 18:57 MHDA- 2026/03/06 13:45 CRDT- 2026/03/02 17:43 PHST- 2026/03/06 13:45 [medline] PHST- 2026/03/02 18:57 [pubmed] PHST- 2026/03/02 17:43 [entrez] AID - 10.1080/13696998.2026.2631920 [doi] PST - ppublish SO - J Med Econ. 2026 Dec;29(1):698-711. doi: 10.1080/13696998.2026.2631920. Epub 2026 Mar 2. PMID- 41765029 OWN - NLM STAT- MEDLINE DCOM- 20260321 LR - 20260924 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 407 IP - 10534 DP - 2026 Mar 21 TI - Efficacy and safety of once-daily oral orforglipron compared with oral semaglutide in adults with type 2 diabetes (ACHIEVE-3): a multinational, multicentre, non-inferiority, open-label, randomised, phase 3 trial. PG - 1147-1160 LID - S0140-6736(26)00202-3 [pii] LID - 10.1016/S0140-6736(26)00202-3 [doi] AB - BACKGROUND: Orforglipron is a novel non-peptide (GLP-1) receptor agonist designed for daily oral administration without food or water restrictions. This study aimed to compare the efficacy and safety of orforglipron with oral semaglutide in individuals with type 2 diabetes inadequately controlled with metformin. METHODS: In this 52-week, randomised, open-label, active-controlled, multicentre, multinational, phase 3 study, we enrolled adults (>/=18 years) with type 2 diabetes inadequately controlled with metformin (>/=1500 mg per day), glycated haemoglobin (HbA(1c)) between 7.0% and 10.5% (53-91 mmol/mol), and BMI at least 25 kg/m(2) from 131 medical research centres and hospitals in Argentina, China, Japan, Mexico, and the USA. Participants were randomly assigned (1:1:1:1) to orforglipron (12 mg or 36 mg) or semaglutide (7 mg or 14 mg); all groups had an up to 4-week lead-in period and 52-week treatment period, with the drugs administered orally once per day. The primary objective of the study was to assess non-inferiority of orforglipron 36 mg versus semaglutide 14 mg and orforglipron 12 mg versus semaglutide 7 mg for mean change at week 52 from baseline in HbA(1c) (with a non-inferiority margin of 0.3%) in the intention-to-treat population. Hierarchical analysis for superiority was prespecified after attainment of non-inferiority. The treatment regimen estimand, based on data from all randomly assigned participants regardless of intercurrent events, was the primary estimand; the efficacy estimand was considered supportive. The safety endpoints used data from all participants who received at least one dose of the study drug. This trial was registered on ClinicalTrials.gov (NCT06045221) and is completed. FINDINGS: From Sept 22, 2023, to Aug 22, 2025, 1698 participants were recruited and randomly assigned to orforglipron (n=424 on 12 mg and n=423 on 36 mg) or semaglutide (n=426 on 7 mg and n=425 on 14 mg). For the treatment regimen estimand, mean changes at week 52 from a baseline HbA(1c) of 8.3% were -1.71% (SE 0.07) with orforglipron 12 mg, -1.91% (0.08) with orforglipron 36 mg, -1.23% (0.05) with semaglutide 7 mg, and -1.47% (0.06) with semaglutide 14 mg. Estimated treatment differences were -0.48% (95% CI -0.65 to -0.31; p<0.0001) for orforglipron 12 mg versus semaglutide 7 mg; -0.44% (-0.62 to -0.26; p<0.0001) for orforglipron 36 mg versus semaglutide 14 mg; -0.24% (95% CI -0.41 to -0.072; p=0.0050) for orforglipron 12 mg versus semaglutide 14 mg; and -0.68% (-0.85 to -0.50; p<0.0001) for orforglipron 36 mg versus semaglutide 7 mg. The primary objective of non-inferiority was met and both orforglipron doses showed superiority to both semaglutide doses, including orforglipron 12 mg versus semaglutide 14 mg. The most frequent adverse events were gastrointestinal events (orforglipron: 249 [59%] of 424 on 12 mg and 245 [58%] of 423 on 36 mg; semaglutide: 157 [37%] of 426 on 7 mg and 193 [45%] of 425 on 14 mg), most of which were mild to moderate in severity. More participants in the orforglipron groups (37 [9%] on 12 mg and 41 [10%] on 36 mg) discontinued study treatment due to adverse events than in the semaglutide groups (19 (4%) on 7 mg and 21 (5%) on 14 mg), and mean increase in pulse rate was greater in the orforglipron groups (12 mg 3.7 bpm; 36 mg 4.7 bpm) than in the semaglutide groups (7 mg 1.0 bpm; 14 mg 1.5 bpm). Four deaths occurred during the study: one in the orforglipron 12 mg group, one in the orforglipron 36 mg group, and two in the semaglutide 7 mg group. INTERPRETATION: In individuals with type 2 diabetes inadequately controlled with metformin, orforglipron 12 mg and 36 mg was non-inferior and superior to semaglutide 7 mg and 14 mg with respect to the mean change in HbA(1c) from baseline to 52 weeks. Although the safety profiles of both orforglipron and semaglutide were generally consistent with the GLP-1 receptor agonist class, the incidence of gastrointestinal events, discontinuations due to adverse events, and mean increase in pulse rate were higher with orforglipron than oral semaglutide. FUNDING: Eli Lilly. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Rosenstock, Julio AU - Rosenstock J AD - Division of Endocrinology, University of Texas, Southwestern Medical Center, Dallas, TX, USA. Electronic address: juliorosenstock@dallasdiabetes.com. FAU - Yabe, Daisuke AU - Yabe D AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan; Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan; Center for One Medicine Innovative Translational Research, Gifu University Institute for Advanced Studies, Gifu, Japan. FAU - Cox, David AU - Cox D AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Li, Jianghao AU - Li J AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Denning, Max AU - Denning M AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Wu, Wen-Shuo AU - Wu WS AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Liu, Rong AU - Liu R AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Zhao, Youna AU - Zhao Y AD - Eli Lilly and Company, Indianapolis, IN, USA. CN - ACHIEVE-3 Investigators LA - eng SI - ClinicalTrials.gov/NCT06045221 PT - Clinical Trial, Phase III PT - Comparative Study PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260226 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (orforglipron) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Fluorine Compounds) RN - 0 (Oxadiazoles) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Administration Schedule MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - Fluorine Compounds/administration & dosage/adverse effects/therapeutic use MH - Oxadiazoles/administration & dosage/adverse effects/therapeutic use MH - Semaglutide/administration & dosage/therapeutic use COIS- Declaration of interests JL, MD, W-SW, RL, DC, and YZ are current employees and shareholders of Eli Lilly. JR has served on scientific advisory boards and received honoraria or consulting fees from Amgen, Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Corcept, Eccogene, Eli Lilly, Novo Nordisk, Oramed Pharmaceuticals, Regeneron, Regor, Sanofi, Scholar Rock, Structure Therapeutics, and Terns Pharmaceuticals and has received grants and research support from Amgen, Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Corcept, Eli Lilly, Hanmi Pharmaceutical, Merck, Novo Nordisk, Oramed Pharmaceuticals, Pfizer, Regeneron, Regor, Sanofi, Structure Therapeutics, and Terns Pharmaceuticals. DY reports support from Eli Lilly for the present manuscript; grants or contracts from Boehringer Ingelheim, Taisho Pharmaceutical, Novo Nordisk, and Arkray; consulting fees from Kansai Medical Net, Eli Lilly, Novo Nordisk, Sanofi, and Boehringer Ingelheim; payments or honoraria from Mitsubishi Tanabe, Ono Pharmaceutical, Boehringer Ingelheim, Kowa, Sumitomo Pharmaceutical, Eli Lilly, Novo Nordisk, Sanofi, and Taisho Pharmaceutical; roles in International Diabetes Federation Western Pacific Region (Executive Board), The European Association for the Study of Diabetes (Global Council), The Japan Association for Diabetes Care and Education (Executive Board), The Japan Society of Clinical Nutrition and Metabolism (Executive Board), The Japan Society of Diabetes Complication (Executive Board), The Asian Association for the Study of Diabetes (Executive Board), The Japan Diabetes Society (Auditor), The Japan Endocrine Society (Executive Board), The Japan Society of Constitutional Medicine (Executive Board), and The Japan Society of Informatics for Diabetes Mellitus (Vice President). FIR - Manghi, Federico Perez IR - Manghi FP FIR - Abalos, Franklin IR - Abalos F FIR - Costanzo, Pablo IR - Costanzo P FIR - Chiesa, Ana IR - Chiesa A FIR - Maldonado, Natacha IR - Maldonado N FIR - Salzberg, Susana IR - Salzberg S FIR - Goycoa, Claudia IR - Goycoa C FIR - Sessa, Horacio IR - Sessa H FIR - Aizenberg, Diego IR - Aizenberg D FIR - Vico, Marisa IR - Vico M FIR - Guerlloy, Fernando IR - Guerlloy F FIR - Schiavoni, Maria IR - Schiavoni M FIR - Chahin, Mariano IR - Chahin M FIR - Villarino, Adriana IR - Villarino A FIR - Bartolacci, Ines IR - Bartolacci I FIR - Hernandez Gauna, Adrian IR - Hernandez Gauna A FIR - Mayer, Marcos IR - Mayer M FIR - Li, Shunbin IR - Li S FIR - An, Zhenmei IR - An Z FIR - Ma, Jianhua IR - Ma J FIR - Li, Shu IR - Li S FIR - Zhou, Jian IR - Zhou J FIR - Yuan, Guoyue IR - Yuan G FIR - Lu, Yibing IR - Lu Y FIR - Wang, Hongman IR - Wang H FIR - Li, Qingju IR - Li Q FIR - Li, Xinyu IR - Li X FIR - Wu, Tian Feng IR - Wu TF FIR - Jiang, Xiaozhen IR - Jiang X FIR - Zhang, Yawei IR - Zhang Y FIR - Li, Yufeng IR - Li Y FIR - Zhu, Hong IR - Zhu H FIR - Wang, Yihua IR - Wang Y FIR - Jiang, Hongwei IR - Jiang H FIR - Shen, Jie IR - Shen J FIR - Dong, Xiaolin IR - Dong X FIR - Cheng, ZhiFeng IR - Cheng Z FIR - Niiya, Tetsuji IR - Niiya T FIR - Nakamoto, Shinya IR - Nakamoto S FIR - Sato, Nobuyuki IR - Sato N FIR - Takai, Masahiko IR - Takai M FIR - Kato, Takehiro IR - Kato T FIR - Shiraiwa, Toshihiko IR - Shiraiwa T FIR - Bando, Hidenori IR - Bando H FIR - Ohishi, Akira IR - Ohishi A FIR - Osonoi, Takeshi IR - Osonoi T FIR - Salazar, Melchor Alpizar IR - Salazar MA FIR - Hernandez, Pedro Garcia IR - Hernandez PG FIR - Cantu, Elias Alberto Garcia IR - Cantu EAG FIR - Ibarra, Manuel de Los Rios IR - Ibarra MLR FIR - Orozco, Emilia Pelayo IR - Orozco EP FIR - Granell, Maria Arechavaleta IR - Granell MA FIR - Soto, Jose Lazcano IR - Soto JL FIR - Carrillo, Luis Virgen IR - Carrillo LV FIR - Castrezana, Laura Castro IR - Castrezana LC FIR - Ramos, Silvia Jimenez IR - Ramos SJ FIR - Gonzalez, Arnulfo IR - Gonzalez A FIR - de Alba, Carlos Alejandro Stobschinski IR - de Alba CAS FIR - Elizondo, Ramiro Banda IR - Elizondo RB FIR - Reza, Raymundo Garcia IR - Reza RG FIR - Galvez, Guillermo Gonzalez IR - Galvez GG FIR - Gonzalez, Jose Gerardo Gonzalez IR - Gonzalez JGG FIR - Shlesinger, Yshay IR - Shlesinger Y FIR - Sarwar, Jawad IR - Sarwar J FIR - Gangi, Sumana IR - Gangi S FIR - Wieskopf, Bram IR - Wieskopf B FIR - Gaufin, Thaidra IR - Gaufin T FIR - Anderson, Rachel IR - Anderson R FIR - Garcia-Torres, Eric IR - Garcia-Torres E FIR - Luna, Eduardo IR - Luna E FIR - Philander, Peter IR - Philander P FIR - Chow, Christopher IR - Chow C FIR - Guduri, Sridhar IR - Guduri S FIR - Gonzalez-Bossolo, Alex IR - Gonzalez-Bossolo A FIR - McConnehey, Brock IR - McConnehey B FIR - Usdan, Lisa IR - Usdan L FIR - Brautigam, Donald IR - Brautigam D FIR - Gomez-Cuellar, Martha IR - Gomez-Cuellar M FIR - Adams, Michael IR - Adams M FIR - Schneider, Alison IR - Schneider A FIR - Tsang, Dennis IR - Tsang D FIR - Mattar, Peter IR - Mattar P FIR - Powell, Talessa IR - Powell T FIR - Mansilla-Letelier, Paola IR - Mansilla-Letelier P FIR - Connery, Lisa IR - Connery L FIR - Lopez, Reynaldo IR - Lopez R FIR - Buynak, Robert IR - Buynak R FIR - Vega, Damaris IR - Vega D FIR - Loy, Juan IR - Loy J FIR - Conaway, Herbert IR - Conaway H FIR - Schultz, James IR - Schultz J FIR - Kim, John IR - Kim J FIR - Finley, Jon IR - Finley J FIR - Beach, James IR - Beach J FIR - Hutchins, Bob IR - Hutchins B FIR - Brian, Susan IR - Brian S FIR - Lynn, Lon IR - Lynn L FIR - Tan, Anjanette IR - Tan A FIR - Vazquez-Tanus, Jose IR - Vazquez-Tanus J FIR - Moran, Joseph IR - Moran J FIR - Crystal, Chad IR - Crystal C FIR - Pant, Nicole IR - Pant N FIR - Palchick, Bryce IR - Palchick B FIR - Packer, Flint IR - Packer F FIR - Broyles, Frances IR - Broyles F FIR - Alleman, Brandon IR - Alleman B FIR - Mandry, Jose IR - Mandry J FIR - Audish, Hanid IR - Audish H FIR - Davidson, Evelyne IR - Davidson E FIR - Ard, Jamy IR - Ard J FIR - Horowitz, Barry IR - Horowitz B FIR - Lucas, Kathryn IR - Lucas K FIR - Puente, Orlando IR - Puente O FIR - Rosenstock, Julio IR - Rosenstock J FIR - Serje, Jorge IR - Serje J FIR - Dennis, Patrick IR - Dennis P FIR - Washington, Tonita IR - Washington T FIR - Murray, Alexander IR - Murray A FIR - Oliver, Michael IR - Oliver M FIR - Busch, Robert IR - Busch R FIR - Ross, Samuel Harrison IR - Ross SH FIR - London, Jeffrey IR - London J FIR - Montano, Charles IR - Montano C FIR - Zimmerman, Michael IR - Zimmerman M FIR - Saad, Abdulhassan IR - Saad A FIR - Al-Karadsheh, Amer IR - Al-Karadsheh A FIR - Dunn, Leonard IR - Dunn L FIR - Hopson, Shannon IR - Hopson S FIR - Freilich, Bradley IR - Freilich B EDAT- 2026/03/02 00:38 MHDA- 2026/03/22 06:07 CRDT- 2026/03/01 18:53 PHST- 2025/12/22 00:00 [received] PHST- 2026/01/28 00:00 [revised] PHST- 2026/01/29 00:00 [accepted] PHST- 2026/03/22 06:07 [medline] PHST- 2026/03/02 00:38 [pubmed] PHST- 2026/03/01 18:53 [entrez] AID - S0140-6736(26)00202-3 [pii] AID - 10.1016/S0140-6736(26)00202-3 [doi] PST - ppublish SO - Lancet. 2026 Mar 21;407(10534):1147-1160. doi: 10.1016/S0140-6736(26)00202-3. Epub 2026 Feb 26. PMID- 41757397 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20260822 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 5 DP - 2026 May TI - Dose-Escalation Regimens for Incretin Mimetics in Type 2 Diabetes Are Associated With Tolerance for Nausea and Vomiting. PG - 4232-4242 LID - 10.1111/dom.70613 [doi] AB - AIMS/HYPOTHESIS: Initial dose-escalation has been shown to mitigate gastrointestinal adverse events in people treated with incretin-based medications. We aimed to analyse dose-response relationships for the proportion of study participants reporting nausea and vomiting among those exposed to incretin mimetics approved for Type 2 diabetes (GLP-1 receptor agonists and the dual GIP/GLP-1 receptor agonist tirzepatide) in Phase 1 (no or short dose escalation) and Phase 3 (with dose escalation) trials. METHODS: Non-linear regression analysis (curve fitting) was used to estimate the dose that would elicit nausea or vomiting in 50% of exposed subjects (ED(50)). We used the ratio of ED(50)ies determined for Phase 1 and Phase 3 trials as an indicator of developing tolerance. RESULTS: The development of tolerance for nausea and vomiting (indicated by a ratio of ED(50)ies Phase 3/Phase 1) for semaglutide (both s.c. and oral) and for tirzepatide was significantly higher than 1. Comparing all approved incretin-based medications, a higher ratio, indicating the development of more tolerance, was associated with (a) a longer drug escalation period and (b) a greater number of dose-escalation steps. This ED(50) ratio (Phase 3/Phase 1) was also significantly associated with effect sizes for intended therapeutic actions of incretin mimetics (reductions in HbA(1c) and body weight). CONCLUSIONS/INTERPRETATION: Taken together, optimised dose-escalation regimens may lead to greater tolerance for nausea and vomiting, which allows to use of higher doses, which are associated with greater therapeutic effectiveness. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism Section Medical Department I, Josef-Hospital, Ruhr University Bochum, Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. FAU - Punov, Viktoria AU - Punov V AD - Diabetes, Endocrinology, Metabolism Section Medical Department I, Josef-Hospital, Ruhr University Bochum, Bochum, Germany. FAU - Kang, Yu Mi AU - Kang YM AUID- ORCID: 0000-0002-6272-0666 AD - Division of Endocrinology, Diabetes and Hypertension and TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Lim, Soo AU - Lim S AUID- ORCID: 0000-0002-4137-1671 AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20260227 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Dose-Response Relationship, Drug MH - Drug Tolerance MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/adverse effects/administration & dosage/analogs & derivatives MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - *Incretins/administration & dosage/adverse effects MH - *Nausea/chemically induced MH - Semaglutide MH - Tirzepatide MH - *Vomiting/chemically induced MH - Clinical Trials, Phase I as Topic MH - Clinical Trials, Phase III as Topic MH - Clinical Trials, Phase IV as Topic PMC - PMC13071187 OTO - NOTNLM OT - GLP-1 analogue OT - pharmaco-epidemiology OT - type 2 diabetes OT - weight control COIS- M.A.N. has been a member on advisory boards or has consulted with Eli Lilly & Co., Pfizer, Regor, Sun Pharma and Structure Therapeutics (Gasherbrum). He has also served on the speakers' bureau of Eli Lilly & Co., Medscape, Medical Learning Institute and NovoNordisk. V.P. and Y.M.K. declare no conflicts of interest. S.L. received research grants from Merck Sharp & Dohme, Novo Nordisk and LG Chem; and honoraria as a consultant or speaker for AstraZeneca, Boehringer Ingelheim, Abbott, LG Chem, Daewoong Pharmaceutical, Chong Kun Dang Pharmaceutical and Novo Nordisk. EDAT- 2026/02/27 06:32 MHDA- 2026/04/13 06:32 PMCR- 2026/04/13 CRDT- 2026/02/27 05:09 PHST- 2026/02/15 00:00 [revised] PHST- 2026/01/09 00:00 [received] PHST- 2026/02/15 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/02/27 06:32 [pubmed] PHST- 2026/02/27 05:09 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - DOM70613 [pii] AID - 10.1111/dom.70613 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):4232-4242. doi: 10.1111/dom.70613. Epub 2026 Feb 27. PMID- 41752784 OWN - NLM STAT- MEDLINE DCOM- 20260709 LR - 20260813 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 62 IP - 2 DP - 2026 Feb 16 TI - Preliminary Real-World Experience with Semaglutide in Obese Patients with Type 2 Diabetes on Chronic Hemodialysis: A Multicenter Pilot Study. LID - 10.3390/medicina62020386 [doi] LID - 386 AB - Background and Objectives: Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) that has demonstrated metabolic and weight benefits in diabetic and obese patients with chronic kidney disease (CKD) who are not on dialysis; however, evidence in the hemodialysis (HD) population is scarce. Weight control and body composition optimization are particularly challenging in HD because of fluid shifts and the risk of protein-energy wasting. Materials and Methods: This prospective, multicenter, real-world, uncontrolled observational pilot study explored the short-term safety and changes in anthropometric and body-composition parameters after semaglutide initiation in obese adults with type 2 diabetes mellitus (T2DM) undergoing chronic HD. Patients were assessed at baseline and at 3 and 6 months. The primary endpoint was the change in body mass index (BMI), dry weight, and fat mass assessed by bioimpedance spectroscopy (BIS). Results: Thirteen patients were included (10 male, 77%), with a median age of 61.9 years (IQR 55-69). Semaglutide was started at 0.25 mg/week and titrated up to 1 mg/week according to tolerance. Three patients (23.1%) experienced transient nausea that was resolved over time or after dose adjustment, without discontinuation. From baseline to month +6, BMI decreased by a median of 1.5 kg/m(2) and dry weight by 5.0 kg, mainly driven by a median reduction in fat mass of 9 kg; lean tissue mass and serum albumin did not change significantly. Conclusions: In this small, uncontrolled exploratory study, semaglutide was generally well tolerated and was associated with short-term reductions in body weight and fat mass in obese patients with T2DM on HD. These findings are hypothesis-generating and require confirmation in larger controlled prospective studies to define safety and clinical benefit in this population. FAU - Yugueros, Alejandra AU - Yugueros A AUID- ORCID: 0000-0002-8020-7276 AD - Servicio de Nefrologia Hospital Lluis Alcanyis de Xativa, 46800 Valencia, Spain. AD - Grupo de Investigacion en Enfermedades Cardiorrenales y Metabolicas, Departamento de Medicina y Cirugia, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, 46113 Valencia, Spain. FAU - D'Marco, Luis AU - D'Marco L AUID- ORCID: 0000-0003-0148-891X AD - Grupo de Investigacion en Enfermedades Cardiorrenales y Metabolicas, Departamento de Medicina y Cirugia, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, 46113 Valencia, Spain. FAU - Valero, Alejandro AU - Valero A AD - Servicio de Nefrologia, Hospital Doctor Peset, 46017 Valencia, Spain. FAU - Vivo, Elena AU - Vivo E AD - Servicio de Nefrologia, Hospital de la Ribera, 46600 Alzira, Spain. FAU - Martinez-Mas, Amparo AU - Martinez-Mas A AD - Servicio de Nefrologia Hospital Lluis Alcanyis de Xativa, 46800 Valencia, Spain. FAU - Calve, Manuel AU - Calve M AD - Servicio de Nefrologia Hospital Lluis Alcanyis de Xativa, 46800 Valencia, Spain. FAU - Alonso, Juan Carlos AU - Alonso JC AD - Servicio de Nefrologia Hospital Lluis Alcanyis de Xativa, 46800 Valencia, Spain. FAU - Vizcaino, Belen AU - Vizcaino B AD - Servicio de Nefrologia, Hospital Doctor Peset, 46017 Valencia, Spain. FAU - Gonzalez-Moya, Mercedes AU - Gonzalez-Moya M AD - Servicio de Nefrologia, Hospital Doctor Peset, 46017 Valencia, Spain. FAU - Checa-Ros, Ana AU - Checa-Ros A AUID- ORCID: 0000-0001-8958-6711 AD - Grupo de Investigacion en Enfermedades Cardiorrenales y Metabolicas, Departamento de Medicina y Cirugia, Facultad de Ciencias de la Salud, Universidad Cardenal Herrera-CEU, CEU Universities, 46113 Valencia, Spain. FAU - Sancho, Asuncion AU - Sancho A AD - Servicio de Nefrologia, Hospital Doctor Peset, 46017 Valencia, Spain. FAU - Molina, Pablo AU - Molina P AUID- ORCID: 0000-0002-8311-6214 AD - Servicio de Nefrologia, Hospital Universitari i Politecnic La Fe, 46026 Valencia, Spain. AD - Departament de Medicina, Facultat de Medicina i Odontlogia, Universitat de Valencia, 46010 Valencia, Spain. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260216 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Pilot Projects MH - Middle Aged MH - Female MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Prospective Studies MH - *Obesity/drug therapy/complications MH - Aged MH - Renal Dialysis/methods MH - Hypoglycemic Agents/therapeutic use MH - Body Mass Index PMC - PMC12942463 OTO - NOTNLM OT - GLP1-RA OT - chronic kidney disease OT - diabetes OT - hemodialysis OT - obesity OT - semaglutide COIS- The author declares no conflicts of interest. EDAT- 2026/02/27 06:31 MHDA- 2026/03/06 09:09 PMCR- 2026/02/16 CRDT- 2026/02/27 01:12 PHST- 2025/12/26 00:00 [received] PHST- 2026/02/02 00:00 [revised] PHST- 2026/02/09 00:00 [accepted] PHST- 2026/03/06 09:09 [medline] PHST- 2026/02/27 06:31 [pubmed] PHST- 2026/02/27 01:12 [entrez] PHST- 2026/02/16 00:00 [pmc-release] AID - medicina62020386 [pii] AID - medicina-62-00386 [pii] AID - 10.3390/medicina62020386 [doi] PST - epublish SO - Medicina (Kaunas). 2026 Feb 16;62(2):386. doi: 10.3390/medicina62020386. PMID- 41748946 OWN - NLM STAT- MEDLINE DCOM- 20260616 LR - 20261010 IS - 1432-1912 (Electronic) IS - 0028-1298 (Linking) VI - 399 IP - 8 DP - 2026 May TI - Musculoskeletal adverse events with incretin-based diabetes drugs: a FAERS pharmacovigilance study. PG - 11975-11991 LID - 10.1007/s00210-026-05113-2 [doi] AB - Incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4is), and the dual GIP/GLP-1 RA tirzepatide, are widely prescribed for type 2 diabetes mellitus (T2DM). Their musculoskeletal adverse events (AEs) remain underexplored. We analyzed FAERS reports (Q1 2004-Q2 2024) for musculoskeletal and connective tissue disorders. After de-duplication, 15,052 reports were subjected to disproportionality analyses using reporting odds ratio (ROR), proportional reporting ratio (PRR), empirical Bayes geometric mean (EBGM), and information component (IC). Differences between serious and non-serious events were assessed, and time to onset was examined by cumulative curves and Weibull models. No signals were detected at the SOC level. At the PT level, GLP-1 RAs were linked to back pain, myalgia, and neck mass, while tirzepatide was associated with muscle atrophy and neck mass. Among DPP-4is, sitagliptin, linagliptin, and alogliptin showed signals for osteoarthritis, rhabdomyolysis, and arthritis. Sex-, age-, and weight-related differences were noted for dulaglutide, liraglutide, semaglutide, sitagliptin, linagliptin, alogliptin, and saxagliptin. Median onset was shorter for GLP-1 RAs and tirzepatide (8% [HR 0.63 (0.52-0.76)] versus /=2000 mg/g [HR 0.53 (0.39-0.72)] versus UACR <100 mg/g [HR 0.90 (0.58-1.39); Pinteraction = .0367]. The semaglutide group had a lower rate of infection SAEs (17.9% versus 21.3%; P = .0070), COVID-19 SAEs (6.7% versus 8.8%; P = .0155), COVID-19 adverse events (20.3% versus 22.9%; P = .0190) and hospitalization due to infection (17.5% versus 20.4%; P = .015). CONCLUSIONS: Semaglutide reduced risks of infection SAEs, hospitalization due to infection, and all-cause death with greater benefit among those with poorer glycemic control and greater baseline albuminuria. These findings support potential clinical benefits of semaglutide beyond kidney, CV and metabolic outcomes in high-risk patients with T2D and CKD. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the ERA. FAU - Rayner, Brian AU - Rayner B AD - Division of Nephrology and Hypertension, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Department of Medicine, Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA, USA. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Centre, Munchen, Germany. AD - University Hospital, Friedrich-Alexander University, Erlangen, Germany. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bosch-Traberg, Heidrun AU - Bosch-Traberg H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jeppesen, Ole Kleist AU - Jeppesen OK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Tran, Minh Chau AU - Tran MC AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Chernin, Gil AU - Chernin G AUID- ORCID: 0000-0001-7514-156X AD - Kaplan Medical Center, Hebrew University of Jerusalem, Rehovot, Israel. FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Division of Nephrology, University of Washington School of Medicine, Seattle, WA, USA. AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA. LA - eng SI - ClinicalTrials.gov/NCT03819153 GR - Novo Nordisk/ PT - Journal Article PT - Randomized Controlled Trial PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *COVID-19/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Pandemics MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - SARS-CoV-2 MH - Semaglutide PMC - PMC13518088 OTO - NOTNLM OT - CKD OT - clinical trial OT - diabetic kidney disease OT - pneumonia OT - type 2 diabetes COIS- B.R. reports receiving honoraria for CME presentations from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim and Novartis; and has served on advisory boards for Astellas, AstraZeneca, Bayer, Boehringer Ingelheim and Novo Nordisk. K.W.M. reports receiving grants from AHA, Apple, Bayer, California Institute Regenerative Medicine (CIRM), CSL Behring, Eidos, Ferring, Gilead, Google (Verify), Idorsia, Johnson & Johnson, Luitpold, Novartis, PAC-12, Precordior and Sanifit; consulting fees from Applied Therapeutics, Bayer, Bristol Myers Squibb, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, PhaseBio, Portola, Quidel and Theravance; and equity in Human, Medeloop, Precordior and Regencor. J.F.E.M. reports receiving grants from Bayer and Novo Nordisk; consulting fees from Bayer and Novo Nordisk; honoraria from AstraZeneca, Bayer, Novartis, UpToDate Inc. and Novo Nordisk; and has participated on a data safety monitoring board for Cytel, Icon, Iqvia, Parexel, WCG and Sanofi; as well as having a leadership role in the KDIGO (Kidney Disease: Improving Global Outcomes) group. R.E.P. reports receiving speaker fees from Eli Lilly, Lilly USA and Novo Nordisk; consulting fees from AbbVie, AstraZeneca, Bayer AG, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Eli Lilly, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui (USA), Intas Pharmaceuticals, Lilly USA, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock and Sun Pharmaceutical Industries; and grants from Biomea Fusion, Carmot Therapeutics, Dompe, Eli Lilly, Endogenex, Fractyl, Novo Nordisk and Sanofi. All grants are directed to R.E.P.'s institution. Through 31 December 2023, payment for R.E.P.'s consultant and speaker services was made directly to his employer, AdventHealth, a nonprofit entity; as of 1 January 2024, payment is directed to R.E.P. personally. P.R. reports receiving grants from AstraZeneca, Bayer and Novo Nordisk; honoraria to the Steno Diabetes Centre Copenhagen from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Merck, Mundipharma, Novo Nordisk and Sanofi; and consulting fees from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma and Sanofi. G.C. reports receiving speaker fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk and Sanofi. K.R.T. is supported by NIH research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568 and OT2OD032581, and CDC project numbers 75D301-21-P-12254 and 75D301-23-C-18264. She has also received investigator-initiated grant support from Bayer, the Doris Duke Foundation and Travere, and outside of the submitted work. She reports consultancy fees from Boehringer Ingelheim, Eli Lilly and Novo Nordisk; and speaker fees from Novo Nordisk. N.B., O.K.J. and M.C.T. are employees of and shareholders in Novo Nordisk. H.B.-T. was an employee of Novo Nordisk until July 2025, and is a current shareholder of Novo Nordisk. EDAT- 2026/02/23 13:05 MHDA- 2026/08/27 05:35 PMCR- 2026/02/23 CRDT- 2026/02/23 08:42 PHST- 2025/11/06 00:00 [received] PHST- 2026/02/04 00:00 [accepted] PHST- 2026/08/27 05:35 [medline] PHST- 2026/02/23 13:05 [pubmed] PHST- 2026/02/23 08:42 [entrez] PHST- 2026/02/23 00:00 [pmc-release] AID - 8494850 [pii] AID - gfag036 [pii] AID - 10.1093/ndt/gfag036 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2026 Aug 27;41(9):1696-1708. doi: 10.1093/ndt/gfag036. PMID- 41725422 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 5 DP - 2026 May TI - Flexible dose of semaglutide reduces early discontinuation while maintaining comparable outcomes in obese patients: FLEX-SEMA 2.4 mg, an Italian real-world study. PG - 3623-3631 LID - 10.1111/dom.70538 [doi] AB - AIMS: To evaluate real-world clinical use of semaglutide in obese patients, focusing on titration, tolerability and short-term efficacy. MATERIALS AND METHODS: This retrospective study included obese patients treated with the weekly injectable semaglutide. Data on body weight, waist circumference, lipid profile, doses, reasons for maintenance, adverse events, and discontinuations were collected at 3 and 6 months. RESULTS: A total of 111 patients were included (80% women; mean age 51.12; median body mass index (BMI) 35.56 kg/m(2); median body weight 97.00 kg). About 81.1% of patients initiated therapy at 0.25 mg, while 72.1% increased to 1 mg after 3 months. By 6 months, 2% remained on 0.5 mg, 40% on 1 mg, and 26% on 2.4 mg. The main reasons for maintaining the dose were satisfaction with the outcomes, followed by cost and adverse events. Significant reductions in weight, BMI, waist circumference and waist-to-height ratio were observed at both time points, with greater improvements seen in patients with a baseline BMI of >/=35. Weight loss of >/=5%, >/=10%, >/=15% and >/=20% was achieved by 23.5%, 34.6%, 30.8% and 11.1% of patients, respectively. There were no differences by sex, previous treatment or final dose. Adverse events occurred in 56.8% of patients at 3 months, leading to discontinuation in three patients. This percentage halved by 6 months (a 32.6% rate), with two cases leading to discontinuation. The rate of early discontinuation was 6.3% at 3 months, rising to 10.5% at 6 months due to cost, adverse events, or inefficacy. CONCLUSION: This real-world analysis provides valuable insights into the use of semaglutide in routine clinical practice, confirming a favourable efficacy profile with flexible dosing patterns. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Pampanelli, Simone AU - Pampanelli S AUID- ORCID: 0000-0003-0255-4210 AD - SS Clinical Nutrition and Dietetics Hospital Santa Maria Novella, Perugia, Italy. FAU - Terzoni, Stefano AU - Terzoni S AD - Department of Biomedical Sciences for Health, University of Study of Milano, Milan, Italy. FAU - Pantanetti, Paola AU - Pantanetti P AD - UOSD Diabetology AST Fermo, Fermo, Italy. FAU - Di Loreto, Chiara AU - Di Loreto C AD - USL Umbria 1, Perugia, Italy. FAU - Mazzieri, Alessio AU - Mazzieri A AD - USL Umbria 1, Perugia, Italy. FAU - Cangelosi, Giovanni AU - Cangelosi G AD - UOSD Diabetology AST Fermo, Fermo, Italy. FAU - Alberti, Sara AU - Alberti S AD - UOSD Diabetology AST Fermo, Fermo, Italy. FAU - Badiali, Cristina AU - Badiali C AD - UOSD Hospital Clinical Nutrition San Donato, Arezzo, Italy. FAU - Grandone, Ilenia AU - Grandone I AD - SC University Department of Andrology and Endocrinology Metabolic Diseases, Terni, Italy. FAU - Migliarelli, Sara AU - Migliarelli S AD - Unveristy of Perugia, Perugia, Italy. FAU - Castagna, Maria Grazia AU - Castagna MG AD - UOC Endocrinology, Siena Hospital, Siena, Italy. FAU - Cerrai Ceroni, Mariaclaudia AU - Cerrai Ceroni M AD - UOC Endocrinology, Siena Hospital, Siena, Italy. FAU - Benenati, Nicoletta AU - Benenati N AD - UOC Endocrinology, Siena Hospital, Siena, Italy. LA - eng PT - Journal Article DEP - 20260223 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - Female MH - Male MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - *Obesity/drug therapy MH - Retrospective Studies MH - Middle Aged MH - Italy/epidemiology MH - Treatment Outcome MH - Adult MH - Weight Loss/drug effects MH - Body Mass Index MH - *Anti-Obesity Agents/administration & dosage/adverse effects MH - Drug Administration Schedule MH - Waist Circumference/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications PMC - PMC13071210 OTO - NOTNLM OT - obesity care OT - real-world evidence OT - semaglutide OT - weight management COIS- The authors have no conflicts of interest to declare. EDAT- 2026/02/23 06:27 MHDA- 2026/04/13 06:32 PMCR- 2026/04/13 CRDT- 2026/02/23 04:03 PHST- 2026/01/22 00:00 [revised] PHST- 2025/12/02 00:00 [received] PHST- 2026/01/27 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/02/23 06:27 [pubmed] PHST- 2026/02/23 04:03 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - DOM70538 [pii] AID - 10.1111/dom.70538 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):3623-3631. doi: 10.1111/dom.70538. Epub 2026 Feb 23. PMID- 41715123 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260915 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 24 IP - 1 DP - 2026 Feb 19 TI - Efficacy and safety of anti-prediabetic drugs in patients with prediabetes: a Bayesian network meta-analysis. LID - 10.1186/s12916-026-04705-2 [doi] LID - 174 AB - BACKGROUND: Prediabetes refers to the transitional stage from normal glucose metabolism to diabetes. The International Diabetes Federation guidelines reported that, as of 2024, approximately 1.12 billion people globally were in the prediabetes stage. Without intervention, individuals with prediabetes are highly likely to progress to type 2 diabetes mellitus. It can be seen that prediabetes is posing a threat to human health and life and leads to a significant global public health concern. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched before March 29, 2025. Eligible randomized controlled trials (RCTs) enrolled adults with prediabetes, compared the efficacy and safety of placebo and anti-prediabetic drugs (e.g., metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and thiazolidinedione) with a follow-up duration of at least 12 weeks. Bayesian network meta-analysis was employed in statistical analysis. RESULTS: Fifty-five eligible RCTs involving 37 interventions with 16,610 participants were included in this study. Compared with placebo, most anti-prediabetic drugs significantly reduced levels of hemoglobin A1c (HbA1c) (mean difference (MD), - 0.94 ~ - 0.27%), fasting plasma glucose (FPG) (MD, - 26.42 ~ - 0.15 mg/dL), weight loss (WL) (MD, - 13.59 ~ - 5.99 kg) and body mass index (BMI) (MD, - 4.50 ~ - 0.08 kg/m(2)). Specifically, 2.4 mg of semaglutide SC demonstrated the most optimal efficacy in WL (MD - 13.59 kg; 95% confidence interval (CI) - 17.30 to - 9.91) and favorable efficacy in lowering HbA1c (MD - 0.39%; 95% CI - 0.55 to - 0.25); 15 mg of tirzepatide showed significant efficacy in lowering FPG (MD - 9.58 mg/dL; 95% CI - 12.00 to - 7.15), and potent efficacy in lowering BMI. Thirty milligrams of pioglitazone showed excellent efficacy in lowering lipid and FPG. Among the interventions, there was no significant difference in the incidence of adverse events (AEs), while 100 mg of sitagliptin demonstrated higher incidence of serious adverse events (SAEs). CONCLUSIONS: Among all the included interventions, GLP-1RAs, GIP/GLP-1RAs, and TZDs demonstrated favorable anti-prediabetic efficacy and acceptable safety. 2.4 mg of semaglutide SC and 15 mg of tirzepatide were the best option among the included interventions considering favorable glucose and BMI control. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42025636991. CI - (c) 2026. The Author(s). FAU - Wu, Yike AU - Wu Y AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Wang, Zihan AU - Wang Z AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Tuersun, Adili AU - Tuersun A AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Yu, Qiuxia AU - Yu Q AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Zhong, Yu AU - Zhong Y AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Ali, Shah Syed Alfakhar AU - Ali SSA AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Liu, Haiyang AU - Liu H AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Hu, Xinyi AU - Hu X AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Zhang, Yanfei AU - Zhang Y AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Pang, Liyuan AU - Pang L AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Li, Longzhou AU - Li L AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Gao, Long AU - Gao L AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Wu, Qiwen AU - Wu Q AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Wang, Shan AU - Wang S AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Cui, Meng AU - Cui M AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Sun, Linglu AU - Sun L AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Wu, Yulin AU - Wu Y AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Yin, Antong AU - Yin A AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Zhang, Lei AU - Zhang L AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. FAU - Ma, Guo AU - Ma G AD - School of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Fudan University, Shanghai, 201203, People's Republic of China. mg0328@fudan.edu.cn. LA - eng GR - 82374133, 82074109, 81873078 and 81374051/National Natural Science Foundation of China/ PT - Journal Article PT - Network Meta-Analysis DEP - 20260219 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Thiazolidinediones) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Prediabetic State/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Metformin/therapeutic use/adverse effects MH - Bayes Theorem MH - Diabetes Mellitus, Type 2/prevention & control MH - Randomized Controlled Trials as Topic MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Thiazolidinediones/therapeutic use MH - Glycated Hemoglobin MH - Semaglutide MH - Blood Glucose/drug effects MH - Treatment Outcome PMC - PMC13020221 OTO - NOTNLM OT - Anti-prediabetic drugs OT - Network meta-analysis OT - Prediabetes OT - Type 2 diabetes mellitus COIS- Declarations. Ethics approval and consent to participate: As this study did not involve clinical trials or animal experiments, and had no access to individual participants or their personal information, obtaining consent for publication was not applicable. Consent for publication: Current study did not involve individual participants directly, so there was no access to participants or their personal information. Therefore, obtaining consent for publication was not applicable. There are no patient representatives or members of the public attend the study's planning, design, conduct, or reporting. Competing interests: The authors declare no competing interests. EDAT- 2026/02/20 07:05 MHDA- 2026/03/27 07:14 PMCR- 2026/02/19 CRDT- 2026/02/20 00:22 PHST- 2025/09/17 00:00 [received] PHST- 2026/02/11 00:00 [accepted] PHST- 2026/03/27 07:14 [medline] PHST- 2026/02/20 07:05 [pubmed] PHST- 2026/02/20 00:22 [entrez] PHST- 2026/02/19 00:00 [pmc-release] AID - 10.1186/s12916-026-04705-2 [pii] AID - 4705 [pii] AID - 10.1186/s12916-026-04705-2 [doi] PST - epublish SO - BMC Med. 2026 Feb 19;24(1):174. doi: 10.1186/s12916-026-04705-2. PMID- 41713959 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260821 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 5 DP - 2026 May TI - Characterisation of real-world patients who discontinued a glucagon-like peptide-1 agonist. PG - 3965-3973 LID - 10.1111/dom.70579 [doi] AB - AIMS: The objective of this analysis was to identify the 6-month discontinuation rate for GLP-1 analogues, reasons for discontinuation, and characteristics associated with discontinuation. MATERIALS AND METHODS: This was a retrospective analysis of adult patients who had an initial GLP-1 (semaglutide or liraglutide) dispensed between January 1, 2018 and June 30, 2023. The primary outcome was the 180-day GLP-1 discontinuation rate, and among those who discontinued, identification of documented reasons for discontinuation. The secondary outcome was the identification of patient characteristics associated with GLP-1 discontinuation. RESULTS: There were 1374 patients included, of whom 436 (31.7%) discontinued GLP-1 therapy. Common reasons for GLP-1 discontinuation included: 26.8% with an adverse drug reaction (ADR), 14.4% with a GLP-1 cost concern, and 11.2% with non-adherence. Asian/Native American/Pacific Islander races (adjusted odds ratio [AOR] 2.51; 95% confidence interval [CI] 1.07-5.91 compared to Whites) and an overweight/obesity indication (AOR 2.46; 95% CI 1.17-5.17 compared to diabetes + overweight/obesity) were associated with GLP-1 discontinuation. CONCLUSIONS: 180-day GLP-1 discontinuation was prevalent. ADR and cost concerns were primary reasons for discontinuation and health disparities among patients who discontinued were identified. These real-world findings offer patients, providers, and policymakers evidence of potential barriers to GLP-1 persistence. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Van Laren, Jessica AU - Van Laren J AD - Pharmacy Department, Kaiser Permanente Colorado, Aurora, Colorado, USA. FAU - Friesleben, Cari AU - Friesleben C AD - Pharmacy Department, Kaiser Permanente Colorado, Aurora, Colorado, USA. FAU - Gershovich, Olga AU - Gershovich O AD - Pharmacy Department, Kaiser Permanente Colorado, Aurora, Colorado, USA. FAU - Helm, Lindsey AU - Helm L AD - Pharmacy Department, Kaiser Permanente Colorado, Aurora, Colorado, USA. FAU - Patel, Rachana J AU - Patel RJ AD - Pharmacy Department, Kaiser Permanente Colorado, Aurora, Colorado, USA. FAU - Delate, Thomas AU - Delate T AUID- ORCID: 0000-0002-6530-8415 AD - Pharmacy Outcomes Research Group, Kaiser Permanente National Pharmacy, Aurora, Colorado, USA. LA - eng PT - Journal Article DEP - 20260219 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Liraglutide/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide 1/agonists/analogs & derivatives MH - Aged MH - Semaglutide MH - *Drug Monitoring MH - Treatment Interruption OTO - NOTNLM OT - adverse events OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - persistence OT - type 2 diabetes EDAT- 2026/02/20 00:32 MHDA- 2026/04/13 06:32 CRDT- 2026/02/19 20:53 PHST- 2026/02/02 00:00 [revised] PHST- 2025/11/26 00:00 [received] PHST- 2026/02/07 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/02/20 00:32 [pubmed] PHST- 2026/02/19 20:53 [entrez] AID - 10.1111/dom.70579 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):3965-3973. doi: 10.1111/dom.70579. Epub 2026 Feb 19. PMID- 41703894 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1365-2125 (Electronic) IS - 0306-5251 (Print) IS - 0306-5251 (Linking) VI - 92 IP - 5 DP - 2026 May TI - GLP-1 agonists and the gut microbiome: A bidirectional relationship. PG - 1309-1325 LID - 10.1002/bcp.70487 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists have transformed the management of type 2 diabetes mellitus (T2DM) and obesity, yet their interactions with the gut microbiome remain an emerging frontier in pharmacological and metabolic research. Mounting evidence suggests that the gut microbiota modulates GLP-1 secretion via microbial metabolites, including short-chain fatty acids and bile acid derivatives, while GLP-1 agonists reciprocally reshape microbial composition, influencing metabolic outcomes beyond their classical incretin functions. This bidirectional interplay has profound implications for precision medicine, as gut microbial signatures have been associated with variability in therapeutic response, raising the possibility that microbiome features could contribute to response stratification in future studies. Advances in pharmacomicrobiomics, multiomics integration and computational modelling now enable a more refined dissection of these interactions, illuminating potential microbial targets for intervention. Study discrepancies may arise from variations in host diet, baseline microbiome composition and genetic factors influencing GLP-1 signalling. Future studies should incorporate stratified analyses accounting for these confounders to understand causative mechanisms. This review collates current evidence on the microbiome-mediated modulation of GLP-1 dynamics, evaluates the pharmacomicrobiomic impact of GLP-1 agonists and outlines future research directions at the interface of gut microbiota and incretin biology. By unravelling the complexities of this host-microbe-drug axis, the field moves closer to a paradigm of personalized metabolic medicine, where future GLP-1 therapeutic strategies may consider host metabolic and microbial context, optimizing efficacy and minimizing variability in patient response. CI - (c) 2026 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. FAU - Kamath, Srinivas AU - Kamath S AD - School of Pharmacy and Biomedical Science, Adelaide University, Adelaide, South Australia, Australia. FAU - Chan, Nicole S L AU - Chan NSL AD - School of Pharmacy and Biomedical Science, Adelaide University, Adelaide, South Australia, Australia. FAU - Joyce, Paul AU - Joyce P AUID- ORCID: 0000-0003-3619-7901 AD - School of Pharmacy and Biomedical Science, Adelaide University, Adelaide, South Australia, Australia. LA - eng GR - 2022-CF-EMCR-004-25314/Hospital Research Foundation/ PT - Journal Article PT - Review DEP - 20260217 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/microbiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Gastrointestinal Microbiome/drug effects/physiology MH - *Glucagon-Like Peptide 1/agonists/metabolism MH - Animals MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Incretins/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Obesity/drug therapy/microbiology MH - Multiomics MH - Precision Medicine PMC - PMC13122291 OTO - NOTNLM OT - GLP-1 agonists OT - gut microbiome OT - liraglutide OT - microbiome-gut-brain axis OT - pharmacomicrobiomics OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors declare no conflict of interest. EDAT- 2026/02/18 10:06 MHDA- 2026/04/28 06:38 PMCR- 2026/02/17 CRDT- 2026/02/18 01:03 PHST- 2026/01/19 00:00 [revised] PHST- 2025/11/17 00:00 [received] PHST- 2026/01/28 00:00 [accepted] PHST- 2026/04/28 06:38 [medline] PHST- 2026/02/18 10:06 [pubmed] PHST- 2026/02/18 01:03 [entrez] PHST- 2026/02/17 00:00 [pmc-release] AID - BCP70487 [pii] AID - 10.1002/bcp.70487 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2026 May;92(5):1309-1325. doi: 10.1002/bcp.70487. Epub 2026 Feb 17. PMID- 41703773 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260819 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - Real-world persistence and dose titration of GLP-1 receptor agonists in type 2 diabetes: A UK population-based cohort study by obesity and cardiovascular disease status. PG - 3386-3395 LID - 10.1111/dom.70535 [doi] AB - AIMS: Real-world medication use varies across clinical trial and healthcare settings; therefore, we evaluated GLP-1 receptor agonist (GLP-1RA) persistence and dose titration among adults with type 2 diabetes in UK primary care, stratified by agent, obesity status, cardiovascular disease (CVD) history, and sex assigned at birth. MATERIALS AND METHODS: Adults with type 2 diabetes initiating GLP-1RAs between 1 March 2018 and 30 June 2023, with follow-up >/=1-year, were identified using the IQVIA Medical Research Data (IMRD) incorporating data from THIN, A Cegedim Database. The absolute 1-year risk of discontinuation was estimated using the Aalen-Johansen estimator, while multivariable cause-specific Cox models assessed associations with patient characteristics. Dosing trajectories were characterised across individual prescriptions during the first therapy year. RESULTS: Among 8200 GLP-1RA initiators (46.5% dulaglutide, 38.7% semaglutide), the 1-year discontinuation risk was 41.1% (95% CI 40.1-42.2), higher among those without obesity (BMI <30 kg/m(2): 49.2%, 46.5-52.0) versus with BMI >/=30 kg/m(2) (BMI 30-<35/>/=35 kg/m(2): 40.4%/37.2%, 38.4-42.4/35.4-39.1). Discontinuation was lower with dulaglutide (36.9%, 35.4-38.4) than with subcutaneous/oral semaglutide (46.4%/55.8%, 44.4-48.4/52.3-59.4). Only 58% of subcutaneous/oral semaglutide initiators reached recommended maintenance doses after 4 weeks, while 21% remained on starting doses. At prescription 10, most common doses were 0.5/1 mg subcutaneous semaglutide (44.0%/48.6%), 7/14 mg oral semaglutide (50.2%/36.6%), and 0.75/1.5/3 mg dulaglutide (20.4%/71.5%/6.7%). Faster dose escalation occurred with higher BMI and subcutaneous semaglutide (1 mg at prescription 5: 20.8%/25.9%/33.2% with BMI <30/30-<35/>/=35 kg/m(2)). Additional analyses (e.g., by CVD history) revealed no further heterogeneity. CONCLUSIONS: In UK primary care, GLP-1RA persistence was suboptimal and dose escalation was frequently delayed across all patient stratifications, including individuals with established CVD. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ulrich, Franziska S AU - Ulrich FS AUID- ORCID: 0009-0005-2278-7400 AD - Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland. FAU - Napoli, Nicola AU - Napoli N AUID- ORCID: 0000-0002-3091-8205 AD - Unit of Endocrinology and Diabetes, Campus, Bio-Medico University of Rome, Rome, Italy. AD - Unit of Metabolic Bone and Thyroid Disorders, Fondazione Policlinico Universitario Campus, Bio-Medico University of Rome, Rome, Italy. AD - Division of Bone and Mineral Diseases, Washington University, St Louis, Missouri, USA. FAU - Nielsen, Morten Frost AU - Nielsen MF AUID- ORCID: 0000-0002-5608-1589 AD - Department of Endocrinology, Odense University Hospital, Odense, Denmark. AD - Steno Diabetes Centre Odense, Odense University Hospital, Odense, Denmark. FAU - Burden, Andrea M AU - Burden AM AUID- ORCID: 0000-0001-7082-8530 AD - Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland. AD - Division of Clinical Immunology and Rheumatology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA. LA - eng GR - 24B110/Novartis Foundation for Medical-Biological Research/ PT - Journal Article DEP - 20260217 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United Kingdom/epidemiology MH - Semaglutide MH - *Obesity/complications/epidemiology MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/therapeutic use MH - Middle Aged MH - *Cardiovascular Diseases/epidemiology/complications MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Immunoglobulin Fc Fragments/administration & dosage/therapeutic use MH - *Recombinant Fusion Proteins/administration & dosage/therapeutic use MH - Cohort Studies MH - Adult MH - Dose-Response Relationship, Drug PMC - PMC12992168 OTO - NOTNLM OT - GLP-1 receptor agonist OT - Type 2 diabetes OT - United Kingdom OT - cardiovascular disease OT - dose titration OT - drug utilisation OT - glucose-lowering therapy OT - obesity OT - primary care OT - real-world evidence OT - treatment discontinuation COIS- The authors declare no conflicts of interest. EDAT- 2026/02/18 10:06 MHDA- 2026/03/17 06:47 PMCR- 2026/03/17 CRDT- 2026/02/18 00:53 PHST- 2026/01/22 00:00 [revised] PHST- 2025/11/24 00:00 [received] PHST- 2026/01/24 00:00 [accepted] PHST- 2026/03/17 06:47 [medline] PHST- 2026/02/18 10:06 [pubmed] PHST- 2026/02/18 00:53 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - DOM70535 [pii] AID - 10.1111/dom.70535 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):3386-3395. doi: 10.1111/dom.70535. Epub 2026 Feb 17. PMID- 41703411 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260727 IS - 1558-2035 (Electronic) IS - 1558-2027 (Linking) VI - 27 IP - 2 DP - 2026 Feb 1 TI - Use of semaglutide after acute coronary syndrome: an exploratory retrospective study. PG - 144-150 LID - 10.2459/JCM.0000000000001837 [doi] AB - AIMS: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated cardiovascular benefit in patients with type 2 diabetes mellitus (T2DM) and established atherosclerotic disease. Its role in the immediate postacute coronary syndrome (ACS) setting, however, remains unexplored. This study evaluated the early real-world use of semaglutide prescribed at hospital discharge after ACS. METHODS: We conducted a retrospective, multicenter observational study of adults with T2DM hospitalized for ACS between January 2022 and December 2024 and discharged with a prescription for semaglutide. Baseline demographics, therapies, and ACS features were collected together with follow-up data on treatment persistence, reasons for discontinuation, adverse events, metabolic parameters, and cardiovascular outcomes. RESULTS: A total of 60 patients (mean age 61.1 +/- 10.8 years, 73% male) were included. At discharge, all received semaglutide (83.3% injectable, 16.7% oral) at the lowest dose. At the first follow-up (108 +/- 39 days), 81% remained on therapy; discontinuations occurred mainly for gastrointestinal intolerance (15%). Body weight decreased by 4.7 +/- 1.6 kg, BMI decreased by 1.7 +/- 0.6 kg/m2, and HbA1c improved from 64.3 +/- 18.2 to 49.6 +/- 10.4 mmol/mol. At the second follow-up (278 +/- 60 days, n = 39), 97.4% were still on semaglutide. Additional weight loss (-2.6 +/- 3.8 kg) and further HbA1c reduction (40.5 +/- 18.6 mmol/mol) were observed. No cardiovascular events, renal decline, or pancreatic events were reported. CONCLUSIONS: In this exploratory real-world cohort, initiating semaglutide at hospital discharge after ACS was feasible, well tolerated, and associated with high persistence and early cardiometabolic improvements. CI - Copyright (c) 2026 Italian Federation of Cardiology - I.F.C. All rights reserved. FAU - Biasin, Marco AU - Biasin M AD - Division of Cardiology, Alto Vicentino Hospital - ULSS 7 Veneto, Santorso, Italy. FAU - Stratinaki, Maria AU - Stratinaki M AD - Venizeleio General Hospital, Heraklion, Greece. FAU - Cordioli, Nicolo AU - Cordioli N AD - Division of Cardiology, Department of Medicine, Universita di Verona, Verona, Italy. FAU - Armani, Ilaria AU - Armani I AD - Division of Cardiology, Department of Medicine, Universita di Verona, Verona, Italy. FAU - De Giovanni, Sara AU - De Giovanni S AD - Division of Cardiology, Department of Medicine, Universita di Verona, Verona, Italy. FAU - Aletras, George AU - Aletras G AD - Venizeleio General Hospital, Heraklion, Greece. FAU - Betta, Davide AU - Betta D AD - Division of Cardiology, Alto Vicentino Hospital - ULSS 7 Veneto, Santorso, Italy. FAU - Callegarin, Luca AU - Callegarin L AD - Division of Cardiology, Alto Vicentino Hospital - ULSS 7 Veneto, Santorso, Italy. FAU - Gambaro, Alessia AU - Gambaro A AD - Division of Cardiology, Department of Medicine, Universita di Verona, Verona, Italy. FAU - Morani, Giovanni AU - Morani G AD - Division of Cardiology, Alto Vicentino Hospital - ULSS 7 Veneto, Santorso, Italy. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260119 PL - United States TA - J Cardiovasc Med (Hagerstown) JT - Journal of cardiovascular medicine (Hagerstown, Md.) JID - 101259752 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - *Acute Coronary Syndrome/drug therapy/diagnosis MH - Retrospective Studies MH - Male MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Aged MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Time Factors MH - Blood Glucose/drug effects/metabolism OTO - NOTNLM OT - acute coronary syndrome OT - cardiometabolic risk OT - glucagon-like peptide-1 receptor agonists OT - secondary prevention OT - semaglutide OT - type 2 diabetes mellitus EDAT- 2026/02/18 00:49 MHDA- 2026/02/18 00:50 CRDT- 2026/02/17 23:36 PHST- 2025/09/21 00:00 [received] PHST- 2025/12/19 00:00 [accepted] PHST- 2026/02/18 00:50 [medline] PHST- 2026/02/18 00:49 [pubmed] PHST- 2026/02/17 23:36 [entrez] AID - 01244665-202602000-00009 [pii] AID - 10.2459/JCM.0000000000001837 [doi] PST - ppublish SO - J Cardiovasc Med (Hagerstown). 2026 Feb 1;27(2):144-150. doi: 10.2459/JCM.0000000000001837. Epub 2026 Jan 19. PMID- 41697744 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 136 IP - 4 DP - 2026 Feb 16 TI - GLP-1 and the cardiovascular system. LID - 10.1172/JCI194748 [doi] LID - e194748 AB - The incretin hormone glucagon-like peptide-1 (GLP-1) exerts potent effects on glucose metabolism, prompting the development of therapeutic strategies that enhance activity of the GLP-1 receptor (GLP-1R) pathway. Inhibitors of dipeptidyl peptidase 4 (DPP-4) prolong the half-life of endogenous GLP-1 and typically achieve reductions in HbA1c of 0.5%-0.8%. However, large-scale cardiovascular (CV) outcomes trials (CVOTs) with DPP-4 inhibitors demonstrated CV safety but did not show a reduction in CV events. A second incretin-based therapeutic approach was the development of GLP-1R agonists (GLP-1RAs). Various GLP-1RAs, including liraglutide, semaglutide, and dulaglutide, demonstrated a reduction in CV outcomes in large CVOTs. Initially, these medications were only available as injectable agents for subcutaneous administration, but recent technological advancements have enabled the development of orally available GLP-1RAs. A third incretin-based approach is tirzepatide, a dual agonist of GLP-1R and glucose-dependent insulinotropic polypeptide receptor (GIPR), which achieves greater HbA1c reduction and weight loss compared with GLP-1RAs alone. Ongoing large-scale CVOTs will determine its effects on hard cardiovascular endpoints. This Review summarizes the effects of GLP-1 and GLP-1RAs in the CV system as well as clinical data of GLP-1RAs in individuals with CV disease or high CV risk. FAU - Kahles, Florian AU - Kahles F AD - Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen, Aachen, Germany. FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AD - German Center for Diabetes Research (DZD), Neuherberg, Germany. AD - Department of Internal Medicine IV, Diabetology, Endocrinology and Nephrology, Eberhard-Karls University Tubingen, Tubingen, Germany. AD - Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich, Tubingen, Germany. AD - School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences and Medicine, Kings College London, London, United Kingdom. FAU - Marx, Nikolaus AU - Marx N AD - Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen, Aachen, Germany. LA - eng PT - Journal Article PT - Review DEP - 20260216 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (GLP1R protein, human) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/metabolism MH - *Cardiovascular Diseases/drug therapy/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Semaglutide MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Tirzepatide MH - *Cardiovascular System/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC12904707 COIS- Conflict of interest: NM has given lectures for Bayer, Boehringer Ingelheim, Sanofi- EDAT- 2026/02/16 12:32 MHDA- 2026/02/16 18:34 PMCR- 2026/02/16 CRDT- 2026/02/16 11:52 PHST- 2026/02/16 18:34 [medline] PHST- 2026/02/16 12:32 [pubmed] PHST- 2026/02/16 11:52 [entrez] PHST- 2026/02/16 00:00 [pmc-release] AID - 194748 [pii] AID - 10.1172/JCI194748 [doi] PST - epublish SO - J Clin Invest. 2026 Feb 16;136(4):e194748. doi: 10.1172/JCI194748. eCollection 2026 Feb 16. PMID- 41692115 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260730 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 133 IP - 6 DP - 2026 Jun TI - Semaglutide and the Risk of Nonarteritic Ischemic Optic Neuropathy: A Systematic Review and Certainty of Evidence Meta-Analysis. PG - 799-810 LID - S0161-6420(26)00082-5 [pii] LID - 10.1016/j.ophtha.2026.02.013 [doi] AB - TOPIC: This systematic review and meta-analysis evaluates whether semaglutide use, compared with non-glucagon-like peptide-1 receptor agonist (GLP-1 RA) receptor agonist therapies, is associated with nonarteritic anterior ischemic optic neuropathy (NAION). CLINICAL RELEVANCE: Nonarteritic anterior ischemic optic neuropathy is a rare, vision-threatening optic neuropathy whose major risk factors overlap with populations prescribed semaglutide, making clarification of any associated risk clinically important for treatment decisions and patient counseling. METHODS: This systematic review and meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was prospectively registered (PROSPERO CRD420251107346). Seven databases and Google Scholar were searched from inception to August 20, 2025. Eligible studies enrolled adults, compared semaglutide with non-GLP-1 RA users, and reported NAION as a distinct outcome with extractable odds ratios (ORs) or adjusted hazard ratios (aHRs). Two reviewers independently performed study selection, data extraction, and Newcastle-Ottawa risk of bias assessment. Random-effects models pooled ORs and aHRs. Prespecified subgroup analyses examined treatment indication. Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Six observational studies (n = 4 831 654) met inclusion. In pooled OR analyses, semaglutide was not associated with a statistically significant increase in NAION compared with non-GLP-1 RA comparators (OR = 2.44; 95% confidence interval [CI], 0.59-10.15; I(2) = 99.34%; very low certainty). Time-stratified ORs at 1 to 3 years were likewise nonsignificant (very low certainty). Compared with SGLT2 inhibitors, the pooled OR was 0.72 (95% CI, 0.38-1.35; I(2) = 81.59%; very low certainty). In adjusted time-to-event analyses, the pooled aHR was 1.63 (95% CI, 0.88-2.39; I(2) = 67.15%; low certainty). Exclusion of 1 influential study shifted the estimate (aHR = 1.92; 95% CI, 1.03-2.81; low certainty), indicating fragility. By indication, pooled aHRs were 1.70 (95% CI, 1.10-2.64; low certainty) for type 2 diabetes and 0.47 (95% CI, 0.19-1.13; moderate certainty) for obesity/overweight. Time-stratified aHRs were insufficient for meta-analysis. CONCLUSION: Across observational studies comparing semaglutide with non-GLP-1 RA therapies, pooled adjusted evidence does not demonstrate a consistent overall increase in NAION risk. However, estimates are limited by substantial heterogeneity, residual confounding, outcome misclassification, and fragility, resulting in low to very low certainty. Apparent indication-based differences should be interpreted cautiously and may reflect underlying disease-related risk rather than a drug-specific effect. Causality cannot be established, and further well-designed studies with standardized NAION ascertainment are needed. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2026 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Abdelaal, Abdelaziz AU - Abdelaal A AD - Clinical Research Scholar, Harvard Medical School, Boston, Massachusetts; Faculty of Medicine, Tanta University, Tanta, Egypt. FAU - Abu Serhan, Hashem AU - Abu Serhan H AD - Department of Ophthalmology, Hamad Medical Corporation, Doha, Qatar. FAU - Alsaadi, Mustafa AU - Alsaadi M AD - Jabir Ibn Hayyan University for Medical and Pharmaceutical Sciences, Kufa, Iraq. FAU - Yaldo, Luke AU - Yaldo L AD - Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. FAU - Gaier, Eric D AU - Gaier ED AD - Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Picower Institute of Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts. FAU - Elhusseiny, Abdelrahman M AU - Elhusseiny AM AD - Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida; Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Ophthalmology, Harvey and Bernice Jones Eye Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas. Electronic address: amelhusseiny@uams.edu. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260213 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Semaglutide MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 OT - NAION OT - Nonarteritic OT - Optic neuropathy OT - Semaglutide EDAT- 2026/02/16 00:31 MHDA- 2026/05/22 00:33 CRDT- 2026/02/15 19:30 PHST- 2025/08/29 00:00 [received] PHST- 2026/02/04 00:00 [revised] PHST- 2026/02/05 00:00 [accepted] PHST- 2026/05/22 00:33 [medline] PHST- 2026/02/16 00:31 [pubmed] PHST- 2026/02/15 19:30 [entrez] AID - S0161-6420(26)00082-5 [pii] AID - 10.1016/j.ophtha.2026.02.013 [doi] PST - ppublish SO - Ophthalmology. 2026 Jun;133(6):799-810. doi: 10.1016/j.ophtha.2026.02.013. Epub 2026 Feb 13. PMID- 41683613 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260707 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 3 DP - 2026 Jan 24 TI - Semaglutide-Mediated Remodeling of Adipose Tissue in Type 2 Diabetes: Molecular Mechanisms Beyond Glycemic Control. LID - 10.3390/ijms27031186 [doi] LID - 1186 AB - Type 2 diabetes mellitus (T2DM) is characterized not only by chronic hyperglycemia but also by profound adipose tissue dysfunction, including impaired lipid handling, low-grade inflammation, mitochondrial dysfunction, and extracellular matrix (ECM) remodeling. These adipose tissue alterations play a central role in the development of systemic insulin resistance, ectopic lipid accumulation, and cardiometabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, have emerged as highly effective therapies for T2DM and obesity. While their glucose-lowering and appetite-suppressive effects are well established, accumulating evidence indicates that semaglutide exerts pleiotropic metabolic actions that extend beyond glycemic control, with adipose tissue representing a key target organ. This review synthesizes current preclinical and clinical evidence on the molecular and cellular mechanisms through which semaglutide modulates adipose tissue biology in T2DM. We discuss depot-specific effects on visceral and subcutaneous adipose tissue, regulation of adipocyte lipid metabolism and lipolysis, enhancement of mitochondrial biogenesis and oxidative capacity, induction of beige adipocyte programming, modulation of adipokine and cytokine secretion, immunometabolic remodeling, and attenuation of adipose tissue fibrosis and ECM stiffness. Collectively, available data indicate that semaglutide promotes a functional shift in adipose tissue from a pro-inflammatory, lipid-storing phenotype toward a more oxidative, insulin-sensitive, and metabolically flexible state. These adipose-centered adaptations likely contribute to improvements in systemic insulin sensitivity, reduction in ectopic fat deposition, and attenuation of cardiometabolic risk observed in patients with T2DM. Despite compelling mechanistic insights, much of the current evidence derives from animal models or in vitro systems. Human adipose tissue-focused studies integrating molecular profiling, advanced imaging, and longitudinal clinical data are therefore needed to fully elucidate the extra-glycemic actions of semaglutide and to translate these findings into adipose-targeted therapeutic strategies. FAU - Abel, Tatjana AU - Abel T AD - Department of Dietetics and Nutritional Sciences, Faculty of Health Sciences, Semmelweis University, 1088 Budapest, Hungary. FAU - Csobod Csajbokne, Eva AU - Csobod Csajbokne E AD - Department of Dietetics and Nutritional Sciences, Faculty of Health Sciences, Semmelweis University, 1088 Budapest, Hungary. LA - eng PT - Journal Article PT - Review DEP - 20260124 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy/pathology MH - *Glucagon-Like Peptides/pharmacology/therapeutic use/metabolism MH - *Adipose Tissue/metabolism/drug effects/pathology MH - Animals MH - Glycemic Control MH - Lipid Metabolism/drug effects MH - Insulin Resistance PMC - PMC12898281 OTO - NOTNLM OT - GLP-1 receptor agonist OT - adipose tissue remodeling OT - beige adipocytes OT - extracellular matrix remodeling OT - immunometabolism OT - mitochondrial biogenesis OT - semaglutide OT - type 2 diabetes mellitus OT - visceral adiposity COIS- The authors declare no conflicts of interest. EDAT- 2026/02/13 06:32 MHDA- 2026/02/13 06:33 PMCR- 2026/01/24 CRDT- 2026/02/13 01:09 PHST- 2025/12/18 00:00 [received] PHST- 2026/01/19 00:00 [revised] PHST- 2026/01/20 00:00 [accepted] PHST- 2026/02/13 06:33 [medline] PHST- 2026/02/13 06:32 [pubmed] PHST- 2026/02/13 01:09 [entrez] PHST- 2026/01/24 00:00 [pmc-release] AID - ijms27031186 [pii] AID - ijms-27-01186 [pii] AID - 10.3390/ijms27031186 [doi] PST - epublish SO - Int J Mol Sci. 2026 Jan 24;27(3):1186. doi: 10.3390/ijms27031186. PMID- 41678180 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260910 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 144 IP - 3 DP - 2026 Mar 1 TI - New-Onset Nonarteritic Anterior Ischemic Optic Neuropathy and Initiators of Semaglutide in US Veterans With Type 2 Diabetes. PG - 259-264 LID - 10.1001/jamaophthalmol.2025.6262 [doi] AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are considered safe, effective medications for type 2 diabetes (T2D) and weight loss, used by millions worldwide. While their cardiometabolic benefits are well established, emerging observations suggest a potential association between GLP-1RA use and new-onset nonarteritic anterior ischemic optic neuropathy (NAION). OBJECTIVE: To emulate a target trial evaluating the risk of NAION associated with initiation of semaglutide (GLP-1RA), compared with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) as second-line therapy for T2D in a nationwide cohort of US veterans. DESIGN, SETTING, AND PARTICIPANTS: This study was conducted nationwide using data from the Veterans Health Administration health care system between March 1, 2018, and March 1, 2025. This active-comparator, new-user, target trial emulation used cause-specific hazard ratios (HRs) that were estimated using overlap weighting to account for confounding. Participants included US veterans with T2D, current metformin use, and no prior GLP-1RA or SGLT2i use. Data analysis was conducted from July 2025 through September 2025. EXPOSURE: Initiation of semaglutide or any SGLT2i. MAIN OUTCOME AND MEASURE: Incident NAION, identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and Systematized Nomenclature of Medicine codes. RESULTS: A total of 102 361 US veterans met inclusion criteria, including 11 478 initiators of semaglutide and 90 883 initiators of an SGLT2i. Baseline characteristics were well balanced between treatment groups after overlap weighting (mean [SD] age, 60.1 [11.7] years; body mass index, 37.8 [6.7]; hemoglobin A1c, 7.0% [1.4]; 85.5% male and 14.5% female; 20.7% Black, 8.1% Hispanic, and 61.9% non-Hispanic White). Over a maximum follow-up of 7.5 years, 173 total incident NAION events occurred. The incidence rate of NAION was 123 per 100 000 person-years among semaglutide initiators and 67 per 100 000 person-years among SGLT2i. In 2.1 years of median follow-up, semaglutide initiators had a 2.33-fold higher risk than SGLT2i initiators (hazard ratio, 2.33; 95% CI, 1.54-3.54; P < .001). The overlap weighted incidence rate of NAION was 0.29% for semaglutide initiators and 0.13% for SGLT2i initiators, with a corresponding average treatment effect of 0.16 percentage points. CONCLUSIONS AND RELEVANCE: In this nationwide cohort of US veterans with T2D, semaglutide initiators had a 2-fold NAION risk than SGLT2i initiators, while the absolute risk was low. Clinicians and patients should be counseled on the rare but evident increased risk of NAION after semaglutide initiation. FAU - Heberer, Kent AU - Heberer K AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. FAU - Bress, Adam P AU - Bress AP AD - VA Salt Lake City Healthcare System, Salt Lake City, Utah. AD - Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City. FAU - Cogill, Steven AU - Cogill S AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. FAU - Maldonado, Ana I AU - Maldonado AI AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. FAU - Kim, Sun H AU - Kim SH AD - Division of Endocrinology, Gerontology, and Metabolism, Department of Medicine, Stanford University School of Medicine, Stanford, California. FAU - Nallamshetty, Shriram AU - Nallamshetty S AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - Division of Cardiovascular Medicine, Stanford School of Medicine, Stanford, California. FAU - Chen, Ying Q AU - Chen YQ AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. AD - Stanford Prevention Research Center, Department of Medicine, Stanford University, Stanford, California. FAU - Shih, Mei-Chiung AU - Shih MC AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. AD - Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, California. FAU - Lynch, Julie A AU - Lynch JA AD - VA Salt Lake City Healthcare System, Salt Lake City, Utah. AD - Division of Epidemiology, School of Medicine, University of Utah, Salt Lake City. FAU - Lee, Jennifer S AU - Lee JS AD - VA Palo Alto Healthcare System, Palo Alto, California. AD - VA Palo Alto Cooperative Studies Program Coordinating Center, Palo Alto, California. AD - Division of Endocrinology, Gerontology, and Metabolism, Department of Medicine, Stanford University School of Medicine, Stanford, California. LA - eng PT - Journal Article PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM EIN - JAMA Ophthalmol. 2026 Jun 1;144(6):571. doi: 10.1001/jamaophthalmol.2026.1060. PMID: 41954895 MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Male MH - Female MH - United States/epidemiology MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Veterans/statistics & numerical data MH - Aged MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced/diagnosis MH - Incidence MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects PMC - PMC12902922 COIS- Conflict of Interest Disclosures: Dr Kim reported personal fees from TeCure Consulting outside the submitted work. Dr Nallamshetty reported grants from Novartis outside the submitted work. Dr Lynch reported grants from the US Department of Veterans Affairs during the conduct of the study and grants from Alnylam, AstraZeneca, Biodesix, Celgene, Janssen, and Novartis through the University of Utah or Western Institute for Veteran Research outside the submitted work. No other disclosures were reported. EDAT- 2026/02/12 12:49 MHDA- 2026/03/19 15:13 PMCR- 2026/02/12 CRDT- 2026/02/12 11:33 PHST- 2026/03/19 15:13 [medline] PHST- 2026/02/12 12:49 [pubmed] PHST- 2026/02/12 11:33 [entrez] PHST- 2026/02/12 00:00 [pmc-release] AID - 2844873 [pii] AID - ebr250010 [pii] AID - 10.1001/jamaophthalmol.2025.6262 [doi] PST - ppublish SO - JAMA Ophthalmol. 2026 Mar 1;144(3):259-264. doi: 10.1001/jamaophthalmol.2025.6262. PMID- 41678136 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 43 IP - 4 DP - 2026 Apr TI - Psychometric Validation of the Simplicity of Diabetes Treatment Questionnaire (Sim-Q) for Type 2 Diabetes. PG - 1521-1535 LID - 10.1007/s12325-025-03448-5 [doi] AB - INTRODUCTION: Over the past 2 decades, treatment for type 2 diabetes (T2D) has evolved with the introduction of medications that offer greater simplicity. The Simplicity of Diabetes Treatment Questionnaire (Sim-Q) was developed to assess the simplicity or complexity of treatment for T2D. This study assessed the psychometric properties of the Sim-Q. METHODS: Eight clinical sites in the USA recruited participants treated for T2D with a variety of medications, including oral medications, insulin, glucagon-like peptide 1 (GLP-1) receptor agonists, and a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist. Psychometric analysis of the Sim-Q focused on item performance, item selection, exploratory factor analysis (EFA), reliability (internal consistency and test-retest), and validity (construct and known-groups). RESULTS: The study included 250 participants (mean age 59.7 years; 54.4% female). On the basis of item performance and EFA, eight items were retained for the Simplicity of Diabetes Management Subscale assessing simplicity of treatment attributes. Two global items assessing simplicity of medication for diabetes and simplicity of overall diabetes management were scored separately. The Simplicity of Diabetes Management Subscale had good internal consistency reliability (Cronbach's alpha 0.90). The Simplicity of Diabetes Management Subscale and two global items had acceptable test-retest reliability (intraclass correlation coefficients 0.80, 0.72, and 0.73). Convergent validity was supported by significant correlations (P < 0.0001) with related measures. The Sim-Q distinguished between groups of participants who differed in their satisfaction with the ease and convenience of their treatment. For example, the two global items differentiated between groups receiving different treatments (tirzepatide and injectable semaglutide). CONCLUSION: The Sim-Q demonstrated good reliability and validity in this psychometric study. This measure may be useful for assessing individuals' perceptions of treatment simplicity in clinical trials and clinical practice. CI - (c) 2026. The Author(s). FAU - Boye, Kristina S AU - Boye KS AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. Boye_Kristina_Secnik@lilly.com. FAU - Cutts, Katelyn N AU - Cutts KN AD - PPD Evidera Patient-Centered Research, Thermo Fisher Scientific, Waltham, MA, USA. FAU - Coyne, Karin S AU - Coyne KS AD - PPD Evidera Patient-Centered Research, Thermo Fisher Scientific, Waltham, MA, USA. FAU - Matza, Louis S AU - Matza LS AD - PPD Evidera Patient-Centered Research, Thermo Fisher Scientific, Waltham, MA, USA. LA - eng PT - Journal Article PT - Multicenter Study PT - Validation Study DEP - 20260212 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Psychometrics MH - Middle Aged MH - Reproducibility of Results MH - Male MH - Surveys and Questionnaires/standards MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Factor Analysis, Statistical MH - Insulin/therapeutic use PMC - PMC13065586 OTO - NOTNLM OT - Diabetes OT - Ease of use OT - Patient experience OT - Patient-reported outcomes OT - Psychometric validation OT - Sim-Q OT - Simplicity of Diabetes Treatment Questionnaire OT - Treatment simplicity OT - Type 2 diabetes COIS- Declarations. Conflict of Interest: Kristina Boye is employed by and owns shares in Eli Lilly and Company. Louis Matza, Katelyn Cutts, and Karin Coyne are employed by Thermo Fisher Scientific, which received funding from Lilly for the time spent conducting this research. Ethical Approval: All study methods and materials, as well as all eight clinical sites participating in the study, were approved by an independent review board (Salus Institutional Review Board study number 23069). The study was performed according to the Helsinki Declaration of 1964 and its later amendments. Participants provided informed consent before completing any study measures and were remunerated for their time. The consent form informed participants that their data may be published, but they would not be personally identified in any publications. EDAT- 2026/02/12 12:49 MHDA- 2026/04/09 12:45 PMCR- 2026/02/12 CRDT- 2026/02/12 11:22 PHST- 2025/09/01 00:00 [received] PHST- 2025/11/20 00:00 [accepted] PHST- 2026/04/09 12:45 [medline] PHST- 2026/02/12 12:49 [pubmed] PHST- 2026/02/12 11:22 [entrez] PHST- 2026/02/12 00:00 [pmc-release] AID - 10.1007/s12325-025-03448-5 [pii] AID - 3448 [pii] AID - 10.1007/s12325-025-03448-5 [doi] PST - ppublish SO - Adv Ther. 2026 Apr;43(4):1521-1535. doi: 10.1007/s12325-025-03448-5. Epub 2026 Feb 12. PMID- 41677473 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 2767-9764 (Electronic) IS - 2767-9764 (Linking) VI - 6 IP - 3 DP - 2026 Mar 1 TI - Weight Loss Patterns and Clinical Outcomes of GLP1 Receptor Agonists in Breast Cancer Survivors. PG - 447-455 LID - 10.1158/2767-9764.CRC-25-0554 [doi] AB - The use of glucagon-like peptide-1 receptor agonists (GLP1-RA) for weight loss is increasing; implications in breast cancer survivors remain unclear. This retrospective cohort study evaluated treatment patterns, weight loss, and outcomes in breast cancer survivors receiving GLP1-RA at an academic institution. We evaluated patients with nonmetastatic [ductal carcinoma in situ (DCIS), stage 1-3] breast cancer who received GLP1-RA (2005-2024). Linear regression models estimated associations between weight change and clinical factors. After excluding DCIS, propensity score matching (1:2) was used to match patients who received GLP1-RA with patients who did not, based on confounding covariates. Kaplan-Meier estimates and log-rank tests compared disease-free survival (DFS) and overall survival (OS) between GLP1-RA users versus nonusers in the subgroup with invasive disease. We identified 1,022 patients; 79% had type 2 diabetes mellitus. The median weight and body mass index at GLP1-RA initiation were 86.8 kg (47.2-175 kg) and 33.5 kg/m2 (18.9-61.8 kg/m2). In semaglutide or tirzepatide users (442, 43.2%), the median weight change at 3, 6, and 12 months after GLP1-RA initiation was -1.9% (-13.2% to 14.9%), -3.1% (-20.2% to 19%), and -2.6% (-27.8% to 11.5%), respectively. Endocrine therapy and metformin use were associated with weight gain and loss, respectively; invasive disease stage was linked to greater weight loss. GLP1-RA was not associated with DFS, but OS significantly differed between GLP1-RA users (n = 810) and nonusers (n = 1,620; hazard ratio, 0.37; 95% confidence interval, 0.27-0.53; P < 0.0001). In conclusion, in this real-world study in breast cancer survivors, GLP1-RA was associated with modest weight loss and improved all-cause survival. Clinical trials are warranted to study GLP1-RA in this population. SIGNIFICANCE: This is the largest study describing real-world patterns of GLP1 receptor agonists in breast cancer survivors. Clinical trials should evaluate these agents for weight management as an adjunct to lifestyle interventions and the potential role in cancer control in breast cancer survivors. CI - (c)2026 The Authors; Published by the American Association for Cancer Research. FAU - Sukumar, Jasmine S AU - Sukumar JS AUID- ORCID: 0000-0001-6994-8527 AD - Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Raghavendra, Akshara S AU - Raghavendra AS AUID- ORCID: 0000-0002-6425-4400 AD - Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Pasyar, Sarah AU - Pasyar S AUID- ORCID: 0000-0003-4914-0728 AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Bassett, Roland L AU - Bassett RL AUID- ORCID: 0000-0002-4534-2042 AD - Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Tripathy, Debu AU - Tripathy D AUID- ORCID: 0000-0002-5711-2404 AD - Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Barcenas, Carlos H AU - Barcenas CH AUID- ORCID: 0000-0001-5377-9167 AD - Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Basen-Engquist, Karen M AU - Basen-Engquist KM AUID- ORCID: 0000-0001-7299-0646 AD - Department of Health Disparities Research, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Arun, Banu K AU - Arun BK AUID- ORCID: 0000-0002-5475-8509 AD - Division of Cancer Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. LA - eng GR - K12 AR084228/AR/NIAMS NIH HHS/United States GR - University Cancer Foundation via the Institutional Research Grant at MD Anderson Cancer Center/ GR - NIH/NCI P30 CA016672/University of Texas MD Anderson Cancer Center (MD Anderson)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Cancer Res Commun JT - Cancer research communications JID - 9918281580506676 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Female MH - *Breast Neoplasms/drug therapy/mortality/pathology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Weight Loss/drug effects MH - Retrospective Studies MH - Middle Aged MH - *Cancer Survivors/statistics & numerical data MH - Semaglutide MH - Aged MH - Tirzepatide MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Adult PMC - PMC13043164 COIS- No disclosures were reported. EDAT- 2026/02/12 12:49 MHDA- 2026/03/07 06:38 PMCR- 2026/03/02 CRDT- 2026/02/12 10:23 PHST- 2025/10/27 00:00 [received] PHST- 2025/12/08 00:00 [revised] PHST- 2026/02/10 00:00 [accepted] PHST- 2026/03/07 06:38 [medline] PHST- 2026/02/12 12:49 [pubmed] PHST- 2026/02/12 10:23 [entrez] PHST- 2026/03/02 00:00 [pmc-release] AID - 774517 [pii] AID - CRC-25-0554 [pii] AID - 10.1158/2767-9764.CRC-25-0554 [doi] PST - ppublish SO - Cancer Res Commun. 2026 Mar 1;6(3):447-455. doi: 10.1158/2767-9764.CRC-25-0554. PMID- 41670332 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1532-6535 (Electronic) IS - 0009-9236 (Print) IS - 0009-9236 (Linking) VI - 119 IP - 5 DP - 2026 May TI - Maternal-to-Infant Transfer of Medications for Type 2 Diabetes Mellitus Via Breastmilk: A Systematic Review of Available Evidence and Clinical Guidelines. PG - 1223-1234 LID - 10.1002/cpt.70211 [doi] AB - This review evaluates the available pharmacokinetic data on the plasma-to-breastmilk transfer of first- and second-line T2DM drugs against available clinical guideline recommendations. A list of drug therapies for treating T2DM was generated from national and international clinical guidelines. A systematic search of research articles reporting human plasma and breastmilk drug concentrations was conducted in Scopus, PubMed, Google Scholar, and LactMed(R) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies evaluating breastmilk drug transfer in T2DM, with fully accessible abstract and main text reported in English, were included. Study quality was evaluated using the ClinPK checklist. Authors evaluated clinical guideline recommendations on the use of T2DM drugs in lactation and the basis upon which such recommendations were made. Only 5 out of 20 drugs (metformin, glyburide, glipizide, tolbutamide, and semaglutide) have clinical data on plasma-to-breastmilk transfer. Metformin and tolbutamide were detectable in maternal plasma and breastmilk. Half (51.7%) of guideline recommendations provide explicit guidance. Only 4.4% of recommendations were based on clinical evidence. Over half (57.8%) of recommendations were accessible online, and most guideline recommendations (78%) were against the use of antiglycemic agents while breastfeeding. The scarce clinical evidence to guide T2DM drug therapy during breastfeeding available has several design and methodological limitations. Published recommendations remain largely inconsistent, thus perpetuating uncertainty in the use of T2DM drug therapies in lactation. Addressing knowledge gaps is critical in developing clinical consensus to optimize T2DM drug therapy among breastfeeding mothers. CI - (c) 2026 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Richardson, Katherine AU - Richardson K AUID- ORCID: 0009-0007-3491-1514 AD - School of Medicine, University of Liverpool, Liverpool, UK. FAU - Kiptoo, Joshua AU - Kiptoo J AUID- ORCID: 0000-0001-8077-6666 AD - Infectious Diseases Institute, Makerere University, Kampala, Uganda. AD - Department of Pharmacy, Faculty of Medicine, Mbarara University of Science & Technology, Mbarara, Uganda. FAU - Mpora Odongkara, Beatrice AU - Mpora Odongkara B AUID- ORCID: 0000-0002-6283-9114 AD - Department of Pediatrics & Child Health, Faculty of Medicine, Gulu University, Gulu, Uganda. FAU - Ojara, Francis Williams AU - Ojara FW AUID- ORCID: 0000-0002-6425-6828 AD - Infectious Diseases Institute, Makerere University, Kampala, Uganda. AD - Department of Pharmacology and Therapeutics, Faculty of Medicine, Gulu University, Gulu, Uganda. FAU - Waitt, Catriona AU - Waitt C AUID- ORCID: 0000-0003-0134-5855 AD - Infectious Diseases Institute, Makerere University, Kampala, Uganda. AD - Department of Women's and Children's Health, School of Medicine, University of Liverpool, Liverpool, UK. LA - eng GR - 222075/Z/20/Z/Wellcome Clinical Research Career Development Fellowship/ GR - NIHR304266/NIHR Global Health Research Professorship/ GR - INV052005/GATES/Gates Foundation/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20260211 PL - United States TA - Clin Pharmacol Ther JT - Clinical pharmacology and therapeutics JID - 0372741 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Milk, Human/metabolism/chemistry MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Female MH - *Hypoglycemic Agents/pharmacokinetics/therapeutic use MH - Practice Guidelines as Topic MH - Lactation/metabolism MH - Pregnancy MH - Breast Feeding MH - Infant, Newborn PMC - PMC13083373 COIS- The authors declare no conflicts of interest. EDAT- 2026/02/11 13:08 MHDA- 2026/04/17 04:10 PMCR- 2026/02/11 CRDT- 2026/02/11 08:53 PHST- 2025/07/25 00:00 [received] PHST- 2026/01/05 00:00 [accepted] PHST- 2026/04/17 04:10 [medline] PHST- 2026/02/11 13:08 [pubmed] PHST- 2026/02/11 08:53 [entrez] PHST- 2026/02/11 00:00 [pmc-release] AID - CPT70211 [pii] AID - 10.1002/cpt.70211 [doi] PST - ppublish SO - Clin Pharmacol Ther. 2026 May;119(5):1223-1234. doi: 10.1002/cpt.70211. Epub 2026 Feb 11. PMID- 41668679 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 Suppl 2 IP - Suppl 2 DP - 2026 Apr TI - Providing holistic care for patients with metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis: Key aspects of clinical assessment and how to develop individualised care plans for surveillance and interventions. PG - 46-62 LID - 10.1111/dom.70545 [doi] AB - Metabolic dysfunction-associated steatotic liver disease (MASLD), characterised by hepatic steatosis and metabolic dysfunction (i.e., obesity, type 2 diabetes, dyslipidaemia, and hypertension), is affecting over 30% of the adult population worldwide. It can progress to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis, cirrhosis and even hepatocellular carcinoma. However, most patients with non-cirrhotic MASLD die from extrahepatic causes, particularly cardiovascular disease and non-hepatic cancers, underscoring the need for a holistic approach to surveillance and treatment. Emerging research on MASLD has revealed a substantial heterogeneity in the MASLD population, driven by sex-specific factors, genetic susceptibility, cardiometabolic risk profile, lifestyle and socio-economic determinants, highlighting the necessity of individualised and holistic management of MASLD patients. Although lifestyle intervention remains the cornerstone of MASLD, the pharmacotherapeutic landscape is rapidly evolving, with resmetirom and semaglutide now approved for non-cirrhotic MASH with moderate-to-advanced fibrosis. In addition, metabolic/bariatric surgery has proven to be a highly effective option for patients with MASH. Given its close association with cardiometabolic and malignant comorbidities, MASLD requires individualised, holistic management integrating hepatic and extrahepatic risks. Multiprofessional care, involving among others behavioural therapists, dieticians and physiotherapists, may improve outcomes of lifestyle interventions, particularly in high-risk settings. A stepwise and integrated care model combining early case-finding, risk stratification, and tailored lifestyle and pharmacological interventions is essential to address both hepatic and extrahepatic complications. This review summarises the current understanding of MASLD heterogeneity, clinical assessment, and therapeutic advances, and outlines principles for individualised and coordinated care. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Chen, Lanlan AU - Chen L AUID- ORCID: 0000-0002-1075-5592 AD - Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charite Mitte (CCM), Charite - Universitatsmedizin Berlin, Berlin, Germany. AD - Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, the First Hospital of Jilin University, Changchun, China. FAU - Horn, Paul AU - Horn P AD - Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charite Mitte (CCM), Charite - Universitatsmedizin Berlin, Berlin, Germany. AD - BIH Biomedical Innovation Academy, BIH Charite Digital Clinician Scientist Program, Berlin Institute of Health at Charite - Universitatsmedizin Berlin, Berlin, Germany. FAU - Tacke, Frank AU - Tacke F AD - Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum (CVK) and Campus Charite Mitte (CCM), Charite - Universitatsmedizin Berlin, Berlin, Germany. LA - eng GR - DFGCRC/TRR412(Project-ID535081457)/Deutsche Forschungsgemeinschaft/ GR - SFB1382(Project-ID403224013)/Deutsche Forschungsgemeinschaft/ GR - EXC3118/1(projectnumber533770413)/Germany's Excellence Strategy/ PT - Journal Article PT - Review DEP - 20260211 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 SB - IM MH - Humans MH - *Non-alcoholic Fatty Liver Disease/therapy/diagnosis MH - *Holistic Health MH - *Fatty Liver/therapy/diagnosis MH - Precision Medicine/methods MH - Diabetes Mellitus, Type 2/complications/therapy MH - Patient Care Planning MH - Bariatric Surgery MH - Obesity/therapy/complications MH - *Metabolic Diseases/therapy/complications MH - Life Style PMC - PMC13094696 OAB - Metabolic dysfunction-associated steatotic liver disease (MASLD) is among the most common liver diseases worldwide, affecting over 30% of the adult population. It is characterised by excessive lipid accumulation in the liver along with cardiometabolic risk factors such as obesity, type 2 diabetes, abnormal serum glucose, abnormal serum lipids, or high blood pressure. If left untreated, MASLD can progress to liver inflammation, fibrosis, cirrhosis, and liver cancer. Yet, most people with early MASLD do not die from liver-related events, but from cardiovascular diseases or cancers outside the liver, showing that MASLD affects the whole body rather than just the liver. MASLD develops differently from person to person, and many factors (e.g., sex, genetics, lifestyle, socio-economic conditions) play important roles as they impact on the liver, heart, kidney, and other organs. This means that healthcare in individuals with MASLD should be holistic, considering liver disease and extrahepatic risk factors alike. A simple stepwise case-finding algorithm helps to identify patients at risk in primary care, and appropriate risk stratification can pave the way for individualised management. Healthy lifestyle modification remains the foundation of treatment. Weight loss, regular exercise, improved diet, and objective assessment of alcohol intake are essential. New medications such as resmetirom and semaglutide now offer options for patients with advanced fibrosis. For some individuals with severe MASLD, bariatric surgery can also be effective. This review provides guidance on early detection, risk stratification, and personalised, holistic care to improve long-term health outcomes in MASLD. OABL- eng OTO - NOTNLM OT - GLP-1 OT - cardiovascular disease OT - diabetes complications OT - fatty liver disease OT - obesity care OT - weight management COIS- Frank Tacke's lab has received research grants (funding to the institution) from AstraZeneca, MSD, Gilead, Agomab. Frank Tacke has received honoraria for consulting or lectures from Gilead, Abbvie, Falk, AstraZeneca, Boehringer, Madrigal, MSD, GSK, Ipsen, Pfizer, Novartis, Novo Nordisk, Sanofi. Paul Horn reports research grants from MSD and Novo Nordisk (to the institution), honoraria for lectures from Falk and Orphalan, and travel support from Falk and Ipsen. Lanlan Chen reports no potential conflict of interest. EDAT- 2026/02/11 06:30 MHDA- 2026/04/21 18:34 PMCR- 2026/04/20 CRDT- 2026/02/11 04:23 PHST- 2026/01/24 00:00 [revised] PHST- 2025/12/15 00:00 [received] PHST- 2026/01/27 00:00 [accepted] PHST- 2026/04/21 18:34 [medline] PHST- 2026/02/11 06:30 [pubmed] PHST- 2026/02/11 04:23 [entrez] PHST- 2026/04/20 00:00 [pmc-release] AID - DOM70545 [pii] AID - 10.1111/dom.70545 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28 Suppl 2(Suppl 2):46-62. doi: 10.1111/dom.70545. Epub 2026 Feb 11. PMID- 41668634 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260710 IS - 1520-7560 (Electronic) IS - 1520-7552 (Linking) VI - 42 IP - 2 DP - 2026 Feb TI - Association Between GLP-1 Receptor Agonists and the Risk of Colon Cancer in Adults With Type 2 Diabetes or Obesity: A Systematic Review and Network Meta-Analysis. PG - e70134 LID - 10.1002/dmrr.70134 [doi] AB - BACKGROUND AND OBJECTIVE: To evaluate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and intestinal cancers and to explore the risk factors for these associations. METHODS: PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched through 13 June 2024, to identify randomised clinical trials (RCTs) assessing the relationship between GLP-1 RA use and colorectal, colon, rectal, and intestinal cancers. Pooled relative risks (RRs) and 95% confidence intervals (CIs) for each outcome were calculated. RESULTS: In 17 RCTs comprising 36,415 patients, GLP-1 RAs was associated with a significantly reduced risk of colon cancer (RR, 0.34; 95% CI, 0.17-0.68; I(2) = 0.0%), and showed a neutral effect on the risk of colorectal carcinoma, rectal, and intestinal cancer, with RRs of 1.13 (95% CI, 0.92-1.39; I(2) = 0.0%), 3.64 (95% CI, 0.76-17.40; I(2) = 0.0%), and 0.76 (95% CI, 0.31-1.84; I(2) = 23.3%), respectively. In the network meta-analysis and subgroup analysis, a potential association was observed between albiglutide and subcutaneous semaglutide and a lower incidence of colon cancer among adults treated for a longer duration and with lower baseline HbA1c levels, regardless of baseline body mass index, age, or type of control group. CONCLUSIONS: GLP-1 RAs may be associated with a lower risk of colon cancer in adults with type 2 diabetes mellitus, warranting further validation in trials among high-risk populations. TRIAL REGISTRATION: The study protocol was pre-registered and published on PROSPERO (CRD: 42024548010; https://www.crd.york.ac.uk/prospero/#recordDetails). CI - (c) 2026 John Wiley & Sons Ltd. FAU - Guo, Man AU - Guo M AUID- ORCID: 0000-0001-7646-669X AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Liu, Yong AU - Liu Y AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. AD - Department of Intensive Care Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Intensive Care Unit, Wangcang People's Hospital, Guangyuan, China. FAU - Zeng, Yan AU - Zeng Y AUID- ORCID: 0000-0002-4083-0127 AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Chen, Jiao AU - Chen J AUID- ORCID: 0000-0003-3414-1170 AD - Department of Endocrinology, Sichuan Mental Health Center, The Third Hospital of Mianyang, Mianyang, China. FAU - Zeng, Chen AU - Zeng C AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Huang, Lin-Lin AU - Huang LL AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Wang, Ji-Ying AU - Wang JY AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Wu, Yang-Hao-Tian AU - Wu YH AD - School of Public Health, Chongqing Medical University, Chongqing, China. FAU - Wu, Qi AU - Wu Q AD - Department of Pathology, The Affiliated Hospital of Southwest Medical University, and Luzhou Key Laboratory of Precision Pathology Diagnosis for Serious Diseases, Luzhou, China. AD - State Key Laboratory of Quality Research in Chinese Medicine, Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, China. FAU - Teng, Fang-Yuan AU - Teng FY AUID- ORCID: 0000-0002-9564-0961 AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. FAU - Xu, Yong AU - Xu Y AUID- ORCID: 0000-0002-9534-6252 AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, and Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, China. AD - State Key Laboratory of Quality Research in Chinese Medicine, Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, China. LA - eng GR - 82300911/Natural Science Foundation of China/ GR - U22A20286/Natural Science Foundation of China/ GR - 82470854/Natural Science Foundation of China/ GR - 32201056/Natural Science Foundation of China/ GR - 2025ZNSFSC1622/Sichuan Province Science and Technology Support Program/ GR - 2025JYJ054/Luzhou Science and Technology Program/ GR - 2025LCYXZX42/Scientific Research Projects of Southwest Medical University/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Colonic Neoplasms/epidemiology/prevention & control/etiology MH - *Obesity/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Semaglutide OTO - NOTNLM OT - colon cancer OT - diabetes OT - glucagon-like peptide-1 receptor agonist OT - meta-analysis OT - obesity OT - semaglutide EDAT- 2026/02/11 06:30 MHDA- 2026/02/11 06:31 CRDT- 2026/02/11 04:03 PHST- 2026/01/19 00:00 [revised] PHST- 2025/10/12 00:00 [received] PHST- 2026/01/29 00:00 [accepted] PHST- 2026/02/11 06:31 [medline] PHST- 2026/02/11 06:30 [pubmed] PHST- 2026/02/11 04:03 [entrez] AID - 10.1002/dmrr.70134 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2026 Feb;42(2):e70134. doi: 10.1002/dmrr.70134. PMID- 41667347 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260723 IS - 1444-2892 (Electronic) IS - 1443-9506 (Linking) VI - 35 IP - 4 DP - 2026 Apr TI - Initiators of Semaglutide in General Practice in New South Wales, 2020-2023: A Retrospective Cohort Study. PG - 554-562 LID - S1443-9506(25)01690-7 [pii] LID - 10.1016/j.hlc.2025.09.012 [doi] AB - AIM: We aimed to analyse trends and demographic and clinical profiles in initial prescriptions of semaglutide ("Ozempic") by general practitioners in New South Wales between 2020 and 2023. METHOD: This retrospective cohort study used electronic medical records from the New South Wales Health Lumos program, covering 680 general practices from January 2020 to November 2023. Individuals aged >/=18 years with a first general practice prescription for semaglutide ("initiators") were included. Counts and proportions of semaglutide initiators by year, sex, age, socioeconomic status, body mass index, and type 2 diabetes mellitus (T2DM) status were compared over time. RESULTS: Between 2020 and 2023, 59,009 individuals had a first general practice prescription for semaglutide, increasing from 448 in 2020 to 36,814 in 2023. Women comprised 63.6% of total initiators. The proportion of initiators with T2DM decreased from 92.2% in 2020 to 65.9% in 2023. Initiators with T2DM had a higher median age (women 53 years, men 59 years) compared to non-T2DM initiators (45 years for both sexes) and were more likely to live in socioeconomically disadvantaged areas. Greater proportions of non-T2DM initiators were aged <40 years, were female, and resided in less disadvantaged areas. Non-T2DM female initiators were less likely to be obese than those with T2DM (75.7% vs 79.3%), but the converse was true for men (91.0% vs 77.3%). Almost 30% of male initiators and 20% of female initiators without T2DM had a body mass index of >40 kg/m(2). CONCLUSIONS: The use of semaglutide in Australia is expanding rapidly, particularly among individuals without T2DM. Patterns in general practice prescribing of semaglutide differ by sex, T2DM status, and socioeconomic factors, raising important questions about equitable access. These trends underscore the need for coordinated policy responses to support fair and sustainable use as demand continues to grow. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Kuo, Nicholas I-Hsien AU - Kuo NI AD - Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia. FAU - Hill, Flynn AU - Hill F AD - New South Wales Ministry of Health, Sydney, NSW, Australia. FAU - Arnott, Clare AU - Arnott C AD - The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia. FAU - Douglas, Kirsty AU - Douglas K AD - College of Health and Medicine, Australian National University, Canberra, ACT, Australia. FAU - Barbieri, Sebastiano AU - Barbieri S AD - Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia; Queensland Digital Health Centre, University of Queensland, Brisbane, Qld, Australia. FAU - Ferdousi, Shahana AU - Ferdousi S AD - Western Sydney Primary Health Network, Westmead, NSW, Australia. FAU - Gandomkar, Ziba AU - Gandomkar Z AD - Sydney School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. FAU - Gallego-Luxan, Blanca AU - Gallego-Luxan B AD - Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia. FAU - Woodward, Mark AU - Woodward M AD - The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; The George Institute for Global Health, School of Public Health, Imperial College London, London, UK. FAU - Jorm, Louisa AU - Jorm L AD - Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia. Electronic address: l.jorm@unsw.edu.au. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20260209 PL - Australia TA - Heart Lung Circ JT - Heart, lung & circulation JID - 100963739 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Middle Aged MH - New South Wales/epidemiology MH - *General Practice MH - Hypoglycemic Agents/therapeutic use MH - Adult MH - Follow-Up Studies OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Obesity OT - Ozempic OT - Population health OT - Primary care OT - Semaglutide OT - Socioeconomic disparities OT - Type 2 diabetes COIS- Declaration of Competing Interests There are no conflicts of interest to disclose. EDAT- 2026/02/11 00:39 MHDA- 2026/04/05 04:22 CRDT- 2026/02/10 21:53 PHST- 2025/06/18 00:00 [received] PHST- 2025/09/02 00:00 [revised] PHST- 2025/09/06 00:00 [accepted] PHST- 2026/04/05 04:22 [medline] PHST- 2026/02/11 00:39 [pubmed] PHST- 2026/02/10 21:53 [entrez] AID - S1443-9506(25)01690-7 [pii] AID - 10.1016/j.hlc.2025.09.012 [doi] PST - ppublish SO - Heart Lung Circ. 2026 Apr;35(4):554-562. doi: 10.1016/j.hlc.2025.09.012. Epub 2026 Feb 9. PMID- 41655226 OWN - NLM STAT- MEDLINE DCOM- 20260616 LR - 20260616 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 111 IP - 7 DP - 2026 Jun 17 TI - Skeletal effect of semaglutide and tirzepatide in patients with increased risk of fractures. PG - 1959-1966 LID - 10.1210/clinem/dgag052 [doi] AB - CONTEXT: Glucagon-like peptide-1 receptor agonists (GLP1-RA) have potent glucose-lowering and weight loss benefits, but their effects on bone remain unclear. OBJECTIVE: To investigate changes in bone mineral density (BMD) in patients using semaglutide (SEM) and tirzepatide (TIR), a dual agonist of GLP-1/glucose dependent insulinotropic polypeptide. METHODS: Single-center retrospective study. Adult patients using SEM/TIR for >/=6 months with DXA scans before initiation and at least 6 months after were matched by age, sex, BMI, and diabetes mellitus (DM) to nonusers with at least 2 DXA scans over the same period. The primary outcome was the percentage change in total hip (TH) BMD. RESULTS: We included 255 patients using SEM or TIR in the GLP-1 RA group (92% female, mean age 64 +/- 9 years, BMI 31.0 +/- 5.6 kg/m(2)) and 255 controls. After a median follow-up of 17 months, the GLP-1 RA group achieved a median 5% weight loss. Both groups had significant declines in BMD at TH and FN, with a similar magnitude between groups. In the GLP-1RA group, weight loss was directly associated with bone loss at the TH and FN (r = 0.32 for TH, r = 0.17 for FN, both P < .01). Among patients without DM, greater TH bone loss was noted in the GLP-1 RA group compared to controls (-1% vs -0.6%, P = .04), whereas TH bone loss was similar between groups among patients with DM. CONCLUSION: SEM/TIR use was associated with greater annualized TH bone loss in patients without DM, whereas TH bone loss was comparable between GLP-1 RA and controls in patients with DM. These findings suggest GLP-1 RA's effects on bone may differ by DM status, with weight loss driving bone loss in patients without DM. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Liu, Yi AU - Liu Y AUID- ORCID: 0009-0003-5448-3626 AD - Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Walzer, Dalia AU - Walzer D AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Schmitz, Sarah AU - Schmitz S AD - Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Shukla, Alpana P AU - Shukla AP AD - Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Ma, Xiaoyue AU - Ma X AD - Division of Biostatistics, Department of Population Health Sciences, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Chirko, Dawn AU - Chirko D AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Pipia, Ilissa AU - Pipia I AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Sathi, Swetha AU - Sathi S AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Shukairy, Uthman AU - Shukairy U AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Greenberg, Michael AU - Greenberg M AD - Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Kashyap, Sangeeta R AU - Kashyap SR AD - Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY 10021, USA. FAU - Stein, Emily M AU - Stein EM AD - Division of Endocrinology, Hospital for Special Surgery, New York, NY 10021, USA. LA - eng PT - Journal Article PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Tirzepatide MH - Semaglutide MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/pharmacology MH - Retrospective Studies MH - *Bone Density/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Weight Loss/drug effects MH - *Fractures, Bone/prevention & control/epidemiology MH - Follow-Up Studies OTO - NOTNLM OT - bone loss OT - diabetes OT - obesity OT - osteoporosis OT - semaglutide OT - tirzepatide EDAT- 2026/02/08 18:28 MHDA- 2026/06/17 00:36 CRDT- 2026/02/08 13:12 PHST- 2025/11/13 00:00 [received] PHST- 2026/02/04 00:00 [accepted] PHST- 2026/06/17 00:36 [medline] PHST- 2026/02/08 18:28 [pubmed] PHST- 2026/02/08 13:12 [entrez] AID - 8467122 [pii] AID - 10.1210/clinem/dgag052 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2026 Jun 17;111(7):1959-1966. doi: 10.1210/clinem/dgag052. PMID- 41651756 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260727 IS - 2530-0180 (Electronic) IS - 2530-0180 (Linking) VI - 73 IP - 3 DP - 2026 Mar TI - Impact of oral semaglutide on quality of life and metabolic parameters in patients with type 2 diabetes mellitus: A multicenter observational study. PG - 501713 LID - S2530-0180(26)00013-2 [pii] LID - 10.1016/j.endien.2026.501713 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) significantly impacts the patients' quality of life due to chronic complications and associated comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated benefits in glycemic control. This study evaluates the effect of oral semaglutide on quality of life, metabolic parameters, and treatment adherence of T2DM patients. PATIENTS AND METHODS: We conducted a multicenter prospective observational study Galicia (Spain). A total of 43 adult T2DM patients on oral semaglutide were evaluated at baseline and 3-6 months later using validated questionnaires (DTSQ and EuroQol), anthropometric measures, and metabolic parameters. Changes in quality of life, HbA1c, weight, lipid profile, and insulin dose were analyzed. RESULTS: Oral semaglutide significantly improved quality of life according to the visual analog scale (from 62.8 to 72.6 points; p < 0.001) and DTSQ questionnaire (from 28.2 to 33.0 points; p < 0.001). Significant reductions were observed in HbA1c (8.3% to 7.2%; p < 0.001) and body weight (-4.9%; p = 0.018). The most common adverse effects were nausea and vomiting, reported by 39.5% of patients, with no impact on the overall quality of life. CONCLUSION: Oral semaglutide significantly improves quality of life and metabolic parameters in T2DM patients, with good tolerance and low discontinuation rates. These findings support its utility in the comprehensive management of T2DM. CI - Copyright (c) 2025 SEEN and SED. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Lago Garma, Javier AU - Lago Garma J AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Vigo, Vigo, Pontevedra, Spain. FAU - Gil Mouce, Cristina AU - Gil Mouce C AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Lucus Augusti, Lugo, Spain. FAU - Rodriguez Novo, Nazareth AU - Rodriguez Novo N AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Lucus Augusti, Lugo, Spain. FAU - Diaz Trastoy, Olaia AU - Diaz Trastoy O AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, A Coruna, Spain; Laboratorio de Endocrinologia Molecular, Instituto de Investigacion Sanitaria Santiago de Compostela (IDIS), Hospital Clinico Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, A Coruna, Spain. FAU - Santamaria Nieto, Alicia AU - Santamaria Nieto A AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Ferrol, Ferrol, A Coruna, Spain. FAU - Perez Castro, Patricia AU - Perez Castro P AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Vigo, Vigo, Pontevedra, Spain. FAU - Diaz Ortega, Carmen AU - Diaz Ortega C AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Ourense, Ourense, Spain. FAU - Fernandez Rodriguez, Eva AU - Fernandez Rodriguez E AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Ourense, Ourense, Spain. FAU - Palmeiro Carballeira, Regina AU - Palmeiro Carballeira R AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Vigo, Vigo, Pontevedra, Spain. FAU - Pinal Osorio, Iria AU - Pinal Osorio I AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Ourense, Ourense, Spain. FAU - Prieto Tenreiro, Alma AU - Prieto Tenreiro A AD - Laboratorio de Endocrinologia Molecular, Instituto de Investigacion Sanitaria Santiago de Compostela (IDIS), Hospital Clinico Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, A Coruna, Spain. FAU - Sanchez Sobrino, Paula AU - Sanchez Sobrino P AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Pontevedra, Pontevedra, Spain. FAU - Tejera Perez, Cristina AU - Tejera Perez C AD - Laboratorio de Endocrinologia Molecular, Instituto de Investigacion Sanitaria Santiago de Compostela (IDIS), Hospital Clinico Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, A Coruna, Spain. FAU - Pita Gutierrez, Francisco AU - Pita Gutierrez F AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario A Coruna, A Coruna, Spain. Electronic address: franciscopitagutierrez@gmail.com. FAU - Villar Taibo, Rocio AU - Villar Taibo R AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, A Coruna, Spain. FAU - Vidal Casariego, Alfonso AU - Vidal Casariego A AD - Servicio de Endocrinologia y Nutricion, Complexo Hospitalario Universitario A Coruna, A Coruna, Spain. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260205 PL - Spain TA - Endocrinol Diabetes Nutr (Engl Ed) JT - Endocrinologia, diabetes y nutricion JID - 101717565 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (Lipids) SB - IM MH - Semaglutide MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood/psychology MH - *Quality of Life MH - Female MH - Male MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects/pharmacology MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - Administration, Oral MH - Prospective Studies MH - Glycated Hemoglobin/analysis MH - Aged MH - Insulin/administration & dosage/therapeutic use MH - Body Weight/drug effects MH - Blood Glucose/analysis MH - Lipids/blood OTO - NOTNLM OT - Calidad de vida OT - Diabetes mellitus tipo 2 OT - Farmacos hipoglucemiantes OT - Hypoglycemic agents OT - Patient satisfaction OT - Quality of life OT - Satisfaccion del paciente OT - Semaglutida OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest None declared. EDAT- 2026/02/07 00:31 MHDA- 2026/03/10 01:06 CRDT- 2026/02/06 21:54 PHST- 2025/05/26 00:00 [received] PHST- 2025/07/19 00:00 [revised] PHST- 2025/08/28 00:00 [accepted] PHST- 2026/03/10 01:06 [medline] PHST- 2026/02/07 00:31 [pubmed] PHST- 2026/02/06 21:54 [entrez] AID - S2530-0180(26)00013-2 [pii] AID - 10.1016/j.endien.2026.501713 [doi] PST - ppublish SO - Endocrinol Diabetes Nutr (Engl Ed). 2026 Mar;73(3):501713. doi: 10.1016/j.endien.2026.501713. Epub 2026 Feb 5. PMID- 41644273 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260730 IS - 1525-6049 (Electronic) IS - 0886-022X (Print) IS - 0886-022X (Linking) VI - 48 IP - 1 DP - 2026 Dec TI - Cardiorenal protective effects of glucagon-like peptide-1 receptor agonists in chronic kidney disease: a systematic review and meta-analysis. PG - 2620155 LID - 10.1080/0886022X.2026.2620155 [doi] LID - 2620155 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in patients with chronic kidney disease (CKD), but existing evidence regarding their efficacy and safety remains inconsistent. To evaluate the cardiorenal outcomes and adverse effects of GLP-1 RAs in this population, we conducted a systematic review and meta-analysis of randomized controlled trials from PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science up to December 2024. Nine trials involving 21,717 patients, the vast majority of whom had T2DM, were included. GLP-1RAs treatment for CKD was associated with decreasing the incidence of major adverse kidney events (MAKE; RR, 0.84; 95% CI, 0.76-0.94) and major adverse cardiac and cerebrovascular events (MACE; RR, 0.84; 95% CI, 0.72-0.97), reducing all-cause mortality (RR, 0.83; 95% CI, 0.76-0.90) and albuminuria level (SMD, -1.22; 95% CI, -1.53 - 0.90). Gastrointestinal events associated with GLP-1 RA treatments including nausea (RR, 4.14; 95% CI, 2.70-6.33), vomiting (RR, 3.05; 95% CI, 1.88-4.97), diarrhea (RR, 2.65; 95% CI, 1.76-3.98), and dyspepsia (RR, 3.79; 95% CI, 1.02-14.12) have garnered significant attention. In conclusion, administration of GLP-1RAs treatment demonstrates excellent cardiorenal protective effects in CKD, primarily in patients with co-existing T2DM, though with notable gastrointestinal concerns. FAU - Wang, Yuqi AU - Wang Y AUID- ORCID: 0009-0003-9580-6145 AD - Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. FAU - Feng, Luda AU - Feng L AUID- ORCID: 0000-0002-7259-4421 AD - Xuanwu Hospital, Capital Medical University, Beijing, China. FAU - Wang, Yajing AU - Wang Y AD - Beijing Tongzhou District Hospital of Integrated Traditional Chinese and Western Medicine, Beijing, China. FAU - Li, Boyang AU - Li B AD - Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. FAU - Liang, Ning AU - Liang N AD - Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China. FAU - Song, Xuan AU - Song X AD - Beijing University of Chinese Medicine, Beijing, China. FAU - Qin, Jianguo AU - Qin J AD - Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. FAU - Zhang, Mianzhi AU - Zhang M AD - Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China. FAU - Li, Yu AU - Li Y AUID- ORCID: 0000-0002-2970-3522 AD - Beijing University of Chinese Medicine, Beijing, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260205 PL - England TA - Ren Fail JT - Renal failure JID - 8701128 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic PMC - PMC12879500 OTO - NOTNLM OT - CKD outcomes OT - GLP-1 receptor agonists OT - Semaglutide OT - liraglutide OT - meta-analysis COIS- The authors declare that they have no competing interests. EDAT- 2026/02/06 00:30 MHDA- 2026/02/06 00:31 PMCR- 2026/02/05 CRDT- 2026/02/05 21:02 PHST- 2026/02/06 00:31 [medline] PHST- 2026/02/06 00:30 [pubmed] PHST- 2026/02/05 21:02 [entrez] PHST- 2026/02/05 00:00 [pmc-release] AID - 2620155 [pii] AID - 10.1080/0886022X.2026.2620155 [doi] PST - ppublish SO - Ren Fail. 2026 Dec;48(1):2620155. doi: 10.1080/0886022X.2026.2620155. Epub 2026 Feb 5. PMID- 41640144 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260813 IS - 2308-1430 (Electronic) IS - 0375-9660 (Print) IS - 0375-9660 (Linking) VI - 71 IP - 5 DP - 2025 Dec 2 TI - [A personalized, evidence-based approach to obesity therapy using clinical algorithms: semaglutide or tirzepatide]. PG - 19-30 LID - 10.14341/probl13677 [doi] AB - On June 26, 2025, a meeting of the expert working group was held in Moscow. The discussion focused on the personalized approach of tirzepatide (<>) and semaglutide (<>) in patients with excess body weight, obesity, and type 2 diabetes. Following the meeting, the objective was set to develop a consensus-based algorithm for prescribing these drugs to ensure their effective use in Russian clinical practice. FAU - Troshina, E A AU - Troshina EA AD - Endocrinology Research Centre. FAU - Antsiferov, M B AU - Antsiferov MB AD - Endocrinological Dispensary. FAU - Ametov, A S AU - Ametov AS AD - Russian Medical Academy of Continuing Professional Education. FAU - Galstyan, G R AU - Galstyan GR AD - Endocrinology Research Centre. FAU - Markova, T N AU - Markova TN AD - Russian University of Medicine. FAU - Romantsova, T I AU - Romantsova TI AD - Russian Medical Academy of Continuing Professional Education. FAU - Mazurina, N V AU - Mazurina NV AD - Endocrinology Research Centre. FAU - Koteshkova, O M AU - Koteshkova OM AD - Endocrinological Dispensary. LA - rus PT - English Abstract PT - Journal Article DEP - 20251202 PL - Russia (Federation) TA - Probl Endokrinol (Mosk) JT - Problemy endokrinologii JID - 0140673 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide MH - *Obesity/drug therapy MH - *Algorithms MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Precision Medicine/methods MH - Hypoglycemic Agents/therapeutic use MH - *Anti-Obesity Agents/therapeutic use MH - Evidence-Based Medicine PMC - PMC12954439 COIS- The authors declare that there are no conflicts of interest present. EDAT- 2026/02/05 06:31 MHDA- 2026/02/05 06:32 PMCR- 2025/12/02 CRDT- 2026/02/05 02:03 PHST- 2025/10/21 00:00 [received] PHST- 2025/10/21 00:00 [accepted] PHST- 2026/02/05 06:32 [medline] PHST- 2026/02/05 06:31 [pubmed] PHST- 2026/02/05 02:03 [entrez] PHST- 2025/12/02 00:00 [pmc-release] AID - 10.14341/probl13677 [doi] PST - epublish SO - Probl Endokrinol (Mosk). 2025 Dec 2;71(5):19-30. doi: 10.14341/probl13677. PMID- 41636679 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260706 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 32 IP - 2 DP - 2026 Feb TI - Beyond glycemic control: Sex differences shaping glucagon-like peptide-1 receptor agonist utilization in the United States. PG - 166-175 LID - 10.18553/jmcp.2026.32.2.166 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a modern class of medications initially approved for type 2 diabetes mellitus (T2DM) but now also widely used for obesity. Although these drugs offer significant benefits for glycemic control, weight loss, and cardiorenal health, studies consistently show a pronounced sex difference in their use. However, there is a scarcity of studies addressing the factors responsible for these sex differences in GLP-1RA utilization in the United States. OBJECTIVE: To examine time- and sex-specific factors associated with GLP-1RA utilization among US adults before and after the landmark approval of semaglutide for chronic weight management. METHODS: We analyzed data from the 2019-2022 Medical Expenditure Panel Survey, a nationally representative survey of US adults (aged >/=18 years). GLP-1RA use was identified via prescription drug files. Descriptive statistics and chi-square tests compared characteristics of GLP-1RA users by time and sex. Multivariable logistic regression models estimated associations between individual characteristics and GLP-1RA use, both overall and among time- and sex-stratified cohorts. Subgroup analysis was conducted in adults with T2DM. RESULTS: The weighted prevalence of GLP-1RA use increased significantly from 6,158,326 (0.47%) in 2019-2020 to 10,410,021 (0.79%) in 2021-2022 (P < 0.0001). The rate of use was 0.48% and 0.46% in women and men, respectively, in 2019-2020 (P = 0.837) and increased to 0.82% in women and 0.76% in men in 2020-2022 (P = 0.964). T2DM was the strongest predictor of GLP-1RA use (odds ratio [OR] = 56.1 [2019-2020] and OR = 32.7 [2021-2022]), but the proportion of users with T2DM slightly decreased over time (92.8% in 2019-2020 to 90.2% in 2021-2022 [P = 0.239]). This decrease was especially pronounced in women during the 2021-2022 period, with men exhibiting a notably higher proportion of T2DM patients (94.4%) compared with women (86.2%) (P = 0.002). The proportion of users with obesity increased significantly (5.3% to 9.2%, P = 0.024), nearly doubling among female users (4.9% to 10.6%). The association with obesity strengthened over time (OR = 1.85 to 5.59), especially among women (OR: 6.43 vs 2.04 in men). Among women, depression was linked to greater use. In patients with T2DM, the use of insulin and oral antidiabetic medications was associated with higher GLP-1RA utilization. CONCLUSIONS: This study confirms the increasing utilization of GLP-1RAs in the United States, particularly among women. Although type 2 diabetes remains the primary predictor of GLP-1RA use, obesity has emerged as a key associated factor, especially among women. The stronger associations observed in women with obesity and depression highlight the role of clinical and psychosocial factors, which underscores the need for sex-sensitive approaches in obesity and diabetes management. FAU - Ofili, Samuel C AU - Ofili SC AD - Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, TX. FAU - Chen, Hua AU - Chen H AD - Department of Pharmaceutical Health Outcomes and Policy, College of Pharmacy, University of Houston, TX. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Male MH - United States MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Sex Factors MH - Middle Aged MH - Adult MH - *Glycemic Control/methods MH - Glucagon-Like Peptides/therapeutic use MH - Aged MH - Obesity/drug therapy MH - Young Adult MH - Blood Glucose/drug effects PMC - PMC12871523 EDAT- 2026/02/04 15:12 MHDA- 2026/02/04 15:13 PMCR- 2026/02/01 CRDT- 2026/02/04 10:33 PHST- 2026/02/04 15:13 [medline] PHST- 2026/02/04 15:12 [pubmed] PHST- 2026/02/04 10:33 [entrez] PHST- 2026/02/01 00:00 [pmc-release] AID - 10.18553/jmcp.2026.32.2.166 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2026 Feb;32(2):166-175. doi: 10.18553/jmcp.2026.32.2.166. PMID- 41635458 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260706 IS - 1844-3117 (Electronic) IS - 1844-122X (Print) IS - 1844-122X (Linking) VI - 18 IP - 12 DP - 2025 Dec TI - Modulation of metabolic syndrome components by oral semaglutide in hypothyroid-T2DM patients: a retrospective analysis. PG - 1094-1099 LID - 10.25122/jml-2025-0144 [doi] AB - Metabolic syndrome (MetS) represents the concurrent manifestation of multiple cardiometabolic risk factors, including visceral obesity, hyperglycemia, hypertension, hypertriglyceridemia, and low HDL-cholesterol, cumulatively predisposing to accelerated atherosclerosis and type 2 diabetes mellitus (T2DM). Hypothyroidism frequently coexists with T2DM and further exacerbates insulin resistance (IR), lipid abnormalities, and systemic inflammation, increasing the prevalence and severity of MetS in this population. Oral semaglutide is a glucagon-like peptide-1 receptor agonist approved for T2DM management; however, its impact on MetS parameters in patients with coexisting hypothyroidism remains insufficiently explored. This study aimed to evaluate the effects of oral semaglutide on key MetS components in this high-risk subgroup. We conducted a single-center retrospective cohort study involving 51 adult patients with confirmed hypothyroidism and T2DM, on oral semaglutide (final dose = 14 mg daily) and monitored for 6 months. Clinical and biochemical parameters were analyzed, including glycated hemoglobin (HbA1c), body mass index (BMI), blood pressure, and lipid profile. At 6 months, mean HbA1c decreased by 6.7% (P < 0.001), BMI was reduced by 4.04% (P < 0.001), triglycerides decreased by 6.7% (P < 0.001), and HDL-C increased by 9% (P = 0.002). In this observational study, treatment with oral semaglutide was associated with improvements in several components of MetS among patients with coexisting hypothyroidism and T2DM. While these findings suggest a potential therapeutic role for semaglutide in complex metabolic profiles, they should be interpreted with caution due to the study's design limitations. Further prospective studies are warranted to confirm these observations and to explore the interaction between semaglutide and levothyroxine. CI - (c) 2025 The Author(s). FAU - Tilici, Dana-Mihaela AU - Tilici DM AD - Doctoral School, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. FAU - Costinescu, Ruxandra-Mihaela AU - Costinescu RM AD - University Emergency Hospital of Bucharest, Bucharest, Romania. FAU - Paun, Diana-Loreta AU - Paun DL AD - Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. FAU - Paun, Sorin Constantin AU - Paun SC AD - Bucharest Emergency Clinical Hospital, Bucharest, Romania. FAU - Guja, Cristian AU - Guja C AD - Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. LA - eng PT - Journal Article PL - Romania TA - J Med Life JT - Journal of medicine and life JID - 101477617 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Metabolic Syndrome/drug therapy/complications MH - Retrospective Studies MH - Female MH - Male MH - *Hypothyroidism/complications/drug therapy MH - Middle Aged MH - Administration, Oral MH - Glycated Hemoglobin/metabolism MH - Adult MH - Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage PMC - PMC12863099 OTO - NOTNLM OT - BMI, body mass index OT - GLP-1 receptor agonist OT - GLP-1, glucagon-like peptide-1 OT - HDL, high-density lipoprotein OT - HbA1c, glycated hemoglobin OT - IR, insulin resistance OT - LDL, low-density lipoprotein OT - MetS, metabolic syndrome OT - SAH, systemic arterial hypertension OT - SCH, subclinical hypothyroidism OT - T2DM, type 2 diabetes mellitus OT - TSH, thyroid-stimulating hormone OT - dyslipidemia OT - hypothyroidism OT - insulin resistance OT - metabolic syndrome OT - oral semaglutide OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2026/02/04 11:32 MHDA- 2026/02/04 11:33 PMCR- 2025/12/01 CRDT- 2026/02/04 04:06 PHST- 2025/09/18 00:00 [received] PHST- 2025/11/04 00:00 [accepted] PHST- 2026/02/04 11:33 [medline] PHST- 2026/02/04 11:32 [pubmed] PHST- 2026/02/04 04:06 [entrez] PHST- 2025/12/01 00:00 [pmc-release] AID - JMedLife-18-1094 [pii] AID - 10.25122/jml-2025-0144 [doi] PST - ppublish SO - J Med Life. 2025 Dec;18(12):1094-1099. doi: 10.25122/jml-2025-0144. PMID- 41634285 OWN - NLM STAT- MEDLINE DCOM- 20260707 LR - 20260813 IS - 1937-6995 (Electronic) IS - 1556-9039 (Print) IS - 1556-9039 (Linking) VI - 22 IP - 2 DP - 2026 Apr TI - National Poison Center Trends in GLP-1 Receptor Agonist Exposures Following FDA Approval for Weight Loss. PG - 275-285 LID - 10.1007/s13181-026-01121-z [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are therapies for type 2 diabetes whose use expanded sharply after semaglutide's 2021 approval for obesity. Although gastrointestinal effects are well described, national patterns of acute GLP-1 RA exposures are poorly characterized. This study evaluated trends in GLP-1 RA exposures reported to U.S. poison centers, focusing on demographic shifts, exposure circumstances, and clinical outcomes before and after the 2021 FDA approval. METHODS: We analyzed human GLP-1 RA exposures reported to the National Poison Data System from 2012 to 2023, using July 1, 2021, to define pre- and post-approval periods. Demographics, exposure characteristics, therapies, and medical outcomes were compared using standardized statistical tests. Quarterly call counts were modeled with segmented Poisson regression to assess changes in reporting trajectory. RESULTS: A total of 10,033 exposures were identified (3,113 pre-approval; 6,920 post-approval). Semaglutide predominated post-approval (64.2%). The exposed population shifted younger and more female. Most cases were unintentional therapeutic errors with mild gastrointestinal symptoms. The proportion managed in or referred to a health care facility increased from 23.0% to 33.5% (RR = 1.46, [95% CI: 1.36, 1.57], p < 0.001). Segmented Poisson modeling demonstrated a significant inflection in call volume, with semaglutide exposures increasing an additional 9.9% per quarter after approval. CONCLUSIONS: GLP-1 RA exposures rose sharply following semaglutide's weight-loss approval, accompanied by increased health care utilization despite generally mild clinical effects. Although multiple factors likely contributed to these trends, improved patient counseling and clearer poison center guidance may help reduce preventable therapeutic errors and unnecessary emergency evaluation. CI - (c) 2026. The Author(s). FAU - Miller, Jordan AU - Miller J AD - College of AI, Cyber and Computing, UT San Antonio, San Antonio, TX, USA. FAU - Miller, Robert AU - Miller R AUID- ORCID: 0009-0000-8647-7552 AD - South Texas Poison Center, Department of Emergency Medicine, Long School of Medicine, UT San Antonio, San Antonio, TX, USA. MillerRS@uthscsa.edu. FAU - Varney, Shawn M AU - Varney SM AD - South Texas Poison Center, Department of Emergency Medicine, Long School of Medicine, UT San Antonio, San Antonio, TX, USA. FAU - Han, David AU - Han D AD - College of AI, Cyber and Computing, UT San Antonio, San Antonio, TX, USA. LA - eng PT - Journal Article DEP - 20260203 PL - United States TA - J Med Toxicol JT - Journal of medical toxicology : official journal of the American College of Medical Toxicology JID - 101284598 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Poison Control Centers/trends/statistics & numerical data MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United States/epidemiology MH - Semaglutide MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Male MH - Middle Aged MH - Adult MH - *Weight Loss/drug effects MH - Aged MH - Adolescent MH - Drug Approval MH - Young Adult MH - Child MH - Child, Preschool MH - United States Food and Drug Administration MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC13076849 OTO - NOTNLM OT - Glucagon-like peptide receptor agonists OT - Pharmacovigilance OT - Poison centers OT - Semaglutide COIS- Declarations. Ethics Approval: This study was determined to be exempt from human subjects review by our Institutional Review Board. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Conflict of Interest: All authors declare that they have no conflict of interest. Previous Presentation: Data in this manuscript were previously presented at the American College of Medical Toxicology's (ACMT) Annual Scientific Meeting, Vancouver, BC, 2025. EDAT- 2026/02/04 05:06 MHDA- 2026/04/13 12:38 PMCR- 2026/02/03 CRDT- 2026/02/03 23:30 PHST- 2025/10/10 00:00 [received] PHST- 2026/01/20 00:00 [accepted] PHST- 2025/12/21 00:00 [revised] PHST- 2026/04/13 12:38 [medline] PHST- 2026/02/04 05:06 [pubmed] PHST- 2026/02/03 23:30 [entrez] PHST- 2026/02/03 00:00 [pmc-release] AID - 10.1007/s13181-026-01121-z [pii] AID - 1121 [pii] AID - 10.1007/s13181-026-01121-z [doi] PST - ppublish SO - J Med Toxicol. 2026 Apr;22(2):275-285. doi: 10.1007/s13181-026-01121-z. Epub 2026 Feb 3. PMID- 41627802 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260823 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 186 IP - 4 DP - 2026 Apr 1 TI - Oral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes: A Secondary Analysis of the SOUL Randomized Clinical Trial. PG - 426-436 LID - 10.1001/jamainternmed.2025.7774 [doi] AB - IMPORTANCE: Heart failure (HF) is a common complication of type 2 diabetes (T2D). Oral semaglutide reduced the risk of major adverse cardiovascular (CV) events (MACE; comprising CV death, nonfatal myocardial infarction, or nonfatal stroke) in people with T2D in the SOUL trial, but the impact on HF outcomes in these participants is unknown. OBJECTIVE: To evaluate the effect of oral semaglutide on HF events, MACE, and safety among participants with or without HF at baseline. DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of the double-blind, placebo-controlled, event-driven, phase 3b SOUL randomized clinical trial, which was conducted at 444 centers in 33 countries. Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline. Data were analyzed from December 2024 to August 2025. INTERVENTION: Once-daily oral semaglutide or placebo in addition to standard of care. MAIN OUTCOMES AND MEASURES: Prespecified composite HF outcome (time to first occurrence of HF hospitalization, urgent HF visit, or CV death). RESULTS: Overall, 9650 participants (median [IQR] age, 66.0 [61.0-72.0] years; 2790 [28.9%] female) were randomized, with a mean (SD) follow-up of 47.5 (10.9) months. Of these participants, 2229 (23.1%) had HF history (991 [10.3%] with preserved ejection fraction, 592 [6.1%] with reduced ejection fraction, and 646 [6.7%] with unknown subtype). For participants with HF at baseline, the hazard ratio (HR) for risk of the composite HF outcome with oral semaglutide vs placebo was 0.78 (95% CI, 0.63-0.96) and was 1.01 (95% CI, 0.84-1.20) in those without HF at baseline (P for interaction = .06). Among participants with HF, the HR was 0.59 (95% CI, 0.39-0.86) in those with preserved ejection fraction and 0.98 (95% CI, 0.70-1.38) in those with reduced ejection fraction. There was no heterogeneity in the risk reduction of MACE with oral semaglutide in participants with HF history (HR, 0.83; 95% CI, 0.68-1.01) or without HF history (HR, 0.86; 95% CI, 0.75-0.98) (P for interaction = .77). Serious adverse event occurrence among participants with HF was similar with oral semaglutide (594 [53.8%]) and placebo (642 [57.1%]). CONCLUSIONS AND RELEVANCE: In this secondary analysis of the SOUL randomized clinical trial, among individuals with T2D, atherosclerotic CV disease, and/or chronic kidney disease, a reduction of HF events was observed with use of oral semaglutide compared with placebo in those with a history of HF, without increasing the risk of serious adverse events. These data support the potential benefit of oral semaglutide in reducing HF events in people with T2D and HF. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03914326. FAU - Pop-Busui, Rodica AU - Pop-Busui R AD - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health & Science University, Portland. AD - Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Sciences, University College London, London, England, United Kingdom. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill. FAU - Marx, Nikolaus AU - Marx N AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, RWTH Aachen University, University Hospital Aachen, Aachen, Germany. FAU - Mulvagh, Sharon L AU - Mulvagh SL AD - Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. FAU - Inzucchi, Silvio E AU - Inzucchi SE AD - Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Center, Munich, Germany. AD - Friedrich Alexander University of Erlangen, Erlangen, Germany. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, School of Public Health, University of Washington, Seattle. FAU - Poulter, Neil R AU - Poulter NR AD - Imperial Clinical Trials Unit, Faculty of Medicine, Imperial College London, London, England, United Kingdom. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bayer Tanggaard, Katrine AU - Bayer Tanggaard K AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AD - Department of Diabetology, Endocrinology and Nephrology, University Hospital Tubingen, Tubingen, Germany. AD - Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich, Eberhard Karls University of Tubingen, Tubingen, Germany. AD - German Center for Diabetes Research (DZD), Tubingen, Germany. FAU - Connelly, Kim A AU - Connelly KA AD - Keenan Research Centre for Biomedical Science, Departments of Medicine and Cardiology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Haluzik, Martin AU - Haluzik M AD - Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czechia. FAU - Cavender, Matthew A AU - Cavender MA AD - University of North Carolina School of Medicine, Chapel Hill. FAU - Kellerer, Monika AU - Kellerer M AD - Department of Diabetology and Endocrinology, Clinic for Internal Medicine, Marienhospital Stuttgart, Stuttgart, Germany. FAU - Jhund, Pardeep S AU - Jhund PS AD - British Heart Foundation Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland, United Kingdom. FAU - Gregersen, Soren AU - Gregersen S AD - Steno Diabetes Center Aarhus, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Nielsen, Olav Wendelboe AU - Nielsen OW AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lam, Carolyn S P AU - Lam CSP AD - National Heart Centre Singapore, Outram, Singapore. AD - Duke-National University of Singapore, Outram, Singapore. FAU - McGuire, Darren K AU - McGuire DK AD - Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Parkland Health System, Dallas. CN - SOUL Study Group LA - eng SI - ClinicalTrials.gov/NCT03914326 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - *Heart Failure/etiology/prevention & control/drug therapy MH - Male MH - Double-Blind Method MH - Administration, Oral MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use PMC - PMC12865694 COIS- Conflict of Interest Disclosures: Dr Pop-Busui reported personal fees from Novo Nordisk during the conduct of the study, as well as grants from the National Institute of Diabetes and Digestive and Kidney Diseases, Breakthrough T1D, Bayer, and Novo Nordisk, and personal fees from Lexicon, Roche Diagnostic, and Vertex outside the submitted work. Dr Rasmussen reported employment with and holding stocks in Novo Nordisk. Prof Deanfield reported honoraria and/or consulting fees from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda; grants from Alzheimer's Research UK, British Heart Foundation, Medical Research Council (UK), National Institute for Health and Care Research, Public Health England, MSD, Pfizer, Aegerion, Colgate, and Roche; personal fees from Caristo Diagnostics, eMed Healthcare, Floe Oral Care, Friede-Springer Cardiovascular Prevention Center, iOWNA, Philip Morris International Harm Reduction Group, and Smarter Cardiovascular Outcomes by Research and Education (SCORE); and serving as a member of study steering committees for Novo Nordisk (SOUL and SELECT) outside the submitted work. Dr Buse reported grants from Novo Nordisk during the conduct of the study, as well as grants from Corcept, Dexcom, GentiBio, and Novo Nordisk; personal fees from Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen, Antag, Aqua Medical, AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Dexcom, Lilly, Embecta, General Medicines, GentiBio, Insulet, Kayothera, Metsera, MiniMed, Novo Nordisk, Recordati, Sparrow Pharmaceuticals, Tandem, Vertex, vTv Therapeutics, and Zealand; and stock options in Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health outside the submitted work. Prof Marx reported serving as a member of a steering committee for Novo Nordisk during the conduct of the study and other support paid to University Hospital from Boehringer Ingelheim, Bayer, MSD, AstraZeneca, Sanofi, Lilly, and Novo Nordisk outside the submitted work. Dr Mulvagh reported personal fees from Novo Nordisk for serving as a steering committee member during the conduct of the study, as well as personal fees from Merck outside the submitted work. Dr Inzucchi reported personal fees from Novo Nordisk during the conduct of the study, as well as personal fees from Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Bayer, and Corcept outside the submitted work. Dr Mann reported personal fees from Novo Nordisk, Bayer, AstraZeneca, Cytel, Icon, IQVIA, and WCG during the conduct of the study. Dr Emerson reported personal fees from Novo Nordisk during the conduct of the study, as well as personal fees from Boehringer Ingelheim, AstraZeneca, Daiichi Sankyo, Vertex, Roche, GSK, Lilly, Novartis, Bristol Myers Squibb, and Sanofi outside the submitted work. Dr Poulter reported personal fees from Servier and Novo Nordisk outside the submitted work. Dr Engelmann reported employment with and shares in Novo Nordisk outside the submitted work. Dr Hovingh reported employment with and shares in Novo Nordisk during the conduct of the study. Dr Bayer Tanggaard reported employment with Novo Nordisk during the conduct of the study. Prof Birkenfeld reported departmental research support from AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk, and Lilly. Dr Connelly reported grants from Novo Nordisk and Lilly during the conduct of the study; personal fees from Abbott, Janssen, Novartis, Sanofi, and GSK, as well as grants from AstraZeneca, Boehringer Ingelheim, Lilly, Merck, Novo Nordisk, and Servier outside the submitted work; and a patent for medical use of a dipeptidyl peptidase-4 inhibitor (Boehringer Ingelheim). Dr Haluzik reported personal fees from Novo Nordisk, Sanofi, Lilly, Berlin Chemie, GSK, and ProMed outside the submitted work. Dr Cavender reported personal fees from Novo Nordisk during the conduct of the study, as well as grants from Cleerly, Janssen, Silence Therapeutics, MGH, Amgen, and Boehringer Ingelheim, and personal fees from AbbVie, AOP Pharma, Corcept, Faraday, and New Amsterdam, outside the submitted work. Dr Kellerer reported trial participation funded by Novo Nordisk during the conduct of the study, as well as personal fees from Abbott Diabetes Care, AstraZeneca, Bayer AG, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, Sanofi, and SCIARC, and trial participation funded by AstraZeneca, Lilly, GSK, and Novo Nordisk outside the submitted work. Dr Jhund reported fees for trial work paid to employer from Novo Nordisk during the conduct of the study; grants and clinical trial fees paid to employer from AstraZeneca and Bayer, as well as grants from Roche and Analog Devices outside the submitted work; and serving as director for GCTP. Prof Nielsen reported employment with and stock in Novo Nordisk. Prof Lam reported grants from the National Medical Research Council of Singapore, Novo Nordisk, and Roche Diagnostics; advisory, consulting, and trial leadership roles with Alnylam Pharma, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Corteria, CPC Clinical Research, Cytokinetics, Lilly, Impulse Dynamics, Intellia Therapeutics, Janssen Research & Development, Medscape/WebMD Global, Merck, Novartis, Novo Nordisk, Pfizer, Quidel Corporation, Radcliffe Group, Roche, and Us2.ai; serving as cofounder and nonexecutive director of Us2.ai; and a patent for PCT/SG2016/050217 pending and US Patent Nos. 10,631,828 B1; US 10,702,247 B2; US 11,301,996 B2; US 11,446,009 B2; US 11,931,207 B2; US 12,001,939; and US 12,400,762 B2 issued. Prof McGuire reported personal fees from Novo Nordisk, Lilly, Boehringer Ingelheim, Lexicon, Amgen, Neurotronic, Kailera, Alveus, Regor, F. Hoffmann-La Roche, New Amsterdam, Metsera, and Novartis during the conduct of the study. No other disclosures were reported. 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Allison, Dale C IR - Allison DC FIR - Awasty, Vivex IR - Awasty V FIR - Ayele, Etsegenet IR - Ayele E FIR - Bajaj, Chris IR - Bajaj C FIR - Budoff, Matthew J IR - Budoff MJ FIR - Busch, Robert IR - Busch R FIR - Casaubon, Luis IR - Casaubon L FIR - Chaidarun, Sushela S IR - Chaidarun SS FIR - Chochinov, Ronald H IR - Chochinov RH FIR - Chu, James W IR - Chu JW FIR - Daboul, Nizar Y IR - Daboul NY FIR - Dang, Andy H IR - Dang AH FIR - Everhart, Brian G IR - Everhart BG FIR - Arambasick, Justin IR - Arambasick J FIR - Fink, Raymond I IR - Fink RI FIR - Fitz-Patrick, David IR - Fitz-Patrick D FIR - Fogarty, Charles M IR - Fogarty CM FIR - Gilbert, Matthew P IR - Gilbert MP FIR - Johnson, David M IR - Johnson DM FIR - Krishnasamy, Sathya S IR - Krishnasamy SS FIR - Lane, Wendy S IR - Lane WS FIR - Nakhle, Samer N IR - Nakhle SN FIR - Levenson, David IR - Levenson D FIR - O'Donnell, Philip IR - O'Donnell P FIR - Weiss, Daniel IR - Weiss D FIR - Risser, Joseph A IR - Risser JA FIR - Wierum, Craig IR - Wierum C FIR - Sivalingam, Kanagaratnam IR - Sivalingam K FIR - Gupta, Dinesh IR - Gupta D FIR - Philis-Tsimikas, Athena IR - Philis-Tsimikas A FIR - Pratley, Richard E IR - Pratley RE FIR - Mirza, Lubna IR - Mirza L FIR - Snyder, Brian IR - Snyder B FIR - Rasouli, Neda IR - Rasouli N FIR - Porter, John IR - Porter J FIR - Ledesma, Gilbert N IR - Ledesma GN FIR - Powell, Talessa IR - Powell T FIR - Tandron, Ileana J IR - Tandron IJ FIR - Lingvay, Ildiko IR - Lingvay I FIR - Reed, John C H 3rd IR - Reed JCH 3rd FIR - Patel, Minesh B IR - Patel MB FIR - Lovre, Dragana IR - Lovre D FIR - Chaicha-Brom, Tira IR - Chaicha-Brom T FIR - Jantzi, Curtis IR - Jantzi C FIR - Brautigam, Donald IR - Brautigam D FIR - Bao, Shichun IR - Bao S FIR - Mbogua, Caroline N IR - Mbogua CN FIR - Zemel, Leonard R IR - Zemel LR FIR - Hasan, Syed IR - Hasan S FIR - Rosenstock, Julio IR - Rosenstock J FIR - Tran, Hien IR - Tran H FIR - Poremba, John IR - Poremba J FIR - Baker, Claire IR - Baker C FIR - Prier, Kevin IR - Prier K FIR - Chilka, Sapna IR - Chilka S FIR - Agaiby, John M IR - Agaiby JM FIR - Condit, Jonathan IR - Condit J FIR - Eagerton, Donald C IR - Eagerton DC FIR - Huffman, David IR - Huffman D FIR - Cornett, George M IR - Cornett GM FIR - Traylor, Henry IR - Traylor H FIR - Brinson, Cynthia IR - Brinson C FIR - Bays, Harold E IR - Bays HE FIR - Jerkins, Terri IR - Jerkins T FIR - Nicol, Philip R IR - Nicol PR FIR - Siddiqui, Imran A IR - Siddiqui IA FIR - Hewitt, Mitzie IR - Hewitt M FIR - Odugbesan, Adeniyi O IR - Odugbesan AO FIR - Lillestol, Michael J IR - Lillestol MJ FIR - Thrasher, James R IR - Thrasher JR FIR - Gandy, Winston H Jr IR - Gandy WH Jr FIR - Pant, Nicole IR - Pant N FIR - Nagelberg, Steven IR - Nagelberg S FIR - Cannon, Kevin IR - Cannon K FIR - Anderson, Marshall W IR - Anderson MW FIR - Bhargava, Anuj IR - Bhargava A FIR - Doshi, Ankur IR - Doshi A FIR - Jardula, Michael F IR - Jardula MF FIR - Montero, Manuel IR - Montero M FIR - Purighalla, Raman S IR - Purighalla RS FIR - Warren, Mark L IR - Warren ML FIR - Harris, Kathleen IR - Harris K FIR - Jackson, Richard A IR - Jackson RA FIR - Khaira, Ajit S IR - Khaira AS FIR - Gonzalez-Orozco, Luis IR - Gonzalez-Orozco L FIR - Gagianas, Peter J IR - Gagianas PJ FIR - Pantalone, Kevin IR - Pantalone K FIR - Murray, Alexander V IR - Murray AV EDAT- 2026/02/03 00:06 MHDA- 2026/04/06 12:36 PMCR- 2026/02/02 CRDT- 2026/02/02 11:33 PHST- 2026/04/06 12:36 [medline] PHST- 2026/02/03 00:06 [pubmed] PHST- 2026/02/02 11:33 [entrez] PHST- 2026/02/02 00:00 [pmc-release] AID - 2844096 [pii] AID - ioi250094 [pii] AID - 10.1001/jamainternmed.2025.7774 [doi] PST - ppublish SO - JAMA Intern Med. 2026 Apr 1;186(4):426-436. doi: 10.1001/jamainternmed.2025.7774. PMID- 41622983 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260819 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - Risk stratification using coronary artery calcium and potential benefit of semaglutide therapy: A cost-effectiveness modelling study. PG - 3229-3237 LID - 10.1111/dom.70515 [doi] AB - AIM: Coronary artery calcium (CAC) scoring is observed to improve risk stratification for major adverse cardiovascular events (MACE). Semaglutide, a recently introduced anti-obesity drug, is very effective, but wider use is limited due to high costs. Hence, this study investigated the cost-effectiveness (CEA) of semaglutide across CAC groups. MATERIALS AND METHODS: CAC scores for 38 058 CLARIFY registry participants meeting SELECT criteria were included. They were stratified into four CAC groups: 0, 1-99, 100-399, >/=400. To determine MACE (composite of myocardial infarction, heart failure, stroke or all-cause mortality) risk across CAC groups, hazard ratios (HR) were estimated from multi-variable adjusted Cox proportional hazard models. Next, lifetime-horizon Markov models were created to simulate semaglutide therapy and the potential clinical benefit (reported as number needed to treat [NNT]) and CEA (estimated with incremental cost-effectiveness ratio [ICER]) were examined for CAC groups. Multiple scenarios to mimic real-world experience were fitted for robust sensitivity analyses. RESULTS: Compared to CAC = 0, MACE risk was higher for CAC >/=400 (HR: 1.97 [95% CI: 1.66-2.35]), heart failure (HR: 1.76 [95% CI: 1.36-2.28]), mortality (HR: 1.62 [95% CI: 1.21-2.17]). Modelling 3.3 years of semaglutide use resulted in potential MACE NNT values of 151 (95% CI: 108-302) and 34 (95% CI: 25-69) for CAC = 0 and CAC >/=400. Markov modelled ICER for semaglutide use reduced across CAC groups ($625 863/QALY [CAC = 0] vs. $168 666/QALY [CAC >/=400]). CONCLUSIONS: CAC scores have potential use as a tool to estimate potential clinical benefit and cost for lifetime semaglutide therapy among obese individuals. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ponnana, Sai Rahul AU - Ponnana SR AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Zhang, Tong AU - Zhang T AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Sirasapalli, Santosh Kumar AU - Sirasapalli SK AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Chen, Zhuo AU - Chen Z AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Dazard, Jean-Eudes AU - Dazard JE AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Surya, Niketh AU - Surya N AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. FAU - Elhussain, Shamsa AU - Elhussain S AD - Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA. AD - Harrington Heart and Vascular Institute, University Hospitals, Cleveland, Ohio, USA. FAU - Sivanantham, Kanimozhi AU - Sivanantham K AD - Harrington Heart and Vascular Institute, University Hospitals, Cleveland, Ohio, USA. FAU - Okyere, Robert AU - Okyere R AD - Department of Internal Medicine, University Hospitals, Cleveland, Ohio, USA. FAU - Neeland, Ian J AU - Neeland IJ AD - Department of Internal Medicine, University Hospitals, Cleveland, Ohio, USA. FAU - Rajagopalan, Sanjay AU - Rajagopalan S AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. AD - Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, USA. AD - Harrington Heart and Vascular Institute, University Hospitals, Cleveland, Ohio, USA. FAU - Deo, Salil V AU - Deo SV AUID- ORCID: 0000-0002-4729-1461 AD - Case School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. AD - Surgical Services, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA. AD - School of Health and Wellbeing, University of Glasgow, Glasgow, UK. LA - eng PT - Journal Article DEP - 20260202 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - SY7Q814VUP (Calcium) RN - 0 (Hypoglycemic Agents) SB - IM MH - Semaglutide MH - Humans MH - Cost-Benefit Analysis MH - Cost-Effectiveness Analysis MH - *Glucagon-Like Peptides/therapeutic use/economics MH - Female MH - Male MH - Middle Aged MH - Risk Assessment MH - Aged MH - *Coronary Artery Disease/economics/epidemiology MH - *Coronary Vessels MH - *Vascular Calcification/epidemiology/economics MH - Calcium/metabolism/analysis MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/economics PMC - PMC12992155 OTO - NOTNLM OT - antiobesity drug OT - cohort study OT - database research OT - risk prediction OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2026/02/02 06:28 MHDA- 2026/03/17 06:47 PMCR- 2026/03/17 CRDT- 2026/02/02 04:34 PHST- 2026/01/09 00:00 [revised] PHST- 2025/11/16 00:00 [received] PHST- 2026/01/18 00:00 [accepted] PHST- 2026/03/17 06:47 [medline] PHST- 2026/02/02 06:28 [pubmed] PHST- 2026/02/02 04:34 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - DOM70515 [pii] AID - 10.1111/dom.70515 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):3229-3237. doi: 10.1111/dom.70515. Epub 2026 Feb 2. PMID- 41620207 OWN - NLM STAT- MEDLINE DCOM- 20260706 LR - 20260729 IS - 1715-3360 (Electronic) IS - 0008-4182 (Linking) VI - 61 IP - 3 DP - 2026 Jun TI - Association between semaglutide use and thyroid eye disease-related outcomes in autoimmune thyroiditis with type II diabetes. PG - 665-669 LID - S0008-4182(26)00011-6 [pii] LID - 10.1016/j.jcjo.2026.01.010 [doi] AB - OBJECTIVE: To evaluate whether semaglutide use is associated with thyroid eye disease (TED)-related outcomes among patients with autoimmune thyroiditis and type II diabetes mellitus (T2DM). METHODS: Adults with thyrotoxicosis (International Classification of Diseases [ICD-10]: E05) and T2DM were identified from the TriNetX US Collaborative Network. T2DM was defined by ICD-10 (E11) or laboratory criteria. The exposed cohort included individuals prescribed semaglutide on or after its Foood and Drug Administration approval (December 5, 2017). The control cohort included patients treated with non-glucogon-like peptide-1 receptor agonist antihyperglycemic agents without prior glucagon-like peptide-1 receptor agonist exposure. Propensity score matching (1:1) was performed using demographics, comorbidities, medications, and health care utilization variables. Five-year outcomes included: (1) TED-related diagnoses; (2) systemic corticosteroid use; (3) TED-related surgical interventions; (4) radiation treatment; and (5) teprotumumab use. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS: After matching, 23,279 patients were included per group (mean age: 60.1 years; 75% female). At 5-year, semaglutide users had lower rates of TED-related diagnoses (2.16% vs 2.82%; RR: 0.76; 95% CI: 0.68-0.86), systemic corticosteroid use (22.71% vs 26.39%; RR: 0.86; 95% CI: 0.82-0.90), TED-related surgical interventions (0.30% vs 0.42%; RR: 0.70; 95% CI: 0.51-0.96), and radiation treatment (1.17% vs 2.05%; RR: 0.57; 95% CI: 0.49-0.67). Teprotumumab use was rare and similar between groups (0.08% vs 0.08%; RR: 1.00; 95% CI: 0.52-1.92). CONCLUSIONS: Semaglutide use was associated with fewer TED-related diagnoses and treatments over 5 years, supporting a potential protective role. Further studies are warranted to confirm these associations and clarify underlying mechanisms. CI - Copyright (c) 2026 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. FAU - Shlomov, Tehila AU - Shlomov T AD - Department of Ophthalmology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. FAU - Nitzan, Itay AU - Nitzan I AD - Department of Ophthalmology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. FAU - Pollack, Rena AU - Pollack R AD - Department of Endocrinology and Metabolism, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. FAU - Zloto, Ofira AU - Zloto O AD - Goldschleger Eye Institute, Sheba Medical Center, Tel-Hashomer, Israel; Faculty of Medicine and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Gur, Zvi AU - Gur Z AD - Department of Ophthalmology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Israel. Electronic address: Zvigur90@gmail.com. LA - eng PT - Journal Article PL - England TA - Can J Ophthalmol JT - Canadian journal of ophthalmology. Journal canadien d'ophtalmologie JID - 0045312 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - *Thyroiditis, Autoimmune/drug therapy/complications MH - *Graves Ophthalmopathy/diagnosis/drug therapy/etiology MH - Aged MH - Retrospective Studies MH - Adult EDAT- 2026/02/01 00:43 MHDA- 2026/05/22 00:33 CRDT- 2026/01/31 19:20 PHST- 2025/06/15 00:00 [received] PHST- 2025/11/22 00:00 [revised] PHST- 2026/01/06 00:00 [accepted] PHST- 2026/05/22 00:33 [medline] PHST- 2026/02/01 00:43 [pubmed] PHST- 2026/01/31 19:20 [entrez] AID - S0008-4182(26)00011-6 [pii] AID - 10.1016/j.jcjo.2026.01.010 [doi] PST - ppublish SO - Can J Ophthalmol. 2026 Jun;61(3):665-669. doi: 10.1016/j.jcjo.2026.01.010. PMID- 41616750 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260806 IS - 1879-1379 (Electronic) IS - 0022-3956 (Linking) VI - 195 DP - 2026 Apr TI - Retrospective chart review on psychiatric manifestations of GLP-1 agonist usage. PG - 92-96 LID - S0022-3956(26)00053-1 [pii] LID - 10.1016/j.jpsychires.2026.01.042 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes mellitus and obesity. Beyond metabolic effects, GLP-1 signaling influences central pathways involved in mood, reward, and stress regulation, raising interest in possible psychiatric implications. METHODS: We conducted a retrospective chart review of adults (>/=18 years) prescribed GLP-1 RAs at a private university hospital between January 2021 and April 2024. Demographic, medication, and psychiatric data were extracted from electronic health records. Primary outcomes included stability, improvement, worsening, or new onset of psychiatric disorders during treatment. RESULTS: Among 226 patients (mean age 53.5 years; 66.8 % female; mean BMI 33.6 kg/m(2)), semaglutide was most frequently prescribed (73 %). The mean treatment duration was 20.2 months, with an average 6.7 % weight loss. Major depressive disorder (MDD) and generalized anxiety disorder (GAD) were most prevalent (68.6 % and 65.9 % of patients, respectively). Most remained stable (MDD: 73.6 %; GAD: 78.5 %). New-onset MDD occurred in 9.0 % and GAD in 8.7 % of affected patients, with mean latencies of 15.8 and 16.8 months, respectively. Adjustment disorder, ADHD, and insomnia also emerged in a subset, with ADHD showing the shortest latency to onset (7.8 months). Rare new-onset alcohol use disorder, trichotillomania, and opioid use disorder were observed. CONCLUSIONS: GLP-1 RAs appear psychiatrically well-tolerated for most patients, though new-onset or worsening symptoms occur in a minority, underscoring the need for monitoring, particularly in high-risk populations. Prospective studies are warranted to clarify causality, mechanisms, and potential therapeutic roles in psychiatric care. CI - Copyright (c) 2026 Elsevier Ltd. All rights reserved. FAU - Sa, Brianna AU - Sa B AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: bcs103@miami.edu. FAU - Maristany, Anthony AU - Maristany A AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Subramaniam, Ashwin AU - Subramaniam A AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Kumbkarni, Nayha AU - Kumbkarni N AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Lange, Rachel AU - Lange R AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Oldak, Sean AU - Oldak S AD - Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. FAU - Buciuc, Adela-Georgiana AU - Buciuc AG AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. FAU - Padilla, Vanessa AU - Padilla V AD - Department of Psychiatry, University of Miami Miller School of Medicine, Miami, FL, USA. LA - eng PT - Journal Article DEP - 20260128 PL - England TA - J Psychiatr Res JT - Journal of psychiatric research JID - 0376331 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Retrospective Studies MH - Middle Aged MH - Male MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Generalized Anxiety Disorder MH - *Major Depressive Disorder/epidemiology/chemically induced MH - *Glucagon-Like Peptides/adverse effects/pharmacology MH - Aged MH - *Hypoglycemic Agents/adverse effects MH - Obesity/drug therapy MH - *Mental Disorders/chemically induced OTO - NOTNLM OT - Anxiety disorders OT - GLP-1 receptor agonists OT - Mood disorders OT - Neuropsychiatric effects OT - Psychiatric manifestations OT - Retrospective chart review OT - Semaglutide COIS- Declaration of competing interest All authors report no competing interests. EDAT- 2026/01/31 00:29 MHDA- 2026/02/19 01:35 CRDT- 2026/01/30 18:10 PHST- 2025/08/13 00:00 [received] PHST- 2025/12/18 00:00 [revised] PHST- 2026/01/27 00:00 [accepted] PHST- 2026/02/19 01:35 [medline] PHST- 2026/01/31 00:29 [pubmed] PHST- 2026/01/30 18:10 [entrez] AID - S0022-3956(26)00053-1 [pii] AID - 10.1016/j.jpsychires.2026.01.042 [doi] PST - ppublish SO - J Psychiatr Res. 2026 Apr;195:92-96. doi: 10.1016/j.jpsychires.2026.01.042. Epub 2026 Jan 28. PMID- 41610839 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 2666-6340 (Electronic) IS - 2666-6340 (Linking) VI - 7 IP - 2 DP - 2026 Feb 13 TI - Divergent effect of diabetes on fibrosis response to semaglutide and resmetirom in noncirrhotic MASH: A meta-analysis of randomized trials. PG - 100959 LID - S2666-6340(25)00386-1 [pii] LID - 10.1016/j.medj.2025.100959 [doi] AB - BACKGROUND: Semaglutide has become an alternative to resmetirom for noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH). However, the effect of type 2 diabetes mellitus (T2DM) on fibrosis response to these drugs is unknown. METHODS: Our primary research question asked whether semaglutide or resmetirom treatment leads to fibrosis improvement in diabetic and nondiabetic noncirrhotic MASH. Data sources included MEDLINE, Cochrane Library, EMBASE, meeting abstracts, clinical trial registries, and regulatory authorities' websites through October 10, 2025, coveringrandomized controlled trials (RCTs) evaluating the effect of semaglutide and/or resmetirom on liver histology in noncirrhotic MASH patients. Three reviewers extracted data for study characteristics, outcomes of interest, and risk of bias and summarized the strength of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Main outcome (a >/=1 stage histological fibrosis improvement) was pooled using a risk ratio (RR) and random-effects model. FINDINGS: Eight out of 3,751 identified records, describing three placebo-controlled RCTs with histological endpoints (2,086 noncirrhotic MASH patients, 62% with T2DM, trial duration range 52-72 weeks) were included. In MASH patients with T2DM, semaglutide did not improve fibrosis stage (RR = 1.21, 95% CI 0.94-1.56, p = 0.13; I(2) = 0%, N comparisons = 4, 646 participants), while resmetirom significantly improved fibrosis vs. placebo (RR = 1.99, 95% CI 1.35-2.93, p = 0.0005, 647 participants). In MASH patients without T2DM, semaglutide improved fibrosis stage (RR = 1.72, 95% CI 1.21-2.44, p = 0.002, N comparisons = 4, I(2) = 3%, 474 participants), while resmetirom did not (RR = 1.37, 95% CI 0.83-2.25, p = 0.21, 319 participants). Resmetirom treatment was associated with significant fibrosis reduction regardless of background treatment with glucagon-like peptide-1 receptor agonists. CONCLUSIONS: T2DM modifies fibrosis response to semaglutide and resmetirom in noncirrhotic MASH. FUNDING: This study received no funding. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Musso, Giovanni AU - Musso G AD - MECAU Department San Luigi Gonzaga Hospital, Orbassano, Turin, Italy. Electronic address: giovanni_musso@yahoo.it. FAU - Pinach, Silvia AU - Pinach S AD - Department of Medical Sciences, Citta della Salute e della Scienza Hospital, University of Turin, Turin, Italy. FAU - Cassader, Maurizio AU - Cassader M AD - Department of Medical Sciences, Citta della Salute e della Scienza Hospital, University of Turin, Turin, Italy. FAU - Mariano, Filippo AU - Mariano F AD - Department of Medical Sciences, Citta della Salute e della Scienza Hospital, University of Turin, Turin, Italy. FAU - Gambino, Roberto AU - Gambino R AD - Department of Medical Sciences, Citta della Salute e della Scienza Hospital, University of Turin, Turin, Italy. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20260128 PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Liver Cirrhosis/drug therapy/pathology/etiology MH - *Non-alcoholic Fatty Liver Disease/drug therapy/pathology OTO - NOTNLM OT - GLP-1 RAs OT - MASH OT - NAFLD OT - NASH OT - incretin OT - thyroid receptor agonists OT - translation to patients OT - weight loss COIS- Declaration of interests The authors declare no competing interests. EDAT- 2026/01/30 00:54 MHDA- 2026/02/15 00:31 CRDT- 2026/01/29 18:41 PHST- 2025/08/13 00:00 [received] PHST- 2025/10/17 00:00 [revised] PHST- 2025/11/24 00:00 [accepted] PHST- 2026/02/15 00:31 [medline] PHST- 2026/01/30 00:54 [pubmed] PHST- 2026/01/29 18:41 [entrez] AID - S2666-6340(25)00386-1 [pii] AID - 10.1016/j.medj.2025.100959 [doi] PST - ppublish SO - Med. 2026 Feb 13;7(2):100959. doi: 10.1016/j.medj.2025.100959. Epub 2026 Jan 28. PMID- 41605684 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260813 IS - 1348-4540 (Electronic) IS - 0918-8959 (Print) IS - 0918-8959 (Linking) VI - 73 IP - 5 DP - 2026 May 8 TI - Effects of semaglutide, a GLP-1 receptor agonist, on food preferences in Japanese subjects with type 2 diabetes and visceral fat accumulation. PG - 607-619 LID - 10.1507/endocrj.EJ25-0402 [doi] AB - Obesity and type 2 diabetes mellitus (T2DM) are growing global health burdens, with dietary patterns, particularly high intake of carbohydrate- and fat-rich foods, contributing to disease progression. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is effective for both lowering blood glucose and reducing weight; however, its effects on food preferences for specific macronutrients remain unclear. In this retrospective observational study, we enrolled 32 obese subjects with T2DM who were hospitalized for glycemic control, including 20 who started semaglutide treatment (the Sema group) and 12 who did not receive GLP-1RA therapy. Eating behaviors were assessed using the Dietary Behavior Questionnaire from the Japan Society for the Study of Obesity (JASSO-DBQ), and food preferences for carbohydrates, fat, protein, and dietary fiber were quantitatively evaluated using the Japan Food Preference Questionnaire (JFPQ). Thirteen subjects in the Sema group and eight in the Non-GLP-1 group completed 6-months of follow-up. The Sema group showed significant decreases in HbA1c levels (-1.1%) and body weight (-5.7 kg), with fat loss exceeding skeletal muscle loss. Significant decreases were observed in eating behavior scores for "Eating Motives," "Way of Eating," and "Dietary Content." Notably, semaglutide significantly reduced preferences for sweet and non-sweet carbohydrates and non-sweet fats, without changing protein or dietary fiber preferences. In particular, significant reductions were observed in preferences for Japanese staple foods (e.g., white rice and udon/soba) and high-fat snacks. The Non-GLP-1 group showed no significant changes in food preferences for any of the nutrient categories. In summary, semaglutide treatment in obese subjects with T2DM facilitated weight loss, in part by altering food preferences, which potentially contributed to its metabolic benefits. FAU - Hara, Tomoyuki AU - Hara T AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Fujishima, Yuya AU - Fujishima Y AUID- ORCID: 0000-0003-0028-1757 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Kimura, Yu AU - Kimura Y AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Fujii, Kohei AU - Fujii K AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Kawachi, Yusuke AU - Kawachi Y AD - Department of Diabetes Endocrinology, Rinku General Medical Center, Osaka 598-0048, Japan. FAU - Nagao, Hirofumi AU - Nagao H AUID- ORCID: 0009-0001-1261-4160 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. AD - Department of Metabolism and Atherosclerosis, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Obata, Yoshinari AU - Obata Y AUID- ORCID: 0000-0002-3443-3635 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Fukuda, Shiro AU - Fukuda S AUID- ORCID: 0000-0003-0712-7154 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Nagai, Naoko AU - Nagai N AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. AD - Division of Nutrition Management, The University of Osaka Hospital, Osaka 565-0871, Japan. FAU - Nishizawa, Hitoshi AU - Nishizawa H AUID- ORCID: 0000-0002-7845-9693 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. AD - Department of Metabolism and Atherosclerosis, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. FAU - Shimomura, Iichiro AU - Shimomura I AUID- ORCID: 0000-0002-0851-9603 AD - Department of Metabolic Medicine, Graduate School of Medicine, The University of Osaka, Osaka 565-0871, Japan. LA - eng PT - Journal Article PT - Observational Study DEP - 20260129 PL - Japan TA - Endocr J JT - Endocrine journal JID - 9313485 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - Japanese people SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Feeding Behavior/drug effects MH - *Food Preferences/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use MH - Japan MH - *Obesity/complications/drug therapy MH - Retrospective Studies MH - *Semaglutide/pharmacology/therapeutic use MH - Weight Loss/drug effects MH - East Asian People PMC - PMC13195457 OTO - NOTNLM OT - Eating behavior OT - Food preference OT - GLP-1 receptor agonist OT - Obesity OT - Type 2 diabetes mellitus COIS- None of the authors has any potential conflicts of interest associated with this research. EDAT- 2026/01/29 01:49 MHDA- 2026/05/11 00:30 PMCR- 2026/01/29 CRDT- 2026/01/28 21:43 PHST- 2026/05/11 00:30 [medline] PHST- 2026/01/29 01:49 [pubmed] PHST- 2026/01/28 21:43 [entrez] PHST- 2026/01/29 00:00 [pmc-release] AID - 10.1507/endocrj.EJ25-0402 [doi] PST - ppublish SO - Endocr J. 2026 May 8;73(5):607-619. doi: 10.1507/endocrj.EJ25-0402. Epub 2026 Jan 29. PMID- 41604151 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260730 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 9 IP - 1 DP - 2026 Jan 2 TI - Glucagon-Like Peptide-1 Receptor Agonists and Prior Major Adverse Limb Events in Patients With Diabetes. PG - e2555952 LID - 10.1001/jamanetworkopen.2025.55952 [doi] LID - e2555952 AB - IMPORTANCE: Patients with diabetes and a history of major adverse limb events (MALEs) are at an increased risk of cardiovascular and limb-related complications; however, effective glucose-lowering therapies for secondary prevention in this population are limited. OBJECTIVE: To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with reduced risk of MALEs and major adverse cardiovascular events (MACE) compared with dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with diabetes and prior MALEs. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, nationwide cohort study used data from the Taiwan National Health Insurance Research Database from October 2012 to December 2023. Patients with diabetes and a history of MALE who initiated GLP-1 RAs or DPP-4 inhibitors were included. MALEs were defined as chronic limb-threatening ischemia, lower limb revascularization, or nontraumatic minor and major amputation. EXPOSURES: Initiation of GLP-1 RAs (liraglutide, dulaglutide, or semaglutide) vs DPP-4 inhibitors. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of lower limb revascularization and nontraumatic major and minor amputation. The secondary outcomes were MACEs (cardiovascular death, ischemic stroke, and myocardial infarction), all-cause mortality, and progression to long-term dialysis. A new-user, active-comparator design with inverse probability of treatment weighting was employed. RESULTS: Among 17 288 patients (mean [SD] age, 70.7 [12.0] years; 10 010 male [57.9%]), 1583 initiated GLP-1 RAs and 15 705 initiated DPP-4 inhibitors. After weighting, the use of GLP-1 RAs was associated with a lower risk of MALEs (subdistribution hazard ratio [SHR], 0.90; 95% CI, 0.83-0.97), primarily due to a marked reduction in amputation (SHR, 0.86; 95% CI, 0.75-0.98). GLP-1 RAs were also associated with reduced risks of MACEs (HR, 0.62; 95% CI, 0.58-0.65), cardiovascular death (HR, 0.57; 95% CI, 0.53-0.61), all-cause mortality (HR 0.63; 95% CI, 0.60-0.66), and progression to dialysis (SHR, 0.61; 95% CI, 0.54-0.70). CONCLUSIONS AND RELEVANCE: In this nationwide cohort study of patients with diabetes and prior MALEs, treatment with GLP-1 RAs was associated with significantly lower risks of recurrent limb events, cardiovascular events, all-cause mortality, and kidney disease progression compared with DPP-4 inhibitors. These findings support the preferential use of GLP-1 RAs for secondary prevention in this high-risk population. FAU - Hsiao, Fu-Chih AU - Hsiao FC AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Hsu, Tzyy-Jer AU - Hsu TJ AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. FAU - Hsieh, Yu-Jui AU - Hsieh YJ AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. FAU - Tung, Ying-Chang AU - Tung YC AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. FAU - Chen, Dong-Yi AU - Chen DY AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. FAU - Lin, Chia-Pin AU - Lin CP AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. FAU - Chen, Shao-Wei AU - Chen SW AD - Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taiwan. AD - Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan, Taiwan. FAU - Chu, Pao-Hsien AU - Chu PH AD - The Cardiovascular Department, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20260102 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Aged MH - Taiwan/epidemiology MH - Middle Aged MH - Female MH - Amputation, Surgical/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Cardiovascular Diseases/epidemiology/prevention & control PMC - PMC12853205 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2026/01/28 13:12 MHDA- 2026/01/28 19:34 PMCR- 2026/01/28 CRDT- 2026/01/28 11:33 PHST- 2026/01/28 19:34 [medline] PHST- 2026/01/28 13:12 [pubmed] PHST- 2026/01/28 11:33 [entrez] PHST- 2026/01/28 00:00 [pmc-release] AID - 2844425 [pii] AID - zoi251490 [pii] AID - 10.1001/jamanetworkopen.2025.55952 [doi] PST - epublish SO - JAMA Netw Open. 2026 Jan 2;9(1):e2555952. doi: 10.1001/jamanetworkopen.2025.55952. PMID- 41589628 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 0332-3102 (Print) IS - 0332-3102 (Linking) VI - 119 IP - 1 DP - 2026 Jan 22 TI - Non-Arteritic Ischaemic Optic Neuropathy Associated with Semaglutide Use. PG - 13 AB - PRESENTATION: A 50-year-old obese male with non-insulin dependent diabetes mellitus (NIDDM) taking Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) presented with sudden, painless vision-loss from his right eye. DIAGNOSIS: Right eye visual acuity was 6/24. There was Frisen grade IV optic nerve head (ONH) oedema. This was confirmed at imaging with ocular coherence tomography (OCT). The patient was diagnosed with non-arteritic anterior ischaemic optic neuropathy. TREATMENT: Semaglutide was ceased. DISCUSSION: GLP-1RAs such as Semaglutide are being increasingly recognised as a potential risk factor for NAION. A case such as this has not yet been reported in Ireland. FAU - Kelly, A AU - Kelly A FAU - Hasif, A AU - Hasif A FAU - McAnena, L AU - McAnena L FAU - O'Brien, C AU - O'Brien C LA - eng PT - Case Reports PT - Journal Article DEP - 20260122 PL - Ireland TA - Ir Med J JT - Irish medical journal JID - 0430275 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Male MH - Middle Aged MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - *Glucagon-Like Peptides/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - Tomography, Optical Coherence COIS- None declared. EDAT- 2026/01/27 12:59 MHDA- 2026/01/27 13:00 CRDT- 2026/01/27 07:30 PHST- 2026/01/27 13:00 [medline] PHST- 2026/01/27 12:59 [pubmed] PHST- 2026/01/27 07:30 [entrez] PST - epublish SO - Ir Med J. 2026 Jan 22;119(1):13. PMID- 41588354 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260813 IS - 1471-2377 (Electronic) IS - 1471-2377 (Linking) VI - 26 IP - 1 DP - 2026 Jan 26 TI - Recurrent bilateral brachial plexus neuritis following rapid semaglutide-induced weight loss: a case report. PG - 123 LID - 10.1186/s12883-026-04664-4 [doi] LID - 123 AB - BACKGROUND: Brachial plexus neuritis, or Parsonage-Turner syndrome, is an uncommon neuropathy marked by acute pain followed by weakness, often triggered by infection, vaccination, trauma, or metabolic stress but the exact cause of this disease remained unknown. Semaglutide is widely used for the treatment of type 2 diabetes and obesity. With its increasing use, there have been reports suggesting a possible association with neuropathies. Currently, there is no information suggesting a possible association between the use of semaglutide and brachial plexus neuritis. CASE PRESENTATION: A 39-year-old man with a prior episode of unilateral brachial neuritis developed recurrent bilateral upper limb weakness after an eight-month, 70-pound semaglutide-associated weight loss. He presented with bilateral radial sensory loss, finger extensor paralysis, right triceps weakness and decreased grip strength on the left side. Corticosteroids provided pain relief, but motor and sensory deficits persisted despite physiotherapy. CONCLUSION: This case highlights a temporal association between rapid pharmacologic weight loss and recurrent idiopathic brachial plexus neuritis, emphasizing the importance of gradual, nutritionally supported weight reduction and vigilance for neuromuscular complications during GLP-1 receptor agonist therapy. FAU - Lesinszki, Lukacs S AU - Lesinszki LS AD - Department of Physiology, Semmelweis University School of Medicine, Tuzolto utca 37-47, Budapest, 1094, Hungary. lesinszki.lukacs.sandor@semmelweis.hu. FAU - Khalili, Radmanesh AU - Khalili R AD - Department of Neurology, Karl Landsteiner University of Health Sciences, Vienna, Austria. FAU - Jiang, Haiyang AU - Jiang H AD - Tongji Medical College of Huazhong, University of Science and Technology, Wuhan, China. FAU - Jha, Shivangi AU - Jha S AD - Albert Szent-Gyorgyi Medical School, University of Szeged, Szeged, Hungary. FAU - Bernad, Peter G AU - Bernad PG AD - Department of Neurology and Rehabilitation Medicine, George Washington University, Washington D.C, United States of America. LA - eng PT - Case Reports PT - Journal Article DEP - 20260126 PL - England TA - BMC Neurol JT - BMC neurology JID - 100968555 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Male MH - Adult MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptides/adverse effects MH - *Brachial Plexus Neuritis/chemically induced/etiology MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Recurrence PMC - PMC12918017 OTO - NOTNLM OT - Brachial plexus neuritis OT - Case report OT - GLP-1 agonists OT - Semaglutide COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: The patient gave written informed consent for their clinical details along with any identifying images to be published in this study. Competing interests: The authors declare no competing interests. EDAT- 2026/01/27 00:52 MHDA- 2026/06/27 06:46 PMCR- 2026/01/26 CRDT- 2026/01/26 23:32 PHST- 2025/10/23 00:00 [received] PHST- 2026/01/20 00:00 [accepted] PHST- 2026/06/27 06:46 [medline] PHST- 2026/01/27 00:52 [pubmed] PHST- 2026/01/26 23:32 [entrez] PHST- 2026/01/26 00:00 [pmc-release] AID - 10.1186/s12883-026-04664-4 [pii] AID - 4664 [pii] AID - 10.1186/s12883-026-04664-4 [doi] PST - epublish SO - BMC Neurol. 2026 Jan 26;26(1):123. doi: 10.1186/s12883-026-04664-4. PMID- 41582648 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 0946-1965 (Print) IS - 0946-1965 (Linking) VI - 64 IP - 5 DP - 2026 May TI - Hemoglobin A1c levels in patients with type 2 diabetes mellitus receiving oral semaglutide with versus without proton pump inhibitors: An exploratory study. PG - 250-258 LID - 10.5414/CP204899 [doi] AB - OBJECTIVE: Oral semaglutide contains salcaprozate sodium, which promotes the opening of epithelial tight junctions and increases gastric pH to prevent its degradation; these actions together improve absorption. Proton pump inhibitors (PPIs) increase gastric pH. However, it is unclear whether PPIs affect the absorption of semaglutide and may therefore enhance the blood glucose lowering effect of semaglutide or affect the reduction of hemoglobin A1c (HbA1c). Therefore, this study investigated differences in HbA1c changes and adverse events between those with and without PPI co-administration. MATERIALS AND METHODS: This single-center retrospective study included patients with type 2 diabetes who received oral semaglutide. Patients were categorized into two groups: those on treatment with PPI (w/PPI) and those not on treatment with PPI (without PPI (w/o PPI)). The primary outcome was the change in HbA1c levels at 52 weeks, while the secondary outcomes included changes at 26 weeks and the incidence of adverse events. RESULTS: A total of 66 patients were included. HbA1c reduction at 52 weeks was significantly greater in the w/PPI group (-1.56 +/- 0.37%) than in the w/o PPI group (-1.08 +/- 0.76%, p = 0.024). The incidences of adverse events were 24.0% and 31.7% in the w/PPI and w/o PPI groups, respectively (p = 0.502). CONCLUSION: HbA1c reduction at 52 weeks was significantly greater in the PPI co-administration group than in the group without PPI. Future research should include larger sample sizes and pharmacokinetic studies to clarify the clinical implications and interactions between oral semaglutide and PPIs. FAU - Matsunuma, Satoru AU - Matsunuma S FAU - Hirota, Yusuke AU - Hirota Y FAU - Yoshimoto, Koichi AU - Yoshimoto K LA - eng PT - Comparative Study PT - Journal Article PL - Germany TA - Int J Clin Pharmacol Ther JT - International journal of clinical pharmacology and therapeutics JID - 9423309 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glycated Hemoglobin) RN - 0 (Proton Pump Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/blood/diagnosis MH - *Glycated Hemoglobin/metabolism MH - Female MH - *Proton Pump Inhibitors/administration & dosage/adverse effects/therapeutic use MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use/pharmacokinetics MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Administration, Oral MH - Aged MH - Drug Therapy, Combination MH - Blood Glucose/drug effects/metabolism MH - Drug Interactions MH - Treatment Outcome EDAT- 2026/01/26 06:27 MHDA- 2026/04/21 18:07 CRDT- 2026/01/26 03:03 PHST- 2026/04/16 00:00 [accepted] PHST- 2026/04/21 18:07 [medline] PHST- 2026/01/26 06:27 [pubmed] PHST- 2026/01/26 03:03 [entrez] AID - 192692 [pii] AID - 10.5414/CP204899 [doi] PST - ppublish SO - Int J Clin Pharmacol Ther. 2026 May;64(5):250-258. doi: 10.5414/CP204899. PMID- 41580697 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260813 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2026 Jan 24 TI - Progression to type 2 diabetes among post-myocardial infarction patients with overweight or obesity: a real-world cohort study. PG - 56 LID - 10.1186/s12933-026-03085-4 [doi] LID - 56 AB - BACKGROUND: Semaglutide has demonstrated the ability to reduce the risk of progression to type 2 diabetes in patients with myocardial infarction and overweight or obesity without diabetes. However, implementation of semaglutide treatment in daily clinical care is challenging due to costs and limited supply. Thus, it is essential to identify patients who are most likely to benefit from this treatment. Therefore, we aimed to investigate the 5-year risk of progression to type 2 diabetes in SELECT-eligible patients with a recent myocardial infarction and overweight or obesity without diabetes, and to assess the estimated preventive potential of semaglutide in a real-world cohort. METHODS: We included patients registered in the Western Denmark Heart Registry with first-time myocardial infarction and body mass index (BMI) >/= 27 kg/m(2) without diabetes, thus meeting the eligibility criteria of the SELECT trial. The cohort was grouped by glycemic status at baseline: HbA1c 6.0-6.4% (prediabetes(6.0-6.4%)), 5.7-6.4% (prediabetes(5.7-6.4%)), or < 5.7% (normoglycemia). A Cox proportional hazards regression model was used to calculate cause-specific hazard ratios (HR), adjusted for sex, age, hypertension, and smoking. The main endpoint was progression to type 2 diabetes. The 5-year number-needed-to-treat (NNT(5)) with semaglutide was estimated based on the SELECT trial. RESULTS: The cohort comprised 7398 patients with median follow-up of 4.7 (Q1-Q3 2.8-5.0) years. At baseline, 1385 (19%) patients had prediabetes(6.0-6.4%), 3751 (51%) had prediabetes(5.7-6.4%), and 3647 (49%) had normoglycemia. The median BMI was similar across the groups: 30 kg/m(2) (Q1-Q3 28-33), 30 kg/m(2) (Q1-Q3 28-32), and 29 kg/m(2) (Q1-Q3 28-31). The 5-year risks of progression to type 2 diabetes were 54%, 30%, and 5%, respectively. Compared with normoglycemia, those with prediabetes(6.0-6.4%) were associated with an 18-fold increased risk of progression to type 2 diabetes (HR 18.3, 95% CI 15.2-22.1) and the estimated NNT(5) with semaglutide to prevent one case of type 2 diabetes was 2.7 in this subgroup. CONCLUSIONS: In real-world patients with recent myocardial infarction and overweight or obesity, prediabetes was much stronger associated with progression to type 2 diabetes than previously reported in the SELECT trial. Further, we estimated that treatment with semaglutide might be able to substantially reduce progression to type 2 diabetes. CI - (c) 2026. The Author(s). FAU - Tonnesen, Pernille Tilma AU - Tonnesen PT AUID- ORCID: 0000-0001-8285-2087 AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. pernille.tilma@clin.au.dk. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. pernille.tilma@clin.au.dk. FAU - Olesen, Kevin Kris Warnakula AU - Olesen KKW AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Gyldenkerne, Christine AU - Gyldenkerne C AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Hansen, Malene Kaerslund AU - Hansen MK AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Stodkilde-Jorgensen, Nina AU - Stodkilde-Jorgensen N AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Thrane, Pernille Gro AU - Thrane PG AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Andersen, Malene Hojgaard AU - Andersen MH AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Poulsen, Per Logstrup AU - Poulsen PL AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. FAU - Thomsen, Reimar Wernich AU - Thomsen RW AD - Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University, Aarhus, Denmark. FAU - Sattar, Naveed AU - Sattar N AD - Institute of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, Scotland. FAU - Sorensen, Henrik Toft AU - Sorensen HT AD - Department of Clinical Epidemiology and Center for Population Medicine, Aarhus University, Aarhus, Denmark. FAU - Maeng, Michael AU - Maeng M AD - Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. LA - eng GR - NNF22OC0074083/Novo Nordisk Fonden/ PT - Journal Article PT - Observational Study DEP - 20260124 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Biomarkers) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Incretins) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/diagnosis/epidemiology/prevention & control/blood MH - Female MH - Disease Progression MH - Male MH - *Myocardial Infarction/diagnosis/epidemiology MH - Aged MH - Middle Aged MH - Risk Factors MH - *Obesity/diagnosis/epidemiology/drug therapy MH - Time Factors MH - Biomarkers/blood MH - Denmark/epidemiology MH - Registries MH - Risk Assessment MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Hypoglycemic Agents/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - Treatment Outcome MH - *Incretins/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism MH - Overweight/diagnosis/epidemiology PMC - PMC12911086 OTO - NOTNLM OT - Coronary artery disease OT - Myocardial infarction OT - Prediabetes OT - SELECT-eligible OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: This study was reported to the Danish Data Protection Agency (record no. 1-16-02-193-18). Patient consent requirements were waived by regional data protection authorities (record no. 14-45-70-24-22). Consent for publication: Not applicable. Competing interests: MHA is a minor shareholder in Novo Nordisk and is supported by the Danish Cardiovascular Academy (grant number PhD2023001-HF), which is funded by the Novo Nordisk Foundation, grant number NNF20SA0067242, and the Danish Heart Foundation. KKWO is supported by a research grant from the Danish Cardiovascular Academy funded by the Danish Heart Association and Novo Nordisk.RWT has given single lectures on medical research for pharmaceutical companies (with and without compensation), including AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi.NS has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GlaxoSmithKline, Hanmi Pharmaceuticals, Menarini-Ricerche, Metsera, Novartis, Novo Nordisk, Pfizer, and Roche; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche outside the submitted work. HTS is head of the Department of Clinical Epidemiology, Aarhus University, which receives funding for other studies in the form of institutional research grants to (and administered by) Aarhus University. The Department of Clinical Epidemiology confirms that none of these studies have any relation to the present study. MM is supported by a grant from the Novo Nordisk Foundation (grant number NNF22OC0074083), has received lecture and/or advisory board fees from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Novo Nordisk, has received research grants from Philips, Bayer and Novo Nordisk, has received a travel grant from Novo Nordisk, has ongoing institutional research contracts with Janssen, Novo Nordisk and Philips, and has equity interests in Novo Nordisk, Eli Lilly & Company, and Verve Therapeutics. The remaining authors did not report any competing interests. EDAT- 2026/01/25 00:37 MHDA- 2026/02/18 10:06 PMCR- 2026/01/24 CRDT- 2026/01/24 23:25 PHST- 2025/11/11 00:00 [received] PHST- 2026/01/07 00:00 [accepted] PHST- 2026/02/18 10:06 [medline] PHST- 2026/01/25 00:37 [pubmed] PHST- 2026/01/24 23:25 [entrez] PHST- 2026/01/24 00:00 [pmc-release] AID - 10.1186/s12933-026-03085-4 [pii] AID - 3085 [pii] AID - 10.1186/s12933-026-03085-4 [doi] PST - epublish SO - Cardiovasc Diabetol. 2026 Jan 24;25(1):56. doi: 10.1186/s12933-026-03085-4. PMID- 41580554 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260701 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 16 IP - 1 DP - 2026 Jan 24 TI - Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake. PG - 6126 LID - 10.1038/s41598-026-36318-3 [doi] LID - 6126 AB - The gut microbiome has been shown to be affected by the use of many human-targeted medications, and the interaction can be bidirectional. This has been clearly demonstrated for type 2 diabetes medications that have been in clinical use for several decades. However, the bidirectional effects of novel type 2 diabetes drugs semaglutide, empagliflozin, and the gut microbiome have yet to be clearly described. Considering this, we investigate the effect of semaglutide and empagliflozin initiation on the gut microbiome of type 2 diabetes patients. In addition, we analyze whether the pre-treatment gut microbiome can predict the treatment efficacy. In the study, patients with type 2 diabetes donated gut microbiome fecal samples at four timepoints (Baseline, Month 1, Month 3, Month 12) that were studied using 16S ribosomal RNA gene sequencing and analysis. Subjects additionally donated plasma and urine samples for quantitative measurement of clinical markers before treatment initiation and at Months 3 and 12. Repeated measures ANOVA paired with paired t-tests were used to analyze the effects of drug initiation on the gut microbiome. Pearson correlation was used to identify microbial features associated with the change in clinical parameters. First, semaglutide and empagliflozin use is associated with changes in the gut microbiome after treatment initiation, but changes in microbial diversity were not detected. Moreover, the baseline gut microbiome predicted changes in glycohemoglobin for semaglutide and empagliflozin users. Based on the results, our findings suggest that semaglutide and empagliflozin impact the gut microbial community during treatment. In addition, the baseline gut microbiome can predict semaglutide treatment effects. CI - (c) 2026. The Author(s). FAU - Klemets, Annabel AU - Klemets A AD - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. FAU - Reppo, Ingrid AU - Reppo I AD - Department of Internal Medicine, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia. AD - Internal Medicine Clinic of Tartu University Hospital, Tartu, Estonia. FAU - Krigul, Kertu Liis AU - Krigul KL AD - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. FAU - Volke, Vallo AU - Volke V AD - Department of Internal Medicine, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia. AD - Internal Medicine Clinic of Tartu University Hospital, Tartu, Estonia. FAU - Aasmets, Oliver AU - Aasmets O AD - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. FAU - Org, Elin AU - Org E AD - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia. elin.org@ut.ee. LA - eng GR - IUT2041/Eesti Teadusagentuur/ GR - PRG1414/Eesti Teadusagentuur/ GR - No. 3573/European Molecular Biology Organization/ PT - Journal Article DEP - 20260124 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) RN - HDC1R2M35U (empagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (RNA, Ribosomal, 16S) SB - IM MH - Humans MH - Semaglutide MH - *Benzhydryl Compounds/therapeutic use/pharmacology MH - *Glucosides/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/microbiology MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Feces/microbiology MH - Male MH - *Gastrointestinal Microbiome/drug effects MH - Female MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Middle Aged MH - Treatment Outcome MH - RNA, Ribosomal, 16S/genetics MH - Aged PMC - PMC12902008 OTO - NOTNLM OT - Empagliflozin OT - Gut microbiome OT - Jardiance OT - Ozempic OT - Semaglutide OT - Type 2 diabetes COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2026/01/25 00:37 MHDA- 2026/02/13 01:27 PMCR- 2026/01/24 CRDT- 2026/01/24 23:17 PHST- 2024/12/21 00:00 [received] PHST- 2026/01/12 00:00 [accepted] PHST- 2026/02/13 01:27 [medline] PHST- 2026/01/25 00:37 [pubmed] PHST- 2026/01/24 23:17 [entrez] PHST- 2026/01/24 00:00 [pmc-release] AID - 10.1038/s41598-026-36318-3 [pii] AID - 36318 [pii] AID - 10.1038/s41598-026-36318-3 [doi] PST - epublish SO - Sci Rep. 2026 Jan 24;16(1):6126. doi: 10.1038/s41598-026-36318-3. PMID- 41574970 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 5 DP - 2026 May TI - Efficacy and safety of once-weekly insulins in type 2 diabetes: A systematic review and meta-analysis. PG - 3491-3501 LID - 10.1111/dom.70497 [doi] AB - AIMS: Once-weekly (OW) insulins represent a promising strategy to reduce injection burden and improve adherence in type 2 diabetes management. This meta-analysis aimed to quantify pooled effect sizes for key biological and clinical outcomes, integrating new findings from the five large trials published in 2025. MATERIALS AND METHODS: We systematically searched PubMed, WoS, ClinicalTrials.gov and EU Clinical Trials databases up to June 2025 for randomized controlled trials (RCTs) evaluating OW insulins in type 2 diabetes. Primary outcomes included efficacy (HbA1c, fasting plasma glucose (FPG), time-in-range (TIR), time-above-range) and safety outcomes (body weight, hypoglycaemia, time-below-range). Data were analysed using both frequentist and Bayesian approaches. RESULTS: Among 435 screened records, 16 RCTs were included. OW insulins achieved a greater reduction in HbA1c compared to once-daily insulin or semaglutide (pooled mean difference: -0.12%, 95% CI: -0.19 to -0.04, p = 0.007). TIR was significantly longer in the OW insulin group (+2.41% of total time, 95% CI: 1.13 to 3.69, p = 0.002), while FPG changes were comparable (-3.37 mg/dL, 95% CI: -7.95 to 1.21 mg/dL, p = 0.14). Body weight changes were generally similar, but excluding trials using IcoSema revealed a modest weight gain (+0.33 kg, 95% CI: 0.04 to 0.62, p = 0.030). The incidence of clinically significant or severe hypoglycaemia did not differ between groups (pooled incidence rate ratio: 1.04, 95% CI: 0.79 to 1.28, p = 0.75). Meta-regression confirmed consistent effect sizes across OW insulin types, treatment durations and prior insulin regimens. CONCLUSIONS: OW insulins modestly improve glycaemic control without increasing hypoglycaemia risk, though slight weight gain may occur. CI - (c) 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Bourron, Olivier AU - Bourron O AUID- ORCID: 0000-0001-7348-7161 AD - Sorbonne Universite, UMRS 1166, AP-HP, Hopital Pitie-Salpetriere, Service de Diabetologie, INSERM, IHU ICAN, Paris, France. FAU - Denimal, Damien AU - Denimal D AUID- ORCID: 0000-0001-5454-954X AD - Universite Bourgogne Europe, CHU Dijon Bourgogne, Service Biochimie, INSERM, U1231, PADYS Team, Dijon, France. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260123 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Drug Administration Schedule MH - Glycated Hemoglobin/analysis MH - *Insulin/administration & dosage/adverse effects MH - Blood Glucose/drug effects MH - Hypoglycemia/chemically induced MH - Semaglutide MH - Randomized Controlled Trials as Topic MH - Treatment Outcome PMC - PMC13071184 OTO - NOTNLM OT - insulin analogues OT - insulin therapy OT - meta-analysis OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2026/01/23 13:05 MHDA- 2026/04/13 06:32 PMCR- 2026/04/13 CRDT- 2026/01/23 08:13 PHST- 2026/01/04 00:00 [revised] PHST- 2025/10/09 00:00 [received] PHST- 2026/01/09 00:00 [accepted] PHST- 2026/04/13 06:32 [medline] PHST- 2026/01/23 13:05 [pubmed] PHST- 2026/01/23 08:13 [entrez] PHST- 2026/04/13 00:00 [pmc-release] AID - DOM70497 [pii] AID - 10.1111/dom.70497 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 May;28(5):3491-3501. doi: 10.1111/dom.70497. Epub 2026 Jan 23. PMID- 41565568 OWN - NLM STAT- MEDLINE DCOM- 20260701 LR - 20260702 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 20 IP - 2 DP - 2026 Apr TI - Semaglutide and tirzepatide in prediabetes: Evidence for diabetes prevention and cardiovascular protection. PG - 178-184 LID - S1751-9918(26)00002-1 [pii] LID - 10.1016/j.pcd.2026.01.003 [doi] AB - BACKGROUND: Prediabetes represents an intermediate stage in the dysglycemia continuum, associated with increased cardiometabolic risk but also substantial opportunity for prevention. The aim of this review was to summarize and critically evaluate the available evidence on the effects of semaglutide and tirzepatide in individuals with prediabetes, focusing on diabetes prevention and cardiovascular (CV) outcomes. METHODS: A narrative synthesis of data from randomized controlled trials, meta-analyses, and real-world studies assessing semaglutide and tirzepatide in people with prediabetes. RESULTS: Across the STEP 1, STEP 5, and SELECT trials, semaglutide 2.4 mg significantly increased regression to normoglycemia (up to 84 %) and reduced the risk of progression to diabetes compared with placebo. In the SURMOUNT-1 trial, tirzepatide reduced the incidence of diabetes by nearly 90 % (Hazard Ratio: 0.07; p < 0.001), an effect largely mediated by substantial weight loss. Regarding CV outcomes, the SELECT trial, of which 66.4 % of participants had prediabetes, demonstrated a significant reduction in the primary composite endpoint of CV death, nonfatal myocardial infarction, or nonfatal stroke with semaglutide versus placebo (hazard ratio 0.80; 95 % CI: 0.72-0.90). A prespecified analysis showed that CV risk reduction was independent of baseline HbA1c, supporting CV benefit in people with prediabetes. The ongoing SURMOUNT-MMO trial will further clarify the CV effects of tirzepatide in individuals with obesity without diabetes. CONCLUSION: Semaglutide and tirzepatide markedly increase regression to normoglycemia and reduce progression to diabetes in people with obesity and prediabetes. Semaglutide has also demonstrated CV benefit in SELECT, including among participants with prediabetes. Ongoing outcome data, particularly from SURMOUNT-MMO, will further define the cardioprotective potential of GLP-1-based medicines across the dysglycemia spectrum. CI - Copyright (c) 2026 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved. FAU - Tentolouris, Anastasios AU - Tentolouris A AD - First Department of Propaedeutic Internal Medicine and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. Electronic address: antentol@med.uoa.gr. FAU - Siafarikas, Christos AU - Siafarikas C AD - First Department of Propaedeutic Internal Medicine and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Ntanasis-Stathopoulos, Ioannis AU - Ntanasis-Stathopoulos I AD - Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece. FAU - Anastasiou, Ioanna A AU - Anastasiou IA AD - First Department of Propaedeutic Internal Medicine and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Kalara, Eirini AU - Kalara E AD - First Department of Propaedeutic Internal Medicine and Diabetes Center, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Briasoulis, Alexandros AU - Briasoulis A AD - Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Alexandra General Hospital, Athens, Greece. LA - eng PT - Journal Article PT - Review DEP - 20260120 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Biomarkers) RN - 0 (Incretins) SB - IM MH - Humans MH - Semaglutide MH - *Tirzepatide/therapeutic use/adverse effects MH - *Prediabetic State/drug therapy/diagnosis/blood/epidemiology MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Cardiovascular Diseases/prevention & control/diagnosis/epidemiology MH - Treatment Outcome MH - *Blood Glucose/drug effects/metabolism MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Biomarkers/blood MH - *Diabetes Mellitus, Type 2/prevention & control/diagnosis/epidemiology/blood MH - *Incretins/therapeutic use/adverse effects MH - Risk Factors OTO - NOTNLM OT - Cardiovascular Disease OT - Diabetes Prevention OT - GLP-1-Based Therapies OT - Prediabetes OT - Semaglutide OT - Tirzepatide COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2026/01/22 01:09 MHDA- 2026/03/20 00:59 CRDT- 2026/01/21 21:54 PHST- 2025/11/10 00:00 [received] PHST- 2025/12/09 00:00 [revised] PHST- 2026/01/04 00:00 [accepted] PHST- 2026/03/20 00:59 [medline] PHST- 2026/01/22 01:09 [pubmed] PHST- 2026/01/21 21:54 [entrez] AID - S1751-9918(26)00002-1 [pii] AID - 10.1016/j.pcd.2026.01.003 [doi] PST - ppublish SO - Prim Care Diabetes. 2026 Apr;20(2):178-184. doi: 10.1016/j.pcd.2026.01.003. Epub 2026 Jan 20. PMID- 41562647 OWN - NLM STAT- MEDLINE DCOM- 20260121 LR - 20260127 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 29 IP - 1 DP - 2026 Dec TI - Calculating cost per event avoided using a composite number needed to treat. PG - 242-248 LID - 10.1080/13696998.2026.2615606 [doi] AB - OBJECTIVE: Number needed to treat (NNT) and cost per event avoided (CPEA) are measures used to represent the clinical and economic value of chronic treatments and are commonly calculated based on primary endpoints from trials. This approach, although widely used, does not reflect the complete value of a treatment, as it does not consider outcomes beyond the primary endpoints. This research aims to overcome this limitation by developing multiple composite NNTs to derive the CPEA to estimate a total value of semaglutide and dulaglutide in people with established cardiovascular disease. METHODS: Two cardiovascular outcomes trials were selected, SELECT (NCT03574597, semaglutide 2.4 mg) and REWIND (NCT01394952, dulaglutide 1.5 mg). NNT was calculated as NNT = 1/ARR where ARR = control event rate - experimental event rate. NNT was estimated for 3-point major adverse cardiovascular events (MACE-3; primary endpoint of the trials), 5-point MACE (MACE-5), and cardiovascular-kidney-metabolic events (CKM). CPEA of MACE-3, MACE-5, and CKM was calculated as NNT*duration of mean follow-up (semaglutide) or duration of median follow-up (dulaglutide)*estimated net price. RESULTS: The NNT decreased as the number of outcomes in the composite endpoint increased, where NNT(MACE-3), NNT(MACE-5), and NNT(CKM) were 67, 49, and 8 for semaglutide, and 72, 64, and 23 for dulaglutide, respectively. Similarly, the CPEA decreased as the number of outcomes in the composite endpoint increased, where the CPEA for MACE-3, MACE-5 and CKM calculations were $1,662,001, $1,232,417, and $190,387 for semaglutide and $1,884,013, $1,670,366, and $607,886 for dulaglutide. CONCLUSIONS: This research illustrates the limitations of using a NNT focused only on the primary endpoint, as it does not capture the total benefit of the treatment. When considering the value of treatments through NNT or CPEA analyses, a composite endpoint capturing broader benefit should be utilized. FAU - Toliver, Joshua AU - Toliver J AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Wang, Julia AU - Wang J AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Bhavsar, Jigish AU - Bhavsar J AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Sullivan, Sean D AU - Sullivan SD AD - Curta, Inc, Seattle, Washington, USA. AD - CHOICE Institute, School of Pharmacy, University of Washington, Seattle, Washington, USA. LA - eng PT - Journal Article DEP - 20260121 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Cardiovascular Diseases/drug therapy MH - Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/analogs & derivatives/economics/therapeutic use MH - *Hypoglycemic Agents/economics/therapeutic use MH - *Immunoglobulin Fc Fragments/economics/therapeutic use MH - *Recombinant Fusion Proteins/economics/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Multicenter Studies as Topic MH - Clinical Trials, Phase III as Topic OAB - This study demonstrates how to assess the clinical and economic value of different drugs and how to assist decision-makers and payers for informed decision-making. This is substantial in diabetes and obesity, due to the surging costs of treating these diseases, both preventive and curative as well. We use data (from clinical trials) for semaglutide and dulaglutide in people with cardiovascular disease as an example. We calculated the number of people that need to be treated to avoid one major adverse cardiovascular event (MACE) and how much it would cost. We show that it is important to include several types of outcomes (here we look at different types of cardiovascular, kidney and metabolic outcomes), beyond the primary endpoint of a trial, to capture the full value of treatment. OABL- eng OTO - NOTNLM OT - Pharmacoeconomics OT - cardiovascular disease OT - disease management OT - health economics OT - number needed to treat EDAT- 2026/01/21 13:00 MHDA- 2026/01/21 13:01 CRDT- 2026/01/21 09:13 PHST- 2026/01/21 13:01 [medline] PHST- 2026/01/21 13:00 [pubmed] PHST- 2026/01/21 09:13 [entrez] AID - 10.1080/13696998.2026.2615606 [doi] PST - ppublish SO - J Med Econ. 2026 Dec;29(1):242-248. doi: 10.1080/13696998.2026.2615606. Epub 2026 Jan 21. PMID- 41555812 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260813 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 17 IP - 3 DP - 2026 Mar TI - Retrospective comparison of the clinical effects of oral semaglutide and SGLT2 inhibitors treatment in patients with type 2 diabetes. PG - 432-438 LID - 10.1111/jdi.70240 [doi] AB - INTRODUCTION: Recent studies have demonstrated that both oral semaglutide and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial effects on glycemic and weight management as well as providing renal and cardiovascular protection. However, direct comparisons of the effects of these two drugs in clinical practice remain limited. MATERIALS AND METHODS: This study is a single-center, retrospective, observational study. Patients with type 2 diabetes who were initiated on oral semaglutide or SGLT2is and continued treatment for 6 months or more were retrospectively analyzed and compared. RESULTS: The semaglutide group (84 patients) and the SGLT2is group (231 patients) showed similar, significant reductions in glycated hemoglobin (HbA1c) (semaglutide: -0.88 +/- 0.14%; P < 0.01, and SGLT2is: -0.86 +/- 0.06%; P < 0.01, at 6 months), body weight (semaglutide: -2.58 +/- 0.37 kg; P < 0.01, and SGLT2is: -2.30 +/- 0.18 kg; P < 0.01, at 6 months), and fat mass (semaglutide: -2.20 +/- 0.50 kg; P < 0.01, and SGLT2is: -1.93 +/- 0.44 kg; P < 0.01, at 6 months), being decreased similarly and significantly in both groups. On the other hand, there was a significant reduction in skeletal muscle mass only in the SGLT2is group (semaglutide: -0.10 +/- 0.30 kg; P = 0.74, and SGLT2is: -0.40 +/- 0.14 kg; P < 0.01 at 6 months). CONCLUSIONS: While both drugs elicited comparable effects on glycemic management and body weight reduction in patients with type 2 diabetes, caution is needed when using SGLT2is in patients at potential risk for sarcopenia, as they may lead to less favorable changes in skeletal muscle mass compared to oral semaglutide. CI - (c) 2026 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Omori, Yasuhiro AU - Omori Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Usui, Ryota AU - Usui R AUID- ORCID: 0000-0002-4641-0158 AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Yamazaki, Yuji AU - Yamazaki Y AUID- ORCID: 0009-0007-5876-8695 AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Kuwata, Hitoshi AU - Kuwata H AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Hamamoto, Yoshiyuki AU - Hamamoto Y AUID- ORCID: 0000-0002-1938-7394 AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Yamada, Yuichiro AU - Yamada Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Seino, Yutaka AU - Seino Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20260120 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Biomarkers) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide MH - Retrospective Studies MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Middle Aged MH - Glycated Hemoglobin/analysis MH - Administration, Oral MH - Aged MH - Blood Glucose/analysis MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Biomarkers/analysis MH - Follow-Up Studies MH - Prognosis PMC - PMC12950920 OTO - NOTNLM OT - Oral semaglutide OT - SGLT2 inhibitors OT - Skeletal muscle mass COIS- YH received grants from Sumitomo Pharma Co. and Nippon Boehringer Ingelheim Co. Ltd.; and honoraria for lectures from Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Daiichi Sankyo Company, Tanabe Pharma Corporation, Taisho Pharmaceutical Co., MSD K.K., and Sumitomo Pharma Co. YY received honoraria for lectures from Sumitomo Pharma Co. and Tanabe Pharma Corporation. HK received grants from Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., and Novo Nordisk Pharma Ltd.; and honoraria for lectures from Sanofi K.K. and Taisho Pharmaceutical Co. YuiY has received honoraria for lectures from Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Novo Nordisk Pharma Ltd., and Teijin Pharma Limited. YS has received grants from Nippon Boehringer Ingelheim Co., Ltd., ARKRAY Marketing, Inc., Taisho Pharmaceutical Co., Novo Nordisk Pharma Ltd., Terumo Corporation, and Sumitomo Pharma Co.; and honoraria for lectures from Taisho Pharmaceutical Co., Nippon Becton Dickinson Company, Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Sumitomo Pharma Co., Ono Pharmaceutical Co., Ltd., and Kyowa Kirin Co., Ltd. The other authors declare no conflict of interest. Approval of the research protocol: N/A. Informed Consent: Opt-out method. Approval date of Registry and the Registration No. of the study/trial: 22-98. Animal Studies: N/A. EDAT- 2026/01/20 07:44 MHDA- 2026/03/06 19:43 PMCR- 2026/01/20 CRDT- 2026/01/20 03:22 PHST- 2025/12/23 00:00 [revised] PHST- 2025/09/12 00:00 [received] PHST- 2026/01/05 00:00 [accepted] PHST- 2026/03/06 19:43 [medline] PHST- 2026/01/20 07:44 [pubmed] PHST- 2026/01/20 03:22 [entrez] PHST- 2026/01/20 00:00 [pmc-release] AID - JDI70240 [pii] AID - 10.1111/jdi.70240 [doi] PST - ppublish SO - J Diabetes Investig. 2026 Mar;17(3):432-438. doi: 10.1111/jdi.70240. Epub 2026 Jan 20. PMID- 41549912 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 1758-8111 (Electronic) IS - 1758-8103 (Linking) VI - 16 IP - 1 DP - 2026 Feb TI - Micronutrient and Nutritional Deficiencies Associated With GLP-1 Receptor Agonist Therapy: A Narrative Review. PG - e70070 LID - 10.1111/cob.70070 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RA) such as semaglutide, liraglutide and tirzepatide are effective for obesity and type 2 diabetes mellitus (T2DM) but may predispose users to micronutrient deficiencies through appetite suppression, delayed gastric emptying and altered absorption. Given the rapid rise in GLP-1RA use, clarifying their nutritional impact is clinically important. We conducted a structured search of PubMed and the Cochrane Database (January 2019-May 2025) for adult studies evaluating nutritional or micronutrient outcomes during GLP-1RA therapy. Paediatric studies, those lacking nutrient endpoints, and review articles were excluded. Methods followed SANRA and PRISMA-ScR guidance, and data were synthesised descriptively. Six studies met the inclusion criteria, encompassing 480 825 adults. Vitamin D deficiency was the most common abnormality, occurring in 7.5% at 6 months and 13.6% at 12 months. Iron depletion was frequent, with GLP-1RA users demonstrating 26%-30% lower ferritin levels than SGLT2 inhibitor comparators. More than 60% of users consumed below estimated requirements for calcium and iron, and vitamin D intake averaged 20% of recommendations. Protein and calcium insufficiency contributed to lean mass loss, while thiamine and cobalamin deficits increased over time. GLP-1RA therapy is associated with meaningful nutritional deficiencies. Targeted nutritional assessment and individualised laboratory evaluation may be appropriate for patients at increased risk of malnutrition. Findings are mainly derived from observational datasets, and causality between GLP-1RA therapy and nutritional deficiencies cannot be definitively established. CI - (c) 2026 World Obesity Federation. FAU - Urbina, Jorge AU - Urbina J AUID- ORCID: 0009-0008-6287-6354 AD - Universidad Autonoma de Guadalajara, Guadalajara, Jalisco, Mexico. FAU - Salinas-Ruiz, Luis Eduardo AU - Salinas-Ruiz LE AD - Instituto Tecnologico de Estudios Superiores de Monterrey, Campus Monterrey, Monterrey, Nuevo Leon, Mexico. FAU - Valenciano, Cesar AU - Valenciano C AD - Universidad Autonoma de Guadalajara, Guadalajara, Jalisco, Mexico. FAU - Clapp, Benjamin AU - Clapp B AUID- ORCID: 0000-0002-9892-4708 AD - Department of Surgery, Texas Tech University Health Sciences Center, El Paso, Texas, USA. LA - eng PT - Journal Article PT - Review PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Micronutrients) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Micronutrients/deficiency MH - Obesity/drug therapy MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Vitamin D Deficiency MH - Tirzepatide OTO - NOTNLM OT - GLP-1 receptor agonists OT - iron and vitamin D deficiency OT - micronutrient deficiency OT - sarcopenia OT - semaglutide EDAT- 2026/01/19 06:28 MHDA- 2026/01/19 06:29 CRDT- 2026/01/19 04:53 PHST- 2025/12/24 00:00 [revised] PHST- 2025/12/01 00:00 [received] PHST- 2026/01/06 00:00 [accepted] PHST- 2026/01/19 06:29 [medline] PHST- 2026/01/19 06:28 [pubmed] PHST- 2026/01/19 04:53 [entrez] AID - 10.1111/cob.70070 [doi] PST - ppublish SO - Clin Obes. 2026 Feb;16(1):e70070. doi: 10.1111/cob.70070. PMID- 41547366 OWN - NLM STAT- MEDLINE DCOM- 20260306 LR - 20260924 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 407 IP - 10531 DP - 2026 Feb 28 TI - Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits. PG - 892-908 LID - S0140-6736(25)02105-1 [pii] LID - 10.1016/S0140-6736(25)02105-1 [doi] AB - GLP-1 receptor agonists were initially developed to treat type 2 diabetes and have had a transformative effect on its therapy, and are highly effective for glycaemic control, with the added benefit of bodyweight reduction and a low risk of causing hypoglycaemia. GLP-1 receptor agonists reduce risks for major adverse cardiovascular events (eg, non-fatal myocardial infarction, stroke, and cardiovascular death), and the risk of admission to or treatment within hospital for heart failure. These drugs reduce albuminuria and slow the decline in estimated glomerular filtration rate over time, therefore delaying or preventing kidney failure. Furthermore, GLP-1 receptor agonists (eg, liraglutide and semaglutide) and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor co-agonist tirzepatide have been approved for treatment of obesity, with clinical trials establishing benefits for various obesity-related conditions: prevention of type 2 diabetes; risk for major adverse cardiovascular events; heart failure, especially with preserved ejection fraction; regression of steatosis and prevention of fibrosis in steatotic liver disease; and symptomatic improvements in obstructive sleep apnoea and knee osteoarthritis. Current developments include the exploration of novel indications (eg, neurodegenerative diseases and substance use disorders) with suggestive evidence of efficacy, and the development of small-molecule GLP-1 receptor agonists for oral treatment to improve convenience. Dual (ie, GLP-1-glucagon and GLP-1-amylin) and triple (ie, GIP-GLP-1-glucagon) receptor agonists activating multiple receptors promise greater efficacy than mono-agonists, especially for weight loss. However, some clinical development programmes have a high burden of adverse gastrointestinal events, and dose-escalation regimens should be optimised to reach acceptable tolerability. CI - Copyright (c) 2026 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved. FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes, Endocrinology, Metabolism Section, Medical Department 1, St Josef-Hospital, Katholisches Klinikum Bochum gGmbH, Ruhr University Bochum, Bochum, Germany; Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. Electronic address: michael.nauck@rub.de. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Providence Inland Northwest Health, Division of Nephrology and Kidney Research Institute, University of Washington School of Medicine, Spokane, WA, USA. FAU - Tschop, Matthias H AU - Tschop MH AD - Division of Metabolic Diseases, Technische Universitat Munchen, Helmholtz Diabetes Center, Helmholtz Zentrum Munchen, Munich, Germany. FAU - Bluher, Matthias AU - Bluher M AD - Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum Munchen, University of Leipzig and University Hospital Leipzig, Leipzig, Germany. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review DEP - 20260114 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 839I73S42A (Liraglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Lancet. 2026 Mar 14;407(10533):1058. doi: 10.1016/S0140-6736(26)00467-8. PMID: 41831846 MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Incretins/therapeutic use MH - Liraglutide/therapeutic use MH - Obesity/drug therapy MH - Tirzepatide/therapeutic use MH - Semaglutide/therapeutic use COIS- Declaration of interests MAN has been member on advisory boards or has consulted with Boehringer Ingelheim, Eli Lilly & Co, Medtronic, Merck, Sharp & Dohme, NovoNordisk, Pfizer, Regor, Sun Pharma, and Structure Therapeutics (Gasherbrum); has received grant support from Merck and Sharp & Dohme; has served on the speakers bureau of Eli Lilly & Co, Merck, Sharp & Dohme, Medscape, Medical Learning Institute, and NovoNordisk; and is on a Data Monitoring and Safety Board for Inventiva. KRT has received investigator-initiated grant support from Travere, Bayer, Benaroya Research Institute, the Doris Duke Charitable Foundation, and Breakthrough-T1D; reports consultancy fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, AstraZeneca, Alnylam, Bayer, and ProKidney; and reports speaker fees from Novo Nordisk, Bayer, and Boehringer Ingelheim. She reports US National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, OT2OD032581, and US Centers for Disease Control and Prevention project numbers 75D301-21-P-12254 and 75D301-23-C-18264. She reports being chair of Data Safety Monitoring boards for the US National Institutes of Health National Institute of Diabetes and Digestive and Kidney Disease, and the George Clinical Institute, and reports being a member of the Data Safety Monitoring Board for AstraZeneca. She reports leadership roles as chair for the Diabetic Kidney Disease Collaborative for the American Society of Nephrology, chair for Kidney Week 2025 Program Committee, member of the American Heart Association publication committee, and a member of the American Heart Association-American College of Cardiology Cardiovascular Kidney Metabolic Guideline Committee. MHT has delivered scientific lectures for Boehringer Ingelheim (2024), KG (2024), AstraZeneca (2024), Lilly Deutschland (2024), and Novo Nordisk (2024). He is co-founder of the biotech startup Bluewater Biotech (founded in 2024). As CEO and CSO of Helmholtz Munich, he is co-responsible for countless collaborations of the employees with a multitude of companies and institutions, worldwide. In this capacity, he discusses potential projects with and has signed/signs contracts for the centre's institute(s) related to research collaborations worldwide, including but not limited to pharmaceutical corporations such as Boehringer Ingelheim, Novo Nordisk, Roche Diagnostics, Arbormed, Eli Lilly, SCG Cell Therapy, and others. As the CEO of Helmholtz Munich, he was/is further overall responsible for commercial technology transfer activities. He confirms that, to the best of his knowledge, none of the above funding sources or collaborations were involved in or had an influence on the preparation of this manuscript. MB received honoraria as a consultant and speaker from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Lilly, MSD, Novo Nordisk, Novartis, Pfizer, and Sanofi; and reports chairing a Clinical Trial Data Safety Monitoring Board for Boehringer Ingelheim. EDAT- 2026/01/18 00:37 MHDA- 2026/03/06 08:57 CRDT- 2026/01/17 18:52 PHST- 2025/04/02 00:00 [received] PHST- 2025/10/13 00:00 [revised] PHST- 2025/10/13 00:00 [accepted] PHST- 2026/03/06 08:57 [medline] PHST- 2026/01/18 00:37 [pubmed] PHST- 2026/01/17 18:52 [entrez] AID - S0140-6736(25)02105-1 [pii] AID - 10.1016/S0140-6736(25)02105-1 [doi] PST - ppublish SO - Lancet. 2026 Feb 28;407(10531):892-908. doi: 10.1016/S0140-6736(25)02105-1. Epub 2026 Jan 14. PMID- 41544899 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 235 DP - 2026 May TI - Target trial emulations for tirzepatide, semaglutide and SGLT2-inhibitors for dementia in patients with type 2 diabetes: Real world evidence from a retrospective cohort study. PG - 113083 LID - S0168-8227(26)00002-1 [pii] LID - 10.1016/j.diabres.2026.113083 [doi] AB - AIMS: Evidence suggests sodium glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists may reduce the onset/progression of dementia. The effect of the dual GLP1/GIP receptor agonist tirzepatide on dementia outcomes remains unknown. We compared tirzepatide, semaglutide and SGLT2-i in relation to incident dementia in patients with type 2 diabetes. METHODS: Three target trial emulations (TTE) were conducted using real-world data from the TriNetX global federated network: TTE1: tirzepatide vs. SGLT2-i, TTE2: semaglutide vs. SGLT2-i and TTE3: tirzepatide vs. semaglutide. Eligible adults with type 2 diabetes without dementia at baseline were included. Follow-up was two years. First diagnosis of dementia, MACE, and all-cause mortality were analysed using survival analysis after propensity score matching. RESULTS: After matching, TTE1 included 14,462 patients; TTE2, 57,959; TTE3 12,246. Tirzepatide was associated with a lower risk of dementia versus semaglutide (HR 0.69, 95% CI 0.48-0.99, p = 0.04) and SGLT2-i (HR 0.66, 95% CI 0.47-0.93, p = 0.02), and lower mortality (HR 0.72, 95% CI 0.58-0.90, p < 0.01; HR 0.29, 95% CI 0.23-0.37, p < 0.01). Tirzepatide and semaglutide reduced MACE vs SGLT2-i. CONCLUSIONS: Tirzepatide is associated with a lower risk of dementia versus semaglutide and SGLT2-i in type 2 diabetes. Our findings are hypothesis generating, requiring confirmation in randomised controlled trials. CI - Copyright (c) 2026 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Younis, Alhena AU - Younis A AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. FAU - Henney, Alex E AU - Henney AE AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK. FAU - Anson, Matthew AU - Anson M AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK. FAU - Zhao, Sizheng S AU - Zhao SS AD - Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. FAU - Ibarburu, Gema H AU - Ibarburu GH AD - TriNetX LLC, Cambridge, MA, USA. FAU - Malik, Rayaz A AU - Malik RA AD - Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar. FAU - Su, Li AU - Su L AD - Sheffield Institute of Translational Neuroscience, School of Medicine and Population Health, University of Sheffield, Sheffield, UK; Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Cambridge, UK. FAU - Lip, Gregory Y H AU - Lip GYH AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK; Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Cardiology, Lipidology and Internal Medicine with Intensive Coronary Care Unit, Medical University of Bialystok, Bialystok, Poland. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK; Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, Merseyside, UK; Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK. Electronic address: Uazman.alam@liverpool.ac.uk. LA - eng PT - Journal Article DEP - 20260114 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Aged MH - Retrospective Studies MH - *Dementia/epidemiology/prevention & control/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Aged, 80 and over OTO - NOTNLM OT - Dementia OT - Diabetes OT - GLP1-RA OT - Tirzepatide COIS- Declaration of competing interest SSZ has received: (1) support for conference attendance from Novartis, UCB, AlfaSigma, Eli Lilly; (2) consultancy/speaker fees from Novartis, UCB, AlfaSigma, AbbVie, Jassen. GYHL is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos (No fees are received personally). He is co-PI of the AFFIRMO project on multimorbidity in AF (grant agreement No 899871), TARGET project on digital twins for personalised management of atrial fibrillation and stroke (grant agreement No 101136244) and ARISTOTELES project on artificial intelligence for management of chronic long term conditions (grant agreement No 101080189), which are all funded by the EU's Horizon Europe Research & Innovation programme. DJC has received investigator-initiated grants from Astra Zeneca and Novo Nordisk, support for education from Perspectum with any financial remuneration from pharmaceutical company consultation made to the University of Liverpool and serves as the Topic Advisor for Type 2 Diabetes medications for The National Institute for Health and Care Excellence (NICE), UK. UA has received honoraria from Procter & Gamble, Viatris, Grunenthal, Daiichi Sankyo, Eli Lilly, Theras and Sanofi for educational meetings and funding for attendance to an educational meeting from Sanofi and Daiichi Sankyo. UA has also received investigator-led funding by Procter & Gamble, consultancy fees from Axonis therapeutics and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. EDAT- 2026/01/17 00:36 MHDA- 2026/04/12 04:37 CRDT- 2026/01/16 19:14 PHST- 2025/11/19 00:00 [received] PHST- 2025/12/28 00:00 [revised] PHST- 2026/01/05 00:00 [accepted] PHST- 2026/04/12 04:37 [medline] PHST- 2026/01/17 00:36 [pubmed] PHST- 2026/01/16 19:14 [entrez] AID - S0168-8227(26)00002-1 [pii] AID - 10.1016/j.diabres.2026.113083 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 May;235:113083. doi: 10.1016/j.diabres.2026.113083. Epub 2026 Jan 14. PMID- 41540866 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20260626 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 22 IP - 945 DP - 2026 Jan 14 TI - [Nephrology : what's new in 2025]. PG - 49-52 LID - 10.53738/REVMED.2026.22.945.47996 [doi] AB - Complement inhibitors are expanding their indications in nephrology. In patients with type 2 diabetes, semaglutide prevents chronic kidney disease (CKD), while retatrutide reduces albuminuria in patients with diabetes and established CKD. Obinutuzumab improves the renal response in patients with lupus nephropathy. A double dose of icodextrin did not reduce mortality, peritonitis, or hospitalization rates compared to standard peritoneal dialysis treatment, though it increased ultrafiltration. In patients on hemodialysis, using a dialysate with an intermediate potassium concentration combined with a potassium chelator appears to stabilize serum potassium levels and reduce the occurrence of arrhythmias. Xenotransplantation and ex vivo perfusion techniques are being perfected in the search for a solution to organ shortage. FAU - Nanchen, Giliane AU - Nanchen G AUID- ORCID: 0000-0002-8522-7524 AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. FAU - Pruijm, Menno AU - Pruijm M AUID- ORCID: 0000-0003-1027-1851 AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. FAU - Lamine, Faiza AU - Lamine F AUID- ORCID: 0000-0001-6299-714X AD - Unite d'endocrinologie-diabetologie, Service de medecine interne, Centre hospitalier de Rennaz, 1847 Rennaz. AD - Service d'endocrinologie, diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Golshayan, Dela AU - Golshayan D AUID- ORCID: 0000-0001-5631-6096 AD - Centre de transplantation d'organes, Departement de medecine, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. FAU - Fakhouri, Fadi AU - Fakhouri F AUID- ORCID: 0000-0001-5390-8002 AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article TT - Nephrologie : ce qui a change en 2025. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Complement Inactivating Agents) SB - IM MH - Humans MH - *Nephrology/trends MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Renal Insufficiency, Chronic/therapy MH - Complement Inactivating Agents/therapeutic use MH - Renal Dialysis/methods COIS- M. Pruijm a participe a des conferences pour Astellas, Vifor, B. Braun, Theramed, Vantive, Boehringer Ingelheim et Astra Zeneca, et il a exerce une fonction d'expert pour Novo Nordisk et Nephrospec. F. Fakhouri a recu des honoraires de consultant de Roche, AstraZeneca, Alexion, Sobi, Novartis. Les autres auteurs n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2026/01/16 17:21 MHDA- 2026/01/16 17:22 CRDT- 2026/01/16 03:35 PHST- 2026/01/16 17:22 [medline] PHST- 2026/01/16 17:21 [pubmed] PHST- 2026/01/16 03:35 [entrez] AID - RMS0945-010 [pii] AID - 10.53738/REVMED.2026.22.945.47996 [doi] PST - ppublish SO - Rev Med Suisse. 2026 Jan 14;22(945):49-52. doi: 10.53738/REVMED.2026.22.945.47996. PMID- 41534460 OWN - NLM STAT- MEDLINE DCOM- 20260204 LR - 20260626 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 57 DP - 2026 Feb TI - Glucagon-like peptide-1 receptor agonists and Wernicke encephalopathy: A pharmacovigilance study and literature review. PG - 106571 LID - S0261-5614(25)00351-6 [pii] LID - 10.1016/j.clnu.2025.106571 [doi] AB - BACKGROUND & AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized the treatment of type 2 diabetes mellitus and obesity in recent years. While gastrointestinal adverse events are common, their association with nutritional deficiencies, including thiamine, has not been comprehensively investigated. This study aimed to evaluate whether treatment with GLP-1 RAs is associated with the occurrence of Wernicke encephalopathy (WE). METHODS: We conducted a pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) and a narrative literature review. Disproportionality analysis assessed WE reporting following GLP-1 RA treatment using the reporting odds ratio (ROR) and the lower bound of the information component (IC) 95 % credibility interval. RESULTS: We identified 15 cases of GLP-1 RA-associated WE: 13 from FAERS, 1 from published literature, and 1 from our medical center. Most cases occurred with semaglutide (n = 8/15) or tirzepatide (6/15), and were reported in 2023-2024 (14/15). Most patients (13/15) reported gastrointestinal manifestations of either weight loss, vomiting, loss of appetite, or malnutrition. Classic WE symptoms were reported in 11 patients, and the full clinical triad in 2 patients. Long-term neurological sequelae were noted in 7 of 11 patients with follow-up data. Disproportionality analysis showed increased reporting of WE with GLP-1 RAs compared with other medications (ROR = 2.35 [95%CI, 1.38-4.01]; IC(025) = 0.29). CONCLUSIONS: WE is a potentially rare but severe adverse event of GLP-1 RA treatment, mainly with semaglutide or tirzepatide. As early detection may prevent neurological sequelae, increased clinical awareness is warranted, especially in individuals experiencing severe gastrointestinal symptoms. CI - Copyright (c) 2026. Published by Elsevier Ltd. FAU - Lev, Dana AU - Lev D AD - Department of Internal Medicine, Sheba Medical Center, Ramat-Gan, Israel. FAU - Leibowitz, Avshalom AU - Leibowitz A AD - Department of Internal Medicine, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medical & Health Sciences, School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Lang, Alon AU - Lang A AD - Gray Faculty of Medical & Health Sciences, School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel. FAU - Shlomai, Gadi AU - Shlomai G AD - Department of Internal Medicine, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medical & Health Sciences, School of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel. FAU - Twig, Gilad AU - Twig G AD - Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, School of Medicine, Tel Aviv University, Tel Aviv, Israel; The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Ramat-Gan, Israel. FAU - Eden-Friedman, Yehudit AU - Eden-Friedman Y AD - Department of Internal Medicine, Sheba Medical Center, Ramat-Gan, Israel; Gray Faculty of Medical & Health Sciences, School of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel. FAU - Engel, Tal AU - Engel T AD - Gray Faculty of Medical & Health Sciences, School of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel. FAU - Cukierman-Yaffe, Tali AU - Cukierman-Yaffe T AD - Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Dankner, Rachel AU - Dankner R AD - Department of Epidemiology and Preventive Medicine, School of Public Health, School of Medicine, Tel Aviv University, Tel Aviv, Israel; The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Ramat-Gan, Israel. FAU - Gerstein, Hertzel C AU - Gerstein HC AD - Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. FAU - Goldman, Adam AU - Goldman A AD - Department of Gastroenterology, Sheba Medical Center, Ramat-Gan, Israel; Department of Epidemiology and Preventive Medicine, School of Public Health, School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: Adam.Goldman@sheba.health.gov.il. LA - eng PT - Journal Article PT - Review DEP - 20260102 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Female MH - Semaglutide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Wernicke Encephalopathy/chemically induced/epidemiology MH - Tirzepatide MH - *Pharmacovigilance MH - Male MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects MH - Adult MH - *Glucagon-Like Peptides/adverse effects MH - Adverse Drug Reaction Reporting Systems MH - United States OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Semaglutide OT - Thiamine deficiency OT - Tirzepatide OT - Wernicke encephalopathy COIS- Conflict of interest The authors declare no conflicts of interest. EDAT- 2026/01/15 16:13 MHDA- 2026/02/05 00:30 CRDT- 2026/01/14 18:09 PHST- 2025/07/04 00:00 [received] PHST- 2025/12/16 00:00 [revised] PHST- 2025/12/25 00:00 [accepted] PHST- 2026/02/05 00:30 [medline] PHST- 2026/01/15 16:13 [pubmed] PHST- 2026/01/14 18:09 [entrez] AID - S0261-5614(25)00351-6 [pii] AID - 10.1016/j.clnu.2025.106571 [doi] PST - ppublish SO - Clin Nutr. 2026 Feb;57:106571. doi: 10.1016/j.clnu.2025.106571. Epub 2026 Jan 2. PMID- 41528611 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20261009 IS - 2162-4968 (Electronic) IS - 2162-4968 (Linking) VI - 15 IP - 1 DP - 2026 Jan 13 TI - Pharmacological Management of Diabesity: Current and Emerging Therapies. PG - 5 LID - 10.1007/s13679-025-00681-5 [doi] AB - PURPOSE OF REVIEW: This review aims to provide a comprehensive synthesis of current clinical evidence on the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonists on body mass index (BMI), body composition, and glucose metabolism in patients with obesity and type 2 diabetes mellitus (T2DM), a condition often referred to as "diabesity." RECENT FINDINGS: The coexistence of obesity and T2DM represents a major clinical and public health challenge due to their synergistic effects on metabolic dysfunction and the increased risk of cardiovascular and renal complications. Traditional approaches focused solely on glycemic control have proven insufficient to address the intertwined pathophysiology of excess adiposity and impaired glucose metabolism. Recently, novel pharmacological agents, including SGLT2 inhibitors, GLP-1 RAs, and dual GIP/GLP-1 receptor agonists, have demonstrated dual benefits in improving glycemic control and reducing body weight. These drugs act through distinct but complementary mechanisms-such as promoting glycosuria, enhancing satiety, delaying gastric emptying, and modulating energy homeostasis-resulting in significant reductions in BMI and visceral fat. Among these agents, tirzepatide has shown superior efficacy in improving metabolic parameters and body composition compared with single receptor agonists. Understanding the multifaceted metabolic benefits of these pharmacotherapies is essential for optimizing individualized therapeutic strategies for patients with diabesity. Integrating these agents into comprehensive diabetes care allows clinicians to more effectively target the complex pathophysiology of diabesity, ultimately improving long-term metabolic and clinical outcomes in this growing patient population. CI - (c) 2026. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Galasso, Martina AU - Galasso M AD - Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesita (C.I.B.O), Universita degli Studi di Napoli Federico II, Via Sergio Pansini 5, Naples, 80131, Italy. FAU - Caporusso, Mariangela AU - Caporusso M AD - Endocrinology Unit, Regional General Hospital "Francesco Miulli", Acquaviva delle Fonti, Bari, 70021, IT, Italy. FAU - Volatile, Alessandra AU - Volatile A AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Verde, Ludovica AU - Verde L AD - Department of Public Health, University of Naples Federico II, Via Sergio Pansini 5, Naples, 80131, Italy. FAU - Esposito, Katherine AU - Esposito K AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Unit of Endocrinology and Metabolic Diseases, AOU University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Giorgino, Francesco AU - Giorgino F AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, 70124, IT, Italy. FAU - Perrini, Sebastio AU - Perrini S AD - Endocrinology Unit, Regional General Hospital "Francesco Miulli", Acquaviva delle Fonti, Bari, 70021, IT, Italy. AD - Section of Endocrinology, Department of Medicine and Surgery, Libera Universita Mediterranea (LUM), Casamassima, Bari, IT, 70010, Italy. FAU - Colao, Annamaria AU - Colao A AD - Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesita (C.I.B.O), Universita degli Studi di Napoli Federico II, Via Sergio Pansini 5, Naples, 80131, Italy. AD - Dipartimento Di Medicina Clinica E Chirurgia, Unita Di Endocrinologia, Universita Degli Studi Di Napoli Federico II, Naples, 80131, Italy. AD - Cattedra Unesco "Educazione Alla Salute E Allo Sviluppo Sostenibile", University Federico II, Naples, 80131, Italy. FAU - Barrea, Luigi AU - Barrea L AD - Dipartimento Di Psicologia e Scienze Della Salute, Universita Telematica Pegaso, Centro Direzionale, Via Porzio, Isola F2, Naples, 80143, Italy. FAU - Muscogiuri, Giovanna AU - Muscogiuri G AD - Dipartimento di Medicina Clinica e Chirurgia, Centro Italiano per la cura e il Benessere del Paziente con Obesita (C.I.B.O), Universita degli Studi di Napoli Federico II, Via Sergio Pansini 5, Naples, 80131, Italy. giovanna.muscogiuri@unina.it. AD - Dipartimento Di Medicina Clinica E Chirurgia, Unita Di Endocrinologia, Universita Degli Studi Di Napoli Federico II, Naples, 80131, Italy. giovanna.muscogiuri@unina.it. AD - Cattedra Unesco "Educazione Alla Salute E Allo Sviluppo Sostenibile", University Federico II, Naples, 80131, Italy. giovanna.muscogiuri@unina.it. AD - University of Naples Federico II, Via Sergio Pansini 5, Naples, 80031, Italy. giovanna.muscogiuri@unina.it. CN - Obesity Programs of nutrition, Education, Research and Assessment (OPERA) Group LA - eng PT - Journal Article PT - Review DEP - 20260113 PL - United States TA - Curr Obes Rep JT - Current obesity reports JID - 101578283 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Diabesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - *Obesity/drug therapy/complications MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - Body Mass Index MH - Body Composition/drug effects OTO - NOTNLM OT - Body composition OT - Diabesity OT - Glycemic control OT - SGLT2 inhibitors OT - Semaglutide OT - Tirzepatide COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2026/01/13 13:16 MHDA- 2026/01/13 13:17 CRDT- 2026/01/13 11:20 PHST- 2025/11/01 00:00 [received] PHST- 2025/12/09 00:00 [accepted] PHST- 2026/01/13 13:17 [medline] PHST- 2026/01/13 13:16 [pubmed] PHST- 2026/01/13 11:20 [entrez] AID - 10.1007/s13679-025-00681-5 [pii] AID - 10.1007/s13679-025-00681-5 [doi] PST - epublish SO - Curr Obes Rep. 2026 Jan 13;15(1):5. doi: 10.1007/s13679-025-00681-5. PMID- 41527269 OWN - NLM STAT- MEDLINE DCOM- 20260326 LR - 20260626 IS - 1365-2036 (Electronic) IS - 0269-2813 (Linking) VI - 63 IP - 8 DP - 2026 Apr TI - Clinical Trial: Semaglutide Versus Placebo in NIT-Assessed MASH-A Multicenter Randomised Placebo-Controlled Trial (SAMARA). PG - 1080-1088 LID - 10.1111/apt.70516 [doi] AB - BACKGROUND/AIMS: Non-invasive test (NIT)-based assessment of eligibility and treatment response with semaglutide is needed to inform clinical practice guidance. Therefore, utilising a randomised, placebo-controlled study design, we evaluated the utility of NITs to assess eligibility and treatment response in patients with suspected at-risk MASH randomised to semaglutide versus placebo. METHODS: In this multicentre, randomised, double-blind placebo-controlled 52-week trial, patients meeting AASLD criteria for MASLD with BMI >/= 27 kg/m(2), or BMI >/= 25 kg/m(2) and prediabetes or type 2 diabetes with liver stiffness by VCTE >/= 8 kPa and a FAST score >/= 0.5 were randomised to either semaglutide 2.4 mg subcutaneously weekly or placebo. The primary outcome was change in the FAST score at end of treatment from baseline. Other endpoints included changes in body weight, MRI-PDFF, ALT and HbA1c. RESULTS: Fifty-five participants were randomised (55% women, 20% with diabetes). Mean (SD) age, BMI, and FAST at baseline were 48.8 (14) years, 40.2 (15) kg/m(2), 0.62 (0.12), respectively. The semaglutide group had a significantly greater reduction in FAST compared with placebo (-0.28 vs. -0.12; p = 0.002). More semaglutide recipients achieved >/= 5% weight loss (64% vs. 8.3%; p < 0.001) and >/= 30% reduction in MRI-PDFF (60% vs. 17%; p = 0.047). Semaglutide led to a significantly greater reduction in ALT, AST, GGT, HbA1c and LDL cholesterol (p < 0.05). Gastrointestinal-related adverse events were common but not significantly different between the two groups (p = 0.59). CONCLUSIONS: A NIT-based approach to identify at-risk MASH patients for semaglutide treatment is feasible and effective. This study provides RCT data showing that FAST, ALT, AST and MRI-PDFF can be used to monitor treatment response. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Ajmera, Veeral AU - Ajmera V AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. AD - Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, California, USA. FAU - Vuppalanchi, Raj AU - Vuppalanchi R AD - Division of Gastroenterology, Indiana University, Bloomington, Indiana, USA. FAU - Khalili, Mandana AU - Khalili M AUID- ORCID: 0000-0001-9178-9139 AD - Department of Medicine, University of California San Francisco, San Francisco, California, USA. AD - Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, California, USA. FAU - Sheikh, Muhammad Y AU - Sheikh MY AD - Fresno Clinical Research Center, Fresno, California, USA. FAU - Risser, Joseph AU - Risser J AD - Herbert Wertheim School of Public Health, University of California at San Diego, San Diego, California, USA. FAU - Klein, Samuel AU - Klein S AD - Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Tincopa, Monica AU - Tincopa M AUID- ORCID: 0000-0002-9954-8548 AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. AD - Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, California, USA. FAU - Madamba, Egbert AU - Madamba E AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Singh, Seema AU - Singh S AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Siddiqi, Harris AU - Siddiqi H AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Cortez-Moreno, Diana AU - Cortez-Moreno D AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Contrano, Darryl AU - Contrano D AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Hofflich, Heather AU - Hofflich H AD - Division of Endocrinology, University of California, San Diego, California, USA. FAU - Abeles, Ruth AU - Abeles R AD - Division of General Internal Medicine, University of California at San Diego, San Diego, California, USA. AD - Center for Advanced Weight Management, University of California at San Diego, San Diego, California, USA. FAU - Lunde, Ottar AU - Lunde O AD - Division of General Internal Medicine, University of California at San Diego, San Diego, California, USA. AD - Center for Advanced Weight Management, University of California at San Diego, San Diego, California, USA. FAU - Grunvald, Eduardo AU - Grunvald E AD - Division of General Internal Medicine, University of California at San Diego, San Diego, California, USA. AD - Center for Advanced Weight Management, University of California at San Diego, San Diego, California, USA. FAU - Bettencourt, Ricki AU - Bettencourt R AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - He, Feng AU - He F AD - Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, California, USA. FAU - Jain, Sonia AU - Jain S AD - Biostatistics Research Center, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, California, USA. FAU - Richards, Lisa AU - Richards L AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. FAU - Loomba, Rohit AU - Loomba R AUID- ORCID: 0000-0002-4845-9991 AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA. AD - Division of Gastroenterology and Hepatology, University of California at San Diego, San Diego, California, USA. LA - eng GR - 5UL1TR001442/TR/NCATS NIH HHS/United States GR - P01HL147835/HL/NHLBI NIH HHS/United States GR - P30DK120515/DK/NIDDK NIH HHS/United States GR - R01DK106419/DK/NIDDK NIH HHS/United States GR - R01DK121378/DK/NIDDK NIH HHS/United States GR - R01DK124318/DK/NIDDK NIH HHS/United States GR - U01DK061734/DK/NIDDK NIH HHS/United States GR - U01DK130190/DK/NIDDK NIH HHS/United States GR - Novo Nordisk Foundation/ GR - John C Martin Foundation/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20260112 PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Male MH - Middle Aged MH - Double-Blind Method MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Adult MH - Treatment Outcome MH - Glycated Hemoglobin/metabolism MH - *Non-alcoholic Fatty Liver Disease/drug therapy OTO - NOTNLM OT - VCTE OT - glucagon-like peptide 1 receptor agonists OT - metabolic dysfunction OT - noninvasive tests OT - steatotic liver disease EDAT- 2026/01/13 07:42 MHDA- 2026/03/27 01:10 CRDT- 2026/01/13 01:03 PHST- 2025/11/27 00:00 [revised] PHST- 2025/11/03 00:00 [received] PHST- 2025/12/22 00:00 [accepted] PHST- 2026/03/27 01:10 [medline] PHST- 2026/01/13 07:42 [pubmed] PHST- 2026/01/13 01:03 [entrez] AID - 10.1111/apt.70516 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2026 Apr;63(8):1080-1088. doi: 10.1111/apt.70516. Epub 2026 Jan 12. PMID- 41520798 OWN - NLM STAT- MEDLINE DCOM- 20260519 LR - 20260625 IS - 1879-3304 (Electronic) IS - 0039-6257 (Linking) VI - 71 IP - 4 DP - 2026 Jul-Aug TI - Too much of a good thing. PG - 1236-1245 LID - S0039-6257(26)00001-9 [pii] LID - 10.1016/j.survophthal.2026.01.001 [doi] AB - A 38-year-old man with poorly controlled type 2 diabetes mellitus and arterial hypertension on semaglutide presented with acute, painless, vision loss in the left eye. Ophthalmic examination revealed optic disc edema (ODE) in the left eye and optic disc pallor (ODP) in the right eye, accompanied by severe nonproliferative diabetic retinopathy and cystoid macular edema in both eyes. The combination of ODE in one eye and ODP in the fellow eye raised concern for the Foster Kennedy syndrome secondary to an intracranial mass; however, neuroimaging and systemic evaluation were unremarkable. Ultimately, it was decided the ODP was due to a prior unrecognized non-arteritic anterior ischemic optic neuropathy (NAION) event, and the ODE was the result of an acute NAION in the symptomatic fellow eye (i.e. pseudo-Foster Kennedy syndrome). CI - Copyright (c) 2026 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Varghese, Danny AU - Varghese D AD - Texas A&M College of Medicine, Bryan, TX, USA. FAU - Abdelsalam, Dina AU - Abdelsalam D AD - Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA. FAU - Ibrahim, Safa AU - Ibrahim S AD - Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA. FAU - Lee, Andrew G AU - Lee AG AD - Texas A&M College of Medicine, Bryan, TX, USA; Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, TX, USA. Electronic address: aglee@houstonmethodist.org. FAU - Bhatti, M Tariq AU - Bhatti MT AD - The Permanente Medical Group. Department of Ophthalmology, Kaiser Permanente, Northern California, Roseville, California, USA. LA - eng PT - Case Reports PT - Journal Article DEP - 20260109 PL - United States TA - Surv Ophthalmol JT - Survey of ophthalmology JID - 0404551 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Papilledema/diagnosis/etiology MH - *Optic Neuropathy, Ischemic/diagnosis/complications MH - Male MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Semaglutide MH - Adult MH - *Diabetic Retinopathy/diagnosis MH - Visual Acuity MH - Tomography, Optical Coherence MH - *Optic Disk/pathology MH - Glucagon-Like Peptides/therapeutic use OTO - NOTNLM OT - Autoregulatory failure OT - Bilateral sequential OT - Glucagon-like peptide-1 receptor agonist OT - Non-arteritic anterior ischemic optic neuropathy OT - Optic disc edema OT - Pseudo-Foster Kennedy syndrome OT - Semaglutide COIS- Declaration of Competing Interest Andrew G. Lee, MD has served as a consultant for the National Aeronautics and Space Administration (NASA), the National Football League (NFL), US Department of Justice, and is a consultant for Amgen, AstraZeneca, Argenx, Bristol-Myers Squibb, Alexion, Celgene, Stoke, Ethyreal, Catalyst, Dompe, and Viridian. Dr. Lee is also on the editorial board of Frontiers in Ophthalmology, JNO, CJO, JJO, and JAMA Ophthalmology. M. Tariq Bhatti, MD: none. EDAT- 2026/01/12 00:37 MHDA- 2026/05/20 00:32 CRDT- 2026/01/11 19:13 PHST- 2025/12/20 00:00 [received] PHST- 2026/01/05 00:00 [revised] PHST- 2026/01/06 00:00 [accepted] PHST- 2026/05/20 00:32 [medline] PHST- 2026/01/12 00:37 [pubmed] PHST- 2026/01/11 19:13 [entrez] AID - S0039-6257(26)00001-9 [pii] AID - 10.1016/j.survophthal.2026.01.001 [doi] PST - ppublish SO - Surv Ophthalmol. 2026 Jul-Aug;71(4):1236-1245. doi: 10.1016/j.survophthal.2026.01.001. Epub 2026 Jan 9. PMID- 41520703 OWN - NLM STAT- MEDLINE DCOM- 20260206 LR - 20260630 IS - 2254-8874 (Electronic) IS - 2254-8874 (Linking) VI - 226 IP - 2 DP - 2026 Feb TI - Patients after acute myocardial infarction: potential of semaglutide in prognosis for reducing events and mortality. PG - 502455 LID - S2254-8874(26)00010-X [pii] LID - 10.1016/j.rceng.2026.502455 [doi] AB - INTRODUCTION: GLP-1 receptor agonists, such as semaglutide, have demonstrated cardiovascular benefits in trials such as SELECT and SOUL. This study assesses the proportion of post-myocardial infarction patients who meet eligibility criteria to benefit from semaglutide. METHODS: A retrospective, single-centre observational study was conducted including 100 consecutive patients following myocardial infarction. Clinical, demographic, and laboratory data were analysed. Eligibility was assessed using the criteria from the SELECT trial (body mass index >/=27kg/m(2), no diabetes, established atherosclerotic disease) and the SOUL trial (type 2 diabetes mellitus and atherosclerotic cardiovascular disease). RESULTS: SELECT criteria were met by 42 patients, SOUL criteria by 34, and both by 76. This combined group was characterised by older age, greater comorbidity burden (hypertension, dyslipidaemia, type 2 diabetes mellitus), higher body mass index, and a more atherogenic lipid profile. DISCUSSION: The high proportion of eligible patients suggests that these trials truly represent real-world clinical practice. The SELECT+SOUL group exhibited features consistent with metabolic syndrome, potentially explaining their elevated cardiovascular risk and the likely benefit from semaglutide. CONCLUSIONS: Semaglutide shows high potential for prescription in specialties managing patients with cardiovascular events, identifying a target group with characteristics typical of metabolic syndrome. CI - Copyright (c) 2026 Elsevier Espana, S.L.U. and Sociedad Espanola de Medicina Interna (SEMI). All rights reserved. FAU - Velasco, A AU - Velasco A AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain; Fundacion para la Investigacion Biomedica del Hospital Universitario 12 de Octubre (FIBH12O), Instituto de Investigacion Sanitaria, Hospital 12 de Octubre (imas12), Madrid, Spain. FAU - Pascual Ramos, I AU - Pascual Ramos I AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain. FAU - Rodriguez Alonso, P AU - Rodriguez Alonso P AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain. FAU - Denche Sanz, C AU - Denche Sanz C AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain. FAU - Tello, R AU - Tello R AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain; Fundacion para la Investigacion Biomedica del Hospital Universitario 12 de Octubre (FIBH12O), Instituto de Investigacion Sanitaria, Hospital 12 de Octubre (imas12), Madrid, Spain; CIBERCV, Madrid, Spain. FAU - Solis, J AU - Solis J AD - Servicio de Cardiologia, Hospital Universitario 12 de Octubre, Madrid, Spain; Fundacion para la Investigacion Biomedica del Hospital Universitario 12 de Octubre (FIBH12O), Instituto de Investigacion Sanitaria, Hospital 12 de Octubre (imas12), Madrid, Spain; CIBERCV, Madrid, Spain. Electronic address: jsolismartin@yahoo.es. LA - eng PT - Case Reports PT - Journal Article PT - Observational Study DEP - 20260109 PL - Spain TA - Rev Clin Esp (Barc) JT - Revista clinica espanola JID - 101632437 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - Retrospective Studies MH - Male MH - Aged MH - *Myocardial Infarction/mortality/drug therapy/complications MH - Middle Aged MH - Prognosis MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/complications/drug therapy OTO - NOTNLM OT - Metabolic syndrome OT - Prevencion secundaria OT - Secondary prevention OT - Semaglutida OT - Semaglutide OT - Sindrome metabolico EDAT- 2026/01/12 00:37 MHDA- 2026/02/07 00:30 CRDT- 2026/01/11 19:11 PHST- 2025/05/04 00:00 [received] PHST- 2025/10/07 00:00 [accepted] PHST- 2026/02/07 00:30 [medline] PHST- 2026/01/12 00:37 [pubmed] PHST- 2026/01/11 19:11 [entrez] AID - S2254-8874(26)00010-X [pii] AID - 10.1016/j.rceng.2026.502455 [doi] PST - ppublish SO - Rev Clin Esp (Barc). 2026 Feb;226(2):502455. doi: 10.1016/j.rceng.2026.502455. Epub 2026 Jan 9. PMID- 41516231 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260625 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 27 IP - 1 DP - 2025 Dec 29 TI - Cardiovascular Disease and Diabetes: A New Challenge in the Treatment and Management. LID - 10.3390/ijms27010354 [doi] LID - 354 AB - Cardiovascular diseases (CVDs) represent one of the leading causes of morbidity and mortality in patients with diabetes. However, a correct and effective glycaemic control obtained by pharmacologic interventions, such as the use the novel glucose-lowering agents, demonstrated efficacy in reducing the risk of both cardiovascular events and mortality. The latest classes of glucose-lowering drugs introduced in the clinical practice are DPP4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin, and alogliptin), GLP-1 receptor agonists (semaglutide, liraglutide, albiglutide, dulaglutide, exenatide, and lixenatide), and SGLT-2 inhibitors (empaglifozin, canaglifozin, and dapaglifozin). Multiple lines of evidence show that all these new drugs associated with the treatment of diabetic disease have the same effectiveness as the traditional antidiabetic drugs, and excellent cardiovascular safety, highlighting their potential in significantly reducing major cardiovascular events and mortality. The aim of our review is to summarise the clinical efficacy of these recently introduced drugs to optimise treatment strategies, especially in the early phase of diabetic disease. FAU - Riccioni, Graziano AU - Riccioni G AD - Cardiology Care Unit, "San Camillo de Lellis" Hospital, 71043 Foggia, Italy. FAU - Notarangelo, Chiara AU - Notarangelo C AUID- ORCID: 0009-0006-2085-9017 AD - Department of Cardiovascular Disease, University of Firenze, 50134 Florence, Italy. FAU - Riccioni, Mario AU - Riccioni M AD - Faculty of Medicine, University of Torino, 10126 Turin, Italy. FAU - D'Orazio, Nicolantonio AU - D'Orazio N AD - Department of Biomedical Sciences, University of Pescara-Chieti, 66100 Chieti, Italy. LA - eng PT - Journal Article PT - Review DEP - 20251229 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Humans MH - *Cardiovascular Diseases/drug therapy/etiology MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Animals PMC - PMC12785618 OTO - NOTNLM OT - DDP-4 inhibitors OT - GLP-1 receptor antagonists OT - SGLT2 inhibitors OT - cardiovascular disease OT - diabetes OT - metformin OT - prevention COIS- The authors declare no conflict of interest. EDAT- 2026/01/10 06:32 MHDA- 2026/01/10 06:33 PMCR- 2025/12/29 CRDT- 2026/01/10 01:10 PHST- 2025/08/03 00:00 [received] PHST- 2025/12/09 00:00 [revised] PHST- 2025/12/09 00:00 [accepted] PHST- 2026/01/10 06:33 [medline] PHST- 2026/01/10 06:32 [pubmed] PHST- 2026/01/10 01:10 [entrez] PHST- 2025/12/29 00:00 [pmc-release] AID - ijms27010354 [pii] AID - ijms-27-00354 [pii] AID - 10.3390/ijms27010354 [doi] PST - epublish SO - Int J Mol Sci. 2025 Dec 29;27(1):354. doi: 10.3390/ijms27010354. PMID- 41512269 OWN - NLM STAT- MEDLINE DCOM- 20260109 LR - 20260115 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 31 IP - Spec. No. 15 DP - 2025 Dec TI - GLP-1 receptor agonists: trend, necessity, or blessing? PG - SP1084-SP1085 LID - 10.37765/ajmc.2025.89854 [doi] AB - The recent endorsement of glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide (Wegovy), by the American College of Cardiology as first-line therapy for weight management marks a paradigm shift in cardiometabolic care. Semaglutide offers significant benefits, including improved glycemic control and substantial weight loss, with emerging data demonstrating its impact even in individuals without diabetes. However, GLP-1 receptor agonists' growing popularity raises important concerns regarding long-term safety, access equity, and health care priorities. Although common adverse effects are gastrointestinal, less frequent but serious risks such as gallbladder disease, pancreatitis, and anesthesia-related complications deserve attention. Obesity, a global epidemic, has traditionally been managed through lifestyle interventions. The increasing reliance on pharmacologic options must not overshadow the foundational role of diet, physical activity, and education. Although GLP-1 receptor agonists represent a powerful advancement in obesity and cardiovascular risk management, its widespread adoption demands a balanced, evidence-based approach that integrates it into a broader, patient-centered strategy. There is a pressing need for comprehensive care models that address both the physiological and behavioral aspects of obesity. As health care systems navigate this therapeutic shift, they must ensure ethical use, cost-effectiveness, and long-term safety. GLP-1 receptor agonists may indeed be a blessing, but only if applied judiciously within the context of holistic obesity management. FAU - Shoaib, Navaira AU - Shoaib N FAU - Azhar, Naveen AU - Azhar N AD - Dow Medical College, House No. A-137, Block 1 FB Area, Karachi, Pakistan. Email: naveen.azhar40@gmail.com. FAU - Shoaib, Maria AU - Shoaib M LA - eng PT - Editorial PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Cardiovascular Diseases/prevention & control MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Obesity/drug therapy MH - Weight Loss/drug effects EDAT- 2026/01/09 18:30 MHDA- 2026/01/09 18:31 CRDT- 2026/01/09 16:33 PHST- 2026/01/09 18:31 [medline] PHST- 2026/01/09 18:30 [pubmed] PHST- 2026/01/09 16:33 [entrez] AID - 89854 [pii] AID - 10.37765/ajmc.2025.89854 [doi] PST - ppublish SO - Am J Manag Care. 2025 Dec;31(Spec. No. 15):SP1084-SP1085. doi: 10.37765/ajmc.2025.89854. PMID- 41508745 OWN - NLM STAT- MEDLINE DCOM- 20260317 LR - 20260815 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - GLP1-1RAs improve walking distance and reduce amputation in people with type 2 diabetes and peripheral artery disease: A systematic review and meta-analysis of randomised controlled trials and cohort studies. PG - 2775-2783 LID - 10.1111/dom.70454 [doi] AB - AIMS: The aim of this systematic review and meta-analysis was to evaluate the effect of GLP-1RAs on functional walking distance and the risk of major adverse limb events (MALE) or lower extremity amputation (LEA) in people with type 2 diabetes and peripheral artery disease (PAD). MATERIALS AND METHODS: We searched many electronic databases up to 10 October 2025 for randomised controlled trials (RCTs) and cohort studies. We included studies enrolling adults with type 2 diabetes and PAD, comparing GLP-1RAs against placebo or other glucose-lowering drugs. The primary outcomes were walking distance, MALE, or LEA. Data were pooled using a random-effects model, with hazard ratios (HR) or risk ratios (RR). Risk of bias was assessed using RoB2 for RCTs and ROBINS-I for cohort studies; evidence certainty was evaluated using the GRADE approach. RESULTS: We included seven studies (3 RCTs, 4 cohorts) enrolling 107 092 participants. The meta-analysis of two RCTs with 847 participants demonstrated a significant improvement in walking distance with liraglutide or semaglutide (HR = 1.10, 95% CI 1.05-1.15, p < 0.001), with no heterogeneity (I(2) = 0.0%) and moderate certainty of evidence. In the additional meta-analysis of two RCTs with 3592 participants, the incidence of MALE or LEA did not differ significantly between patients receiving exenatide or semaglutide and those receiving placebo. The meta-analysis of four cohort studies with 104 292 participants showed that GLP-1RAs reduced the risk of LEA (RR = 0.53, 95% CI 0.39-0.73, p < 0.001), with high heterogeneity (I(2) = 85.96%), totally related to one study, and very low certainty of evidence. Subgroup analyses showed a significant difference (p < 0.001) between GLP-1RA therapies, with the strongest associations with LEA reduction for tirzepatide and semaglutide (55% and 54% risk reduction, respectively); there was no difference in the LEA outcome excluding from the analysis patients with type 2 diabetes and diabetic foot ulcers at baseline. CONCLUSIONS: This meta-analysis suggests that GLP-1RAs are associated with a significant improvement in functional walking distance and a reduction in the risk of LEA in people with type 2 and PAD. Further dedicated RCTs are needed to confirm these limb-specific benefits of GLP-1RAs. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Longo, Miriam AU - Longo M AUID- ORCID: 0000-0002-6459-5854 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Department of Life Sciences, Health and Health Professions, Link Campus University, Rome, Italy. FAU - Di Martino, Nicole AU - Di Martino N AUID- ORCID: 0009-0001-8062-3958 AD - PhD Program of Translational Medicine, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Scappaticcio, Lorenzo AU - Scappaticcio L AUID- ORCID: 0009-0007-7628-2226 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Caruso, Paola AU - Caruso P AUID- ORCID: 0000-0002-4756-2022 AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Bellastella, Giuseppe AU - Bellastella G AUID- ORCID: 0000-0002-4748-321X AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Maiorino, Maria Ida AU - Maiorino MI AUID- ORCID: 0000-0003-4659-7546 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AUID- ORCID: 0000-0002-3652-5154 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - PhD Program of Translational Medicine, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Division of Endocrinology and Metabolic Diseases, University Hospital, University of Campania "Luigi Vanvitelli", Naples, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20260108 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Peripheral Arterial Disease/drug therapy/complications MH - Randomized Controlled Trials as Topic MH - *Amputation, Surgical/statistics & numerical data MH - *Walking/physiology MH - Semaglutide MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Cohort Studies MH - Diabetic Angiopathies MH - Tirzepatide OTO - NOTNLM OT - GLP-1RA OT - cohort studies OT - meta-analysis OT - peripheral artery disease OT - randomised controlled trials OT - systematic review OT - type 2 diabetes EDAT- 2026/01/09 07:06 MHDA- 2026/03/17 06:48 CRDT- 2026/01/09 02:24 PHST- 2025/12/17 00:00 [revised] PHST- 2025/10/30 00:00 [received] PHST- 2025/12/29 00:00 [accepted] PHST- 2026/03/17 06:48 [medline] PHST- 2026/01/09 07:06 [pubmed] PHST- 2026/01/09 02:24 [entrez] AID - 10.1111/dom.70454 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):2775-2783. doi: 10.1111/dom.70454. Epub 2026 Jan 8. PMID- 41508706 OWN - NLM STAT- MEDLINE DCOM- 20260317 LR - 20260815 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 4 DP - 2026 Apr TI - Comparison of cardiovascular outcomes between once-weekly semaglutide and dulaglutide in adults with type 2 diabetes and established atherosclerotic cardiovascular disease in the United States. PG - 2661-2671 LID - 10.1111/dom.70440 [doi] AB - AIMS: This study aims to compare the risk of major adverse cardiovascular events (MACE) among United States individuals with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) treated with once-weekly semaglutide vs. dulaglutide. MATERIALS AND METHODS: This was a retrospective cohort study using Optum's de-identified Clinformatics Data Mart (Optum CDM) from 1 January 2007 through 30 September 2024. New initiators of semaglutide or dulaglutide >/=18 years with both T2D and ASCVD were included. The index date was the first date of a prescription claim for semaglutide or dulaglutide within the index medication identification period (1 January 2018 through 31 March 2024). The primary outcome was 3-point MACE (stroke, myocardial infarction [MI], cardiovascular [CV]-related death). Entropy balancing was applied to balance baseline characteristics. Weighted incidence rates per 1000 person-years and doubly robust Cox proportional hazard ratios were reported. RESULTS: There were 75 243 enrolees included (semaglutide, 42 007; dulaglutide, 33 236). The mean age was 68.2 and 69.3 years (unweighted) in the semaglutide and dulaglutide cohorts, respectively. After balancing, standardized mean differences were <0.1 for all variables. The incidence rates of the primary outcome, 3-point MACE, were 25.7 and 33.0 in the semaglutide and dulaglutide cohorts, respectively. Compared with the dulaglutide cohort, the semaglutide cohort had a 22% lower risk of 3-point MACE (hazard ratio, 0.78 [95% CI, 0.70-0.87]; p < 0.001). CONCLUSIONS: Among United States Medicare Optum CDM enrolees with T2D and ASCVD, semaglutide was associated with reduced risks of CV outcomes compared with dulaglutide. These results help to address an important evidence gap in selecting glucagon-like peptide-1 receptor agonists for this high-risk population. CI - (c) 2026 Novo Nordisk, Genesis Research, LLC and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Tan, Xi AU - Tan X AUID- ORCID: 0000-0002-2409-5927 AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Liang, Yuanjie AU - Liang Y AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Harton, Joanna AU - Harton J AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Gutierrez, Cynthia AU - Gutierrez C AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Muhammad, Chalak AU - Muhammad C AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - de Havenon, Adam AU - de Havenon A AD - Department of Neurology, Center for Brain and Mind Health, Yale University, New Haven, Connecticut, USA. LA - eng GR - Novo Nordisk/ PT - Comparative Study PT - Journal Article DEP - 20260108 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/adverse effects/therapeutic use MH - *Immunoglobulin Fc Fragments/administration & dosage/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Recombinant Fusion Proteins/administration & dosage/adverse effects MH - Female MH - Male MH - United States/epidemiology MH - Retrospective Studies MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Aged MH - Middle Aged MH - *Atherosclerosis/epidemiology/complications/drug therapy MH - *Cardiovascular Diseases/epidemiology MH - Drug Administration Schedule PMC - PMC12992163 OTO - NOTNLM OT - cardiovascular disease OT - cohort study OT - dulaglutide OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- XT, YL, LX, CM, and CS are employees of Novo Nordisk Inc. JH and CG are employees of Genesis Research Group (Hoboken, NJ), which was contracted by Novo Nordisk Inc. to perform the analyses. AdH receives research funding from the American Academy of Neurology and National Institutes of Health (UG3NS133209, UH3NS130228, R01NS130189, R21NS138995), consultant fees from Novo Nordisk, royalty fees from UpToDate, and has equity in TitinKM and Certus. EDAT- 2026/01/09 07:06 MHDA- 2026/03/17 06:48 PMCR- 2026/03/17 CRDT- 2026/01/09 02:23 PHST- 2025/12/19 00:00 [revised] PHST- 2025/10/17 00:00 [received] PHST- 2025/12/22 00:00 [accepted] PHST- 2026/03/17 06:48 [medline] PHST- 2026/01/09 07:06 [pubmed] PHST- 2026/01/09 02:23 [entrez] PHST- 2026/03/17 00:00 [pmc-release] AID - DOM70440 [pii] AID - 10.1111/dom.70440 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Apr;28(4):2661-2671. doi: 10.1111/dom.70440. Epub 2026 Jan 8. PMID- 41501776 OWN - NLM STAT- MEDLINE DCOM- 20260625 LR - 20260921 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 24 IP - 1 DP - 2026 Jan 8 TI - Prevalence of use and interest in using glucagon-like peptide-1 receptor agonists for weight loss: a population study in Great Britain. PG - 1 LID - 10.1186/s12916-025-04528-7 [doi] LID - 1 AB - BACKGROUND: This study aimed to assess the prevalence of glucagon-like peptide-1 (GLP-1) receptor agonist use and interest in using medications for weight loss among adults (>/= 18 years) in Great Britain. METHODS: Nationally representative household survey, January-March 2025 (n = 5893). Participants were asked whether they had used medication in the past year to manage type 2 diabetes (excluding insulin), reduce the risk of heart disease, or support weight loss and, if so, whether they had used any of five specific GLP-1 or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists. Those who had not used medication to support weight loss in the past year were asked how likely they would be to consider doing so in the next year. Estimates were reported stratified by participant characteristics and extrapolated to the national population. RESULTS: Overall, 2.9% [2.4-3.4%]- approximately 1.6 million adults-reported using a GLP-1 or GLP-1/GIP medication to support weight loss in the past year, with 1.7% [1.4-2.1%] (~ 910,000 adults) using them exclusively for this purpose. Of those who used them exclusively for weight loss, the majority (91.4% [85.6-97.2%]) reported using medications licensed for this purpose in Great Britain, most commonly Mounjaro (tirzepatide; 80.2% [71.9-88.6%]). Of those who had not used weight-loss medication in the past year, 6.5% [5.7-7.3%] (~ 3.3 million adults) expressed an interest in doing so in the next year. Use and interest were more prevalent among women, people in mid-life, and those reporting past-month psychological distress. Interest was also higher among people facing greater socioeconomic disadvantage. CONCLUSIONS: In the first quarter of 2025, an estimated 4.9 million adults in Great Britain-nearly one in ten-either had recently used a GLP-1 or GLP-1/GIP medication to support weight loss or were interested in doing so in the near future. A substantial minority reported using a type of GLP-1 medication that was not licensed for weight management, suggesting off-label use. Interest was particularly high among less advantaged socioeconomic groups, while use was similar across groups, highlighting the importance of addressing equity in access. These findings underscore the need to monitor who is accessing these medications and to ensure their safe, appropriate, and equitable provision. CI - (c) 2025. The Author(s). FAU - Jackson, Sarah E AU - Jackson SE AD - Department of Behavioural Science and Health, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK. s.e.jackson@ucl.ac.uk. FAU - Brown, Jamie AU - Brown J AD - Department of Behavioural Science and Health, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK. FAU - Llewellyn, Clare AU - Llewellyn C AD - Department of Behavioural Science and Health, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK. FAU - Mytton, Oliver AU - Mytton O AD - Institute for Child Health, University College London, London, UK. FAU - Shahab, Lion AU - Shahab L AD - Department of Behavioural Science and Health, University College London, 1-19 Torrington Place, London, WC1E 7HB, UK. LA - eng GR - PRCRPG-Nov21\100002/CRUK_/Cancer Research UK/United Kingdom GR - ES/Y001044/1/Economic and Social Research Council/ PT - Journal Article DEP - 20260108 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - United Kingdom/epidemiology MH - Female MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Middle Aged MH - Male MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Prevalence MH - Young Adult MH - Adolescent MH - Tirzepatide PMC - PMC12781702 OTO - NOTNLM OT - Liraglutide OT - Mounjaro OT - Ozempic OT - Saxenda OT - Semaglutide OT - Tirzepatide OT - Wegovy COIS- Declarations. Ethics approval and consent to participate: Ethical approval for the STS was granted originally by the UCL Ethics Committee (ID 0498/001). All participants provided verbal consent which was recorded on computers by trained interviewers. All methods are carried out in accordance with relevant regulations. The data are not collected by UCL and are anonymised when received by UCL. Consent for publication: Not applicable. Competing interests: LS has acted as paid reviewer for grant awarding bodies and as a paid consultant for health care companies. EDAT- 2026/01/08 07:13 MHDA- 2026/01/08 07:14 PMCR- 2026/01/08 CRDT- 2026/01/08 00:02 PHST- 2025/06/20 00:00 [received] PHST- 2025/11/13 00:00 [accepted] PHST- 2026/01/08 07:14 [medline] PHST- 2026/01/08 07:13 [pubmed] PHST- 2026/01/08 00:02 [entrez] PHST- 2026/01/08 00:00 [pmc-release] AID - 10.1186/s12916-025-04528-7 [pii] AID - 4528 [pii] AID - 10.1186/s12916-025-04528-7 [doi] PST - epublish SO - BMC Med. 2026 Jan 8;24(1):1. doi: 10.1186/s12916-025-04528-7. PMID- 41500509 OWN - NLM STAT- MEDLINE DCOM- 20260504 LR - 20260813 IS - 1467-789X (Electronic) IS - 1467-7881 (Print) IS - 1467-7881 (Linking) VI - 27 IP - 6 DP - 2026 Jun TI - Nutrition Strategies for Next-Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence. PG - e70079 LID - 10.1111/obr.70079 [doi] LID - e70079 AB - Next-generation incretin therapies, including semaglutide and tirzepatide, have transformed obesity and Type 2 diabetes management. However, evidence-based nutritional strategies to support safe and effective use of these agents remain limited. To address this gap, we conducted a systematic scoping review across five databases of studies published between January 2015 and April 2025 to map and appraise clinical trials incorporating nutritional interventions or dietary assessments during semaglutide or tirzepatide therapy in adults with obesity or Type 2 diabetes. Eligible studies included adults receiving semaglutide or tirzepatide with either an active dietary intervention or measured nutrition-related outcomes. Study quality was assessed using established tools. Twelve studies were included: 10 randomized controlled trials, one non-randomized comparative study, and one cross-sectional observational study. Interventions ranged from structured very-low-energy or ketogenic diets to general lifestyle counseling and observational dietary assessments. Across studies, energy intake decreased by 24% to 39%, but lean tissue loss accounted for up to 40% of total weight reduction. Only three studies involved nutrition professionals, and systematic assessment of protein or micronutrient intake was rare. One observational study found widespread nutrient inadequacies and limited access to dietetic support. Despite the effectiveness of semaglutide and tirzepatide for weight loss, evidence on optimal dietary strategies is sparse. Early dietitian involvement, high-protein, nutrient-dense diets, and routine nutritional monitoring should be prioritized. Robust trials are needed to define best practice for integrating dietary care alongside pharmacotherapy. CI - (c) 2026 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation. FAU - Spreckley, Marie AU - Spreckley M AUID- ORCID: 0000-0002-8346-2408 AD - MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. FAU - Ruggiero, Cara F AU - Ruggiero CF AUID- ORCID: 0000-0001-6498-991X AD - MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. FAU - Brown, Adrian AU - Brown A AUID- ORCID: 0000-0003-1818-6192 AD - Centre for Obesity Research, University College London, Longdon, UK. AD - Bariatric Centre for Weight Management and Metabolic Surgery, University College London Hospital NHS Foundation Trust, London, UK. AD - National Institute for Health and Care Research, University College London Hospitals Biomedical Research Centre, London, UK. LA - eng GR - 303041/National Institute for Health and Care Research/ PT - Journal Article PT - Scoping Review DEP - 20260107 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy MH - *Obesity/drug therapy/diet therapy MH - *Glucagon-Like Peptides/therapeutic use MH - Weight Loss PMC - PMC13136787 OTO - NOTNLM OT - GLP-1 receptor agonists OT - nutrition OT - semaglutide OT - tirzepatide COIS- M.S. and C.F.R. declare no competing interests. A.B. declares researcher-led grants from the National Institute for Health Research, Rosetrees Trust, MRC, INNOVATE UK, British Dietetic Association, British Association of Parenteral and Enteral Nutrition, BBSRC, the Office of Health Improvement and Disparities and NovoNordisk. A.B. reports honoraria from Novo Nordisk and Eli Lilly outside the submitted work and is on the Medical Advisory Board and a shareholder of Reset Health Clinics Ltd. EDAT- 2026/01/08 00:27 MHDA- 2026/05/04 12:34 PMCR- 2026/05/04 CRDT- 2026/01/07 19:20 PHST- 2025/09/22 00:00 [revised] PHST- 2025/06/13 00:00 [received] PHST- 2025/12/10 00:00 [accepted] PHST- 2026/05/04 12:34 [medline] PHST- 2026/01/08 00:27 [pubmed] PHST- 2026/01/07 19:20 [entrez] PHST- 2026/05/04 00:00 [pmc-release] AID - OBR70079 [pii] AID - 10.1111/obr.70079 [doi] PST - ppublish SO - Obes Rev. 2026 Jun;27(6):e70079. doi: 10.1111/obr.70079. Epub 2026 Jan 7. PMID- 41493256 OWN - NLM STAT- MEDLINE DCOM- 20260106 LR - 20260127 IS - 1545-9616 (Print) IS - 1545-9616 (Linking) VI - 25 IP - 1 DP - 2026 Jan 1 TI - Cutaneous Adverse Events Associated With GLP-1 Receptor Agonists: A FAERS Database Analysis From 2018-2024. PG - 11-16 LID - 10.36849/JDD.9448 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for conditions beyond type 2 diabetes, including psoriasis and hidradenitis suppurativa. Despite this, little is known about their dermatologic safety profiles. METHODS: We analyzed FDA Adverse Event Reporting System (FAERS) data from 2018 to 2024 for semaglutide, liraglutide, exenatide, and dulaglutide. Cutaneous adverse events (AEs) were identified using MedDRA-coded terms: "rash," "pruritus," "urticaria," "alopecia," and "angioedema". Frequency and proportional reporting ratios (PRRs) were calculated using dipeptidyl peptidase-4 (DPP-4) inhibitors as a comparator. Logistic regression assessed predictors of cutaneous AEs, with dulaglutide as a reference and sex, age, and GLP-1 RA type as independent variables. RESULTS: Cutaneous AEs were reported in up to 8.16% of GLP-1 RA cases, more often in females, with a mean patient age of 60. Semaglutide was associated with the highest rate, and dulaglutide the lowest. PRR analysis (0.27; 95% CI: 0.257-0.284) showed these AEs were proportionally less common relative to DPP-4 inhibitor users. Exenatide was associated with increased odds (OR = 5.01, 95% CI: 4.69–5.35), while liraglutide and semaglutide showed decreased odds. DISCUSSION: Possibly influenced by dosage, immune modulation, and patient perception of efficacy, cutaneous GLP-1RA adverse effects were less frequent than DPP-4 inhibitors, but still warrant clinician awareness. These reactions might impact patient adherence, which highlights the need for further investigation into their mechanisms. CONCLUSION: Cutaneous AEs are infrequent but vary by GLP-1 RA. Greater awareness may improve patient counseling as indications expand.  . FAU - Fat, Marisa N AU - Fat MN FAU - Johnson, Hayden C AU - Johnson HC FAU - Farberg, Aaron S AU - Farberg AS LA - eng PT - Journal Article PL - United States TA - J Drugs Dermatol JT - Journal of drugs in dermatology : JDD JID - 101160020 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives/administration & dosage MH - Middle Aged MH - Exenatide/adverse effects/administration & dosage MH - Liraglutide/adverse effects/administration & dosage MH - Aged MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Adult MH - Databases, Factual/statistics & numerical data MH - Recombinant Fusion Proteins/adverse effects/administration & dosage MH - United States/epidemiology MH - Diabetes Mellitus, Type 2/drug therapy MH - *Drug Eruptions/etiology/epidemiology MH - United States Food and Drug Administration/statistics & numerical data MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects MH - Young Adult MH - Immunoglobulin Fc Fragments MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2026/01/06 19:17 MHDA- 2026/01/06 19:18 CRDT- 2026/01/06 12:42 PHST- 2026/01/06 19:18 [medline] PHST- 2026/01/06 19:17 [pubmed] PHST- 2026/01/06 12:42 [entrez] AID - S1545961626P9448X [pii] AID - 10.36849/JDD.9448 [doi] PST - ppublish SO - J Drugs Dermatol. 2026 Jan 1;25(1):11-16. doi: 10.36849/JDD.9448. PMID- 41492180 OWN - NLM STAT- MEDLINE DCOM- 20260210 LR - 20260814 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 3 DP - 2026 Mar TI - Oral semaglutide and survival in heart failure with preserved ejection fraction and type 2 diabetes. PG - 2374-2382 LID - 10.1111/dom.70433 [doi] AB - AIMS: Heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D) commonly coexist and are associated with poor outcomes. Although injectable semaglutide has demonstrated benefits in HFpEF, the effectiveness of oral semaglutide in this setting remains uncertain. This study compared all-cause death and hospitalisation between oral semaglutide and sitagliptin in patients with HFpEF and T2D. MATERIALS AND METHODS: Using a global healthcare data and analytics platform, the TriNetX research network, we conducted a retrospective multi-centre observational study. We identified patients aged >/=18 years with HFpEF diagnosed before December 31, 2023 (N = 1 731 548), of whom 812 259 had concomitant T2D. Among them, 3470 initiated oral semaglutide and 22 840 initiated sitagliptin between October 1, 2019, and December 31, 2023. After propensity score matching, each group included 3452 patients. The primary outcome was all-cause death; the secondary outcome was hospitalisation. RESULTS: Over 1 year, the risk for all-cause death in patients who received oral semaglutide relative to those who received sitagliptin was significantly lower (4.3% [145/3452] vs. 7.0% [229/3452]; log-rank p < 0.001; hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.50 to 0.75). Similarly, patients who received oral semaglutide experienced fewer hospitalisations than those who received sitagliptin (37.1% vs. 42.4%; log-rank p < 0.001; HR, 0.83; 95% CI, 0.77 to 0.90). CONCLUSIONS: Oral semaglutide appeared to be associated with a lower 1-year risk of all-cause death compared with sitagliptin in patients with HFpEF and T2D. CI - (c) 2026 John Wiley & Sons Ltd. FAU - Kishimori, Takefumi AU - Kishimori T AUID- ORCID: 0009-0000-9639-5470 AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Kato, Takao AU - Kato T AUID- ORCID: 0000-0001-8213-7999 AD - Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Iwasaki, Yoshihiro AU - Iwasaki Y AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Shimada, Takenobu AU - Shimada T AD - Department of Cardiovascular Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan. FAU - Wada, Atsuyuki AU - Wada A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Tani, Akira AU - Tani A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yamaji, Ryosuke AU - Yamaji R AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Koike, Jumpei AU - Koike J AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Matsumoto, Takehiro AU - Matsumoto T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yagi, Takafumi AU - Yagi T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Okada, Masaharu AU - Okada M AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20260105 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - *Heart Failure/mortality/drug therapy/complications/physiopathology MH - Aged MH - Retrospective Studies MH - Stroke Volume/drug effects MH - Middle Aged MH - Sitagliptin Phosphate/therapeutic use/administration & dosage MH - Administration, Oral MH - Hospitalization/statistics & numerical data MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged, 80 and over MH - Cause of Death OTO - NOTNLM OT - all-cause death OT - heart failure with preserved ejection fraction OT - hospitalisation OT - oral semaglutide OT - type 2 diabetes EDAT- 2026/01/06 13:06 MHDA- 2026/02/11 00:39 CRDT- 2026/01/06 11:47 PHST- 2025/12/16 00:00 [revised] PHST- 2025/10/14 00:00 [received] PHST- 2025/12/26 00:00 [accepted] PHST- 2026/02/11 00:39 [medline] PHST- 2026/01/06 13:06 [pubmed] PHST- 2026/01/06 11:47 [entrez] AID - 10.1111/dom.70433 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Mar;28(3):2374-2382. doi: 10.1111/dom.70433. Epub 2026 Jan 5. PMID- 41489846 OWN - NLM STAT- MEDLINE DCOM- 20260626 LR - 20261009 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 91 IP - 1 DP - 2026 Jan 5 TI - Exploring the rates of Gastrointestinal adverse effects among five GLP-1 receptor agonists: A systematic review and Meta-Analysis of randomized controlled trials. PG - 23 LID - 10.1007/s12020-025-04494-3 [doi] AB - PURPOSE: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective and commonly used agents in treating type 2 diabetes and obesity. Due to their success in weight loss, usage of this class of medications is becoming more common. Yet any use of GLP-1 RAs does not come without disadvantages. This meta-analysis aimed to analyze the gastrointestinal (GI)-related adverse effects (AEs) of GLP-1 RAs use. METHODS: A systematic review search following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was performed in three databases for studies reporting GI AEs after GLP-1 RA usage. A pair-wise meta-analysis evaluating the six most common GI AEs (nausea, vomiting, diarrhea, constipation, decreased appetite, and pancreatitis) among GLP-1 RAs was performed, along with a network meta-analysis comparing semaglutide, liraglutide, exenatide, dulaglutide, and tirzepatide to one another in the context of GI AEs. RESULTS: 101 randomized controlled studies were included in final analysis, with 41,443 of 57,684 patients receiving one of five GLP-1 RAs: liraglutide (37 studies), semaglutide (28 studies), exenatide (25 studies), dulaglutide (18 studies), and tirzepatide (8 studies). All six GI AEs analyzed were found to have a statistically significant risk ratio compared to placebo, with a 95% confidence interval and p < 0.00001: nausea (RR: 2.90; Incidence: 22.8%), vomiting (3.60; 9.12%), diarrhea (1.97; 13%), constipation (2.41; 7.39%), decreased appetite (3.51; 2.61%), and pancreatitis (2.24; 1.07%). Head-to-head comparisons revealed tirzepatide to carry the highest risk ratios for nausea and diarrhea while semaglutide carries the highest risk ratios for vomiting and constipation. CONCLUSIONS: Regardless of the GLP-1 RAs used, it is apparent that GI AEs are significant and highly prevalent. Thus, it is crucial that patients and providers alike are aware of these AEs when considering their use. FAU - Joy, Bethany AU - Joy B AUID- ORCID: 0009-0002-5707-146X AD - California Northstate University College of Medicine, California, USA. Bethany.Joy7985@cnsu.edu. FAU - Ramsamooj, Anya AU - Ramsamooj A AD - California Northstate University College of Medicine, California, USA. FAU - Ibrahim, Steven AU - Ibrahim S AD - California Northstate University College of Medicine, California, USA. FAU - Wen, Jimmy AU - Wen J AD - California Northstate University College of Medicine, California, USA. FAU - Hsu, Neil AU - Hsu N AD - California Northstate University College of Medicine, California, USA. FAU - Frezza, Eldo AU - Frezza E AD - California Northstate University College of Medicine, California, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Network Meta-Analysis PT - Systematic Review DEP - 20260105 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Tirzepatide MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Randomized Controlled Trials as Topic MH - *Gastrointestinal Diseases/chemically induced/epidemiology MH - Exenatide/adverse effects MH - Liraglutide/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Immunoglobulin Fc Fragments/adverse effects MH - Pancreatitis/chemically induced MH - Vomiting/chemically induced MH - Diarrhea/chemically induced MH - Nausea/chemically induced MH - Diabetes Mellitus, Type 2/drug therapy MH - Recombinant Fusion Proteins OTO - NOTNLM OT - GLP-1 OT - GLP-1 analogue OT - Meta-analysis OT - Systematic review OT - Weight management COIS- Declarations. Conflict of interests: The authors declare no competing interests. Consent to participate: This study did not involve the use of human subjects. Consent to publish: This study did not involve the use of human subjects. EDAT- 2026/01/05 12:47 MHDA- 2026/06/27 00:51 CRDT- 2026/01/05 11:56 PHST- 2025/07/25 00:00 [received] PHST- 2025/11/20 00:00 [accepted] PHST- 2026/06/27 00:51 [medline] PHST- 2026/01/05 12:47 [pubmed] PHST- 2026/01/05 11:56 [entrez] AID - 10.1007/s12020-025-04494-3 [pii] AID - 10.1007/s12020-025-04494-3 [doi] PST - epublish SO - Endocrine. 2026 Jan 5;91(1):23. doi: 10.1007/s12020-025-04494-3. PMID- 41484761 OWN - NLM STAT- MEDLINE DCOM- 20260307 LR - 20260813 IS - 1708-0428 (Electronic) IS - 0960-8923 (Print) IS - 0960-8923 (Linking) VI - 36 IP - 2 DP - 2026 Feb TI - Roux-en-Y Gastric Bypass Compared to Glucagon-Like Peptide-1 Receptor Agonists is Associated with Lower Out-of-Pocket Costs in Insured Patients with Type 2 Diabetes and Obesity: A Matched Analysis Over Two Years. PG - 376-385 LID - 10.1007/s11695-025-08467-3 [doi] AB - OBJECTIVE: To evaluate two-year costs to insured patients treated with Roux-en-Y gastric bypass (RYGB) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for type 2 diabetes (T2D) and obesity. METHODS: Using the 2017 to 2023 Merative claims database, we identified adult patients with severe obesity and T2D who were treated with a RYGB or GLP-1 RAs. Patients with RYGB had no treatment with GLP-1 RAs, and those who received GLP-1 RAs therapy with tirzepatide or semaglutide for >/= 2 years had no metabolic and bariatric surgery (MBS) procedures. The study cohorts were matched on demographics including obesity, associated medical problems, and baseline direct or out-of-pocket (OOP) costs to patients in the year prior to treatment initiation. Direct costs included those from outpatient services, inpatient admissions, and outpatient prescription filled that were paid directly by patients. We compared this cost up to two years after treatment initiation using paired t-tests. RESULTS: 1012 matched RYGB and GLP-1 RAs patients were analyzed, including 35% male. At 1-year after treatment initiation, healthcare costs paid directly by patients were similar for the RYGB ($2,301) and GLP-1 RAs ($2,179) (delta = $122, p = 0.15) cohorts. From one to two years after index treatment date, OOP costs were significantly lower in the RYGB treatment group ($1,277 vs. $2,104, p < 0.01). Two years after treatment initiation, RYGB patients spent $704 less in OOP costs than similar patients treated with GLP-1 RAs medications (p < 0.01). CONCLUSIONS: Direct OOP healthcare costs were lower for RYGB compared to treatment with GLP-1 RAs two years after treatment initiation. CI - (c) 2026. The Author(s). FAU - Thiyagarajan, Sibi AU - Thiyagarajan S AD - Division of Advanced GI and Bariatric Surgery, Mayo Clinic, Jacksonville, FL, USA. FAU - Wall-Wieler, Elizabeth AU - Wall-Wieler E AD - Global Health Economics and Outcomes Research, Intuitive Surgical (United States), Sunnyvale, CA, USA. FAU - Liu, Yuki AU - Liu Y AD - Global Health Economics and Outcomes Research, Intuitive Surgical (United States), Sunnyvale, CA, USA. FAU - Zheng, Feibi AU - Zheng F AD - Global Health Economics and Outcomes Research, Intuitive Surgical (United States), Sunnyvale, CA, USA. AD - DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA. FAU - Edwards, Michael AU - Edwards M AD - Division of Advanced GI and Bariatric Surgery, Mayo Clinic, Jacksonville, FL, USA. maeedw@gmail.com. LA - eng PT - Comparative Study PT - Journal Article DEP - 20260103 PL - United States TA - Obes Surg JT - Obesity surgery JID - 9106714 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/economics/drug therapy/complications MH - *Gastric Bypass/economics MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - *Health Expenditures/statistics & numerical data MH - *Obesity, Morbid/economics/surgery/complications MH - *Hypoglycemic Agents/therapeutic use/economics MH - Retrospective Studies PMC - PMC12957123 OTO - NOTNLM OT - Glucagon-like peptide 1 receptor agonists OT - Obesity OT - Out-of-Pocket Costs OT - Roux-en-Y gastric bypass OT - Type-2 Diabetes COIS- Declarations. Competing interests: Intuitive Surgical Inc. funded access to the Merative MarketScan Research Databases used for this study. Three co-authors are employed by Intuitive Surgical, Inc. (EW, YL, FZ) and were involved in the design, analysis, or preparation of this manuscript. Author MAE is a recipient of an Intuitive Foundation Research Grant Award for another research project. EDAT- 2026/01/04 06:35 MHDA- 2026/03/08 01:38 PMCR- 2026/01/03 CRDT- 2026/01/04 01:55 PHST- 2025/09/15 00:00 [received] PHST- 2025/12/21 00:00 [accepted] PHST- 2025/12/07 00:00 [revised] PHST- 2026/03/08 01:38 [medline] PHST- 2026/01/04 06:35 [pubmed] PHST- 2026/01/04 01:55 [entrez] PHST- 2026/01/03 00:00 [pmc-release] AID - 10.1007/s11695-025-08467-3 [pii] AID - 8467 [pii] AID - 10.1007/s11695-025-08467-3 [doi] PST - ppublish SO - Obes Surg. 2026 Feb;36(2):376-385. doi: 10.1007/s11695-025-08467-3. Epub 2026 Jan 3. PMID- 41482652 OWN - NLM STAT- MEDLINE DCOM- 20260519 LR - 20260813 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 111 IP - 6 DP - 2026 May 19 TI - GLP-1 receptor agonists in patients with cancer are associated with reduced all-cause mortality and hospitalization. PG - 1604-1612 LID - 10.1210/clinem/dgaf703 [doi] AB - CONTEXT: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been reported to decrease cancer incidence, but less is known about their potential in patients with active cancer. Preclinical studies have demonstrated that GLP-1RAs inhibit progression of solid tumor malignancies via downregulation of cellular proliferation pathways and improved glycemic control. Despite these promising findings, studies characterizing the effects of GLP-1RAs in patients with active cancer are limited. OBJECTIVE: To evaluate the effects of GLP-1RAs on mortality and hospitalization in patients with type 2 diabetes and active cancer compared to those receiving metformin. METHODS: Using TriNetX, a global database comprising more than 120 million patients, we identified an overall cohort of 3747 patients with type 2 diabetes who received GLP-1RAs within 3 months of starting systemic therapy and identified 52 061 patients receiving metformin in the same timeframe as a control cohort. Additional subanalyses stratified patients by glycated hemoglobin A1c (HbA1c) range, obesity, and by participants "newly started" on their first instance of GLP-1 RA within 3 months of starting cancer treatment. RESULTS: Patients receiving GLP-1RAs had significantly reduced mortality both in the overall monotherapy setting (hazard ratio [HR]: 0.875; 95% CI, 0.778-0.985; P = .0268) and the new-start setting (HR: 0.786; 95% CI, 0.662-0.934; P = .0062) cohorts. Secondary analyses found lower rates of all-cause hospitalization, sepsis, major adverse cardiovascular events, pulmonary embolism, and pneumonia in patients on GLP-1RAs. Subanalyses stratified by body mass index and HbA1c did not meet statistical significance. CONCLUSION: Patients with diabetes and cancer who received GLP-1RAs experienced superior survival outcomes and reduced rates of hospitalization compared to patients receiving metformin. Additionally, patients already on metformin and newly started on GLP-1RAs demonstrated superior survival outcomes compared to patients newly started on insulin. Further prospective, well-controlled studies are needed to evaluate the benefits of GLP-1RAs in patients with diabetes and cancer. CI - (c) The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Mahadevan, Aditya AU - Mahadevan A AUID- ORCID: 0000-0002-2834-5487 AD - Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Vosooghi, Aidan AU - Vosooghi A AD - Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA. FAU - Arora, Jagmeet S AU - Arora JS AD - School of Medicine, University of California, Irvine, CA 92617, USA. FAU - Kumar, Ruthvik Sunil AU - Kumar RS AD - Department of Medicine, University of Kentucky, Lexington, KY 40506, USA. FAU - Singh, Gagandeep AU - Singh G AD - Department of Computer Science, University of California, Davis, CA 95616, USA. FAU - Tsai, Katy K AU - Tsai KK AD - Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Quandt, Zoe AU - Quandt Z AUID- ORCID: 0000-0002-4568-4368 AD - Division of Endocrinology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA. AD - Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. LA - eng GR - K12DK133995/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Neoplasms/complications/mortality/therapy MH - *Metformin/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Proportional Hazards Models MH - Hospitalization/statistics & numerical data MH - Treatment Outcome MH - Kaplan-Meier Estimate MH - Humans MH - Male MH - Female MH - Middle Aged MH - Aged MH - Retrospective Studies PMC - PMC13183429 OTO - NOTNLM OT - GLP-1RA OT - cancer OT - dulaglutide OT - exenatide OT - liraglutide OT - semaglutide OT - survival OT - tirzepatide EDAT- 2026/01/03 06:30 MHDA- 2026/05/19 06:20 PMCR- 2026/01/02 CRDT- 2026/01/03 00:33 PHST- 2025/09/10 00:00 [received] PHST- 2025/12/30 00:00 [accepted] PHST- 2026/05/19 06:20 [medline] PHST- 2026/01/03 06:30 [pubmed] PHST- 2026/01/03 00:33 [entrez] PHST- 2026/01/02 00:00 [pmc-release] AID - 8413119 [pii] AID - dgaf703 [pii] AID - 10.1210/clinem/dgaf703 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2026 May 19;111(6):1604-1612. doi: 10.1210/clinem/dgaf703. PMID- 41475990 OWN - NLM STAT- MEDLINE DCOM- 20260212 LR - 20260212 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 36 IP - 3 DP - 2026 Mar TI - Sex specific responses to oral vs. subcutaneous semaglutide in type 2 diabetes mellitus: A 12-month real-world study. PG - 104462 LID - S0939-4753(25)00617-9 [pii] LID - 10.1016/j.numecd.2025.104462 [doi] AB - BACKGROUND AND AIM: Semaglutide therapy improves glycaemic control, weight loss, and cardiovascular risk reduction in patients with type 2 diabetes mellitus (T2D). Sex-specific differences in the response to oral versus subcutaneous formulation remain unexplored in real-world settings. This interventional pilot study compares the 12-month effectiveness of oral and subcutaneous semaglutide in a real-world cohort of T2D patients, with focus to sex-based differences in treatment outcomes. METHODS AND RESULTS: Two-hundred and twelve T2D patients, equally assigned to oral or subcutaneous semaglutide (n = 106 per group), were enrolled. The primary endpoint was the change in HbA1c. Secondary endpoints included variations in anthropometric and metabolic parameters, analysed both in the overall cohort and through a sex-stratified approach. Two-hundred and eight patients completed the study. In men, subcutaneous semaglutide resulted in significant reductions in delta(Delta)_weight (p = 0.010), Delta_HbA1c (p = 0.037), and Delta_LDL (p = 0.038) compared to the oral formulation. In women, subcutaneous semaglutide led to significantly lower Delta_hepatic steatosis index (p = 0.024). Additionally, women treated with subcutaneous semaglutide showed a significantly greater reduction in Delta_GOT (p = 0.035) compared to men. CONCLUSIONS: This real-world study suggests that subcutaneous semaglutide provides greater metabolic benefits than the oral formulation, particularly in men. Women treated with subcutaneous semaglutide experience more favorable liver responses, emphasizing the personalization of T2D treatment. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Piccione, Alessandra AU - Piccione A AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Bonsangue, Maria AU - Bonsangue M AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Barone, Martina AU - Barone M AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Vigneri, Enrica AU - Vigneri E AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Mineo, Mariagrazia Irene AU - Mineo MI AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Tomasello, Laura AU - Tomasello L AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. Electronic address: laura.tomasello@unipa.it. FAU - Maniscalco, Laura AU - Maniscalco L AD - Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Via del Vespro 133, Palermo, 90127, Italy. FAU - Panto, Felicia AU - Panto F AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Arnaldi, Giorgio AU - Arnaldi G AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. FAU - Guarnotta, Valentina AU - Guarnotta V AD - Unit of Endocrinology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, Policlinico Paolo Giaccone, Universita degli Studi di Palermo, 90127, Palermo, Italy. LA - eng PT - Comparative Study PT - Journal Article DEP - 20251115 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - Middle Aged MH - Administration, Oral MH - Treatment Outcome MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Aged MH - Glycated Hemoglobin/metabolism MH - Pilot Projects MH - *Blood Glucose/metabolism/drug effects MH - Sex Factors MH - Injections, Subcutaneous MH - Time Factors MH - Biomarkers/blood MH - Glycemic Control/adverse effects MH - Weight Loss/drug effects OTO - NOTNLM OT - Female OT - Gender OT - Glucagon-like peptide-1 receptor agonist (GLP-1RA) OT - Male OT - Sex COIS- Declaration of competing interest The authors declare that they have no competing interests. EDAT- 2026/01/01 00:35 MHDA- 2026/02/13 01:27 CRDT- 2025/12/31 22:04 PHST- 2025/07/05 00:00 [received] PHST- 2025/10/01 00:00 [revised] PHST- 2025/11/05 00:00 [accepted] PHST- 2026/02/13 01:27 [medline] PHST- 2026/01/01 00:35 [pubmed] PHST- 2025/12/31 22:04 [entrez] AID - S0939-4753(25)00617-9 [pii] AID - 10.1016/j.numecd.2025.104462 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2026 Mar;36(3):104462. doi: 10.1016/j.numecd.2025.104462. Epub 2025 Nov 15. PMID- 41453566 OWN - NLM STAT- MEDLINE DCOM- 20260111 LR - 20260111 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 231 DP - 2026 Jan TI - GLP-1 receptor agonist use during immune checkpoint inhibitor therapy is associated with mortality and Immune-Related adverse events across cancer types in People with type 2 Diabetes: A Target-Trial emulation. PG - 113073 LID - S0168-8227(25)01088-5 [pii] LID - 10.1016/j.diabres.2025.113073 [doi] AB - AIMS: To evaluate whether Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use at immune checkpoint inhibitor (ICI) start is associated with mortality, healthcare use, and immune-related adverse events in adults with type 2 diabetes (T2D). METHODS: A target-trial emulation was conducted in the TriNetX US Collaborative Network among adults with cancer and T2D starting an ICI, with or without overlapping GLP-1 RA at ICI start. A new-user 1:1 propensity-score-matched, intention-to-treat design yielded 2,903 per group and 36-month follow-up. Primary endpoint was all-cause mortality; key secondaries were hospitalization, and composite immune-related adverse events (irAEs). Prespecified per-protocol, 90-day landmark, and semaglutide-only analyses assessed robustness. RESULTS: GLP-1 RA co-exposure was associated with lower mortality (hazard ratio [HR] 0.55, 95 % CI 0.51-0.61; 36-month absolute risk difference [ARD] - 16.41 %; number needed to treat [NNT] 5). Hospitalization (HR 0.76; ARD - 7.06 %; NNT 11), and composite irAEs (43.93 % vs 51.51 %; ARD - 7.58 %; NNT 11) were also lower. Diabetic-retinopathy progression (HR 1.75; ARD + 2.71 %) and non-arteritic anterior ischemic optic neuropathy (HR 1.51) were higher; hypoglycaemia, acute kidney injury, and dehydration/orthostatic hypotension were lower. CONCLUSIONS: GLP-1 RA use during ICI therapy correlated with lower mortality, reduced acute care, fewer irAEs; ophthalmic signals warrant monitoring. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Chan, Shan-Ho AU - Chan SH AD - Department of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan. Electronic address: shchan@ms.szmc.edu.tw. FAU - Li, Pei-Yun AU - Li PY AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University Taichung, Taiwan. Electronic address: peiyunli@csh.org.tw. FAU - Li, Pin-Hung AU - Li PH AD - Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University Taichung, Taiwan. Electronic address: s0617034@gm.csmu.edu.tw. FAU - Lin, Yu-Jung AU - Lin YJ AD - Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan. Electronic address: tch32233@tzuchi.com.tw. FAU - Wang, Wei-Hsun AU - Wang WH AD - Department of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua, Taiwan; Department of Golden-Ager Industry Management, Chaoyang University of Technology, Taichung, Taiwan. Electronic address: wangweihsun@nchu.edu.tw. FAU - Huang, Yu-Nan AU - Huang YN AD - Department of Medical Imaging and Radiology, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan; Division of Genetics and Endocrinology, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan; School of Medicine, Chung Shan Medical University Taichung, Taiwan. Electronic address: yunanhuang@csh.org.tw. FAU - Chen, Jia-Yuh AU - Chen JY AD - Division of Neonatology, Changhua Christian Children's Hospital, Changhua, Taiwan; Division of Metabolism and Endocrinology, Yunlin Christian Hospital, Changhua, Taiwan. Electronic address: 182288@cch.org.tw. LA - eng PT - Journal Article DEP - 20251224 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Immune Checkpoint Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - Female MH - Male MH - *Immune Checkpoint Inhibitors/adverse effects/therapeutic use MH - *Neoplasms/drug therapy/mortality/complications/immunology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects OTO - NOTNLM OT - All-cause mortality OT - Diabetic retinopathy OT - GLP-1 receptor agonists OT - Immune checkpoint inhibitors OT - Immune-related adverse events COIS- Declaration of competing interest Shan-Ho Chan, Pei-Yun Li, Pin-Hung Li, Yu-Jung Lin, Wei-Hsun Wang, Yu-Nan Huang, and Jia-Yuh Chen declare no competing interests. The funding bodies had no role in the study design, data collection, analysis, interpretation, or manuscript preparation. The authors affirm independence in the conduct of this research and in the decision to publish. EDAT- 2025/12/27 00:54 MHDA- 2026/01/12 00:37 CRDT- 2025/12/26 19:34 PHST- 2025/11/07 00:00 [received] PHST- 2025/12/16 00:00 [revised] PHST- 2025/12/23 00:00 [accepted] PHST- 2026/01/12 00:37 [medline] PHST- 2025/12/27 00:54 [pubmed] PHST- 2025/12/26 19:34 [entrez] AID - S0168-8227(25)01088-5 [pii] AID - 10.1016/j.diabres.2025.113073 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2026 Jan;231:113073. doi: 10.1016/j.diabres.2025.113073. Epub 2025 Dec 24. PMID- 41451880 OWN - NLM STAT- MEDLINE DCOM- 20260128 LR - 20260129 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 IP - 2 DP - 2026 Feb TI - Weight Loss With SGLT2 Inhibitors, Semaglutide, and Transcranial Magnetic Stimulation in Type 2 Diabetes and Obesity. PG - 317-322 LID - 10.1002/oby.70105 [doi] AB - OBJECTIVE: This study compared the efficacy of a GLP-1 receptor agonist (GLP1-RA) (semaglutide, 0.5 mg/week), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and repetitive transcranial magnetic stimulation (rTMS), a new emerging treatment for obesity, in reducing body weight (BW) after 1 year in patients with obesity and type 2 diabetes (T2D). METHODS: We included 40 patients with T2D treated with a SGLT2i, 37 patients with T2D treated with the GLP1-RA semaglutide, and 30 patients treated with rTMS in this retrospective comparative analysis. rTMS was administered three times per week for 5 weeks. All patients received dietary advice about moderate caloric restriction (-300 kcal/day). RESULTS: After 12 months the weight loss with rTMS (-8.2 +/- 1.0 kg) was not significantly different from that with semaglutide (-5.7 +/- 0.9 kg). Weight loss with SGLT2i (-2.0 +/- 0.7 kg) was significantly less than with both semaglutide (p = 0.01) and rTMS (p < 0.0001). Individuals receiving SGLT2i therapy experienced weight regain from month 6 to month 12, while BW declined progressively in patients treated with semaglutide and rTMS. CONCLUSIONS: Treatment with rTMS produced a comparable reduction in BW to that observed with the GLP1-RA semaglutide (at the dose of 0.5 mg/week) and represents a promising intervention for the treatment of obesity and T2D. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03009695. CI - (c) 2025 The Obesity Society. FAU - Ferrulli, Anna AU - Ferrulli A AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. FAU - Senesi, Pamela AU - Senesi P AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. FAU - Sonaglioni, Andrea AU - Sonaglioni A AD - Division of Cardiology, IRCCS MultiMedica, Milan, Italy. FAU - Cannavaro, Daniele AU - Cannavaro D AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. FAU - Massarini, Stefano AU - Massarini S AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. FAU - Macri, Concetta AU - Macri C AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. FAU - Cipponeri, Elisa AU - Cipponeri E AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. FAU - DeFronzo, Ralph A AU - DeFronzo RA AD - Division of Diabetes, UT Health San Antonio, San Antonio, Texas, USA. AD - Texas Diabetes Institute, San Antonio, Texas, USA. FAU - Luzi, Livio AU - Luzi L AUID- ORCID: 0000-0003-3183-0552 AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, Milan, Italy. LA - eng SI - ClinicalTrials.gov/NCT03009695 GR - Ricerca Corrente-IRCCS MultiMedica/ GR - RF-2011-02349303/Italian Ministry of Health/ PT - Clinical Trial PT - Journal Article DEP - 20251226 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/therapy/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/therapy/drug therapy/complications MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Transcranial Magnetic Stimulation MH - Treatment Outcome MH - *Weight Loss/drug effects OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT2 inhibitors OT - obesity OT - transcranial magnetic stimulation OT - type 2 diabetes EDAT- 2025/12/26 13:38 MHDA- 2026/01/28 19:20 CRDT- 2025/12/26 06:54 PHST- 2025/10/28 00:00 [revised] PHST- 2025/08/12 00:00 [received] PHST- 2025/10/31 00:00 [accepted] PHST- 2026/01/28 19:20 [medline] PHST- 2025/12/26 13:38 [pubmed] PHST- 2025/12/26 06:54 [entrez] AID - 10.1002/oby.70105 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Feb;34(2):317-322. doi: 10.1002/oby.70105. Epub 2025 Dec 26. PMID- 41437637 OWN - NLM STAT- MEDLINE DCOM- 20260128 LR - 20260129 IS - 1464-3677 (Electronic) IS - 1353-4505 (Linking) VI - 38 IP - 1 DP - 2026 Jan 10 TI - Income disparities and accessibility to Semaglutide: implications for diabetes management and policy reform. LID - mzaf131 [pii] LID - 10.1093/intqhc/mzaf131 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1(GLP-1) receptor agonist, is an effective treatment for type 2 diabetes and weight loss. However, its high cost poses a significant barrier to access for those who need it more. This study investigated if socioeconomic factors affected the use of semaglutide among patients with type 2 diabetes and if there are income disparities in its utilization. METHODS: This analysis utilized data from the 2022 Medical Expenditure Panel Survey (MEPS), focusing on US adults diagnosed with type 2 diabetes. The sample included 2542 individuals, representing approximately 30.3 million adults in the USA. Descriptive statistics were calculated to summarize demographic and socioeconomic characteristics. Bivariate associations between income, insurance status, and semaglutide use were assessed using chi-square tests. A multivariable logistic regression model was applied to identify the relationship between income levels and Semaglutide use while adjusting for potential confounders, including insurance status, education, and employment. RESULTS: The analysis revealed a significant association between income and semaglutide use. Individuals with incomes above the median were more likely to use semaglutide than those with lower incomes [odds ratio (OR) = 1.61, 95% CI: 1.14-2.26]. Private insurance also significantly increased the likelihood of semaglutide use (OR = 1.52, 95% CI: 1.04-2.22). Education level and employment status were additional significant predictors of access. Racial and ethnic disparities were observed but did not reach statistical significance after adjustment. DISCUSSION: These findings highlighted the significant barriers to accessing semaglutide for low-income individuals. Such individuals are disproportionately affected by diabetes. The affordability of drugs like semaglutide underlines the need for policy interventions to address income-related disparities in healthcare. Expanding insurance coverage, implementing subsidy programs, and introducing price regulation strategies, such as external reference pricing, are potential solutions to improve access to this essential treatment. This study emphasizes the importance of ensuring equitable access to such essential medications regardless of income level. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Vaidya, Varun AU - Vaidya V AUID- ORCID: 0000-0002-7943-3479 AD - Department of Pharmacy Practice, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Health Science Campus, Toledo, OH, United States. FAU - Estep, Sophia AU - Estep S AD - College of Pharmacy & Pharmaceutical Sciences, The University of Toledo, Toledo, OH, United States. FAU - Gupte, Renuka AU - Gupte R AD - Humana Ohio Medicaid, Perrysburg, OH, United States. LA - eng PT - Journal Article PL - England TA - Int J Qual Health Care JT - International journal for quality in health care : journal of the International Society for Quality in Health Care JID - 9434628 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Female MH - *Glucagon-Like Peptides/therapeutic use/economics MH - Male MH - Adult MH - *Hypoglycemic Agents/therapeutic use/economics MH - United States MH - *Income/statistics & numerical data MH - *Health Services Accessibility/statistics & numerical data MH - Aged MH - Socioeconomic Factors MH - *Healthcare Disparities/statistics & numerical data MH - Insurance Coverage/statistics & numerical data OTO - NOTNLM OT - Semaglutide OT - diabetes management OT - healthcare access OT - income disparities EDAT- 2025/12/24 07:43 MHDA- 2026/01/28 19:21 CRDT- 2025/12/24 02:03 PHST- 2025/05/09 00:00 [received] PHST- 2025/11/05 00:00 [revised] PHST- 2025/11/18 00:00 [accepted] PHST- 2026/01/28 19:21 [medline] PHST- 2025/12/24 07:43 [pubmed] PHST- 2025/12/24 02:03 [entrez] AID - 8403748 [pii] AID - 10.1093/intqhc/mzaf131 [doi] PST - ppublish SO - Int J Qual Health Care. 2026 Jan 10;38(1):mzaf131. doi: 10.1093/intqhc/mzaf131. PMID- 41429246 OWN - NLM STAT- MEDLINE DCOM- 20260214 LR - 20260214 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 283 DP - 2026 Mar TI - Potential Eye Disorders in People With and Without Type 2 Diabetes Mellitus Exposed to GLP-1 Receptor Agonists: An Examination of the FAERS (FDA Adverse Event Reporting System) Database. PG - 279-290 LID - S0002-9394(25)00666-X [pii] LID - 10.1016/j.ajo.2025.12.015 [doi] AB - PURPOSE: As use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for Type 2 diabetes (T2DM) and weight management increases, emerging research identifies various adverse drug reactions. This study aimed to expand this research base, focusing on eye disorders in people with and without T2DM, a novel consideration. DESIGN: A retrospective clinical cohort disproportionality analysis of reports made to the Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: FAERS was queried regarding selected GLP-1RAs. Python 3.11 was adopted to develop a program, quantifying reported cases between January 2017 - September 2025 (January 2022-September 2025 for tirzepatide) meeting the criteria for cases with and without T2DM. Main outcome measures Reporting Odds Ratios (RORs) >4.000 and 95% confidence intervals were calculated, with metformin and orlistat as controls. RESULTS: Compared to metformin, semaglutide showed increased reporting of optic ischemic neuropathy (ROR: 12.269 [0.915-1.967]), cataract (ROR: 31.879 [2.463-4.461]) and retinopathy (ROR: 5.185 [0.556-2.736]) in T2DM patients, and retinopathy (ROR: 9.424 [1.081-3.406]) and retinal hemorrhage (ROR: 10.253 [0.319-4.336]) in non-T2DM patients. Tirzepatide showed increased reporting of optic ischemic neuropathy (ROR: 4.619 [0.726-2.335]) and macular degeneration (ROR: 15.579 [0.554-4.938]) in T2DM patients and eye swelling (ROR: 6.475 [0.407-3.329]) in non-T2DM patients. Liraglutide showed increased reporting of cataract (ROR: 53.866 [2.945-5.028]), diabetic retinopathy (ROR: 18.162 [1.753-4.045]) and macular degeneration (ROR: 26.261 [1.076-5.460]) in T2DM patients and cataract (ROR: 9.628 [1.387-3.142]) and macular degeneration (ROR: 9.557 [0.110-4.405]) in non-T2DM patients. CONCLUSIONS: These results provide a signal of increased reporting of various eye disorders with GLP-1RA use compared to metformin across T2DM and non-T2DM patient cases. Further research is required to support these findings and confirm a biological causation. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Murray, Mya AU - Murray M AD - From Pharmacy, the Singleton Campus (M.M., A.G.), Swansea University, Wales, UK. FAU - Schifano, Fabrizio AU - Schifano F AD - Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit (F.S., J.M.C.), College Lane Campus, University of Hertfordshire, Hatfield, UK. FAU - Chiappini, Stefania AU - Chiappini S AD - Psychiatry, UniCamillus University (S.C.), Rome, Italy. FAU - Corkery, John Martin AU - Corkery JM AD - Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit (F.S., J.M.C.), College Lane Campus, University of Hertfordshire, Hatfield, UK. FAU - Guirguis, Amira AU - Guirguis A AD - From Pharmacy, the Singleton Campus (M.M., A.G.), Swansea University, Wales, UK. Electronic address: amira.guirguis@swansea.ac.uk. LA - eng PT - Journal Article DEP - 20251220 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Retrospective Studies MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - United States/epidemiology MH - United States Food and Drug Administration/statistics & numerical data MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Female MH - Male MH - Databases, Factual MH - Middle Aged MH - Aged MH - *Eye Diseases/chemically induced/epidemiology MH - Glucagon-Like Peptides/adverse effects EDAT- 2025/12/23 00:27 MHDA- 2026/02/15 00:31 CRDT- 2025/12/22 19:28 PHST- 2025/10/23 00:00 [received] PHST- 2025/12/17 00:00 [revised] PHST- 2025/12/18 00:00 [accepted] PHST- 2026/02/15 00:31 [medline] PHST- 2025/12/23 00:27 [pubmed] PHST- 2025/12/22 19:28 [entrez] AID - S0002-9394(25)00666-X [pii] AID - 10.1016/j.ajo.2025.12.015 [doi] PST - ppublish SO - Am J Ophthalmol. 2026 Mar;283:279-290. doi: 10.1016/j.ajo.2025.12.015. Epub 2025 Dec 20. PMID- 41424191 OWN - NLM STAT- MEDLINE DCOM- 20260210 LR - 20260812 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 3 DP - 2026 Mar TI - Impact of glucagon-like peptide-1 receptor agonism-based therapies on limb outcomes in peripheral artery disease and type 2 diabetes: An updated systematic review and meta-analysis. PG - 2075-2084 LID - 10.1111/dom.70391 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonism (GLP1RA)-based therapies (GLP1RA-BTs) form the cornerstone for managing type 2 diabetes (T2D) and obesity. However, their impact on limb-specific outcomes in peripheral artery disease (PAD) remains unclear. This systematic-review and meta-analysis evaluated the safety and efficacy of GLP1RA-BTs on limb outcomes in PAD and T2D. MATERIALS AND METHODS: Electronic databases were searched for studies involving GLP1RA-BTs in PAD and/or T2D. Primary outcome was the major adverse limb events (MALEs). Secondary outcomes were all-cause mortality, revascularization, amputation, major adverse cardiovascular events (MACE), cardiovascular mortality, myocardial infarction (MI), stroke, hospitalization for heart-failure (HHF), and amputations. Analyses were performed separately for studies exclusively enrolling patients with PAD (PAD cohort) and for those in broader T2D populations reporting limb outcomes but not limited to PAD, in which PAD comprised <15% of participants (T2D cohort). RESULTS: Data from 10 studies for PAD cohort (352 743 patients) and 7 studies for T2D cohort (1 759 799 patients) were analysed. In PAD cohort, MALE [OR 0.66 (0.44, 1.00); p = 0.05; I(2) = 94%], all-cause mortality [OR 0.55 (0.38, 0.78); p = 0.0008; I(2) = 97%], MACE [OR 0.68 (0.52, 0.88); p = 0.004; I(2) = 85%], and MI [OR 0.68 (0.51, 0.91); p = 0.009; I(2) = 42%] were lower in patients on GLP1RA-BTs compared to controls. In the PAD cohort, need for revascularization was significantly lower in GLP1RA-BTs than in controls [OR 0.85 (0.80, 0.90); p < 0.001; I(2) = 0%]. In the T2D cohort, MALE [OR 0.70 (0.57, 0.85); p = 0.0005; I(2) = 0%], amputations [OR 0.58 (0.48, 0.69); p < 0.001; I(2) = 0%], and all-cause mortality [OR 0.55 (0.43, 0.69); p < 0.001; I(2) = 85%] were significantly lower in GLP1RA-BT compared to controls. CONCLUSIONS: GLP1RA-BTs are beneficial in PAD, especially in reducing the need for revascularization. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Dutta, Deep AU - Dutta D AUID- ORCID: 0000-0003-4915-8805 AD - Department of Endocrinology, CEDAR Superspeciality Healthcare, New Delhi, India. FAU - Mahajan, Kunal AU - Mahajan K AUID- ORCID: 0000-0001-9378-6505 AD - Department of Cardiology, Himachal Heart Institute, Mandi, India. FAU - Kamrul-Hasan, Abul Bashar Mohammad AU - Kamrul-Hasan ABM AUID- ORCID: 0000-0002-5681-6522 AD - Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh. FAU - Mahajan, Nitin AU - Mahajan N AUID- ORCID: 0000-0002-0907-6410 AD - Translational Research and Data Science Consultant, USA. FAU - Sharma, Meha AU - Sharma M AD - Department of Rheumatology, CEDAR Superspeciality Healthcare, New Delhi, India. FAU - Vohra, Shekhar AU - Vohra S AUID- ORCID: 0009-0008-6909-5454 AD - Mount Sinai Morningside, Icahn School of Medicine at Mount Sinai, New York, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251222 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Peripheral Arterial Disease/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Amputation, Surgical/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - *Diabetic Angiopathies/drug therapy MH - Male OTO - NOTNLM OT - cardiovascular outcomes OT - liraglutide OT - peripheral artery disease OT - semaglutide OT - tirzepatide EDAT- 2025/12/22 06:29 MHDA- 2026/02/11 00:39 CRDT- 2025/12/22 04:23 PHST- 2025/12/02 00:00 [revised] PHST- 2025/11/05 00:00 [received] PHST- 2025/12/09 00:00 [accepted] PHST- 2026/02/11 00:39 [medline] PHST- 2025/12/22 06:29 [pubmed] PHST- 2025/12/22 04:23 [entrez] AID - 10.1111/dom.70391 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Mar;28(3):2075-2084. doi: 10.1111/dom.70391. Epub 2025 Dec 22. PMID- 41422027 OWN - NLM STAT- MEDLINE DCOM- 20260203 LR - 20261004 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 25 IP - 1 DP - 2025 Dec 20 TI - Once-weekly semaglutide versus placebo for the treatment of type 2 diabetes and chronic kidney disease in Denmark: A long-term cost-effectiveness analysis based on FLOW. PG - 32 LID - 10.1186/s12933-025-03002-1 [doi] LID - 32 AB - BACKGROUND: The FLOW clinical trial recently demonstrated that the glucagon-like peptide-1 receptor agonist once-weekly semaglutide 1 mg was associated with kidney- and cardio-protective effects (the latter already shown in the SUSTAIN 6 trial) compared with placebo, both in addition to standard of care (SoC), in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This study assessed the long-term cost-effectiveness of semaglutide versus placebo in people with T2D and CKD in Denmark, based on outcomes from FLOW. METHODS: Life expectancy, quality-adjusted life expectancy, cumulative incidence of diabetes-related complications, and costs were projected over a lifetime time horizon using the PRIME T2D Model. Baseline cohort characteristics and changes in risk factors with semaglutide and placebo were taken from FLOW, with extrapolation over patient lifetimes. Outcomes were assessed for the full population and subgroups receiving/not receiving sodium-glucose cotransporter-2 (SGLT-2) inhibitors at baseline. Quality-of-life disutilities and Denmark-specific costs (expressed in 2023 Danish Kroner [DKK]) were applied to capture the impact of diabetes-related complications and pharmacy costs. RESULTS: Treatment with semaglutide was projected to improve long-term quality-adjusted life expectancy by 0.60 quality-adjusted life years (QALYs) compared with placebo in the full population and by 0.44 and 0.62 QALYs in subgroups receiving/not receiving SGLT-2 inhibitors at baseline, respectively. Differences were predominantly driven by a reduced incidence of kidney failure with semaglutide versus placebo. Semaglutide was associated with long-term, per-person cost savings of DKK 6,068 in the full population and DKK 9,212 in those not receiving SGLT-2 inhibitors at baseline, leading to semaglutide being a dominant treatment compared with placebo. In patients receiving SGLT-2 inhibitors at baseline, semaglutide was cost-effective with an ICER of DKK 19,167 per QALY gained. CONCLUSIONS: Adding semaglutide to SoC was projected to be highly cost-effective over the long term in people with T2D and CKD in a Danish healthcare setting, based on patient characteristics and treatment effects from FLOW. Trial registration NCT03819153, first submitted on January 18, 2019. CI - (c) 2026. The Author(s). FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Complication Research, Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Lindhardt, Morten AU - Lindhardt M AUID- ORCID: 0000-0001-6063-1718 AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. AD - Department of Internal Medicine, Copenhagen University Hospital Holbaek, Holbaek, Denmark. FAU - Tikkanen, Christian Klyver AU - Tikkanen CK AUID- ORCID: 0000-0003-4474-6237 AD - Novo Nordisk Denmark A/S, Copenhagen, Denmark. FAU - Menon, Jyothi AU - Menon J AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Cattin, Juliette AU - Cattin J AUID- ORCID: 0009-0001-2528-4359 AD - Ossian Health Economics and Communications GmbH, Baumleingasse 20, 4051, Basel, Switzerland. FAU - Hunt, Barnaby AU - Hunt B AUID- ORCID: 0000-0001-5420-279X AD - Ossian Health Economics and Communications GmbH, Baumleingasse 20, 4051, Basel, Switzerland. hunt@ossianconsulting.com. FAU - Malkin, Samuel J P AU - Malkin SJP AUID- ORCID: 0000-0003-1306-7784 AD - Ossian Health Economics and Communications GmbH, Baumleingasse 20, 4051, Basel, Switzerland. FAU - Chubb, Barrie AU - Chubb B AUID- ORCID: 0000-0001-7271-051X AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Damgaard, Tina AU - Damgaard T AUID- ORCID: 0009-0005-8595-6187 AD - Novo Nordisk Denmark A/S, Copenhagen, Denmark. FAU - Borg, Rikke AU - Borg R AUID- ORCID: 0000-0002-2283-3578 AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. AD - Department of Medicine, Zealand University Hospital, Roskilde, Denmark. LA - eng SI - ClinicalTrials.gov/NCT03819153 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20251220 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Cost-Benefit Analysis MH - Denmark/epidemiology MH - *Glucagon-Like Peptides/administration & dosage/economics/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/economics/diagnosis/epidemiology/mortality MH - Time Factors MH - *Renal Insufficiency, Chronic/economics/drug therapy/diagnosis/epidemiology/mortality MH - Treatment Outcome MH - Male MH - Female MH - *Hypoglycemic Agents/administration & dosage/adverse effects/economics MH - Quality-Adjusted Life Years MH - *Drug Costs MH - Middle Aged MH - Drug Administration Schedule MH - Models, Economic MH - Aged MH - Sodium-Glucose Transporter 2 Inhibitors/economics/adverse effects/administration & dosage MH - Cost Savings MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Blood Glucose/drug effects/metabolism MH - Life Expectancy MH - Cost-Effectiveness Analysis PMC - PMC12862915 OTO - NOTNLM OT - Chronic kidney disease OT - Cost-effectiveness analysis OT - End-stage kidney disease OT - GLP-1 receptor agonist OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors. Consent for publication: No individual patient data is included in the manuscript. Competing interests: PR has served as consultant on advisory boards for Astra Zeneca, Abbott, Bayer, Novartis, Boehringer Ingelheim, Gilead and Sanofi (honoraria to his institution); has received unrestricted grants (to his institution) from Astra Zeneca, Bayer, and Novo Nordisk; and grants from Bayer, Novo Nordisk and Lexicon pharmaceuticals (study medication to investigator initiated study). ML has received speaker and consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk and GlaxoSmithKline. RB reports honoraria for education and consultancy from Astra Zeneca, Bayer, Novo Nordisk and Boehringer Ingelheim. She is an investigator in clinical studies sponsored by Boehringer Ingelheim, AstraZeneca or Bayer; and has received unrestricted research grants from Boehringer Ingelheim. JM and BC are employees of Novo Nordisk A/S. CKT and TD are employees of Novo Nordisk Denmark A/S. JC, BH and SJPM are employees of Ossian Health Economics and Communications. Ossian received consulting fees from Novo Nordisk A/S to support the preparation of the analysis. EDAT- 2025/12/21 01:48 MHDA- 2026/02/03 07:41 PMCR- 2025/12/20 CRDT- 2025/12/20 23:15 PHST- 2025/08/29 00:00 [received] PHST- 2025/10/28 00:00 [accepted] PHST- 2026/02/03 07:41 [medline] PHST- 2025/12/21 01:48 [pubmed] PHST- 2025/12/20 23:15 [entrez] PHST- 2025/12/20 00:00 [pmc-release] AID - 10.1186/s12933-025-03002-1 [pii] AID - 3002 [pii] AID - 10.1186/s12933-025-03002-1 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Dec 20;25(1):32. doi: 10.1186/s12933-025-03002-1. PMID- 41419618 OWN - NLM STAT- MEDLINE DCOM- 20260322 LR - 20261009 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 69 IP - 5 DP - 2026 May TI - Efficacy of tirzepatide versus semaglutide in achieving therapeutic targets in type 2 diabetes: a post hoc analysis of the SURPASS-2 Trial. PG - 1216-1225 LID - 10.1007/s00125-025-06637-7 [doi] AB - AIMS/HYPOTHESIS: Simultaneous control of HbA(1c), lipid profile, BP and body weight is essential for preventing chronic complications of type 2 diabetes. Glucagon-like peptide-1 (GLP-1)-based therapies improve all these variables but whether the dual GLP-1 / glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide is superior to semaglutide in attaining therapeutic targets remains unclear. METHODS: We performed a post hoc analysis of the SURPASS-2 trial, a randomised phase 3 study including 1879 adults with type 2 diabetes. Participants were randomised to receive tirzepatide (5, 10 or 15 mg) or semaglutide (1 mg). In this analysis, we compared the effects of tirzepatide vs semaglutide on the attainment of standard (HbA(1c) <53 mmol/mol [7%], BP <140/90 mmHg, LDL-cholesterol <1.8 mmol/l, >10% weight loss) and intensive (HbA(1c) <48 mmol/mol [6.5%], BP <130/80 mmHg, LDL-cholesterol <1.4 mmol/l , >15% weight loss) therapeutic targets at 40 weeks. RESULTS: In the SURPASS-2 trial, at baseline, 19% of participants were on target for attaining no standard goals, 59% for one goal and 21% for two or more goals. For intensive therapeutic targets, 58% of participants were on target for attaining zero goals, 38% for one goal and 4% for two goals. All doses of tirzepatide increased the number of achieved standard and intensive targets compared with semaglutide. For standard targets, 34% of participants treated with semaglutide met three or more targets, compared with 42%, 53% and 57% with tirzepatide 5, 10 and 15 mg, respectively. For intensive targets, 8% of participants treated with semaglutide met three or more targets, vs 15%, 20% and 29% with tirzepatide. Regarding specific therapeutic goals, tirzepatide increased the odds of achieving standard and intensive targets for HbA(1c) (HbA(1c) <53 mmol/mol [7%], OR 1.50 [95% CI 1.12, 2.00]; HbA(1c) <48 mmol/mol [6.5%], OR 1.88 [95%CI 1.49, 2.36]) and weight loss (weight loss >10%, OR 2.72 [95% CI 2.14, 3.47]; weight loss >15%, OR 3.86 [95% CI 2.69, 5.55]) and the intensive target for BP (OR 1.45 [95% CI 1.17, 1.81]). CONCLUSIONS/INTERPRETATION: Tirzepatide improves therapeutic target attainment compared with semaglutide in type 2 diabetes. Longer trials are needed to confirm benefits on long-term prognosis. DATA AVAILABILITY: Data for this post hoc analysis was accessed through the Vivli (Center for Global Clinical Research Data) platform ( https://vivli.org ) with the Vivli ID 00009964. CI - (c) 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Neves, Joao Sergio AU - Neves JS AUID- ORCID: 0000-0002-8173-8255 AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. jsneves@med.up.pt. AD - Department of Endocrinology, Diabetes and Metabolism, ULS Sao Joao, Porto, Portugal. jsneves@med.up.pt. FAU - Leite, Ana Rita AU - Leite AR AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Endocrinology, Diabetes and Metabolism, ULS Sao Joao, Porto, Portugal. FAU - Vale, Catarina AU - Vale C AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Internal Medicine, ULS Sao Joao, Porto, Portugal. FAU - Marques, Pedro AU - Marques P AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Internal Medicine, ULS Sao Joao, Porto, Portugal. FAU - Vasques-Novoa, Francisco AU - Vasques-Novoa F AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Internal Medicine, ULS Sao Joao, Porto, Portugal. FAU - Leite-Moreira, Adelino AU - Leite-Moreira A AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Department of Cardiothoracic Surgery, ULS Sao Joao, Porto, Portugal. FAU - Ferreira, Joao Pedro AU - Ferreira JP AD - RISE-Health, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal. AD - Universite de Lorraine, Inserm, Centre d'Investigations Cliniques - Plurithematique 14-33, Nancy, France. AD - Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial DEP - 20251219 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Tirzepatide/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Aged MH - Blood Glucose/metabolism/drug effects MH - Adult MH - Gastric Inhibitory Polypeptide MH - Blood Pressure/drug effects MH - Treatment Outcome OTO - NOTNLM OT - GLP-1/GIP agonist OT - Glucagon-like peptide-1 therapies OT - Post hoc analysis OT - Semaglutide OT - Therapeutic goals OT - Tirzepatide OT - Type 2 diabetes COIS- Acknowledgements: This publication is based on research using data from data contributors Eli Lilly that have been made available through Vivli. Vivli has not contributed to or approved, and Vivli and Eli Lilly are not in any way responsible for, the contents of this publication. An abstract reporting part of the results presented here was submitted to the Endocrine Society's annual meeting ENDO 2025 (12 July 2025 to 15 July 2025, San Francisco, CA, USA). Data availability: Data for this post hoc analysis was accessed through the Vivli (Center for Global Clinical Research Data) platform ( https://vivli.org ) with the Vivli ID 00009964. Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Authors' relationships and activities: JSN reports having received consulting and speaker fees from AstraZeneca, BIAL, Boehringer Ingelheim, Eli Lilly and Novo Nordisk and speaker fees from Merck. ARL reports having received consulting fees from BIAL. PM received salary support from an educational grant by Janssen. FVN has received consultancy fees and/or research support from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Novartis and Ultragenyx. ALM has received research support from Boehringer Ingelheim, AstraZeneca, Novartis. JPF has received research support from Boehringer Ingelheim, AstraZeneca, Novartis, Bial, Salamandra and Bayer. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: JSN, ARL and JPF conceived and designed the study. JSN and ARL performed the data analysis. CV, PM, FVN, ALM and JPF provided methodological and statistical guidance. All authors contributed to the interpretation of the data. JSN and ARL drafted the first version of the manuscript. All authors critically revised the manuscript for important intellectual content and approved the final version to be submitted. JSN and ARL are the guarantors of this work and, as such, had full access to all the data in the analysis and take responsibility for the integrity of the data and the accuracy of the data analysis. EDAT- 2025/12/20 00:41 MHDA- 2026/03/22 07:35 CRDT- 2025/12/19 23:31 PHST- 2025/05/17 00:00 [received] PHST- 2025/10/21 00:00 [accepted] PHST- 2026/03/22 07:35 [medline] PHST- 2025/12/20 00:41 [pubmed] PHST- 2025/12/19 23:31 [entrez] AID - 10.1007/s00125-025-06637-7 [pii] AID - 10.1007/s00125-025-06637-7 [doi] PST - ppublish SO - Diabetologia. 2026 May;69(5):1216-1225. doi: 10.1007/s00125-025-06637-7. Epub 2025 Dec 19. PMID- 41419187 OWN - NLM STAT- MEDLINE DCOM- 20260416 LR - 20260730 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 32 IP - 4 DP - 2026 Apr TI - Semaglutide Beyond Diabetes and Obesity: Systematic Review and Meta-Analysis of Multisystem Therapeutic Benefits. PG - 623-635 LID - S1530-891X(25)01331-X [pii] LID - 10.1016/j.eprac.2025.11.018 [doi] AB - OBJECTIVES: To evaluate semaglutide's multisystem therapeutic benefits across 12 health domains. Primary outcomes were major adverse cardiovascular events, resolution of metabolic dysfunction-associated steatohepatitis, and composite renal endpoints. METHODS: PubMed, Embase, and Cochrane Central were searched through June 30, 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Eligible studies included randomized controlled trials in adults (>/=18 years) with >/=24-week follow-up comparing semaglutide (>/=0.5 mg weekly subcutaneous or >/=7 mg daily oral) versus placebo or active comparators. Two reviewers independently extracted data and assessed bias (RoB 2) and certainty (GRADE). RESULTS: Thirty-five trials (n = 36 847; mean age 54.2 years; body mass index: 34.8 kg/m(2)) were included. Semaglutide reduced glycated hemoglobin (-1.52%, 95% confidence interval [CI]: -1.60 to -1.44) and weight (-12.4 kg, 95% CI: -13.0 to -11.8). Non-glycemic benefits included major adverse cardiovascular events reduction (16%, risk ratio [RR]: 0.84, 95% CI: 0.77-0.92), metabolic dysfunction-associated steatohepatitis resolution (62.9%, RR: 1.84, 95% CI: 1.49-2.27), renal protection (HR: 0.76, 95% CI: 0.68-0.85), improved vascular function (+87 m walking distance), favorable body composition (87:13 fat-to-lean ratio), and better quality of life (+3.8 SF-36 points). No increase was observed in psychiatric or cancer risk. CONCLUSIONS: Semaglutide confers robust, consistent multisystem benefits-including cardiovascular, hepatic, and renal protection-supporting its role as a transformative, disease-modifying therapy for metabolic disease beyond diabetes and obesity management. These findings support using semaglutide as a comprehensive, disease-modifying therapy for complex metabolic disorders, guiding clinicians to integrate it into patient-centered care for multisystem benefits beyond glycemic and obesity control. CI - Copyright (c) 2025 AACE. Published by Elsevier Inc. All rights reserved. FAU - Eisa, Naseem AU - Eisa N AD - Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, Community Health Partners, Fresno, California. Electronic address: NEisa@communitymedical.org. FAU - Barood, Omar AU - Barood O AD - Damascus University, Faculty of Medicine, Damascus, Syria. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251217 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Cardiovascular Diseases/prevention & control MH - Randomized Controlled Trials as Topic MH - Glycated Hemoglobin OTO - NOTNLM OT - GLP-1 receptor agonist OT - MASH OT - Semaglutide OT - cardiometabolic disease OT - obesity OT - type 2 diabetes COIS- Disclosure The authors declare no conflicts of interest related to this work. Neither author has received consulting fees, honoraria, stock ownership, or any other financial relationship with pharmaceutical companies or entities related to semaglutide or GLP-1 receptor agonists. EDAT- 2025/12/20 00:41 MHDA- 2026/04/19 17:41 CRDT- 2025/12/19 19:41 PHST- 2025/10/08 00:00 [received] PHST- 2025/11/05 00:00 [revised] PHST- 2025/11/21 00:00 [accepted] PHST- 2026/04/19 17:41 [medline] PHST- 2025/12/20 00:41 [pubmed] PHST- 2025/12/19 19:41 [entrez] AID - S1530-891X(25)01331-X [pii] AID - 10.1016/j.eprac.2025.11.018 [doi] PST - ppublish SO - Endocr Pract. 2026 Apr;32(4):623-635. doi: 10.1016/j.eprac.2025.11.018. Epub 2025 Dec 17. PMID- 41410846 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20261010 IS - 1534-6242 (Electronic) IS - 1523-3804 (Linking) VI - 28 IP - 1 DP - 2025 Dec 18 TI - Semaglutide and Tirzepatide for the Treatment of Obesity and Weight-Related Comorbidities: A Narrative Review. PG - 2 LID - 10.1007/s11883-025-01369-w [doi] AB - PURPOSE OF REVIEW: This review provides practitioners with an up-to-date overview of the efficacy and safety data of the currently approved weekly Nutrient-Stimulated Hormone (NuSH) therapies, semaglutide and tirzepatide, in managing obesity and weight-related comorbidities. RECENT FINDINGS: In people with overweight/obesity without diabetes, semaglutide achieved 10.8-14.8% and tirzepatide 17.4-20.8% greater weight loss than placebo. These agents' pleotropic effects have translated into clinicals trials showing improvement in cardiovascular outcomes, improved quality of life and/or heart failure events in heart failure with preserved ejection fraction, resolution of steatohepatitis and improvement in liver fibrosis, prevention and treatment of type 2 diabetes, and improvement in renal function in chronic kidney disease. Semaglutide has additionally been shown to improve osteoarthritis symptoms and tirzepatide reduces obstructive sleep apnea severity. FAU - Saeed, Zeb Ijaz AU - Saeed ZI AUID- ORCID: 0000-0002-8195-5890 AD - Center for Weight Management and Wellness, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, USA. zisaeed@bwh.harvard.edu. AD - Harvard Medical School, Boston, MA, USA. zisaeed@bwh.harvard.edu. AD - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, BL 347E, Boston, MA, 02115, USA. zisaeed@bwh.harvard.edu. FAU - Apovian, Caroline M AU - Apovian CM AUID- ORCID: 0000-0002-8029-1922 AD - Center for Weight Management and Wellness, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. AD - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Avenue, BL 347E, Boston, MA, 02115, USA. LA - eng PT - Journal Article PT - Review DEP - 20251218 PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - Semaglutide MH - Tirzepatide/therapeutic use MH - *Obesity/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Weight Loss/drug effects MH - Comorbidity MH - Diabetes Mellitus, Type 2/drug therapy MH - *Anti-Obesity Agents/therapeutic use OTO - NOTNLM OT - Cardiometabolic outcomes OT - Nutrient-Stimulated hormone (NuSH) therapies OT - Safety and efficacy OT - Semaglutide OT - Tirzepatide OT - Weight-Related comorbidities COIS- Declarations. Competing interests: Dr. Saeed's receives research funding from Amylyx pharmaceutics and is a consultant for Alosa health. In the previous 36 months, Dr. Apovian has participated on advisory boards for AbbVie Inc., Altimmune, Inc., Arrowhead Pharmaceuticals, Inc., BioAge, Biolinq Incorporated, Caribou Biosciences, Inc., CinFina Pharma, Inc., Covidien LP, Cowen and Company, LLC, Currax Pharmaceuticals, LLC, EPG Communication Holdings Ltd., Form Health, Inc., Fractyl Health, Inc., Keros Therapeutics, Inc., Lilly USA, LLC, L-Nutra, Inc., Mediflix Inc., NeuroBo Pharmaceuticals, Inc., Neurocrine Biosciences, Inc., NodThera Limited, Novo Nordisk, Nutrisystem, OptumRx, Inc., Pain Script Corporation, Palatin Technologies, Inc., Pursuit By You, Redesign Health Inc., ReShape Lifesciences Inc., Riverview School, Roman Health Ventures Inc., Scholar Rock, Inc., Terns, Inc., Verily Life Sciences LLC, Veru Inc., Vida Health, Inc., Wave Life Sciences, WondrHealth, Xeno Biosciences and Zyversa Therapeutics, Inc. Dr. Apovian has also received research funding from PCORI and GI Dynamics, Inc. All these conflicts are outside this paper.Dr. Saeed's receives research funding from Amylyx pharmaceutics and is a consultant for Alosa health. In the previous 36 months, Dr. Apovian has participated on advisory boards for AbbVie Inc., Altimmune, Inc., Arrowhead Pharmaceuticals, Inc., BioAge, Biolinq Incorporated, Caribou Biosciences, Inc., CinFina Pharma, Inc., Covidien LP, Cowen and Company, LLC, Currax Pharmaceuticals, LLC, EPG Communication Holdings Ltd., Form Health, Inc., Fractyl Health, Inc., Keros Therapeutics, Inc., Lilly USA, LLC, L-Nutra, Inc., Mediflix Inc., NeuroBo Pharmaceuticals, Inc., Neurocrine Biosciences, Inc., NodThera Limited, Novo Nordisk, Nutrisystem, OptumRx, Inc., Pain Script Corporation, Palatin Technologies, Inc., Pursuit By You, Redesign Health Inc., ReShape Lifesciences Inc., Riverview School, Roman Health Ventures Inc., Scholar Rock, Inc., Terns, Inc., Verily Life Sciences LLC, Veru Inc., Vida Health, Inc., Wave Life Sciences, WondrHealth, Xeno Biosciences and Zyversa Therapeutics, Inc. Dr. Apovian has also received research funding from PCORI and GI Dynamics, Inc. All these conflicts are outside this paper. Human and Animal Rights and Informed Consent: No animal or human subjects by the authors were used in this study. EDAT- 2025/12/18 13:06 MHDA- 2026/06/27 06:45 CRDT- 2025/12/18 11:18 PHST- 2025/08/15 00:00 [received] PHST- 2025/11/15 00:00 [accepted] PHST- 2026/06/27 06:45 [medline] PHST- 2025/12/18 13:06 [pubmed] PHST- 2025/12/18 11:18 [entrez] AID - 10.1007/s11883-025-01369-w [pii] AID - 10.1007/s11883-025-01369-w [doi] PST - epublish SO - Curr Atheroscler Rep. 2025 Dec 18;28(1):2. doi: 10.1007/s11883-025-01369-w. PMID- 41388533 OWN - NLM STAT- MEDLINE DCOM- 20251213 LR - 20260127 IS - 1336-0329 (Electronic) IS - 1210-0668 (Linking) VI - 59 IP - 1 DP - 2025 Jan 1 TI - Mirtazapine for gastrointestinal side effects of glucagon-like peptide-1 receptor agonist therapy in older adults. PG - 260-264 LID - 10.2478/enr-2025-0030 [doi] AB - Objective. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) play a role in management of type 2 diabetes (T2D) and obesity by promoting glycemic control and weight reduction. Beyond these benefits, GLP-1 RAs have demonstrated positive effects on cardiovascular, renal, and neurological health, with emerging evidence supporting their therapeutic potential in conditions such as chronic kidney disease, asthma, obstructive sleep apnea, Parkinson's disease, and Alzheimer's disease. However, their widespread clinical use is often hindered by gastrointestinal side effects including nausea, anorexia, vomiting, and diarrhea that limit adherence and dose titration. Effective management of these adverse effects is essential to optimize treatment outcomes and maintain long-term therapy. Case report. A 72-year-old woman with a history of cognitive impairment, T2D, atrial fibrillation, obesity, and mood disorders presented with persistent gastrointestinal symptoms while receiving semaglutide. Dose escalation was restricted due to severe nausea, vomiting, and diarrhea, which markedly affected her quality of life. To manage these symptoms, mirtazapine was initiated. Following its introduction, the patient reported significant improvement in gastrointestinal tolerance enabling continued semaglutide therapy and successful dose advancement. Additional benefits included enhanced mood, better sleep, and overall well-being. No adverse effects related to mirtazapine were observed throughout the treatment. Conclusion. This case suggests that mirtazapine may be beneficial in mitigating GLP-1 RA-induced gastrointestinal side effects, thereby improving adherence and therapeutic efficacy. Further research is needed to evaluate the safety, mechanism, and generalizability of this approach in broader clinical practice. CI - (c) 2025 Ali R. Khan et al., published by Slovak Academy of Sciences, Biomedical Research Center, Institute of Experimental Endocrinology. FAU - Khan, Ali R AU - Khan AR AD - 1John Sealy School of Medicine, University of Texas Medical Branch at Galveston, TX, USA. FAU - Makhoul, Gennifer Wahbah AU - Makhoul GW AD - 2Division of Geriatrics, Department of Internal Medicine, University of Texas Medical Branch at Galveston, TX, USA. FAU - Raji, Mukaila A AU - Raji MA AD - 2Division of Geriatrics, Department of Internal Medicine, University of Texas Medical Branch at Galveston, TX, USA. LA - eng PT - Case Reports PT - Journal Article DEP - 20251212 PL - Germany TA - Endocr Regul JT - Endocrine regulations JID - 9112018 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - A051Q2099Q (Mirtazapine) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Aged MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Mirtazapine/therapeutic use MH - *Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptides/adverse effects MH - *Gastrointestinal Diseases/chemically induced/drug therapy MH - Nausea/chemically induced/drug therapy MH - Vomiting/chemically induced/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonists OT - cognitive impairment OT - diabetes OT - gastrointestinal side effects OT - mirtazapine OT - older adults EDAT- 2025/12/13 06:29 MHDA- 2025/12/13 06:30 CRDT- 2025/12/13 01:13 PHST- 2025/12/13 06:30 [medline] PHST- 2025/12/13 06:29 [pubmed] PHST- 2025/12/13 01:13 [entrez] AID - enr-2025-0030 [pii] AID - 10.2478/enr-2025-0030 [doi] PST - epublish SO - Endocr Regul. 2025 Dec 12;59(1):260-264. doi: 10.2478/enr-2025-0030. Print 2025 Jan 1. PMID- 41380027 OWN - NLM STAT- MEDLINE DCOM- 20260120 LR - 20260625 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 49 IP - 2 DP - 2026 Feb 1 TI - Impact of Oral Semaglutide on Kidney Outcomes in People With Type 2 Diabetes: Results From the SOUL Randomized Trial. PG - 257-265 LID - 10.2337/dc25-1080 [doi] AB - OBJECTIVE: To examine the effects of oral semaglutide on kidney outcomes in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: SOUL (NCT03914326), a double-blind randomized controlled trial, compared oral semaglutide with placebo in people with T2D, ASCVD, and/or CKD, showing a 14% reduction in risk of major adverse cardiovascular (CV) events. Prespecified kidney outcomes included a five-point composite (>/=50% decrease in estimated glomerular filtration rate [eGFR], persistent eGFR <15 mL/min/1.73 m2, initiation of chronic kidney replacement therapy, or death from kidney or CV causes); a four-point composite (excluding CV death); and eGFR decline. Prespecified subgroups were also assessed, including those with eGFR <60 mL/min/1.73 m2 at baseline. RESULTS: Among 9,650 participants, mean eGFR was 73.8 mL/min/1.73 m2, and follow-up was 47.5 months. The five-point outcome occurred in 403 (8.4%) and 435 (9.0%) participants taking oral semaglutide versus placebo, respectively (hazard ratio [HR] 0.91; 95% CI 0.80, 1.05; P = 0.19). The four-point outcome occurred in 112 (2.3%) and 129 (2.7%) participants, respectively (HR 0.86; 95% CI 0.66, 1.10; P = 0.22). Mean annual eGFR decline was less with oral semaglutide than placebo (-1.67 vs. -2.06 mL/min/1.73 m2; estimated treatment difference 0.40 [95% CI 0.27, 0.53; P < 0.0001). These effects were similar across most subgroups, including those with eGFR <60 mL/min/1.73 m2. Serious adverse events occurred at similar rates in both groups. CONCLUSIONS: In people with T2D and ASCVD and/or CKD but with overall mostly preserved eGFR, orally administered semaglutide, compared with placebo, did not significantly reduce adverse kidney outcomes but did slow the decline in eGFR. CI - (c) 2025 by the American Diabetes Association. FAU - Mann, Johannes F E AU - Mann JFE AUID- ORCID: 0000-0002-3154-5332 AD - KfH Kidney Center, Munich, Germany. AD - Friedrich Alexander University, Erlangen, Germany. FAU - Marx, Nikolaus AU - Marx N AD - RWTH Aachen University, University Hospital Aachen, Aachen, Germany. FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Sciences, University College London, London, U.K. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle, WA. FAU - Inzucchi, Silvio E AU - Inzucchi SE AD - Section of Endocrinology, Yale University School of Medicine, New Haven, CT. FAU - McGuire, Darren K AU - McGuire DK AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX. AD - Parkland Health and Hospital System, Dallas, TX. FAU - Mulvagh, Sharon L AU - Mulvagh SL AD - Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. FAU - Pop-Busui, Rodica AU - Pop-Busui R AD - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health and Science University, Portland, OR. FAU - Poulter, Neil R AU - Poulter NR AD - Imperial Clinical Trials Unit, Imperial College London, London, U.K. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jeppesen, Ole Kleist AU - Jeppesen OK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AD - Department of Diabetology, Endocrinology and Nephrology, University Hospital Tubingen, Tubingen, Germany. AD - German Center for Diabetes Research and Institute for Diabetes Research and Metabolic Diseases, Helmholtz Munich, Germany. FAU - Amod, Aslam AU - Amod A AD - Life Chatsmed Garden Hospital and University of KwaZulu-Natal, Durban, South Africa. FAU - Mankovsky, Boris AU - Mankovsky B AD - Institute of Gerontology, Kyiv, Ukraine. FAU - Desouza, Cyrus AU - Desouza C AD - Division of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE. FAU - Gorgojo-Martinez, Juan J AU - Gorgojo-Martinez JJ AD - Department of Endocrinology and Nutrition, Hospital Universitario Fundacion Alcorcon, Madrid, Spain. FAU - Arechavaleta, Rosario AU - Arechavaleta R AD - Department of Endocrinology, Universidad Autonoma de Guadalajara, Jalisco, Mexico. FAU - Tu, Shih-Te AU - Tu ST AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill, NC. CN - SOUL Study Group* LA - eng SI - ClinicalTrials.gov/NCT03914326 GR - n/a/Novo Nordisk/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Female MH - Middle Aged MH - Glomerular Filtration Rate/drug effects MH - Double-Blind Method MH - Aged MH - *Renal Insufficiency, Chronic/drug therapy MH - Administration, Oral MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Kidney/drug effects PMC - PMC12824789 COIS- Duality of Interest. J.F.E.M. reports grants from Novo Nordisk, the European Union, and McMaster University Hamilton, Canada; consulting fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; honoraria from Novo Nordisk, AstraZeneca, Bayer, and Novartis; participation on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi, and Boehringer Ingelheim; authorship for UpToDate; and a leadership role in the Kidney Disease: Improving Global Outcomes (KDIGO) group. N.M. is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TRR 219; Project-ID 322900939 [M03, M05]) and has given lectures for Bayer, Boehringer Ingelheim, Sanofi Aventis, MSD, Bristol-Myers Squibb, AstraZeneca, Eli Lilly, and Novo Nordisk; received unrestricted research grants from Boehringer Ingelheim; served as an advisor for Bayer, Boehringer Ingelheim, Sanofi Aventis, MSD, Bristol-Myers Squibb, AstraZeneca, and Novo Nordisk; and served in trial leadership for Boehringer Ingelheim and Novo Nordisk. N.M. declines all personal compensation from pharma or device companies. J.E.D. reports grants or contracts in 2022-2025 from Alzheimer's Research UK and in 2019-2022 from the British Heart Foundation and consulting fees/honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer. S.S.E. declares consulting fees from Novo Nordisk for steering committee participation and from Boehringer Ingelheim for consulting for veterinary CHF; support for attending or travel from meetings and/or travel from Novo Nordisk; and participation on advisory boards for Novo Nordisk, AstraZeneca, Daiichi Sankyo, Vertex, Roche, GlaxoSmithKline, Eli Lilly, Novartis, Bristol-Myers Squibb, and Sanofi. S.E.I. has served as a consultant or on advisory boards for Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, and Bayer; given lectures sponsored by AstraZeneca and Boehringer Ingelheim/Lilly; received royalties from McGraw-Hill and Wolters Kluwer Health; and received support for attending meetings and/or travel from Novo Nordisk, AstraZeneca, Boehringer Ingelheim/Lilly, and Bayer. D.K.M. has received consulting fees from Novo Nordisk, AstraZeneca, Pfizer, Altimmune, Ventyx Pharmaceuticals, Bayer, Lexicon, Applied Therapeutics, Intercept Pharmaceuticals, Esperion, Lilly USA, Boehringer Ingelheim, New Amsterdam, CSL Behring, Amgen, Neurotronics, Metsera, Kailera, and Alveus Pharma. S.L.M. has served as a consultant or on advisory boards for Novo Nordisk and Merck. R.P.-B. has received research grant support to her institutions from the National Institute of Diabetes and Digestive and Kidney Diseases, Breakthrough T1D (formerly JDRF), Bayer, Lexicon Pharmaceuticals, and Novo Nordisk; consulting fees from Averitas Pharma, Biogen, Lexicon Pharmaceuticals, Nevro Inc., Novo Nordisk, and Roche Diagnostic; support for attending meetings and/or travel from Roche; participation on an advisory board for Biogen/Reata; and membership on the board of directors of the American Diabetes Association. N.R.P. has received financial support from several pharmaceutical companies that manufacture blood pressure-lowering, lipid-lowering, and glucose-lowering agents for consultancy fees, research projects and staff, and for arranging and speaking at educational meetings, including Servier, Pfizer, AstraZeneca, Amgen, Sanofi, and Novo Nordisk; he holds no stocks and shares in any such companies. M.D.M.E., N.B., T.I., and O.K.J. are employees and shareholders of Novo Nordisk. G.K.H. has received funding from the Klinkerpadfonds, paid out to his former academic institution (Amsterdam UMC, the Netherlands) and is an employee and shareholder of Novo Nordisk. A.L.B. is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; GRK2816; BI1292/12-1; 10-1; 9-1) and the German Federal Ministry for Education and Research (01GI0925) via the German Center for Diabetes Research (DZD e.V.); has given lectures for Novo Nordisk and Daiichi Sankyo; has received unrestricted research grants from Boehringer Ingelheim and AstraZeneca; has served as an advisor for Bayer and Novo Nordisk; and has served in trial leadership for Boehringer Ingelheim, Novo Nordisk, and Eli Lilly. A.L.B. declines all personal compensation from pharma or device companies. A.A. reports contract research fees, advisory board fees, and lecture fees from Novo Nordisk, and advisory board fees and lecture fees from Aspen Pharma (SA) and Lilly (SA). B.M. has served on advisory boards and received speaking fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, Sanofi, Servier, and Worwag Pharma. C.D. reports Novo Nordisk research grants (payments to institution) and has personally received consulting fees from Eli Lilly and consulting fees and support for attending meetings and/or travel from Novo Nordisk. J.J.G.-M. has the following financial relationships: advisor on scientific boards for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, and Novo Nordisk; lectures for Amarin, AstraZeneca, Boehringer Ingelheim, Menarini, and Novo Nordisk; and research activities for AstraZeneca, Mundipharma, and Novo Nordisk. R.A. has given lectures for Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, and Sanofi; received advisory board fees from Novo Nordisk and Eli Lilly; and received honoraria for clinical trials from Novo Nordisk and Eli Lilly. S.-T.T. has given lectures for Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, and Sanofi; received advisory board fees from Novo Nordisk and Eli Lilly; and received honoraria for clinical trials from Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. J.B.B. reports research support from Corcept, Dexcom, and Novo Nordisk; consulting fees from Altimmune, Antag, Amgen, ApStem, Aqua Medical, AstraZeneca, Boehringer Ingelheim, CeQur, Corcept Therapeutics, Dexcom, Eli Lilly, Embecta, GentiBio, Glyscend, Insulet, Medtronic MiniMed, Mellitus Health, Metsera, Novo Nordisk, Pendulum Therapeutics, Praetego, Stability Health, Tandem, Terns Inc., Vertex, and Zealand; and stock options from Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. No other potential conflicts of interest relevant to this article were reported. FIR - McGuire, D K IR - McGuire DK FIR - Buse, J B IR - Buse JB FIR - Mann, J F E IR - Mann JFE FIR - Marx, N IR - Marx N FIR - Deanfield, J E IR - Deanfield JE FIR - Emerson, S S IR - Emerson SS FIR - Inzucchi, S E IR - Inzucchi SE FIR - Mulvagh, S L IR - Mulvagh SL FIR - Pop-Busui, R IR - Pop-Busui R FIR - Poulter, N R IR - Poulter NR FIR - Engelmann, M D M IR - Engelmann MDM FIR - Hovingh, G K IR - Hovingh GK FIR - Schelde, P B IR - Schelde PB FIR - Birkenfeld, A L IR - Birkenfeld AL FIR - Amod, A IR - Amod A FIR - Mankovsky, B IR - Mankovsky B FIR - Desouza, C IR - Desouza C FIR - Gorgojo-Martinez, J J IR - Gorgojo-Martinez JJ FIR - Arechavaleta, R IR - Arechavaleta R FIR - Tu, S-T IR - Tu ST FIR - Francisco, J IR - Francisco J FIR - Sanchez Garcia, R IR - Sanchez Garcia R FIR - Chow, F Chun Chung IR - Chow FCC FIR - Watada, Hirotaka IR - Watada H FIR - Yoon, Kun Ho IR - Yoon KH FIR - Singh, Pardeep Jhund IR - Singh PJ FIR - Matthew IR - Matthew FIR - Perez Manghi, F IR - Perez Manghi F FIR - Pozzi, J M IR - Pozzi JM FIR - Lorenzatti, A J IR - Lorenzatti AJ FIR - Visco, V E IR - Visco VE FIR - Piskorz, D IR - Piskorz D FIR - Nardone, L IR - Nardone L FIR - Chahin, M I IR - Chahin MI FIR - Bustamante Labarta, M IR - Bustamante Labarta M FIR - Luquez, C IR - Luquez C FIR - MacKinnon, I J IR - MacKinnon IJ FIR - Pieber, T IR - Pieber T FIR - Prager, R IR - Prager R FIR - Fliesser-Gorzer, E IR - Fliesser-Gorzer E FIR - Ebenbichler, C IR - Ebenbichler C FIR - Fasching, P IR - Fasching P FIR - Mathieu, C IR - Mathieu C FIR - De Block, C IR - De Block C FIR - Duyck, F IR - Duyck F FIR - Heyns, E IR - Heyns E FIR - Lapauw, B IR - Lapauw B FIR - Turatti, L A A IR - Turatti LAA FIR - Franco, D R IR - Franco DR FIR - Rea, R R IR - Rea RR FIR - Kurtz Lisboa, R IR - Kurtz Lisboa R FIR - Salles, J E IR - Salles JE FIR - Saraiva, J F K IR - Saraiva JFK FIR - Fonseca, A G T IR - Fonseca AGT FIR - Vidotti, M H IR - Vidotti MH FIR - Leite, S O IR - Leite SO FIR - Aggarwal, N IR - Aggarwal N FIR - Bajaj, H IR - Bajaj H FIR - Schlosser, R IR - Schlosser R FIR - Noronha, L IR - Noronha L FIR - Pedersen, S IR - Pedersen S FIR - Peterson, S IR - Peterson S FIR - Tellier, G IR - Tellier G FIR - Weisnagel, J IR - Weisnagel J FIR - Beca, S IR - Beca S FIR - Alasaad, H IR - Alasaad H FIR - Punthakee, Z IR - Punthakee Z FIR - Mancini, J G B IR - Mancini JGB FIR - Tytus, R IR - Tytus R FIR - Ransom, T P P IR - Ransom TPP FIR - Connelly, K IR - Connelly K FIR - Husain, M IR - Husain M FIR - Tsoukas, M IR - Tsoukas M FIR - Ji, L IR - Ji L FIR - Liu, J IR - Liu J FIR - Yuan, G IR - Yuan G FIR - Ye, X IR - Ye X FIR - Dong, X IR - Dong X FIR - Bian, F IR - Bian F FIR - Angelo, A A IR - Angelo AA FIR - Sanchez Garcia, R IR - Sanchez Garcia R FIR - Hernandez Erazo, I D IR - Hernandez Erazo ID FIR - Hernandez Ruiz, E A IR - Hernandez Ruiz EA FIR - Gomez Mesa, J E IR - Gomez Mesa JE FIR - Canecki-Varzic, S IR - Canecki-Varzic S FIR - Vucak Loncar, J IR - Vucak Loncar J FIR - Simegi-Djekic, V IR - Simegi-Djekic V FIR - Ticinovic Kurir, T IR - Ticinovic Kurir T FIR - Tusek, S IR - Tusek S FIR - Rahelic, D IR - Rahelic D FIR - Marusic, S IR - Marusic S FIR - Kruljac, I IR - Kruljac I FIR - Fabris Vitkovic, D IR - Fabris Vitkovic D FIR - Oznerova, M IR - Oznerova M FIR - Vrkoc, J IR - Vrkoc J FIR - Dolezalova, B IR - Dolezalova B FIR - Haluzik, M IR - Haluzik M FIR - Jankovec, Z IR - Jankovec Z FIR - Olsovsky, J IR - Olsovsky J FIR - Zemanova, J IR - Zemanova J FIR - Kyselova, P IR - Kyselova P FIR - Smahelova, A IR - Smahelova A FIR - Gregersen, S IR - Gregersen S FIR - Olsen, A-M Z IR - Olsen AZ FIR - Mikkelsen, D IR - Mikkelsen D FIR - Egstrup, K IR - Egstrup K FIR - Pedersen-Bjergaard, U IR - Pedersen-Bjergaard U FIR - Potier, L IR - Potier L FIR - Borot, S IR - Borot S FIR - Gaborit, B IR - Gaborit B FIR - Monier, A IR - Monier A FIR - Pradignac, A IR - Pradignac A FIR - Verges, B IR - Verges B FIR - Larroumet, A IR - Larroumet A FIR - Thuan, J-F IR - Thuan JF FIR - Kellerer, M IR - Kellerer M FIR - Ludemann, J IR - Ludemann J FIR - Esser, M IR - Esser M FIR - Kahrmann, G IR - Kahrmann G FIR - Kempe, H-P IR - Kempe HP FIR - Koch, T IR - Koch T FIR - Axthelm, C IR - Axthelm C FIR - Paschen, B IR - Paschen B FIR - Rose, L IR - Rose L FIR - Schaum, T IR - Schaum T FIR - Schulze, J IR - Schulze J FIR - Staudenmeyer, A IR - Staudenmeyer A FIR - Wenzl-Bauer, V IR - Wenzl-Bauer V FIR - Ma, R C W IR - Ma RCW FIR - Thomas, N IR - Thomas N FIR - Mohan, V IR - Mohan V FIR - Reddy, V S IR - Reddy VS FIR - Rao, P V IR - Rao PV FIR - Sahay, R IR - Sahay R FIR - Singh, J IR - Singh J FIR - Prakash, A IR - Prakash A FIR - Tandon, N IR - Tandon N FIR - Marwah, T IR - Marwah T FIR - Chaudhury, T IR - Chaudhury T FIR - Ghosh, S IR - Ghosh S FIR - Kanungo, A K IR - Kanungo AK FIR - Mittal, N IR - Mittal N FIR - Jacob, J J IR - Jacob JJ FIR - Chadha, M IR - Chadha M FIR - Chawla, M IR - Chawla M FIR - Bhagwat, N M IR - Bhagwat NM FIR - Jain, S M IR - Jain SM FIR - Thulaseedharan, N K IR - Thulaseedharan NK FIR - Girithara, G IR - Girithara G FIR - Desai, A IR - Desai A FIR - Sharma, S K IR - Sharma SK FIR - Murthy, S IR - Murthy S FIR - Sethi, B K IR - Sethi BK FIR - Kadam, Y IR - Kadam Y FIR - Kesavadev, J IR - Kesavadev J FIR - Daxini, B IR - Daxini B FIR - Chawla, R IR - Chawla R FIR - Gopalakrishnan, U A IR - Gopalakrishnan UA FIR - Baruah, M P IR - Baruah MP FIR - Reddy, S P IR - Reddy SP FIR - Suryanarayana, K M IR - Suryanarayana KM FIR - Singh, K P IR - Singh KP FIR - Saboo, B IR - Saboo B FIR - Aharon-Hananel, G IR - Aharon-Hananel G FIR - Hochberg, I IR - Hochberg I FIR - Sofer, Y IR - Sofer Y FIR - Tirosh, A IR - Tirosh A FIR - Shimon, I IR - Shimon I FIR - Vishlitzky, V IR - Vishlitzky V FIR - Bashkin, A IR - Bashkin A FIR - Tsur, A IR - Tsur A FIR - Shechter, M IR - Shechter M FIR - Andreozzi, F IR - Andreozzi F FIR - Setola, E IR - Setola E FIR - Consoli, A IR - Consoli A FIR - Lupoli, R IR - Lupoli R FIR - Genovese, S IR - Genovese S FIR - Maranghi, M IR - Maranghi M FIR - Lauro, D IR - Lauro D FIR - Citarrella, R IR - Citarrella R FIR - Fadini, G P IR - Fadini GP FIR - Murdolo, G IR - Murdolo G FIR - Di Carlo, A IR - Di Carlo A FIR - Giorgino, F IR - Giorgino F FIR - Buscemi, S IR - Buscemi S FIR - Hanaoka, K IR - Hanaoka K FIR - Osonoi, T IR - Osonoi T FIR - Ohashi, H IR - Ohashi H FIR - Ezaki, H IR - Ezaki H FIR - Yuki, H IR - Yuki H FIR - Kiyosue, A IR - Kiyosue A FIR - Hata, Y IR - Hata Y FIR - Sugawara, M IR - Sugawara M FIR - Domae, H IR - Domae H FIR - Iwata, H IR - Iwata H FIR - Nishida, Y IR - Nishida Y FIR - Igarashi, M IR - Igarashi M FIR - Fujino, S IR - Fujino S FIR - Oiwa, A IR - Oiwa A FIR - Oh, F IR - Oh F FIR - Sueyoshi, A IR - Sueyoshi A FIR - Murakami, T IR - Murakami T FIR - Tanaka, M IR - Tanaka M FIR - Idogaki, A IR - Idogaki A FIR - Onaka, H IR - Onaka H FIR - Mizote, I IR - Mizote I FIR - Doi, M IR - Doi M FIR - Ebisui, O IR - Ebisui O FIR - Tanabe, M IR - Tanabe M FIR - Natsuaki, M IR - Natsuaki M FIR - Jinnouchi, H IR - Jinnouchi H FIR - Nakamura, S IR - Nakamura S FIR - Wan Mohamed, W M I IR - Wan Mohamed WMI FIR - Yahaya, N IR - Yahaya N FIR - Ratnasingam, J IR - Ratnasingam J FIR - Ong, T K IR - Ong TK FIR - Mohamad, M IR - Mohamad M FIR - Yusoff Azmi Merican, N S IR - Yusoff Azmi Merican NS FIR - Abdul Ghani, R IR - Abdul Ghani R FIR - Adam, N L IR - Adam NL FIR - Fam, T L IR - Fam TL FIR - Tan, F H S IR - Tan FHS FIR - Morales Villegas, E C IR - Morales Villegas EC FIR - Gonzalez-Galvez, G IR - Gonzalez-Galvez G FIR - Espinoza Peralta, D IR - Espinoza Peralta D FIR - Medina Pech, C E IR - Medina Pech CE FIR - Garcia Ulloa, A C IR - Garcia Ulloa AC FIR - Laviada Molina, H A IR - Laviada Molina HA FIR - Banda Elizondo, R G IR - Banda Elizondo RG FIR - Garza Ruiz, J A IR - Garza Ruiz JA FIR - Garcia Cantu, E A IR - Garcia Cantu EA FIR - van Bemmel, T IR - van Bemmel T FIR - de Valk, H W IR - de Valk HW FIR - Kooy, A IR - Kooy A FIR - Lieverse, L IR - Lieverse L FIR - Landewe-Cleuren, S A N T IR - Landewe-Cleuren SANT FIR - Hoogenberg, K IR - Hoogenberg K FIR - van Raalte, D IR - van Raalte D FIR - Jebbink, M IR - Jebbink M FIR - Oldenburg-Ligtenberg, C IR - Oldenburg-Ligtenberg C FIR - Abbink-Zandbergen, E IR - Abbink-Zandbergen E FIR - Mihai, B IR - Mihai B FIR - Crisan, C IR - Crisan C FIR - Filip, I IR - Filip I FIR - Busegeanu, M M IR - Busegeanu MM FIR - Roman, G IR - Roman G FIR - Mot, A C IR - Mot AC FIR - Nicoara, A IR - Nicoara A FIR - Anghel, V IR - Anghel V FIR - Pletea, N N IR - Pletea NN FIR - Suciu, M IR - Suciu M FIR - Strajer, D IR - Strajer D FIR - Cernea, S IR - Cernea S FIR - Zilov, A IR - Zilov A FIR - Kobalava, Z IR - Kobalava Z FIR - Ruyatkina, L A IR - Ruyatkina LA FIR - Suplotova, L A IR - Suplotova LA FIR - Sergeeva-Kondrachenko, M Y IR - Sergeeva-Kondrachenko MY FIR - Yanovskaya, M E IR - Yanovskaya ME FIR - Kargina, L IR - Kargina L FIR - Ignatyeva, A IR - Ignatyeva A FIR - Astamirova, K IR - Astamirova K FIR - Zalevskaya, A IR - Zalevskaya A FIR - Zagrebelnaya, O IR - Zagrebelnaya O FIR - Frolova, E V IR - Frolova EV FIR - Peskov, A B IR - Peskov AB FIR - Mishchenko Golinskaya, O IR - Mishchenko Golinskaya O FIR - Otroshchenko, O IR - Otroshchenko O FIR - Gaysina, L IR - Gaysina L FIR - Shabelnikova, O Y IR - Shabelnikova OY FIR - Saprina, T V IR - Saprina TV FIR - Lysenko, T A IR - Lysenko TA FIR - Kunitsyna, M IR - Kunitsyna M FIR - Zyangirova, S T IR - Zyangirova ST FIR - Lalic, N IR - Lalic N FIR - Lalic, K IR - Lalic K FIR - Beljic Zivkovic, T IR - Beljic Zivkovic T FIR - Kikovic, S IR - Kikovic S FIR - Djukic, A IR - Djukic A FIR - Pesic, M IR - Pesic M FIR - Dimic, D IR - Dimic D FIR - Stokic, E IR - Stokic E FIR - Mitrovic, M IR - Mitrovic M FIR - Polovina, S IR - Polovina S FIR - Djordjevic, M IR - Djordjevic M FIR - Sosovec, D IR - Sosovec D FIR - Pella, D IR - Pella D FIR - Donicova, V IR - Donicova V FIR - Hanackova Prasekova, S IR - Hanackova Prasekova S FIR - Koleny, D IR - Koleny D FIR - Culak, J IR - Culak J FIR - Cerna, K IR - Cerna K FIR - Hundza, V IR - Hundza V FIR - Gmitrov, J IR - Gmitrov J FIR - Lacka, J IR - Lacka J FIR - Plasil, R IR - Plasil R FIR - Bacus, H B IR - Bacus HB FIR - Bhorat, Q E IR - Bhorat QE FIR - Joshi, P IR - Joshi P FIR - Lakha, D R IR - Lakha DR FIR - Makan, V IR - Makan V FIR - Ntusi, N IR - Ntusi N FIR - Padayachee, T IR - Padayachee T FIR - Seeber, M E IR - Seeber ME FIR - Pillay, D IR - Pillay D FIR - Joshi, M IR - Joshi M FIR - Mayet, L IR - Mayet L FIR - Lee, J IR - Lee J FIR - Kim, S G IR - Kim SG FIR - Min, K W IR - Min KW FIR - Kang, E S IR - Kang ES FIR - Lee, W J IR - Lee WJ FIR - Choi, S H IR - Choi SH FIR - Lee, C B IR - Lee CB FIR - Lopez Suarez, A IR - Lopez Suarez A FIR - Garcia Ordonez, M A IR - Garcia Ordonez MA FIR - Garcia Quintana, A IR - Garcia Quintana A FIR - Mazon Ramos, P IR - Mazon Ramos P FIR - Cigarran, S IR - Cigarran S FIR - Barrios, C IR - Barrios C FIR - Soto Gonzalez, A IR - Soto Gonzalez A FIR - Jodar, E IR - Jodar E FIR - Delgado Lista, J IR - Delgado Lista J FIR - Morales Portillo, C IR - Morales Portillo C FIR - Montalban Carrasco, C IR - Montalban Carrasco C FIR - Tinahones, F IR - Tinahones F FIR - Cigarran, S IR - Cigarran S FIR - Huang, C-N IR - Huang CN FIR - Chen, S-T IR - Chen ST FIR - Buranasupkajorn, P IR - Buranasupkajorn P FIR - Sriwijitkamol, A IR - Sriwijitkamol A FIR - Buranapin, S IR - Buranapin S FIR - Suwanagool, A IR - Suwanagool A FIR - Tantiwong, P IR - Tantiwong P FIR - Boonyavarakul, A IR - Boonyavarakul A FIR - Benjachareonwong, S IR - Benjachareonwong S FIR - Leelawattana, R IR - Leelawattana R FIR - Vathesatogkit, P IR - Vathesatogkit P FIR - Deerochanawong, C IR - Deerochanawong C FIR - Sonmez, Y A IR - Sonmez YA FIR - Oguz, A IR - Oguz A FIR - Tabak, O IR - Tabak O FIR - Kocak, M IR - Kocak M FIR - Sariakcali, B IR - Sariakcali B FIR - Bayram, F IR - Bayram F FIR - Guclu, M IR - Guclu M FIR - Gurkan, E IR - Gurkan E FIR - Kebapci, N IR - Kebapci N FIR - Comlekci, A IR - Comlekci A FIR - Acibucu, F IR - Acibucu F FIR - Ahbab, S IR - Ahbab S FIR - Bilen, H IR - Bilen H FIR - Urbanovych, A IR - Urbanovych A FIR - Kuskalo, P IR - Kuskalo P FIR - Bondarets, I IR - Bondarets I FIR - Petrosyan, O IR - Petrosyan O FIR - Pashkovska, N IR - Pashkovska N FIR - Oleksyk, O IR - Oleksyk O FIR - Kaydashev, I IR - Kaydashev I FIR - Maliar, K IR - Maliar K FIR - Myshanych, G IR - Myshanych G FIR - Bain, S C IR - Bain SC FIR - Black, D IR - Black D FIR - Johnston, P IR - Johnston P FIR - Dang, C IR - Dang C FIR - Dhatariya, K IR - Dhatariya K FIR - English, P IR - English P FIR - Field, B IR - Field B FIR - Grimmer, P IR - Grimmer P FIR - Gunstone, A IR - Gunstone A FIR - Ray, S IR - Ray S FIR - Tatovic, D IR - Tatovic D FIR - Kernohan, A IR - Kernohan A FIR - Lindsay, R IR - Lindsay R FIR - Mcknight, J A IR - Mcknight JA FIR - Park, A IR - Park A FIR - Patel, D IR - Patel D FIR - Philip, S IR - Philip S FIR - Randeva, H IR - Randeva H FIR - Sathyapalan, T IR - Sathyapalan T FIR - Turner, W IR - Turner W FIR - Wyatt, N IR - Wyatt N FIR - Allison, D C IR - Allison DC FIR - Awasty, V IR - Awasty V FIR - Ayele, E IR - Ayele E FIR - Bajaj, C IR - Bajaj C FIR - Budoff, M J IR - Budoff MJ FIR - Busch, R IR - Busch R FIR - Casaubon, L IR - Casaubon L FIR - Chaidarun, S S IR - Chaidarun SS FIR - Chochinov, R H IR - Chochinov RH FIR - Chu, J W IR - Chu JW FIR - Daboul, N Y IR - Daboul NY FIR - Dang, A H IR - Dang AH FIR - Everhart, B G IR - Everhart BG FIR - Arambasick, J IR - Arambasick J FIR - Fink, R I IR - Fink RI FIR - Fitz-Patrick, D IR - Fitz-Patrick D FIR - Fogarty, C M IR - Fogarty CM FIR - Gilbert, M P IR - Gilbert MP FIR - Johnson, D M IR - Johnson DM FIR - Krishnasamy, S S IR - Krishnasamy SS FIR - Lane, W S IR - Lane WS FIR - Nakhle, S N IR - Nakhle SN FIR - Levenson, D IR - Levenson D FIR - O'Donnell, P IR - O'Donnell P FIR - Weiss, D IR - Weiss D FIR - Risser, J A IR - Risser JA FIR - Wierum, C IR - Wierum C FIR - Sivalingam, K IR - Sivalingam K FIR - Gupta, D IR - Gupta D FIR - Philis-Tsimikas, A IR - Philis-Tsimikas A FIR - Pratley, R E IR - Pratley RE FIR - Mirza, L IR - Mirza L FIR - Snyder, B IR - Snyder B FIR - Rasouli, N IR - Rasouli N FIR - Porter, J IR - Porter J FIR - Ledesma, G N IR - Ledesma GN FIR - Powell, T IR - Powell T FIR - Tandron, I J IR - Tandron IJ FIR - Lingvay, I IR - Lingvay I FIR - Reed, J C H IR - Reed JCH FIR - Patel, M B IR - Patel MB FIR - Lovre, D IR - Lovre D FIR - Chaicha-Brom, T IR - Chaicha-Brom T FIR - Jantzi, C IR - Jantzi C FIR - Brautigam, D IR - Brautigam D FIR - Bao, S IR - Bao S FIR - Mbogua, C N IR - Mbogua CN FIR - Zemel, L R IR - Zemel LR FIR - Hasan, S IR - Hasan S FIR - Rosenstock, J IR - Rosenstock J FIR - Tran, H IR - Tran H FIR - Poremba, J IR - Poremba J FIR - Baker, C IR - Baker C FIR - Prier, K IR - Prier K FIR - Chilka, S IR - Chilka S FIR - Agaiby, J M IR - Agaiby JM FIR - Condit, J IR - Condit J FIR - Eagerton, D C IR - Eagerton DC FIR - Huffman, D IR - Huffman D FIR - Cornett, G M IR - Cornett GM FIR - Traylor, H IR - Traylor H FIR - Brinson, C IR - Brinson C FIR - Bays, H E IR - Bays HE FIR - Jerkins, T IR - Jerkins T FIR - Nicol, P R IR - Nicol PR FIR - Siddiqui, I A IR - Siddiqui IA FIR - Hewitt, M IR - Hewitt M FIR - Odugbesan, A O IR - Odugbesan AO FIR - Lillestol, M J IR - Lillestol MJ FIR - Thrasher, J R IR - Thrasher JR FIR - Gandy, W H IR - Gandy WH FIR - Pant, N IR - Pant N FIR - Nagelberg, S IR - Nagelberg S FIR - Cannon, K IR - Cannon K FIR - Anderson, M W IR - Anderson MW FIR - Bhargava, A IR - Bhargava A FIR - Doshi, A IR - Doshi A FIR - Jardula, M F IR - Jardula MF FIR - Montero, M IR - Montero M FIR - Purighalla, R S IR - Purighalla RS FIR - Warren, M L IR - Warren ML FIR - Harris, K IR - Harris K FIR - Jackson, R A IR - Jackson RA FIR - Khaira, A S IR - Khaira AS FIR - Gonzalez-Orozco, B L IR - Gonzalez-Orozco BL FIR - Gagianas, P J IR - Gagianas PJ FIR - Pantalone, K IR - Pantalone K FIR - Murray, A V IR - Murray AV EDAT- 2025/12/11 19:42 MHDA- 2026/01/20 19:20 PMCR- 2025/12/04 CRDT- 2025/12/11 15:03 PHST- 2025/05/08 00:00 [received] PHST- 2025/10/22 00:00 [accepted] PHST- 2026/01/20 19:20 [medline] PHST- 2025/12/11 19:42 [pubmed] PHST- 2025/12/11 15:03 [entrez] PHST- 2025/12/04 00:00 [pmc-release] AID - 163945 [pii] AID - 251080 [pii] AID - 10.2337/dc25-1080 [doi] PST - ppublish SO - Diabetes Care. 2026 Feb 1;49(2):257-265. doi: 10.2337/dc25-1080. PMID- 41371743 OWN - NLM STAT- MEDLINE DCOM- 20251210 LR - 20260127 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 15 IP - 12 DP - 2025 Dec 10 TI - Effects of glucagon-like peptide-1 analogues on hard binary outcomes for patients at increased risk of cardiovascular events: a protocol for a systematic review with network meta-analysis and Trial Sequential Analysis. PG - e098205 LID - 10.1136/bmjopen-2024-098205 [doi] LID - e098205 AB - BACKGROUND: Cardiovascular diseases, overweight, type 2 diabetes and chronic kidney disease increase the risk of cardiovascular events.Glucagon-like peptide-1 analogues are recommended by the European Society of Cardiology and the American College of Cardiology to lower the risk of death and progression of cardiovascular disease in patients with cardiovascular disease and type 2 diabetes. Semaglutide, tirzepatide and liraglutide are approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of type 2 diabetes mellitus and overweight. CagriSema is currently not approved, but several phase III trials are ongoing.No previous systematic review has investigated the effects of semaglutide, tirzepatide, CagriSema and liraglutide, which may not be disease-specific, on hard binary outcomes for all trial populations at increased risk of cardiovascular events. METHODS AND ANALYSES: We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Latin American and Caribbean Health Sciences Literature, Science Citation Index Expanded, Conference Proceedings Citation Index-Science) and clinical trial registries from their inception and onwards to identify relevant randomised trials. We expect to perform the literature search in December 2025. Two review authors will independently extract data and assess the risk of bias. We will include randomised trials assessing the effects of semaglutide, tirzepatide, CagriSema and/or liraglutide in participants with an increased risk of cardiovascular events. The primary outcome will be all-cause mortality. Secondary outcomes will be myocardial infarction, stroke and all-cause hospitalisation. Data will be synthesised by aggregate data meta-analyses, Trial Sequential Analyses and network meta-analysis, risk of bias will be assessed with Cochrane Risk of Bias tool V. 2, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations and the Confidence in Network Meta-Analysis approach. ETHICS AND DISSEMINATION: This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals. PROSPERO REGISTRATION NUMBER: CRD42024623312. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Sillassen, Christina Dam Bjerregaard AU - Sillassen CDB AUID- ORCID: 0009-0004-9247-5245 AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark christina.sillassen@ctu.dk. AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Faltermeier, Pascal AU - Faltermeier P AUID- ORCID: 0000-0002-6684-2070 AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Petersen, Johanne Juul AU - Petersen JJ AUID- ORCID: 0000-0001-9837-1958 AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. FAU - Kamp, Caroline Barkholt AU - Kamp CB AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. FAU - Grand, Johannes AU - Grand J AUID- ORCID: 0000-0002-5511-4668 AD - Department of Cardiology, Copenhagen University Hospital - Amager-Hvidovre Hospital, Hvidovre, Denmark. FAU - Dominguez, Helena AU - Dominguez H AD - Department of Cardiology, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark. AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Frolich, Anne AU - Frolich A AD - Innovation and Research Centre for Multimorbidity, Slagelse Hospital, Slagelse, Denmark. AD - Section of General Practice, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Gaede, Peter Haulund AU - Gaede PH AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Gluud, Christian AU - Gluud C AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Mathiesen, Ole AU - Mathiesen O AD - Centre for Anaesthesiological Research, Department of Anaesthesiology, Zealand University Hospital, Koge, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Jakobsen, Janus C AU - Jakobsen JC AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article DEP - 20251210 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Systematic Reviews as Topic MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Network Meta-Analysis as Topic MH - *Glucagon-Like Peptide 1/analogs & derivatives/therapeutic use MH - Research Design MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Liraglutide/therapeutic use MH - Meta-Analysis as Topic MH - Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC12699605 OTO - NOTNLM OT - Meta-Analysis OT - Network Meta-Analysis OT - PUBLIC HEALTH OT - Safety OT - Systematic Review COIS- Competing interests: CDBS's husband was employed at Novo Nordisk, Kalundborg, Denmark, as a 'facility manager' and 'sprinkler technician' from 1 September 2024 to 31 August 2025. PHG has received lecture fees for Novo Nordisk, AstraZeneca, Eli Lilly, Bayer and MSD, and has served in Advisory Boards for Novo Nordisk, AstraZeneca and Bayer. All other authors have no known competing interests. EDAT- 2025/12/11 01:22 MHDA- 2025/12/11 01:23 PMCR- 2025/12/10 CRDT- 2025/12/10 20:43 PHST- 2025/12/11 01:23 [medline] PHST- 2025/12/11 01:22 [pubmed] PHST- 2025/12/10 20:43 [entrez] PHST- 2025/12/10 00:00 [pmc-release] AID - bmjopen-2024-098205 [pii] AID - 10.1136/bmjopen-2024-098205 [doi] PST - epublish SO - BMJ Open. 2025 Dec 10;15(12):e098205. doi: 10.1136/bmjopen-2024-098205. PMID- 41370744 OWN - NLM STAT- MEDLINE DCOM- 20251210 LR - 20251210 IS - 1526-632X (Electronic) IS - 0028-3878 (Linking) VI - 106 IP - 1 DP - 2026 Jan 13 TI - Association Between GLP-1 Receptor Agonist Use and Epilepsy Risk in Type 2 Diabetes. PG - e214509 LID - 10.1212/WNL.0000000000214509 [doi] AB - BACKGROUND AND OBJECTIVES: Individuals with type 2 diabetes mellitus (T2DM) are at an increased risk of developing epilepsy, particularly in later life. While preclinical studies suggest neuroprotective properties of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), real-world comparative effectiveness data remain limited. We aimed to evaluate whether GLP-1 RA use is associated with a lower risk of incident epilepsy compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) use in adults with T2DM. METHODS: We conducted a retrospective cohort study using the TriNetX network from 2015 to 2023, including adults aged 18 years or older with T2DM who were new users of either GLP-1 RAs or DPP-4is. Patients with a previous diagnosis of epilepsy or seizure, or those using antiepileptic drugs, were excluded. The primary outcome was incident epilepsy, identified using ICD-10-CM codes. Propensity score matching (1:1) was performed based on demographics, socioeconomic status, body mass index, comorbidities, and baseline medications. Cox proportional hazard models estimated hazard ratios (HRs) with 95% CIs. We also conducted prespecified subgroup and sensitivity analyses to assess the robustness of the findings. RESULTS: After matching, 452,766 patients were included (226,383 in each group; mean age 60.5 years; 47.1% female). During follow-up, 1,670 individuals in the GLP-1 RA group and 1,886 in the DPP-4i group developed epilepsy, corresponding to cumulative incidences of 2.35% vs 2.41%. GLP-1 RA use was associated with a significantly lower risk of epilepsy (HR 0.84, 95% CI 0.78-0.90), with protective associations evident at 1 year (HR 0.71, 95% CI 0.62-0.80), 3 years (HR 0.81, 95% CI 0.74-0.88), and 5 years (HR 0.82, 95% CI 0.76-0.88). Among individual agents, semaglutide showed the strongest association (HR 0.68, 95% CI 0.60-0.77). The results were consistent across major subgroups, including both age and sex. Sensitivity analyses excluding patients with overlapping or switching exposure yielded similar findings (HR 0.71, 95% CI 0.64-0.78). DISCUSSION: GLP-1 RA therapy was associated with a significantly lower epilepsy risk compared with DPP-4i use in adults with T2DM. These results support the hypothesis that GLP-1 RAs may exert neurologic benefits beyond glycemic control. Limitations include the observational design and potential residual confounding. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the use of GLP-1 RAs in people with T2DM results in a lower risk of developing epilepsy compared with those treated with DPP-4i. FAU - Cheng, Ching-Yang AU - Cheng CY AD - Chung Shan Medical University, School of Medicine, Taichung, Taiwan. FAU - Lo, Shih-Chang AU - Lo SC AD - Chung Shan Medical University Hospital, Department of Internal Medicine, Division of Endocrinology and Metabolism, Taichung, Taiwan. FAU - Huang, Chien-Ning AU - Huang CN AD - Chung Shan Medical University, School of Medicine, Taichung, Taiwan. AD - Chung Shan Medical University Hospital, Department of Internal Medicine, Division of Endocrinology and Metabolism, Taichung, Taiwan. AD - Chung Shan Medical University, Institute of Medicine, Taichung, Taiwan; and. FAU - Yang, Yi-Sun AU - Yang YS AD - Chung Shan Medical University, School of Medicine, Taichung, Taiwan. AD - Chung Shan Medical University Hospital, Department of Internal Medicine, Division of Endocrinology and Metabolism, Taichung, Taiwan. FAU - Wang, Yu-Hsun AU - Wang YH AD - Chung Shan Medical University Hospital, Department of Medical Research, Taichung, Taiwan. FAU - Kornelius, Edy AU - Kornelius E AUID- ORCID: 0000-0002-9342-5467 AD - Chung Shan Medical University, School of Medicine, Taichung, Taiwan. AD - Chung Shan Medical University Hospital, Department of Internal Medicine, Division of Endocrinology and Metabolism, Taichung, Taiwan. LA - eng PT - Journal Article DEP - 20251210 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Retrospective Studies MH - *Epilepsy/epidemiology MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Cohort Studies MH - Risk Factors EDAT- 2025/12/10 19:22 MHDA- 2025/12/10 19:23 CRDT- 2025/12/10 16:03 PHST- 2025/12/10 19:23 [medline] PHST- 2025/12/10 19:22 [pubmed] PHST- 2025/12/10 16:03 [entrez] AID - 10.1212/WNL.0000000000214509 [doi] PST - ppublish SO - Neurology. 2026 Jan 13;106(1):e214509. doi: 10.1212/WNL.0000000000214509. Epub 2025 Dec 10. PMID- 41370018 OWN - NLM STAT- MEDLINE DCOM- 20251210 LR - 20261010 IS - 1573-7322 (Electronic) IS - 1382-4147 (Linking) VI - 31 IP - 1 DP - 2025 Dec 10 TI - The impact of oral semaglutide on cardiovascular events in patients with type 2 diabetes: review of results from the SOUL trial. PG - 11 LID - 10.1007/s10741-025-10579-y [doi] AB - Subcutaneous glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to reduce risk of major adverse cardiac events (MACE) for patients with type 2 diabetes (T2DM) who have or are at high risk of cardiovascular disease, but the evaluation of cardiovascular efficacy of oral GLP-1 RAs has yet to be performed. This article reviews results from the SOUL (Semaglutide Cardiovascular Outcomes) trial, whose aim was to assess the cardiovascular benefit in oral semaglutide in high-risk individuals. SOUL was a randomized, double blind, parallel-group, placebo-controlled superiority trial that enrolled 9,650 adults with T2DM who had established atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or both, to receive a maximum daily dose of 14 mg oral semaglutide or placebo. The primary outcome in this study was a composite of time to first CV death, non-fatal MI, or non-fatal stroke. In prespecified secondary analyses, treatment groups were analyzed for an expanded list of CV, CKD, PAD, and HF outcomes. Over a median follow-up of 49.5 months, the risk for MACE was significantly lower in the oral semaglutide compared with the placebo group (HR 0.86; 95% CI, 0.77; 0.96; p = 0.006), and these results were consistent across subgroup analysis, including by sodium glucose co-transporter 2 inhibitor (SGLT2i) drug use. Oral semaglutide reduces the risk of MACE in high-risk patients with T2DM. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Lehenbauer, Katy S AU - Lehenbauer KS AD - University of Colorado, Aurora, CO, USA. FAU - Nelson, Adam J AU - Nelson AJ AD - University of Adelaide, Adelaide, South Australia. FAU - Nodari, Savina AU - Nodari S AD - University and ASST Spedali Civili of Brescia, Brescia, Italy. FAU - Sverdlov, Aaron L AU - Sverdlov AL AD - University of Newcastle, Callaghan, Australia. FAU - Harrington, Josephine AU - Harrington J AD - University of Colorado, Aurora, CO, USA. Josephine.harrington@cuanschutz.edu. LA - eng PT - Journal Article PT - Review DEP - 20251210 PL - United States TA - Heart Fail Rev JT - Heart failure reviews JID - 9612481 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage MH - *Cardiovascular Diseases/prevention & control/etiology/epidemiology MH - Administration, Oral MH - Hypoglycemic Agents/administration & dosage MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - Semaglutide OT - Type 2 diabetes COIS- Declarations. Disclosures: AN has served as a consultant or as a speaker for Amgen, Boehringer Ingelheim, Eli Lilly, GSK, Novartis, Novo Nordisk, Pfizer and VAXXINITY. SN has received grants and/or speakers' fees from Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, AMGEN, Menarini. AS has received grants and/or speakers' fees and/or advisory board fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Galaxo Smith Kline, Janssen, Novartis, Novo Nordisk and RACE Oncology. He is supported by the National Heart Foundation of Australia Future Leader Fellowship (Award ID: 106025). JH has served as a consultant for Novo Nordisk. Competing interests: The authors declare no competing interests. EDAT- 2025/12/10 13:52 MHDA- 2025/12/10 19:21 CRDT- 2025/12/10 11:53 PHST- 2025/06/10 00:00 [received] PHST- 2025/10/14 00:00 [accepted] PHST- 2025/10/13 00:00 [revised] PHST- 2025/12/10 19:21 [medline] PHST- 2025/12/10 13:52 [pubmed] PHST- 2025/12/10 11:53 [entrez] AID - 10.1007/s10741-025-10579-y [pii] AID - 10.1007/s10741-025-10579-y [doi] PST - epublish SO - Heart Fail Rev. 2025 Dec 10;31(1):11. doi: 10.1007/s10741-025-10579-y. PMID- 41366934 OWN - NLM STAT- MEDLINE DCOM- 20251210 LR - 20260513 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 104 IP - 49 DP - 2025 Dec 5 TI - Assessing the shadows: A meta-analysis of GLP-1 agonists and suicidal ideation. PG - e46173 LID - 10.1097/MD.0000000000046173 [doi] LID - e46173 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 agonist) have revolutionized the treatment of obesity. However, regulatory agencies have reported an association with suicidality. To the best of our knowledge, this is the first meta-analysis to assess the association between GLP-1 agonist use, suicidal ideation, and suicide completion. We aimed to assess the same in patients with diabetes and obesity. METHODS: We searched 6 databases for relevant articles, from the first published article to October 2024. The keywords used were GLP-1 agonists, suicidal ideation, suicide, suicidal behavior, semaglutide, liraglutide, tripeptide, exenatide, and lixisenatide. We identified 354 studies and 126 stands after the removal of duplicates, of which 23 were eligible, and only 12 studies were included in the final meta-analysis. RESULTS: No significant statistical difference was found in suicidal ideations in patients on GLP-1 agonists compared to their counterparts on other obesity and diabetes drugs (odds ratio [OR], 1.0; 95% confidence interval [CI]: 1.0-1.0). No significant difference was observed between patients on GLP-1 agonists and their counterparts regarding complete suicide (OR, 1.77; 95% CI: 0.80-3.91). In a subgroup analysis, suicide was higher among patients on liraglutide compared to their counterparts on semaglutide (OR, 1.48; 95% CI: 1.17-1.89). No significant statistical difference was observed when comparing monjaro and semaglutide (OR, 0.98; 95% CI: 0.94-1.03). CONCLUSION: No significant statistical difference was found between GLP-1 agonists and other obesity and diabetes drugs regarding suicide/suicidal ideation. In a subgroup analysis, suicide was higher in patients on liraglutide compared to semaglutide, with no significant difference between semaglutide and monjaro. Randomized controlled trials that assess the association between GLP-1 agonists and suicidality are highly recommended. CI - Copyright (c) 2025 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Alansari, Amal Omar AU - Alansari AO AUID- ORCID: 0009-0001-9022-1389 AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alharbi, Ahlam Saleem AU - Alharbi AS AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alshehri, Khaled Mohammad AU - Alshehri KM AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alhabib, Ali Tareq AU - Alhabib AT AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alsalmi, Bodour Saleh AU - Alsalmi BS AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Almosfer, Waleed Abdulaziz AU - Almosfer WA AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - AlAjlan, Fadiyah Abdullah AU - AlAjlan FA AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alharbi, Abeer Abdullah AU - Alharbi AA AD - Department of Family Medicine, Madinah Health Cluster, Ministry of Health, Madinah, Saudi Arabia. FAU - Alzahrani, Basmah Saleh AU - Alzahrani BS AD - Saudi Commission for Health Specialties, Riyadh, Saudi Arabia. FAU - Alamer, Bader AU - Alamer B AD - Department of Family Medicine, Third Health Cluster, Ministry of Health, Riyadh, Saudi Arabia. FAU - Alatawi, Amirah M AU - Alatawi AM AD - Department of Family Medicine, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article PT - Meta-Analysis PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Suicidal Ideation MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/psychology MH - Liraglutide/adverse effects MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12688971 OTO - NOTNLM OT - glucagon-like receptors-1 agonists OT - liraglutide OT - semaglutide OT - suicidal ideation OT - suicide OT - tirzepatide COIS- The authors have no conflicts of interest to disclose. EDAT- 2025/12/10 06:28 MHDA- 2025/12/10 06:29 PMCR- 2026/05/12 CRDT- 2025/12/10 01:00 PHST- 2025/07/22 00:00 [received] PHST- 2025/10/20 00:00 [accepted] PHST- 2025/12/10 06:29 [medline] PHST- 2025/12/10 06:28 [pubmed] PHST- 2025/12/10 01:00 [entrez] PHST- 2026/05/12 00:00 [pmc-release] AID - 00005792-202512050-00050 [pii] AID - MD-D-25-09174 [pii] AID - 10.1097/MD.0000000000046173 [doi] PST - ppublish SO - Medicine (Baltimore). 2025 Dec 5;104(49):e46173. doi: 10.1097/MD.0000000000046173. PMID- 41360342 OWN - NLM STAT- MEDLINE DCOM- 20260214 LR - 20260820 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 283 DP - 2026 Mar TI - Tirzepatide is Associated With Reduced Risk of Primary Open-Angle Glaucoma and Ocular Hypertension in Patients With Type 2 Diabetes. PG - 120-128 LID - S0002-9394(25)00653-1 [pii] LID - 10.1016/j.ajo.2025.12.003 [doi] AB - PURPOSE: Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has shown superior efficacy in glycemic control, weight loss, and cardiometabolic outcomes compared to GLP-1 RAs alone. While GLP-1 RAs may offer neuroprotective effects relevant to glaucoma, the impact of dual-incretin therapies like tirzepatide on glaucoma remains unknown. This study investigates the association between tirzepatide initiation and the risk of primary open-angle glaucoma (POAG), ocular hypertension (OHTN), and glaucoma treatment initiation in patients with type 2 diabetes mellitus (T2DM), compared to those initiating selective GLP-1 RAs. DESIGN: Retrospective clinical cohort study using a nationwide electronic health records network from June 2022 to May 2025. SUBJECTS: Adults with T2DM who initiated tirzepatide or selective GLP-1 RA therapy. Patients with prior exposure to either drug class, recent addition of second-line antihyperglycemic agents, previous glaucoma diagnosis or surgery, or ocular trauma were excluded. METHODS: Data from 71 U.S. healthcare organizations were analyzed. Propensity score matching (1:1) was conducted to balance cohorts for demographics, comorbidities, medication use, and ophthalmic encounters. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for each outcome. MAIN OUTCOME MEASURES: Incidence of POAG, OHTN, and first-line glaucoma treatments (medications or surgery). RESULTS: We identified 41,850 patients who initiated tirzepatide and 147,828 patients who initiated selective GLP-1 RAs. After matching, 41,849 patients remained in each cohort. Tirzepatide use was associated with a significantly lower risk of POAG (RR 0.50, 95% CI 0.34-0.74), OHTN (RR 0.59, 95% CI 0.40-0.88), and need for glaucoma treatment (RR 0.54, 95% CI 0.45-0.64) compared to selective GLP-1 RAs. Risk reductions persisted in subgroups with concomitant metformin or insulin use. Sensitivity analyses limited to patients aged >/=60 years and comparisons with individual GLP-1 RAs (semaglutide and dulaglutide) yielded consistent trends. CONCLUSIONS: Tirzepatide use was associated with a significantly reduced risk of developing POAG, OHTN, and need for first-line glaucoma treatment compared to selective GLP-1 RAs in patients with T2DM. These findings suggest a potential additional ocular benefit of tirzepatide and support further investigation into its role in glaucoma management. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Hong, Alexander T AU - Hong AT AD - From the Keck School of Medicine of University of Southern California (A.T.H. and F.L.), Los Angeles, California, USA. FAU - Lin, Forest AU - Lin F AD - From the Keck School of Medicine of University of Southern California (A.T.H. and F.L.), Los Angeles, California, USA. FAU - Baxter, Sally AU - Baxter S AD - Hamilton Glaucoma Center (S.B. and R.N.W.), Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California, USA; Division of Biomedical Informatics (S.B.), Department of Medicine, University of California San Diego, La Jolla, California, USA. FAU - Weinreb, Robert N AU - Weinreb RN AD - Hamilton Glaucoma Center (S.B. and R.N.W.), Viterbi Family Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California, USA. Electronic address: rweinreb@health.ucsd.edu. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20251206 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glaucoma, Open-Angle/epidemiology/prevention & control/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Retrospective Studies MH - Female MH - *Ocular Hypertension/epidemiology/prevention & control/etiology MH - Middle Aged MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Intraocular Pressure/physiology/drug effects MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - Incidence MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Incretins/therapeutic use MH - United States/epidemiology MH - Tirzepatide EDAT- 2025/12/09 00:31 MHDA- 2026/02/15 00:31 CRDT- 2025/12/08 19:34 PHST- 2025/06/23 00:00 [received] PHST- 2025/12/01 00:00 [revised] PHST- 2025/12/03 00:00 [accepted] PHST- 2026/02/15 00:31 [medline] PHST- 2025/12/09 00:31 [pubmed] PHST- 2025/12/08 19:34 [entrez] AID - S0002-9394(25)00653-1 [pii] AID - 10.1016/j.ajo.2025.12.003 [doi] PST - ppublish SO - Am J Ophthalmol. 2026 Mar;283:120-128. doi: 10.1016/j.ajo.2025.12.003. Epub 2025 Dec 6. PMID- 41359966 OWN - NLM STAT- MEDLINE DCOM- 20260216 LR - 20260730 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 179 IP - 2 DP - 2026 Feb TI - Risk for Cancer With Glucagon-Like Peptide-1 Receptor Agonists and Dual Agonists : A Systematic Review and Meta-analysis. PG - 216-229 LID - 10.7326/ANNALS-25-02237 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for type 2 diabetes mellitus (T2DM) and overweight or obesity, but their association with cancer is unclear. PURPOSE: To investigate the risk for obesity-related cancer associated with GLP-1RAs. DATA SOURCES: PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials from inception to August 2025. STUDY SELECTION: Randomized placebo-controlled trials reporting any of the following cancer outcomes: thyroid, pancreatic, colorectal, gastric, esophageal, liver, gallbladder, breast, ovarian, endometrial, or kidney cancer; multiple myeloma; or meningioma. DATA EXTRACTION: Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool, and certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Odds ratios (ORs) were pooled using random-effects meta-analysis. DATA SYNTHESIS: The review included 48 trials involving 94 245 participants. GLP-1RAs probably have little or no effect on risk for thyroid cancer (OR, 1.37 [95% CI, 0.82 to 2.31]; 1 fewer to 9 more cases per 10 000 patients treated), pancreatic cancer (OR, 0.84 [CI, 0.53 to 1.35]; 9 fewer to 6 more per 10 000), breast cancer (OR, 0.95 [CI, 0.60 to 1.49]; 10 fewer to 12 more per 10 000), or kidney cancer (OR, 1.12 [CI, 0.78 to 1.60]; 5 fewer to 13 more per 10 000) (moderate certainty). GLP-1RAs may have little or no effect on colorectal, esophageal, liver, gallbladder, ovarian, or endometrial cancer; multiple myeloma; or meningioma (low certainty). The effect on gastric cancer is very uncertain. Results were consistent in sensitivity analyses of trials with low risk of bias and studies of semaglutide or tirzepatide and across subgroups stratified by follow-up duration, population, GLP-1RA class, weight loss profile, dose, and duration of action. LIMITATION: The included trials were not designed to evaluate cancer outcomes and had short follow-up. CONCLUSION: GLP-1RAs may have little or no effect on risk for obesity-related cancers. Longer-term studies are needed to clarify potential risks or benefits. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42024608365). FAU - Ko, Albert AU - Ko A AUID- ORCID: 0009-0004-5939-1947 AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts (A.K., S.-W.L.). FAU - Chang, Yu-Cheng AU - Chang YC AD - Department of Medicine, Danbury Hospital, Danbury, Connecticut (Y.-C.C., R.J.-L.H.). FAU - Bahar, Furkan AU - Bahar F AUID- ORCID: 0000-0002-4672-5977 AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts (F.B., N.X.). FAU - Wang, Tsu Hsien AU - Wang TH AD - Department of Medicine, University at Buffalo-Catholic Health System, Buffalo, New York (T.H.W.). FAU - Xanthavanij, Nutchapon AU - Xanthavanij N AUID- ORCID: 0000-0003-3198-0657 AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts (F.B., N.X.). FAU - Yu, Chun-Chiao AU - Yu CC AD - Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, New York (C.-C.Y.). FAU - Hsieh, Rebecca Jen-Ling AU - Hsieh RJ AD - Department of Medicine, Danbury Hospital, Danbury, Connecticut (Y.-C.C., R.J.-L.H.). FAU - See, Xin Ya AU - See XY AUID- ORCID: 0000-0001-5388-9112 AD - School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (X.Y.S.). FAU - Lo, Shao-Wei AU - Lo SW AUID- ORCID: 0009-0004-7027-3132 AD - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts (A.K., S.-W.L.). FAU - Song, Junmin AU - Song J AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York (J.S.). FAU - Hsia, Yuan Ping AU - Hsia YP AD - Department of Family Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan (Y.P.H.). FAU - Chiang, Cho-Hung AU - Chiang CH AUID- ORCID: 0000-0002-7910-2338 AD - Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (Cho-Hung Chiang). FAU - Xu, Xiaocao AU - Xu X AUID- ORCID: 0000-0003-1895-7428 AD - Division of Hematology and Oncology, Department of Medicine, University of Vermont Medical Center, Burlington, Vermont (X.X.). FAU - Lin, Shuwen AU - Lin S AUID- ORCID: 0009-0003-9197-7887 AD - Department of Oncology, Montefiore Medical Center, Montefiore Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York (S.L.). FAU - Chiang, Cho-Han AU - Chiang CH AUID- ORCID: 0000-0002-5757-6161 AD - Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Cambridge, Massachusetts, and Northwell Health Cancer Institute, New Hyde Park, New York (Cho-Han Chiang). LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251209 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasms/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy/complications MH - Randomized Controlled Trials as Topic COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/12/08 19:23 MHDA- 2026/02/16 18:34 CRDT- 2025/12/08 17:03 PHST- 2026/02/16 18:34 [medline] PHST- 2025/12/08 19:23 [pubmed] PHST- 2025/12/08 17:03 [entrez] AID - 10.7326/ANNALS-25-02237 [doi] PST - ppublish SO - Ann Intern Med. 2026 Feb;179(2):216-229. doi: 10.7326/ANNALS-25-02237. Epub 2025 Dec 9. PMID- 41354136 OWN - NLM STAT- MEDLINE DCOM- 20251207 LR - 20260127 IS - 1748-1716 (Electronic) IS - 1748-1708 (Linking) VI - 242 IP - 1 DP - 2026 Jan TI - Effect of Weight-Neutral Treatment With Semaglutide or Tirzepatide on beta-Cell Identity in db/db Mice. PG - e70141 LID - 10.1111/apha.70141 [doi] AB - AIM: Insulin resistance and pancreatic beta-cell failure are key characteristics of type 2 diabetes (T2D). Impaired beta-cell function is associated with loss of beta-cell identity, resulting in beta-cell dedifferentiation or trans-differentiation to other endocrine cells. We have shown that beta-cell dedifferentiation can be reversed, restoring insulin secretion. The aim of this study was to investigate whether semaglutide or tirzepatide treatment can reverse early stages of beta-cell dedifferentiation in db/db mice independent of their effect on body weight. METHODS: After 4 weeks of treatment, 12-week-old db/db mice were assessed by oral glucose tolerance test and immunofluorescence to evaluate glucose clearance capacity and effects on pancreatic beta-cell. Body weight, fasting blood glucose, and plasma insulin levels were monitored weekly. Bulk RNA sequencing from islets was performed to identify potential targets. RESULTS: At the doses employed, tirzepatide stabilized, whereas semaglutide was unable to reverse the weight gain of db/db mice. After a 4-week course, both groups showed comparable glucose lowering and increased insulin levels. However, both treatments failed to reverse pancreatic beta-cell dedifferentiation, as assessed by either the percentage of cells expressing the dedifferentiation marker ALDH1A3(+) or FOXO1 translocation. Furthermore, the number of beta-cells expressing low levels of PDX1 was higher in both treatment groups than in controls. Gene expression analyses showed a muted transcriptional response in overlapping patterns in islets treated with either compound but no obvious candidate target genes. CONCLUSION: The findings highlight that the early glucose-lowering effects of semaglutide and tirzepatide in db/db mice occur independently of changes to beta-cell identity. CI - (c) 2025 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd. FAU - Deng, Zhaobin AU - Deng Z AUID- ORCID: 0009-0009-4278-8178 AD - Naomi Berrie Diabetes Center and Department of Medicine, Vagelos College of Physicians & Surgeons of Columbia University, New York, New York, USA. FAU - Zheng, Dongxu AU - Zheng D AD - Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands. FAU - Son, Jinsook AU - Son J AD - Naomi Berrie Diabetes Center and Department of Medicine, Vagelos College of Physicians & Surgeons of Columbia University, New York, New York, USA. FAU - Du, Wen AU - Du W AD - School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, People's Republic of China. FAU - McKimpson, Wendy M AU - McKimpson WM AD - Naomi Berrie Diabetes Center and Department of Medicine, Vagelos College of Physicians & Surgeons of Columbia University, New York, New York, USA. FAU - Liu, Qingli AU - Liu Q AD - Naomi Berrie Diabetes Center and Department of Medicine, Vagelos College of Physicians & Surgeons of Columbia University, New York, New York, USA. FAU - Accili, Domenico AU - Accili D AD - Naomi Berrie Diabetes Center and Department of Medicine, Vagelos College of Physicians & Surgeons of Columbia University, New York, New York, USA. LA - eng GR - DK63618/NH/NIH HHS/United States GR - DK64819/NH/NIH HHS/United States PT - Journal Article PL - England TA - Acta Physiol (Oxf) JT - Acta physiologica (Oxford, England) JID - 101262545 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Insulin-Secreting Cells/drug effects/metabolism MH - *Glucagon-Like Peptides/pharmacology MH - Mice MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Blood Glucose/drug effects/metabolism MH - Insulin/blood/metabolism MH - Mice, Inbred C57BL MH - Body Weight/drug effects MH - *Hypoglycemic Agents/pharmacology MH - Insulin Resistance MH - Cell Dedifferentiation/drug effects MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - insulin OT - semaglutide OT - tirzepatide OT - type 2 diabetes OT - beta-Cell dedifferentiation EDAT- 2025/12/08 01:37 MHDA- 2025/12/08 01:38 CRDT- 2025/12/07 19:33 PHST- 2025/10/29 00:00 [revised] PHST- 2025/08/19 00:00 [received] PHST- 2025/11/21 00:00 [accepted] PHST- 2025/12/08 01:38 [medline] PHST- 2025/12/08 01:37 [pubmed] PHST- 2025/12/07 19:33 [entrez] AID - 10.1111/apha.70141 [doi] PST - ppublish SO - Acta Physiol (Oxf). 2026 Jan;242(1):e70141. doi: 10.1111/apha.70141. PMID- 41348220 OWN - NLM STAT- MEDLINE DCOM- 20260120 LR - 20260625 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 49 IP - 2 DP - 2026 Feb 1 TI - Socioeconomic Factors and Initiation of Semaglutide or Tirzepatide Among Medicare Beneficiaries With Type 2 Diabetes. PG - 277-281 LID - 10.2337/dc25-1619 [doi] AB - OBJECTIVE: Identifying social and economic factors associated with initiation of semaglutide or tirzepatide may inform strategies to support equitable uptake. RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted using 100% of Medicare claims of patients >/=65 years with type 2 diabetes mellitus (T2DM). The outcome was initiation of semaglutide or tirzepatide. We calculated adjusted odds ratios (aORs) for each exposure (self-reported race and ethnicity, dual enrollment in Medicare and Medicaid, rurality, and social vulnerability index), accounting for demographic and clinical characteristics. RESULTS: Among 13,922,387 patients with T2DM, 673,776 (4.8%) initiated semaglutide or tirzepatide in 2023. Minoritized racial and ethnic identity (e.g., non-Hispanic Black compared with White; aOR 0.72; 95% CI 0.71-0.72), dual enrollment (aOR 0.90; 0.89-0.91), and residence in the most versus least vulnerable socially vulnerable neighborhoods (aOR 0.93; 0.92-0.93) were associated with lower initiation. CONCLUSIONS: Minoritized racial and ethnic identity and adverse socioeconomic factors were associated with lower odds of initiation among Medicare beneficiaries with T2DM. CI - (c) 2025 by the American Diabetes Association. FAU - Decker, Sergio R R AU - Decker SRR AUID- ORCID: 0000-0001-6989-3079 AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA. AD - Harvard Medical School, Boston, MA. AD - Department of Internal Medicine and MOVE Outcomes Research Lab, Moinhos de Vento Hospital, Porto Alegre, Brazil. FAU - Chaudhary, Richard S AU - Chaudhary RS AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA. AD - Harvard Medical School, Boston, MA. FAU - Inoue, Kosuke AU - Inoue K AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA. AD - Department of Health Promotion and Behavioral Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Hakubi Center, Kyoto University, Kyoto, Japan. FAU - Song, Yang AU - Song Y AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA. FAU - Ndumele, Chiadi E AU - Ndumele CE AUID- ORCID: 0000-0002-1603-282X AD - Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. FAU - Khan, Sadiya S AU - Khan SS AUID- ORCID: 0000-0003-0643-1859 AD - Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. AD - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. FAU - Kazi, Dhruv S AU - Kazi DS AUID- ORCID: 0000-0002-9510-2979 AD - Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA. AD - Harvard Medical School, Boston, MA. AD - Harvard T.H. Chan School of Public Health, Boston, MA. LA - eng PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - United States MH - *Medicare/statistics & numerical data MH - Aged MH - Male MH - Cross-Sectional Studies MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Socioeconomic Factors MH - *Hypoglycemic Agents/therapeutic use MH - Aged, 80 and over MH - Tirzepatide EDAT- 2025/12/05 13:07 MHDA- 2026/01/20 19:20 CRDT- 2025/12/05 11:13 PHST- 2025/07/05 00:00 [received] PHST- 2025/10/27 00:00 [accepted] PHST- 2026/01/20 19:20 [medline] PHST- 2025/12/05 13:07 [pubmed] PHST- 2025/12/05 11:13 [entrez] AID - 163978 [pii] AID - 10.2337/dc25-1619 [doi] PST - ppublish SO - Diabetes Care. 2026 Feb 1;49(2):277-281. doi: 10.2337/dc25-1619. PMID- 41344888 OWN - NLM STAT- MEDLINE DCOM- 20260630 LR - 20260813 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 41 IP - 7 DP - 2026 Jun 30 TI - Cardiorenal outcomes of weight loss interventions in people with CKD and type 2 diabetes. PG - 1262-1273 LID - 10.1093/ndt/gfaf258 [doi] AB - BACKGROUND AND HYPOTHESIS: In patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), there remains a paucity of data from large, high-quality, real-world studies on the efficacy of weight-lowering interventions, including the glucagon-like peptide-1-based therapies semaglutide and tirzepatide, as well as bariatric surgery (BS). This retrospective cohort study evaluates these interventions on cardiorenal outcomes and mortality using health records from TriNetX US Collaborative Network. METHODS: Three cohorts with T2DM and CKD living with overweight or obesity, prescribed semaglutide or tirzepatide, or with a BS procedure were propensity-score matched with a cohort receiving dipeptidyl peptidase 4 inhibitors (DPP4i, weight-neutral control). We investigated the hazard ratio (HR) of: (i) end-stage renal disease (ESRD); (ii) myocardial infarction (MI); (iii) stroke; and (iv) all-cause mortality. RESULTS: Cohorts included 17 749 (semaglutide, age 64.1 +/- 10.9 years, 57.4% female), 4211 (tirzepatide, 63.7 +/- 10.8, 58.1%) and 2603 (BS, 56.1 +/- 11.2, 74.1%) patients. Compared with DPP4i, semaglutide reduced the risk of ESRD [HR 0.78 (95% confidence interval 0.71 to 0.85)], while tirzepatide showed a reduction of 42% (0.0.58, 0.45 to 0.75). BS lowered ESRD risk (0.79, 0.67 to 0.92). Semaglutide reduced MI (0.80, 0.72 to 0.88) and stroke (0.85, 0.77 to 0.95) risk, while tirzepatide lowered MI and stroke by 24%. BS was associated with reduced MI (0.45, 0.35 to 0.58) and stroke (0.57, 0.44 to 0.74) risk. All-cause mortality risk was reduced by semaglutide (0.64, 0.59 to 0.70), tirzepatide (0.47, 0.35 to 0.63) and BS (0.68, 0.57 to 0.81). CONCLUSIONS: Using a real-world dataset, semaglutide, tirzepatide and BS-interventions shown to elicit weight loss and improve glycaemic control-have a myriad of benefits on cardio-renal outcomes and mortality, supporting their use as disease-modifying therapy options in T2DM and CKD. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the ERA. FAU - Wilkinson, Thomas J AU - Wilkinson TJ AUID- ORCID: 0000-0002-7855-7752 AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Goldney, Jonathan AU - Goldney J AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Yates, Thomas AU - Yates T AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Henson, Joseph AU - Henson J AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Zaccardi, Francesco AU - Zaccardi F AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Khunti, Kamlesh AU - Khunti K AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. AD - NIHR Applied Research Collaboration East Midlands, Leicester Diabetes Centre, Leicester, UK. FAU - Webb, David AU - Webb D AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. AD - University of Hospitals Leicester NHS Trust, Leicester, UK. FAU - Papamargaritis, Dimitris AU - Papamargaritis D AUID- ORCID: 0000-0001-5044-1515 AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. AD - NIHR Applied Research Collaboration East Midlands, Leicester Diabetes Centre, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AD - NIHR Leicester Biomedical Research Centre, Leicester Diabetes Centre, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. AD - NIHR Applied Research Collaboration East Midlands, Leicester Diabetes Centre, Leicester, UK. LA - eng GR - NIHR Leicester Biomedical Research Centre/ PT - Journal Article PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/therapy MH - Female MH - Semaglutide MH - Retrospective Studies MH - Male MH - Tirzepatide MH - *Weight Loss MH - Middle Aged MH - *Renal Insufficiency, Chronic/complications/therapy MH - *Bariatric Surgery MH - Aged MH - Glucagon-Like Peptides/therapeutic use MH - Follow-Up Studies MH - *Obesity/complications/therapy MH - Prognosis MH - Glomerular Filtration Rate MH - Kidney Function Tests MH - Risk Factors PMC - PMC13314376 OTO - NOTNLM OT - bariatric surgery OT - obesity OT - semaglutide OT - tirzepatide OT - type 2 diabetes COIS- M.J.D. receives funding from AstraZeneca, Boehringer Ingelheim and Novo Nordisk; consulting fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi; honoraria from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Sanofi and Eli Lilly; support for meetings/travel from Boehringer Ingelheim, Novo Nordisk, Lilly, Amgen, AstraZeneca, Biomea Fusion, Regeneron and Zealand Pharma; and participation on advisory boards for Amgen, AstraZeneca, Biomea Fusion, Sanofi, Zealand Pharma, Carmot/Roche and Regeneron. K.K. receives funding from AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, Sanofi, Servier, Oramed Pharmaceuticals, Roche, Daiichi-Sankyo and Applied Therapeutics; consulting fees from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, Servier, Pfizer, Roche, Daiichi-Sankyo, Embecta and Nestle Health Science; and honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Novo Nordisk, Sanofi, Servier, Pfizer, Roche, Daiichi-Sankyo, Embecta and Nestle Health Science. D.P. receives funding from Novo Nordisk A/S, National Institute for Health and Care Research and Novo Nordisk UK Research Foundation; and honoraria from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Johnson and Johnson, and Academy of Medical Sciences/Diabetes UK. EDAT- 2025/12/05 01:01 MHDA- 2026/06/30 06:31 PMCR- 2025/12/04 CRDT- 2025/12/04 21:32 PHST- 2025/05/16 00:00 [received] PHST- 2025/11/26 00:00 [accepted] PHST- 2026/06/30 06:31 [medline] PHST- 2025/12/05 01:01 [pubmed] PHST- 2025/12/04 21:32 [entrez] PHST- 2025/12/04 00:00 [pmc-release] AID - 8365542 [pii] AID - gfaf258 [pii] AID - 10.1093/ndt/gfaf258 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2026 Jun 30;41(7):1262-1273. doi: 10.1093/ndt/gfaf258. PMID- 41340366 OWN - NLM STAT- MEDLINE DCOM- 20260323 LR - 20260802 IS - 1467-789X (Electronic) IS - 1467-7881 (Linking) VI - 27 IP - 4 DP - 2026 Apr TI - GLP-1 Receptor Agonist Medications for Obesity and Type 2 Diabetes Treatment: A Rapid Review of Changes in Eating Behaviors and Eating Disorder Risk. PG - e70049 LID - 10.1111/obr.70049 [doi] AB - This rapid review aimed to evaluate the effects of GLP-1 RAs on eating behaviors and eating disorder risk. Databases were searched to January 2025 to identify studies evaluating GLP-1 RA treatment for adolescents or adults with obesity or Type 2 diabetes. Eligible studies reported adverse events, changes in eating disorder risk, or eating behaviors post-intervention or follow-up. Data were synthesized narratively. Of 1597 records screened, 25 studies (k) were included (two adolescent, n = 275; 23 adult, n = 8722). Two studies reported eating disorder adverse events, and two reported no binge eating adverse events. Liraglutide reduced global eating disorder risk scores, with no differences between groups (k = 1). Binge eating episodes and prevalence reduced following liraglutide and semaglutide, respectively. Binge eating scores improved with liraglutide compared to placebo (k = 2). Food cravings following liraglutide (k = 1) or semaglutide (k = 6) were improved (k = 6) or unchanged (k = 1). There was no difference in disinhibition between liraglutide and comparator (k = 2) with one study reporting a reduction in both groups. Three non-RCTs reported reduced disinhibition with liraglutide. Limited data are available on GLP-1 RAs, eating behaviors and eating disorders. For most, eating behaviors may improve or remain unchanged. Comprehensive assessment of eating behaviors is needed to understand the benefits and risks of treatment. CI - (c) 2025 World Obesity Federation. FAU - Jebeile, Hiba AU - Jebeile H AUID- ORCID: 0000-0002-8623-6174 AD - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, Australia. FAU - Danielsen, Yngvild Sorebo AU - Danielsen YS AUID- ORCID: 0000-0002-4117-8900 AD - Department of Clinical Psychology, University of Bergen, Bergen, Norway. AD - Regional Department of Eating Disorders, Haukeland University Hospital, Bergen, Norway. FAU - Sumithran, Priya AU - Sumithran P AUID- ORCID: 0000-0002-9576-1050 AD - Department of Surgery, School of Translational Medicine, Monash University, Melbourne, Australia. AD - Department of Endocrinology and Diabetes, Alfred Health, Melbourne, Australia. FAU - Lorien, Sasha AU - Lorien S AD - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia. FAU - Jardine, Isabelle R AU - Jardine IR AD - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia. FAU - Baur, Louise A AU - Baur LA AUID- ORCID: 0000-0002-4521-9482 AD - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, Australia. FAU - Lister, Natalie B AU - Lister NB AUID- ORCID: 0000-0002-9148-8632 AD - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20251203 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - Liraglutide/therapeutic use MH - *Feeding and Eating Disorders MH - *Feeding Behavior/drug effects MH - Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Adolescent MH - Adult OTO - NOTNLM OT - binge eating OT - disordered eating OT - liraglutide OT - obesity treatment OT - semaglutide OT - tirzepatide EDAT- 2025/12/04 06:27 MHDA- 2026/03/24 00:30 CRDT- 2025/12/04 02:05 PHST- 2025/09/18 00:00 [revised] PHST- 2025/04/07 00:00 [received] PHST- 2025/11/06 00:00 [accepted] PHST- 2026/03/24 00:30 [medline] PHST- 2025/12/04 06:27 [pubmed] PHST- 2025/12/04 02:05 [entrez] AID - 10.1111/obr.70049 [doi] PST - ppublish SO - Obes Rev. 2026 Apr;27(4):e70049. doi: 10.1111/obr.70049. Epub 2025 Dec 3. PMID- 41338557 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260127 IS - 0578-1426 (Print) IS - 0578-1426 (Linking) VI - 64 IP - 12 DP - 2025 Dec 1 TI - [Effect of semaglutide on serum metabolomics in obese patients with type 2 diabetes mellitus complicated with metabolic-associated fatty liver disease]. PG - 1218-1225 LID - 10.3760/cma.j.cn112138-20250424-00235 [doi] AB - Objective: To investigate the effect of semaglutide on the metabolomics of obese patients with type 2 diabetes mellitus (T2DM) complicated by metabolic-associated fatty liver disease (MAFLD). Methods: A prospective non-randomized controlled study was conducted. Obese patients with T2DM complicated by MAFLD who attended the Department of Endocrinology of Shijiazhuang People's Hospital from October 2022 to June 2023 were selected as the semaglutide group, and healthy individuals from the physical examination center were selected as the control group. Clinical data of both groups were collected. The semaglutide group was subcutaneously injected with semaglutide following a basic hypoglycemic regimen (starting dose of 0.25 mg once a week, which was changed to 0.5 mg once a week after 1 week for 12 weeks). Liquid chromatography-tandem mass spectrometry was used for qualitative and quantitative analyses of plasma metabolites, and multivariate analysis methods were used to analyze the metabolomics data. Results: In total, 69 patients in the semaglutide group completed the treatment, with 49 males (71%) and a median age of 46 (36, 54) years, and the healthy control group consisted of 100 individuals, with 38 males (38%) and a median age of 40 (35, 45) years. The body mass index and levels of fasting blood glucose, alanine aminotransferase, and interleukin-6 (IL-6) in the semaglutide group before treatment were significantly higher than those in the control group (all P<0.001). The body mass index [23.65 (22.33, 24.45) vs. 28.72 (27.50, 32.07) kg/m(2)], liver stiffness measurement [1.61 (0.91, 2.00) vs. 5.78 (5.51, 6.10) kPa], and homeostasis model assessment of insulin resistance index [5.10 (2.90, 7.95) vs. 9.00 (6.25, 11.80)] in the semaglutide group were significantly lower after treatment than before treatment (all P<0.001), and the blood glucose, blood lipid, liver function indicator, and IL-6 levels all significantly decreased after treatment. Metabolomics analysis revealed that there were 219 differential metabolites (131 up-regulated and 88 down-regulated) between the semaglutide group (n=27) before treatment and the control group (n=12), with glycerophospholipids and free fatty acids being significantly up-regulated. The semaglutide group showed 203 differential metabolites (121 up-regulated and 82 down-regulated) after treatment compared with before, with significant down-regulation of long-chain fatty acids and significant up-regulation of metabolites including carnitines, branched-chain amino acids, and taurine. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differential metabolites identified before and after semaglutide treatment were involved in several signaling pathways, such as biosynthesis of unsaturated fatty acids, linoleic acid metabolism, aldosterone synthesis and secretion, and the mTOR signaling pathway, etc. Conclusion: Semaglutide alters the serum metabolite levels in obese patients with T2DM complicated by MAFLD. FAU - Niu, S AU - Niu S AD - Department of Endocrinology, Shijiazhuang People's Hospital, Shijiazhuang 050081, China. FAU - Wang, C X AU - Wang CX AD - Hebei Medical University, Shijiazhuang 050017, China. FAU - Zhao, Y B AU - Zhao YB AD - Department of Gastroenterology, Shijiazhuang People's Hospital, Shijiazhuang 050081, China. FAU - Wu, D AU - Wu D AD - Department of Gastroenterology, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang 050051, China. FAU - Yang, K L AU - Yang KL AD - Hebei Medical University, Shijiazhuang 050017, China. LA - chi GR - 2024127/2024 Annual Instructional Project of Hebei Administration of Traditional Chinese Medicine/ PT - English Abstract PT - Journal Article PL - China TA - Zhonghua Nei Ke Za Zhi JT - Zhonghua nei ke za zhi JID - 16210490R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/blood/metabolism MH - Male MH - Middle Aged MH - Female MH - Metabolomics MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/complications/blood/drug therapy MH - Prospective Studies MH - Adult MH - *Fatty Liver/complications/blood/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/12/04 02:11 MHDA- 2025/12/04 02:12 CRDT- 2025/12/03 19:47 PHST- 2025/12/04 02:12 [medline] PHST- 2025/12/04 02:11 [pubmed] PHST- 2025/12/03 19:47 [entrez] AID - 10.3760/cma.j.cn112138-20250424-00235 [doi] PST - ppublish SO - Zhonghua Nei Ke Za Zhi. 2025 Dec 1;64(12):1218-1225. doi: 10.3760/cma.j.cn112138-20250424-00235. PMID- 41335431 OWN - NLM STAT- MEDLINE DCOM- 20260204 LR - 20260813 IS - 2168-6238 (Electronic) IS - 2168-622X (Print) IS - 2168-622X (Linking) VI - 83 IP - 2 DP - 2026 Feb 1 TI - Semaglutide and Early-Stage Metabolic Abnormalities in Individuals With Schizophrenia Spectrum Disorders: A Randomized Clinical Trial. PG - 128-138 LID - 10.1001/jamapsychiatry.2025.3639 [doi] AB - IMPORTANCE: Individuals with schizophrenia spectrum disorders treated with second-generation antipsychotics (SGAs) are at heightened risk for obesity, prediabetes, and type 2 diabetes, contributing to increased cardiovascular morbidity and premature mortality. Early intervention with glucagon-like peptide-1 receptor agonists (GLP-1RAs) may help mitigate long-term cardiometabolic risk. OBJECTIVE: To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, double-blind, placebo-controlled, randomized clinical trial. Participants were enrolled from 3 clinical sites in Denmark between September 2021 and August 2024. Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years. Participants had early-stage glycemic dysregulation (hemoglobin A1c [HbA1c], 5.4%-7.4%) and were not receiving antidiabetic therapy. INTERVENTIONS: Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks. MAIN OUTCOMES AND MEASURES: The prespecified primary outcome was change in HbA1c level from baseline to week 26. The primary analysis adhered to the intention-to-treat principle. RESULTS: Of 104 individuals screened, 73 were randomized and 57 (78%) completed the trial. Baseline characteristics were comparable between groups. Mean (SD) age was 35 (12) years, 48 were female (65%), and mean (SD) body mass index was 36.1 (7.9). At week 26, semaglutide significantly reduced HbA1c level compared with placebo (mean difference, -0.25%; 95% CI, -0.33 to -0.16; P < .001); 43% of participants (12 of 28) treated with semaglutide achieved low-risk HbA1c levels (<5.4%) vs 3% with placebo. Greater reductions in body weight (-9.2 kg; 95% CI, -13.3 to -5.1 kg; P < .001), waist circumference (-7.0 cm; 95% CI, -10.6 to -3.3 cm; P < .001), and fat mass (-6.1 kg; 95% CI, -10.2 to -1.9 kg; P = .006) were observed with semaglutide. No differences in lipid levels, liver function, blood pressure, or psychiatric symptoms were observed. Gastrointestinal adverse events were common but mild and transient; psychiatric adverse events were similar across groups. CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial show that adjunctive semaglutide significantly improved glycemic control and weight outcomes in individuals with schizophrenia spectrum disorders. Secondary outcomes were exploratory. These findings support the use of GLP-1RAs as a potential early intervention strategy to reduce cardiometabolic risk in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04892199. FAU - Sass, Marie R AU - Sass MR AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. AD - Now with Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Klausen, Mette Kruse AU - Klausen MK AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Schwarz, Christine R AU - Schwarz CR AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark. FAU - Rasmussen, Line AU - Rasmussen L AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Giver, Malte E B AU - Giver MEB AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Hviid, Malthe AU - Hviid M AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Schilling, Christoffer AU - Schilling C AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Zamorski, Alexandra AU - Zamorski A AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. FAU - Jensen, Andreas AU - Jensen A AD - Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Denmark. FAU - Gefke, Maria AU - Gefke M AD - Mental Health Centre, Northern Zealand, Copenhagen University Hospital-Mental Health Services CPH, Copenhagen, Denmark. AD - The Early Multimodular Prevention and Intervention Research Institution, Hillerod, Denmark. FAU - Storgaard, Heidi AU - Storgaard H AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark. FAU - Oturai, Peter S AU - Oturai PS AD - Department of Clinical Physiology and Nuclear Medicine, Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. FAU - Kjaer, Andreas AU - Kjaer A AD - Department of Clinical Physiology and Nuclear Medicine, Cluster for Molecular Imaging, Department of Biomedical Sciences, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark. FAU - Hartmann, Bolette AU - Hartmann B AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Holst, Jens J AU - Holst JJ AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Ekstrom, Claus T AU - Ekstrom CT AD - Department of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark. FAU - Vinberg, Maj AU - Vinberg M AD - Mental Health Centre, Northern Zealand, Copenhagen University Hospital-Mental Health Services CPH, Copenhagen, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. FAU - Correll, Christoph U AU - Correll CU AD - The Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, New York. AD - Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofsta/Northwell, Hempstead, New York. AD - Department of Child and Adolescent Psychiatry, Charite Universitatsmedizin, Berlin, Germany. AD - German Center for Mental Health, partner site Berlin, Berlin, Germany. FAU - Vilsboll, Tina AU - Vilsboll T AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. FAU - Fink-Jensen, Anders AU - Fink-Jensen A AD - Mental Health Center Copenhagen, Mental Health Services in the Capitol Region of Denmark, Copenhagen, Denmark. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng SI - ClinicalTrials.gov/NCT04892199 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - JAMA Psychiatry JT - JAMA psychiatry JID - 101589550 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Antipsychotic Agents) RN - N7U69T4SZR (Olanzapine) RN - 0 (Glycated Hemoglobin) RN - J60AR2IKIC (Clozapine) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - Adult MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/pharmacology MH - *Schizophrenia/drug therapy MH - Double-Blind Method MH - *Antipsychotic Agents/adverse effects/therapeutic use MH - Olanzapine/adverse effects/therapeutic use MH - Glycated Hemoglobin/analysis MH - Young Adult MH - Clozapine/adverse effects/therapeutic use MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Adolescent MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Diabetes Mellitus, Type 2/chemically induced MH - Drug Therapy, Combination PMC - PMC12676471 COIS- Conflict of Interest Disclosures: Dr Sass reported institution received unrestricted grants from Novo Nordisk A/S, Mental Health Services in the Capital Region of Denmark, The Lundbeck Foundation, the Novo Nordisk Foundation, and P. Carl Petersen Foundation and being a full-time employee of Novo Nordisk A/S outside the submitted work. Dr Schwarz reported receiving personal fees from Novo Nordisk and Eli Lilly outside the submitted work. Dr Rasmussen reported receiving a pregraduate fellowship grant from Novo Nordisk Foundation during the conduct of the study. Dr Giver reported receiving grants from Novo Nordisk during the conduct of the study. Dr Hviid reported receiving grants from Dagmar Foundation and The Lundbeck Foundation during the conduct of the study. Dr Schilling reported institution received grants from Novo Nordisk A/S, Mental Health Services in the Capital Region of Denmark, The Lundbeck Foundation, Novo Nordisk Foundation, and P. Carl Petersen Foundation during the conduct of the study. Dr Gefke reported receiving grants from Jascha Foundation during the conduct of the study. Dr Kjaer reported receiving consultant fees from Novo Nordisk A/S outside the submitted work. Dr Holst reported receiving grants from Novo Nordisk Foundation during the conduct of the study. Dr Vinberg reported receiving grants from Jascha Foundation during the conduct of the study. Dr Correll reported receiving royalties from UpToDate; consultant and/or advisor fees from AbbVie, Alkermes, Allergan, Angelini, Aristo, Autobahn, Boehringer Ingelheim, Bristol Meyers Squibb, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Delpor, Denovo, Draig, Eli Lilly, Eumentis Therapeutics, Gedeon Richter, GH, Hikma, Holmusk, Intra-Cellular Therapies, Jamjoom Pharma, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedInCell, Med-Link, Merck, Mindpax, Mitsubishi Tanabe Pharma, Maplight, Mylan, Neumora Therapeutics, Neuraxpharm, Neurocrine, Neurelis, NeuShen, Newron, Noven, Novo Nordisk, Orion Pharma, Otsuka, PPD Biotech, Recognify Life Science, Recordati, Relmada, Response Pharmaceutical, Re-viva, Rovi, Saladax, Sanofi, Seqirus, Servier, Sumitomo Pharma America, Sunovion, Sun Pharma, Supernus, Tabuk, Takeda, Teva, Terran, Tolmar, Vertex, Viatris and Xenon Pharmaceuticals; providing expert testimony for Janssen, Lundbeck, Neurocrine, and Otsuka; serving on a Data Safety Monitoring Board for Compass Pathways, Intra-Cellular Therapies, Relmada, Reviva, and Rovi; receiving grant support from Boehringer-Ingelheim, Janssen, and Takeda; and having stock options for Cardio Diagnostics, Kuleon Biosciences, LB Pharma, MedLink Global, Mindpax, Quantic, and Terran. Dr Vilsboll reported receiving advisory fees from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Mass Medicine, Novo Nordisk, Carmot/Roche, Regor, Sanofi, Sun Pharmaceuticals, and Zealand Pharma Global outside the submitted work. Dr Fink-Jensen reported receiving an unrestricted research grant from Novo Nordisk A/S during the conduct of the study and serving as an unpaid member of the advisory board for Novo Nordisk A/S outside the submitted work. No other disclosures were reported. EDAT- 2025/12/03 14:10 MHDA- 2026/02/04 15:12 PMCR- 2026/12/03 CRDT- 2025/12/03 11:33 PHST- 2026/02/04 15:12 [medline] PHST- 2025/12/03 14:10 [pubmed] PHST- 2025/12/03 11:33 [entrez] PHST- 2026/12/03 00:00 [pmc-release] AID - 2842202 [pii] AID - yoi250062 [pii] AID - 10.1001/jamapsychiatry.2025.3639 [doi] PST - ppublish SO - JAMA Psychiatry. 2026 Feb 1;83(2):128-138. doi: 10.1001/jamapsychiatry.2025.3639. PMID- 41334697 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260609 IS - 1099-1557 (Electronic) IS - 1053-8569 (Linking) VI - 34 IP - 12 DP - 2025 Dec TI - Cardiovascular Effectiveness of Semaglutide Versus Dulaglutide in Type 2 Diabetes. PG - e70276 LID - 10.1002/pds.70276 [doi] AB - OBJECTIVE: Randomized clinical trials show that subcutaneous semaglutide is modestly superior to dulaglutide in reducing HbA1c and body weight, but no trial has compared their effectiveness on hard cardiovascular outcomes. This study aimed to examine whether semaglutide and dulaglutide differ in cardiovascular effectiveness. RESEARCH DESIGN AND METHODS: This new-user, active-comparator cohort study used nationwide population-based Danish healthcare data to emulate a target trial of adults with type 2 diabetes receiving standard care who initiated subcutaneous semaglutide compared with dulaglutide. Up to five semaglutide initiators were matched to one dulaglutide initiator on a propensity score estimated from 52 variables. The outcome was a major adverse cardiovascular event (MACE), including myocardial infarction, ischemic stroke, heart failure, coronary revascularization, and cardiovascular death. In per-protocol analyses, Aalen-Johansen estimates were used to calculate risks, risk differences, and risk ratios at 3 years, accounting for informative censoring at nonadherence to the assigned treatment via time-varying inverse probability of censoring weights. RESULTS: The semaglutide group included 2535 individuals, and the dulaglutide group 569 (median age [IQR], 61 [52-71] years; 1105 female individuals [36%]). Within 3 years, the risk of MACE was 6.0% (95% CI, 4.5%-7.8%) in the semaglutide group and 6.2% (95% CI, 4.0%-8.9%) in the dulaglutide group, corresponding to a risk difference of -0.2% (95% CI, -3.2% to 2.8%) and a risk ratio of 0.97 (95% CI, 0.59-1.61). CONCLUSIONS: This target trial emulation did not provide evidence for a substantial difference in cardiovascular outcomes between individuals with type 2 diabetes initiating semaglutide and dulaglutide. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Bonnesen, Kasper AU - Bonnesen K AUID- ORCID: 0000-0002-8626-2372 AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Clinical Pharmacology, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark. FAU - Heide-Jorgensen, Uffe AU - Heide-Jorgensen U AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Christensen, Diana H AU - Christensen DH AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. FAU - Lash, Timothy L AU - Lash TL AD - Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA. FAU - Pedersen, Lars AU - Pedersen L AUID- ORCID: 0000-0002-9341-3888 AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Thomsen, Reimar W AU - Thomsen RW AUID- ORCID: 0000-0001-9135-3474 AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Matthews, Anthony A AU - Matthews AA AUID- ORCID: 0000-0002-1290-271X AD - Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Schmidt, Morten AU - Schmidt M AD - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Cardiology, Godstrup Hospital, Herning, Denmark. LA - eng GR - Danish Diabetes and Endocrine Academy/ GR - NNF22SA0079901/Novo Nordisk Foundation/ GR - NNF19OC0054908/Novo Nordisk Foundation/ GR - 2018-03028/Swedish Research Council/ GR - 2021-02236/Swedish Research Council/ GR - 2020-00029/Forte/ PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM EIN - Pharmacoepidemiol Drug Saf. 2026 Feb;35(2):e70333. doi: 10.1002/pds.70333. PMID: 41566767 MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Recombinant Fusion Proteins/administration & dosage/therapeutic use/adverse effects MH - *Immunoglobulin Fc Fragments/administration & dosage/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Aged MH - *Cardiovascular Diseases/epidemiology/prevention & control/etiology MH - Denmark/epidemiology MH - Cohort Studies MH - Glycated Hemoglobin/analysis MH - Treatment Outcome MH - Injections, Subcutaneous MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - cardiovascular diseases OT - glucagon-like peptide-1 receptor agonists OT - type 2 diabetes mellitus EDAT- 2025/12/03 14:11 MHDA- 2025/12/03 14:12 CRDT- 2025/12/03 06:53 PHST- 2025/11/13 00:00 [revised] PHST- 2025/04/09 00:00 [received] PHST- 2025/11/18 00:00 [accepted] PHST- 2025/12/03 14:12 [medline] PHST- 2025/12/03 14:11 [pubmed] PHST- 2025/12/03 06:53 [entrez] AID - 10.1002/pds.70276 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2025 Dec;34(12):e70276. doi: 10.1002/pds.70276. PMID- 41326727 OWN - NLM STAT- MEDLINE DCOM- 20260122 LR - 20261009 IS - 1432-2218 (Electronic) IS - 0930-2794 (Linking) VI - 40 IP - 1 DP - 2026 Jan TI - Bariatric surgery vs. GLP-1 receptor agonists among primarily medicare and medicaid patients with diabetes: a 3-year analysis. PG - 671-678 LID - 10.1007/s00464-025-12403-y [doi] AB - BACKGROUND: Bariatric surgery has long been established as an effective treatment option for obesity and diabetes [Kalainov et al. in J Am Acad Orthop Surg [32(10):427-438, 2025] and Ogden et al. in JAMA 311(8):806-806, 2025. 10.1001/jama.2014.732]. Recently, GLP-1 Receptor Agonists' (GLP-1RAs) use has expanded as an alternative therapy for weight loss and diabetes management. While GLP1RAs are known to be safe and effective, few have compared long term outcomes of GLP-1RAs versus the "gold standard" of bariatric surgery among Medicare/Medicaid patients, who make up the largest payer group in the U.S. [Kalainov et al. in J Am Acad Orthop Surg [32(10):427-438, 2025]. METHODS: This was a retrospective, multicenter study of obese, type-2 diabetic patients (T2D) >/= 18 years old, who initiated weekly injectable semaglutide or tirzepatide or underwent bariatric surgery between January 1st, 2018 to July 31st, 2024. Patients with a baseline BMI /=1% alongside BW reductions of >/=3% or >/=5%, respectively. Treatment satisfaction increased significantly (mean change in DTSQs +8.7 and DTSQc 14.9; both p < 0.0001). At EoS, 49.5% of participants remained on oral semaglutide, of whom 47.4% were receiving the 14.0 mg dose. CONCLUSIONS: This real-world population of adults with T2D in Saudi Arabia experienced clinically significant reductions in HbA1c and BW, increased treatment satisfaction and a favourable safety profile, consistent with previously published PIONEER REAL studies. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - ElBadawi, Hussein AU - ElBadawi H AD - Wayne State University School of Medicine, Detroit, Michigan, USA. FAU - Albalkhi, Nader AU - Albalkhi N AD - Specialized Medical Center Hospital, Riyadh, Saudi Arabia. FAU - Al Kadhim, Ibrahim AU - Al Kadhim I AD - Almoosa Specialist Hospital, Al Mubarraz, Saudi Arabia. FAU - Elsadig, Ahmed AU - Elsadig A AD - Dr Suliaman Al Habib Hospitals, Riyadh, Saudi Arabia. FAU - Baltzis, Dimitrios AU - Baltzis D AD - Mouwasat Hospital, Khobar, Saudi Arabia. FAU - Hatahet, Mohamed Hassan AU - Hatahet MH AD - Almoosa Specialist Hospital, Al Mubarraz, Saudi Arabia. FAU - Ismail, Mahmoud AU - Ismail M AUID- ORCID: 0000-0002-3164-6969 AD - Novo Nordisk Saudia Arabia, Riyadh, Saudi Arabia. FAU - Khader, Said AU - Khader S AD - Dr Suliaman Al Habib Hospitals, Riyadh, Saudi Arabia. FAU - Rasmussen, Christina Louise AU - Rasmussen CL AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Scheuer, Stine Hedegaard AU - Scheuer SH AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Shalaby, Ahmed AU - Shalaby A AD - Novo Nordisk Saudia Arabia, Riyadh, Saudi Arabia. FAU - Almehthel, Mohammed AU - Almehthel M AD - Obesity, Endocrine and Metabolism Center, King Fahad Medical City, Riyadh, Saudi Arabia. AD - Division of Endocrinology, University of British Columbia, Vancouver, British Columbia, Canada. LA - eng GR - Novo Nordisk Saudi Arabia/ PT - Journal Article PT - Multicenter Study DEP - 20251127 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - Saudi Arabia/epidemiology MH - Female MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Middle Aged MH - Male MH - Prospective Studies MH - Adult MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Administration, Oral MH - Treatment Outcome MH - Patient Satisfaction MH - Drug Administration Schedule MH - Blood Glucose MH - Aged MH - Body Weight/drug effects MH - Waist Circumference/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12803558 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonist OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- Ibrahim Al Kadhim: lecturer/advisory panel member: Novo Nordisk, AstraZeneca, Novartis, Sanofi, Eli Lilly, MSD, Spimaco. Research support: Novo Nordisk, Eli Lilly, IQVIA. Mahmoud Ismail is an employee of Novo Nordisk Saudi Arabia. Christina Louise Rasmussen is an employee of Novo Nordisk A/S. Stine Hedegaard Scheuer is an employee of Novo Nordisk A/S. Ahmed Shalaby is an employee of Novo Nordisk Saudi Arabia. Mohammed Almehthel received lecturing and consultation fees from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Novartis, MSD, Merk, Bayer, Boeringer Ingelheim, Abbott, Vital Aire, Dexcom, Sibionics, Syai, and research support from Vital Aire, Novo Nordisk, Eli Lilly, Sanofi, Syai and Bayer. EDAT- 2025/11/28 00:26 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/27 21:43 PHST- 2025/11/12 00:00 [revised] PHST- 2025/06/04 00:00 [received] PHST- 2025/11/12 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/28 00:26 [pubmed] PHST- 2025/11/27 21:43 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70317 [pii] AID - 10.1111/dom.70317 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):1304-1314. doi: 10.1111/dom.70317. Epub 2025 Nov 27. PMID- 41307691 OWN - NLM STAT- MEDLINE DCOM- 20260627 LR - 20260813 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 63 IP - 2 DP - 2026 Feb TI - Influence of GLP1 receptor rs6923761 and rs761387 genetic variants on oral semaglutide response in patients with type 2 diabetes. PG - 303-311 LID - 10.1007/s00592-025-02626-9 [doi] AB - AIMS: Glucagon-like peptide-1 receptor (GLP-1R) has become one of the most promising ligand-receptor systems to target for type 2 diabetes mellitus (T2DM) treatment. Over the last two decades, several GLP-1 receptor agonists (GLP-1RAs) have been developed and semaglutide is the first and only GLP-1RA available as an oral formulation. GLP1R single nucleotide polymorphisms may affect GLP-1R response to oral semaglutide. Here we aimed to evaluate the impact of rs6923761 and rs761387 GLP1R polymorphisms on the response to oral semaglutide. METHODS: This is a retrospective cohort study including adult patients with T2DM who had been treated with oral semaglutide for at least one year. Patients were enrolled between November 2023 and April 2024, and then genotyped. RESULTS: We selected 210 adult patients with a median age of 71 years. Their median BMI was 29.1 kg/m2, HbA1c was 7.2% (55 mmol/mol), duration of diabetes was 12 years. After a median follow-up of 18 months, oral semaglutide reduced HbA1c by -0.3% (-3 mmol/mol), BMI by -1.1 kg/m2, SBP by -5 mmHg, total cholesterol by -8 mg/dL, triglycerides by -6.5 mg/dL. In addition, a reduction of ACR by -44.02 mg/g was observed in patients with baseline ACR > 30 mg/g, along with a decrease of liver transaminases in patients with baseline levels >/= 35 U/L. Multivariate linear regression did not show any significant association between rs6923761 or rs761387 GLP1R genotypes and changes in HbA1c, BMI, SBP and DBP. CONCLUSIONS: Our findings confirm the effectiveness of oral semaglutide in improving metabolic control and providing cardiorenal protection in different clinical scenarios. Conversely, they fail to show a clear benefit of GLP1R genotyping to guide treatment decisions, at least in patients with HbA1c < 7.5% (< 58 mmol/mol). Further studies are needed to confirm and extend our findings. FAU - Candido, Riccardo AU - Candido R AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. AD - SC Patologie Diabetiche, ASUGI (Azienda Sanitaria Universitaria Giuliano Isontina), Via Sai 7, 34128, Trieste, Italy. FAU - Toffoli, Barbara AU - Toffoli B AUID- ORCID: 0000-0002-6854-5782 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Baccichetto, Gabriele AU - Baccichetto G AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Marchese, Francesca AU - Marchese F AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Carpene, Silvia AU - Carpene S AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Gaiotti, Sara AU - Gaiotti S AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Fabris, Bruno AU - Fabris B AUID- ORCID: 0000-0001-5226-1833 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. AD - SS Endocrinologia (Medicina Clinica), ASUGI (Azienda Sanitaria Universitaria Giuliano Isontina), Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. FAU - Bernardi, Stella AU - Bernardi S AUID- ORCID: 0000-0002-7429-3075 AD - Department of Medical Surgical and Health Sciences, University of Trieste, Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. stella.bernardi@units.it. AD - SS Endocrinologia (Medicina Clinica), ASUGI (Azienda Sanitaria Universitaria Giuliano Isontina), Cattinara Teaching Hospital, Strada di Fiume 447, 34149, Trieste, Italy. stella.bernardi@units.it. LA - eng PT - Journal Article DEP - 20251127 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor/genetics MH - Female MH - Male MH - Aged MH - *Polymorphism, Single Nucleotide MH - Middle Aged MH - Retrospective Studies MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - Blood Glucose MH - Genotype PMC - PMC12957030 OTO - NOTNLM OT - rs6923761 OT - rs761387 OT - GLP1R OT - Oral semaglutide OT - Polymorphism OT - Type 2 diabetes COIS- Declarations. Conflict of interest: All the authors have no conflict of interests. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol was approved by the Institutional Review Board of the University of Trieste, Trieste, Italy (University of Trieste Comitato Etico di Ateneo #136 date 30/11/2023). Informed consent: Informed consent was obtained from all subjects involved in this study, prior to study enrollment and genotyping. EDAT- 2025/11/27 12:29 MHDA- 2026/06/27 10:10 PMCR- 2025/11/27 CRDT- 2025/11/27 11:13 PHST- 2025/09/14 00:00 [received] PHST- 2025/11/17 00:00 [accepted] PHST- 2026/06/27 10:10 [medline] PHST- 2025/11/27 12:29 [pubmed] PHST- 2025/11/27 11:13 [entrez] PHST- 2025/11/27 00:00 [pmc-release] AID - 10.1007/s00592-025-02626-9 [pii] AID - 2626 [pii] AID - 10.1007/s00592-025-02626-9 [doi] PST - ppublish SO - Acta Diabetol. 2026 Feb;63(2):303-311. doi: 10.1007/s00592-025-02626-9. Epub 2025 Nov 27. PMID- 41307513 OWN - NLM STAT- MEDLINE DCOM- 20260907 LR - 20260911 IS - 2724-6116 (Electronic) IS - 2724-6116 (Linking) VI - 51 IP - 3 DP - 2026 Sep TI - Efficacy and safety of oral semaglutide as add-on therapy in poorly controlled type 2 diabetes on background SGLT2 inhibitors: a real-world, multi-center, retrospective, observational study (RYS2). PG - 248-256 LID - 10.23736/S2724-6507.25.04376-3 [doi] AB - BACKGROUND: Treatment of type 2 diabetes mellitus (T2DM) relies on diverse glucose-lowering medications, championing sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists as viable options to address concurrent cardiovascular risk. An oral formulation of semaglutide (Rybelsus((R)), Novo Nordisk) has been recently introduced to clinical use for managing T2DM. Accordingly, there is a paucity of practice evidence while building experience on its combination with SGLT2i. METHODS: In this observational, single-arm, retrospective study, data collected from 142 T2DM patients (66% males, 68% older than 60 years, 85% overweight/obese) treated with oral semaglutide in combination with SGLT2i were analyzed. RESULTS: After 6.8+/-2.6 months of treatment, both glycosylated hemoglobin (HbA1c) and fasting plasma glucose levels significantly improved: 39.6% of patients achieved HbA1cDCCT IFCC /=1% and a weight loss >/=5%. In addition, body weight, body mass index, waist circumference, triglycerides, and total cholesterol levels were significantly reduced. Regarding safety, 94.7% of reported adverse events were non-serious gastrointestinal symptoms and 1 patient experienced hypoglycemia. CONCLUSIONS: The herein presented real-world data suggest that oral semaglutide can be regarded as safe and effective, when used as add-on medication for uncontrolled T2DM on background SGLT2i. FAU - Malighetti, Maria E AU - Malighetti ME AD - Ambulatory of Diabetology, Casa di Cura Ambrosiana, Cesano Boscone, Milan, Italy. FAU - Vescini, Fabio AU - Vescini F AD - Section of Endocrinology, Azienda Sanitaria-Universitaria Friuli Centrale, Udine, Italy. FAU - Carpentieri, Maria AU - Carpentieri M AD - Section of Endocrinology, Azienda Sanitaria-Universitaria Friuli Centrale, Udine, Italy. FAU - Altomari, Anna AU - Altomari A AD - Center of Diabetology, S. Maria del Prato Hospital, Feltre, Belluno, Italy. FAU - Turchi, Federica AU - Turchi F AD - Metabolic Diseases and Diabetology Unit, IRCCS INRCA, Ancona, Italy. FAU - DA Porto, Andrea AU - DA Porto A AD - Clinica Medica, University of Udine, Udine, Italy. FAU - Dauriz, Marco AU - Dauriz M AD - Section of Endocrinology and Diabetes, Department of Internal Medicine, South-Tyrolean Healthcare System (SABES-ASDAA), Bolzano General Hospital, Bolzano, Italy - marco.dauriz@sabes.it. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20251127 PL - Italy TA - Minerva Endocrinol (Torino) JT - Minerva endocrinology JID - 101777342 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects/analysis MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Therapy, Combination MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Retrospective Studies MH - *Semaglutide/administration & dosage/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use EDAT- 2025/11/27 12:29 MHDA- 2026/09/07 11:37 CRDT- 2025/11/27 10:18 PHST- 2026/09/07 11:37 [medline] PHST- 2025/11/27 12:29 [pubmed] PHST- 2025/11/27 10:18 [entrez] AID - S2724-6507.25.04376-3 [pii] AID - 10.23736/S2724-6507.25.04376-3 [doi] PST - ppublish SO - Minerva Endocrinol (Torino). 2026 Sep;51(3):248-256. doi: 10.23736/S2724-6507.25.04376-3. Epub 2025 Nov 27. PMID- 41301492 OWN - NLM STAT- MEDLINE DCOM- 20251127 LR - 20260327 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 15 IP - 11 DP - 2025 Nov 10 TI - Current and Emerging Roles of GLP1 Receptor Agonists Across the Spectrum of Left Ventricular Ejection Fraction in Heart Failure. LID - 10.3390/biom15111574 [doi] LID - 1574 AB - Glucagon-like peptide-1 receptor agonists (GLP1-RAs) have demonstrated significant cardiometabolic benefits, particularly in patients with type 2 diabetes and obesity. Their role in heart failure (HF) is gaining increasing attention, with growing evidence supporting their efficacy in HF with preserved ejection fraction (HFpEF). Recent trials have shown that semaglutide improves symptoms, functional capacity, and weight loss in patients with HFpEF. However, these trials did not demonstrate a reduction in HF hospitalizations or mortality. In contrast, tirzepatide has revealed a significant reduction in cardiovascular death and worsening HF events in patients with obesity-related HFpEF, suggesting broader cardioprotective effects. Concordantly, the benefit of GLP1-RAs in the setting of HF with reduced ejection fraction (HFrEF) remains uncertain. Although their mechanisms suggest potential advantages, particularly for patients with a cardiometabolic phenotype, clinical evidence supporting improvements in major clinical outcomes is lacking. Additionally, concerns regarding risk of increased HF hospitalizations, fluid retention and arrhythmic risk have led to a cautious approach in this population. As HF management continues to evolve, GLP1-RAs emerge as a promising yet complex therapeutic option. This review synthesizes the current evidence, highlights key knowledge gaps, and explores how these medications might be integrated into guideline-directed medical therapy (GDMT) to determine their optimal role across the LVEF spectrum in HF. FAU - Crispino, Simone Pasquale AU - Crispino SP AUID- ORCID: 0000-0002-0051-5253 AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. AD - Department of Biomedical Engineering, Intelligent Technology Laboratory for Health and Wellbeing, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. FAU - Nusca, Annunziata AU - Nusca A AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. FAU - Ferro, Aurora AU - Ferro A AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. FAU - Cricco, Riccardo AU - Cricco R AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. FAU - Ciancio, Martina AU - Ciancio M AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. FAU - Segreti, Andrea AU - Segreti A AUID- ORCID: 0000-0003-2631-8642 AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. AD - Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", 00135 Rome, Italy. FAU - Cavallari, Ilaria AU - Cavallari I AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. FAU - Sabatino, Mario AU - Sabatino M AD - Heart Failure and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy. FAU - Potena, Luciano AU - Potena L AD - Heart Failure and Transplant Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy. FAU - Ussia, Gian Paolo AU - Ussia GP AUID- ORCID: 0000-0001-8849-3097 AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. FAU - Grigioni, Francesco AU - Grigioni F AD - Department of Medicine and Surgery, Universita Campus Bio-Medico di Roma, 00128 Rome, Italy. AD - Department of Medicine and Surgery, Fondazione Policlinico Campus Bio-Medico, 00128 Rome, Italy. LA - eng PT - Journal Article PT - Review DEP - 20251110 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Stroke Volume/drug effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Ventricular Function, Left/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12650310 OTO - NOTNLM OT - cardio-kidney-metabolic syndrome OT - cardiometabolic disease OT - cardiovascular prevention OT - glucagon-like peptide 1 receptor agonists OT - heart failure OT - heart failure with preserved ejection fraction OT - heart failure with reduced ejection fraction COIS- The authors declare no conflicts of interest. EDAT- 2025/11/27 06:28 MHDA- 2025/11/27 06:29 PMCR- 2025/11/10 CRDT- 2025/11/27 01:07 PHST- 2025/10/09 00:00 [received] PHST- 2025/10/28 00:00 [revised] PHST- 2025/10/30 00:00 [accepted] PHST- 2025/11/27 06:29 [medline] PHST- 2025/11/27 06:28 [pubmed] PHST- 2025/11/27 01:07 [entrez] PHST- 2025/11/10 00:00 [pmc-release] AID - biom15111574 [pii] AID - biomolecules-15-01574 [pii] AID - 10.3390/biom15111574 [doi] PST - epublish SO - Biomolecules. 2025 Nov 10;15(11):1574. doi: 10.3390/biom15111574. PMID- 41297885 OWN - NLM STAT- MEDLINE DCOM- 20260319 LR - 20260319 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 32 IP - 3 DP - 2026 Mar TI - Cardiovascular Outcomes in Adults With Type 2 Diabetes Treated With Tirzepatide: A Systematic Review and Meta-Analysis of Real-World Studies. PG - 369-379 LID - S1530-891X(25)01292-3 [pii] LID - 10.1016/j.eprac.2025.11.010 [doi] AB - OBJECTIVE: Tirzepatide shows benefits on cardiovascular (CV) parameters and major adverse cardiovascular events (MACE) in clinical trials, but real-world data, especially for type 2 diabetes (T2D), are limited. This systematic review and meta-analysis seeks to address this gap. METHODS: Multiple databases and registries were searched for real-world observational studies involving individuals with T2D receiving tirzepatide. The co-primary outcomes were acute coronary syndrome (ACS), heart failure (HF), sudden cardiac death, and stroke. RevMan Web was used to conduct meta-analyses employing random-effects models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Eight retrospective cohort studies (N = 118 252) were included. Compared to the control group, tirzepatide reduced risks of ACS (HR 0.74 [0.62-0.89], P = .001), HF (HR 0.65 [0.53-0.82], P = .0002), stroke (HR 0.71 [0.62-0.81], P < .00001), MACE (HR 0.72 [0.60-0.86], P = .0004), and all-cause mortality (HR 0.49 [0.37-0.67], P < .00001). However, the risk of sudden cardiac death was similar between groups. The risk of composite outcomes of all-cause mortality plus CV outcomes was also lower with tirzepatide (HR 0.65 [0.54-0.79], P < .0001). Compared to semaglutide, tirzepatide had lower risks of stroke and MACE but similar risks for ACS, HF, sudden cardiac death, all-cause mortality, and composite outcomes. CONCLUSIONS: Tirzepatide offers the potential to reduce the risks of ACS, HF, stroke, MACE, and death in real-world patients with T2D, suggesting CV benefits. Larger trials are needed to confirm long-term CV effects and define its role in T2D and CV management. CI - Copyright (c) 2025 AACE. Published by Elsevier Inc. All rights reserved. FAU - Kamrul-Hasan, A B M AU - Kamrul-Hasan ABM AD - Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh. Electronic address: rangassmc@gmail.com. FAU - Chatterjee, Subhankar AU - Chatterjee S AD - Department of Endocrinology, Medical College and Hospital, Kolkata, West Bengal, India. FAU - Ashraf, Hamid AU - Ashraf H AD - Rajiv Gandhi Centre for Diabetes and Endocrinology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India. FAU - Nagendra, Lakshmi AU - Nagendra L AD - Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, India. FAU - Dutta, Deep AU - Dutta D AD - Department of Endocrinology, CEDAR Superspeciality Healthcare, Dwarka, New Delhi, Delhi, India. FAU - Pappachan, Joseph M AU - Pappachan JM AD - Faculty of Science, Manchester Metropolitan University, Manchester, United Kingdom; Department of Endocrinology, Countess of Chester Hospital NHS Foundation Trust, Chester, Cheshire, United Kingdom; Department of Endocrinology, Kasturba Medical College, Manipal and Manipal Academy of Higher Education, Manipal, Karnataka, India. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251124 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Cardiovascular Diseases/epidemiology/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Adult MH - Tirzepatide OTO - NOTNLM OT - Acute coronary syndrome OT - All-cause mortality OT - Major adverse cardiovascular events OT - Real-world study OT - Tirzepatide OT - Type 2 diabetes COIS- Disclosure The authors assert the absence of any identifiable financial conflicts or personal relationships that could be perceived as impacting the integrity of the findings reported in this manuscript. EDAT- 2025/11/27 00:27 MHDA- 2026/03/20 00:59 CRDT- 2025/11/26 19:34 PHST- 2025/09/16 00:00 [received] PHST- 2025/11/12 00:00 [revised] PHST- 2025/11/12 00:00 [accepted] PHST- 2026/03/20 00:59 [medline] PHST- 2025/11/27 00:27 [pubmed] PHST- 2025/11/26 19:34 [entrez] AID - S1530-891X(25)01292-3 [pii] AID - 10.1016/j.eprac.2025.11.010 [doi] PST - ppublish SO - Endocr Pract. 2026 Mar;32(3):369-379. doi: 10.1016/j.eprac.2025.11.010. Epub 2025 Nov 24. PMID- 41297711 OWN - NLM STAT- MEDLINE DCOM- 20251218 LR - 20260127 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 445 DP - 2026 Feb 15 TI - Early glucagon-like peptide-1 receptor agonist use after myocardial infarction in patients with type 2 diabetes. PG - 134042 LID - S0167-5273(25)01085-X [pii] LID - 10.1016/j.ijcard.2025.134042 [doi] AB - AIMS: Acute myocardial infarction (AMI) is among the leading causes of mortality in patients with type 2 diabetes (T2DM). This study evaluated whether initiation of glucagon-like peptide-1 receptor agonists (GLP1RAs) post-AMI improves cardiovascular outcomes in this population. METHODS: This retrospective cohort study used the TriNetX Research Network to identify adult patients with T2DM who experienced an AMI between January 1, 2017, and December 31, 2023. Patients were included if they initiated tirzepatide or semaglutide within 14 days post-AMI. Propensity score matching (PSM) was performed to balance baseline characteristics. The primary outcome was recurrent coronary events, and secondary outcomes included all-cause mortality and hospitalizations, heart failure (HF) hospitalizations, acute kidney injury (AKI), and cardiac arrest. Hazard ratios (HR) were estimated using Cox proportional hazard models. RESULTS: 5338 patients were included in each cohort. Mean follow-up was 327.7 days (GLP1RA group) vs. 307.9 days (non-GLP1RA group). GLP1RA use did not significantly reduce recurrent coronary events (3.7 % vs 3.8 %; HR 0.913, 95 % CI 0.750-1.111). GLP1RA use was associated with significantly lower all-cause mortality (HR 0.484, 95 % CI 0.413-0.567), HF hospitalizations (HR 0.578, 95 % CI 0.531-0.630), AKI (HR 0.688, 95 % CI 0.610-0.732), cardiac arrest (HR 0.549, 95 % CI 0.418-0.722), and all-cause hospitalizations (HR 0.673, 95 % CI 0.636-0.713). CONCLUSIONS: GLP1RA initiation in patients with T2DM post-AMI was not associated with a reduction in recurrent coronary events, but was linked to improvements in other cardiovascular outcomes, suggesting a potential role for GLP1RAs as part of a secondary prevention strategy. CI - Copyright (c) 2024. Published by Elsevier B.V. FAU - Ahmad, Omar AU - Ahmad O AD - College of Medicine, Alfaisal University, Riyadh, Saudi Arabia. FAU - Ibrahim, Ramzi AU - Ibrahim R AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. Electronic address: Ibrahim.ramzi@mayo.edu. FAU - Pham, Hoang Nhat AU - Pham HN AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA; Department of Medicine, University of Arizona, Tucson, AZ, USA. FAU - Abdelnabi, Mahmoud AU - Abdelnabi M AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Elbenawi, Hossam AU - Elbenawi H AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA. FAU - Salih, Mohammed AU - Salih M AD - Department of Cardiology, Baylor Scott and White-The Heart Hospital, Plano, TX, United States of America. FAU - Farina, Juan AU - Farina J AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Bhakta, Mayurkumar D AU - Bhakta MD AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Sell-Dottin, Kristen A AU - Sell-Dottin KA AD - Department of Cardiothoracic Surgery, Mayo Clinic, Phoenix, AZ, United States of America. FAU - Yang, Eric H AU - Yang EH AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Sweeney, John P AU - Sweeney JP AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Fortuin, F David AU - Fortuin FD AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Simper, David AU - Simper D AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Al-Kindi, Sadeer AU - Al-Kindi S AD - Center for CV Computational and Precision Health, Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. FAU - Lee, Kwan AU - Lee K AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Nasir, Khurram AU - Nasir K AD - Center for CV Computational and Precision Health, Division of Cardiovascular Prevention and Wellness, Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. FAU - Ayoub, Chadi AU - Ayoub C AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. FAU - Arsanjani, Reza AU - Arsanjani R AD - Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, AZ, USA. LA - eng PT - Journal Article DEP - 20251124 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/complications/epidemiology MH - Male MH - Female MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Myocardial Infarction/drug therapy/diagnosis/mortality/epidemiology MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Follow-Up Studies MH - Cohort Studies MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of competing interest None. EDAT- 2025/11/27 00:27 MHDA- 2025/12/19 01:45 CRDT- 2025/11/26 19:13 PHST- 2025/08/07 00:00 [received] PHST- 2025/11/08 00:00 [revised] PHST- 2025/11/23 00:00 [accepted] PHST- 2025/12/19 01:45 [medline] PHST- 2025/11/27 00:27 [pubmed] PHST- 2025/11/26 19:13 [entrez] AID - S0167-5273(25)01085-X [pii] AID - 10.1016/j.ijcard.2025.134042 [doi] PST - ppublish SO - Int J Cardiol. 2026 Feb 15;445:134042. doi: 10.1016/j.ijcard.2025.134042. Epub 2025 Nov 24. PMID- 41287564 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260808 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - Assessment of thyroid cancer risk associated with glucagon-like peptide 1 receptor agonist use. PG - 1499-1507 LID - 10.1111/dom.70291 [doi] AB - AIMS: Published literature has raised concerns regarding a causal association between glucagon-like peptide 1 receptor agonist (GLP-1RA) use and thyroid cancer risk in adults. In this analysis, we evaluated the association between thyroid cancer risk and GLP-1RA use. MATERIALS AND METHODS: Our evaluation included data from (i) 93 liraglutide or semaglutide phase 2 and 3 clinical trials, of which six were cardiovascular outcome trials (CVOTs); (ii) post-marketing surveillance from the Novo Nordisk safety database (evaluating data for liraglutide and semaglutide); and (iii) the US Merative MarketScan(R) Commercial Database. Hazard ratios (HRs) were estimated for overall thyroid cancer risk for treatment groups in the clinical trials and for individuals with type 2 diabetes treated with any GLP-1RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT2is) for the real-world data. RESULTS: Data from all clinical trials across 101 732 participants (totalling 206 950 patient-years of exposure [PYE]) reported low numbers of thyroid cancer events; across all trials, HRs were 1.70 (95% confidence interval [CI] 0.99, 3.03) and 1.83 (0.70, 6.71) for pooled GLP-1RA versus pooled placebo and active comparator, respectively. For CVOTs, the HR (95% CI) for pooled GLP-1RA versus pooled placebo was 1.41 (0.72, 2.81). Post-marketing surveillance data showed a low thyroid cancer reporting rate of 0.001 cases/100 PYE and did not support an association between liraglutide or semaglutide exposure and the number of thyroid cancer events. Analysis of the US Merative MarketScan(R) Commercial Database reported an HR of 0.87 (95% CI 0.58, 1.29) for the occurrence of thyroid cancer in individuals using any GLP-1RAs versus SGLT2is. CONCLUSIONS: The totality of data analysed did not suggest an association between liraglutide or semaglutide use and thyroid cancer risk in adults. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Vilsboll, Tina AU - Vilsboll T AUID- ORCID: 0000-0002-0456-6787 AD - Clinical Research, Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Stellfeld, Michael AU - Stellfeld M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Dandanell, Sune AU - Dandanell S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - David, Jens-Peter AU - David JP AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kristiansen, Ceyda T P AU - Kristiansen CTP AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Roberts, Fiona L AU - Roberts FL AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hegedus, Laszlo AU - Hegedus L AD - Department of Endocrinology, Odense University Hospital, University of Southern Denmark, Odense, Denmark. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article DEP - 20251125 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Thyroid Neoplasms/epidemiology/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Liraglutide/adverse effects/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Adult MH - Risk Assessment MH - Clinical Trials, Phase II as Topic MH - Aged MH - Product Surveillance, Postmarketing MH - Risk Factors MH - Clinical Trials, Phase III as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12803555 OTO - NOTNLM OT - GLP-1 analogue OT - clinical trial OT - real-world evidence OT - type 2 diabetes OT - weight management COIS- Tina Vilsboll has served on scientific advisory panels and/or speakers' bureaus for or has served as a consultant to and/or received research support from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD/Merck, Novo Nordisk, Regor, Roche/Carmot, Zealand Pharma, Sanofi, and Sun Pharmaceuticals. Michael Stellfeld, Sune Dandanell, Jens-Peter David, Ceyda T. P. Kristiansen, Soren Rasmussen, and Fiona L. Roberts are employees of, and shareholders in, Novo Nordisk. Vanita R. Aroda reports research grant support (to institution) from Amgen, Applied Therapeutics, AstraZeneca, Biomea, Boehringer Ingelheim, Corcept Therapeutics, Eli Lilly, Fractyl Health, Novo Nordisk A/S, Pfizer, Recordati, Rhythm Pharmaceuticals, and Servier, and consulting fees from Mediflix and Sanofi. Laszlo Hegedus has served on scientific advisory panels and/or speakers' bureaus or has served as a consultant to and/or received research support from Amgen, Berlin-Chemie, Horizon, IBSA, Linical, Merck, and Novo Nordisk. EDAT- 2025/11/25 06:27 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/25 04:36 PHST- 2025/10/27 00:00 [revised] PHST- 2025/07/25 00:00 [received] PHST- 2025/10/28 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/25 06:27 [pubmed] PHST- 2025/11/25 04:36 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70291 [pii] AID - 10.1111/dom.70291 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):1499-1507. doi: 10.1111/dom.70291. Epub 2025 Nov 25. PMID- 41286875 OWN - NLM STAT- MEDLINE DCOM- 20251125 LR - 20261022 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 23 IP - 1 DP - 2025 Nov 24 TI - The adverse effects associated with semaglutide use in patients at increased risk of cardiovascular events: a systematic review with meta-analysis and Trial Sequential Analysis. PG - 654 LID - 10.1186/s12916-025-04486-0 [doi] LID - 654 AB - BACKGROUND: Semaglutide's disease-specific weight-reducing effects are well established, but its adverse effects, which may not be disease-specific, have not been systematically assessed. The aim of this review was to assess the adverse effects associated with semaglutide use compared with placebo in patients at increased risk of cardiovascular events. METHODS: We searched six electronic databases and other sources from inception to 31/03/2025. Randomized trials comparing semaglutide (oral or subcutaneous) with placebo in patients at increased risk of cardiovascular events were eligible. The search identified 8370 records. Two review authors independently screened all studies for eligibility. Data were synthesized using meta-analysis and Trial Sequential Analysis (TSA). Risk of bias was assessed with the Cochrane Risk of Bias tool - version 2; our eight-step procedure was used to assess if the thresholds for statistical significance were crossed, and the certainty of the evidence was assessed by the Grading of Recommendations, Assessment, Development and Evaluations. Primary outcomes were all-cause mortality and serious adverse events (SAEs). Secondary outcomes included myocardial infarction and non-serious adverse events (AEs). RESULTS: The analysis included 50 trials, with a total of 54,972 participants randomized. Nineteen (38%) enrolled participants with type 2 diabetes (T2DM), 17 (34%) with overweight, 5 (10%) with T2DM and chronic kidney disease, 5 (10%) with T2DM and overweight, and 4 (8%) involved other patient populations. Meta-analysis and TSA showed evidence of beneficial effects of semaglutide on all-cause mortality (relative risk (RR) 0.85; 95% CI 0.79 to 0.91; I(2) = 0.0%; p < 0.01) and myocardial infarction (RR 0.77, 95% CI 0.69 to 0.85; I(2) = 0.0%; p < 0.01). None of these analyses showed signs of heterogeneity, and the evidence was of high certainty. Meta-analysis showed that semaglutide decreased the risk of SAEs (RR 0.93, 95% CI 0.88 to 0.98; I(2) = 24.1%; p < 0.01), but increased the risk of several non-serious gastrointestinal AEs including nausea (RR 3.00, 95% CI 2.63 to 3.42), vomiting (RR 4.12, 95% CI 3.47 to 4.90), and diarrhea (RR 1.88, 95% CI 1.68 to 2.11). CONCLUSIONS: In patients at increased risk of cardiovascular events, semaglutide reduced the risk of mortality, SAEs, and myocardial infarction but increased the risk of several non-serious gastrointestinal AEs. REGISTRATION: PROSPERO, CRD42024499511. CI - (c) 2025. The Author(s). FAU - Sillassen, Christina Dam Bjerregaard AU - Sillassen CDB AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. christina.sillassen@ctu.dk. AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Region of Zealand, Denmark. christina.sillassen@ctu.dk. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. christina.sillassen@ctu.dk. FAU - Petersen, Johanne Juul AU - Petersen JJ AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Faltermeier, Pascal AU - Faltermeier P AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Yucel, Delal AU - Yucel D AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Siddiqui, Faiza AU - Siddiqui F AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Andersen, Rebecca Kjaer AU - Andersen RK AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Graever, Leonardo AU - Graever L AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Department of Clinical Medicine, Faculty of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Bjerg, Jonas Leth AU - Bjerg JL AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Kamp, Caroline Barkholt AU - Kamp CB AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. FAU - Grand, Johannes AU - Grand J AD - Department of Cardiology, Copenhagen University Hospital - Amager-Hvidovre Hospital, Copenhagen, Denmark. FAU - Dominguez, Helena AU - Dominguez H AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Department of Cardiology, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark. FAU - Frolich, Anne AU - Frolich A AD - Innovation and Research Centre for Multimorbidity, Slagelse Hospital, Slagelse, Region of Zealand, Denmark. AD - Section of General Practice, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Gaede, Peter AU - Gaede P AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Region of Zealand, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Gluud, Christian AU - Gluud C AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Mathiesen, Ole AU - Mathiesen O AD - Department of Anaesthesiology, Centre for Anaesthesiological Research, Zealand University Hospital, Koge, Denmark. AD - Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark. FAU - Jakobsen, Janus Christian AU - Jakobsen JC AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital -Rigshospitalet, The Capital Region, Copenhagen, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251124 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Cardiovascular Diseases/epidemiology MH - Randomized Controlled Trials as Topic MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12642075 OTO - NOTNLM OT - Meta-analysis OT - Placebo OT - Safety OT - Semaglutide OT - Systematic review OT - Trial sequential analysis COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: CDBS's husband has previously been employed at Novo Nordisk, Kalundborg, as 'facility manager' and 'sprinkler technician' (employed from September 1, 2024, to August 31, 2025). PG has received lecture fees for Novo Nordisk, AstraZeneca, Eli Lilly, Bayer, and MSD and has served in Advisory Boards for Novo Nordisk, AstraZeneca, and Bayer. The remaining authors declare no known competing interests. EDAT- 2025/11/25 06:27 MHDA- 2025/11/25 06:28 PMCR- 2025/11/24 CRDT- 2025/11/25 03:28 PHST- 2025/06/07 00:00 [received] PHST- 2025/10/27 00:00 [accepted] PHST- 2025/11/25 06:28 [medline] PHST- 2025/11/25 06:27 [pubmed] PHST- 2025/11/25 03:28 [entrez] PHST- 2025/11/24 00:00 [pmc-release] AID - 10.1186/s12916-025-04486-0 [pii] AID - 4486 [pii] AID - 10.1186/s12916-025-04486-0 [doi] PST - epublish SO - BMC Med. 2025 Nov 24;23(1):654. doi: 10.1186/s12916-025-04486-0. PMID- 41286734 OWN - NLM STAT- MEDLINE DCOM- 20251230 LR - 20260908 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Nov 24 TI - Temporal and subgroup disparities in mediation effects on cardiovascular outcomes with liraglutide and semaglutide: a post-hoc analysis of LEADER and SUSTAIN-6 trials. PG - 465 LID - 10.1186/s12933-025-03007-w [doi] LID - 465 AB - BACKGROUND: It is unclear whether the time-varying mediation effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the three-point major adverse cardiovascular event (3P-MACE) outcomes, including nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death, via HbA(1c), urine albumin-to-creatinine ratio (UACR), and systolic blood pressure (SBP) vary by types of GLP-1RAs, and patient subgroups. METHODS: A causal mediation analysis was applied to assess the mediation effects of HbA(1c), UACR, and SBP on the 3P-MACE with liraglutide and semaglutide over time, using the LEADER and SUSTAIN-6 trials. We further explored the heterogeneity in mediation effects in subsets of vulnerable patients, including those with an estimated glomerular filtration rate (eGFR) level of < 60 ml/min/1.73 m(2) or established cardiovascular diseases (CVDs). RESULTS: Individual-level data consisting of 9340 (liraglutide: 4668; placebo: 4672) and 3297 (semaglutide: 1648; placebo: 1649) subjects from the LEADER and SUSTAIN-6 trials, respectively, was utilized for this study. The study population aged around 64.2-64.4/64.4-64.8 years old, with 64.0%-64.5%/58.5%-63.0% of males, and having a diabetes duration of 12.8-12.9/13.2-14.3 years in the LEADER/SUSTAIN-6 trials, respectively. Among study populations, those established CVDs (e.g., heart failure, stroke, myocardial infarction) accounted for 14.0%-35.4% in the LEADER trial, whereas 13.7%-61.9% in the SUSTAIN-6 trial. At the end of each trial, HbA(1c) contributed the most to liraglutide's/semaglutide's effect on 3P-MACE (38.2%, 95% confidence interval: 13.8%-194.5%/51.8%, 29.6%-86.7%), followed by UACR (17.9%, 8.5%-61.9%/12.4%, 6.1%-32.4%) and SBP (6.8%, 2.2%-31.0%/6.7%, 2.9%-11.7%), respectively. Over the trial period, the effect of liraglutide mediated by HbA(1c) increased from 31.3% to 38.2%, whereas the effects of semaglutide mediated by HbA(1c) remained stable from 52.5% to 51.8%. For patients with eGFR < 60 ml/min/1.73 m(2), HbA(1c) was the leading mediator (35.2%) of semaglutide-associated 3P-MACE, while the mediation effects via HbA(1c) (7.2%), UACR (11.8%), and SBP (5.1%) on liraglutide-associated 3P-MACE seemed similar and smaller. For patients with established CVDs, HbA(1c) was the leading mediator of liraglutide- (25.3%) and semaglutide-associated 3P-MACE (51.2%). CONCLUSIONS: The HbA(1c)-mediated effects of liraglutide and semaglutide varied over time and across patient subgroups. HbA(1c) consistently explained a larger proportion of mediation compared to UACR and SBP, with patterns suggesting that mediation through HbA(1c) may differ by underlying risk factors. CI - (c) 2025. The Author(s). FAU - Peng, Zi-Yang AU - Peng ZY AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lee, Yu-Hsuan AU - Lee YH AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Ou, Huang-Tz AU - Ou HT AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. huangtz@mail.ncku.edu.tw. AD - Department of Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan. huangtz@mail.ncku.edu.tw. FAU - Kuo, Shihchen AU - Kuo S AD - Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. AD - Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America. LA - eng GR - grant NSTC 112-2628-B-006-008-MY3/National Science and Technology Council in Taiwan/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251124 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Incretins) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Liraglutide/adverse effects/therapeutic use MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Time Factors MH - Male MH - Treatment Outcome MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/mortality/diagnosis/physiopathology/prevention & control MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/blood MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glycated Hemoglobin/metabolism MH - *Incretins/adverse effects/therapeutic use MH - Risk Assessment MH - Biomarkers/blood/urine MH - Aged MH - *Blood Glucose/metabolism/drug effects MH - Randomized Controlled Trials as Topic MH - Glomerular Filtration Rate/drug effects MH - Albuminuria MH - Blood Pressure/drug effects MH - *Kidney/physiopathology MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12751512 COIS- Declarations. Ethics approval and consent to participate: To comply with the Declaration of Helsinki, both trials adhered to the policy of the institutional review board or ethics committee at the corresponding study site, with written informed consent provided to the trial participants at enrollment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/11/25 06:27 MHDA- 2025/12/30 07:41 PMCR- 2025/11/24 CRDT- 2025/11/25 03:10 PHST- 2025/08/05 00:00 [received] PHST- 2025/11/04 00:00 [accepted] PHST- 2025/12/30 07:41 [medline] PHST- 2025/11/25 06:27 [pubmed] PHST- 2025/11/25 03:10 [entrez] PHST- 2025/11/24 00:00 [pmc-release] AID - 10.1186/s12933-025-03007-w [pii] AID - 3007 [pii] AID - 10.1186/s12933-025-03007-w [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Nov 24;24(1):465. doi: 10.1186/s12933-025-03007-w. PMID- 41283266 OWN - NLM STAT- MEDLINE DCOM- 20251124 LR - 20260707 IS - 2076-3271 (Electronic) IS - 2076-3271 (Linking) VI - 13 IP - 4 DP - 2025 Nov 12 TI - Semaglutide from Bench to Bedside: The Experimental Journey Towards a Transformative Therapy for Diabetes, Obesity and Metabolic Liver Disorders. LID - 10.3390/medsci13040265 [doi] LID - 265 AB - BACKGROUND/OBJECTIVES: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly evolved from a theoretical concept to a crucial component of modern metabolic care. This review explores the comprehensive development journey of semaglutide, drawing on evidence from medicinal chemistry, animal studies, initial human trials, the pivotal SUSTAIN and STEP programs, and real-world post-marketing surveillance. METHODS: We conducted a detailed analysis of preclinical data sets, Phase I-III clinical trials, regulatory documents, and pharmaco-epidemiological studies published between 2008 and 2025. RESULTS: Through strategic molecular modifications, such as specific amino-acid substitutions and the addition of a C18 fatty-diacid side chain to enhance albumin binding, the half-life of the peptide was extended to approximately 160 h, allowing for weekly dosing. Studies in rodents and non-human primates showed that semaglutide effectively lowered blood glucose levels, reduced body weight, and preserved beta-cells while maintaining a favorable safety profile. Phase I trials confirmed consistent pharmacokinetics and tolerability, while Phase II trials identified 0.5 mg and 1.0 mg once weekly as the most effective doses. The extensive SUSTAIN program validated significant reductions in HbA1c levels and weight loss compared to other treatments, as well as a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). Subsequent STEP trials expanded the use of semaglutide to chronic weight management, revealing that nearly two-thirds of patients experienced a body weight reduction of at least 15%. Regulatory approvals from the FDA, EMA, and other regulatory agencies were obtained between 2017 and 2021, with ongoing research focusing on metabolic dysfunction-associated steatohepatitis, cardiovascular events, and chronic kidney disease. CONCLUSIONS: The trajectory of semaglutide exemplifies how intentional peptide design, iterative translational research, and outcome-driven clinical trial design can lead to groundbreaking therapies for complex metabolic disorders. FAU - Weiskirchen, Ralf AU - Weiskirchen R AUID- ORCID: 0000-0003-3888-0931 AD - Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany. FAU - Lonardo, Amedeo AU - Lonardo A AUID- ORCID: 0000-0001-9886-0698 AD - Ospedale Civile di Baggiovara (-2023), Department of Internal Medicine, AOU Modena, 41100 Modena, Italy. LA - eng PT - Journal Article PT - Review DEP - 20251112 PL - Switzerland TA - Med Sci (Basel) JT - Medical sciences (Basel, Switzerland) JID - 101629322 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Humans MH - Animals MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Liver Diseases/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12642005 OTO - NOTNLM OT - GLP-1 receptor agonist OT - MACE OT - MASLD/MASH OT - STEP and SUSTAIN clinical trials OT - heart failure OT - obesity OT - semaglutide OT - translational pharmacology OT - type 2 diabetes OT - weight management COIS- A.L. is member of the Editorial Board of Medical Sciences. However, he was not involved in any phase of the Editorial processing of this manuscript. R.W. declares no conflicts of interest. EDAT- 2025/11/24 12:39 MHDA- 2025/11/24 18:38 PMCR- 2025/11/12 CRDT- 2025/11/24 09:21 PHST- 2025/10/25 00:00 [received] PHST- 2025/11/10 00:00 [revised] PHST- 2025/11/11 00:00 [accepted] PHST- 2025/11/24 18:38 [medline] PHST- 2025/11/24 12:39 [pubmed] PHST- 2025/11/24 09:21 [entrez] PHST- 2025/11/12 00:00 [pmc-release] AID - medsci13040265 [pii] AID - medsci-13-00265 [pii] AID - 10.3390/medsci13040265 [doi] PST - epublish SO - Med Sci (Basel). 2025 Nov 12;13(4):265. doi: 10.3390/medsci13040265. PMID- 41277213 OWN - NLM STAT- MEDLINE DCOM- 20251124 LR - 20251215 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 73 IP - 11 DP - 2025 Nov TI - The Weight of the Matter in Diabetes Care. PG - 87-88 LID - 10.59556/japi.73.1201 [doi] AB - The weight of the matter in diabetes care challenges the traditional glucose-centric model of diabetes management and argues for a paradigm shift toward prioritizing weight-specifically fat reduction-as the central lever in achieving metabolic health. Drawing insights from landmark trials such as SURMOUNT and Diabetes Remission Clinical Trial (DiRECT), as well as real-world Indian experience with agents like oral semaglutide, the article emphasizes that visceral adiposity is a root cause driving insulin resistance, beta-cell dysfunction, and multiorgan complications. Addressing weight early can lead to improved glycemic control, cardiorenal protection, and even disease remission-outcomes that far exceed glucose lowering alone. In the Indian context, where the "thin-fat" phenotype and central obesity present unique challenges, this weight-first approach demands culturally sensitive strategies and redefined success metrics beyond body mass index (BMI) or hemoglobin A1c (HbA1c). With the advent of incretin-based therapies, clinicians now have the tools to treat upstream rather than manage symptoms downstream. The piece calls for a unified therapeutic strategy that targets excess adiposity to deliver both glycemic and vascular legacy benefits-reframing weight not merely as a number but as a powerful determinant of risk, response, and recovery. CI - (c) Journal of The Association of Physicians of India 2025. FAU - Bhattacharyya, Supratik AU - Bhattacharyya S AD - Consultant Endocrinologist, SKN Diabetes and Endocrine Centre, Kolkata, West Bengal, India, Orcid: https://orcid.org/0000-0002-2351-7470, Corresponding Author. LA - eng PT - Journal Article PT - Review PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/therapy/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - India MH - Insulin Resistance EDAT- 2025/11/24 06:27 MHDA- 2025/11/24 06:28 CRDT- 2025/11/24 02:47 PHST- 2025/11/24 06:28 [medline] PHST- 2025/11/24 06:27 [pubmed] PHST- 2025/11/24 02:47 [entrez] AID - 10.59556/japi.73.1201 [doi] PST - ppublish SO - J Assoc Physicians India. 2025 Nov;73(11):87-88. doi: 10.59556/japi.73.1201. PMID- 41276951 OWN - NLM STAT- MEDLINE DCOM- 20251124 LR - 20260127 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 8 IP - 6 DP - 2025 Nov TI - Safety and Efficacy of Semaglutide in Patients With Chronic Kidney Disease, With or Without Type 2 Diabetes: A Systematic Review and Meta-Analysis. PG - e70136 LID - 10.1002/edm2.70136 [doi] LID - e70136 AB - BACKGROUND: Chronic kidney disease (CKD) affects over half a billion people globally and significantly increases the risk of cardiovascular complications, particularly in those with type 2 diabetes mellitus (T2DM). Although semaglutide, a glucagon-like peptide-1 receptor agonist, has shown favourable cardiorenal effects in T2DM patients, prior meta-analyses were limited by small sample sizes and few studies. This updated meta-analysis includes both diabetic and non-diabetic CKD patients, incorporates recently published RCTs and addresses gaps in the literature to enhance result generalizability. METHODS: MEDLINE, Embase and Cochrane CENTRAL were searched from inception to May 2025 following PRISMA and AMSTAR guidelines. Studies comparing semaglutide with placebo or standard care in adults (>/= 18 years) with CKD, with or without T2DM were included. Primary outcomes included cardiovascular mortality, major adverse cardiovascular events (MACE), major kidney-related adverse events, nonfatal myocardial infarction and nonfatal stroke. Risk of bias was assessed using Cochrane RoB 2.0. RESULTS: Five RCTs involving 12,785 participants were included. The findings showed that semaglutide substantially decreased major kidney-related adverse events (defined as a composite outcome encompassing the onset of kidney failure (including long-term dialysis, kidney transplantation or a sustained eGFR reduction to < 15 mL/min/1.73 m(2)), a sustained 50% or greater reduction in eGFR from baseline, or death due to kidney-related causes) (RR: 0.79; 95% CI: 0.71-0.87; p < 0.00001; I(2) = 0%), cardiovascular mortality (RR: 0.74; 95% CI: 0.62-0.88; p = 0.0008; I(2) = 36%) and MACE (defined as a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) (RR: 0.78; 95% CI: 0.70-0.87; p < 0.00001; I(2) = 0%). CONCLUSION: Semaglutide demonstrates a favourable safety profile and significant cardiorenal benefits in CKD patients, with or without T2DM. Further research is needed to confirm its effects in non-diabetic CKD populations. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD420251019235. CI - (c) 2025 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Abdullah, Ali AU - Abdullah A AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Sagreeka, F N U AU - Sagreeka FNU AD - Ghulam Muhammad Mahar Medical College, Sukkur, Pakistan. FAU - Aniket, Gurdas Alias AU - Aniket GA AD - Ghulam Muhammad Mahar Medical College, Sukkur, Pakistan. FAU - Lal, Rohan AU - Lal R AD - Ghulam Muhammad Mahar Medical College, Sukkur, Pakistan. FAU - Geeta, F N U AU - Geeta FNU AD - Chandka Medical College, Larkana, Pakistan. FAU - Bai, Anusha AU - Bai A AD - Chandka Medical College, Larkana, Pakistan. FAU - Ahmed, Ghazi Uddin AU - Ahmed GU AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Raza, Ahmed Asad AU - Raza AA AUID- ORCID: 0009-0004-2930-8188 AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Shaikh, Varisha Fatima AU - Shaikh VF AD - Dow Medical College, Karachi, Pakistan. FAU - Sanaullah, Owais AU - Sanaullah O AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Sabahat, Syeda Elezeh AU - Sabahat SE AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Ghori, Ahzam Khan AU - Ghori AK AD - Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Bhutto, Seema Habib AU - Bhutto SH AD - Jinnah Medical and Dental College, Karachi, Pakistan. FAU - Tesfaye, Mahir AU - Tesfaye M AUID- ORCID: 0009-0003-7324-5121 AD - Addis Ababa University, Addis Ababa, Ethiopia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Cardiovascular Diseases/prevention & control MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12640882 OTO - NOTNLM OT - GLP-1 receptor agonist OT - cardiovascular outcomes OT - chronic kidney disease OT - major adverse cardiovascular events OT - major kidney adverse events OT - meta-analysis OT - renal outcomes OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2025/11/24 06:27 MHDA- 2025/11/24 06:28 PMCR- 2025/11/23 CRDT- 2025/11/24 00:33 PHST- 2025/07/29 00:00 [revised] PHST- 2025/05/23 00:00 [received] PHST- 2025/11/07 00:00 [accepted] PHST- 2025/11/24 06:28 [medline] PHST- 2025/11/24 06:27 [pubmed] PHST- 2025/11/24 00:33 [entrez] PHST- 2025/11/23 00:00 [pmc-release] AID - EDM270136 [pii] AID - 10.1002/edm2.70136 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2025 Nov;8(6):e70136. doi: 10.1002/edm2.70136. PMID- 41272444 OWN - NLM STAT- MEDLINE DCOM- 20251230 LR - 20260423 IS - 1471-2261 (Electronic) IS - 1471-2261 (Linking) VI - 25 IP - 1 DP - 2025 Nov 21 TI - Cardiovascular benefits of semaglutide: a systematic review and meta-analysis of randomized controlled trials. PG - 881 LID - 10.1186/s12872-025-05278-3 [doi] LID - 881 AB - BACKGROUND: Semaglutide, a GLP-1 receptor agonist (GLP-1RA), has shown potential in controlling type 2 diabetes due to their ability to lower blood glucose and improve cardiovascular outcomes. Although semaglutide is the newest GLP-1RA available, its cardiovascular effects have not yet been systematically reviewed. METHODS: This meta-analysis adhered to a pre-registered protocol (PROSPERO ID: CRD42024538847). PubMed, Scopus, and Web of Science were searched comprehensively on February 26, 2024, to locate randomized controlled trials (RCTs) assessing semaglutide's impact on cardiovascular outcomes. A random effects model was used to analyze the data and the Cochrane risk of bias 2 tool was used to assess the quality of included studies. RESULTS: There were four RCTs involving 27,617 individuals (13,809 receiving semaglutide and 13,808 receiving placebo). There was a significant reduction in the risk of major adverse cardiovascular events (MACE) after administration of semaglutide (RR: 0.81, 95% CI: 0.74-0.88, p < 0.001, I(2): 0.00%). Additionally, benefits were observed for particular findings such as cardiovascular death and nonfatal myocardial infarction. However, semaglutide showed no significant effect on nonfatal stroke, heart failure hospitalizations, or admissions for unstable angina. The treatment also led to fewer serious adverse events (RR: 0.91, 95% CI: 0.88-0.94, p < 0.001, I(2): 0.01%), though it was linked to a higher rate of treatment discontinuation (RR: 1.67, 95% CI: 1.27-2.21, p < 0.001, I(2): 91.09%), which was underemphasized in its clinical implications and should be interpreted more cautiously considering the trade-off with benefits. CONCLUSION: Semaglutide effectively reduces the risk of MACE and modestly improves cardiovascular mortality rates and nonfatal myocardial infarction, without significantly affecting nonfatal stroke incidence and hospitalizations (for angina and heart failure). While it lowers the occurrence of serious adverse events, it also increases the likelihood of discontinuing treatment. CI - (c) 2025. The Author(s). FAU - Sadraei, Samin AU - Sadraei S AD - School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Aarabi, Aryan AU - Aarabi A AD - School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Rajai Firouzabadi, Shahryar AU - Rajai Firouzabadi S AD - Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Alinejadfard, Mohammadreza AU - Alinejadfard M AD - School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Mohammadi, Ida AU - Mohammadi I AUID- ORCID: 0000-0002-0662-0329 AD - Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. idamohammadi2000@gmail.com. FAU - Jolfayi, Amir Ghaffari AU - Jolfayi AG AD - Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251121 PL - England TA - BMC Cardiovasc Disord JT - BMC cardiovascular disorders JID - 100968539 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - *Cardiovascular Diseases/mortality/prevention & control/diagnosis/epidemiology MH - Treatment Outcome MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality/blood MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Risk Assessment MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Blood Glucose/drug effects/metabolism MH - Female MH - Male MH - Middle Aged MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12752371 OTO - NOTNLM OT - Cardiovascular mortality OT - GLP-1 receptor agonist OT - Major Adverse Cardiac Events OT - Myocardial infarction OT - Semaglutide OT - Stroke COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/11/22 06:29 MHDA- 2025/12/30 07:41 PMCR- 2025/11/21 CRDT- 2025/11/22 00:06 PHST- 2025/05/23 00:00 [received] PHST- 2025/10/10 00:00 [accepted] PHST- 2025/12/30 07:41 [medline] PHST- 2025/11/22 06:29 [pubmed] PHST- 2025/11/22 00:06 [entrez] PHST- 2025/11/21 00:00 [pmc-release] AID - 10.1186/s12872-025-05278-3 [pii] AID - 5278 [pii] AID - 10.1186/s12872-025-05278-3 [doi] PST - epublish SO - BMC Cardiovasc Disord. 2025 Nov 21;25(1):881. doi: 10.1186/s12872-025-05278-3. PMID- 41270831 OWN - NLM STAT- MEDLINE DCOM- 20260116 LR - 20261022 IS - 2212-8778 (Electronic) IS - 2212-8778 (Linking) VI - 103 DP - 2026 Jan TI - Additive effects of GLY-200 (oral pharmacologic duodenal exclusion therapy) and GLP-1R agonist in obesity management. PG - 102287 LID - S2212-8778(25)00194-2 [pii] LID - 10.1016/j.molmet.2025.102287 [doi] LID - 102287 AB - Type 2 diabetes and obesity impact billions of people and the global prevalence is only growing. Current treatment options, which include pharmacotherapy, e.g., GLP-1 receptor agonists (GLP-1RA) and bariatric surgical approaches have limitations. GLY-200 is an investigational clinical-stage oral non-absorbed polymeric drug designed to target proximal intestinal mucin and enhance its barrier function, emulating duodenal exclusion physiology for the treatment of diabetes and obesity. The efficacy of GLY-200 as a monotherapy and in combination with semaglutide, a leading GLP-1 receptor agonist (GLP-1RA) for obesity weight management was evaluated in diet-induced obesity (DIO) mice. Significant improvements in metabolic parameters were seen in mice treated with GLY-200 monotherapy. Moreover, an additive effect was observed when GLY-200 was combined with semaglutide, resulting in enhanced weight loss and metabolic improvements beyond those achieved with either treatment alone. GLY-200 showed promise as a weight maintenance drug, significantly blunting the weight rebound seen after GLP-1RA discontinuation. Phase 2a data from patients with type 2 diabetes (T2D) showed reductions in fasting and postprandial blood glucose, improved fasting lipid profiles, and progressive weight loss with GLY-200 treatment. These findings suggest that GLY-200, in combination with GLP-1RAs, holds promise as a novel therapeutic strategy for obesity, potentially offering a valuable approach for GLP-1RA dose reduction or weight maintenance following GLP-1RA discontinuation. CI - Copyright (c) 2025 The Author(s). Published by Elsevier GmbH.. All rights reserved. FAU - Carlson, Taylor L AU - Carlson TL AD - Glyscend Therapeutics, Inc., Baltimore, MD, USA. FAU - Fineman, Mark AU - Fineman M AD - Glyscend Therapeutics, Inc., Baltimore, MD, USA. FAU - Kernodle, Stace AU - Kernodle S AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - Hutch, Chelsea R AU - Hutch CR AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - Bryant, Christine AU - Bryant C AD - Glyscend Therapeutics, Inc., Baltimore, MD, USA. FAU - Colbert, Kevin AU - Colbert K AD - Glyscend Therapeutics, Inc., Baltimore, MD, USA. FAU - Seeley, Randy J AU - Seeley RJ AD - Department of Surgery, University of Michigan, Ann Arbor, MI, USA. FAU - Nimgaonkar, Ashish AU - Nimgaonkar A AD - Glyscend Therapeutics, Inc., Baltimore, MD, USA; Center for Bioengineering Innovation and Design, Department of Biomedical Engineering, The Johns Hopkins Hospital, Baltimore, MD, USA; Division of Gastroenterology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, MD, USA. Electronic address: animgao1@jh.edu. LA - eng GR - P30 DK020572/DK/NIDDK NIH HHS/United States GR - P30 DK089503/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251119 PL - Germany TA - Mol Metab JT - Molecular metabolism JID - 101605730 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Animals MH - Humans MH - Male MH - Mice MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Duodenum/drug effects/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - Mice, Inbred C57BL MH - *Obesity/drug therapy/metabolism MH - Obesity Management/methods MH - Weight Loss/drug effects PMC - PMC12719563 OTO - NOTNLM OT - Bariatric surgery OT - Combination therapy OT - Duodenal exclusion OT - GLP-1RA OT - GLY-200 OT - Weight loss OT - Weight maintenance COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TLC, MF, CB, KC, AN report equity or stock options in Glyscend. RJS has received research support from Novo Nordisk, Fractyl, AstraZeneca, Congruence Therapeutics, Eli Lilly, Bullfrog AI, Glyscend Therapeutics, Diasome and Amgen. RJS has been a paid consultant for Novo Nordisk, Eli Lilly, CinRx, Fractyl, Structure Therapeutics, Crinetics, Amgen, Congruence Therapeutics, Heliocore, Gallant and Nuanced Health. RJS has equity in Nuanced Health, Coro Bio, Eccogene, Fractyl and Rewind. The research was funded by Glyscend Therapeutics. There are no patents or intellectual property to report. EDAT- 2025/11/22 00:28 MHDA- 2026/01/17 00:37 PMCR- 2025/11/19 CRDT- 2025/11/21 19:12 PHST- 2025/07/24 00:00 [received] PHST- 2025/11/09 00:00 [revised] PHST- 2025/11/16 00:00 [accepted] PHST- 2026/01/17 00:37 [medline] PHST- 2025/11/22 00:28 [pubmed] PHST- 2025/11/21 19:12 [entrez] PHST- 2025/11/19 00:00 [pmc-release] AID - S2212-8778(25)00194-2 [pii] AID - 102287 [pii] AID - 10.1016/j.molmet.2025.102287 [doi] PST - ppublish SO - Mol Metab. 2026 Jan;103:102287. doi: 10.1016/j.molmet.2025.102287. Epub 2025 Nov 19. PMID- 41266832 OWN - NLM STAT- MEDLINE DCOM- 20251223 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 34 IP - 1 DP - 2026 Jan TI - Semaglutide Versus Dulaglutide and Liraglutide in Chinese Patients With T2DM: A Multicenter Real-World Study. PG - 101-113 LID - 10.1002/oby.70065 [doi] AB - OBJECTIVE: We aimed to compare the effectiveness and safety of semaglutide 1.0 mg versus dulaglutide 1.5 mg and liraglutide 1.8 mg in patients with type 2 diabetes mellitus (T2DM) under routine clinical care. METHODS: This multicenter, retrospective, real-world study enrolled Chinese adults with T2DM who initiated GLP-1 receptor agonist therapy in endocrinology clinics between January 1, 2022, and August 31, 2024. We compared the effectiveness of these agents on HbA1c and weight loss, with safety as a key exploratory endpoint. Additionally, the UK Prospective Diabetes Study Outcomes Model 2.1 was utilized to project long-term health outcomes. RESULTS: This multicenter retrospective study included 111, 74, and 107 patients treated with semaglutide 1.0 mg, dulaglutide 1.5 mg, and liraglutide 1.8 mg, respectively. After 1:1 propensity score matching, semaglutide demonstrated significantly greater HbA1c reduction compared to both dulaglutide (-0.27% +/- 0.70%, p = 0.008) and liraglutide (-0.39% +/- 0.87%, p < 0.001), along with higher glycemic target achievement rates. Semaglutide was associated with improved outcomes in all death, cardiovascular death, and other death endpoints. No significant differences in safety profiles were observed among the three treatment groups. CONCLUSIONS: Semaglutide demonstrated superior glycemic control and weight loss compared to both dulaglutide and liraglutide, whereas dulaglutide and liraglutide exhibited comparable clinical efficacy. CI - (c) 2025 The Obesity Society. FAU - Xie, Zeyu AU - Xie Z AUID- ORCID: 0000-0002-1609-4377 AD - Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, China. FAU - Gan, Bin AU - Gan B AD - Department of Pharmacy, Shenzhen Baoan People's Hospital, Shenzhen, Guangdong, China. FAU - Cao, Weiling AU - Cao W AD - Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, China. FAU - Liu, Jiang AU - Liu J AD - Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, China. FAU - Chen, Jisheng AU - Chen J AD - Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China. LA - eng GR - SZSM201801060/Sanming Project of Medicine in Shenzen Municipality/ GR - 2024-0808-03/the 2024 "Real-World Evidence and Health Technology Assessment for Clinical Use of Medicines" Special Project/ PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20251120 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (hemoglobin A1c protein, human) RN - Chinese people SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Liraglutide/therapeutic use/adverse effects/administration & dosage MH - Male MH - Female MH - Middle Aged MH - *Recombinant Fusion Proteins/therapeutic use/adverse effects/administration & dosage MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glycated Hemoglobin/analysis MH - *Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - Aged MH - China MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Weight Loss/drug effects MH - Blood Glucose/drug effects MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide MH - East Asian People OTO - NOTNLM OT - GLP-1 receptor agonists OT - effectiveness OT - observational OT - real-world OT - safety OT - semaglutide EDAT- 2025/11/21 00:27 MHDA- 2025/12/23 12:48 CRDT- 2025/11/20 23:51 PHST- 2025/08/19 00:00 [revised] PHST- 2025/07/26 00:00 [received] PHST- 2025/09/10 00:00 [accepted] PHST- 2025/12/23 12:48 [medline] PHST- 2025/11/21 00:27 [pubmed] PHST- 2025/11/20 23:51 [entrez] AID - 10.1002/oby.70065 [doi] PST - ppublish SO - Obesity (Silver Spring). 2026 Jan;34(1):101-113. doi: 10.1002/oby.70065. Epub 2025 Nov 20. PMID- 41260459 OWN - NLM STAT- MEDLINE DCOM- 20251226 LR - 20260127 IS - 1559-2030 (Electronic) IS - 1551-7144 (Linking) VI - 160 DP - 2026 Jan TI - Mazdutide versus Semaglutide for the treatment of type 2 diabetes and obesity: Rationale, design and baseline data of DREAMS-3 phase 3 trial. PG - 108150 LID - S1551-7144(25)00344-1 [pii] LID - 10.1016/j.cct.2025.108150 [doi] AB - BACKGROUND: Effective weight management and glycemic control are both important in people with type 2 diabetes (T2D) and obesity. Despite the proven benefits of GLP-1 receptor agonists, there is a persistent need for more effective weight management strategies in the treatment of T2D and obesity. Glucagon receptor-based co-agonists, such as mazdutide, represent a promising therapeutic class with the potential for enhanced weight loss compared to current standards of care. However, robust clinical evidence for these agents in populations with T2D and obesity is still lacking. The DREAMS-3 trial is designed to address this gap by directly comparing the efficacy and safety of mazdutide against semaglutide, a widely used GLP-1 receptor agonist, in Chinese adults with T2D and obesity. The results will provide crucial evidence to inform clinical decision-making for this large patient population. METHODS: DREAMS-3 is a randomized, open-label phase 3 trial. Obese Participants (BMI >/= 28 kg/m(2)) diagnosed with T2D (/=10 % at week 32. RESULTS: A total of 349 participants were enrolled and randomized, the overall mean age was 42.4 years, 44.7 % of participants were male. The mean baseline duration of T2D was 1.8 years, and 39.5 % of participants were on metformin. The mean glycated hemoglobin was 8.0 %, body weight was 90.5 kg, BMI was 33.0 kg/m(2). Most participants had at least one comorbidity. The prevalence of some comorbidities (such as metabolic associated fatty liver disease, gout/hyperuricemia) showed strong association of BMI. CONCLUSION: DERAMS-3 is the first head-to-head trial to compare the efficacy and safety of mazdutide versus semaglutide in Chinese adults with T2D and obesity, with an expected completion date in early 2026. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - Luo, Yingying AU - Luo Y AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Jiang, Hongwei AU - Jiang H AD - Department of Endocrinology, The First Affiliated Hospital and Clinical Medicine College, Henan University of Science and Technology, Luoyang, China. FAU - Shi, Bimin AU - Shi B AD - Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou, China. FAU - Cai, Hanqing AU - Cai H AD - Department of Endocrinology, The Second Hospital of Jilin University, Changchun, China. FAU - Wang, Haifang AU - Wang H AD - Department of Endocrinology, Handan First Hospital, Handan, China. FAU - Li, Shu AU - Li S AD - Department of Endocrinology, Huizhou Municipal Central Hospital, Huizhou, China. FAU - Qiu, Wei AU - Qiu W AD - Department of Endocrinology, Huzhou Central Hospital, Huzhou, China. FAU - Li, Yunfeng AU - Li Y AD - Department of Endocrinology, Inner Mongolia People's Hospital, Hohhot, China. FAU - Zhou, Runze AU - Zhou R AD - Innovent Biologics, Inc., Suzhou, China. FAU - Deng, Huan AU - Deng H AD - Innovent Biologics, Inc., Suzhou, China. FAU - Guo, Qun AU - Guo Q AD - Innovent Biologics, Inc., Suzhou, China. FAU - Li, Li AU - Li L AD - Innovent Biologics, Inc., Suzhou, China. FAU - Pei, Lijuan AU - Pei L AD - Innovent Biologics, Inc., Suzhou, China. FAU - Zhang, Han Han AU - Zhang HH AD - Innovent Biologics, Inc., Suzhou, China. FAU - Qian, Lei AU - Qian L AD - Innovent Biologics, Inc., Suzhou, China. Electronic address: cnradium@126.com. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. Electronic address: jiln@bjmu.edu.cn. LA - eng PT - Clinical Trial Protocol PT - Journal Article DEP - 20251117 PL - United States TA - Contemp Clin Trials JT - Contemporary clinical trials JID - 101242342 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 9100L32L2N (Metformin) RN - 0 (Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - MB76Z4IBZ5 (mazdutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - *Obesity/drug therapy/complications MH - Male MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Female MH - Middle Aged MH - Adult MH - Clinical Trials, Phase III as Topic MH - Glycated Hemoglobin MH - Weight Loss/drug effects MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Blood Glucose MH - Metformin/therapeutic use MH - Peptides MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Mazdutide OT - Obesity OT - Semaglutide OT - Study design OT - Type 2 diabetes COIS- Declaration of competing interest Linong Ji, and Yingying Luo, Hongwei Jiang, Bimin Shi, Hanqing Cai, Haifang Wang, Shu Li, Wei Qiu, and Yunfeng Li report personal fees from Innovent Biologics, Inc., during the conduct of the study. Runze Zhou, Huan Deng, Qun Guo, Li Li, Lijuan Pei, HanHan Zhang, and Lei Qian are employees of Innovent Biologics, Inc. EDAT- 2025/11/20 00:29 MHDA- 2025/12/27 00:54 CRDT- 2025/11/19 19:19 PHST- 2025/06/26 00:00 [received] PHST- 2025/11/10 00:00 [revised] PHST- 2025/11/16 00:00 [accepted] PHST- 2025/12/27 00:54 [medline] PHST- 2025/11/20 00:29 [pubmed] PHST- 2025/11/19 19:19 [entrez] AID - S1551-7144(25)00344-1 [pii] AID - 10.1016/j.cct.2025.108150 [doi] PST - ppublish SO - Contemp Clin Trials. 2026 Jan;160:108150. doi: 10.1016/j.cct.2025.108150. Epub 2025 Nov 17. PMID- 41255528 OWN - NLM STAT- MEDLINE DCOM- 20251119 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Development of a risk prediction model for gastrointestinal adverse events associated with semaglutide administration in patients with type 2 diabetes mellitus. PG - 1684395 LID - 10.3389/fendo.2025.1684395 [doi] LID - 1684395 AB - OBJECTIVE: This study aims to identify the risk factors associated with gastrointestinal adverse events induced by semaglutide in patients with type 2 diabetes mellitus (T2DM) and to develop a predictive risk model. METHODS: A total of 215 patients with T2DM admitted to our hospital between June 2022 and December 2024 were enrolled. Participants were divided into two groups based on the presence (n = 41) or absence (n = 174) of gastrointestinal adverse events associated with semaglutide use. Univariate and multivariate logistic regression analyses were performed to identify significant risk factors for these adverse events. Subsequently, a nomogram was developed using R software to predict the likelihood of gastrointestinal adverse events in this patient population. The predictive performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration plots, and the Hosmer-Lemeshow goodness-of-fit test. RESULTS: In a cohort of 215 patients with T2DM, 41 individuals (19.07%) experienced gastrointestinal adverse events attributed to semaglutide administration. Logistic regression analysis identified concomitant gastrointestinal disorders [95% confidence interval (CI): 2.074-9.808, P < 0.001], alcohol consumption (95% CI: 1.304-6.633, P = 0.009), and concurrent use of alpha-glucosidase inhibitors (95% CI: 1.368-6.460, P = 0.006) as independent risk factors for semaglutide-induced gastrointestinal adverse events in this population. The predictive model demonstrated an area under the ROC curve of 0.763 (95% CI: 0.691-0.836). Calibration assessment revealed a slope approximating unity, and the Hosmer-Lemeshow goodness-of-fit test indicated an adequate model fit (chi(2) = 5.633, P = 0.228). CONCLUSION: Patients with T2DM exhibit a significant incidence of gastrointestinal adverse events associated with semaglutide use. The presence of gastrointestinal comorbidities, alcohol consumption, and alpha-glucosidase inhibitor therapy are independent risk factors. The developed nomogram effectively predicts the likelihood of semaglutide-related gastrointestinal adverse events in this patient population. CI - Copyright (c) 2025 Yue, Hua, Zhu, Wang, Gu, Yuan, Jian, Chen and Meng. FAU - Yue, Deyong AU - Yue D AD - Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming, Shanghai, China. AD - Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China. FAU - Hua, Xuesheng AU - Hua X AD - Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming, Shanghai, China. FAU - Zhu, Ling AU - Zhu L AD - Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming, Shanghai, China. FAU - Wang, Jun AU - Wang J AD - Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming, Shanghai, China. FAU - Gu, Lihua AU - Gu L AD - Chongming Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Chongming, Shanghai, China. FAU - Yuan, Zhengxia AU - Yuan Z AD - Nantong University Xinglin College, Nantong, Jiangsu, China. FAU - Jian, Wenle AU - Jian W AD - Nantong University Xinglin College, Nantong, Jiangsu, China. FAU - Chen, Yirong AU - Chen Y AD - General Surgery Department of Wuxi No.8 People's Hospital, Wuxi, Jiangsu, China. FAU - Meng, Guoliang AU - Meng G AD - Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China. LA - eng PT - Journal Article DEP - 20251103 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - Female MH - Male MH - Middle Aged MH - Aged MH - Risk Factors MH - *Gastrointestinal Diseases/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - Nomograms MH - Risk Assessment MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12620217 OTO - NOTNLM OT - alcohol OT - gastrointestinal adverse events OT - risk prediction model OT - semaglutide OT - type 2 diabetes mellitus OT - alpha-glucosidase inhibitors COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2025/11/19 06:32 MHDA- 2025/11/19 06:33 PMCR- 2025/11/03 CRDT- 2025/11/19 05:15 PHST- 2025/09/09 00:00 [received] PHST- 2025/10/20 00:00 [accepted] PHST- 2025/11/19 06:33 [medline] PHST- 2025/11/19 06:32 [pubmed] PHST- 2025/11/19 05:15 [entrez] PHST- 2025/11/03 00:00 [pmc-release] AID - 10.3389/fendo.2025.1684395 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Nov 3;16:1684395. doi: 10.3389/fendo.2025.1684395. eCollection 2025. PMID- 41251033 OWN - NLM STAT- MEDLINE DCOM- 20260323 LR - 20260323 IS - 1528-1167 (Electronic) IS - 0013-9580 (Linking) VI - 67 IP - 3 DP - 2026 Mar TI - Seizure recurrence after GLP-1 receptor agonist initiation in adults with epilepsy. PG - 1246-1255 LID - 10.1111/epi.70022 [doi] AB - OBJECTIVE: To examine whether initiation of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is associated with seizure recurrence and related outcomes in adults with epilepsy and type 2 diabetes. METHODS: We conducted a retrospective cohort study using de-identified electronic health records from the TriNetX Research Network (January 2003-August 2025), including adults >/=18 years with >/=3 epilepsy or recurrent seizure diagnoses. Patients initiating a GLP-1 RA (exenatide, liraglutide, dulaglutide, lixisenatide, semaglutide, or tirzepatide) without prior comparator therapy were compared with those initiating other glucose-lowering agents (sodium-glucose cotransporter 2 inhibitors, dipeptidyl peptidase 4 inhibitors, sulfonylureas, or insulin) without GLP-1 RA exposure. Propensity score matching (1:1) was performed on 82 covariates, yielding 8688 matched pairs. Outcomes were assessed using Cox proportional hazards models. RESULTS: After matching, the mean age was 52.6 years, and 67.6% were female. Median follow-up was 514 days (interquartile range [IQR] 671) for GLP-1 RA initiators and 415 days (IQR 769) for comparators. GLP-1 RA initiation was associated with lower risk of seizure recurrence (HR .82, 95% confidence interval [CI] .78-.86; RD -2.1%), hospitalization (HR .35, 95% CI .29-.43; RD -2.6%), and all-cause mortality (HR .40, 95% CI .34-.47; RD -4.8%). Associations with status epilepticus (HR .75, 95% CI .66-.85; RD -.7%) and ICU admission (HR .82, 95% CI .69-.96; RD -.3%) were smaller; the latter was not statistically significant. SIGNIFICANCE: In this large multinational cohort, GLP-1 RA initiation was associated with reduced risks of seizure recurrence, hospitalization, and mortality compared with other glucose-lowering therapies. These hypothesis-generating findings warrant confirmation in prospective studies before translation into clinical practice. CI - (c) 2025 International League Against Epilepsy. FAU - AbuAlrob, Majd A AU - AbuAlrob MA AUID- ORCID: 0000-0002-9707-9266 AD - Neuroscience Institute, Hamad Medical Corporation, Doha, Qatar. FAU - Hussein, Abdullah AU - Hussein A AUID- ORCID: 0000-0002-2408-2691 AD - Department of Internal Medicine, Virtua Health, Camden, USA. FAU - Abdellatif, Rand AU - Abdellatif R AUID- ORCID: 0000-0001-5879-1990 AD - Department of Internal Medicine, Jenin Governmental Hospital, Palestinian Health Ministry, Nablus, Palestine. FAU - Itbaisha, Adham AU - Itbaisha A AUID- ORCID: 0009-0007-2630-0107 AD - Department of Internal Medicine, Jenin Governmental Hospital, Palestinian Health Ministry, Nablus, Palestine. FAU - Zammar, Khaled AU - Zammar K AUID- ORCID: 0009-0006-5530-1136 AD - Neuroscience Institute, Hamad Medical Corporation, Doha, Qatar. FAU - Mesraoua, Boulenouar AU - Mesraoua B AUID- ORCID: 0000-0001-8625-7365 AD - Neuroscience Institute, Hamad Medical Corporation, Doha, Qatar. LA - eng PT - Journal Article DEP - 20251118 PL - United States TA - Epilepsia JT - Epilepsia JID - 2983306R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Recurrence MH - Adult MH - *Epilepsy/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - *Seizures/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Cohort Studies OTO - NOTNLM OT - GLP-1 receptor agonists OT - epilepsy OT - real-world evidence OT - seizure recurrence OT - type 2 diabetes EDAT- 2025/11/18 06:26 MHDA- 2026/03/23 19:54 CRDT- 2025/11/18 05:13 PHST- 2025/10/31 00:00 [revised] PHST- 2025/08/22 00:00 [received] PHST- 2025/11/03 00:00 [accepted] PHST- 2026/03/23 19:54 [medline] PHST- 2025/11/18 06:26 [pubmed] PHST- 2025/11/18 05:13 [entrez] AID - 10.1111/epi.70022 [doi] PST - ppublish SO - Epilepsia. 2026 Mar;67(3):1246-1255. doi: 10.1111/epi.70022. Epub 2025 Nov 18. PMID- 41243611 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260805 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - Real-world evaluation of clinical outcomes in Dutch patients with type 2 diabetes treated with oral semaglutide: A retrospective, observational cohort study using the PHARMO data network. PG - 895-905 LID - 10.1111/dom.70251 [doi] AB - AIM: A retrospective observational cohort study, in the Netherlands, evaluated clinical outcomes with oral semaglutide. METHODS: Glucagon-like peptide-1 receptor agonists (GLP-1ra) naive type 2 diabetes (T2D) patients who initiated oral semaglutide between 1 January 2020 and 31 December 2022 were identified from the PHARMO Data Network. Change from baseline was evaluated in glycated haemoglobin (HbA1c), body weight, blood lipids, and blood pressure over 12 months of follow-up. Outcomes were analysed in patients with at least a baseline and >/=1 follow-up measurement, using mixed-effect models for repeated measurements. RESULTS: Of 932 T2D patients initiating oral semaglutide identified, 731 were GLP-1ra naive (mean [standard deviation] age, 62 [11] years; baseline HbA1c, 70 [14] mmol/mol; baseline body weight, 102 [19] kg). In 320 patients with an average follow-up of 8.1 months the mean (95% confidence interval) change in HbA1c from baseline was -16.05 (-12.57, -19.54) mmol/mol at 12 months, of whom 70% achieved personalized HbA1c targets. Body weight was reduced by -4.73 (-3.63, -5.83) kg at 12 months in 260 patients over an average of 8.2 months follow-up. Minimal changes were observed in blood lipid parameters and diastolic blood pressure, with moderate changes in systolic blood pressure. CONCLUSIONS: Among Dutch T2D patients who were GLP-1ra naive and initiated oral semaglutide, significant reductions in HbA1c and body weight were observed over 12 months, consistent with prospective clinical trial data. These results provide a first-look insight into real-world glycaemic control and body weight reduction in early adopters of oral semaglutide in the Netherlands. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Postema, Abigail AU - Postema A AUID- ORCID: 0009-0006-4897-827X AD - The PHARMO Institute, Utrecht, The Netherlands. FAU - Gaspersz, Jordy AU - Gaspersz J AD - The PHARMO Institute, Utrecht, The Netherlands. FAU - Baak, Brenda N AU - Baak BN AD - The PHARMO Institute, Utrecht, The Netherlands. FAU - Huisman, Eline L AU - Huisman EL AD - Novo Nordisk, Amsterdam, The Netherlands. FAU - Hoogstraten, Charlotte AU - Hoogstraten C AD - Novo Nordisk, Amsterdam, The Netherlands. FAU - Hagelund, Lise Meinicke AU - Hagelund LM AD - Novo Nordisk, Amsterdam, The Netherlands. FAU - Penning-van Beest, Fernie J A AU - Penning-van Beest FJA AD - The PHARMO Institute, Utrecht, The Netherlands. FAU - Overbeek, Jetty A AU - Overbeek JA AD - The PHARMO Institute, Utrecht, The Netherlands. LA - eng GR - Novo Nordisk/ PT - Journal Article PT - Observational Study DEP - 20251117 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Lipids) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - Female MH - Middle Aged MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Retrospective Studies MH - Netherlands/epidemiology MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - Aged MH - Administration, Oral MH - Treatment Outcome MH - Blood Glucose/analysis MH - Blood Pressure/drug effects MH - Body Weight/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Lipids/blood MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12803591 OTO - NOTNLM OT - body weight OT - glucagon-like peptide-1 receptor agonist OT - glycaemic control OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- Abigail Postema, Jordy Gaspersz, Brenda N. Baak, Fernie J. A. Penning-van Beest, and Jetty A. Overbeek are employees of the PHARMO Institute, part of Lumanity. This independent research institute performs financially supported studies for government and related health care authorities and several pharmaceutical companies. Eline L. Huisman, Charlotte Hoogstraten, and Lise Meinicke Hagelund are employees and shareholders of Novo Nordisk. EDAT- 2025/11/17 09:07 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/17 03:42 PHST- 2025/10/14 00:00 [revised] PHST- 2025/07/25 00:00 [received] PHST- 2025/10/22 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/17 09:07 [pubmed] PHST- 2025/11/17 03:42 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70251 [pii] AID - 10.1111/dom.70251 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):895-905. doi: 10.1111/dom.70251. Epub 2025 Nov 17. PMID- 41235513 OWN - NLM STAT- MEDLINE DCOM- 20251114 LR - 20251114 IS - 0040-3660 (Print) IS - 0040-3660 (Linking) VI - 97 IP - 10 DP - 2025 Nov 11 TI - [The perspectives in obesity and type 2 diabetes therapy: the present and future of incretin therapy]. PG - 823-829 LID - 10.26442/00403660.2025.10.203366 [doi] AB - The rates of increase in the incidence of type 2 diabetes mellitus (T2DM) and obesity in the world are steadily increasing and exceed even the wildest forecasts, which forces specialists to seek, develop and implement more effective therapeutic methods for these two interrelated non-communicable pandemics. This article discusses promising areas in the pharmacotherapy of obesity and T2DM with an emphasis on the development of a class of incretin hormone receptor agonists. Monoagonists (liraglutide, dulaglutide, semaglutide) and dual incretin receptor agonists (tirzepatide), as well as triple- and tetra-agonists of gastrointestinal hormones currently under development, which are expected to be even more effective in the complex treatment of both type T2DM and obesity, are being discussed. FAU - Shestakova, M V AU - Shestakova MV AUID- ORCID: 0000-0002-5057-127X AD - Endocrinology Research Centre. FAU - Bashlykova, R O AU - Bashlykova RO AUID- ORCID: 0009-0006-0444-3732 AD - Endocrinology Research Centre. LA - rus PT - English Abstract PT - Journal Article PT - Review DEP - 20251111 PL - Russia (Federation) TA - Ter Arkh JT - Terapevticheskii arkhiv JID - 2984818R RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Incretins/pharmacology/therapeutic use MH - *Obesity/drug therapy/epidemiology MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/analogs & derivatives OTO - NOTNLM OT - diabetes mellitus OT - glucagon OT - glucagon-like peptide-1 OT - glucose-dependent insulinotropic polypeptide OT - glycemic control OT - incretins OT - metabolic process OT - multiagnestics OT - obesity OT - pharmacotherapy OT - weight EDAT- 2025/11/14 06:28 MHDA- 2025/11/14 06:29 CRDT- 2025/11/14 05:43 PHST- 2025/07/02 00:00 [received] PHST- 2025/07/02 00:00 [accepted] PHST- 2025/11/14 06:29 [medline] PHST- 2025/11/14 06:28 [pubmed] PHST- 2025/11/14 05:43 [entrez] AID - 10.26442/00403660.2025.10.203366 [doi] PST - epublish SO - Ter Arkh. 2025 Nov 11;97(10):823-829. doi: 10.26442/00403660.2025.10.203366. PMID- 41228390 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260127 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 17 IP - 21 DP - 2025 Oct 22 TI - Exploring Dietary Intake in Adults with Type 2 Diabetes Using GLP-1 Receptor Agonists: A Cross-Sectional Analysis. LID - 10.3390/nu17213318 [doi] LID - 3318 AB - Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used in type 2 diabetes (T2D) management for their glycemic and weight benefits. However, their appetite-suppressing effects may influence dietary intake and nutrient adequacy, yet real-world evidence is scarce. Objective: To evaluate dietary intake and adherence to the Mediterranean diet in adults with T2D treated with GLP-1RAs compared to those receiving other oral hypoglycemic agents. Methods: In this cross-sectional study, 103 adults with T2D (mean age 66 +/- 8 years; 65% male) attending a diabetes clinic in Turin, Italy, were enrolled between February and June 2025. Dietary habits were assessed using a validated food frequency questionnaire, and adherence to the Mediterranean diet was evaluated via the Mediterranean Diet Score (MDS). Anthropometric, biochemical, and lifestyle data were collected. Results: Fifty-two participants (50.5%) were treated with GLP-1RAs (semaglutide 55.8%, dulaglutide 40.4%). No significant differences in energy intake, macronutrient distribution, or MDS were observed between groups. Overall, diets were characterized by low carbohydrate intake (~44% of energy), inadequate fiber ( approximately 11 g/1000 kcal), and high fat intake ( approximately 39-40% of energy), with saturated fat below 10%. None of the GLP-1RA users met fiber recommendations. Subgroup analysis by treatment duration (<1 year, 1-2 years, >2 years) revealed no significant differences in dietary patterns. Conclusions: Patients with T2D, regardless of pharmacological treatment, exhibited poor adherence to dietary guidelines. These findings highlight the need for structured nutritional counseling alongside GLP-1RA therapy to optimize metabolic outcomes and prevent nutritional deficiencies. FAU - Ponzo, Valentina AU - Ponzo V AD - Department of Medical Science, University of Torino, c.so Dogliotti 14, 10126 Torino, Italy. FAU - Vitale, Marilena AU - Vitale M AUID- ORCID: 0000-0001-9951-4674 AD - Nutrition, Diabetes and Metabolism Research Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Via S. Pansini 5, 80131 Naples, Italy. FAU - Bo, Simona AU - Bo S AUID- ORCID: 0000-0001-6862-8628 AD - Department of Medical Science, University of Torino, c.so Dogliotti 14, 10126 Torino, Italy. FAU - Broglio, Fabio AU - Broglio F AD - Department of Medical Science, University of Torino, c.so Dogliotti 14, 10126 Torino, Italy. FAU - Goitre, Ilaria AU - Goitre I AD - Department of Medical Science, University of Torino, c.so Dogliotti 14, 10126 Torino, Italy. FAU - Cioffi, Iolanda AU - Cioffi I AUID- ORCID: 0000-0002-1408-209X AD - Division of Human Nutrition, Department of Food, Environmental and Nutritional Sciences-DeFENS, University of Milan, Via G. Celoria 2, 20133 Milan, Italy. LA - eng PT - Journal Article DEP - 20251022 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Cross-Sectional Studies MH - Female MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diet, Mediterranean MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Italy MH - Energy Intake MH - *Eating MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC12610383 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Mediterranean diet OT - Pharmacotherapy OT - Type 2 diabetes OT - diet quality OT - dietary intake OT - nutritional adequacy COIS- The authors declare no conflicts of interest. EDAT- 2025/11/13 06:30 MHDA- 2025/11/13 18:29 PMCR- 2025/10/22 CRDT- 2025/11/13 01:11 PHST- 2025/09/10 00:00 [received] PHST- 2025/10/18 00:00 [revised] PHST- 2025/10/20 00:00 [accepted] PHST- 2025/11/13 18:29 [medline] PHST- 2025/11/13 06:30 [pubmed] PHST- 2025/11/13 01:11 [entrez] PHST- 2025/10/22 00:00 [pmc-release] AID - nu17213318 [pii] AID - nutrients-17-03318 [pii] AID - 10.3390/nu17213318 [doi] PST - epublish SO - Nutrients. 2025 Oct 22;17(21):3318. doi: 10.3390/nu17213318. PMID- 41226444 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 21 DP - 2025 Oct 26 TI - Long-Term Effects of Semaglutide and Sitagliptin on Circulating IGFBP-1, IGFBP-3 and IGFBP-rp1: Results from a One-Year Study in Type 2 Diabetes. LID - 10.3390/ijms262110404 [doi] LID - 10404 AB - The role of insulin-like growth factor-binding proteins (IGFBPs) in the regulation of carbohydrate metabolism and the development of complications is well established; however, the impact of the glucagon-like peptide-1 receptor agonist semaglutide on IGFBPs has not been previously investigated. We aimed to examine the effects of semaglutide and dipeptidyl peptidase-4 inhibitor sitagliptin therapy on serum levels of IGFBP-1, IGFBP-3, and IGFBP-rp1, and to analyze their associations with anthropometric variables and markers of carbohydrate and lipid metabolism. In this prospective study, we enrolled 34 patients with type 2 diabetes mellitus (T2DM) on metformin monotherapy and 31 age-, sex- and BMI-matched controls. Among the patients, 18 received semaglutide, and 16 were treated with sitagliptin. Anthropometric and laboratory assessments were performed at baseline, 26 and 52 weeks. IGFBP levels were measured using ELISA. Both semaglutide and sitagliptin treatment significantly increased IGFBP-1 levels. IGFBP-3 levels were significantly decreased following sitagliptin therapy. No significant change in IGFBP-rp1 levels was observed with either treatment. Based on multiple regression analysis, the best predictors of IGFBP-1 were insulin and hsCRP, while the best predictor of IGFBP-3 was LDL-C level. Our findings suggest that semaglutide and sitagliptin may exert favorable effects on the GH/IGF-1 axis, potentially contributing to their beneficial metabolic outcomes in patients with T2DM. FAU - Daniel, Eszter AU - Daniel E AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Sztanek, Ferenc AU - Sztanek F AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Csiha, Sara AU - Csiha S AD - Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. AD - Department of Clinical Basics, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Ratku, Balazs AU - Ratku B AUID- ORCID: 0000-0002-0991-8622 AD - Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Institute of Health Studies, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Somodi, Sandor AU - Somodi S AD - Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Institute of Health Studies, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Paragh, Gyorgy AU - Paragh G AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Harangi, Mariann AU - Harangi M AUID- ORCID: 0000-0001-9761-9595 AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Institute of Health Studies, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Lorincz, Hajnalka AU - Lorincz H AUID- ORCID: 0009-0000-5303-3082 AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. LA - eng GR - K142273/National Research, Development and Innovation Office/ GR - Hungarian Society for Endocrinology and Metabolism/ PT - Journal Article DEP - 20251026 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Insulin-Like Growth Factor Binding Protein 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Insulin-Like Growth Factor Binding Protein 3) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Insulin-Like Growth Factor Binding Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (IGFBP1 protein, human) RN - 0 (IGFBP3 protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Sitagliptin Phosphate/therapeutic use/pharmacology MH - Male MH - Female MH - Middle Aged MH - *Insulin-Like Growth Factor Binding Protein 1/blood MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Insulin-Like Growth Factor Binding Protein 3/blood MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Prospective Studies MH - Metformin/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Insulin-Like Growth Factor Binding Proteins/blood MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12609315 OTO - NOTNLM OT - C-peptide OT - C-reactive protein OT - insulin OT - insulin-like growth factor-binding protein OT - lipid parameters OT - semaglutide OT - sitagliptin OT - type 2 diabetes mellitus OT - waist circumference COIS- The authors declare no conflicts of interest. EDAT- 2025/11/13 06:29 MHDA- 2025/11/13 18:29 PMCR- 2025/10/26 CRDT- 2025/11/13 01:04 PHST- 2025/09/12 00:00 [received] PHST- 2025/10/18 00:00 [revised] PHST- 2025/10/25 00:00 [accepted] PHST- 2025/11/13 18:29 [medline] PHST- 2025/11/13 06:29 [pubmed] PHST- 2025/11/13 01:04 [entrez] PHST- 2025/10/26 00:00 [pmc-release] AID - ijms262110404 [pii] AID - ijms-26-10404 [pii] AID - 10.3390/ijms262110404 [doi] PST - epublish SO - Int J Mol Sci. 2025 Oct 26;26(21):10404. doi: 10.3390/ijms262110404. PMID- 41219651 OWN - NLM STAT- MEDLINE DCOM- 20260307 LR - 20260408 IS - 1525-1497 (Electronic) IS - 0884-8734 (Print) IS - 0884-8734 (Linking) VI - 41 IP - 3 DP - 2026 Feb TI - Ethical Considerations in the Use of Weight Loss Medications. PG - 852-855 LID - 10.1007/s11606-025-10026-6 [doi] AB - The emergence of GLP-1 receptor agonists, such as semaglutide and tirzepatide, has transformed the landscape of weight management and diabetes treatment. Initially developed for type 2 diabetes mellitus, these medications have gained widespread popularity due to their weight-loss effects, spurred by media attention and celebrity endorsements. However, their increasing demand raises ethical concerns regarding accessibility, affordability, and medical necessity. Patients with genuine clinical indications often struggle to obtain these medications due to shortages and high costs, while wealthier individuals use them for cosmetic weight loss. Additionally, unregulated alternatives, such as compounded injections and celebrity-endorsed supplements, further complicate the landscape by introducing safety risks and misinformation. Physicians face the challenge of balancing evidence-based prescribing with resource allocation, ensuring medications reach those in need. Patients have a responsibility to critically evaluate information and engage in informed decision-making. Policymakers must address disparities by implementing equitable policies that prioritize medical necessity over commercial interests. As the use of GLP-1 agonists continues to rise, a collaborative approach, rooted in ethical responsibility, patient education, and regulatory oversight, is essential to prevent healthcare inequities and uphold the integrity of medical practice. CI - (c) 2025. The Author(s), under exclusive licence to Society of General Internal Medicine. FAU - Savla, Riya AU - Savla R AUID- ORCID: 0009-0001-4073-3829 AD - Hackensack Meridian School of Medicine, Nutley, NJ, USA. riya.savla@hmhn.org. FAU - Van Hoven, Anne Marie AU - Van Hoven AM AD - Office of Medical Education, Hackensack Meridian School of Medicine, Nutley, NJ, USA. FAU - Pilkington, Bryan AU - Pilkington B AD - Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, USA. LA - eng PT - Editorial DEP - 20251111 PL - United States TA - J Gen Intern Med JT - Journal of general internal medicine JID - 8605834 RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Anti-Obesity Agents/therapeutic use/economics MH - *Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12960898 COIS- Declarations. Human Ethics and Consent to Participate: Not applicable. Conflict of interest: The authors declare that they do not have a conflict of interest. EDAT- 2025/11/12 00:26 MHDA- 2026/03/07 06:40 PMCR- 2027/02/01 CRDT- 2025/11/11 23:38 PHST- 2025/02/20 00:00 [received] PHST- 2025/10/31 00:00 [accepted] PHST- 2026/03/07 06:40 [medline] PHST- 2025/11/12 00:26 [pubmed] PHST- 2025/11/11 23:38 [entrez] PHST- 2027/02/01 00:00 [pmc-release] AID - 10.1007/s11606-025-10026-6 [pii] AID - 10026 [pii] AID - 10.1007/s11606-025-10026-6 [doi] PST - ppublish SO - J Gen Intern Med. 2026 Feb;41(3):852-855. doi: 10.1007/s11606-025-10026-6. Epub 2025 Nov 11. PMID- 41217382 OWN - NLM STAT- MEDLINE DCOM- 20260505 LR - 20260724 IS - 1930-613X (Electronic) IS - 0026-4075 (Linking) VI - 191 IP - 5-6 DP - 2026 May 1 TI - Semaglutide Decreases Risk of Non-Arteritic Anterior Ischemic Optic Neuroapthy in Type 2 Diabetic Patients. PG - e1020-e1025 LID - 10.1093/milmed/usaf522 [doi] AB - INTRODUCTION: Although the association between semaglutide use for diabetes or obesity and non-arteritic ischemic optic neuropathy (NAION) has been investigated, the relative risk has not been established in large, racially diverse populations. Given the increasing use of glucagon-like peptide 1 receptor agonist (GLP-1 RA) medications, it is vital to study the odds of this serious adverse event. MATERIALS AND METHODS: We conducted a retrospective cohort study to investigate the relationship between semaglutide use and NAION in Military Health System beneficiaries ages 18 and older with diabetes or overweight and obesity who received care from December 7, 2017 to September 30, 2023. A subset analysis was performed using phosphodiesterase-5 inhibitors. This study was carried out as part of the Burden of Diseases and Injuries in the U.S. Military Health System, 2001-2018: Incidence, Prevalence, and Years Lived project and was found exempt by the Institutional Review Board at the Uniformed Services University of the Health Sciences. RESULTS: A total of 1,212,775 individuals (973,529 patients with type 2 diabetes and 239,246 with overweight or obesity) were included. There were 2,447 NAION events identified. After adjusting for comorbidities, patients with type 2 diabetes prescribed semaglutide had a significantly lower risk of NAION (OR = 0.36, 95% CI = 0.25-0.51) compared to those prescribed non-GLP-1 RA medications. Among patients who had overweight or obesity, there was no significant difference in the odds of receiving a NAION diagnosis (OR = 0.10, 95% CI = 0.01-1.35). Use of phosphodiesterase-5 inhibitors was associated with lower odds of NAION in both populations (Type 2 diabetes: OR = 0.78, 95% CI = 0.69-0.87; overweight/obesity: OR = 0.49, 95% CI = 0.26-0.93) compared with those who did not use these medications. CONCLUSION: This retrospective cohort study found a lower risk of NAION in patients with type 2 diabetes taking semaglutide compared with those taking non-GLP-1 RA medications in a large, diverse population. There was no association between NAION and semaglutide use in patients with overweight or obesity. These findings suggest that the risk of NAION should not preclude the use of this medication. CI - Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2025. This work is written by (a) US Government employee(s) and is in the public domain in the US. FAU - Lieberman, Rachel A AU - Lieberman RA AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. AD - Walter Reed National Military Medical Center, Bethesda, MD 20814, United States. FAU - Korona-Bailey, Jessica AU - Korona-Bailey J AUID- ORCID: 0000-0002-0314-5171 AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. AD - The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD 20817, United States. FAU - Banaag, Amanda AU - Banaag A AUID- ORCID: 0000-0001-6660-1229 AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. AD - The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc, Bethesda, MD 20817, United States. FAU - Furhman, Barbara AU - Furhman B AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. FAU - Corrado, Richele AU - Corrado R AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. FAU - Koehlmoos, Tracey Perez AU - Koehlmoos TP AD - Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States. LA - eng GR - # HU0001-11-1-0023/Department of Defense, Defense Health Agency/ PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - England TA - Mil Med JT - Military medicine JID - 2984771R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Retrospective Studies MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Adult MH - Aged MH - *Optic Neuropathy, Ischemic/epidemiology/prevention & control/drug therapy MH - Cohort Studies MH - United States/epidemiology MH - Hypoglycemic Agents/therapeutic use MH - Incidence MH - Obesity EDAT- 2025/11/11 12:29 MHDA- 2026/05/06 00:34 CRDT- 2025/11/11 10:34 PHST- 2026/05/06 00:34 [medline] PHST- 2025/11/11 12:29 [pubmed] PHST- 2025/11/11 10:34 [entrez] AID - 8320596 [pii] AID - 10.1093/milmed/usaf522 [doi] PST - ppublish SO - Mil Med. 2026 May 1;191(5-6):e1020-e1025. doi: 10.1093/milmed/usaf522. PMID- 41212550 OWN - NLM STAT- MEDLINE DCOM- 20260113 LR - 20260629 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 335 IP - 2 DP - 2026 Jan 13 TI - Metabolic Dysfunction-Associated Steatotic Liver Disease in Adults: A Review. PG - 163-174 LID - 10.1001/jama.2025.19615 [doi] AB - IMPORTANCE: Metabolic dysfunction-associated steatotic liver disease (MASLD) includes a range of liver conditions, progressing from isolated steatosis (characterized by fat accumulation in the liver without inflammation) to metabolic dysfunction-associated steatohepatitis (MASH), which involves fat accumulation and inflammation in the liver. The presence of MASLD is associated with increased morbidity and mortality due to liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. OBSERVATIONS: The most common chronic liver disease worldwide, MASLD affects approximately 30% to 40% of the general adult population globally (with varying prevalence across continents), including approximately 60% to 70% of individuals with type 2 diabetes and approximately 70% to 80% of those with obesity. It is typically diagnosed based on an ultrasonographic finding of hepatic steatosis, along with at least 1 of 5 features of the metabolic syndrome (abdominal overweight or obesity, prediabetes or type 2 diabetes, hypertension, elevated level of plasma triglycerides, and low level of high-density lipoprotein cholesterol) for women who consume less than 140 g/wk of alcohol (<2 standard drinks/d) and for men who consume less than 210 g/wk (<3 standard drinks/d) and have no other known causes of steatosis such as use of a particular medication (eg, corticosteroids, tamoxifen, or methotrexate), hepatitis C, or iron overload. Other risk factors for MASLD include older age (>/=50 years) and male sex (male:female ratio approximately 2). The Fibrosis-4 index (a scoring system incorporating age, serum levels of aspartate aminotransferase and alanine aminotransferase, and platelet count) and vibration-controlled transient elastography (a noninvasive imaging technique) are commonly used to stage hepatic fibrosis in patients with MASLD. Cardiovascular disease is the leading cause of death, followed by certain extrahepatic cancers (primarily gastrointestinal, breast, and gynecologic cancer) and liver-related complications, including cirrhosis, hepatic decompensation (ascites, hepatic encephalopathy, or variceal bleeding), and hepatocellular carcinoma. First-line treatment of MASLD involves behavioral modifications (including hypocaloric low-carbohydrate and low-fat diets, physical exercise, and avoidance of alcohol) and management of type 2 diabetes, obesity, hypertension, and hyperlipidemia. Bariatric surgery should be considered for patients with MASLD and a body mass index greater than 35. Resmetirom (a liver-directed, thyroid hormone receptor beta-selective agonist) and subcutaneous semaglutide (a glucagon-like peptide-1 receptor agonist) are conditionally approved by the US Food and Drug Administration (FDA) for the treatment of adults with MASH who have moderate to advanced fibrosis. CONCLUSIONS: A highly prevalent condition among adults worldwide, MASLD is associated with liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. First-line treatment includes behavioral modifications, including a weight-reducing diet, physical exercise, and avoidance of alcohol. Resmetirom and semaglutide are conditionally FDA-approved medications for the treatment of adults with MASH and moderate to advanced fibrosis. FAU - Tilg, Herbert AU - Tilg H AD - Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, and Metabolism, Medical University of Innsbruck, Innsbruck, Austria. FAU - Petta, Salvatore AU - Petta S AD - Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties Promise, University of Palermo, Palermo, Italy. FAU - Stefan, Norbert AU - Stefan N AD - Department of Internal Medicine IV, Division of Endocrinology, Diabetology, and Nephrology, University of Tubingen, Tubingen, Germany. AD - Institute of Diabetes Research and Metabolic Diseases, Helmholtz Center Munich, Tubingen, Germany. FAU - Targher, Giovanni AU - Targher G AD - Department of Medicine, University of Verona, Verona, Italy. AD - Metabolic Diseases Research Unit, IRCCS Sacro Cuore-Don Calabria Hospital, Negrar di Valpolicella, Italy. LA - eng PT - Journal Article PT - Review PL - United States TA - JAMA JT - JAMA JID - 7501160 SB - IM EIN - JAMA. 2026 Jul 28;336(4):347. doi: 10.1001/jama.2026.11797. PMID: 42371640 MH - Adult MH - Female MH - Humans MH - Male MH - Diabetes Mellitus, Type 2/complications/diagnosis/epidemiology MH - *Metabolic Syndrome/complications/diagnosis/epidemiology/therapy MH - Obesity/complications/diagnosis/epidemiology MH - Risk Factors MH - *Non-alcoholic Fatty Liver Disease/complications/diagnosis/epidemiology/therapy MH - Carcinoma, Hepatocellular/epidemiology/etiology/prevention & control MH - Liver Neoplasms/epidemiology/etiology/prevention & control MH - Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - Liver/metabolism/pathology MH - Liver Cirrhosis/epidemiology/etiology/pathology/prevention & control MH - Age Factors MH - Sex Factors EDAT- 2025/11/10 12:35 MHDA- 2026/01/13 13:15 CRDT- 2025/11/10 11:33 PHST- 2026/01/13 13:15 [medline] PHST- 2025/11/10 12:35 [pubmed] PHST- 2025/11/10 11:33 [entrez] AID - 2841071 [pii] AID - 10.1001/jama.2025.19615 [doi] PST - ppublish SO - JAMA. 2026 Jan 13;335(2):163-174. doi: 10.1001/jama.2025.19615. PMID- 41211586 OWN - NLM STAT- MEDLINE DCOM- 20251112 LR - 20260708 IS - 2090-0716 (Electronic) IS - 2090-0708 (Print) IS - 2090-0708 (Linking) VI - 2025 DP - 2025 TI - Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Obesity Management in Adults With and Without Type 2 Diabetes: A Systematic Review. PG - 3897161 LID - 10.1155/jobe/3897161 [doi] LID - 3897161 AB - OBJECTIVE: This systematic review aimed to assess the efficacy and safety of GLP-1 RAs in adults with obesity or overweight, by comparing different GLP-1 RAs, identifying the most effective agents, and evaluating adverse effects. METHODS: We systematically searched Embase, MEDLINE, and Cochrane for phase 3 and 4 randomized controlled trials (RCTs) with a minimum duration of 40 weeks. Included studies compared GLP-1 RAs to placebo or to each other in adults with obesity (BMI >/= 30 kg/m(2)) or overweight (BMI >/= 27 kg/m(2)), with or without type 2 diabetes (T2DM). We excluded crossover trials, open-label studies, early-phase trials, and studies focusing on specific subpopulations. RESULTS: A total of 22 RCTs involving 41,757 participants were included. Among adults with T2DM, the greatest weight reductions were observed with tirzepatide 15 mg (-9.5 kg at 40 weeks; 72% lost >/= 5% of baseline weight) and semaglutide 2.4 mg (-9.6% body weight at 68 weeks; 69% lost >/= 5%). In participants without T2DM, semaglutide 2.4 mg (-14.9% body weight at 68 weeks) and tirzepatide 15 mg (-20.9% at 72 weeks) produced the most substantial effects, while semaglutide 50 mg was also effective in nondiabetic patients. Liraglutide 3 mg showed modest efficacy. Across trials, GLP-1 RAs were consistently associated with a higher frequency of gastrointestinal adverse events compared to placebo, including nausea (14%-28% vs. 5%-10%), vomiting (6%-12% vs. 2%-4%), and diarrhea (8%-20% vs. 4%-7%). The risk of pancreatitis and serious adverse events remained comparable to placebo. CONCLUSIONS: GLP-1 RAs, especially semaglutide and tirzepatide, are effective for weight management. Liraglutide may remain a viable, cost-effective alternative. CI - Copyright (c) 2025 Jena Velji-Ibrahim et al. Journal of Obesity published by John Wiley & Sons Ltd. FAU - Velji-Ibrahim, Jena AU - Velji-Ibrahim J AUID- ORCID: 0000-0002-5282-0727 AD - Gastroenterology and Liver Center, Prisma Health-Upstate, University of South Carolina School of Medicine, Greenville, South Carolina, USA. FAU - Radadiya, Dhruvil AU - Radadiya D AD - Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA. FAU - Devani, Kalpit AU - Devani K AD - Gastroenterology and Liver Center, Prisma Health-Upstate, University of South Carolina School of Medicine, Greenville, South Carolina, USA. FAU - Patel, Harsh AU - Patel H AD - Department of Gastroenterology, Hepatology and Motility, University of Kansas Medical Center, Kansas City, Kansas, USA. FAU - Nathani, Piyush AU - Nathani P AD - Department of Gastroenterology, Hepatology and Motility, University of Kansas Medical Center, Kansas City, Kansas, USA. FAU - Hassan, Cesare AU - Hassan C AD - Department of Gastroenterology and Hepatology, Humanitas Research Hospital, Milan, Italy. FAU - Pugliese, Nicola AU - Pugliese N AUID- ORCID: 0000-0001-6466-1412 AD - Department of Gastroenterology and Hepatology, Humanitas Research Hospital, Milan, Italy. FAU - Thompson, Christopher AU - Thompson C AD - Department of Advanced Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Sharma, Prateek AU - Sharma P AD - Department of Gastroenterology, Hepatology and Motility, University of Kansas Medical Center, Kansas City, Kansas, USA. AD - Department of Gastroenterology, Kansas City VA Medical Center, Kansas City, Missouri, USA. LA - eng PT - Journal Article PT - Systematic Review DEP - 20251019 PL - United States TA - J Obes JT - Journal of obesity JID - 101526295 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - J Obes. 2026 Feb 03;2026:9821679. doi: 10.1155/jobe/9821679. PMID: 41641176 MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use MH - Adult MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12591819 OTO - NOTNLM OT - diabetes mellitus OT - glucagon-like peptide-1 receptor agonist OT - obesity OT - tirzepatide OT - weight loss COIS- Dhruvil Radadiya: Consultant: Castle Biosciences. Prateek Sharma: Consultant: Boston Scientific, Olympus Inc. Grant support: US Endoscopy, Medtronics, Fujifilms, Ironwood, Cosmo Pharmaceuticals, Erbe. Christopher Thompson: Consultant and Research Support from Apollo Endosurgery; Founder, Board Member, Ownership Interest with Bariendo; Founder and General Partner with BlueFlame Healthcare Venture Fund; Consultant and Research Support from Boston Scientific; Consultant with Medtronic; Founder, Board Member, Ownership Interest with ELLES; Consultant and Research Support from Endoquest Robotics; Founder, Consultant, Board Member, Ownership Interest with Enterasense Ltd; Founder, Board Member, Consultant, Ownership Interest with EnVision Endoscopy; Research Support from ERBE; Consultant, Advisory Board Member, Research Support from Fractyl; Consultant and Research Support from FujiFilm; Consultant and Research Support from GI Dynamics; Founder, Board Member, Ownership interest with GI Windows; Consultant and Research Support from Lumendi; Consultant and Research Support from Olympus/Spiration; Founder, President, Ownership Interest with Society for Metabolic and Bariatric Endoscopy; Consultant and Ownership Interest with Softac; Consultant, Advisory Board Member, Research Support from USGI Medical; and Consultant, Scientific Advisory Board, Ownership Interest with Xenter. No other disclosures were reported. EDAT- 2025/11/10 18:15 MHDA- 2025/11/13 00:31 PMCR- 2025/10/19 CRDT- 2025/11/10 06:18 PHST- 2025/05/05 00:00 [received] PHST- 2025/09/14 00:00 [revised] PHST- 2025/09/23 00:00 [accepted] PHST- 2025/11/13 00:31 [medline] PHST- 2025/11/10 18:15 [pubmed] PHST- 2025/11/10 06:18 [entrez] PHST- 2025/10/19 00:00 [pmc-release] AID - 10.1155/jobe/3897161 [doi] PST - epublish SO - J Obes. 2025 Oct 19;2025:3897161. doi: 10.1155/jobe/3897161. eCollection 2025. PMID- 41207920 OWN - NLM STAT- MEDLINE DCOM- 20260121 LR - 20260127 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 32 IP - 1 DP - 2026 Jan TI - Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice. PG - 342-352 LID - 10.1038/s41591-025-04102-x [doi] AB - Cardiovascular outcome trials of the incretin-based medicines tirzepatide and semaglutide have shown benefits in populations with varying levels of cardiovascular risk. However, without direct head-to-head comparisons, treatment decisions rely on indirect evidence from heterogeneous trial populations, leaving optimal treatment choices uncertain. Here we conducted five cohort studies to assess the effectiveness of tirzepatide and semaglutide in patients with elevated cardiovascular risk, including obesity and type 2 diabetes, enrolled in insurance programs in the USA between 2018 and 2025. First, we emulated two cardiovascular outcome trials, SUSTAIN-6 (semaglutide versus sitagliptin as placebo proxy) and SURPASS-CVOT (tirzepatide versus dulaglutide), to benchmark and critically evaluate our design, data and analytic framework. Second, we assessed each drug in expanded populations reflective of patients routinely seen in clinical practice. Third, we directly compared tirzepatide versus semaglutide. Baseline confounders were balanced using propensity score matching. For the primary composite endpoint of myocardial infarction, stroke or all-cause mortality, benchmarking identified high agreement between the reference trials and their emulations for all individual endpoints except for all-cause mortality in SUSTAIN-6, informing subsequent analyses. In expanded populations, comparing semaglutide versus sitagliptin for the composite outcome of myocardial infarction or stroke yielded a hazard ratio of 0.82 (95% confidence interval (CI) 0.74 to 0.91), and comparing tirzepatide versus dulaglutide for the composite outcome including mortality yielded a hazard ratio of 0.87 (95% CI 0.75 to 1.01). In the head-to-head comparison of tirzepatide versus semaglutide, the hazard ratio was 1.06 (95% CI 0.95 to 1.18). These findings support a comparable cardiovascular benefit of tirzepatide and semaglutide in clinical practice and demonstrate how rigorously designed real-world evidence can complement randomized clinical trials. ClinicalTrials.gov registration: NCT06659744 , NCT07088718 , NCT07096063 . CI - (c) 2026. The Author(s). FAU - Kruger, Nils AU - Kruger N AUID- ORCID: 0009-0008-3190-0462 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. nkruger1@bwh.harvard.edu. AD - Harvard Medical School, Boston, MA, USA. nkruger1@bwh.harvard.edu. AD - Department of Cardiology, TUM University Hospital German Heart Center, Technical University of Munich, Munich, Germany. nkruger1@bwh.harvard.edu. AD - Deutsches Zentrum fur Herz-Kreislauf-Forschung (DZHK), Partner Site Munich Heart Alliance, Munich, Germany. nkruger1@bwh.harvard.edu. FAU - Schneeweiss, Sebastian AU - Schneeweiss S AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Desai, Rishi J AU - Desai RJ AUID- ORCID: 0000-0003-0299-7273 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Sreedhara, Sushama Kattinakere AU - Sreedhara SK AUID- ORCID: 0000-0002-9182-304X AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. FAU - Kehoe, Anna R AU - Kehoe AR AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Fuse, Kenshiro AU - Fuse K AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Hahn, Georg AU - Hahn G AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Schunkert, Heribert AU - Schunkert H AUID- ORCID: 0000-0001-6428-3001 AD - Department of Cardiology, TUM University Hospital German Heart Center, Technical University of Munich, Munich, Germany. AD - Deutsches Zentrum fur Herz-Kreislauf-Forschung (DZHK), Partner Site Munich Heart Alliance, Munich, Germany. FAU - Wang, Shirley V AU - Wang SV AUID- ORCID: 0000-0001-7761-7090 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. LA - eng SI - ClinicalTrials.gov/NCT06659744 SI - ClinicalTrials.gov/NCT07096063 SI - ClinicalTrials.gov/NCT07088718 GR - R01-HL141505/U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ GR - R01 HL141505/HL/NHLBI NIH HHS/United States GR - S/02/24/Deutsche Herzstiftung (German Heart Foundation)/ GR - SRF-HF/24/Deutsche Herzstiftung (German Heart Foundation)/ GR - R01-AR080194/U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ GR - R01 AR080194/AR/NIAMS NIH HHS/United States PT - Journal Article DEP - 20251109 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Sitagliptin Phosphate/therapeutic use MH - *Tirzepatide/therapeutic use MH - Treatment Outcome MH - Observational Studies as Topic PMC - PMC12823426 COIS- Competing interests: S.S. reports personal fees from Aetion Inc., a software-enabled analytics company, and grants from Bayer, UCB and Boehringer Ingelheim to Brigham and Women's Hospital outside the submitted work. H.S. reports personal fees from AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, MSD, Novartis, Pharmacosmos, Sanofi, Servier, Synlab, Amgen and Amarin outside the submitted work. S.V.W. reports personal fees from MITRE, a federally funded research and development center for the Centers for Medicare and Medicaid Services and personal fees from Cytel Inc. during the conduct of the study. The other authors declare no competing interests. EDAT- 2025/11/10 00:53 MHDA- 2026/01/22 01:09 PMCR- 2025/11/09 CRDT- 2025/11/09 23:14 PHST- 2025/09/03 00:00 [received] PHST- 2025/11/04 00:00 [accepted] PHST- 2026/01/22 01:09 [medline] PHST- 2025/11/10 00:53 [pubmed] PHST- 2025/11/09 23:14 [entrez] PHST- 2025/11/09 00:00 [pmc-release] AID - 10.1038/s41591-025-04102-x [pii] AID - 4102 [pii] AID - 10.1038/s41591-025-04102-x [doi] PST - ppublish SO - Nat Med. 2026 Jan;32(1):342-352. doi: 10.1038/s41591-025-04102-x. Epub 2025 Nov 9. PMID- 41207620 OWN - NLM STAT- MEDLINE DCOM- 20260104 LR - 20260922 IS - 1523-1755 (Electronic) IS - 0085-2538 (Linking) VI - 109 IP - 1 DP - 2026 Jan TI - REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide. PG - 6-16 LID - S0085-2538(25)00861-0 [pii] LID - 10.1016/j.kint.2025.10.005 [doi] AB - Chronic kidney disease poses a major global health burden and is one of the most common complications of type 2 diabetes. Drug trials have demonstrated that treatments, including sodium-glucose cotransporter-2 inhibitors, a glucagon-like peptide-1 receptor agonist, and a nonsteroidal mineralocorticoid receptor antagonist, mitigate chronic kidney disease progression, but the underlying nephroprotective mechanisms of action remain incompletely understood, partly ascribed to their pleiotropic actions. New innovative trial designs are needed to tackle simultaneously the hemodynamic and structural effects induced by these drugs. The REMODEL trial (REnal MODE of action of semagLutide in patients with type 2 diabetes and chronic kidney disease; ClinicalTrials.gov identifier: NCT04865770) is designed to explore the mechanisms of action of semaglutide with a novel multiparametric approach, integrating functional magnetic resonance imaging and research kidney biopsies for structural and molecular interrogation and blood and urine biomarker analysis. Better understanding of these mechanisms will help explain semaglutide's beneficial effects on kidney disease outcomes, reported in the FLOW (Evaluate Renal Function with Semaglutide Once Weekly; ClinicalTrials.gov identifier: NCT03819153) trial, and may identify patient subpopulations to optimize treatment strategies. By combining diverse and state-of-the-art methods, REMODEL aims to pave the way to a larger use of mechanism of action trials in the near future. To this purpose, this article describes the REMODEL framework, methods, technical challenges, and lessons learned as a platform for future mechanistic trials of chronic kidney disease therapies and beyond. CI - Copyright (c) 2025 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. FAU - Pruijm, Menno AU - Pruijm M AD - Service of Nephrology, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland. Electronic address: menno.pruijm@chuv.ch. FAU - Belmar, Nicolas AU - Belmar N AD - Global Medical Affairs, Product and Portfolio Strategy, Novo Nordisk A/S, Soborg, Denmark. FAU - Bjornstad, Petter AU - Bjornstad P AD - Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington Medicine Diabetes Institute, Seattle, Washington, USA; Department of Pediatrics, Division of Endocrinology, University of Washington, Seattle, Washington, USA; Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; Department of Pediatrics, Section of Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. FAU - Cherney, David Z I AU - Cherney DZI AD - Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada. FAU - Das, Vivek AU - Das V AD - Clinical Omics Science, Data Science, Research & Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Gunnarsson, Thomas AU - Gunnarsson T AD - Global Medical Affairs, Product and Portfolio Strategy, Novo Nordisk A/S, Soborg, Denmark. FAU - Hodgin, Jeffrey B AU - Hodgin JB AD - Department of Pathology and Clinical Laboratories, University of Michigan, Ann Arbor, Michigan, USA. FAU - Schytz, Philip A AU - Schytz PA AD - Medical and Science, Research & Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Providence, Medical Research Center, Providence Inland Northwest Health, Spokane, Washington, USA; Kidney Research Institute and Nephrology Division, University of Washington School of Medicine, Seattle, Washington, USA. FAU - Kretzler, Matthias AU - Kretzler M AD - Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. Electronic address: kretzler@umich.edu. LA - eng SI - ClinicalTrials.gov/NCT03819153 SI - ClinicalTrials.gov/NCT04865770 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20251107 PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Biomarkers) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Biomarkers/urine/blood MH - Biopsy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies/drug therapy/etiology MH - Disease Progression MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Hypoglycemic Agents/therapeutic use MH - *Kidney/drug effects/pathology/diagnostic imaging/physiopathology MH - Magnetic Resonance Imaging MH - *Renal Insufficiency, Chronic/drug therapy/etiology/pathology MH - Multicenter Studies as Topic MH - Clinical Trials, Phase III as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - chronic kidney disease OT - clinical trials OT - type 2 diabetes EDAT- 2025/11/10 00:53 MHDA- 2026/01/05 00:49 CRDT- 2025/11/09 19:15 PHST- 2025/08/01 00:00 [received] PHST- 2025/10/27 00:00 [revised] PHST- 2025/10/27 00:00 [accepted] PHST- 2026/01/05 00:49 [medline] PHST- 2025/11/10 00:53 [pubmed] PHST- 2025/11/09 19:15 [entrez] AID - S0085-2538(25)00861-0 [pii] AID - 10.1016/j.kint.2025.10.005 [doi] PST - ppublish SO - Kidney Int. 2026 Jan;109(1):6-16. doi: 10.1016/j.kint.2025.10.005. Epub 2025 Nov 7. PMID- 41204831 OWN - NLM STAT- MEDLINE DCOM- 20251229 LR - 20260127 IS - 1365-2125 (Electronic) IS - 0306-5251 (Print) IS - 0306-5251 (Linking) VI - 92 IP - 1 DP - 2026 Jan TI - GLP-1 agonist-associated presentations to unscheduled care: An opportunistic pilot study. PG - 312-316 LID - 10.1002/bcp.70335 [doi] AB - The impact of GLP-1 or GIP/GLP-1 receptor agonist use on unscheduled care is not well-described. We conducted a prospective, observational study using opportunistic screening by clinicians as a first step to understanding the effect of GLP-1 or GIP/GLP-1 agonists on Emergency Department presentations and to guide future studies. Data were collected from April to August 2025 at a single centre for any nontrauma adult patient who self-reported GLP-1 or GIP/GLP-1 agonist exposure. Fifty-six cases were identified, 51 reported tirzepatide use, three subcutaneous semaglutide, one oral semaglutide and one dulaglutide. In 79% of cases (CI95% 66% to 88%), the presenting features were due to GLP-1 or agonist use. Presentations were greatest in the lowest and highest deprivation quintiles and a significant number had coexisting depression. There is a need for formal observational studies to assess the impact of GLP-1 or GIP/GLP-1 agonists on unscheduled care and explore these tentative associations. CI - (c) 2025 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. FAU - Thomas, Oliver AU - Thomas O AUID- ORCID: 0009-0002-9448-2639 AD - Cardiff & Vale University Health Board, University Hospital of Wales, Heath Park Campus, Cardiff, UK. FAU - Coulson, James Michael AU - Coulson JM AD - All Wales Therapeutics & Toxicology Centre, Cardiff & Vale University Health Board, University Hospital, Llandough, Penarth, UK. AD - School of Medicine, Cardiff University, Cardiff, UK. LA - eng PT - Journal Article PT - Observational Study DEP - 20251108 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Pilot Projects MH - Male MH - Female MH - Middle Aged MH - Prospective Studies MH - Glucagon-Like Peptides/analogs & derivatives/adverse effects/administration & dosage MH - Aged MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - *Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Recombinant Fusion Proteins/adverse effects/administration & dosage MH - Adult MH - *Emergency Service, Hospital/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy MH - Immunoglobulin Fc Fragments/adverse effects/administration & dosage MH - Gastric Inhibitory Polypeptide/agonists MH - Semaglutide PMC - PMC12746371 OTO - NOTNLM OT - GIP/GLP-1 OT - GLP-1 receptor agonist OT - unscheduled care COIS- The authors declare no conflicts of interest. EDAT- 2025/11/08 12:45 MHDA- 2025/12/29 13:02 PMCR- 2025/11/08 CRDT- 2025/11/08 06:02 PHST- 2025/10/11 00:00 [revised] PHST- 2025/09/16 00:00 [received] PHST- 2025/10/15 00:00 [accepted] PHST- 2025/12/29 13:02 [medline] PHST- 2025/11/08 12:45 [pubmed] PHST- 2025/11/08 06:02 [entrez] PHST- 2025/11/08 00:00 [pmc-release] AID - BCP70335 [pii] AID - 10.1002/bcp.70335 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2026 Jan;92(1):312-316. doi: 10.1002/bcp.70335. Epub 2025 Nov 8. PMID- 41204243 OWN - NLM STAT- MEDLINE DCOM- 20251108 LR - 20260908 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Nov 7 TI - Neurodegeneration onset with glucagon-like peptide-1 receptor agonists in people with type 2 diabetes: a real-world multinational cohort study. PG - 426 LID - 10.1186/s12933-025-02962-8 [doi] LID - 426 AB - BACKGROUND: Type 2 diabetes (T2D), affecting approximately 12% of the global population and over 30% of older adults, is among the most prevalent and fast-growing risk factors for neurodegenerative disorders. Evidence is lacking on whether specific glucose-lowering agents may reduce the risk of neurodegeneration onset in people living with T2D. METHODS: In this retrospective cohort study, we utilized the TriNetX platform, which contains electronic health records of over 170 million people worldwide. We propensity-score matched (1:1) people with T2D lacking evidence of neurodegeneration who initiated glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or dipeptidyl peptidase-4 inhibitors (DPP4i) (2010-2021). In a separate analytical cohort, we compared individuals initiating GLP-1 RA with those initiating basal insulin. Follow-up continued for /= 65 years old (0.82 [0.78 to 0.87]) or < 65 years old (0.84 [0.70 to 1.00]), and in those initiating semaglutide (0.75 [0.67 to 0.84]), liraglutide (0.77 [0.70 to 0.84]), or dulaglutide (0.82 [0.77 to 0.88]). The hazard ratios for dementia, Alzheimer's disease, vascular dementia, and Parkinson's disease onset were 0.76 [0.72 to 0.81], 0.77 [0.68 to 0.87], 0.75 [0.67 to 0.85], and 1.04 [0.93 to 1.17] with GLP-1 RAs versus DPP4i, respectively. The results were in the same direction when comparing individuals initiating GLP-1 RAs with those initiating basal insulin. CONCLUSIONS: In a real-world cohort of people living with T2D with a multinational representation, the initiation of GLP-1 RAs, compared to DPP4i or basal insulin, was associated with a lower risk of new-onset neurodegeneration. These data support the rationale for dedicated clinical trials to assess the potential neuroprotective properties of GLP-1 RAs in this population. CI - (c) 2025. The Author(s). FAU - Schechter, Meir AU - Schechter M AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Ein Kerem Medical Center, P.O.B 12000, 9112001, Jerusalem, Israel. meir.schechter@mail.huji.ac.il. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. meir.schechter@mail.huji.ac.il. AD - The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Ramat Gan, Israel. meir.schechter@mail.huji.ac.il. AD - Dina Recanati School of Medicine, Reichman University, Herzliya, Israel. meir.schechter@mail.huji.ac.il. FAU - Fishkin, Alisa AU - Fishkin A AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Ein Kerem Medical Center, P.O.B 12000, 9112001, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. AD - Regeneron Pharmaceuticals Inc., New York, NY, USA. FAU - Sehtman-Shachar, Dvora R AU - Sehtman-Shachar DR AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Ein Kerem Medical Center, P.O.B 12000, 9112001, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Cukierman-Yaffe, Tali AU - Cukierman-Yaffe T AD - Division of Endocrinology, Diabetes and Metabolism, Sheba Medical Center, Ramat Gan, Israel. AD - Department of Epidemiology and Preventive Medicine, School of Public Health, Dear Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel Aviv, Israel. FAU - Leibowitz, Gil AU - Leibowitz G AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Ein Kerem Medical Center, P.O.B 12000, 9112001, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Aharon-Hananel, Genya AU - Aharon-Hananel G AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Ein Kerem Medical Center, P.O.B 12000, 9112001, Jerusalem, Israel. AD - Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20251107 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Incretins) RN - 0 (GLP1R protein, human) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Neurodegenerative Diseases/epidemiology/diagnosis/prevention & control MH - Risk Factors MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - *Incretins/therapeutic use/adverse effects MH - Time Factors MH - Treatment Outcome MH - Risk Assessment MH - Biomarkers/blood MH - *Blood Glucose/drug effects/metabolism MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Electronic Health Records MH - Glucagon-Like Peptide-1 Receptor PMC - PMC12595915 OTO - NOTNLM OT - Alzheimer's disease OT - Dementia OT - Glucagon-like peptide-1 receptor agonists OT - Neurodegeneration OT - Neuroprotection OT - Parkinson's disease COIS- Declarations. Conflict of interest: MS reports travel support from Novo Nordisk and AstraZeneca through Hadassah Medical Center, and lecturing fees from AstraZeneca (2022). AF and DRSS report no conflict of interest. OM reports Advisory Board membership for Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and BOL Pharma, research grant support through Hadassah Hebrew University Hospital from Novo Nordisk and AstraZeneca, and Speaker's Bureau participation for AstraZeneca, Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp & Dohme, and Boehringer Ingelheim. From May 1st, 2023, OM has been an employee of Regeneron Pharmaceuticals Inc. This work was not funded by Regeneron Pharmaceuticals, Inc.; it was not part of OM's job responsibilities; and the company had no role in conception, data acquisition, analysis, interpretation, or manuscript preparation. TCY reports receiving research support from Medtronic, Regeneron, Novo Nordisk, and Merck Sharp & Dohme. Honorarium for lecture/advisory board from Medtronic, Sanofi, Novo Nordisk, Boehringer Ingelheim, AstraZeneca, and Amgen. GL reports participation in previous Advisory Boards: Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca and Medtronic. He reports travel support from Novo Nordisk, Boehringer Ingelheim and AstraZeneca through Hadassah Medical Center. Speaker's Bureau: AstraZeneca, Novo Nordisk, Eli Lilly, Boehringer Ingelheim. GAH reported previous Advisory Board: Sanofi and Eli Lilly. She is a current PI in several RCTs conducted by Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca and Bayer including the CONFIDENCE study, through Hadassah Medical Center. GAH reports travel support from Novo Nordisk and Medetronic through Hadassah Medical Center and AstraZeneca through Sheba medical center. Speaker's Bureau: AstraZeneca, Novo Nordisk, Eli Lilly and Sanofi. EDAT- 2025/11/08 00:28 MHDA- 2025/11/08 06:29 PMCR- 2025/11/07 CRDT- 2025/11/07 23:53 PHST- 2025/08/02 00:00 [received] PHST- 2025/09/26 00:00 [accepted] PHST- 2025/11/08 06:29 [medline] PHST- 2025/11/08 00:28 [pubmed] PHST- 2025/11/07 23:53 [entrez] PHST- 2025/11/07 00:00 [pmc-release] AID - 10.1186/s12933-025-02962-8 [pii] AID - 2962 [pii] AID - 10.1186/s12933-025-02962-8 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Nov 7;24(1):426. doi: 10.1186/s12933-025-02962-8. PMID- 41196592 OWN - NLM STAT- MEDLINE DCOM- 20251106 LR - 20260726 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 11 DP - 2025 Nov 3 TI - Cost-Effectiveness of MASH Diagnosis and Management Approaches Among Those With Type 2 Diabetes. PG - e2542750 LID - 10.1001/jamanetworkopen.2025.42750 [doi] LID - e2542750 AB - IMPORTANCE: Metabolic dysfunction-associated steatohepatitis (MASH) represents a high, underprioritized burden among noncommunicable diseases (NCDs) and people living with type 2 diabetes (T2D). OBJECTIVE: To identify cost-effective management approaches to prevent, detect, and treat MASH and liver fibrosis in people living with T2D. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation consisted of a generalized cost-effectiveness analysis (GCEA) that was conducted for 12 countries (Brazil, Chile, Germany, Italy, Japan, Saudi Arabia, South Africa, Spain, Sweden, Tanzania, Thailand, and the United States), across all 6 World Health Organization (WHO) regions. A cohort state-transition model simulated liver disease development and its impact on a synthetic cohort, aged 19 years and older and living with T2D, over their lifespan across 10 liver health states. EXPOSURES: Using an 80% coverage level, 14 management approaches were compared, including screening via the Fibrosis-4 (FIB-4) test and Enhanced Liver Fibrosis (ELF) test or vibration-controlled transient elastography (VCTE) as well as treatment with pharmacological and nonpharmacological interventions. MAIN OUTCOMES AND MEASURES: The main outcomes were the average cost-effectiveness ratios (ACERs) and the incremental cost-effectiveness ratios (ICERs), which were used to construct care expansion paths by ranking the management approaches in order of cost-effectiveness. The main measures were the total incremental costs and the total incremental quality-adjusted life-years (QALYs) of each intervention. RESULTS: In this GCEA, the outcomes were evaluated with respect to country-specific willingness-to-pay thresholds. The standard of care had the lowest ACERs in 8 countries (not in Chile, Germany, Saudi Arabia, or the United States). Treatment with intensive lifestyle interventions (ILIs), after screening via ELF or VCTE, was cost-effective in all countries. ILIs and treatment with semaglutide was cost-effective in 11 countries (not in Tanzania); ILIs and treatment with resmetirom was cost-effective in 8 countries (not in Brazil, South Africa, Tanzania, or Thailand). CONCLUSION AND RELEVANCE: In this economic evaluation, screening followed by ILIs was found to be a cost-effective management approach for MASH and liver fibrosis among people living with T2D in all countries. Screening followed by pharmacological treatment was cost-effective in most countries. These results can inform health policy decision-making and further the development of WHO recommended interventions to address NCDs. FAU - Lazarus, Jeffrey V AU - Lazarus JV AD - City University of New York Graduate School of Public Health and Health Policy (CUNY SPH), New York. AD - Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. AD - Faculty of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Spain. FAU - Agirre-Garrido, Leire AU - Agirre-Garrido L AD - Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. FAU - Diaz, Luis Antonio AU - Diaz LA AD - Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile. AD - Observatorio Multicentrico de Enfermedades Gastrointestinales, OMEGA, Santiago, Chile. AD - MASLD Research Center, Division of Gastroenterology and Hepatology, University of California, San Diego, La Jolla. FAU - Danpanichkul, Pojsakorn AU - Danpanichkul P AD - Department of Internal Medicine, Texas Tech University Health Science Center, Lubbock. FAU - Kivuyo, Sokoine L AU - Kivuyo SL AD - Faculty of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Spain. AD - National Institutes for Medical Research, Dar es Salaam, Tanzania. FAU - Kondili, Loreta A AU - Kondili LA AD - National Center for Global Health, Istituto Superiore di Sanita, Rome, Italy. FAU - Hagstrom, Hannes AU - Hagstrom H AD - Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. AD - Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden. FAU - Takahashi, Hirokazu AU - Takahashi H AD - Liver Center, Saga University Hospital, Saga City, Saga, Japan. FAU - Pericas, Juan M AU - Pericas JM AD - Liver Unit, Vall d'Hebron University Hospital, Vall d'Hebron Institute for Research, Universitat Autonoma de Barcelona, Centros de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBERehd), Barcelona, Spain. FAU - Spearman, C Wendy AU - Spearman CW AD - Division of Hepatology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. FAU - Oliveira, Claudia P AU - Oliveira CP AD - Department of Gastroenterology, Faculdade de Medicina da Universidade de Sao Paulo (LIM07), Sao Paulo, Brazil. FAU - Villela-Nogueira, Cristiane A AU - Villela-Nogueira CA AD - School of Medicine, Hepatology Division, Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Schattenberg, Jorn M AU - Schattenberg JM AD - Department of Internal Medicine II, Saarland University Medical Centre, Homburg, Germany. AD - Faculty of Medicine, Saarland University, Saarbrucken, Germany. FAU - Toresson Grip, Emilie AU - Toresson Grip E AD - Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden. FAU - Alkhouri, Naim AU - Alkhouri N AD - Steatotic Liver Disease Program, Arizona Liver Health, Phoenix. FAU - Marcellusi, Andrea AU - Marcellusi A AD - Department of Pharmaceutical Sciences, University of Milan, Milan, Italy. FAU - Mark, Henry E AU - Mark HE AD - Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. FAU - Allen, Alina M AU - Allen AM AD - Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Carvalho Leite, Nathalie AU - Carvalho Leite N AD - Hepatology Division, Hospital Universitario Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Al-Omar, Hussain A AU - Al-Omar HA AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Alqahtani, Saleh A AU - Alqahtani SA AD - King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia. FAU - Brachowicz, Nicolai AU - Brachowicz N AD - Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20251103 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/economics MH - *Cost-Benefit Analysis MH - Female MH - Middle Aged MH - Male MH - Liver Cirrhosis/economics/diagnosis/therapy MH - Adult MH - *Non-alcoholic Fatty Liver Disease/therapy/economics/diagnosis MH - Aged MH - Quality-Adjusted Life Years PMC - PMC12593099 COIS- Conflict of Interest Disclosures: Dr Lazarus reported receiving grants to the institution (ISGlobal) from Gilead Science, Echosens, Novo Nordisk, Pfizer, Madrigal Pharmaceuticals, Boehringer Ingelheim, AbbVie, Moderna, MSD, and Roche Diagnostics; receiving personal fees from GSK, Echosens, Novovax, Novo Nordisk, and Pfizer; having held a paid leadership role at the Global NASH/MASH Council; receiving honoraria from AbbVie, Echosens, Gilead Science, GSK, Moderna, MSD, Novo Nordisk, Pfizer and Prosciento; participating on a data safety monitoring board for the QuickStart Study; having a leadership role in Healthy Livers, Health Lives; and serving as director of the Global Think-tank on Steatotic Liver Disease and MASH Cities outside the submitted work. Dr Kondili reported receiving grants to her institution from Gilead Science and personal fees from Gilead Science for participation in a scientific meeting outside the submitted work. Dr Hagstrom reported receiving grants to his institution from AstraZeneca, Echosens, Gilead Science, Intercept, MSD, Novo Nordisk and Pfizer; receiving consulting fees from AstraZeneca and Novo Nordisk; receiving payment for lectures from Gilead Science and Novo Nordisk; and participating on hepatic events adjudication committees for Arrowhead, KOWA, GW Pharma, and Boehringer Ingelheim outside of the submitted work. Dr Takahashi reported receiving honoraria for lectures from Novo Nordisk, Tisho Pharma, and Kowa outside of the submitted work. Dr Pericas reported receiving consulting fees from MSD, Madrigal Pharmaceuticals, Boehringer Ingelheim, and Novo Nordisk; receiving speaking fees from Madrigal Pharmaceuticals, Gilead Science, Intercept, Boehringer Ingelheim, Novo Nordisk, Asociacion Espanola para el Estudio del Higado, and International Meeting on Therapy in Liver Diseases; travel expenses from Gilead Science, Rubio, Pfizer, Astellas, MSD, and Novo Nordisk; receiving educational and research support from Madrigal Pharmaceuticals, Boehringe Ingelheim, Gilead Science, Pfizer, Astellas, Accelerate, Novartis, AbbVie, ViiV, Siemens and MSD; and receiving competitive funding from Vall d'Hebron University Hospital Campus (research intensification grant 2024-2025), ISCIII PI19/01898, PI22/01770, European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, HLTH-2023-TOOL-05-03, MICIN IBEC_ProyectCompl22, DTS24/00035, and "La Caixa" Foundation and Barcelona City Council (COVID-SHINE and StopALD) outside of the submitted work. Dr Spearman reported receiving honoraria for lectures from Novo Nordisk, Gilead Science, and Sanofi; receiving travel support from Gilead Science, and having a leadership or fiduciary role for the Society on Liver Disease in Africa (SOLDA) outside the submitted work. Dr Oliveira reported receiving consulting fees from Novo Nordisk, Boehringer Ingelheim, Inventiva AstraZeneca, and Pfizer; receiving payment or honoraria for lectures from Novo Nordisk, Boehringer Ingelheim, Inventiva, AstraZeneca, and Pfizer, and receiving support for attending meetings from Novo Nordisk and Mertz outside of the submitted work. Dr Villela-Nogueira reported receiving honoraria from Novo Nordisk, Boehringer Ingelheim, and Mantecorp; receiving travel support from Novo Nordisk; and serving on the advisory boards of Novo Nordisk and Boehringer Ingelheim outside of the submitted work. Dr Schattenberg reported receiving speaker fees from AbbVie, Boehringer Ingelheim, Echosens, Gilead Science, Ipsen, Eli Lilly and Co, Madrigal Pharmaceuticals, MedScape, MSD, and Novo Nordisk; receiving personal fees from Akero, Alentis, Alexion, Altimmune, AstraZeneca, 89Bio, Bionorica, Boehringer Ingelheim, Boston Pharmaceuticals, Gilead Science, GSK, HistoIndex, Ipsen, Inventiva Pharma, Madrigal Pharmaceuticals, Kriya Therapeutics, Eli Lilly and Co, MSD Sharp & Dohme GmbH, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers; and having stock options in Hepta Bio outside the submitted work. Mrs Grip reported receiving consulting fees from Quantify Research outside of the submitted work. Dr Alkhouri reported receiving grants to Arizona Liver Health from 89bio, Akero Therapeutics, Allergan, Arbutus Biopharma, AstraZeneca, Better Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Corcept Therapeutics, CymaBay Therapeutics, DSM, Galectin Therapeutics, Genentech, Genfit, Gilead Science, Healio, Hepagene Therapeutics, Intercept Pharmaceuticals, Inventiva Pharma, Ionis Pharmaceuticals, Ipsen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Noom, NorthSea Therapeutics, Novo Nordisk, Perspectum, Pfizer, Poxel, Viking Therapeutics, and Zydus Pharmaceuticals during the conduct of the study as well as receiving personal fees from 89bio, Akero, Boehringer Ingelheim, Echosens, Fibronostics, Gilead Science, Intercept Pharmaceuticals, Ipsen, Madrigal Pharmaceuticals, NorthSea Therapeutics, Novo Nordisk, Perspectum, Pfizer, Regeneron, and Zydus Pharmaceuticals; receiving honoraria for lectures from AbbVie, AstraZeneca, Intercept Pharmaceuticals, Ipsen, Madrigal Pharmaceuticals, and Perspectum outside the submitted work. Mr Mark reported being a director of HEM Consultancy and receiving consulting fees from Panorma Global, Barcelona Institute for Global Health, the European Association for the Study of the Liver, GBCHealth, and the United Nations University-IIGH outside of the submitted work. Dr Allen reported receiving grants to Mayo Clinic from the National Institutes of Health, Novo Nordisk, Madrigal Pharmaceuticals, Target Pharma, Siemens, Oncoustics, Escopics, and Pfizer as well as receiving consulting fees from Boehringer Ingelheim, Madrigal Pharmaceuticals, Novo Nordisk, and GSK outside the submitted work. Mr Brachowicz reported receiving support from the Ministerio de Ciencia, Innovacion y Universidades/Agencia Estatal de Investigacion (MCIN/AEI) and the Generalitat de Catalunya, through the CERCA Programme. No other disclosures were reported. EDAT- 2025/11/06 12:33 MHDA- 2025/11/06 12:34 PMCR- 2025/11/06 CRDT- 2025/11/06 11:33 PHST- 2025/11/06 12:34 [medline] PHST- 2025/11/06 12:33 [pubmed] PHST- 2025/11/06 11:33 [entrez] PHST- 2025/11/06 00:00 [pmc-release] AID - 2841038 [pii] AID - zoi251164 [pii] AID - 10.1001/jamanetworkopen.2025.42750 [doi] PST - epublish SO - JAMA Netw Open. 2025 Nov 3;8(11):e2542750. doi: 10.1001/jamanetworkopen.2025.42750. PMID- 41192935 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260429 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 13 IP - 6 DP - 2025 Nov 4 TI - Semaglutide and diabetic retinopathy: an OHDSI network study. LID - 10.1136/bmjdrc-2025-005424 [doi] LID - e005424 AB - INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) used to treat type 2 diabetes mellitus (T2D), has potential associations with higher rates of diabetic retinopathy (DR) complications including proliferative DR (PDR) and diabetic macular edema (DME). The purpose of this study was to determine whether an association exists between semaglutide and PDR and treatment-requiring DR/DME. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study of 14 databases (six administrative claims and eight electronic health records) in the Observational Health Data Sciences and Informatics Evidence Network. Adults with T2D on semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from 1 December 2017 to 31 December 2023 were included. The association between semaglutide and PDR or treatment-requiring DR/DME was assessed using an active-comparator cohort design comparing new users of semaglutide as second-line T2D treatment to those on other GLP-1RAs and non-GLP-1RAs. Propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs). Network-wide HR estimates were generated using a random-effects meta-analysis. RESULTS: The study included 810 390 new semaglutide users for T2D. PDR risk for semaglutide was similar to dulaglutide (HR 0.81, 95% CI 0.42 to 1.54, p=0.51), empagliflozin (HR 0.83, 95% CI 0.53 to 1.30, p=0.41) and sitagliptin (HR 0.83, 95% CI 0.45 to 1.55, p=0.57) but was lower than glipizide (HR 0.59, 95% CI 0.39 to 0.88, p=0.01). The risk for treatment-requiring DR/DME for semaglutide was similar to empagliflozin (HR 0.66, 95% CI 0.43 to 1.02, p=0.06) but lower than dulaglutide (HR 0.53, 95% CI 0.31 to 0.91, p=0.02), sitagliptin (HR 0.46, 95% CI 0.26 to 0.81, p=0.008) and glipizide (HR 0.55, 95% CI 0.33 to 0.91, p=0.02). CONCLUSIONS AND RELEVANCE: We did not identify increased risk for either PDR or treatment-requiring DR/DME comparing semaglutide with other GLP-1RAs or non-GLP-1RAs. Patients with T2D should still undergo close eye care follow-up, particularly when initiating new antihyperglycemic medications. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Cai, Cindy Xinji AU - Cai CX AUID- ORCID: 0000-0003-3752-7239 AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA ccai6@jhmi.edu. AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Baxter, Sally AU - Baxter S AD - Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, California, USA. AD - Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, CA, USA. FAU - Goetz, Kerry AU - Goetz K AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. FAU - Hribar, Michelle AU - Hribar M AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. AD - Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA. AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA. FAU - Toy, Brian AU - Toy B AD - Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. FAU - Barkmeier, Andrew AU - Barkmeier A AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Wang, Sophia AU - Wang S AD - Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, California, USA. FAU - Swaminathan, Swarup AU - Swaminathan S AD - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA. FAU - Flowers, Alexis AU - Flowers A AD - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Brown, Eric AU - Brown E AD - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Xu, Benjamin AU - Xu B AD - Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. FAU - Chen, John AU - Chen J AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Chen, Aiyin AU - Chen A AD - Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA. AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA. FAU - Leng, Theodore AU - Leng T AD - Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, California, USA. FAU - Boland, Michael AU - Boland M AD - Department of Ophthalmology, Mass Eye and Ear, Boston, Massachusetts, USA. FAU - Alshammari, Thamir AU - Alshammari T AD - Department of Clinical Practice, Jazan University, Jazan, Jazan, Saudi Arabia. AD - Pharmacy Practice Research Unit, Jazan University, Jazan, Saudi Arabia. FAU - Bu, Fan AU - Bu F AD - Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University, New York, New York, USA. FAU - Martin, Benjamin AU - Martin B AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Westlund, Erik AU - Westlund E AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. FAU - Mathioudakis, Nestoras AU - Mathioudakis N AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Zhang, Linying AU - Zhang L AD - Institute for Informatics, Data Science and Biostatistics,Department of Medicine, Washington University in St Louis, St. Louis, Missouri, USA. FAU - Fan, Ruochong AU - Fan R AD - Institute for Informatics, Data Science and Biostatistics,Department of Medicine, Washington University in St Louis, St. Louis, Missouri, USA. FAU - Wilcox, Adam AU - Wilcox A AD - Institute for Informatics, Data Science and Biostatistics,Department of Medicine, Washington University in St Louis, St. Louis, Missouri, USA. FAU - Lai, Albert AU - Lai A AD - Institute for Informatics, Data Science and Biostatistics,Department of Medicine, Washington University in St Louis, St. Louis, Missouri, USA. FAU - Stocking, Jacqueline C AU - Stocking JC AUID- ORCID: 0000-0003-0775-684X AD - Department of Internal Medicine, University of California Davis, Davis, California, USA. FAU - Xie, Yangyiran AU - Xie Y AD - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Lee, Lok Hin AU - Lee LH AD - Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Dorr, David AU - Dorr D AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA. FAU - Humes, Izabelle AU - Humes I AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR, USA. FAU - McCoy, David AU - McCoy D AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR, USA. FAU - Adibuzzaman, Mohammad AU - Adibuzzaman M AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland, OR, USA. FAU - Areaux, Raymond Jr AU - Areaux R Jr AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA. FAU - Brash, James AU - Brash J AD - IQVIA, Real World Solutions, Brighton, England, UK. FAU - Weiskopf, Nicole AU - Weiskopf N AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, USA. FAU - Morgan-Cooper, Hannah AU - Morgan-Cooper H AD - Stanford School of Medicine and Stanford Health Care, Stanford, California, USA. FAU - Desai, Priya AU - Desai P AD - Stanford School of Medicine and Stanford Health Care, Stanford, California, USA. FAU - Tran, Diep AU - Tran D AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. FAU - Rustam, Zainab AU - Rustam Z AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. FAU - Zhu, Gina AU - Zhu G AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. FAU - Swerdel, Joel AU - Swerdel J AD - Janssen Research & Development, Titusville, New Jersey, USA. FAU - Sena, Anthony AU - Sena A AD - Janssen Research & Development, Titusville, New Jersey, USA. AD - Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, Netherlands. FAU - Nagy, Paul AU - Nagy P AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. FAU - Suchard, Marc AU - Suchard M AD - Department of Biostatistics, University of California Los Angeles School of Public Health, Los Angeles, California, USA. AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, UT, USA. FAU - Schuemie, Martijn AU - Schuemie M AD - Department of Biostatistics, University of California Los Angeles School of Public Health, Los Angeles, California, USA. AD - Johnson and Johnson, Horsham, PA, USA. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University, New York, New York, USA. FAU - Ryan, Patrick AU - Ryan P AD - Department of Biomedical Informatics, Columbia University, New York, New York, USA. AD - Johnson and Johnson, Horsham, PA, USA. LA - eng GR - K01 HL168222/HL/NHLBI NIH HHS/United States GR - P30 DK092950/DK/NIDDK NIH HHS/United States GR - P30 EY010572/EY/NEI NIH HHS/United States GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - T15 LM011271/LM/NLM NIH HHS/United States GR - R35 GM160458/GM/NIGMS NIH HHS/United States GR - R01 LM013426/LM/NLM NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20251104 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Retinopathy/chemically induced/epidemiology MH - Follow-Up Studies MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Retrospective Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12587949 OTO - NOTNLM OT - Diabetes Complications OT - Diabetic Retinopathy COIS- Competing interests: CXC: Regeneron Pharmaceuticals, Inc. (grant support), Optomed USA (equipment support), Boehringer Ingelheim (travel), 4D Molecular Therapeutics (travel). AN: none. SB: Consulting fees Topcon, Equipment support Optomed. KG: none. MH: none. BT: none. AB: none. SW: none. SS: Heidelberg Engineering (support), Lumata Health (Consulting, Equity), AbbVie (Consulting); Topcon (Consulting), Elios Vision (Consulting). AF: none. EB: none. BX: none. JC: none. AC: none. TL: Grants: Astellas, Consultant: Astellas, Boehringer Ingelheim, Roche/Genentech, Toku, Topcon, Virtual Field. MB: Carl Zeiss Meditec-consulting, speaking; Topcon healthcare, consulting; AbbVie-consulting; TA: none. FB: none. TF: none. BM: none. EW: none. NM: none. LZ: none. RF: none. AW: none. AL: none. JCS: none. YX: none. LHL: none. DD: none. IH: none. DM: none. MA: none. RA: none. JB: Employee of IQVIA. NW: none. HM-C: none. PD: none. DT: none. ZR: none. GZ: none. JS: Employee and Stockholder of Johnson & Johnson. AS: Employee and Stockholder of Johnson & Johnson. PN: none. MSu: Contracts and grants from Johnson & Johnson, Gilead and the US Food & Drug Administration. MSc: Employee and Stockholder of Johnson & Johnson. GH: none. PR: is an employee and shareholder of Johnson & Johnson. EDAT- 2025/11/06 00:27 MHDA- 2025/11/06 00:28 PMCR- 2025/11/04 CRDT- 2025/11/05 20:33 PHST- 2025/07/14 00:00 [received] PHST- 2025/10/11 00:00 [accepted] PHST- 2025/11/06 00:28 [medline] PHST- 2025/11/06 00:27 [pubmed] PHST- 2025/11/05 20:33 [entrez] PHST- 2025/11/04 00:00 [pmc-release] AID - 13/6/e005424 [pii] AID - bmjdrc-2025-005424 [pii] AID - 10.1136/bmjdrc-2025-005424 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2025 Nov 4;13(6):e005424. doi: 10.1136/bmjdrc-2025-005424. PMID- 41189335 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260805 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - One-year usage patterns of SGLT-2 inhibitors and GLP-1 receptor agonists in individuals with type 2 diabetes in a real-world population. PG - 972-981 LID - 10.1111/dom.70269 [doi] AB - AIMS: Real-world studies of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) typically assess adherence and discontinuation as separate outcomes. We applied a novel approach that integrates these measures to categorize patterns of drug usage. We describe patterns across individual subclasses, and in overall class-level models, we examined clinical characteristics associated with each category with particular interest in poor adherence and intolerance. MATERIALS AND METHODS: We conducted an observational cohort study using electronic health records from the Scottish Care Information Diabetes Collaboration database, including individuals with type 2 diabetes who initiated a SGLT2i or GLP-1RA. Each initiation was followed for 1 year and classified into five mutually exclusive groups: adherent, poor adherence and three discontinuation categories including a proxy for intolerance. RESULTS: Among SGLT2is, poor adherence was more common in younger individuals, with greater socioeconomic deprivation, and higher HbA(1c), while intolerance was more frequent in older, leaner females and in those with prior genital thrush. For GLP-1RAs, newer agents were associated with more favourable usage patterns. Poor adherence was more frequent with liraglutide, lixisenatide, and exenatide compared to semaglutide, and intolerance was more common with lixisenatide. In addition, poor adherence was associated with younger age and prior GLP-1RA use, while intolerance was linked to lower BMI, female sex, and more advanced CKD. CONCLUSIONS: Distinct clinical and biochemical characteristics are associated with poor adherence versus discontinuation. Understanding these patterns is crucial for developing targeted strategies to improve sustained use, ultimately enhancing treatment outcomes for people with type 2 diabetes. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Donnelly, Louise A AU - Donnelly LA AUID- ORCID: 0000-0003-4902-1040 AD - Diabetes Endocrinology and Reproductive Biology, School of Medicine, University of Dundee, Dundee, UK. FAU - Singh, Katyayeni AU - Singh K AUID- ORCID: 0000-0002-2702-3611 AD - Diabetes Endocrinology and Reproductive Biology, School of Medicine, University of Dundee, Dundee, UK. FAU - McCrimmon, Rory J AU - McCrimmon RJ AUID- ORCID: 0000-0002-3957-1981 AD - Diabetes Endocrinology and Reproductive Biology, School of Medicine, University of Dundee, Dundee, UK. FAU - Pearson, Ewan R AU - Pearson ER AUID- ORCID: 0000-0001-9237-8585 AD - Diabetes Endocrinology and Reproductive Biology, School of Medicine, University of Dundee, Dundee, UK. LA - eng GR - 875534/Innovative Medicines Initiative 2 Joint Undertaking/ PT - Journal Article PT - Observational Study DEP - 20251104 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/blood MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Scotland/epidemiology MH - Glycated Hemoglobin/analysis MH - Cohort Studies MH - Medication Adherence PMC - PMC12803620 OTO - NOTNLM OT - GLP-1 analogue OT - SGLT2 inhibitor OT - cohort study OT - database research OT - real-world evidence OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2025/11/05 06:29 MHDA- 2026/01/15 06:07 PMCR- 2026/01/14 CRDT- 2025/11/05 01:52 PHST- 2025/10/24 00:00 [revised] PHST- 2025/09/10 00:00 [received] PHST- 2025/10/25 00:00 [accepted] PHST- 2026/01/15 06:07 [medline] PHST- 2025/11/05 06:29 [pubmed] PHST- 2025/11/05 01:52 [entrez] PHST- 2026/01/14 00:00 [pmc-release] AID - DOM70269 [pii] AID - 10.1111/dom.70269 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):972-981. doi: 10.1111/dom.70269. Epub 2025 Nov 4. PMID- 41188987 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260127 IS - 2047-783X (Electronic) IS - 0949-2321 (Print) IS - 0949-2321 (Linking) VI - 30 IP - 1 DP - 2025 Nov 4 TI - Semaglutide reduces cardiovascular events in type 2 diabetes: a systematic review and meta-analysis highlighting enhanced benefits in chronic kidney disease. PG - 1059 LID - 10.1186/s40001-025-03241-8 [doi] LID - 1059 AB - BACKGROUND: Cardiovascular disease (CVD) disproportionately affects type 2 diabetes (T2D) patients with chronic kidney disease (CKD). Although semaglutide shows cardiometabolic benefits, its efficacy across CVD endpoints and high-risk CKD subgroups remains underexplored. METHODS: We systematically reviewed PubMed, Embase, Cochrane, Web of Science (through September 2025) for randomized trials and observational studies evaluating oral semaglutide versus placebo in T2D. Data synthesis employed hazard ratios (HRs) and mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Across 17 studies (n = 40, 632 patients), semaglutide significantly reduced the risk of cardiovascular (CV) death by 23% [HR 0.77, 95% CI (0.68, 0.88)], major adverse cardiovascular events (MACE) by 18% [HR 0.82, 95% CI (0.75, 0.90)], expanded MACE by 22% [HR 0.78, 95% CI (0.70, 0.85)], nonfatal myocardial infarction (MI) by 18% [HR 0.82, 95% CI (0.68, 0.92)], and nonfatal stroke by 32% [HR 0.68, 95% CI (0.56, 0.83)]. The reductions in CV events were most pronounced in T2D patients with CKD (24-37% risk reduction vs. 13-35% in T2D alone or with CVD). Semaglutide also significantly improved modifiable CV risk factors, reducing systolic/diastolic blood pressure (SBP/DBP) decreased by 8.02/3.71 mmHg, and low-density Lipoprotein (LDL) decreased by 12.62 mg/dL, while increasing high-density lipoprotein (HDL) by 1.44 mg/dL. However, semaglutide had no significant effect on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). CONCLUSION: Semaglutide confers robust cardiovascular protection in T2D, with amplified benefits in patients with comorbid CKD. It confers a collective advantage by simultaneously addressing multiple risk factors including blood pressure and lipoprotein, positioning it as a comprehensive treatment strategy for high-risk populations. This analysis is the first to synthesize evidence across CKD subgroups, supporting prioritizing semaglutide in T2D patients with CKD. Further research should clarify mechanisms underlying CKD-specific benefits and refine risk-stratified treatment algorithms. CI - (c) 2025. The Author(s). FAU - Yao, Yanni AU - Yao Y AD - Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, China. FAU - Liu, Nairong AU - Liu N AD - Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, China. FAU - Chen, Siyan AU - Chen S AD - Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, China. FAU - Sun, Meng AU - Sun M AD - Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, China. FAU - Guo, Yanjie AU - Guo Y AD - Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an, China. yaoyanni-2021@qq.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251104 PL - England TA - Eur J Med Res JT - European journal of medical research JID - 9517857 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12584374 OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - Meta-analysis OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: Formal ethics committee approval was not required for this study, as it involves the secondary analysis of publicly available, de-identified data from previously published clinical trials. All original trials included in our analysis have been documented to have adhered to the Good Clinical Practice guidelines and/or the principles of the Declaration of Helsinki. Competing interests: The authors declare no competing interests. EDAT- 2025/11/05 00:28 MHDA- 2025/11/05 06:29 PMCR- 2025/11/04 CRDT- 2025/11/04 23:57 PHST- 2025/06/16 00:00 [received] PHST- 2025/09/18 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/11/05 00:28 [pubmed] PHST- 2025/11/04 23:57 [entrez] PHST- 2025/11/04 00:00 [pmc-release] AID - 10.1186/s40001-025-03241-8 [pii] AID - 3241 [pii] AID - 10.1186/s40001-025-03241-8 [doi] PST - epublish SO - Eur J Med Res. 2025 Nov 4;30(1):1059. doi: 10.1186/s40001-025-03241-8. PMID- 41187787 OWN - NLM STAT- MEDLINE DCOM- 20260307 LR - 20260307 IS - 1439-3646 (Electronic) IS - 0947-7349 (Linking) VI - 134 IP - 2 DP - 2026 Feb TI - The Impact of Semaglutide on Weight Loss and Inflammation in People with HIV. An Observational Prospective Study in Greek Population. PG - 29-35 LID - 10.1055/a-2737-6227 [doi] AB - The existing literature on the effects of semaglutide in people with HIV (PWH) and diabetes mellitus remains limited. In this study, the effects of semaglutide on weight control and inflammation in PWH were evaluated.This is a prospective observational study that included PWH with type 2 diabetes mellitus monitored at the HIV Unit of the University General Hospital of Alexandroupolis and a matched control group of non-HIV individuals. Demographic, anthropometric, and clinical characteristics, including HIV-related data and comorbidities, were reported. All participants received semaglutide with a gradual dose increase to 1 mg once weekly. Body Mass Index (BMI), glycosylated haemoglobin (HbA1c), and inflammatory markers (IL-6, TNF, hsCRP, sCD14, CD4/CD8 ratio) were recorded at baseline and at 6, 12, 18, and 24 months.Fifty participants (PWH: n=25; non-HIV: n=25) were included. At baseline, the mean BMI was 35.2+/-8.0 kg/m(2) for PWH and 36.1+/-6.0 kg/m(2) for non-HIV controls. Semaglutide treatment resulted in significant and sustained weight loss in both groups (p<0.001). At 24 months, the median weight loss was -14.6 kg in the PWH group and -18.8 kg in the non-HIV group for those with a baseline BMI>35 kg/m(2). Glycemic control also improved significantly, with mean HbA1c decreasing from 7.7%+/-1.23 to 5.2%+/-1.02 in PWH (p<0.001), and from 7.9%+/-1.16 to 5.6%+/-1.21 in non-HIV controls (p<0.001). Significant reductions were observed in hsCRP and sCD14 levels in both cohorts. A unique finding was the significant increase in the CD4/CD8 ratio in the PWH group, from a mean baseline of 0.54+/-0.12 to 0.83+/-0.14 at 24 months (p<0.001), a change not seen in the non-HIV controls.Semaglutide appears to be an effective and safe option for weight reduction and inflammation control in PWHIV. Further studies with a larger number of patients are necessary to substantiate these findings. CI - Thieme. All rights reserved. FAU - Petrakis, Vasileios AU - Petrakis V AD - 2nd University Department of Internal Medicine, Department of Infectious Diseases, Democritus University of Thrace, General University Hospital of Alexandroupolis, Alexandroupolis, Greece. FAU - Rafailidis, Petros AU - Rafailidis P AD - 2nd University Department of Internal Medicine, Department of Infectious Diseases, University General Hospital Alexandroupolis, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. FAU - Panopoulou, Maria AU - Panopoulou M AD - Univeristy Laboratory of Microbiology, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. FAU - Konstantinidis, Theocharis AU - Konstantinidis T AD - Univeristy Laboratory of Microbiology, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. FAU - Tsantes, Andreas G AU - Tsantes AG AUID- ORCID: 0000-0002-3695-0759 AD - Laboratory of Haematology and Blood Bank Unit, School of Medicine, National and Kapodistrian University of Athens, Panepistemiako Geniko Nosokomeio Attikon, Athens, Greece. AD - Microbiology Department, Agios Savvas General Cancer and Oncology Hospital of Athens, Athens, Greece. FAU - Babaka, Nikoleta AU - Babaka N AD - 2nd University Department of Internal Medicine, Department of Infectious Diseases, University General Hospital Alexandroupolis, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. FAU - Papazoglou, Dimitrios AU - Papazoglou D AD - 2nd University Department of Internal Medicine, Department of Infectious Diseases, University General Hospital Alexandroupolis, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. FAU - Panagopoulos, Periklis AU - Panagopoulos P AD - 2nd University Department of Internal Medicine, Department of Infectious Diseases, University General Hospital Alexandroupolis, Democritus University Thrace, General University Hospital of Evros Sector of Alexandroupolis, Alexandroupolis, Greece. LA - eng PT - Journal Article PT - Observational Study DEP - 20251104 PL - Germany TA - Exp Clin Endocrinol Diabetes JT - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JID - 9505926 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Female MH - Male MH - Middle Aged MH - *Weight Loss/drug effects MH - *HIV Infections/drug therapy/complications/blood MH - *Glucagon-Like Peptides/administration & dosage/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Inflammation/drug therapy/blood MH - Greece MH - Adult MH - Prospective Studies MH - *Hypoglycemic Agents/administration & dosage/pharmacology MH - Glycated Hemoglobin COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2025/11/05 00:28 MHDA- 2026/03/07 06:38 CRDT- 2025/11/04 18:53 PHST- 2026/03/07 06:38 [medline] PHST- 2025/11/05 00:28 [pubmed] PHST- 2025/11/04 18:53 [entrez] AID - 10.1055/a-2737-6227 [doi] PST - ppublish SO - Exp Clin Endocrinol Diabetes. 2026 Feb;134(2):29-35. doi: 10.1055/a-2737-6227. Epub 2025 Nov 4. PMID- 41183330 OWN - NLM STAT- MEDLINE DCOM- 20260119 LR - 20260919 IS - 1539-3704 (Electronic) IS - 0003-4819 (Print) IS - 0003-4819 (Linking) VI - 179 IP - 1 DP - 2026 Jan TI - Comparative Gastrointestinal Safety of Dulaglutide, Semaglutide, and Tirzepatide in Adults With Type 2 Diabetes. PG - 1-11 LID - 10.7326/ANNALS-25-01724 [doi] AB - BACKGROUND: The comparative gastrointestinal safety across glucagon-like peptide-1 receptor agonists and tirzepatide is still unclear. OBJECTIVE: To compare the risk for severe gastrointestinal adverse events across dulaglutide, subcutaneous semaglutide, and tirzepatide in patients with type 2 diabetes (T2D) in routine clinical practice. DESIGN: New-user, active-comparator cohort study. SETTING: Population-based study. PARTICIPANTS: Adults with T2D initiating dulaglutide, subcutaneous semaglutide, and tirzepatide between 1 January 2019 and 30 August 2024 in 3 cohorts corresponding to 3 pairwise comparisons. MEASUREMENTS: The primary outcome was a composite of acute pancreatitis, biliary disease, bowel obstruction, gastroparesis, and severe constipation. Secondary outcomes of interest were the individual components of the primary outcome. Patients were 1:1 propensity score matched within each comparison. We calculated hazard ratios (HRs) with 95% CIs. RESULTS: There were 65 238 matched pairs in the semaglutide versus dulaglutide cohort, 20 893 in the tirzepatide versus dulaglutide cohort, and 46 620 in the tirzepatide versus semaglutide cohort. The HR of gastrointestinal events was 0.96 (95% CI, 0.87 to 1.06) in the semaglutide versus dulaglutide cohort, 0.96 (CI, 0.77 to 1.20) in the tirzepatide versus dulaglutide cohort, and 1.07 (CI, 0.90 to 1.26) in the tirzepatide versus semaglutide cohort. LIMITATION: Possible residual confounding by glycemic control and body mass index. CONCLUSION: These findings suggest that dulaglutide, semaglutide, and tirzepatide have similar gastrointestinal safety profiles in adults with T2D. This study provides clinicians with evidence to weigh the benefits and risks of these medications. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases. FAU - Crisafulli, Salvatore AU - Crisafulli S AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and Department of Diagnostics and Public Health, University of Verona, Verona, Italy (S.C.). FAU - Alkabbani, Wajd AU - Alkabbani W AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, and School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada (W.A.). FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School; Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital; and New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts (J.M.P.). FAU - Bykov, Katsiaryna AU - Bykov K AUID- ORCID: 0000-0003-3336-5412 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.B., R.J.G., P.T.H., E.P.). FAU - Tavakkoli, Ali AU - Tavakkoli A AUID- ORCID: 0000-0002-7430-1848 AD - Division of General and Gastrointestinal Surgery, Brigham and Women's Hospital, Boston, Massachusetts (A.T.). FAU - Glynn, Robert J AU - Glynn RJ AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.B., R.J.G., P.T.H., E.P.). FAU - Htoo, Phyo T AU - Htoo PT AUID- ORCID: 0000-0003-4742-8306 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.B., R.J.G., P.T.H., E.P.). FAU - Yu, Elaine W AU - Yu EW AD - Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, and Mongan Institute, Massachusetts General Hospital, Boston, Massachusetts (E.W.Y.). FAU - Trifiro, Gianluca AU - Trifiro G AUID- ORCID: 0000-0003-1147-7296 AD - Department of Diagnostics and Public Health, University of Verona, Verona, Italy (G.T.). FAU - Wexler, Deborah J AU - Wexler DJ AUID- ORCID: 0000-0001-6979-402X AD - Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (D.J.W.). FAU - Patorno, Elisabetta AU - Patorno E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (K.B., R.J.G., P.T.H., E.P.). LA - eng GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01 AR075117/AR/NIAMS NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States GR - K01 AG068365/AG/NIA NIH HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20251104 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Recombinant Fusion Proteins/adverse effects/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Immunoglobulin Fc Fragments/adverse effects/therapeutic use MH - *Tirzepatide/adverse effects/therapeutic use MH - Aged MH - *Gastrointestinal Diseases/chemically induced MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12718079 MID - NIHMS2125278 COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/11/03 18:30 MHDA- 2026/01/19 18:33 PMCR- 2025/12/21 CRDT- 2025/11/03 17:02 PHST- 2026/01/19 18:33 [medline] PHST- 2025/11/03 18:30 [pubmed] PHST- 2025/11/03 17:02 [entrez] PHST- 2025/12/21 00:00 [pmc-release] AID - 10.7326/ANNALS-25-01724 [doi] PST - ppublish SO - Ann Intern Med. 2026 Jan;179(1):1-11. doi: 10.7326/ANNALS-25-01724. Epub 2025 Nov 4. PMID- 41177923 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260730 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Evolving trends of antidiabetic agents stratified by age, kidney function and body mass index: Insights from a nationwide claims database. PG - 701-710 LID - 10.1111/dom.70255 [doi] AB - AIMS: To analyse prescribing trends in antidiabetic agents stratified by background characteristics among individuals with type 2 diabetes. MATERIALS AND METHODS: This retrospective study used a large-scale database between 2015 and 2024 in Japan. Adults with type 2 diabetes receiving at least one antidiabetic prescription were included, and annual prescription rates were assessed by drug class. Trends were evaluated overall and stratified by age, sex, heart failure (HF) status, estimated glomerular filtration rate (eGFR), body mass index, haemoglobin A1c and clinical setting, because these factors are important determinants of efficacy and safety in prescribing antidiabetic agents. RESULTS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) prescriptions showed a marked increase, rising from 4.1% (95% confidence interval [CI], 4.0%-4.2%) in 2015 to 38.9% (95% CI, 38.7%-39.0%) in 2024. Particularly high prescription rates were seen in individuals aged <65 years, with HF, eGFR <30 mL/min/1.73 m(2), and obesity. A temporal increase was also noted among individuals aged >/=80 years, reaching 33.1% (95% CI, 32.8%-33.3%) in 2024. Glucagon-like peptide-1 receptor agonists were prescribed at a relatively low rate, reaching only 8.0% (95% CI, 7.9%-8.1%) in 2024; however, an upward trend was observed among individuals aged <65 years and with obesity, especially after the launch of oral semaglutide in 2021. CONCLUSIONS: In this large-scale analysis, SGLT2i use increased substantially across diverse individual traits, supporting their integration into diverse clinical contexts in real-world practice. Our findings may provide valuable insights into diabetes care in the forthcoming era of super-aged societies. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Aoyama, Kazuki AU - Aoyama K AD - Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. FAU - Okada, Akira AU - Okada A AUID- ORCID: 0000-0001-6480-3388 AD - Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Kaneko, Hidehiro AU - Kaneko H AUID- ORCID: 0000-0003-2553-6170 AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan. FAU - Azegami, Tatsuhiko AU - Azegami T AD - Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. FAU - Suzuki, Yuta AU - Suzuki Y AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. AD - Center for Outcomes Research and Economic Evaluation for Health, National Institute of Public Health, Saitama, Japan. FAU - Meguro, Shu AU - Meguro S AUID- ORCID: 0000-0003-3528-128X AD - Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. FAU - Fujiu, Katsuhito AU - Fujiu K AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. AD - Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan. FAU - Takeda, Norifumi AU - Takeda N AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. FAU - Morita, Hiroyuki AU - Morita H AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. FAU - Node, Koichi AU - Node K AUID- ORCID: 0000-0002-2534-0939 AD - Department of Cardiovascular Medicine, Saga University, Saga, Japan. FAU - Yamauchi, Toshimasa AU - Yamauchi T AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Nangaku, Masaomi AU - Nangaku M AD - Division of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Takeda, Norihiko AU - Takeda N AD - Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan. FAU - Yasunaga, Hideo AU - Yasunaga H AD - Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, Tokyo, Japan. FAU - Hayashi, Kaori AU - Hayashi K AD - Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. LA - eng GR - 2024-YNG-031/Japan Association for Diabetes Education and Care/ GR - 23AA2003/Ministry of Health, Labour and Welfare, Japan/ GR - 20H03907/Ministry of Education, Culture, Sports, Science and Technology, Japan/ GR - 21H03159/Ministry of Education, Culture, Sports, Science and Technology, Japan/ GR - 21K08123/Ministry of Education, Culture, Sports, Science and Technology, Japan/ PT - Journal Article DEP - 20251102 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications/physiopathology MH - Male MH - Female MH - Retrospective Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Body Mass Index MH - Aged, 80 and over MH - Japan/epidemiology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Databases, Factual MH - Age Factors MH - Glomerular Filtration Rate MH - Adult MH - *Practice Patterns, Physicians'/trends MH - Glycated Hemoglobin/analysis MH - Kidney/physiopathology PMC - PMC12673422 OTO - NOTNLM OT - antidiabetic drug OT - pharmaco-epidemiology OT - real-world evidence OT - type 2 diabetes COIS- Research funding and scholarship funds (Hidehiro Kaneko and Katsuhito Fujiu) from Medtronic Japan Co., Ltd., Abbott Medical Japan Co., Ltd., Boston Scientific Japan Co., Ltd., and Fukuda Denshi, Central Tokyo Co., Ltd. Akira Okada is a member of the Department of Prevention of Diabetes and Lifestyle-Related Diseases, which is a cooperative programme between the University of Tokyo and Asahi Mutual Life Insurance Company. Hidehiro Kaneko holds shares in PrevMed Co., Ltd. and Japan Preventive Medical Development Institute Co., Ltd. Norihiko Takeda has received collaborative research funding from AstraZeneca and Ono Pharmaceutical. Koichi Node has received honoraria from Boehringer Ingelheim, research grants from Astellas, and scholarship funds from Daiichi Sankyo and Mitsubishi Tanabe Pharma. Masaomi Nangaku has received scholarship funds from Boehringer Ingelheim. Kaori Hayashi has received scholarship funds from Boehringer Ingelheim. The remaining authors have nothing to disclose. EDAT- 2025/11/03 00:26 MHDA- 2025/12/03 07:41 PMCR- 2025/12/03 CRDT- 2025/11/02 23:33 PHST- 2025/10/13 00:00 [revised] PHST- 2025/08/09 00:00 [received] PHST- 2025/10/22 00:00 [accepted] PHST- 2025/12/03 07:41 [medline] PHST- 2025/11/03 00:26 [pubmed] PHST- 2025/11/02 23:33 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70255 [pii] AID - 10.1111/dom.70255 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):701-710. doi: 10.1111/dom.70255. Epub 2025 Nov 2. PMID- 41177308 OWN - NLM STAT- MEDLINE DCOM- 20260330 LR - 20260918 IS - 1872-8227 (Electronic) IS - 0168-8227 (Print) IS - 0168-8227 (Linking) VI - 230 DP - 2025 Dec TI - Risk of lower extremity complications with GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors in peripheral artery disease. PG - 112982 LID - S0168-8227(25)00996-9 [pii] LID - 10.1016/j.diabres.2025.112982 [doi] AB - AIMS: To compare the association of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and dipeptidyl peptidase-4 inhibitors (DPP-4i) therapies on lower extremity vascular complications and mortality in PAD. METHODS: We conducted a retrospective cohort study using a nationwide U.S. electronic health records database. Adults with PAD and type 2 diabetes who initiated GLP-1RA, SGLT2i, or DPP4i therapy (May 2013-January 2025) were included. Propensity score matching (1:1) balanced baseline characteristics. Cox models estimated hazard ratios (HR) with 95 % confidence intervals (CI) for major amputation (primary outcome), lower extremity revascularization (LER), and all-cause mortality over 3 years follow-up. Subgroup analyses included symptomatic PAD, prior LER, and drug-level comparisons. RESULTS: GLP-1RAs were associated with lower risks of major amputation (HR 0.79 [95 % CI 0.70-0.90]), LER (HR 0.82 [0.76-0.88]), and mortality (HR 0.71 [0.68-0.73]) compared with SGLT2i (n = 77,393 each). Similar reductions were seen versus DPP-4is (n = 39,907 each); SGLT2is and DPP-4is showed comparable risks (n = 42,924 each). GLP-1RA benefits remained significant in symptomatic PAD (p < 0.05) and were associated with lower mortality in LER patients (p < 0.05). Semaglutide and tirzepatide showed the greatest benefit. CONCLUSION: GLP-1RAs were associated with lower limb complication and mortality risks in PAD, supporting a potential vascular benefit that warrants prospective evaluation. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Hong, Alexander T AU - Hong AT AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Lin, Forest AU - Lin F AD - University of South Florida Health Morsani College of Medicine, Tampa, FL, USA. FAU - Luu, Ivan Y AU - Luu IY AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Shin, Laura AU - Shin L AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Han, Sukgu M AU - Han SM AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Armstrong, David G AU - Armstrong DG AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. FAU - Tan, Tze-Woei AU - Tan TW AD - Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: tze-woei.tan@med.usc.edu. LA - eng GR - K23 DK122126/DK/NIDDK NIH HHS/United States GR - R03 DK140420/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20251101 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Peripheral Arterial Disease/complications/drug therapy/mortality MH - *Glucagon-Like Peptide-1 Receptor MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Amputation, Surgical/statistics & numerical data MH - Hypoglycemic Agents/therapeutic use PMC - PMC12645714 MID - NIHMS2121410 OTO - NOTNLM OT - Diabetes mellitus OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonists OT - Limb amputation OT - Peripheral artery disease OT - Sodium-glucose cotransporter-2 inhibitors COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/11/03 00:26 MHDA- 2025/11/30 00:30 PMCR- 2025/12/03 CRDT- 2025/11/02 19:13 PHST- 2025/09/12 00:00 [received] PHST- 2025/10/20 00:00 [revised] PHST- 2025/10/28 00:00 [accepted] PHST- 2025/11/30 00:30 [medline] PHST- 2025/11/03 00:26 [pubmed] PHST- 2025/11/02 19:13 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - S0168-8227(25)00996-9 [pii] AID - 10.1016/j.diabres.2025.112982 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Dec;230:112982. doi: 10.1016/j.diabres.2025.112982. Epub 2025 Nov 1. PMID- 41176849 OWN - NLM STAT- MEDLINE DCOM- 20251128 LR - 20251218 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 19 IP - 9 DP - 2025 Sep TI - Compounded incretins in clinical practice: An opinion of the endocrine and metabolism practice and research network of the American College of Clinical Pharmacy. PG - 103314 LID - S1871-4021(25)00131-6 [pii] LID - 10.1016/j.dsx.2025.103314 [doi] AB - AIMS: This article aims to summarize the role of compounded incretin mimetics in clinical practice and in the context of drug shortages. METHODS: The Endocrine and Metabolism Practice and Research Network, a focused group of the American College of Clinical Pharmacy members, convened an independent committee to evaluate the role of compounded incretin mimetics. RESULTS: There is limited data demonstrating positive clinical outcomes in small cohorts of patients receiving compounded semaglutide and tirzepatide. However, there remain significant legal and safety concerns since compounded incretins do not undergo approval by the Food and Drug Administration. CONCLUSION: Whenever possible, healthcare providers should make every effort to assist patients with obtaining approved medications. If patients choose to obtain compounded incretins, providers can encourage safety by ensuring use of reputable compounding pharmacies and routinely monitoring patients for safety and efficacy of the compounded product. CI - Copyright (c) 2025 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Courtney, Lindsay A AU - Courtney LA AD - Texas Tech University Health Sciences Center Jerry H. Hodge School of Pharmacy, Amarillo, TX, USA. Electronic address: lindsay.courtney@ttuhsc.edu. FAU - Clements, Jennifer N AU - Clements JN AD - University of South Carolina College of Pharmacy, Greenville, SC, USA. FAU - Isaacs, Diana AU - Isaacs D AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Pitlick, Jamie M AU - Pitlick JM AD - Drake University College of Pharmacy and Health Sciences, Des Moines, IA, USA. FAU - Reece, Sara Mandy AU - Reece SM AD - Philadelphia College of Osteopathic Medicine Georgia School of Pharmacy, Suwanee, GA, USA. FAU - Whitley, Heather P AU - Whitley HP AD - Auburn University, Harrison College of Pharmacy, Auburn, AL, USA. LA - eng PT - Journal Article PT - Review DEP - 20251021 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Incretins/therapeutic use/chemistry MH - *Drug Compounding/standards MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Endocrinology MH - United States OTO - NOTNLM OT - Compounding OT - Glucagon-like peptide-1 receptor agonist OT - Incretin mimetic OT - Obesity OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jennifer N. Clements is a speaker for Eli Lilly and Novo Nordisk and a consultant for Sanofi. Diana Isaacs is a speaker for Eli Lilly and Novo Nordisk. Sara Reece is a speaker for Novo Nordisk and serves on the Eli Lilly advisory board. Jamie M. Pitlick reports that a family member began employment with Novo Nordisk in January 2024, after her involvement with this manuscript. Lindsay A. Courtney and Heather P. Whitley have no relevant conflicts of interest. EDAT- 2025/11/03 00:26 MHDA- 2025/11/29 02:21 CRDT- 2025/11/02 18:02 PHST- 2024/12/14 00:00 [received] PHST- 2025/10/17 00:00 [revised] PHST- 2025/10/21 00:00 [accepted] PHST- 2025/11/29 02:21 [medline] PHST- 2025/11/03 00:26 [pubmed] PHST- 2025/11/02 18:02 [entrez] AID - S1871-4021(25)00131-6 [pii] AID - 10.1016/j.dsx.2025.103314 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2025 Sep;19(9):103314. doi: 10.1016/j.dsx.2025.103314. Epub 2025 Oct 21. PMID- 41163197 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260127 IS - 1520-4804 (Electronic) IS - 0022-2623 (Linking) VI - 68 IP - 21 DP - 2025 Nov 13 TI - Chemoenzymatic Synthesis of Rhamnolipid-Modified Exendin-4: A Dual Approach for Long-Acting Glycemic Control through Endogenous Antibody Recruitment and Albumin Interaction. PG - 23324-23334 LID - 10.1021/acs.jmedchem.5c02146 [doi] AB - Effective management of Type 2 diabetes requires therapies that balance potency with sustained action. Glycosylation of glucagon-based drugs improves stability and reduces aggregation but does not significantly enhance pharmacokinetics. This study develops a novel glycosylation strategy horizontal line a rhamnolipid conjugation platform horizontal line to address this challenge. Using sortase A-mediated enzymatic ligation, we synthesized Ex4-rhamnolipid bioconjugates that prolong action through a dual mechanism: carbohydrate-mediated antibody engagement and lipophilic albumin binding. These conjugates potently activated GLP-1 receptors (EC(50) = 0.14-0.21 nM) and elicited rapid blood glucose reduction in diabetic rodent models. In immunized subjects, glucose-lowering effects persisted for 24 h, reflecting a 6.7-fold improvement in circulation half-life. In extended-duration studies, once-daily administration of the lead conjugate achieved glycemic control and pancreatic beta-cell protection comparable to semaglutide without adverse effects. This methodology capitalizes on natural immune components and plasma protein interactions to address the challenges of peptide-based treatments, offering a promising platform for sustained-release antidiabetic drugs. FAU - Dai, Shijie AU - Dai S AD - Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. AD - State Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. FAU - Liu, Haiyan AU - Liu H AD - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China. FAU - Mi, Baojing AU - Mi B AD - State Key Laboratory of Macromolecular Drugs and Large-Scale Manufacturing, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. FAU - Li, Yanchu AU - Li Y AD - Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. FAU - Zhao, Kai AU - Zhao K AD - Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. FAU - Hong, Haofei AU - Hong H AD - Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. FAU - Wu, Zhimeng AU - Wu Z AUID- ORCID: 0000-0001-7583-7268 AD - Key Laboratory of Carbohydrate Chemistry & Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China. LA - eng PT - Journal Article DEP - 20251029 PL - United States TA - J Med Chem JT - Journal of medicinal chemistry JID - 9716531 RN - 0 (Glycolipids) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 0 (rhamnolipid) RN - 0 (Blood Glucose) RN - EC 2.3.2.- (sortase A) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - EC 2.3.2.- (Aminoacyltransferases) RN - 0 (Bacterial Proteins) RN - EC 3.4.22.- (Cysteine Endopeptidases) SB - IM MH - Animals MH - *Glycolipids/chemistry MH - *Exenatide/chemistry/pharmacology/therapeutic use/chemical synthesis MH - *Hypoglycemic Agents/pharmacology/therapeutic use/chemical synthesis/chemistry MH - Humans MH - Mice MH - Diabetes Mellitus, Experimental/drug therapy MH - Rats MH - Blood Glucose/drug effects MH - Male MH - Diabetes Mellitus, Type 2/drug therapy MH - Glycemic Control MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Aminoacyltransferases/metabolism MH - Bacterial Proteins MH - Cysteine Endopeptidases EDAT- 2025/10/30 06:29 MHDA- 2025/11/13 18:29 CRDT- 2025/10/30 01:00 PHST- 2025/11/13 18:29 [medline] PHST- 2025/10/30 06:29 [pubmed] PHST- 2025/10/30 01:00 [entrez] AID - 10.1021/acs.jmedchem.5c02146 [doi] PST - ppublish SO - J Med Chem. 2025 Nov 13;68(21):23324-23334. doi: 10.1021/acs.jmedchem.5c02146. Epub 2025 Oct 29. PMID- 41161770 OWN - NLM STAT- MEDLINE DCOM- 20251029 LR - 20260127 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 13 IP - 5 DP - 2025 Oct 29 TI - Using real-world data to predict findings of an ongoing phase IV trial: glycemic control of semaglutide versus standard of care. LID - 10.1136/bmjdrc-2025-005180 [doi] LID - e005180 AB - OBJECTIVE: Using national claims databases, we sought to emulate the design of the ongoing SEPRA trial and predict its findings, comparing the effects of once weekly semaglutide to SoC medications on glycemic control (A1C <7%) in type-2 diabetes mellitus (T2D). RESEARCH DESIGN AND METHODS: Using Optum Clinformatics (July 2017 - May 2022), we identified a 1:1 propensity score-matched (PSM) cohort of adults with T2D on metformin monotherapy, who had recorded A1C and initiated either injectable semaglutide or SoC medications (dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, SUs, or glucagon-like peptide-1 agonists) and met eligibility criteria adapted from the SEPRA trial. The primary outcome was the proportion of patients achieving A1C <7%. The study protocol was preregistered (NCT05577728, ClinicalTrials.gov) before any etiologic analyses. Risk ratios and corresponding 95% CIs were estimated. RESULTS: We identified 1,144 PSM pairs of injectable semaglutide and SoC initiators with balance in pre-exposure covariates. Semaglutide initiators were 30% (risk ratio (95% CI), 1.30 (1.16 to 1.45)) more likely to achieve glycemic control (A1C <7%) than those initiating SoC. Additionally, semaglutide initiators had a 1.3% reduction in A1C, compared with a 1.1% reduction in the SoC group. These results were consistent with interim results of the SEPRA trial, which were released after the protocol for our database study was preregistered. CONCLUSION: This claims database study, designed to predict the results of the SEPRA trial, found results consistent with interim trial results. Our findings support the notion that well-designed non-randomized studies using fit-for-purpose data can effectively complement pragmatic randomized controlled trials. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group. FAU - Kattinakere Sreedhara, Sushama AU - Kattinakere Sreedhara S AUID- ORCID: 0000-0002-9182-304X AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA skattinakeresreedhara@bwh.harvard.edu. FAU - Schneeweiss, Sebastian AU - Schneeweiss S AUID- ORCID: 0000-0003-2575-467X AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - D'Andrea, Elvira AU - D'Andrea E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Weberpals, Janick G AU - Weberpals JG AUID- ORCID: 0000-0003-0404-7394 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - DiCesare, Elyse C AU - DiCesare EC AUID- ORCID: 0009-0000-2244-6378 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Tsacogianis, Theodore AU - Tsacogianis T AUID- ORCID: 0009-0003-4529-5287 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Bradley, Marie AU - Bradley M AUID- ORCID: 0000-0002-6266-4414 AD - Office of Medical Policy, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA. FAU - Concato, John AU - Concato J AUID- ORCID: 0000-0003-2846-0503 AD - Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Wang, Shirley V AU - Wang SV AUID- ORCID: 0000-0001-7761-7090 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. LA - eng SI - ClinicalTrials.gov/NCT05577728 GR - R01 HL141505/HL/NHLBI NIH HHS/United States GR - R01 AR080194/AR/NIAMS NIH HHS/United States GR - R01 AG053302/AG/NIA NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States PT - Clinical Trial, Phase IV PT - Comparative Study PT - Journal Article DEP - 20251029 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 9100L32L2N (Metformin) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Middle Aged MH - *Glycemic Control/methods/statistics & numerical data MH - Glycated Hemoglobin/analysis MH - Blood Glucose/analysis MH - *Standard of Care/statistics & numerical data MH - Aged MH - Metformin/therapeutic use MH - Biomarkers/analysis MH - Adult MH - Clinical Trials, Phase IV as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12574359 OTO - NOTNLM OT - Cohort Studies OT - Database OT - Glycated Hemoglobin A OT - Pharmacoepidemiology COIS- Competing interests: Dr. Wang has been an ad hoc consultant to Exponent Inc, Cytel Inc, and MITRE, a federally funded research and development center for the Centers for Medicare and Medicaid Services. Dr. Schneeweiss is principal investigator of the FDA Sentinel Innovation Center funded by the FDA and co-principal investigator of an investigator-initiated grant to the Brigham and Women's Hospital from UCB Pharma unrelated to the topic of this study. He is a consultant to Aetion Inc., a software manufacturer of which he owns equity. His interests were declared, reviewed, and approved by the Brigham and Women's Hospital and MGB HealthCare System in accordance with their institutional compliance policies. Dr.D'Andrea is currently an employee and owns stocks of AbbVie Inc. and not related to the topic of this work. Dr. Patorno is principal investigator of a research grant to the Brigham and Women's Hospital from Boehringer Ingelheim, not related to the topic of this work. She receives royalties from UpToDate. EDAT- 2025/10/30 00:26 MHDA- 2025/10/30 00:27 PMCR- 2025/10/29 CRDT- 2025/10/29 21:24 PHST- 2025/04/22 00:00 [received] PHST- 2025/09/26 00:00 [accepted] PHST- 2025/10/30 00:27 [medline] PHST- 2025/10/30 00:26 [pubmed] PHST- 2025/10/29 21:24 [entrez] PHST- 2025/10/29 00:00 [pmc-release] AID - 13/5/e005180 [pii] AID - bmjdrc-2025-005180 [pii] AID - 10.1136/bmjdrc-2025-005180 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2025 Oct 29;13(5):e005180. doi: 10.1136/bmjdrc-2025-005180. PMID- 41155271 OWN - NLM STAT- MEDLINE DCOM- 20251029 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 20 DP - 2025 Oct 14 TI - GLP-1 Receptor Agonists Are Associated with Reduced Ascending Aorta Dilatation in Patients with Type 2 Diabetes: A Prospective Study. LID - 10.3390/ijms26209977 [doi] LID - 9977 AB - The aim was to assess the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RA) treatment on the progression of ascending aorta dilatation in patients with type 2 diabetes mellitus (T2DM). A total of 127 T2DM patients with subclinical ascending aortic dilatation (35-45 mm) were prospectively enrolled. Fifty-seven initiated GLP-1 RA therapy (liraglutide, semaglutide, or dulaglutide), while 70 continued on standard care. Ascending aortic diameter was measured by computed tomography angiography (CTA) at baseline and 24 months, alongside circulating markers of vascular remodeling: matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), C-reactive protein (CRP), and osteoprotegerin (OPG). Progression of aortic dilatation was significantly lower in the GLP-1 RA group compared with controls (+0.36 +/- 0.20 mm vs. +1.05 +/- 0.28 mm; p < 0.001). Therapy correlated with decreased MMP-9 and CRP (p < 0.01) and increased TIMP-1 and OPG (p < 0.05). The use of GLP-1 RA was an independent predictor of low progression, even in multivariate models after adjusting for demographic, metabolic, and biomarker data. GLP-1 RA therapy was associated with reduced progression of ascending aortic dilatation in T2DM, supporting a potential vasoprotective role beyond glucose lowering. FAU - Sardu, Celestino AU - Sardu C AUID- ORCID: 0000-0001-5099-3790 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. FAU - Marfella, Ludovica Vittoria AU - Marfella LV AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Fumagalli, Carlo AU - Fumagalli C AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Rinaldi, Luca AU - Rinaldi L AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Sasso, Ferdinando Carlo AU - Sasso FC AUID- ORCID: 0000-0002-9142-7848 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. FAU - Cozzolino, Domenico AU - Cozzolino D AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Nappo, Francesco AU - Nappo F AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Sellitto, Ausilia AU - Sellitto A AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Romano, Ciro AU - Romano C AUID- ORCID: 0000-0002-5807-6601 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Carusone, Caterina AU - Carusone C AUID- ORCID: 0009-0007-8644-9843 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Russo, Pasquale AU - Russo P AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Marfella, Lorenza AU - Marfella L AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. FAU - Tarantino, Nicola Maria AU - Tarantino NM AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Carpinella, Gerardo AU - Carpinella G AD - Department of Cardiology, AORN Antonio Cardarelli, 80131 Naples, Italy. FAU - Furbatto, Fulvio AU - Furbatto F AD - Department of Cardiology, AORN Antonio Cardarelli, 80131 Naples, Italy. FAU - Gentile, Sandro AU - Gentile S AD - Department of Clinical Research, Nefrocenter Research Network, Via XXV Luglio, 160, 84013 Cava de Tirreni, Italy. FAU - Guarino, Giuseppina AU - Guarino G AD - Department of Clinical Research, Nefrocenter Research Network, Via XXV Luglio, 160, 84013 Cava de Tirreni, Italy. FAU - Satta, Ersilia AU - Satta E AD - Department of Clinical Research, Nefrocenter Research Network, Via XXV Luglio, 160, 84013 Cava de Tirreni, Italy. FAU - Bellis, Alessandro AU - Bellis A AUID- ORCID: 0000-0003-3476-5696 AD - Department of Cardiology, AORN Antonio Cardarelli, 80131 Naples, Italy. FAU - Marinelli, Luca AU - Marinelli L AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Donisi, Isabella AU - Donisi I AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - D'Onofrio, Nunzia AU - D'Onofrio N AUID- ORCID: 0000-0002-5300-9530 AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Mauro, Ciro AU - Mauro C AD - Department of Cardiology, AORN Antonio Cardarelli, 80131 Naples, Italy. FAU - Cappabianca, Salvatore AU - Cappabianca S AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Balestrieri, Maria Luisa AU - Balestrieri ML AUID- ORCID: 0000-0001-6001-1789 AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. AD - Department of Precision Medicine, University of Campania "Luigi Vanvitelli", 80138 Naples, Italy. FAU - Marfella, Raffaele AU - Marfella R AUID- ORCID: 0000-0003-3960-9270 AD - Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", 80126 Naples, Italy. AD - Pollution and Cardiovascular Diseases Research Centre, University of Campania "Luigi Vanvitelli", 81100 Caserta, Italy. LA - eng PT - Journal Article DEP - 20251014 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9007-41-4 (C-Reactive Protein) RN - 0 (Osteoprotegerin) RN - 0 (Biomarkers) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - EC 3.4.24.35 (MMP9 protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Prospective Studies MH - *Aorta/drug effects/pathology/diagnostic imaging MH - Matrix Metalloproteinase 9/blood/metabolism MH - Aged MH - Tissue Inhibitor of Metalloproteinase-1/blood MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - C-Reactive Protein/metabolism MH - Osteoprotegerin/blood MH - Biomarkers/blood MH - Immunoglobulin Fc Fragments/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12563610 OTO - NOTNLM OT - GLP-1 receptor agonists OT - ascending aortic dilatation OT - computed tomography angiography OT - inflammation OT - type 2 diabetes mellitus OT - vascular biomarkers COIS- The authors declare no conflicts of interest. EDAT- 2025/10/29 06:27 MHDA- 2025/10/29 06:28 PMCR- 2025/10/14 CRDT- 2025/10/29 01:14 PHST- 2025/09/15 00:00 [received] PHST- 2025/10/09 00:00 [revised] PHST- 2025/10/12 00:00 [accepted] PHST- 2025/10/29 06:28 [medline] PHST- 2025/10/29 06:27 [pubmed] PHST- 2025/10/29 01:14 [entrez] PHST- 2025/10/14 00:00 [pmc-release] AID - ijms26209977 [pii] AID - ijms-26-09977 [pii] AID - 10.3390/ijms26209977 [doi] PST - epublish SO - Int J Mol Sci. 2025 Oct 14;26(20):9977. doi: 10.3390/ijms26209977. PMID- 41153084 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260718 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Effectiveness and safety of GLP-1 receptor agonists in craniopharyngioma patients with obesity: A multicentre real-world study. PG - 443-451 LID - 10.1111/dom.70216 [doi] AB - AIMS: Acquired hypothalamic obesity (aHO) following craniopharyngioma (CP) is a challenging condition with limited therapeutic options. This study aimed to assess the real-world effectiveness and safety of GLP-1 RAs in this population. MATERIALS AND METHODS: CranioGLP1 is a retrospective multicentre study including 116 adults with aHO treated with one or more GLP-1 RAs across 16 French obesity centres. Demographic, clinical, and therapeutic data were collected from medical records. Weight outcomes, adverse events, and predictors of response were analysed. RESULTS: Patients had a mean age of 44.4 +/- 13.5 years and a mean BMI of 40.1 +/- 8.6 kg/m(2), 42% had type 2 diabetes. Over a mean follow-up of 44 months, mean weight loss was -4.6% (+/-12.5), with high interindividual variability; 51% achieved >/=5% weight loss, and 28% >/=10%. Semaglutide (mean dose 1.2 mg/week) was associated with the greatest reduction (-6.8%), particularly in patients without diabetes (-8.5% +/- 12.3 vs. -3.9% +/- 10.0 in those with diabetes; p = 0.032). Endocrine adverse events occurred in 12% and 10% of patients with adrenal or vasopressin deficiency decompensation, respectively, with 8% requiring hospitalisation. Gastrointestinal intolerance led to treatment discontinuation in 13% of cases. CONCLUSIONS: GLP-1 RAs at submaximal doses induce moderate, yet clinically meaningful weight loss in adults with aHO, with semaglutide showing the highest efficacy. Given the non-negligible risk of hormonal decompensation, specific endocrine monitoring is essential. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Lambert, Flora AU - Lambert F AD - Nutrition Department, Reference Center for Rare Diseases PRADORT, Assistance Publique-Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France. FAU - Guillon, Emilie AU - Guillon E AD - Nutrition Department, Reference Center for Rare Diseases PRADORT, Assistance Publique-Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France. AD - Nutrition and Obesities, Systemic Approaches-NutriOmique Research Group, Sorbonne Universite, Inserm, Paris, France. FAU - Gatta-Cherifi, Blandine AU - Gatta-Cherifi B AD - Endocrinology, Diabetology, Nutrition and Metabolic Diseases Department, Haut-Leveque Hospital, Bordeaux, France. CN - CranioGLP1_FORCE Group FAU - Soula, Hedi AU - Soula H AD - Nutrition and Obesities, Systemic Approaches-NutriOmique Research Group, Sorbonne Universite, Inserm, Paris, France. FAU - Poitou, Christine AU - Poitou C AD - Nutrition Department, Reference Center for Rare Diseases PRADORT, Assistance Publique-Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France. AD - Nutrition and Obesities, Systemic Approaches-NutriOmique Research Group, Sorbonne Universite, Inserm, Paris, France. FAU - Faucher, Pauline AU - Faucher P AUID- ORCID: 0000-0001-5472-3851 AD - Nutrition Department, Reference Center for Rare Diseases PRADORT, Assistance Publique-Hopitaux de Paris, Pitie-Salpetriere Hospital, Paris, France. AD - Nutrition and Obesities, Systemic Approaches-NutriOmique Research Group, Sorbonne Universite, Inserm, Paris, France. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20251028 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Craniopharyngioma/complications/drug therapy MH - Male MH - Female MH - Adult MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications/etiology MH - *Pituitary Neoplasms/complications/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives/adverse effects MH - Weight Loss/drug effects MH - Treatment Outcome MH - Diabetes Mellitus, Type 2/complications MH - France/epidemiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12673446 OTO - NOTNLM OT - GLP-1 analogue OT - anti-obesity drug OT - obesity therapy OT - real-world evidence OT - semaglutide COIS- The authors declare no conflicts of interest. FIR - Lambert, Flora IR - Lambert F FIR - Guillon, Emilie IR - Guillon E FIR - Soula, Hedi IR - Soula H FIR - Poitou, Christine IR - Poitou C FIR - Faucher, Pauline IR - Faucher P FIR - Albarel, Frederique IR - Albarel F FIR - Bonnet, Jean-Baptiste IR - Bonnet JB FIR - Borel, Anne-Laure IR - Borel AL FIR - Brindisi, Marie-Claude IR - Brindisi MC FIR - Carette, Claire IR - Carette C FIR - Drui, Delphine IR - Drui D FIR - Fagour, Cedric IR - Fagour C FIR - Farigon, Nicolas IR - Farigon N FIR - Gaborit, Benedicte IR - Gaborit B FIR - Gatta-Cherifi, Blandine IR - Gatta-Cherifi B FIR - Illouz, Frederic IR - Illouz F FIR - Jouini-Bouhamri, Ryme IR - Jouini-Bouhamri R FIR - Maiga, Ibrahima IR - Maiga I FIR - Montastier, Emilie IR - Montastier E FIR - Mosbah, Helena IR - Mosbah H FIR - Vitellius, Geraldine IR - Vitellius G FIR - Ziegler, Olivier IR - Ziegler O EDAT- 2025/10/29 06:28 MHDA- 2025/12/03 14:11 PMCR- 2025/12/03 CRDT- 2025/10/29 00:59 PHST- 2025/10/09 00:00 [revised] PHST- 2025/06/30 00:00 [received] PHST- 2025/10/09 00:00 [accepted] PHST- 2025/12/03 14:11 [medline] PHST- 2025/10/29 06:28 [pubmed] PHST- 2025/10/29 00:59 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70216 [pii] AID - 10.1111/dom.70216 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):443-451. doi: 10.1111/dom.70216. Epub 2025 Oct 28. PMID- 41147324 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260721 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Comparison of the renal outcomes of novel antidiabetic agents in patients with type 2 diabetes with chronic kidney disease: A systematic review and network meta-analysis of randomized controlled trials. PG - 518-528 LID - 10.1111/dom.70224 [doi] AB - AIMS: To investigate the renal outcomes of dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose transport protein-2 (SGLT-2) inhibitors in patients with type 2 diabetes mellitus (T2DM) with chronic renal disease (CKD). MATERIALS AND METHODS: PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were searched through July 2025 for randomized controlled trials with >/=24 weeks of follow-up in patients with T2DM and CKD. Outcomes included composite renal outcome, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR). A network meta-analysis was conducted, and the certainty of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation used to evaluate evidence certainty (GRADE). RESULTS: Twenty RCTs enrolling 80,670 participants were included. Compared with placebo, several agents significantly reduced composite renal outcomes, with dapagliflozin 10 mg showing the greatest efficacy (OR 0.55, 95% CI 0.42-0.72; high-certainty evidence), followed by canagliflozin, empagliflozin, efpeglenatide, sotagliflozin 400 mg, semaglutide, and dulaglutide 1.5 mg. Canagliflozin 100-300 mg significantly reduced UACR, whereas dapagliflozin had no effect. None of the novel antidiabetic agents significantly altered eGFR. Certainty of evidence ranged from high for placebo-controlled comparisons to low or very low for indirect estimates. CONCLUSIONS: In patients with T2DM and CKD, SGLT2 inhibitors provide the most consistent renal protection, while GLP-1 receptor agonists offer additional but variable benefits. Dapagliflozin showed the greatest efficacy, and canagliflozin most strongly reduced albuminuria, highlighting meaningful heterogeneity across agents. DPP-4 inhibitors conferred no renal benefit. Overall, evidence from placebo-controlled trials was robust, whereas certainty was lower for indirect estimates, highlighting the need for drug-specific evaluation in clinical practice. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Lin, Rong AU - Lin R AD - Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan. FAU - Hsu, Chia-Li AU - Hsu CL AD - Ministry of Health and Welfare Shuang-Ho Hospital, New Taipei City, Taiwan. FAU - Shih, Ming-Chieh AU - Shih MC AD - School of Medicine, National Tsing Hua University, Hsinchu, Taiwan. FAU - Chien, Kuo-Liong AU - Chien KL AD - Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. AD - Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. FAU - Wu, Hon-Yen AU - Wu HY AUID- ORCID: 0000-0003-3121-3351 AD - Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan. AD - Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. AD - Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan. AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. LA - eng GR - NHRI-EX112-11026PI/National Health Research Institutes/ GR - NHRI-EX114-11433PI/National Health Research Institutes/ GR - FEMH-2022-C-014/Far Eastern Memorial Hospital/ GR - FEMH-2023-C-010/Far Eastern Memorial Hospital/ GR - FEMH-2025-C-019/Far Eastern Memorial Hospital/ PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20251028 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Diabetic Nephropathies/prevention & control MH - Glomerular Filtration Rate/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome PMC - PMC12673457 OTO - NOTNLM OT - DPP-IV inhibitor OT - GLP-1 analogue OT - SGLT2 inhibitor OT - antidiabetic drug OT - diabetic nephropathy OT - network meta-analysis COIS- The authors declare that there are no conflicts of interest related to this manuscript. EDAT- 2025/10/28 12:29 MHDA- 2025/12/03 14:11 PMCR- 2025/12/03 CRDT- 2025/10/28 06:13 PHST- 2025/09/26 00:00 [revised] PHST- 2025/06/11 00:00 [received] PHST- 2025/10/11 00:00 [accepted] PHST- 2025/12/03 14:11 [medline] PHST- 2025/10/28 12:29 [pubmed] PHST- 2025/10/28 06:13 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70224 [pii] AID - 10.1111/dom.70224 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):518-528. doi: 10.1111/dom.70224. Epub 2025 Oct 28. PMID- 41130371 OWN - NLM STAT- MEDLINE DCOM- 20251207 LR - 20260127 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 281 DP - 2026 Jan TI - Glucagon-like Peptide-1 Receptor Agonist Use and Risk of Cataract Development. PG - 666-673 LID - S0002-9394(25)00558-6 [pii] LID - 10.1016/j.ajo.2025.10.021 [doi] AB - OBJECTIVE: To evaluate the risk of developing age-related cataract among nondiabetic patients who are overweight or obese prescribed glucagon-like peptide-1 receptor agonists (GLP-1RAs) compared to other weight loss drugs (OWLD). DESIGN: Retrospective cohort study using the TriNetX Global Collaborative Network. SUBJECTS: Overweight or obese patients aged 55 years and greater were included. Patients with a diabetes mellitus or prior age-related cataract were excluded. METHODS: Patients in the GLP-1RA group were prescribed either semaglutide or liraglutide. Patients in the OWLD group were lorcaserin, setmelanotide, diethylpropion, sibutramine, fenfluramine, mazindol, phentermine, or orlistat A third cohort included patients not prescribed any weight loss medications. Propensity score matching was performed to minimize baseline differences between cohorts. MAIN OUTCOME MEASURES: The primary outcome was development of age-related cataract at 5-, 7-, and 10-year intervals. Risk ratios with 95% confidence intervals and corresponding P-values were reported. Standardized mean differences (SMDs) were calculated to assess covariate balance. RESULTS: In the primary analysis of GLP-1RA vs OWLD usage, covariate balance was achieved across all matched variables with SMDs < 0.2. In this primary analysis, GLP-1RA use was associated with a decreased risk of age-related cataract at 5 (RR: 0.278; 95% CI: 0.246-0.314; P < .0001), 7 (RR: 0.269; 95% CI: 0.241-0.299; P < .0001), and 10 (RR: 0.198; 95% CI: 0.176-0.222; P < .0001) years compared to OWLD use. GLP-1RA use was also associated with decreased risk at 5 (RR: 0.605; 95% CI: 0.553-0.661; P < .0001), 7 (RR: 0.499; 95% CI: 0.458-0.542; P < .0001), and 10 (RR: 0.437; 95% CI: 0.403-0.475; P < .0001) years compared to no drug use. Conversely, OWLD use was associated with increased risk at 5 (RR: 2.142; 95% CI: 1.957-2.345; P < .0001), 7 (RR: 2.093; 95% CI: 1.931-2.268; P < .0001) and 10 (RR: 2.111; 95% CI: 1.961-2.273; P < .0001) years compared to no drug use. CONCLUSIONS: GLP-1RA use was associated with a significantly reduced risk of age-related cataract compared to OWLD use and no pharmacologic treatment. These findings support the need for randomized prospective trials and mechanistic studies to better understand this observed association. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Ahuja, Abhimanyu S AU - Ahuja AS AD - From the Department of Ophthalmology (A.S.A., B.K.Y.), Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA. FAU - Paredes, Alfredo A 3rd AU - Paredes AA 3rd AD - Charles E. Schmidt College of Medicine (A.A.P.), Florida Atlantic University, Boca Raton, FL, USA. FAU - Ahuja, Sejal A AU - Ahuja SA AD - Windsor University School of Medicine (S.A.A.), Oakbrook, IL, USA. FAU - Young, Benjamin K AU - Young BK AD - From the Department of Ophthalmology (A.S.A., B.K.Y.), Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA. Electronic address: youngbe@ohsu.edu. LA - eng PT - Journal Article DEP - 20251021 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Retrospective Studies MH - *Cataract/epidemiology/chemically induced/diagnosis MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Aged MH - Risk Factors MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Obesity/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Liraglutide/therapeutic use/adverse effects MH - Overweight/drug therapy/complications MH - Incidence MH - Diabetes Mellitus, Type 2/drug therapy MH - Follow-Up Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/10/24 00:26 MHDA- 2025/12/08 01:37 CRDT- 2025/10/23 19:34 PHST- 2025/06/16 00:00 [received] PHST- 2025/10/16 00:00 [revised] PHST- 2025/10/17 00:00 [accepted] PHST- 2025/12/08 01:37 [medline] PHST- 2025/10/24 00:26 [pubmed] PHST- 2025/10/23 19:34 [entrez] AID - S0002-9394(25)00558-6 [pii] AID - 10.1016/j.ajo.2025.10.021 [doi] PST - ppublish SO - Am J Ophthalmol. 2026 Jan;281:666-673. doi: 10.1016/j.ajo.2025.10.021. Epub 2025 Oct 21. PMID- 41129847 OWN - NLM STAT- MEDLINE DCOM- 20251128 LR - 20260127 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 19 IP - 9 DP - 2025 Sep TI - Effects of GLP-1 agonists on 10-year cardiovascular risk reduction in primary prevention: A 44-week open label prospective study. PG - 103312 LID - S1871-4021(25)00129-8 [pii] LID - 10.1016/j.dsx.2025.103312 [doi] AB - AIMS: Patients with Type 2 diabetes mellitus face elevated cardiovascular risk. We assessed the effect of GLP-1 receptor agonists on 10-year CVR in a primary prevention cohort. METHODS: In this 44-week prospective, non-randomized study, 135 patients with type 2 diabetes mellitus and obesity were included across 13 healthcare centers. The primary endpoint was the change in 10-year cardiovascular risk, estimated using the AHA ASCVD Risk Estimator Plus tool at baseline and week 44. Secondary endpoints included weight loss, HbA1c, fasting plasma glucose, and lipid profiles. Patients received subcutaneous semaglutide, oral semaglutide, dulaglutide, or other GLP-1RAs. RESULTS: In the primary prevention cohort (n = 105), mean 10-year CVR decreased by 3.28 percentage points, a relative reduction of 13.45 % (p < 0.001). Subcutaneous semaglutide showed the greatest weight loss (-8.1 kg), followed by oral semaglutide (-6.5 kg) and dulaglutide (-5.6 kg). HbA1c improved from 8.1 % to 6.6 %, and fasting plasma glucose decreased by 45.8 mg/dL (both p < 0.001). CONCLUSIONS: GLP-1 receptor agonists reduce 10-year cardiovascular risk in primary prevention and improve metabolic control. Findings support early use in high-risk people with type 2 diabetes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT05136287. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Seijas-Amigo, Jose AU - Seijas-Amigo J AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Universidade de Santiago de Compostela, Spain. Electronic address: jose.seijas@rai.usc.es. FAU - Salgado-Barreira, Angel AU - Salgado-Barreira A AD - Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiologia y Salud Publica CIBERESP), Carlos III Health Institute, Madrid, Spain. Electronic address: angel.salgado.barreira@usc.es. FAU - Castelo-Dominguez, Rosana AU - Castelo-Dominguez R AD - Centro de Salud, Ribeira, A Coruna, Spain. FAU - Perez-Alvarez, Maria Teresa AU - Perez-Alvarez MT AD - Centro de Salud de Culleredo, A Coruna, Spain. FAU - Ponce-Pinon, Belen AU - Ponce-Pinon B AD - Centro de Salud de Fene, A Coruna, Spain. FAU - Fernandez-Silva, Marlen AU - Fernandez-Silva M AD - Centro de Salud O Ventorillo, A Coruna, Spain. FAU - Rodriguez-Barreiro, Marta AU - Rodriguez-Barreiro M AD - Centro de Salud. Virxe Peregrina, Pontevedra, Spain. FAU - Pereira-Pia, Mercedes AU - Pereira-Pia M AD - Centro de Salud de San Roque, Lugo, Spain. FAU - Iglesias-Moreno, Jose Manuel AU - Iglesias-Moreno JM AD - Centro de Salud de Val Minor, Nigran, Pontevedra, Spain. FAU - Gago-Garcia, Mar AU - Gago-Garcia M AD - Centro de Salud de Ribadeo, Lugo, Spain. FAU - Montans-Garcia, Raquel AU - Montans-Garcia R AD - Centro de Salud de Cee, A Coruna, Spain. FAU - Fernandez-Perez, Agustina AU - Fernandez-Perez A AD - Centro de Salud Vilalba, Lugo, Spain. FAU - Fraga-Gayoso, Dolores AU - Fraga-Gayoso D AD - Centro de Salud de Sarria, Lugo, Spain. FAU - Fernandez-Montenegro, Montse AU - Fernandez-Montenegro M AD - Centro de Salud de O Carballino, Ourense, Spain. FAU - Riveiro-Barciela, Beatriz AU - Riveiro-Barciela B AD - Centro de Salud O Temple, A Coruna, Spain. FAU - Rilla-Villar, Natalia AU - Rilla-Villar N AD - Centro de Salud de Arriondas, Asturias, Spain. FAU - Cardeso-Paredes, Begona AU - Cardeso-Paredes B AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. FAU - Ribeiro-Ferreiro, Marta AU - Ribeiro-Ferreiro M AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Spain. FAU - Rodriguez-Penas, Diego AU - Rodriguez-Penas D AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Spain. FAU - Cordero, Alberto AU - Cordero A AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Cardiology Department, Hospital IMED Elche, Alicante, Spain; Grupo de Investigacion Cardiovascular (GRINCAVA), Universidad Miguel Hernandez, Elche, Spain. FAU - Rodriguez-Manero, Moises AU - Rodriguez-Manero M AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. FAU - Gonzalez-Juanatey, Jose R AU - Gonzalez-Juanatey JR AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, University of Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. CN - SEVERAL INVESTIGATORS LA - eng SI - ClinicalTrials.gov/NCT05136287 PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20251019 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Biomarkers/analysis MH - Blood Glucose/analysis MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Follow-Up Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Glycated Hemoglobin/analysis MH - Heart Disease Risk Factors MH - *Hypoglycemic Agents/therapeutic use MH - *Primary Prevention/methods MH - Prognosis MH - Prospective Studies MH - Recombinant Fusion Proteins/therapeutic use MH - Immunoglobulin Fc Fragments MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular risk OT - GLP-1 receptor agonists OT - Primary prevention OT - Type 2 diabetes OT - Weight loss COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/10/23 18:26 MHDA- 2025/11/29 02:21 CRDT- 2025/10/23 17:59 PHST- 2024/11/19 00:00 [received] PHST- 2025/10/15 00:00 [revised] PHST- 2025/10/18 00:00 [accepted] PHST- 2025/11/29 02:21 [medline] PHST- 2025/10/23 18:26 [pubmed] PHST- 2025/10/23 17:59 [entrez] AID - S1871-4021(25)00129-8 [pii] AID - 10.1016/j.dsx.2025.103312 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2025 Sep;19(9):103312. doi: 10.1016/j.dsx.2025.103312. Epub 2025 Oct 19. PMID- 41129133 OWN - NLM STAT- MEDLINE DCOM- 20260106 LR - 20261024 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 143 IP - 12 DP - 2025 Dec 1 TI - Glucagon-Like Peptide-1 Receptor Agonists and Age-Related Macular Degeneration. PG - 999-1003 LID - 10.1001/jamaophthalmol.2025.3821 [doi] AB - IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for weight loss, but their ocular effects in nondiabetic individuals remain unclear. Prior studies suggest GLP-1RA use reduced age-related macular degeneration (AMD) risk in patients with diabetes, but applicability to nondiabetic populations is unknown. OBJECTIVE: To evaluate the risk of developing nonexudative AMD and its progression to exudative AMD among patients with obesity but not diabetes prescribed GLP-1RAs compared with those prescribed other weight-loss drugs (OWLDs). DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used electronic health record data obtained from the multicenter TriNetX Global Collaborative Network on patients aged 55 years or older diagnosed with overweight or obesity but not diabetes from January 2004 to July 2025. For the primary analysis, patients with preexisting nonexudative AMD were excluded. For the secondary analysis, patients with preexisting nonexudative AMD were included, while those with preexisting exudative AMD were excluded. Propensity score matching balanced baseline demographics and comorbidities. Data were analyzed on March 21, 2025, and August 2, 2025. EXPOSURES: Patients were prescribed either the GLP-1RAs liraglutide or semaglutide or OWLDs including lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion. MAIN OUTCOMES AND MEASURES: The primary outcome was development of nonexudative AMD at 5, 7, and 10 years. The secondary outcome was progression to exudative AMD at 10 years. Risk ratios (RRs) with 95% CIs were calculated. Standardized mean differences were used to assess covariate balance after matching. RESULTS: A total of 91 408 patients were included. After propensity score matching for the primary analysis, 45 704 patients remained in each of the GLP-1RA and OWLD cohorts. The GLP-1RA cohort included 35 753 (78.2%) females and 7852 (17.2%) males with a mean (SD) age of 61.1 (5.76) years, while the OWLD cohort included 35 732 (78.2%) females and 7815 (17.1%) males with a mean [SD] age of 61.0 (5.86) years. Covariate balance was achieved across all variables for the GLP-1RA and OWLD cohorts in the primary analysis. GLP-1RA use was associated with reduced risk of nonexudative AMD compared with OWLDs at 5 years (RR, 0.16; 95% CI, 0.10-0.28; P < .001), 7 years (RR, 0.13; 95% CI, 0.08-0.22; P < .001), and 10 years (RR, 0.09; 95% CI, 0.05-0.16; P < .001). No differences were observed in progression to exudative AMD. CONCLUSIONS AND RELEVANCE: In this cohort study, GLP-1RA use was associated with reduced risk of developing nonexudative AMD but was not associated with progression to exudative AMD among individuals with nonexudative AMD. These findings may inform future randomized trials evaluating the ocular effects of GLP-1RAs in nondiabetic populations. FAU - Ahuja, Abhimanyu S AU - Ahuja AS AD - Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland. FAU - Paredes, Alfredo A 3rd AU - Paredes AA 3rd AD - Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton. FAU - Young, Benjamin K AU - Young BK AD - Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA Ophthalmol. 2025 Dec 1;143(12):1004-1005. doi: 10.1001/jamaophthalmol.2025.4090. PMID: 41129138 MH - Humans MH - Retrospective Studies MH - Male MH - Female MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Hypoglycemic Agents/therapeutic use MH - *Macular Degeneration/epidemiology MH - Obesity/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use MH - Liraglutide/therapeutic use MH - Disease Progression MH - Diabetes Mellitus, Type 2/drug therapy MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12550735 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2025/10/23 12:28 MHDA- 2026/01/06 19:17 PMCR- 2026/10/23 CRDT- 2025/10/23 11:33 PHST- 2026/01/06 19:17 [medline] PHST- 2025/10/23 12:28 [pubmed] PHST- 2025/10/23 11:33 [entrez] PHST- 2026/10/23 00:00 [pmc-release] AID - 2840121 [pii] AID - eoi250061 [pii] AID - 10.1001/jamaophthalmol.2025.3821 [doi] PST - ppublish SO - JAMA Ophthalmol. 2025 Dec 1;143(12):999-1003. doi: 10.1001/jamaophthalmol.2025.3821. PMID- 41127515 OWN - NLM STAT- MEDLINE DCOM- 20251023 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Severe euglycemic ketoacidosis following combined therapy with GLP-1 receptor agonist and SGLT-2 inhibitor, refractory to standard treatment: a case report. PG - 1649270 LID - 10.3389/fendo.2025.1649270 [doi] LID - 1649270 AB - BACKGROUND: Euglycemic diabetic ketoacidosis (euDKA) is a rare but potentially life-threatening complication of diabetes, increasingly linked to SGLT-2 inhibitors (SGLT-2i) and, less frequently, GLP-1 receptor agonists (GLP-1 RA), especially in combination. CASE PRESENTATION: We present the case of a 36-year-old man with newly diagnosed type 2 diabetes who developed severe euDKA within days of starting combined therapy with semaglutide and dapagliflozin. Despite prior patient education and adherence to antidiabetic therapy, persistent vomiting and carbohydrate deficiency-likely related to GLP-1 RA side effects-led to decreased insulin administration and metabolic decompensation. This case was characterized by very early onset after initiation of therapy, absence of infection or other common triggers, and resistance to standard treatment with insulin, glucose, and fluid resuscitation. Intensive care with continuous veno-venous hemodiafiltration was required, resulting in full recovery. CONCLUSION: This case emphasizes the potential severity of euDKA induced by GLP-1 RA and SGLT-2i combination therapy and highlights the risk of treatment resistance. The decision to initiate SGLT2i and GLP-1RA concurrently should be individualized or possibly spread apart in time, weighing the potential therapeutic benefits against the risk of rare but severe complication such as euDKA. Comprehensive education on ketone monitoring and insulin administration during intercurrent illness are essential to prevent this rare but serious complication. CI - Copyright (c) 2025 Gandecka-Pempera, Naskret, Adamska and Zozulinska-Ziolkiewicz. FAU - Gandecka-Pempera, Agnieszka AU - Gandecka-Pempera A AD - Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Naskret, Dariusz AU - Naskret D AD - Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Adamska, Anna AU - Adamska A AD - Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Zozulinska-Ziolkiewicz, Dorota AU - Zozulinska-Ziolkiewicz D AD - Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Poznan, Poland. LA - eng PT - Case Reports PT - Journal Article DEP - 20251007 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Benzhydryl Compounds) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucosides) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 1ULL0QJ8UC (dapagliflozin) SB - IM MH - Humans MH - Male MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/administration & dosage MH - Adult MH - *Diabetic Ketoacidosis/chemically induced/pathology MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Benzhydryl Compounds/adverse effects/administration & dosage MH - Drug Therapy, Combination/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - *Glucosides/adverse effects/administration & dosage MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12537370 OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT-2 inhibitor OT - adverse drug reaction OT - euglycemic diabetic ketoacidosis (euDKA) OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/10/23 11:46 MHDA- 2025/10/23 12:29 PMCR- 2025/10/07 CRDT- 2025/10/23 04:55 PHST- 2025/06/18 00:00 [received] PHST- 2025/09/22 00:00 [accepted] PHST- 2025/10/23 12:29 [medline] PHST- 2025/10/23 11:46 [pubmed] PHST- 2025/10/23 04:55 [entrez] PHST- 2025/10/07 00:00 [pmc-release] AID - 10.3389/fendo.2025.1649270 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Oct 7;16:1649270. doi: 10.3389/fendo.2025.1649270. eCollection 2025. PMID- 41125326 OWN - NLM STAT- MEDLINE DCOM- 20260819 LR - 20260819 IS - 2047-9956 (Print) IS - 2047-9956 (Linking) VI - 33 IP - 5 DP - 2026 Aug 19 TI - Hypoglycaemic coma induced by a falsified semaglutide product: a case report. PG - 486-489 LID - 10.1136/ejhpharm-2025-004656 [doi] AB - Semaglutide (Ozempic, Rybelsus, Wegovy) is a GLP-1 receptor agonist used for the treatment of type 2 diabetes and, more recently, weight management. Due to its efficacy in weight loss, semaglutide has gained worldwide popularity, particularly the branded version Ozempic, resulting in off-label use by people seeking rapid weight loss. The resulting high demand has led to an increase in falsified products sold by unregulated online marketplaces. We present a case of a 31-year-old woman who was admitted to the emergency room in a hypoglycaemic coma after self-administrating semaglutide (Ozempic) obtained from a website. Toxicological analysis showed that the vial contained insulin instead of semaglutide, therefore leading to severe hypoglycaemia. This case highlights the growing concern regarding falsified medicines sold in the online drug market and the associated risk of severe adverse events. We reported the case to the Italian Medicines Agency (AIFA) and local authorities. We propose regulatory measures to mitigate similar incidents in the future. CI - (c) European Association of Hospital Pharmacists 2026. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Antonacci, Giulia AU - Antonacci G AUID- ORCID: 0009-0007-6968-6337 AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Bortignon, Erika AU - Bortignon E AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Bolognesi, Massimo AU - Bolognesi M AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Piano, Salvatore Silvio AU - Piano SS AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Cadore, Alessandro AU - Cadore A AD - Hospital Pharmacy Department, Padova University Hospital, Padova, Italy. FAU - Camuffo, Laura AU - Camuffo L AUID- ORCID: 0009-0001-8710-486X AD - Hospital Pharmacy Department, Padova University Hospital, Padova, Italy. FAU - Venturini, Francesca AU - Venturini F AUID- ORCID: 0000-0003-0396-4377 AD - Hospital Pharmacy Department, Padova University Hospital, Padova, Italy. FAU - Faoro, Sonia AU - Faoro S AD - Hospital Pharmacy Department, Padova University Hospital, Padova, Italy. FAU - Favretto, Donata AU - Favretto D AD - Forensic Toxicologist, Universita degli Studi di Padova, Padua, Italy. FAU - Romano, Antonietta AU - Romano A AD - Department of Medicine, University of Padova, Padua, Italy antonietta.romano@aopd.veneto.it. FAU - Mengato, Daniele AU - Mengato D AUID- ORCID: 0000-0003-1374-1505 AD - Hospital Pharmacy Department, Padova University Hospital, Padova, Italy. LA - eng PT - Case Reports PT - Journal Article DEP - 20260819 PL - England TA - Eur J Hosp Pharm JT - European journal of hospital pharmacy : science and practice JID - 101578294 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - Female MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Adult MH - *Hypoglycemia/chemically induced/diagnosis MH - Diabetes Mellitus, Type 2/drug therapy MH - *Coma/chemically induced/diagnosis OTO - NOTNLM OT - Diabetes Mellitus OT - Drug Monitoring OT - Metabolic Side Effects of Drugs and Substances OT - PHARMACISTS OT - PUBLIC HEALTH COIS- Competing interests: None declared. EDAT- 2025/10/23 00:26 MHDA- 2026/08/19 23:42 CRDT- 2025/10/22 21:03 PHST- 2025/07/10 00:00 [received] PHST- 2025/10/13 00:00 [accepted] PHST- 2026/08/19 23:42 [medline] PHST- 2025/10/23 00:26 [pubmed] PHST- 2025/10/22 21:03 [entrez] AID - ejhpharm-2025-004656 [pii] AID - 10.1136/ejhpharm-2025-004656 [doi] PST - epublish SO - Eur J Hosp Pharm. 2026 Aug 19;33(5):486-489. doi: 10.1136/ejhpharm-2025-004656. PMID- 41122783 OWN - NLM STAT- MEDLINE DCOM- 20251211 LR - 20251230 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 41 IP - 10 DP - 2025 Oct TI - Comparative effectiveness of GLP-1 RAs and other glucose-lowering therapies among Medicare Advantage beneficiaries with T2D and ASCVD. PG - 1787-1798 LID - 10.1080/03007995.2025.2577762 [doi] AB - OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended as glucose-lowering therapies for people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). Real-world evidence is limited comparing cardiovascular (CV) outcomes between once-weekly (OW) GLP-1 RAs vs other non-insulin glucose lowering therapies (ONIGLTs) including SGLT2is. This study aimed to compare CV outcomes among Medicare Advantage (MA) beneficiaries with T2D and ASCVD initiating OW GLP-1 RAs or ONIGLTs. METHODS: This observational cohort study included MA beneficiaries with T2D and ASCVD within Optum's de-identified Clinformatics Data Mart Database (01/2007-03/2024). Propensity score matching was used to compare adults initiating OW GLP-1 RAs or ONIGLTs. Incidence rates and time to the first event of ischemic stroke (IS), myocardial infarction (MI), 2-, 3-, and 5-point major adverse cardiovascular event (MACE) during follow-up were assessed. Individual OW GLP-1 RAs were compared with SGLT2is. RESULTS: Post-matching, 41,835 adults were treated with OW GLP-1 RAs and 77,599 with ONIGLTs. Compared with ONIGLTs, OW GLP-1 RAs had 18% lower risk for IS, 14% lower for MI, 17% lower for 2-point MACE, 28% lower for 3-point MACE, and 27% lower for 5-point MACE. Compared with SGLT2is, OW GLP-1 RAs had 14% lower risk of 2-point MACE, 15% lower risk of 3-point MACE, and 14% lower risk of 5-point MACE. Semaglutide had lower risk of all CV outcomes vs SGLT2is. CONCLUSION: Among MA beneficiaries with T2D and ASCVD, risk of CV outcomes was lower with OW GLP-1 RAs, particularly semaglutide, vs ONIGLTs including SGLT2is. FAU - Tan, Xi AU - Tan X AD - Novo Nordisk Inc, Plainsboro Township, New Jersey, USA. FAU - Liang, Yuanjie AU - Liang Y AD - Novo Nordisk Inc, Plainsboro Township, New Jersey, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc, Plainsboro Township, New Jersey, USA. FAU - Gutierrez, Cynthia AU - Gutierrez C AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Harton, Joanna AU - Harton J AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Muhammad, Chalak AU - Muhammad C AD - Novo Nordisk Inc, Plainsboro Township, New Jersey, USA. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk Inc, Plainsboro Township, New Jersey, USA. FAU - de Havenon, Adam AU - de Havenon A AD - Department of Neurology, Center for Brain and Mind Health, Yale University, New Haven, Connecticut, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20251106 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology/blood MH - Female MH - Male MH - Aged MH - United States/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Medicare Part C/statistics & numerical data MH - *Atherosclerosis/drug therapy/epidemiology MH - Aged, 80 and over MH - Cardiovascular Diseases/epidemiology MH - Treatment Outcome OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Medicare Advantage OT - atherosclerotic cardiovascular disease OT - major adverse cardiovascular events OT - semaglutide OT - sodium-glucose co-transporter-2 inhibitors OT - type 2 diabetes EDAT- 2025/10/22 06:33 MHDA- 2025/12/11 07:42 CRDT- 2025/10/22 04:24 PHST- 2025/12/11 07:42 [medline] PHST- 2025/10/22 06:33 [pubmed] PHST- 2025/10/22 04:24 [entrez] AID - 10.1080/03007995.2025.2577762 [doi] PST - ppublish SO - Curr Med Res Opin. 2025 Oct;41(10):1787-1798. doi: 10.1080/03007995.2025.2577762. Epub 2025 Nov 6. PMID- 41117588 OWN - NLM STAT- MEDLINE DCOM- 20251218 LR - 20261005 IS - 1897-9483 (Electronic) IS - 0032-3772 (Linking) VI - 135 IP - 12 DP - 2025 Dec 18 TI - Assessment of noninferiority of oral vs subcutaneous semaglutide: a systematic review and meta-analysis. LID - 17141 [pii] LID - 10.20452/pamw.17141 [doi] AB - INTRODUCTION: This systematic review and meta‑analysis is the first to comprehensively compare oral and subcutaneous semaglutide for type 2 diabetes (T2D) management. OBJECTIVES: Our aim was to determine whether oral semaglutide is noninferior to the subcutaneous preparation, assess potential superiority, and provide evidence‑based guidance for clinical decisions. PATIENTS AND METHODS: We searched clinical trial registries and bibliographic databases through April 30, 2025. Twelve randomized controlled trials involving 6253 adults with T2D were analyzed. Following the PRISMA and Cochrane guidelines (PROSPERO, CRD420251017953), the data were extracted on efficacy, safety, and clinical outcomes. Noninferiority was assessed using predefined margins, and post hoc superiority analyses examined secondary end points. Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation criteria. RESULTS: Both formulations of semaglutide significantly reduced the level of glycated hemoglobin (HbA1c), that is, oral by 1.16 percentage points (95% CI, -1.22 to -1.09) and subcutaneous by 1.4 percentage points (95% CI, -1.47 to -1.33). Oral semaglutide met the noninferiority margin at 50% of the subcutaneous effect. Subcutaneous semaglutide was superior for weight loss (2.19 kg; 95% CI, -3.57 to -0.81; P <0.002), body mass index (BMI) reduction (0.88 kg/m2; 95% CI, -1.55 to -0.21; P <0.011), and triglyceride level lowering (0.09 mmol/l; 95% CI, -0.14 to -0.04; P <0.001). CONCLUSIONS: Both forms of semaglutide effectively improve glycemic control in T2D. Oral semaglutide is noninferior to subcutanous semaglutide in lowering HbA1c level, while subcutaneous semaglutide is superior in weight, BMI, and triglyceride reduction. Given similar safety profiles and modest differences in other outcomes, treatment selection should be guided by clinical goals and patient preferences. FAU - Drygalski, Krzysztof AU - Drygalski K AUID- ORCID: 0000-0003-0645-7020 AD - Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland. FAU - Pastuszak, Krzysztof AU - Pastuszak K AD - Department of Algorithms and System Modeling, Gdansk University of Technology, Gdansk, Poland. AD - Department of Translational Oncology, Medical University of Gdansk, Gdansk, Poland. AD - Centre of Biostatistics and Bioinformatics Analysis, Medical University of Gdansk, Gdansk, Poland. FAU - Modzelewska, Beata AU - Modzelewska B AD - Department of Biophysics, Medical University of Bialystok, Bialystok, Poland. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20251021 PL - Poland TA - Pol Arch Intern Med JT - Polish archives of internal medicine JID - 101700960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Injections, Subcutaneous MH - Glycated Hemoglobin/analysis MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/10/21 12:35 MHDA- 2025/12/18 07:20 CRDT- 2025/10/21 09:31 PHST- 2025/12/18 07:20 [medline] PHST- 2025/10/21 12:35 [pubmed] PHST- 2025/10/21 09:31 [entrez] AID - 17141 [pii] AID - 10.20452/pamw.17141 [doi] PST - ppublish SO - Pol Arch Intern Med. 2025 Dec 18;135(12):17141. doi: 10.20452/pamw.17141. Epub 2025 Oct 21. PMID- 41105066 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260418 IS - 1531-6564 (Electronic) IS - 0363-5023 (Linking) VI - 50 IP - 12 DP - 2025 Dec TI - Endoscopic and Open Carpal Tunnel Release in Patients With Type II Diabetes Mellitus: Influence of Preoperative Semaglutide Use on Postoperative Outcomes. PG - 1467-1475 LID - S0363-5023(25)00504-0 [pii] LID - 10.1016/j.jhsa.2025.09.003 [doi] AB - PURPOSE: Patients with type II diabetes mellitus are at greater risk of carpal tunnel syndrome and of complications following carpal tunnel release (CTR). Although recent orthopedic literature suggests preoperative semaglutide use may reduce complication and reoperation rates, its impact has not been studied in hand surgery. Given the overall favorable complication profile of CTR, it remains unknown if similar risk modification exists. METHODS: Type II diabetes mellitus patients undergoing endoscopic carpal tunnel release (ECTR) and open carpal tunnel release (OCTR) were identified from the PearlDiver database. Exclusion criteria included the following: age <18, revision CTR, traumatic, neoplastic, or infectious diagnoses within 90 days before surgery, <90 days follow-up, and other concurrent upper-extremity procedures. Patients using semaglutide within 1 year before surgery were identified and matched 1:4 with (-)semaglutide controls. Ninety-day complications were compared by multivariable logistic regression, and 2-year reoperation was assessed by Kaplan-Meier survival analysis and log-rank test. RESULTS: Semaglutide was used by 689 (1.2%) of ECTR and 1,966 (0.8%) of OCTR patients. Once matched, there were 426 ECTR and 1,673 OCTR patients receiving semaglutide. Relative to ECTR (-)semaglutide controls, semaglutide reduced the odds of pneumonia (OR, 0.30 [0.13-0.58]) and urinary tract infection (OR, 0.28 [0.18-0.44]). Relative to OCTR (-)semaglutide controls, semaglutide reduced the odds of surgical site infection (SSI) (OR, 0.31 [0.18-0.51]), sepsis (OR, 0.61 [0.43-0.85]), wound dehiscence (OR, 0.25 [0.13-0.42]), pneumonia (OR, 0.26 [0.19-0.35]), and urinary tract infection (OR, 0.33 [0.27-0.40]). For both ECTR and OCTR, 2-year reoperation rates were similar for those with versus without semaglutide. CONCLUSIONS: The current study reinforces the low overall incidence of complications following CTR. The most clinically relevant findings were observed in OCTR patients, including reduced odds of SSI and wound dehiscence. However, 2-year reoperation rates were similar across both surgical approaches regardless of semaglutide use. These findings may have implications in the context of perioperative risk stratification. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II. CI - Copyright (c) 2025 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved. FAU - Seddio, Anthony E AU - Seddio AE AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. FAU - Day, Wesley AU - Day W AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. FAU - Rancu, Albert L AU - Rancu AL AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. FAU - Modrak, Maxwell AU - Modrak M AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. FAU - Joo, Peter Y AU - Joo PY AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. FAU - Grauer, Jonathan N AU - Grauer JN AD - Yale School of Medicine, Department of Orthopaedics & Rehabilitation, New Haven, CT. Electronic address: jonathan.grauer@yale.edu. LA - eng PT - Journal Article DEP - 20251017 PL - United States TA - J Hand Surg Am JT - The Journal of hand surgery JID - 7609631 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Female MH - Male MH - *Carpal Tunnel Syndrome/surgery/complications MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Middle Aged MH - *Postoperative Complications/prevention & control/epidemiology MH - Reoperation/statistics & numerical data MH - Aged MH - *Endoscopy MH - Treatment Outcome MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - Preoperative Care MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Carpal tunnel release OT - complications OT - preoperative optimization OT - surgical site infection OT - wound dehiscence COIS- Conflicts of Interest No benefits in any form have been received or will be received related directly to this article. EDAT- 2025/10/17 12:29 MHDA- 2025/12/04 02:11 CRDT- 2025/10/17 10:31 PHST- 2025/02/27 00:00 [received] PHST- 2025/08/03 00:00 [revised] PHST- 2025/09/03 00:00 [accepted] PHST- 2025/12/04 02:11 [medline] PHST- 2025/10/17 12:29 [pubmed] PHST- 2025/10/17 10:31 [entrez] AID - S0363-5023(25)00504-0 [pii] AID - 10.1016/j.jhsa.2025.09.003 [doi] PST - ppublish SO - J Hand Surg Am. 2025 Dec;50(12):1467-1475. doi: 10.1016/j.jhsa.2025.09.003. Epub 2025 Oct 17. PMID- 41104517 OWN - NLM STAT- MEDLINE DCOM- 20260114 LR - 20260919 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 2 DP - 2026 Feb TI - GLP-1RA and the risk of non-arteritic anterior ischaemic optic neuropathy in patients with type 2 diabetes: A population-based study. PG - 1517-1528 LID - 10.1111/dom.70200 [doi] AB - AIMS: Evidence on the safety of semaglutide and other glucagon-like peptide-1 receptor agonists (GLP-1RA) concerning non-arteritic anterior ischemic optic neuropathy (NAION) is inconclusive, with several studies published to date presenting methodological challenges. We sought to compare the risk of presumed NAION in patients with type 2 diabetes (T2D), initiating a GLP-1RA versus a sodium-glucose cotransporter-2 inhibitor (SGLT2i), using a new-user active comparator cohort study design within a target trial emulation framework. MATERIALS AND METHODS: Using insurance claims data from three databases (01/2016-08/2024), we identified 482 912 propensity score matched (1:1) pairs of GLP-1RA and SGLT2i adult initiators with T2D and without prior ischemic optic neuropathy (ION) or other optic nerve disorders. NAION was defined as a diagnosis of ION without other causes of optic neuropathy, combined with an ophthalmologist or optometrist visit on the same day. We estimated pooled hazard ratios (HRs) and rate differences (RDs). RESULTS: Over a median follow-up of 6.7 months on treatment, the risk of incident NAION was higher among initiators of GLP-1RA compared with SGLT2i [HR, 1.85; 95% CI (1.51-2.27); RD, 0.29 (0.19, 0.39) per 1000 person-years]. Results were consistent across subgroups and sensitivity analyses. A meta-analysis of our semaglutide analysis with previously published results also showed an elevated risk, with a HR of 2.78 (1.39-5.56). CONCLUSIONS: In this large observational study, the initiation of GLP-1RA was associated with an 85% increase in the risk of presumed NAION, compared with the initiation of SGLT2is, though incidence rates and absolute increase in risk were small. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Tesfaye, Helen AU - Tesfaye H AUID- ORCID: 0000-0002-6264-2813 AD - Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. AD - New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts, USA. FAU - Wexler, Deborah J AU - Wexler DJ AD - MGH Diabetes Center, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Hathaway, Jimena Tatiana AU - Hathaway JT AD - Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. AD - Neuro-Ophthalmology Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. FAU - Yu, Elaine W AU - Yu EW AD - Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Freedman, Ariel AU - Freedman A AD - Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Rizzo, Joseph F 3rd AU - Rizzo JF 3rd AD - Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. AD - Neuro-Ophthalmology Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA. LA - eng GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01DK138036/DK/NIDDK NIH HHS/United States GR - R01 AR075117/AR/NIAMS NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States GR - R01DK138036/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20251017 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced MH - Female MH - Male MH - Middle Aged MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Adult MH - Incidence MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12718077 MID - NIHMS2125282 OTO - NOTNLM OT - GLP-1 analogue OT - pharmacoepidemiology OT - real-world evidence OT - type 2 diabetes EDAT- 2025/10/17 06:27 MHDA- 2026/01/16 04:07 PMCR- 2025/12/21 CRDT- 2025/10/17 05:32 PHST- 2025/10/02 00:00 [revised] PHST- 2025/08/13 00:00 [received] PHST- 2025/10/03 00:00 [accepted] PHST- 2026/01/16 04:07 [medline] PHST- 2025/10/17 06:27 [pubmed] PHST- 2025/10/17 05:32 [entrez] PHST- 2025/12/21 00:00 [pmc-release] AID - 10.1111/dom.70200 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Feb;28(2):1517-1528. doi: 10.1111/dom.70200. Epub 2025 Oct 17. PMID- 41103643 OWN - NLM STAT- MEDLINE DCOM- 20251017 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Multi-omics analysis of hepatic outcomes in T2DM-MAFLD patients treated with semaglutide: a single-centre, longitudinal, data-driven study. PG - 1650729 LID - 10.3389/fendo.2025.1650729 [doi] LID - 1650729 AB - BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease and is closely linked to type 2 diabetes mellitus (T2DM). The pathogenesis of MAFLD involves complex metabolic imbalances, including impaired fatty acid beta-oxidation and chronic inflammation. GLP-1 receptor agonists (GLP-1 RAs) have shown promise in improving metabolic outcomes, but their specific effects on MAFLD remain unclear. This study aims to investigate the molecular mechanisms underlying the hepatic benefits of semaglutide, a GLP-1 RA, in T2DM patients with MAFLD using serum proteomics and metabolomics. METHODS: We conducted a single-centre, longitudinal, data-driven study involving 75 T2DM patients with MAFLD (pre-treatment, PT) and 100 healthy controls (health control, HC). Patients received semaglutide treatment (0.25 mg/week initially, escalated to 0.5 mg/week) for 12 weeks. Serum proteomic and metabolomic profiles were analyzed using 4D-DIA proteomics and LC-MS before and after treatment. Biomarker discovery involved the identification of differential metabolites and proteins, pathway analysis, and integration of proteomic and metabolomic data. Clinical and biochemical parameters were also assessed. RESULTS: Semaglutide significantly improved metabolic and liver parameters, including HbA1c, BMI, HOMA-IR, liver function, IL-6, and liver stiffness (p < 0.01). Multivariate analysis revealed distinct proteomic and metabolomic profiles between baseline and post-treatment groups. A total of 203 differential metabolites and 61 proteins were identified, with key changes including reductions in long-chain fatty acids and inflammatory mediators, alongside increases in carnitine derivatives and anti-inflammatory proteins. Pathway analysis highlighted effects on fatty acid metabolism, PPAR signaling, and NAFLD-related pathways. CONCLUSION: Our study provides a comprehensive multi-omics analysis revealing that semaglutide modulates serum proteomic and metabolomic profiles in T2DM-MAFLD patients, potentially through enhancing mitochondrial beta-oxidation, reducing lipid toxicity, and suppressing inflammation. These findings offer mechanistic insights into the hepatic benefits of semaglutide and support its potential as a therapeutic agent for MAFLD. This innovative approach advances our understanding of GLP-1 RAs' multi-organ protective effects and provides a foundation for developing precision medicine strategies for MAFLD. CI - Copyright (c) 2025 Niu, Chen, Wu, Wang, Xu, Yin and Zhao. FAU - Niu, Shu AU - Niu S AD - Department of Endocrine, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, China. FAU - Chen, Shuchun AU - Chen S AD - Department of Endocrine, Hebei Provincial People's Hospital, Shijiazhuang, Hebei, China. FAU - Wu, Di AU - Wu D AD - Shijiazhuang Hospital of Traditional Chinese Medicine, Shijiazhuang, Hebei, China. FAU - Wang, Chenxi AU - Wang C AD - Department of Endocrine, Medical University, Shijiazhuang, Hebei, China. FAU - Xu, Jianchao AU - Xu J AD - Department of Endocrine, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, China. FAU - Yin, Jiantong AU - Yin J AD - Department of Endocrine, Medical University, Shijiazhuang, Hebei, China. FAU - Zhao, Yubin AU - Zhao Y AD - Department of Endocrine, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, China. LA - eng PT - Journal Article DEP - 20251001 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Middle Aged MH - Longitudinal Studies MH - Metabolomics/methods MH - Proteomics/methods MH - *Liver/metabolism/drug effects MH - *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - Biomarkers/blood MH - Aged MH - Treatment Outcome MH - Multiomics MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12521249 OTO - NOTNLM OT - MAFLD-T2DM OT - hepatic outcomes OT - multi-omics analysis OT - proteomics OT - semaglutide COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/10/17 06:27 MHDA- 2025/10/17 06:28 PMCR- 2025/10/01 CRDT- 2025/10/17 04:49 PHST- 2025/06/20 00:00 [received] PHST- 2025/09/18 00:00 [accepted] PHST- 2025/10/17 06:28 [medline] PHST- 2025/10/17 06:27 [pubmed] PHST- 2025/10/17 04:49 [entrez] PHST- 2025/10/01 00:00 [pmc-release] AID - 10.3389/fendo.2025.1650729 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Oct 1;16:1650729. doi: 10.3389/fendo.2025.1650729. eCollection 2025. PMID- 41094027 OWN - NLM STAT- MEDLINE DCOM- 20251208 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 69 IP - 1 DP - 2026 Jan TI - Pre-stroke weight loss by glucagon-like peptide 1 receptor and neuropeptide Y receptor Y2 activation improves post-stroke functional recovery in male diabetic mouse models. PG - 230-243 LID - 10.1007/s00125-025-06567-4 [doi] AB - AIMS/HYPOTHESIS: Type 2 diabetes is associated with worsened stroke outcome and lasting disability. The underlying mechanisms are undetermined, and no therapy is available. We experimentally investigated whether pharmacologically targeting obesity, which is highly prevalent in type 2 diabetes, before stroke enhances neurological recovery in type 2 diabetes. To induce weight loss, we employed the glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide and the neuropeptide Y receptor Y2 (NPY2R) agonist BI8271, which potentiates GLP-1R-mediated weight loss. We also investigated potential acute neuroprotective effects induced by these treatments, independently of metabolic regulation. METHODS: C57BL/6J mice were fed with a high-fat diet for 5 months to induce obesity and features of type 2 diabetes (i.e. hyperglycaemia and insulin resistance). Weight loss was induced by 4-week administration of semaglutide and/or BI8271. As a control for the effect of weight loss, a vehicle (PBS)-treated group was switched to standard diet to achieve the same weight range and the same percentage weight loss within the same time frame as those receiving semaglutide/BI8271. Thereafter, mice were subjected to stroke by transient middle cerebral artery occlusion (tMCAO). Stroke recovery (the primary outcome) was assessed by measuring the recovery of grip strength and the lateralised sensorimotor integration. Brains and serum were collected, and stroke volume and serum IGF-1 levels were quantified (secondary outcomes). In additional studies, type 2 diabetic mice were subjected to tMCAO and injected with semaglutide and/or BI8271 1 and 24 h after reperfusion. Acute neuroprotection (the primary outcome) was assessed by a grip strength test and by quantifying stroke volume and the number of surviving neuronal nuclear marker (NeuN)-positive neurons. RESULTS: We report that pre-stroke weight loss by GLP-1R activation, and more potently by dual co-activation of GLP-1 and NPY2 receptors, is a pharmacologically targetable mechanism, upstream of glycaemic regulation, through which post-stroke recovery is achieved. Moreover, we show that post-stroke recovery in type 2 diabetes is inversely associated with peripheral IGF-1 levels. Finally, GLP-1R and NPY2R activation can also improve stroke recovery through acute neuroprotection if they are given acutely after stroke, independently of their metabolic effects. CONCLUSIONS/INTERPRETATION: The diabetes and obesity epidemics are increasing the incidence of stroke, and consequently the need for treatments to improve stroke outcome. Our results indicate that clinically used type 2 diabetes treatments could be employed in a preventive role to improve stroke outcome by exerting dual pharmacological action: weight loss and acute neuroprotection. These findings could have novel therapeutic implications for many people. CI - (c) 2025. The Author(s). FAU - Vercalsteren, Ellen AU - Vercalsteren E AUID- ORCID: 0000-0002-9425-4209 AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Karampatsi, Dimitra AU - Karampatsi D AUID- ORCID: 0000-0002-5316-088X AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Neicu, Maria AU - Neicu M AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Romanitan, Mihaela Oana AU - Romanitan MO AUID- ORCID: 0009-0001-4719-6624 AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Haebel, Peter AU - Haebel P AUID- ORCID: 0009-0000-5861-9613 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Bleymehl, Katherin AU - Bleymehl K AUID- ORCID: 0009-0007-6269-1061 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Nystrom, Thomas AU - Nystrom T AUID- ORCID: 0000-0002-3462-7990 AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Klein, Thomas AU - Klein T AUID- ORCID: 0000-0001-5762-9166 AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. FAU - Darsalia, Vladimer AU - Darsalia V AUID- ORCID: 0000-0002-6693-934X AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. vladimer.darsalia@ki.se. FAU - Patrone, Cesare AU - Patrone C AUID- ORCID: 0000-0003-0470-4606 AD - Department of Clinical Science and Education, Sodersjukhuset, Internal Medicine, Karolinska Institutet, Stockholm, Sweden. cesare.patrone@ki.se. LA - eng PT - Journal Article DEP - 20251015 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Receptors, Neuropeptide Y) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (neuropeptide Y2 receptor) SB - IM MH - Animals MH - Male MH - Mice MH - Mice, Inbred C57BL MH - *Weight Loss/drug effects/physiology MH - *Stroke/metabolism/physiopathology/drug therapy MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy MH - *Receptors, Neuropeptide Y/metabolism/agonists MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - Recovery of Function/drug effects MH - Diet, High-Fat MH - *Diabetes Mellitus, Experimental/metabolism MH - Obesity/metabolism MH - Disease Models, Animal MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12686085 OTO - NOTNLM OT - Glucagon-like peptide 1 receptor OT - Neuropeptide Y receptor Y2 OT - Stroke OT - Type 2 diabetes OT - Weight loss COIS- Acknowledgements: We thank F. Bahram (Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden) for technical assistance, and H. Pettersson (Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden) for advice on statistical analyses. Data availability: The data that support the findings of this study are not openly available for reasons of sensitivity, but are available from the corresponding author upon reasonable request. Data are located in controlled-access data storage (data repository) at the Karolinska Institutet. Funding: Open access funding provided by Karolinska Institute. Funding was provided by the Swedish Medical Research Council (to CP), the FANG Foundation and the Swedish Brain Foundation (to CP), the Swedish Heart-Lung Foundation (to TN), the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse (to TN), the Ulla Hamberg Angeby och Lennart Angebys Stiftelse (to VD and EV), the Swedish Stroke Foundation (to CP, VD and EV), the Foundation for Geriatric Diseases at Karolinska Institutet (to EV), ALF Stockholm (to TN) and by a grant from Boehringer Ingelheim Pharma GmbH & Co. KG. Authors' relationships and activities: TN has received consultancy fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Merck and Sanofi. TK, PH and KB are employed at Boehringer Ingelheim Pharma GmbH & Co. KG. The remaining authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: EV substantially contributed to the design of the work, performed part of the drug administration and diabetic tests in studies 1-3, and part of the immunohistochemical and stereology analysis. Moreover, she drafted and critically reviewed the article with DK, and approved the final version of the manuscript. DK substantially contributed to the design of the work, performed part of the drug administration and diabetic tests in studies 1 and 3 and part of the immunohistochemical and stereology analysis, and acquired/processed images. Moreover, she drafted and critically reviewed the article with EV, and approved the final version of the manuscript. MN performed part of the immunohistochemical studies and reviewed the article critically. MOR provided resources and contributed to the conception of the work. She also reviewed the manuscript. TN contributed to the conception of the study, provided resources, and critically revised the manuscript. PH synthesised the BI8271 compound and substantially contributed to the analysis and interpretation of data and critically reviewed the article. KB provided the data used to determine the doses of the compounds, contributed to the analysis and interpretation of data and critically reviewed the article. TK conceived the study and provided resources, including semaglutide/BI8271, and revised the manuscript. VD conceived and designed the study, performed the stroke experiments and part of the diabetic/functional tests, and edited the manuscript. CP conceived, designed and coordinated the research plan, and wrote the manuscript. All authors approved the final version to be published. EV, VD and CP are responsible for the integrity of the work as a whole. EDAT- 2025/10/16 05:31 MHDA- 2025/12/08 13:20 PMCR- 2025/10/15 CRDT- 2025/10/15 23:31 PHST- 2025/05/13 00:00 [received] PHST- 2025/07/23 00:00 [accepted] PHST- 2025/12/08 13:20 [medline] PHST- 2025/10/16 05:31 [pubmed] PHST- 2025/10/15 23:31 [entrez] PHST- 2025/10/15 00:00 [pmc-release] AID - 10.1007/s00125-025-06567-4 [pii] AID - 6567 [pii] AID - 10.1007/s00125-025-06567-4 [doi] PST - ppublish SO - Diabetologia. 2026 Jan;69(1):230-243. doi: 10.1007/s00125-025-06567-4. Epub 2025 Oct 15. PMID- 41093600 OWN - NLM STAT- MEDLINE DCOM- 20251015 LR - 20260127 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 13 IP - 5 DP - 2025 Oct 15 TI - Long-term comparative effectiveness of once-weekly semaglutide versus alternative treatments in a real-world US adult population with type 2 diabetes: a randomized pragmatic clinical trial. LID - 10.1136/bmjdrc-2025-005161 [doi] LID - e005161 AB - INTRODUCTION: This study evaluated the long-term effectiveness of once-weekly subcutaneous semaglutide versus alternative treatment in adults with type 2 diabetes (T2D) in routine clinical practice. RESEARCH DESIGN AND METHODS: The SEmaglutide PRAgmatic (SEPRA) was a 2-year, randomized, open-label, pragmatic clinical trial (NCT03596450). Adults with T2D and inadequate glycemic control on one or two oral antidiabetic medications were randomized to receive once-weekly subcutaneous semaglutide or alternative treatment (chosen by the treating physician) as add-on therapy. Endpoints included proportion of participants achieving glycated hemoglobin (HbA(1c))<7.0% at year 1 (primary endpoint) and year 2; changes in HbA(1c) (percentage point), body weight, and patient-reported outcomes (PROs) at years 1 and 2; and treatment changes (baseline to year 2). Missing data were imputed for some analyses. RESULTS: Participants were randomized to semaglutide (n=644) or alternative treatment (n=634). Proportions of participants achieving HbA(1c) <7.0% were significantly higher with semaglutide versus alternative treatment at years 1 (53.1% vs 45.5%; OR (95% CI): 1.36 (1.03 to 1.79); p=0.033) and 2 (49.9% vs 38.9%; OR (95% CI): 1.56 (1.13 to 2.16); p=0.007). Mean HbA(1c) decreases were larger with semaglutide versus alternative treatment at year 1 (-1.35% vs -1.16%; estimated treatment difference (ETD) (95% CI): -0.20% (-0.39% to 0.00%); p=0.046) and year 2 (-1.27% vs -0.96%; ETD (95% CI): -0.31% (-0.57% to -0.05%); p=0.018). Semaglutide was associated with larger reductions in body weight at year 1 (-3.57% vs -1.91%; ETD (95% CI): -1.65% (-2.92% to -0.39%); p=0.010) but not year 2 (p=0.175). Treatment changes occurred less frequently with semaglutide than with alternative treatments. Some PROs indicated greater improvement with semaglutide versus alternative treatment. No new safety concerns were identified. CONCLUSIONS: SEPRA demonstrates that semaglutide is an appropriate choice for treatment intensification among individuals with T2D in the USA who are receiving 1-2 antidiabetic medications. Findings support semaglutide as an effective and well-tolerated option in clinical practice. TRIAL REGISTRATION NUMBER: NCT03596450. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA jbuse@med.unc.edu. FAU - Nordahl Christensen, Helene AU - Nordahl Christensen H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Harty, Brian J AU - Harty BJ AD - Carelon Research, Newton, Massachusetts, USA. FAU - Cziraky, Mark J AU - Cziraky MJ AD - Carelon Research, Wilmington, Delaware, USA. FAU - Willey, Vincent J AU - Willey VJ AD - Carelon Research, Wilmington, Delaware, USA. FAU - Skibsted, Simon AU - Skibsted S AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT03596450 PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Pragmatic Clinical Trial PT - Randomized Controlled Trial DEP - 20251015 PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - United States/epidemiology MH - Blood Glucose/analysis MH - Aged MH - Adult MH - Drug Administration Schedule MH - Follow-Up Studies MH - Treatment Outcome MH - *Biomarkers/analysis MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12530410 OTO - NOTNLM OT - Diabetes Mellitus, Type 2 OT - Glucagon-Like Peptide 1 COIS- Competing interests: JBB reports research support from Corcept, Dexcom, and Novo Nordisk; consulting fees from Altimmune, Antag, Amgen, ApStem, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Corcept Therapeutics, Dexcom, Eli Lilly, Embecta, GentiBio, Glyscend, Insulet, Medtronic MiniMed, Mellitus Health, Metsera, Novo Nordisk, Pendulum Therapeutics, Praetego, Stability Health, Tandem, Terns, Vertex, and Zealand Pharma; and stock options from Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. HNC received support for the present manuscript from Novo Nordisk as an employee and holds stock or stock options for Novo Nordisk A/S. BJH received support for the present manuscript from Novo Nordisk as sponsor of the SEPRA trial; and contracted with his employer, Carelon Research, to serve as the data coordinating center for the trial, performing all data collection and analysis and supporting manuscript writing activities. MJC received support for the present manuscript from his employer, Carelon Research, which received funding from Novo Nordisk to perform the study services. He also holds stock or stock options for Elevance Health as a stockholder in ELV, which is the parent company of Carelon Research. VJW received support for the present manuscript from his employer, Carelon Research, which received funding from Novo Nordisk to perform the study services. He also holds stock or stock options for Elevance Health as a stockholder in ELV, which is the parent company of Carelon Research. SS received support for the present manuscript from Novo Nordisk as a full-time employee and holds stock or stock options for Novo Nordisk. EDAT- 2025/10/16 05:32 MHDA- 2025/10/16 05:33 PMCR- 2025/10/15 CRDT- 2025/10/15 21:22 PHST- 2025/04/09 00:00 [received] PHST- 2025/09/06 00:00 [accepted] PHST- 2025/10/16 05:33 [medline] PHST- 2025/10/16 05:32 [pubmed] PHST- 2025/10/15 21:22 [entrez] PHST- 2025/10/15 00:00 [pmc-release] AID - 13/5/e005161 [pii] AID - bmjdrc-2025-005161 [pii] AID - 10.1136/bmjdrc-2025-005161 [doi] PST - epublish SO - BMJ Open Diabetes Res Care. 2025 Oct 15;13(5):e005161. doi: 10.1136/bmjdrc-2025-005161. PMID- 41090945 OWN - NLM STAT- MEDLINE DCOM- 20251028 LR - 20260127 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 28 IP - 1 DP - 2025 Dec TI - The cost-effectiveness of subcutaneous semaglutide 2.4 mg in the management of people living with obesity and prediabetes in England. PG - 1887-1898 LID - 10.1080/13696998.2025.2575692 [doi] AB - BACKGROUND: Prediabetes and type 2 diabetes (T2D) are more prevalent amongst people living with obesity (PwO). T2D and obesity increase the risk of cardiovascular disease. In the STEP clinical development program, once-weekly subcutaneous semaglutide (2.4 mg) reduced body weight by 10-15% and reversed prediabetes in about 80% of patients. The aim of this study was to assess the cost-effectiveness of semaglutide plus diet and exercise (D&E) compared with D&E alone in PwO and prediabetes in England based on the STEP-10 trial. METHODS: The published Core Obesity Model was populated with baseline characteristics and treatment efficacy from STEP-10. This study assessed the reversal of prediabetes at 52 weeks. Baseline age and body mass index (BMI) were 53 (SD = 11) years and 40.1 (6.9) kg/m(2). At 52 weeks, semaglutide plus D&E and D&E alone reversed prediabetes in 80% and 12% of patients, and decreased BMI by 13.9% and 2.7%, respectively. The perspective of the NHS was considered using annual discounting rates of 3.5% on costs and outcomes. Several subgroups were assessed: Different baseline BMI, number of comorbidities, proportions of prediabetes and different treatment durations. Individuals losing >/= 5% of body weight after 20 weeks (responders) were analysed separately. RESULTS: The treatment duration in the base case analysis was 20 years. The use of semaglutide resulted in 1.105 QALY gained at an additional cost of 19,391 GBP. The resulting ICER was 17,547 GBP/QALY gained. Treatment with semaglutide extended life expectancy by 1.68 years. Ranging treatment duration between 1 year as per STEP 10 trial and lifelong resulted in an ICER of 7,152 to 17,695 GBP/QALY. Results did not differ significantly by subgroup. The probabilistic sensitivity analysis indicated a 90% chance of semaglutide being cost-effective at a willingness-to-pay threshold of 20,000 GBP/QALY. CONCLUSION: Semaglutide is a cost-effective treatment option for PwO and prediabetes in England based on the results of the STEP-10 trial. FAU - Ramos, Mafalda AU - Ramos M AUID- ORCID: 0000-0002-8472-3841 AD - Th(is)2Modeling bv, Asse, Belgium. FAU - Larsen, Sara AU - Larsen S AUID- ORCID: 0000-0002-3887-4948 AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Fusco, Francesco AU - Fusco F AUID- ORCID: 0000-0001-5515-3977 AD - Novo Nordisk A/S, Copenhagen, Denmark. FAU - Lamotte, Mark AU - Lamotte M AD - Th(is)2Modeling bv, Asse, Belgium. FAU - Capehorn, Matthew AU - Capehorn M AUID- ORCID: 0000-0002-8196-2505 AD - Rotherham Institute for Obesity, Rotherham, UK. LA - eng PT - Journal Article DEP - 20251028 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Cost-Benefit Analysis MH - *Glucagon-Like Peptides/economics/administration & dosage/therapeutic use MH - *Prediabetic State/drug therapy/therapy/complications MH - Female MH - Middle Aged MH - England MH - *Obesity/drug therapy/complications/therapy MH - Male MH - Body Mass Index MH - Diabetes Mellitus, Type 2/drug therapy MH - Quality-Adjusted Life Years MH - Adult MH - *Hypoglycemic Agents/economics/therapeutic use/administration & dosage MH - Injections, Subcutaneous MH - Exercise Therapy/economics MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - B41 OT - Core Obesity Model OT - Cost-effectiveness OT - I10 OT - I15 OT - Markov model OT - cardiovascular disease OT - obesity OT - prediabetes OT - semaglutide EDAT- 2025/10/15 12:31 MHDA- 2025/10/28 18:27 CRDT- 2025/10/15 09:04 PHST- 2025/10/28 18:27 [medline] PHST- 2025/10/15 12:31 [pubmed] PHST- 2025/10/15 09:04 [entrez] AID - 10.1080/13696998.2025.2575692 [doi] PST - ppublish SO - J Med Econ. 2025 Dec;28(1):1887-1898. doi: 10.1080/13696998.2025.2575692. Epub 2025 Oct 28. PMID- 41088952 OWN - NLM STAT- MEDLINE DCOM- 20260102 LR - 20260127 IS - 2093-5978 (Electronic) IS - 2093-596X (Print) IS - 2093-596X (Linking) VI - 40 IP - 6 DP - 2025 Dec TI - Early Dose Escalation of Tirzepatide after Switching from Semaglutide in Type 2 Diabetes Mellitus. PG - 1012-1015 LID - 10.3803/EnM.2025.2420 [doi] AB - Tirzepatide has demonstrated greater efficacy than semaglutide in improving glycemic control and reducing body weight in patients with type 2 diabetes mellitus (T2DM). However, the optimal tirzepatide dose following a switch from 1.0 mg of semaglutide remains unclear. This retrospective study included 15 T2DM patients who switched to tirzepatide due to inadequate weight loss. All patients started tirzepatide at 2.5 mg, with escalation to either 7.5 mg (n=10) or 10 mg (n=5). Changes in glycated hemoglobin (HbA1c) and body weight were assessed over a 3-month period. The 10 mg group experienced a significant reduction in HbA1c (-0.7%+/-0.3%, P<0.01) and a non-significant trend toward weight loss (-6.6+/-5.4 kg, P=0.07). In contrast, no significant changes were observed in the 7.5 mg group. There were no statistically significant differences between groups. Since 10 mg of tirzepatide significantly improved glycemic control after switching from 1.0 mg of semaglutide, early escalation to 10 mg may be beneficial for patients who respond inadequately to semaglutide. FAU - Kurinami, Noboru AU - Kurinami N AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. AD - Kurinami Clinic, Kanzaki, Kumamoto, Japan. FAU - Takada, Masafumi AU - Takada M AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Sugiyama, Seigo AU - Sugiyama S AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Division of Cardiovascular Medicine, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Yoshida, Akira AU - Yoshida A AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Hieshima, Kunio AU - Hieshima K AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Suzuki, Tomoko AU - Suzuki T AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Miyamoto, Fumio AU - Miyamoto F AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Kajiwara, Keizo AU - Kajiwara K AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Jinnouchi, Katsunori AU - Jinnouchi K AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Ashida, Kenji AU - Ashida K AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Nomura, Masatoshi AU - Nomura M AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. FAU - Jinnouchi, Hideaki AU - Jinnouchi H AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Division of Preventive Cardiology, Department of Cardiovascular Medicine, Kumamoto University Hospital, Kumamoto, Japan. LA - eng PT - Journal Article DEP - 20251015 PL - Korea (South) TA - Endocrinol Metab (Seoul) JT - Endocrinology and metabolism (Seoul, Korea) JID - 101554139 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - Aged MH - Tirzepatide MH - Blood Glucose/analysis MH - Drug Substitution MH - Dose-Response Relationship, Drug MH - Follow-Up Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12765867 OTO - NOTNLM OT - Body weight reduction OT - Diabetes mellitus, type 2 OT - Dose escalation OT - Semaglutide OT - Tirzepatide COIS- CONFLICTS OF INTEREST Hideaki Jinnouchi has received honoraria from Novo Nordisk, Sanofi, Eli Lilly, Mitsubishi Tanabe Pharma, and Otsuka Pharmaceutical. Seigo Sugiyama has received honoraria from Astra-Zeneca Pharmaceuticals and Ono Pharmaceutical. All other authors declare no conflicts of interest. EDAT- 2025/10/15 06:30 MHDA- 2026/01/02 06:28 PMCR- 2025/12/01 CRDT- 2025/10/15 03:40 PHST- 2025/04/18 00:00 [received] PHST- 2025/06/09 00:00 [accepted] PHST- 2026/01/02 06:28 [medline] PHST- 2025/10/15 06:30 [pubmed] PHST- 2025/10/15 03:40 [entrez] PHST- 2025/12/01 00:00 [pmc-release] AID - EnM.2025.2420 [pii] AID - enm-2025-2420 [pii] AID - 10.3803/EnM.2025.2420 [doi] PST - ppublish SO - Endocrinol Metab (Seoul). 2025 Dec;40(6):1012-1015. doi: 10.3803/EnM.2025.2420. Epub 2025 Oct 15. PMID- 41082229 OWN - NLM STAT- MEDLINE DCOM- 20251013 LR - 20260723 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 10 DP - 2025 Oct 1 TI - Liraglutide vs Semaglutide vs Dulaglutide in Veterans With Type 2 Diabetes. PG - e2537297 LID - 10.1001/jamanetworkopen.2025.37297 [doi] LID - e2537297 AB - IMPORTANCE: The head-to-head comparative effectiveness and safety of individual glucagon-like peptide-1 receptor agonists (GLP-1RAs) are not well understood. OBJECTIVE: To compare risks of kidney, cardiovascular, and death outcomes among patients with type 2 diabetes initiating GLP-1RAs in the Department of Veterans Affairs (VA) health system. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study used an active-comparator, new-user target trial-emulation design with national data linked among the VA, Medicare, and US Renal Data System. Participants were GLP-1RA-naive veterans with type 2 diabetes and without end-stage kidney disease treated with metformin who started liraglutide, semaglutide, or dulaglutide between January 1, 2018, and December 31, 2021. Data were analyzed from September 2024 to June 2025. EXPOSURE: Liraglutide, semaglutide, or dulaglutide. MAIN OUTCOMES AND MEASURES: Kidney failure (sustained estimated glomerular filtration rate <15 mL/min/1.73 m2 or initiation of kidney replacement therapy), composite cardiovascular and kidney metabolic (CKM) events (kidney failure or major adverse cardiovascular events [MACE]; myocardial infarction, heart failure, or stroke/transient ischemic attack), MACE, all-cause death, and adverse gastrointestinal events (gastroparesis, intestinal obstruction, gallstones, acute cholecystitis, acute pancreatitis) were evaluated separately through March 31, 2023. RESULTS: Of 21 790 included veterans (mean [SD] age, 63.5 [10.8] years, 19 823 [91.0%] male), 5425 (24.9%), 10 838 (49.7%), and 5527 (24.9%) initiated liraglutide, semaglutide, and dulaglutide, respectively. In weighted Cox regression models, compared with initiation of semaglutide, liraglutide initiation had similar hazards for kidney failure (hazard ratio [HR], 0.93; 95% CI, 0.60-1.44), the CKM composite outcome (HR, 0.96; 95% CI, 0.84-1.10), and MACE (HR, 0.95; 95% CI, 0.83-1.09). Results were similar with liraglutide vs dulaglutide and dulaglutide vs semaglutide comparisons. Liraglutide had significantly lower hazard of all-cause death compared with semaglutide under intent-to-treat analyses (HR, 0.83; 95% CI, 0.69-0.99), which lost significance in per-protocol models. Compared with dulaglutide, liraglutide was associated with a lower risk of all-cause mortality in both the intent-to-treat (HR, 0.69; 95% CI, 0.58-0.83) and per-protocol (HR, 0.50; 95% CI, 0.31-0.82) analyses, but compared with semaglutide, dulaglutide had higher hazard of mortality only in the per-protocol model (HR, 1.72; 95% CI, 1.20-2.47). The only observed difference for the gastrointestinal adverse events was a decreased risk for gallstones and acute cholecystitis with dulaglutide vs semaglutide (gallstones: HR, 0.72; 95% CI, 0.54-0.95; acute cholecystitis: HR, 0.62; 95% CI, 0.39-0.99). CONCLUSIONS AND RELEVANCE: In this comparative effectiveness study in veterans with diabetes, liraglutide, semaglutide, and dulaglutide initiators had similar risks for kidney and cardiovascular outcomes. Head-to-head randomized trials are needed to confirm these findings. FAU - Derington, Catherine G AU - Derington CG AD - Department of Medicine, Division of Cardiology, University of Colorado School of Medicine, Aurora. AD - Adult & Child Center for Outcomes Research & Delivery Science, University of Colorado Anschutz Medical Campus, Aurora. FAU - Sarwal, Amara AU - Sarwal A AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Wei, Guo AU - Wei G AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Hartsell, Sydney E AU - Hartsell SE AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. AD - Nora Eccles Harrison Cardiovascular Research & Training Institute, University of Utah, Salt Lake City. FAU - Throolin, Michael AU - Throolin M AD - Division of Biostatistics, Departments of Population Health Sciences, University of Utah School of Medicine, Salt Lake City. FAU - Singh, Ravinder AU - Singh R AD - Division of Biostatistics, Departments of Population Health Sciences, University of Utah School of Medicine, Salt Lake City. FAU - Nevers, McKenna R AU - Nevers MR AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Informatics, Decision-Enhancement, and Analytic Sciences Center of Innovation, Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. FAU - Zhang, Chong AU - Zhang C AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Katkam, Niharika AU - Katkam N AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Takyi, Augustine AU - Takyi A AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Chakravartula, Akhil R AU - Chakravartula AR AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Babu, Poorvika AU - Babu P AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Deshmukh, Vikrant G AU - Deshmukh VG AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. FAU - Boucher, Robert E AU - Boucher RE AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. FAU - Drakos, Stavros G AU - Drakos SG AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. AD - Nora Eccles Harrison Cardiovascular Research & Training Institute, University of Utah, Salt Lake City. AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Greene, Tom AU - Greene T AD - Division of Biostatistics, Departments of Population Health Sciences, University of Utah School of Medicine, Salt Lake City. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Shen, Jincheng AU - Shen J AD - Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. AD - Division of Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Beddhu, Srinivasan AU - Beddhu S AD - Division of Nephrology and Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. AD - Cardiovascular, Renal and Metabolism Center, University of Utah School of Medicine, Salt Lake City. AD - Veterans Affairs Salt Lake City Health Care System, Salt Lake City, Utah. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20251001 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM CIN - doi: 10.1001/jamanetworkopen.2025.37304 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - Male MH - Female MH - *Recombinant Fusion Proteins/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Liraglutide/therapeutic use/adverse effects MH - Aged MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Veterans/statistics & numerical data MH - Middle Aged MH - United States MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Comparative Effectiveness Research MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12519307 COIS- Conflict of Interest Disclosures: Dr Hartsell reported receiving grants from National Kidney Foundation, Bayer, and Women in Nephrology outside the submitted work. Dr Drakos reported receiving personal fees from Abbott and Novartis outside the submitted work. Dr Greene reported receiving research funding from National Kidney Foundation, The Collaborative Study Group, National Institutes of Health (NIH), and Patient-Centered Outcomes Research Institute outside the submitted work. No other disclosures were reported. EDAT- 2025/10/13 12:30 MHDA- 2025/10/13 18:29 PMCR- 2025/10/13 CRDT- 2025/10/13 11:33 PHST- 2025/10/13 18:29 [medline] PHST- 2025/10/13 12:30 [pubmed] PHST- 2025/10/13 11:33 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - 2840010 [pii] AID - zoi251028 [pii] AID - 10.1001/jamanetworkopen.2025.37297 [doi] PST - epublish SO - JAMA Netw Open. 2025 Oct 1;8(10):e2537297. doi: 10.1001/jamanetworkopen.2025.37297. PMID- 41079186 OWN - NLM STAT- MEDLINE DCOM- 20251013 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Predictive factors of body weight loss in patients with type 2 diabetes treated with GLP-1 receptor agonists: a 52-week prospective real-life study. PG - 1674308 LID - 10.3389/fendo.2025.1674308 [doi] LID - 1674308 AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely prescribed for their efficacy in glycemic control and weight reduction, but patient response is heterogeneous and predictors of weight loss remain insufficiently defined. This 52-week prospective, observational study aimed to identify predictors of weight reduction (>/=5% from baseline) in patients with type 2 diabetes mellitus (T2D) undergoing GLP-1RA therapy (semaglutide or dulaglutide, including oral formulations). METHODS: A total of 194 adults with T2D initiating GLP-1RA therapy were evaluated at baseline, and after 6, and 12 months of therapy. To identify predictors of weight loss, variables differing between Responders (weight loss >/=5% than baseline) and Non-Responders were evaluated by ROC analysis and tested in univariate and multivariate logistic regression models adjusted for age, gender, GLP-1RA type and dosage. RESULTS: At 6 and 12 months, 58% and 49% of patients, respectively, achieved the primary outcome. Responders at 12 months exhibited elevated BMI, waist circumference, hepatic steatosis indices, fat mass, and insulin levels at baseline, along with reduced muscle-to-fat and muscle-to-visceral adipose tissue ratios. Moreover, female gender, younger age, shorter disease duration, and non-use of metformin prior to enrollment were significantly associated with response. Notably, early response at 6 months strongly predicted 12-month success. CONCLUSIONS: Our results highlight a valuable interplay between body composition, liver involvement, and the incretin response, also suggesting a maximal synergistic effect between metformin and GLP-1RAs when treatments are initiated concurrently rather than sequentially. These data provide valuable insights for the development of individualized treatment strategies. CI - Copyright (c) 2025 Vozza, Triggiani, Fanelli, Lisco, Coletto, Custodero, Volpe, Racaniello, Colaianni, Lavarra, Maggipinto, Portacci, Tortorella, Moschetta and Piazzolla. FAU - Vozza, Alfredo AU - Vozza A AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Triggiani, Domenico AU - Triggiani D AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Fanelli, Margherita AU - Fanelli M AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Lisco, Giuseppe AU - Lisco G AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Coletto, Deborah AU - Coletto D AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Custodero, Carlo AU - Custodero C AD - Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", Bari, Italy. FAU - Volpe, Sara AU - Volpe S AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Racaniello, Davide AU - Racaniello D AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Colaianni, Valentina AU - Colaianni V AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Lavarra, Valentina AU - Lavarra V AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Maggipinto, Rosselia AU - Maggipinto R AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Portacci, Andrea AU - Portacci A AD - Department of Translational Biomedicine and Neuroscience, University of Bari "Aldo Moro", Bari, Italy. FAU - Tortorella, Cosimo AU - Tortorella C AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Moschetta, Antonio AU - Moschetta A AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Piazzolla, Giuseppina AU - Piazzolla G AD - Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy. LA - eng PT - Journal Article PT - Observational Study DEP - 20250925 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Prospective Studies MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Immunoglobulin Fc Fragments/therapeutic use MH - *Recombinant Fusion Proteins/therapeutic use MH - Prognosis MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12507565 OTO - NOTNLM OT - GLP-1 receptor agonists OT - body weight loss OT - fat mass OT - hepatic steatosis OT - metformin OT - predictive factors OT - skeletal muscle mass OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2025/10/13 12:31 MHDA- 2025/10/13 12:32 PMCR- 2025/09/25 CRDT- 2025/10/13 07:23 PHST- 2025/07/27 00:00 [received] PHST- 2025/09/08 00:00 [accepted] PHST- 2025/10/13 12:32 [medline] PHST- 2025/10/13 12:31 [pubmed] PHST- 2025/10/13 07:23 [entrez] PHST- 2025/09/25 00:00 [pmc-release] AID - 10.3389/fendo.2025.1674308 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Sep 25;16:1674308. doi: 10.3389/fendo.2025.1674308. eCollection 2025. PMID- 41076575 OWN - NLM STAT- MEDLINE DCOM- 20251031 LR - 20260127 IS - 1752-2978 (Electronic) IS - 1752-296X (Linking) VI - 32 IP - 6 DP - 2025 Dec 1 TI - Effect of GLP-1 receptor agonists on body composition. PG - 279-285 LID - 10.1097/MED.0000000000000934 [doi] AB - PURPOSE OF REVIEW: Obesity is present in up to 85% of individuals with type 2 diabetes mellitus (T2DM) and poses a major therapeutic challenge. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for T2DM, are now widely used for obesity management and increasingly recognized for their impact on body composition beyond weight reduction. This review summarizes evidence on the effects of GLP-1RAs, particularly semaglutide and liraglutide, on fat mass, lean body mass (LBM), visceral adipose tissue (VAT), and resting energy expenditure (REE). RECENT FINDINGS: Clinical trials and meta-analyses show GLP-1RAs achieve marked fat mass loss, preferentially reducing VAT, with modest proportional declines in LBM. Despite reductions in absolute LBM, relative preservation or improvement is observed, and REE is largely maintained, with some reports of increases during prolonged therapy. In both diabetic and nondiabetic populations, GLP-1RAs improve metabolic health without accelerating sarcopenia. Rodent data support protective muscle effects through anti-inflammatory and myogenic mechanisms. Withdrawal, however, predictably results in weight regain, primarily as fat mass, highlighting the importance of continued therapy or supportive lifestyle strategies. SUMMARY: GLP-1RAs confer favourable body composition outcomes, with clinical implications for obesity, sarcopenic obesity, and broader metabolic disease management. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Bhandarkar, Akhila AU - Bhandarkar A AD - Nitte (deemed to be University) KS Hegde Medical Academy (KSHEMA), Mangalore Department of Endocrinology and Metabolism. FAU - Bhat, Sowrabha AU - Bhat S AD - Department of Endocrinology and Metabolism, Yenepoya Medical College, Faculty of Center for Nutrition Studies, Yenepoya University, Mangalore, Karnataka, India. FAU - Kapoor, Nitin AU - Kapoor N AD - Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore, India; Noncommunicable Disease Unit, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PT - Review DEP - 20251010 PL - England TA - Curr Opin Endocrinol Diabetes Obes JT - Current opinion in endocrinology, diabetes, and obesity JID - 101308636 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Body Composition/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/metabolism MH - *Obesity/drug therapy/metabolism/complications MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Liraglutide/therapeutic use/pharmacology MH - Animals MH - Energy Metabolism/drug effects MH - Glucagon-Like Peptides/therapeutic use/pharmacology MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1RA OT - body composition OT - fat mass OT - lean body mass OT - visceral adipose tissue EDAT- 2025/10/12 12:31 MHDA- 2025/10/31 17:30 CRDT- 2025/10/12 07:43 PHST- 2025/10/31 17:30 [medline] PHST- 2025/10/12 12:31 [pubmed] PHST- 2025/10/12 07:43 [entrez] AID - 01266029-990000000-00143 [pii] AID - 10.1097/MED.0000000000000934 [doi] PST - ppublish SO - Curr Opin Endocrinol Diabetes Obes. 2025 Dec 1;32(6):279-285. doi: 10.1097/MED.0000000000000934. Epub 2025 Oct 10. PMID- 41075262 OWN - NLM STAT- MEDLINE DCOM- 20251011 LR - 20260127 IS - 1399-0012 (Electronic) IS - 0902-0063 (Linking) VI - 39 IP - 10 DP - 2025 Oct TI - Bridging the Gap to Waitlist Activation: Semaglutide's Weight Loss Efficacy and Safety in Patients With Obesity on Dialysis Seeking Kidney Transplantation. PG - e70344 LID - 10.1111/ctr.70344 [doi] AB - Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated efficacy for weight loss and glycemic control in patients with obesity and type 2 diabetes mellitus, but data are limited for patients with end-stage kidney disease on dialysis. We examined the weight loss efficacy and safety of semaglutide when prescribed to patients on dialysis to improve transplant candidacy and activation status. We conducted a retrospective chart review of 36 patients on dialysis who were prescribed semaglutide through a metabolic clinic between September 2021 and December 2023. Outcomes included weight loss efficacy, safety, and change in waitlist status at 1 year. Patients achieved a mean total body weight loss of 7.8% (SD 6.1). Of patients who were ineligible for transplant due to elevated body mass index, 48.2% achieved waitlist activation after successful weight loss. Treatment-limiting gastrointestinal side effects occurred in 16.7% of patients. Patients on peritoneal dialysis (PD, 30.8%) versus hemodialysis (8.7%) discontinued therapy more frequently. In a single-center cohort, patients who received semaglutide experienced significantly greater weight loss and increased rates of waitlist activation compared with a lifestyle-only intervention. Semaglutide was generally well-tolerated. Prospective studies should examine whether patients on PD experience severe GI side effects more frequently on semaglutide. CI - (c) 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Wade, Francis G AU - Wade FG AUID- ORCID: 0009-0002-1313-8335 AD - Division of General Internal Medicine, Department of Internal Medicine, SSM Health/Saint Louis University, St. Louis, Missouri, USA. FAU - Lentine, Krista L AU - Lentine KL AUID- ORCID: 0000-0002-9423-4849 AD - SSM Health Saint Louis University Hospital Transplant Center, Saint Louis University, St. Louis, Missouri, USA. FAU - Turk, David AU - Turk D AUID- ORCID: 0009-0009-3534-6283 AD - School of Medicine, Saint Louis University, St. Louis, Missouri, USA. FAU - Kirbach, Kyleigh AU - Kirbach K AUID- ORCID: 0000-0002-4513-3662 AD - Division of General Internal Medicine, Department of Internal Medicine, SSM Health/Saint Louis University, St. Louis, Missouri, USA. FAU - Knobloch, Taylor AU - Knobloch T AUID- ORCID: 0009-0005-6778-4633 AD - Department of Nutrition & Dietetics, SSM Health Saint Louis University Hospital, St. Louis, Missouri, USA. FAU - Schnitzler, Mark AU - Schnitzler M AUID- ORCID: 0000-0001-8547-5643 AD - SSM Health Saint Louis University Hospital Transplant Center, Saint Louis University, St. Louis, Missouri, USA. FAU - Qureshi, Kamran AU - Qureshi K AUID- ORCID: 0000-0002-0389-7269 AD - Division of Gastroenterology & Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA. FAU - Syn, Wing-Kin AU - Syn WK AUID- ORCID: 0000-0001-7966-0500 AD - Division of Gastroenterology & Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA. AD - Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country, UPV/EHU, Vizcaya, Spain. FAU - Fleetwood, Vidya A AU - Fleetwood VA AUID- ORCID: 0000-0002-7655-9375 AD - Division of Transplantation, Michael E. DeBakey Department of Surgery, Baylor Medical College, Houston, Texas, USA. LA - eng GR - R01DK102981/Mid-America Transplant/Jane A. Beckman Endowed Chair in Transplantation and National Institute of Diabetes and Digestive and Kidney Diseases/ PT - Journal Article PL - Denmark TA - Clin Transplant JT - Clinical transplantation JID - 8710240 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - *Waiting Lists/mortality MH - Male MH - *Kidney Transplantation MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use MH - *Weight Loss/drug effects MH - *Renal Dialysis MH - *Kidney Failure, Chronic/therapy/complications MH - *Obesity/drug therapy/complications MH - Follow-Up Studies MH - Prognosis MH - Risk Factors MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - diabetes mellitus OT - glucagon-like peptide 1 receptor agonist OT - kidney transplantation OT - obesity OT - patient selection OT - renal dialysis OT - semaglutide EDAT- 2025/10/11 22:19 MHDA- 2025/10/11 22:20 CRDT- 2025/10/11 12:52 PHST- 2025/09/04 00:00 [revised] PHST- 2025/07/03 00:00 [received] PHST- 2025/09/26 00:00 [accepted] PHST- 2025/10/11 22:20 [medline] PHST- 2025/10/11 22:19 [pubmed] PHST- 2025/10/11 12:52 [entrez] AID - 10.1111/ctr.70344 [doi] PST - ppublish SO - Clin Transplant. 2025 Oct;39(10):e70344. doi: 10.1111/ctr.70344. PMID- 41070406 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 18 IP - 10 DP - 2025 Oct TI - Semaglutide for the treatment of MASH: reaching into the ESSENCE of cardio-metabolic health? PG - 1-5 LID - 10.1080/17512433.2025.2573785 [doi] AB - Metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis poses a significant clinical challenge, especially given its strong association with obesity and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated impressive results in managing obesity and T2DM, prompting interest in their potential therapeutic role for MASH with fibrosis. The ESSENCE trial recently investigated the effectiveness of once-weekly semaglutide in patients with biopsy-proven MASH and moderate-to-advanced fibrosis. Interim analysis at 72 weeks demonstrated that semaglutide substantially improved liver histology, effectively resolving steatohepatitis and showing improvement in liver fibrosis, compared to placebo. Consistent with these findings, the U.S. Food and Drug Administration has granted accelerated approval to semaglutide (Wegovy) for adults with noncirrhotic MASH and stage 2 or 3 fibrosis. Those hepatic benefits were accompanied with notable improvements in body weight, insulin sensitivity and inflammatory markers. While these preliminary results are encouraging, their clinical relevance will depend on whether they translate into reduced long-term liver complications and amelioration of overall cardio-renal risk. Thus, semaglutide represents a highly promising therapeutic strategy for patients with MASH and fibrosis, addressing critical unmet needs by simultaneously targeting liver pathology and cardiometabolic health. FAU - Mademlis, Christos AU - Mademlis C AD - Second Propedeutic Department of Internal Medicine, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Patoulias, Dimitrios AU - Patoulias D AD - Second Propedeutic Department of Internal Medicine, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AUID- ORCID: 0000-0002-5853-1352 AD - Second Propedeutic Department of Internal Medicine, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Teperikidis, Eleftherios AU - Teperikidis E AD - Clinical Research Unit, Special Unit for Biomedical Research and Education (SUBRE), School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Giouleme, Olga AU - Giouleme O AD - Second Propedeutic Department of Internal Medicine, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. FAU - Doumas, Michael AU - Doumas M AD - Second Propedeutic Department of Internal Medicine, Faculty of Health Sciences, School of Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20251013 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/pharmacology/therapeutic use/administration & dosage MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Liver Cirrhosis/drug therapy/etiology/pathology/physiopathology MH - Obesity/drug therapy/complications MH - Hypoglycemic Agents/pharmacology/administration & dosage MH - *Fatty Liver/drug therapy/physiopathology/pathology/etiology MH - Animals MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Fibrosis OT - glucagon-like peptide-1 receptor agonist OT - metabolic dysfunction-associated Steatohepatitis OT - semaglutide OT - steatohepatitis resolution EDAT- 2025/10/10 06:28 MHDA- 2025/11/13 12:32 CRDT- 2025/10/10 05:00 PHST- 2025/11/13 12:32 [medline] PHST- 2025/10/10 06:28 [pubmed] PHST- 2025/10/10 05:00 [entrez] AID - 10.1080/17512433.2025.2573785 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2025 Oct;18(10):1-5. doi: 10.1080/17512433.2025.2573785. Epub 2025 Oct 13. PMID- 41068996 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260526 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study. PG - 112-121 LID - 10.1111/dom.70141 [doi] AB - AIMS: Semaglutide, a GLP-1 receptor agonist, has shown efficacy in promoting weight loss. However, limited data exist on its impact on lean mass, muscle function, and metabolic adaptations. The SEMALEAN study aims to evaluate these parameters in patients with obesity treated with Semaglutide (2.4 mg). MATERIALS AND METHODS: This prospective study enrolled 115 patients with obesity between February 2022 and November 2024. Body weight, body composition (measured by DXA), muscle function (handgrip strength), and resting energy expenditure (REE) were assessed at baseline (M0), 7 months (M7), and 12 months (M12). Subgroup analyses examined the impact of sex, type 2 diabetes, previous GLP-1 use, and history of bariatric surgery. RESULTS: A total of 106 patients (68.9% female; mean BMI 46.3 kg/m(2)) completed the study. Weight loss was significant, with mean reductions of 10% at M7 and 13% at M12; 59% of patients achieved >/=10% weight loss. Total fat mass decreased by 14% at M7 and 18% at M12, while lean mass initially declined (-3 kg at M7) but stabilised thereafter. Handgrip strength improved significantly (+4.5 kg at M12), and the prevalence of sarcopenic obesity decreased from 49% at baseline to 33% at M12. REE normalised to lean mass increased significantly from M7 to M12. Subgroup analyses revealed greater weight and fat mass loss in women, while patients with type 2 diabetes or prior GLP-1 analogue use showed attenuated responses. Patients with a history of bariatric surgery exhibited the most pronounced reductions in body composition parameters. CONCLUSIONS: The SEMALEAN study highlights the significant impact of Semaglutide 2.4 mg on weight loss, fat mass reduction, and muscle function improvement, with preserved lean mass and metabolic efficiency. These findings underscore the importance of a comprehensive approach to obesity management, addressing not only weight loss but also functional and metabolic adaptation. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Alissou, Mathieu AU - Alissou M AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Demangeat, Thomas AU - Demangeat T AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Folope, Vanessa AU - Folope V AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Van Elslande, Helene AU - Van Elslande H AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Lelandais, Helene AU - Lelandais H AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Blanchemaison, Julia AU - Blanchemaison J AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Cailleaux, Pierre-Emmanuel AU - Cailleaux PE AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Guney, Suzan AU - Guney S AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Aupetit, Alexandra AU - Aupetit A AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Aubourg, Agnes AU - Aubourg A AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Rapp, Clement AU - Rapp C AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Petit, Andre AU - Petit A AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Godin, Morgane AU - Godin M AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Vignal, Luc AU - Vignal L AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Grigioni, Sebastien AU - Grigioni S AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Dechelotte, Pierre AU - Dechelotte P AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Colange, Guillaume AU - Colange G AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. FAU - Coeffier, Moise AU - Coeffier M AUID- ORCID: 0000-0002-7469-2682 AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. FAU - Achamrah, Najate AU - Achamrah N AD - Department of Nutrition and CIC-CRB 1404, CSO Rouen Normandie, CHU Rouen, Rouen, France. AD - Univ Rouen Normandie, INSERM, Normandie Univ, ADEN UMR 1073 "Nutrition, Inflammation and Microbiota-Gut-Brain Axis", Rouen, France. LA - eng PT - Journal Article DEP - 20251009 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Obesity/drug therapy/physiopathology/metabolism MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Prospective Studies MH - *Body Composition/drug effects MH - Weight Loss/drug effects MH - Adult MH - Hand Strength MH - *Muscle, Skeletal/drug effects/physiopathology MH - *Adipose Tissue/drug effects MH - Diabetes Mellitus, Type 2 MH - Energy Metabolism/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12673431 OTO - NOTNLM OT - Semaglutide OT - antiobesity drug OT - body composition OT - obesity care COIS- Vanessa Folope is currently employed by Novo Nordisk. However, her involvement in the study design occurred before joining the company. The other authors declare no conflicts of interest related to this publication. EDAT- 2025/10/10 06:29 MHDA- 2025/12/03 14:12 PMCR- 2025/12/03 CRDT- 2025/10/10 00:19 PHST- 2025/09/09 00:00 [revised] PHST- 2025/06/25 00:00 [received] PHST- 2025/09/10 00:00 [accepted] PHST- 2025/12/03 14:12 [medline] PHST- 2025/10/10 06:29 [pubmed] PHST- 2025/10/10 00:19 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70141 [pii] AID - 10.1111/dom.70141 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):112-121. doi: 10.1111/dom.70141. Epub 2025 Oct 9. PMID- 41064855 OWN - NLM STAT- MEDLINE DCOM- 20251118 LR - 20260127 IS - 1941-3084 (Electronic) IS - 1941-3084 (Linking) VI - 18 IP - 11 DP - 2025 Nov TI - Effect of Semaglutide on Atrial Arrhythmias Recurrence Following Ablation for Atrial Fibrillation: A Prospective Study. PG - e014069 LID - 10.1161/CIRCEP.125.014069 [doi] AB - BACKGROUND: Recurrence of atrial arrhythmias remains a significant challenge following catheter ablation for atrial fibrillation. The potential role of semaglutide in reducing atrial arrhythmia recurrence postablation is unclear. METHODS: A consecutive sample of 437 patients with a body mass index >/=24 kg/m(2) and type 2 diabetes who underwent their first atrial fibrillation ablation procedure between January 2022 and March 2024 were enrolled. Participants were divided into a semaglutide group and a control group based on patient preference. The primary outcome was the freedom from atrial arrhythmia recurrence during the 12-month follow-up period after the 3-month blanking period postablation. RESULTS: Of the 437 enrolled patients, 158 opted for semaglutide therapy and 279 declined. At baseline, the semaglutide group had higher body mass index (27.5 [2.2] versus 27.0 [2.4]; P=0.038) and glycated hemoglobin levels (8.0 [1.0] versus 7.6 [1.1]; P<0.001) compared with controls. During the 12-month follow-up, the semaglutide group showed a higher event-free rate for recurrent atrial arrhythmias (hazard ratio, 0.68 [95% CI, 0.49-0.95]; P=0.030), greater weight loss (-8.2% [3.2] versus -4.6% [2.9]; P<0.001), and larger reductions in glycated hemoglobin (-1.3% [0.8] versus -0.6% [0.8]; P<0.001). CONCLUSIONS: Semaglutide treatment following catheter ablation for atrial fibrillation is associated with a lower rate of atrial arrhythmia recurrence over 12 months and may lead to improvements in weight and glycated hemoglobin levels. FAU - Guo, Jiongchao AU - Guo J AUID- ORCID: 0009-0002-7957-878X AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Song, Ziliang AU - Song Z AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Wang, Shiyi AU - Wang S AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Yao, Die AU - Yao D AUID- ORCID: 0009-0003-8021-7479 AD - Department of Nutrition, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (D.Y.). FAU - Hong, Yu AU - Hong Y AD - Department of Cardiology, Anhui Second Provincial People's Hospital, Hefei, China (Y.H.). FAU - Fu, Minmin AU - Fu M AD - Department of Cardiology, The Third Affiliated Hospital of Anhui Medical University (Hefei First People's Hospital) (M.F.). FAU - Chen, Min AU - Chen M AD - Department of Cardiology, Hefei Second People's Hospital, China (M.C.). FAU - Jiang, Weifeng AU - Jiang W AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Zhang, Yu AU - Zhang Y AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Wu, Shaohui AU - Wu S AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Liu, Xu AU - Liu X AUID- ORCID: 0009-0001-4219-5606 AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Hou, Xumin AU - Hou X AUID- ORCID: 0009-0005-6506-7083 AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). FAU - Qin, Mu AU - Qin M AUID- ORCID: 0000-0002-1645-4758 AD - Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine (J.G., Z.S., S. Wang, W.J., Y.Z., S. Wu, X.L., X.H., M.Q.). LA - eng PT - Journal Article DEP - 20251009 PL - United States TA - Circ Arrhythm Electrophysiol JT - Circulation. Arrhythmia and electrophysiology JID - 101474365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Circ Arrhythm Electrophysiol. 2025 Nov;18(11):e014508. doi: 10.1161/CIRCEP.125.014508. PMID: 41159264 MH - Humans MH - *Atrial Fibrillation/surgery/physiopathology/diagnosis MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Middle Aged MH - Prospective Studies MH - *Catheter Ablation/adverse effects MH - Recurrence MH - Treatment Outcome MH - Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Time Factors MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - atrial fibrillation OT - body mass index OT - catheter ablation OT - glycated hemoglobin OT - semaglutide COIS- None. EDAT- 2025/10/09 06:28 MHDA- 2025/11/18 18:30 CRDT- 2025/10/09 05:09 PHST- 2025/11/18 18:30 [medline] PHST- 2025/10/09 06:28 [pubmed] PHST- 2025/10/09 05:09 [entrez] AID - 10.1161/CIRCEP.125.014069 [doi] PST - ppublish SO - Circ Arrhythm Electrophysiol. 2025 Nov;18(11):e014069. doi: 10.1161/CIRCEP.125.014069. Epub 2025 Oct 9. PMID- 41063381 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260623 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Histological efficacy of anti-diabetic agents in MASH and the mediating role of weight loss: A network meta-analysis. PG - 287-295 LID - 10.1111/dom.70187 [doi] AB - BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease with rising global prevalence, closely linked to type 2 diabetes. While several anti-diabetic agents show promise, a comprehensive analysis comparing their efficacy on biopsy-confirmed histological outcomes, including dose-dependent effects and the mediating role of weight loss, remains unexplored. METHODS: A frequentist random-effects network meta-analysis (NMA) was conducted to explore histological efficacy of anti-diabetic agents in biopsy-confirmed MASH without cirrhosis. The primary outcome was fibrosis improvement (>/=1 stage) without worsening steatohepatitis; the secondary outcome was MASH resolution without fibrosis worsening. Incretin-based agents were dose-stratified. Treatment ranking used surface-under the cumulative-ranking curve (SUCRA). Meta-regression investigated the impact of percentage weight loss and baseline covariates on the proportion of individuals achieving histological end-points. RESULTS: Data from five RCTs (N = 1667) were included. All active treatments, including Dapagliflozin 10 mg, Survodutide (2.4 mg/wk, 4.8-6 mg/wk), Tirzepatide (5 mg/wk, 10-15 mg/wk), and Semaglutide (0.7-1.4 mg/wk, 2.4 or 2.8 mg/wk), improved fibrosis versus placebo (I(2) = 0%). For MASH resolution, dose-dependent effects led to significant heterogeneity (I(2) = 73%), with lower-dose Semaglutide demonstrating no benefits and Dapagliflozin showing benefits in the F2-F3 subgroup only on sensitivity analysis. Survodutide exhibited the highest ranking (SUCRA = 0.822-0.849), followed by Tirzepatide (SUCRA = 0.622-0.681) and higher-dose Semaglutide (SUCRA = 0.327) for MASH resolution. Meta-regression using data from 16 interventions, including placebo arms, showed that weight loss significantly explained heterogeneity in treatment effects on fibrosis improvement (R(2) = 54.26%) and MASH resolution (R(2) = 78.16%). CONCLUSIONS: SGLT2 inhibitor and incretin-based agents improved fibrosis in MASH, with weight loss being a significant mediator. Targeting multiple incretin pathways, especially involving glucagon receptors, may offer greater MASH resolution. Dose-dependent effects were more prominent for MASH resolution than fibrosis improvement, indicating potential weight-loss-independent anti-fibrotic pathways. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Banerjee, Mainak AU - Banerjee M AUID- ORCID: 0000-0002-6656-8569 AD - Department of Endocrinology, R N Tagore Hospital, Kolkata, India. AD - Department of Endocrinology, Ramakrishna Mission Seva Pratisthan & Vivekananda Institute of Medical Sciences, Kolkata, India. FAU - Pal, Rimesh AU - Pal R AUID- ORCID: 0000-0003-4859-9393 AD - Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India. FAU - Pal, Sandip AU - Pal S AD - Department of Gastroenterology, R N Tagore Hospital, Kolkata, India. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20251008 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Incretins/therapeutic use MH - Liver/pathology/drug effects MH - *Non-alcoholic Fatty Liver Disease/drug therapy/pathology MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - *Weight Loss/drug effects OTO - NOTNLM OT - MAFLD OT - MASH OT - SGLT2 inhibitors OT - diabetes OT - fibrosis OT - incretin agents OT - weight loss EDAT- 2025/10/09 06:28 MHDA- 2025/12/03 14:11 CRDT- 2025/10/09 00:33 PHST- 2025/09/29 00:00 [revised] PHST- 2025/08/01 00:00 [received] PHST- 2025/09/29 00:00 [accepted] PHST- 2025/12/03 14:11 [medline] PHST- 2025/10/09 06:28 [pubmed] PHST- 2025/10/09 00:33 [entrez] AID - 10.1111/dom.70187 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):287-295. doi: 10.1111/dom.70187. Epub 2025 Oct 8. PMID- 41062312 OWN - NLM STAT- MEDLINE DCOM- 20260517 LR - 20260813 IS - 1349-7235 (Electronic) IS - 0918-2918 (Print) IS - 0918-2918 (Linking) VI - 65 IP - 10 DP - 2026 May 15 TI - Adding Semaglutide to SGLT2 Inhibitors Reduces Liver Enzymes in Patients with Type 2 Diabetes Complicated by Metabolic Dysfunction Associated Steatotic Liver Disease: A Retrospective Observational Study. PG - 1334-1341 LID - 10.2169/internalmedicine.6239-25 [doi] AB - Objective To investigate the additive effects of semaglutide on liver function indicators in patients with type 2 diabetes mellitus (T2DM) complicated by metabolic dysfunction-associated steatotic liver disease (MASLD), who received sodium-glucose cotransporter 2 inhibitors (SGLT2-Is). Methods Liver function indicators at baseline were compared with those 6 months after the initiation of semaglutide. Patients Forty-seven patients (mean age, 56.2+/-10.4 years; 74.5% men) with T2DM complicated by MASLD who were prescribed SGLT2-Is continuously for at least 12 months were retrospectively selected. Results Six months of semaglutide treatment significantly decreased body weight (BW; 80.9+/-16.4 kg to 77.3+/-17.0 kg, p<0.001), body mass index (BMI; 28.9+/-4.5 kg/m(2) to 27.7+/-4.6 kg/m(2), p<0.001), and the levels of glycated hemoglobin (HbA1c; 7.4+/-0.7% to 6.9+/-0.7%, p<0.001), aspartate aminotransferase (AST; 30.4+/-15.9 U/L to 26.3+/-12.5 U/L, p=0.014), alanine aminotransferase (ALT; 42.4+/-28.7 U/L to 35.7+/-22.8 U/L, p=0.022), and gamma-glutamyl transpeptidase (gamma-GTP; 46.5+/-36.8 U/L to 38.0+/-30.0 U/L, p=0.001). The fibrosis-4 index, an indicator of liver fibrosis, did not improve. Changes in ALT levels were significantly correlated with changes in metabolic parameters, including BW (p=0.004), BMI (p=0.004), HbA1c (p=0.005), and triglycerides (p=0.011). Conclusion The addition of semaglutide to SGLT2-Is reduced liver enzyme levels in patients with T2DM complicated with MASLD. Future randomized controlled trials are needed to investigate the additive effects of semaglutide on MASLD in patients with T2DM receiving SGLT2-Is. FAU - Sato, Kanako AU - Sato K AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Irie, Yoko AU - Irie Y AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Asai, Hiroaki AU - Asai H AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Yoshioka, Saori AU - Yoshioka S AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Murakawa, Keisuke AU - Murakawa K AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Sho, Hiroyuki AU - Sho H AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Inui, Ryoko AU - Inui R AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Kosugi, Motohiro AU - Kosugi M AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Hazama, Yoji AU - Hazama Y AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. FAU - Yasuda, Tetsuyuki AU - Yasuda T AD - Department of Diabetes, Endocrinology and Metabolism, Osaka International Medical & Science Center (Osaka Keisatsu Hospital), Japan. LA - eng PT - Journal Article PT - Observational Study DEP - 20251009 PL - Japan TA - Intern Med JT - Internal medicine (Tokyo, Japan) JID - 9204241 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - EC 2.6.1.1 (Aspartate Aminotransferases) RN - EC 2.6.1.2 (Alanine Transaminase) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Aged MH - *Liver/enzymology/drug effects MH - *Fatty Liver/drug therapy/complications/enzymology MH - Drug Therapy, Combination MH - Aspartate Aminotransferases/blood MH - Alanine Transaminase/blood MH - Glycated Hemoglobin/metabolism PMC - PMC13265098 OTO - NOTNLM OT - Type 2 diabetes OT - metabolic dysfunction-associated steatotic liver disease OT - semaglutide OT - sodium-glucose cotransporter 2 inhibitors COIS- Tetsuyuki Yasuda received lecture fees from Eli Lilly Japan K.K., Sumitomo Pharma, Novo Nordisk Pharma, and Mitsubishi Tanabe Pharma. The authors declare that they have no conflicts of interest. EDAT- 2025/10/09 00:30 MHDA- 2026/05/18 00:30 PMCR- 2026/05/15 CRDT- 2025/10/08 21:43 PHST- 2026/05/18 00:30 [medline] PHST- 2025/10/09 00:30 [pubmed] PHST- 2025/10/08 21:43 [entrez] PHST- 2026/05/15 00:00 [pmc-release] AID - 10.2169/internalmedicine.6239-25 [doi] PST - ppublish SO - Intern Med. 2026 May 15;65(10):1334-1341. doi: 10.2169/internalmedicine.6239-25. Epub 2025 Oct 9. PMID- 41058240 OWN - NLM STAT- MEDLINE DCOM- 20251203 LR - 20260623 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 28 IP - 1 DP - 2026 Jan TI - Relative efficacy of GLP-1 and GLP-1/GIP receptor agonists in the prevention of alcohol-use disorders using a target trial emulation approach. PG - 137-150 LID - 10.1111/dom.70169 [doi] AB - AIMS: There is growing evidence that the GLP-1 system is implicated in alcohol and other substance use disorders, and that GLP-1-based therapies may have therapeutic relevance in alcohol use disorder (AUD). We aimed to determine the impact of GLP-1 based therapies on incident AUDs in a real-world setting in patients with T2D. MATERIAL AND METHODS: We conducted emulation target trials based on a real-world network of electronic health records (EHRs) from over 120 million patients in the United States of America. Four target trials were emulated among eligible patients with type 2 diabetes (T2D) who had no prior AUD diagnosis by comparing tirzepatide, semaglutide, liraglutide, and dulaglutide with DPP4 inhibitors (DPP4i). First-ever diagnosis of AUD occurred within an 18-month follow-up period and was examined using Kaplan-Meier survival analyses. Four target trial cohorts were generated and compared with a reference arm of patients treated with DPP4i: cohort (1) treatment with tirzepatide; cohort (2) treatment with semaglutide; cohort (3) treatment with liraglutide; and cohort (4) treatment with dulaglutide. Cohorts underwent propensity score matching 1:1 for confounders. We examined rates of incident AUD (ICD-10 code F10) and performed head-to-head analyses of the incretin-based therapies. We also performed sensitivity analyses relating to whether treatment was adjunctive therapy with metformin and by treatment adherence. RESULTS: After propensity-score matching, we identified four target trials of patients treated with tirzepatide (n = 7165), semaglutide (n = 20 198), liraglutide (n = 6565), and dulaglutide (n = 19 061); 1:1 with the reference (DPP4i) patients. Tirzepatide and semaglutide (but not liraglutide or dulaglutide) were associated with significant risk reduction of incident AUD compared to DPP4i (hazard ratio 0.47 [95% confidence interval 0.29, 0.75] and 0.68 [0.52, 0.89], respectively). Head-to-head comparison revealed tirzepatide had a significant risk reduction compared to liraglutide in incident AUD (0.47 [0.24, 0.92]). CONCLUSION: In patients with T2D, tirzepatide and semaglutide treatment is associated with a lower incidence of AUD; robust randomised, controlled evidence for the use of these drugs for this novel indication is appropriate. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Henney, Alex E AU - Henney AE AUID- ORCID: 0000-0002-8066-9470 AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Heague, Megan AU - Heague M AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Roberts, Carl A AU - Roberts CA AD - Department of Psychology, Institute of Population Health, University of Liverpool, Merseyside, UK. FAU - Hydes, Theresa J AU - Hydes TJ AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Anson, Matthew AU - Anson M AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Hughes, David M AU - Hughes DM AD - Deparment of Health Data Science, Institute of Population Health, University of Liverpool, Liverpool, UK. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Merseyside, Liverpool, UK. LA - eng PT - Journal Article DEP - 20251007 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Incretins) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) SB - IM MH - Humans MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Male MH - Liraglutide/therapeutic use MH - Female MH - Middle Aged MH - *Alcoholism/prevention & control/epidemiology MH - Recombinant Fusion Proteins/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Immunoglobulin Fc Fragments/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Glucagon-Like Peptide 1/agonists/analogs & derivatives/therapeutic use MH - Tirzepatide/therapeutic use MH - Adult MH - Aged MH - Treatment Outcome MH - Drug Therapy, Combination MH - Incretins/therapeutic use MH - Receptors, Gastrointestinal Hormone MH - Semaglutide PMC - PMC12673470 OTO - NOTNLM OT - GLP-1 analogue OT - cohort study OT - real-world evidence OT - type 2 diabetes COIS- MA receives a fellowship from the Novo Nordisk UK research foundation and JDRF. CAR has acted as a consultant for Boehringer Ingelheim and has received grant funding from Unilever. DJC has received investigator-initiated grants from Astra Zeneca and Novo Nordisk, support for education from Perspectum, with any financial remuneration from pharmaceutical company consultation made to the University of Liverpool, and serves as the Topic Advisor for Type 2 Diabetes medications for The National Institute for Health and Care Excellence (NICE), UK. GHI is an employee of TriNetX LLC. UA has received honoraria from Procter & Gamble, Viatris, Grunenthal, and Sanofi for educational meetings and funding for attendance at an educational meeting from Daiichi Sankyo. UA has also received investigator-led funding from Procter & Gamble and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. All other authors declare that there are no financial relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript. EDAT- 2025/10/08 06:29 MHDA- 2025/12/03 14:11 PMCR- 2025/12/03 CRDT- 2025/10/08 03:03 PHST- 2025/09/15 00:00 [revised] PHST- 2025/04/08 00:00 [received] PHST- 2025/09/21 00:00 [accepted] PHST- 2025/12/03 14:11 [medline] PHST- 2025/10/08 06:29 [pubmed] PHST- 2025/10/08 03:03 [entrez] PHST- 2025/12/03 00:00 [pmc-release] AID - DOM70169 [pii] AID - 10.1111/dom.70169 [doi] PST - ppublish SO - Diabetes Obes Metab. 2026 Jan;28(1):137-150. doi: 10.1111/dom.70169. Epub 2025 Oct 7. PMID- 41054801 OWN - NLM STAT- MEDLINE DCOM- 20260311 LR - 20260614 IS - 1945-7189 (Electronic) IS - 0163-769X (Linking) VI - 47 IP - 2 DP - 2026 Mar 11 TI - Novel GLP-1-based Medications for Type 2 Diabetes and Obesity. PG - 159-177 LID - 10.1210/endrev/bnaf036 [doi] AB - The approvals of semaglutide and tirzepatide have set new benchmarks in the treatment of type 2 diabetes and obesity. Building on their success, novel glucagon-like peptide-1 (GLP-1)-based therapeutics are rapidly advancing. These next-generation agents engage not only GLP-1 receptors but also those for other gastro-entero-pancreatic hormones such as glucose-dependent insulinotropic polypeptide (GIP), glucagon, amylin, and peptide YY to enhance energy uptake, storage, and expenditure through synergistic mechanisms. Both GIP receptor agonism and antagonism, particularly in combination with GLP-1 receptor agonism, have shown promise. Maridebart cafraglutide, combining GLP-1 receptor agonism with GIP receptor antagonism, exemplifies this innovative approach. Glucagon coagonists like survodutide and mazdutide have demonstrated significant weight loss and improved glycemic control. Amylin-based agents, including CagriSema (cagrilintide + semaglutide) and amycretin, enhance satiety and glycemic outcomes through complementary actions. Further innovation is seen in triple agonists such as retatrutide, which targets GIP, GLP-1, and glucagon receptors to amplify metabolic effects. Meanwhile, the emergence of orally active small-molecule GLP-1 receptor agonists like danuglipron and orforglipron, which are resistant to enzymatic degradation, marks a major advance in patient-friendly drug delivery. This review explores the mechanisms, clinical development, and therapeutic potential of these novel agents, excluding already approved drugs like liraglutide, semaglutide, and tirzepatide. We highlight how multireceptor agonists and oral GLP-1-based therapies may reshape the future landscape of obesity and type 2 diabetes treatment by offering more effective and better-tolerated options. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Son, Jang Won AU - Son JW AUID- ORCID: 0000-0003-0339-0131 AD - Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - Diabetes Complications Research Centre, University College Dublin, Dublin D04 C1P1, Ireland. FAU - Bluher, Matthias AU - Bluher M AD - Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum Munchen at the University of Leipzig and University Hospital Leipzig, Leipzig 04103, Germany. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum, St. Josef Hospital (Ruhr University Bochum), Bochum 44791, Germany. FAU - Lim, Soo AU - Lim S AUID- ORCID: 0000-0002-4137-1671 AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul 03080, South Korea. LA - eng PT - Journal Article PT - Review PL - United States TA - Endocr Rev JT - Endocrine reviews JID - 8006258 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptide 1/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use MH - Animals OTO - NOTNLM OT - amylin OT - glucagon OT - glucagon-like peptide-1 OT - glucose-dependent insulinotropic polypeptide OT - obesity EDAT- 2025/10/07 06:29 MHDA- 2026/03/11 19:00 CRDT- 2025/10/07 04:32 PHST- 2025/05/10 00:00 [received] PHST- 2025/09/24 00:00 [accepted] PHST- 2026/03/11 19:00 [medline] PHST- 2025/10/07 06:29 [pubmed] PHST- 2025/10/07 04:32 [entrez] AID - 8276515 [pii] AID - 10.1210/endrev/bnaf036 [doi] PST - ppublish SO - Endocr Rev. 2026 Mar 11;47(2):159-177. doi: 10.1210/endrev/bnaf036. PMID- 41051803 OWN - NLM STAT- MEDLINE DCOM- 20251006 LR - 20260127 IS - 1997-7298 (Print) IS - 1997-7298 (Linking) VI - 125 IP - 9 DP - 2025 TI - [Effects of semaglutide on mental health]. PG - 28-36 LID - 10.17116/jnevro202512509128 [doi] AB - Semaglutide is a glucagon-like peptide-1 receptor agonist, approved and currently actively used worldwide for the treatment of type 2 diabetes mellitus and obesity. With the growing popularity of the drug, reports of both adverse and beneficial effects of the drug on mental health have become more frequent. The purpose of this study is to review the impact of semaglutide on mental health by collecting, analyzing, and synthesizing current scientific evidence. The authors conclude that currently there is no unequivocal opinion on this matter, which opens up new horizons for future research. FAU - Rozhdestvenskaya, V A AU - Rozhdestvenskaya VA AUID- ORCID: 0009-0000-8348-4706 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Yuzbashyan, P G AU - Yuzbashyan PG AUID- ORCID: 0000-0002-7441-5546 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Romanov, D V AU - Romanov DV AUID- ORCID: 0000-0002-1822-8973 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. AD - Centre for Mental Health Research, Moscow, Russia. FAU - Shchurenkov, A V AU - Shchurenkov AV AUID- ORCID: 0009-0005-7128-0171 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Kazaryan, P A AU - Kazaryan PA AUID- ORCID: 0009-0009-8501-9336 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Sheyanov, A M AU - Sheyanov AM AUID- ORCID: 0009-0009-9601-0193 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Zubacheva, E O AU - Zubacheva EO AUID- ORCID: 0009-0004-8702-3834 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. FAU - Fedyainova, I K AU - Fedyainova IK AUID- ORCID: 0009-0006-3281-6962 AD - I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia. LA - rus PT - English Abstract PT - Journal Article PT - Review TT - Vliyanie semaglutida na psikhicheskoe zdorov'e. PL - Russia (Federation) TA - Zh Nevrol Psikhiatr Im S S Korsakova JT - Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova JID - 9712194 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity/drug therapy MH - *Mental Health MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 agonists OT - addiction OT - alcohol dependence OT - anxiety OT - autoaggression OT - cognitive functions OT - depression OT - diabetes mellitus OT - obesity OT - semaglutide OT - suicidal behavior OT - weight loss EDAT- 2025/10/06 12:31 MHDA- 2025/10/06 12:32 CRDT- 2025/10/06 11:46 PHST- 2025/10/06 12:32 [medline] PHST- 2025/10/06 12:31 [pubmed] PHST- 2025/10/06 11:46 [entrez] AID - 10.17116/jnevro202512509128 [doi] PST - ppublish SO - Zh Nevrol Psikhiatr Im S S Korsakova. 2025;125(9):28-36. doi: 10.17116/jnevro202512509128. PMID- 41039650 OWN - NLM STAT- MEDLINE DCOM- 20251121 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 33 IP - 12 DP - 2025 Dec TI - Reasons for Discontinuation of Obesity Pharmacotherapy With Semaglutide or Tirzepatide in Clinical Practice. PG - 2296-2303 LID - 10.1002/oby.70058 [doi] AB - OBJECTIVE: This study aimed to characterize the reasons for treatment discontinuation with injectable semaglutide or tirzepatide for obesity in regular clinical practice. METHODS: This cross-sectional study used electronic health record data between January 2022 and December 2024 from a single integrated health system in Ohio and Florida. The primary reason for treatment discontinuation was examined in a randomly selected sample of adults with overweight or obesity and without type 2 diabetes who initiated injectable semaglutide or tirzepatide and discontinued treatment within the first year. RESULTS: We randomly selected 288 patients; 145 received semaglutide and 143 tirzepatide. Overall, 137 patients (47.6%) discontinued their medication due to cost or insurance-related issues, 42 (14.6%) due to inability to tolerate the side effects, 34 (11.8%) as they were unable to fill the medication due to shortages, 7 (2.4%) as they switched to a compounded medication, and 5 (1.7%) due to unsatisfactory weight loss; 31 (10.8%) discontinued for other reasons, and for 32 (11.1%) patients the discontinuation reason was not specified in the electronic health record. CONCLUSIONS: High cost or insurance-related issues are the most common reasons for treatment discontinuation with semaglutide or tirzepatide for obesity. Our findings highlight the need for policies to address cost and could inform discussions between healthcare providers and patients concerning cost and side effects. CI - (c) 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Gasoyan, Hamlet AU - Gasoyan H AUID- ORCID: 0000-0002-1627-9777 AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Butsch, W Scott AU - Butsch WS AUID- ORCID: 0000-0001-7137-9423 AD - Department of Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Casacchia, Nicholas J AU - Casacchia NJ AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Schulte, Rebecca AU - Schulte R AD - Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Criswell, Victoria AU - Criswell V AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Fox, Jacqueline AU - Fox J AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Renner, Holly AU - Renner H AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Le, Phuc AU - Le P AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Alpert, Jordan AU - Alpert J AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Rothberg, Michael B AU - Rothberg MB AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. LA - eng GR - RPC8755/Cleveland Clinic Research Program Committees/ PT - Journal Article DEP - 20251002 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/economics/administration & dosage/adverse effects MH - Male MH - Female MH - Middle Aged MH - Cross-Sectional Studies MH - *Obesity/drug therapy MH - Adult MH - *Tirzepatide/therapeutic use/economics/administration & dosage/adverse effects MH - *Anti-Obesity Agents/therapeutic use/economics MH - Aged MH - Diabetes Mellitus, Type 2 MH - Ohio MH - Florida MH - Electronic Health Records MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12636059 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - obesity pharmacotherapy OT - treatment discontinuation COIS- Dr. Butsch reported advisory board fees from Novo Nordisk A/S, Eli Lilly and Co., Boehringer Ingelheim, and Abbott and research funding from Eli Lilly and Co. outside the submitted work. Dr. Rothberg reported receiving consulting fees from the Blue Cross Blue Shield Association outside the submitted work. Other authors declare no conflicts of interest. EDAT- 2025/10/03 06:31 MHDA- 2025/11/21 12:50 PMCR- 2025/11/21 CRDT- 2025/10/03 00:03 PHST- 2025/08/26 00:00 [revised] PHST- 2025/06/16 00:00 [received] PHST- 2025/08/27 00:00 [accepted] PHST- 2025/11/21 12:50 [medline] PHST- 2025/10/03 06:31 [pubmed] PHST- 2025/10/03 00:03 [entrez] PHST- 2025/11/21 00:00 [pmc-release] AID - OBY70058 [pii] AID - 10.1002/oby.70058 [doi] PST - ppublish SO - Obesity (Silver Spring). 2025 Dec;33(12):2296-2303. doi: 10.1002/oby.70058. Epub 2025 Oct 2. PMID- 41036135 OWN - NLM STAT- MEDLINE DCOM- 20251002 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Predictive factors for HbA1c and weight loss associated with semaglutide treatment in type 2 diabetes mellitus: real-world clinical evidence. PG - 1621892 LID - 10.3389/fendo.2025.1621892 [doi] LID - 1621892 AB - OBJECTIVE: This study aimed to identify clinical predictors associated with reductions in HbA1c and weight among patients with type 2 diabetes mellitus (T2DM) treated with semaglutide in real-world clinical settings in Bulgaria. METHODS: A retrospective analysis was conducted on 168 T2DM patients receiving dispensary monitoring at the University Specialized Hospital for Active Treatment in Endocrinology "Acad. Ivan Penchev," Sofia. Clinical data, including comorbidities, HbA1c, weight, and BMI, were collected from medical records at baseline and after one year of treatment. Patients were administered subcutaneous semaglutide beginning at 0.25 mg weekly, titrated to 0.5 mg after four weeks, and to 1 mg thereafter, maintained over a one-year period. RESULTS: At baseline, 92.3% of patients had obesity (BMI >/=30 kg/m(2)), with 53.6% categorized as Obesity Class 1. After one year of GLP - 1RA therapy, significant improvements in metabolic parameters were observed. Median weight reduced from 100.0 kg to 91.5 kg (p<0.001), and median BMI decreased from 33.6 to 30.9 kg/m(2) (p<0.001). HbA1c levels declined from 7.80% to 6.90% (p<0.001). Transitions to lower obesity classes occurred in 81 patients, while 15 remained in Class 3 obesity. CONCLUSIONS: Semaglutide significantly improves glycemic control and promotes weight and BMI reduction in T2DM patients in routine clinical practice. These findings suggest that structured follow-up under endocrinologist supervision, as required by national protocols, may enhance therapeutic response. Further prospective studies with extended follow-up are warranted to evaluate the long-term sustainability of these effects and to identify predictors of optimal patient response. CI - Copyright (c) 2025 Milushewa, Mitreva, Chakarova, Tankova, Naseva and Petkova. FAU - Milushewa, Petya AU - Milushewa P AD - Department of Organization and Economics of Pharmacy, Medical University of Sofia, Sofia, Bulgaria. FAU - Mitreva, Yoanna AU - Mitreva Y AD - Department of Endocrinology, Medical University of Sofia, Sofia, Bulgaria. FAU - Chakarova, Nevena AU - Chakarova N AD - Department of Endocrinology, Medical University of Sofia, Sofia, Bulgaria. FAU - Tankova, Tsvetalina AU - Tankova T AD - Department of Endocrinology, Medical University of Sofia, Sofia, Bulgaria. FAU - Naseva, Emilia AU - Naseva E AD - Department of Health Management and Health Economics, Medical University of Sofia, Sofia, Bulgaria. FAU - Petkova, Valentina AU - Petkova V AD - Department of Organization and Economics of Pharmacy, Medical University of Sofia, Sofia, Bulgaria. LA - eng PT - Journal Article DEP - 20250916 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - Male MH - *Glucagon-Like Peptides/therapeutic use MH - Middle Aged MH - Retrospective Studies MH - *Glycated Hemoglobin/analysis/metabolism MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Obesity/drug therapy MH - Adult MH - Follow-Up Studies MH - Body Mass Index MH - Prognosis MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12479283 OTO - NOTNLM OT - glycemic control OT - obesity OT - real-world data OT - semaglutide OT - type 2 diabetes OT - weight loss COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/10/02 06:28 MHDA- 2025/10/02 06:29 PMCR- 2025/09/16 CRDT- 2025/10/02 04:54 PHST- 2025/05/02 00:00 [received] PHST- 2025/09/01 00:00 [accepted] PHST- 2025/10/02 06:29 [medline] PHST- 2025/10/02 06:28 [pubmed] PHST- 2025/10/02 04:54 [entrez] PHST- 2025/09/16 00:00 [pmc-release] AID - 10.3389/fendo.2025.1621892 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Sep 16;16:1621892. doi: 10.3389/fendo.2025.1621892. eCollection 2025. PMID- 41034888 OWN - NLM STAT- MEDLINE DCOM- 20251002 LR - 20251005 IS - 1472-6963 (Electronic) IS - 1472-6963 (Linking) VI - 25 IP - 1 DP - 2025 Oct 1 TI - Information pharmacists assist in the construction of GLP-1RA prescription review rules in a tertiary hospital in China. PG - 1276 LID - 10.1186/s12913-025-13377-2 [doi] LID - 1276 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for type 2 diabetes mellitus (T2DM) due to their multifaceted benefits, including glycemic control and cardiovascular protection. However, variations in prescribing practices and potential adverse drug events (ADEs) necessitate standardized prescription review protocols to ensure medication safety and efficacy. OBJECTIVE: This study aimed to develop and implement GLP-1RA prescription review rules through a multidisciplinary information pharmacist team, evaluate their impact on prescription rationality, and identify ADE risk signals using real-world data, thereby promoting rational clinical medication use and ensuring patient safety. METHODS: A multidisciplinary information pharmacist team was established at a tertiary hospital to develop GLP-1RA prescription review protocols. China-approved GLP-1RA formulations and their clinical parameters were systematically reviewed to establish standardized prescribing criteria, including indications, dosing, and safety considerations. Adverse drug events were analyzed using FDA Adverse Event Reporting System data (2018-2023) to identify risk patterns. A dual review system integrating prospective prescription screening and retrospective evaluation was implemented. The intervention's efficacy was evaluated by comparing prescription approval rates pre- (2022) and post-implementation (2023). RESULTS: The GLP-1RA audit rules represented by liraglutide and semaglutide were successfully created, as well as their potential adverse event signals were successfully obtained. The process of prescription review and medication monitoring enabled them to be put into clinical practice. After the rules were put in place in 2023, the pass rates of GLP-1RA prescriptions significantly improved, and the rationalization of these prescriptions was also notably enhanced compared to the same period in 2022 (p < 0.001). CONCLUSIONS: Standardized GLP-1RA review rules enhanced prescription rationality and ADE risk awareness, demonstrating the value of information pharmacists in optimizing clinical decision-making. This model is scalable for other high-risk medications, promoting safer drug use and pharmacist-led innovation in healthcare. CI - (c) 2025. The Author(s). FAU - Zhou, Li AU - Zhou L AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. zhouli1007@126.com. FAU - Duanmu, Wenjing AU - Duanmu W AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. FAU - Tan, Feilong AU - Tan F AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. FAU - Gu, Xi AU - Gu X AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. FAU - Che, Hongyi AU - Che H AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. FAU - Yin, Wenjie AU - Yin W AD - Department of Pharmacy, The Affiliated Yan'an Hospital of Kunming Medical University, 245 Renmin East Road, Kunming, Panlong District, Yunnan Province, China. yinwj123@126.com. LA - eng GR - NO.2024J0277/Scientific Research Fund Project of Education Department of Yunnan Province/ GR - NO.2021-SW (reserve)-08/Kunming Health Science and Technology "Thousand Project" Talents Project/ PT - Journal Article DEP - 20251001 PL - England TA - BMC Health Serv Res JT - BMC health services research JID - 101088677 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - China MH - Tertiary Care Centers/organization & administration MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Pharmacists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Retrospective Studies PMC - PMC12487512 OTO - NOTNLM OT - Adverse drug events OT - Glucagon-like peptide-1 receptor agonist OT - Information pharmacists OT - Prescription review rules OT - Rational drug use COIS- Declarations. Ethics approval and consent to participate: The information on prior prescription data involved in this study was obtained from our hospital's prescription audit management system, and the ADEs data information was obtained from the FAERS database. Ethical approval was not considered necessary given the use of the identified data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/10/02 06:28 MHDA- 2025/10/02 06:29 PMCR- 2025/10/01 CRDT- 2025/10/02 00:03 PHST- 2024/06/11 00:00 [received] PHST- 2025/08/13 00:00 [accepted] PHST- 2025/10/02 06:29 [medline] PHST- 2025/10/02 06:28 [pubmed] PHST- 2025/10/02 00:03 [entrez] PHST- 2025/10/01 00:00 [pmc-release] AID - 10.1186/s12913-025-13377-2 [pii] AID - 13377 [pii] AID - 10.1186/s12913-025-13377-2 [doi] PST - epublish SO - BMC Health Serv Res. 2025 Oct 1;25(1):1276. doi: 10.1186/s12913-025-13377-2. PMID- 41026313 OWN - NLM STAT- MEDLINE DCOM- 20250930 LR - 20261010 IS - 1573-2630 (Electronic) IS - 0165-5701 (Linking) VI - 45 IP - 1 DP - 2025 Sep 30 TI - Blinded by the drug? A vigilyze signal linking semaglutide to NAION. PG - 398 LID - 10.1007/s10792-025-03760-7 [doi] AB - INTRODUCTION: Semaglutide, available widely as Ozempic, Wegovy, and Rybelsus, has significantly improved the management of type 2 diabetes and obesity due to its beneficial adverse drug reactions and safer use in diverse population. However, as its use grows widely, rare but serious side effects are coming to light. One such emerging concern is Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION), a condition causing sudden, often irreversible vision loss. METHODOLOGY: A retrospective, post-market observational study was conducted using data collected from VigiBase(R) until June 2025, using mapped terms under Medical Dictionary for Regulatory Activities (MedDRA). RESULT: Of 73,636 global Individual Case Safety Reports (ICSRs) related to Semaglutide reported adverse reactions globally, 91 were associated with the adverse reaction NAION. The cases were reported globally with increased number of cases reported by Denmark (N = 38, 41.80%), Australia (N = 9, 9.90%) and France (N = 7, 7.70%), primarily affected patients aged 45-74 years (N = 50, 54.90%). Most cases (97.80%) were classified as serious with a significant of the cases reported of males. The co-reported reactions involved serious 'eye-related' conditions like Visual Impairment (N = 12,13.20%), Blindness (N = 9, 9.90%), Visual field defect (N = 5, 5.50%), Optic atrophy (N = 4, 4.40%), Vision blurred (N = 4, 4.40%) among other serious reactions. CONCLUSION: This study raises awareness of a rare yet significant safety concern with Semaglutide. Early detection of NAION symptoms and timely drug discontinuation may be critical in preventing permanent vision loss. Moreover, the reaction should be mentioned in the patient information leaflet/ summary of the product characteristic of the drug to create awareness among the healthcare providers as well as the consumers taking the drug. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature B.V. FAU - Suresh, Jaishree AU - Suresh J AD - Indian Pharmacopoeia Commission, Ministry of Health & Family Welfare, Government of India, Sector-23, Raj Nagar, Ghaziabad, Uttar Pradesh, 201002, India. drjaishreesuresh@gmail.com. FAU - Vivekanandan, Kalaiselvan AU - Vivekanandan K AD - Indian Pharmacopoeia Commission, Ministry of Health & Family Welfare, Government of India, Sector-23, Raj Nagar, Ghaziabad, Uttar Pradesh, 201002, India. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250930 PL - Netherlands TA - Int Ophthalmol JT - International ophthalmology JID - 7904294 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Retrospective Studies MH - *Glucagon-Like Peptides/adverse effects MH - Male MH - Middle Aged MH - Female MH - Aged MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology/diagnosis MH - *Hypoglycemic Agents/adverse effects MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Global data OT - NAION OT - Non-arteritic anterior ischemic optic neuropathy OT - Pharmacovigilance OT - Semaglutide COIS- Declarations. Conflict of interest: The authors declare no competing interests EDAT- 2025/09/30 14:16 MHDA- 2025/09/30 14:17 CRDT- 2025/09/30 11:19 PHST- 2025/07/10 00:00 [received] PHST- 2025/09/14 00:00 [accepted] PHST- 2025/09/30 14:17 [medline] PHST- 2025/09/30 14:16 [pubmed] PHST- 2025/09/30 11:19 [entrez] AID - 10.1007/s10792-025-03760-7 [pii] AID - 10.1007/s10792-025-03760-7 [doi] PST - epublish SO - Int Ophthalmol. 2025 Sep 30;45(1):398. doi: 10.1007/s10792-025-03760-7. PMID- 41022666 OWN - NLM STAT- MEDLINE DCOM- 20251218 LR - 20260825 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 111 IP - 1 DP - 2025 Dec 18 TI - GLP-1 Receptor Agonists and Non-Arteritic Anterior Ischemic Optic Neuropathy: What an Endocrinologist Needs to Know. PG - e308-e313 LID - 10.1210/clinem/dgaf541 [doi] AB - CONTEXT: There is emerging evidence suggesting a possible association between glucagon-like peptide-1 receptor agonists (GLP-1 RA) and non-arteritic anterior ischemic optic neuropathy (NAION). Retrospective cohort studies supporting this association report hazard ratios ranging from 2.19 to 7.74 when comparing exposed vs unexposed groups. This article explores the current research surrounding the risk of NAION with GLP-1 RA use in patients with type 2 diabetes and obesity, analyses patient factors that may increase susceptibility and highlights key areas warranting further research to guide endocrinologists in future prescribing. CONCLUSION: Whilst the emerging evidence suggests a possible association between commencement of GLP-1 RAs and NAION, absolute risk remains low and needs to be balanced with the known substantial benefits of GLP-1 RAs. Further research is needed to investigate whether specific patient characteristics such as optic disc parameters, blood pressure changes, degree of weight loss, or improvement of glycemic control can assist clinicians in identifying those at higher risk. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Liu, Livia AU - Liu L AUID- ORCID: 0009-0007-7034-1635 AD - Department of Endocrinology, Concord Repatriation General Hospital, Sydney 2137, Australia. FAU - Mohan, Sharanya AU - Mohan S AD - Department of Endocrinology, Concord Repatriation General Hospital, Sydney 2137, Australia. FAU - Wu, Linda AU - Wu L AD - Department of Endocrinology, Concord Repatriation General Hospital, Sydney 2137, Australia. AD - Department of Diabetes and Endocrinology, Royal North Shore Hospital, Sydney 2065, Australia. AD - Faculty of Medicine and Health, University of Sydney, Sydney 2006, Australia. LA - eng PT - Journal Article PT - Review PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Obesity/drug therapy/complications MH - Endocrinologists MH - Risk Factors OTO - NOTNLM OT - GLP-1 agonists OT - non-arteritic ischemic optic neuropathy OT - obesity OT - semaglutide OT - type 2 diabetes EDAT- 2025/09/30 05:16 MHDA- 2025/12/18 13:06 CRDT- 2025/09/29 22:43 PHST- 2025/08/14 00:00 [received] PHST- 2025/09/26 00:00 [accepted] PHST- 2025/12/18 13:06 [medline] PHST- 2025/09/30 05:16 [pubmed] PHST- 2025/09/29 22:43 [entrez] AID - 8268255 [pii] AID - 10.1210/clinem/dgaf541 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2025 Dec 18;111(1):e308-e313. doi: 10.1210/clinem/dgaf541. PMID- 41021211 OWN - NLM STAT- MEDLINE DCOM- 20260221 LR - 20261009 IS - 1720-8386 (Electronic) IS - 0391-4097 (Linking) VI - 49 IP - 2 DP - 2026 Feb TI - Multi-database pharmacovigilance assessment of GLP-1 receptor agonist-related ophthalmic risks using advanced signal detection in FAERS and vigibase. PG - 425-433 LID - 10.1007/s40618-025-02712-3 [doi] AB - BACKGROUND: The expanding clinical use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for type 2 diabetes and obesity has raised concerns about underrecognized ocular adverse events (AEs). Despite their metabolic benefits, fragmented evidence and methodological limitations in pharmacovigilance systems hinder comprehensive risk characterization. This study aimed to systematically evaluate ocular toxicity signals associated with GLP-1 RAs using advanced signal mining across the FDA Adverse Event Reporting System (FAERS) and VigiBase. METHODS: Data from FAERS (2005-2025 Q1) and VigiBase (1987-2025 Q1) were analyzed for ocular AEs linked to five GLP-1 RAs (exenatide, liraglutide, dulaglutide, semaglutide, lixisenatide). Disproportionality analyses using Bayesian (Information Component, IC(025) > 0) and frequentist (Reporting Odds Ratio, ROR 95% CI > 1) methods identified significant signals. Duplicate reports and incomplete data were excluded, with statistical processing performed in R packages and Excel software. RESULTS: Across both databases, ocular AEs predominantly occurred in individuals aged 45-64 and females. Semaglutide exhibited the strongest signals, notably for NAION (ROR = 40.18, IC(025) = 2.06 in VigiBase and ROR = 31.46, IC(025) = 4.84 in FAERS), with 2,878 cases in VigiBase and 2,047 in FAERS. Dulaglutide showed high rates of visual impairment and diabetic retinopathy. Early-onset AEs ( 360 days. Discrepancies between databases emerged, such as absent liraglutide/lixisenatide signals in VigiBase but moderate activity in FAERS. Furthermore, review of the prescribing information for these GLP-1RAs indicates that ocular adverse events are incompletely characterized. Diabetic retinopathy is reported solely for semaglutide and dulaglutide, while blurred vision is the only ocular event listed for lixisenatide. Other potential ocular risks are not mentioned in any of the respective drug labels. CONCLUSION: This large-scale pharmacovigilance analysis suggests underrecognized ocular safety signals associated with GLP-1 RAs, most prominently NAION with semaglutide and visual impairment/diabetic retinopathy with dulaglutide. The distinct AE profiles, temporal patterns (early vs. late onset), and database discrepancies highlight the complexity of GLP-1 RA ocular toxicity. These findings underscore the need for enhanced clinical vigilance, targeted post-marketing surveillance, and consideration of label updates to reflect these emerging ocular safety concerns. CI - (c) 2025. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE). FAU - Cheng, Xiao AU - Cheng X AD - Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China. FAU - Jiang, Ziwei AU - Jiang Z AD - Department of Pharmacy, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China. FAU - Li, Guangyao AU - Li G AD - Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China. FAU - Wang, Jiawei AU - Wang J AD - Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China. wangjw2023@126.com. FAU - Han, Furong AU - Han F AD - Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China. furonghan@mail.ccmu.edu.cn. LA - eng PT - Journal Article DEP - 20250929 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - WTT295HSY5 (dulaglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Pharmacovigilance MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects MH - Databases, Factual/statistics & numerical data MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Male MH - Recombinant Fusion Proteins/adverse effects MH - United States/epidemiology MH - Middle Aged MH - United States Food and Drug Administration/statistics & numerical data MH - *Eye Diseases/chemically induced/epidemiology MH - Adult MH - Exenatide/adverse effects MH - Immunoglobulin Fc Fragments/adverse effects OTO - NOTNLM OT - Disproportionality analysis OT - GLP-1 receptor agonists OT - NAION OT - Ocular adverse events OT - Pharmacovigilance COIS- Declarations. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/09/29 13:19 MHDA- 2026/02/21 12:29 CRDT- 2025/09/29 11:26 PHST- 2025/07/08 00:00 [received] PHST- 2025/09/20 00:00 [accepted] PHST- 2026/02/21 12:29 [medline] PHST- 2025/09/29 13:19 [pubmed] PHST- 2025/09/29 11:26 [entrez] AID - 10.1007/s40618-025-02712-3 [pii] AID - 10.1007/s40618-025-02712-3 [doi] PST - ppublish SO - J Endocrinol Invest. 2026 Feb;49(2):425-433. doi: 10.1007/s40618-025-02712-3. Epub 2025 Sep 29. PMID- 41014747 OWN - NLM STAT- MEDLINE DCOM- 20251206 LR - 20260428 IS - 1578-8989 (Electronic) IS - 0025-7753 (Linking) VI - 165 IP - 6 DP - 2025 Dec TI - Clinical factors influencing the systolic blood pressure benefits of once-weekly semaglutide in patients with type 2 diabetes. PG - 107179 LID - S0025-7753(25)00407-5 [pii] LID - 10.1016/j.medcli.2025.107179 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM), a major cardiovascular risk, is often associated with obesity and hypertension. Once-weekly subcutaneous semaglutide (OWS-Sema) can improve these conditions, but factors influencing blood pressure (BP) effects are not well studied. This study aimed to assess the impact of OWS-Sema on systolic BP (SBP) and identify clinical factors associated with its reduction in patients with T2DM. METHODS: Sub-analysis of the REALSEM-SP study involving OWS-Sema-naive patients with T2DM. Changes in SBP and diastolic BP (DBP) and influencing factors were analyzed over 12 months. RESULTS: One hundred seventy-eight patients were included (mean age 61+/-10 years, 43.8% female, 79.2% with hypertension). Median baseline SBP and DBP were 132 [122-145] and 80 [72-88]mmHg, respectively. SBP decreased by -4mmHg at 6 months and -2mmHg at 12 months (p=0.014), while DBP showed no significant change (p=0.395). Factors independently associated with SBP reduction at 6 months included uncontrolled BP and a glomerular filtration rate >/=60mL/min/1.73m(2), while at 12 months, only uncontrolled BP remained significant. A SBP >/=10mmHg reduction was associated with uncontrolled BP, dyslipidemia and renal function at 6-month, and only with uncontrolled BP at 12-month. CONCLUSION: OWS-Sema was associated with significant reductions in office SBP in T2DM patients, especially those with uncontrolled baseline BP, independent of BMI changes or dose. Patients with baseline uncontrolled BP appear to benefit the most. CI - Copyright (c) 2025 Elsevier Espana, S.L.U. All rights reserved. FAU - Ruiz-Sanchez, Jorge Gabriel AU - Ruiz-Sanchez JG AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Instituto de Investigacion Sanitaria Fundacion Jimenez-Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), Hospital Universitario Fundacion Jimenez Diaz, Madrid 28040, Spain. Electronic address: jorgeg.ruiz@quironsalud.es. FAU - Sierra Poyatos, Roberto Miguel AU - Sierra Poyatos RM AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Endocrinology Department, Hospital Universitario General de Villalba, Madrid, Spain. FAU - Luiza Luca, Bogdana AU - Luiza Luca B AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Sanchez-Lechuga, Begona AU - Sanchez-Lechuga B AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Modrono Mostoles, Naiara AU - Modrono Mostoles N AD - Endocrinology Department, Hospital Universitario Infanta Elena, Madrid, Spain. FAU - Montoya Alvarez, Teresa AU - Montoya Alvarez T AD - Endocrinology Department, Hospital Universitario Infanta Elena, Madrid, Spain. FAU - Meneses, Diego AU - Meneses D AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Sanchez-Lopez, Raquel AU - Sanchez-Lopez R AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Endocrinology Department, Hospital Universitario Infanta Elena, Madrid, Spain. FAU - Casado Cases, Carlos AU - Casado Cases C AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Perez de Arenaza Pozo, Victor AU - Perez de Arenaza Pozo V AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Vazquez, Clotilde AU - Vazquez C AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Instituto de Investigacion Sanitaria Fundacion Jimenez-Diaz (IIS-FJD), Universidad Autonoma de Madrid (UAM), Hospital Universitario Fundacion Jimenez Diaz, Madrid 28040, Spain; Endocrinology Department, Hospital Universitario General de Villalba, Madrid, Spain; Endocrinology Department, Hospital Universitario Infanta Elena, Madrid, Spain; Endocrinology Department, Hospital Universitario Rey Juan Carlos, Madrid, Spain. FAU - Cardenas-Salas, Jersy Jair AU - Cardenas-Salas JJ AD - Endocrinology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain; Endocrinology Department, Hospital Universitario Infanta Elena, Madrid, Spain. LA - eng LA - spa PT - Journal Article DEP - 20250926 PL - Spain TA - Med Clin (Barc) JT - Medicina clinica JID - 0376377 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - Female MH - Middle Aged MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Blood Pressure/drug effects MH - *Hypertension/drug therapy/complications/etiology MH - Aged MH - Drug Administration Schedule MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Blood pressure OT - Diabetes tipo 2 OT - Hipertension arterial OT - Hypertension OT - Obesidad OT - Obesity OT - Presion arterial OT - Semaglutida OT - Semaglutide OT - Type 2 diabetes EDAT- 2025/09/28 01:02 MHDA- 2025/12/07 00:40 CRDT- 2025/09/27 18:04 PHST- 2025/03/30 00:00 [received] PHST- 2025/06/12 00:00 [revised] PHST- 2025/06/17 00:00 [accepted] PHST- 2025/12/07 00:40 [medline] PHST- 2025/09/28 01:02 [pubmed] PHST- 2025/09/27 18:04 [entrez] AID - S0025-7753(25)00407-5 [pii] AID - 10.1016/j.medcli.2025.107179 [doi] PST - ppublish SO - Med Clin (Barc). 2025 Dec;165(6):107179. doi: 10.1016/j.medcli.2025.107179. Epub 2025 Sep 26. PMID- 41011082 OWN - NLM STAT- MEDLINE DCOM- 20250927 LR - 20250930 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 61 IP - 9 DP - 2025 Sep 18 TI - Impact of Incretin-Based Therapy on Skeletal Muscle Health. LID - 10.3390/medicina61091691 [doi] LID - 1691 AB - Skeletal muscle is the largest insulin-sensitive tissue in the human body, playing a crucial role in glucose homeostasis, body mobility and overall metabolic health. In obesity and type 2 diabetes (T2D), skeletal muscle undergoes structural, functional, and metabolic alterations, including reduced muscle mass, impaired contractile function, increased myosteatosis, mitochondrial dysfunction, and chronic low-grade inflammation. Incretin-based therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RAs are highly effective treatments for T2D and obesity, producing substantial weight loss. While clinical trials suggest proportional loss of fat and lean mass when using incretin-based therapies, emerging preclinical and translational data indicate potential muscle-specific beneficial effects such as attenuation of atrophy, improved myogenesis, enhanced mitochondrial function and reduced myosteatosis. This review comprehensively summarizes the current preclinical and clinical evidence on the impact of incretin-based therapies on skeletal muscle mass, composition, metabolism, and performance, focusing on mechanistic insights from animal models and translational findings from human studies. FAU - Koceva, Andrijana AU - Koceva A AD - Department of Endocrinology and Diabetology, University Medical Center Maribor, 2000 Maribor, Slovenia. AD - Faculty of Medicine, University of Maribor, 2000 Maribor, Slovenia. FAU - Janez, Andrej AU - Janez A AUID- ORCID: 0000-0002-6594-5254 AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. FAU - Jensterle, Mojca AU - Jensterle M AUID- ORCID: 0000-0002-8861-8803 AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. LA - eng PT - Journal Article PT - Review DEP - 20250918 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use/pharmacology MH - *Muscle, Skeletal/drug effects/physiopathology MH - Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12471476 OTO - NOTNLM OT - incretin-based treatment OT - liraglutide OT - muscle function OT - muscle quality OT - obesity OT - semaglutide OT - tirzepatide COIS- A.K. reports receiving lecture honoraria from Eli Lilly, Novo Nordisk, Pfeizer, AstraZeneca, Boehringer Ingelheim and Sanofi and having served as a consultant for Novo Nordisk. A.J. has served as a consultant and is on Speakers Bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Abbott, Novo Nordisk, Medtronic, and Sanofi. M.J. reports receiving lecture honoraria from Novo Nordisk, Eli Lilly, Pfeizer, Amgen, Novartis and Sanofi and being an advisory board member of Novo Nordisk, Eli Lilly, Amgen and Pfeizer. EDAT- 2025/09/27 06:34 MHDA- 2025/09/27 06:35 PMCR- 2025/09/18 CRDT- 2025/09/27 01:21 PHST- 2025/08/14 00:00 [received] PHST- 2025/09/11 00:00 [revised] PHST- 2025/09/15 00:00 [accepted] PHST- 2025/09/27 06:35 [medline] PHST- 2025/09/27 06:34 [pubmed] PHST- 2025/09/27 01:21 [entrez] PHST- 2025/09/18 00:00 [pmc-release] AID - medicina61091691 [pii] AID - medicina-61-01691 [pii] AID - 10.3390/medicina61091691 [doi] PST - epublish SO - Medicina (Kaunas). 2025 Sep 18;61(9):1691. doi: 10.3390/medicina61091691. PMID- 41008590 OWN - NLM STAT- MEDLINE DCOM- 20250927 LR - 20260925 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 15 IP - 9 DP - 2025 Sep 5 TI - The Impact of Glucagon-like Peptide-1 Receptor Agonists on Erectile Function: Friend or Foe? LID - 10.3390/biom15091284 [doi] LID - 1284 AB - Erectile dysfunction (ED) is a common yet frequently underrecognized microvascular complication of diabetes, affecting up to three out of four individuals. Key contributing factors include advancing age, long-standing disease duration, and suboptimal glycemic control, as well as insulin resistance and androgen deficiency-the latter being particularly common in men with type 2 diabetes (T2D) and obesity. While numerous studies have investigated the effects of various antidiabetic therapies on diabetes-related ED, the results remain inconsistent, limiting definitive conclusions. In recent years, increasing attention has focused on a novel class of antidiabetic medications, namely glucagon-like peptide-1 receptor agonists (GLP-1 RAs). These agents have become central to the treatment of T2D due to their potent glucose-lowering properties and well-documented benefits on cardiovascular outcomes, and weight loss. Given these pleiotropic effects, GLP-1 RAs have been presumed to positively influence erectile function-a hypothesis supported by a growing body of experimental and clinical research. However, preliminary reports have also raised concerns about a possible association between GLP-1 RA use and ED. This narrative review aims to synthesize current evidence regarding the impact of GLP-1 RAs on erectile function, providing a platform for future research in this evolving field. FAU - Kounatidis, Dimitris AU - Kounatidis D AUID- ORCID: 0000-0003-4338-4879 AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. FAU - Vallianou, Natalia G AU - Vallianou NG AUID- ORCID: 0000-0003-3874-5393 AD - First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece. FAU - Rebelos, Eleni AU - Rebelos E AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. AD - Turku PET Centre, University of Turku, 20014 Turku, Finland. AD - Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy. FAU - Vallianou, Kalliopi AU - Vallianou K AD - Clinic of Nephrology and Renal Transplantation, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. FAU - Diakoumopoulou, Evanthia AU - Diakoumopoulou E AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. FAU - Makrilakis, Konstantinos AU - Makrilakis K AUID- ORCID: 0000-0002-4160-0577 AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. FAU - Tentolouris, Nikolaos AU - Tentolouris N AUID- ORCID: 0000-0003-0615-2534 AD - Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece. LA - eng PT - Journal Article PT - Review DEP - 20250905 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Erectile Dysfunction/drug therapy/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects/pharmacology MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Penile Erection/drug effects PMC - PMC12467596 OTO - NOTNLM OT - GIP OT - GLP-1 receptor agonists OT - diabetes OT - dulaglutide OT - erectile dysfunction OT - hypogonadism OT - liraglutide OT - semaglutide OT - testosterone OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2025/09/27 06:33 MHDA- 2025/09/27 06:34 PMCR- 2025/09/05 CRDT- 2025/09/27 01:09 PHST- 2025/07/28 00:00 [received] PHST- 2025/09/02 00:00 [revised] PHST- 2025/09/04 00:00 [accepted] PHST- 2025/09/27 06:34 [medline] PHST- 2025/09/27 06:33 [pubmed] PHST- 2025/09/27 01:09 [entrez] PHST- 2025/09/05 00:00 [pmc-release] AID - biom15091284 [pii] AID - biomolecules-15-01284 [pii] AID - 10.3390/biom15091284 [doi] PST - epublish SO - Biomolecules. 2025 Sep 5;15(9):1284. doi: 10.3390/biom15091284. PMID- 40996853 OWN - NLM STAT- MEDLINE DCOM- 20251103 LR - 20260527 IS - 1744-6880 (Electronic) IS - 1744-6872 (Linking) VI - 36 IP - 1 DP - 2026 Jan 1 TI - GLP1R and OCT1 variants modulate semaglutide and metformin response in type 2 diabetes. PG - 9-17 LID - 10.1097/FPC.0000000000000577 [doi] AB - BACKGROUND: Large consortia link variants in SLC22A1 , SLC47A1 , and GLP1R to antidiabetic response, yet few data confirm these effects in small real-world cohorts. We tested whether three common polymorphisms translate into measurable 3-month metabolic changes. METHODS: Twenty-seven Bulgarian adults with type 2 diabetes [BMI >/= 25 kg/m(2); mean glycated hemoglobin (HbA1c): 8.3 +/- 0.9%] received metformin XR 2000 mg ( n = 17) or oral semaglutide 14 mg ( n = 10). Sanger sequencing identified SLC22A1 rs628031, SLC47A1 rs2252281, and GLP1R rs6923761. Primary endpoints were 3-month changes (Delta) in weight and HbA1c; analysis of variance and ordinary least squares regression assessed genotype and treatment effects, as well as covariate-adjusted linear models of 3-month change (Delta). RESULTS: Semaglutide produced greater weight loss than metformin [-6.5 +/- 3.6 vs. -1.6 +/- 2.5 kg; 95% confidence interval (CI) -7.6 to -2.2; P = 0.001] and larger BMI reduction (-2.0 +/- 1.2 vs. -0.3 +/- 0.9 kg/m(2); P = 0.001). At an exploratory 10% FDR, only OCT1 rs34130495 dosage was associated with high-density lipoprotein (HDL) change in metformin-treated participants ( beta = +0.340 mmol/L per minor allele; P = 0.0026; q = 0.063; N = 16). GLP1R rs6923761 showed nominal trends for weight and BMI change in semaglutide users that did not survive FDR ( P approximately 0.06-0.07; q approximately 0.29; N = 10). CONCLUSION: Semaglutide outperformed metformin for short-term weight loss. An HDL signal for OCT1 rs34130495 at an exploratory 10% FDR warrants replication. These hypothesis-generating data support the feasibility of genotype-guided studies in local clinical settings. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Tourtourikov, Ivan AU - Tourtourikov I AD - Department of Chemistry and Biochemistry, Medical Faculty, Medical University. AD - Genetic Medico-Diagnostic Laboratory Genica and Genome Center Bulgaria. FAU - Kalinkova, Maria AU - Kalinkova M AD - Department of Pharmacology and Toxicology. FAU - Ivanov, Peter AU - Ivanov P AD - Department of Physiology and Pathophysiology, Medical Faculty, Medical University,- Sofia, Bulgaria. FAU - Mileva-Popova, Rene AU - Mileva-Popova R AD - Department of Physiology and Pathophysiology, Medical Faculty, Medical University,- Sofia, Bulgaria. FAU - Tafradjiiska-Hadjiolova, Radka AU - Tafradjiiska-Hadjiolova R AD - Department of Physiology and Pathophysiology, Medical Faculty, Medical University,- Sofia, Bulgaria. FAU - Handjieva-Darlenska, Teodora AU - Handjieva-Darlenska T AD - Department of Pharmacology and Toxicology. FAU - Kadiyska, Tanya AU - Kadiyska T AD - Genetic Medico-Diagnostic Laboratory Genica and Genome Center Bulgaria. AD - Department of Physiology and Pathophysiology, Medical Faculty, Medical University,- Sofia, Bulgaria. LA - eng PT - Journal Article DEP - 20251028 PL - United States TA - Pharmacogenet Genomics JT - Pharmacogenetics and genomics JID - 101231005 RN - 9100L32L2N (Metformin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Octamer Transcription Factor-1) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (POU2F1 protein, human) SB - IM MH - Humans MH - *Metformin/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor/genetics MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Octamer Transcription Factor-1/genetics MH - Glycated Hemoglobin MH - Polymorphism, Single Nucleotide MH - Aged MH - Adult MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - metformin OT - pharmacogenetics OT - semaglutide OT - type 2 diabetes EDAT- 2025/09/25 18:30 MHDA- 2025/11/03 06:27 CRDT- 2025/09/25 12:23 PHST- 2025/05/29 00:00 [received] PHST- 2025/09/06 00:00 [accepted] PHST- 2025/11/03 06:27 [medline] PHST- 2025/09/25 18:30 [pubmed] PHST- 2025/09/25 12:23 [entrez] AID - 01213011-990000000-00099 [pii] AID - 10.1097/FPC.0000000000000577 [doi] PST - ppublish SO - Pharmacogenet Genomics. 2026 Jan 1;36(1):9-17. doi: 10.1097/FPC.0000000000000577. Epub 2025 Oct 28. PMID- 40990658 OWN - NLM STAT- MEDLINE DCOM- 20260123 LR - 20260124 IS - 1743-9159 (Electronic) IS - 1743-9191 (Print) IS - 1743-9159 (Linking) VI - 112 IP - 1 DP - 2026 Jan 1 TI - The different colorectal tumor risk related to GLP-1 receptor agonists and SGLT2 inhibitors use: a network meta-analysis of 68 randomized controlled trials. PG - 443-459 LID - 10.1097/JS9.0000000000003450 [doi] AB - BACKGROUND: Recent evidence has raised concerns about potential pro-oncogenic effects associated with glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors, particularly regarding gastrointestinal malignancies. Colorectal tumors, the third most diagnosed cancer globally, already show increased incidence in patients with metabolic disorders who typically require these medications. For example, obese subjects had a significantly higher risk of colorectal tumors than healthy subjects. However, existing evidence on this association remains inconsistent. This network meta-analysis (NMA) evaluated the comparative incidence of colorectal tumors associated with specific GLP-1 receptor agonists and SGLT2 inhibitors. MATERIALS AND METHODS: We conducted a confirmatory NMA focused specifically on colorectal tumor incidence as an adverse effect, following Cochrane methodological recommendations. We performed a frequentist-based NMA of randomized controlled trials (RCTs) evaluating GLP-1 receptor agonists or SGLT2 inhibitors. Our primary outcome was colorectal tumor incidence, with safety profiles assessed by dropout rates as a secondary outcome. RESULTS: This NMA encompassing 68 RCTs with 207 200 participants found that only semaglutide was associated with increased incidence of colorectal tumors compared to controls. A dose-stratified analysis revealed that high-dose injectable semaglutide (2.4 mg/week) was the only regimen associated with increased incidence. Furthermore, when focusing on RCTs of obese subjects, the increased colorectal tumor rate related to semaglutide still existed. Neither other GLP-1 receptor agonists nor any SGLT2 inhibitors demonstrated significant associations with colorectal tumor development. CONCLUSION: Our study provides the first comprehensive NMA addressing the incidence of colorectal tumors related to individual GLP-1 receptor agonists and SGLT2 inhibitors, suggesting a dose-dependent relationship to semaglutide, particularly in its high-dose injectable form (2.4 mg/week). These findings represent a potential risk signal that requires further validation, given the already elevated baseline colorectal tumor risk in the target population, especially in subjects with obesity. Future research should focus on long-term follow-up studies to better characterize the mechanisms and clinical implications of this semaglutide-specific risk signal. WHAT THIS ADDS TO THE EXISTING LITERATURE: This network meta-analysis, based on 68 randomized controlled trials, suggested that only semaglutide, especially in highdose injectable form (2.4 mg/week), was associated with increased incidence of colorectal tumors compared to controls, especially in obese patients. Neither other GLP-1 receptor agonists nor any SGLT2 inhibitors demonstrated significant associations with colorectal tumor development. LEARNING POINTS: Our study provides evidence regarding the increased incidence of colorectal tumors related to semaglutide in a dose dependent way (2.4 mg/week). CI - Copyright (c) 2025 The Author(s). Published by Wolters Kluwer Health, Inc. FAU - Hung, Chao-Ming AU - Hung CM AD - Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan. AD - School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan. FAU - Zeng, Bing-Yan AU - Zeng BY AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. AD - Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan. FAU - Hsu, Chih-Wei AU - Hsu CW AD - Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. FAU - Chen, Po-Huang AU - Chen PH AD - Division of Hematology and Oncology, Department of Internal Medicine, Tri-Service General Hospital; School of Medicine, National Defense Medical University, Taipei, Taiwan. AD - School of Medicine, National Defense Medical Center, Taipei, Taiwan. FAU - Sun, Cheuk-Kwan AU - Sun CK AD - Department of Emergency Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan. AD - School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan. FAU - Carvalho, Andre F AU - Carvalho AF AD - Innovation in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia. FAU - Stubbs, Brendon AU - Stubbs B AD - Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. AD - Department of Sport, University of Vienna, Vienna, Austria. FAU - Chen, Yen-Wen AU - Chen YW AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan. FAU - Chen, Tien-Yu AU - Chen TY AD - School of Medicine, National Defense Medical Center, Taipei, Taiwan. AD - Department of Psychiatry, Tri-Service General Hospital, Taipei, Taiwan. AD - Department of Psychiatry, College of Medicine, National Defense Medical University, Taipei, Taiwan. FAU - Lei, Wei-Te AU - Lei WT AD - Section of Immunology, Rheumatology, and Allergy Department of Pediatrics, Hsinchu Munipical MacKay Children's Hospital, Hsinchu, Taiwan. AD - Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan. FAU - Chen, Jiann-Jy AU - Chen JJ AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan. AD - Department of Otorhinolaryngology, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan. FAU - Shiue, Yow-Ling AU - Shiue YL AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. AD - Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. FAU - Su, Kuan-Pin AU - Su KP AD - Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan. AD - College of Medicine, China Medical University, Taichung, Taiwan. AD - An-Nan Hospital, China Medical University, Tainan, Taiwan. FAU - Liang, Chih-Sung AU - Liang CS AD - Department of Psychiatry, Beitou Branch, Tri-Service General Hospital; School of Medicine, National Defense Medical Center, Taipei, Taiwan. AD - Department of Psychiatry, National Defense Medical Center, Taipei, Taiwan. FAU - Tseng, Ping-Tao AU - Tseng PT AUID- ORCID: 0000-0001-5761-7800 AD - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. AD - Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan. AD - Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan. AD - Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20250911 PL - United States TA - Int J Surg JT - International journal of surgery (London, England) JID - 101228232 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Colorectal Neoplasms/epidemiology/chemically induced MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Incidence MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects PMC - PMC12825905 OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT2 inhibitor OT - colorectal malignancy OT - colorectal tumor OT - network meta-analysis OT - semaglutide COIS- The authors report no financial interests or potential conflicts of interest. EDAT- 2025/09/24 13:01 MHDA- 2026/01/23 06:30 PMCR- 2026/01/22 CRDT- 2025/09/24 09:53 PHST- 2025/04/14 00:00 [received] PHST- 2025/08/27 00:00 [accepted] PHST- 2026/01/23 06:30 [medline] PHST- 2025/09/24 13:01 [pubmed] PHST- 2025/09/24 09:53 [entrez] PHST- 2026/01/22 00:00 [pmc-release] AID - 01279778-990000000-03299 [pii] AID - IJS-D-25-01794 [pii] AID - 10.1097/JS9.0000000000003450 [doi] PST - ppublish SO - Int J Surg. 2026 Jan 1;112(1):443-459. doi: 10.1097/JS9.0000000000003450. Epub 2025 Sep 11. PMID- 40990044 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260907 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Effectiveness of oral semaglutide versus empagliflozin for the management of type 2 diabetes. PIONEER-2 trial emulation with real-world data. PG - 7431-7440 LID - 10.1111/dom.70151 [doi] AB - BACKGROUND AND AIMS: Oral semaglutide and empagliflozin are commonly used for the management of type 2 diabetes (T2D), but head-to-head comparisons in real-world settings are limited. We aimed to emulate the PIONEER-2 trial using electronic health records to compare the effectiveness and persistence of oral semaglutide versus empagliflozin. METHODS: This was a retrospective multicentre study using electronic health records from Italian diabetes clinics. New users of oral semaglutide or empagliflozin were matched 1:2 and followed for up to 18 months. The primary outcome was HbA1c change; secondary outcomes included weight change and treatment persistence. Analyses used mixed models for repeated measures under both treatment policy and trial product estimands. RESULTS: After matching, we included new users of oral semaglutide (n = 105) or empagliflozin (n = 207). Mean age was 65 years, diabetes duration 10 years, baseline HbA1c 7.6%, BMI 29 kg/m(2), and 94% were on metformin. Only 28.6% of new users of oral semaglutide reached the 14 mg dose and 31.4% of empagliflozin new users reached the 25 mg dose. HbA1c reduction was significantly greater with oral semaglutide than with empagliflozin (mean difference - 0.35%, p <0.001). Weight loss over time was similar, with oral semaglutide showing a modest advantage at 18 months among persistent patients. Persistence was lower for semaglutide (HR for discontinuation 1.47, p = 0.007). CONCLUSIONS: Under routine care, new users of oral semaglutide achieved better glycaemic control compared with empagliflozin new users, with similar weight loss but lower treatment persistence. These findings support the results of PIONEER-2 and its transferability to clinical practice. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Fadini, Gian Paolo AU - Fadini GP AUID- ORCID: 0000-0002-6510-2097 AD - Department of Medicine, University of Padova, Padua, Italy. AD - Laboratory of Experimental Diabetology, Veneto Institute of Molecular Medicine, Padua, Italy. FAU - Longato, Enrico AU - Longato E AD - Department of Information Engineering, University of Padova, Padua, Italy. FAU - Poletto, Sara AU - Poletto S AD - Department of Information Engineering, University of Padova, Padua, Italy. FAU - Giaccari, Andrea AU - Giaccari A AUID- ORCID: 0000-0002-7462-7792 AD - Endocrine and Metabolic Center, Fondazione Policlinico Universitario A. Gemelli IRCCS and Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Ghiani, Mariangela AU - Ghiani M AD - Diabetology Unit, Azienda Sanitaria Locale 8 Cagliari Quartu S. Elena, Cagliari, Italy. FAU - Strazzabosco, Marco AU - Strazzabosco M AD - Diabetology and Metabolic Diseases Unit, S. Bortolo Hospital, Vicenza, Italy. FAU - Trombetta, Maddalena AU - Trombetta M AUID- ORCID: 0000-0002-0825-1117 AD - Endocrinology, Diabetology and Metabolic Diseases, University of Verona and University Hospital of Verona, Verona, Italy. FAU - Penno, Giuseppe AU - Penno G AUID- ORCID: 0000-0002-2834-4847 AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Avogaro, Angelo AU - Avogaro A AUID- ORCID: 0000-0002-1177-0516 AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Solini, Anna AU - Solini A AUID- ORCID: 0000-0002-7855-8253 AD - Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Consoli, Agostino AU - Consoli A AD - Endocrinology and Metabolism Unit, ASL, Pescara, Italy. AD - Department of Medicine and Aging Sciences DMSI and Center for Advanced Studies and Technology CAST, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy. CN - GLIMPLES study investigators and DARWIN-Renal study investigators LA - eng GR - Italian Diabetes Society/ PT - Comparative Study PT - Journal Article PT - Multicenter Study DEP - 20250924 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucosides) RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucosides/administration & dosage/therapeutic use MH - *Benzhydryl Compounds/administration & dosage/therapeutic use MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Male MH - Retrospective Studies MH - Aged MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - Administration, Oral MH - Treatment Outcome MH - Blood Glucose MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/therapeutic use MH - Weight Loss/drug effects MH - Italy/epidemiology MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12587239 OTO - NOTNLM OT - cohort study OT - empagliflozin OT - real-world evidence OT - semaglutide COIS- GPF received honoraria, lecture, or advisory board fees from AstraZeneca, Boehringer, Guidotti, Lilly, Novartis, Novo Nordisk, and Sanofi. AG has received lecture fees from AstraZeneca, Lilly, and Novo Nordisk. GP reports consulting, advisory board, or speaking honoraria from Eli Lilly, consulting or participation on advisory boards for Bayer, and consulting for Novo Nordisk. AA received research grants, lecture, or advisory board fees from Merck Sharp & Dohme, AstraZeneca, Novartis, Boehringer-Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier, and Takeda. AS served on the advisory board of Novo Nordisk, Sankyo, and Sanofi and received speaker fees from AstraZeneca, Bayer, Lilly, Novo Nordisk, and Sanofi. AC received grants from AstraZeneca, Lilly, and Novo Nordisk. He also received speaker fees and provided advisory board services for Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Lilly, Merck Sharp & Dohme, Menarini, Novo Nordisk, Sanofi, Sigma-Tau, and Takeda. EL, SP, MG, MS, and MT have nothing to disclose. FIR - Baldassarre, Maria Antonia Pompea IR - Baldassarre MAP FIR - Formoso, Gloria IR - Formoso G FIR - Consoli, Agostino IR - Consoli A FIR - Leto, Gaetano IR - Leto G FIR - Leonetti, Frida IR - Leonetti F FIR - Fazion, Stefano IR - Fazion S FIR - Meregalli, Giancarla IR - Meregalli G FIR - Zavattaro, Marco IR - Zavattaro M FIR - Aimaretti, Gianluca IR - Aimaretti G FIR - Melchionda, Elena IR - Melchionda E FIR - Barale, Cristina IR - Barale C FIR - Cau, Rosella IR - Cau R FIR - Ghiani, Mariangela IR - Ghiani M FIR - Muscara, Andrea IR - Muscara A FIR - Russo, Giuseppina IR - Russo G FIR - Anichini, Roberto IR - Anichini R FIR - Fattor, Bruno IR - Fattor B FIR - Fadini, Gian Paolo IR - Fadini GP FIR - Avogaro, Angelo IR - Avogaro A FIR - Nollino, Laura IR - Nollino L FIR - Paccagnella, Agostino IR - Paccagnella A FIR - Strazzabosco, Marco IR - Strazzabosco M FIR - Baldassarre, Mariella IR - Baldassarre M FIR - Consoli, Agostino IR - Consoli A FIR - Morganet, Sara IR - Morganet S FIR - Zugaro, Antonella IR - Zugaro A FIR - Baroni, Marco Giorgio IR - Baroni MG FIR - Andreozzi, Francesco IR - Andreozzi F FIR - Gatti, Adriano IR - Gatti A FIR - De Riu, Stefano IR - De Riu S FIR - Del Buono, Andrea IR - Del Buono A FIR - Aldigeri, Raffaella IR - Aldigeri R FIR - Bonadonna, Riccardo IR - Bonadonna R FIR - Cas, Alessandra Dei IR - Cas AD FIR - Vazzana, Angela IR - Vazzana A FIR - Antonini, Monica IR - Antonini M FIR - Moretti, Valentina IR - Moretti V FIR - Volsi, Patrizia Li IR - Volsi PL FIR - Cesare, Miranda IR - Cesare M FIR - Zanette, Giorgio IR - Zanette G FIR - Carletti, Silvia IR - Carletti S FIR - D'Angelo, Paola IR - D'Angelo P FIR - Leto, Gaetano IR - Leto G FIR - Leonetti, Frida IR - Leonetti F FIR - D'Onofrio, Luca IR - D'Onofrio L FIR - Maddaloni, Ernesto IR - Maddaloni E FIR - Buzzetti, Raffaella IR - Buzzetti R FIR - Picconi, Fabiana IR - Picconi F FIR - Frontoni, Simona IR - Frontoni S FIR - Cavallo, Gisella IR - Cavallo G FIR - Morano, Susanna IR - Morano S FIR - Filardi, Tiziana IR - Filardi T FIR - Cinti, Francesca IR - Cinti F FIR - Giaccari, Andrea IR - Giaccari A FIR - Bossi, Antonio C IR - Bossi AC FIR - Meregalli, Giancarla IR - Meregalli G FIR - Querci, Fabrizio IR - Querci F FIR - Gaglio, Alessia IR - Gaglio A FIR - Resi, Veronica IR - Resi V FIR - Orsi, Emanuela IR - Orsi E FIR - Fazion, Stefano IR - Fazion S FIR - Franzetti, Ivano G IR - Franzetti IG FIR - Berra, Cesare IR - Berra C FIR - Manfrini, Silvia IR - Manfrini S FIR - Garrapa, Gabriella IR - Garrapa G FIR - Lucarelli, Giulio IR - Lucarelli G FIR - Riccialdelli, Lara IR - Riccialdelli L FIR - Tortato, Elena IR - Tortato E FIR - Zavattaro, Marco IR - Zavattaro M FIR - Aimaretti, Gianluca IR - Aimaretti G FIR - Cavalot, Franco IR - Cavalot F FIR - Beccuti, Guglielmo IR - Beccuti G FIR - Broglio, Fabio IR - Broglio F FIR - Fattor, Bruno IR - Fattor B FIR - Cazzetta, Giuliana IR - Cazzetta G FIR - Lamacchia, Olga IR - Lamacchia O FIR - Rauseo, Anna IR - Rauseo A FIR - De Cosmo, Salvatore IR - De Cosmo S FIR - Cau, Rosella IR - Cau R FIR - Ghiani, Mariangela IR - Ghiani M FIR - Di Benedetto, Antonino IR - Di Benedetto A FIR - Di Pino, Antonino IR - Di Pino A FIR - Piro, Salvatore IR - Piro S FIR - Purrello, Francesco IR - Purrello F FIR - Frittitta, Lucia IR - Frittitta L FIR - Milluzzo, Agostino IR - Milluzzo A FIR - Russo, Giuseppina IR - Russo G FIR - Solini, Anna IR - Solini A FIR - Garofolo, Monia IR - Garofolo M FIR - Penno, Giuseppe IR - Penno G FIR - Del Prato, Stefano IR - Del Prato S FIR - Anichini, Roberto IR - Anichini R FIR - Fadini, Gian Paolo IR - Fadini GP FIR - Avogaro, Angelo IR - Avogaro A FIR - Gottardo, Lucia IR - Gottardo L FIR - Rigato, Mauro IR - Rigato M FIR - Paccagnella, Agostino IR - Paccagnella A FIR - Strazzabosco, Marco IR - Strazzabosco M FIR - Cigolini, Massimo IR - Cigolini M FIR - Bonora, Enzo IR - Bonora E EDAT- 2025/09/24 06:29 MHDA- 2025/11/05 06:29 PMCR- 2025/11/05 CRDT- 2025/09/24 05:33 PHST- 2025/09/04 00:00 [revised] PHST- 2025/07/22 00:00 [received] PHST- 2025/09/14 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/09/24 06:29 [pubmed] PHST- 2025/09/24 05:33 [entrez] PHST- 2025/11/05 00:00 [pmc-release] AID - DOM70151 [pii] AID - 10.1111/dom.70151 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Dec;27(12):7431-7440. doi: 10.1111/dom.70151. Epub 2025 Sep 24. PMID- 40988099 OWN - NLM STAT- MEDLINE DCOM- 20250924 LR - 20250927 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 8 IP - 5 DP - 2025 Sep TI - Evaluating the Rates of Pancreatitis and Pancreatic Cancer Among GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. PG - e70113 LID - 10.1002/edm2.70113 [doi] LID - e70113 AB - AIMS: This meta-analysis evaluates the rates of pancreatitis/pancreatic cancer among glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in randomised controlled trials (RCTs). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic search was performed in PubMed, Embase, and Cochrane Library for GLP-1 RA RCTs that evaluated pancreatitis/pancreatic cancer. A meta-analysis was conducted to evaluate this risk; subgroup analysis was performed with and without background medications. RESULTS: 62 studies utilising dulaglutide, exenatide, liraglutide, semaglutide, beinaglutide, retatrutide, or tirzepatide, with 66,232 patients, mean age of 58.3 years (14.4 to 68), and mean follow-up of 43.5 weeks (1 to 198) were included in this study. Meta-analysis showed a significantly increased risk of pancreatitis (RR: 1.44, 95% CI 1.09-1.89, p = 0.009), but not when stratified by background medications (RR: 1.28, 95% CI 0.87-1.87) and without background medications (RR: 1.37, 95% CI 0.91-2.05). Pancreatic cancer and GLP-1 RA use showed no significant association (RR: 1.30, 95% CI 0.86-1.97). However, a significant increase was found with background medications (RR: 1.85, 95% CI 1.05-3.26, p = 0.03), but not without (RR: 0.81, 95% CI 0.43-1.55). CONCLUSION: GLP-1 RAs carry a slightly increased risk of pancreatitis, which is not significant when stratified by background medication use. Overall risk for pancreatic cancer was not observed, but a slight association was found when stratified with background medications. However, this difference is likely minimal, given the numerous studies excluded from the meta-analysis where both treatment arms had zero events. CI - (c) 2025 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Wen, Jimmy AU - Wen J AUID- ORCID: 0009-0007-5412-8551 AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Nadora, Denise AU - Nadora D AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Bernstein, Ethan AU - Bernstein E AUID- ORCID: 0009-0007-7510-2246 AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - How-Volkman, Christiane AU - How-Volkman C AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Truong, Alina AU - Truong A AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Joy, Bethany AU - Joy B AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Kou, Megan AU - Kou M AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Muttalib, Zohaer AU - Muttalib Z AD - College of Medicine, California Northstate University, Elk Grove, California, USA. FAU - Alam, Arsh AU - Alam A AD - University of California, Davis, California, USA. FAU - Frezza, Eldo AU - Frezza E AD - College of Medicine, California Northstate University, Elk Grove, California, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Pancreatic Neoplasms/epidemiology/chemically induced MH - *Pancreatitis/chemically induced/epidemiology MH - Randomized Controlled Trials as Topic PMC - PMC12457091 OTO - NOTNLM OT - GLP-1 RA OT - pancreatic cancer OT - pancreatitis COIS- The authors declare no conflicts of interest. EDAT- 2025/09/24 06:29 MHDA- 2025/09/24 06:30 PMCR- 2025/09/23 CRDT- 2025/09/24 00:03 PHST- 2025/09/09 00:00 [revised] PHST- 2025/06/18 00:00 [received] PHST- 2025/09/13 00:00 [accepted] PHST- 2025/09/24 06:30 [medline] PHST- 2025/09/24 06:29 [pubmed] PHST- 2025/09/24 00:03 [entrez] PHST- 2025/09/23 00:00 [pmc-release] AID - EDM270113 [pii] AID - 10.1002/edm2.70113 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2025 Sep;8(5):e70113. doi: 10.1002/edm2.70113. PMID- 40986866 OWN - NLM STAT- MEDLINE DCOM- 20250923 LR - 20260812 IS - 1929-0748 (Electronic) IS - 1929-0748 (Linking) VI - 14 DP - 2025 Sep 23 TI - Effect of Adherence to Oral Semaglutide on Glycemic Control in People With Type 2 Diabetes Treated With Metformin: Protocol for an Open-Label Clinical Trial. PG - e64899 LID - 10.2196/64899 [doi] LID - e64899 AB - BACKGROUND: Treatment adherence by people with type 2 diabetes (T2D) is overall suboptimal, which can hinder glycemic control. Multiple adherence barriers have been identified, such as the dislike and fear of injections. Several of the recommended antidiabetic drugs are available in oral formulations, which may be a good alternative to injection therapy when possible. However, strict dosing instruction could pose adherence barriers; for example, oral semaglutide requires predose and postdose fasting and restricted water intake at dosing time. Currently, oral semaglutide is the only oral glucagon-like peptide-1 receptor agonist and has only been available for a few years; therefore, limited knowledge exists on adherence to it. OBJECTIVE: The aim of this study is to investigate the effect of adherence to oral semaglutide dosing instructions on glycemic control in people with T2D who are dysregulated on metformin and optionally a sodium-glucose cotransporter-2 inhibitor and naive to oral semaglutide. METHODS: This prospective, noninterventional, open-label, clinical trial with a duration of 12 weeks will be conducted in Denmark. Eligible participants are adults (aged >/=18 years) with dysregulated T2D (hemoglobin A1c of 53-75 mmol/mol) currently treated with metformin and optionally a sodium-glucose cotransporter-2 inhibitor for whom the next natural step in the treatment is to add an antidiabetic drug to the treatment regimen. Potential participants are recruited through announcements on social media and digital mail sent to their official digital mailbox (e-boks). During the trial, 20 participants will be initiated on oral semaglutide and escalated in dosage in accordance with the label. Information on the participants' behavior related to the dosing instructions will be collected using the following devices: a smartwatch to track activity and sleep time, a smart pill bottle to track dosing time, a smart bottle to track time and volume of water intake at dosing time, and a smartphone to take a photo of their breakfast to log time of breakfast. Glycemic control will be assessed using an unblinded continuous glucose monitoring sensor that the participants will wear. Participants are asked to report any cases of nausea or vomiting in terms of time of occurrence, duration, and severity. The primary endpoint is change from baseline to end-of-study time-in-range derived from continuous glucose monitoring data. RESULTS: The first participant visit was in April 2024. Three months of high frequency temporal data on adherence behavior will be collected, despite the relatively few expected participants included. CONCLUSIONS: Participants may change their behavior due to awareness of being observed. Regardless, the knowledge gained from this trial might be integrated into a decision support system, providing people with diabetes with guidance on how to increase adherence and potentially improving glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov NCT06333080.; https://clinicaltrials.gov/study/NCT06333080. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64899. CI - (c)Nynne Sophie Holdt-Caspersen, Claus Dethlefsen, Ole Hejlesen, Erik Christiansen, Stine Hangaard, Peter Vestergaard, Morten Hasselstrom Jensen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 23.09.2025. FAU - Holdt-Caspersen, Nynne Sophie AU - Holdt-Caspersen NS AUID- ORCID: 0000-0003-3263-0966 AD - Department of Data Science, Novo Nordisk A/S, Aalborg, Denmark. AD - Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. FAU - Dethlefsen, Claus AU - Dethlefsen C AUID- ORCID: 0000-0003-3994-6189 AD - Department of Data Science, Novo Nordisk A/S, Aalborg, Denmark. AD - Department of Mathematical Sciences, Aalborg University, Aalborg, Denmark. FAU - Hejlesen, Ole AU - Hejlesen O AUID- ORCID: 0000-0003-3578-8750 AD - Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. FAU - Christiansen, Erik AU - Christiansen E AUID- ORCID: 0000-0002-0291-8136 AD - Department of Medical & Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Hangaard, Stine AU - Hangaard S AUID- ORCID: 0000-0003-0395-3563 AD - Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. AD - Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark. FAU - Vestergaard, Peter AU - Vestergaard P AUID- ORCID: 0000-0002-9046-2967 AD - Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. FAU - Jensen, Morten Hasselstrom AU - Jensen MH AUID- ORCID: 0000-0002-6649-8644 AD - Department of Data Science, Novo Nordisk A/S, Aalborg, Denmark. AD - Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT06333080 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250923 PL - Canada TA - JMIR Res Protoc JT - JMIR research protocols JID - 101599504 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Metformin/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - *Glycemic Control/methods MH - Blood Glucose/drug effects/analysis MH - Prospective Studies MH - Female MH - Adult MH - Male MH - Middle Aged MH - Denmark MH - Glycated Hemoglobin/analysis MH - *Medication Adherence MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12504889 OTO - NOTNLM OT - continuous glucose monitoring OT - dosing instructions OT - medication adherence OT - observational study OT - oral antidiabetic drug OT - oral semaglutide COIS- Conflicts of Interest: Authors EC, CD, NSH-C, and MHJ are employees and shareholders of Novo Nordisk. PV is Head of Research at Steno Diabetes Center North Denmark funded by the Novo Nordisk Foundation. EDAT- 2025/09/23 18:28 MHDA- 2025/09/23 18:29 PMCR- 2025/09/23 CRDT- 2025/09/23 16:53 PHST- 2024/08/01 00:00 [received] PHST- 2025/07/02 00:00 [accepted] PHST- 2025/03/31 00:00 [revised] PHST- 2025/09/23 18:29 [medline] PHST- 2025/09/23 18:28 [pubmed] PHST- 2025/09/23 16:53 [entrez] PHST- 2025/09/23 00:00 [pmc-release] AID - v14i1e64899 [pii] AID - 10.2196/64899 [doi] PST - epublish SO - JMIR Res Protoc. 2025 Sep 23;14:e64899. doi: 10.2196/64899. PMID- 40986735 OWN - NLM STAT- MEDLINE DCOM- 20250923 LR - 20260707 IS - 1538-9766 (Electronic) IS - 1042-895X (Linking) VI - 48 IP - 5 DP - 2025 Sep-Oct 01 TI - Glucagon-Like Peptide-1 (GLP-1a) Receptor Agonist Use in Patients Presenting for Gastroenterology Procedures: A Review of Concerns. PG - 389-395 LID - 10.1097/SGA.0000000000000891 [doi] AB - Glucagon-like peptide-1 receptor agonist (GLP1a) agonists are one of the most recent discoveries to improve blood glucose control and provide satiety. The U.S. Food and Drug Administration (FDA) approved the first of these therapeutics for the management of type 2 diabetes in 2005 (Dungan et al., 2023). In 2014, the FDA approved semaglutide, a GLP1a, for weight management of patients with a BMI of 27 kg/m2 or greater and one weight-related ailment for patients with a BMI of at least 30 kg/m2. Although these pharmacologic agents provide many benefits, there is a growing concern for patients who currently use GLP1a medication during the perioperative period, especially relating to delayed gastric emptying. With the increasing use of GLP1a, health care practitioners require in-depth knowledge of implications and treatment for these patients to provide an evidence-based safety net for those requiring endoscopic services. CI - Copyright (c) 2025 Society of Gastroenterology Nurses and Associates. FAU - Wunder, Linda AU - Wunder L AD - About the authors: Linda Wunder, PhD, CRNA, APRN, FAANA, is Assistant Program Director, Didactic Curricula, Associate Professor, Anesthesiology Nursing Program, Barry University, Maini Shores, FL. AD - Rebecca Lee, DNP, CRNA, APRN, FAANA, is Program Director, Associate Professor of Anesthesiology Nursing Programs, Barry University, Maini Shores, FL. AD - Dawn Dalpe Welliver, DNP, CRNA, APRN, is Assistant Professor of Anesthesiology Nursing Program, Barry University, Maini Shores, FL. FAU - Lee, Rebecca AU - Lee R AD - About the authors: Linda Wunder, PhD, CRNA, APRN, FAANA, is Assistant Program Director, Didactic Curricula, Associate Professor, Anesthesiology Nursing Program, Barry University, Maini Shores, FL. AD - Rebecca Lee, DNP, CRNA, APRN, FAANA, is Program Director, Associate Professor of Anesthesiology Nursing Programs, Barry University, Maini Shores, FL. AD - Dawn Dalpe Welliver, DNP, CRNA, APRN, is Assistant Professor of Anesthesiology Nursing Program, Barry University, Maini Shores, FL. FAU - Dalpe Welliver, Dawn AU - Dalpe Welliver D AD - About the authors: Linda Wunder, PhD, CRNA, APRN, FAANA, is Assistant Program Director, Didactic Curricula, Associate Professor, Anesthesiology Nursing Program, Barry University, Maini Shores, FL. AD - Rebecca Lee, DNP, CRNA, APRN, FAANA, is Program Director, Associate Professor of Anesthesiology Nursing Programs, Barry University, Maini Shores, FL. AD - Dawn Dalpe Welliver, DNP, CRNA, APRN, is Assistant Professor of Anesthesiology Nursing Program, Barry University, Maini Shores, FL. LA - eng PT - Journal Article PT - Review DEP - 20250923 PL - United States TA - Gastroenterol Nurs JT - Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates JID - 8915377 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Glucagon-Like Peptides/therapeutic use MH - Gastric Emptying/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- The authors declare no conflict of interest. EDAT- 2025/09/23 18:28 MHDA- 2025/09/23 18:29 CRDT- 2025/09/23 14:54 PHST- 2023/01/30 00:00 [received] PHST- 2024/01/06 00:00 [accepted] PHST- 2025/09/23 18:29 [medline] PHST- 2025/09/23 18:28 [pubmed] PHST- 2025/09/23 14:54 [entrez] AID - 00001610-202509000-00007 [pii] AID - 10.1097/SGA.0000000000000891 [doi] PST - ppublish SO - Gastroenterol Nurs. 2025 Sep-Oct 01;48(5):389-395. doi: 10.1097/SGA.0000000000000891. Epub 2025 Sep 23. PMID- 40983112 OWN - NLM STAT- MEDLINE DCOM- 20251030 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 229 DP - 2025 Nov TI - Comparative effectiveness of GLP-1 receptor agonists on cardiovascular outcomes among adults with type 2 diabetes and moderate cardiovascular risk: emulation of a target trial. PG - 112910 LID - S0168-8227(25)00924-6 [pii] LID - 10.1016/j.diabres.2025.112910 [doi] AB - AIM: To compare the cardiovascular outcomes of glucagon-like peptide-1 receptor agonists (GLP-1RAs) among adults with type 2 diabetes mellitus (T2D) at moderate cardiovascular risk. METHODS: We emulated a target trial using claims data of adults with T2D at moderate cardiovascular risk who initiated dulaglutide, exenatide, liraglutide, or semaglutide between 01/01/2014-12/31/2021. Random treatment assignment was emulated by propensity scores and incorporated into inverse probability of treatment weighted (IPTW) Cox models. Outcomes were time to composite major adverse cardiovascular events (MACE: myocardial infarction, stroke, and all-cause mortality), expanded MACE (MACE, hospitalization for heart failure, and revascularization) and its components, and severe hypoglycemia. RESULTS: After IPTW, 35,572 patients initiated dulaglutide, 4376 initiated exenatide, 8843 initiated liraglutide, and 33,063 initiated semaglutide. Compared to dulaglutide, semaglutide was associated with lower risk of MACE (HR 0.85, 95CI % 0.78-0.93), expanded MACE (HR 0.92, 95CI % 0.87-0.96), all-cause mortality (HR 0.81, 95CI % 0.71-0.92), stroke (HR 0.82, 95CI % 0.70-0.97), and revascularization (HR 0.93, 95CI % 0.88-0.99), while liraglutide was associated with lower risk of MACE (HR 0.84, 95CI % 0.72-0.97) and all-cause mortality (HR 0.79, 95CI % 0.64-0.99). CONCLUSIONS: Among GLP-1RAs, semaglutide and liraglutide were associated with the greatest cardiovascular risk reduction in patients with T2D at moderate cardiovascular risk. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Sklepinski, Stacey M AU - Sklepinski SM AD - University of Maryland School of Medicine, 655 W Baltimore St, Baltimore, MD 21201, USA. FAU - Deng, Yihong AU - Deng Y AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA; OptumLabs, 1 Optum Circle, Eden Prairie, MN 55344, USA. FAU - Swarna, Kavya Sindu AU - Swarna KS AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA; OptumLabs, 1 Optum Circle, Eden Prairie, MN 55344, USA. FAU - Herrin, Jeph AU - Herrin J AD - Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, 333 Cedar Street, PO Box 208017, New Haven, CT 06520-8017, USA. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, 5841 S. Maryland Ave MC2000, Chicago, IL 60637, USA. FAU - Neumiller, Joshua J AU - Neumiller JJ AD - Department of Pharmacotherapy, Washington State University, 412 East Spokane Falls Blvd., PBS 130, Spokane, WA 99202-2131, USA; Providence Medical Research Center, 105 W 8th Ave, Suite 250E, Spokane, WA 99204, USA. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, 1600 NW 10th Ave #1140, Miami, FL 33136, USA. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, Emory University School of Medicine, 100 Woodruff Circle, Atlanta, GA 30322, USA. FAU - Ross, Joseph S AU - Ross JS AD - Department of Internal Medicine, Yale School of Medicine, 333 Cedar Street, PO Box 208017, New Haven, CT 06520-8017, USA; Department of Health Policy and Management, Yale School of Public Health, 60 College St, New Haven, CT 06510, USA. FAU - Borah, Bijan J AU - Borah BJ AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA. FAU - Maron, Bradley A AU - Maron BA AD - University of Maryland Institute for Health Computing, 6116 Executive Boulevard, North Bethesda, MD 20852, USA; Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine, 655 W Baltimore St, Baltimore, MD 21201, USA. FAU - Mickelson, Mindy M AU - Mickelson MM AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, 200 First St. SW, Rochester, MN 55905, USA. FAU - McCoy, Rozalina G AU - McCoy RG AD - OptumLabs, 1 Optum Circle, Eden Prairie, MN 55344, USA; University of Maryland Institute for Health Computing, 6116 Executive Boulevard, North Bethesda, MD 20852, USA; Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, 670 W Baltimore St, Baltimore, MD 21201, USA. Electronic address: Rozalina.McCoy@som.umaryland.edu. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250920 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Liraglutide/therapeutic use MH - Exenatide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Aged MH - Immunoglobulin Fc Fragments/therapeutic use MH - Heart Disease Risk Factors MH - Treatment Outcome MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Comparative effectiveness OT - Glucagon-like peptide-1 receptor agonists OT - Hypoglycemia OT - Major adverse cardiovascular event OT - Target trial emulation OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: In the last 36 months, JH received support from the Centers for Medicare and Medicaid Services, NIH, Agency for Healthcare Research and Quality, PCORI, and the American Heart Association. JJN is supported by a NIH research grant and a foundation grant from the American College of Clinical Pharmacy, serves as a consultant to Bayer, Eli Lilly, Boehringer Ingelheim, and Proteomics International, and receives support from the American Diabetes Association for projects unrelated to this work. RJG is supported by grants from NIDDK of NIH. RJG received research support from Novo Nordisk, Boehringer, Eli Lilly, and Dexcom, and consulting/advisory from Abbott Diabetes, Astra-Zeneca, Bayer, Boehringer, Dexcom, Eli Lilly, and Novo Nordisk, and Medtronic. GEU is supported by research grants from NIH and National Center for Research Resources and has received research support (to Emory University) from Abbott, Dexcom, Corcept, and Bayer, and served as a member of advisory boards for Dexcom, Glucotrack and GlyCare. JSR receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from FDA for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation program (U01FD005938), from the Agency for Healthcare Research and Quality (R01HS022882), and from Arnold Ventures; formerly received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology; and was an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen Inc. that was settled September 2022. BJB serves as a consultant to Boehringer-Ingelheim on projects unrelated to this study. RGM has received support from the NIDDK of NIH, the National Institute on Aging of the NIH, the National Center for Advancing Translational Sciences, and the American Diabetes Association for projects unrelated to this work. She also served as a consultant to EmmiEducate(R) (Wolters Kluwer) and the Yale-New Haven Health System and received speaking honoraria and travel support from the American Diabetes Association. EDAT- 2025/09/23 03:17 MHDA- 2025/10/31 00:29 CRDT- 2025/09/22 19:29 PHST- 2025/07/21 00:00 [received] PHST- 2025/08/31 00:00 [revised] PHST- 2025/09/17 00:00 [accepted] PHST- 2025/10/31 00:29 [medline] PHST- 2025/09/23 03:17 [pubmed] PHST- 2025/09/22 19:29 [entrez] AID - S0168-8227(25)00924-6 [pii] AID - 10.1016/j.diabres.2025.112910 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Nov;229:112910. doi: 10.1016/j.diabres.2025.112910. Epub 2025 Sep 20. PMID- 40980971 OWN - NLM STAT- MEDLINE DCOM- 20250922 LR - 20260925 IS - 1478-3231 (Electronic) IS - 1478-3223 (Print) IS - 1478-3223 (Linking) VI - 45 IP - 10 DP - 2025 Oct TI - Target Trial Emulations of GLP-1 and Dual GLP-1/GIP Agonists to Reduce Major Adverse Liver Outcomes in Type 2 Diabetes. PG - e70367 LID - 10.1111/liv.70367 [doi] LID - e70367 AB - BACKGROUND: Clinical trials suggest GLP-1 receptor agonists (RAs) and dual glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) RAs improve metabolic dysfunction associated with steatohepatitis (MASH) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to compare the estimate of the relative effect of tirzepatide, semaglutide, and liraglutide in reducing the risk of major adverse liver outcomes (MALOs) in patients with type 2 diabetes (T2D). DESIGN, SETTING AND PARTICIPANTS: We emulated target trials based on a real-world network of electronic health records (EHRs) from over 150 million patients. Three target trials were emulated, among eligible patients with T2D who had no prior MALO diagnosis, by comparing therapy involving tirzepatide, semaglutide, and liraglutide versus DPP4 inhibitor (DPP4i) therapy. We identified the first-ever diagnosis of MALO occurring within a 2-year follow-up period and compared across the treatment groups using Kaplan-Meier survival analyses. Cohorts underwent propensity score matching 1:1 for confounders. We performed sensitivity analyses relating to geographical location, combination with metformin, and by treatment adherence. We also performed head-to-head analyses of the incretin-based therapies. RESULTS: After matching, we identified three target trials comprised of 10 165, 56 702, and 8 301 patients treated with tirzepatide, semaglutide, and liraglutide, respectively (1:1 with reference patients) for a 2-year period. Tirzepatide (HR 0.53 [95% CI 0.40, 0.71]) and semaglutide (HR 0.81 [0.72, 0.90]) were associated with a significant reduction in the risk of incident MALO compared with DPP4i, whereas liraglutide was not (HR 1.04 [95% CI 0.79, 1.36]). In head-to-head comparisons, tirzepatide was associated with a significantly lower risk of incident MALO compared with liraglutide (HR 0.56 [95% CI 0.39, 0.79]), but not semaglutide (HR 0.83 [95% CI 0.63, 1.09]). Semaglutide was not associated with a reduced risk compared with liraglutide (HR 0.77 [95% CI 0.57, 1.05]). CONCLUSION: Treatment with tirzepatide and, to a lesser extent, semaglutide, in patients with T2D, was associated with a lower incidence of MALO compared with DPP4i after 2 years; largely driven by a reduction in the rates of compensated and decompensated cirrhosis. A reduction in MALO was not demonstrated with the use of liraglutide. These findings highlight a comparative benefit of tirzepatide (and semaglutide) versus DPP4i and should prompt more robust, longer-term randomised controlled studies to evaluate their role in preventing MALO in this increasingly prevalent patient population with co-existing T2D and MASLD. CI - (c) 2025 The Author(s). Liver International published by John Wiley & Sons Ltd. FAU - Henney, Alex E AU - Henney AE AUID- ORCID: 0000-0002-8066-9470 AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Anson, Matthew AU - Anson M AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. FAU - Azmi, Shazli AU - Azmi S AD - Division of Cardiovascular Sciences, University of Manchester, Manchester, UK. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Centre for Musculoskeletal Research, Faculty of Biology Medicine and Health, The University of Manchester, Manchester, UK. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular & Metabolic Medicine, University of Liverpool, Liverpool, UK. AD - Metabolism & Nutrition Research Group, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. AD - Liverpool Centre for Cardiovascular Sciences, University of Liverpool and Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK. LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Liraglutide/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Male MH - Female MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Tirzepatide/therapeutic use MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Gastric Inhibitory Polypeptide/agonists MH - Glucagon-Like Peptide 1/agonists MH - Incretins/therapeutic use MH - Semaglutide PMC - PMC12452214 COIS- M.A. receives a fellowship from the Novo Nordisk UK research foundation and JDRF. D.J.C. has received investigator-initiated grants from Astra Zeneca and Novo Nordisk, support for education from Perspectum with any financial remuneration from pharmaceutical company consultation made to the University of Liverpool and serves as the Topic Advisor for Type 2 Diabetes medications for The National Institute for Health and Care Excellence (NICE), UK. G.H.I. is an employee of TriNetX LLC. U.A. has received honoraria from Procter & Gamble, Viatris, Grunenthal and Sanofi for educational meetings and funding for attendance to an educational meeting from Diiachi Sankyo. U.A. has also received investigator-led funding by Procter & Gamble and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. All other authors declare that there are no financial relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript. EDAT- 2025/09/22 12:46 MHDA- 2025/09/22 12:47 PMCR- 2025/09/22 CRDT- 2025/09/22 08:48 PHST- 2025/09/09 00:00 [revised] PHST- 2025/04/22 00:00 [received] PHST- 2025/09/16 00:00 [accepted] PHST- 2025/09/22 12:47 [medline] PHST- 2025/09/22 12:46 [pubmed] PHST- 2025/09/22 08:48 [entrez] PHST- 2025/09/22 00:00 [pmc-release] AID - LIV70367 [pii] AID - 10.1111/liv.70367 [doi] PST - ppublish SO - Liver Int. 2025 Oct;45(10):e70367. doi: 10.1111/liv.70367. PMID- 40976663 OWN - NLM STAT- MEDLINE DCOM- 20250921 LR - 20250926 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 15 IP - 9 DP - 2025 Sep 21 TI - Cardiovascular effects of incretin-based drugs in patients with and without a history of heart failure: a protocol for a systematic review, meta-analysis and trial sequential analysis of randomised controlled trials. PG - e103668 LID - 10.1136/bmjopen-2025-103668 [doi] LID - e103668 AB - BACKGROUND: Incretin-based drugs, including glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RAs, are increasingly used in the management of type 2 diabetes mellitus and obesity. While these agents have shown cardiovascular benefits, their effects on both cardiovascular outcomes and cardiac structure and function remain uncertain-particularly in patients with and without a history of heart failure (HF). METHODS AND ANALYSIS: We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica Database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index-Science (CPCI-S)), as well as clinical trial registries from their inception and onwards to identify relevant randomised trials. The literature search is scheduled for July 2025. Two review authors will independently extract data and assess risk of bias. We will include randomised controlled trials assessing the effects of cagrilintide/semaglutide, liraglutide, semaglutide and tirzepatide in patients with and without a history of HF. The primary outcome will be cardiovascular mortality. Secondary outcomes will include HF hospitalisation, myocardial infarction, stroke, heart rate, systolic blood pressure, N-terminal pro B-type natriuretic peptide, left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume. Data will be synthesised by aggregate data meta-analyses and trial sequential analysis. Risk of bias will be assessed with the Cochrane Risk of Bias tool, version 2, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE). ETHICS AND DISSEMINATION: As this study is a systematic review based on secondary analysis of published data, ethical approval is not required. Findings will be published in international peer-reviewed scientific journals. PROSPERO REGISTRATION NUMBER: CRD420251003374. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - El-Sheikh, Mohammed AU - El-Sheikh M AUID- ORCID: 0000-0003-0549-2203 AD - Department of Cardiology, Copenhagen University Hospital, Amager and Hvidovre Hospital, Hvidovre, Denmark, Hvidovre Hospital, Hvidovre, Denmark mo-sheikh@hotmail.com. FAU - Sillassen, Christina Dam Bjerregaard AU - Sillassen CDB AUID- ORCID: 0009-0004-9247-5245 AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital ̶ Rigshospitalet, Copenhagen, Denmark, Rigshospitalet, Copenhagen, Denmark. AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark, University of Southern Denmark, Odense, Denmark. FAU - Wisborg, Frederik Dencker AU - Wisborg FD AD - Department of Cardiology, Copenhagen University Hospital, Amager and Hvidovre Hospital, Hvidovre, Denmark, Hvidovre Hospital, Hvidovre, Denmark. FAU - Hove, Jens Dahlgaard AU - Hove JD AD - Department of Cardiology, Copenhagen University Hospital, Amager and Hvidovre Hospital, Hvidovre, Denmark, Hvidovre Hospital, Hvidovre, Denmark. FAU - Dirksen, Carsten AU - Dirksen C AD - Department of Respiratory Diseases and Endocrinology, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark, Hvidovre Hospital, Hvidovre, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark, Hvidovre Hospital, Hvidovre, Denmark. FAU - Lee, Matthew Meng Yang AU - Lee MMY AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom, University of Glasgow, Glasgow, UK. FAU - Jakobsen, Janus C AU - Jakobsen JC AD - Copenhagen Trial Unit, Centre for Clinical Intervention Research, The Capital Region, Copenhagen University Hospital ̶ Rigshospitalet, Copenhagen, Denmark, Rigshospitalet, Copenhagen, Denmark. AD - Department of Regional Health Research, The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark, University of Southern Denmark, Odense, Denmark. FAU - Grand, Johannes AU - Grand J AUID- ORCID: 0000-0002-5511-4668 AD - Department of Cardiology, Copenhagen University Hospital, Amager and Hvidovre Hospital, Hvidovre, Denmark, Hvidovre Hospital, Hvidovre, Denmark. LA - eng PT - Journal Article DEP - 20250921 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Heart Failure/drug therapy/complications MH - Systematic Reviews as Topic MH - *Incretins/therapeutic use/pharmacology MH - Randomized Controlled Trials as Topic MH - Meta-Analysis as Topic MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Research Design MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12458674 OTO - NOTNLM OT - Cardiovascular Disease OT - Drug Therapy OT - Heart failure OT - Meta-Analysis OT - Safety OT - Systematic Review COIS- Competing interests: ME-S and JDH have received lecture fees from Novo Nordisk. CDBS's husband was employed at Novo Nordisk, Kalundborg site, as a sprinkler technician from September 1, 2024, to August 31, 2025. CD has received research funding from the Novo Nordisk Foundation, and over the past three years received personal fees (lecturer, consultant) from Novo Nordisk, AstraZeneca and Amylyx, and served in various unpaid roles (lecturer, chairperson, investigator) for Novo Nordisk, Amgen, AstraZeneca and Eli Lilly. MMYL has received research grants through his institution, the University of Glasgow, from AstraZeneca, Boehringer Ingelheim and Roche Diagnostics; is a member of Trial Steering Committees for Amgen and Cytokinetics; and Clinical Event Committees for Bayer and GSK. All other authors have no known competing interests. EDAT- 2025/09/22 00:30 MHDA- 2025/09/22 00:31 PMCR- 2025/09/21 CRDT- 2025/09/21 21:53 PHST- 2025/09/22 00:31 [medline] PHST- 2025/09/22 00:30 [pubmed] PHST- 2025/09/21 21:53 [entrez] PHST- 2025/09/21 00:00 [pmc-release] AID - bmjopen-2025-103668 [pii] AID - 10.1136/bmjopen-2025-103668 [doi] PST - epublish SO - BMJ Open. 2025 Sep 21;15(9):e103668. doi: 10.1136/bmjopen-2025-103668. PMID- 40975962 OWN - NLM STAT- MEDLINE DCOM- 20251011 LR - 20260127 IS - 1768-3254 (Electronic) IS - 0223-5234 (Linking) VI - 300 DP - 2025 Dec 15 TI - Unraveling the safety profile of GLP-1 receptor agonists: Mechanistic insights with a focus on semaglutide. PG - 118163 LID - S0223-5234(25)00928-6 [pii] LID - 10.1016/j.ejmech.2025.118163 [doi] AB - Semaglutide, a novel glucagon-like peptide-1 receptor agonist (GLP-1RA), has demonstrated remarkable therapeutic efficacy in managing type 2 diabetes (T2D) and obesity in recent years, emerging as a focal point in clinical research. However, with the expansion of its clinical application, there is increasing evidence that semaglutide can cause multisystem adverse reactions, leading to reduced patient compliance and safety. Recent research findings indicate that adverse events associated with semaglutide involve pathological changes across multiple systems (digestive, cardiovascular, neurological, reproductive, immune and respiratory) and organs (liver, kidneys, thyroid and retina). The precise mechanisms underlying these effects remain incompletely characterized, hindering early detection and targeted intervention in clinical practice. This review integrates evidence from preclinical studies, randomized controlled trials (RCTs), and real-world data to systematically evaluate the safety profile of GLP-1RAs, with semaglutide as the primary focus. It elucidates the biological mechanisms underlying organ/system-specific adverse effects broadly applicable to the GLP-1RA class. Furthermore, we propose a stratified management framework to guide personalized treatment strategies aligned with precision medicine principles, aiming to optimize the dynamic equilibrium between therapeutic efficacy and safety risks. CI - Copyright (c) 2025 Elsevier Masson SAS. All rights reserved. FAU - He, Xinyi AU - He X AD - Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, 110022, Liaoning Province, China; Clinical Department I, China Medical University, Shenyang, 110122, Liaoning Province, China. Electronic address: neveah_he@163.com. FAU - Zhao, Zimo AU - Zhao Z AD - First Clinical Medical College, China Medical University, Shenyang, 110122, Liaoning Province, China. FAU - Sun, Yan AU - Sun Y AD - Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, 110022, Liaoning Province, China. Electronic address: suny6@sj-hospital.org. FAU - Jiang, Xi AU - Jiang X AD - Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, 110022, Liaoning Province, China. Electronic address: xijiang1985@126.com. LA - eng PT - Journal Article PT - Review DEP - 20250910 PL - France TA - Eur J Med Chem JT - European journal of medicinal chemistry JID - 0420510 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/pharmacology/therapeutic use/chemistry MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - Animals MH - *Hypoglycemic Agents/adverse effects/pharmacology/chemistry/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adverse reactions OT - Clinical applications OT - GLP-1 receptor agonists OT - Mechanisms OT - Semaglutide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/09/22 00:30 MHDA- 2025/10/12 00:33 CRDT- 2025/09/21 18:02 PHST- 2025/07/13 00:00 [received] PHST- 2025/08/31 00:00 [revised] PHST- 2025/09/09 00:00 [accepted] PHST- 2025/10/12 00:33 [medline] PHST- 2025/09/22 00:30 [pubmed] PHST- 2025/09/21 18:02 [entrez] AID - S0223-5234(25)00928-6 [pii] AID - 10.1016/j.ejmech.2025.118163 [doi] PST - ppublish SO - Eur J Med Chem. 2025 Dec 15;300:118163. doi: 10.1016/j.ejmech.2025.118163. Epub 2025 Sep 10. PMID- 40966636 OWN - NLM STAT- MEDLINE DCOM- 20250918 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 31 IP - 9 DP - 2025 Sep TI - Navigating compounded semaglutide: what health care providers need to know. PG - 480-484 LID - 10.37765/ajmc.2025.89787 [doi] AB - Semaglutide, a glucagon-like peptide-1 receptor agonist, is FDA approved under the brand names Ozempic for treatment of type 2 diabetes and Wegovy for the treatment of overweight or obesity. The soaring popularity of these drugs, driven by social media and their overall efficacy, has resulted in nationwide shortages. The high costs associated with the FDA-approved products for both insurers and patients have also led to additional restrictions in access. In response to the unmet growing demand for semaglutide, suppliers have started to sell compounded versions of these products, both legally and illegally. This narrative review examines the implications of these compounded products on our health care system, highlighting concerns regarding their safety, efficacy, and regulatory status. Compounding, when done following federal and state regulations, can fill an important need in our health care marketplace. However, the compounded semaglutide products currently available to patients may lack the quality controls historically seen with compounded formulations, resulting in risks for dosing errors and adverse health outcomes. In addition, the compounded semaglutide market worldwide has seen batches of fraudulent products. Pharmacists and other health care providers have a unique opportunity to help guide patients in navigating this compounded semaglutide market, including directing them to lawful sources of compounded semaglutide, providing counseling on dosage and administration, and minimizing safety concerns. FAU - Liu, Grace AU - Liu G FAU - Jarema, Marissa AU - Jarema M AD - Blue Cross Blue Shield of Michigan, 600 E Lafayette Blvd, Mail Code 512C, Detroit, MI 48226. Email: mjarema@bcbsm.com. FAU - Mo, Millie AU - Mo M FAU - Stievater, Trish AU - Stievater T LA - eng PT - Journal Article PT - Review PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/therapeutic use MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Drug Compounding/standards MH - United States MH - *Hypoglycemic Agents/therapeutic use MH - United States Food and Drug Administration MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/09/18 18:32 MHDA- 2025/09/18 18:33 CRDT- 2025/09/18 16:35 PHST- 2025/09/18 18:33 [medline] PHST- 2025/09/18 18:32 [pubmed] PHST- 2025/09/18 16:35 [entrez] AID - 89787 [pii] AID - 10.37765/ajmc.2025.89787 [doi] PST - ppublish SO - Am J Manag Care. 2025 Sep;31(9):480-484. doi: 10.37765/ajmc.2025.89787. PMID- 40962119 OWN - NLM STAT- MEDLINE DCOM- 20260129 LR - 20260130 IS - 2162-0989 (Electronic) IS - 2162-0989 (Linking) VI - 15 IP - 1 DP - 2026 Jan-Feb TI - Does semaglutide increase the risk of non-arteritic anterior ischemic optic neuropathy? A systematic review and meta-analysis of emerging evidence. PG - 100245 LID - S2162-0989(25)00112-4 [pii] LID - 10.1016/j.apjo.2025.100245 [doi] AB - BACKGROUND: Semaglutide, a GLP-1 receptor agonist widely prescribed for type 2 diabetes and obesity, has recently been linked to rare ocular adverse events, including non-arteritic anterior ischemic optic neuropathy (NAION). Given the growing concerns and limited clarity, this systematic review and meta-analysis aims to critically assess the potential association between semaglutide use and NAION risk. OBJECTIVES: To evaluate the association between semaglutide use and the development of NAION. METHODS: A comprehensive literature search was conducted via different databases from inception to June 3rd, 2025. A reviewer screened the potential articles against prespecified eligibility criteria. The risk of bias in the eligible studies was then evaluated using the Newcastle Ottawa Scale (NOS). Data were then systematically extracted and analyzed. RESULTS: The database search yielded 3539 records, of which 10 research articles investigating the association between Semaglutide and NAION were included in this study. Semaglutide use was associated with a significantly increased risk of NAION compared to control medications, with a pooled hazard ratio of 2.620 (95 % CI: 1.808-3.795, P < 0.001). Risk elevation showed time-dependency, becoming statistically significant after 2 years of exposure. Identified risk factors included older age, male sex, prolonged diabetes duration, elevated HbA1c, diabetic retinopathy, and obesity. Among GLP-1 receptor agonists, semaglutide accounted for 86.5 % of reported NAION cases. Clinical presentations featured optic disc edema, intraretinal fluid on OCT, and crowded optic discs. Cumulative incidence rates were substantially higher in semaglutide users versus non-GLP-1 receptor agonist comparators. CONCLUSIONS: Semaglutide use shows association with increased NAION risk, particularly with prolonged exposure and in patients with predisposing factors. Risk-benefit assessment and targeted ophthalmologic monitoring are recommended while maintaining appropriate therapeutic use. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - Chen, Kai-Yang AU - Chen KY AD - Department of General Medicine, Chang Gung Memorial Hospital (Linkou branch), Taoyuan, Taiwan. FAU - Chan, Hoi-Chun AU - Chan HC AD - School of Pharmacy, China Medical University, Taichung, Taiwan. FAU - Chan, Chi-Ming AU - Chan CM AD - Department of Ophthalmology, Cardinal Tien Hospital, New Taipei CityTaiwan; School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan. Electronic address: m212092001@tmu.edu.tw. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250915 PL - United States TA - Asia Pac J Ophthalmol (Phila) JT - Asia-Pacific journal of ophthalmology (Philadelphia, Pa.) JID - 101583622 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - *Glucagon-Like Peptides/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Risk Factors MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Diabetic retinopathy OT - NAION OT - Non-Arteritic Anterior Ischemic Optic Neuropathy OT - Optic nerve ischemia OT - Semaglutide COIS- Declaration of Competing Interest The authors declare that they have no competing interests. EDAT- 2025/09/18 00:31 MHDA- 2026/01/30 00:54 CRDT- 2025/09/17 19:15 PHST- 2025/06/25 00:00 [received] PHST- 2025/09/02 00:00 [revised] PHST- 2025/09/08 00:00 [accepted] PHST- 2026/01/30 00:54 [medline] PHST- 2025/09/18 00:31 [pubmed] PHST- 2025/09/17 19:15 [entrez] AID - S2162-0989(25)00112-4 [pii] AID - 10.1016/j.apjo.2025.100245 [doi] PST - ppublish SO - Asia Pac J Ophthalmol (Phila). 2026 Jan-Feb;15(1):100245. doi: 10.1016/j.apjo.2025.100245. Epub 2025 Sep 15. PMID- 40961953 OWN - NLM STAT- MEDLINE DCOM- 20251016 LR - 20260925 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 13 IP - 11 DP - 2025 Nov TI - Once-weekly semaglutide 7.2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial. PG - 935-948 LID - S2213-8587(25)00225-6 [pii] LID - 10.1016/S2213-8587(25)00225-6 [doi] AB - BACKGROUND: Semaglutide 2.4 mg is approved for weight management in adults with obesity or overweight in the presence of at least one obesity-related complication; however, many people with obesity and type 2 diabetes do not reach their bodyweight reduction goals with this dose. We aimed to investigate the efficacy and safety of a new 7.2 mg maintenance dose of once-weekly subcutaneous semaglutide in people with obesity and type 2 diabetes. METHODS: STEP UP T2D was a randomised, phase 3b, double-blind controlled, three-arm, parallel-group trial conducted at 68 hospitals, specialist clinics, and medical centres in Bulgaria, Canada, Hungary, Poland, Portugal, Slovakia, South Africa, and the USA. Adults aged 18 years or older (BMI >/=30.0 kg/m(2), HbA(1c) 7.0-10.0% [53-86 mmol/mol]) were randomly assigned (3:1:1) to receive once-weekly subcutaneous semaglutide 7.2 mg, 2.4 mg, or placebo, alongside a lifestyle intervention, for 72 weeks. Coprimary endpoints were the percentage change in bodyweight and the proportion of participants reaching a bodyweight reduction of 5% or greater with semaglutide 7.2 mg versus placebo. Confirmatory secondary endpoints were the proportion of participants reaching a bodyweight reduction of 10% or greater, 15% or greater, and 20% or greater, and changes in waist circumference (cm) and HbA(1c) (%) with semaglutide 7.2 mg versus placebo. Efficacy was assessed in all randomly assigned participants, and safety was assessed in all randomly assigned participants who received at least one dose of the trial product. This trial is registered with ClinicalTrials.gov (NCT05649137) and is now closed and completed. FINDINGS: Between Jan 4 and May 4, 2023, 512 participants were randomly assigned to receive semaglutide 7.2 mg (n=307), semaglutide 2.4 mg (n=103), or placebo (n=102). 265 (51.8%) of 512 participants were female, the mean age was 56 (SD 10) years, mean bodyweight was 110.1 (22.9) kg, mean BMI was 38.6 (7.1) kg/m(2), and mean HbA(1c) was 8.1% (0.9). Compared with placebo, semaglutide 7.2 mg led to greater reductions in mean bodyweight (-13.2% vs -3.9%; estimated treatment difference [ETD] -9.3% [95% CI -11.0 to -7.7]; p<0.0001); more participants reaching bodyweight reductions of 5% or greater (odds ratio 10.0 [95% CI 6.0 to 16.9]; p<0.0001), 10% or greater (11.3 [5.9 to 21.4]; p<0.0001), 15% or greater (8.1 [3.7 to 17.7]; p<0.0001), and 20% or greater (12.3 [3.0 to 51.0]; p=0.0006); and reduced waist circumference (ETD -6.5 cm [95% CI -9.0 to -4.1]; p<0.0001) and HbA(1c) (ETD -1.5% [95% CI -1.8 to -1.2]; p<0.0001). Level 2-3 hypoglycaemia risk was low and comparable between semaglutide doses and placebo. Gastrointestinal events were reported by 163 (53.1%) of 307 participants with semaglutide 7.2 mg, 53 (51.5%) of 103 participants with semaglutide 2.4 mg, 26 (25.5%) of 102 participants with placebo; and serious adverse events were reported by 28 (9.1%) participants with semaglutide 7.2 mg, nine (8.7%) participants with semaglutide 2.4 mg, and nine (8.8%) participants with placebo. Dysaesthesia was more common with semaglutide 7.2 mg (58 [18.9%] of 307) versus 2.4 mg (five [4.9%] of 103) and placebo (none). INTERPRETATION: Among people with obesity and type 2 diabetes, semaglutide 7.2 mg was superior to placebo in reducing bodyweight, waist circumference, and HbA(1c). Safety and tolerability were comparable between semaglutide 7.2 mg and 2.4 mg, except for the imbalance in dysaesthesia. FUNDING: Novo Nordisk. TRANSLATIONS: For the Bulgarian, Hungarian and Polish translations of the abstract see Supplementary Materials section. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: ildiko.lingvay@utsouthwestern.edu. FAU - Bergenheim, Sara J AU - Bergenheim SJ AD - Novo Nordisk, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. FAU - Freitas, Paula AU - Freitas P AD - Department of Medicine, Faculty of Medicine and I3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; Integrated Responsibility Center for Obesity, Sao Joao Local Health Unit, Porto, Portugal. FAU - Garvey, W Timothy AU - Garvey WT AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA. FAU - Harder-Lauridsen, Nina M AU - Harder-Lauridsen NM AD - Novo Nordisk, Soborg, Denmark. FAU - Rosenstock, Julio AU - Rosenstock J AD - Velocity Clinical Research at Medical City, Dallas, TX, USA. FAU - Sahu, Kushal AU - Sahu K AD - Novo Nordisk, Bangalore, India. FAU - Wharton, Sean AU - Wharton S AD - Faculty of Medicine, University of Toronto, Toronto, ON, Canada; Faculty of Health and Kinesiology, York University, Toronto, ON, Canada; Faculty of Medicine, McMaster University, Hamilton, ON, Canada; Wharton Medical Clinic Weight and Diabetes Management, Burlington, ON, Canada. CN - STEP UP T2D trial group LA - eng SI - ClinicalTrials.gov/NCT05649137 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250914 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Lancet Diabetes Endocrinol. 2026 Jun;14(6):e9. doi: 10.1016/S2213-8587(26)00078-1. PMID: 41932351 MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - Drug Administration Schedule MH - *Obesity/drug therapy/complications MH - Treatment Outcome MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide 1/administration & dosage/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Semaglutide COIS- Declaration of interests IL has received grants from Boehringer Ingelheim, Dexcom, Eli Lilly, Novo Nordisk, Roche, and Pfizer, with all payments made to her institution; has received payment or honoraria from AbbVie, Altimmune, Alveus Therapeutics, Amgen, Antag Therapeutics, AstraZeneca, Bayer, Betagenon, Bioio, Biomea, Boehringer Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen/J&J, Juvena, Keros Therapeutics, Mediflix, Merck, Metsera, Neurocrine, Novo Nordisk, Pharmaventures, Pfizer, Regeneron, Roche, Sanofi, Shionogi, Source Bio, Structure Therapeutics, TARGET RWE, Terns Pharma, The Comm Group, Verdiva Bio, WebMD, and Zealand Pharma; and has received support to attend meetings from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, and Eli Lilly. SJB is a full-time employee of, and has received gifts from, Novo Nordisk and holds an unpaid affiliation with the University of Copenhagen. JBB has received grants or consulting fees, or both, from Altimmune, Antag, Amgen, ApStem, Aqua Medical, AstraZeneca, Boehringer Ingelheim, CeQur, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, GentiBio, Glyscend, Insulet, Medtronic MiniMed, Mellitus Health, Metsera, Novo Nordisk, Pendulum Therapeutics, Praetego, Stability Health, Tandem, Terns, Vertex, and Zealand, with all payments made to his institution; has received payment for expert testimony from Medtronic MiniMed and Novo Nordisk, with all payments made to his institution; has participated on a data safety monitoring board or advisory board for Altimmune, AstraZeneca, and Tandem Diabetes Care; holds stock or options in Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health; and has an unpaid leadership role for the Association for Clinical and Translational Science. PF has received payment or honoraria from Amryt, Bial, Boehringer Ingelheim, FaesFarma, Janssen, Lilly, Merck, Novartis, Novo Nordisk, Pronokal, and Sanofi, along with support to attend meetings from Bial, Medinfar, Novo Nordisk, and Sanofi. WTG has received grants as a principal investigator from Novo Nordisk, Eli Lilly & Co, Pfizer, Epitomee, Neurovalens, Zealand, Carmot/Roche, Terns Pharmaceuticals, and Viking Therapeutics; has received grants for research from the UAB Diabetes Research Center (DK079626) funded by the US National Institutes of Health (NIH) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), with all payments made to his institution; has received consulting fees as an advisory board member from Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand, Allurion, Carmot/Roche, Terns Pharmaceuticals, Neurocrine, Keros Therapeutics, Gan & Lee, NodThera, and Regeneron; has received fees to participate on a data safety monitoring board or advisory board for Boehringer Ingelheim and Eli Lilly; and is an unpaid member for the Lancet Commission on Obesity, American Association of Clinical Endocrinology (AACE) update of obesity treatment algorithm, American Diabetes Association (ADA) nutrition recommendations update, and ADA Standards of Care for Obesity. NMHL and KS are full-time employees of, and hold shares in, Novo Nordisk. JR has received research grants from Amgen, Applied Therapeutics, AstraZeneca, Biomea Fusion, Boehringer Ingelheim, Carmot, Corcept, Eli Lilly, Hanmi, Merck, Novartis, Novo Nordisk, Oramed, Regeneron, Pfizer, Sanofi, Structure Therapeutics, and TERNS; and has served on scientific advisory boards and received honorarium or consulting fees from Amgen, Applied Therapeutics, Biomea Fusion, Eli Lilly, Hanmi, Novo Nordisk, Oramed, Regeneron, Regor, Roche, Sanofi, Structure Therapeutics, and TERNS; and received honoraria for lectures from Eli Lilly, Novo Nordisk, and Sanofi. SW has received payment or honoraria from AstraZeneca, Bausch Health Canada, Boehringer Ingelheim, Eli Lilly, Metsera, Neurogastrix, Novo Nordisk, and Regeneron for academic talks to colleagues; has been provided with medical writing support from AstraZeneca, Boehringer Ingelheim, Bausch Health Canada, Eli Lilly, and Novo Nordisk; and has an unpaid leadership role in The Obesity Society and Obesity Canada. EDAT- 2025/09/18 00:31 MHDA- 2025/10/17 00:31 CRDT- 2025/09/17 18:52 PHST- 2025/06/05 00:00 [received] PHST- 2025/07/11 00:00 [revised] PHST- 2025/07/17 00:00 [accepted] PHST- 2025/10/17 00:31 [medline] PHST- 2025/09/18 00:31 [pubmed] PHST- 2025/09/17 18:52 [entrez] AID - S2213-8587(25)00225-6 [pii] AID - 10.1016/S2213-8587(25)00225-6 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2025 Nov;13(11):935-948. doi: 10.1016/S2213-8587(25)00225-6. Epub 2025 Sep 14. PMID- 40938549 OWN - NLM STAT- MEDLINE DCOM- 20260513 LR - 20260517 IS - 1573-7241 (Electronic) IS - 0920-3206 (Linking) VI - 40 IP - 3 DP - 2026 Jun TI - Superior Cerebrovascular Outcomes with Tirzepatide versus Semaglutide in Diabetic CABG Patients: A Global Network Study of Propensity-Matched Patients. PG - 1001-1011 LID - 10.1007/s10557-025-07757-3 [doi] AB - PURPOSE: To compare the effectiveness of tirzepatide (a dual GLP-1/GIP receptor agonist) versus semaglutide (a GLP-1 receptor agonist) in improving postoperative outcomes among patients with type 2 diabetes mellitus (T2DM) undergoing coronary artery bypass grafting (CABG). METHODS: We conducted a retrospective analysis using the TriNetX global research network, identifying 226,742 adults with T2DM who underwent isolated CABG between 2022 and 2024. Among these, 3,669 received tirzepatide and 19,521 received semaglutide. After 1:1 propensity score matching, 3,667 matched pairs were analyzed. Primary outcomes included cerebrovascular and cardiovascular events, postoperative complications, healthcare utilization, and all-cause mortality, assessed at 6-month and 3-year intervals. P-values were adjusted for multiple testing using the Benjamini-Hochberg procedure. RESULTS: Tirzepatide was associated with significantly lower risks of cerebrovascular events at both follow-up points, including reduced incidence of cerebrovascular disease (11.8% vs. 17.5%; HR = 0.831), cerebral infarction (4.6% vs. 7.3%; HR = 0.788), and cerebral occlusion without infarction (6.8% vs. 10.4%; HR = 0.838)-all of which remained statistically significant after multiple comparison correction (adjusted p = 0.0024). Cardiovascular outcomes also favored tirzepatide, with significant reductions in major adverse cardiovascular events (MACE) (39.7% vs. 49.5%; HR = 0.911), myocardial infarction (7.0% vs. 10.8%; HR = 0.838), and acute coronary disease (1.1% vs 2.3%; HR = 0.691); several of these remained significant after correction at both timepoints. While tirzepatide was associated with lower rates of surgical site infection, venous thrombosis, and CABG-specific complications, only venous thrombosis remained statistically significant after adjustment (adjusted p = 0.021). Additionally, tirzepatide users had reduced healthcare utilization and lower all-cause mortality, with 3-year readmission (16.4% vs. 23.4%; HR = 0.871) and mortality (1.9% vs. 4.7%; HR = 0.595) both remaining significant after adjustment (adjusted p = 0.002). Kaplan-Meier analysis confirmed sustained survival benefit. CONCLUSION: In patients with T2DM undergoing CABG, tirzepatide was associated with improved cerebrovascular and cardiovascular outcomes, reduced venous thrombotic complications, and lower long-term mortality and healthcare utilization compared to semaglutide. These findings support the therapeutic potential of dual GLP-1/GIP receptor agonism in high-risk post-CABG populations. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Chunduri, Shriya AU - Chunduri S AD - Tulane University School of Medicine, New Orleans, LA, USA. FAU - Bidaoui, Ghassan AU - Bidaoui G AD - Tulane Research Innovation for Arrhythmia Discovery (TRIAD) Center, Tulane University School of Medicine, New Orleans, LA, USA. FAU - Hussein, Mohammad H AU - Hussein MH AD - Ochsner Clinic Foundation, New Orleans, LA, USA. FAU - Patel, Milee AU - Patel M AD - Tulane University School of Medicine, New Orleans, LA, USA. FAU - Abdelmaksoud, Ahmed AU - Abdelmaksoud A AD - Department of Internal Medicine, University of California, Riverside, CA, 92521, USA. FAU - Mohamed, Mohamed AU - Mohamed M AD - Department of Internal Medicine, University of California, Riverside, CA, 92521, USA. FAU - Attia, Abdallah AU - Attia A AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, 70112, USA. FAU - Tatum, Danielle AU - Tatum D AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, 70112, USA. FAU - Borgi, Jamil AU - Borgi J AUID- ORCID: 0000-0001-9267-3787 AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, 70112, USA. FAU - Toraih, Eman A AU - Toraih EA AD - Department of Cardiovascular Perfusion, College of Health Professions, Upstate Medical University, New York, NY, USA. etoraih@tulane.edu. AD - Genetics Unit, Histology and Cell Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt. etoraih@tulane.edu. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250912 PL - United States TA - Cardiovasc Drugs Ther JT - Cardiovascular drugs and therapy JID - 8712220 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Coronary Artery Bypass/adverse effects/mortality MH - Middle Aged MH - Aged MH - Retrospective Studies MH - *Cerebrovascular Disorders/prevention & control/mortality/epidemiology/diagnosis MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Coronary Artery Disease/surgery/mortality MH - Propensity Score MH - Risk Factors MH - Risk Assessment MH - Time Factors MH - Postoperative Complications/prevention & control MH - Tirzepatide OTO - NOTNLM OT - CABG OT - Cardiovascular outcomes OT - Cerebrovascular disease OT - GLP-1/GIP receptor agonist OT - Mortality OT - Semaglutide OT - Tirzepatide OT - Type 2 diabetes COIS- Declarations. Ethics Approval: This study utilized de-identified data from the TriNetX global federated health research network, therefore, ethics committee approval and informed consent were waived. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Consent to Participate: This study used de-identified patient data from TriNetX. As such, individual informed consent was not required. Consent for Publication: This study used de-identified patient data from TriNetX. As such, individual consent for publication was not required. Competing interests: The authors have no relevant financial or non-financial interests to disclose. EDAT- 2025/09/12 12:30 MHDA- 2026/05/13 12:32 CRDT- 2025/09/12 11:20 PHST- 2025/08/04 00:00 [accepted] PHST- 2026/05/13 12:32 [medline] PHST- 2025/09/12 12:30 [pubmed] PHST- 2025/09/12 11:20 [entrez] AID - 10.1007/s10557-025-07757-3 [pii] AID - 10.1007/s10557-025-07757-3 [doi] PST - ppublish SO - Cardiovasc Drugs Ther. 2026 Jun;40(3):1001-1011. doi: 10.1007/s10557-025-07757-3. Epub 2025 Sep 12. PMID- 40937414 OWN - NLM STAT- MEDLINE DCOM- 20250915 LR - 20250915 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Emerging perspectives on once-weekly insulins in type 1 and type 2 diabetes: a mini-review. PG - 1656884 LID - 10.3389/fendo.2025.1656884 [doi] LID - 1656884 AB - The development of once-weekly basal insulin analogues, such as insulin icodec and efsitora alfa, represents a promising strategy to reduce injection burden and improve adherence in diabetes management. This mini-review summarizes the recent findings from clinical trials evaluating once-weekly insulin therapies in both type 1 and type 2 diabetes. In type 1 diabetes, available data remain limited; however, the ONWARDS 6 and QWINT-5 trials demonstrated that once-weekly icodec and efsitora, respectively, achieved comparable reductions in HbA1c to once-daily insulin degludec, when used in combination with prandial insulin. In type 2 diabetes, accumulating evidences from randomized clinical trials supports the efficacy of once-weekly icodec and efsitora, showing non-inferiority-and in some cases, superiority-compared to once-daily basal insulin, both in insulin-naive individuals and in those previously treated with insulin. Safety profiles of once-weekly insulins in type 2 diabetes are reassuring, with similar rates of clinically significant and severe hypoglycemia compared to once-daily regimens. In contrast, trials in type 1 diabetes reported higher hypoglycemia rates with once-weekly insulins. Recent findings from the COMBINE program demonstrated that the fixed-ratio combination of icodec and semaglutide (IcoSema) produced superior HbA1c reductions compared to either agent alone, though not superior to a basal-bolus regimen with glargine and aspart insulin. However, several important questions remain to be addressed regarding once-weekly insulins, including their long-term efficacy on cardiovascular outcomes and overall long-term safety. CI - Copyright (c) 2025 Denimal. FAU - Denimal, Damien AU - Denimal D AD - Universite Bourgogne Europe, CHU Dijon Bourgogne, Department of Clinical Biochemistry, INSERM, CTM UMR 1231, PADYS team, Dijon, France. LA - eng PT - Journal Article PT - Review DEP - 20250827 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin, Long-Acting) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Diabetes Mellitus, Type 1/drug therapy MH - *Hypoglycemic Agents/administration & dosage MH - Drug Administration Schedule MH - Insulin, Long-Acting/administration & dosage MH - Randomized Controlled Trials as Topic PMC - PMC12420296 OTO - NOTNLM OT - diabetes mellitus OT - glycemic control OT - insulin efsitora OT - insulin icodec OT - long-acting insulin COIS- The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/09/12 06:29 MHDA- 2025/09/16 00:32 PMCR- 2025/08/27 CRDT- 2025/09/12 04:44 PHST- 2025/06/30 00:00 [received] PHST- 2025/08/11 00:00 [accepted] PHST- 2025/09/16 00:32 [medline] PHST- 2025/09/12 06:29 [pubmed] PHST- 2025/09/12 04:44 [entrez] PHST- 2025/08/27 00:00 [pmc-release] AID - 10.3389/fendo.2025.1656884 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Aug 27;16:1656884. doi: 10.3389/fendo.2025.1656884. eCollection 2025. PMID- 40935040 OWN - NLM STAT- MEDLINE DCOM- 20260820 LR - 20260820 IS - 1879-0003 (Electronic) IS - 0141-8130 (Linking) VI - 328 IP - Pt 1 DP - 2025 Nov TI - Development of a potent Xenopus GLP-1-derived GLP-1/GIP/Y(2) receptor tri-agonist for obesity and type 2 diabetes. PG - 147553 LID - S0141-8130(25)08110-3 [pii] LID - 10.1016/j.ijbiomac.2025.147553 [doi] AB - The drug development strategy of combining the complementary effects of different endogenous metabolism related hormones into one molecule is receiving increasing attention. In this study, we developed the unimolecular GLP-1/GIP/Y(2) receptor triple agonist, aiming to simultaneously activating the GLP-1 and GIP receptors together with the appetite-curbing Y(2) receptor to achieve better weight loss and blood glucose control. One strategy for constructing this triple agonist peptide involves coupling the GLP-1/GIP receptor dual agonist moiety with the PYY moiety through a maleimide-thiol specific reaction. Another strategy is to directly synthesize peptides with essentially identical sequences through solid-phase synthesis. Through long-acting modifications and comprehensive receptor screening, we identified a novel triple agonist, GP-38, exhibiting potent and balanced activity at GIP, GLP-1, and Y(2) receptor. In diet-induced obesity mice, GP-38 showed favourable effects on lipid metabolism, weight reduction, and glucose homeostasis with semaglutide and cagrisema used as control. Collectively, these data demonstrate that GP-38, a highly potent triple agonist targeting GLP-1, GIP, and Y(2) receptor, significantly outperforms GLP-1 receptor monotherapy in improving glucose homeostasis and reducing body weight, offers a promising pathway for the development of new treatments for obesity and type 2 diabetes. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Liu, Xiyu AU - Liu X AD - College of Medicine, Jiaxing University, Jiaxing, 314001, China. FAU - Gong, Binbin AU - Gong B AD - College of Medicine, Jiaxing University, Jiaxing, 314001, China; College of Pharmacy, Zhejiang University of Technology, Hangzhou, 310000, China. FAU - Wang, Ting AU - Wang T AD - College of Medicine, Jiaxing University, Jiaxing, 314001, China. FAU - Hu, Guoqiang AU - Hu G AD - Taizhou Hospital, Zhejiang University, Taizhou, 317000, China. FAU - Han, Jing AU - Han J AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou, 221116, China. FAU - Sun, Lidan AU - Sun L AD - College of Medicine, Jiaxing University, Jiaxing, 314001, China; Taizhou Hospital, Zhejiang University, Taizhou, 317000, China. Electronic address: slidan89@zjxu.edu.cn. LA - eng PT - Journal Article DEP - 20250909 PL - Netherlands TA - Int J Biol Macromol JT - International journal of biological macromolecules JID - 7909578 RN - 0 (Receptors, Gastrointestinal Hormone) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Neuropeptide Y) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (neuropeptide Y2 receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Blood Glucose) SB - IM MH - Animals MH - *Receptors, Gastrointestinal Hormone/agonists MH - *Obesity/drug therapy/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Glucagon-Like Peptide 1/chemistry MH - Mice MH - *Receptors, Neuropeptide Y/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Humans MH - Semaglutide MH - Hypoglycemic Agents/pharmacology/chemistry MH - Male MH - Gastric Inhibitory Polypeptide MH - Blood Glucose OTO - NOTNLM OT - Glucagon-like peptide-1 OT - Glucose dependent insulinotropic polypeptide OT - Obesity OT - Peptide YY OT - Triple agonist COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/09/12 00:29 MHDA- 2026/08/20 11:41 CRDT- 2025/09/11 19:12 PHST- 2025/06/13 00:00 [received] PHST- 2025/08/26 00:00 [revised] PHST- 2025/09/07 00:00 [accepted] PHST- 2026/08/20 11:41 [medline] PHST- 2025/09/12 00:29 [pubmed] PHST- 2025/09/11 19:12 [entrez] AID - S0141-8130(25)08110-3 [pii] AID - 10.1016/j.ijbiomac.2025.147553 [doi] PST - ppublish SO - Int J Biol Macromol. 2025 Nov;328(Pt 1):147553. doi: 10.1016/j.ijbiomac.2025.147553. Epub 2025 Sep 9. PMID- 40934962 OWN - NLM STAT- MEDLINE DCOM- 20251030 LR - 20251202 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 229 DP - 2025 Nov TI - Comparative effectiveness of OW GLP-1 RAs and other glucose-lowering therapies among Medicare beneficiaries with T2D and ASCVD. PG - 112473 LID - S0168-8227(25)00487-5 [pii] LID - 10.1016/j.diabres.2025.112473 [doi] AB - AIMS: To compare the incidence rates for cardiovascular (CV) outcomes and healthcare resource utilization (HCRU) and costs among patients treated with once-weekly (OW) glucagon-like peptide-1 receptor agonists (GLP-1 RAs) compared with other non-insulin glucose lowering therapies (ONIGLTs). METHODS: This was an observational cohort study using Medicare fee-for-service claims data (2006-2022). Medicare beneficiaries with T2D and ASCVD treated with OW GLP-1 RAs or ONIGLTs were matched using propensity score matching. RESULTS: Among the total 398,470 Medicare beneficiaries, OW GLP-1 RAs were associated with reduced risk of CV events (hazard ratios [HRs] range: 0.72 to 0.88, P < 0.05 for all) compared with ONIGLTs, in addition to lower HCRU and costs including ASCVD-related total medical visits (incidence rate ratio [95 % CI]: 0.91 [0.90-0.93]; P < 0.001) and total medical costs (mean cost ratio [95 %CI]: 0.88 [0.86-0.91]; P < 0.001). Among OW GLP-1 RAs, semaglutide had the lowest risk of all CV outcomes when compared with SGLT2is (HRs range: 0.80 to 0.85, P < 0.05 for all) and DPP-4is (HRs range: 0.58 to 0.73; P < 0.001 for all). CONCLUSION: The study findings corroborate current guideline recommendations for GLP-1 RAs in people with T2D and ASCVD, and extend findings to lower HCRU and costs in a real-world setting, most notably for semaglutide. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Tan, Xi AU - Tan X AD - Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ 08536, USA. FAU - Harton, Joanna AU - Harton J AD - Genesis Research Group, 111 River St Ste 1120, Hoboken, NJ 07030, USA. FAU - Gutierrez, Cynthia AU - Gutierrez C AD - Genesis Research Group, 111 River St Ste 1120, Hoboken, NJ 07030, USA. FAU - Liang, Yuanjie AU - Liang Y AD - Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ 08536, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ 08536, USA. FAU - Muhammad, Chalak AU - Muhammad C AD - Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ 08536, USA. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk Inc., 800 Scudders Mill Rd, Plainsboro, NJ 08536, USA. FAU - de Havenon, Adam AU - de Havenon A AD - Department of Neurology, Center for Brain and Mind Health, Yale University, 15 York St, New Haven, CT 06510, USA. Electronic address: adam.dehavenon@yale.edu. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20250909 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - United States/epidemiology MH - Medicare/statistics & numerical data MH - Female MH - Male MH - Aged MH - *Hypoglycemic Agents/therapeutic use/economics/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/complications/economics/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Aged, 80 and over OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Glucagon-like peptide-1 receptor agonists OT - Healthcare cost OT - Major adverse cardiovascular events OT - Semaglutide OT - Type 2 diabetes COIS- Declaration of competing interest AdH reports NIH/NINDS funding (K23NS105924, R01NS130189, UG3NS130228, R21NS138995), has received investigator-initiated clinical research funding from the AAN, receives consultant fees from Novo Nordisk, receives royalty fees from UpToDate, and has equity in Titin KM and Certus. XT, YL, LX, CM, and CS are employees of Novo Nordisk Inc. JH and CG are employees of Genesis Research Group. EDAT- 2025/09/12 00:29 MHDA- 2025/10/31 00:29 CRDT- 2025/09/11 19:11 PHST- 2025/04/30 00:00 [received] PHST- 2025/08/28 00:00 [revised] PHST- 2025/09/07 00:00 [accepted] PHST- 2025/10/31 00:29 [medline] PHST- 2025/09/12 00:29 [pubmed] PHST- 2025/09/11 19:11 [entrez] AID - S0168-8227(25)00487-5 [pii] AID - 10.1016/j.diabres.2025.112473 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Nov;229:112473. doi: 10.1016/j.diabres.2025.112473. Epub 2025 Sep 9. PMID- 40933383 OWN - NLM STAT- MEDLINE DCOM- 20250915 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Effect of semaglutide on arrhythmic, major cardiovascular, and microvascular outcomes in patients with type 2 diabetes: a systematic review and meta-analysis. PG - 1554795 LID - 10.3389/fendo.2025.1554795 [doi] LID - 1554795 AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promise in managing hyperglycemia and reducing cardiovascular (CV) outcomes. However, its effects on arrhythmic, major CV, and microvascular outcomes remain uncertain. This systematic review and meta-analysis aimed to evaluate these outcomes in patients with type 2 diabetes (T2D) treated with semaglutide. METHODS: We searched the PubMed, Embase, and Cochrane databases for eligible randomized controlled trials (RCTs) reported up to November 2024. We performed a meta-analysis via a random-effects model to estimate overall relative risks (RRs) with 95% confidence intervals (CIs) for arrhythmic, major CV, and microvascular outcomes. We conducted subgroup analyses on the basis of different administration types, treatment comparisons, and treatment durations. Additionally, we performed a meta-regression for retinopathy complications on the basis of baseline patient characteristics. RESULTS: This meta-analysis included 30 RCTs encompassing 32490 patients with T2D. Compared with the controls, semaglutide significantly reduced the incidence of atrial fibrillation (AF) (RR 0.73, 95% CI 0.54 to 0.98), complete atrioventricular (AV) block (RR 0.22, 95% CI 0.06 to 0.80), death from CV causes (RR 0.76, 95% CI 0.58 to 0.98), and revascularization (RR 0.68, 95% CI 0.52 to 0.88). Subgroup analyses revealed that semaglutide (long-term treatment) reduced the risk of AF, supraventricular tachycardia, and complete AV block. Meta-regression analysis revealed that the heterogeneity of retinopathy complications was not associated with baseline patient characteristics. CONCLUSION: Semaglutide reduces the risk of AF, complete AV block, death from CV causes, and revascularization in patients with T2D, with long-term treatment showing greater benefits for arrhythmic outcomes. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024618146. CI - Copyright (c) 2025 Wu, Xing, Huang, Zhou, Sun, Yu and Wang. FAU - Wu, Rui AU - Wu R AD - School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, Liaoning, China. AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Xing, Bo AU - Xing B AD - School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, Liaoning, China. AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Huang, Yuting AU - Huang Y AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Zhou, Zijun AU - Zhou Z AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Sun, Boxuan AU - Sun B AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Yu, Liming AU - Yu L AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. FAU - Wang, Huishan AU - Wang H AD - School of Life Sciences and Biopharmaceuticals, Shenyang Pharmaceutical University, Shenyang, Liaoning, China. AD - State Key Laboratory of Frigid Zone Cardiovascular Disease, Department of Cardiovascular Surgery, General Hospital of Northern Theater Command, Shenyang, Liaoning, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250826 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Diseases/etiology/drug therapy/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - *Arrhythmias, Cardiac/drug therapy/etiology/prevention & control MH - Randomized Controlled Trials as Topic MH - *Microvessels/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12417197 OTO - NOTNLM OT - arrhythmic OT - cardiovascular OT - meta-analysis OT - microvascular OT - semaglutide OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/09/11 18:29 MHDA- 2025/09/16 00:32 PMCR- 2025/08/26 CRDT- 2025/09/11 12:35 PHST- 2025/01/10 00:00 [received] PHST- 2025/08/15 00:00 [accepted] PHST- 2025/09/16 00:32 [medline] PHST- 2025/09/11 18:29 [pubmed] PHST- 2025/09/11 12:35 [entrez] PHST- 2025/08/26 00:00 [pmc-release] AID - 10.3389/fendo.2025.1554795 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Aug 26;16:1554795. doi: 10.3389/fendo.2025.1554795. eCollection 2025. PMID- 40933382 OWN - NLM STAT- MEDLINE DCOM- 20250915 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - The impact of oral semaglutide on glycemic control and weight reduction: a database analysis of dosing effects in Japanese individuals with type 2 diabetes. PG - 1615516 LID - 10.3389/fendo.2025.1615516 [doi] LID - 1615516 AB - OBJECTIVE: GLP-1 receptor agonists (GLP-1 RAs) reduce cardiovascular events in type 2 diabetes (T2D), and oral formulations improve accessibility. However, their real-world effectiveness and predictors of response remain unclear. This study assessed the proportions of individuals achieving HbA1c < 7.0% and experiencing >/=3.0% weight reduction after 180 days of maintenance-dose therapy (no dose modification for >/=180 days). METHODS: We retrospectively analyzed 169 participants with T2D (3 mg: n=45; 7 mg: n=92; 14 mg: n=32) treated at a single medical care center in Japan. The cohort included participants with HbA1c >/= 7.0% at baseline. We evaluated semaglutide changes in HbA1c and weight, and predictors of glycemic response after 180 days of maintenance therapy using logistic regression. RESULTS: Baseline characteristics included median age 63.0 years, body mass index (BMI) 27.2 kg/m(2), diabetes duration 10.0 years, and HbA1c 7.7%. Oral semaglutide was initiated as the first or second choice in 45.0% of participants. HbA1c < 7.0% was achieved in 60.0%, 53.3%, and 46.9% of the 3 mg, 7 mg, and 14 mg groups, respectively. Weight reduction >/= 3.0% occurred in approximately half of participants across all groups. Lower baseline HbA1c (B = -1.330, p < 0.001) and earlier semaglutide use (first/second choice; B = 1.070, p = 0.013) were significant predictors of HbA1c < 7.0%. CONCLUSION: Approximately 50% of participants across all dosing groups achieved HbA1c < 7.0% after 180 days of maintenance therapy. Weight reduction (>/= 3.0%) occurred frequently in parallel with HbA1c reduction. Early semaglutide use (first/second choice) and lower baseline HbA1c predicted HbA1c < 7.0% on maintenance therapy. CI - Copyright (c) 2025 Ishiguro and Nishimura. FAU - Ishiguro, Mizuki AU - Ishiguro M AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. FAU - Nishimura, Rimei AU - Nishimura R AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20250826 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects MH - Databases, Factual MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/administration & dosage MH - Glycated Hemoglobin/analysis MH - *Glycemic Control/methods MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Japan/epidemiology MH - Retrospective Studies MH - *Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12417148 OTO - NOTNLM OT - GLP-1 receptor agonists OT - HbA1c OT - oral antidiabetic drugs OT - semaglutide OT - type 2 diabetes COIS- The authors of this manuscript have the following competing interests: RN has received honoraria from Sanofi Co., Ltd., Japan Medtronic Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Teijin, Kissei Pharmaceutical Co., Ltd., Abbott, Eli Lilly Japan Co., Ltd., Novo Nordisk Pharma Co., Ltd., and Astellas Pharma Inc. RN has also received research funding from Kowa Co., Ltd. and Mitsubishi Electric Corporation. In addition, commercial entities have endowed departments with which RN is affiliated, including Taisho Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Mitsubishi Electric Corporation, Nippon Boehringer Ingelheim Co., Ltd., Abbott, Arkley Co., Ltd., and Kowa Co., Ltd. The remaining author declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/09/11 18:30 MHDA- 2025/09/15 18:34 PMCR- 2025/08/26 CRDT- 2025/09/11 12:35 PHST- 2025/04/21 00:00 [received] PHST- 2025/08/04 00:00 [accepted] PHST- 2025/09/15 18:34 [medline] PHST- 2025/09/11 18:30 [pubmed] PHST- 2025/09/11 12:35 [entrez] PHST- 2025/08/26 00:00 [pmc-release] AID - 10.3389/fendo.2025.1615516 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Aug 26;16:1615516. doi: 10.3389/fendo.2025.1615516. eCollection 2025. PMID- 40931739 OWN - NLM STAT- MEDLINE DCOM- 20250911 LR - 20250912 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 80 IP - 9 DP - 2025 Sep TI - [Tirzepatide (Mounjaro(R)) : a GIP/GLP-1 receptor dual agonist for the treatment of type 2 diabetes]. PG - 618-624 AB - Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, recently commercialized and reimbursed in Belgium for the treatment of type 2 diabetes (T2D). Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg as a once-weekly subcutaneous injection), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, semaglutide 1 mg, basal insulin and preprandial boluses of insulin lispro in six studies of the SURPASS programme. Tirzepatide tolerance is almost similar to that of pure GLP-1 receptor agonists, with digestive adverse events, most often during the first weeks after initiation, which justifies the recommendation of progressive titration every four weeks. Tirzepatide is now refunded under conditions in Belgium for the treatment of TD2 in patients with a body mass index >/= 30 kg/m(2) and a HbA1c level > 7.5 % with antihyperglycaemic therapy including metformin. These reimbursement conditions are similar to those of pure GLP-1 receptor agonists but are more restrictive than the indications validated by the European Medicines Agency and the latest guidelines by international scientific societies. FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. AD - Unite de Pharmacologie clinique, Centre Interdisciplinaire de Recherche sur le Medicament (CIRM), Liege Universite, Belgique. LA - fre PT - English Abstract PT - Journal Article PT - Review TT - Le medicament du mois. Le tirzepatide (Mounjaro(R))▼: un agoniste double des recepteurs GIP/GLP-1 pour le traitement du diabete de type 2. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Tirzepatide MH - *Gastric Inhibitory Polypeptide/therapeutic use/analogs & derivatives MH - *Glucagon-Like Peptide 1/analogs & derivatives/therapeutic use OTO - NOTNLM OT - Body Weight OT - GIP/GLP-1 dual agonist OT - Glycated Haemoglobin OT - Obesity OT - Tirzepatide OT - Type 2 diabetes EDAT- 2025/09/11 06:28 MHDA- 2025/09/11 06:29 CRDT- 2025/09/11 03:52 PHST- 2025/09/11 06:29 [medline] PHST- 2025/09/11 06:28 [pubmed] PHST- 2025/09/11 03:52 [entrez] PST - ppublish SO - Rev Med Liege. 2025 Sep;80(9):618-624. PMID- 40926360 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Lower risk of cardiovascular events in patients initiated on semaglutide 2.4 mg in the real-world: Results from the SCORE study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World). PG - 6691-6704 LID - 10.1111/dom.70080 [doi] AB - AIMS: In this first interim analysis of the SCORE study, we investigated the risk of major adverse cardiovascular events (MACE) among individuals with atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity but without diabetes who initiated semaglutide 2.4 mg in real-world settings. MATERIALS AND METHODS: Individuals initiating semaglutide 2.4 mg aged >/=45 years with ASCVD and overweight/obesity but without diabetes were identified in a US database (01/01/2016-12/31/2023) and matched 1:2 to those not on semaglutide based on a non-parsimonious propensity-score model. The primary outcomes included revised 3-point MACE (rMACE-3: myocardial infarction, stroke, and all-cause mortality) and revised 5-point MACE (rMACE-5: rMACE-3, coronary revascularisation, and hospitalisation for heart failure). Secondary outcomes included MACE-3 and MACE-5, defined similarly to rMACE-3 and rMACE-5 but replacing all-cause mortality with cardiovascular-related mortality. Exploratory outcomes included incident type 2 diabetes, major adverse kidney events, and major obesity-related adverse events. RESULTS: A total of 9321 individuals on semaglutide 2.4 mg were matched to 18,642 individuals not on semaglutide; patient characteristics were well-balanced between cohorts. Over a mean follow-up of 200 days, semaglutide 2.4 mg was associated with significantly lower risks of rMACE-5 (hazard ratio: 0.55; p < 0.001), rMACE-3 (0.43; p < 0.001), MACE-5 (0.65; p < 0.001), and MACE-3 (0.58; p < 0.01). Semaglutide 2.4 mg was also associated with lower risks of all-cause mortality, cardiovascular-related mortality, hospitalisation for heart failure, and all exploratory outcomes. CONCLUSIONS: In this real-world study of US individuals with ASCVD and overweight/obesity but without diabetes, semaglutide 2.4 mg was associated with significantly reduced risk of MACEs and other obesity-related morbidities (NCT06874751). CI - (c) 2025 Novo Nordisk Inc and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Smolderen, Kim G AU - Smolderen KG AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. AD - Section of Psychology, Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Mena-Hurtado, Carlos AU - Mena-Hurtado C AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Zhao, Zhenxiang AU - Zhao Z AD - Novo Nordisk, Inc, Plainsboro Township, New Jersey, USA. FAU - Michalak, Wojciech AU - Michalak W AD - Novo Nordisk, Inc, Plainsboro Township, New Jersey, USA. FAU - Faurby, Mads AU - Faurby M AD - Novo Nordisk, Inc, Plainsboro Township, New Jersey, USA. FAU - Smolarz, B Gabriel AU - Smolarz BG AUID- ORCID: 0000-0002-8591-3858 AD - Novo Nordisk, Inc, Plainsboro Township, New Jersey, USA. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. FAU - Song, Jinlin AU - Song J AD - Analysis Group, Inc, Los Angeles, California, USA. FAU - Chen, Yan AU - Chen Y AUID- ORCID: 0000-0002-5317-1909 AD - Analysis Group, Inc, Los Angeles, California, USA. FAU - Boland, Joanna AU - Boland J AD - Analysis Group, Inc, Los Angeles, California, USA. FAU - Nanna, Michael G AU - Nanna MG AUID- ORCID: 0000-0001-5745-1636 AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA. LA - eng SI - ClinicalTrials.gov/NCT06874751 GR - K76 AG088428/AG/NIA NIH HHS/United States GR - P30 AG021342/AG/NIA NIH HHS/United States GR - Novo Nordisk, Inc./ PT - Journal Article PT - Observational Study DEP - 20250909 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Atherosclerosis/complications/epidemiology MH - *Cardiovascular Diseases/epidemiology/prevention & control/etiology MH - Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Obesity/complications/drug therapy/epidemiology MH - *Overweight/complications/drug therapy/epidemiology MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12515752 OTO - NOTNLM OT - GLP-1 OT - cardiovascular disease OT - cohort study OT - observational study OT - real-world evidence OT - semaglutide COIS- Zhenxiang Zhao, Wojciech Michalak, Mads Faurby, and B. Gabriel Smolarz are employees of Novo Nordisk, Inc. and hold stock/options. Jinlin Song, Yan Chen, and Joanna Boland are employees of Analysis Group, Inc., which has received consulting fees from Novo Nordisk, Inc. for this work. Kim G. Smolderen receives research grants from Johnson & Johnson, Merck, and Abbott. She is a consultant for Dario Health, Terumo, Novo Nordisk, and Merck. She is the owner of BoboDream LLC. She receives funding from the National Institutes of Health (R01HL163640-03S1; R01HL163640-02S1; R21AT012430-01). Carlos Mena-Hurtado is a consultant for Terumo, Novo Nordisk, and Cook. He receives research grants from Merck, Shockwave, and the National Institutes of Health. Michael G. Nanna: Dr. Nanna reports current research support from the American College of Cardiology Foundation supported by the George F. and Ann Harris Bellows Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342), and the National Institute on Aging (K76AG088428). Dr. Nanna also reports being a consultant for Novo Nordisk, Heartflow, and Merck. Mikhail N. Kosiborod has served as a consultant or on an advisory board for 35Pharma, Alnylam, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pfizer, Pharmacosmos, Regeneron, Roche, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor, and Youngene Therapeutics; has received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer; holds stock options in Artera Health and Saghmos Therapeutics; has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; has received other research support from AstraZeneca and Vifor; and is employed by AstraZeneca R&D, effective January 6, 2025. EDAT- 2025/09/10 06:29 MHDA- 2025/10/13 00:27 PMCR- 2025/10/13 CRDT- 2025/09/10 01:03 PHST- 2025/08/18 00:00 [revised] PHST- 2025/07/17 00:00 [received] PHST- 2025/08/20 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/09/10 06:29 [pubmed] PHST- 2025/09/10 01:03 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - DOM70080 [pii] AID - 10.1111/dom.70080 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6691-6704. doi: 10.1111/dom.70080. Epub 2025 Sep 9. PMID- 40912924 OWN - NLM STAT- MEDLINE DCOM- 20251008 LR - 20260127 IS - 1444-2892 (Electronic) IS - 1443-9506 (Linking) VI - 34 IP - 10 DP - 2025 Oct TI - Real-World Prescribing of Renal and Cardiovascular Protective Drugs in Patients With Type 2 Diabetes and Chronic Kidney Disease: Analysis of Data From a Western Australian Quaternary Hospital. PG - 1089-1097 LID - S1443-9506(25)01554-9 [pii] LID - 10.1016/j.hlc.2025.07.007 [doi] AB - BACKGROUND: In patients with type 2 diabetes (T2D) and chronic kidney disease (CKD), sodium-glucose cotransporter 2 (SGLT2) inhibitors, semaglutide (glucagon-like peptide-1 [GLP-1] agonist), and finerenone (non-steroidal mineralocorticoid receptor antagonist) improve renal and cardiovascular outcomes. We assessed real-world prescribing of these drugs in patients with T2D and CKD. METHOD: The ReDiCare project retrospectively identified patients with T2D and CKD admitted to an Australian hospital between January 2020 and September 2024 using International Statistical Classification of Diseases and Related Health Problems 10th Revision Australian Modification codes. CKD was also defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m(2) for >3 months. Patients with an eGFR <15 mL/min/1.73 m(2), acute kidney injury, renal transplant, or those receiving dialysis were excluded. Drugs prescribed at discharge were obtained. RESULTS: Of 2,216 patients (mean age 78.2+/-10.9 years and 41.3% female), an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker was prescribed in 1,243 (56.1%) patients, an SGLT2 inhibitor in 472 (21.3%), a GLP-1 agonist in 163 (7.4%), and a mineralocorticoid receptor antagonist in 305 (13.8%). Specifically, semaglutide was prescribed in 79 (3.6%) patients and finerenone in three (0.1%). Overall, 735 (33.2%) patients were prescribed none, 919 (41.5%) one, 433 (19.5%) two, 115 (5.2%) three, and 14 (0.6%) all four drug groups. From January to March 2020 to July to September 2024, there was an increased prescribing of SGLT2 inhibitors (7.9%-38.7%; p<0.001) and GLP-1 agonists (6.3%-11.7%; p=0.007). CONCLUSIONS: In patients admitted to the hospital with T2D and CKD, one-quarter were prescribed an SGLT2 inhibitor and/or a GLP-1 agonist at discharge. Further studies are required to identify barriers and enablers to prescribing these drugs. CI - Copyright (c) 2025 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Lan, Nick S R AU - Lan NSR AD - Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, WA, Australia; Department of Cardiology, Fiona Stanley Hospital, Perth, WA, Australia; Medical School, The University of Western Australia, Perth, WA, Australia; Harry Perkins Institute of Medical Research, Perth, WA, Australia. Electronic address: nick.lan@uwa.edu.au. FAU - McFadden, Ben AU - McFadden B AD - Patient Safety and Clinical Quality, Clinical Excellence, Department of Health, Government of Western Australia, Perth, WA, Australia. FAU - Johnson, Andrew AU - Johnson A AD - Patient Safety and Clinical Quality, Clinical Excellence, Department of Health, Government of Western Australia, Perth, WA, Australia. FAU - Shedden, Phillip AU - Shedden P AD - Patient Safety and Clinical Quality, Clinical Excellence, Department of Health, Government of Western Australia, Perth, WA, Australia. FAU - Fegan, P Gerry AU - Fegan PG AD - Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, WA, Australia; Medical School, Curtin University, Perth, WA, Australia. FAU - Puttagunta, Harish AU - Puttagunta H AD - Department of Nephrology and Renal Transplant, Fiona Stanley Hospital, Perth, WA, Australia. FAU - Ho, Sharon AU - Ho S AD - Department of Nephrology and Renal Transplant, Fiona Stanley Hospital, Perth, WA, Australia; Department of Pharmacy, Fiona Stanley Hospital, Perth, WA, Australia. FAU - Gillett, Richard AU - Gillett R AD - Patient Safety and Clinical Quality, Clinical Excellence, Department of Health, Government of Western Australia, Perth, WA, Australia. FAU - Swaminathan, Ramyasuda AU - Swaminathan R AD - Department of Nephrology and Renal Transplant, Fiona Stanley Hospital, Perth, WA, Australia. FAU - Dwivedi, Girish AU - Dwivedi G AD - Centre of Excellence for Cardiometabolic Health, Fiona Stanley Hospital, Perth, WA, Australia; Department of Cardiology, Fiona Stanley Hospital, Perth, WA, Australia; Medical School, The University of Western Australia, Perth, WA, Australia; Harry Perkins Institute of Medical Research, Perth, WA, Australia; CardioInnovate Translational Lab - Western Australia, Victor Chang Cardiac Research Institute, Sydney, NSW, Australia. LA - eng PT - Journal Article DEP - 20250905 PL - Australia TA - Heart Lung Circ JT - Heart, lung & circulation JID - 100963739 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (finerenone) RN - 0 (Naphthyridines) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Female MH - Male MH - Aged MH - *Renal Insufficiency, Chronic/drug therapy/complications/epidemiology/physiopathology MH - Retrospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glomerular Filtration Rate MH - Mineralocorticoid Receptor Antagonists/therapeutic use MH - Western Australia/epidemiology MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Drug Prescriptions/statistics & numerical data MH - Follow-Up Studies MH - Naphthyridines OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - Diabetes OT - Implementation OT - Prevention OT - Risk factors COIS- Declaration of Competing Interests N.S.R.L. has received research funding from Sanofi as part of a Clinical Fellowship in Endocrinology and Diabetes, education support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, CSL Seqirus, Eli Lilly, Novartis, and Pfizer; speaker honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, and Sanofi; and has participated in advisory boards for Eli Lilly. S.H. has provided consultancy services to CSL Seqirus and has received education support from CSL Seqirus. G.D. reports paid lectures from AstraZeneca, Pfizer, and Amgen and provides consultancy services and has equity interest in Artrya Ltd. All other authors have no conflicts of interest to disclose. EDAT- 2025/09/06 00:35 MHDA- 2025/10/09 00:30 CRDT- 2025/09/05 21:51 PHST- 2025/04/29 00:00 [received] PHST- 2025/07/04 00:00 [revised] PHST- 2025/07/06 00:00 [accepted] PHST- 2025/10/09 00:30 [medline] PHST- 2025/09/06 00:35 [pubmed] PHST- 2025/09/05 21:51 [entrez] AID - S1443-9506(25)01554-9 [pii] AID - 10.1016/j.hlc.2025.07.007 [doi] PST - ppublish SO - Heart Lung Circ. 2025 Oct;34(10):1089-1097. doi: 10.1016/j.hlc.2025.07.007. Epub 2025 Sep 5. PMID- 40908778 OWN - NLM STAT- MEDLINE DCOM- 20250905 LR - 20260127 IS - 1752-8984 (Electronic) IS - 1479-1641 (Print) IS - 1479-1641 (Linking) VI - 22 IP - 5 DP - 2025 Sep-Oct TI - US eligibility and preventable cardiovascular disease events from semaglutide in type 2 diabetes. PG - 14791641251376551 LID - 10.1177/14791641251376551 [doi] LID - 14791641251376551 AB - BackgroundThe SUSTAIN-6 trial showed the cardiovascular disease (CVD) benefits of semaglutide among patients with type 2 diabetes mellitus (T2DM). We estimated the US population eligibility and preventable CVD events from semaglutide.MethodsUS adults with T2DM were selected from the National Health and Nutrition Examination Survey 2011-2020 based on SUSTAIN-6 eligibility criteria. We estimated composite and secondary CVD events from SUSTAIN-6 treated and placebo published event rates multiplied by the weighted US eligible population, the difference being the number of preventable events which was then divided by 2.1 years to provide annualized estimates.ResultsAmong 4755 (projected to 33.6 million [M]) adults with T2DM, 1132 (6.9 million) fit SUSTAIN-6 criteria. Compared to SUSTAIN-6, our sample more likely had female and black patients, shorter diabetes duration, and was less likely with prior CVD. We estimated 75,681 primary outcome CVD events, 128,329 expanded composite CVD events, 72,390 combined nonfatal MI, nonfatal stroke, and all-cause deaths, 36,195 non-fatal stroke events, 85,552 revascularizations, and 75,681 cases of nephropathy could be prevented annually if eligible T2DM subjects were on semaglutide.ConclusionSemaglutide may prevent over 75,000 CVD events annually if provided to eligible T2DM US adults. Efforts to improve use of these therapies are needed. FAU - Karthikeyan, Hridhay AU - Karthikeyan H AD - Mary and Steve Wen Cardiovascular Division, School of Medicine, University of California, Irvine, CA, USA. FAU - Fan, Wenjun AU - Fan W AD - Mary and Steve Wen Cardiovascular Division, School of Medicine, University of California, Irvine, CA, USA. AD - Center for Global Cardiometabolic Health and Nutrition, University of California, Irvine, CA, USA. FAU - Wong, Nathan D AU - Wong ND AUID- ORCID: 0000-0003-1102-7324 AD - Mary and Steve Wen Cardiovascular Division, School of Medicine, University of California, Irvine, CA, USA. AD - Center for Global Cardiometabolic Health and Nutrition, University of California, Irvine, CA, USA. LA - eng PT - Journal Article DEP - 20250904 PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/mortality MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Cardiovascular Diseases/prevention & control/diagnosis/epidemiology/mortality MH - Female MH - Middle Aged MH - United States/epidemiology MH - Male MH - *Eligibility Determination MH - Treatment Outcome MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Time Factors MH - Risk Assessment MH - Nutrition Surveys MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12413520 OTO - NOTNLM OT - GLP1 receptor agonists OT - cardiovascular disease OT - diabetes OT - semaglutide COIS- Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Wong receives research support from Amgen, Novartis, Novo Nordisk, and Regeneron and is an advisory board member for Amgen and consultant for Heart Lung, Novartis and Ionis. No other authors have any disclosures. EDAT- 2025/09/05 06:34 MHDA- 2025/09/05 06:35 PMCR- 2025/09/04 CRDT- 2025/09/05 02:54 PHST- 2025/09/05 06:35 [medline] PHST- 2025/09/05 06:34 [pubmed] PHST- 2025/09/05 02:54 [entrez] PHST- 2025/09/04 00:00 [pmc-release] AID - 10.1177_14791641251376551 [pii] AID - 10.1177/14791641251376551 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2025 Sep-Oct;22(5):14791641251376551. doi: 10.1177/14791641251376551. Epub 2025 Sep 4. PMID- 40903861 OWN - NLM STAT- MEDLINE DCOM- 20251105 LR - 20260904 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 12 DP - 2025 Dec TI - Weight loss interventions and obesity-associated cancers in people with type 2 diabetes and overweight/obesity: A real-world observational study. PG - 6914-6926 LID - 10.1111/dom.70090 [doi] AB - AIMS: To evaluate whether weight-loss interventions are associated with obesity-associated cancers (OAC) in individuals with overweight/obesity and type 2 diabetes (T2D). MATERIALS AND METHODS: This retrospective cohort study utilised the TriNetX federated research network. Three cohorts of adults with overweight/obesity and T2D, treated with either semaglutide, tirzepatide or bariatric surgery (BS) between June 2005 and June 2025, were propensity score matched (1:1) to cohorts treated with dipeptidyl peptidase-4 inhibitors (DPP-4i) using potential confounding factors. Using Cox regression analysis, we estimated hazard ratios (HRs) of composite and individual OAC: breast, colorectal, gallbladder, liver, multiple myeloma, oesophageal, ovarian, pancreatic, renal, gastric cardia, thyroid and uterine cancers. RESULTS: In 64,178 matched pairs (mean follow-up 911 days), semaglutide (vs. DPP-4i) was associated with lower rates of composite OAC (HR: 0.88; 95% CI: 0.82-0.95), colorectal (0.80; 0.67-0.97), liver (0.75; 0.60-0.95) and pancreatic (0.76; 0.60-0.96) cancers. In 19,682 matched pairs (mean follow-up 435 days), tirzepatide (vs. DPP-4i) was associated with a non-significant lower rate of composite OAC (0.84; 0.69-1.01) but a significant lower rate of ovarian cancer (0.31; 0.10-0.95). In 9642 matched pairs (mean follow-up 1746 days), BS (vs. DPP-4i) was associated with lower rates of composite OAC (0.85; 0.74-0.98), liver (0.56; 0.32-0.97) and uterine cancers (0.59; 0.38-0.90), and higher rates of gastric cardia cancer (10.54; 1.35-82.38) and oesophageal cancer (4.78; 1.04-21.87). CONCLUSIONS: Semaglutide and BS were associated with lower cancer rates in individuals with overweight/obesity and T2D, with non-significant lower rates also observed with tirzepatide. These findings suggest weight-loss interventions may contribute to cancer prevention in this population. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ipaye, Testimony AU - Ipaye T AUID- ORCID: 0009-0000-3190-4975 AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. AD - Leicester Cancer Research Centre, University of Leicester, Leicester, UK. FAU - Goldney, Jonathan AU - Goldney J AUID- ORCID: 0000-0001-8553-8296 AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Wilkinson, Thomas J AU - Wilkinson TJ AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Zaccardi, Francesco AU - Zaccardi F AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Yates, Thomas AU - Yates T AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AUID- ORCID: 0000-0002-9987-9371 AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. FAU - Brown, Karen AU - Brown K AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Cancer Research Centre, University of Leicester, Leicester, UK. FAU - Papamargaritis, Dimitris AU - Papamargaritis D AD - NIHR Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University of Leicester, Leicester, UK. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - NIHR Leicester Biomedical Research Centre/ GR - 223512/Z/21/Z/Wellcome Trust Leicestershire Healthcare Inequalities Improvement Doctoral Training Programme/ PT - Journal Article PT - Observational Study DEP - 20250903 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/complications/therapy/epidemiology MH - Middle Aged MH - Retrospective Studies MH - *Obesity/complications/therapy MH - *Overweight/complications/therapy MH - Male MH - *Neoplasms/epidemiology/etiology/prevention & control MH - Aged MH - Adult MH - Glucagon-Like Peptides/therapeutic use MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Bariatric Surgery MH - Weight Loss MH - *Weight Reduction Programs MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12587238 OTO - NOTNLM OT - TriNetX OT - bariatric surgery OT - cancer OT - obesity OT - overweight OT - semaglutide OT - tirzepatide OT - type 2 diabetes OT - weight loss COIS- D.P. has received honoraria for lectures from Novo Nordisk, Eli Lilly, Boehringer Ingelheim and Johnson & Johnson; consultancy fees from Regeneron; and research grants from Novo Nordisk, the Novo Nordisk UK Research Foundation, the Academy of Medical Sciences/Diabetes UK, and the National Institute for Health and Care Research (NIHR). MJD has acted as a consultant/advisor and speaker for Eli Lilly, Novo Nordisk and Sanofi, has attended advisory boards for AbbVie, Amgen, AstraZeneca, Biomea Fusion, Carmot/Roche, Daewoong Pharmaceutical, Sanofi, Zealand Pharma, Regeneron, GSK and EktaH, and as a speaker for AstraZeneca, Boehringer Ingelheim and Zuellig Pharma. She has received grants from AstraZeneca, Boehringer Ingelheim and Novo Nordisk. TJW has received consulting fees from Regeneron and Baxter Int. FZ has received consulting fees from Servier, Menarini and Daiichi Sankyo. TY has received investigated initiated funding from Astra Zeneca, has acted as a consultant for Regeneron, and has received contacted research funding from the Reinsurance Group of America. EDAT- 2025/09/04 06:37 MHDA- 2025/11/05 06:29 PMCR- 2025/11/05 CRDT- 2025/09/04 01:03 PHST- 2025/08/15 00:00 [revised] PHST- 2025/05/12 00:00 [received] PHST- 2025/08/22 00:00 [accepted] PHST- 2025/11/05 06:29 [medline] PHST- 2025/09/04 06:37 [pubmed] PHST- 2025/09/04 01:03 [entrez] PHST- 2025/11/05 00:00 [pmc-release] AID - DOM70090 [pii] AID - 10.1111/dom.70090 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Dec;27(12):6914-6926. doi: 10.1111/dom.70090. Epub 2025 Sep 3. PMID- 40897378 OWN - NLM STAT- MEDLINE DCOM- 20260106 LR - 20260305 IS - 1365-2133 (Electronic) IS - 0007-0963 (Linking) VI - 194 IP - 1 DP - 2026 Jan 6 TI - Glucagon-like peptide-1 receptor agonists and reduced mortality, cardiovascular and psychiatric risks in patients with psoriasis: a large-scale cohort study. PG - 59-66 LID - 10.1093/bjd/ljaf346 [doi] AB - BACKGROUND: Psoriasis is associated with a significant comorbidity burden, especially cardiovascular and metabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, used to treat obesity and diabetes, could potentially reduce comorbidities in patients with psoriasis. OBJECTIVES: To investigate all-cause mortality, cardiovascular, inflammatory and psychiatric outcomes, and adverse events in patients with psoriasis treated with GLP-1RAs. METHODS: This retrospective population-based cohort study used real-world data from the US TriNetX database. Patients with psoriasis who were treated for diabetes or obesity with a GLP-1RA during the follow-up period of 2 years were compared with those treated with other systemic antidiabetic or antiobesity drugs. After 1 : 1 propensity score matching for relevant risk factors, 3048 participants were included in each cohort. Primary outcomes included the risk of cardiometabolic, psychiatric and autoimmune sequelae of psoriasis, as well as all-cause mortality and potential adverse drug events. The analysis was repeated using cohorts without psoriasis and the results were further validated through two sensitivity analyses involving (i) later follow-up periods or (ii) the exclusion of patients with pustular psoriasis. RESULTS: In the matched cohorts of 3048 patients with psoriasis treated with a GLP-1RA [60.4% women, mean (SD) age 56.94 (12.02) years] vs. other antidiabetic and antiobesity drugs [61.9% women, mean (SD) age 56.42 (14.16) years], GLP-1RA treatment was associated with significantly decreased all-cause mortality [hazard ratio (HR) 0.219, 95% confidence interval (CI) 0.123-0.391; P < 0.001] and reduced risk of major adverse cardiac events (HR 0.561, 95% CI 0.442-0.714; P < 0.001). Additionally, lower risks for alcohol (HR 0.346, 95% CI 0.174-0.685; P = 0.009) and substance abuse (HR 0.510, 95% CI 0.350-0.743; P = 0.002) were found. Typical adverse drug events were not more frequent in the GLP-1RA cohort. The risk reductions were more pronounced in the cohorts with psoriasis than in those with obesity or diabetes without psoriasis. The findings were consistent across all sensitivity analyses. CONCLUSIONS: GLP-1RA treatment was safe and associated with reduced risks of cardiovascular and psychiatric comorbidities, as well as lower mortality in patients with psoriasis, with risk reductions markedly higher than in cohorts without psoriasis. Physicians should consider this drug class for patients with psoriasis and comorbid obesity or diabetes. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Olbrich, Henning AU - Olbrich H AUID- ORCID: 0000-0003-0863-7148 AD - Department of Dermatology, Allergy, and Venerology, University of Lubeck, Lubeck, Germany. FAU - Kridin, Khalaf AU - Kridin K AUID- ORCID: 0000-0001-9971-9151 AD - Unit of Dermatology and Skin Research Laboratory, Galilee Medical Center, Nahariya, Israel. AD - Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel. AD - Lubeck Institute of Experimental Dermatology, University of Lubeck, Lubeck, Germany. FAU - Zirpel, Henner AU - Zirpel H AUID- ORCID: 0000-0003-0053-4312 AD - Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lubeck, Germany. FAU - Hernandez, Gema AU - Hernandez G AD - TriNetX, LLC, Cambridge, MA, USA. AD - Biomedical Informatics Group Artificial Intelligence Department, E.T.S.I. Informaticos, Universidad Politecnica de Madrid, Madrid, Spain. FAU - Sadik, Christian D AU - Sadik CD AUID- ORCID: 0000-0001-6701-048X AD - Department of Dermatology, Allergy, and Venerology, University of Lubeck, Lubeck, Germany. FAU - Gaffal, Evelyn AU - Gaffal E AUID- ORCID: 0000-0002-4639-9841 AD - Department of Dermatology, Allergy, and Venerology, University of Lubeck, Lubeck, Germany. FAU - Thaci, Diamant AU - Thaci D AUID- ORCID: 0000-0001-8513-550X AD - Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lubeck, Germany. FAU - Ludwig, Ralf J AU - Ludwig RJ AUID- ORCID: 0000-0002-1394-1737 AD - Department of Dermatology, Allergy, and Venerology, University of Lubeck, Lubeck, Germany. AD - Lubeck Institute of Experimental Dermatology, University of Lubeck, Lubeck, Germany. AD - Comprehensive Center for Inflammation Medicine, University-Hospital Schleswig-Holstein, Lubeck, Germany. LA - eng GR - Cluster of Excellence 'Precision Medicine in Chronic Inflammation'/ GR - Deutsche Forschungsgemeinschaft/ GR - Schleswig-Holstein/ PT - Journal Article PL - England TA - Br J Dermatol JT - The British journal of dermatology JID - 0004041 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Br J Dermatol. 2026 Jan 6;194(1):5-6. doi: 10.1093/bjd/ljaf382. PMID: 41037492 MH - Humans MH - *Psoriasis/mortality/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Cardiovascular Diseases/prevention & control/mortality/epidemiology MH - *Obesity/drug therapy/mortality MH - Adult MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Glucagon-Like Peptides/therapeutic use MH - *Mental Disorders/prevention & control/epidemiology MH - Anti-Obesity Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Follow-Up Studies MH - Comorbidity MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OAB - Psoriasis is a common skin condition. It affects 2% to 3% of the world's population. People with psoriasis can have a higher risk of heart diseases and mental health conditions like depression. A new class of drugs called 'GLP-1RA' is being used to treat people with obesity and type 2 diabetes. These drugs have been effective in reducing risks of heart disease and suicidal thoughts. We are researchers from Germany, Israel and Spain. We used data from the USA to investigate whether patients with psoriasis could benefit from GLP-1RA treatment. We analysed electronic records collected by healthcare providers in the USA. Patients with psoriasis were selected. We then identified who was treated with GLP-1RA or with other drugs for diabetes and obesity. Next, we looked at how many of these patients developed heart, mental health and autoimmune conditions. Afterwards, we performed the same analysis with patients without psoriasis. We found that patients with psoriasis treated with GLP-1RA had a lower risk of dying. They also had lower risks of heart disease and alcohol or drug abuse. However, the risk was no different for unwanted drug effects or other autoimmune diseases. The risk reductions were higher than in people without psoriasis. Our study findings suggest that people with psoriasis could benefit from GLP-1RA treatment for obesity or type 2 diabetes. This could help lead clinicians to provide more treatment choices for people with psoriasis. OABL- eng EDAT- 2025/09/02 22:41 MHDA- 2026/01/06 19:17 CRDT- 2025/09/02 20:03 PHST- 2024/09/02 00:00 [received] PHST- 2025/07/22 00:00 [revised] PHST- 2025/08/27 00:00 [accepted] PHST- 2026/01/06 19:17 [medline] PHST- 2025/09/02 22:41 [pubmed] PHST- 2025/09/02 20:03 [entrez] AID - 8246223 [pii] AID - 10.1093/bjd/ljaf346 [doi] PST - ppublish SO - Br J Dermatol. 2026 Jan 6;194(1):59-66. doi: 10.1093/bjd/ljaf346. PMID- 40892617 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20260127 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 86 IP - 20 DP - 2025 Nov 18 TI - Sex Differences in Effectiveness of Semaglutide in Patients With Peripheral Artery Disease: The STRIDE Trial. PG - 1843-1857 LID - S0735-1097(25)07554-0 [pii] LID - 10.1016/j.jacc.2025.08.046 [doi] AB - BACKGROUND: Peripheral artery disease (PAD) is prevalent in women and men with type 2 diabetes (T2D). Sex-based differences exist in its epidemiology, clinical presentation, functional impact, outcomes, and potentially in responses to treatments. Recently, semaglutide 1.0 mg has been shown to improve functional outcomes and health-related quality of life in individuals with early symptomatic PAD and T2D in the STRIDE trial. OBJECTIVES: The objective of this study was to describe baseline characteristics, functional status, and therapeutic efficacy of once-weekly semaglutide 1.0 mg between females and males with PAD and T2D as a post hoc analysis from the STRIDE trial. METHODS: The primary endpoint in STRIDE was the ratio to baseline in maximum walking distance (MWD) at week 52 on a constant load treadmill. Confirmatory secondary endpoints included change in MWD at week 57, change in pain-free walking distance at week 52, and change in PAD-specific Vascular Quality of Life Questionnaire-6 total score from baseline to week 52. Herein, we report the outcomes analyzed by sex. RESULTS: Of 792 participants, 195 (24.6%) were female and 597 (75.4%) were male. Females were younger, had lower rates of smoking, lower prevalence of concomitant coronary artery disease and heart failure, and less frequent use of antiplatelet therapies compared with males. Geometric mean MWD at baseline was 187.3 m (coefficient of variation: 0.6) and 191.5 m (coefficient of variation: 0.6) in females and males, respectively. At week 52, there was a consistent improvement in MWD across sexes, which favored semaglutide treatment (P-interaction value = 0.65). At week 57, there was a consistent trend for improved MWD that favored semaglutide treatment for both females and males (P interaction = 0.53). Improvement in pain-free walking distance was consistent across sexes at week 52 in favor of semaglutide (P interaction = 0.80). Likewise, PAD-specific quality of life (assessed using Vascular Quality of Life Questionnaire-6) improvements with semaglutide in both sexes were consistent with the overall trial. CONCLUSIONS: In this post hoc analysis from STRIDE, semaglutide 1.0 mg exhibited consistent improvements in functional outcomes in people with early symptomatic PAD and T2D regardless of sex. Females with PAD demonstrated differences in baseline demographics and treatment patterns compared with males, highlighting the importance of sex-specific evaluation in PAD trials. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiovascular Surgery, St Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. Electronic address: subodh.verma@unityhealth.to. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Houlind, Kim AU - Houlind K AD - Horsens Regional Hospital, Horsens, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. FAU - Ludvik, Bernhard AU - Ludvik B AD - 1st Medical Department and Karl Landsteiner Institute of Obesity and Metabolic Disorders, Landstrasse Clinic, Vienna, Austria. FAU - Nordanstig, Joakim AU - Nordanstig J AD - Institute of Medicine, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Rasouli, Neda AU - Rasouli N AD - Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, Aurora, Colorado, USA. FAU - Sourij, Harald AU - Sourij H AD - Cardiometabolic Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. FAU - Thomas, Sebastian AU - Thomas S AD - Novo Nordisk GBS India, Bangalore, India. FAU - Norgaard, Sidse K AU - Norgaard SK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bonaca, Marc P AU - Bonaca MP AD - CPC Clinical Research and Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado, USA. Electronic address: marc.bonaca@cpcmed.org. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250831 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Peripheral Arterial Disease/drug therapy/epidemiology/physiopathology MH - Quality of Life MH - Sex Factors MH - Treatment Outcome MH - Walking/physiology MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - STRIDE OT - glucagon-like peptide-1 receptor agonist OT - peripheral artery disease OT - semaglutide OT - sex-based differences OT - type 2 diabetes COIS- Funding Support and Author Disclosures This work was supported by the trial sponsor; Novo Nordisk A/S, Denmark. Dr Verma has received payment or honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Heart Research Centre, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Humber River Health, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management, Sanofi, and Sun Pharma; has served on advisory boards for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, and Sanofi. Dr Catarig is an employee of and owns shares in Novo Nordisk. Dr Houlind has received payment or honoraria, along with travel support, to give a presentation at a workshop organized by LeMaitre. Dr Ludvik has received consulting fees, payment, or honoraria from Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; has received travel support from Novo Nordisk, with unpaid roles as a National Leader for the Novo Nordisk ESSENCE trial; is a National Leader for the Eli Lilly Triumph-Outcome Study; and is an advisor for an advisory board for the Austrian Obesity Society. Dr Nordanstig has received payment or honoraria from Novo Nordisk; has received travel support from Philips Medical and Abbott; has served on advisory boards for AstraZeneca, Novo Nordisk, and iThera Medical; and has a research grant from the Swedish Heart and Lung Foundation 2021-26, with unpaid roles as President of the Swedish Society for Vascular Surgery and the Swedish Councillor for the European Society for Vascular Surgery 2020-23. Dr Rasouli has served on advisory boards for Eli Lilly and Novo Nordisk; and has received research grants from Eli Lilly, Novo Nordisk, and Soma Scan. Dr Sourij has received payment or honoraria from Amarin, Amgen, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, and Novo Nordisk; has received travel support from Boehringer Ingelheim, Daiichi-Sankyo, and Novo Nordisk; and has served on advisory boards for Amarin, Amgen, Daiichi-Sankyo, Novartis, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, with unpaid roles as a board member of the Austrian Diabetes Association. Dr Thomas is an employee and shareholder at Novo Nordisk. Dr Norgaard is an employee of Novo Nordisk. Dr Bonaca is the Executive Director of the Colorado Prevention Center, a nonprofit academic research organization affiliated with the University of Colorado, that receives or has received research grant or consulting funding between August, 2021 and the present from: Abbott Laboratories, Agios Pharmaceuticals, Alexion Pharma, Alnylam Pharmaceuticals, Amgen, Angionetics, Anthos Therapeutics, Array BioPharma, AstraZeneca and Affiliates, Atentiv, Audentes Therapeutics, Bayer and Affiliates, Bristol Myers Squibb, Cambrian Biopharma, Cardiol Therapeutics, CellResearch, Cleerly, Cook Regentec, CSL Behring, Eidos Therapeutics, EP Trading, Epizon Pharma, Esperion Therapeutics, Everly Well, Exicon Consulting, Faraday Pharmaceuticals, Foresee Pharmaceuticals, Fortress Biotech, HDL Therapeutics, HeartFlow, Hummingbird Bioscience, Insmed, Ionis Pharmaceuticals, Janssen and Affiliates, Kowa Research Institute, Lexicon Pharmaceuticals, Medimmune, Merck and Affiliates, Nectero Medical, Novartis Pharmaceuticals, Novo Nordisk, Osiris Therapeutics, Pfizer, PhaseBio Pharmaceuticals, Prairie Education and Research Cooperative, Prothena Biosciences, Regeneron Pharmaceuticals, Regio Biosciences, Sanofi-Aventis Group, Silence Therapeutics, Smith & Nephew, Stealth BioTherapeutics, Tourmaline, VarmX, and Virta Health Corporation. EDAT- 2025/09/02 22:21 MHDA- 2025/11/13 06:30 CRDT- 2025/09/02 12:57 PHST- 2025/07/07 00:00 [received] PHST- 2025/08/15 00:00 [revised] PHST- 2025/08/19 00:00 [accepted] PHST- 2025/11/13 06:30 [medline] PHST- 2025/09/02 22:21 [pubmed] PHST- 2025/09/02 12:57 [entrez] AID - S0735-1097(25)07554-0 [pii] AID - 10.1016/j.jacc.2025.08.046 [doi] PST - ppublish SO - J Am Coll Cardiol. 2025 Nov 18;86(20):1843-1857. doi: 10.1016/j.jacc.2025.08.046. Epub 2025 Aug 31. PMID- 40892610 OWN - NLM STAT- MEDLINE DCOM- 20251113 LR - 20251209 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 86 IP - 20 DP - 2025 Nov 18 TI - Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of 99,599 Patients. PG - 1805-1819 LID - S0735-1097(25)07492-3 [pii] LID - 10.1016/j.jacc.2025.08.027 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant cardiovascular (CV) benefits, particularly in patients with diabetes mellitus, but the safety and efficacy of different GLP-1 RAs across diverse populations remain insufficiently defined. OBJECTIVES: Previous meta-analyses of GLP-1 RAs have been limited by restricted populations, omission of recent trials, or incomplete safety synthesis; this study integrates the latest evidence across 21 randomized controlled trials and diverse populations using advanced meta-analytic methods. METHODS: Randomized controlled trials comparing GLP-1 RAs vs controls or placebo were included. Analyses were conducted in prespecified subgroups based on the GLP-1 RA used. Prespecified subgroups according to diabetes mellitus, kidney function, obesity, or heart failure were also performed. Main outcomes comprised mortality (all-cause and CV), trial-defined major adverse cardiovascular events (MACE) and serious adverse events. GRADE (Grading of Recommendations Assessment, Development and Evaluation) and trial sequential analyses were performed to evaluate certainty and conclusiveness of findings, respectively. RESULTS: A total of 21 trials encompassing 99,599 patients were included. Eight different GLP-1 RAs were used (lixisenatide, liraglutide, exenatide, semaglutide, efpeglenatide, dulaglutide, albiglutide, and tirzepatide), each administered at therapeutic doses and compared vs placebo or controls. Mean follow-up duration was 2.4 years. We found conclusive, high-certainty evidence that GLP-1 RAs reduced all-cause death (incidence rate ratio [IRR]: 0.88; 95% CI: 0.84-0.92; needed to treat [NNT] = 121), CV death (IRR: 0.87; 95% CI: 0.81-0.92; NNT = 170), and MACE (IRR: 0.87; 95% CI: 0.83-0.91; NNT = 66), compared with controls. GLP-1 RAs reduced serious adverse events (-9%), myocardial infarction (-15%), acute kidney failure (-9%), heart failure (-15%), and infections (-10%), but increased gastrointestinal (+63%) and gallbladder (+26%) disorders. There were no differences in stroke, pancreatitis, or neoplasm between groups. Results were mostly consistent across subgroups. Analysis by GLP-1 RA type revealed potential differences in efficacy and safety profiles. CONCLUSIONS: GLP-1 RAs reduce mortality and MACE in high-risk populations, highlighting benefits beyond glycemic control. These come at increased gastrointestinal and gallbladder risks. Variation in efficacy and tolerability supports tailoring GLP-1 RA therapy to individual patient characteristics and treatment goals. (PROSPERO [GLP-1 RAs Reduce Mortality and Cardiovascular Events Across the Spectrum of Treated Patients: A Systematic Review and Meta-Analysis]; CRD420251032222). CI - Copyright (c) 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Galli, Mattia AU - Galli M AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; Cardiovascular Department, Maria Cecilia Hospital, GVM Care & Research, Cotignola, Italy. Electronic address: mattia.galli@uniroma1.it. FAU - Benenati, Stefano AU - Benenati S AD - Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, IRCCS Italian Cardiology Network, Genova, Italy. FAU - Laudani, Claudio AU - Laudani C AD - Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA. FAU - Simeone, Beatrice AU - Simeone B AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. FAU - Sarto, Gianmarco AU - Sarto G AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. FAU - Ortega-Paz, Luis AU - Ortega-Paz L AD - Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA. FAU - Rocco, Erica AU - Rocco E AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. FAU - Bernardi, Marco AU - Bernardi M AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. FAU - Spadafora, Luigi AU - Spadafora L AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. FAU - D'Amario, Domenico AU - D'Amario D AD - Department of Translational Medicine, Division of Cardiology, Universita del Piemonte Orientale, AOU Maggiore della Carita, Novara, Italy. FAU - Greco, Ernesto AU - Greco E AD - Department of Health and Life Sciences, European University of Rome, Rome, Italy. FAU - Frati, Giacomo AU - Frati G AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; IRCCS NeuroMed, Pozzilli, Italy. FAU - Federici, Massimo AU - Federici M AD - Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy. FAU - Mehran, Roxana AU - Mehran R AD - Center for Interventional Cardiovascular Research & Clinical Trials, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Crea, Filippo AU - Crea F AD - Center of Excellence of Cardiovascular Sciences, Ospedale Isola Tiberina - Gemelli Isola, Rome, Italy; Catholic University of the Sacred Heart, Rome, Italy. FAU - Angiolillo, Dominick J AU - Angiolillo DJ AD - Division of Cardiology, University of Florida College of Medicine-Jacksonville, Jacksonville, Florida, USA. FAU - Sciarretta, Sebastiano AU - Sciarretta S AD - Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; IRCCS NeuroMed, Pozzilli, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250827 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Cardiovascular Diseases/drug therapy/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic/methods OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular effects OT - efficacy OT - mortality OT - safety COIS- Funding Support and Author Disclosures Dr Galli has received consulting fees from Genomadix; is the principal investigator of the following active grant: Sapienza University of Rome (Grant protocol n. RG1241910F5A1A50); and is an associate editor at European Heart Journal. Dr Federici has received consulting fees or honoraria from Amgen, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Merck Sharp and Dohme, Novartis, Novo Nordisk, and Sanofi. Dr Mehran has received institutional research funding from Abbott, Abiomed, Alleviant Medical, AM-Pharma, Amgen, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi-Sankyo, Element Science, Faraday, Humacyte, Idorsia Pharmaceuticals, Janssen, Medtronic, Novartis, OrbusNeich, PhaseBio, Philips, Pi-Cardia, RenalPro, Shockwave, Vivasure, and Zoll; has received personal fees from Cine-Med Research and WebMD; has equity <1% in Applied Therapeutics, Elixir Medical, Stel, and ControlRad (spouse); serves on scientific advisory board for the American Medical Association, American College of Cardiology (board of trustees member), Society for Cardiovascular Angiography and Interventions (Women in Innovations committee member), and an associate editor at JAMA; and is unpaid faculty of the Cardiovascular Research Foundation. Dr Angiolillo has received consulting fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, CSL Behring, Daiichi-Sankyo, Eli Lilly, Faraday, Haemonetics, Janssen, Merck, Novartis, Novo Nordisk, PhaseBio, PLx Pharma, Pfizer, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Faraday, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co, Merck, Novartis, and the Scott R. MacKenzie Foundation. Dr Sciarretta has received honoraria for speeches and/or advisory board participation from Novo Nordisk. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2025/09/02 22:22 MHDA- 2025/11/13 12:32 CRDT- 2025/09/02 12:57 PHST- 2025/07/23 00:00 [received] PHST- 2025/08/13 00:00 [revised] PHST- 2025/08/13 00:00 [accepted] PHST- 2025/11/13 12:32 [medline] PHST- 2025/09/02 22:22 [pubmed] PHST- 2025/09/02 12:57 [entrez] AID - S0735-1097(25)07492-3 [pii] AID - 10.1016/j.jacc.2025.08.027 [doi] PST - ppublish SO - J Am Coll Cardiol. 2025 Nov 18;86(20):1805-1819. doi: 10.1016/j.jacc.2025.08.027. Epub 2025 Aug 27. PMID- 40892247 OWN - NLM STAT- MEDLINE DCOM- 20251223 LR - 20251226 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 62 IP - 12 DP - 2025 Dec TI - The impact of type 2 diabetes on aging: multidimensional approaches to preserve cognitive health. PG - 2223-2234 LID - 10.1007/s00592-025-02583-3 [doi] AB - The growing prevalence of type 2 diabetes (T2D) among older adults represents a major public health concern, given its association with accelerated cognitive decline and increased risk of neurodegenerative diseases. Several diabetes-related mechanisms, including chronic hyperglycaemia, oxidative stress, vascular dysfunction, and insulin resistance in the brain, negatively impact key cognitive domains, including memory and executive functions. These neuropathophysiological alterations are also linked to structural brain changes, contributing to vulnerability to dementia. This narrative review examines both established and emerging strategies aimed at counteracting the cognitive impact of T2D in aging populations. Traditional interventions, especially structured physical activity programs, have consistently demonstrated benefits for global cognitive functioning. In parallel, new pharmacological treatments, such as GLP-1 receptor agonists (e.g., semaglutide), not only improve glycemic control but may also exert neuroprotective effects. Multidomain approaches integrating metabolic management, nutritional optimization, physical exercise, and social engagement, such as those tested in the J-MIND-Diabetes study, have yielded promising outcomes in preserving cognitive functions. We argue that combining pharmacological and behavioral strategies holds significant potential for supporting cognitive health in elderly individuals with T2D. Such multimodal interventions may enhance resilience to cognitive decline, improve quality of life, and promote healthy brain aging in this at-risk population. CI - (c) 2025. The Author(s). FAU - Lucia, Stefania AU - Lucia S AUID- ORCID: 0000-0002-5033-2121 AD - Neuroscience Area, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy. slucia@sissa.it. FAU - Fornaro, Silvia AU - Fornaro S AD - Neuroscience Area, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy. FAU - Federici, Massimo AU - Federici M AD - Department of Systems Medicine, University of Roma Tor Vergata, 00133, Rome, Italy. FAU - Rumiati, Raffaella Ida AU - Rumiati RI AD - Neuroscience Area, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy. AD - Department of Systems Medicine, University of Roma Tor Vergata, 00133, Rome, Italy. LA - eng PT - Journal Article PT - Review DEP - 20250902 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/therapy/psychology MH - *Aging/physiology/psychology MH - *Cognition/physiology MH - *Cognitive Dysfunction/prevention & control MH - Exercise MH - Aged MH - Brain PMC - PMC12727764 OTO - NOTNLM OT - Aging OT - Cognition OT - Physical activity OT - Semaglutide OT - Type 2 diabetes COIS- Declarations. Conflict of interest: The authors declare no conflicts of interest. EDAT- 2025/09/02 22:20 MHDA- 2025/12/23 12:48 PMCR- 2025/09/02 CRDT- 2025/09/02 11:14 PHST- 2025/07/11 00:00 [received] PHST- 2025/08/13 00:00 [accepted] PHST- 2025/12/23 12:48 [medline] PHST- 2025/09/02 22:20 [pubmed] PHST- 2025/09/02 11:14 [entrez] PHST- 2025/09/02 00:00 [pmc-release] AID - 10.1007/s00592-025-02583-3 [pii] AID - 2583 [pii] AID - 10.1007/s00592-025-02583-3 [doi] PST - ppublish SO - Acta Diabetol. 2025 Dec;62(12):2223-2234. doi: 10.1007/s00592-025-02583-3. Epub 2025 Sep 2. PMID- 40889707 OWN - NLM STAT- MEDLINE DCOM- 20251204 LR - 20260527 IS - 1665-2681 (Print) IS - 1665-2681 (Linking) VI - 30 IP - 2 DP - 2025 Jul-Dec TI - Alterations in one-carbon metabolism in metabolic dysfunction associated steatotic liver disease may be modified by semaglutide. PG - 102107 LID - S1665-2681(25)00332-1 [pii] LID - 10.1016/j.aohep.2025.102107 [doi] AB - INTRODUCTION AND OBJECTIVES: Disruptions in one-carbon metabolism (OCM) have been linked to cardiometabolic diseases. We evaluated alterations in OCM metabolites and enzymes and the impact of semaglutide in MASLD. MATERIALS AND METHODS: Using targeted metabolomics and bulk-transcriptomics, we analyzed components of OCM in plasma samples and liver biopsies from MASLD patients (n = 100 with F0-F4 fibrosis, 51 % type 2 diabetes) and healthy controls (n = 50). Untargeted metabolomics and transcriptomics were used to analyze plasma and liver specimens from mice with diet-induced obesity and steatohepatitis (DIO-MASH) treated with vehicle or semaglutide compared with chow for 12 weeks. RESULTS: In patients with MASLD vs healthy controls, changes in the concentrations of folate and pyridoxal 5'-phosphate (vitamin B6), betaine, serine, and glycine suggested alteration to the activity of the transsulfuration pathway as well as the methionine and folate cycles. Increased concentrations of metabolites related to enhanced homocysteine conversion and elevated glutamate were also observed. These findings were supported by corresponding alterations in the activity of key enzymes. Similar patterns were identified in comparisons of patients with significant vs no/mild fibrosis and in DIO-MASH mice vs chow. Treatment with semaglutide led to reductions in body weight, hepatic inflammation, and fibrosis and largely reversed the metabolic and gene expression changes observed in DIO-MASH mice. CONCLUSIONS: MASLD may be linked to alterations in key metabolites and enzymes involved in OCM. The changes in humans were replicated in a MASLD mouse model, and reversal was found after treatment with semaglutide. CI - Copyright (c) 2025 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Werge, Mikkel Parsberg AU - Werge MP AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - McCann, Adrian AU - McCann A AD - Bevital AS, Bergen, Norway. FAU - Rashu, Elias Badal AU - Rashu EB AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Lam, Shi Min AU - Lam SM AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Hetland, Liv Eline AU - Hetland LE AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Thing, Mira AU - Thing M AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Nabilou, Puria AU - Nabilou P AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Junker, Anders Ellekaer AU - Junker AE AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Norlin, Jenny AU - Norlin J AD - Global Translation, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Veidal, Sanne AU - Veidal S AD - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Holst, Dorte AU - Holst D AD - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Bugge, Anne AU - Bugge A AD - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Viuff, Birgitte Martine AU - Viuff BM AD - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Hvid, Henning AU - Hvid H AD - Global Drug Discovery, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Bendtsen, Kristian M AU - Bendtsen KM AD - Digital Science & Innovation, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Mazzoni, Gianluca AU - Mazzoni G AD - Digital Science & Innovation, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Harder, Lea Moerch AU - Harder LM AD - Digital Science & Innovation, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Vyberg, Mogens AU - Vyberg M AD - Department of Pathology, Copenhagen University Hospital Hvidovre, Denmark; Center for RNA medicine, Aalborg University, Campus Copenhagen, Denmark. FAU - Serizawa, Reza AU - Serizawa R AD - Department of Pathology, Copenhagen University Hospital Hvidovre, Denmark. FAU - Bendtsen, Flemming AU - Bendtsen F AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark. FAU - Ueland, Per Magne AU - Ueland PM AD - Bevital AS, Bergen, Norway. FAU - Galsgaard, Elisabeth Douglas AU - Galsgaard ED AD - Global Translation, Novo Nordisk A/S, Novo Nordisk Park, Malov, Denmark. FAU - Wewer Albrechtsen, Nicolai J AU - Wewer Albrechtsen NJ AD - Clinical Proteomic Group, NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Dept Clinical Biochemistry, Copenhagen University Hospital Bispebjerg and Frederiksberg, Denmark. FAU - Gluud, Lise Lotte AU - Gluud LL AD - Gastro Unit, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark; Department of Clinical Medicine, University of Copenhagen, Denmark. Electronic address: lise.lotte.gluud.01@regionh.dk. LA - eng PT - Journal Article DEP - 20250830 PL - Mexico TA - Ann Hepatol JT - Annals of hepatology JID - 101155885 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Animals MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Male MH - *Liver/metabolism/pathology/drug effects MH - Female MH - Metabolomics/methods MH - Middle Aged MH - Disease Models, Animal MH - Mice, Inbred C57BL MH - Case-Control Studies MH - *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism/genetics/blood MH - Mice MH - Liver Cirrhosis/metabolism MH - Diabetes Mellitus, Type 2/complications MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Biomarker OT - GAN DIONASH OT - Keywords: Non-alcoholic steatohepatitis OT - Metabolomics OT - OCM OT - RNAseq OT - Semaglutide OT - Transcriptomics OT - mRNA COIS- Declaration of interests Lise Lotte Gluud has received consulting fees and payment or honoraria for lectures, presentations or manuscript writing from: Boehringer Ingelheim, Novo Nordisk, Pfizer, Gilead, AstraZeneca, Norgine, Sobi, Becton Dickinson, and Alexion. Jenny Norlin, Sanne Veidal, Dorte Holst, Anne Bugge, Lea Morch Harder, Gianluca Mazzoni, Birgitte Martine Viuff, Henning Hvid, Kristian Moss Bendtsen and Elisabeth Douglas Galsgaard are employed at Novo Nordisk A/S. EDAT- 2025/09/02 00:44 MHDA- 2025/12/05 01:02 CRDT- 2025/09/01 19:14 PHST- 2025/01/02 00:00 [received] PHST- 2025/06/04 00:00 [revised] PHST- 2025/06/13 00:00 [accepted] PHST- 2025/12/05 01:02 [medline] PHST- 2025/09/02 00:44 [pubmed] PHST- 2025/09/01 19:14 [entrez] AID - S1665-2681(25)00332-1 [pii] AID - 10.1016/j.aohep.2025.102107 [doi] PST - ppublish SO - Ann Hepatol. 2025 Jul-Dec;30(2):102107. doi: 10.1016/j.aohep.2025.102107. Epub 2025 Aug 30. PMID- 40887719 OWN - NLM STAT- MEDLINE DCOM- 20250901 LR - 20250904 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 17 IP - 9 DP - 2025 Sep TI - Impact of GLP-1 Receptor Agonists on Suicide Behavior: A Meta-Analysis Based on Randomized Controlled Trials. PG - e70151 LID - 10.1111/1753-0407.70151 [doi] LID - e70151 AB - BACKGROUND: This meta-analysis aims to assess the association between exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the incidence of suicidal behavior in patients with type 2 diabetes mellitus (T2DM)/obesity. METHODS: A comprehensive search of electronic databases, including PubMed, Web of Science, the Cochrane Library, and ClinicalTrials.gov, was conducted from the inception of the databases. The risk ratio (RR) and 95% confidence intervals (95% CI) were calculated. RESULTS: This meta-analysis included data from 25 randomized controlled trials (RCTs). The results indicated no significant difference in the incidence of suicidal behavior between the GLP-1 RA exposure group and the control group (RR = 0.84, 95% CI: 0.54-1.32, p = 0.46, I(2) = 0%). Subgroup analysis showed no significant differences in the incidence of suicidal behavior among participants with T2DM (RR = 0.74), obesity (RR = 1.07), adolescents (RR = 0.91), and adults (RR = 0.84). Additionally, no significant differences were observed between the two groups in any type of suicidal behavior, including suicidal ideation (RR = 1.04), suicide attempts (RR = 0.68), depression-related suicides (RR = 0.65), and completed suicides (RR = 1.06). There were also no significant differences between the groups for any type of GLP-1 RA, including dulaglutide (RR = 0.46), exenatide (RR = 0.98), semaglutide (RR = 0.82), lixisenatide (RR = 1.25), and liraglutide (RR = 0.92). No significant differences were observed between the exposure group and control group according to different comparators, including placebo (RR = 0.91) and others (RR = 1.08). All subgroup analyses showed p-values greater than 0.05 (two-sided tests) and I(2) values of 0%. CONCLUSION: Our findings suggest that there is no significant association between GLP-1 RA exposure and suicidal behaviors in patients with T2DM or obesity. CI - (c) 2025 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Chen, Jingqi AU - Chen J AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Zhang, Qiufeng AU - Zhang Q AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Wu, Qingping AU - Wu Q AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Zhang, Xiaoming AU - Zhang X AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Xiang, Zhiyi AU - Xiang Z AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Zhu, Sidong AU - Zhu S AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Dai, Tianfu AU - Dai T AD - The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China. FAU - Si, Yuexiu AU - Si Y AUID- ORCID: 0000-0002-3488-2860 AD - Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, China. LA - eng PT - Journal Article PT - Meta-Analysis PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Obesity/drug therapy/psychology MH - Suicidal Ideation MH - *Suicide/psychology/statistics & numerical data MH - Liraglutide/therapeutic use MH - Adult MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives PMC - PMC12399406 OTO - NOTNLM OT - GLP-1 RAs OT - meta-analysis OT - obesity OT - suicidal behavior OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2025/09/02 04:46 MHDA- 2025/09/02 04:47 PMCR- 2025/08/31 CRDT- 2025/09/01 00:04 PHST- 2025/07/16 00:00 [revised] PHST- 2025/04/09 00:00 [received] PHST- 2025/07/31 00:00 [accepted] PHST- 2025/09/02 04:47 [medline] PHST- 2025/09/02 04:46 [pubmed] PHST- 2025/09/01 00:04 [entrez] PHST- 2025/08/31 00:00 [pmc-release] AID - JDB70151 [pii] AID - 10.1111/1753-0407.70151 [doi] PST - ppublish SO - J Diabetes. 2025 Sep;17(9):e70151. doi: 10.1111/1753-0407.70151. PMID- 40886075 OWN - NLM STAT- MEDLINE DCOM- 20251014 LR - 20260223 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 334 IP - 14 DP - 2025 Oct 14 TI - Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. PG - 1255-1266 LID - 10.1001/jama.2025.14092 [doi] AB - IMPORTANCE: Heart failure with preserved ejection fraction (HFpEF) is a major cause of hospitalization, often occurring in patients with cardiometabolic comorbidities such as obesity and type 2 diabetes. Although early trials of semaglutide and tirzepatide have shown promising results in improving symptoms, those findings were based on few clinical events, leaving treatment recommendations uncertain. OBJECTIVE: To evaluate the effectiveness and safety of semaglutide and tirzepatide in patients with cardiometabolic HFpEF in clinical practice. DESIGN, SETTING, AND PARTICIPANTS: Five cohort studies using national US health care claims data from 2018 to 2024. Two cohort studies emulated the STEP-HFpEF DM (semaglutide) and SUMMIT (tirzepatide) trials to benchmark results. Eligibility criteria were then expanded to evaluate treatment effects in patients typically treated in clinical practice. Finally, a head-to-head comparison of tirzepatide and semaglutide was implemented. Follow-up was up to 52 weeks. EXPOSURES: New use of semaglutide, tirzepatide, or sitagliptin as a placebo proxy. MAIN OUTCOMES AND MEASURES: The primary end point was a composite of hospitalization for heart failure or all-cause mortality. Negative control outcomes, secondary end points, subgroups, and sensitivity analyses were prespecified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by fitting proportional hazards models with propensity score weighting to adjust for a comprehensive set of pretreatment patient characteristics. RESULTS: Benchmarking of the 2 trial emulations demonstrated high agreement on all prespecified metrics. In analyses using expanded eligibility criteria, 58 333 patients were included in the semaglutide vs sitagliptin cohort, 11 257 for tirzepatide vs sitagliptin, and 28 100 for tirzepatide vs semaglutide. Initiators of semaglutide (HR, 0.58 [95% CI, 0.51-0.65]) and tirzepatide (HR, 0.42 [95% CI, 0.31-0.57]) had substantially lower risk of the primary end point compared with sitagliptin. Tirzepatide had no meaningfully lowered risk compared with semaglutide (HR, 0.86 [95% CI, 0.70-1.06]). Negative controls, secondary end points, subgroups, and sensitivity analyses showed consistent results. No substantially increased risk was observed for select safety end points. CONCLUSIONS AND RELEVANCE: In patients with cardiometabolic HFpEF, semaglutide and tirzepatide showed more than 40% risk reduction for the composite of hospitalization for heart failure or all-cause mortality compared with a placebo proxy. Tirzepatide showed no meaningful benefit over semaglutide. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT06914102, NCT06914154, NCT06914141. FAU - Kruger, Nils AU - Kruger N AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. AD - Harvard Medical School, Boston, Massachusetts. AD - Department of Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany. AD - Deutsches Zentrum fur Herz- und Kreislauferkrankungen, Partner Site Munich Heart Alliance, Munich, Germany. FAU - Schneeweiss, Sebastian AU - Schneeweiss S AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. AD - Harvard Medical School, Boston, Massachusetts. FAU - Fuse, Kenshiro AU - Fuse K AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. AD - Harvard Medical School, Boston, Massachusetts. FAU - Matseyko, Sofiya AU - Matseyko S AD - Department of Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany. FAU - Sreedhara, Sushama Kattinakere AU - Sreedhara SK AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Hahn, Georg AU - Hahn G AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. AD - Harvard Medical School, Boston, Massachusetts. FAU - Schunkert, Heribert AU - Schunkert H AD - Department of Cardiology, German Heart Center Munich, Technical University of Munich, Munich, Germany. AD - Deutsches Zentrum fur Herz- und Kreislauferkrankungen, Partner Site Munich Heart Alliance, Munich, Germany. FAU - Wang, Shirley V AU - Wang SV AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. AD - Harvard Medical School, Boston, Massachusetts. LA - eng SI - ClinicalTrials.gov/NCT06914154 SI - ClinicalTrials.gov/NCT06914141 SI - ClinicalTrials.gov/NCT06914102 GR - R01 HL141505/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Observational Study PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - TS63EW8X6F (Sitagliptin Phosphate) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - doi: 10.1001/jama.2023.16674 CIN - doi: 10.1001/jama.2024.21051 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cohort Studies MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - *Heart Failure/drug therapy/etiology/mortality/physiopathology MH - Hospitalization/statistics & numerical data MH - Sitagliptin Phosphate/therapeutic use/adverse effects MH - Stroke Volume/physiology MH - *Tirzepatide/administration & dosage/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - *Glucagon-Like Peptide 1/administration & dosage/adverse effects MH - Follow-Up Studies MH - Obesity/complications/drug therapy MH - Administrative Claims, Healthcare/statistics & numerical data MH - Semaglutide PMC - PMC12400167 MID - NIHMS2138072 COIS- Conflict of Interest Disclosures: Dr Schneeweiss reported personal fees from Aetion Inc, a software-enabled analytics company, and grants from Bayer, UCB, and Boehringer Ingelheim to Brigham and Women's Hospital outside the submitted work. Dr Schunkert reported personal fees from AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, MSD, Novartis, Pharmacosmos, Sanofi, Servier, Synlab, Amgen, and Amarin outside the submitted work. Dr Wang reported personal fees from MITRE, a federally funded research and development center for the Centers for Medicare & Medicaid Services and personal fees from Cytel Inc during the conduct of the study. No other disclosures were reported. EDAT- 2025/09/02 04:46 MHDA- 2025/10/14 12:29 PMCR- 2026/03/03 CRDT- 2025/08/31 04:33 PHST- 2025/10/14 12:29 [medline] PHST- 2025/09/02 04:46 [pubmed] PHST- 2025/08/31 04:33 [entrez] PHST- 2026/03/03 00:00 [pmc-release] AID - 2838293 [pii] AID - joi250060 [pii] AID - 10.1001/jama.2025.14092 [doi] PST - ppublish SO - JAMA. 2025 Oct 14;334(14):1255-1266. doi: 10.1001/jama.2025.14092. PMID- 40889359 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260918 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 178 IP - 9 DP - 2025 Sep TI - In symptomatic peripheral artery disease with T2D, semaglutide increased maximum walking distance at 1 y. PG - JC100 LID - 10.7326/ANNALS-25-03196-JC [doi] AB - GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text] Endocrinology: [Formula: see text]. FAU - Ades, Matthew AU - Ades M AD - McGill University, Montreal, Quebec, Canada (M.A.). FAU - Anand, Sonia S AU - Anand SS AUID- ORCID: 0000-0003-3692-7441 AD - McMaster University, Hamilton, Ontario, Canada (S.S.A.). CN - ACP Journal Club Editorial Team at McMaster University LA - eng PT - Journal Article DEP - 20250902 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Peripheral Arterial Disease/drug therapy/physiopathology/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Female MH - *Walking MH - *Diabetes Mellitus, Type 2/complications/drug therapy/physiopathology MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/09/01 20:44 MHDA- 2025/09/16 18:31 CRDT- 2025/09/01 17:02 PHST- 2025/09/16 18:31 [medline] PHST- 2025/09/01 20:44 [pubmed] PHST- 2025/09/01 17:02 [entrez] AID - 10.7326/ANNALS-25-03196-JC [doi] PST - ppublish SO - Ann Intern Med. 2025 Sep;178(9):JC100. doi: 10.7326/ANNALS-25-03196-JC. Epub 2025 Sep 2. PMID- 40886061 OWN - NLM STAT- MEDLINE DCOM- 20260308 LR - 20260920 IS - 1522-9645 (Electronic) IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 47 IP - 10 DP - 2026 Mar 9 TI - Semaglutide promotes bone marrow-derived progenitor cell flux towards an anti-inflammatory and pro-regenerative profile in high-risk patients: the SEMA-VR CardioLink-15 trial. PG - 1171-1182 LID - 10.1093/eurheartj/ehaf690 [doi] AB - BACKGROUND AND AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce major atherosclerotic cardiovascular events in individuals living with either diabetes or obesity. Since the turnover of vascular regenerative (VR) stem and progenitor cells has been demonstrated to modulate vessel repair and atherothrombotic risk, this study aimed to determine the effect of the GLP-1RA semaglutide on the levels of circulating VR cells. METHODS: SEMA-VR CardioLink-15 was a randomized translational trial of usual care vs semaglutide for 6 months in 46 participants with either type 2 diabetes and/or obesity plus atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk factors. Vascular regenerative cells were enumerated using multi-parametric flow cytometry for high aldehyde dehydrogenase activity (ALDHhi) and lineage-specific cell surface marker expression. The primary endpoint was the 6-month change in VR cell content. RESULTS: Compared with usual care (n = 24), semaglutide (n = 22) led to a greater increase in the number of VR cells [high aldehyde dehydrogenase 1A1 activity and low side scatter (ALDHhiSSClow): +0.8% vs +34.8%; P = .036], pan-haematopoietic myeloid progenitors (ALDHhiSSClowCD45+: +2.8% vs +40.1%; P = .017), and endothelial precursors (ALDHhiSSClowCD34+ CD133+ CD45-: -2.3% vs +66.2%; P = .037) from baseline. Semaglutide also decreased granulocyte precursors (ALDHhiSSChi: +0.3% vs -50.8%; P = .002), particularly those expressing the neutrophil activation marker CD66b and chemokine receptor CXCR2. Semaglutide down-regulated serum proteins over-represented in pro-inflammatory tumour necrosis factor and interleukin signalling pathways. CONCLUSIONS: In people living with either type 2 diabetes or obesity plus ASCVD risk, semaglutide increased circulating VR cell content while reducing pro-inflammatory granulocyte precursors and cytokine production. Collectively, these findings suggest that semaglutide may improve endogenous progenitor cell-mediated blood vessel repair processes. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Park, Brady AU - Park B AUID- ORCID: 0000-0001-6629-285X AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. FAU - Dennis, Fallon AU - Dennis F AUID- ORCID: 0009-0008-7645-7599 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. FAU - He, Arianna Z AU - He AZ AUID- ORCID: 0009-0002-5998-4983 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. FAU - Krishnaraj, Aishwarya AU - Krishnaraj A AUID- ORCID: 0000-0003-3763-478X AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. FAU - Bakbak, Ehab AU - Bakbak E AUID- ORCID: 0000-0003-4687-6553 AD - Faculty of Medicine, University of Queensland, Brisbane, Australia. FAU - Dennis, Cole J AU - Dennis CJ AUID- ORCID: 0009-0000-1075-8139 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. FAU - Pan, Yi AU - Pan Y AUID- ORCID: 0009-0003-3383-1943 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. FAU - Misner, Elizabeth AU - Misner E AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. FAU - Thayanithy, Veena AU - Thayanithy V AD - North York Diagnostic and Cardiac Centre, Toronto, ON, Canada. AD - Legacy Medical Centre, Toronto, ON, Canada. FAU - Lambotharan, Bhavaani AU - Lambotharan B AD - Legacy Medical Centre, Toronto, ON, Canada. FAU - Lambotharan, Vaasudevan AU - Lambotharan V AD - Legacy Medical Centre, Toronto, ON, Canada. AD - North West of England School of Foundation Training and Physician Associates, Manchester, United Kingdom. FAU - Lambotharan, Aruna AU - Lambotharan A AD - Legacy Medical Centre, Toronto, ON, Canada. FAU - Mazer, C David AU - Mazer CD AUID- ORCID: 0000-0003-2566-4308 AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. AD - Department of Anesthesia, St. Michael's Hospital of Unity Health Toronto, Toronto, ON, Canada. AD - Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada. AD - Department of Physiology, University of Toronto, Toronto, ON, Canada. FAU - Quan, Adrian AU - Quan A AUID- ORCID: 0000-0001-8008-028X AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. FAU - Teoh, Hwee AU - Teoh H AUID- ORCID: 0000-0003-1036-4767 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Division of Endocrinology and Metabolism, St. Michael's Hospital of Unity Health Toronto, Toronto, ON, Canada. FAU - Hess, David A AU - Hess DA AUID- ORCID: 0000-0003-2186-3166 AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. AD - Department of Physiology and Pharmacology, Western University, London, ON, Canada. AD - Molecular Medicine Research Laboratories, Robarts Research Institute, London, ON, Canada. FAU - Verma, Subodh AU - Verma S AUID- ORCID: 0000-0002-4018-8533 AD - Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto M5B 1W8, ON, Canada. AD - Keenan Research Centre of Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, 209 Victoria Street, Toronto M5B 1X3, ON, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Toronto M5S 3K3, ON, Canada. AD - Department of Surgery, University of Toronto, 149 College Street, Toronto M5T 1P5, ON, Canada. LA - eng GR - 186065/CAPMC/CIHR/Canada PT - Journal Article PT - Randomized Controlled Trial PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - doi: 10.1093/eurheartj/ehaf983 MH - Humans MH - Male MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - *Stem Cells/drug effects MH - Aged MH - *Atherosclerosis/prevention & control/drug therapy MH - Obesity/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Regeneration/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC13016833 OTO - NOTNLM OT - Atherosclerosis OT - Cardiometabolic disease OT - GLP-1 receptor agonists OT - Obesity OT - Progenitor cell OT - Semaglutide EDAT- 2025/08/31 08:44 MHDA- 2026/03/09 00:36 PMCR- 2025/08/31 CRDT- 2025/08/31 02:23 PHST- 2025/07/06 00:00 [received] PHST- 2025/08/16 00:00 [revised] PHST- 2025/08/19 00:00 [accepted] PHST- 2026/03/09 00:36 [medline] PHST- 2025/08/31 08:44 [pubmed] PHST- 2025/08/31 02:23 [entrez] PHST- 2025/08/31 00:00 [pmc-release] AID - 8243693 [pii] AID - ehaf690 [pii] AID - 10.1093/eurheartj/ehaf690 [doi] PST - ppublish SO - Eur Heart J. 2026 Mar 9;47(10):1171-1182. doi: 10.1093/eurheartj/ehaf690. PMID- 40870438 OWN - NLM STAT- MEDLINE DCOM- 20250828 LR - 20260127 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 61 IP - 8 DP - 2025 Jul 31 TI - The Effectiveness of Semaglutide on a Composite Endpoint of Glycemic Control and Weight Reduction and Its Effect on Lipid Profile Among Obese Type 2 Diabetes Patients. LID - 10.3390/medicina61081393 [doi] LID - 1393 AB - Background and Objectives: Obesity and type 2 diabetes (T2D) are closely linked and associated with a higher risk of complications. This study aims to evaluate the effectiveness of once-weekly semaglutide in achieving a composite endpoint of A1C and weight reduction. Materials and Methods: This retrospective cohort study assessed the effectiveness of semaglutide in obese patients with T2D at a tertiary care hospital in Saudi Arabia. This study included patients who received semaglutide treatment for 12 months, and the endpoint was reducing A1C by >/= 1% and body weight by >/= 5% after 12 months of starting semaglutide. Secondary endpoints include predictors of achieving the composite endpoint and the effect on the lipid profile. Results: The present study enrolled 459 participants, with dyslipidemia and hypertension being the most common comorbidities. After 12 months of treatment with semaglutide, 42% of the patients achieved the composite endpoint. Semaglutide significantly reduced weight, BMI, A1C, FBG, total cholesterol, LDL, and triglycerides. The subgroup analysis showed that patients who achieved the composite endpoint were younger and had significantly lower use of insulin. Females in the study had significantly higher BMI, A1C, and HDL levels and lower levels of triglycerides compared to males. Multivariate analysis revealed that baseline BMI (aOR = 0.953; 95% CI: 0.915 to 0.992; p = 0.02), baseline A1C (aOR = 1.213; 95% CI: 1.062 to 1.385; p = 0.004), and receiving insulin (aOR = 0.02; 95% CI: 0.001 to 0.343; p = 0.007) were significant predictors of composite endpoint achievement. Conclusions: Semaglutide is a valuable option for the treatment of obese patients with T2D. This study found that semaglutide is effective in reducing weight and A1C and improving the lipid profile. The predictors of achievement of the composite endpoint were lower baseline BMI, higher baseline A1C, and insulin non-use. FAU - Alarfaj, Sumaiah J AU - Alarfaj SJ AUID- ORCID: 0000-0002-3144-8305 AD - Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia. LA - eng PT - Journal Article DEP - 20250731 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Lipids) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Obesity/drug therapy/complications MH - Saudi Arabia MH - *Glycemic Control/methods/standards/statistics & numerical data MH - *Weight Loss/drug effects MH - *Lipids/blood/analysis MH - Hypoglycemic Agents/therapeutic use MH - Adult MH - Aged MH - Glycated Hemoglobin/analysis MH - Cohort Studies MH - Blood Glucose/analysis/drug effects MH - Body Mass Index MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12387961 OTO - NOTNLM OT - A1C OT - Saudi OT - composite OT - diabetes mellitus OT - effectiveness OT - glucagon-like peptide-1 receptor agonist OT - lipid profile OT - semaglutide OT - type 2 OT - weight reduction COIS- The author declares no conflicts of interest. EDAT- 2025/08/30 04:50 MHDA- 2025/08/30 04:51 PMCR- 2025/07/31 CRDT- 2025/08/28 01:15 PHST- 2025/07/03 00:00 [received] PHST- 2025/07/25 00:00 [revised] PHST- 2025/07/28 00:00 [accepted] PHST- 2025/08/30 04:51 [medline] PHST- 2025/08/30 04:50 [pubmed] PHST- 2025/08/28 01:15 [entrez] PHST- 2025/07/31 00:00 [pmc-release] AID - medicina61081393 [pii] AID - medicina-61-01393 [pii] AID - 10.3390/medicina61081393 [doi] PST - epublish SO - Medicina (Kaunas). 2025 Jul 31;61(8):1393. doi: 10.3390/medicina61081393. PMID- 40849680 OWN - NLM STAT- MEDLINE DCOM- 20250824 LR - 20260127 IS - 1941-5923 (Electronic) IS - 1941-5923 (Linking) VI - 26 DP - 2025 Aug 24 TI - Semaglutide Overdose in a Diabetic Patient: Suicidal Behavior and Multiorgan Failure. PG - e947682 LID - 10.12659/AJCR.947682 [doi] LID - e947682 AB - BACKGROUND Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained popularity in recent years. Consequently, Semaglutide prescription rates have increased for both its indicated and off-label uses. A possible link between GLP-1 RAs and suicidal behavior has been proposed. CASE REPORT We describe a rare case of suicide-related behavior, adverse outcomes, and a self-injected Semaglutide overdose in a 67-year-old man with diabetes mellitus and overweight. The patient had been on a weekly 1-mg Semaglutide regimen for 1 year prior to hospitalization. He presented with multiorgan failure, hypoglycemia, cholestatic liver dysfunction, and 2 duodenal ulcers, and reported weakness, appetite loss, epigastric pain, severe diarrhea, and melena over 2 weeks, and syncope the day before admission. His clinical status improved gradually, including duodenal ulcers upon discharge. In further questioning, the patient recalled feeling moody and injecting his monthly Semaglutide prescription all at 1 time, 14 days before admission. The self-injection of an overdose 4 times greater than permitted may be considered suicidal behavior for 6 reasons: (1) Semaglutide treatment began more than 1 year before the event; (2) The patient was experienced in self-injecting; (3) A single injection is limited to the weekly recommended dose; (4) If multiple injections exceed the pre-filled monthly amount, an overdose might occur; (5) Semaglutide application by pen is very safe; and (6) He reported being dysphoric prior to the event. CONCLUSIONS Patients receiving GLP-1 Ras, such as Semaglutide, should be screened for common mental disorders in clinical practice. Also, we suggest multiorgan failure should be excluded in Semaglutide-treated patients with acute illness onset. FAU - Zamir, Doron AU - Zamir D AD - Department of Internal Medicine D, Barzilai University Medical Center, Ashkelon, Israel. AD - Faculty of Health Sciences, Ben-Gurion University of Negev, Beersheba, Israel. FAU - Ovadia, Yaniv S AU - Ovadia YS AD - Department of Internal Medicine D, Barzilai University Medical Center, Ashkelon, Israel. AD - Research and Development Authority, Barzilai University Medical Center, Ashkelon, Israel. FAU - Ben-Bassat, Ofer AU - Ben-Bassat O AD - Gastroenterology Institute, Barzilai University Medical Center, Ashkelon, Israel. FAU - Zamir, Mariana AU - Zamir M AD - Division of Dermatology, Sheba Medical Center, Tel Hashomer, Israel. FAU - Malnick, Stephen D H AU - Malnick SDH AD - Department of Internal Medicine C, Kaplan Medical Center, Rehovot, Israel. AD - Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. LA - eng PT - Case Reports PT - Journal Article DEP - 20250824 PL - United States TA - Am J Case Rep JT - The American journal of case reports JID - 101489566 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Aged MH - *Glucagon-Like Peptides/adverse effects/poisoning/administration & dosage MH - *Drug Overdose MH - *Hypoglycemic Agents/poisoning/adverse effects MH - *Multiple Organ Failure/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Suicide, Attempted MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12396086 COIS- Conflict of interest: None declared EDAT- 2025/08/30 04:49 MHDA- 2025/08/30 04:50 PMCR- 2025/08/24 CRDT- 2025/08/24 01:23 PHST- 2025/08/30 04:50 [medline] PHST- 2025/08/30 04:49 [pubmed] PHST- 2025/08/24 01:23 [entrez] PHST- 2025/08/24 00:00 [pmc-release] AID - 947682 [pii] AID - 10.12659/AJCR.947682 [doi] PST - epublish SO - Am J Case Rep. 2025 Aug 24;26:e947682. doi: 10.12659/AJCR.947682. PMID- 40875186 OWN - NLM STAT- MEDLINE DCOM- 20251101 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 42 IP - 11 DP - 2025 Nov TI - Real-World Weight Loss Observed With Semaglutide and Tirzepatide in Patients with Overweight or Obesity and Without Type 2 Diabetes (SHAPE). PG - 5468-5480 LID - 10.1007/s12325-025-03340-2 [doi] AB - INTRODUCTION: Semaglutide 2.4 mg injection (Wegovy((R))), a glucagon-like peptide-1 (GLP-1) receptor agonist, was approved by the US Food and Drug Administration for weight management in June 2021. Tirzepatide, a glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, was approved for type 2 diabetes mellitus (T2DM; Mounjaro((R))) in May 2022 and weight management (Zepbound((R))) in November 2023. Due to limited data on the long-term effectiveness of these medications, this study assessed real-world weight loss with semaglutide 2.4 mg or tirzepatide after 1 year in patients with overweight or obesity and without T2DM. METHODS: This retrospective cohort study included adults with overweight or obesity and >/= 1 pharmacy claim for semaglutide 2.4 mg or tirzepatide in the US Komodo Health database between June 4, 2021, and December 15, 2023. Patients had continuous enrollment for 1 year before (baseline period) and 1 year after (follow-up period) the index date (date of treatment initiation) and persistence on therapy (no gap of > 30 days' supply) during follow-up. Patients with T2DM at baseline were excluded. Weight change from index to 1 year was descriptively assessed. RESULTS: Overall, 9916 patients were included (semaglutide 2.4 mg, n = 6794; tirzepatide, n = 3122). Baseline characteristics were descriptively similar for semaglutide 2.4 mg and tirzepatide: mean age was 47.8 and 49.5 years, 79.8% and 77.9% were female, and mean index weight was 104.5 and 104.9 kg, respectively. After 1 year of follow-up, the mean weight loss from baseline with semaglutide 2.4 mg and tirzepatide was - 14.6 and - 17.2 kg, respectively, with percent weight loss of - 14.1% and - 16.5%. Most (83.5%) patients treated with semaglutide 2.4 mg reached the maximum dose (2.4 mg), while 25.9% of patients treated with tirzepatide reached the maximum dose (15 mg). CONCLUSION: Findings suggest semaglutide 2.4 mg and tirzepatide are used in descriptively similar populations and both resulted in clinically meaningful weight loss after 1 year of treatment. CI - (c) 2025. The Author(s). FAU - Ng, Carmen D AU - Ng CD AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. cevn@novonordisk.com. FAU - Divino, Victoria AU - Divino V AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - Wang, Julia AU - Wang J AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - Toliver, Joshua C AU - Toliver JC AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - Buss, Marcio AU - Buss M AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. LA - eng PT - Journal Article DEP - 20250828 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Weight Loss/drug effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Overweight/drug therapy MH - *Obesity/drug therapy MH - *Tirzepatide/therapeutic use/administration & dosage MH - Adult MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12579654 OAB - Obesity, a condition of higher than normal body fat, is common among adults. Obesity contributes to many health problems and higher medical costs compared with adults with normal weight. This study examined the weight loss of patients treated with two drugs recently approved by the US Food and Drug Administration for weight management: semaglutide and tirzepatide. Both drugs affect weight by impacting the glucagon-like peptide-1 system. The US Komodo Health database, which provides patient medical history for over 140 million US patients, including medical and pharmacy claims, clinical observations, and laboratory results, was used to examine data for adults with overweight or obesity who had at least one pharmacy claim for semaglutide or tirzepatide. Weight change 1 year after the start of treatment was measured. This study found that patients treated with semaglutide and tirzepatide had generally similar characteristics, such as age, gender, and starting weight before treatment. After 1 year of treatment, the average weight loss with semaglutide was -14.6 kg, or 14.1% of body weight; the average weight loss with tirzepatide was -17.2 kg, or 16.5% of body weight. Findings from this study suggest that semaglutide and tirzepatide are used for patients with similar characteristics and both led to meaningful weight loss after 1 year of treatment. Given the study size and patient information from the database, the results likely reflect outcomes for real-world patients taking semaglutide or tirzepatide for obesity management. OABL- eng OTO - NOTNLM OT - Clinical practice OT - Obesity OT - Overweight OT - Real-world evidence OT - Semaglutide OT - Tirzepatide OT - Weight loss OT - Weight management COIS- Declarations. Conflict of Interest: Carmen D. Ng, Victoria Divino, Julia Wang, Joshua C. Toliver, and Marcio Buss are employees and shareholders of Novo Nordisk Inc. Ethical Approval: This study was conducted in accordance with relevant guidelines and regulations, including the principals of the Declaration of Helsinki of 1964 and its later amendments. This study used only de-identified patient records and did not involve the collection, use, or transmittal of individually identifiable data. The Department of Health and Human Services does not consider analysis of de-identified secondary data to meet the definition for human subject research. Therefore, this study was exempt from federal regulations covering human subject research and did not require institutional review board review. This is as per exemption (d)4 from 45 CFR 46.104. Novo Nordisk Inc. has a data access license to the Komodo Health database. EDAT- 2025/08/28 20:45 MHDA- 2025/11/01 21:22 PMCR- 2025/08/28 CRDT- 2025/08/28 11:24 PHST- 2025/06/18 00:00 [received] PHST- 2025/08/05 00:00 [accepted] PHST- 2025/11/01 21:22 [medline] PHST- 2025/08/28 20:45 [pubmed] PHST- 2025/08/28 11:24 [entrez] PHST- 2025/08/28 00:00 [pmc-release] AID - 10.1007/s12325-025-03340-2 [pii] AID - 3340 [pii] AID - 10.1007/s12325-025-03340-2 [doi] PST - ppublish SO - Adv Ther. 2025 Nov;42(11):5468-5480. doi: 10.1007/s12325-025-03340-2. Epub 2025 Aug 28. PMID- 40874398 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260903 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Cardiovascular and kidney outcomes of GLP-1 receptor agonists in adults with obesity: A target trial emulation study. PG - 6527-6536 LID - 10.1111/dom.70054 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide cardiovascular and renal benefits in type 2 diabetes, but their real-world effects in individuals with obesity without diabetes are unclear. This study aimed to evaluate the cardiovascular and kidney outcomes of GLP-1RAs versus other anti-obesity medications (AOMs) in adults with obesity. MATERIALS AND METHODS: This target trial emulation used TriNetX electronic health records (July 2021-May 2025) to identify adults with obesity and no diabetes history who initiated GLP-1RAs (liraglutide, semaglutide, or tirzepatide) or other AOMs. Outcomes included major adverse cardiovascular events (MACE), major adverse kidney events (MAKE), all-cause mortality, mental health conditions, and safety outcomes. Propensity score matching (1:1) balanced baseline characteristics; Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The study included 140 169 matched pairs of GLP-1RA and AOM initiators. Mean follow-up was 392 days for GLP-1RA users and 564 days for AOM users. Compared to AOMs, GLP-1RA use was associated with lower risks of MACE (HR, 0.76; 95% CI, 0.72-0.81), MAKE (HR, 0.64; 95% CI, 0.55-0.74), and all-cause mortality (HR, 0.49; 95% CI, 0.42-0.57). Mental health outcomes also improved, with reduced risks of depression (HR, 0.63), suicidal ideation/attempt (HR, 0.42), and substance use disorder (HR, 0.58). GLP-1RAs were not associated with increased risks of acute pancreatitis (HR, 1.17), hypoglycemia (HR, 1.08), or gastrointestinal symptoms (HR, 0.99). CONCLUSIONS: Among adults with obesity but without diabetes, GLP-1RA use was associated with reduced cardiovascular, kidney, mortality, and mental health risks compared to other AOMs. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Tang, Huilin AU - Tang H AUID- ORCID: 0000-0002-5814-6657 AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Lu, Yiwen AU - Lu Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Zhang, Bingyu AU - Zhang B AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Zhou, Ting AU - Zhou T AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Zhang, Dazheng AU - Zhang D AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Chen, Jiajie AU - Chen J AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Chen, Yong AU - Chen Y AD - Pfizer Inc., New York City, New York, USA. FAU - Asch, David A AU - Asch DA AD - Leonard Davis Institute of Health Economics, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Wharton School, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Division of General Internal Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Chen, Yong AU - Chen Y AD - The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. AD - The Graduate Group in Applied Mathematics and Computational Science, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Penn Medicine Center for Evidence-Based Practice (CEP), University of Pennsylvania, Philadelphia, Pennsylvania, USA. AD - Penn Institute for Biomedical Informatics (IBI), University of Pennsylvania, Philadelphia, Pennsylvania, USA. LA - eng GR - U01TR003709/CL/CLC NIH HHS/United States GR - R01AG073435/CL/CLC NIH HHS/United States GR - R01DK128237/CL/CLC NIH HHS/United States GR - R21AI167418/CL/CLC NIH HHS/United States GR - R01 DK128237/DK/NIDDK NIH HHS/United States GR - RF1 AG077820/AG/NIA NIH HHS/United States GR - R01 LM013519/LM/NLM NIH HHS/United States GR - R01LM013519/CL/CLC NIH HHS/United States GR - R56AG074604/CL/CLC NIH HHS/United States GR - RF1AG077820/CL/CLC NIH HHS/United States GR - U24 MH136069/MH/NIMH NIH HHS/United States GR - R21 EY034179/EY/NEI NIH HHS/United States GR - R21 AI167418/AI/NIAID NIH HHS/United States GR - U01 TR003709/TR/NCATS NIH HHS/United States GR - R56 AG074604/AG/NIA NIH HHS/United States GR - R01 AG073435/AG/NIA NIH HHS/United States GR - R21EY034179/CL/CLC NIH HHS/United States GR - U24MH136069/CL/CLC NIH HHS/United States PT - Journal Article DEP - 20250828 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Anti-Obesity Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - *Obesity/drug therapy/complications MH - Middle Aged MH - *Cardiovascular Diseases/epidemiology/prevention & control/chemically induced MH - Adult MH - Liraglutide/therapeutic use MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - *Kidney Diseases/epidemiology/chemically induced MH - Aged MH - Kidney/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12515787 OTO - NOTNLM OT - GLP-1 receptor agonists OT - anti-obesity medication OT - major adverse cardiovascular events OT - major adverse kidney events COIS- Dr. David A. Asch is a partner and part-owner of VAL Health and serves on the advisory boards of Thrive Global and Morpheus. Dr. Yong Chen (Pfizer, New York City, NY, USA) reported receiving personal fees from Merck & Co., Inc. and Pfizer Inc. outside the submitted work. All other authors declare no conflict of interest. EDAT- 2025/08/28 08:45 MHDA- 2025/10/13 00:27 PMCR- 2025/10/13 CRDT- 2025/08/28 06:07 PHST- 2025/08/13 00:00 [revised] PHST- 2025/06/16 00:00 [received] PHST- 2025/08/14 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/08/28 08:45 [pubmed] PHST- 2025/08/28 06:07 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - DOM70054 [pii] AID - 10.1111/dom.70054 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6527-6536. doi: 10.1111/dom.70054. Epub 2025 Aug 28. PMID- 40855709 OWN - NLM STAT- MEDLINE DCOM- 20251229 LR - 20260127 IS - 1365-2125 (Electronic) IS - 0306-5251 (Linking) VI - 92 IP - 1 DP - 2026 Jan TI - Semaglutide use is associated with neuromuscular junction degradation in older adults with type II diabetes mellitus. PG - 149-161 LID - 10.1002/bcp.70253 [doi] AB - AIMS: Older men with type 2 diabetes mellitus (T2DM) face a heightened risk of sarcopenia. This study aimed to compare the longitudinal effects of semaglutide, a glucagon-like peptide-1 receptor agonist and sitagliptin as the control group on sarcopenia indicators and biomarkers of neuromuscular junction and neuronal health in patients with T2DM over 1 year. METHODS: A cohort of 141 older men with T2DM (semaglutide, n = 68; sitagliptin group, n = 73) underwent assessments at baseline, 6 months and 1 year. Measured parameters included handgrip strength (HGS), gait speed, appendicular skeletal muscle mass index (ASMI), short physical performance battery (SPPB) and plasma concentrations of C-terminal agrin fragment 22 (CAF22), neurofilament light chain (NfL) and brain-derived neurotrophic factor (BDNF). RESULTS: Over the study period, the semaglutide group exhibited significant reductions in HGS, gait speed, ASMI and SPPB scores (all P < .05). Concurrently, this group exhibited more pronounced elevation of plasma CAF22 and NfL levels compared to the sitagliptin group (all P < .05). Among the patients taking semaglutide, higher CAF22 and NfL levels generally correlated with poorer HGS, ASMI and SPPB scores. In contrast, lower BDNF levels were associated with reduced ASMI and SPPB at specific time points (all P < .05). Multiple regression analysis confirmed significant negative associations between CAF22 and NfL, and a positive association between BDNF and sarcopenia parameters, specifically among patients taking semaglutide. CONCLUSIONS: Semaglutide treatment in older men with T2DM may be associated with a decline in muscle strength and physical performance, potentially associated with neuromuscular junction degradation and neuronal damage. These findings underscore the importance of closely monitoring musculoskeletal health in patients receiving semaglutide. CI - (c) 2025 British Pharmacological Society. FAU - Qaisar, Rizwan AU - Qaisar R AUID- ORCID: 0000-0001-8485-7172 AD - Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. AD - Space Medicine Research Group, Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates. AD - Cardiovascular Research Group, Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates. FAU - Khan, Imran Ullah AU - Khan IU AD - Department of Pulmonology, Rehman Medical Institute, Peshawar, Pakistan. FAU - Rehman, Atif Ur AU - Rehman AU AD - Department of Medicine, Divisional Headquarters Hospital, Kohat, Pakistan. FAU - Iqbal, M Shahid AU - Iqbal MS AD - Department of Neurology and Stroke Medicine, Rehman Medical Institute, Peshawar, Pakistan. FAU - Ahmad, Firdos AU - Ahmad F AUID- ORCID: 0000-0001-6530-6068 AD - Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. AD - Space Medicine Research Group, Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates. AD - Cardiovascular Research Group, Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates. FAU - Karim, Asima AU - Karim A AUID- ORCID: 0000-0002-6288-0686 AD - Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. AD - Iron Biology Research Group, Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates. LA - eng GR - 24010901166/University of Sharjah/ PT - Comparative Study PT - Journal Article DEP - 20250825 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - Aged MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Sarcopenia/chemically induced MH - Hand Strength MH - *Neuromuscular Junction/drug effects/pathology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Sitagliptin Phosphate/therapeutic use/pharmacology MH - Biomarkers/blood MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Muscle, Skeletal/drug effects MH - Middle Aged MH - Longitudinal Studies MH - Aged, 80 and over MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - C-terminal agrin fragment 22 OT - brain-derived neurotrophic factor OT - handgrip strength OT - neurofilament light chain OT - neuromuscular junction OT - sarcopenia OT - semaglutide EDAT- 2025/08/26 08:45 MHDA- 2025/12/29 13:02 CRDT- 2025/08/26 02:23 PHST- 2025/07/29 00:00 [revised] PHST- 2025/06/12 00:00 [received] PHST- 2025/08/05 00:00 [accepted] PHST- 2025/12/29 13:02 [medline] PHST- 2025/08/26 08:45 [pubmed] PHST- 2025/08/26 02:23 [entrez] AID - 10.1002/bcp.70253 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2026 Jan;92(1):149-161. doi: 10.1002/bcp.70253. Epub 2025 Aug 25. PMID- 40851184 OWN - NLM STAT- MEDLINE DCOM- 20250831 LR - 20250831 IS - 1538-8689 (Electronic) IS - 0360-4039 (Linking) VI - 55 IP - 9 DP - 2025 Sep 1 TI - The physiologic and psychologic effects of glucagon-like peptide-1 receptor agonists. PG - 48-54 LID - 10.1097/NSG.0000000000000223 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were approved by the FDA to treat type 2 diabetes (T2D) and to reduce the risk of major cardiovascular events in patients with T2D and known heart disease. With an alarming rise in T2D prevalence as well as its associated complications, the need for adequate treatment strategies for this chronic disease has never been higher. GLP-1 RAs have beneficial effects in treating T2D. This article discusses updates on the safety and effectiveness of GLP-1 RAs for obesity and many related conditions. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Browne-Bradwisch, Sarah A AU - Browne-Bradwisch SA AD - At Kingsborough Community College in Brooklyn, N.Y., Sarah A. Browne-Bradwisch is a Professor and Jonas Veterans Scholar; Erin Murphy Smith is a Professor; Catherine Wilson-Mooney is an Assistant Professor and Co-Deputy chairperson of Clinical Affiliations; and Courtney Donahue-Stathis is an Assistant Professor and Co-Deputy chairperson of Clinical Affiliations. FAU - Smith, Erin Murphy AU - Smith EM FAU - Wilson-Mooney, Catherine AU - Wilson-Mooney C FAU - Donahue-Stathis, Courtney AU - Donahue-Stathis C LA - eng PT - Journal Article PT - Review DEP - 20250825 PL - United States TA - Nursing JT - Nursing JID - 7600137 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Diabetes Mellitus, Type 2/drug therapy/nursing MH - *Glucagon-Like Peptide-1 Receptor MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - Heart Diseases/drug therapy/nursing MH - Humans MH - Child MH - Adolescent MH - Young Adult MH - Adult MH - Middle Aged MH - Aged OTO - NOTNLM OT - GLP-1 RA OT - TD2 OT - diabetes OT - glucagon-like-peptide-1 receptor agonists OT - obesity OT - semaglutide OT - type 2 diabetes EDAT- 2025/08/25 08:44 MHDA- 2025/08/25 08:45 CRDT- 2025/08/25 00:13 PHST- 2025/08/25 08:45 [medline] PHST- 2025/08/25 08:44 [pubmed] PHST- 2025/08/25 00:13 [entrez] AID - 00152193-202509000-00012 [pii] AID - 10.1097/NSG.0000000000000223 [doi] PST - ppublish SO - Nursing. 2025 Sep 1;55(9):48-54. doi: 10.1097/NSG.0000000000000223. Epub 2025 Aug 25. PMID- 40843773 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 11 DP - 2025 Nov TI - Efficacy and safety of oral semaglutide in Chinese participants with type 2 diabetes: Subgroup analyses by baseline characteristics in the PIONEER 11 and 12 randomised controlled trials. PG - 6386-6394 LID - 10.1111/dom.70031 [doi] AB - AIMS: This post hoc analysis investigates the impact of baseline characteristics on the efficacy and safety of oral semaglutide in a Chinese population with type 2 diabetes. MATERIALS AND METHODS: Chinese participants from the PIONEER 11 and 12 trials with type 2 diabetes aged >/=18 years were randomised to once-daily oral semaglutide 3, 7, or 14 mg, or placebo (PIONEER 11) or sitagliptin 100 mg (PIONEER 12). Changes from baseline in HbA(1c) and body weight at week 26 were analysed in subgroups according to the following baseline characteristics: age, HbA(1c), body mass index, duration of diabetes, and presence of gastrointestinal disease. Adverse events (AEs) by baseline subgroups were also assessed. RESULTS: In total, 390 (PIONEER 11) and 1084 (PIONEER 12) Chinese participants with type 2 diabetes were evaluated. Most baseline characteristics were similar across the two trials in the different subgroups. Overall, greater reductions in HbA(1c) and body weight were observed with oral semaglutide versus comparators across the subgroups. A significant difference was observed for change in HbA(1c) by baseline HbA(1c) subgroups (p(int) <0.05), with greater reductions observed in the subgroups with higher baseline HbA(1c). Most AEs were gastrointestinal-related and mild-to-moderate. CONCLUSIONS/INTERPRETATION: Oral semaglutide reduces HbA(1c) and body weight across a range of baseline subgroups in a Chinese population with type 2 diabetes without any unexpected additional safety concerns. These results support the use of oral semaglutide in a broad population in clinical practice. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0003-1305-1598 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Yuan, Guoyue AU - Yuan G AUID- ORCID: 0000-0003-0822-6066 AD - Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Liu, Jun AU - Liu J AD - Department of Endocrinology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China. FAU - Zhang, Bingjie AU - Zhang B AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Liu, Wenyan AU - Liu W AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Shen, Zewei AU - Shen Z AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. LA - eng GR - N/A/Novo Nordisk Shanghai (Ltd)/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20250822 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - Chinese people SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose MH - Body Weight/drug effects MH - China/epidemiology/ethnology MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Double-Blind Method MH - Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/administration & dosage MH - *Sitagliptin Phosphate/administration & dosage MH - Treatment Outcome MH - *East Asian People/statistics & numerical data MH - *Glucagon-Like Peptide 1/administration & dosage MH - Semaglutide PMC - PMC12515755 OTO - NOTNLM OT - GLP-1RA OT - HbA1c OT - body weight OT - oral semaglutide OT - safety OT - type 2 diabetes COIS- Linong Ji reports receiving consulting or lecture fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Innovent Biologics, Gan & Lee Pharmaceuticals, Merck, MSD, Novo Nordisk, Sanofi-Aventis, Sibionics, and Sinocare. Linong Ji is also the independent Director of Shanghai Benemae Pharmaceutical Corporation. Jun Liu and Guoyue Yuan declared no conflicts of interest. Bingjie Zhang, Wenyan Liu, and Zewei Shen are employees of Novo Nordisk and own stock in the company. EDAT- 2025/08/22 12:45 MHDA- 2025/10/13 00:27 PMCR- 2025/10/13 CRDT- 2025/08/22 06:43 PHST- 2025/08/05 00:00 [revised] PHST- 2025/03/04 00:00 [received] PHST- 2025/08/05 00:00 [accepted] PHST- 2025/10/13 00:27 [medline] PHST- 2025/08/22 12:45 [pubmed] PHST- 2025/08/22 06:43 [entrez] PHST- 2025/10/13 00:00 [pmc-release] AID - DOM70031 [pii] AID - 10.1111/dom.70031 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Nov;27(11):6386-6394. doi: 10.1111/dom.70031. Epub 2025 Aug 22. PMID- 40839017 OWN - NLM STAT- MEDLINE DCOM- 20260708 LR - 20260813 IS - 1861-0692 (Electronic) IS - 1861-0684 (Print) IS - 1861-0684 (Linking) VI - 115 IP - 8 DP - 2026 Aug TI - GLP-1 receptor agonists in atherosclerotic cardiovascular disease and diabetes mellitus or obesity: investigation of the potential role in a German inpatient dataset. PG - 1343-1350 LID - 10.1007/s00392-025-02735-z [doi] AB - BACKGROUND: GLP-1 receptor agonists (GLP-1 RA) reduce major adverse cardiovascular events in patients with diabetes mellitus and atherosclerotic cardiovascular disease (ASCVD) or increased cardiovascular risk. Recently, the GLP-1 RA semaglutide was reported to reduce cardiovascular events in ASCVD patients with overweight or obesity even in the absence of diabetes mellitus. Accordingly, this was included in the current European Society of Cardiology guidelines for secondary prevention. We aimed to assess the number of inpatients with ASCVD who could qualify for therapy with GLP-1 RA. METHODS: Using nationwide data from the Research Data Centre of the Federal Statistical Office of Germany, a random 10% sample of all adult inpatients in 2022 was analyzed. The proportions of ASCVD, obesity, and diabetes mellitus were examined. RESULTS: The 10% sample included 1,446,420 patients with a mean age of 63.16 years, 52.50% were female. ASCVD was present in 229,619 inpatients (15.87%), including those with coronary artery disease, history of myocardial infarction, peripheral vascular disease or stroke. Among ASCVD patients, 79,516 individuals (34.63% of ASCVD patients) also suffered from type 2 diabetes mellitus and 15,624 individuals were diagnosed with obesity. Approximately half of those (N = 7,256) had ASCVD and obesity without diabetes mellitus (3.16% of ASCVD patients). Overall, 37.79% of ASCVD patients also suffered from type 2 diabetes mellitus or obesity. CONCLUSION: In this data sampling of German inpatients, more than one-third of ASCVD patients may qualify for GLP-1 RA therapy due to concomitant diabetes mellitus or obesity. That corresponds to about 6% of inpatients in Germany. CI - (c) 2025. The Author(s). FAU - Oettinger, Vera AU - Oettinger V AUID- ORCID: 0000-0003-4460-2102 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. vera.oettinger@uniklinik-freiburg.de. AD - Center for Big Data Analysis in Cardiology (CeBAC), Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. vera.oettinger@uniklinik-freiburg.de. FAU - von Zur Muhlen, Constantin AU - von Zur Muhlen C AUID- ORCID: 0000-0003-2767-8009 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. AD - Center for Big Data Analysis in Cardiology (CeBAC), Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Kaier, Klaus AU - Kaier K AUID- ORCID: 0000-0003-0837-6945 AD - Center for Big Data Analysis in Cardiology (CeBAC), Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. AD - Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany. FAU - Wolf, Dennis AU - Wolf D AUID- ORCID: 0000-0003-1525-4348 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. FAU - Rilinger, Jonathan AU - Rilinger J AUID- ORCID: 0000-0001-9333-3629 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. FAU - Maier, Alexander AU - Maier A AUID- ORCID: 0000-0003-0200-7495 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. AD - Center for Big Data Analysis in Cardiology (CeBAC), Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Jackel, Markus AU - Jackel M AUID- ORCID: 0000-0001-8638-5228 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. AD - Center for Big Data Analysis in Cardiology (CeBAC), Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Westermann, Dirk AU - Westermann D AUID- ORCID: 0000-0002-7542-1956 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. FAU - Hilgendorf, Ingo AU - Hilgendorf I AUID- ORCID: 0000-0002-0024-1643 AD - Department of Cardiology and Angiology, University Heart Center, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany. FAU - Bockelmann, Dalibor AU - Bockelmann D AD - Medical Strategy Unit, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. LA - eng PT - Journal Article DEP - 20250821 PL - Germany TA - Clin Res Cardiol JT - Clinical research in cardiology : official journal of the German Cardiac Society JID - 101264123 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Female MH - Male MH - Germany/epidemiology MH - Middle Aged MH - *Obesity/drug therapy/epidemiology/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Atherosclerosis/epidemiology/drug therapy MH - Aged MH - *Inpatients MH - Semaglutide MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Adult PMC - PMC13346366 OTO - NOTNLM OT - ASCVD OT - Atherosclerotic cardiovascular disease OT - Diabetes mellitus OT - Electronic health records OT - GLP-1 receptor agonist OT - Obesity COIS- Declarations. Ethics approval and informed consent: The investigators in this study did not have direct access to individual patient data for this analysis. Access was granted by Destatis only for summarized results. Ethics committee approval and informed consent were therefore not required according to German law. Destatis anonymised all pooled results and any information that could potentially identify an individual patient or an individual center has been censored by Destatis to ensure privacy. Conflicts of interest: The authors declare that they have no conflict of interest. EDAT- 2025/08/21 12:47 MHDA- 2026/07/08 18:50 PMCR- 2025/08/21 CRDT- 2025/08/21 11:03 PHST- 2025/03/30 00:00 [received] PHST- 2025/08/01 00:00 [accepted] PHST- 2026/07/08 18:50 [medline] PHST- 2025/08/21 12:47 [pubmed] PHST- 2025/08/21 11:03 [entrez] PHST- 2025/08/21 00:00 [pmc-release] AID - 10.1007/s00392-025-02735-z [pii] AID - 2735 [pii] AID - 10.1007/s00392-025-02735-z [doi] PST - ppublish SO - Clin Res Cardiol. 2026 Aug;115(8):1343-1350. doi: 10.1007/s00392-025-02735-z. Epub 2025 Aug 21. PMID- 40836732 OWN - NLM STAT- MEDLINE DCOM- 20250821 LR - 20250821 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 73 IP - 7 DP - 2025 Jul TI - MASLD Pharmacotherapy: Current Standards, Emerging Treatments, and Practical Guidance for Indian Physicians. PG - e45-e60 LID - 10.59556/japi.73.1058 [doi] AB - Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), has become a significant public health issue worldwide, with a pronounced impact in India due to the escalating rates of obesity and type 2 diabetes mellitus (T2DM) driving its prevalence. This condition spans a range of hepatic disorders, from uncomplicated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), accompanied by differing levels of hepatic fibrosis, heightening the likelihood of progression to cirrhosis, liver cancer, and cardiovascular complications. While lifestyle modification remains the cornerstone of MASLD management, pharmacologic therapies are increasingly recognized as essential for patients with progressive disease or those at higher risk of complications. Recent insights into the pathogenesis of MASLD have led to the development of innovative therapies targeting key mechanisms such as hepatic steatosis, insulin resistance, inflammation, and hepatic fibrosis. Several pharmacological agents have shown encouraging results in clinical trials, including thyroid hormone receptor-beta agonist resmetirom, glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide, peroxisome proliferator-activated receptor (PPAR) agonists such as pioglitazone and saroglitazar, sodium-glucose cotransporter-2 inhibitors (SGLT2i), and vitamin E. Furthermore, emerging therapies, including the dual incretin agonist tirzepatide and fibroblast growth factor (FGF) analogs, hold the potential to transform future treatment strategies. This review provides a comprehensive overview of current and evolving pharmacologic options for MASLD, with a focus on practical recommendations tailored for Indian physicians. A structured treatment algorithm for noncirrhotic MASLD (F0-F3 fibrosis) is presented, incorporating only drugs currently available in India and stratified based on diabetes status and hepatic fibrosis severity. Given India's vast and diverse patient population, ensuring access to cost-effective therapies remains a challenge, necessitating a pragmatic approach that balances efficacy, affordability, and real-world feasibility. This review serves as a practical clinical guide, equipping physicians with evidence-based recommendations to optimize MASLD management in routine practice. CI - (c) Journal of The Association of Physicians of India 2025. FAU - Kumar, Ashish AU - Kumar A AD - Professor, Department of Gastroenterology, Institute of Liver, Gastroenterology, and Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Delhi, India, Corresponding Author, Orcid: https://orcid.org/0000-0001-6680-7227. LA - eng PT - Journal Article PT - Review PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - India MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Diabetes Mellitus, Type 2/complications MH - Practice Guidelines as Topic MH - Hypoglycemic Agents/therapeutic use EDAT- 2025/08/21 06:28 MHDA- 2025/08/21 06:29 CRDT- 2025/08/21 03:33 PHST- 2025/08/21 06:29 [medline] PHST- 2025/08/21 06:28 [pubmed] PHST- 2025/08/21 03:33 [entrez] AID - 10.59556/japi.73.1058 [doi] PST - ppublish SO - J Assoc Physicians India. 2025 Jul;73(7):e45-e60. doi: 10.59556/japi.73.1058. PMID- 40832978 OWN - NLM STAT- MEDLINE DCOM- 20251215 LR - 20251217 IS - 1758-8111 (Electronic) IS - 1758-8103 (Linking) VI - 16 IP - 1 DP - 2026 Feb TI - Effect of Tirzepatide on the Risk of Developing Type 2 Diabetes Mellitus Among the People Living With Obesity or Overweight: A Systematic Review. PG - e70042 LID - 10.1111/cob.70042 [doi] AB - Tirzepatide provides superior efficacy in weight reduction and metabolic control compared to existing therapies. The present systematic review assessed the effect of Tirzepatide on the risk of developing type 2 diabetes mellitus (T2DM) among people living with obesity or overweight. Six major databases [MEDLINE (PubMed), ClinicalTrials.gov, EMBASE, Scopus, Web of Science and Cochrane Library] were searched for potential studies published till 10 July 2025. Two-stage dual screening with third-person adjudication was adopted for screening of studies. PROSPERO ID: CRD42024614466. RoB 2.0 and the Newcastle-Ottawa Scale were used to assess the quality of randomised controlled trials (RCTs) and cohort studies, respectively. Database search yielded 2601 studies, among which three studies were eligible (one RCT and two cohort studies) for systematic review. The hazard ratio (HR) for the new-onset diabetes at 12 months following the Tirzepatide intake was significantly lower than that of the Semaglutide group of patients (HR = 0.73, p < 0.001 [95% CI: 0.58-0.92]). The risk of the new-onset diabetes for 176 weeks (HR = 0.07, p < 0.001 [95% CI: < 0.01-0.1]) and 193 weeks (HR = 0.12, p < 0.001 [95% CI: 0.1-0.2]) following the Tirzepatide intake was significantly lower than that of the placebo group of patients. Tirzepatide might have significant efficacy in the prevention of T2DM in patients with obesity or overweight. CI - (c) 2025 World Obesity Federation. FAU - Pardeshi, Geeta AU - Pardeshi G AUID- ORCID: 0000-0001-6670-0235 AD - Department of Community Medicine, Grant Government Medical College and Sir JJ Group of Hospitals, Mumbai, India. FAU - Kumbhar, Uddhav T AU - Kumbhar UT AUID- ORCID: 0000-0002-6735-0748 AD - Department of Community Medicine, KIMS, Karad, India. FAU - Kaviprawin, Mogan AU - Kaviprawin M AUID- ORCID: 0000-0002-1659-059X AD - South Asia Field Epidemiology and Technology Network, Inc., (SAFETYNET), Chennai, India. FAU - Debnath, Aninda AU - Debnath A AUID- ORCID: 0000-0002-2117-4195 AD - Department of Community Medicine, Maulana Azad Medical College, New Delhi, India. FAU - Dubey, Ashok Kumar AU - Dubey AK AUID- ORCID: 0000-0002-4246-8627 AD - Department of Pharmacology, AIIMS, Bilaspur, India. FAU - Deshmukh, Kalyani AU - Deshmukh K AUID- ORCID: 0009-0009-7125-4896 AD - Technical Resource Centre, Centre for Evidence based Guidelines, All India Institute of Medical Sciences, Nagpur, India. FAU - Goyal, Chanchal AU - Goyal C AUID- ORCID: 0009-0002-8484-1255 AD - Centre for Evidence based Guidelines, ICMR-DHR, New Delhi, India. FAU - Gandhi, Aravind P AU - Gandhi AP AUID- ORCID: 0000-0003-3898-5450 AD - Department of Community Medicine, All India Institute of Medical Sciences, Nagpur, India. LA - eng PT - Journal Article PT - Systematic Review DEP - 20250820 PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/prevention & control/etiology/epidemiology MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - *Tirzepatide/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Randomized Controlled Trials as Topic MH - Adult OTO - NOTNLM OT - Tirzepatide OT - glycemic control OT - obesity OT - type 2 diabetes mellitus OT - weight loss EDAT- 2025/08/20 12:31 MHDA- 2025/12/16 00:34 CRDT- 2025/08/20 07:43 PHST- 2025/07/21 00:00 [revised] PHST- 2025/04/06 00:00 [received] PHST- 2025/08/13 00:00 [accepted] PHST- 2025/12/16 00:34 [medline] PHST- 2025/08/20 12:31 [pubmed] PHST- 2025/08/20 07:43 [entrez] AID - 10.1111/cob.70042 [doi] PST - ppublish SO - Clin Obes. 2026 Feb;16(1):e70042. doi: 10.1111/cob.70042. Epub 2025 Aug 20. PMID- 40829097 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 31 IP - 8 DP - 2025 Aug 1 TI - Trends in glucagon-like peptide 1 receptor agonist prescribing patterns. PG - e228-e234 LID - 10.37765/ajmc.2025.89778 [doi] AB - OBJECTIVE: Obesity affects more than 40% of US adults, increasing risks for cardiovascular disease and type 2 diabetes. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), initially indicated for diabetes, show promise in weight loss but face coverage issues, high costs, and premature prescribing from physicians. Research is needed to assess prescribing patterns, especially in patients without diabetes. STUDY DESIGN: We conducted a retrospective, population-based, observational study using the Merative MarketScan Commercial Database and the Merative MarketScan Medicare Supplemental Database, which capture person-specific clinical utilization and expenditures. We analyzed GLP-1 RA prescribing rates from 2018 to 2023, comparing semaglutide with other GLP-1 RAs and stratifying by diabetes and overweight/obesity indications. METHODS: The study included individuals 18 years or older with 12 months of continuous enrollment from 2018 to 2023, categorizing GLP-1 RA users into 4 groups based on diabetes and obesity/overweight diagnosis codes within a year of their index date. RESULTS: Prescribing of GLP-1 RA medications, particularly semaglutides, increased notably over the years, whereas dulaglutide, liraglutide, and exenatide use declined. When investigating possible premature prescribing by examining users with no diabetes indication, the number of prediabetes or abnormal glucose diagnoses increased slightly before the index GLP-1 RA prescribing index date. However, less than 9% received a diabetes or prediabetes diagnosis 30 days after starting a GLP-1 RA. CONCLUSIONS: From 2018 to 2023, GLP-1 RA prescribing increased significantly, with semaglutide approved for weight loss rising to 60% share in the nondiabetic obese/overweight group. Trends showed a notable rise in prescriptions for nondiabetic and obese/overweight patients. FAU - Ukhanova, Maria AU - Ukhanova M AD - UTHealth Houston School of Public Health, Center for Health Care Data, 1200 Pressler St, Houston, TX 77030. Email: maria.ukhanova.1@uth.tmc.edu. FAU - Wozny, Joseph S AU - Wozny JS FAU - Truong, Chau N AU - Truong CN FAU - Ghosh, Lopita AU - Ghosh L FAU - Krause, Trudy M AU - Krause TM LA - eng PT - Journal Article PT - Observational Study DEP - 20250801 PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Practice Patterns, Physicians'/trends/statistics & numerical data MH - Male MH - Female MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Obesity/drug therapy MH - United States MH - Aged MH - Adult MH - Liraglutide/therapeutic use MH - Exenatide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Overweight/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/08/19 18:30 MHDA- 2025/08/31 20:08 CRDT- 2025/08/19 16:03 PHST- 2025/08/31 20:08 [medline] PHST- 2025/08/19 18:30 [pubmed] PHST- 2025/08/19 16:03 [entrez] AID - 89778 [pii] AID - 10.37765/ajmc.2025.89778 [doi] PST - epublish SO - Am J Manag Care. 2025 Aug 1;31(8):e228-e234. doi: 10.37765/ajmc.2025.89778. PMID- 40816061 OWN - NLM STAT- MEDLINE DCOM- 20250918 LR - 20260127 IS - 1532-866X (Electronic) IS - 0049-0172 (Linking) VI - 74 DP - 2025 Oct TI - Impact of oral semaglutide on serum urate levels in people with type 2 diabetes: A retrospective real-world analysis (URISEMA study). PG - 152807 LID - S0049-0172(25)00178-7 [pii] LID - 10.1016/j.semarthrit.2025.152807 [doi] AB - BACKGROUND: Evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on serum urate (SU) levels in people with type 2 diabetes (PWT2D) is limited. This study investigates the effect of oral semaglutide on SU levels. METHODS: Retrospective, observational study including PWT2D who were prescribed oral semaglutide. The primary endpoint was achieving SU levels below 6 mg/dL at 12 months of follow-up (FU). Secondly, we assessed baseline factors associated with achieving SU levels of <6 mg/dL and average reductions in SU levels. RESULTS: The study included 236 patients (median age 64 years, BMI 33.8 kg/m(2), HbA1c 7.6 %, 40.7 % women, 52.3 % on SGLT2 inhibitors). Baseline SU was 5.2 mg/dL, 66.1 % had SU levels <6 mg/dL, and 23.7 % had hyperuricemia. Under oral semaglutide, 70.7 % and 76 % showed SU <6 mg/dL at 6 and 12 months, respectively. After multivariate adjustment, only SU >/=7 mg/dL (OR 4.54, 95 %CI 1.08-19.25) and switching from a DPP-4 inhibitor (OR 6.53, 95 %CI 1.57-27.32) were associated with achieving the SU target. SU decreased by 0.1 mg/dL after 6 months (p = 0.52) and by 0.2 mg/dL (p = 0.01) at 12 months FU. Greater reductions were observed in those with baseline SU >6 mg/dL (0.6 mg/dL and 0.8 mg/dl, respectively; all p < 0.001). Changes in SU levels were independent of improved metabolic control, weight loss, or baseline use of GLP-1 RAs or SGLT2 inhibitors. CONCLUSION: Oral semaglutide in real-world settings showed a modest reduction in SU levels in PWT2D, particularly linked to baseline hyperuricemia (with notable reduction figures) and switching from DPP-4 inhibitors. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Moreno-Perez, Oscar AU - Moreno-Perez O AD - Department of Endocrinology and Nutrition. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain; Department of Clinical Medicine. Miguel Hernandez University, Spain. Electronic address: omorenoperez@hotmail.es. FAU - Tejera-Munoz, Antonio AU - Tejera-Munoz A AD - Department of Endocrinology and Nutrition. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain; Health Science Faculty-HM Hospitals, Camilo Jose Cela University, Madrid, Spain; HM Hospitals Health Research Institute, Madrid, Spain. FAU - Carreno-Valdivia, Ruben AU - Carreno-Valdivia R AD - Medical School. Miguel Hernandez University, Spain. FAU - Rodriguez-Bedoya, Maria AU - Rodriguez-Bedoya M AD - Department of Endocrinology and Nutrition. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain. FAU - Guillen-Morote, Cristina AU - Guillen-Morote C AD - Department of Endocrinology and Nutrition. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain. FAU - Roldan-Sanchez, Ada AU - Roldan-Sanchez A AD - Department of Endocrinology and Nutrition. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain. FAU - Andres, Mariano AU - Andres M AD - Department of Clinical Medicine. Miguel Hernandez University, Spain; Department of Rheumatology. General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL). Alicante, Alicante, Spain. LA - eng PT - Journal Article PT - Observational Study DEP - 20250807 PL - United States TA - Semin Arthritis Rheum JT - Seminars in arthritis and rheumatism JID - 1306053 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 268B43MJ25 (Uric Acid) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Uric Acid/blood MH - Administration, Oral MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Associated factors OT - Gout OT - Observational study OT - Oral semaglutide OT - Real-World data OT - Serum urate OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Oscar Moreno Perez reports financial support was provided by Eli Lilly and Company. Oscar Moreno Perez reports financial support was provided by Boehringer Ingelheim Corp USA. Oscar Moreno Perez reports financial support was provided by Bayer Corporation. Oscar Moreno Perez reports financial support was provided by AstraZeneca Pharmaceuticals LP. Oscar Moreno Perez reports financial support was provided by Novo Nordisk Inc. Mariano Andres reports financial support was provided by Sobi. Mariano Andres reports financial support was provided by Grunenthal Laboratories LLC. Oscar Moreno Perez reports a relationship with Eli Lilly and Company that includes: consulting or advisory and speaking and lecture fees. Oscar Moreno Perez reports a relationship with Boehringer Ingelheim Corp USA that includes: consulting or advisory and speaking and lecture fees. Oscar Moreno Perez reports a relationship with Bayer Corporation that includes: consulting or advisory and speaking and lecture fees. Oscar Moreno Perez reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory and speaking and lecture fees. Oscar Moreno Perez reports a relationship with Novo Nordisk Inc that includes: consulting or advisory, funding grants, and speaking and lecture fees. Mariano Andres reports a relationship with Sobi that includes: consulting or advisory. Mariano Andres reports a relationship with Grunenthal Laboratories LLC that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/08/16 00:29 MHDA- 2025/09/19 00:36 CRDT- 2025/08/15 18:12 PHST- 2025/06/03 00:00 [received] PHST- 2025/07/15 00:00 [revised] PHST- 2025/08/04 00:00 [accepted] PHST- 2025/09/19 00:36 [medline] PHST- 2025/08/16 00:29 [pubmed] PHST- 2025/08/15 18:12 [entrez] AID - S0049-0172(25)00178-7 [pii] AID - 10.1016/j.semarthrit.2025.152807 [doi] PST - ppublish SO - Semin Arthritis Rheum. 2025 Oct;74:152807. doi: 10.1016/j.semarthrit.2025.152807. Epub 2025 Aug 7. PMID- 40815181 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20260710 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 45 IP - 9 DP - 2025 Sep TI - Safety Choice Drivers of the Coming Treatment Options for Non-Cirrhotic Metabolic Steatohepatitis. PG - e70271 LID - 10.1111/liv.70271 [doi] AB - Metabolic dysfunction associated steatohepatitis (MASH), formerly known as NASH, represents one of the leading causes of chronic liver disease worldwide. Its high prevalence is driven by insulin resistance, obesity and type 2 diabetes (T2D) and is associated with cardiovascular disease. The main driver of liver damage is fat accumulation in hepatocytes leading to inflammation and fibrosis development. People with MASH and clinically significant fibrosis (stage F2/F3) are 'at risk' of progressing to cirrhosis and hepatocellular carcinoma and are considered in need of treatment. Metabolic drivers of MASH originating outside the liver, for example, from the adipose tissue and the gut, and genetic heterogeneity contribute to making the prevalent pathogenetic factor difficult to dissect at an individual level. In this scenario, the Food and Drug Administration's conditional approval of the liver-directed thyroid hormone receptor beta agonist Resmetirom as the first pharmacological treatment for MASH last March 2024 and the expected extension of the glucagon-like protein-1 receptor agonist Semaglutide indication from diabetes and obesity to MASH mark a key milestone. Both drugs are also under evaluation by the European Medicines Agency. The proven efficacy of these compounds in clinical trials needs to be balanced against safety profiles and patient preferences. To investigate future trajectories and possible uses as mono-therapy or in combination, we examined available results of clinical trials and real-life studies. Despite the need to await the final results of outcome studies to exclude any possible challenges for both compounds, safety profiles and external factors including reimbursement policies or supply limitations may currently guide the individual choice. CI - (c) 2025 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Mangia, Alessandra AU - Mangia A AUID- ORCID: 0000-0002-2600-3555 AD - Liver Unit, Fondazione IRCCS, "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy. FAU - Valenti, Luca V C AU - Valenti LVC AD - Biological Resource Center/Biobank, Fondazione "Ca Granda" IRCCS Ospedale Maggiore Policlinico, Milano, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - 0 (2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Propionates) RN - 0 (Chalcones) SB - IM MH - Humans MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Diabetes Mellitus, Type 2/complications MH - Liver Cirrhosis/etiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity/complications MH - Liver/pathology MH - Propionates MH - Chalcones OTO - NOTNLM OT - Efruxifermin OT - Lanifibranor OT - MASH/MASLD OT - Resmetirom OT - Semaglutide OT - Survodutide EDAT- 2025/08/15 12:35 MHDA- 2025/08/31 20:08 CRDT- 2025/08/15 09:18 PHST- 2025/07/21 00:00 [revised] PHST- 2025/06/21 00:00 [received] PHST- 2025/07/29 00:00 [accepted] PHST- 2025/08/31 20:08 [medline] PHST- 2025/08/15 12:35 [pubmed] PHST- 2025/08/15 09:18 [entrez] AID - 10.1111/liv.70271 [doi] PST - ppublish SO - Liver Int. 2025 Sep;45(9):e70271. doi: 10.1111/liv.70271. PMID- 40798976 OWN - NLM STAT- MEDLINE DCOM- 20260415 LR - 20260415 IS - 1873-4286 (Electronic) IS - 1381-6128 (Linking) VI - 32 IP - 14 DP - 2026 TI - An Insight into Pharmaceutical Design and Pharmacokinetic Characteristics of GLP-1 RAs. PG - 1095-1106 LID - 10.2174/0113816128375766250720234005 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the most effective treatments for type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic receptors, improving glycemia by boosting insulin secretion while decreasing glucagon secretion. GLP-1 receptors are present in pancreatic tissue. They are also found in extra-pancreatic tissue and have been shown to reduce body weight while also protecting the heart and endothelial cells. The most prevalent types of GLP-1 RAs can be injected twice daily (exenatide), once daily (lixisenatide and liraglutide), or once weekly (albiglutide, dulaglutide, exenatide once, semaglutide, tirzepatide). GLP-1 receptor agonists also reduce gastric emptying, preventing substantial post-meal glycaemic increases. Many publications have been written regarding GLP-1 RAs, covering various features of this family. However, the purpose of this study is to investigate the pharmacological design models and pharmacokinetic characteristics of the most regularly used members of this class, as well as to highlight contemporary developments in GLP-1 RAs. It also describes the physicochemical features, techniques of manufacture, the effects of molecular structure, and structural modifications on pharmacological activity. METHODS: The literature review was completed using a structured approach to identify and integrate relevant literature. It involved a broad search of reputable medical databases using inclusion and exclusion criteria. RESULTS: They are classified as short-acting or long-acting based on the length of their action. Short-acting GLP-1 RAs and long-acting GLP-1 RAs have differing efficacy profiles. Furthermore, the methods of administration, mode of action, and side effects of these medications are relevant to their pharmacological design and pharmacokinetic properties. DISCUSSION: The treatment of type 2 diabetes and obesity has evolved with the advent of GLP-1 RAs. These drugs have a multifaceted approach, emphasizing glycemic regulation, weight loss, and reduction of cardiovascular risk. Their unique mode of action, strong safety profile, and ability to be individualized according to each patient's needs make them a valuable therapeutic option in the management of metabolic disorders. Their pharmacological activities are also influenced by their different structural and pharmacokinetic properties. CONCLUSION: GLP-1 RAs have a complex strategy due to their pharmacological nature. The variations in their design have led to various members with varying pharmacodynamic and pharmacokinetic features. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Zayed, Mohamed F AU - Zayed MF AUID- ORCID: 0000-0001-8683-5460 AD - Pharmaceutical Sciences Department, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia. FAU - Khayat, Nada O AU - Khayat NO AD - Bachelor of Science of Doctor of Pharmacy Program, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia. FAU - Alsibyani, Rawan W AU - Alsibyani RW AD - Bachelor of Science of Doctor of Pharmacy Program, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia. FAU - Alshami, Rahaf Z AU - Alshami RZ AD - Bachelor of Science of Doctor of Pharmacy Program, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia. FAU - Alsubahi, Ramzyah A AU - Alsubahi RA AD - Bachelor of Science of Doctor of Pharmacy Program, Fakeeh College for Medical Sciences, Jeddah, 21461, Saudi Arabia. FAU - Alamoudi, Mariam K AU - Alamoudi MK AD - Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Pharm Des JT - Current pharmaceutical design JID - 9602487 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Hypoglycemic Agents/pharmacokinetics/chemistry/pharmacology/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Drug Design MH - *Glucagon-Like Peptide 1 MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism OTO - NOTNLM OT - GLP-1 receptors agonists OT - glucagon OT - insulin OT - pharmacokinetic OT - physicochemical OT - type 2 diabetes mellitus EDAT- 2025/08/13 06:30 MHDA- 2026/04/15 06:29 CRDT- 2025/08/13 02:23 PHST- 2024/12/19 00:00 [received] PHST- 2025/03/11 00:00 [accepted] PHST- 2026/04/15 06:29 [medline] PHST- 2025/08/13 06:30 [pubmed] PHST- 2025/08/13 02:23 [entrez] AID - CPD-EPUB-150007 [pii] AID - 10.2174/0113816128375766250720234005 [doi] PST - ppublish SO - Curr Pharm Des. 2026;32(14):1095-1106. doi: 10.2174/0113816128375766250720234005. PMID- 40798974 OWN - NLM STAT- MEDLINE DCOM- 20260218 LR - 20260528 IS - 2212-4063 (Electronic) IS - 1871-529X (Linking) VI - 25 IP - 4 DP - 2025 TI - Oral Semaglutide: A Step Forward in Cardiovascular Risk Management for Type 2 Diabetes. PG - 227-230 LID - 10.2174/011871529X421551250801194823 [doi] AB - Recent cardiovascular outcome trials (CVOTs) have reshaped the therapeutic landscape of type 2 diabetes mellitus (T2DM), revealing that certain glucose-lowering agents, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), offer substantial cardiovascular benefits beyond glycemic control. Injectable GLP-1RAs, such as semaglutide and liraglutide, have been shown to reduce major adverse cardiovascular events (MACE), but barriers, including cost, access, and the burden of injections, persist. The SOUL trial marks a significant milestone by evaluating oral semaglutide in high-risk patients, demonstrating a 14% reduction in MACE versus placebo and reinforcing GLP-1RAs cardioprotective potential in an oral formulation. This advancement holds promise for patient populations underrepresented in prior trials. However, gastrointestinal side effects and strict dosing requirements challenge long-term adherence. While the findings suggest improved accessibility and real-world applicability, further comparative trials with injectables, extended follow-up, and cost-effectiveness studies are essential. As evidence evolves, oral GLP-1RAs may represent a more patient-centered approach to managing diabetes and cardiovascular risk. This perspective article aims to explore the implications of the SOUL trial, highlight ongoing challenges in adherence and implementation, and discuss the future role of oral GLP-1RAs in cardiovascular and diabetes care. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Luna-Ceron, Eder AU - Luna-Ceron E AUID- ORCID: 0000-0002-6484-4304 AD - Internal Medicine Department, Texas Tech University Health Sciences Center, El Paso, Texas, 79905, United States. FAU - Kattamuri, Lakshmi AU - Kattamuri L AD - Internal Medicine Department, Texas Tech University Health Sciences Center, El Paso, Texas, 79905, United States. FAU - Duvvuru, Sparsha Reddy AU - Duvvuru SR AD - Internal Medicine Department, Texas Tech University Health Sciences Center, El Paso, Texas, 79905, United States. FAU - Mukherjee, Debabrata AU - Mukherjee D AD - Internal Medicine Department, Texas Tech University Health Sciences Center, El Paso, Texas, 79905, United States. AD - Cardiovascular Medicine Department, Texas Tech University Health Sciences Center, El Paso, Texas, 79905, United States. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Cardiovasc Hematol Disord Drug Targets JT - Cardiovascular & hematological disorders drug targets JID - 101269160 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Cardiovascular Diseases/prevention & control/etiology MH - Administration, Oral MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Heart Disease Risk Factors OTO - NOTNLM OT - GLP-1 receptor agonists OT - Oral semaglutide OT - SOUL trial OT - cardiovascular outcomes OT - medication adherence. OT - type 2 diabetes EDAT- 2025/08/13 06:30 MHDA- 2026/02/18 10:06 CRDT- 2025/08/13 02:23 PHST- 2025/06/10 00:00 [received] PHST- 2025/07/03 00:00 [revised] PHST- 2025/07/10 00:00 [accepted] PHST- 2026/02/18 10:06 [medline] PHST- 2025/08/13 06:30 [pubmed] PHST- 2025/08/13 02:23 [entrez] AID - CHDDT-EPUB-150002 [pii] AID - 10.2174/011871529X421551250801194823 [doi] PST - ppublish SO - Cardiovasc Hematol Disord Drug Targets. 2025;25(4):227-230. doi: 10.2174/011871529X421551250801194823. PMID- 40788646 OWN - NLM STAT- MEDLINE DCOM- 20250811 LR - 20260717 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 8 DP - 2025 Aug 1 TI - Semaglutide or Tirzepatide and Optic Nerve and Visual Pathway Disorders in Type 2 Diabetes. PG - e2526327 LID - 10.1001/jamanetworkopen.2025.26327 [doi] LID - e2526327 AB - IMPORTANCE: Semaglutide and tirzepatide, the new generation of glucagon-like peptide-1 receptor agonist used to treat type 2 diabetes and obesity, were recently reported to be associated with increased risk of nonarteritic anterior ischemic optic neuropathy (NAION). However, reported associations were inconsistent, and it remains unknown if semaglutide or tirzepatide is associated with other disorders of the optic nerve and visual pathways. OBJECTIVE: To examine associations of treatment with either semaglutide or tirzepatide with first-time diagnoses of optic nerve and visual pathway disorders in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: This cohort study emulated target trials based on a nationwide, population-based database of US patient electronic health records from December 2017 to January 2023. Models were adjusted by propensity score matching. Eligible patients had type 2 diabetes and no prior diagnosis of eye disorders and were prescribed semaglutide, tirzepatide, or other antidiabetic medications. EXPOSURES: Prescription of semaglutide or tirzepatide vs other antidiabetic medications (insulins, metformin, dipeptidyl-peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, thiazolidinediones, and other glucagon-like peptide 1 receptor agonists). MAIN OUTCOMES AND MEASURES: First-time diagnoses of NAION and other optic nerve disorders during a 2-year follow-up were examined using Cox proportional hazards and Kaplan-Meier survival analyses. RESULTS: After propensity score matching among 1 511 637 eligible patients, the study population comprised 159 398 matched patients with type 2 diabetes (mean [SD] age, 56.5 [13.3] years; 83 123 women [52.15%]), including 79 699 patients in the semaglutide or tirzepatide group and 79 699 patients in the comparison group. During the 2-year follow-up, there were 35 patients (0.04%) with NAION in the semaglutide or tirzepatide group and 19 patients (0.02%) with NAION in the matched comparison group (hazard ratio, 1.76 [95% CI, 1.01-3.07]). There were 93 patients (0.12%) with other optic nerve disorders in the semaglutide or tirzepatide group and 54 patients (0.07%) with other optic nerve disorders in the matched comparison group (hazard ratio, 1.65 [95% CI, 1.18-2.31]). No association was found with other disorders of the optic nerve or visual pathways. CONCLUSIONS AND RELEVANCE: In this study of patients with type 2 diabetes who had no prior eye disorders, patients prescribed semaglutide or tirzepatide had an increased risk of NAION and other optic nerve disorders, although the overall risk was low. These findings highlight the need for close monitoring of these conditions. FAU - Wang, Lindsey AU - Wang L AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio. FAU - Volkow, Nora D AU - Volkow ND AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, North Bethesda, Maryland. FAU - Kaelber, David C AU - Kaelber DC AD - Center for Clinical Informatics Research and Education, MetroHealth System, Cleveland, Ohio. FAU - Xu, Rong AU - Xu R AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio. LA - eng GR - UM1 TR004528/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250801 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - doi: 10.1001/jamanetworkopen.2025.26336 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Aged MH - Cohort Studies MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12340659 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2025/08/11 12:33 MHDA- 2025/08/11 12:34 PMCR- 2025/08/11 CRDT- 2025/08/11 11:42 PHST- 2025/08/11 12:34 [medline] PHST- 2025/08/11 12:33 [pubmed] PHST- 2025/08/11 11:42 [entrez] PHST- 2025/08/11 00:00 [pmc-release] AID - 2837377 [pii] AID - zoi250741 [pii] AID - 10.1001/jamanetworkopen.2025.26327 [doi] PST - epublish SO - JAMA Netw Open. 2025 Aug 1;8(8):e2526327. doi: 10.1001/jamanetworkopen.2025.26327. PMID- 40788007 OWN - NLM STAT- MEDLINE DCOM- 20251212 LR - 20260130 IS - 1743-9159 (Electronic) IS - 1743-9191 (Print) IS - 1743-9159 (Linking) VI - 111 IP - 12 DP - 2025 Dec 1 TI - Association of semaglutide use with outcomes in chronic plantar heel pain: a prospective observational cohort and a pilot interventional study. PG - 9333-9341 LID - 10.1097/JS9.0000000000003156 [doi] AB - BACKGROUND: Whether patients with chronic plantar heel pain (PHP) can benefit from glucagon-like peptide-1 receptor agonists (GLP1-RAs) remained unclear. METHODS: This study included a prospective observational cohort and a pilot interventional component. In the observational arm, more than 3000 adults with chronic PHP (duration of symptoms >6 months) were recruited with at least 2-year follow-up from two medical centers. The primary endpoint was the change from baseline of Foot Health Status Questionnaire (FHSQ) pain subdomain at the last follow-up. Secondary endpoints included first-step pain, FHSQ function subdomain, the amount of NSAIDs consumption, number of injection therapies/extracorporeal shockwave therapy (ESWT) sessions/manual stretching, days of orthosis wearing and thickness of plantar fascia. As supporting evidence, a pilot interventional study was conducted in 30 patients with chronic PHP who received semaglutide, with outcomes assessed over 12 months using before-and-after evaluations of pain, function, and imaging. RESULTS: In the prospective observational cohort, 92 out of 2902 patients who received semaglutide in purpose of treating type 2 diabetes (T2DM) and/or weight loss in the final analysis were identified. Change from baseline in FHSQ pain subdomain was significantly higher in semaglutide group compared with control group (adjusted mean difference, 14.86 [95% CI, 9.97 to 19.75], P < 0.001), favoring semaglutide. Similar results were observed from the analysis of FHSQ function subdomain, first-step pain and several therapeutic interventions (oral and topical NSAIDs, corticosteroid injection and orthosis wearing). For structural alterations, plantar fascia thickening velocity was significantly lower in the semaglutide group when compared with control group (-0.25 mm/year [-0.41 to -0.09], P = 0.002). For interventional use of semaglutide, improvements in all measured outcomes (FHSQ pain/function subscales, first-step pain and thickness of plantar fascia) were observed with all P values less than 0.001. In the interventional substudy, mean FHSQ pain scores improved from 28.09 +/- 10.34 at baseline to 60.28 +/- 21.34 at follow-up ( P < 0.001). FHSQ function subdomain scores increased from 27.23 +/- 17.44 to 80.71 +/- 19.55 ( P < 0.001). CONCLUSIONS: Semaglutide might be a potential therapeutic candidate for chronic PHP patients by improving patient-reported outcomes and plantar fascia thickening. Further randomized trial is warranted by our study to further evaluate the therapeutic effects of GLP-1RAs on chronic PHP. CI - Copyright (c) 2025 The Author(s). Published by Wolters Kluwer Health, Inc. FAU - Yang, Fan AU - Yang F AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Zhou, Lenian AU - Zhou L AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Zhang, Jieyuan AU - Zhang J AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Wang, Qiuke AU - Wang Q AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Cai, Qianying AU - Cai Q AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Wang, Jiazheng AU - Wang J AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Wu, Chenglin AU - Wu C AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Li, Xueqian AU - Li X AD - Department of Orthopaedics, Huashan Hospital, Fudan University, Shanghai, People's Republic of China. FAU - Zhang, Jinshan AU - Zhang J AD - Department of Orthopaedics, Jinjiang Municipal Hospital, Fujian, People's Republic of China. FAU - Zheng, Yongqiang AU - Zheng Y AD - Department of Orthopaedics, Jinjiang Municipal Hospital, Fujian, People's Republic of China. FAU - Ma, Xin AU - Ma X AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Zhu, Hongyi AU - Zhu H AUID- ORCID: 0000-0001-9643-0790 AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. FAU - Shi, Zhongmin AU - Shi Z AD - Department of Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. AD - Institute of Clinical Research, National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, People's Republic of China. LA - eng PT - Journal Article PT - Observational Study DEP - 20250808 PL - United States TA - Int J Surg JT - International journal of surgery (London, England) JID - 101228232 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Pilot Projects MH - Male MH - Middle Aged MH - Prospective Studies MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Aged MH - Treatment Outcome MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - *Chronic Pain/drug therapy/etiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Fasciitis, Plantar/drug therapy MH - Heel MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - Pain Measurement MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12695207 OTO - NOTNLM OT - GLP1-RA OT - obesity OT - plantar fasciitis OT - plantar heel pain OT - semaglutide OT - weight loss COIS- Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. The authors declare no competing interests. EDAT- 2025/08/11 12:33 MHDA- 2025/12/12 07:20 PMCR- 2025/12/10 CRDT- 2025/08/11 09:03 PHST- 2025/04/24 00:00 [received] PHST- 2025/07/20 00:00 [accepted] PHST- 2025/12/12 07:20 [medline] PHST- 2025/08/11 12:33 [pubmed] PHST- 2025/08/11 09:03 [entrez] PHST- 2025/12/10 00:00 [pmc-release] AID - 01279778-202512000-00044 [pii] AID - IJS-D-25-01986 [pii] AID - 10.1097/JS9.0000000000003156 [doi] PST - ppublish SO - Int J Surg. 2025 Dec 1;111(12):9333-9341. doi: 10.1097/JS9.0000000000003156. Epub 2025 Aug 8. PMID- 40787019 OWN - NLM STAT- MEDLINE DCOM- 20250811 LR - 20260127 IS - 0026-6620 (Print) IS - 0026-6620 (Linking) VI - 122 IP - 4 DP - 2025 Jul-Aug TI - Injections vs. Scalpels: Where Do Surgery and GLP-1's Align in Modern Obesity treatment? PG - 340-344 AB - Recent advancements in pharmacologic treatment of obesity and metabolic disease with nutrient-stimulated hormones (NuSH), particularly Semaglutide and Tirzepatide, have been revolutionary, showing weight reduction results comparable to some surgical options. This is especially promising as, despite the proven efficacy and safety of metabolic/bariatric surgery (MBS), its utilization has remained quite limited. This review article discusses the current literature on the comparative effectiveness of these two treatments and their impact on comorbidities such as type 2 diabetes mellitus (DM2) and cardiovascular disease. While weight reduction with these NewSH's (sic) appears similar to a sleeve gastrectomy, though significantly less than gastric bypass, MBS remains the gold standard treatment for patients with more severe obesity especially those with higher cardiometabolic disease burden. CI - Copyright 2025 by the Missouri State Medical Association. FAU - Lindquist, Matthew AU - Lindquist M AD - Owner and Founder of MoKan Weight Loss and Metabolic Health LLC, Prairie Village, Kansas, Missouri, USA. FAU - Varghese, Esther AU - Varghese E AD - Internal Medicine Resident at Thomas Hospital, Fairhope, Alabama, USA. FAU - Bassham, Cooper AU - Bassham C AD - Medical Student at the University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. LA - eng PT - Journal Article PT - Review PL - United States TA - Mo Med JT - Missouri medicine JID - 0400744 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Obesity/surgery/drug therapy/therapy MH - *Bariatric Surgery/methods MH - *Glucagon-Like Peptide 1/therapeutic use/administration & dosage MH - Diabetes Mellitus, Type 2 MH - Weight Loss/drug effects MH - Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Injections MH - Semaglutide PMC - PMC12331298 COIS- Disclosure: This manuscript is based on a lecture presented April 5, 2024, at the 2024 Missouri State Medical Association Annual Convention in St. Louis, Missouri. ML is a member of the Obesity Speaker's Bureau for Novo Nordisk and Eli Lilly. Artificial intelligence, language models, machine learning, or similar technologies were not used in the conceptualization, study, research, preparation, or writing of this manuscript. EDAT- 2025/08/11 17:20 MHDA- 2025/08/11 17:21 PMCR- 2025/07/01 CRDT- 2025/08/11 06:24 PHST- 2025/08/11 17:21 [medline] PHST- 2025/08/11 17:20 [pubmed] PHST- 2025/08/11 06:24 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - ms122_p0340 [pii] PST - ppublish SO - Mo Med. 2025 Jul-Aug;122(4):340-344. PMID- 40784425 OWN - NLM STAT- MEDLINE DCOM- 20251119 LR - 20260711 IS - 1532-8406 (Electronic) IS - 0883-5403 (Linking) VI - 40 IP - 12 DP - 2025 Dec TI - As Few as Three Months of Preoperative Semaglutide Exposure Prior to Total Knee Arthroplasty Is Associated With Reduced Postoperative Adverse Events in Patients Who Have Type II Diabetes. PG - 3089-3096.e1 LID - S0883-5403(25)01008-3 [pii] LID - 10.1016/j.arth.2025.08.003 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, has been increasingly used for the management of type II diabetes mellitus (T2DM). Although recent literature suggests semaglutide may reduce postoperative total knee arthroplasty (TKA) complications, to our knowledge, the minimum duration of semaglutide exposure associated with superior outcomes has never been studied. METHODS: A retrospective cohort of patients with T2DM was identified from a national database and stratified into one of five mutually exclusive groups of semaglutide exposure before TKA: six to 12 months, three to six months, two to three months, one to two months, or less than one month. Each cohort was individually matched 1:4 with non-semaglutide T2DM TKA controls. The occurrence of 90-day severe adverse events including surgical site infection, sepsis, venous thromboembolism, cardiac events, pancreatitis, and minor adverse events (MAEs) including wound dehiscence, hematoma, transfusion, acute kidney injury, pneumonia, and urinary tract infection, was compared using multivariable logistic regression. RESULTS: After matching, patient cohorts with preoperative semaglutide exposure for six to 12 months, three to six months, two to three months, one to two months, and less than one month included 745, 451, 210, 113, and 91, respectively. Patients initiating semaglutide less than one month before TKA revealed lower odds of MAE (odds ratio 0.16, P < 0.001), with consistent reduction in MAE across all increased exposure durations (P < 0.001 for all). Reduced odds of severe adverse events were significant after a minimum of two to three months of preoperative exposure (odds ratio 0.25, P < 0.001). CONCLUSIONS: A 3-month period of preoperative semaglutide exposure before TKA appears to be sufficient to reduce both minor and severe postoperative adverse events. Although these observational findings cannot establish causation, they have major clinical implications and lay the foundation for prospective analysis aimed at optimizing preoperative care pathways. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Seddio, Anthony E AU - Seddio AE AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. FAU - Vasudevan, Rajiv S AU - Vasudevan RS AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. FAU - Gouzoulis, Michael J AU - Gouzoulis MJ AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. FAU - Ansah-Twum, Jeremy K AU - Ansah-Twum JK AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. FAU - Grauer, Jonathan N AU - Grauer JN AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. FAU - Rubin, Lee E AU - Rubin LE AD - Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, Connecticut. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250808 PL - United States TA - J Arthroplasty JT - The Journal of arthroplasty JID - 8703515 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Arthroplasty, Replacement, Knee/adverse effects MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Aged MH - Retrospective Studies MH - Middle Aged MH - *Postoperative Complications/prevention & control/epidemiology/etiology MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Time Factors MH - Preoperative Care/methods MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - glucagon-like peptide-1 OT - preoperative optimization OT - semaglutide OT - total knee arthroplasty OT - type II diabetes EDAT- 2025/08/11 00:26 MHDA- 2025/11/20 00:30 CRDT- 2025/08/10 19:33 PHST- 2025/04/10 00:00 [received] PHST- 2025/08/01 00:00 [revised] PHST- 2025/08/03 00:00 [accepted] PHST- 2025/11/20 00:30 [medline] PHST- 2025/08/11 00:26 [pubmed] PHST- 2025/08/10 19:33 [entrez] AID - S0883-5403(25)01008-3 [pii] AID - 10.1016/j.arth.2025.08.003 [doi] PST - ppublish SO - J Arthroplasty. 2025 Dec;40(12):3089-3096.e1. doi: 10.1016/j.arth.2025.08.003. Epub 2025 Aug 8. PMID- 40782670 OWN - NLM STAT- MEDLINE DCOM- 20250809 LR - 20260608 IS - 2666-6340 (Electronic) IS - 2666-6340 (Linking) VI - 6 IP - 8 DP - 2025 Aug 8 TI - SOUL searching in GLP-1 therapy: Oral semaglutide confirms cardioprotection in type 2 diabetes. PG - 100774 LID - S2666-6340(25)00201-6 [pii] LID - 10.1016/j.medj.2025.100774 [doi] AB - Semaglutide's evolution from weekly injections to an SNAC-enabled tablet preserved its metabolic and cardiovascular efficacy. Large injectable CVOTs have demonstrated robust cardioprotection, and the SOUL trial now shows a 14% reduction in major adverse cardiovascular events with the oral formulation.(1) These data confirm formulation-independent benefit, positioning oral semaglutide as the only cardioprotective, non-injectable, GLP-1RA for high-risk type 2 diabetes. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Schwarz, Christine Rode AU - Schwarz CR AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark. Electronic address: christine.rode.schwarz@regionh.dk. FAU - Vilsboll, Tina AU - Vilsboll T AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Cardiotonic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Humans MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Cardiotonic Agents/administration & dosage/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of interests C.R.S. has served as a consultant to and/or received research support from Eli Lilly and Novo Nordisk. T.V. has served on scientific advisory panels, been part of speaker's bureaus, and served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Mundipharma, MSD/Merck, Novo Nordisk, Regor, Roche, Sanofi, Sun Pharmaceuticals, and Zealand Pharma. EDAT- 2025/08/10 06:16 MHDA- 2025/08/10 06:17 CRDT- 2025/08/09 18:17 PHST- 2025/06/17 00:00 [received] PHST- 2025/06/18 00:00 [revised] PHST- 2025/06/19 00:00 [accepted] PHST- 2025/08/10 06:17 [medline] PHST- 2025/08/10 06:16 [pubmed] PHST- 2025/08/09 18:17 [entrez] AID - S2666-6340(25)00201-6 [pii] AID - 10.1016/j.medj.2025.100774 [doi] PST - ppublish SO - Med. 2025 Aug 8;6(8):100774. doi: 10.1016/j.medj.2025.100774. PMID- 40782266 OWN - NLM STAT- MEDLINE DCOM- 20250809 LR - 20260127 IS - 1432-0827 (Electronic) IS - 0171-967X (Linking) VI - 116 IP - 1 DP - 2025 Aug 9 TI - Effect of Oral Semaglutide on Volumetric BMD and Bone Microarchitecture in Overweight/Obese Individuals with Type 2 Diabetes. PG - 105 LID - 10.1007/s00223-025-01417-2 [doi] AB - Obesity, type 2 diabetes, and therapeutic weight loss are all associated with impaired bone quantity and microarchitecture. Glucagon-like peptide receptor analogs (GLP1RAs) have direct beneficial effects on bone microarchitecture, in preclinical settings. This study aimed to evaluate the net impact of GLP1RA on microarchitecture in overweight/obese type 2 diabetes individuals. It was an interventional, paired-sample cohort study with oral semaglutide in consecutive type 2 diabetes patients with overweight/obesity and metabolic-dysfunction associated steatotic liver disease. Oral semaglutide was initiated at 3 mg daily, with escalation to 14 mg at the end of 12 weeks. Bone turnover markers (P1NP, beta-CTX) were estimated by electrochemiluminescence and body composition by DXA. Volumetric bone mineral density (vBMD) and bone microarchitecture were assessed using HRpQCT (XtremeCT II, Scanco Medical). There were 36 patients (44% males) with a mean (+/- SD) age of 50.8 +/- 10.1 years, mean BMI of 34.3 +/- 6.2 kg/m(2) and median duration of diabetes being 7 (IQR 2-13) years. At 52 weeks, there was an increase in tibial total vBMD (317.4 +/- 47.4 vs. 331.6 +/- 52.7 mg HA/cm(3), p = 0.06) and cortical vBMD at both radius and tibia (trend towards significance). Trabecular vBMD and trabecular bone volume fraction at radius were also increased. Males showed significantly increased tibial total and cortical vBMD, and trabecular bone volume fraction, but there was no significant change in females. There were no significant differences in bone microarchitecture based on steatosis or fibrosis reduction. Oral semaglutide improves vBMD in overweight/obese type 2 diabetes, despite a significant reduction in body weight. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Das, Liza AU - Das L AUID- ORCID: 0000-0002-9701-9554 AD - Department of Internal Medicine, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. AD - Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), 001, Nehru Extension Block, Chandigarh, India. FAU - Bhadada, Sanjay Kumar AU - Bhadada SK AUID- ORCID: 0000-0002-0410-8778 AD - Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), 001, Nehru Extension Block, Chandigarh, India. bhadadask@gmail.com. FAU - Arjunan, Durairaj AU - Arjunan D AUID- ORCID: 0000-0001-5110-334X AD - Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), 001, Nehru Extension Block, Chandigarh, India. FAU - Duseja, Ajay AU - Duseja A AUID- ORCID: 0000-0003-3590-2664 AD - Department of Hepatology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. LA - eng PT - Journal Article DEP - 20250809 PL - United States TA - Calcif Tissue Int JT - Calcified tissue international JID - 7905481 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - *Bone Density/drug effects MH - Middle Aged MH - *Glucagon-Like Peptides/pharmacology/therapeutic use/administration & dosage MH - *Obesity/complications/drug therapy MH - Adult MH - *Overweight/complications/drug therapy MH - *Bone and Bones/drug effects MH - Hypoglycemic Agents/therapeutic use/pharmacology/administration & dosage MH - Administration, Oral MH - Cohort Studies MH - Bone Remodeling/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Bone microarchitecture OT - Glucagon-like peptide receptor analogs OT - HRpQCT OT - MASLD OT - Obesity OT - Semaglutide OT - Weight loss COIS- Declarations. Conflict of interest: The authors have no conflicts of interest to declare. Research Involving Human Participants and/or Animals: The study was approved by the Institutional Ethics Committee (PGIMER IEC) and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Informed Consent: Written, informed consent was obtained from all participants. EDAT- 2025/08/09 13:48 MHDA- 2025/08/09 13:49 CRDT- 2025/08/09 11:16 PHST- 2025/04/20 00:00 [received] PHST- 2025/07/22 00:00 [accepted] PHST- 2025/08/09 13:49 [medline] PHST- 2025/08/09 13:48 [pubmed] PHST- 2025/08/09 11:16 [entrez] AID - 10.1007/s00223-025-01417-2 [pii] AID - 10.1007/s00223-025-01417-2 [doi] PST - epublish SO - Calcif Tissue Int. 2025 Aug 9;116(1):105. doi: 10.1007/s00223-025-01417-2. PMID- 40779264 OWN - NLM STAT- MEDLINE DCOM- 20250808 LR - 20260717 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 8 DP - 2025 Aug 1 TI - Changes in Cardiovascular Risk Factors and Health Care Expenditures Among Patients Prescribed Semaglutide. PG - e2526013 LID - 10.1001/jamanetworkopen.2025.26013 [doi] LID - e2526013 AB - IMPORTANCE: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored. OBJECTIVE: To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 23 522 adults (>/=18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System. EXPOSURE: The first prescription of semaglutide identified at the ingredient level, stratified by type 2 diabetes status. MAIN OUTCOMES AND MEASURES: Primary outcomes included changes in weight (% baseline), blood pressure (BP), total cholesterol, and hemoglobin A1c. Secondary outcomes assessed health care expenditures using Medicare-based cost estimates. A staggered difference-in-differences design compared outcomes of patients after the first semaglutide prescription with those of patients who had not yet received their prescription during the same period. RESULTS: The study cohort included 23 522 patients (mean [SD] age at initiation of semaglutide, 56.2 [12.9] years; 66.7% female; 68.6% with diabetes). In the overall cohort, initiation of semaglutide was significantly associated with a -3.8% (95% CI, -3.9% to -3.7%) reduction in weight at 13 to 24 months, with a -5.1% (95% CI, -5.5% to -4.7%) reduction in weight among patients without diabetes. Significant reductions in diastolic BP (-1.5 mm Hg; 95% CI, -1.7 to -1.4 mm Hg), systolic BP (-1.1 mm Hg; 95% CI, -1.4 to -0.8 mm Hg), and total cholesterol (-12.8 mg/dL; 95% CI, -14.3 to -11.4 mg/dL) were also observed. Hemoglobin A1c reductions were greater among patients with diabetes (-0.3%; 95% CI, -0.3% to -0.2%) compared with patients without diabetes (-0.1%; 95% CI, -0.2% to -0.01%). Imputed health care expenditures, excluding the cost of semaglutide, increased by $80 per month (95% CI, $68-$92 per month) during the 13- to 24-month period, which was associated with inpatient stays shifting to more expensive circulatory and metabolic diagnoses. CONCLUSIONS AND RELEVANCE: In this cohort study of adults prescribed semaglutide, initiation was associated with reductions in weight and cardiovascular risk factors but increases in health care expenditures, excluding semaglutide costs. These findings suggest potential clinical benefits in routine practice, while highlighting the need to evaluate the long-term impact of semaglutide on economic outcomes. FAU - Lu, Yuan AU - Lu Y AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut. AD - Department of Biomedical Informatics and Data Sciences, Yale School of Medicine, New Haven, Connecticut. FAU - Liu, Yuntian AU - Liu Y AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut. AD - Department of Biomedical Informatics and Data Sciences, Yale School of Medicine, New Haven, Connecticut. FAU - Totojani, Tedi AU - Totojani T AD - Yale School of Management, New Haven, Connecticut. FAU - Kim, Chungsoo AU - Kim C AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut. FAU - Khera, Rohan AU - Khera R AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut. FAU - Xu, Hua AU - Xu H AD - Department of Biomedical Informatics and Data Sciences, Yale School of Medicine, New Haven, Connecticut. FAU - Brush, John E Jr AU - Brush JE Jr AD - Sentara Health Research Center, Sentara Health, Virginia Beach, Virginia. AD - Macon & Joan Brock Virginia Health Sciences at Old Dominion University, Norfolk, Virginia. FAU - Krumholz, Harlan M AU - Krumholz HM AD - Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. AD - Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, Connecticut. AD - Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut. FAU - Abaluck, Jason AU - Abaluck J AD - Yale School of Management, New Haven, Connecticut. AD - National Bureau of Economic Research, New Haven, Connecticut. LA - eng GR - R01 HL169954/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural DEP - 20250801 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Pressure/drug effects MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Glycated Hemoglobin/analysis MH - *Health Expenditures/statistics & numerical data MH - *Heart Disease Risk Factors MH - Retrospective Studies MH - United States MH - *Glucagon-Like Peptide-1 Receptor Agonists/economics/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12334959 COIS- Conflict of Interest Disclosures: Dr Lu reported receiving grants from the National Institutes of Health, the Patient-Centered Outcomes Research Institute, Sentara Research Foundation, and Novartis outside the submitted work. Dr Khera reported receiving grants from the National Heart, Lung, and Blood Institute, the Doris Duke Charitable Foundation, Bristol Myers Squibb (through Yale), Novo Nordisk (through Yale), and BridgeBio (through Yale); and being an academic cofounder of Ensight-AI and Evidence2Health outside the submitted work. Dr Krumholz reported receiving options from Element Science and Identifeye; receiving payments from F-Prime for advisory roles; being a co-founder of, and holding equity in, Hugo Health, Refactor Health, and ENSIGHT-AI; and being associated with research contracts through Yale University with Janssen, Kenvue, Novartis, and Pfizer. No other disclosures were reported. EDAT- 2025/08/08 12:29 MHDA- 2025/08/08 12:30 PMCR- 2025/08/08 CRDT- 2025/08/08 11:33 PHST- 2025/08/08 12:30 [medline] PHST- 2025/08/08 12:29 [pubmed] PHST- 2025/08/08 11:33 [entrez] PHST- 2025/08/08 00:00 [pmc-release] AID - 2837364 [pii] AID - zoi250733 [pii] AID - 10.1001/jamanetworkopen.2025.26013 [doi] PST - epublish SO - JAMA Netw Open. 2025 Aug 1;8(8):e2526013. doi: 10.1001/jamanetworkopen.2025.26013. PMID- 40774571 OWN - NLM STAT- MEDLINE DCOM- 20260205 LR - 20260205 IS - 2468-6530 (Electronic) IS - 2468-6530 (Linking) VI - 10 IP - 2 DP - 2026 Feb TI - Risk of Sight-Threatening Diabetic Retinopathy with Glucagon-Like Peptide-1 Receptor Agonist Use in Routine Clinical Practice: Comparative Effectiveness of Semaglutide, Dulaglutide, Liraglutide, and Exenatide. PG - 142-151 LID - S2468-6530(25)00355-0 [pii] LID - 10.1016/j.oret.2025.07.019 [doi] AB - PURPOSE: To investigate whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) agents differ with respect to the risk of developing sight-threatening diabetic retinopathy complications in patients with type 2 diabetes at moderate cardiovascular risk. DESIGN: Retrospective observational study under the target trial emulation framework involving adult (>/=21 years) enrollees in United States commercial, Medicare Advantage, and Medicare fee-for-service plans from January 1, 2014 to December 31, 2022. The study population included adults with type 2 diabetes, moderate cardiovascular disease risk, no baseline advanced diabetic retinopathy, and minimum 1 year enrollment before GLP-1 RA treatment. METHODS: Because of differences in GLP-1 RA agent use over time, we performed both a 3-way comparison of patients initiating liraglutide, dulaglutide, or exenatide from January 1, 2015, to December 31, 2021, and a 2-way comparison of patients initiating semaglutide or dulaglutide between January 1, 2019, and December 31, 2021. We assessed differences in complications using inverse propensity score weighted Cox proportional hazards models. MAIN OUTCOME MEASURES: Treatment for diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR). RESULTS: When comparing patients who initiated treatment with exenatide (n = 14 076, median follow-up 969 days; interquartile range [IQR] 578-1444) to those starting dulaglutide (n = 54 787, median follow-up 948 days; IQR 551-1457) or liraglutide (n = 25 562, median follow-up 1007 days; IQR 575-1494), no differences were found in the hazard (hazard ratio [HR]) of composite treatment for DME or PDR: exenatide versus dulaglutide (HR 0.90; 95% confidence interval (CI): 0.73-1.12), liraglutide versus dulaglutide (HR: 0.97; 95% CI: 0.79-1.19), or liraglutide versus exenatide (HR: 1.08; 95% CI: 0.83-1.38), nor were differences found in any comparisons for treatment of DME (HR: 0.93 [95% CI: 0.74-1.18]; HR 0.99 [95% CI: 0.79-1.24]; HR: 1.06 [95% CI: 0.80-1.40]) or PDR individually (HR: 1.16 [95% CI: 0.81-1.67]; HR: 1.05 [95% CI: 0.73-1.51]; HR: 0.91 [95% CI: 0.58-1.40). Likewise, when comparing patients initiating semaglutide (n = 30 911, median follow-up 625 days [IQR: 455-850]) versus dulaglutide (n = 32 844, median follow-up 639 days [IQR: 459-878]), the hazards for treatment of DME or PDR (HR: 0.88; 95% CI: 0.70-1.11), DME (HR: 0.89; 95% CI: 0.69-1.14), and PDR (HR: 0.70; 95% CI: 0.45-1.09) all found no difference between drugs. CONCLUSIONS: Despite the differences in systemic efficacy among the examined GLP-1 RAs, we identified no difference in the risk of sight-threatening diabetic retinopathy after initiation of different GLP-1 RA agents among adults with type 2 diabetes at moderate cardiovascular risk. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. CI - Copyright (c) 2025 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Barkmeier, Andrew J AU - Barkmeier AJ AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. Electronic address: barkmeier.andrew@mayo.edu. FAU - Deng, Yihong AU - Deng Y AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota; OptumLabs, Eden Prairie, Minnesota. FAU - Swarna, Kavya Sindhu AU - Swarna KS AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota; OptumLabs, Eden Prairie, Minnesota. FAU - Herrin, Jeph AU - Herrin J AD - Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut. FAU - Polley, Eric C AU - Polley EC AD - Department of Public Health Sciences, University of Chicago, Chicago, Illinois. FAU - Umpierrez, Guillermo E AU - Umpierrez GE AD - Division of Endocrinology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida. FAU - Ross, Joseph S AU - Ross JS AD - Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut. FAU - Mickelson, Mindy M AU - Mickelson MM AD - Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, Minnesota. FAU - McCoy, Rozalina G AU - McCoy RG AD - OptumLabs, Eden Prairie, Minnesota; Division of Endocrinology, Diabetes, & Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; University of Maryland Institute for Health Computing, North Bethesda, Maryland. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250806 PL - United States TA - Ophthalmol Retina JT - Ophthalmology. Retina JID - 101695048 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Diabetic Retinopathy/epidemiology/etiology/drug therapy/diagnosis MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Exenatide/therapeutic use MH - Retrospective Studies MH - Male MH - Female MH - *Recombinant Fusion Proteins/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Liraglutide/therapeutic use MH - Aged MH - Immunoglobulin Fc Fragments MH - Middle Aged MH - Follow-Up Studies OTO - NOTNLM OT - Diabetic macular edema OT - Diabetic retinopathy OT - Glucagon-like protein-1 receptor agonist OT - Proliferative diabetic retinopathy OT - Semaglutide EDAT- 2025/08/08 00:28 MHDA- 2026/02/06 00:30 CRDT- 2025/08/07 19:50 PHST- 2025/02/27 00:00 [received] PHST- 2025/07/28 00:00 [revised] PHST- 2025/07/30 00:00 [accepted] PHST- 2026/02/06 00:30 [medline] PHST- 2025/08/08 00:28 [pubmed] PHST- 2025/08/07 19:50 [entrez] AID - S2468-6530(25)00355-0 [pii] AID - 10.1016/j.oret.2025.07.019 [doi] PST - ppublish SO - Ophthalmol Retina. 2026 Feb;10(2):142-151. doi: 10.1016/j.oret.2025.07.019. Epub 2025 Aug 6. PMID- 40760786 OWN - NLM STAT- MEDLINE DCOM- 20250919 LR - 20260701 IS - 1749-6632 (Electronic) IS - 0077-8923 (Linking) VI - 1551 IP - 1 DP - 2025 Sep TI - Generalizability of glucagon-like peptide 1 receptor agonist clinical trial results to product labeling and the real world. PG - 15-18 LID - 10.1111/nyas.70025 [doi] AB - "Generalizability" refers to when trial results are applied to populations that did not participate in the trial. It is important when pre-licensing trial results are used by regulators to authorize the use of a drug in different countries. To "generalize" the results, the trial sample must represent the population from which participants are drawn. They must also ensure that the trial will mimic usual clinical practice. Double-blind, placebo-controlled phase 3 trials are very different from usual practice. Investigators have flagged that samples from phase 3 trials of liraglutide, semaglutide, and tirzepatide excluded one-third of US adults without diabetes who were eligible for weight loss. The authors advised caution on "generalizing" the results to populations excluded from these trials. However, they erroneously used "generalizability" when referring to "representativeness." Similarly, in studies assessing whether real-world populations from China, the United Kingdom, the United States, and Spain were represented in cardiovascular outcomes phase 3 trials in type 2 diabetes with dulaglutide, exenatide, liraglutide, and semaglutide, the authors used "generalizability" in the texts of the articles. The enrolled trial samples were not representative of the real-world population: the term "generalizable" should not have been used. There is widespread confusion among investigators regarding the correct use of the term "generalizability." CI - (c) 2025 The New York Academy of Sciences. FAU - Dal-Re, Rafael AU - Dal-Re R AUID- ORCID: 0000-0002-0980-2486 AD - Epidemiology Unit, Health Research Institute-Fundacion Jimenez Diaz University Hospital, Universidad Autonoma de Madrid, Madrid, Spain. LA - eng PT - Journal Article DEP - 20250804 PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Clinical Trials, Phase III as Topic MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - *Drug Labeling MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Liraglutide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - PRECIS-2 OT - applicability OT - explanatory trials OT - pivotal trials OT - pragmatic trials OT - representativeness OT - semantics EDAT- 2025/08/05 06:28 MHDA- 2025/09/19 18:30 CRDT- 2025/08/05 01:32 PHST- 2025/09/19 18:30 [medline] PHST- 2025/08/05 06:28 [pubmed] PHST- 2025/08/05 01:32 [entrez] AID - 10.1111/nyas.70025 [doi] PST - ppublish SO - Ann N Y Acad Sci. 2025 Sep;1551(1):15-18. doi: 10.1111/nyas.70025. Epub 2025 Aug 4. PMID- 40759509 OWN - NLM STAT- MEDLINE DCOM- 20250804 LR - 20260127 IS - 1757-790X (Electronic) IS - 1757-790X (Linking) VI - 18 IP - 8 DP - 2025 Aug 4 TI - Neuropsychiatric side effects of semaglutide in patients with dementia. LID - e262743 [pii] LID - 10.1136/bcr-2024-262743 [doi] AB - An older woman with dementia and type 2 diabetes was started on semaglutide and subsequently developed severe psychological and physical symptoms, including apathy, significant weight loss and decreased appetite. These symptoms markedly improved after the medication was discontinued. This case underscores the importance of recognising potential psychiatric side effects of semaglutide, especially in older adults with cognitive impairment. The experience highlights the need for careful monitoring when prescribing semaglutide in this population and suggests that discontinuation should be considered if adverse symptoms arise. It also raises awareness about the limited safety data on semaglutide in older patients, emphasising the necessity of further research to understand its effects on this vulnerable group. CI - (c) BMJ Publishing Group Limited 2025. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Jamshed, Namirah AU - Jamshed N AUID- ORCID: 0000-0002-3471-703X AD - Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USA namirah.jamshed@utsouthwestern.edu. FAU - Rehman, Syed Tabish AU - Rehman ST AUID- ORCID: 0000-0003-1532-5978 AD - The Aga Khan University, Karachi, Sindh, Pakistan. FAU - Khan, Noor AU - Khan N AD - Internal Medicine, UPMC, Pittsburgh, Pennsylvania, USA. LA - eng PT - Case Reports PT - Journal Article DEP - 20250804 PL - England TA - BMJ Case Rep JT - BMJ case reports JID - 101526291 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Apathy/drug effects MH - *Dementia/complications/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Dementia, Alzheimer's type OT - Depressive disorder OT - Diabetes OT - Memory Disorders COIS- Competing interests: None declared. EDAT- 2025/08/05 00:29 MHDA- 2025/08/05 00:30 CRDT- 2025/08/04 21:24 PHST- 2025/08/05 00:30 [medline] PHST- 2025/08/05 00:29 [pubmed] PHST- 2025/08/04 21:24 [entrez] AID - 18/8/e262743 [pii] AID - 10.1136/bcr-2024-262743 [doi] PST - epublish SO - BMJ Case Rep. 2025 Aug 4;18(8):e262743. doi: 10.1136/bcr-2024-262743. PMID- 40758358 OWN - NLM STAT- MEDLINE DCOM- 20251006 LR - 20260806 IS - 2168-6114 (Electronic) IS - 2168-6106 (Print) IS - 2168-6106 (Linking) VI - 185 IP - 10 DP - 2025 Oct 1 TI - Oral Semaglutide in an East Asian Population With Overweight or Obesity, With or Without Type 2 Diabetes: The OASIS 2 Randomized Clinical Trial. PG - 1206-1217 LID - 10.1001/jamainternmed.2025.3599 [doi] AB - IMPORTANCE: The efficacy and safety of oral semaglutide, 50 mg, in an East Asian population that also includes individuals with type 2 diabetes (T2D), who are prone to weight-related complications at lower body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) thresholds than other ethnic groups, is currently unknown. OBJECTIVE: To assess the efficacy and safety of once-daily oral semaglutide, 50 mg, for the treatment of overweight and obesity in East Asian individuals with or without T2D. DESIGN, SETTING, AND PARTICIPANTS: The OASIS 2 trial was a 68-week (plus 7 weeks of follow-up) multicenter, double-blind, placebo-controlled phase 3a randomized clinical trial conducted from November 2021 to September 2023 in Japan and South Korea. Adults with a BMI of 27.0 or greater with 2 or more related complications or a BMI of 35.0 or greater with 1 or more related complications were enrolled. Approximately 25% of participants were planned to have T2D at screening. Data were analyzed from March 2022 to July 2025. INTERVENTIONS: Participants were assigned 2:1 to once-daily oral semaglutide, 50 mg, or placebo, plus lifestyle recommendations, for 68 weeks. MAIN OUTCOMES AND MEASURES: The coprimary end points were percentage change in body weight from baseline and the proportion of participants who achieved 5% or greater body weight reductions. Changes in physical function, cardiometabolic risk factors, and safety were also evaluated. RESULTS: Overall, 201 participants (mean [SD] age, 49 [11] years; mean [SD] body weight, 91.9 [18.2] kg; 87 [43.3%] female; 51 [25.4%] with T2D) were randomized to semaglutide (n = 134) or placebo (n = 67). The mean (SEM) percentage change in body weight was -14.3% (0.8) with semaglutide vs -1.3% (1.1) with placebo (estimated treatment difference, -13.07 percentage points; 95% CI, -15.61 to -10.52; P < .001). More participants had 5% or greater body weight reductions with semaglutide vs placebo (107 of 127 [84.3%] vs 11 of 64 [17.2%]; odds ratio, 23.00; 95% CI, 10.28-51.42; P < .001). Gastrointestinal tract adverse events were reported by 85 of 134 participants (63.4%) with semaglutide and 23 of 66 with placebo (34.8%). Adverse events led to treatment discontinuation in 6 of 134 participants (4.5%) in the semaglutide arm. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, among East Asian adults with overweight or obesity, with or without T2D, oral semaglutide, 50 mg, led to a superior and clinically meaningful reduction in body weight compared with placebo, with a safety profile consistent with the glucagon-like peptide-1 receptor agonist class. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05132088. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Toranomon Hospital, Tokyo, Japan. FAU - Heftdal, Line Dam AU - Heftdal LD AD - Novo Nordisk, Soborg, Denmark. FAU - Ko, Hae-Jin AU - Ko HJ AD - Kyungpook National University School of Medicine, Kyungpook National University Hospital, Daegu, South Korea. FAU - Overvad, Maria AU - Overvad M AD - Novo Nordisk, Soborg, Denmark. FAU - Shimomura, Iichiro AU - Shimomura I AD - Graduate School of Medicine, Osaka University, Osaka, Japan. FAU - Thamattoor, Usha K AU - Thamattoor UK AD - Novo Nordisk, Bangalore, India. FAU - Kim, Kyoung-Kon AU - Kim KK AD - Gachon University College of Medicine, Gachon University Gil Medical Center, Incheon, South Korea. CN - OASIS 2 Investigators LA - eng SI - ClinicalTrials.gov/NCT05132088 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Intern Med JT - JAMA internal medicine JID - 101589534 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA Intern Med. 2025 Oct 1;185(10):1217. doi: 10.1001/jamainternmed.2025.3618. PMID: 40758368 MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Double-Blind Method MH - East Asian People MH - Glucagon-Like Peptide 1 MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Hypoglycemic Agents/administration & dosage MH - Japan/epidemiology MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - Republic of Korea/epidemiology MH - Semaglutide MH - Treatment Outcome MH - Weight Loss/drug effects PMC - PMC12322823 COIS- Conflict of Interest Disclosures: Dr Kadowaki reported grants and personal fees from Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co Ltd, Novo Nordisk Pharma Ltd, Mitsubishi Tanabe Pharma Corporation, Taisho Pharmaceutical Co Ltd, Sumitomo Pharma Co Ltd, Kyowa Kirin, Daiichi Sankyo, and Takeda Pharma; personal fees from MSD Corporation, Abbott Japan Ltd, Teijin Pharma Ltd, Ono Pharmaceutical Co Ltd, FUJIFILM Toyama Chemical Co Ltd, Medtronic Japan, and AstraZeneca outside the submitted work. Dr Heftdal reported nonfinancial support from OPEN Health Communications during the conduct of the study and is an employee and shareholder of Novo Nordisk outside the submitted work. Dr Ko reported grants from Novo Nordisk during the conduct of the study; grants from Boehringer Ingelheim, Huons, and Hanmi Pharma Korea; and personal fees from Novo Nordisk, Hanmi Pharma Korea, Amgen Korea, and Alvogen Korea outside the submitted work. Dr Overvad is an employee of Novo Nordisk and reported nonfinancial support from OPEN Health Communications during the conduct of the study. Dr Shimomura reported grants from Eli Lilly Japan K.K., Teijin Pharma, Mochida Pharmaceutical, Kowa, Kyowa Kirin, Sumitomo Pharma, Rohto Pharmaceutical, Kobayashi Pharmaceutical, Nissin Foods Holdings, Cancerscan, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Osaka Central Hospital, Hakuhokai Central Hospital, Midori Health Care Center, Kyowakai Medical Corporation, Ono Medical Research Foundation, Suzuken Memorial Foundation, Manpei Suzuki Diabetes Foundation, and Japan Agency for Medical Research and Development; consulting fees from Merck Sharpe & Dohme K.K., Taisho Pharmaceutical, Nippon Boehringer Ingelheim, and Novo Nordisk Pharma; and personal fees from Arcray, Merck Sharpe & Dohme K.K., Astellas Pharma, AstraZeneca K.K., Abbott Japan, Ono Pharmaceutical, Otsuka Pharmaceutical, Kyorin Pharmaceutical, Johnson & Johnson K.K., Kyowa Kirin, Kowa, Sanofi, Sumitomo Pharma, Sanwa Kagaku Kenkyusho, Teijin Pharma, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Chugai Pharmaceutical, Nipro Corporation, Eli Lilly Japan K.K., Nippon Boehringer Ingelheim, Novartis Pharma K.K., Novo Nordisk Pharma, Mochida Pharmaceutical, Bayer Yakuhin, Pfizer Japan, and Lotte outside the submitted work; participates on the advisory board for AstraZeneca K.K., Novo Nordisk Pharma, Eli Lilly Japan K.K., Amgen, Shionogi & Co., Sumitomo Pharma, and Nissin Foods Holdings; and is an unpaid member of boards for the Japan Society for the Study of Obesity, Japan Endocrine Society, Japan Diabetes Society, Japanese Society for Treatment of Obesity, Japanese Society of Molecular Medicine, Japanese Society of Internal Medicine, Japan Atherosclerosis Society, Japan Society of Metabolism and Clinical Nutrition, and Japanese Society of Anti-Aging Medicine. Dr Thamattoor is an employee of Novo Nordisk and reported nonfinancial support from OPEN Health Communications during the conduct of the study. Dr Kim reported grants from Novo Nordisk during the conduct of the study; grants from Hanmi Pharmaceutical, Alvogen Korea, Huons, Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; and personal fees from Eli Lilly Korea, Novo Nordisk, Hanmi Pharmaceutical, Alvogen Korea, and Chong Kun Dang outside the submitted work. No other disclosures were reported. FIR - Kunishige, Hideyuki IR - Kunishige H FIR - Okude, Jun IR - Okude J FIR - Sato, Naoki IR - Sato N FIR - Takeda, Satoshi IR - Takeda S FIR - Uemura, Koji IR - Uemura K FIR - Osonoi, Takeshi IR - Osonoi T FIR - Isshiki, Satomi IR - Isshiki S FIR - Ito, Naoaki IR - Ito N FIR - Naito, Hitoshi IR - Naito H FIR - Oka, Norihiko IR - Oka N FIR - Hosoya, Mitsuru IR - Hosoya M FIR - Saito, Miyoko IR - Saito M FIR - Takizawa, Hiroki IR - Takizawa H FIR - Asano, Hiroshi IR - Asano H FIR - Shirabe, Shinichiro IR - Shirabe S FIR - Asakura, Taro IR - Asakura T FIR - Kaneshiro, Mizuki IR - Kaneshiro M FIR - Matsuura, Hitoshi IR - Matsuura H FIR - Ohira, Akeo IR - Ohira A FIR - Nakano, Saburo IR - Nakano S FIR - Mori, Yasumichi IR - Mori Y FIR - Matsumura, Kimio IR - Matsumura K FIR - Nagasawa, Kaoru IR - Nagasawa K FIR - Kadowaki, Takashi IR - Kadowaki T FIR - Uchida, Takayasu IR - Uchida T FIR - Kikuno, Shota IR - Kikuno S FIR - Suzuki, Yuya IR - Suzuki Y FIR - Kaneko, Shizuka IR - Kaneko S FIR - Onaka, Haruhiko IR - Onaka H FIR - Ueba, Yoko IR - Ueba Y FIR - Onda, Yoshiyuki IR - Onda Y FIR - Minami, Tomoko IR - Minami T FIR - Osugi, Tomoaki IR - Osugi T FIR - Tokumoto, Shinsuke IR - Tokumoto S FIR - Motohashi, Kazuya IR - Motohashi K FIR - Okada, Mutsumi IR - Okada M FIR - Machida, Nao IR - Machida N FIR - Kizawa, Shun IR - Kizawa S FIR - Nishizawa, Hitoshi IR - Nishizawa H FIR - Maeda, Norikazu IR - Maeda N FIR - Shimomura, Iichiro IR - Shimomura I FIR - Fujishima, Yuya IR - Fujishima Y FIR - Fukuda, Shiro IR - Fukuda S FIR - Nagashima, Hirotaka IR - Nagashima H FIR - Horie, Yoshimasa IR - Horie Y FIR - Ohyama, Takako IR - Ohyama T FIR - Yoshida, Kazu IR - Yoshida K FIR - Yamamoto, Asaji IR - Yamamoto A FIR - Kishi, Akiko IR - Kishi A FIR - Soeda, Koutarou IR - Soeda K FIR - Fujita, Hayato IR - Fujita H FIR - Tsuji, Aki IR - Tsuji A FIR - Takahashi, Yuichi IR - Takahashi Y FIR - Inoue, Satoshi IR - Inoue S FIR - Yagi, Michio IR - Yagi M FIR - Owada, Yasuko IR - Owada Y FIR - Kanada, Shigeto IR - Kanada S FIR - Furuie, Hidetoshi IR - Furuie H FIR - Suga, Yasuhiko IR - Suga Y FIR - Inomoto, Takuya IR - Inomoto T FIR - Yamaguchi, Daiki IR - Yamaguchi D FIR - Yoshida, Kayo IR - Yoshida K FIR - Yamahara, Kenichi IR - Yamahara K FIR - Nanto, Masanobu IR - Nanto M FIR - Kobayashi, Sumiko IR - Kobayashi S FIR - Soma, Yuko IR - Soma Y FIR - Matsuoka, Osamu IR - Matsuoka O FIR - Kawai, Makoto IR - Kawai M FIR - Kawai, Mie IR - Kawai M FIR - Ito, Miki IR - Ito M FIR - Yamaguchi, Izumi IR - Yamaguchi I FIR - Matsuda, Hideki IR - Matsuda H FIR - Otake, Sachiko IR - Otake S FIR - Sung, Eunju IR - Sung E FIR - Cho, InYoung IR - Cho I FIR - Yoon, HyunJung IR - Yoon H FIR - Kang, HyunJun IR - Kang H FIR - Kim, Kyoung-Kon IR - Kim KK FIR - Ko, Hae-Jin IR - Ko HJ FIR - Hong, Hee-Eun IR - Hong HE FIR - Kim, Ju Young IR - Kim JY FIR - Koo, Hyeyeon IR - Koo H FIR - Lee, Sumi IR - Lee S FIR - Cho, Eun-Byul IR - Cho EB FIR - Yoo, MunYoung IR - Yoo M EDAT- 2025/08/04 12:27 MHDA- 2025/10/06 12:31 PMCR- 2026/08/04 CRDT- 2025/08/04 11:34 PHST- 2025/10/06 12:31 [medline] PHST- 2025/08/04 12:27 [pubmed] PHST- 2025/08/04 11:34 [entrez] PHST- 2026/08/04 00:00 [pmc-release] AID - 2836932 [pii] AID - ioi250046 [pii] AID - 10.1001/jamainternmed.2025.3599 [doi] PST - ppublish SO - JAMA Intern Med. 2025 Oct 1;185(10):1206-1217. doi: 10.1001/jamainternmed.2025.3599. PMID- 40755350 OWN - NLM STAT- MEDLINE DCOM- 20260206 LR - 20260206 IS - 1699-5848 (Electronic) IS - 0213-3911 (Linking) VI - 41 IP - 3 DP - 2026 Mar TI - The role of GIP in carbohydrate metabolism: Implications in the development of therapies for T2DM, a narrative review. PG - 371-381 LID - 10.14670/HH-18-967 [doi] AB - INTRODUCTION: For the last three decades, bariatric/metabolic surgeries have highlighted the relevance of certain gastrointestinal hormones in controlling and regulating glucose metabolism. The incretins have been a significant focus in developing therapies against Type 2 Diabetes Mellitus (T2DM). Glucagon-like peptide-1 (GLP-1) has been a primary focus in this field, leading to the development of analogues with high therapeutic potential and efficiency, such as semaglutide. However, recently another incretin, glucose-dependent insulinotropic polypeptide (GIP), has become a key target in T2DM drug development due to its complex pleiotropic effects, which include modulating insulin/glucagon secretion, acting on adipose tissue, and regulating appetite. The description of GIP properties as dual can be ambiguous, as this may refer either to its capacity to regulate both insulin and glucagon or to its distinct actions at the central versus peripheral level. Connecting this multifaceted activity was the rationale for developing combined GIP/GLP-1 analogues, like tirzepatide, and has culminated in triple-receptor agonists such as retratutide, which also engages the glucagon receptor (LY3437943). These multi-agonists potentially enhance the therapeutic potential of GLP-1 analogues. COMMENTARIES: This review covers GIP physiology, its role within the context of T2DM, and the properties of GIP analogues, which represent a new line of drugs against T2DM. This field includes not only GIP analogues, since some are dual or triple agonists that also target GLP-1. We aim to elucidate the future perspectives offered by the use of these drugs. CI - (c)The Author(s) 2025. Open Access. This article is licensed under a Creative Commons CC-BY International License. FAU - Almorza-Gomar, David AU - Almorza-Gomar D AD - Department of Operative Statistics and Research, University of Cadiz, Cadiz, Spain. FAU - Diaz-Gomez, Alfredo AU - Diaz-Gomez A AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - San Carlos Hospital, Andalusian Health System, Cadiz, Spain. FAU - Visiedo, Francisco AU - Visiedo F AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - Institute for Biomedical Science Research and Innovation (INIBICA), University of Cadiz, Cadiz, Spain. FAU - Garcia-Ortiz, Jose-Carlos AU - Garcia-Ortiz JC AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - Jerez University Hospital, University of Cadiz, Cadiz, Spain. FAU - Camacho-Ramirez, Alonso AU - Camacho-Ramirez A AD - Institute for Biomedical Science Research and Innovation (INIBICA), University of Cadiz, Cadiz, Spain. AD - Surgery Service, Puerta del Mar University Hospital, University of Cadiz, Cadiz, Spain. FAU - Ribelles-Garcia, Antonio AU - Ribelles-Garcia A AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - Social Sustainable Development Research Institute, University of Cadiz, Cadiz, Spain. FAU - Prada-Oliveira, Jose-Arturo AU - Prada-Oliveira JA AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - Institute for Biomedical Science Research and Innovation (INIBICA), University of Cadiz, Cadiz, Spain. arturo.prada@uca.es. FAU - Perez-Arana, Gonzalo-Martin AU - Perez-Arana GM AD - Department of Human Anatomy and Embryology, University of Cadiz, Cadiz, Spain. AD - Institute for Biomedical Science Research and Innovation (INIBICA), University of Cadiz, Cadiz, Spain. gonzalo.perez@uca.es. LA - eng PT - Journal Article PT - Review DEP - 20250715 PL - Spain TA - Histol Histopathol JT - Histology and histopathology JID - 8609357 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Incretins) SB - IM MH - Humans MH - *Gastric Inhibitory Polypeptide/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Carbohydrate Metabolism/drug effects/physiology MH - Animals MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1/metabolism MH - Incretins/metabolism EDAT- 2025/08/04 06:27 MHDA- 2026/02/06 14:37 CRDT- 2025/08/04 05:13 PHST- 2026/02/06 14:37 [medline] PHST- 2025/08/04 06:27 [pubmed] PHST- 2025/08/04 05:13 [entrez] AID - HH-18-967 [pii] AID - 10.14670/HH-18-967 [doi] PST - ppublish SO - Histol Histopathol. 2026 Mar;41(3):371-381. doi: 10.14670/HH-18-967. Epub 2025 Jul 15. PMID- 40752805 OWN - NLM STAT- MEDLINE DCOM- 20250831 LR - 20260821 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 440 DP - 2025 Dec 1 TI - Effects of oral semaglutide on cardiovascular outcomes: A systematic review and meta-analysis. PG - 133683 LID - S0167-5273(25)00726-0 [pii] LID - 10.1016/j.ijcard.2025.133683 [doi] AB - BACKGROUND: Cardiovascular disease remains a leading cause of morbidity and mortality in type 2 diabetic mellitus (T2DM) patients. While injectable GLP-1 RAs have demonstrated efficacy in reducing cardiovascular risk, an oral formulation of semaglutide was developed to improve accessibility and treatment adherence, however, its therapeutic potential has yet to be fully elucidated. This meta-analysis evaluates the efficacy of oral semaglutide on cardiovascular outcomes to better inform clinical decision-making. METHODS: A systematic search was conducted in major databases for randomized controlled trials (RCTs) up to May 2025, with a primary outcome of cardiovascular events, expanded outcomes included nonfatal stroke, death from cardiovascular cause, and nonfatal myocardial infarction, and the secondary outcome was all-cause mortality. Statistical analysis was performed using RStudio, with heterogeneity assessed via I(2) statistics. RESULTS: A total of 13,875 patients were included, of whom 6935 received oral semaglutide and 6940 received placebo from the 5 eligible studies. A significant difference was observed for cardiovascular events with a risk ratio (RR) of 0.86 (95 % CI: 0.78-0.95; p = 0.0029; I(2) = 0 %) and hazard ratio (HR) of 0.85 (95 % CI: 0.77-0.95), respectively. In contrast, no significant difference was found for nonfatal stroke, all-cause mortality, death from cardiovascular causes, and nonfatal myocardial infarction. CONCLUSION: The meta-analysis revealed that oral semaglutide was cardioprotective in T2DM patients with consistent reductions in cardiovascular event risk. However, the lack of significance in the remaining outcomes underscores the need for further investigation. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Rebelo, Thiago Gorayeb AU - Rebelo TG AD - University of Ottawa, ON, Ottawa, Canada. Electronic address: thiagogrebelo@hotmail.com. FAU - de Araujo Paysano, Maria Lucia Brito AU - de Araujo Paysano MLB AD - Professor Rubem David Azulay Institute of Dermatology, RJ, Rio de Janeiro, Brazil. FAU - Matheus, Gustavo Tadeu Freitas Uchoa AU - Matheus GTFU AD - Federal University of Triangulo Mineiro, MG, Uberaba, Brazil. FAU - Ribeiro, Danilo Monteiro AU - Ribeiro DM AD - University Anhembi Morumbi, SP, Sao Paulo, Brazil. FAU - Said, Thomas Benevides AU - Said TB AD - Federal University of Amazonas, AM, Manaus, Brazil. FAU - Kelly, Francinny Alves AU - Kelly FA AD - Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250731 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage MH - *Cardiovascular Diseases/drug therapy/prevention & control/epidemiology/diagnosis MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Randomized Controlled Trials as Topic/methods MH - Hypoglycemic Agents/administration & dosage MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular outcomes OT - GLP-1 receptor agonists OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare no conflict of interest. EDAT- 2025/08/03 03:46 MHDA- 2025/09/01 00:44 CRDT- 2025/08/02 19:41 PHST- 2025/05/17 00:00 [received] PHST- 2025/07/24 00:00 [revised] PHST- 2025/07/30 00:00 [accepted] PHST- 2025/09/01 00:44 [medline] PHST- 2025/08/03 03:46 [pubmed] PHST- 2025/08/02 19:41 [entrez] AID - S0167-5273(25)00726-0 [pii] AID - 10.1016/j.ijcard.2025.133683 [doi] PST - ppublish SO - Int J Cardiol. 2025 Dec 1;440:133683. doi: 10.1016/j.ijcard.2025.133683. Epub 2025 Jul 31. PMID- 40746012 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260826 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - HbA1c reduction with tirzepatide in people with type 2 diabetes: The contribution of weight loss assessed by a mediation analysis. PG - 5498-5505 LID - 10.1111/dom.16592 [doi] AB - AIM: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist for type 2 diabetes, chronic weight management and obstructive sleep apnoea (in the US). To assess the contribution of weight loss (WL) to the observed glycaemic effect, we performed mediation analysis of three randomized, controlled, parallel, 4-arm SURPASS(S)-trials; 1, 2 and 5, for a total of 2831 participants. MATERIALS AND METHODS: WL dependent (WL-D) and WL independent (WL-IND) effects on comparator-adjusted glycated haemoglobin A1c (HbA1c) reduction at Week 40 were estimated using mediation analysis, adjusted for baseline HbA1c and study-specific stratification factors. RESULTS: The difference in mean HbA1c change from baseline at 40 weeks (total effect) between tirzepatide and the placebo group ranged from -20.0 to -14.6 mmol/mol, and that between tirzepatide and semaglutide (1 mg) ranged from -5.1 to -1.9 mmol/mol. In the placebo-controlled trials, 12%-27% of the difference in HbA1c change between tirzepatide dose arms and placebo was estimated as being mediated through WL when given as monotherapy (S1), and 25%-45% when on the background of insulin with or without metformin (S5). Compared with semaglutide, 54%-71% of the difference in HbA1c change between tirzepatide and semaglutide was estimated as being WL-D. CONCLUSION: The tirzepatide-induced HbA1c reductions from baseline, compared with placebo or semaglutide, were mediated through both WL-D and WL-IND effects. Estimated contributions of WL to the difference in glycaemic efficacy varied and were highest when tirzepatide was compared with semaglutide and less pronounced when compared with placebo. These results help to understand that other factors beyond weight reduction contribute to HbA1c reduction with tirzepatide. CI - (c) 2025 Eli Lilly and Company and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Vilsboll, Tina AU - Vilsboll T AD - Clinical Research, Steno Diabetes Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Malecki, Maciej T AU - Malecki MT AD - Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland. FAU - Sharma, Palash AU - Sharma P AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Thieu, Vivian T AU - Thieu VT AUID- ORCID: 0000-0001-9803-4134 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Chivukula, Krishna Karthik AU - Chivukula KK AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Kiljanski, Jacek AU - Kiljanski J AUID- ORCID: 0000-0003-0354-0558 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Journal Article DEP - 20250731 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood/complications MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use MH - *Glycated Hemoglobin/analysis/metabolism/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - *Tirzepatide/therapeutic use MH - Treatment Outcome MH - *Weight Loss/drug effects MH - Randomized Controlled Trials as Topic MH - Clinical Trials, Phase III as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12409195 OTO - NOTNLM OT - HbA1c OT - SURPASS studies OT - mediation analysis OT - tirzepatide OT - weight loss OT - weight-loss dependent effects OT - weight-loss independent effects COIS- TV has served on scientific advisory panels, been part of speaker's bureaus, served as a consultant to and/or received research support from Amgen, Astra-Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Mundipharma, Novo Nordisk, Carmot/Roche, Regor, Sanofi, Sun Pharmaceuticals, and Zealand Pharma. MTM has served on scientific advisory panels, been part of speaker's bureaus, served as a consultant to and/or received research support from Abbott, AstraZeneca, Ascentia, Adamed, Bayer, Berlin-Chemie, Boehringer Ingelheim, Dexcom, Eli Lilly and Company, Krka, Medtronic, Merck, Novo Nordisk, Sanofi, and Servier. PS, VTT, KC, and JK are all employees and shareholders of Eli Lilly and Company. EDAT- 2025/08/01 06:28 MHDA- 2025/09/04 06:36 PMCR- 2025/09/04 CRDT- 2025/08/01 02:42 PHST- 2025/06/12 00:00 [revised] PHST- 2025/03/26 00:00 [received] PHST- 2025/06/24 00:00 [accepted] PHST- 2025/09/04 06:36 [medline] PHST- 2025/08/01 06:28 [pubmed] PHST- 2025/08/01 02:42 [entrez] PHST- 2025/09/04 00:00 [pmc-release] AID - DOM16592 [pii] AID - 10.1111/dom.16592 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5498-5505. doi: 10.1111/dom.16592. Epub 2025 Jul 31. PMID- 40738102 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260609 IS - 2666-6340 (Electronic) IS - 2666-6340 (Linking) VI - 6 IP - 9 DP - 2025 Sep 12 TI - Recognizing overweight and obesity as chronic diseases and acknowledging root causes. PG - 100782 LID - S2666-6340(25)00209-0 [pii] LID - 10.1016/j.medj.2025.100782 [doi] AB - As obesity increases in the global population, it is important to recognize that obesity is not a willpower failure but a chronic disease regulated by genetic, environmental, and hormonal control of energy balance. Obesity is also caused by social and political factors, including poor regulation of the food industry and lack of access to healthy, affordable foods. To de-stigmatize obesity, we need to understand and teach the pathophysiology of overweight and obesity in the same way we teach the pathophysiology of cardiovascular disease or type 2 diabetes. The controversy surrounding the need for new incretin-mimetic obesity medications illustrates the lack of understanding of obesity as a chronic disease. While we may not be able to change social conditions, modify genetic or environmental factors, or regulate the food industry, we can de-stigmatize obesity and overweight in our clinics and offer appropriate treatment. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Falahee, Bryn E AU - Falahee BE AD - Division of Endocrinology Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. FAU - Kim, Dong Wook AU - Kim DW AD - Division of Endocrinology Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. FAU - Apovian, Caroline M AU - Apovian CM AD - Division of Endocrinology Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: capovian@mgb.org. LA - eng PT - Journal Article PT - Review DEP - 20250729 PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 SB - IM MH - Humans MH - *Obesity/etiology/physiopathology/complications MH - Chronic Disease MH - *Overweight/physiopathology/etiology/complications MH - Diabetes Mellitus, Type 2/etiology MH - Cardiovascular Diseases/etiology OTO - NOTNLM OT - Obesity OT - Semaglutide OT - anti-obesity medications OT - chronic disease OT - food policy OT - hormonal control of metabolism OT - social determinants of health OT - tirzepatide COIS- Declaration of interests C.M.A. reports serving on advisory boards for Altimmune, Inc., BioAge, Bioinq, CinFina Pharma, Inc., Cowen and Company, LLC, EPG Communication Holdings Ltd., Form Health, Inc., Fractyl Health, Inc., Gelesis, Srl., Lilly USA, LLC, L-Nutra, Inc., NeuroBo Pharmaceuticals, Inc., Neurocrine, Nutrisystem, OptumRx, Inc., Pain Script Corporation, Palatin Technologies, Inc., Pursuit By You, Redesign Health Inc., ReShape Lifesciences, Inc., Riverview School, Roman Health, Vida Ventures, Inc., Veru, Inc., Wave Life Sciences, and Xeno Biosciences. EDAT- 2025/07/31 00:28 MHDA- 2025/09/16 13:02 CRDT- 2025/07/30 18:42 PHST- 2025/04/11 00:00 [received] PHST- 2025/06/11 00:00 [revised] PHST- 2025/07/03 00:00 [accepted] PHST- 2025/09/16 13:02 [medline] PHST- 2025/07/31 00:28 [pubmed] PHST- 2025/07/30 18:42 [entrez] AID - S2666-6340(25)00209-0 [pii] AID - 10.1016/j.medj.2025.100782 [doi] PST - ppublish SO - Med. 2025 Sep 12;6(9):100782. doi: 10.1016/j.medj.2025.100782. Epub 2025 Jul 29. PMID- 40732973 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20260127 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 17 IP - 14 DP - 2025 Jul 17 TI - Clinical Effectiveness of Oral Semaglutide in Women with Type 2 Diabetes: A Nationwide, Multicentre, Retrospective, Observational Study (Women_ENDO2S-RWD Substudy). LID - 10.3390/nu17142349 [doi] LID - 2349 AB - Background: Sex differences in type 2 diabetes (T2D) are a growing area of diabetes research. No data have been reported on sex differences with oral semaglutide (oSEMA) in a real-world setting. Methods: We included people with T2D who started treatment with oSEMA in routine clinical practice between November 2021 and November 2022, with at least one report of clinical follow-up (FU) data at 3 months. We evaluated in women with T2D (WWT2D) the clinical effectiveness of oSEMA and factors associated with clinical response and persistence. We also analyzed differences in baseline characteristics, clinical effectiveness, persistence rates and safety according to biological sex. Results: Of the 1018 subjects [median age: 63 years, body mass index (BMI): 33.8 kg/m(2), HbA1c: 7.8%], 469 were WWT2D. In WWT2D, oSEMA reduced HbA1c by 0.7% [-0.1 to -1.3] and 0.9% [-0.2 to -1.5] at the 6- and 12-month FU visits, while weight decreased by 4.6% [2.0 to 7.9] and 7.2% [2.5 to 10.9], respectively. Weight loss was >10% in 29.8% of WWT2D (95% CI 25.8 to 34.1); meanwhile, the combined endpoint (HbA1c decrease >/= 1% + weight reduction >/= 5%) was achieved in 23.5% (95% CI 19.8 to 27.5%) of WWT2D at the 12-month FU visit. Achievement of glycaemic targets was similar in women and men (59.3% vs. 61.1%). We found no sex differences in weight loss (6.9% vs. 6.8%), oSEMA maintenance dose, persistence rate (76.3% vs. 77.3%), or adverse events. Conclusions: oSEMA was effective and safe in WWT2D in a real-world setting, with nearly one-third of patients reporting weight loss >10% and more than two-thirds achieving HbA1c < 7%. oSEMA showed no sex bias in terms of effectiveness and safety. FAU - Reyes-Garcia, Rebeca AU - Reyes-Garcia R AUID- ORCID: 0000-0003-1729-4431 AD - Endocrinology Unit, University Hospital of Torrecardenas, 04009 Almeria, Spain. AD - CIBER de Fragilidad y Envejecimiento Saludable "CIBERFES", Instituto de Salud Carlos III, 28029 Madrid, Spain. FAU - Moreno-Perez, Oscar AU - Moreno-Perez O AUID- ORCID: 0000-0002-8670-6404 AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), 03010 Alicante, Spain. AD - Department of Clinical Medicine, Miguel Hernandez University, 03550 Elche, Spain. FAU - Guillen-Morote, Cristina AU - Guillen-Morote C AUID- ORCID: 0000-0002-6803-6988 AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), 03010 Alicante, Spain. FAU - Modrego-Pardo, Ines AU - Modrego-Pardo I AUID- ORCID: 0000-0003-3060-449X AD - Department of Endocrinology and Nutrition, Marina Baixa Hospital, 03570 Villajoyosa, Spain. FAU - Doulatram-Gamgaram, Viyey Kishore AU - Doulatram-Gamgaram VK AUID- ORCID: 0000-0002-0178-0040 AD - Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, 29010 Malaga, Spain. AD - Biomedical Research Institute of Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29010 Malaga, Spain. FAU - Casado Cases, Carlos AU - Casado Cases C AD - Department of Endocrinology and Nutrition, University Hospital Fundacion Jimenez Diaz, 28040 Madrid, Spain. FAU - Arias Mendoza, Nieves AU - Arias Mendoza N AD - Department of Endocrinology and Nutrition, General University Hospital of Elda, 03600 Alicante, Spain. FAU - Tejera-Perez, Cristina AU - Tejera-Perez C AUID- ORCID: 0000-0002-2987-5922 AD - Department of Endocrinology and Nutrition, University Hospital Complex of Ferrol, 15405 A Coruna, Spain. FAU - Cardenas-Salas, Jersy AU - Cardenas-Salas J AUID- ORCID: 0000-0002-2485-484X AD - Department of Endocrinology and Nutrition, University Hospital Fundacion Jimenez Diaz, 28040 Madrid, Spain. FAU - Martinez-Fuster, Sandra AU - Martinez-Fuster S AD - Department of Endocrinology and Nutrition, General University Hospital of Elda, 03600 Alicante, Spain. FAU - Lardies-Sanchez, Beatriz AU - Lardies-Sanchez B AD - Department of Endocrinology and Nutrition, Obispo Polanco Hospital, 44002 Teruel, Spain. FAU - Marquez-Pardo, Rosa AU - Marquez-Pardo R AUID- ORCID: 0000-0002-4914-4131 AD - Department of Endocrinology and Nutrition, Hospital Juan Ramon Jimenez, 21005 Huelva, Spain. FAU - Pines, Pedro AU - Pines P AD - Department of Endocrinology and Nutrition, Albacete University Hospital Complex, 02006 Albacete, Spain. FAU - Tejera-Munoz, Antonio AU - Tejera-Munoz A AUID- ORCID: 0000-0002-7954-5753 AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante, Institute of Health and Biomedical Research of Alicante (ISABIAL), 03010 Alicante, Spain. AD - Health Science Faculty-HM Hospitals, Camilo Jose Cela University, 28692 Madrid, Spain. AD - HM Hospitals Health Research Institute, 28015 Madrid, Spain. FAU - Fernandez-Garcia, Jose Carlos AU - Fernandez-Garcia JC AD - Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, 29010 Malaga, Spain. AD - Biomedical Research Institute of Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29010 Malaga, Spain. AD - Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas, Asociadas (CIBERDEM), Instituto de Salud Carlos III, 28029 Madrid, Spain. FAU - On Behalf Of The Seen Diabetes Area AU - On Behalf Of The Seen Diabetes Area LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250717 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Retrospective Studies MH - Glycated Hemoglobin/analysis MH - Administration, Oral MH - Aged MH - Treatment Outcome MH - Blood Glucose/drug effects MH - Male MH - Sex Factors MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12300082 OTO - NOTNLM OT - GLP-1 Agonist OT - cardiovascular disease OT - effectiveness OT - real life OT - women COIS- R.R.-G. has received honoraria as speaker and consulting fees by from Eli Lilly, Astra Zeneca, Dexcom and Novo Nordisk; O.M.-P. has received honoraria as speaker and consulting fees by from Eli Lilly, Boehringer-Ingelheim, Astra Zeneca and Novo Nordisk; C.T.-P. received honoraria as speaker and consulting fees by NovoNordisk, Astra Zeneca, Eli Lilly, Boehringer-Ingelheim, Esteve, MSD and Abbott; J.C.F.-G. has received speaker honoraria from Novo Nordisk, Lilly, Boehringer-Ingelheim, Esteve, Menarini, and AstraZeneca; J.C.-S. has received speaker honoraria from Novo Nordisk, Eli Lilly, Boehringer-Ingelheim, Sanofi Aventis and AstraZeneca; B.L.-S. has received honoraria as a speaker by from Novo Nordisk, Boehringer Ingelheim, AstraZeneca, Lilly, Merck Sharp & Dohme, Sanofi and Mundipharma; P.P. has received honoraria as a speaker by from Astra Zeneca, Boehringer-Ingelheim, Dexcom, Eli Lilly, Novo Nordisk, and Sanofi; IM-P has received speaker honoraria from Novo Nordisk, Nestle and AstraZeneca; V.K.D.-G., N.A.M., S.M.-F., C.G.-M., C.C.C. and R.M.-P. have no conflicts of interest. EDAT- 2025/07/30 06:30 MHDA- 2025/07/30 06:31 PMCR- 2025/07/17 CRDT- 2025/07/30 01:13 PHST- 2025/06/05 00:00 [received] PHST- 2025/07/03 00:00 [revised] PHST- 2025/07/15 00:00 [accepted] PHST- 2025/07/30 06:31 [medline] PHST- 2025/07/30 06:30 [pubmed] PHST- 2025/07/30 01:13 [entrez] PHST- 2025/07/17 00:00 [pmc-release] AID - nu17142349 [pii] AID - nutrients-17-02349 [pii] AID - 10.3390/nu17142349 [doi] PST - epublish SO - Nutrients. 2025 Jul 17;17(14):2349. doi: 10.3390/nu17142349. PMID- 40730031 OWN - NLM STAT- MEDLINE DCOM- 20251020 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 11 DP - 2025 Nov 1 TI - Effects of Semaglutide With or Without Concomitant Mineralocorticoid Receptor Antagonist Use in Participants With Type 2 Diabetes and Chronic Kidney Disease: A FLOW Trial Prespecified Secondary Analysis. PG - 1878-1887 LID - 10.2337/dc25-0472 [doi] AB - OBJECTIVE: In the Evaluate Renal Function With Semaglutide Once Weekly (FLOW) trial, semaglutide reduced the risk of major kidney and cardiovascular (CV) outcomes and all-cause mortality in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This prespecified analysis assessed the effects of semaglutide on kidney, CV, and mortality outcomes by baseline mineralocorticoid receptor antagonist (MRA) use. RESEARCH DESIGN AND METHODS: Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary kidney outcome was a composite of time to first persistent >/=50% eGFR reduction from baseline, kidney failure, or death from kidney/CV causes. Baseline MRA was predominantly spironolactone; finerenone was only available after recruitment ended. RESULTS: Effects were analyzed by baseline MRA use (n = 257 [136 in the semaglutide group and 121 in the placebo group]) and nonuse (n = 3,276 [1,631 in the semaglutide group and 1,645 in the placebo group]). Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; HR 0.79 [95% CI 0.68, 0.92]; P-interaction = 0.12) versus placebo in MRA and non-MRA subgroups, respectively. There was no heterogeneity, favoring the effects of semaglutide on major adverse CV events (MACE) and all-cause mortality in both MRA subgroups (P-interaction > 0.7). Albuminuria at 104 weeks was reduced from baseline with semaglutide by 15% (95% CI -41, 31) in MRA users and 33% (26, 39) in nonusers versus placebo (P-interaction = 0.22). Estimated glomerular filtration rate decline was similarly reduced with semaglutide (P-interaction = 0.71). The safety profile of semaglutide was comparable between subgroups. CONCLUSIONS: In participants with T2D and CKD, consistent benefits of semaglutide on major kidney outcomes, MACE, and all-cause mortality were observed regardless of baseline MRA use. CI - (c) 2025 by the American Diabetes Association. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - University of Copenhagen, Copenhagen, Denmark. FAU - Bakris, George AU - Bakris G AD - University of Chicago Medicine, Chicago, IL. FAU - Perkovic, Vlado AU - Perkovic V AD - University of New South Wales, Sydney, Australia. FAU - Pratley, Richard AU - Pratley R AD - AdventHealth Translational Research Institute, Orlando, FL. FAU - Tuttle, Katherine R AU - Tuttle KR AD - University of Washington, Seattle, WA. AD - Providence Inland Northwest Health, Spokane, WA. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Palo Alto, CA. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bosch-Traberg, Heidrun AU - Bosch-Traberg H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Busch, Robert S AU - Busch RS AD - Albany Medical College, Albany, NY. FAU - Schmieder, Ronald E AU - Schmieder RE AD - University Hospital Erlangen, Erlangen, Germany. FAU - Gillard, Pieter AU - Gillard P AD - Department of Endocrinology, University Hospitals Leuven, KU Leuven, Leuven, Belgium. FAU - Mann, Johannes F E AU - Mann JFE AD - University Hospital Erlangen, Erlangen, Germany. AD - KfH Kidney Centre, Munich, Germany. CN - FLOW Investigator Group LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Diabetes Care. 2025 Nov 1;48(11):1875-1877. doi: 10.2337/dci25-0088. PMID: 41115233 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Female MH - *Renal Insufficiency, Chronic/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - Middle Aged MH - *Mineralocorticoid Receptor Antagonists/therapeutic use MH - Aged MH - Glomerular Filtration Rate/drug effects MH - Double-Blind Method MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12583412 FIR - Porto, A IR - Porto A FIR - Oviedo, A IR - Oviedo A FIR - Elbert, A IR - Elbert A FIR - Gelersztein, E IR - Gelersztein E FIR - Chertkoff, A IR - Chertkoff A FIR - Wassermann, A IR - Wassermann A FIR - Quevedo, M A IR - Quevedo MA FIR - MacIsaac, R IR - MacIsaac R FIR - Roger, S IR - Roger S FIR - Phoon, R IR - Phoon R FIR - Kerr, P IR - Kerr P FIR - Ajani, A IR - Ajani A FIR - Tan, S J IR - Tan SJ FIR - Colquhoun, D IR - Colquhoun D FIR - Mather, A IR - Mather A FIR - Gillard, P IR - Gillard P FIR - De Block, C IR - De Block C FIR - Debroye, C IR - Debroye C FIR - Duyck, F IR - Duyck F FIR - Krzesinski, J M IR - Krzesinski JM FIR - Lapauw, B IR - Lapauw B FIR - Preumont, V IR - Preumont V FIR - Vercammen, C IR - Vercammen C FIR - Kamenov, Z IR - Kamenov Z FIR - Bobeva, R IR - Bobeva R FIR - Levterov, G IR - Levterov G FIR - Gerilovska, S IR - Gerilovska S FIR - Yabrudi, N IR - Yabrudi N FIR - Stoyanovska-Elencheva, B IR - Stoyanovska-Elencheva B FIR - Nikitov, Z IR - Nikitov Z FIR - Franco, D IR - Franco D FIR - Akerman Augusto, G IR - Akerman Augusto G FIR - Salles, J IR - Salles J FIR - Canani, L IR - Canani L FIR - Krakauer, M IR - Krakauer M FIR - Cerqueira, M J IR - Cerqueira MJ FIR - Riella, M IR - Riella M FIR - Bajaj, H IR - Bajaj H FIR - Schlosser, R IR - Schlosser R FIR - Ajala, B IR - Ajala B FIR - Aggarwal, N IR - Aggarwal N FIR - Dumas, R IR - Dumas R FIR - O'Keefe, D IR - O'Keefe D FIR - Peterson, S IR - Peterson S FIR - Tsoukas, G IR - Tsoukas G FIR - Tailor, C IR - Tailor C FIR - Tytus, R IR - Tytus R FIR - Akhras, R IR - Akhras R FIR - Khandwala, H IR - Khandwala H FIR - Steen, O IR - Steen O FIR - Carbonneau, D IR - Carbonneau D FIR - Cha, J IR - Cha J FIR - Steele, A IR - Steele A FIR - Bailey, G IR - Bailey G FIR - Berlingieri, J IR - Berlingieri J FIR - Dzongowski, P IR - Dzongowski P FIR - Cherney, D IR - Cherney D FIR - Elliott, T IR - Elliott T FIR - Kovacs, C IR - Kovacs C FIR - Hamet, P IR - Hamet P FIR - Perkins, B IR - Perkins B FIR - Tennankore, K IR - Tennankore K FIR - Gupta, A IR - Gupta A FIR - Ji, L IR - Ji L FIR - Li, Y IR - Li Y FIR - Yuan, G IR - Yuan G FIR - Dong, X IR - Dong X FIR - Cariou, B IR - Cariou B FIR - Clavel, S IR - Clavel S FIR - Marchand, L IR - Marchand L FIR - Reznik, Y IR - Reznik Y FIR - Moulin, P IR - Moulin P FIR - Legrand, E IR - Legrand E FIR - Benoit Tricaud, I IR - Benoit Tricaud I FIR - Gourdy, P IR - Gourdy P FIR - Zaoui, P IR - Zaoui P FIR - Monier, A IR - Monier A FIR - Kazes, I IR - Kazes I FIR - Dahl, D IR - Dahl D FIR - Esser, M IR - Esser M FIR - Kruger, T IR - Kruger T FIR - Rose, L IR - Rose L FIR - Schmieder, R IR - Schmieder R FIR - Segner, A IR - Segner A FIR - Lee-Barkey, Y H IR - Lee-Barkey YH FIR - Vidal, S IR - Vidal S FIR - Schurholz, T IR - Schurholz T FIR - Boletis, I IR - Boletis I FIR - Raptis, A IR - Raptis A FIR - Lanaras, L IR - Lanaras L FIR - Pagkalos, E IR - Pagkalos E FIR - Doupis, J IR - Doupis J FIR - Bekiari, E IR - Bekiari E FIR - Goumenos, D IR - Goumenos D FIR - Papadopoulou, D IR - Papadopoulou D FIR - Tziomalos, K IR - Tziomalos K FIR - Karousos, G IR - Karousos G FIR - Somali, M IR - Somali M FIR - Markou, A IR - Markou A FIR - Zografou, I IR - Zografou I FIR - Wittmann, I IR - Wittmann I FIR - Brasnyo, P IR - Brasnyo P FIR - Balla, J IR - Balla J FIR - Petro, G IR - Petro G FIR - Baranyai, M IR - Baranyai M FIR - Dudas, M IR - Dudas M FIR - Vangel, S IR - Vangel S FIR - Konyves, L IR - Konyves L FIR - Vasas, S IR - Vasas S FIR - Tanczer, T IR - Tanczer T FIR - Shah, M IR - Shah M FIR - Anil, B T IR - Anil BT FIR - Bhalla, A IR - Bhalla A FIR - Gireesh, M S IR - Gireesh MS FIR - Prasad, N IR - Prasad N FIR - Sahay, M IR - Sahay M FIR - Jamale, T IR - Jamale T FIR - Jain, M IR - Jain M FIR - Magdum, M IR - Magdum M FIR - Dewan, D IR - Dewan D FIR - Dinesh, K IR - Dinesh K FIR - Kumar, H IR - Kumar H FIR - Jayakumar, K IR - Jayakumar K FIR - Murthy, S IR - Murthy S FIR - Srikanth, K IR - Srikanth K FIR - Gupta, S IR - Gupta S FIR - Aharon-Hananel, G IR - Aharon-Hananel G FIR - Wainstein, J IR - Wainstein J FIR - Chernin, G IR - Chernin G FIR - Kenis, I IR - Kenis I FIR - Trevisan, R IR - Trevisan R FIR - Bosi, E IR - Bosi E FIR - Setola, E IR - Setola E FIR - Fiorina, P IR - Fiorina P FIR - Penno, G IR - Penno G FIR - Pugliese, G IR - Pugliese G FIR - Giordano, C IR - Giordano C FIR - Orsi, E IR - Orsi E FIR - Cavallo, M G IR - Cavallo MG FIR - Tsuchida, K IR - Tsuchida K FIR - Sasaki, T IR - Sasaki T FIR - Seino, H IR - Seino H FIR - Kawada, T IR - Kawada T FIR - Osonoi, T IR - Osonoi T FIR - Ohashi, H IR - Ohashi H FIR - Shimizu, Y IR - Shimizu Y FIR - Mitomo, S IR - Mitomo S FIR - Nakamura, C IR - Nakamura C FIR - Takai, K IR - Takai K FIR - Maeda, H IR - Maeda H FIR - Nishi, H IR - Nishi H FIR - Nishida, Y IR - Nishida Y FIR - Yamada, M IR - Yamada M FIR - Fukushima, Y IR - Fukushima Y FIR - Kato, M IR - Kato M FIR - Sugawara, M IR - Sugawara M FIR - Araki, H IR - Araki H FIR - Nakagawa, A IR - Nakagawa A FIR - Onaka, H IR - Onaka H FIR - Sueyoshi, A IR - Sueyoshi A FIR - Kidokoro, K IR - Kidokoro K FIR - Tanabe, M IR - Tanabe M FIR - Jinnouchi, H IR - Jinnouchi H FIR - Nakamura, S IR - Nakamura S FIR - Hasumi, S IR - Hasumi S FIR - Gonzalez-Galvez, G IR - Gonzalez-Galvez G FIR - Aguilar Salinas, C IR - Aguilar Salinas C FIR - Morales de Teresa, M IR - Morales de Teresa M FIR - Violante Ortiz, R M IR - Violante Ortiz RM FIR - Correa Rotter, J IR - Correa Rotter J FIR - Irizar Santana, S IR - Irizar Santana S FIR - Lim, S K IR - Lim SK FIR - Yoon, C K IR - Yoon CK FIR - Tan, F IR - Tan F FIR - Goh, B L IR - Goh BL FIR - Loh, C L IR - Loh CL FIR - Yusoff Azmi Merican, N S IR - Yusoff Azmi Merican NS FIR - Bax, W A IR - Bax WA FIR - van Raalte, D IR - van Raalte D FIR - Luik, P T IR - Luik PT FIR - de Vries, P A M IR - de Vries PAM FIR - Dorresteijn, J IR - Dorresteijn J FIR - AlHakim, M IR - AlHakim M FIR - van Wissen, S IR - van Wissen S FIR - Kamphuisen, P IR - Kamphuisen P FIR - Verhave, J IR - Verhave J FIR - Gumprecht, J IR - Gumprecht J FIR - Majcher-Witczak, G IR - Majcher-Witczak G FIR - Mlodawska-Choluj, D IR - Mlodawska-Choluj D FIR - Stompor, T IR - Stompor T FIR - Ciechanowski, W K IR - Ciechanowski WK FIR - Malecki, R IR - Malecki R FIR - Wasilewska, K IR - Wasilewska K FIR - Shamkhalova, M IR - Shamkhalova M FIR - Ruyatkina, L IR - Ruyatkina L FIR - Vagapova, G IR - Vagapova G FIR - Sergeeva-Kondrachenko, M IR - Sergeeva-Kondrachenko M FIR - Kargina, L IR - Kargina L FIR - Peskov, A IR - Peskov A FIR - Zhdanova, E IR - Zhdanova E FIR - Lysenko, T IR - Lysenko T FIR - Frolova, E IR - Frolova E FIR - Mishchenko, O IR - Mishchenko O FIR - Belousova, L IR - Belousova L FIR - Astamirova, K IR - Astamirova K FIR - Antonova, E IR - Antonova E FIR - Pergaeva, Y IR - Pergaeva Y FIR - Palyutin, S IR - Palyutin S FIR - Krasnopeeva Kabachkova, A N IR - Krasnopeeva Kabachkova AN FIR - Tyugaeva, A IR - Tyugaeva A FIR - Krasilnikova, E IR - Krasilnikova E FIR - Romasheva, E IR - Romasheva E FIR - Sorokin, M IR - Sorokin M FIR - Martinka, E IR - Martinka E FIR - Ilavska, A IR - Ilavska A FIR - Tomasova, L IR - Tomasova L FIR - Porubska, K IR - Porubska K FIR - Skripova, D IR - Skripova D FIR - Buganova, I IR - Buganova I FIR - Rociakova, J IR - Rociakova J FIR - Rosenberger, J IR - Rosenberger J FIR - Pavelcikova, A IR - Pavelcikova A FIR - Smik, R IR - Smik R FIR - Gorriz, J IR - Gorriz J FIR - Castro, C IR - Castro C FIR - Cigarran, S IR - Cigarran S FIR - Barrios, C IR - Barrios C FIR - Soler, M IR - Soler M FIR - Martins, J IR - Martins J FIR - Sriwijitkamol, A IR - Sriwijitkamol A FIR - Phornphutkul, M IR - Phornphutkul M FIR - Supasyndh, O IR - Supasyndh O FIR - Kiattisunthorn, K IR - Kiattisunthorn K FIR - Buranasupkajorn, P IR - Buranasupkajorn P FIR - Susantitaphong, P IR - Susantitaphong P FIR - Helvaci, O IR - Helvaci O FIR - Ates, K IR - Ates K FIR - Arikan, I IR - Arikan I FIR - Arici, M IR - Arici M FIR - Suleymanlar, G IR - Suleymanlar G FIR - Yazici, H IR - Yazici H FIR - Alisir Ecder, S IR - Alisir Ecder S FIR - Gungor, O IR - Gungor O FIR - Ok, E IR - Ok E FIR - Seyahi, N IR - Seyahi N FIR - Eren, N IR - Eren N FIR - Yenicerioglu, Y IR - Yenicerioglu Y FIR - Chabanna, O IR - Chabanna O FIR - Panina, S IR - Panina S FIR - Semenovykh, P IR - Semenovykh P FIR - Leonidova, V IR - Leonidova V FIR - Zinych, O IR - Zinych O FIR - Legun, O IR - Legun O FIR - Kaydashev, I IR - Kaydashev I FIR - Bellary, S IR - Bellary S FIR - Boyle, J IR - Boyle J FIR - Chen, M IR - Chen M FIR - Mcknight, J IR - Mcknight J FIR - Pearson, E IR - Pearson E FIR - Philip, S IR - Philip S FIR - Sharma, S IR - Sharma S FIR - Wakeling, J IR - Wakeling J FIR - Tindall, H IR - Tindall H FIR - Yousseif, A IR - Yousseif A FIR - Aw, T IR - Aw T FIR - Guerrero, A IR - Guerrero A FIR - Arif, A IR - Arif A FIR - Betts, J IR - Betts J FIR - Busch, R IR - Busch R FIR - Desouza, C IR - Desouza C FIR - Gonzalez-Orozco, L IR - Gonzalez-Orozco L FIR - Dukes, C IR - Dukes C FIR - Hammoud, J IR - Hammoud J FIR - Houser, P IR - Houser P FIR - Jackson, T IR - Jackson T FIR - Kayali, Z IR - Kayali Z FIR - Young, L IR - Young L FIR - Klein, E IR - Klein E FIR - Nicol, P IR - Nicol P FIR - Smith, S IR - Smith S FIR - Snyder, B IR - Snyder B FIR - Soroka, E IR - Soroka E FIR - Wysham, C IR - Wysham C FIR - Akyea-Djamson, A IR - Akyea-Djamson A FIR - Arauz-Pacheco, C IR - Arauz-Pacheco C FIR - Horeish, A IR - Horeish A FIR - Chang, A IR - Chang A FIR - Connery, L IR - Connery L FIR - Gandy, W IR - Gandy W FIR - Gilbert, M IR - Gilbert M FIR - Hernandez, G IR - Hernandez G FIR - Hewitt, M IR - Hewitt M FIR - Huffman, D IR - Huffman D FIR - Lovell, C IR - Lovell C FIR - Masani, N IR - Masani N FIR - McGill, J IR - McGill J FIR - Siddiqui, I IR - Siddiqui I FIR - Perez, R IR - Perez R FIR - Reed, J IR - Reed J FIR - Sivalingam, K IR - Sivalingam K FIR - London, J IR - London J FIR - Saha, S IR - Saha S FIR - Awad, A IR - Awad A FIR - Billings, L IR - Billings L FIR - Blaze, K IR - Blaze K FIR - Stricklin, D IR - Stricklin D FIR - Brinson, C IR - Brinson C FIR - Bornfreund, J IR - Bornfreund J FIR - McCall, N IR - McCall N FIR - Buynak, R IR - Buynak R FIR - Cannon, K IR - Cannon K FIR - Daboul, N IR - Daboul N FIR - Acosta, I IR - Acosta I FIR - Diaz, J IR - Diaz J FIR - Greenwood, G IR - Greenwood G FIR - Hart, T IR - Hart T FIR - Hasan, S IR - Hasan S FIR - Iranmanesh, A IR - Iranmanesh A FIR - Koilpillai, R IR - Koilpillai R FIR - Latif, K IR - Latif K FIR - Lawrence, M IR - Lawrence M FIR - Chen, C IR - Chen C FIR - Marar, I IR - Marar I FIR - East, C IR - East C FIR - Patel, R IR - Patel R FIR - Rovner, S IR - Rovner S FIR - Seco, G IR - Seco G FIR - Shaikh, Z IR - Shaikh Z FIR - Traylor, H IR - Traylor H FIR - Zieve, F IR - Zieve F FIR - Aroda, V IR - Aroda V FIR - Ahmed, A IR - Ahmed A FIR - Biscoveanu, M IR - Biscoveanu M FIR - Budoff, M IR - Budoff M FIR - ElShahawy, M IR - ElShahawy M FIR - Garza, J IR - Garza J FIR - Hanson, L IR - Hanson L FIR - Reddy, J IR - Reddy J FIR - Rodriguez, H IR - Rodriguez H FIR - Shrestha, A IR - Shrestha A FIR - Bernardo, M IR - Bernardo M FIR - Christensen, T IR - Christensen T FIR - Denker, P IR - Denker P FIR - Dua, S IR - Dua S FIR - El Shahawy, M IR - El Shahawy M FIR - Farias, A IR - Farias A FIR - Fernando, R IR - Fernando R FIR - Jamal, A IR - Jamal A FIR - Jardula, M IR - Jardula M FIR - Moustafa, M IR - Moustafa M FIR - Posada, J IR - Posada J FIR - Sanchez, W IR - Sanchez W FIR - Vega, D IR - Vega D FIR - Kumar, J IR - Kumar J FIR - Sultan, S IR - Sultan S FIR - Bansal, S IR - Bansal S FIR - Benjamin, S IR - Benjamin S FIR - Brusco, O IR - Brusco O FIR - Wayne, J IR - Wayne J FIR - Gaona, R IR - Gaona R FIR - Degani, O IR - Degani O FIR - Figueroa, C IR - Figueroa C FIR - Montero, M IR - Montero M FIR - Rasouli, N IR - Rasouli N FIR - Zemel, L IR - Zemel L FIR - Fadda, G IR - Fadda G FIR - Shlesinger, Y IR - Shlesinger Y FIR - Charytan, D IR - Charytan D FIR - Butuk, D IR - Butuk D FIR - Stringam, S IR - Stringam S FIR - Espinosa, V IR - Espinosa V FIR - Brandon, D IR - Brandon D FIR - Shea, H IR - Shea H FIR - Cheung, D IR - Cheung D FIR - Sanchez, Y IR - Sanchez Y FIR - Kudva, Y IR - Kudva Y FIR - Beddhu, S IR - Beddhu S FIR - Rayner, B IR - Rayner B FIR - Bhorat, Q IR - Bhorat Q FIR - Badat, A IR - Badat A FIR - Makan, H IR - Makan H FIR - Joshi, M IR - Joshi M FIR - Basson, M IR - Basson M FIR - Naidoo, V IR - Naidoo V FIR - Amod, A IR - Amod A EDAT- 2025/07/30 00:30 MHDA- 2025/10/20 18:29 PMCR- 2025/07/29 CRDT- 2025/07/29 18:23 PHST- 2025/02/26 00:00 [received] PHST- 2025/06/12 00:00 [accepted] PHST- 2025/10/20 18:29 [medline] PHST- 2025/07/30 00:30 [pubmed] PHST- 2025/07/29 18:23 [entrez] PHST- 2025/07/29 00:00 [pmc-release] AID - 163056 [pii] AID - 250472 [pii] AID - 10.2337/dc25-0472 [doi] PST - ppublish SO - Diabetes Care. 2025 Nov 1;48(11):1878-1887. doi: 10.2337/dc25-0472. PMID- 40712696 OWN - NLM STAT- MEDLINE DCOM- 20251126 LR - 20260127 IS - 2352-3840 (Electronic) IS - 1499-2671 (Linking) VI - 49 IP - 7 DP - 2025 Oct TI - In the Eye of Controversy: A Deeper Look Into the Impact of Glucagon-like Peptide-1 Receptor Agonists on Diabetic Retinopathy and Nonarteritic Anterior Ischemic Optic Neuropathy. PG - 401-410 LID - S1499-2671(25)00149-2 [pii] LID - 10.1016/j.jcjd.2025.07.002 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP1-RAs), a relatively new class of drugs, are used widely in treating type 2 diabetes mellitus and obesity. Maintaining long-term glycemic management lowers the risk of development and progression of diabetic retinopathy. However, recent literature has raised concerns about transient worsening of the condition with use of GLP1-RAs. In this review we evaluate the association between GLP1-RAs and retinopathy in patients with diabetes mellitus. We also analyzed the available evidence on the potential association between semaglutide therapy and nonarteritic anterior ischemic optic neuropathy (NAION). Our review consists of relevant publications, including meta-analyses, randomized controlled trials, and post hoc analyses, and outcomes of in vitro and in vivo research. The article search was conducted using several databases, including the WorldCat Discovery service provided by the Al Maktoum Medical Library, PubMed, and Google Scholar. Preclinical studies hint at possible protective effects on the retina, but a more complex picture is presented by clinical evidence. Although there have been cases of retinopathy development after GLP1-RA use, this may be due to a swift reduction in glycated hemoglobin levels rather than the drug's mechanism of action itself. Evidence linking semaglutide to NAION remains inconclusive and limited by methodological constraints. Large-scale studies with robust design are warranted to elucidate the potential association and to guide clinical practice. CI - Copyright (c) 2025 Diabetes Canada. Published by Elsevier Inc. All rights reserved. FAU - Nadeem, Nadia AU - Nadeem N AD - Department of Internal Medicine, Rashid Hospital, Dubai Health, Dubai, United Arab Emirates. Electronic address: nadianadeem24@gmail.com. FAU - Al Issa, Raghad Mazin AU - Al Issa RM AD - Department of Internal Medicine, Rashid Hospital, Dubai Health, Dubai, United Arab Emirates. FAU - Shah, Asnin AU - Shah A AD - Department of Endocrinology, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates. FAU - Wardeh, Rahaf AU - Wardeh R AD - Department of Endocrinology, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates. FAU - Rashid, Fauzia AU - Rashid F AD - Department of Endocrinology, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates. FAU - Abdelgadir, Elamin Ibrahim AU - Abdelgadir EI AD - Department of Endocrinology, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates. FAU - Bashier, Alaaeldin AU - Bashier A AD - Department of Endocrinology, Dubai Hospital, Dubai Health, Dubai, United Arab Emirates. LA - eng PT - Journal Article PT - Review DEP - 20250723 PL - Canada TA - Can J Diabetes JT - Canadian journal of diabetes JID - 101148810 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Optic Neuropathy, Ischemic/chemically induced/drug therapy MH - *Diabetic Retinopathy/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptides/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP1-RA OT - GLP1RA OT - agonistes du recepteur du peptide 1 similaire au glucagon OT - controle glycemique OT - diabetic retinopathy OT - diabete sucre de type 2 OT - glucagon-like peptide-1 receptor agonists OT - glycemic management OT - neuropathie optique ischemique anterieure non arteritique OT - nonarteritic anterior ischemic optic neuropathy OT - retinopathie diabetique OT - type 2 diabetes mellitus EDAT- 2025/07/28 08:44 MHDA- 2025/11/27 00:27 CRDT- 2025/07/25 19:36 PHST- 2025/04/19 00:00 [received] PHST- 2025/06/26 00:00 [revised] PHST- 2025/07/12 00:00 [accepted] PHST- 2025/11/27 00:27 [medline] PHST- 2025/07/28 08:44 [pubmed] PHST- 2025/07/25 19:36 [entrez] AID - S1499-2671(25)00149-2 [pii] AID - 10.1016/j.jcjd.2025.07.002 [doi] PST - ppublish SO - Can J Diabetes. 2025 Oct;49(7):401-410. doi: 10.1016/j.jcjd.2025.07.002. Epub 2025 Jul 23. PMID- 40711887 OWN - NLM STAT- MEDLINE DCOM- 20251002 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 16 IP - 10 DP - 2025 Oct TI - A multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice (PIONEER REAL Japan): Subgroup analyses. PG - 1794-1807 LID - 10.1111/jdi.70099 [doi] AB - AIMS: HbA(1c) and body weight were assessed across selected subgroups of adults with type 2 diabetes receiving oral semaglutide in clinical practice. METHODS: In this non-interventional study, changes in HbA(1c) and body weight to end of study (EoS) and safety were assessed by subgroup: baseline age, body mass index (BMI), type 2 diabetes duration, participants switching from dipeptidyl peptidase-4 inhibitors, and semaglutide dose at EoS. RESULTS: All subgroups experienced reductions in HbA(1c) and body weight. Younger participants had greater reductions in HbA(1c) than older participants (-0.9, -0.7, -0.7, and -0.5 percentage points for participants aged <55, >/=55-<65, >/=65-<75, and >/=75 years, respectively [P = 0.0467]). Shorter type 2 diabetes duration and lower EoS semaglutide dose were associated with greater HbA(1c) reductions (-0.8, -0.7, and -0.6 percentage points with 5-10 years' duration, respectively [P < 0.0001]; -1.2, -0.7, and -0.4 percentage points with 3, 7, and 14 mg, respectively [P < 0.0001]). Changes in HbA(1c) were not significantly different across other subgroups. Lower EoS semaglutide dose was associated with greater body weight reductions (-3.8, -2.9, and -2.8 kg with 3, 7, and 14 mg, respectively [P < 0.0001]); body weight reductions were not significantly different across other subgroups. Adverse events were similar between subgroups, except that older subgroups experienced more events. CONCLUSIONS: HbA(1c) and body weight decreased across all subgroups, providing insights into oral semaglutide use in clinical practice for individuals with different characteristics in the real-world setting. CI - (c) 2025 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Department of Diabetes, Endocrinology and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, Japan. AD - Center for One Medicine Innovative Translational Research, Gifu University Institute of Advanced Studies, Gifu, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Hamamoto, Yoshiyuki AU - Hamamoto Y AUID- ORCID: 0000-0002-1938-7394 AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. FAU - Kawanami, Daiji AU - Kawanami D AUID- ORCID: 0000-0002-8926-4701 AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan. FAU - Nishimura, Rimei AU - Nishimura R AD - Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. FAU - Amadid, Hanan AU - Amadid H AD - Clinical Development and Project Leadership, Novo Nordisk A/S, Soborg, Denmark. FAU - Braae, Uffe Christian AU - Braae UC AD - Real-World Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Major-Pedersen, Atheline AU - Major-Pedersen A AD - Global Patient Safety, Novo Nordisk A/S, Soborg, Denmark. FAU - Suzuki, Ryo AU - Suzuki R AUID- ORCID: 0000-0002-2965-6906 AD - Department of Diabetes, Metabolism and Endocrinology, Tokyo Medical University, Tokyo, Japan. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Multicenter Study DEP - 20250725 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - Japanese people SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Aged MH - Glycated Hemoglobin/analysis MH - Prospective Studies MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - Japan MH - Body Weight/drug effects MH - Adult MH - Blood Glucose/analysis MH - Prognosis MH - Follow-Up Studies MH - *Biomarkers/analysis MH - Glucagon-Like Peptide 1 MH - Semaglutide MH - East Asian People PMC - PMC12489328 OTO - NOTNLM OT - Oral semaglutide OT - Real-world study OT - Type 2 diabetes COIS- Daisuke Yabe: received consulting/lecture fees from Eli Lilly Japan K.K., Kyowa Kirin Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd, Sanofi K.K., and Sumitomo Pharma Co., Ltd.; and research funding/grants from Arkray Inc., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Taisho Pharmaceutical Co., Ltd., and Terumo Corporation. Professor Yabe is an Editorial Board member of the Journal of Diabetes Investigation and a co-author of this article. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication. Yoshiyuki Hamamoto: received consulting/lecture fees from Eli Lilly Japan K.K., Daiichi Sankyo, Mitsubishi Tanabe Pharma Ltd., Novo Nordisk Pharma Ltd., Taisho Pharmaceutical Co., Ltd., MSD K.K., and Sumitomo Pharma Co., Ltd.; and research funding from Nippon Boehringer Ingelheim Co., Ltd. and Sumitomo Pharma Co., Ltd. Dr. Hamamoto is an Editorial Board member of the Journal of Diabetes Investigation and a co-author of this article. To minimize bias, he was excluded from all editorial decision-making related to the acceptance of this article for publication. Daiji Kawanami received consulting/lecture fees from Bayer Yakuhin Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Sanofi K.K., and Sumitomo Pharma Co., Ltd.; and grants from Bayer Yakuhin Ltd., Nippon Boehringer Ingelheim Co., Ltd., Nipro Corporation, and Sumitomo Pharma Co., Ltd. Rimei Nishimura received consulting/lecture fees from Abbott Japan LLC, Astellas Pharma Inc., AstraZeneca K.K., Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company Ltd., Medtronic Japan Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Pharma Co., Ltd., and Teijin Pharma Ltd.; and research funding/grants from Abbott Japan LLC, Mitsubishi Electric Corporation, Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., and Taisho Pharmaceutical Co., Ltd. Yasuo Terauchi received consulting/lecture fees from Novo Nordisk Pharma Ltd., Astellas Pharma Inc., AstraZeneca K.K., Eli Lilly Japan K.K., Kowa Company Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Sanofi K.K., and Sumitomo Pharma Co., Ltd.; and grants from Nippon Boehringer Ingelheim Co., Ltd., and Sumitomo Pharma Co., Ltd. Hanan Amadid is employed by and a shareholder in Novo Nordisk. Uffe Christian Braae is employed by and a shareholder in Novo Nordisk. Atheline Major-Pedersen is employed by and a shareholder in Novo Nordisk. Ryo Suzuki received lecture fees from Astellas Pharma Inc., Eli Lilly Japan K.K., Kowa Company Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novo Nordisk Pharma Ltd., Sanofi K.K., Sumitomo Pharma Co., Ltd., Teijin Healthcare Ltd; and grants from Nippon Boehringer Ingelheim Co., Ltd. Approval of the research protocol: The protocol for this research project was approved by suitably constituted ethics committees or institutional review boards of the institutions, and it conforms to the provisions of the Declaration of Helsinki. Ethics committees, institutional review boards, and approval numbers have been previously described. Informed consent: All informed consent was obtained from the participants and/or their guardians. Registry and the registration no. of the study/trial: This study is registered with ClinicalTrials.gov (NCT04878393; first submitted May 5, 2021). Animal studies: N/A. EDAT- 2025/07/25 18:26 MHDA- 2025/10/02 06:28 PMCR- 2025/07/25 CRDT- 2025/07/25 12:42 PHST- 2025/05/19 00:00 [revised] PHST- 2025/02/11 00:00 [received] PHST- 2025/05/31 00:00 [accepted] PHST- 2025/10/02 06:28 [medline] PHST- 2025/07/25 18:26 [pubmed] PHST- 2025/07/25 12:42 [entrez] PHST- 2025/07/25 00:00 [pmc-release] AID - JDI70099 [pii] AID - 10.1111/jdi.70099 [doi] PST - ppublish SO - J Diabetes Investig. 2025 Oct;16(10):1794-1807. doi: 10.1111/jdi.70099. Epub 2025 Jul 25. PMID- 40704485 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260827 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - Effect of semaglutide versus placebo on cardiorenal outcomes by prior cardiovascular disease and baseline body mass index: Pooled post hoc analysis of SUSTAIN 6 and PIONEER 6. PG - 5706-5715 LID - 10.1111/dom.16621 [doi] AB - AIMS: Cardiorenal effects of semaglutide in people with type 2 diabetes (T2D) at high cardiovascular (CV) risk were investigated. MATERIALS AND METHODS: Post hoc analyses of pooled SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716) data assessed time to primary major adverse CV events (MACE; CV death, non-fatal myocardial infarction, or non-fatal stroke), expanded MACE (MACE + hospitalisation for unstable angina or heart failure), CV death, all-cause death, and new or worsening nephropathy. The impact of body weight (BW) changes on primary MACE risk was also evaluated. Participants were stratified by prior CV disease (CVD) status and baseline body mass index (BMI). RESULTS: Semaglutide significantly reduced the risk of primary and expanded MACE, with a nonsignificant risk reduction of CV and all-cause death versus placebo in the overall population; the effect was consistent across all subgroups (p(INT) >0.05 for all comparisons). Semaglutide consistently reduced nephropathy risk versus placebo in the SUSTAIN 6 population (HR [95% CI]: 0.64 [0.46; 0.88], p = 0.0054) and across all subgroups (p(INT) >0.05 for all comparisons). When accounting for BW changes, treatment effects on primary MACE risk in the overall population and by BMI subgroups remained similar compared with the results of the main analysis. CONCLUSIONS: Semaglutide treatment improved cardiorenal outcomes versus placebo in people with T2D, regardless of prior CVD and baseline BMI. This improvement was observed even when accounting for changes in BW, indicating direct effects of semaglutide on the cardiorenal system. This analysis supports the broad efficacy of semaglutide in a diverse T2D population. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Zhou, Jingmin AU - Zhou J AUID- ORCID: 0000-0003-0195-2727 AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Husain, Mansoor AU - Husain M AUID- ORCID: 0000-0002-3740-6739 AD - Ted Rogers Centre for Heart Research, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Li, Yang AU - Li Y AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Liu, Wenyan AU - Liu W AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Shen, Zewei AU - Shen Z AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Vilsboll, Tina AU - Vilsboll T AD - Clinical Research, Steno Diabetes Center Copenhagen, Copenhagen, Denmark. FAU - Ge, Junbo AU - Ge J AD - Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China. LA - eng GR - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd/ PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250724 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Mass Index MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies/prevention & control/epidemiology MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12409197 OTO - NOTNLM OT - GLP-1 analogue OT - body composition OT - cardiovascular disease OT - diabetic nephropathy OT - semaglutide OT - type 2 diabetes COIS- Jingmin Zhou declares no conflicts of interest. Mansoor Husain has received research grants from AstraZeneca, Merck, and Novo Nordisk; consultancy fees for participation in advisory board meetings from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, and Roche; speaker fees from AstraZeneca, Boehringer Ingelheim, Janssen, Merck, and Novo Nordisk; and holds two patents relating to glucagon-like peptides. Yang Li, Wenyan Liu, and Zewei Shen are employees of Novo Nordisk and own stocks in the company. Tina Vilsboll has served on scientific advisory panels, been part of speaker's bureaus, served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Mundipharma, Novo Nordisk, Roche, Sun Pharmaceuticals, and Zealand Pharma. Junbo Ge declares no conflicts of interest. EDAT- 2025/07/24 12:28 MHDA- 2025/09/04 06:37 PMCR- 2025/09/04 CRDT- 2025/07/24 06:02 PHST- 2025/07/04 00:00 [revised] PHST- 2025/05/05 00:00 [received] PHST- 2025/07/07 00:00 [accepted] PHST- 2025/09/04 06:37 [medline] PHST- 2025/07/24 12:28 [pubmed] PHST- 2025/07/24 06:02 [entrez] PHST- 2025/09/04 00:00 [pmc-release] AID - DOM16621 [pii] AID - 10.1111/dom.16621 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5706-5715. doi: 10.1111/dom.16621. Epub 2025 Jul 24. PMID- 40701453 OWN - NLM STAT- MEDLINE DCOM- 20250910 LR - 20260617 IS - 1096-3650 (Electronic) IS - 1044-579X (Linking) VI - 115 DP - 2025 Oct TI - Cancer prevention and interception with antidiabetic and anti-obesity drugs: Current and future perspectives. PG - 40-52 LID - S1044-579X(25)00102-6 [pii] LID - 10.1016/j.semcancer.2025.07.008 [doi] AB - Obesity and type 2 diabetes are major risk factors for cardiovascular diseases and multiple malignancies, and epidemiology reveals an increasing burden of obesity-related cancers, in particular liver, pancreatic and endometrial. Obesity is also clearly associated with an increased risk of breast cancer, particularly in postmenopausal women. Chronic hyperinsulinemia, systemic inflammation, and metabolic dysregulation create a tumor-promoting environment, emphasizing the need for interventions that target metabolic health and can provide cancer prevention or interception. This review examines the potential cancer-preventive effects of antidiabetic and anti-obesity drugs, summarizing current preclinical and clinical evidence on their mechanisms and efficacy. Among these agents, metformin has been extensively studied, demonstrating anticancer properties through AMP-activated protein kinase activation, mammalian target of rapamycin inhibition, and reduced insulin-like growth factor 1 signaling. Glucagon-like peptide-1 receptor agonists, including semaglutide and tirzepatide, promote weight loss, insulin sensitivity, and anti-inflammatory effects, with emerging evidence suggesting direct tumor-suppressive actions. Sodium-glucose cotransporter 2 inhibitors modulate tumor metabolism by reducing glucose availability and mitigating systemic inflammation. Other agents, including dipeptidyl peptidase-4 inhibitors, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors, have shown mixed evidence regarding their potential anticancer effects, necessitating further investigation. While observational studies and meta-analyses suggest a potential reduction in cancer risk with certain antidiabetic and anti-obesity agents, randomized controlled trials specifically assessing cancer prevention are limited. Additionally, long-term safety concerns, including potential tumor-promoting effects in specific contexts, warrant further investigation. Future research should focus on large-scale clinical trials and mechanistic studies to validate the oncologic benefits and risks of these agents. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved. FAU - Albini, Adriana AU - Albini A AD - Scientific Directorate, European Institute of Oncology IEO, IRCCS, Milan, Italy. Electronic address: adriana.albini@ieo.it. FAU - Cantelmo, Anna Rita AU - Cantelmo AR AD - Universite de Lille, Inserm, CHU Lille, Institute Pasteur de Lille, U1011-EGID, Lille F-59000, France. FAU - Mortara, Lorenzo AU - Mortara L AD - Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; Unit of Molecular Pathology, Biochemistry and Immunology, MultiMedica, IRCCS, Milan, Italy. FAU - Noonan, Douglas M AU - Noonan DM AD - Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy; Unit of Molecular Pathology, Biochemistry and Immunology, MultiMedica, IRCCS, Milan, Italy. FAU - Corso, Giovanni AU - Corso G AD - Division of Breast Surgery, European Institute of Oncology IEO, IRCCS, Milan, Italy; Department of Oncology and Hematology, University of Milano, Milan, Italy. Electronic address: giovanni.corso@ieo.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20250721 PL - England TA - Semin Cancer Biol JT - Seminars in cancer biology JID - 9010218 RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Neoplasms/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Anti-Obesity Agents/therapeutic use/pharmacology MH - *Obesity/drug therapy/complications MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy/complications OTO - NOTNLM OT - Anti-obesity drugs OT - Antidiabetic drugs OT - Diabetes, Cancer, Prevention, Interception OT - Metabolic reprogramming OT - Obesity COIS- Declaration of Competing Interest Authors state no conflict of interest. EDAT- 2025/07/24 00:25 MHDA- 2025/09/11 00:28 CRDT- 2025/07/23 19:38 PHST- 2025/02/17 00:00 [received] PHST- 2025/07/15 00:00 [revised] PHST- 2025/07/18 00:00 [accepted] PHST- 2025/09/11 00:28 [medline] PHST- 2025/07/24 00:25 [pubmed] PHST- 2025/07/23 19:38 [entrez] AID - S1044-579X(25)00102-6 [pii] AID - 10.1016/j.semcancer.2025.07.008 [doi] PST - ppublish SO - Semin Cancer Biol. 2025 Oct;115:40-52. doi: 10.1016/j.semcancer.2025.07.008. Epub 2025 Jul 21. PMID- 40701338 OWN - NLM STAT- MEDLINE DCOM- 20251005 LR - 20260603 IS - 1524-4733 (Electronic) IS - 1098-3015 (Linking) VI - 28 IP - 10 DP - 2025 Oct TI - Comprehensive Access to Semaglutide: Clinical and Economic Implications for Medicare. PG - 1488-1496 LID - S1098-3015(25)02472-6 [pii] LID - 10.1016/j.jval.2025.07.007 [doi] AB - OBJECTIVES: The objective of this study was to estimate comprehensive value of semaglutide in the Medicare population for current and future FDA-approved indications. METHODS: We used data from government reports, published clinical studies, and real-world claims to model clinical outcomes and costs in patients with diabetes, overweight/obesity, and metabolic-associated steatohepatitis over a 10-year period (2026 to 2035). We estimated the financial impact to the Medicare program by comparing the impact of costs of averted clinical events and anticipated treatment costs under various treatment utilization and price assumptions with a scenario in which no patients were treated with semaglutide. We used estimates of the net price of semaglutide, an estimated negotiated price based on a 10% discount from net price starting in year 2, and accounted for patient out-of-pocket costs. RESULTS: Over the 10-year period, we estimated that broad access to semaglutide would result in 38 950 cardiovascular events avoided, and 6180 deaths avoided due to reduction in cardiovascular events and improvement in chronic kidney disease or metabolic-associated steatohepatitis progression. The net financial impact to Medicare was estimated to be savings of $715 million over 10 years. Alternative scenarios yielded net savings ranging from $1.04 billion to $412 million. A scenario that accounted for loss of exclusivity of semaglutide and other treatments produced 10-year cost savings to Medicare of approximately $1.71 billion. CONCLUSIONS: Availability of semaglutide in Medicare for all FDA-approved indications would have a substantial impact on health outcomes at net savings of between $1.04 billion and $412 million over 10 years. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - Dayer, Victoria W AU - Dayer VW AD - The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA; Curta, Inc., Seattle, WA, USA. Electronic address: vwinslow@uw.edu. FAU - Nourhussein, Iman AU - Nourhussein I AD - Curta, Inc., Seattle, WA, USA. FAU - Kasle, Adam AU - Kasle A AD - Curta, Inc., Seattle, WA, USA. FAU - Hansen, Ryan N AU - Hansen RN AD - The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA; Curta, Inc., Seattle, WA, USA. FAU - Navas, Angelo AU - Navas A AD - UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA. FAU - Sullivan, Sean D AU - Sullivan SD AD - The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA; Curta, Inc., Seattle, WA, USA. LA - eng PT - Journal Article DEP - 20250721 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - United States MH - *Glucagon-Like Peptides/economics/therapeutic use MH - *Medicare/economics MH - *Hypoglycemic Agents/economics/therapeutic use MH - Drug Costs MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Cost-Benefit Analysis MH - Aged MH - Obesity/drug therapy/economics MH - Male MH - Female MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - MASH OT - Medicare OT - diabetes OT - obesity OT - semaglutide COIS- Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. EDAT- 2025/07/24 00:25 MHDA- 2025/10/06 00:27 CRDT- 2025/07/23 19:37 PHST- 2025/04/25 00:00 [received] PHST- 2025/07/11 00:00 [revised] PHST- 2025/07/15 00:00 [accepted] PHST- 2025/10/06 00:27 [medline] PHST- 2025/07/24 00:25 [pubmed] PHST- 2025/07/23 19:37 [entrez] AID - S1098-3015(25)02472-6 [pii] AID - 10.1016/j.jval.2025.07.007 [doi] PST - ppublish SO - Value Health. 2025 Oct;28(10):1488-1496. doi: 10.1016/j.jval.2025.07.007. Epub 2025 Jul 21. PMID- 40694751 OWN - NLM STAT- MEDLINE DCOM- 20250722 LR - 20250722 IS - 1526-632X (Electronic) IS - 0028-3878 (Linking) VI - 105 IP - 3 DP - 2025 Aug 12 TI - GLP-1RA-Associated Diabetic Lumbosacral Radiculoplexus and Common Fibular Neuropathies: A Case-Control Evaluation. PG - e213916 LID - 10.1212/WNL.0000000000213916 [doi] AB - BACKGROUND AND OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used to treat obesity and diabetes. Semaglutide, a GLP-1RA, is linked to nonarteritic ischemic optic neuropathy (NAION), macular edema, and retinopathy. Because diabetic lumbosacral radiculoplexus neuropathy (DLRPN) and common fibular neuropathy (CFN) are associated with weight loss, we examined whether GLP-1RA usage is linked to these neuropathies. METHODS: We conducted a retrospective case-controlled study from April 28, 2005 (the first GLP-1RA Food and Drug Administration approval), to December 25, 2024. Patients diagnosed with DLRPN or CFN were analyzed for GLP-1RA exposure and clinical characteristics. A control group, matched for age, sex, body mass index (BMI), and diabetes status, was used to assess for an association with GLP-1RA use. RESULTS: We identified 26 individuals who developed 27 DLRPN episodes, with median symptom onset 6 months (range 3-35 months) after GLP-1RA initiation. At onset, they had a median glycated hemoglobin A1c (HbA1c) reduction of 2.4% (range 1%-8.5%) and a BMI decrease of 4 units (range 1-15), reflecting a 13.9% (range 3.6%-28.5%) weight loss. Microvasculitis was present in 4 of 5 nerve biopsies. Among 77 individuals with CFN, 82 episodes developed, with a mean GLP-1RA duration of 15 months (range 1-112 months). In individuals with CFN, the median HbA1c reduction was 1.2% (range -0.4% to 5%) and the BMI decrease was 4 units (range 0-15), corresponding to a 15.7% (range 3.0%-37.0%) weight loss. Patients with DLRPN experienced greater HbA1c reductions than patients with CFN (2.4% vs 1.2%, p < 0.001). New NAION, macular edema, or retinopathy were not seen with episodes. Compared with controls, GLP-1RA users were 51% more likely to develop DLRPN (odds ratio [OR] 1.5, 95% CI 1.2-1.9, p = 0.0008) and 30% more likely to develop CFN (OR 1.3, 95% CI 1.0-1.5, p = 0.018). All episodes occurred after 2015, with 3 DLRPN events and 7 CFN events occurring between 2015 and 2019, rising to 24 and 70 cases in 2020-2024, reflecting increases of 700% and 900%. DISCUSSION: GLP-1RA use is associated with an increased likelihood of DLRPN and CFN. DLRPN and its associated nerve microvasculitis seem more strongly linked to metabolic changes, particularly significant HbA1c reductions, while CFN has compressive neuropathy characteristics and is more influenced by weight loss. FAU - Triplett, James D AU - Triplett JD AUID- ORCID: 0000-0001-9402-1248 AD - Department of Neurology, Mayo Clinic, Rochester, MN. AD - Centre for Research Excellence (CRE) Translating Nutritional Science to Good Health, University of Adelaide, Australia. FAU - Pinto, Marcus V AU - Pinto MV AUID- ORCID: 0000-0002-9890-6657 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Young, Nathan P AU - Young NP AUID- ORCID: 0000-0001-7788-6493 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Staff, Nathan P AU - Staff NP AUID- ORCID: 0000-0001-6760-3859 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Chinmay, Marathe S AU - Chinmay MS AD - Centre for Research Excellence (CRE) Translating Nutritional Science to Good Health, University of Adelaide, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Australia. FAU - Horowitz, Michael AU - Horowitz M AUID- ORCID: 0000-0002-0942-0306 AD - Centre for Research Excellence (CRE) Translating Nutritional Science to Good Health, University of Adelaide, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Australia. FAU - Aragon Pinto, Catarina AU - Aragon Pinto C AUID- ORCID: 0000-0003-2929-3313 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Laughlin, Ruple S AU - Laughlin RS AUID- ORCID: 0000-0002-1884-5824 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Shouman, Kamal AU - Shouman K AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Berini, Sarah E AU - Berini SE AUID- ORCID: 0009-0005-5988-4255 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Mauermann, Michelle L AU - Mauermann ML AUID- ORCID: 0000-0001-9619-7802 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Dubey, Divyanshu AU - Dubey D AUID- ORCID: 0000-0001-6865-9045 AD - Department of Neurology, Mayo Clinic, Rochester, MN. AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; and. FAU - Mandrekar, Jay AU - Mandrekar J AUID- ORCID: 0000-0002-9718-4082 AD - Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN. FAU - Dyck, P James B AU - Dyck PJB AUID- ORCID: 0000-0003-0212-8254 AD - Department of Neurology, Mayo Clinic, Rochester, MN. FAU - Klein, Christopher J AU - Klein CJ AUID- ORCID: 0000-0002-4012-8856 AD - Department of Neurology, Mayo Clinic, Rochester, MN. AD - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; and. LA - eng PT - Journal Article DEP - 20250722 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Diabetic Neuropathies/chemically induced/epidemiology MH - Case-Control Studies MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Peroneal Neuropathies/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - *Radiculopathy/chemically induced MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy EDAT- 2025/07/23 11:24 MHDA- 2025/07/23 11:25 CRDT- 2025/07/22 16:03 PHST- 2025/07/23 11:25 [medline] PHST- 2025/07/23 11:24 [pubmed] PHST- 2025/07/22 16:03 [entrez] AID - 10.1212/WNL.0000000000213916 [doi] PST - ppublish SO - Neurology. 2025 Aug 12;105(3):e213916. doi: 10.1212/WNL.0000000000213916. Epub 2025 Jul 22. PMID- 40693572 OWN - NLM STAT- MEDLINE DCOM- 20251012 LR - 20260512 IS - 1445-5994 (Electronic) IS - 1444-0903 (Print) IS - 1444-0903 (Linking) VI - 55 IP - 10 DP - 2025 Oct TI - Is semaglutide cost-effective at closing the gap for Aboriginal and Torres Strait Islander Australians with cardiovascular disease and obesity without type 2 diabetes? PG - 1725-1732 LID - 10.1111/imj.70160 [doi] AB - BACKGROUND: Aboriginal and Torres Strait Islander Australians experience worse healthcare outcomes due to increased prevalence of cardiovascular disease (CVD). A large proportion of this is preventable if CVD risk factors, such as obesity, are effectively treated. In the SELECT (Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity) trial, the use of semaglutide for patients with CVD and obesity without type 2 diabetes (T2D) significantly reduced the prevalence of CVD. AIM: To determine the cost-benefit to the Australian healthcare system of funding early-access semaglutide for treating Aboriginal and Torres Strait Islander Australians with CVD and obesity without T2D. METHODS: A Markov cohort state-transition model was annually cycled for 25 years. The population was Aboriginal and Torres Strait Islander Australians with CVD and obesity without T2D. They received either semaglutide or standard care. Transition probabilities, utilities, costs and discounting were literature-derived. The incremental cost-effectiveness ratio (ICER) was our primary outcome. Disability-adjusted life-years (DALYs) and fatal and non-fatal CVD events prevented were secondary outcomes. Sensitivity analysis for various scenarios was performed. RESULTS: In the estimated 13 650 Aboriginal and Torres Strait Islander Australians with CVD and obesity without T2D, semaglutide was modelled to prevent an additional 929 fatal CVD events, 13 480 non-fatal CVD events and 8628 DALYs over 25 years at an additional cost to the Australian government of $25 956 522/year (<0.2% of annual CVD expenditure). The ICER was $75 206/DALYs. CONCLUSION: A strategy of early-access funding and use of semaglutide for Aboriginal and Torres Strait Islander Australians with CVD and obesity without T2D may be cost-effective to the Australian healthcare system while closing the gap in healthcare disparities. CI - (c) 2025 The Author(s). Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians. FAU - Hargovan, Satyen AU - Hargovan S AUID- ORCID: 0000-0002-5194-5317 AD - Department of Cardiology, The Prince Charles Hospital, Brisbane, Queensland, Australia. AD - College of Medicine, James Cook University, Townsville, Queensland, Australia. FAU - Hunt, Nadine AU - Hunt N AD - National Centre for Aboriginal and Torres Strait Islander Wellbeing Research and National Centre for Epidemiology and Population Health, College of Health and Medicine, The Australian National University, Canberra, Australian Capital Territory, Australia. FAU - Kostakis, Hara AU - Kostakis H AD - Department of Public Health and Policy, London School of Hygiene and Tropical Medicine, University of London, London, UK. FAU - Chow, Clara K AU - Chow CK AD - Westmead Applied Research Centre, University of Sydney, Sydney, New South Wales, Australia. AD - Department of Cardiology, Westmead Hospital, Sydney, New South Wales, Australia. LA - eng PT - Journal Article DEP - 20250722 PL - Australia TA - Intern Med J JT - Internal medicine journal JID - 101092952 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Female MH - Humans MH - Male MH - Middle Aged MH - Australia/epidemiology MH - *Australian Aboriginal and Torres Strait Islander Peoples/statistics & numerical data MH - *Cardiovascular Diseases/economics/drug therapy/ethnology/epidemiology MH - Cohort Studies MH - Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/economics/epidemiology/drug therapy/ethnology MH - Markov Chains MH - *Obesity/drug therapy/economics/ethnology/epidemiology MH - *Glucagon-Like Peptide 1/economics/therapeutic use MH - Semaglutide PMC - PMC12515466 OTO - NOTNLM OT - Aboriginal and Torres Strait Islander OT - cardiovascular disease OT - economic analysis OT - obesity OT - prevention OT - semaglutide EDAT- 2025/07/23 10:54 MHDA- 2025/10/12 12:31 PMCR- 2025/10/12 CRDT- 2025/07/22 07:22 PHST- 2025/03/19 00:00 [received] PHST- 2025/06/15 00:00 [accepted] PHST- 2025/10/12 12:31 [medline] PHST- 2025/07/23 10:54 [pubmed] PHST- 2025/07/22 07:22 [entrez] PHST- 2025/10/12 00:00 [pmc-release] AID - IMJ70160 [pii] AID - 10.1111/imj.70160 [doi] PST - ppublish SO - Intern Med J. 2025 Oct;55(10):1725-1732. doi: 10.1111/imj.70160. Epub 2025 Jul 22. PMID- 40690352 OWN - NLM STAT- MEDLINE DCOM- 20251222 LR - 20260226 IS - 1529-4242 (Electronic) IS - 0032-1052 (Linking) VI - 157 IP - 1 DP - 2026 Jan 1 TI - Disruptions in Aesthetic Medicine: A Global Analysis of GLP-1 Agonists Using Punctuated Equilibrium Framework. PG - 84-102 LID - 10.1097/PRS.0000000000012307 [doi] AB - BACKGROUND: The adoption of glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, has significantly improved obesity and type 2 diabetes management. However, their unintended side effects, particularly facial volume loss, termed "Ozempic face," have disrupted aesthetic medicine. This intersection between metabolic health and aesthetics raises ethical dilemmas and growing dependency on corrective interventions such as dermal fillers. METHODS: A mixed-methods approach was used, incorporating content analysis, social media sentiment analysis, and social network modeling. Data were collected from 15 peer-reviewed studies, clinical reports, and 3.79 million social media posts across global regions. Sentiment analysis identified public perceptions, whereas network analysis examined influencer dominance in promoting aesthetic solutions. RESULTS: Findings revealed a 40% increase in filler consultations attributed to GLP-1-related aesthetic concerns. Sentiment analysis showed that 72% of high-engagement content was driven by influencers normalizing fillers as necessary adjuncts to GLP-1 therapies. Ethical concerns were prominent, particularly in regions such as Asia and South America, where commercial narratives dominate. In contrast, North America and Europe demonstrated a more balanced approach, prioritizing informed patient care under regulatory frameworks. CONCLUSIONS: GLP-1 therapies represent a transformative shift in metabolic care but introduce significant aesthetic, ethical, and psychological challenges. Social media amplifies commercial influences, often at the cost of evidence-based practice. Regulatory reforms, longitudinal studies, and enhanced patient education are critical to navigating this evolving landscape and ensuring patient well-being. CI - Copyright (c) 2025 by the American Society of Plastic Surgeons. FAU - Rahman, Eqram AU - Rahman E AD - From the Research and Innovation Hub, Innovation Aesthetics. FAU - Webb, William Richard AU - Webb WR AD - From the Research and Innovation Hub, Innovation Aesthetics. FAU - Sadeghi-Esfahlani, Shabnam AU - Sadeghi-Esfahlani S AD - Medical Technology Research Centre, Anglia Ruskin University. FAU - Rao, Parinitha AU - Rao P AD - The Skin Address (aesthetic dermatology practice). FAU - Garcia, Patricia E AU - Garcia PE AD - private practice. FAU - Sayed, Karim AU - Sayed K AD - Nomi Oslo. FAU - Ioannidis, Sotirios AU - Ioannidis S AD - Plastic Surgery Clinic. FAU - Yu, Nanze AU - Yu N AD - Department of Plastic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College. FAU - Nassif, Alexander D AU - Nassif AD AD - Departamento de Pesquisa, Nucleo Nassif-Ensino Medico e Pesquisa. FAU - Goodman, Greg J AU - Goodman GJ AD - Monash University Australia. AD - Dermatology Institute of Victoria. FAU - Carruthers, Jean D A AU - Carruthers JDA AD - Department of Ophthalmology, University of British Columbia. LA - eng GR - DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20250715 PL - United States TA - Plast Reconstr Surg JT - Plastic and reconstructive surgery JID - 1306050 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Dermal Fillers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cosmetic Techniques/ethics/adverse effects MH - Social Media/statistics & numerical data MH - *Glucagon-Like Peptides/adverse effects MH - *Dermal Fillers/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - Esthetics MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/07/21 18:31 MHDA- 2025/12/22 12:55 CRDT- 2025/07/21 12:23 PHST- 2025/12/22 12:55 [medline] PHST- 2025/07/21 18:31 [pubmed] PHST- 2025/07/21 12:23 [entrez] AID - 00006534-990000000-02701 [pii] AID - 10.1097/PRS.0000000000012307 [doi] PST - ppublish SO - Plast Reconstr Surg. 2026 Jan 1;157(1):84-102. doi: 10.1097/PRS.0000000000012307. Epub 2025 Jul 15. PMID- 40685589 OWN - NLM STAT- MEDLINE DCOM- 20251028 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 33 IP - 11 DP - 2025 Nov TI - Efficacy and Safety of GLP-1 Receptor Agonists, Dual Agonists, and Retatrutide for Weight Loss in Adults With Overweight or Obesity: A Bayesian NMA. PG - 2046-2054 LID - 10.1002/oby.24360 [doi] AB - OBJECTIVE: To compare the efficacy and safety of GLP-1 receptor agonists (GLP-1RAs), dual agonists (GLP-1RAs/GIP or GCGR), and retatrutide (GLP-1/GIP/glucagon) for weight loss in adults with overweight or obesity. METHODS: We conducted a systematic review and Bayesian network meta-analysis (NMA) of 19 randomized controlled trials (RCTs) including 29,506 adults (BMI >/= 25 kg/m(2)), assessing liraglutide, semaglutide, survodutide, tirzepatide, retatrutide, and placebo. Outcomes included mean weight loss, achievement of >/= 5%, >/= 10%, and >/= 15% weight loss, waist circumference (WC), BMI, and adverse events (AEs) at >/= 36 weeks. Subgroup and meta-regression analyses evaluated the impact of diabetes status, sex, age, and BMI. RESULTS: Retatrutide and dual agonists achieved equivalent mean weight loss (-11.0 kg), surpassing GLP-1RAs (-9.0 kg), with retatrutide excelling at achieving >/= 15% weight loss (OR 54.6). Dual agonists and GLP-1RAs followed (OR 16.4 and 9.0, respectively). Retatrutide had the highest AE risk. Meta-regression showed type 2 diabetes mellitus (T2DM) reduced weight loss by 4.338 kg for GLP-1RAs and 5.016 kg for dual agonists, with enhanced outcomes in female-dominant or high-BMI cohorts. CONCLUSIONS: Retatrutide offers superior weight loss efficacy but with a higher AE risk. Dual agonists provide a favorable efficacy-safety balance. Personalized treatment selection based on patient characteristics is recommended. CI - (c) 2025 The Obesity Society. FAU - Sinha, Binayak AU - Sinha B AD - Department of Endocrinology, Manipal Hospital, Kolkata, India. FAU - Ghosal, Samit AU - Ghosal S AUID- ORCID: 0000-0002-4141-5187 AD - Department of Internal Medicine, Nightingale Hospital, Kolkata, India. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250720 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Fatty Acids) RN - 0 (Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (retatrutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Bayes Theorem MH - Body Mass Index MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - *Obesity/drug therapy MH - *Overweight/drug therapy MH - Randomized Controlled Trials as Topic MH - Tirzepatide MH - Treatment Outcome MH - *Weight Loss/drug effects MH - Fatty Acids MH - Peptides MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonists OT - adverse events OT - dual agonists OT - network meta-analysis OT - obesity OT - retatrutide OT - weight loss EDAT- 2025/07/21 06:30 MHDA- 2025/10/28 06:30 CRDT- 2025/07/21 00:43 PHST- 2025/05/14 00:00 [revised] PHST- 2025/03/30 00:00 [received] PHST- 2025/05/15 00:00 [accepted] PHST- 2025/10/28 06:30 [medline] PHST- 2025/07/21 06:30 [pubmed] PHST- 2025/07/21 00:43 [entrez] AID - 10.1002/oby.24360 [doi] PST - ppublish SO - Obesity (Silver Spring). 2025 Nov;33(11):2046-2054. doi: 10.1002/oby.24360. Epub 2025 Jul 20. PMID- 40679854 OWN - NLM STAT- MEDLINE DCOM- 20250820 LR - 20260520 IS - 1520-4812 (Electronic) IS - 1043-1802 (Linking) VI - 36 IP - 8 DP - 2025 Aug 20 TI - Innovative Glucagon-like Peptide 1 Receptor Agonists: Exploring the Therapeutic Potential of Specific Modified Monomer, Dimer, and Tetramer in Type 2 Diabetes Treatment. PG - 1753-1766 LID - 10.1021/acs.bioconjchem.5c00261 [doi] AB - Modified glucagon-like peptide 1 (GLP-1) plays a crucial role in type 2 diabetes (T2D) treatment. The comparative hypoglycemic effect among fatty-acid-modified GLP-1 monomer G20, dimer 2G21, and tetramer 4G18 was evaluated in T2D mice. The polymers exhibited an opposite solubility with their monomers. After single administration, the oral glucose tolerance test results showed that the monomers, dimer, or tetramer, respectively, had 3-9, 21, or 35 days of hypoglycemic effect or plasma stability. G20 had a moderate hypoglycemic effect, and its peak effect occurred in week 1 as semaglutide. 2G21 showed a strongly hypoglycemic effect in week 1-10, and its peak effect occurred in week 4. 4G18 had a weak effect initially but rapidly strengthened in weeks 6-10 and reached its peak effect in week 10. After the 10 week interference, compared to the model control group, G20 (-19.7 or -4.3%), 2G21-L/M/H (-15.9/-34.3/-26.7% or -6.0/-34.4/-36.2%), and 4G18-L/M/H groups (-44.3/-49.8/-53.8% or -40.9/-50.6/-50.8%) significantly exhibited hypoglycemic effects in postprandial glucose or fasting plasma glucose changes. Insulin altered +4.1% (G20), -9.6/+10.0/+36.5% (2G21-L/M/H), and +38.5/+28.7/+84.8% (4G18-L/M/H). HbA(1c) or body weight reduced -11.9 or -0.18% (G20), -5.2/-15.2/-19.1% or +0.5/-4.7/-1.2% (2G21-L/M/H), and -5.8/-4.8/-5.4% or -2.9/-2.1/-3.1% (4G18-L/M/H), showing a dose-dependent reduction in 2G21, whereas the 4G18 had lower variations. 2G21 induced a hypoglycemic effect and diet stress, whereas 4G18 only did a hypoglycemic effect and showed a stronger protection to the model organs and more improvement in the nerve muscle than G20 or 2G21. The endogenous insulin release depends not only on the GLP-1 peptide dose but also on the peptide chain in the polymer skeleton. FAU - Du, Yan AU - Du Y AD - Department of Clinical Laboratories & Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou 510507, China. FAU - Liu, Tao AU - Liu T AD - Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Li, Hua-Lin AU - Li HL AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Luo, Qun AU - Luo Q AD - Translational Medicine Center, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China. FAU - Guo, Xiao-Yuan AU - Guo XY AD - Department of Pathology, Sanya People's Hospital, Sanya, Hainan Province 572000, China. FAU - Wang, Jian-Yun AU - Wang JY AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Wang, Xin-Rui AU - Wang XR AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Zhou, Ya-Man AU - Zhou YM AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Pan, Ya-Wen AU - Pan YW AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. FAU - Yu, Li-Cheng AU - Yu LC AD - Department of Clinical Laboratories & Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou 510507, China. FAU - Tan, Hong-Mei AU - Tan HM AD - Department of Clinical Laboratories, Luopu Community Health Service Center, Guangzhou 511431, China. FAU - Hu, Ke-Sheng AU - Hu KS AD - Department of Clinical Laboratories & Pathology, Guangdong Provincial Corps Hospital of Chinese People's Armed Police Forces, Guangzhou 510507, China. FAU - Tang, Song-Shan AU - Tang SS AUID- ORCID: 0009-0000-9991-8636 AD - Department of Biochemistry and Molecular Biology, Guangdong Pharmaceutical University, Guangzhou 510006, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250718 PL - United States TA - Bioconjug Chem JT - Bioconjugate chemistry JID - 9010319 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/chemistry/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Mice MH - Male MH - *Glucagon-Like Peptide 1/chemistry/therapeutic use MH - Blood Glucose/analysis MH - Glucose Tolerance Test MH - Diabetes Mellitus, Experimental/drug therapy MH - Mice, Inbred C57BL MH - Semaglutide EDAT- 2025/07/18 12:29 MHDA- 2025/08/20 06:31 CRDT- 2025/07/18 11:52 PHST- 2025/08/20 06:31 [medline] PHST- 2025/07/18 12:29 [pubmed] PHST- 2025/07/18 11:52 [entrez] AID - 10.1021/acs.bioconjchem.5c00261 [doi] PST - ppublish SO - Bioconjug Chem. 2025 Aug 20;36(8):1753-1766. doi: 10.1021/acs.bioconjchem.5c00261. Epub 2025 Jul 18. PMID- 40678871 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20260514 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 Suppl 7 IP - Suppl 7 DP - 2025 Aug TI - An overview of randomized clinical trials of fixed-ratio combinations of basal insulin plus GLP-1RA (injectable therapy): Lessons for advancing therapy in people with type 2 diabetes. PG - 14-25 LID - 10.1111/dom.16616 [doi] AB - Advancing therapy in T2DM with injectables, i.e., basal insulin (BI) and GLP-1 receptor agonists (GLP-1RAs) is recommended after the failure of oral glucose lowering agents (OGLAs), BI alone, or BI in combination with OGLAs, especially in persons with, or at high risk of atherosclerotic cardiovascular disease (ASCVD). BI and GLP-1RAs can be administered separately or as fixed-ratio combinations (FRCs) for daily use (degludec+liraglutide, IDegLira, glargine-100 + lixisenatide iGlarLixi) or weekly use (icodec+semaglutide, IcoSema). The currently available FRCs IDegLira and iGlarLixi differ in their respective BI as well as GLP-1RA components. Liraglutide predominantly stimulates glucose-dependent endogenous insulin secretion in response to nutrient challenges. In contrast, the rapid-acting lixisenatide primarily delays gastric emptying over a few hours post-dosing with little or no impact on insulin secretion. IDegLira in DUAL studies and iGlarLixi in LixiLan studies appear to have equivalent lowering effects on HbA1c, although IDegLira achieves a greater reduction in body weight. The weekly FRC IcoSema is superior to weekly insulin icodec (COMBINE 1), to semaglutide (COMBINE 2), and non-inferior to basal-bolus insulin therapy (COMBINE 3). Comparison of IcoSema with glargine-100 is ongoing (COMBINE 4). However, all FRCs are limited by the low GLP-1RA dose relative to the insulin delivered. Whenever higher GLP-1RA doses are required (i.e., in obese people), the option of separate dosing of BI and GLP-1RA with independent titration of each component should be considered. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Bolli, Geremia B AU - Bolli GB AUID- ORCID: 0000-0003-4966-4003 AD - Department of Medicine and Surgery, Perugia University Medical School, Perugia, Italy. FAU - Porcellati, Francesca AU - Porcellati F AD - Department of Medicine and Surgery, Perugia University Medical School, Perugia, Italy. FAU - Lucidi, Paola AU - Lucidi P AD - Centro Diabetologia Asl 2 Umbria 'Centro Storico', Foligno, Italy. FAU - Fanelli, Carmine G AU - Fanelli CG AUID- ORCID: 0000-0003-4063-158X AD - Department of Medicine and Surgery, Perugia University Medical School, Perugia, Italy. FAU - Perseghin, Gianluca AU - Perseghin G AD - Department of Medicine and Surgery, Universita degli Studi di Milano Bicocca & Policlinico, di Monza, Monza, Italy. FAU - Horowitz, Michael AU - Horowitz M AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, Australia. FAU - Owens, David R AU - Owens DR AUID- ORCID: 0000-0003-1002-1238 AD - Cardiff University Medical School, Cardiff, UK. LA - eng GR - University of Perugia/ GR - 2022KZ4KMY/MUR -PRIN/ PT - Journal Article PT - Review DEP - 20250717 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Drug Combinations) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Insulin, Long-Acting) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Peptides) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 74O62BB01U (lixisenatide) RN - 0 (IDegLira) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Combinations MH - Insulin Glargine/administration & dosage MH - Insulin, Long-Acting/administration & dosage/therapeutic use MH - Liraglutide/administration & dosage MH - Drug Therapy, Combination MH - Glucagon-Like Peptides/administration & dosage MH - Peptides/administration & dosage MH - *Insulin/administration & dosage MH - Blood Glucose/drug effects MH - Glucagon-Like Peptide-2 Receptor MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12308269 OTO - NOTNLM OT - GLP-1RA OT - basal insulin OT - fixed-ratio combinations basal insulin GLP-1RAs OT - type 2 diabetes COIS- G.B.B. has received honoraria for lecturing from Sanofi. F.P. receives clinical trial funding, advisory board, and lecture fees from Abbott, AstraZeneca, Lilly, Novo Nordisk, Sanofi. P.L. and C.G.F. have no conflicts of interest. G.P. has received honoraria for lecturing and advisory boards for Amgen, Bruno Farmaceutici, EG, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Echosens, Lilly, Menarini Diag, Merck, Novartis, Novo Nordisk, Pfizer, PikDare, Roche Diag, Sanofi, Servier; clinical trial funding from Novartis, Novo Nordisk, Merck. M.H. and D.R.O. have received lecture fees from Bayer, Boehringer Ingelheim, Roche, and Sanofi. EDAT- 2025/07/18 06:25 MHDA- 2025/07/30 06:30 PMCR- 2025/07/30 CRDT- 2025/07/18 05:43 PHST- 2025/06/24 00:00 [revised] PHST- 2025/05/04 00:00 [received] PHST- 2025/07/04 00:00 [accepted] PHST- 2025/07/30 06:30 [medline] PHST- 2025/07/18 06:25 [pubmed] PHST- 2025/07/18 05:43 [entrez] PHST- 2025/07/30 00:00 [pmc-release] AID - DOM16616 [pii] AID - 10.1111/dom.16616 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27 Suppl 7(Suppl 7):14-25. doi: 10.1111/dom.16616. Epub 2025 Jul 17. PMID- 40676725 OWN - NLM STAT- MEDLINE DCOM- 20251218 LR - 20260127 IS - 2058-1742 (Electronic) IS - 2058-1742 (Linking) VI - 11 IP - 8 DP - 2025 Dec 19 TI - Cardiovascular outcomes and safety of semaglutide in non-overweight populations with type 2 diabetes: a comparison with dipeptidyl peptidase 4 inhibitors. PG - 1319-1328 LID - 10.1093/ehjqcco/qcaf065 [doi] AB - AIMS: The effects of semaglutide on non-overweight patients with type 2 diabetes (T2D) remain unclear. We retrospectively compared all-cause mortality, cardiovascular outcomes, and adverse events in patients with T2D with a body mass index (BMI) < 25 kg/m(2) who received semaglutide or dipeptidyl peptidase 4 (DPP-4) inhibitors. METHODS AND RESULTS: Based on the TriNetX database of electronic medical records between 2018 and 2020, we identified 340 721 patients with T2D with a BMI <25 kg/m(2). Of the 6789 patients who received semaglutide, 2454 who received DPP-4 inhibitors after diagnosis were excluded. Of the 41 141 patients who received DPP-4 inhibitors, 5252 patients who received GLP-1 receptor agonists after diagnosis were excluded. After propensity score matching, 4194 patients were included in each group. The primary outcome was the 3-year cumulative incidence of all-cause mortality; the secondary outcomes were acute myocardial infarction (AMI) and stroke. The adverse events included nausea, vomiting, diarrhoea, and hypoglycaemia. The semaglutide group had a significantly lower risk of all-cause mortality compared to the DPP-4 inhibitor group [6.1% vs. 10.7%, P < 0.001; hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.45-0.65]. Semaglutide was not associated with the incidence of AMI (6.1% vs. 7.1%, P = 0.173; HR 0.87, 95% CI 0.72-1.06) or stroke (8.4% vs. 7.7%, P = 0.220; HR 1.11, 95% CI 0.94-1.32). Adverse events, including nausea and vomiting, diarrhoea, and hypoglycaemia, were not significantly different between the groups. CONCLUSION: In patients with T2D and BMI <25 kg/m2, semaglutide was associated with a lower 3-year risk of all-cause mortality than DPP-4 inhibitors. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Kishimori, Takefumi AU - Kishimori T AUID- ORCID: 0009-0000-9639-5470 AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Kato, Takao AU - Kato T AUID- ORCID: 0000-0001-8213-7999 AD - Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. FAU - Wada, Atsuyuki AU - Wada A AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Tani, Akira AU - Tani A AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Yamaji, Ryosuke AU - Yamaji R AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Koike, Jumpei AU - Koike J AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Iwasaki, Yoshihiro AU - Iwasaki Y AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Matsumoto, Takehiro AU - Matsumoto T AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Yagi, Takafumi AU - Yagi T AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. FAU - Okada, Masaharu AU - Okada M AD - Department of Cardiovascular Medicine, Omi Medical Center, 1660 Yabase-cho, Kusatsu, Shiga 525-8585, Japan. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study PL - England TA - Eur Heart J Qual Care Clin Outcomes JT - European heart journal. Quality of care & clinical outcomes JID - 101677796 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Eur Heart J Qual Care Clin Outcomes. 2025 Dec 19;11(8):1487. doi: 10.1093/ehjqcco/qcaf082. PMID: 40796132 CIN - Eur Heart J Qual Care Clin Outcomes. 2025 Dec 19;11(8):1263-1264. doi: 10.1093/ehjqcco/qcaf116. PMID: 40991735 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Mass Index MH - *Cardiovascular Diseases/epidemiology/etiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Follow-Up Studies MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Hypoglycemic Agents/therapeutic use MH - Incidence MH - Retrospective Studies MH - Survival Rate/trends MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adverse event OT - All-cause mortality OT - Dipeptidyl peptidase-4 inhibitor OT - Glucagon-like peptide-1 receptor agonist OT - Non-overweight OT - Type 2 diabetes COIS- Conflict of interest: None. EDAT- 2025/07/18 01:38 MHDA- 2025/12/19 01:45 CRDT- 2025/07/17 23:52 PHST- 2025/03/02 00:00 [received] PHST- 2025/05/08 00:00 [revised] PHST- 2025/07/13 00:00 [accepted] PHST- 2025/12/19 01:45 [medline] PHST- 2025/07/18 01:38 [pubmed] PHST- 2025/07/17 23:52 [entrez] AID - 8205756 [pii] AID - 10.1093/ehjqcco/qcaf065 [doi] PST - ppublish SO - Eur Heart J Qual Care Clin Outcomes. 2025 Dec 19;11(8):1319-1328. doi: 10.1093/ehjqcco/qcaf065. PMID- 40676576 OWN - NLM STAT- MEDLINE DCOM- 20250718 LR - 20260925 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 25 IP - 1 DP - 2025 Jul 17 TI - Incretin-based approaches for type 2 diabetes therapy: effects on circulating cytokines and adipocyte's secretome. PG - 182 LID - 10.1186/s12902-025-01999-w [doi] LID - 182 AB - BACKGROUND: Adipose tissue secretome plays a crucial role in the mechanisms of metabolic diseases. Weight loss has a favourable effect on the adipose tissue secretome and prevents the development of type 2 diabetes mellitus (T2DM) and its complications. The most effective methods of glycaemic control are bariatric surgery (BS) and pharmacotherapy. The aim of our study is to evaluate changes in adipose tissue secretome after BS and semaglutide injections. METHODS: 17 patients with T2DM were examined before and 6 months after BS or semaglutide therapy. The examination protocol included anthropometry, clinical biochemistry, insulin resistance evaluation and collection of subcutaneous adipose tissue biopsies. Adipose derived stem cells (ADSC) were isolated from biopsies according to a standard enzymatic protocol and differentiated into white and beige adipocytes. Adipogenesis and thermogenesis were assessed by confocal microscopy. Secretome of adipocytes and cytokines plasma levels were analyzed using a MILLIPLEX panel. RESULTS: Following BS and semaglutide therapy, a decline in BMI, total fat content, HbA1c, and fasting blood glucose was observed. Insulin sensitivity increased only 6 months after BS. Semaglutide therapy resulted in the elevation of angiogenic and proinflammatory cytokines in adipocyte secretory profile. After BS we also detected the increase in proinflammatory cytokines both in adipocyte secretome and in plasma levels. However, the adipocyte secretome subsequent to bariatric surgery (BS) exhibited a reduced proinflammatory response in comparison to that observed following semaglutide therapy. CONCLUSIONS: The effect of semaglutide injections directly on adipose tissue can change the function of ADSC, making them more angiogenic and adipogenic. A decrease in BMI, HbA1c and insulin resistance is achieved to a significant extent only after BS. BS-induced T2DM remission is related to lower pro-inflammatory secretion from adipocytes as compared to semaglutide. The regulation of inflammation in adipocytes may serve as a potential mechanism underlying BS-induced T2DM remission. CI - (c) 2025. The Author(s). FAU - Agareva, Margarita AU - Agareva M AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. AD - Lomonosov Moscow State University, Moscow, 119991, Russia. FAU - Michurina, Svetlana AU - Michurina S AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. FAU - Tomilova, Alina AU - Tomilova A AD - Endocrinology Research Centre, Moscow, 117292, Russia. FAU - Shestakova, Ekaterina AU - Shestakova E AD - Endocrinology Research Centre, Moscow, 117292, Russia. FAU - Voznesenskaya, Anastasia AU - Voznesenskaya A AD - Endocrinology Research Centre, Moscow, 117292, Russia. FAU - Sineokaya, Maria AU - Sineokaya M AD - Endocrinology Research Centre, Moscow, 117292, Russia. FAU - Zubkova, Ekaterina AU - Zubkova E AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. FAU - Ratner, Elizaveta AU - Ratner E AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. FAU - Stafeev, Iurii AU - Stafeev I AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. yuristafeev@gmail.com. FAU - Parfyonova, Yelena AU - Parfyonova Y AD - National Medical Research Centre of Cardiology named after academician E.I.Chazov, Moscow, 121552, Russia. AD - Lomonosov Moscow State University, Moscow, 119991, Russia. FAU - Shestakova, Marina AU - Shestakova M AD - Lomonosov Moscow State University, Moscow, 119991, Russia. AD - Endocrinology Research Centre, Moscow, 117292, Russia. LA - eng GR - 22-15-00365-capital PE, Cyrillic/Russian Science Foundation/ PT - Journal Article DEP - 20250717 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 0 (Incretins) RN - 0 (Cytokines) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood/pathology MH - Male MH - Female MH - Middle Aged MH - *Incretins/therapeutic use MH - Bariatric Surgery MH - *Cytokines/blood/metabolism MH - *Adipocytes/metabolism/drug effects MH - *Secretome/drug effects/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - *Glucagon-Like Peptides/therapeutic use MH - Insulin Resistance MH - Follow-Up Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12269230 OTO - NOTNLM OT - Adipocytes OT - Adipose-derived stem cells OT - Cytokines OT - Plasma OT - Secretome OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: The study protocol is in compliance with Declaration of Helsinki and was approved by the local ethics committee of the Endocrinology Research Centre (Moscow, Russia) in the framework of prolonged project "Dynamics of hormonal-metabolic factors, markers of "metabolic memory" and phenotypic characteristics of mature and progenitor cells of adipose tissue against the background of postbariatric remission of type 2 diabetes mellitus" (protocol #13 from 13 July 2022). Written informed consent was obtained from each of the volunteers. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Disclosure summary: Authors have nothing to disclose. EDAT- 2025/07/18 01:41 MHDA- 2025/07/18 06:25 PMCR- 2025/07/17 CRDT- 2025/07/17 23:45 PHST- 2025/04/07 00:00 [received] PHST- 2025/07/07 00:00 [accepted] PHST- 2025/07/18 06:25 [medline] PHST- 2025/07/18 01:41 [pubmed] PHST- 2025/07/17 23:45 [entrez] PHST- 2025/07/17 00:00 [pmc-release] AID - 10.1186/s12902-025-01999-w [pii] AID - 1999 [pii] AID - 10.1186/s12902-025-01999-w [doi] PST - epublish SO - BMC Endocr Disord. 2025 Jul 17;25(1):182. doi: 10.1186/s12902-025-01999-w. PMID- 40673973 OWN - NLM STAT- MEDLINE DCOM- 20250820 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 48 IP - 9 DP - 2025 Sep 1 TI - Gradual Titration of Semaglutide Results in Better Treatment Adherence and Fewer Adverse Events: A Randomized Controlled Open-Label Pilot Study Examining a 16-Week Flexible Titration Regimen Versus Label-Recommended 8-Week Semaglutide Titration Regimen. PG - 1607-1611 LID - 10.2337/dc25-0690 [doi] AB - OBJECTIVE: To determine whether a slower, flexible titration regimen of semaglutide would improve adherence and reduce gastrointestinal adverse events (GI-AEs) compared with the label-recommended regimen in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 104 patients with T2D were randomized to label-recommended titration (0.25 mg, 0.5 mg, 1 mg at 4-week intervals) or flexible titration (starting at 0.0675 mg [measured as five clicks made by the dose selector dial], with gradual increases by 0.0675 mg/week and delays for GI-AEs) for 26 weeks. RESULTS: While final doses were similar between groups, only 2% of patients in the flexible arm withdrew due to GI-AEs vs. 19% in the label arm (P = 0.005). The flexible arm reported less nausea (45.1% vs. 64.2%; P = 0.051) and asthenia (9.8% vs. 24.5%; P = 0.047), with fewer days experiencing nausea (2.88 vs. 6.3 days; P = 0.017). HbA1c and BMI changes were similar between groups. CONCLUSIONS: Slower, flexible titration improved adherence and reduced adverse events without compromising efficacy. CI - (c) 2025 by the American Diabetes Association. FAU - Eldor, Roy AU - Eldor R AUID- ORCID: 0000-0002-1151-1370 AD - Diabetes Unit, Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. AD - The Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Avraham, Noa AU - Avraham N AD - Diabetes Unit, Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. AD - The Gray Faculty of Medical and Health Sciences, Tel-Aviv University, Tel-Aviv, Israel. FAU - Rosenberg, Orit AU - Rosenberg O AD - Diabetes Unit, Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. FAU - Shpigelman, Miriam AU - Shpigelman M AD - Clalit Health Services, Dan-Petah Tikva District, Israel. FAU - Golan-Cohen, Avivit AU - Golan-Cohen A AD - Medical Division, Leumit Health Services, Tel-Aviv, Israel. AD - Department of Family Medicine, The Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel-Aviv, Israel. FAU - Cukierman-Yaffe, Tali AU - Cukierman-Yaffe T AUID- ORCID: 0000-0003-1289-5633 AD - Division of Endocrinology, Diabetes and Metabolism, Gertner Institute, Sheba Medical Centre, Ramat Gan, Israel. AD - Epidemiology Department, Herczeg Institute on Aging, The Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. FAU - Merzon, Eugene AU - Merzon E AUID- ORCID: 0000-0001-5469-0236 AD - Medical Division, Leumit Health Services, Tel-Aviv, Israel. AD - Adelson School of Medicine, Ariel University, Ariel, Israel. FAU - Buch, Assaf AU - Buch A AD - Diabetes Unit, Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel-Aviv, Israel. AD - Department of Nutritional Sciences, School of Health Sciences, Ariel University, Ariel, Israel. LA - eng PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Diabetes Care. 2026 Feb 1;49(2):361. doi: 10.2337/dc26-er02a. PMID: 41337783 MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Middle Aged MH - Pilot Projects MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Aged MH - Glycated Hemoglobin/metabolism MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/07/17 12:30 MHDA- 2025/09/08 08:05 CRDT- 2025/07/17 11:13 PHST- 2025/03/21 00:00 [received] PHST- 2025/06/16 00:00 [accepted] PHST- 2025/09/08 08:05 [medline] PHST- 2025/07/17 12:30 [pubmed] PHST- 2025/07/17 11:13 [entrez] AID - 162990 [pii] AID - 10.2337/dc25-0690 [doi] PST - ppublish SO - Diabetes Care. 2025 Sep 1;48(9):1607-1611. doi: 10.2337/dc25-0690. PMID- 40665260 OWN - NLM STAT- MEDLINE DCOM- 20250716 LR - 20250721 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 25 IP - 1 DP - 2025 Jul 16 TI - The effects of non-insulin anti-diabetic medications on the diabetic microvascular complications: a systematic review and meta-analysis of randomized clinical trials. PG - 179 LID - 10.1186/s12902-025-01985-2 [doi] LID - 179 AB - INTRODUCTION: Although the onset and progression of diabetic microvascular complications are linked to glycemic control, various antihyperglycemic drugs with distinct treatment targets may positively impact microvascular lesions beyond their glucose-lowering effects. Therefore, this systematic review emphasizes the clinical therapeutic implications of non-insulin anti-diabetic medications for diabetic microvascular complications. METHODS: We retrieved published literature reporting randomized clinical trials (RCTs) on the effects of microvascular complications, including diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), and diabetic retinopathy (DR), from authenticated clinical databases: PubMed, Excerpta Medica database (EMBASE), and Web of Science. We synthesized data, including the continuous variable indices: estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (UACR), and urinary albumin excretion rate (UAE). Indices measuring cardiovascular autonomic neuropathy (CAN), vibration detection threshold (VDT), and retinal nerve fiber thickness (RNFL) were used to calculate microvascular effects. We also synthesized dichotomous variable indices, including the risks for DR and DPN. RESULTS: According to our analyses, there was sparse evidence strongly supporting that metformin (MET), Sulfonylurea (SUs), Repaglinide (Repa), or alpha-Glucosidase inhibitors (alpha-GIs) could benefit diabetic microvascular complications when adopted as monotherapy. Regardless of the no change in eGFR, two trials reporting Thiazolidinediones (TZDs) significantly reduced the UACR, while other clinical trials reported an increase in VDT and improvement in DR. Sodium glucose co-transporter inhibitors (SGLT-2i) and Glucagon-like peptide-1 receptor agonists (GLP-1RA) both showed protective effects in preventing eGFR decline, with only SGLT-2i demonstrating a significant reduction in UACR. A recent trial showed that Dipeptidyl Peptidase IV inhibitors (DPP-IVi) may potentially reduce the risk of DPN, while GLP-1RA did not prove to alter the measures of CAN and DPN. However, the SUSTAIN 6 trial revealed that Semaglutide may increase the risk of DR. CONCLUSION: Besides their anti-hyperglycemic properties, some currently reviewed medications may exhibit unique anti-microvascular abilities. Due to ambiguous and conflicting available results, more emerging or ongoing trials will address this issue and could benefit clinical strategies for personalized treatment practices. CLINICAL TRIAL NUMBER: Not applicable. CI - (c) 2025. The Author(s). FAU - Wen, Song AU - Wen S AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. 379295093@qq.com. AD - Fudan Zhangjiang Institute, Shanghai Pudong Hospital, Shanghai, China. 379295093@qq.com. FAU - Yuan, Yue AU - Yuan Y AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Li, Yanyan AU - Li Y AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Xu, Chenglin AU - Xu C AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Chen, Lijiao AU - Chen L AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Ren, Yishu AU - Ren Y AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Wang, Congcong AU - Wang C AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - He, Yanju AU - He Y AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Li, Xiucai AU - Li X AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Gong, Min AU - Gong M AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Yuan, Xinlu AU - Yuan X AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Xu, Dongxiang AU - Xu D AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Wang, Chaoxun AU - Wang C AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. FAU - Zhou, Ligang AU - Zhou L AD - Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, 201399, China. zhouligang1n1@163.com. AD - Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai, 201399, China. zhouligang1n1@163.com. LA - eng GR - KP0202118/Fudan Zhangjiang Clinical Medicine Innovation Fund Project/ GR - YC-2023-0404/Integrated Traditional Chinese and Western Medicine/ GR - FD2023A227/Fudan Good Practice Program of Teaching and Learning/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250716 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetic Angiopathies/drug therapy MH - *Diabetic Nephropathies/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Retinopathy/drug therapy MH - *Diabetic Neuropathies/drug therapy PMC - PMC12265122 OTO - NOTNLM OT - Diabetic microvascular complication OT - Diabetic nephropathy OT - Diabetic neuropathy OT - Diabetic retinopathy OT - Non-insulin anti-diabetic medication COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/07/16 00:26 MHDA- 2025/07/16 06:25 PMCR- 2025/07/16 CRDT- 2025/07/15 23:49 PHST- 2025/04/07 00:00 [received] PHST- 2025/06/19 00:00 [accepted] PHST- 2025/07/16 06:25 [medline] PHST- 2025/07/16 00:26 [pubmed] PHST- 2025/07/15 23:49 [entrez] PHST- 2025/07/16 00:00 [pmc-release] AID - 10.1186/s12902-025-01985-2 [pii] AID - 1985 [pii] AID - 10.1186/s12902-025-01985-2 [doi] PST - epublish SO - BMC Endocr Disord. 2025 Jul 16;25(1):179. doi: 10.1186/s12902-025-01985-2. PMID- 40663350 OWN - NLM STAT- MEDLINE DCOM- 20250715 LR - 20260127 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 7 DP - 2025 Jul 1 TI - Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity. PG - e2521016 LID - 10.1001/jamanetworkopen.2025.21016 [doi] AB - IMPORTANCE: Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide and tirzepatide, provide cardiometabolic benefits to patients with type 2 diabetes and obesity, but their potential benefits in mitigating neurodegenerative and cerebrovascular diseases remain unclear. OBJECTIVE: To evaluate the association of semaglutide and tirzepatide with the incidence of dementia, Parkinson disease, ischemic stroke, intracerebral hemorrhage, and all-cause mortality compared with other antidiabetic drugs in adults with type 2 diabetes and obesity. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study analyzed electronic health record-based data from the TriNetX US network (December 1, 2017, to June 30, 2024) in adults aged 40 years or older with type 2 diabetes and obesity initiating semaglutide, tirzepatide, or other antidiabetic drugs, excluding those with prior neurodegenerative or cerebrovascular diseases. Propensity score matching was used to balance the baseline characteristics. EXPOSURES: Patients treated with antidiabetic drugs were categorized as GLP-1RA (semaglutide or tirzepatide) or other antidiabetic drug (biguanides, sulfonylureas, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, thiazolidinediones, and alpha-glucosidase inhibitors) users. MAIN OUTCOMES AND MEASURES: The primary outcomes were the incidence of neurodegenerative diseases (dementia, Parkinson disease, and mild cognitive impairment) and cerebrovascular (stroke and intracerebral hemorrhage) diseases, while the secondary outcome was all-cause mortality. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% CIs. RESULTS: A total of 60 860 adults with type 2 diabetes and obesity were included, with 30 430 each in the GLP-1RA group (mean [SD] age, 57.9 [9.9] years; 50.2% female) and the other antidiabetic drug group (mean [SD] age, 58.0 [10.8] years; 51.4% female) after propensity score matching. During a 7-year follow-up, GLP-1RA users had a lower risk of dementia (HR, 0.63; 95% CI, 0.50-0.81), stroke (HR, 0.81; 95% CI, 0.70-0.93), and all-cause mortality (HR, 0.70; 95% CI, 0.63-0.78), with no significant differences in the risk of Parkinson disease or intracerebral hemorrhage. Subgroup analyses revealed greater benefits in patients aged 60 years or older, women, and patients with a body mass index of 30 to 40. CONCLUSIONS AND RELEVANCE: In this cohort study, the use of GLP-1RAs semaglutide and tirzepatide was associated with a lower risk of dementia, stroke, and all-cause mortality in adults with type 2 diabetes and obesity. These findings suggest potential neuroprotective and cerebrovascular benefits of GLP-1RAs beyond glycemic control, warranting further trials to confirm these outcomes. FAU - Lin, Huan-Tang AU - Lin HT AD - Department of Anesthesiology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. FAU - Tsai, Yung-Fong AU - Tsai YF AD - Department of Anesthesiology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. AD - College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Liao, Pei-Lun AU - Liao PL AD - Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan. AD - Center for Health Data Science, Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Department of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. AD - Institute of Medicine, Department of Nursing, Chung Shan Medical University, Taichung, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250701 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Aged MH - *Obesity/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Stroke/epidemiology/chemically induced MH - *Neurodegenerative Diseases/epidemiology/chemically induced MH - Incidence MH - Parkinson Disease/epidemiology MH - Dementia/epidemiology MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/07/15 12:29 MHDA- 2025/07/15 12:30 CRDT- 2025/07/15 11:32 PHST- 2025/07/15 12:30 [medline] PHST- 2025/07/15 12:29 [pubmed] PHST- 2025/07/15 11:32 [entrez] AID - 2836412 [pii] AID - 10.1001/jamanetworkopen.2025.21016 [doi] PST - epublish SO - JAMA Netw Open. 2025 Jul 1;8(7):e2521016. doi: 10.1001/jamanetworkopen.2025.21016. PMID- 40660809 OWN - NLM STAT- MEDLINE DCOM- 20260507 LR - 20260507 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 33 IP - 1 DP - 2026 Jan 6 TI - Expert perspectives on incorporating glucagon-like peptide-1 receptor agonist in diabetes and chronic kidney disease: challenges and opportunities. PG - 8-18 LID - 10.1093/eurjpc/zwaf426 [doi] AB - Chronic kidney disease (CKD) is a complex and progressive condition ultimately leading to premature death. Diabetes is the leading cause of end-stage kidney disease worldwide. Up till 2024, international clinical guidelines have established three therapeutic pillars to delay CKD progression in people with type 2 diabetes (T2D): renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, and the non-steroidal mineralocorticoid receptor antagonist finerenone. With the recent results from the Evaluate Renal Function with Semaglutide Once Weekly study, the glucagon-like peptide-l receptor agonist (GLP-1 RA) class is now considered a new therapeutic pillar in reducing CKD complications in this patient population. In this expert opinion, we identify patient populations at risk of developing new onset or worsening pre-existing CKD to explore optimal therapeutic strategies, introducing GLP-1 RAs. We highlight the important challenges that remain in optimising, sequencing, and combining these four therapeutic pillars. Even though the conventional approach of combining the pillars has been based on the historical emergence of evidence, we discuss the factors that would influence physicians' decision for preferring one pillar over another, and for selecting a certain combination, whether performed simultaneously or sequentially. These factors include the grade of CKD and the level of albuminuria; diabetic control (glycaemia); comorbidities: atherosclerotic cardiovascular disease, heart failure, obesity; concomitant medications; biological variables: potassium serum levels. The efficacy and safety profiles of each pillar, as demonstrated in landmark trials that have clearly shown the nephroprotective effects, along with real-world data, should also be carefully considered when selecting the most appropriate therapeutic option. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Halimi, Jean-Michel AU - Halimi JM AUID- ORCID: 0000-0002-0723-7735 AD - Department of Nephrology-Hypertension, Renal Dialysis and Transplantation, CHRU de Tours, 2 Boulevard Tonnelle, Tours 37000, France. AD - INSERM UMR 1327, ISCHEMIA, University of Tours, Tours, France. AD - INI-CRCT, Tours, France. FAU - Fauchier, Laurent AU - Fauchier L AD - Department of Cardiology, Centre Hospitalier Regional Universitaire de Tours, Tours, France. FAU - Karras, Alexandre AU - Karras A AD - Department of Nephrology, Assistance Publique-Hopitaux de Paris, Georges Pompidou European Hospital, Paris, France. AD - Department of Medicine, Universite Paris Cite, Paris, France. FAU - Amouyal, Chloe AU - Amouyal C AD - Diabetology Department, Institute of Cardiometabolism and Nutrition (ICAN), Pitie-Salpetriere Hospital, Assistance Publique-Hopitaux de Paris, Paris 75013, France. AD - Sorbonne Universite, INSERM, Nutriomic Team, Paris, France. FAU - Eladari, Dominique AU - Eladari D AD - Medecine de Precision des maladies Metaboliques et Renales, Service de Nephrologie, CHU Amiens-Picardie, Universite de Picardie Jules Verne, Amiens 80054, France. AD - Paris Cardiovascular Research Center (PARCC), INSERM U970, Paris F-75015, France. AD - FCRIN-INI-CRCT, Vandoeuvre-les-Nancy 54500, France. FAU - Rossignol, Patrick AU - Rossignol P AD - Universite de Lorraine, INSERM CIC-P 1433, CHRU de Nancy, INSERM U1116, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. AD - Department of Medical Specialties and Nephrology-Hemodialysis, Princess Grace Hospital, and Centre d'Hemodialyse Prive de Monaco, and M-CRIN, Monaco, Monaco. FAU - Choukroun, Gabriel AU - Choukroun G AD - Nephrology Dialysis Transplantation Department, CHU Amiens Picardie and Jules Verne University, Amiens 80000, France. FAU - Zaoui, Philippe AU - Zaoui P AD - Department of Medicine, Universite Grenoble Alpes, La Tronche 38700, France. FAU - Girerd, Nicolas AU - Girerd N AD - University of Lorraine, Center of Plurithematic Clinical Investigations 1433 and INSERM U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. FAU - Hadjadj, Samy AU - Hadjadj S AUID- ORCID: 0000-0001-7110-6994 AD - L'Institut du Thorax, Nantes University, CHU Nantes, CNRS, INSERM, Nantes, France. LA - eng GR - Novo Nordisk/ PT - Journal Article PT - Review PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - DE2O63YV8R (finerenone) RN - 0 (Naphthyridines) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Renal Insufficiency, Chronic/drug therapy/physiopathology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Renin-Angiotensin System/drug effects MH - Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use MH - Naphthyridines/pharmacology/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Humans MH - Diabetic Nephropathies/drug therapy MH - Treatment Outcome OTO - NOTNLM OT - Chronic kidney disease OT - GLP-1 RA OT - Non-steroidal mineralocorticoid receptor antagonists OT - Renin-angiotensin system inhibitors OT - Renoprotection OT - SGLT2 inhibitor OT - Type 2 diabetes COIS- Conflict of interest: J.-M.H. received fees for advisory boards or lectures from Alexion, Astra Zeneca, Bayer, Boehringer Ingelheim France, Novo Nordisk, Servier, and Vifor Fresenius Pharma. L.F. received consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb-Pfizer, Boehringer Ingelheim, and Novo Nordisk; and lecture fees from AstraZeneca, Bristol Myers Squibb-Pfizer, Boehringer Ingelheim, Boston Scientific, Medtronic, Novo Nordisk, and Zoll Medical. A.K. received consultancy fees from GSK, Vifor, Novartis, and Otsuka; received honoraria from Pfizer, Astra-Zeneca, GSK, Novartis, Vifor, Otsuka, and Bohringer-Ingelheim; has an advisory or leadership role for Novartis, Vifor, and Otsuka; and Speakers Bureau for Otsuka, Vifor, Pfizer, Astra-Zeneca, and Boehringer-Ingelheim. C.A. received honoraria from Lilly, Sanofi, Novo Nordisk, Decom. D.E. received travel grant and honoraria from Alnylam and participated to the advisory board of Alnylam and Novo Nordisk. P.R. reports receiving personal fees from AstraZeneca, Bayer, Boehringer Ingelheim, Fresenius, Idorsia, Novo Nordisk, and Vifor. G.C. received honoraria for advisory board and participating symposia by Astellas Pharma, GSK, CSL, Vifor, and Novo Nordisk. P.Z. received honoraria and consulting fees from Novo Nordisk, Astra-Zeneca, Boehringer Lilly, and Bayer. N.G. received honoraria from AstraZeneca, Bayer, Boehringer, Lilly, Novartis, Novo Nordisk. S.H. received institutional research grants from Astra-Zeneca, Asten Sante, Air Liquide Health Science, Bayer, Boehringer Ingelheim, Eli Lilly, Homeperf, ISIS Diabete, LVL, Nestle Home Care, Novo Nordisk, Pierre Fabre, Sanofi, Valbiotis and Vitalaire and served as consultant and/or received honoraria from Astra-Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Mundi-pharma, Novo Nordisk, Novartis, Sanofi, Servier and Valbiotis. EDAT- 2025/07/15 06:28 MHDA- 2026/01/06 19:17 CRDT- 2025/07/15 03:12 PHST- 2025/04/19 00:00 [received] PHST- 2025/06/13 00:00 [revised] PHST- 2025/06/27 00:00 [accepted] PHST- 2026/01/06 19:17 [medline] PHST- 2025/07/15 06:28 [pubmed] PHST- 2025/07/15 03:12 [entrez] AID - 8201743 [pii] AID - 10.1093/eurjpc/zwaf426 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2026 Jan 6;33(1):8-18. doi: 10.1093/eurjpc/zwaf426. PMID- 40657828 OWN - NLM STAT- MEDLINE DCOM- 20250714 LR - 20260613 IS - 1878-7177 (Electronic) IS - 0003-3006 (Print) IS - 0003-3006 (Linking) VI - 72 IP - 1 DP - 2025 Mar 12 TI - Implications of GLP-1 Agonists on Office-Based Sedation and General Anesthesia for Dentistry. PG - 52-58 LID - 10.2344/anpr-72-1-ANPR_Agonists [doi] AB - Incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are produced in the gut and play critical roles linking the processes of eating and digestion with the release of insulin from the pancreas and glucose homeostasis. GLP-1 receptor agonist and combination GLP-1/GIP receptor agonist medications are exogenous incretins that mimic their endogenous counterparts, but their significantly longer half-lives allow them to be clinically useful for managing diabetes mellitus type 2 (DMT2) and obesity. Recently, their use for weight loss has grown exponentially, increasing the potential that a provider of sedation or general anesthesia for dentistry will encounter a patient taking a GLP-1 or GLP-1/GIP combination receptor agonist. One of the clinical effects produced by these medications is decreased gastric emptying which increases satiety and decreases oral intake. While these medications are effective in the management of DMT2 and obesity, delayed gastric emptying can cause concerns for sedation and general anesthesia providers. Retained gastric contents can increase risks for emesis and subsequent pulmonary aspiration in the perioperative period. In 2024, a multisociety guidance document was published to provide recommendations for the management of these patients in the perioperative period. Recommendations emphasized risk stratification of individual patients and weighing the risks vs the benefits of holding or continuing GLP-1 and GLP-1/GIP combination receptor agonist medications. The recommendations also suggested shared decision making between the sedation or general anesthesia provider, the prescribing physician, and the patient should be used when developing a plan regarding the preoperative use of these medications. FAU - McKenzie, Craig AU - McKenzie C FAU - DeBernardo, Alexander AU - DeBernardo A FAU - Schwartz, Paul AU - Schwartz P LA - eng PT - Journal Article PT - Review DEP - 20250312 PL - United States TA - Anesth Prog JT - Anesthesia progress JID - 0043533 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Anesthesia, General/methods/adverse effects MH - *Anesthesia, Dental/methods MH - *Procedural Sedation/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Gastric Emptying/drug effects MH - *Glucagon-Like Peptide 1/agonists MH - Diabetes Mellitus, Type 2/drug therapy PMC - PMC11922517 OTO - NOTNLM OT - Diabetes mellitus type 2 OT - GIP receptor agonist OT - GLP-1 receptor agonist OT - Obesity OT - Semaglutide OT - Tirzepatide EDAT- 2025/07/14 12:29 MHDA- 2025/07/14 12:30 PMCR- 2025/09/01 CRDT- 2025/07/14 08:27 PHST- 2024/03/21 00:00 [received] PHST- 2025/01/14 00:00 [accepted] PHST- 2025/07/14 12:30 [medline] PHST- 2025/07/14 12:29 [pubmed] PHST- 2025/07/14 08:27 [entrez] PHST- 2025/09/01 00:00 [pmc-release] AID - anpr721ANPRAgonists [pii] AID - 10.2344/anpr-72-1-ANPR_Agonists [doi] PST - epublish SO - Anesth Prog. 2025 Mar 12;72(1):52-58. doi: 10.2344/anpr-72-1-ANPR_Agonists. PMID- 40652323 OWN - NLM STAT- MEDLINE DCOM- 20250713 LR - 20260127 IS - 1473-2300 (Electronic) IS - 0300-0605 (Print) IS - 0300-0605 (Linking) VI - 53 IP - 7 DP - 2025 Jul TI - Association of semaglutide use with depressive symptoms and suicidal behavior in a patient with type 2 diabetes: A case report. PG - 3000605251349393 LID - 10.1177/03000605251349393 [doi] LID - 03000605251349393 AB - Semaglutide is a glucagon-like peptide-1 receptor agonist used in the treatment of type 2 diabetes mellitus and management of obesity. Associations of glucagon-like peptide-1 receptor agonist use with psychiatric adverse events and suicidal behavior have been reported. A man in his late 70s with type 2 diabetes and no history of psychiatric illness or cognitive deficits was admitted to our clinic after his first suicide attempt involving the impulsive ingestion of brush cleaner liquid. A month before his presentation, he reported restlessness and depressive mood without any apparent trigger. This period was consistent with the time of semaglutide introduction. His psychiatric symptoms improved after semaglutide discontinuation. This case report highlights the importance of regular monitoring of depression and anxiety symptoms and the possibility of suicidal ideation in individuals with type 2 diabetes treated with semaglutide. This may enable early detection and prevention of serious psychiatric adverse events. FAU - Stojkovska, Anisija AU - Stojkovska A AD - University Psychiatric Clinic Ljubljana, Slovenia. FAU - Rus Prelog, Polona AU - Rus Prelog P AD - University Psychiatric Clinic Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, Slovenia. FAU - Kokalj Palandacic, Anja AU - Kokalj Palandacic A AUID- ORCID: 0000-0002-4539-0044 AD - University Psychiatric Clinic Ljubljana, Slovenia. LA - eng PT - Case Reports PT - Journal Article DEP - 20250712 PL - England TA - J Int Med Res JT - The Journal of international medical research JID - 0346411 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology/complications MH - Male MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Depression/chemically induced MH - Aged MH - *Suicidal Ideation MH - Suicide, Attempted/psychology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12255853 OTO - NOTNLM OT - Semaglutide OT - adverse effect OT - case report OT - depression OT - pharmacovigilance OT - suicide behavior EDAT- 2025/07/13 06:27 MHDA- 2025/07/13 06:28 PMCR- 2025/07/12 CRDT- 2025/07/13 01:12 PHST- 2025/07/13 06:28 [medline] PHST- 2025/07/13 06:27 [pubmed] PHST- 2025/07/13 01:12 [entrez] PHST- 2025/07/12 00:00 [pmc-release] AID - 10.1177_03000605251349393 [pii] AID - 10.1177/03000605251349393 [doi] PST - ppublish SO - J Int Med Res. 2025 Jul;53(7):3000605251349393. doi: 10.1177/03000605251349393. Epub 2025 Jul 12. PMID- 40649729 OWN - NLM STAT- MEDLINE DCOM- 20250712 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 13 DP - 2025 Jun 20 TI - Semaglutide Improves Lipid Subfraction Profiles in Type 2 Diabetes: Insights from a One-Year Follow-Up Study. LID - 10.3390/ijms26135951 [doi] LID - 5951 AB - Recent studies have demonstrated the efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in enhancing glycemic control, regulating body weight, and modulating lipid metabolism. However, their effects on lipoprotein subfractions have not been clarified. The objective of this 52-week, single-center, randomized trial was to compare the effects of subcutaneous semaglutide administered once weekly and oral sitagliptin administered once daily on anthropometric measurements and lipoprotein subfractions measured by Lipoprint gelelectrophoresis in patients with type 2 diabetes mellitus (T2DM). A total of 34 obese individuals with T2DM were enrolled in the study and randomly assigned to receive semaglutide (n = 18) or sitagliptin (n = 16). Thirty-one age- and body weight-matched non-diabetic obese individuals served as controls. Semaglutide treatment resulted in significant reductions in body mass index (BMI), waist circumference, and Hb(A1c), along with improvements in lipid parameters, including reductions in LDL cholesterol and non-HDL cholesterol levels, and redistribution of LDL and HDL subfractions toward a less atherogenic profile. Conversely, sitagliptin elicited modest glycemic improvements without substantial alterations in lipid composition. Multivariate regression analysis demonstrated that fluctuations in lipoprotein subfractions were not influenced by changes in BMI or HbA1c. These results support the pleiotropic metabolic benefits of semaglutide and its potential role in managing the cardiometabolic risk of T2DM. FAU - Toth, Laszlo Imre AU - Toth LI AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Harsanyi, Adrienn AU - Harsanyi A AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Csiha, Sara AU - Csiha S AD - Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. AD - Department of Clinical Basics, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Molnar, Agnes AU - Molnar A AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Lorincz, Hajnalka AU - Lorincz H AUID- ORCID: 0009-0000-5303-3082 AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Nagy, Attila Csaba AU - Nagy AC AUID- ORCID: 0000-0002-0554-7350 AD - Department of Health Informatics, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Paragh, Gyorgy AU - Paragh G AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Harangi, Mariann AU - Harangi M AUID- ORCID: 0000-0001-9761-9595 AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. AD - Institute of Health Studies, Faculty of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary. AD - ELKH-UD Vascular Pathophysiology Research Group 11003, University of Debrecen, H-4032 Debrecen, Hungary. FAU - Sztanek, Ferenc AU - Sztanek F AD - Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary. LA - eng GR - K142273/National Research, Development and Innovation Office - NKFIH/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20250620 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Lipids) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/pharmacology MH - Male MH - Female MH - Middle Aged MH - Sitagliptin Phosphate/therapeutic use/administration & dosage MH - Follow-Up Studies MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glycated Hemoglobin/metabolism MH - Body Mass Index MH - *Lipids/blood MH - Lipid Metabolism/drug effects MH - Aged MH - Adult MH - Blood Glucose MH - Obesity/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12250273 OTO - NOTNLM OT - GLP-1 receptor agonist OT - cardiometabolic risk OT - lipoprotein subfractions OT - semaglutide OT - sitagliptin OT - type 2 diabetes mellitus COIS- The authors declare no conflicts of interest. EDAT- 2025/07/13 03:37 MHDA- 2025/07/13 03:38 PMCR- 2025/06/20 CRDT- 2025/07/12 01:20 PHST- 2025/05/19 00:00 [received] PHST- 2025/06/16 00:00 [revised] PHST- 2025/06/19 00:00 [accepted] PHST- 2025/07/13 03:38 [medline] PHST- 2025/07/13 03:37 [pubmed] PHST- 2025/07/12 01:20 [entrez] PHST- 2025/06/20 00:00 [pmc-release] AID - ijms26135951 [pii] AID - ijms-26-05951 [pii] AID - 10.3390/ijms26135951 [doi] PST - epublish SO - Int J Mol Sci. 2025 Jun 20;26(13):5951. doi: 10.3390/ijms26135951. PMID- 40641020 OWN - NLM STAT- MEDLINE DCOM- 20260624 LR - 20260624 IS - 1873-4286 (Electronic) IS - 1381-6128 (Linking) VI - 32 IP - 20 DP - 2026 TI - Incretin-based Agents and Metabolic Dysfunction-associated Steatotic Liver Disease. PG - 1567-1591 LID - 10.2174/0113816128378484250619080753 [doi] AB - Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide, primarily driven by the rising prevalence of both obesity and type 2 diabetes mellitus (T2DM). Historically, treatment options for patients with more advanced stages of hepatic dysfunction (steatohepatitis, fibrosis, cirrhosis) have been limited, with only resmetirom, a thyroid hormone receptor-beta agonist, recently being approved for use as a metabolic dysfunction-associated steatohepatitis (MASH)-specific treatment option. Incretin-based receptor agonists are emerging as promising treatments for MASLD, and multiple liver-biopsy powered trials are underway. This group of drugs has gained attention as possible treatment options for MASLD/MASH, due to their significant weight-loss and body fat reduction effects, and there is also a growing body of evidence that incretin-based agents lead to a significant reduction in liver fat content. However, the evidence concerning improvement of steatohepatitis and/or fibrosis is limited. Most authorities consider incretin mimetics to be only one contributing factor to the treatment paradigm of the MASLD/MASH/ fibrosis/cirrhosis continuum. Specifically, according to the data to date, incretin-based treatments may improve metabolic abnormalities in MASLD/MASH patients, especially in patients with obesity and/or T2DM, and may mitigate its progression at the early stages. However, no incretin-based treatment is officially approved in this indication yet. This review discusses the rationale for the use of incretin-based treatment options in patients with MASLD/MASH, explaining the pathophysiological background of this disorder and describing the possible mechanism of action of these drugs. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Muzurovic, Emir AU - Muzurovic E AUID- ORCID: 0000-0003-2022-3298 AD - Department of Internal Medicine, Endocrinology Section, Clinical Centre of Montenegro, Podgorica, Montenegro. AD - Faculty of Medicine, University of Montenegro, Podgorica, Montenegro. FAU - Haluzik, Martin AU - Haluzik M AD - Diabetes Centre, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Praha 4, Czech Republic. AD - First Faculty of Medicine, Charles University, Katerinska 1660/32, 121 08 Nove Mesto, Prague, Czech Republic. FAU - Horvath, Ludek AU - Horvath L AD - Diabetes Centre, Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Praha 4, Czech Republic. AD - First Faculty of Medicine, Charles University, Katerinska 1660/32, 121 08 Nove Mesto, Prague, Czech Republic. FAU - Vlacho, Bogdan AU - Vlacho B AD - DAP-Cat group, Unitat de Suport a la Recerca Barcelona, Fundacio Institut Universitari per a la recerca a l'Atencio Primaria de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. AD - Centro de Investigacion Biomedica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. FAU - Mauricio, Didac AU - Mauricio D AD - DAP-Cat group, Unitat de Suport a la Recerca Barcelona, Fundacio Institut Universitari per a la recerca a l'Atencio Primaria de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain. AD - Centro de Investigacion Biomedica en Red (CIBER) of Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. AD - Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. AD - Department of Medicine, University of Vic - Central University of Catalonia, Vic, Spain. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Pharm Des JT - Current pharmaceutical design JID - 9602487 RN - 0 (Incretins) SB - IM MH - Humans MH - *Incretins/therapeutic use/pharmacology MH - *Fatty Liver/drug therapy/metabolism MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism MH - Obesity/drug therapy/metabolism OTO - NOTNLM OT - Metabolic-dysfunction associated steatotic liver disease OT - incretin-based agents OT - metabolic dysfunction/associated steatohepatitis OT - pathophysiology. OT - semaglutide OT - survodutide OT - tirzepatide EDAT- 2025/07/11 06:27 MHDA- 2026/06/25 00:33 CRDT- 2025/07/11 00:23 PHST- 2025/01/03 00:00 [received] PHST- 2025/03/21 00:00 [revised] PHST- 2025/04/17 00:00 [accepted] PHST- 2026/06/25 00:33 [medline] PHST- 2025/07/11 06:27 [pubmed] PHST- 2025/07/11 00:23 [entrez] AID - CPD-EPUB-149297 [pii] AID - 10.2174/0113816128378484250619080753 [doi] PST - ppublish SO - Curr Pharm Des. 2026;32(20):1567-1591. doi: 10.2174/0113816128378484250619080753. PMID- 40637847 OWN - NLM STAT- MEDLINE DCOM- 20250913 LR - 20250913 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 68 IP - 9 DP - 2025 Sep TI - Early worsening of diabetic retinopathy in individuals with type 2 diabetes treated with tirzepatide: a real-world cohort study. PG - 2069-2076 LID - 10.1007/s00125-025-06466-8 [doi] AB - AIMS/HYPOTHESIS: Early worsening of diabetic retinopathy (EWDR) has been described during treatment with glucagon-like peptide-1 receptor agonists including subcutaneous semaglutide. Whether EWDR occurs after initiating treatment with the potent glucagon-like peptide 1 / gastric inhibitory polypeptide receptor agonist tirzepatide is unknown. METHODS: In this retrospective cohort study using real-world clinical data, we matched 3435 tirzepatide-exposed (>/=180 days treatment) individuals with type 2 diabetes 1:1 with 3434 tirzepatide-unexposed individuals for sex, diabetes duration, retinopathy status, HbA(1c), number of retinal screening episodes and use of glucose-lowering medications. New-onset diabetic retinopathy and retinopathy progression were explored using conditional logistic regression. RESULTS: Individuals included in the study had tight baseline glycaemic control (mean HbA(1c) 56.1 +/- 15.8 mmol/mol [7.28 +/- 1.43%]). New-onset proliferative diabetic retinopathy (PDR) (grade R3M0, R3M1) occurred in 1.1% of tirzepatide-exposed (n=33) and 0.5% of tirzepatide-unexposed (n=17) individuals. Tirzepatide was significantly associated with new-onset PDR in multivariate analysis after adjustment for established risk factors (OR 2.15 [95% CI 1.24, 3.74], p<0.01). However, tirzepatide was also associated with reduced odds of new onset of retinopathy (OR 0.73 [95% CI 0.62, 0.86], p<0.001) in individuals without diabetic retinopathy (R0M0) at initiation in multivariate analysis, and was not significantly associated with retinopathy progression in individuals with mild non-proliferative diabetic retinopathy (NPDR, grade R1M0 or R1M1). CONCLUSIONS/INTERPRETATION: Tirzepatide therapy resulted in significantly increased odds of incident PDR, particularly in individuals with mild NPDR with maculopathy (grade R1M1), or moderate-to-severe NPDR with or without maculopathy (grade R2M0, R2M1). The increase in odds of progression would justify specialist ophthalmologist referral by Early Treatment Diabetic Retinopathy Study (ETDRS) criteria. CI - (c) 2025. The Author(s). FAU - Buckley, Adam J AU - Buckley AJ AUID- ORCID: 0000-0001-7471-0273 AD - Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates. abuckley@icldc.ae. FAU - Tan, Garry D AU - Tan GD AD - OCDEM, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. Garry.tan@ocdem.ox.ac.uk. AD - Oxford NIHR Biomedical Research Centre, Oxford, UK. Garry.tan@ocdem.ox.ac.uk. FAU - Gruszka-Goh, Marta AU - Gruszka-Goh M AD - Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK. FAU - Scanlon, Peter H AU - Scanlon PH AD - Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK. FAU - Ansari, Imran AU - Ansari I AD - Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates. FAU - Suliman, Sara G I AU - Suliman SGI AD - Imperial College London Diabetes Centre, Abu Dhabi, United Arab Emirates. LA - eng PT - Journal Article DEP - 20250710 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetic Retinopathy/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Disease Progression MH - Glycated Hemoglobin/metabolism MH - Cohort Studies MH - Tirzepatide PMC - PMC12361273 OTO - NOTNLM OT - GIP OT - GLP-1RA OT - Retinopathy OT - Tirzepatide OT - Type 2 diabetes COIS- Acknowledgements: The authors wish to acknowledge the contributions of A. Lari, A. Thampi, C. Suangco, J. Espinosa, J. Vasquez, M. Marquez, M. Jadoun, S. Cyriac and S. Alberto, retinal graders at ICLDC. GDT is supported by the National Institute for Health Research (NIHR). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Data availability: Data that underlie the results reported in this article after de-identification (text, tables and figures) will be available. Data will be available for up to 5 years following publication for sharing with researchers who submit a study question which, in the opinion of the authors, can reasonably be addressed by the data. Enquiries should be directed to abuckley@icldc.ae. An institutional contract and data sharing agreement will be required. Funding: No external funding was received. Authors' relationships and activities: The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: AJB performed data collection and statistical analysis and wrote the first draft of the manuscript. GDT, MG-G, PHS, IA and SGIS contributed to study methodology and revised and edited the final draft of the manuscript. The manuscript was approved for submission by all authors. AJB had access to the data used in this project and is the guarantor. EDAT- 2025/07/10 12:30 MHDA- 2025/09/13 18:29 PMCR- 2025/07/10 CRDT- 2025/07/10 11:13 PHST- 2024/12/06 00:00 [received] PHST- 2025/04/14 00:00 [accepted] PHST- 2025/09/13 18:29 [medline] PHST- 2025/07/10 12:30 [pubmed] PHST- 2025/07/10 11:13 [entrez] PHST- 2025/07/10 00:00 [pmc-release] AID - 10.1007/s00125-025-06466-8 [pii] AID - 6466 [pii] AID - 10.1007/s00125-025-06466-8 [doi] PST - ppublish SO - Diabetologia. 2025 Sep;68(9):2069-2076. doi: 10.1007/s00125-025-06466-8. Epub 2025 Jul 10. PMID- 40631351 OWN - NLM STAT- MEDLINE DCOM- 20250709 LR - 20260127 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 19 DP - 2025 TI - Semaglutide Therapy and Accelerated Sarcopenia in Older Adults with Type 2 Diabetes: A 24-Month Retrospective Cohort Study. PG - 5645-5652 LID - 10.2147/DDDT.S531778 [doi] AB - PURPOSE: This study aimed to investigate changes in muscle mass and strength among older adults with type 2 diabetes who were treated with Semaglutide. METHODS: This was a retrospective cohort study comparing elderly patients with type 2 diabetes receiving Semaglutide to a matched control group. Changes in muscle mass and function over 24 months were assessed. Muscle mass was measured using the appendicular skeletal muscle mass index (ASMI), while muscle function was evaluated through grip strength and gait speed measurements. Differences between the two groups and changes before and after treatment were analyzed using the t-test. Additionally, multivariable linear regression models were constructed to identify clinical predictors of accelerated muscle loss during Semaglutide treatment. RESULTS: The study involved 220 patients treated with Semaglutide and 212 control subjects. The prevalence of sarcopenia among participants was 27.7%. Semaglutide treatment significantly reduced both body mass index and muscle mass compared to controls. Notably, divergent patterns emerged in functional measures. Grip strength initially improved but then declined in men, while it continued to decrease in women. Gait speed significantly reduced in both genders. Multivariable analysis identified Semaglutide dosage, baseline ASMI, and gait speed as independent predictors of muscle loss. CONCLUSION: The use of Semaglutide is associated with muscle loss and functional decline in older adults with type 2 diabetes, particularly at higher doses. This effect is especially significant in patients with sarcopenia. Consequently, it is crucial to assess the risks and benefits for each elderly patient individually and to implement appropriate monitoring and interventions. The potential for nutritional supplementation and targeted exercise regimens to counteract semaglutide-associated muscle decline merits systematic investigation. CI - (c) 2025 Ren et al. FAU - Ren, Qingjuan AU - Ren Q AD - Department of Geriatrics, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, People's Republic of China. FAU - Zhi, Lei AU - Zhi L AD - Department of Geriatrics, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, People's Republic of China. FAU - Liu, Hongfang AU - Liu H AD - Department of Geriatrics, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, People's Republic of China. LA - eng PT - Journal Article DEP - 20250703 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sarcopenia/chemically induced MH - Retrospective Studies MH - Male MH - Female MH - Aged MH - *Glucagon-Like Peptides/adverse effects/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/adverse effects/administration & dosage/therapeutic use MH - Cohort Studies MH - Hand Strength MH - Aged, 80 and over MH - Muscle, Skeletal/drug effects MH - Middle Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12235021 OTO - NOTNLM OT - mass strength OT - muscle mass OT - older adults OT - sarcopenia OT - semaglutide OT - type 2 diabetes COIS- The authors declare that they have no competing interests in this work. EDAT- 2025/07/09 06:27 MHDA- 2025/07/09 06:28 PMCR- 2025/07/03 CRDT- 2025/07/09 05:11 PHST- 2025/04/01 00:00 [received] PHST- 2025/06/25 00:00 [accepted] PHST- 2025/07/09 06:28 [medline] PHST- 2025/07/09 06:27 [pubmed] PHST- 2025/07/09 05:11 [entrez] PHST- 2025/07/03 00:00 [pmc-release] AID - 531778 [pii] AID - 10.2147/DDDT.S531778 [doi] PST - epublish SO - Drug Des Devel Ther. 2025 Jul 3;19:5645-5652. doi: 10.2147/DDDT.S531778. eCollection 2025. PMID- 40629903 OWN - NLM STAT- MEDLINE DCOM- 20250806 LR - 20260825 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 9 DP - 2025 Sep TI - Glucagon-like peptide-1 receptor agonist treatment associated weight fluctuation and influencing factors in patients with overweight or obesity. PG - 5042-5051 LID - 10.1111/dom.16552 [doi] AB - OBJECTIVE: To characterize the weight fluctuation and explore its influencing factors after glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment in patients with overweight or obesity. METHODS: This retrospective cohort study enrolled 679 patients with overweight or obesity who initiated GLP-1RA treatment between November 2022 and October 2024. The weight measurements were collected during in-person clinic visits by uniform weighing scales and documented in the electronic medical record (EMR). The weight fluctuation curves were stratified into three phenotypes (Successful Weight Reduction, Remaining Stable and Weight Regain) and went through intergroup analyses. Subsequently, the association between potential influencing factors and weight fluctuations were estimated by univariate and multivariate logistic regression, where the weight fluctuation phenotypes were dichotomized into a binary variable, classified as "successful weight reduction" or "unsuccessful weight reduction". Subgroup analyses were performed in participants with obesity, prediabetes, liraglutide users and semaglutide users. RESULTS: Patients with a longer duration of GLP-1RA treatment (OR = 1.014, 95% CI, 1.008-1.019) and higher HOMA-beta (Homeostasis Model Assessment of beta-Cell Function) levels (OR = 4.912, 95% CI, 1.480 to 16.034) were more likely to achieve successful weight reduction at follow-up of 12 months. Non-diabetic status (OR = 2.176, 95% CI, 1.242-3.812) and using semaglutide (OR = 2.138, 95% CI, 1.162-3.935) were associated with successful weight reduction at the follow-up of 6 months. Additionally, a higher percentage body fat (PBF) in both male (OR = 3.990, 95% CI, 1.118-14.246) and female (OR = 2.266, 95% CI, 1.179-4.354) was associated with successful weight reduction. The weight regain group had a higher baseline eGFR than other two groups at the 3-month follow-up especially in participants with prediabetes (p = 0.009). Moreover, the J-shaped associations of basal metabolic rate, skeletal muscle mass, abdominal and limb muscle mass with the probability of successful weight reduction within 6 months, and a positive non-linear association of serum creatinine with the probability of successful weight reduction within 12 months have been characterized. CONCLUSION: A longer duration of GLP-1RA treatment, using semaglutide, non-diabetic status and higher PBF might be associated with better weight reduction. Basal metabolic rate, skeletal muscle mass, muscle mass of abdomen and limbs, and serum creatinine were non-linearly associated with the probability of successful weight reduction. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Wang, Jingxuan AU - Wang J AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Lin, Chu AU - Lin C AUID- ORCID: 0000-0002-2365-9831 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Cai, Xiaoling AU - Cai X AUID- ORCID: 0000-0002-7881-0543 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Wang, Yiran AU - Wang Y AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Wei, Tingyang AU - Wei T AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Wang, Yuan AU - Wang Y AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Tie, Changjie AU - Tie C AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Yang, Yuteng AU - Yang Y AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Lv, Fang AU - Lv F AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Yang, Wenjia AU - Yang W AUID- ORCID: 0000-0003-0610-5121 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. LA - eng GR - 2023ZD0508200/Noncommunicable Chronic Diseases-National Science and Technology Major Project/ GR - 2023ZD0508205/Noncommunicable Chronic Diseases-National Science and Technology Major Project/ PT - Journal Article DEP - 20250709 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Middle Aged MH - *Obesity/drug therapy MH - *Overweight/drug therapy MH - Adult MH - *Weight Loss/drug effects MH - Liraglutide/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - Weight Gain/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide 1 receptor agonist OT - obesity OT - type 2 diabetes OT - weight fluctuation EDAT- 2025/07/09 06:26 MHDA- 2025/08/06 12:29 CRDT- 2025/07/09 04:03 PHST- 2025/06/06 00:00 [revised] PHST- 2025/02/28 00:00 [received] PHST- 2025/06/10 00:00 [accepted] PHST- 2025/08/06 12:29 [medline] PHST- 2025/07/09 06:26 [pubmed] PHST- 2025/07/09 04:03 [entrez] AID - 10.1111/dom.16552 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Sep;27(9):5042-5051. doi: 10.1111/dom.16552. Epub 2025 Jul 9. PMID- 40628673 OWN - NLM STAT- MEDLINE DCOM- 20250708 LR - 20260127 IS - 2053-3624 (Print) IS - 2053-3624 (Electronic) IS - 2053-3624 (Linking) VI - 12 IP - 2 DP - 2025 Jul 8 TI - Effectiveness of semaglutide on survival outcomes in patients with type 2 diabetes and chronic kidney disease. LID - 10.1136/openhrt-2025-003382 [doi] LID - e003382 AB - BACKGROUND: Type 2 diabetes (T2D) and chronic kidney disease (CKD) significantly increase the risk of cardiovascular events, including death and heart failure (HF). The FLOW trial demonstrated that semaglutide reduces all-cause death, cardiovascular events and HF risk in patients with T2D and CKD. Since there is a difference in patient characteristics between clinical trials and real-world data, this study aims to investigate the association of semaglutide and all-cause death, acute HF or cardiovascular outcomes in patients with T2D and CKD using the data platform. METHODS: This multicentre retrospective observational study using TriNetX, a global healthcare data platform. We identified 1 151 750 patients aged >/=18 years with T2D and CKD diagnosed before 31 December 2020. Among these, 14 511 patients initiated semaglutide and 69 700 initiated sitagliptin between 1 January 2018 and 31 December 2020. After propensity score matching, 13 703 patients were included in each group. The primary outcome was the 3-year incidence of all-cause death. Secondary outcomes included acute HF, acute myocardial infarction and stroke. RESULTS: The 3-year risk of all-cause death in the semaglutide group relative to the sitagliptin group was significantly lower (7.2% (943/13 703) vs 9.5% (1196/13 703); p<0.001; HR, 0.76; 95% CI, 0.70 to 0.83). Similarly, the semaglutide group was less likely to have acute HF (12.1% vs 13.1%; HR, 0.92; 95% CI, 0.86 to 0.98). However, the risks of acute myocardial infarction and stroke in the semaglutide group relative to the sitagliptin group were not significant (9.6% vs 9.5%; HR, 1.01; 95% CI, 0.93 to 1.09 in acute myocardial infarction, and 9.2% vs 9.0%; HR, 1.02; 95% CI, 0.94 to 1.10 in stroke). CONCLUSIONS: In patients with T2D and CKD, semaglutide was associated with a lower 3-year risk of all-cause death compared with sitagliptin. CI - (c) Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Kishimori, Takefumi AU - Kishimori T AUID- ORCID: 0009-0000-9639-5470 AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Kato, Takao AU - Kato T AUID- ORCID: 0000-0001-8213-7999 AD - Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Faculty of Medicine, Kyoto, Japan tkato75@kuhp.kyoto-u.ac.jp. AD - Department of clinical trial facilitation, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Wada, Atsuyuki AU - Wada A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Tani, Akira AU - Tani A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yamaji, Ryosuke AU - Yamaji R AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Koike, Jumpei AU - Koike J AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Iwasaki, Yoshihiro AU - Iwasaki Y AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Matsumoto, Takehiro AU - Matsumoto T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yagi, Takafumi AU - Yagi T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Okada, Masaharu AU - Okada M AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250708 PL - England TA - Open Heart JT - Open heart JID - 101631219 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications/diagnosis MH - Female MH - Male MH - *Glucagon-Like Peptides/therapeutic use MH - Retrospective Studies MH - *Renal Insufficiency, Chronic/mortality/drug therapy/complications/diagnosis MH - Middle Aged MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Cause of Death/trends MH - Survival Rate/trends MH - Risk Factors MH - Follow-Up Studies MH - Risk Assessment MH - Incidence MH - Time Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12243591 OTO - NOTNLM OT - Diabetes Mellitus OT - Pharmacology, Clinical OT - RISK FACTORS COIS- Competing interests: None declared. EDAT- 2025/07/09 00:27 MHDA- 2025/07/09 00:28 PMCR- 2025/07/08 CRDT- 2025/07/08 22:53 PHST- 2025/04/11 00:00 [received] PHST- 2025/06/19 00:00 [accepted] PHST- 2025/07/09 00:28 [medline] PHST- 2025/07/09 00:27 [pubmed] PHST- 2025/07/08 22:53 [entrez] PHST- 2025/07/08 00:00 [pmc-release] AID - openhrt-2025-003382 [pii] AID - 10.1136/openhrt-2025-003382 [doi] PST - epublish SO - Open Heart. 2025 Jul 8;12(2):e003382. doi: 10.1136/openhrt-2025-003382. PMID- 40628316 OWN - NLM STAT- MEDLINE DCOM- 20250820 LR - 20260127 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 378 DP - 2025 Oct 1 TI - Characterization of 0839 - A tool compound for pre-clinical mode-of-action studies of amylin analogues such as cagrilintide. PG - 123845 LID - S0024-3205(25)00480-1 [pii] LID - 10.1016/j.lfs.2025.123845 [doi] AB - Cagrilintide (also known as 0833) is an amylin and calcitonin receptor agonist in clinical development for weight management and type-2-diabetes in a fixed-dose combination with semaglutide. Here, we introduce 0174-0839 (0839) as a tool compound for mouse and rat in vivo and in vitro studies of amylin analogues such as cagrilintide. Structurally, 0839 shares 95 % sequence homology with 0833 and contains an identical acylation sidechain. Acute administration of 0839 and 0833 to normal weight rats' dose-dependently reduced food intake to a similar degree. Sub-chronically, 0839 and 0833 had comparable small and transient reducing effects on food intake and body weight in DIO mice, with similar additional add-on effects on top of semaglutide. In DIO rats, sub-chronic administration of 0833 and 0839 profoundly reduced food intake and body weight, and both potentiated semaglutide's effects on food intake and body weight to an equal extended. Both compounds mainly reduced body weight by fat mass reduction and equally improved metabolic parameters. Notably, 0839 is available through Novo Nordisk Compound Sharing, enabling advancement of mode-of-action studies in mice and rats whilst usage of cagrilintide and other amylin analogues in clinical development are restricted due to pharmacovigilance rules. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Gabery, Sanaz AU - Gabery S AD - Medical & Science, Clinical Drug Development, Novo Nordisk A/S, Denmark. FAU - Glendorf, Tine AU - Glendorf T AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. FAU - Ballarin-Gonzalez, Borja AU - Ballarin-Gonzalez B AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. FAU - Pedersen, Kent AU - Pedersen K AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. FAU - Kruse, Thomas AU - Kruse T AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. FAU - Raun, Kirsten AU - Raun K AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. FAU - Kuhre, Rune Ehrenreich AU - Kuhre RE AD - Global Drug Discovery, Novo Nordisk A/S, Malov, Denmark. Electronic address: RUKU@novonordisk.com. LA - eng PT - Journal Article DEP - 20250706 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Islet Amyloid Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - Rats MH - *Islet Amyloid Polypeptide/pharmacology/chemistry MH - Mice MH - Male MH - Eating/drug effects MH - Body Weight/drug effects MH - Mice, Inbred C57BL MH - Rats, Sprague-Dawley MH - Humans MH - Hypoglycemic Agents/pharmacology MH - Dose-Response Relationship, Drug MH - Glucagon-Like Peptides/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Amylin OT - Cagrilintide OT - Diet-induced obese mice and rats OT - Obesity-treatment OT - Tool compound COIS- Declaration of competing interest Rune Ehrenreich Kuhre reports a relationship with Novo Nordisk that includes: employment. All authors of this manuscript are employed by Novo Nordisk If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/07/09 00:27 MHDA- 2025/08/31 20:04 CRDT- 2025/07/08 19:22 PHST- 2025/03/12 00:00 [received] PHST- 2025/06/26 00:00 [revised] PHST- 2025/07/04 00:00 [accepted] PHST- 2025/08/31 20:04 [medline] PHST- 2025/07/09 00:27 [pubmed] PHST- 2025/07/08 19:22 [entrez] AID - S0024-3205(25)00480-1 [pii] AID - 10.1016/j.lfs.2025.123845 [doi] PST - ppublish SO - Life Sci. 2025 Oct 1;378:123845. doi: 10.1016/j.lfs.2025.123845. Epub 2025 Jul 6. PMID- 40620210 OWN - NLM STAT- MEDLINE DCOM- 20250904 LR - 20260826 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 10 DP - 2025 Oct TI - Association of semaglutide with less limb events in people with type 2 diabetes and peripheral artery disease or foot ulcers: An observational study comparing matched cohorts. PG - 5506-5513 LID - 10.1111/dom.16594 [doi] AB - AIMS: To compare major limb events in individuals with type 2 diabetes who initiated either injective or oral semaglutide versus other glucose-lowering therapies (GLT) in a real-world setting. MATERIALS AND METHODS: This was a single-centre retrospective observational study on new users of diabetes medications. Participants had to have type 2 diabetes and a diagnosis of peripheral artery disease (PAD) or foot ulcers. Participant characteristics were assessed before and after propensity score matching. The primary outcome was major limb events (a composite of peripheral percutaneous transluminal angioplasty [PTA] or critical limb ischaemia [CLI]); secondary outcomes included singularly PTA, CLI, gangrene and lower extremity amputation (LEA). RESULTS: We analysed two matched groups of 167 participants each, who were predominantly males (57%), aged 61 years, with a 12-year duration of diabetes, a baseline HbA1c of 8.0% and body mass index (BMI) of 31 kg/m(2). During a median follow-up of 30.1 months, a primary-outcome event occurred in 72 of the participants (43.0%; incidence, 8.1 events per 100 person-years) in the semaglutide group, as compared with 93 of the participants (56.0%; incidence, 10.4 events per 100 person-years) in the GLT group (hazard ratio [HR] = 0.77; 95% confidence interval [CI], 0.61-0.97; p = 0.029). Among the secondary outcomes, LEA (both major and minor) was 50% lower (HR = 0.50; 95% CI, 0.30-0.83, p = 0.008) in the semaglutide group as compared with the other group. CONCLUSIONS: Among people with type 2 diabetes and PAD or foot ulcers, the use of semaglutide was associated with a significantly lower risk of major limb events than other GLTs. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Caruso, Paola AU - Caruso P AUID- ORCID: 0000-0002-4756-2022 AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Angelino, Silvia AU - Angelino S AD - University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Matrone, Rita AU - Matrone R AD - University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Scappaticcio, Lorenzo AU - Scappaticcio L AUID- ORCID: 0000-0003-2972-9551 AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Longo, Miriam AU - Longo M AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Life Science, Health, and Health Professions, Link Campus University, Rome, Italy. FAU - Volatile, Alessandra AU - Volatile A AD - University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Petrizzo, Michela AU - Petrizzo M AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Pontillo, Alessandro AU - Pontillo A AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Caputo, Mariangela AU - Caputo M AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Carbone, Carla AU - Carbone C AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Gicchino, Maurizio AU - Gicchino M AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. FAU - Bellastella, Giuseppe AU - Bellastella G AUID- ORCID: 0000-0002-4748-321X AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AUID- ORCID: 0000-0002-3652-5154 AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. AD - University of Campania Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. FAU - Maiorino, Maria Ida AU - Maiorino MI AUID- ORCID: 0000-0003-4659-7546 AD - Division of Endocrinology and Metabolic Diseases, University Hospital Luigi Vanvitelli, Naples, Italy. AD - Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20250707 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Retrospective Studies MH - *Peripheral Arterial Disease/complications/epidemiology MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Diabetic Foot/prevention & control/epidemiology/complications MH - Aged MH - Amputation, Surgical/statistics & numerical data MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - critical limb ischaemia OT - gangrene OT - lower limb amputations OT - peripheral artery disease OT - peripheral percutaneous transluminal angioplasty OT - real-world OT - semaglutide OT - type 2 diabetes EDAT- 2025/07/07 06:26 MHDA- 2025/09/04 06:37 CRDT- 2025/07/07 04:54 PHST- 2025/06/19 00:00 [revised] PHST- 2025/05/10 00:00 [received] PHST- 2025/06/25 00:00 [accepted] PHST- 2025/09/04 06:37 [medline] PHST- 2025/07/07 06:26 [pubmed] PHST- 2025/07/07 04:54 [entrez] AID - 10.1111/dom.16594 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Oct;27(10):5506-5513. doi: 10.1111/dom.16594. Epub 2025 Jul 7. PMID- 40619508 OWN - NLM STAT- MEDLINE DCOM- 20250706 LR - 20260127 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 15 IP - 1 DP - 2025 Jul 6 TI - Efficacy and safety of GLP-1 agonists in the treatment of T2DM: A systematic review and network meta-analysis. PG - 24103 LID - 10.1038/s41598-025-09807-0 [doi] LID - 24103 AB - To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in subjects with type 2 diabetes (T2DM). Electronic databases were searched from inception to 2nd October 2024 for randomised controlled trials comparing GLP-1RAs treating T2DM. Bayesian network meta-analyses were conducted to analyze metabolic and safety outcomes. 64 trials comprising of 25,572 participants were identified. Compared to placebo, tirzepatide showed the greatest reduction in HbA1-c (MD: -2.3%) and FPG (MD: -3.1mmol/L); semaglutide was second (HbA1-c: MD: -1.5%; FPG: MD: -2mmol/L); liraglutide was third (HbA1-c: MD: -1.2% FPG: MD: -1.6mmol/L) (P<0.05). All treatments showed no statistically significant differences in BMI, SBP, DBP, TC, HDL-C and LDL-C compared to placebo. Tirzepatide (MD: -9.1 kg), semaglutide (MD: -2.8 kg) and liraglutide (MD: -1.2 kg) (P<0.05) had significant reduction in body weight compared to placebo. GLP-1 RAs had higher risk of gastrointestinal symptoms. Semaglutide increased the risk of hypoglycemia compared to placebo while liraglutide reduced the risk of hypoglycemia compared to traditional antidiabetic drugs. GLP-1RAs improve glycaemic control, with tirzepatide, semaglutide and liraglutide exhibiting the most significant improvements. Tirzepatide is more suitable for treating T2DM with obesity. For individuals with normal weight, both semaglutide and liraglutide are generally more effective for treating T2DM. However, considering the potential for semaglutide to cause hypoglycemia, liraglutide may be the optimal choice for T2DM treatment to minimize the risk of hypoglycemia. CI - (c) 2025. The Author(s). FAU - Ren, Xiaoyu AU - Ren X AD - Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, 730000, Gansu, P.R. China. FAU - Hua, Honghao AU - Hua H AD - Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China. FAU - Wu, Yuanqin AU - Wu Y AD - Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China. FAU - Zhang, Wei AU - Zhang W AD - Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, 730000, Gansu, P.R. China. FAU - Long, Xianzhen AU - Long X AD - Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China. FAU - Bai, Yana AU - Bai Y AD - Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, P.R. China. FAU - Cheng, Ning AU - Cheng N AD - Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic Medical College, Lanzhou University, Lanzhou, 730000, Gansu, P.R. China. 1184231755@qq.com. LA - eng GR - (NO. 81673248/National Natural Science Foundation of China/ GR - (NO. 81673248/National Natural Science Foundation of China/ PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250706 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use/adverse effects MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Liraglutide/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Tirzepatide/therapeutic use/adverse effects MH - Treatment Outcome MH - Semaglutide PMC - PMC12230154 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - Network meta-analysis OT - Type 2 diabetes mellitus COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/07/07 00:26 MHDA- 2025/07/07 00:27 PMCR- 2025/07/06 CRDT- 2025/07/06 23:28 PHST- 2025/01/18 00:00 [received] PHST- 2025/06/30 00:00 [accepted] PHST- 2025/07/07 00:27 [medline] PHST- 2025/07/07 00:26 [pubmed] PHST- 2025/07/06 23:28 [entrez] PHST- 2025/07/06 00:00 [pmc-release] AID - 10.1038/s41598-025-09807-0 [pii] AID - 9807 [pii] AID - 10.1038/s41598-025-09807-0 [doi] PST - epublish SO - Sci Rep. 2025 Jul 6;15(1):24103. doi: 10.1038/s41598-025-09807-0. PMID- 40617160 OWN - NLM STAT- MEDLINE DCOM- 20250727 LR - 20260127 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 51 DP - 2025 Aug TI - Psychiatric and psychological adverse effects associated with dulaglutide, semaglutide, and liraglutide: A vigibase study. PG - 252-265 LID - S0261-5614(25)00165-7 [pii] LID - 10.1016/j.clnu.2025.06.011 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are crucial in managing type 2 diabetes mellitus (T2DM) and obesity. Agents like dulaglutide, semaglutide, and liraglutide mimic endogenous GLP-1, enhancing insulin secretion and promoting satiety. Beyond glycemic control, they offer cardioprotective and neuroprotective benefits. However, concerns about psychiatric adverse effects have emerged, necessitating a systematic assessment of their safety profile. MATERIAL & METHODS: This multinational pharmacovigilance study utilized VigiBase(R) data up to December 1, 2024, focusing on adverse drug reaction (ADR) reports for GLP-1 RAs. Psychiatric ADRs were classified using MedDRA terminology. Disproportionality analyses were conducted via logistic regression to calculate reporting adjusted Reporting Odds Ratios (aRORs) within reports involving antidiabetic or anti-obesity medications. A causal forest model assessed the individual treatment effect (ITE) of semaglutide on depression and suicidality reporting. RESULTS: Among 2,061,901 reports, 21,414 involved psychiatric ADRs for GLP-1 RAs. Significant signals were observed for anxiety (aROR: 1.26, 95%CI: 1.18-1.35), depressed mood disorders (aROR: 1.70, 95%CI: 1.57-1.84) and suicidality (aROR 1.45, 95%CI: 1.29-1.63) with semaglutide, and eating disorders with all three GLP-1 RAs (aRORs between 4.17 and 6.80). The causal forest model estimated an average treatment effect of 0.0046 for semaglutide on depression and suicidality reporting, with significant heterogeneity across regions and demographic groups. DISCUSSION: The study found no significant increase in overall psychiatric ADR reporting for GLP-1 RAs, except for eating disorders and depression/suicidality in semaglutide-treated patients. Sensitivity analyses before June 4, 2021, found no signals, aligning with RCT data. Post-marketing reports linked semaglutide to depression and suicidal ideation, prompting regulatory investigations. The causal forest model revealed significant heterogeneity in the psychiatric safety profile of semaglutide, with regional factors influencing ADR reporting. CONCLUSION: While GLP-1 RAs do not show a significant increase in overall psychiatric ADR reporting, findings suggest that clinicians should remain vigilant for potential depressive symptoms and suicidality, particularly in individuals with obesity treated with semaglutide since its approval for weight management. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Nishida, Kazuki AU - Nishida K AD - Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; Department of Biostatistics, Kyoto University School of Public Health, Kyoto, Japan. FAU - Chretien, Basile AU - Chretien B AD - Department of Advanced Medicine, Nagoya University Hospital, Nagoya, Japan; Neuropresage Team, Normandie University, UNICAEN, INSERM, UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Institute Blood and Brain @ Caen-Normandie (BB@C), GIP Cyceron, 14000, Caen, France. Electronic address: chretien.basile.jean.bernard.u4@s.mail.nagoya-u.ac.jp. FAU - Dolladille, Charles AU - Dolladille C AD - Department of Pharmacology, Caen Normandie University Hospital, Caen, France. FAU - Ebina, Takumi AU - Ebina T AD - Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan. FAU - Aleksic, Branko AU - Aleksic B AD - Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan. FAU - Cabe, Nicolas AU - Cabe N AD - Neuropresage Team, Normandie University, UNICAEN, INSERM, UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Institute Blood and Brain @ Caen-Normandie (BB@C), GIP Cyceron, 14000, Caen, France; Department of Addictology, Caen Normandie University Hospital, Caen, France. FAU - Savey, Veronique AU - Savey V AD - Department of Nutrition, Caen Normandie University Hospital, Caen, France. FAU - Onoue, Takeshi AU - Onoue T AD - Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan. FAU - Yatsuya, Hiroshi AU - Yatsuya H AD - Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine, Nagoya, Japan. LA - eng PT - Journal Article DEP - 20250623 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - *Liraglutide/adverse effects MH - Female MH - Male MH - Middle Aged MH - *Recombinant Fusion Proteins/adverse effects MH - *Immunoglobulin Fc Fragments/adverse effects MH - *Hypoglycemic Agents/adverse effects MH - Adult MH - Pharmacovigilance MH - Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Mental Disorders/chemically induced MH - Adverse Drug Reaction Reporting Systems MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adverse effects OT - GLP-1 receptor agonists OT - Pharmacovigilance OT - Psychiatry OT - Psychology COIS- Conflict of interest All authors declare no conflicts of interest. EDAT- 2025/07/06 06:18 MHDA- 2025/07/28 08:45 CRDT- 2025/07/05 18:09 PHST- 2025/04/22 00:00 [received] PHST- 2025/06/05 00:00 [revised] PHST- 2025/06/15 00:00 [accepted] PHST- 2025/07/28 08:45 [medline] PHST- 2025/07/06 06:18 [pubmed] PHST- 2025/07/05 18:09 [entrez] AID - S0261-5614(25)00165-7 [pii] AID - 10.1016/j.clnu.2025.06.011 [doi] PST - ppublish SO - Clin Nutr. 2025 Aug;51:252-265. doi: 10.1016/j.clnu.2025.06.011. Epub 2025 Jun 23. PMID- 40614622 OWN - NLM STAT- MEDLINE DCOM- 20250908 LR - 20260710 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 10 DP - 2025 Oct TI - Association of tirzepatide with erectile dysfunction in people with type 2 diabetes. PG - 109116 LID - S1056-8727(25)00169-2 [pii] LID - 10.1016/j.jdiacomp.2025.109116 [doi] AB - AIMS: To evaluate the association between tirzepatide and the risk of developing erectile dysfunction (ED) in men with type 2 diabetes (T2D), compared with sitagliptin, injectable semaglutide, and dulaglutide. METHODS: This retrospective cohort study used the TriNetX global health research network from May 13, 2022 to May 17, 2025. Male patients aged 18-70 with T2D and no prior ED were included. Three 1:1 propensity score-matched comparisons were conducted: tirzepatide vs. sitagliptin, injectable semaglutide, or dulaglutide. The outcome was a diagnosis of ED or prescription of a PDE-5 inhibitor. RESULTS: Tirzepatide was associated with a significantly reduced risk of ED across all comparisons. Risk ratios (RR) for the composite outcome of ED diagnosis or PDE-5 inhibitor use were: tirzepatide vs. sitagliptin: RR, 0.70 (95 % CI: 0.64,0.76); tirzepatide vs. injectable semaglutide: RR, 0.67 (95 % CI: 0.62,0.72); tirzepatide vs. dulaglutide: RR, 0.55 (95 % CI: 0.51,0.59). All comparisons were statistically significant (p < 0.001). CONCLUSIONS: Tirzepatide was associated with a lower risk of ED in men with T2D compared to sitagliptin, injectable semaglutide, and dulaglutide. Randomized trials are needed to confirm these findings and explore potential mechanisms. CI - Copyright (c) 2025 Elsevier Inc. All rights reserved. FAU - Cowart, Kevin AU - Cowart K AD - Taneja College of Pharmacy, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA; Morsani College of Medicine, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA; College of Public Health, University of South Florida, 13201 Bruce B. Downs Blvd., Tampa, FL 33612, USA. Electronic address: kcowart2@usf.edu. FAU - Murphy, Christopher AU - Murphy C AD - Taneja College of Pharmacy, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA. FAU - Carris, Nicholas AU - Carris N AD - Taneja College of Pharmacy, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA; Morsani College of Medicine, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA. LA - eng PT - Journal Article DEP - 20250630 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - *Erectile Dysfunction/epidemiology/prevention & control/etiology MH - Retrospective Studies MH - Adult MH - Aged MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - Sitagliptin Phosphate/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Recombinant Fusion Proteins/therapeutic use/adverse effects MH - Young Adult MH - Adolescent MH - Immunoglobulin Fc Fragments/therapeutic use MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Dulaglutide OT - Erectile dysfunction OT - Mens health OT - PDE-5 inhibitor OT - Semaglutide OT - Sitagliptin OT - Tirzepatide OT - Type 2 diabetes COIS- Declaration of competing interest KC has received research funding from Sanofi Winthrop Industrie and Abbott Diabetes Care. NC has received research funding from Sanofi Winthrop Industrie. CM declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/07/05 00:28 MHDA- 2025/09/09 00:33 CRDT- 2025/07/04 18:11 PHST- 2025/05/30 00:00 [received] PHST- 2025/06/25 00:00 [revised] PHST- 2025/06/27 00:00 [accepted] PHST- 2025/09/09 00:33 [medline] PHST- 2025/07/05 00:28 [pubmed] PHST- 2025/07/04 18:11 [entrez] AID - S1056-8727(25)00169-2 [pii] AID - 10.1016/j.jdiacomp.2025.109116 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Oct;39(10):109116. doi: 10.1016/j.jdiacomp.2025.109116. Epub 2025 Jun 30. PMID- 40609682 OWN - NLM STAT- MEDLINE DCOM- 20250925 LR - 20261014 IS - 1544-3450 (Electronic) IS - 1086-5802 (Linking) VI - 65 IP - 5 DP - 2025 Sep-Oct TI - New onset diabetic retinopathy with glucagon-like peptide-1 receptor agonists: A case report. PG - 102475 LID - S1544-3191(25)00154-2 [pii] LID - 10.1016/j.japh.2025.102475 [doi] AB - BACKGROUND: Diabetic retinopathy (DR) is a leading cause of acquired vision loss in middle-aged adults. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are widely used in the management of type 2 diabetes (T2D). Emerging evidence has suggested a possible link between GLP-1 RAs and the acceleration of DR. However, the evidence on the association between GLP-1RA therapies and risk for DR has been mixed, and there is limited guidance on how to manage new onset or worsening DR for patients taking GLP-1RA therapy. The objective of this case report is to describe the clinical decision-making involved in the management of a patient with T2D who developed new-onset and worsening retinopathy following the initiation of several GLP-1RA therapies. CASE SUMMARY: A 43-year-old female with T2D and class II obesity was diagnosed with mild nonproliferative DR after taking various GLP1-RA therapy (ie, exenatide ER and dulaglutide) and maintaining glycemic control for 19 months. The patient was later transitioned to subcutaneous semaglutide for additional weight loss, and diabetic macular edema was detected in the right eye 2 months after. Due to a potentially lower risk of DR complications, treatment was promptly switched to oral semaglutide. The patient's eye exam revealed that her DR improved and diabetic macular edema had significantly resolved 8 months after switching therapy. PRACTICE IMPLICATIONS: This case highlights a progressive decline in retinal health despite well-controlled T2D and the possible contribution of GLP-1RA therapy to DR progression. Switching to GLP-1RA agents with potentially lower risk for DR, such as oral semaglutide, may be beneficial when patients develop DR on GLP1-RA therapy. Further studies that evaluate the risk of DR while using GLP-1RA therapy, as well as the risk across the GLP1-RA class, are needed. Additional guidance on managing possible new onset or worsening DR on GLP-1RA therapy is especially necessary. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Ko, Jennifer AU - Ko J FAU - Jahromi, Yaseman AU - Jahromi Y LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250702 PL - United States TA - J Am Pharm Assoc (2003) JT - Journal of the American Pharmacists Association : JAPhA JID - 101176252 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetic Retinopathy/chemically induced/diagnosis MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Female MH - Adult MH - *Hypoglycemic Agents/adverse effects/administration & dosage/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/adverse effects/therapeutic use/administration & dosage MH - Exenatide/adverse effects MH - Recombinant Fusion Proteins/adverse effects MH - Immunoglobulin Fc Fragments/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosure The authors declare no relevant conflicts of interest or financial relationships. EDAT- 2025/07/04 00:27 MHDA- 2025/09/26 00:30 CRDT- 2025/07/03 19:12 PHST- 2025/04/11 00:00 [received] PHST- 2025/06/26 00:00 [revised] PHST- 2025/06/27 00:00 [accepted] PHST- 2025/09/26 00:30 [medline] PHST- 2025/07/04 00:27 [pubmed] PHST- 2025/07/03 19:12 [entrez] AID - S1544-3191(25)00154-2 [pii] AID - 10.1016/j.japh.2025.102475 [doi] PST - ppublish SO - J Am Pharm Assoc (2003). 2025 Sep-Oct;65(5):102475. doi: 10.1016/j.japh.2025.102475. Epub 2025 Jul 2. PMID- 40608828 OWN - NLM STAT- MEDLINE DCOM- 20250703 LR - 20260127 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 20 IP - 7 DP - 2025 TI - Semaglutide ameliorates diabetes-associated cognitive dysfunction in mouse model of type 2 diabetes. PG - e0326897 LID - 10.1371/journal.pone.0326897 [doi] LID - e0326897 AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction, which significantly impacts the quality of life. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown potential neuroprotective effects. This study investigates the efficacy of semaglutide in ameliorating cognitive dysfunction in a mouse model of T2DM. METHODS: Male C57BL/6J mice were fed a high-fat diet for four weeks and received a single intraperitoneal injection of streptozotocin (150 mg/kg) to induce T2DM. All mice were divided into four groups: control, diabetes control (T2DM), semaglutide treatment (semaglutide, 0.1 mg/kg) and dapagliflozin treatment (dapagliflozin 1 mg/kg). Cognitive function was assessed using the Morris water maze (MWM) test. Histomorphological analysis of hippocampal tissues was performed using H&E and Nissl staining. Immunofluorescence was used to assess LRP1 expression and apoptosis. Biochemical analyses measured oxidative stress markers (SOD, MDA) and inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, CRP). RESULTS: Semaglutide treatment significantly reduced blood glucose levels in diabetic mice. In the MWM test, semaglutide-treated mice showed reduced escape latencies, indicating improved spatial learning and memory. Histomorphological analysis revealed preserved neuronal structure in the hippocampus with reduced neuronal damage and apoptosis in the semaglutide-treated group. Immunofluorescence showed increased LRP1 expression and decreased apoptosis. Biochemical analyses indicated that semaglutide reduced oxidative stress and inflammatory markers, further supporting its neuroprotective effects. CONCLUSIONS: Semaglutide effectively ameliorates cognitive dysfunction in T2DM mice, likely through mechanisms involving the reduction of oxidative stress, inflammation, and neuronal apoptosis. These findings suggest that semaglutide has potential as a therapeutic agent for managing diabetes-associated cognitive decline. Further research, including long-term studies and clinical trials, is necessary to validate these findings and explore the broader applicability of semaglutide in treating cognitive impairments in diabetic patients. CI - Copyright: (c) 2025 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Zhu, Yan AU - Zhu Y AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - He, Yi AU - He Y AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - Yang, Hongyan AU - Yang H AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - Gao, Yanbo AU - Gao Y AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - Wang, Yan AU - Wang Y AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - Liu, Peiqing AU - Liu P AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. FAU - Zhang, Mengjuan AU - Zhang M AUID- ORCID: 0009-0007-7370-8113 AD - Department of Endocrinology, Baotou Central Hospital, Baotou, China. LA - eng PT - Journal Article DEP - 20250703 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Benzhydryl Compounds) RN - 0 (Neuroprotective Agents) RN - 0 (Blood Glucose) RN - 0 (Glucosides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 1ULL0QJ8UC (dapagliflozin) SB - IM MH - Animals MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Male MH - Mice MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Cognitive Dysfunction/drug therapy/etiology MH - Mice, Inbred C57BL MH - *Diabetes Mellitus, Experimental/complications/drug therapy MH - Oxidative Stress/drug effects MH - Disease Models, Animal MH - Hippocampus/drug effects/metabolism/pathology MH - Apoptosis/drug effects MH - Diet, High-Fat/adverse effects MH - Benzhydryl Compounds/pharmacology MH - Neuroprotective Agents/pharmacology MH - Blood Glucose MH - Glucosides/pharmacology MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12225814 COIS- The authors have declared that no competing interests exist. EDAT- 2025/07/03 18:26 MHDA- 2025/07/03 18:27 PMCR- 2025/07/03 CRDT- 2025/07/03 13:53 PHST- 2024/11/03 00:00 [received] PHST- 2025/06/05 00:00 [accepted] PHST- 2025/07/03 18:27 [medline] PHST- 2025/07/03 18:26 [pubmed] PHST- 2025/07/03 13:53 [entrez] PHST- 2025/07/03 00:00 [pmc-release] AID - PONE-D-24-42194 [pii] AID - 10.1371/journal.pone.0326897 [doi] PST - epublish SO - PLoS One. 2025 Jul 3;20(7):e0326897. doi: 10.1371/journal.pone.0326897. eCollection 2025. PMID- 40608494 OWN - NLM STAT- MEDLINE DCOM- 20251029 LR - 20260917 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 40 IP - 11 DP - 2025 Oct 30 TI - Rationale, design and baseline characteristics of REMODEL, a mechanism-of-action trial with semaglutide in people with type 2 diabetes and chronic kidney disease. PG - 2182-2192 LID - 10.1093/ndt/gfaf114 [doi] AB - BACKGROUND: Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD) and kidney failure globally. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces the risk of major kidney, cardiovascular and mortality outcomes in people with T2D and CKD, but the mechanism of action remains unclear. METHODS: The REMODEL trial (NCT04865770) is a 52-week placebo-controlled, double-blind, parallel-group, randomized trial in adults with T2D and CKD. Inclusion criteria include haemoglobin A1c (HbA1c) /=30-/=20-<5000 mg/g. The co-primary outcomes were magnetic resonance imaging (MRI) based, including change in kidney oxygenation, perfusion and inflammation. Secondary outcomes include change from baseline in creatine clearance rate, urinary sodium excretion, albumin excretion rate and kidney fibrosis and blood flow parameters measured by MRI. A subgroup had kidney biopsies at baseline and at the end of the treatment for tissue-based interrogation, including single nucleus and spatial transcriptomics, pathology and advanced histological assessment. RESULTS: Across eight countries, 106 participants (n = 33, biopsy subgroup) were enrolled. The mean age was 65.3 years [standard deviation (SD) 9.9] at baseline with HbA1c of 7.1% (SD 0.9), creatinine-based eGFR of 51.1 ml/min/1.73 m2 (SD 10.4) and median UACR of 187.3 mg/g (interquartile range 60.5-546.4). Renin-angiotensin system inhibitor use was 98.1% and sodium-glucose co-transporter 2 inhibitor use was 38.7%. In the kidney biopsy subgroup, baseline characteristics were like those of the full population. Histological analysis of kidney tissues revealed 17 participants with primarily diabetic nephropathy, 6 participants with primarily vascular features, 9 with mixed diabetic nephropathy and vascular characteristics and 1 with membranous nephropathy. CONCLUSION: The REMODEL trial leverages multipronged approaches to investigate the kidney-specific effects and underlying mechanisms of semaglutide in a representative population of people with T2D and CKD, which supports the generalizability and clinical relevance of the findings. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the ERA. FAU - Cherney, David Z I AU - Cherney DZI AD - Department of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bjornstad, Petter AU - Bjornstad P AD - Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, and Division of Endocrinology, Department of Pediatrics, University of Washington, Seattle, WA, USA. AD - Division of Renal Diseases and Hypertension, Department of Medicine, Section of Pediatric Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. FAU - Chacko, Milenta M AU - Chacko MM AD - Novo Nordisk GBS India, Bangalore, India. FAU - Gunnarsson, Thomas P AU - Gunnarsson TP AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hodgin, Jeffrey B AU - Hodgin JB AD - Department of Pathology and Clinical Laboratories, University of Michigan, Ann Arbor, MI, USA. FAU - Kretzler, Matthias AU - Kretzler M AD - Department of Internal Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. FAU - Pruijm, Menno AU - Pruijm M AUID- ORCID: 0000-0003-1027-1851 AD - Service of Nephrology, University Hospital of Lausanne and University of Lausanne, Lausanne, Switzerland. FAU - Schytz, Philip A AU - Schytz PA AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane WA, USA. AD - Kidney Research Institute and Nephrology Division, University of Washington School of Medicine, Seattle, WA, USA. LA - eng GR - P30 DK020572/DK/NIDDK NIH HHS/United States GR - Novo Nordisk/ PT - Clinical Trial Protocol PT - Journal Article PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - Follow-Up Studies MH - Glomerular Filtration Rate MH - *Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/therapeutic use MH - Prognosis MH - *Renal Insufficiency, Chronic/drug therapy/etiology/pathology MH - Clinical Trials, Phase III as Topic MH - Multicenter Studies as Topic MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12559791 OTO - NOTNLM OT - functional magnetic resonance imaging OT - gene expression OT - incretin therapy OT - kidney OT - nutrient-stimulated hormone (NuSH) therapy COIS- D.Z.I.C. has received honoraria from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, AbbVie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK and Novo Nordisk and has received operational funding for clinical trials from Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo Nordisk. N.B., T.P.G. and P.A.S. are employees and stockholders of Novo Nordisk A/S. P.B. is a consultant and advisory board or steering committee member for Lilly, Novo Nordisk, AstraZeneca, Boehringer Ingelheim and Horizon Pharma/Amgen; DMC chair for Bayer; and received research funding from Lilly, Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Horizon Pharma/Amgen and Merck. MMC: Employee and Stockholder of Novo Nordisk A/S. J.B.H. is a consultant for Sygnamap. M.K. is a consultant or receives funding all via the University of Michigan from Boehringer Ingelheim, Certa, Travere, Maze Therapeutics, Roche, AstraZeneca, Novo Nordisk, Moderna, Chinook, Angion Pharmaceuticals, RenalytixAI, Lilly, Gilead, Sanofi, Regeneron, Janssen, Vera Therapeutics and Dimerix. M.P. has served on advisory boards for GSK, Boehringer Ingelheim, Baxter, Novo Nordisk and Bayer; was a speaker for AstraZeneca, Astellas, Vifor, Baxter and Braun and received investigator-initiated grant support from Nephrospec. K.T. has received investigator-initiated grant support from Travere and Bayer to Providence Inland Northwest Health outside of the submitted work and consultancy fees from AstraZeneca, Boehringer Ingelheim, Bayer, Lilly, Novo Nordisk, Travere and Pfizer. EDAT- 2025/07/03 18:27 MHDA- 2025/10/30 00:26 PMCR- 2025/07/03 CRDT- 2025/07/03 12:33 PHST- 2024/12/20 00:00 [received] PHST- 2025/10/30 00:26 [medline] PHST- 2025/07/03 18:27 [pubmed] PHST- 2025/07/03 12:33 [entrez] PHST- 2025/07/03 00:00 [pmc-release] AID - 8185402 [pii] AID - gfaf114 [pii] AID - 10.1093/ndt/gfaf114 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2025 Oct 30;40(11):2182-2192. doi: 10.1093/ndt/gfaf114. PMID- 40605133 OWN - NLM STAT- MEDLINE DCOM- 20250808 LR - 20260311 IS - 1728-7731 (Electronic) IS - 1726-4901 (Print) IS - 1726-4901 (Linking) VI - 88 IP - 8 DP - 2025 Aug 1 TI - Incretin-based therapy: An update focusing on the major revolution in cardiovascular-kidney-metabolic health. PG - 585-593 LID - 10.1097/JCMA.0000000000001263 [doi] AB - Type 2 diabetes mellitus and obesity have become the rising burden across various geographic and economic regions, and they are also the common causes of chronic kidney disease, which further contributes to the development and progression of cardiovascular disease. The recently proposed cardiovascular-kidney-metabolic syndrome-the new paradigm of recognizing excess or dysfunctional adipose tissue as the shared pathophysiology-has signaled the interconnection of type 2 diabetes mellitus, obesity, chronic kidney disease, and cardiovascular disease beyond the disturbance of glucose homeostasis, for which recently developed incretin-based therapy has offered an avenue of holistic management. Glucagon-like peptide-1 (GLP1) is one of the incretins and potentiates insulin secretion after food intake, additionally offering extra-pancreatic metabolic effects-reduced hepatic gluconeogenesis and steatosis, increased muscular glucose uptake, and increased lipolysis and glucose uptake in the adipose tissue. Seven different GLP1 receptor agonists have been licensed globally. For those with type 2 diabetes mellitus, GLP1 receptor agonists overall reduce major adverse cardiovascular events by 14% (hazard ratio 0.86, 95% confidence interval 0.80-0.93) and all-cause death by 18% (hazard ratio 0.82, 95% confidence interval 0.82-0.94), and semaglutide, a long-acting GLP1 receptor agonist for once weekly injection, reduces major renal events by 24% (hazard ratio 0.76, 95% confidence interval 0.66-0.88). For obese patients without diabetes mellitus, semaglutide results in a 12.4% (95% confidence interval -13.4 to -11.5) reduction in body weight and 20% lower in the risk of major adverse cardiovascular events (hazard ratio 0.80, 95% confidence interval 0.72-0.90), while the burden of heart failure can also be improved by 7.8 points (95% confidence interval 4.8-10.9) in those with heart failure with preserved ejection fraction and obesity. These findings highlight the transformative role of GLP1 receptor agonists in the management of cardiovascular-kidney-metabolic syndrome. We reviewed the updated clinical evidence of incretin-based therapy and summarized its outcome benefits. CI - Copyright (c) 2025, the Chinese Medical Association. FAU - Chiang, Chern-En AU - Chiang CE AUID- ORCID: 0000-0002-1151-1047 AD - General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Wang, Kang-Ling AU - Wang KL AD - General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Cheng, Hao-Min AU - Cheng HM AD - Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. AD - Division of Faculty Development, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. FAU - Chao, Tze-Fan AU - Chao TF AD - Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. FAU - Sung, Shih-Hsien AU - Sung SH AD - General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC. LA - eng PT - Journal Article PT - Review DEP - 20250703 PL - Netherlands TA - J Chin Med Assoc JT - Journal of the Chinese Medical Association : JCMA JID - 101174817 RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Cardiovascular Diseases/etiology/drug therapy/prevention & control MH - *Metabolic Syndrome/drug therapy MH - *Renal Insufficiency, Chronic/drug therapy MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC12637135 OTO - NOTNLM OT - Cardiovascular-kidney OT - Glucagon-like peptide-1 OT - Incretin OT - Obesity OT - metabolic syndrome COIS- Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. EDAT- 2025/07/03 06:28 MHDA- 2025/08/08 06:29 PMCR- 2025/07/03 CRDT- 2025/07/03 00:50 PHST- 2025/08/08 06:29 [medline] PHST- 2025/07/03 06:28 [pubmed] PHST- 2025/07/03 00:50 [entrez] PHST- 2025/07/03 00:00 [pmc-release] AID - 02118582-990000000-00541 [pii] AID - JCMA-D-25-00164 [pii] AID - 10.1097/JCMA.0000000000001263 [doi] PST - ppublish SO - J Chin Med Assoc. 2025 Aug 1;88(8):585-593. doi: 10.1097/JCMA.0000000000001263. Epub 2025 Jul 3. PMID- 40600464 OWN - NLM STAT- MEDLINE DCOM- 20250806 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 9 DP - 2025 Sep TI - The cost-utility and budget impact analyses of Tirzepatide versus once-weekly Semaglutide as add-on therapy to metformin in patients with type 2 diabetes mellitus in China. PG - 5269-5279 LID - 10.1111/dom.16580 [doi] AB - AIM: To evaluate the long-term economic implications and potential budgetary consequences for the national health insurance system (NHIS) of tirzepatide versus semaglutide as add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM) in China. METHODS: The demographic and clinical efficacy data were derived from the SURPASS-2 trial. The cost-utility analysis was performed to estimate the cost-utility by UK Prospective Diabetes Study Outcomes Model Version 2.2 from the Chinese health care providers' perspective, incorporating costs and quality-adjusted life years (QALYs). Sensitivity analyses were employed to investigate the presence of uncertainty. The financial implications for the relevant budgetary authority over 5 years were estimated. RESULTS: In the long-term treatment simulation, tirzepatide 5 and 10 mg yielded incremental QALYs of 0.05 and 0.09, in comparison with semaglutide 1 mg, respectively. The associated incremental costs for these treatments were $23 563.42 and $47 583.74, respectively. Consequently, the incremental cost-utility ratios were calculated to be $445 125.24/QALY and $543 829.19/QALY, both of which exceeded the established threshold of $29 599.90/QALY. These base-case results were validated through robust sensitivity analyses. The budget impact analysis showed that such an expansion would incur an additional budgetary burden of approximately $80 million to $490 million for the NHIS over a simulated 5-year period. CONCLUSION: This dual analysis provides policymakers and payers with a comprehensive basis for decision-making. Tirzepatide offered substantial long-term health benefits, but they were not cost-effective compared with semaglutide 1 mg in T2DM patients inadequately controlled with metformin under China's health care providers' perspective. The entry of tirzepatide 5 mg into the NHIS may increase the financial burden of national medical insurance, but overall health care expenditures are expected to decrease, driven primarily by significantly reduced out-of-pocket expenses for patients. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Wang, Sihua AU - Wang S AUID- ORCID: 0000-0001-6550-5059 AD - Department of Pharmacy, Haining People's Hospital, Haining City, China. FAU - Fan, Duncong AU - Fan D AD - Department of Pharmacy, Haining People's Hospital, Haining City, China. FAU - Yao, Qinhong AU - Yao Q AD - Department of Pharmacy, Haining People's Hospital, Haining City, China. FAU - Sun, Xiaojie AU - Sun X AUID- ORCID: 0009-0003-7629-8296 AD - Department of Pharmacy, Haining People's Hospital, Haining City, China. LA - eng GR - YS2024-3-010/Zhejiang Medical Association/ PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250702 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucagon-Like Peptides/economics/administration & dosage/therapeutic use MH - Cost-Benefit Analysis MH - *Metformin/economics/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/economics/administration & dosage/therapeutic use MH - China/epidemiology MH - Quality-Adjusted Life Years MH - Drug Therapy, Combination/economics MH - Female MH - Male MH - Middle Aged MH - Budgets MH - Aged MH - Drug Administration Schedule MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - budget impact analysis OT - cost-utility analysis OT - semaglutide OT - tirzepatide OT - type 2 diabetes mellitus EDAT- 2025/07/02 12:30 MHDA- 2025/08/06 12:29 CRDT- 2025/07/02 07:23 PHST- 2025/06/19 00:00 [revised] PHST- 2025/04/07 00:00 [received] PHST- 2025/06/19 00:00 [accepted] PHST- 2025/08/06 12:29 [medline] PHST- 2025/07/02 12:30 [pubmed] PHST- 2025/07/02 07:23 [entrez] AID - 10.1111/dom.16580 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Sep;27(9):5269-5279. doi: 10.1111/dom.16580. Epub 2025 Jul 2. PMID- 40594279 OWN - NLM STAT- MEDLINE DCOM- 20250702 LR - 20260127 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 15 IP - 1 DP - 2025 Jul 1 TI - Comparative cardiovascular outcomes of semaglutide to dulaglutide in patients with type 2 diabetes. PG - 21333 LID - 10.1038/s41598-025-06245-w [doi] LID - 21333 AB - Type 2 diabetes significantly increases cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce major adverse cardiovascular events, heart failure hospitalizations, and death. However, the comparison among GLP-1 RAs on cardiovascular outcomes is limited. We compared all-cause death and cardiovascular events in patients using semaglutide or dulaglutide in patients with type 2 diabetes. This retrospective observational study used the TriNetX database of deidentified electronic medical records from January 1, 2018, to December 31, 2020. We identified 4,691,652 patients with type 2 diabetes, among whom 231,075 initiated semaglutide and 189,103 initiated dulaglutide. After propensity score matching, 171,105 patients were included in each group. The primary outcome measure was all-cause death during the 3-year follow-up period.; secondary outcomes were acute myocardial infarction, stroke, and acute heart failure.Over 3 years, the risk for all-cause death in patients who received semaglutide relative to those who received dulaglutide was significantly lower (4.2% vs. 5.6%, p < 0.001; hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.72-0.78). Similarly, patients who received semaglutide were less likely to have acute myocardial infarction (5.2% vs. 5.6%; HR, 0.94; 95% CI, 0.91-0.97; p < 0.001), stroke (5.8% vs. 6.4%; HR, 0.90; 95% CI, 0.87-0.93; p < 0.001), and acute heart failure (5.3% vs. 6.1%; HR, 0.88; 95% CI, 0.85-0.91; p < 0.001).In this multicenter, retrospective, observational study, semaglutide was associated with lower 3-year risks of all-cause death, acute myocardial infarction, stroke, and acute heart failure compared with dulaglutide in patients with type 2 diabetes. CI - (c) 2025. The Author(s). FAU - Kishimori, Takefumi AU - Kishimori T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Kato, Takao AU - Kato T AD - Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. tkato75@kuhp.kyoto-u.ac.jp. FAU - Wada, Atsuyuki AU - Wada A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Tani, Akira AU - Tani A AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yamaji, Ryosuke AU - Yamaji R AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Koike, Jumpei AU - Koike J AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Iwasaki, Yoshihiro AU - Iwasaki Y AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Matsumoto, Takehiro AU - Matsumoto T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Yagi, Takafumi AU - Yagi T AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. FAU - Okada, Masaharu AU - Okada M AD - Department of Cardiovascular Medicine, Omi Medical Center, Kusatsu, Japan. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20250701 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Male MH - Female MH - *Recombinant Fusion Proteins/therapeutic use MH - Middle Aged MH - Aged MH - *Immunoglobulin Fc Fragments/therapeutic use MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/etiology/mortality MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12217050 COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/07/02 06:28 MHDA- 2025/07/02 06:29 PMCR- 2025/07/01 CRDT- 2025/07/02 00:55 PHST- 2025/04/15 00:00 [received] PHST- 2025/06/06 00:00 [accepted] PHST- 2025/07/02 06:29 [medline] PHST- 2025/07/02 06:28 [pubmed] PHST- 2025/07/02 00:55 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - 10.1038/s41598-025-06245-w [pii] AID - 6245 [pii] AID - 10.1038/s41598-025-06245-w [doi] PST - epublish SO - Sci Rep. 2025 Jul 1;15(1):21333. doi: 10.1038/s41598-025-06245-w. PMID- 40590655 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20260626 IS - 2325-6621 (Electronic) IS - 2325-6621 (Linking) VI - 22 IP - 7 DP - 2025 Jul TI - Comparative Efficacy of Tirzepatide, Liraglutide, and Semaglutide in Reduction of Risk of Major Adverse Cardiovascular Events in Patients with Obstructive Sleep Apnea and Type 2 Diabetes: Real-World Evidence. PG - 1042-1052 LID - 10.1513/AnnalsATS.202409-923OC [doi] AB - Rationale: Glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide, semaglutide) and dual glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonists (tirzepatide) are approved for treatment of type 2 diabetes (T2D) and obesity. Objective: To compare the relative efficacy of tirzepatide, liraglutide, and semaglutide in reducing major adverse cardiovascular events (MACEs) in patients with obstructive sleep apnea (OSA) and T2D. Methods: We performed a retrospective cohort analysis in a large global federated database of patients with OSA and T2D. Two cohorts were generated, both with a treatment arm of patients prescribed tirzepatide. Liraglutide and semaglutide-treated patients provided the reference arms in cohort 1 and cohort 2, respectively. Cohorts underwent propensity-score matching at a 1:1 ratio for confounders. We examined rates of incident MACEs (composite outcome and individual components) over an 18-month follow up, and performed stratified analyses by body mass index, age, sex, and ethnicity. Finally, we assessed incident OSA in a secondary analysis of patients with T2D treated with tirzepatide compared with liraglutide and semaglutide. Results: After matching, each treatment arm included 7,836 patients in cohort 1 and 7,394 patients in cohort 2. Tirzepatide reduced the risk of incident MACEs compared with liraglutide (hazard ratio, 0.58; 95% confidence interval, 0.51-0.66) and semaglutide (0.86; 0.74-0.99). Tirzepatide was more efficacious in younger, male patients of White ethnicity. Moreover, tirzepatide reduced incident OSA compared with liraglutide (0.89; 0.82-0.97) but not semaglutide (0.94; 0.86-1.02). Conclusions: In patients with OSA and T2D, tirzepatide is associated with a lower incidence of MACEs compared with liraglutide and semaglutide. More robust randomized, controlled evidence is needed for these drugs in patients who are at such high risk. FAU - Henney, Alex E AU - Henney AE AUID- ORCID: 0000-0002-8066-9470 AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. FAU - Riley, David R AU - Riley DR AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. FAU - Anson, Matthew AU - Anson M AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. FAU - Heague, Megan AU - Heague M AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. FAU - Hernadez, Gema AU - Hernadez G AD - TriNetX LLC, Cambridge, Massachusetts. FAU - Alam, Uazman AU - Alam U AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. FAU - Craig, Sonya AU - Craig S AD - Liverpool University Hospital National Health Service Foundation Trust, Liverpool, United Kingdom. FAU - Cuthbertson, Daniel J AU - Cuthbertson DJ AD - Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, United Kingdom. AD - Department of Diabetes, Obesity and Endocrinology, University Hospital Aintree, Liverpool University National Health Service Foundation Trust, Liverpool, United Kingdom. AD - Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom. LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Ann Am Thorac Soc JT - Annals of the American Thoracic Society JID - 101600811 RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Liraglutide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - *Sleep Apnea, Obstructive/complications/drug therapy MH - Retrospective Studies MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology MH - Aged MH - *Tirzepatide/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - major adverse cardiovascular events OT - obstructive sleep apnoea OT - tirzepatide OT - type 2 diabetes EDAT- 2025/07/01 21:14 MHDA- 2025/07/01 21:15 CRDT- 2025/07/01 09:43 PHST- 2025/07/01 21:15 [medline] PHST- 2025/07/01 21:14 [pubmed] PHST- 2025/07/01 09:43 [entrez] AID - 10.1513/AnnalsATS.202409-923OC [doi] PST - ppublish SO - Ann Am Thorac Soc. 2025 Jul;22(7):1042-1052. doi: 10.1513/AnnalsATS.202409-923OC. PMID- 40590228 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20260625 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 135 IP - 13 DP - 2025 Jul 1 TI - Therapeutic horizons in metabolic dysfunction-associated steatohepatitis. LID - 10.1172/JCI186425 [doi] LID - e186425 AB - Metabolic dysfunction-associated steatohepatitis (MASH), the progressive inflammatory form of MASLD, is now a leading cause of chronic liver disease worldwide. Driven by obesity and type 2 diabetes, MASH significantly increases the risk of cirrhosis, hepatocellular carcinoma, and liver failure. While public health interventions remain essential, therapeutic strategies targeting metabolic dysfunction, inflammation, and fibrosis are urgently needed. This Review focuses on pharmacological treatments in advanced development, including incretin-based therapies (GLP-1, dual, and triple agonists), metabolic modulators (PPAR, FGF21, and THR-beta agonists), and novel agents such as fatty acid synthase inhibitors. Current regulatory approval is based on histological end points, with increasing interest in noninvasive biomarkers and personalized treatment approaches. Recent trials with agents such as semaglutide, tirzepatide, survodutide, lanifibranor, pegozafermin, and resmetirom demonstrate substantial promise in resolving MASH and improving fibrosis, but unresolved issues remain regarding treatment duration, response heterogeneity, and long-term adherence. Genetic variants (e.g., PNPLA3 polymorphisms) and emerging molecular biomarkers may enhance stratification, while artificial intelligence is beginning to shape trial design and drug development. As the field moves toward combination therapies and precision medicine, the definition of therapeutic success will likely evolve to reflect both histological improvement and patient-reported outcomes. This Review provides a timely synthesis of the landscape, challenges, and future directions in MASH therapeutics. FAU - Newsome, Philip N AU - Newsome PN AD - Roger Williams Institute of Liver Studies, School of Immunology & Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, Foundation for Liver Research and King's College Hospital, London, United Kingdom. FAU - Loomba, Rohit AU - Loomba R AD - MASLD Research Center, Division of Gastroenterology and Hepatology, and. AD - Division of Epidemiology, Department of Family Medicine and Public Health, UCSD, La Jolla, California, USA. LA - eng GR - P30 DK120515/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20250701 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Incretins) SB - IM MH - Humans MH - Animals MH - *Fatty Liver/drug therapy/metabolism/pathology MH - *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism MH - Incretins/therapeutic use MH - Liver Cirrhosis/metabolism/drug therapy/pathology MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy PMC - PMC12208534 COIS- Conflict of interest: PNN discloses the following financial relationship(s) on behalf of the University of Birmingham within the past 24 months: grant/research support from Boehringer Ingelheim and Novo Nordisk and consulting fees from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Intercept, Madrigal, Novo Nordisk, Sagimet, and 89 Bio. RL serves as a consultant to Aardvark Therapeutics, Altimmune, Arrowhead Pharmaceuticals, AstraZeneca, Cascade Pharmaceuticals, Eli Lilly, Gilead, Glympse Bio, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Lipidio, Madrigal, Neurobo, Novo Nordisk, Merck, Pfizer, Sagimet, 89 bio, Takeda, Terns Pharmaceuticals, and Viking Therapeutics. RL has stock options in Sagimet Biosciences. In addition, his institution received research grants from Arrowhead Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Eli Lilly, Galectin Therapeutics, Gilead, Intercept, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sonic Incytes, and Terns Pharmaceuticals. RL is Co-founder of LipoNexus Inc. EDAT- 2025/07/01 21:14 MHDA- 2025/07/01 21:15 PMCR- 2025/07/01 CRDT- 2025/07/01 06:03 PHST- 2025/07/01 21:15 [medline] PHST- 2025/07/01 21:14 [pubmed] PHST- 2025/07/01 06:03 [entrez] PHST- 2025/07/01 00:00 [pmc-release] AID - 186425 [pii] AID - 10.1172/JCI186425 [doi] PST - epublish SO - J Clin Invest. 2025 Jul 1;135(13):e186425. doi: 10.1172/JCI186425. eCollection 2025 Jul 1. PMID- 40589512 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20250702 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Case Report: long-term misdiagnosis and follow-up of a patient with HNF4A-MODY carrying a new de novo mutation. PG - 1509135 LID - 10.3389/fendo.2025.1509135 [doi] LID - 1509135 AB - BACKGROUND: HNF4A-MODY constitutes 5%-10% of MODY cases; however, treatment options remain unclearly recommended, and long-term follow-up of patients with HNF4A-MODY is lacking due to limited research. Here, we report a case carrying a new de novo variant of HNF4A. The patient had been using insulin for up to 25 years before genetic diagnosis. CASE DESCRIPTION: A 38-year-old man sought consultation due to an increased daily insulin requirement and inadequate glycemic control. At the age of 13, the patent's parents discovered that he had significantly elevated fasting blood glucose levels accompanied by weight loss. He was subsequently diagnosed with type 1 diabetes and began insulin therapy. At a routine follow-up at age 21, another physician observed that his pancreatic islet function remained preserved, with negative results for diabetes-related antibodies. Consequently, his diagnosis was revised to type 2 diabetes, and the antihyperglycemic therapy was added in metformin and acarbose. Before the current consultation, the patient's insulin dosage had gradually increased to 80 units per day; however, glycemic control remained unsatisfactory. Whole exome sequencing identified a heterozygous variant, c.272G > A (p.R91H), in exon 3 of the HNF4A gene (NM_175914.5) in the patient. The patient's treatment regimen was modified to include metformin at a dosage of 1.0 g twice daily, semaglutide at 0.5 mg once weekly, and insulin glargine was gradually discontinued. The patient achieved adequate glycemic control during follow-up. CONCLUSION: This case emphasizes that spontaneous HNF4A-MODY is prone to misdiagnosis and the prolonged rate of pancreatic function decline in HNF4A-MODY. Glycemic control and complication progression could be acceptable in HNF4A-MODY cases treated with long-time insulin, but risks of hypoglycemic events, obesity, and atherosclerosis remain. Switching to GLP1RA treatment in HNF4A-MODY still yields a good effect after a prolonged disease course. CI - Copyright (c) 2025 Luo, Li and Wang. FAU - Luo, Jing AU - Luo J AD - Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China. AD - Department of Endocrinology and Metabolism, Tieling Central Hospital, Tieling, China. FAU - Li, Ai AU - Li A AD - Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China. AD - Department of Endocrinology and Metabolism, Tieling Central Hospital, Tieling, China. FAU - Wang, Xiaoli AU - Wang X AD - Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, China. LA - eng SI - figshare/10.6084/m9.figshare.29236490 PT - Case Reports PT - Journal Article DEP - 20250616 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hepatocyte Nuclear Factor 4) RN - 0 (HNF4A protein, human) SB - IM MH - Humans MH - *Hepatocyte Nuclear Factor 4/genetics MH - Adult MH - Male MH - *Diabetes Mellitus, Type 2/genetics/diagnosis/drug therapy MH - *Diagnostic Errors MH - *Mutation MH - Follow-Up Studies PMC - PMC12207682 OTO - NOTNLM OT - GLP1RA OT - HNF4A OT - case report OT - maturity-onset diabetes of the young OT - mutation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/07/01 09:30 MHDA- 2025/07/01 21:16 PMCR- 2025/06/16 CRDT- 2025/07/01 04:14 PHST- 2024/10/10 00:00 [received] PHST- 2025/05/20 00:00 [accepted] PHST- 2025/07/01 21:16 [medline] PHST- 2025/07/01 09:30 [pubmed] PHST- 2025/07/01 04:14 [entrez] PHST- 2025/06/16 00:00 [pmc-release] AID - 10.3389/fendo.2025.1509135 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Jun 16;16:1509135. doi: 10.3389/fendo.2025.1509135. eCollection 2025. PMID- 40587855 OWN - NLM STAT- MEDLINE DCOM- 20250714 LR - 20260918 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 178 IP - 7 DP - 2025 Jul TI - In high-risk type 2 diabetes, adding oral semaglutide to standard care reduced MACE at a mean 48 mo. PG - JC80 LID - 10.7326/ANNALS-25-02173-JC [doi] AB - GIM/FP/GP: [Formula: see text] Cardiology: [Formula: see text] Endocrinology: [Formula: see text] Nephrology: [Formula: see text]. FAU - Bandi, Satya Sai Sri AU - Bandi SSS AUID- ORCID: 0009-0003-3698-2309 AD - Mayo Clinic, Rochester, Minnesota, USA (S.S.B., V.M.M.). FAU - Montori, Victor M AU - Montori VM AUID- ORCID: 0000-0003-0595-2898 AD - Mayo Clinic, Rochester, Minnesota, USA (S.S.B., V.M.M.). CN - ACP Journal Club Editorial Team at McMaster University LA - eng PT - Journal Article DEP - 20250701 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Administration, Oral MH - *Cardiovascular Diseases/prevention & control MH - Male MH - Female MH - Middle Aged MH - Aged MH - Drug Therapy, Combination MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/07/01 04:51 MHDA- 2025/07/14 18:27 CRDT- 2025/06/30 17:02 PHST- 2025/07/14 18:27 [medline] PHST- 2025/07/01 04:51 [pubmed] PHST- 2025/06/30 17:02 [entrez] AID - 10.7326/ANNALS-25-02173-JC [doi] PST - ppublish SO - Ann Intern Med. 2025 Jul;178(7):JC80. doi: 10.7326/ANNALS-25-02173-JC. Epub 2025 Jul 1. PMID- 40587084 OWN - NLM STAT- MEDLINE DCOM- 20260520 LR - 20260520 IS - 2724-6116 (Electronic) IS - 2724-6116 (Linking) VI - 51 IP - 2 DP - 2026 Jun TI - Mechanisms of efficacy of drug therapy in type 2 diabetes: the role of microbiomes. PG - 224-236 LID - 10.23736/S2724-6507.25.04306-4 [doi] AB - The gut microbiota plays a crucial role in the human body and has an impact on the physiological function of the host. In particular, changes in the gut microbiota are especially pronounced in patients with type 2 diabetes. There is ample evidence that glucose-lowering drugs exert their therapeutic effects precisely through their interactions with the gut microbiota, but there is a lack of summarization. An overall comparison of the effects of each hypoglycemic agent on the gut flora can provide new inspiration for combinations. In this paper, we selected several representative glucose-lowering drugs, such as metformin, sodium-dependent glucose transporters 2 inhibitors (dapagliflozin), glucagon-like peptide-1 receptor agonists (semaglutide, liraglutide), and the traditional Chinese medicine (berberine), and illustrated how they can affect the disease process by regulating metabolic homeostasis, immune response, and gut barrier. We found that each of these four hypoglycemic agents can have conflicting effects on the gut flora depending on the timing and mode of administration. Meanwhile, the potential impact of gut microbiota on drug safety is explored, and an outlook for the optimization of future type 2 diabetes treatment regimens is presented. FAU - Li, Yushan AU - Li Y AD - Human Microbiome and Health Group, School of Basic Medical Science, Department of Microbiology, Central South University, Changsha, China. FAU - He, Ziling AU - He Z AD - Human Microbiome and Health Group, School of Basic Medical Science, Department of Microbiology, Central South University, Changsha, China. FAU - Li, Chunyan AU - Li C AD - Human Microbiome and Health Group, School of Basic Medical Science, Department of Microbiology, Central South University, Changsha, China. FAU - Huang, Jing AU - Huang J AD - School of Basic Medical Science, Department of Parasitology, Central South University, Changsha, China. FAU - Yu, Zheng AU - Yu Z AD - Human Microbiome and Health Group, School of Basic Medical Science, Department of Microbiology, Central South University, Changsha, China - yuzheng@csu.edu.cn. LA - eng PT - Journal Article PT - Review DEP - 20250630 PL - Italy TA - Minerva Endocrinol (Torino) JT - Minerva endocrinology JID - 101777342 RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/microbiology MH - Humans MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Gastrointestinal Microbiome/drug effects MH - Metformin/therapeutic use/pharmacology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2025/07/01 04:48 MHDA- 2026/05/20 06:32 CRDT- 2025/06/30 11:21 PHST- 2026/05/20 06:32 [medline] PHST- 2025/07/01 04:48 [pubmed] PHST- 2025/06/30 11:21 [entrez] AID - S2724-6507.25.04306-4 [pii] AID - 10.23736/S2724-6507.25.04306-4 [doi] PST - ppublish SO - Minerva Endocrinol (Torino). 2026 Jun;51(2):224-236. doi: 10.23736/S2724-6507.25.04306-4. Epub 2025 Jun 30. PMID- 40586870 OWN - NLM STAT- MEDLINE DCOM- 20251031 LR - 20251031 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 10 DP - 2025 Oct TI - New generation agents for glycemic control and diabetic retinopathy progression: what we need to know? PG - 1573-1583 LID - 10.1007/s00592-025-02552-w [doi] AB - AIMS: To report on the current evidence of early worsening of diabetic retinopathy (EWDR) in patients treated with new-generation antidiabetic agents, with a focus on glucagon-like peptide-1 receptor agonists (GLP1-RA). METHODS: A comprehensive analysis of current literature was conducted, with a focus on studies evaluating the impact of glycemic control strategies and GLP1-RA on DR progression. References from landmark studies and recent trials were analyzed. RESULTS: Intensive glycemic control, while effective in reducing long-term microvascular complications including DR, has been associated with EWDR, particularly in cases with rapid HbA1c reductions. Emerging evidence links novel antidiabetic agents, including GLP1-RA, with increased risk of EWDR, though different studies have conflicting results. However, the risk of EWDR seems not to be directly linked to retinal toxicity from specific antidiabetic agents, but more likely to the rapid glycemic improvement. Risk factors for EWDR in these patients include higher baseline HbA1c, rapid and significant reductions in HbA1c levels during the first months of treatment, longer duration of diabetes, and more advanced stages of DR at baseline, while mild or moderate non-proliferative DR seem not be at higher risk of DR progression. CONCLUSIONS: While new antidiabetic therapies offer significant benefits for diabetes management, clinicians must be cautious when implementing intensive glycemic control in patients at risk for EWDR. Individualized treatment plans and close monitoring are essential to mitigate risks and optimize outcomes for patients with DR. CI - (c) 2025. Associazione Medici Diabetologi / Association of Diabetologists (AMD), Societa Italiana di Diabetologia / Italian Society of Diabetology (SID). FAU - Vujosevic, Stela AU - Vujosevic S AUID- ORCID: 0000-0001-6773-9967 AD - Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via San Vittore 12, 20123, Milan, Italy. stela.vujosevic@unimi.it. AD - Eye Clinic, IRCCS MultiMedica, 20123, Milan, Italy. stela.vujosevic@unimi.it. FAU - Toma, Caterina AU - Toma C AUID- ORCID: 0000-0002-1505-6029 AD - Eye Clinic, University Hospital Maggiore della Carita, 28100, Novara, Italy. AD - Department of Health Sciences, Universita del Piemonte Orientale "Amedeo Avogadro", 28100, Novara, Italy. FAU - Ferrulli, Anna AU - Ferrulli A AUID- ORCID: 0000-0002-8518-5547 AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, 20142, Milan, Italy. FAU - De Cilla, Stefano AU - De Cilla S AUID- ORCID: 0000-0002-0267-3650 AD - Eye Clinic, University Hospital Maggiore della Carita, 28100, Novara, Italy. AD - Department of Health Sciences, Universita del Piemonte Orientale "Amedeo Avogadro", 28100, Novara, Italy. FAU - Nucci, Paolo AU - Nucci P AUID- ORCID: 0000-0002-4036-703X AD - Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via San Vittore 12, 20123, Milan, Italy. FAU - Luzi, Livio AU - Luzi L AUID- ORCID: 0000-0003-3183-0552 AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, 20142, Milan, Italy. AD - Department of Biomedical Sciences for Health, University of Milan, 20123, Milan, Italy. LA - eng PT - Journal Article PT - Review DEP - 20250630 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetic Retinopathy/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Disease Progression MH - *Glycemic Control/methods MH - Blood Glucose/drug effects/metabolism MH - Glycated Hemoglobin/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Early worsening of diabetic retinopathy OT - Glucagon-like peptide-1 receptor agonists OT - SUSTAIN-6 trial OT - Semaglutide COIS- Declarations. Conflict of interest: The Authors have no conflicts of interest to declare. EDAT- 2025/07/01 04:47 MHDA- 2025/10/31 18:28 CRDT- 2025/06/30 11:13 PHST- 2025/02/25 00:00 [received] PHST- 2025/06/09 00:00 [accepted] PHST- 2025/10/31 18:28 [medline] PHST- 2025/07/01 04:47 [pubmed] PHST- 2025/06/30 11:13 [entrez] AID - 10.1007/s00592-025-02552-w [pii] AID - 10.1007/s00592-025-02552-w [doi] PST - ppublish SO - Acta Diabetol. 2025 Oct;62(10):1573-1583. doi: 10.1007/s00592-025-02552-w. Epub 2025 Jun 30. PMID- 40582734 OWN - NLM STAT- MEDLINE DCOM- 20250629 LR - 20250629 IS - 1558-2264 (Electronic) IS - 0733-8651 (Linking) VI - 43 IP - 3 DP - 2025 Aug TI - Role of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide/Glucagon-Like Peptide-1 Receptor Agonists in Management of Cardiovascular-Kidney-Metabolic (CKM) Conditions. PG - 415-432 LID - S0733-8651(24)00113-9 [pii] LID - 10.1016/j.ccl.2024.12.003 [doi] AB - Use of glucagon-like peptide-1 (GLP-1) and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists, initially developed as glucose-lowering therapies for the management of type 2 diabetes, continues to expand in parallel with our understanding of their beneficial effects on cardiovascular-kidney-metabolic conditions. Large clinical outcome trials have established GLP-1 receptor agonists as guideline-directed therapies to improve glycemia, achieve, and maintain weight management goals, and mitigate cardiovascular and kidney risk, with early evidence suggesting similar benefits with the dual GIP/GLP-1 receptor agonist tirzepatide. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Alicic, Radica Z AU - Alicic RZ AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA. Electronic address: Radica.Alicic@providence.org. FAU - Neumiller, Joshua J AU - Neumiller JJ AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA; Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, 412 E. Spokane Falls Boulevard, Spokane, WA 99210, USA. LA - eng PT - Journal Article PT - Review DEP - 20250502 PL - Netherlands TA - Cardiol Clin JT - Cardiology clinics JID - 8300331 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/drug therapy MH - *Glucagon-Like Peptide 1/agonists/therapeutic use MH - *Gastric Inhibitory Polypeptide/agonists/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Cardiovascular outcome trials OT - Dulaglutide OT - Exenatide OT - Incretin hormones OT - Liraglutide OT - Pathomechanisms OT - Semaglutide OT - Tirzepatide COIS- Disclosures R.Z. Alicic is supported by NIH, United States research grants OT2HL161847, OT2OD032581, U24TR001608 and CDC project numbers 75D301 to 21-P-12254 and 75D301 to 23-C-18264; and reports other support from Brigham Research Institute, United States, Travere Therapeutics, United States, the Doris Duke Charitable Foundation, United States, Bayer AG, Germany, AstraZeneca, United Kingdom, Novo Nordisk, Denmark, The George Institute for Global Health, Australia, CareDx, United States, and KBP BioSciences, and personal fees from Boehringer Ingelheim, Bayer Pharmaceuticals, and Eli Lilly. J.J. Neumiller is supported by a NIH research grant OT2OD032581 and reports personal fees and other support from American College of Clinical Pharmacy, United States, Bayer AG, Sanofi, United States, Novo Nordisk, Boehringer Ingelheim, United States, Eli Lilly, Proteomics International, and Dexcom, United States. EDAT- 2025/07/01 04:06 MHDA- 2025/07/01 04:07 CRDT- 2025/06/29 20:53 PHST- 2025/07/01 04:07 [medline] PHST- 2025/07/01 04:06 [pubmed] PHST- 2025/06/29 20:53 [entrez] AID - S0733-8651(24)00113-9 [pii] AID - 10.1016/j.ccl.2024.12.003 [doi] PST - ppublish SO - Cardiol Clin. 2025 Aug;43(3):415-432. doi: 10.1016/j.ccl.2024.12.003. Epub 2025 May 2. PMID- 40562309 OWN - NLM STAT- MEDLINE DCOM- 20250828 LR - 20260603 IS - 1524-4733 (Electronic) IS - 1098-3015 (Linking) VI - 28 IP - 9 DP - 2025 Sep TI - Use and Potential Misuse of Glucagon-Like Peptide-1 Receptor Agonists in France: A Nationwide Cohort Study. PG - 1335-1343 LID - S1098-3015(25)02404-0 [pii] LID - 10.1016/j.jval.2025.06.001 [doi] AB - OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), introduced in France in 2008 for type 2 diabetes mellitus (T2DM), have been indicated in the treatment of obesity with comorbidities since 2021. Their sharply increasing use over the last years led to supply shortages. Additionally, misuse is suspected in participants searching for weight loss. Consequently, this study aimed to describe the use of GLP-1 RAs in France and evaluate its potential misuse. METHODS: Incident users of GLP-1 RAs between January 01, 2017 and June 30, 2023 were identified in the French national health database based on the following possible indications: T2DM, obesity, and absence of T2DM or obesity. Monthly trends in GLP-1 RA use by indications were analyzed. Profiles of incident users from January 01, 2017 to June 30, 2023 were described. RESULTS: As incident GLP-1 RA users increased (5117 in January 2017 to 15 193 in June 2023), the proportion of GLP-1 RA users without T2DM or obesity rose from approximately 2% in 2020 to >5% in May 2022. These latter users, predominantly women (68.7%) who are younger than T2DM users (48.9 vs 62.0 years), included 4683 individuals (2.2% of all users) without comorbidities associated with overweight. They used predominantly OZEMPIC(R) (semaglutide). The use of GLP-1 RAs by these users was marked by a high proportion of single dispensing. Their consumption was equivalent to the annual treatment for approximately 1700 patients with T2DM or obesity. CONCLUSIONS: GLP-1 RA use has risen sharply, particularly among individuals without T2DM or obesity. Potential misuse was identified in 2.2% of users. This misuse still warrants further monitoring because the risks are unclear. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - du Soulier, Nathan AU - du Soulier N AD - Univ Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France. Electronic address: nathan.du-soulier@u-bordeaux.fr. FAU - Pariente, Antoine AU - Pariente A AD - Univ Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France; CHU de Bordeaux, Department of Medical Pharmacology, INSERM, U1219, Bordeaux, France. FAU - Bezin, Julien AU - Bezin J AD - Univ Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France; CHU de Bordeaux, Department of Medical Pharmacology, INSERM, U1219, Bordeaux, France. FAU - Grenet, Guillaume AU - Grenet G AD - Department of Medical Pharmacotoxicology, Hospices Civils de Lyon, Lyon, France. FAU - Faillie, Jean-Luc AU - Faillie JL AD - Department of Medical Pharmacology and Toxicology, CHU Montpellier, Univ. Montpellier, Montpellier, France; IDESP INSERM, Montpellier, France. FAU - de Germay, Sibylle AU - de Germay S AD - Univ Bordeaux, INSERM, BPH, U1219, Team AHeaD, Bordeaux, France; CHU de Bordeaux, Department of Medical Pharmacology, INSERM, U1219, Bordeaux, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250623 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - France/epidemiology MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - *Obesity/drug therapy/epidemiology MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Cohort Studies MH - Adult MH - Databases, Factual OTO - NOTNLM OT - GLP-1 receptor agonist OT - diabetes OT - misuse OT - obesity OT - weight management COIS- Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. EDAT- 2025/06/26 00:27 MHDA- 2025/08/31 20:02 CRDT- 2025/06/25 19:14 PHST- 2024/12/12 00:00 [received] PHST- 2025/06/05 00:00 [revised] PHST- 2025/06/06 00:00 [accepted] PHST- 2025/08/31 20:02 [medline] PHST- 2025/06/26 00:27 [pubmed] PHST- 2025/06/25 19:14 [entrez] AID - S1098-3015(25)02404-0 [pii] AID - 10.1016/j.jval.2025.06.001 [doi] PST - ppublish SO - Value Health. 2025 Sep;28(9):1335-1343. doi: 10.1016/j.jval.2025.06.001. Epub 2025 Jun 23. PMID- 40560166 OWN - NLM STAT- MEDLINE DCOM- 20260130 LR - 20260201 IS - 1460-2385 (Electronic) IS - 0931-0509 (Print) IS - 0931-0509 (Linking) VI - 41 IP - 2 DP - 2026 Jan 30 TI - GLP-1-based therapeutics for cardiorenal protection in metabolic diseases. PG - 207-219 LID - 10.1093/ndt/gfaf110 [doi] AB - Over the last decade, significant progress has been made in cardiorenal protection for metabolic diseases such as type 2 diabetes (T2D) and obesity. With an expanding range of pharmacological options and continuously evolving guidelines, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have garnered substantial clinical and societal attention for their role in T2D and weight management. GLP-1RAs have consistently demonstrated robust HbA1c- and body weight-reducing efficacy in clinical and real-world studies. In addition, mounting data established their cardiorenal benefits beyond glycaemic control in select high-risk populations. In T2D, GLP-1RAs have been shown to improve both hard cardiovascular and, more recently, relevant kidney outcomes. Meanwhile, in individuals with obesity but without T2D, semaglutide (at a higher dose than in T2D) reduces body weight by up to 15% and lowers the risk of major adverse cardiovascular events by 20%. The success of GLP-1-based therapy fuelled the development of new single molecules that combine GLP-1R agonism with activation of other entero-pancreatic hormone receptors [e.g. glucose-dependent insulinotropic polypeptide (GIP), glucagon and amylin] aiming to achieve complementary and potentially synergistic effects. These next-generation GLP-1-based therapeutics for metabolic diseases, either already available or approaching clinical approval, appear to enhance metabolic and weight-reducing efficacy compared with existing GLP-1RAs. An example is tirzepatide, a dual GLP-1/GIP receptor agonist, which has been approved for both T2D and obesity management, demonstrating up to 22.5% weight loss in phase 3 trials. This review explores the landscape of current and emerging GLP-1-based therapies, their efficacy in managing hyperglycaemia and body weight, recent evidence supporting their cardiorenal benefits and clinical implications of these advancements. CI - (c) The Author(s) 2025. Published by Oxford University Press on behalf of the ERA. FAU - Apperloo, Ellen M AU - Apperloo EM AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - van Raalte, Daniel H AU - van Raalte DH AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands. FAU - Muskiet, Marcel H A AU - Muskiet MHA AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUMC, Amsterdam, The Netherlands. LA - eng PT - Journal Article PT - Review PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Metabolic Diseases/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/prevention & control/etiology MH - *Obesity/drug therapy PMC - PMC12855604 OTO - NOTNLM OT - GLP-1 OT - cardiovascular disease OT - kidney disease OT - obesity OT - type 2 diabetes COIS- E.M.A. reports no conflicts of interest. H.J.L.H. reports funding to conduct clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen and Novo Nordisk (all to the University of Groningen); consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Behring, Dimerix, Lilly, Fresenius, Gilead, Janssen, Novo Nordisk, Novartis and Travere Therapeutics; payment of honoraria for lectures from AstraZeneca, Novo Nordisk and Bayer; support for travel to and attending the American Diabetes Association meeting and American Society of Nephrology meeting from AstraZeneca and Lilly (to H.J.L.H. and the University of Groningen); and receipt of the study drug from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen and Novo Nordisk. D.H.v.R. has acted as a consultant and received honoraria from Boehringer Ingelheim, Lilly, Merck, Novo Nordisk, Sanofi and AstraZeneca and has received research operating funds from the Boehringer Ingelheim-Lilly Diabetes Alliance, AstraZeneca and Novo Nordisk. M.H.A.M. has served as a consultant or on the advisory board for AstraZeneca, Bayer, Boehringer Ingelheim, Lilly and Novo Nordisk. EDAT- 2025/06/25 12:27 MHDA- 2026/01/30 06:30 PMCR- 2025/06/25 CRDT- 2025/06/25 10:53 PHST- 2025/04/26 00:00 [received] PHST- 2026/01/30 06:30 [medline] PHST- 2025/06/25 12:27 [pubmed] PHST- 2025/06/25 10:53 [entrez] PHST- 2025/06/25 00:00 [pmc-release] AID - 8173760 [pii] AID - gfaf110 [pii] AID - 10.1093/ndt/gfaf110 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2026 Jan 30;41(2):207-219. doi: 10.1093/ndt/gfaf110. PMID- 40556828 OWN - NLM STAT- MEDLINE DCOM- 20250625 LR - 20250630 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Evaluation of three mechanisms of action (SGLT2 inhibitors, GLP-1 receptor agonists, and sulfonylureas) in treating type 2 diabetes with heart failure: a systematic review and network meta-analysis of RCTs. PG - 1562815 LID - 10.3389/fendo.2025.1562815 [doi] LID - 1562815 AB - OBJECTIVE: We aimed to evaluate and compare the efficacy and safety of three antidiabetic drug classes-SGLT2 inhibitors, GLP-1 receptor agonists, and sulfonylureas-in patients with type 2 diabetes mellitus (T2DM) complicated by heart failure (HF). We focused on their differential effects on both cardiovascular outcomes (e.g., heart failure biomarkers and cardiac function) and metabolic outcomes (e.g., glycemic control and body weight), aiming to determine whether the newer agents offer superior cardiometabolic benefits. A network meta-analysis was conducted to integrate available evidence and compare all interventions simultaneously. METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and the Cochrane Library. encompassing all available records up to December 10, 2024. Fourteen RCTs were included. A Bayesian network meta-analysis was utilized to integrate direct and indirect evidence, facilitating a comparative ranking of various SGLT2 inhibitors-canagliflozin (CANA), ipragliflozin (IPRA), empagliflozin (EMPA), remogliflozin (REMO), licogliflozin (LICO), and dapagliflozin (DAPA)-as well as one GLP-1 receptor agonist-semaglutide (SEMA)-and a sulfonylurea-glimepiride (GLIM)-with respect to their efficacy and safety profiles. RESULTS: SEMA (SMD = -0.22, 95% CI: -1.31 to 0.87) demonstrated the most favorable outcome in reducing BNP levels. LICO (SMD = -0.91, 95% CI: -1.76 to -0.06) ranked highest for body weight reduction, indicating the greatest impact. GLIM (SMD = -0.64, 95% CI: -1.12 to -0.17) showed the strongest effect on lowering HbA1c, while DAPA (SMD = 0.34, 95% CI: -0.97 to 1.65) was the top-ranked agent for improving LVEF. Safety analysis indicated that LICO and IPRA had the lowest incidence of adverse events. GLIM was associated with an increased risk of hypoglycemia, whereas DAPA was linked to a higher risk of urinary tract infections. CONCLUSION: SEMA significantly improves both metabolic control and BNP levels, making it suitable for patients requiring comprehensive management of metabolic abnormalities and heart failure. LICO offers a distinct advantage in weight management, particularly benefiting individuals with obesity. DAPA demonstrates notable efficacy in optimizing HbA1c and LVEF, making it a preferred option for patients needing more intensive cardiac support. Despite its moderate efficacy, GLIM remains a viable choice for certain patients due to its favorable safety profile and cost-effectiveness. Collectively, these findings provide essential evidence-based insights to guide individualized therapeutic strategies in type 2 diabetes complicated by heart failure. CI - Copyright (c) 2025 Gao, Wei, Zou, Yu, Song, Li, Han and Liu. FAU - Gao, Huize AU - Gao H AD - Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Wei, Qian AU - Wei Q AD - The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Zou, Anqi AU - Zou A AD - Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Yu, Keying AU - Yu K AD - The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Song, Da AU - Song D AD - Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Li, Jian AU - Li J AD - Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Han, Huize AU - Han H AD - Changchun University of Chinese Medicine, Changchun, Jilin, China. FAU - Liu, Aidong AU - Liu A AD - The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, China. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250610 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Heart Failure/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Sulfonylurea Compounds/therapeutic use PMC - PMC12185272 OTO - NOTNLM OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - efficacy and safety OT - network meta-analysis OT - type 2 diabetes with heart failure COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/06/25 06:25 MHDA- 2025/06/25 06:26 PMCR- 2025/06/10 CRDT- 2025/06/25 04:27 PHST- 2025/01/18 00:00 [received] PHST- 2025/05/23 00:00 [accepted] PHST- 2025/06/25 06:26 [medline] PHST- 2025/06/25 06:25 [pubmed] PHST- 2025/06/25 04:27 [entrez] PHST- 2025/06/10 00:00 [pmc-release] AID - 10.3389/fendo.2025.1562815 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Jun 10;16:1562815. doi: 10.3389/fendo.2025.1562815. eCollection 2025. PMID- 40555703 OWN - NLM STAT- MEDLINE DCOM- 20250806 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 9 DP - 2025 Sep TI - PIONEER REAL Spain: A multicentre, prospective, real-world study of oral semaglutide use in adults with type 2 diabetes. PG - 4812-4824 LID - 10.1111/dom.16523 [doi] AB - AIMS: This study evaluated clinical outcomes of oral semaglutide treatment in adults with type 2 diabetes (T2D) in a real-world setting in Spain as part of the 13-country PIONEER REAL programme. MATERIALS AND METHODS: This multicentre, prospective, non-interventional, single-arm study (NCT05443334) followed participants for 34-44 weeks. Participants were treated as part of routine clinical practice and were naive to injectable glucose-lowering medication. The primary endpoint was the change in glycated haemoglobin (HbA(1c)) from baseline to end of study (EOS). Secondary endpoints included changes in body weight, the proportion of participants with HbA(1c) <7% at EOS, and treatment satisfaction. Selected outcomes were stratified (post hoc) by sodium-glucose cotransporter-2 inhibitor (SGLT2i) co-use and T2D duration. RESULTS: While 430 participants completed the study, 392 were on treatment at EOS. Estimated change in HbA(1c) was -1.4%-points (95%CI -1.5, -1.3; p < 0.0001) and in body weight -6.8% (95%CI -7.4, -6.1; p < 0.0001). In participants using SGLT2is, change in HbA(1c) was -1.8%-points (95%CI -2.1, -1.6; p < 0.0001) versus -1.2%-points (95%CI -1.3, -1.1; p < 0.0001) in participants without SGLT2is. HbA(1c) change was -1.4%-points (95%CI -1.6, -1.3; p < 0.0001) in participants with T2D duration 5 years. At EOS, 77.4% of participants achieved an HbA(1c) level <7% and 33.3% had >/=1%-point reduction in HbA(1c) and >/=5% body weight reduction. Treatment satisfaction increased, and no new safety concerns were identified. CONCLUSIONS: Oral semaglutide treatment improved glycaemic control and reduced body weight in Spanish clinical practice. Early intervention and SGLT2i co-treatment were associated with more favourable outcomes. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Delgado Alvarez, Elias AU - Delgado Alvarez E AUID- ORCID: 0000-0001-6114-9712 AD - Hospital Universitario Central de Asturias, Universidad de Oviedo, Instituto de Investigacion Sanitaria del Principado de Asturias, Oviedo, Spain. AD - Centro de Investigacion Biomedica en Red Enfermedades Raras (CIBERER), Madrid, Spain. FAU - Morales Portillo, Cristobal AU - Morales Portillo C AUID- ORCID: 0000-0003-0348-826X AD - Hospital Vithas Sevilla, Servicio de Endocrinologia, Sevilla, Spain. FAU - Abreu Padin, Cristina AU - Abreu Padin C AUID- ORCID: 0000-0002-9238-443X AD - Complejo Asistencial de Segovia, Servicio de Endocrinologia, Segovia, Spain. FAU - Aliaga Verdugo, Alberto AU - Aliaga Verdugo A AUID- ORCID: 0000-0002-4717-4345 AD - Clinica Nuevas Tecnologias en Diabetes y Endocrinologia, Sevilla, Spain. FAU - Piera Carbonell, Ana AU - Piera Carbonell A AUID- ORCID: 0000-0003-3948-0833 AD - Naranco Health Center, Public Health Service of the Principality of Asturias (SESPA), Oviedo, Spain. AD - Department of Medicine, University of Oviedo, Oviedo, Spain. FAU - Cadenas Gonzalez, Aida AU - Cadenas Gonzalez A AUID- ORCID: 0000-0002-7657-433X AD - Hospital Universitario Galdakao - Usansolo, Bizkaia, Spain. FAU - Amor Valero, Jaime AU - Amor Valero J AUID- ORCID: 0000-0001-6186-0846 AD - Novo Nordisk Pharma SA, Madrid, Spain. FAU - Gonzalez Lopez, Veronica AU - Gonzalez Lopez V AD - Novo Nordisk Pharma SA, Madrid, Spain. FAU - Rasmussen, Christina Louise AU - Rasmussen CL AUID- ORCID: 0000-0003-3920-373X AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Scheuer, Stine Hedegaard AU - Scheuer SH AUID- ORCID: 0000-0002-1244-9871 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bellido Guerrero, Diego AU - Bellido Guerrero D AUID- ORCID: 0000-0003-0631-2710 AD - Clinica de Endocrinologia y Nutricion Dr. Bellido, Ferrol, Spain. LA - eng SI - ClinicalTrials.gov/NCT05443334 GR - N/A (sponsor of the clinical study)/Novo Nordisk A/S/ PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20250624 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood/epidemiology MH - Glycated Hemoglobin/analysis MH - Prospective Studies MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Spain/epidemiology MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12326947 OTO - NOTNLM OT - GLP-1 analogue OT - glycaemic control OT - real-world evidence OT - semaglutide OT - type 2 diabetes OT - weight control COIS- The authors disclose the following competing interests: Elias Delgado Alvarez has received unrestricted research support from AstraZeneca, Novo Nordisk, Sanofi, Pfizer, and Roche and has received consulting fees and/or honoraria for membership on advisory boards and speakers bureaus from AstraZeneca, Novo Nordisk, Eli Lilly, Sanofi, GlaxoSmithKline, Pfizer, Almirall, Novartis, Abbott Laboratories, Esteve, and Merck Sharp & Dohme. Cristobal Morales Portillo has collaborated on clinical studies with Novo Nordisk, Sanofi, AstraZeneca, Pfizer, Eli Lilly, Merck, Lexicon, Hanmi, Janssen, Boehringer Ingelheim, Takeda, Roche, and Theracos and has served on advisory boards for Novo Nordisk, Eli Lilly, MSD, Boehringer Ingelheim, AstraZeneca, Sanofi, and Abbot and has received speaker fees from Sanofi, Novo Nordisk, AstraZeneca, Roche, Eli Lilly, Boehringer Ingelheim, MSD, Ferrer, Janssen, and Abbot. Cristina Abreu Padin has received research support from Sanofi, Novo Nordisk, Boehringer Ingelheim and Eli Lilly and has acted as a speaker for Sanofi, Novo Nordisk, Boehringer Ingelheim, AstraZeneca and Bristol-Myers Squibb. Alberto Aliaga Verdugo has received research support from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Gan & Lee, Janssen, Kowa, Lexicon, MSD, Novo Nordisk, Pfizer, and Sanofi and has received honoraria for membership on advisory boards and speakers bureaus from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi. Ana Piera Carbonell has received fees for participation in presentations, talks, courses, conferences, or publications from Novo Nordisk, Novartis, MSD, Ferrer, Bayer, Sanofi-Aventis, AstraZeneca, Esteve, Boehringer Ingelheim, and Mylan. Aida Cadenas Gonzalez has received support for training, research, or outreach from GSK, Boehringer Ingelheim, Menarini, Janssen, Novo Nordisk, Pfizer, Esteve, Sanofi, Eli Lilly, Viatris, Faes, Alter, AstraZeneca, MSD, Fresenius, Rovi, Mundipharma, Daiichi Sankyo, Novartis, and Amarin. Jaime Amor Valero is an employee of Novo Nordisk Pharma SA. Veronica Gonzalez Lopez is an employee of Novo Nordisk Pharma SA. Christina Louise Rasmussen is an employee of Novo Nordisk A/S. Stine Hedegaard Scheuer is an employee of Novo Nordisk A/S. Diego Bellido Guerrero has received unrestricted research support from Novo Nordisk, Sanofi, Pfizer, Nestle HC, Persan Pharma, Abbott Laboratories and Eli Lilly and has received consulting fees and/or honoraria for membership on advisory boards and speakers bureaus from Novo Nordisk, Sanofi, Abbott Laboratories, and Eli Lilly. EDAT- 2025/06/25 00:28 MHDA- 2025/08/06 12:29 PMCR- 2025/08/06 CRDT- 2025/06/24 23:03 PHST- 2025/05/22 00:00 [revised] PHST- 2025/04/08 00:00 [received] PHST- 2025/05/30 00:00 [accepted] PHST- 2025/08/06 12:29 [medline] PHST- 2025/06/25 00:28 [pubmed] PHST- 2025/06/24 23:03 [entrez] PHST- 2025/08/06 00:00 [pmc-release] AID - DOM16523 [pii] AID - 10.1111/dom.16523 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Sep;27(9):4812-4824. doi: 10.1111/dom.16523. Epub 2025 Jun 24. PMID- 40552638 OWN - NLM STAT- MEDLINE DCOM- 20250913 LR - 20260829 IS - 1875-8908 (Electronic) IS - 1387-2877 (Print) IS - 1387-2877 (Linking) VI - 106 IP - 4 DP - 2025 Aug TI - Associations of semaglutide with Alzheimer's disease-related dementias in patients with type 2 diabetes: A real-world target trial emulation study. PG - 1509-1522 LID - 10.1177/13872877251351329 [doi] AB - BACKGROUND: Almost half of the dementia cases are preventable. Semaglutide treats several medical conditions that are risk factors for dementia. OBJECTIVE: We aim to investigate if semaglutide is associated with a decreased risk of dementia. METHODS: We conducted emulation target trials based on a nationwide population-based database of patient electronic health records (EHRs) in the US among 1,710,995 eligible patients with type 2 diabetes (T2D) comparing semaglutide with other antidiabetic medications. First-time diagnosis of Alzheimer's disease-related dementia (ADRD) including vascular dementia, frontotemporal dementia, Lewy body dementia and other dementias were examined using Cox proportional hazards and Kaplan-Meier survival analyses during a 3-year follow-up. Models were adjusted by propensity-score matching. RESULTS: We show that semaglutide was associated with a significantly reduced risk of overall ADRD incidence with a hazard ratio ranging from 0.54 (0.49-0.59) compared with insulin, 0.67 (0.61-0.74) compared with metformin, to 0.80 (0.72-0.89) compared with older generation glucagon-like peptide-1 agonists (GLP-1RAs). The association varied for specific dementia types, with significantly reduced risk of vascular dementia and no evidence of associations with frontotemporal and Lewy body dementias. CONCLUSIONS: These findings provide evidence supporting protective effects of semaglutide on dementias in patients with T2D. Future works are needed to establish the causal relationships through randomized clinical trials and to characterize the underlying mechanisms. FAU - Wang, William AU - Wang W AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Davis, Pamela B AU - Davis PB AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Qi, Xin AU - Qi X AD - Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Gurney, Mark AU - Gurney M AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Perry, George AU - Perry G AUID- ORCID: 0000-0002-6547-0172 AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA. AD - Department of Neuroscience, Development and Regenerative Biology, College of Sciences, The University of Texas at San Antonio, San Antonio, TX, USA. FAU - Volkow, Nora D AU - Volkow ND AD - National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, North Bethesda, MD, USA. FAU - Kaelber, David C AU - Kaelber DC AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, OH, USA. FAU - Xu, Rong AU - Xu R AUID- ORCID: 0000-0003-3127-4795 AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA. LA - eng GR - R01 AG057557/AG/NIA NIH HHS/United States GR - R01 AG076649/AG/NIA NIH HHS/United States GR - R01 AG076051/AG/NIA NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States GR - R01 AG074346/AG/NIA NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States GR - R01 AG065240/AG/NIA NIH HHS/United States GR - RF1 AG076649/AG/NIA NIH HHS/United States GR - UM1 TR004528/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20250624 PL - United States TA - J Alzheimers Dis JT - Journal of Alzheimer's disease : JAD JID - 9814863 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - *Alzheimer Disease/epidemiology/prevention & control MH - Aged MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Aged, 80 and over MH - *Dementia/epidemiology MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12262134 MID - NIHMS2093772 OTO - NOTNLM OT - Alzheimer's disease related dementias OT - Alzheimer's disease OT - Lewy body dementia OT - dementia OT - frontotemporal dementia OT - semaglutide OT - target trial emulation OT - type 2 diabetes OT - vascular dementia COIS- Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: George Perry is an Editor-in-Chief of this journal but was not involved in the peer-review process of this article nor had access to any information regarding its peer-review. The remaining authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/06/24 13:08 MHDA- 2025/09/13 12:30 PMCR- 2025/07/15 CRDT- 2025/06/24 07:13 PHST- 2025/09/13 12:30 [medline] PHST- 2025/06/24 13:08 [pubmed] PHST- 2025/06/24 07:13 [entrez] PHST- 2025/07/15 00:00 [pmc-release] AID - 10.1177/13872877251351329 [doi] PST - ppublish SO - J Alzheimers Dis. 2025 Aug;106(4):1509-1522. doi: 10.1177/13872877251351329. Epub 2025 Jun 24. PMID- 40549942 OWN - NLM STAT- MEDLINE DCOM- 20250801 LR - 20260127 IS - 1940-5480 (Electronic) IS - 1067-151X (Linking) VI - 33 IP - 16 DP - 2025 Jun 17 TI - Reduced 90-Day Cardiovascular and Infectious Complications After Open Reduction Internal Fixation of Ankle Fractures in Type II Diabetic Patients Using Semaglutide Preoperatively. PG - e971-e978 LID - 10.5435/JAAOS-D-25-00439 [doi] AB - BACKGROUND: Patients with type II diabetes mellitus (T2DM) are known to have inferior postoperative outcomes after open reduction and internal fixation (ORIF) of ankle fractures. Semaglutide (the active agent in Ozempic) has encouragingly been associated with improved postoperative outcomes across multiple elective orthopaedic surgeries; however, this has not been assessed for patients with T2DM undergoing ankle fracture ORIF. METHODS: Adult patients with T2DM who underwent ankle fracture ORIF were identified from the 2010-Q1 2023 PearlDiver M170Ortho database. Exclusion criteria included the following: age younger than 18, high-energy injury mechanisms, concomitant tibial plafond fracture, other non-ankle traumatic injuries, neoplastic or infectious diagnoses within 30 days preoperatively, and those with <90 days of follow-up. Patients with T2DM who used semaglutide within 1 year before ankle fracture ORIF were identified and matched 1:1 with patients with T2DM who had not used semaglutide based on age, sex, Elixhauser Comorbidity Index, end-organ diabetes complications, obesity (body mass index <30 vs. >30), insulin use, metformin use, sodium-glucose cotransport-2 inhibitor use, and insurance plan. The odds of 90-day adverse events were compared by multivariable logistic regression controlling for age, sex, and Elixhauser Comorbidity Index. Bonferroni correction of P < 0.005 was used to reduce the risk of type I error. RESULTS: Among patients with T2DM undergoing ankle fracture ORIF, semaglutide use was noted for 2,700 patients (2.73%). After matching, there were 804 (+)semaglutide and 804 (-)semaglutide patients. On multivariable analysis, (+)semaglutide patients had significantly lower odds of 90-day deep vein thrombosis (odds ratio [OR] 0.24), myocardial infarction (OR 0.34), surgical site infection (OR 0.30), sepsis (OR 0.38), pneumonia (OR 0.27), urinary tract infection (OR 0.27), wound dehiscence (OR 0.31), and emergency department visit (OR 0.45; P < 0.001 for all). CONCLUSION: This study found reductions in 90-day cardiovascular and infectious complications after ORIF of ankle fractures for patients with T2DM using semaglutide preoperatively as part of their glycemic control regimen. LEVEL OF EVIDENCE: Level III. CI - Copyright (c) 2025 by the American Academy of Orthopaedic Surgeons. FAU - Seddio, Anthony E AU - Seddio AE AD - From the Department of Orthopaedics and Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Vasudevan, Rajiv S AU - Vasudevan RS FAU - Jonnalagadda, Anshu AU - Jonnalagadda A FAU - Slevin, John P AU - Slevin JP FAU - Grauer, Jonathan N AU - Grauer JN AUID- ORCID: 0000-0002-2626-7278 FAU - Fram, Brianna R AU - Fram BR LA - eng PT - Journal Article DEP - 20250617 PL - United States TA - J Am Acad Orthop Surg JT - The Journal of the American Academy of Orthopaedic Surgeons JID - 9417468 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Female MH - *Ankle Fractures/surgery/complications MH - *Fracture Fixation, Internal/adverse effects/methods MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology MH - *Postoperative Complications/prevention & control/epidemiology MH - *Surgical Wound Infection/epidemiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Retrospective Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/06/24 11:03 MHDA- 2025/08/01 18:34 CRDT- 2025/06/23 15:13 PHST- 2025/04/06 00:00 [received] PHST- 2025/05/03 00:00 [accepted] PHST- 2025/08/01 18:34 [medline] PHST- 2025/06/24 11:03 [pubmed] PHST- 2025/06/23 15:13 [entrez] AID - 00124635-990000000-01352 [pii] AID - 10.5435/JAAOS-D-25-00439 [doi] PST - epublish SO - J Am Acad Orthop Surg. 2025 Jun 17;33(16):e971-e978. doi: 10.5435/JAAOS-D-25-00439. PMID- 40544432 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 393 IP - 7 DP - 2025 Aug 14 TI - Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. PG - 648-659 LID - 10.1056/NEJMoa2502082 [doi] AB - BACKGROUND: Cagrilintide and semaglutide have each been shown to induce weight loss as monotherapies. Data are needed on the coadministration of cagrilintide and semaglutide (called CagriSema) for weight management in adults with type 2 diabetes, including those in a subgroup who are undergoing continuous glucose monitoring. METHODS: In this phase 3a, double-blind, randomized, placebo-controlled trial conducted in 12 countries, we assigned adults with a body-mass index of 27 or more, a glycated hemoglobin level of 7 to 10%, and type 2 diabetes in a 3:1 ratio to receive once-weekly cagrilintide-semaglutide (2.4 mg each) or placebo, along with lifestyle intervention, for 68 weeks. The two primary end points were the percent change in body weight and the percentage of patients with a weight reduction of at least 5%. Additional end points were changes in glycemic measures and safety assessments. Effect estimates were calculated with the use of the treatment-policy estimand (consistent with the intention-to-treat principle). RESULTS: A total of 1206 patients underwent randomization to either the cagrilintide-semaglutide group (904 patients) or the placebo group (302 patients). The estimated mean change in body weight from baseline to week 68 was -13.7% in the cagrilintide-semaglutide group and -3.4% in the placebo group (estimated difference, -10.4 percentage points; 95% confidence interval, -11.2 to -9.5; P<0.001). More patients in the cagrilintide-semaglutide group than in the placebo group had a weight reduction of 5% or more (P<0.001); the same was true of reductions of at least 10%, 15%, and 20% (P<0.001 for the last comparison). The percentage of patients who had a glycated hemoglobin level of 6.5% or less was 73.5% in the cagrilintide-semaglutide group and 15.9% in the placebo group. Gastrointestinal adverse events were reported by 72.5% of the patients in the cagrilintide-semaglutide group and 34.4% in the placebo group, most of which were transient and mild or moderate in severity. CONCLUSIONS: Once-weekly cagrilintide-semaglutide (at a dose of 2.4 mg each) resulted in a significantly lower body weight than placebo in adults with obesity and type 2 diabetes. (Funded by Novo Nordisk; REDEFINE 2 ClinicalTrials.gov number, NCT05394519.). CI - Copyright (c) 2025 Massachusetts Medical Society. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, United Kingdom. AD - NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom. FAU - Bajaj, Harpreet S AU - Bajaj HS AD - Endocrine and Metabolic Research, LMC Healthcare, Brampton, ON, Canada. FAU - Broholm, Christa AU - Broholm C AD - Novo Nordisk, Soborg, Denmark. FAU - Eliasen, Astrid AU - Eliasen A AD - Novo Nordisk, Soborg, Denmark. FAU - Garvey, W Timothy AU - Garvey WT AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham. FAU - le Roux, Carel W AU - le Roux CW AD - Diabetes Complications Research Centre, University College Dublin School of Medicine, Dublin. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine, Endocrinology Division, University of Texas Southwestern Medical Center, Dallas. AD - Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas. FAU - Lyndgaard, Christian Boge AU - Lyndgaard CB AD - Novo Nordisk, Soborg, Denmark. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Velocity Clinical Research at Medical City, Dallas. FAU - Pedersen, Sue D AU - Pedersen SD AD - C-ENDO Diabetes and Endocrinology Clinic Calgary, Calgary, AB, Canada. CN - REDEFINE 2 Study Group LA - eng SI - ClinicalTrials.gov/NCT05394519 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250622 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Islet Amyloid Polypeptide) RN - 0 (Drug Combinations) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - AO43BIF1U8 (cagrilintide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/analysis MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Double-Blind Method MH - Glycated Hemoglobin/analysis MH - Hypoglycemia/blood/chemically induced/diagnosis MH - Life Style MH - *Obesity/blood/complications/drug therapy MH - *Overweight/blood/complications/drug therapy MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - *Islet Amyloid Polypeptide/administration & dosage/adverse effects MH - Drug Combinations MH - Treatment Outcome MH - Intention to Treat Analysis MH - Continuous Glucose Monitoring MH - Glucagon-Like Peptide 1 MH - Semaglutide FIR - Sourij, Harald IR - Sourij H FIR - Kautzky-Willer, Alexandra IR - Kautzky-Willer A FIR - Adlbrecht, Christopher IR - Adlbrecht C FIR - Ludvik, Bernhard IR - Ludvik B FIR - Clodi, Martin IR - Clodi M FIR - Fliesser-Gorzer, Evelyn IR - Fliesser-Gorzer E FIR - Ajala, Buki IR - Ajala B FIR - Akhras, Ronald IR - Akhras R FIR - Bajaj, Harpreet IR - Bajaj H FIR - Dzongowski, Peter IR - Dzongowski P FIR - Jones, Michael IR - Jones M FIR - Khandwala, Hasnain IR - Khandwala H FIR - Noronha, Luis IR - Noronha L FIR - O'Keefe, Dennis IR - O'Keefe D FIR - Pedersen, Sue IR - Pedersen S FIR - Sahyouni, Elie IR - Sahyouni E FIR - Tailor, Chetna IR - Tailor C FIR - Wharton, Sean IR - Wharton S FIR - Garg, Naveen IR - Garg N FIR - Dahl, Dominik IR - Dahl D FIR - Erlinger, Moritz Mauro IR - Erlinger MM FIR - Hagenow, Andreas IR - Hagenow A FIR - Rose, Ludger IR - Rose L FIR - Sauter, Joachim IR - Sauter J FIR - Zeller, Helga IR - Zeller H FIR - Stahl, Hans-Detlev IR - Stahl HD FIR - Vidal, Simon IR - Vidal S FIR - Segner, Alexander IR - Segner A FIR - Katona, Eva IR - Katona E FIR - Pall, Istvan IR - Pall I FIR - Szocs, Albert IR - Szocs A FIR - Barta, Gyorgy IR - Barta G FIR - Nadas, Judit IR - Nadas J FIR - Revesz, Katalin IR - Revesz K FIR - Valkusz, Zsuzsanna IR - Valkusz Z FIR - Lavanya, Alapati IR - Lavanya A FIR - Prakash, Anupam IR - Prakash A FIR - Selvan, Chitra IR - Selvan C FIR - R, Chandni IR - R C FIR - Gupta, Yashdeep IR - Gupta Y FIR - Kashiva, Reema IR - Kashiva R FIR - Jabbar, P K IR - Jabbar PK FIR - Lila, Anurag IR - Lila A FIR - V, Mohan IR - V M FIR - Gupta, Sunil IR - Gupta S FIR - Marwah, Tiven IR - Marwah T FIR - Gadve, Sharvil IR - Gadve S FIR - Bhadada, Sanjay IR - Bhadada S FIR - Chaudhury, Tirthankar IR - Chaudhury T FIR - Seshadri, Krishna G IR - Seshadri KG FIR - Sharma, Balram IR - Sharma B FIR - Bhagwat, Nikhil IR - Bhagwat N FIR - le Roux, Carel IR - le Roux C FIR - Byrne, Maria IR - Byrne M FIR - Dunne, Fidelma IR - Dunne F FIR - Phelan, Niamh IR - Phelan N FIR - Sreenan, Seamus IR - Sreenan S FIR - Tokuyama, Takahiko IR - Tokuyama T FIR - Tosaki, Takahiro IR - Tosaki T FIR - Nishizawa, Hitoshi IR - Nishizawa H FIR - Yoshimitsu, Yamasaki IR - Yoshimitsu Y FIR - Osonoi, Takeshi IR - Osonoi T FIR - Mohamed Shah, Fatimah Zaherah IR - Mohamed Shah FZ FIR - Tan, Florence IR - Tan F FIR - Lee, Siow Ping IR - Lee SP FIR - Fam, Tem Lom IR - Fam TL FIR - Karim, Nor Afidah IR - Karim NA FIR - Hussein, Zanariah IR - Hussein Z FIR - Mustafa, Norlaila IR - Mustafa N FIR - Lee, Li Yuan IR - Lee LY FIR - Abdullah Hashim, Suraya Hanim IR - Abdullah Hashim SH FIR - Sorobka, Barbara IR - Sorobka B FIR - Ostrowska, Lucyna IR - Ostrowska L FIR - Madej, Andrzej IR - Madej A FIR - Hoffmann, Michal IR - Hoffmann M FIR - Matyjaszek-Matuszek, Beata IR - Matyjaszek-Matuszek B FIR - Pankowska, Ewa IR - Pankowska E FIR - Poplawska-Kita, Anna IR - Poplawska-Kita A FIR - Jankowski, Piotr IR - Jankowski P FIR - Rucinski, Gabriel IR - Rucinski G FIR - Bogdanski, Pawel IR - Bogdanski P FIR - Palka, Katarzyna IR - Palka K FIR - Gierach, Marcin IR - Gierach M FIR - Kedzierska-Kapuza, Karolina IR - Kedzierska-Kapuza K FIR - Wosko, Edyta IR - Wosko E FIR - Sriphrapradang, Chutintorn IR - Sriphrapradang C FIR - Piyayotai, Dilok IR - Piyayotai D FIR - Deerochanawong, Chaicharn IR - Deerochanawong C FIR - Pongchaiyakul, Chatlert IR - Pongchaiyakul C FIR - Boonchaya-Anant, Patchaya IR - Boonchaya-Anant P FIR - Sriwijitkamol, Apiradee IR - Sriwijitkamol A FIR - Bain, Stephen IR - Bain S FIR - Capehorn, Matt IR - Capehorn M FIR - Clark, Rebecca IR - Clark R FIR - Creely, Steven IR - Creely S FIR - Davies, Melanie IR - Davies M FIR - Wilson, Laurie IR - Wilson L FIR - Gunstone, Anthony IR - Gunstone A FIR - King, Rhodri IR - King R FIR - Krzeminski, Andre IR - Krzeminski A FIR - Nyekiova, Maria IR - Nyekiova M FIR - Paul, Carolyn IR - Paul C FIR - Paul, Neil IR - Paul N FIR - Philbey, Chris IR - Philbey C FIR - Russell, Georgina IR - Russell G FIR - Singh, Ivor IR - Singh I FIR - Strzelecka, Anna IR - Strzelecka A FIR - Wyatt, Nell IR - Wyatt N FIR - Donnell, Philip O IR - Donnell PO FIR - Al-Karadsheh, Amer IR - Al-Karadsheh A FIR - Bailey, Timothy IR - Bailey T FIR - Barranco-Santana, Elizabeth A IR - Barranco-Santana EA FIR - Bartilucci, Darlene IR - Bartilucci D FIR - Bays, Harold IR - Bays H FIR - Malaeb, Samar IR - Malaeb S FIR - Bhargava, Anuj IR - Bhargava A FIR - Biggs, William IR - Biggs W FIR - Blevins, Thomas IR - Blevins T FIR - Broker, Robert IR - Broker R FIR - Bressler, Peter IR - Bressler P FIR - Brian, Susan IR - Brian S FIR - Chaicha-Brom, Tira IR - Chaicha-Brom T FIR - Chang, Anna IR - Chang A FIR - Christiansen, Mark IR - Christiansen M FIR - Dunn, Leonard IR - Dunn L FIR - Guzman, David IR - Guzman D FIR - Gerety, Gregg IR - Gerety G FIR - Harris, Kathleen IR - Harris K FIR - Hewitt, Mitzie IR - Hewitt M FIR - Houser, Patricia IR - Houser P FIR - Jardula, Michael IR - Jardula M FIR - Klein, Eric IR - Klein E FIR - Morin, David IR - Morin D FIR - Murray, Alexander IR - Murray A FIR - Oliver, David IR - Oliver D FIR - Pratley, Richard IR - Pratley R FIR - Pullman, John IR - Pullman J FIR - Reed, John 3rd IR - Reed J 3rd FIR - Rosenblit, Paul IR - Rosenblit P FIR - Rosenstock, Julio IR - Rosenstock J FIR - Scott, John IR - Scott J FIR - Smith, Timothy IR - Smith T FIR - Snyder, Brian IR - Snyder B FIR - Sugimoto, Danny IR - Sugimoto D FIR - Sultan, Senan IR - Sultan S FIR - Welch, Michelle IR - Welch M FIR - Woolley, Joseph IR - Woolley J FIR - Lingvay, Ildiko IR - Lingvay I FIR - Pau, Cindy IR - Pau C FIR - Gilbert, John IR - Gilbert J FIR - Greenway, Frank IR - Greenway F FIR - Wayne, Jeffrey IR - Wayne J FIR - Block, Bradley IR - Block B FIR - Cruz, Humberto IR - Cruz H EDAT- 2025/06/23 04:45 MHDA- 2025/08/31 20:02 CRDT- 2025/06/22 11:43 PHST- 2025/08/31 20:02 [medline] PHST- 2025/06/23 04:45 [pubmed] PHST- 2025/06/22 11:43 [entrez] AID - 10.1056/NEJMoa2502082 [doi] PST - ppublish SO - N Engl J Med. 2025 Aug 14;393(7):648-659. doi: 10.1056/NEJMoa2502082. Epub 2025 Jun 22. PMID- 40543068 OWN - NLM STAT- MEDLINE DCOM- 20250820 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 9 DP - 2025 Sep 1 TI - Benefit of Semaglutide in Symptomatic Peripheral Artery Disease by Baseline Type 2 Diabetes Characteristics: Insights From STRIDE, a Randomized, Placebo-Controlled, Double-Blind Trial. PG - 1529-1535 LID - 10.2337/dc25-1082 [doi] AB - OBJECTIVE: The Semaglutide and Walking Capacity in People with Symptomatic Peripheral Artery Disease and Type 2 Diabetes (STRIDE) trial (NCT04560998) showed that once-weekly subcutaneous semaglutide 1.0 mg significantly improved functional outcomes, symptoms, and quality of life in individuals with symptomatic peripheral artery disease (PAD) and type 2 diabetes. Whether these benefits are consistent across diabetes-related characteristics remains unclear. RESEARCH DESIGN AND METHODS: The primary outcome was the ratio to baseline (ETR) in maximum walking distance (MWD), with pain-free walking distance (PFWD) as a key secondary end point. Both were measured at 52 weeks using a constant load treadmill. Subgroup analyses were performed by diabetes duration, BMI, HbA1c, and diabetes medications. A mixed model for repeated measurements was used, incorporating treatment, region, and subgroup as fixed factors, and baseline value as covariate, along with the treatment-by-subgroup interaction. RESULTS: Among 792 participants (median diabetes duration 12.2 years, HbA1c 7.1%, and BMI 28.7 kg/m2), 35.1% used sodium-glucose cotransporter 2 inhibitors and 31.7% used insulin. Semaglutide significantly improved MWD regardless of diabetes duration (ETR of 1.15 vs. 1.13 for <10 vs. >/=10 years, P = 0.80), BMI (1.12 vs. 1.16 for <30 vs. >/=30 kg/m2, P = 0.58), HbA1c (1.13 for <7% and >/=7%, P = 0.99), or medication use. Semaglutide also improved PFWD across subgroups (P > 0.1 for all interactions). BMI reduction correlated weakly with MWD improvements and was more pronounced in the control individuals with higher baseline BMI. Safety outcomes were consistent across subgroups. CONCLUSIONS: Semaglutide improved walking function in people with PAD and type 2 diabetes, including individuals without obesity and those with well-controlled HbA1c. Benefits were consistent across BMI and HbA1c categories, supporting effectiveness beyond weight or glycemic changes. CI - (c) 2025 by the American Diabetes Association. FAU - Rasouli, Neda AU - Rasouli N AUID- ORCID: 0000-0003-1269-3580 AD - Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, and VA Eastern Colorado Health Care, Aurora, CO. FAU - Guder Arslan, Ecenur AU - Guder Arslan E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Houlind, Kim AU - Houlind K AD - Department of Vascular Surgery, Lillebaelt Hospital, Kolding, Denmark. AD - Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. FAU - Ludvik, Bernhard AU - Ludvik B AD - 1st Medical Department and Karl Landsteiner Institute of Obesity and Metabolic Disorders, Landstrasse Clinic, Vienna, Austria. FAU - Nordanstig, Joakim AU - Nordanstig J AD - Institute of Medicine, Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden. FAU - Sourij, Harald AU - Sourij H AUID- ORCID: 0000-0003-3510-9594 AD - Cardiometabolic Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. FAU - Thomas, Sebastian AU - Thomas S AD - Novo Nordisk GBS India, Bangalore, India. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiovascular Surgery, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. FAU - Bonaca, Marc P AU - Bonaca MP AD - CPC Clinical Research and Division of Cardiology, University of Colorado School of Medicine, Aurora, CO. LA - eng GR - Novo Nordisk A/S, Denmark/ PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/blood/complications/drug therapy MH - Double-Blind Method MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - *Peripheral Arterial Disease/blood/drug therapy/etiology MH - Walking MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12368379 COIS- Duality of Interest. N.R. has received consultation fees and/or research funding from Novo Nordisk, Eli Lilly, Sanofi, and SomaLogic. E.G.A. is an employee at Novo Nordisk. A.-M.C. is an employee and shareholder at Novo Nordisk. K.H. has received fees for consulting from Novo Nordisk and LeMaitre and funding for research from the Novo Nordisk Foundation. B.L. has received research support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Madrigal, MSD, Novo Nordisk, and Sanofi, and has received honoraria as a consultant and speaker from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk. H.S. has received consulting fees and speaker honoraria from Amgen, Amarin, Boehringer Ingelheim, Novo Nordisk, Novartis, Daiichi Sankyo, Eli Lilly, and Cancom, and has received research funding from Boehringer Ingelheim, Novo Nordisk, and Eli Lilly (paid to the Medical University of Graz, Austria). S.T. is an employee and shareholder at Novo Nordisk. S.V. reports receiving research grants and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Anthos, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, S&L Solutions Event Management, and Sanofi. M.P.B. is the executive director of CPC, a nonprofit academic research organization affiliated with the University of Colorado that receives or has received research grant/consulting funding between August 2021 and the present from Abbott Laboratories, Agios Pharmaceuticals, Alexion Pharma, Alnylam Pharmaceuticals, Amgen, Angionetics, Anthos Therapeutics, ARCA Biopharma, Array BioPharma, AstraZeneca and affiliates, Atentiv, Audentes Therapeutics, Bayer and affiliates, Beth Israel Deaconess Medical Center, Better Therapeutics, Boston Clinical Research Institute, Bristol-Myers Squibb, Cambrian Biopharma, Cardiol Therapeutics, CellResearch, Cleerly, Cook Regentec, CSL Behring, Eidos Therapeutics, EP Trading, EPG Communication Holdings, Epizon Pharma, Esperion Therapeutics, Everlywell, Exicon Consulting, Faraday Pharmaceuticals, Foresee Pharmaceuticals, Fortress Biotech, HDL Therapeutics, Heartflow, Hummingbird Bioscience, Insmed, Ionis Pharmaceuticals, IQVIA, Janssen and affiliates, Kowa Research Institute, Lexicon Pharmaceuticals, Medimmune, Medpace, Merck and affiliates, Nectero Medical, Novartis, Novo Nordisk, Osiris Therapeutics, Pfizer, PhaseBio Pharmaceuticals, PPD Development, Prairie Education and Research Cooperative, Prothena Biosciences, Regeneron Pharmaceuticals, Regio Biosciences, Sanifit Therapeutics, Sanofi-Aventis Groupe, Silence Therapeutics, Silence Therapeutics, Smith & Nephew, Stealth BioTherapeutics, Brigham & Women's Hospital, The Feinstein Institutes for Medical Research, Thrombosis Research Institute, VarmX, Virta Health, Worldwide Clinical Trials, WraSer Pharmaceuticals, and Yale Cardiovascular Research Group. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/06/21 20:44 MHDA- 2025/08/31 20:02 PMCR- 2025/06/21 CRDT- 2025/06/21 14:32 PHST- 2025/05/08 00:00 [received] PHST- 2025/05/30 00:00 [accepted] PHST- 2025/08/31 20:02 [medline] PHST- 2025/06/21 20:44 [pubmed] PHST- 2025/06/21 14:32 [entrez] PHST- 2025/06/21 00:00 [pmc-release] AID - 160652 [pii] AID - 251082 [pii] AID - 10.2337/dc25-1082 [doi] PST - ppublish SO - Diabetes Care. 2025 Sep 1;48(9):1529-1535. doi: 10.2337/dc25-1082. PMID- 40538007 OWN - NLM STAT- MEDLINE DCOM- 20250901 LR - 20260127 IS - 1440-1746 (Electronic) IS - 0815-9319 (Linking) VI - 40 IP - 9 DP - 2025 Sep TI - Mechanism of Semaglutide in MASLD Treatment: Where Is the Master Key? PG - 2163-2175 LID - 10.1111/jgh.17037 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is used for weight reduction and metabolic improvement. Semaglutide effectively improves MASH but not confers histological fibrosis resolution. The key question remains whether semaglutide exerts direct, independent effects in ameliorating MASH or if its benefits are merely secondary to improvements in weight, insulin resistance, and glycemic control. The exact mechanisms of action through which semaglutide or other GLP-1 RAs offer liver protection are not entirely clear. METHODS: A comprehensive search in PubMed and EMBASE was conducted using the keywords "Semaglutide and NAFLD/MASLD", "glucagon-like peptide-1 receptor agonist and MASLD/NALFD", and "Semaglutide and type II diabetes/obesity and hypertension". Relevant papers published before February, 2025, were included. RESULTS: Semaglutide modulates several lipid-associated molecular pathways through unknown mechanisms. Preclinical and clinical studies suggest that semaglutide acts by (i) reducing appetite and increasing satiety, thereby decreasing dietary intake and subsequent free fatty acid export to the liver; (ii) reducing insulin resistance and improving insulin sensitivity and adipose dysfunction; (iii) reducing de novo lipogenesis by downregulating ChREBP and SREBP-1c signaling, as well as the expression of lipid-synthesizing genes; (iv) reducing the weight of white and brown adipose tissue; and (v) reducing inflammation by decreasing pro-inflammatory markers in GLP-1-expressing macrophages and favorably altering the gut microbiota. CONCLUSION: While this review explores the potential mechanisms of semaglutide action, the lack of GLP-1 receptor expression in the livers of mice and humans suggests that these mechanisms are associated with indirect modulation. Consequently, further mechanistic studies are needed to elucidate these pathways. TRIAL REGISTRATION: NOT APPLICABLE. CI - (c) 2025 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. FAU - Ezhilarasan, Devaraj AU - Ezhilarasan D AUID- ORCID: 0000-0002-5068-2383 AD - Department of Pharmacology, Hepatology and Molecular Medicine Lab, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai, Tamil Nadu, India. LA - eng GR - Adhoc 2020-4160/Indian Council of Medical Research/ PT - Journal Article PT - Review DEP - 20250619 PL - Australia TA - J Gastroenterol Hepatol JT - Journal of gastroenterology and hepatology JID - 8607909 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Humans MH - *Non-alcoholic Fatty Liver Disease/drug therapy/metabolism MH - Animals MH - Insulin Resistance MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Liver/metabolism/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Lipogenesis/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - MASH OT - fatty liver OT - fibrosis OT - glucagon-like peptide-1 OT - obesity OT - steatosis OT - type 2 diabetes EDAT- 2025/06/20 11:31 MHDA- 2025/09/01 16:44 CRDT- 2025/06/20 01:13 PHST- 2025/05/27 00:00 [revised] PHST- 2025/04/01 00:00 [received] PHST- 2025/06/08 00:00 [accepted] PHST- 2025/09/01 16:44 [medline] PHST- 2025/06/20 11:31 [pubmed] PHST- 2025/06/20 01:13 [entrez] AID - 10.1111/jgh.17037 [doi] PST - ppublish SO - J Gastroenterol Hepatol. 2025 Sep;40(9):2163-2175. doi: 10.1111/jgh.17037. Epub 2025 Jun 19. PMID- 40537987 OWN - NLM STAT- MEDLINE DCOM- 20250806 LR - 20260824 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 9 DP - 2025 Sep TI - Indirect comparative efficacy and safety of tirzepatide 10 and 15 mg versus semaglutide 2.4 mg for the management of obesity and overweight in patients with type 2 diabetes. PG - 4709-4719 LID - 10.1111/dom.16508 [doi] AB - AIMS: This indirect treatment comparison (ITC) compared the efficacy and safety of tirzepatide with semaglutide for managing obesity or overweight in participants with type 2 diabetes (T2D), informed by the pivotal trials SURMOUNT-2 and STEP 2. MATERIALS AND METHODS: Participants had body mass index (BMI) >/= 27 kg/m(2), with >/=1 unsuccessful prior dietary weight reduction effort and glycated haemoglobin (HbA1c) 7%-10% on stable therapy. A heterogeneity assessment confirmed that study and patient baseline characteristics were similar. Bucher ITCs compared tirzepatide 10 and 15 mg once-weekly (QW) to semaglutide 2.4 mg QW via placebo, all adjunct to a reduced-calorie diet and increased physical activity. RESULTS: Tirzepatide 10 and 15 mg were associated with statistically significant greater reductions in weight, BMI and HbA1c versus semaglutide. Tirzepatide 15 mg was associated with statistically significant greater odds versus semaglutide of >/=5% and >/=15% weight reduction and statistically significant improvements in several cardiometabolic risk factors, including waist circumference, fasting plasma glucose and triglycerides. Both tirzepatide doses showed non-significant trends of greater improvements in high-density lipoprotein, low-density lipoprotein, systolic blood pressure and diastolic blood pressure versus semaglutide as well as a generally comparable safety profile to semaglutide. CONCLUSIONS: In this ITC versus semaglutide 2.4 mg, tirzepatide 10 and 15 mg were associated with statistically significant greater weight, BMI and HbA1c reduction and tirzepatide 15 mg with statistically significant improvements in multiple cardiometabolic risk factors crucial in managing obesity or overweight among patients with T2D. Both tirzepatide doses also had a generally similar safety profile to semaglutide. PLAIN LANGUAGE SUMMARY: What is the context and purpose of this research study? Excess weight and type 2 diabetes (T2D) are strongly connected, where most patients with T2D have obesity or overweight. Weight management is crucial for improving T2D outcomes and preventing its progression. Weight management comprises behavioural interventions, psychological support, dietary changes and physical activity programmes. Medications may also be prescribed or surgical options may also be considered. Two such medications for weight management are tirzepatide (up to 15 mg) and semaglutide (up to 2.4 mg), which are injected subcutaneously once per week to help control appetite by prolonging patients' feeling of fullness. These medications are also used at different doses to treat T2D. Because there were no clinical trials directly comparing tirzepatide and semaglutide, particularly in patients with both T2D and either obesity or overweight, this study aimed to indirectly compare the effectiveness and safety of tirzepatide and semaglutide for weight management in patients with overweight or obesity and T2D. What was done? We indirectly compared the efficacy and safety of two doses of tirzepatide (10 and 15 mg per week) versus semaglutide 2.4 mg per week for weight management in adults with both T2D and either obesity or overweight. We used data from two large clinical trials, SURMOUNT-2 and STEP 2, which tested tirzepatide and semaglutide, respectively, against a placebo, all adjunct to diet and exercise. An indirect treatment comparison of tirzepatide and semaglutide was then possible via the placebo arm acting as the common comparator. The similarity of study design and patient populations in the two trials was evaluated and found to be sufficiently close to allow meaningful comparisons. Appropriate statistical methodology was used to facilitate comparisons of the two trials. What were the main results? Compared to semaglutide 2.4 mg, the higher dose of tirzepatide (15 mg) was associated with a statistically significant improvement in several outcomes such as weight reduction, glycaemic outcomes and triglycerides, while the lower dose of tirzepatide (10 mg) was associated with some statistically significant improvements (e.g., weight reduction and HbA1c) and had otherwise comparable outcomes to semaglutide. However, both doses of tirzepatide were associated with statistically significant greater reductions in glycated haemoglobin A1c (HbA1c) compared to semaglutide, which is a key target of T2D treatment. Both doses of tirzepatide had a generally similar safety profile compared to semaglutide. What is the originality and relevance of this study? Currently, there are no clinical trials that compare tirzepatide and semaglutide directly for the management of obesity and overweight in patients with T2D. Previous studies have compared tirzepatide and semaglutide results from different clinical trials for weight management in patients without T2D, not specifically focusing on patients with T2D. This is the first study to indirectly compare tirzepatide and semaglutide for weight management in people with T2D who also have obesity or overweight. The findings of this study suggest that higher doses of tirzepatide may be more effective than semaglutide for weight reduction and improving other health-related outcomes in these patients. CI - (c) 2025 Eli Lilly and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ciudin, Andreea AU - Ciudin A AD - Endocrinology and Nutrition, Vall d'Hebron University Hospital, Barcelona, Spain. FAU - Johansson, Erin AU - Johansson E AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Zimner-Rapuch, Sarah AU - Zimner-Rapuch S AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Dimitriadis, Georgios K AU - Dimitriadis GK AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Bertrand, Marine AU - Bertrand M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Curteis, Tristan AU - Curteis T AD - Costello Medical, Manchester, UK. FAU - Clark, Laura J AU - Clark LJ AD - Costello Medical, Manchester, UK. FAU - Fan, Ludi AU - Fan L AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Sapin, Helene AU - Sapin H AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Bergmann, Jean-Francois AU - Bergmann JF AD - Department of Internal Medicine, Lariboisiere Hospital, AP-HP, University Paris-Cite, Paris, France. LA - eng GR - Eli Lilly and Company/ PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250619 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Anti-Obesity Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Anti-Obesity Agents/administration & dosage/adverse effects MH - Blood Glucose MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/complications/drug therapy/blood MH - Glycated Hemoglobin/analysis MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - *Tirzepatide/administration & dosage/adverse effects MH - Treatment Outcome MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12326929 OTO - NOTNLM OT - GIP OT - GLP-1 OT - type 2 diabetes OT - weight management COIS- AC: Honoraria from AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk; Member of the DMC of Boehringer Ingelheim clinical trials-SYNCRONIZE program; EJ, SZR, GKD, MB, LF, HS: Employee and shareholder of Eli Lilly and Company; TC, LJC: Employees of Costello Medical, which received payment from Eli Lilly and Company for analytical services for this study; JFB: Received honoraria from Abbvie, Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Gilead, GSK, IQVIA, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Takeda. EDAT- 2025/06/20 11:31 MHDA- 2025/08/06 12:30 PMCR- 2025/08/06 CRDT- 2025/06/20 01:03 PHST- 2025/05/13 00:00 [revised] PHST- 2025/01/31 00:00 [received] PHST- 2025/05/22 00:00 [accepted] PHST- 2025/08/06 12:30 [medline] PHST- 2025/06/20 11:31 [pubmed] PHST- 2025/06/20 01:03 [entrez] PHST- 2025/08/06 00:00 [pmc-release] AID - DOM16508 [pii] AID - 10.1111/dom.16508 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Sep;27(9):4709-4719. doi: 10.1111/dom.16508. Epub 2025 Jun 19. PMID- 40523289 OWN - NLM STAT- MEDLINE DCOM- 20250714 LR - 20260703 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 178 IP - 7 DP - 2025 Jul TI - Comparison of Semaglutide or Dulaglutide Versus Empagliflozin for Risk for Death and Cardiovascular Outcomes Among Patients With Type 2 Diabetes : Two Target Trial Emulation Studies. PG - 930-939 LID - 10.7326/ANNALS-24-00775 [doi] AB - BACKGROUND: Reduction of premature death and adverse cardiovascular outcomes is a key goal in type 2 diabetes management. OBJECTIVE: To compare mortality and cardiovascular event risks in patients treated with semaglutide versus empagliflozin and, secondarily, dulaglutide versus empagliflozin. DESIGN: Target trial emulation studies from observational data comparing semaglutide- or dulaglutide-treated patients with propensity score-matched patients treated with empagliflozin. SETTING: Health care system of 703 academic and community clinical practices. PARTICIPANTS: Patients aged 45 years or older with type 2 diabetes treated from 1 January 2019 to 31 December 2024 with semaglutide, dulaglutide, or empagliflozin. INTERVENTION: Initial treatment with semaglutide, dulaglutide, or empagliflozin. At baseline, concomitant treatment with other diabetes medication was permitted, excluding other glucagon-like peptide-1 receptor agonists or sodium-glucose cotransporter-2 inhibitors. MEASUREMENTS: A composite of death, myocardial infarction (MI), or stroke was the primary outcome, and secondary composite outcomes included death or MI, MI or stroke, and individual cardiac events. RESULTS: Patients treated with semaglutide (n = 7899) versus empagliflozin (n = 7899) were followed for a median of 2.2 years; the respective rates of the composite of death, MI, or stroke were 3.7% versus 4.5% at 2 years and 5.9% versus 6.9% at 3 years. Corresponding incidence rates for the composite outcome were 20.99 versus 23.56 per 1000 person-years, with a hazard ratio (HR) of 0.89 (95% CI, 0.78 to 1.02). The HRs for the individual outcomes were 0.97 (CI, 0.81 to 1.15) for death, 0.85 (CI, 0.68 to 1.05) for MI, and 0.62 (CI, 0.43 to 0.89) for stroke. Risks for dulaglutide- and empagliflozin-treated patients were similar for the composite outcome (HR, 1.03 [CI, 0.90 to 1.16]) and for death, MI, and stroke separately. LIMITATION: Observational study design, lack of data on cause-specific mortality, and residual confounding. CONCLUSION: Semaglutide treatment seems to confer some advantage over empagliflozin. This advantage was not observed for dulaglutide. PRIMARY FUNDING SOURCE: American Heart Association. FAU - Saeed, Anum AU - Saeed A AUID- ORCID: 0000-0003-1783-678X AD - School of Medicine, University of Pittsburgh, and Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania (A.S., A.K., S.R., O.M.). FAU - Mulukutla, Suresh R AU - Mulukutla SR AD - School of Medicine, University of Pittsburgh; Heart and Vascular Institute, UPMC; and Clinical Analytics, UPMC, Pittsburgh, Pennsylvania (S.R.M.). FAU - Thoma, Floyd AU - Thoma F AD - Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania (F.T.). FAU - Lemon, Lara AU - Lemon L AUID- ORCID: 0000-0001-6806-7787 AD - Clinical Analytics, UPMC, Pittsburgh, Pennsylvania (L.L., K.K.). FAU - Koczo, Agnes AU - Koczo A AD - School of Medicine, University of Pittsburgh, and Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania (A.S., A.K., S.R., O.M.). FAU - Reis, Steven AU - Reis S AD - School of Medicine, University of Pittsburgh, and Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania (A.S., A.K., S.R., O.M.). FAU - Marroquin, Oscar AU - Marroquin O AD - School of Medicine, University of Pittsburgh, and Heart and Vascular Institute, UPMC, Pittsburgh, Pennsylvania (A.S., A.K., S.R., O.M.). FAU - Kip, Kevin AU - Kip K AD - Clinical Analytics, UPMC, Pittsburgh, Pennsylvania (L.L., K.K.). LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20250617 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Benzhydryl Compounds) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/mortality/complications MH - *Glucosides/therapeutic use/adverse effects MH - *Recombinant Fusion Proteins/therapeutic use/adverse effects MH - *Benzhydryl Compounds/therapeutic use/adverse effects MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - *Immunoglobulin Fc Fragments/therapeutic use MH - *Cardiovascular Diseases/mortality/prevention & control MH - Myocardial Infarction/epidemiology MH - Propensity Score MH - Stroke/epidemiology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/06/16 18:26 MHDA- 2025/07/14 18:27 CRDT- 2025/06/16 17:03 PHST- 2025/07/14 18:27 [medline] PHST- 2025/06/16 18:26 [pubmed] PHST- 2025/06/16 17:03 [entrez] AID - 10.7326/ANNALS-24-00775 [doi] PST - ppublish SO - Ann Intern Med. 2025 Jul;178(7):930-939. doi: 10.7326/ANNALS-24-00775. Epub 2025 Jun 17. PMID- 40518344 OWN - NLM STAT- MEDLINE DCOM- 20250903 LR - 20260127 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 139 DP - 2025 Sep TI - Efficacy and safety of once-daily oral semaglutide in patients with heart failure with preserved ejection fraction, type 2 diabetes and obesity: a real-world study. PG - 106378 LID - S0953-6205(25)00236-5 [pii] LID - 10.1016/j.ejim.2025.06.007 [doi] AB - BACKGROUND: There is limited evidence on the role of glucagon-like peptide-1 receptor agonists in heart failure. This work analyzes the efficacy of once-daily oral semaglutide in terms of health status and change in body weight in patients with heart failure with preserved ejection fraction, type 2 diabetes, and obesity. METHODS: This prospective, real-world study included patients treated with once-daily semaglutide (O-Sema Group) and without glucagon-like peptide-1 receptor agonists (Control Group). The primary outcome was the heart failure status, defined as the >/=5 point difference in the Kansas City Cardiomyopathy Questionnaire total symptom score, and change in body weight at 18 months. RESULTS: After a 1:1 propensity score matching, 202 patients were included in each group (mean age 77.8 years, mean body mass index 33.5, 59.2 % females). Patients in the O-Sema Group were more likely to have an improvement in heart failure health status from baseline to 18 months (OR:2.92; 95 %CI: 1.45-4.90; p < 0.01). The mean change in body weight was -9.5 +/- 3.2 kg in patients with oral semaglutide and -2.0 +/- 1.1 kg in control patients (p < 0.01). After treatment, there were negative correlations between the Kansas City Cardiomyopathy Questionnaire total symptom score and the body weight (r=-0.577, p < 0.01) and glycated hemoglobin (r=-0.499, p = 0.011). It had good tolerability and safety. CONCLUSIONS: Once-daily oral semaglutide was associated with an improvement in heart failure health status, and weight loss in patients with heart failure with preserved ejection fraction, type 2 diabetes, and obesity. Further research on glucagon-like peptide-1 receptor agonists in heart failure with preserved ejection fraction is needed. CI - Copyright (c) 2025 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. FAU - Trenas, Alicia AU - Trenas A AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain. FAU - Perez-Velasco, Miguel A AU - Perez-Velasco MA AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain. FAU - Bernal-Lopez, Maria-Rosa AU - Bernal-Lopez MR AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain; Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. FAU - Lopez-Carmona, Maria-Dolores AU - Lopez-Carmona MD AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain. FAU - Gomez-Doblas, Juan J AU - Gomez-Doblas JJ AD - Servicio de Cardiologia, Hospital Universitario Virgen de la Victoria, Malaga, Spain; Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. FAU - Martinez-Esteban, Maria-Dolores AU - Martinez-Esteban MD AD - Servicio de Nefrologia, Hospital Regional Universitario de Malaga, Universidad de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND, RICORS2040 (RD21/0005/0012 and RD24/0004/0026), Malaga, Spain. FAU - Bouarich, Oumayma AU - Bouarich O AD - Servicio de Nefrologia, Hospital Regional Universitario de Malaga, Universidad de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND, RICORS2040 (RD21/0005/0012 and RD24/0004/0026), Malaga, Spain. FAU - Garcia-Casares, Natalia AU - Garcia-Casares N AD - Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND, Malaga, Spain. FAU - Fernandez-Garcia, Diego AU - Fernandez-Garcia D AD - Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; Servicio de Endocrinologia y Nutricion. Hospital Universitario Virgen de la Victoria, Malaga, Spain. FAU - de Lucas, Maria-Dolores Garcia AU - de Lucas MG AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain. FAU - Gomez-Huelgas, Ricardo AU - Gomez-Huelgas R AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain; Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND, Malaga, Spain. Electronic address: ricardogomezhuelgas@hotmail.com. FAU - Perez-Belmonte, Luis M AU - Perez-Belmonte LM AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND. Universidad de Malaga, Malaga, Spain; Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA) - Plataforma BIONAND, Malaga, Spain. Electronic address: luismiguelpb1984@gmail.com. LA - eng PT - Journal Article DEP - 20250614 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Heart Failure/drug therapy/complications/physiopathology MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Aged MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Obesity/complications MH - Prospective Studies MH - Stroke Volume MH - Aged, 80 and over MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Middle Aged MH - Propensity Score MH - Glycated Hemoglobin MH - Body Weight MH - Weight Loss MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Heart failure OT - Obesity OT - Preserved left ventricular ejection fraction OT - Semaglutide OT - Type 2 diabetes COIS- Declaration of competing interest The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. EDAT- 2025/06/16 00:26 MHDA- 2025/09/03 12:34 CRDT- 2025/06/15 21:52 PHST- 2025/03/09 00:00 [received] PHST- 2025/06/03 00:00 [revised] PHST- 2025/06/05 00:00 [accepted] PHST- 2025/09/03 12:34 [medline] PHST- 2025/06/16 00:26 [pubmed] PHST- 2025/06/15 21:52 [entrez] AID - S0953-6205(25)00236-5 [pii] AID - 10.1016/j.ejim.2025.06.007 [doi] PST - ppublish SO - Eur J Intern Med. 2025 Sep;139:106378. doi: 10.1016/j.ejim.2025.06.007. Epub 2025 Jun 14. PMID- 40515833 OWN - NLM STAT- MEDLINE DCOM- 20251025 LR - 20261010 IS - 1432-1912 (Electronic) IS - 0028-1298 (Linking) VI - 398 IP - 11 DP - 2025 Nov TI - Progress and challenges in obesity pharmacotherapy: semaglutide as a milestone. PG - 15257-15267 LID - 10.1007/s00210-025-04319-0 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs), including semaglutide, have emerged as effective therapies for glycaemic control and weight reduction in type 2 diabetes and obesity. Both injectable and oral formulations have been investigated in large phase III clinical trials, with growing interest in their long-term efficacy and safety. To review and compare the efficacy, safety, and tolerability of injectable and oral semaglutide formulations, with a focus on their role in chronic weight and glycaemic management. A narrative review was conducted based on data from pivotal clinical trials and real-world studies. Efficacy outcomes included changes in body weight and glycated haemoglobin (HbA1c). Safety profiles, adverse events, and patient adherence factors were also assessed. Injectable semaglutide (2.4 mg weekly) showed a mean weight reduction of 14.9% over 68 weeks in the STEP 1 trial, compared to 15.1% with oral semaglutide (50 mg daily) in the OASIS 1 study. Both formulations demonstrated significant improvements in HbA1c and cardiometabolic parameters. A real-world study found comparable efficacy between formulations. Gastrointestinal adverse events were most common, while serious events were rare. Long-term use was essential for sustained weight loss, as discontinuation led to significant weight regain. No consistent associations with increased cancer or psychiatric adverse events were confirmed. Both oral and injectable semaglutide are effective and generally well-tolerated options for chronic management of type 2 diabetes and obesity. Treatment adherence, long-term safety, and cost considerations should guide therapeutic choices. Ongoing monitoring is warranted to optimize outcomes and minimize risks. CI - (c) 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Ferrara, Francesco AU - Ferrara F AD - Pharmaceutical Department, Asl Napoli 3 Sud, Dell' Amicizia Street 72, Nola, Naples, Italy. f.ferrara@aslnapoli3sud.it. FAU - Bazzani, Denise AU - Bazzani D AD - Pharmaceutical Department, ATS Val Padana via Dei Toscani 1, 46100, Mantua, Italy. FAU - Crivelli, Barbara AU - Crivelli B AD - Hospital Pharmacy, IRCCS Ospedale Galeazzi - Sant'Ambrogio, via Cristina Belgioioso 173, 20157, Milan, Italy. FAU - Danieli, Elisa AU - Danieli E AD - Hospital Pharmacy, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy. FAU - Gazzola, Pietro AU - Gazzola P AD - Hospital Pharmacy, IRCCS Humanitas Research Hospital, Via Alessandro Manzoni, 56 , 20089, Rozzano, Milan, Italy. FAU - Guarnieri, Greta AU - Guarnieri G AD - Hospital Pharmacy, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy. FAU - Handschin, Giulia AU - Handschin G AD - Hospital Pharmacy, ASST Papa Giovanni XXIII, piazza OMS, 1, 24127, Bergamo, Italy. FAU - Lauria, Claudia AU - Lauria C AD - Hospital Pharmacy, Istituto Nazionale Dei Tumori, Via Giacomo Venezian, 1, 20133, Milan, Italy. FAU - Marchetti, Carlotta AU - Marchetti C AD - Pharmaceutical Department, ATS Montagna, Via Nazario Sauro, 36/38, 23100, Sondrio, Italy. FAU - Sbraga, Emanuele AU - Sbraga E AD - Hospital Pharmacy, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy. FAU - Zero, Carmen AU - Zero C AD - Hospital Pharmacy, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy. FAU - Zovi, Andrea AU - Zovi A AD - Hospital Pharmacist, Ministry of Health, Viale Giorgio Ribotta 5, 00144, Rome, Italy. FAU - Langella, Roberto AU - Langella R AD - Italian Society of Hospital Pharmacy (SIFO), SIFO Secretariat of the Lombardy Region, Via Carlo Farini, 81, 20159, Milan, Italy. FAU - Parati, Chiara AU - Parati C AD - Hospital Pharmacy, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy. LA - eng PT - Journal Article PT - Review DEP - 20250614 PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - *Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Anti-Obesity Agents/administration & dosage/adverse effects/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Administration, Oral MH - Blood Glucose/drug effects/metabolism MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Market dynamics OT - Safety OT - Semaglutide, GLP-1RA OT - Treatment of obesity COIS- Declarations. Ethical approval: Not applicable. Consent to participate: Not applicable. Consent to publish: The authors consent to the publication of the manuscript. Conflicts of interest: The authors declare no competing interests. Clinical trial number: Not applicable. Disclosure: AZ declares that the opinions expressed are of a personal nature and do not in any way commit the responsibility of the Administration to which him belongs. EDAT- 2025/06/14 17:09 MHDA- 2025/10/25 06:29 CRDT- 2025/06/14 11:16 PHST- 2025/04/16 00:00 [received] PHST- 2025/05/20 00:00 [accepted] PHST- 2025/10/25 06:29 [medline] PHST- 2025/06/14 17:09 [pubmed] PHST- 2025/06/14 11:16 [entrez] AID - 10.1007/s00210-025-04319-0 [pii] AID - 10.1007/s00210-025-04319-0 [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 2025 Nov;398(11):15257-15267. doi: 10.1007/s00210-025-04319-0. Epub 2025 Jun 14. PMID- 40514554 OWN - NLM STAT- MEDLINE DCOM- 20250828 LR - 20261010 IS - 2731-7099 (Electronic) IS - 2731-7080 (Linking) VI - 66 IP - 9 DP - 2025 Sep TI - [Weight reduction with incretin mimetics-Opportunities and risks]. PG - 979-985 LID - 10.1007/s00108-025-01918-0 [doi] AB - BACKGROUND: Obesity affects a growing number of people worldwide and is associated with severe metabolic, cardiovascular and oncological complications. Obesity not only represents an individual health burden but is also a socioeconomic challenge. With the incretin mimetics liraglutide, semaglutide and tirzepatide, a new class of drugs is now available that for the first time enables substantial and clinically relevant weight reduction. OBJECTIVE: The article sheds light on the efficacy, safety and prospects of obesity treatment based on glucagon-like peptide 1 (GLP-1). In addition to the results of key clinical trials, potential risks, limitations of use, typical side effects and drug interactions are discussed. Economic aspects are also explained. RESULTS: Clinical trials show an average weight reduction of 15-20%, with tirzepatide in particular being highly effective. Positive side effects of the treatment mainly concern metabolism (prediabetes and type 2 diabetes regression) and cardiovascular diseases. The main side effects are the frequently occurring gastrointestinal disorders, such as nausea and vomiting. The long-term safety of the substances has not yet been conclusively proven. High costs, limited access and the potential for abuse pose additional challenges. Combination preparations and orally available drugs are currently under development. CONCLUSION: Incretin mimetics represent a major advance in the treatment of obesity but require careful selection, close monitoring and long-term integration into lifestyle measures. CI - (c) 2025. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature. FAU - Zech, Thomas J AU - Zech TJ FAU - Kirchweger, Benjamin AU - Kirchweger B FAU - Furst, Robert AU - Furst R AD - Pharmazeutische Biologie, Department Pharmazie - Zentrum fur Pharmaforschung, Ludwig-Maximilians-Universitat Munchen, Butenandtstr. 5, 81377, Munchen, Deutschland. robert.fuerst@cup.lmu.de. LA - ger PT - English Abstract PT - Journal Article PT - Review TT - Gewichtsreduktion mit Inkretinmimetika - Chancen und Risiken. DEP - 20250613 PL - Germany TA - Inn Med (Heidelb) JT - Innere Medizin (Heidelberg, Germany) JID - 9918384885306676 RN - 0 (Incretins) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Incretins/therapeutic use/adverse effects MH - *Obesity/drug therapy MH - Liraglutide/therapeutic use/adverse effects MH - Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide 1/therapeutic use/analogs & derivatives/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Semaglutide OTO - NOTNLM OT - Cardiovascular diseases OT - Diabetes mellitus, type 2 OT - Glucagon-like peptide 1 OT - Incretin mimetics/adverse effects OT - Obesity COIS- Einhaltung ethischer Richtlinien. Interessenkonflikt: T.J. Zech halt Aktien von Eli Lilly und Novo Nordisk. B. Kirchweger und R. Furst geben an, dass kein Interessenkonflikt besteht. Fur diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgefuhrt. Fur die aufgefuhrten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. EDAT- 2025/06/14 16:46 MHDA- 2025/08/31 20:01 CRDT- 2025/06/13 23:20 PHST- 2025/05/12 00:00 [accepted] PHST- 2025/08/31 20:01 [medline] PHST- 2025/06/14 16:46 [pubmed] PHST- 2025/06/13 23:20 [entrez] AID - 10.1007/s00108-025-01918-0 [pii] AID - 10.1007/s00108-025-01918-0 [doi] PST - ppublish SO - Inn Med (Heidelb). 2025 Sep;66(9):979-985. doi: 10.1007/s00108-025-01918-0. Epub 2025 Jun 13. PMID- 40501244 OWN - NLM STAT- MEDLINE DCOM- 20250612 LR - 20260127 IS - 3105-9686 (Electronic) IS - 1011-601X (Linking) VI - 38 IP - 2 DP - 2025 Mar-Apr TI - Effect of Semaglutide on C-peptide levels in patients with type 2 diabetes. PG - 457-461 AB - The study evaluated the effect of semaglutide treatment for type 2 diabetes mellitus (T2DM), specifically examining its effect on C-peptide levels. A total of 80 patients hospitalized for T2DM were included (January 2022-December 2023), and all patients had conventional treatment with oral metformin. Patients in the control group received subcutaneous insulin aspart, while patients in the observation group received subcutaneous semaglutide. Key variables, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2h-PBG), and time to target blood glucose, were assessed at the baseline and again after three months. Serum endothelin-1 (ET-1), functional vasodilation (FMD), fasting C-peptide, fasting insulin (FINS), and the insulin resistance index (Homa-IR) were also measured. At the end of three months, the observation group had significantly lower 2h-PBG (9.01+/-0.53 mmol/L) and FBG (6.13+/-0.68 mmol/L) than the control group (P<0.05). Additionally, the time to target glucose was shorter in the observation group (3.88+/-0.69 vs. 5.73+/-1.01 days, P<0.05). The observation group also had lower ET-1, higher FMD, and increased Homa-IR (P<0.05). In conclusion, semaglutide optimizes glycemic control, lowers insulin resistance, and increases vasorelaxation function. Semaglutide has great potential as a therapeutic agent in T2DM. FAU - Fan, Pengxiang AU - Fan P AD - Department of Endocrinology, Tianshui Traditional Chinese Medicine Hospital, Tianshui, Gansu China. FAU - Ma, Xiaojun AU - Ma X AD - Department of Endocrinology, Tianshui Traditional Chinese Medicine Hospital, Tianshui, Gansu China. LA - eng PT - Journal Article PL - Pakistan TA - Pak J Pharm Sci JT - Pakistan journal of pharmaceutical sciences JID - 9426356 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (C-Peptide) RN - 0 (Endothelin-1) RN - 0 (Insulin) RN - 9100L32L2N (Metformin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Male MH - Female MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - *C-Peptide/blood MH - Insulin Resistance MH - Aged MH - Endothelin-1/blood MH - Insulin/blood MH - Vasodilation/drug effects MH - Metformin/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/06/12 06:30 MHDA- 2025/06/12 06:31 CRDT- 2025/06/12 04:03 PHST- 2025/06/12 06:31 [medline] PHST- 2025/06/12 06:30 [pubmed] PHST- 2025/06/12 04:03 [entrez] PST - ppublish SO - Pak J Pharm Sci. 2025 Mar-Apr;38(2):457-461. PMID- 40499315 OWN - NLM STAT- MEDLINE DCOM- 20250717 LR - 20260127 IS - 1464-3391 (Electronic) IS - 0968-0896 (Linking) VI - 128 DP - 2025 Oct 1 TI - Design, synthesis, and biological evaluation of long-acting glucagon-like peptide-1 (GLP-1) conjugates modified with dual fatty acids and a proline-alanine-serine (PAS) polypeptide. PG - 118266 LID - S0968-0896(25)00207-X [pii] LID - 10.1016/j.bmc.2025.118266 [doi] AB - The increasing prevalence of type 2 diabetes presents a major global health challenge. Glucagon-like peptide-1 (GLP-1) receptor agonists offer glycemic control, weight loss, and cardiovascular benefits but are limited by rapid enzymatic degradation and short half-life. Semaglutide, modified with a C18 diacid, extends its half-life to one week. Building on this, we developed GLP-1 analogues incorporating a hydrophilic proline-alanine-serine (PAS) sequence, referred to as PAS100, which comprises 100 amino acids with repetitive Pro, Ala, and Ser residues, along with dual fatty acid modifications, to evaluate their long-term therapeutic effects on glycemic control and body weight regulation. Fifteen conjugates were synthesized, featuring dual fatty acid modifications at Lys(26) of Gly(8)-Arg(34)-GLP-1(7-37), with a PAS sequence at the C-terminus to mitigate lipidation-induced hydrophobicity. Seven exhibited enhanced GLP-1 receptor activation compared to their counterparts. Among them, B1, with two C14 monoacids and PAS100, exhibited approximately 3-fold increase in receptor activation compared to semaglutide. These seven conjugates were further evaluated in vivo, categorized into two groups based on their structural features, and compared with semaglutide for weight loss and blood glucose reduction in mice. Among these conjugates, compounds D1, D3, and D4 demonstrated glucose-lowering and weight-reducing effects comparable to semaglutide in vivo. Solubility measurements further confirmed that all d-series compounds displayed improved aqueous solubility, with D1 (bearing both a C14 monoacid and a C12 diacid and a PAS100) achieving the greatest enhancement, approximately two-fold higher than semaglutide. Surface plasmon resonance (SPR) analysis revealed that D1 exhibited a K(D) approximately three-fold lower than that of semaglutide, indicating an enhanced receptor-binding tendency. In conclusion, D1 emerges as a promising GLP-1 analogue with significant therapeutic potential for the treatment of type 2 diabetes. Moreover, the dual-fatty acid conjugation strategy combined with PASylation represents a versatile platform that may be extended to other lipidated peptide therapeutics. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved. FAU - Wang, Chengcheng AU - Wang C AD - Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, 200240 Shanghai, China; National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China. FAU - Zhang, Jinhua AU - Zhang J AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China; Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, Fudan University School of Pharmacy, 201203 Shanghai, China. FAU - Dong, Yuanzhen AU - Dong Y AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China; Shanghai Duomirui Biotech Co., Ltd., 201203 Shanghai, China. FAU - Xu, Jun AU - Xu J AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China; Shanghai Duomirui Biotech Co., Ltd., 201203 Shanghai, China. FAU - Lu, Jianguang AU - Lu J AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China; Shanghai Duomirui Biotech Co., Ltd., 201203 Shanghai, China. FAU - Ding, Chunyong AU - Ding C AD - Shanghai Frontiers Science Center of Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, 200240 Shanghai, China. Electronic address: chunding@sjtu.edu.cn. FAU - Cai, Zhengyan AU - Cai Z AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China. Electronic address: caizy2007@163.com. FAU - Feng, Jun AU - Feng J AD - National Key Laboratory of Lead Druggability Research, China State Institute of Pharmaceutical Industry Co., Ltd., 201203 Shanghai, China; Shanghai Duomirui Biotech Co., Ltd., 201203 Shanghai, China. Electronic address: fengjdmr@163.com. LA - eng PT - Journal Article DEP - 20250606 PL - England TA - Bioorg Med Chem JT - Bioorganic & medicinal chemistry JID - 9413298 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Fatty Acids) RN - 0 (Blood Glucose) RN - 9DLQ4CIU6V (Proline) RN - 0 (Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptide 1/chemistry/pharmacology/chemical synthesis MH - Animals MH - *Drug Design MH - *Hypoglycemic Agents/chemical synthesis/chemistry/pharmacology/therapeutic use MH - *Fatty Acids/chemistry MH - Mice MH - Humans MH - Structure-Activity Relationship MH - Diabetes Mellitus, Type 2/drug therapy MH - Blood Glucose MH - Molecular Structure MH - Male MH - Proline/chemistry MH - *Peptides/chemistry/pharmacology MH - Mice, Inbred C57BL MH - Semaglutide OTO - NOTNLM OT - Bioconjugates OT - Glucagon-like peptide-1 OT - Lipidation OT - Long-acting peptide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/06/12 00:38 MHDA- 2025/07/18 01:39 CRDT- 2025/06/11 18:14 PHST- 2025/03/02 00:00 [received] PHST- 2025/05/22 00:00 [revised] PHST- 2025/05/31 00:00 [accepted] PHST- 2025/07/18 01:39 [medline] PHST- 2025/06/12 00:38 [pubmed] PHST- 2025/06/11 18:14 [entrez] AID - S0968-0896(25)00207-X [pii] AID - 10.1016/j.bmc.2025.118266 [doi] PST - ppublish SO - Bioorg Med Chem. 2025 Oct 1;128:118266. doi: 10.1016/j.bmc.2025.118266. Epub 2025 Jun 6. PMID- 40491239 OWN - NLM STAT- MEDLINE DCOM- 20250827 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 33 IP - 9 DP - 2025 Sep TI - Changes in weight and glycemic control following obesity treatment with semaglutide or tirzepatide by discontinuation status. PG - 1657-1667 LID - 10.1002/oby.24331 [doi] AB - OBJECTIVE: The objective of this study was to characterize changes in body weight and glycated hemoglobin (in those with prediabetes at baseline) through 12 months by obesity pharmacotherapy discontinuation status. METHODS: This retrospective cohort study used electronic health record data from a large health system in Ohio and Florida to identify adults with overweight or obesity without type 2 diabetes who initiated injectable semaglutide or tirzepatide between 2021 and 2023. Treatment discontinuation was defined by a >90-day gap between exhaustion of previous supply and next dispense or end of study follow-up (December 2024) and was classified into early discontinuation (i.e., within 3 months of index date) and late discontinuation (i.e., within 3-12 months). RESULTS: We identified 7881 patients; 6109 received semaglutide, and 1772 received tirzepatide. A total of 80.8% had low maintenance dosages. Mean (SD) percentage weight reduction at 1 year was 8.7% (9.6%); and it was 3.6% (8.1%) with early discontinuation, 6.8% (9.1%) with late discontinuation, and 11.9% (9.2%) with non-discontinuation (p < 0.001). The mean (SD) absolute reduction in percent glycated hemoglobin at 1 year was 0.1 (0.4) with early discontinuation, 0.2 (0.4) with late discontinuation, and 0.4 (0.4) with non-discontinuation (p < 0.001). CONCLUSIONS: The average weight reduction in this cohort was lower than that observed in the main phase 3 trials, likely because of higher rates of discontinuation and lower maintenance dosages. CI - (c) 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Gasoyan, Hamlet AU - Gasoyan H AUID- ORCID: 0000-0002-1627-9777 AD - Center for Value-Based Care Research, Departments of Internal Medicine and Geriatrics, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Butsch, W Scott AU - Butsch WS AUID- ORCID: 0000-0001-7137-9423 AD - Department of Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio, USA. AD - Departments of Internal Medicine and Geriatrics, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Schulte, Rebecca AU - Schulte R AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Casacchia, Nicholas J AU - Casacchia NJ AD - Center for Value-Based Care Research, Departments of Internal Medicine and Geriatrics, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Le, Phuc AU - Le P AD - Center for Value-Based Care Research, Departments of Internal Medicine and Geriatrics, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Boyer, Christopher B AU - Boyer CB AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Griebeler, Marcio L AU - Griebeler ML AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Burguera, Bartolome AU - Burguera B AUID- ORCID: 0000-0001-9808-8327 AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Rothberg, Michael B AU - Rothberg MB AD - Center for Value-Based Care Research, Departments of Internal Medicine and Geriatrics, Cleveland Clinic, Cleveland, Ohio, USA. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. LA - eng GR - RPC8755/Cleveland Clinic Research Program Committees/ PT - Journal Article DEP - 20250610 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Male MH - Retrospective Studies MH - Female MH - Middle Aged MH - *Obesity/drug therapy MH - Glycated Hemoglobin/analysis MH - *Glycemic Control MH - Adult MH - Weight Loss/drug effects MH - *Tirzepatide/therapeutic use/administration & dosage MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2 MH - Ohio MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12381620 COIS- W. Scott Butsch reported advisory board fees from Novo Nordisk A/S, Eli Lilly and Company, Boehringer Ingelheim, and Abbott Laboratories, as well as research funding from Eli Lilly and Company, outside the submitted work. Christopher B. Boyer reported consulting fees from Janssen Pharmaceuticals outside the submitted work. Marcio L. Griebeler reported research funding from Novo Nordisk A/S outside the submitted work. Michael B. Rothberg reported receiving consulting fees from the Blue Cross Blue Shield Association outside the submitted work. The other authors declared no conflicts of interest. EDAT- 2025/06/10 06:28 MHDA- 2025/08/31 20:01 PMCR- 2025/08/27 CRDT- 2025/06/10 03:04 PHST- 2025/05/01 00:00 [revised] PHST- 2025/02/13 00:00 [received] PHST- 2025/05/02 00:00 [accepted] PHST- 2025/08/31 20:01 [medline] PHST- 2025/06/10 06:28 [pubmed] PHST- 2025/06/10 03:04 [entrez] PHST- 2025/08/27 00:00 [pmc-release] AID - OBY24331 [pii] AID - 10.1002/oby.24331 [doi] PST - ppublish SO - Obesity (Silver Spring). 2025 Sep;33(9):1657-1667. doi: 10.1002/oby.24331. Epub 2025 Jun 10. PMID- 40490304 OWN - NLM STAT- MEDLINE DCOM- 20250624 LR - 20250624 IS - 1936-086X (Electronic) IS - 1936-0851 (Linking) VI - 19 IP - 24 DP - 2025 Jun 24 TI - Harnessing Surface Hydrophilicity of Inhalable Nanoparticles for Precision Delivery of Glucagon-like Peptide-1 Receptor Agonists or Anti-Asthmatic Therapeutics. PG - 22357-22375 LID - 10.1021/acsnano.5c05745 [doi] AB - Rational adjustment of surface physicochemical properties of inhalable nanocarriers significantly influences their in vivo fate during pulmonary delivery. Among these, surface hydrophilicity/hydrophobicity has been recognized as a critical factor in the transmucosal process. However, the impacts of surface hydrophilicity/hydrophobicity on the transcellular performance and ultimate therapeutic effects of pulmonary-delivered nanosystems still remain unelucidated. In this study, we developed a series of liposomes with varying surface hydrophilicity to investigate the effect of surface properties on both local and systemic drug delivery. Interestingly, low-hydrophilic liposomes exhibited enhanced systemic absorption, whereas high-hydrophilic liposomes demonstrated prolonged pulmonary residence after inhalation. To validate this principle, we applied two disease models. In a type II diabetes mellitus model, low hydrophilic liposomes loaded with GLP-1 receptor agonists (Liraglutide or Semaglutide) showed excellent systemic drug delivery and hypoglycemic effects. In an OVA-induced allergic asthma model, budesonide-loaded high hydrophilic liposomes significantly alleviated symptoms while reducing dosing frequency. Mechanistic studies further revealed that liposomes with lower surface hydrophilicity could enhance the transcellular transport efficiency of the drug through alveolar epithelial cells, while those with higher surface hydrophilicity prolonged the pulmonary residence of the drug by decreasing alveolar epithelium transportation and the avoidance of macrophage clearance. Lastly, we evaluated the biocompatibility of these liposomes following inhalation. Overall, tuning the surface hydrophilicity/hydrophobicity of inhalable nanocarriers to suit local or systemic delivery goals offers valuable insights for the rational design of advanced pulmonary delivery systems. FAU - Liu, Xi AU - Liu X AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Zhang, Lie AU - Zhang L AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Li, Sa AU - Li S AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Xing, Liyun AU - Xing L AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Ni, Mingjie AU - Ni M AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Huang, Minyi AU - Huang M AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Huang, Yuan AU - Huang Y AUID- ORCID: 0000-0003-3410-8602 AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. LA - eng PT - Journal Article DEP - 20250609 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 0 (Liposomes) RN - 0 (Anti-Asthmatic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 51333-22-3 (Budesonide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Animals MH - Hydrophobic and Hydrophilic Interactions MH - Administration, Inhalation MH - *Nanoparticles/chemistry MH - Mice MH - Liposomes/chemistry MH - *Asthma/drug therapy/chemically induced MH - *Anti-Asthmatic Agents/administration & dosage/chemistry/pharmacology/therapeutic use MH - Surface Properties MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Liraglutide/administration & dosage/chemistry/pharmacology/therapeutic use MH - Budesonide/administration & dosage/therapeutic use/chemistry MH - Drug Delivery Systems MH - Male MH - Hypoglycemic Agents/administration & dosage MH - Diabetes Mellitus, Experimental/drug therapy OTO - NOTNLM OT - GLP-1RAs OT - budesonide OT - inhalable liposome OT - pulmonary delivery OT - respiratory disease OT - surface hydrophilicity/hydrophobicity OT - systemic absorption EDAT- 2025/06/10 00:30 MHDA- 2025/06/24 13:16 CRDT- 2025/06/09 21:03 PHST- 2025/06/24 13:16 [medline] PHST- 2025/06/10 00:30 [pubmed] PHST- 2025/06/09 21:03 [entrez] AID - 10.1021/acsnano.5c05745 [doi] PST - ppublish SO - ACS Nano. 2025 Jun 24;19(24):22357-22375. doi: 10.1021/acsnano.5c05745. Epub 2025 Jun 9. PMID- 40489337 OWN - NLM STAT- MEDLINE DCOM- 20250709 LR - 20260127 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 26 IP - 10 DP - 2025 Jul TI - External control arm with real world data to assess the effect of semaglutide on chronic kidney disease risk among patients with type 2 diabetes. PG - 1237-1243 LID - 10.1080/14656566.2025.2518329 [doi] AB - BACKGROUND: Clinical trials have shown semaglutide effective in mitigating risks associated with type 2 diabetes and chronic kidney disease. However, semaglutide's real-world effectiveness and long-term outcomes are not fully established. RESEARCH DESIGN & METHODS: Using 2019-2024 Kythera Labs data, an external control arm was created using criteria identified in the FLOW clinical trial. Primary outcomes were major kidney disease events (kidney failure onset and >/= 50% reduction in estimated glomerular filtration rate from baseline). Propensity score matching and Cox regression were used to determine risk-adjusted outcomes. RESULTS: The control arm (n = 896,257) was compared with the clinical trial cohort (n = 1,766). After propensity score matching on age, sex, socioeconomic status, and comorbidities, semaglutide treatment was associated with a 26% reduction in primary event risk compared with the comparator group (702 vs 1,068 events; HR: 0.74; 95% CI, 0.67-0.81), consistent with the 24% risk reduction observed in the clinical trial. CONCLUSION: Semaglutide treatment was linked to a significantly lower risk of clinically relevant renal outcomes. Our findings provide robust real-world evidence that supports the FLOW trial results regarding the renoprotective effects of semaglutide, highlighting its promise as an effective therapeutic option for managing renal complications. FAU - Baser, Onur AU - Baser O AD - Department of Economics, Bogazici Univerisity, Istanbul, Turkiye. AD - School of Public Health, City University of New York, New York, NY, USA. FAU - Lu, Yuanqing AU - Lu Y AD - Department of Outcomes Research, Columbia Data Analytics, New York, NY, USA. LA - eng PT - Journal Article DEP - 20250613 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/pharmacology MH - Female MH - Male MH - *Renal Insufficiency, Chronic/prevention & control/etiology/epidemiology MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/pharmacology MH - Aged MH - Propensity Score MH - Glomerular Filtration Rate/drug effects MH - *Diabetic Nephropathies/prevention & control/etiology MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Semaglutide OT - chronic kidney disease OT - comparative effectiveness OT - observational study OT - real-world evidence OT - survival analysis OT - type 2 diabetes EDAT- 2025/06/09 18:28 MHDA- 2025/07/09 12:29 CRDT- 2025/06/09 12:42 PHST- 2025/07/09 12:29 [medline] PHST- 2025/06/09 18:28 [pubmed] PHST- 2025/06/09 12:42 [entrez] AID - 10.1080/14656566.2025.2518329 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2025 Jul;26(10):1237-1243. doi: 10.1080/14656566.2025.2518329. Epub 2025 Jun 13. PMID- 40482671 OWN - NLM STAT- MEDLINE DCOM- 20250624 LR - 20260924 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 13 IP - 7 DP - 2025 Jul TI - Once‑weekly IcoSema versus once‑weekly insulin icodec in type 2 diabetes management (COMBINE 1): an open‑label, multicentre, treat‑to‑target, randomised, phase 3a trial. PG - 568-579 LID - S2213-8587(25)00096-8 [pii] LID - 10.1016/S2213-8587(25)00096-8 [doi] AB - BACKGROUND: IcoSema is a once‑weekly combination therapy of basal insulin icodec (icodec) and semaglutide (a GLP‑1 analogue) currently in development. COMBINE 1 compared the efficacy and safety of IcoSema with once‑weekly icodec alone in adults with inadequately controlled type 2 diabetes on daily basal insulin therapy. METHODS: COMBINE 1, a 52‑week, open‑label, treat‑to‑target, randomised, phase 3a trial, was done at 192 outpatient clinics and hospital departments across 20 countries and regions. Individuals aged 18 years or older with a BMI of 40 kg/m(2) or less and type 2 diabetes (HbA(1c) 7.0-10.0% [53.0-85.8 mmol/mol]) treated with daily basal insulin with or without oral glucose‑lowering medications were randomly assigned (1:1) via a randomisation and trial supply management system to IcoSema (700 U/mL plus 2 mg/mL) or icodec (700 U/mL), both administered as subcutaneous injections on the same day each week, at any time of the day. There was no stratification based on participants' baseline characteristics. The primary endpoint was change in HbA(1c) from baseline to week 52, evaluated in the full analysis set (all randomly assigned participants). The trial is registered with ClinicalTrials.gov, NCT05352815, and has been completed. FINDINGS: Between June 1, 2022, and March 13, 2023, 1671 individuals were screened, of whom 1291 (mean age 60.6 years [SD 10.3]; 799 [62%] males and 492 [38%] females) were randomly assigned to IcoSema (n=646) or icodec (n=645). At week 52, from a baseline value of 8.22% (SD 0.83; 66.3 mmol/mol [9.1]), estimated mean change in HbA(1c) was -1.55 percentage points (SE 0.03; -16.9 mmol/mol [0.4]) with IcoSema and -0.89 percentage points (SE 0.03]; -9.7 mmol/mol [0.4]) with icodec (estimated treatment difference [ETD] -0.66 percentages points [95% CI -0.76 to -0.57]; -7.3 mmol/mol [-8.3 to -6.2]; p<0.0001; superiority confirmed). The rate of combined clinically significant or severe hypoglycaemia from baseline to week 57 was significantly lower with IcoSema than with icodec (0.14 vs 0.63 episodes per person‑year of exposure; estimated rate ratio 0.22 [95% CI 0.14 to 0.36]; p<0.0001; superiority confirmed). The most frequently reported adverse events were within the system organ class of gastrointestinal disorders in the IcoSema group (303 [47%] of 644 participants had 1033 events during the trial) and infections and infestations in the icodec group (275 [43%] of 644 participants had 466 events. 59 (9%) participants in the IcoSema group and 69 (11%) participants in the icodec group had a serious adverse event. No treatment-related deaths occurred. INTERPRETATION: In adults with inadequately controlled type 2 diabetes on daily basal insulin therapy, once‑weekly IcoSema showed superiority to once-weekly icodec alone in changes in HbA(1c) and in overall lower rate of combined clinically significant or severe hypoglycaemia. IcoSema might provide an option for insulin therapy intensification in adults with type 2 diabetes. FUNDING: Novo Nordisk. TRANSLATIONS: For the Chinese and Japanese translations of the abstract see Supplementary Materials section. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Mathieu, Chantal AU - Mathieu C AD - Clinical and Experimental Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium. FAU - Giorgino, Francesco AU - Giorgino F AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Kim, Sin Gon AU - Kim SG AD - Department of Internal Medicine, Korea University College of Medicine, Seoul, South Korea. FAU - Larsen, Jonas Hughes AU - Larsen JH AD - Novo Nordisk, Aalborg, Denmark. FAU - Philis-Tsimikas, Athena AU - Philis-Tsimikas A AD - Scripps Whittier Diabetes Institute, San Diego, CA, USA. FAU - Ramachandran, Ambady AU - Ramachandran A AD - India Diabetes Research Foundation and Dr A Ramachandran's Diabetes Hospitals, Guindy, Chennai, India. FAU - Pagliaro Rocha, Thais M AU - Pagliaro Rocha TM AD - Novo Nordisk, Soborg, Denmark. FAU - Shankarappa, Vinay Babu AU - Shankarappa VB AD - Novo Nordisk, Soborg, Denmark. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. Electronic address: jiln@bjmu.edu.cn. LA - eng SI - ClinicalTrials.gov/NCT05352815 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250604 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Glycated Hemoglobin/analysis MH - *Glucagon-Like Peptides/administration & dosage MH - Adult MH - Drug Administration Schedule MH - *Insulin Glargine/administration & dosage/therapeutic use MH - Drug Therapy, Combination MH - Blood Glucose MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of interests CM serves or has served on advisory panels for Abbott, Bayer, Biomea Fusion, Boehringer Ingelheim, Eli Lilly, Insulet, Medtronic, Novartis, Novo Nordisk, Roche, SAB Bio, Sanofi, and Vertex (financial compensation paid to institution); has received research support to institution from ActoBio Therapeutics, Medtronic, Novo Nordisk, and Sanofi; serves or has served on speaker bureaus for Abbott, Dexcom, Eli Lilly, Medtronic, Novo Nordisk, Roche, Sanofi, and Vertex (financial compensation paid to institution); and is President of the European Association for the Study of Diabetes (EASD; all external support from EASD is to be found on www.easd.org) and Vice-President of the European Diabetes Forum. FG has received grants from Eli Lilly and Roche Diabetes Care; consulting fees from Eli Lilly and Novo Nordisk; support for attending meetings from AstraZeneca, Boehringer Ingelheim, Eli Lilly, LifeScan, Merck Sharp & Dohme, Medtronic, Novo Nordisk, Roche Diabetes Care, and Sanofi Aventis; serves or has served on advisory panels for AstraZeneca, Biomea, Boehringer Ingelheim, Eli Lilly, LifeScan, Merck Sharp & Dohme, MedImmune, Medtronic, Novo Nordisk, Roche Diabetes Care, and Sanofi Aventis; has had unpaid leadership roles at EASD/EFSD, Societa Italiana di Endocrinologia (SIE), and FO.Ri.SIE; and has received support for medical writing and statistical analysis from AstraZeneca, Biomea, Eli Lilly, Novo Nordisk, and Sanofi Aventis. SGK has received consulting fees and honoraria from AstraZeneca, Boehringer Ingelheim, Celltrion, Eli Lilly, Novo Nordisk, and Sanofi; and grants for medical research from Abbott, AstraZeneca, Boehringer Ingelheim, Celltrion, and Viatris. JHL, TMPR, and VBS are employees of Novo Nordisk and hold stock options in Novo Nordisk. AP-T provides consultation and advisory services on behalf of her employer Scripps Health for Dexcom, Eli Lilly, Medtronic, and Novo Nordisk; has received honoraria and support for presentations and travel or attendance to meetings from Corcept, Dexcom, Eli Lilly, and Novo Nordisk; and participated on behalf of her employer Scripps Health on an advisory board for Medtronic. YT has received consulting or lecture fees from Astellas Pharma, AstraZeneca, Eli Lilly Japan, Kowa Company, Mitsubishi Tanabe Pharma, MSD, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Sanofi, and Sumitomo Pharma; and grants from Nippon, Boehringer Ingelheim, and Sumitomo Pharma. LJ has received consulting fees or honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Gan & Lee Pharmaceuticals, Innovent Biologics, MSD, Novo Nordisk, and Sanofi-Aventis; and has served on advisory panels for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Haisco Pharmaceutical, Innovent Biologics, Merck, MSD, Novo Nordisk, Sanofi Aventis, Sibionics, and Sinocare. AR declares no competing interests. EDAT- 2025/06/08 03:37 MHDA- 2025/06/24 11:10 CRDT- 2025/06/07 18:52 PHST- 2024/12/06 00:00 [received] PHST- 2025/04/02 00:00 [revised] PHST- 2025/04/03 00:00 [accepted] PHST- 2025/06/24 11:10 [medline] PHST- 2025/06/08 03:37 [pubmed] PHST- 2025/06/07 18:52 [entrez] AID - S2213-8587(25)00096-8 [pii] AID - 10.1016/S2213-8587(25)00096-8 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2025 Jul;13(7):568-579. doi: 10.1016/S2213-8587(25)00096-8. Epub 2025 Jun 4. PMID- 40482670 OWN - NLM STAT- MEDLINE DCOM- 20250624 LR - 20260924 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 13 IP - 7 DP - 2025 Jul TI - Once-weekly IcoSema versus multiple daily insulin injections in type 2 diabetes management (COMBINE 3): an open-label, multicentre, treat-to-target, non-inferiority, randomised, phase 3a trial. PG - 556-567 LID - S2213-8587(25)00052-X [pii] LID - 10.1016/S2213-8587(25)00052-X [doi] AB - BACKGROUND: IcoSema is a once-weekly combination therapy of basal insulin icodec (icodec) and semaglutide (a GLP-1 analogue) developed for the treatment of type 2 diabetes. We aimed to evaluate the efficacy and safety of IcoSema versus basal-bolus therapy (BBT) in adults with type 2 diabetes inadequately controlled on daily basal insulin. METHODS: COMBINE 3, a 52-week, open-label, treat-to-target, non-inferiority, randomised, phase 3a trial, was done across 109 outpatient clinics and hospital departments in 14 countries. Individuals aged 18 years or older with type 2 diabetes (HbA(1c) 7.0-10.0% [53.0-85.8 mmol/mol]) receiving daily basal insulin (20-80 U per day) were randomly assigned (1:1) to receive once-weekly IcoSema injection using a pen device or BBT (once-daily insulin glargine U100 with two to four daily insulin aspart injections) using an automated, interactive central web-response system. The primary endpoint was change in HbA(1c) from baseline to week 52, tested for non-inferiority (0.3 percentage-point margin). Confirmatory secondary endpoints were change in bodyweight from baseline to week 52; weekly total insulin dose during weeks 50-52; and combined clinically significant hypoglycaemic episodes (<3.0 mmol/L [<54 mg/dL], confirmed by blood glucose meter) or severe hypoglycaemic episodes (associated with severe cognitive impairment requiring external assistance for recovery) from baseline to week 57. The primary and confirmatory secondary endpoints were evaluated using the full analysis set (all randomly assigned participants). Descriptive statistics for safety endpoints were based on the safety analysis set (participants exposed to a trial product), with statistical analyses based on the full analysis set. This trial is registered with ClinicalTrials.gov (NCT05013229) and is complete. FINDINGS: Between Nov 30, 2021, and Sept 28, 2022, 844 participants were screened; 679 (mean age 59.6 years [SD 10.4]; 399 [59%] males and 280 [41%] females) were randomly assigned to IcoSema (n=340) or BBT (n=339). At week 52, estimated mean change in HbA(1c) was -1.47 percentage points (SE 0.05; -16.0 mmol/mol [0.6]) with IcoSema and -1.40 percentage points (0.06; -15.3 mmol/mol [0.7]) with BBT, confirming non-inferiority of IcoSema versus BBT (estimated treatment difference [ETD] -0.06 percentage points [95% CI -0.22 to 0.09; -0.70 mmol/mol [-2.39 to 0.99]; p<0.0001). Superiority was confirmed for IcoSema versus BBT for change in bodyweight from baseline to week 52 (ETD -6.72 kg [95% CI -7.58 to -5.86]; p<0.0001), weekly total insulin dose during weeks 50-52 (ETD -270 U [-303 to -236]; p<0.0001), and overall rate of clinically significant or severe hypoglycaemia from baseline to week 57 (0.21 vs 2.23 episodes per person-year of exposure; estimated rate ratio 0.12 [0.08 to 0.17]; p<0.0001). The most frequently reported adverse events during the trial were gastrointestinal disorders with IcoSema (148 [44%] of 340 participants had 443 events) and infections and infestations with BBT (116 [35%] of 328 participants had 193 events). INTERPRETATION: Once-weekly IcoSema achieved non-inferior HbA(1c) reduction and superiority in change in bodyweight, weekly total insulin dose, and hypoglycaemia rates versus daily BBT, suggesting that there is a potentially beneficial treatment intensification option for adults with type 2 diabetes. FUNDING: Novo Nordisk. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Billings, Liana K AU - Billings LK AD - Department of Medicine, Endeavor Health/NorthShore Hospitals, and University of Chicago Pritzker School of Medicine, Skokie, IL, USA. Electronic address: lbillings@northshore.org. FAU - Andreozzi, Francesco AU - Andreozzi F AD - Department of Medical and Surgical Sciences and Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Graecia of Catanzaro, Catanzaro, Italy. FAU - Frederiksen, Marie AU - Frederiksen M AD - Novo Nordisk, Soborg, Denmark. FAU - Gourdy, Pierre AU - Gourdy P AD - Department of Diabetology, Toulouse University Hospital, Toulouse, France; Institute of Metabolic and Cardiovascular Diseases, UMR1297 INSERM/UT3, Toulouse University, Toulouse, France. FAU - Gowda, Amoolya AU - Gowda A AD - Novo Nordisk, Soborg, Denmark. FAU - Ji, Linong AU - Ji L AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Pletsch-Borba, Laura AU - Pletsch-Borba L AD - Novo Nordisk, Soborg, Denmark. FAU - Suzuki, Ryo AU - Suzuki R AD - Department of Diabetes, Metabolism, and Endocrinology, Tokyo Medical University, Tokyo, Japan. FAU - Unnikrishnan, A G AU - Unnikrishnan AG AD - Chellaram Diabetes Institute, Pune, Maharashtra, India. FAU - Vianna, Andre G D AU - Vianna AGD AD - Curitiba Diabetes Center, Department of Endocrine Diseases, Hospital Nossa Senhora das Gracas, Curitiba, Brazil. LA - eng SI - ClinicalTrials.gov/NCT05013229 PT - Clinical Trial, Phase III PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250604 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Glycated Hemoglobin/analysis MH - *Insulin/administration & dosage MH - *Insulin Glargine/administration & dosage MH - Blood Glucose/analysis MH - Drug Administration Schedule MH - Adult MH - *Glucagon-Like Peptides/administration & dosage MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of interests LKB has received research support or consultant fees, or has served on advisory panels for Bayer, Dexcom, Endogenex, Eli Lilly, Novo Nordisk, Sanofi, Pfizer, and Xeris. FA has received consultant fees for Novo Nordisk. MF, AG, and LP-B are employees of Novo Nordisk and hold stock options. PG has received research support or consultant fees, or has served on advisory panels for Abbott, AbbVie, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Organon, Pfizer, and Sanofi. LJ has received research support or consultant fees, or has served on advisory panels for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Fosun Pharma, Gan & Lee Pharmaceuticals, Haisco Pharmaceutical, Innovent Biologics, Merck, MSD, Novo Nordisk, Sanofi-Aventis, Sibionics, and Sinocare. RS has received research support or consultant fees, or has served on advisory panels for Astellas, Eli Lilly, Kowa, Mitsubishi Tanabe, MSD, Novo Nordisk, Sanofi, Sumitomo, and Teijin. AGU has received research support and served on advisory panels for Novo Nordisk and has received consulting fees for Abbott, Boehringer Ingelheim, and Novo Nordisk. AGDV has received research support or consultant fees or has served on advisory panels for Abbott Diabetes Care, AstraZeneca, Bayer, Eli Lilly, Eurofarma, Medtronic, Novo Nordisk, Roche Diabetes Care, and Servier. EDAT- 2025/06/08 03:37 MHDA- 2025/06/24 13:08 CRDT- 2025/06/07 18:52 PHST- 2024/10/11 00:00 [received] PHST- 2025/01/31 00:00 [revised] PHST- 2025/02/13 00:00 [accepted] PHST- 2025/06/24 13:08 [medline] PHST- 2025/06/08 03:37 [pubmed] PHST- 2025/06/07 18:52 [entrez] AID - S2213-8587(25)00052-X [pii] AID - 10.1016/S2213-8587(25)00052-X [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2025 Jul;13(7):556-567. doi: 10.1016/S2213-8587(25)00052-X. Epub 2025 Jun 4. PMID- 40473254 OWN - NLM STAT- MEDLINE DCOM- 20250707 LR - 20260127 IS - 1439-4286 (Electronic) IS - 0018-5043 (Linking) VI - 57 IP - 6 DP - 2025 Jun TI - Efficacy of Semaglutide Injection in the Treatment of Type 2 Diabetes Mellitus and its Impact on C-Peptide Levels. PG - 378-384 LID - 10.1055/a-2618-7509 [doi] AB - Type 2 Diabetes Mellitus (T2DM) remains a significant global health challenge, necessitating more effective therapeutic strategies. This study was to observe the impact of semaglutide on the C-Peptide levels and glycemic variability. This retrospective evaluation was conducted from January 2020 to January 2023 at our hospital, involving 172 patients diagnosed with T2DM. Patients were stratified into two groups: the observation group (86 patients) received semaglutide injections plus metformin, and the control group (86 patients) received only metformin. Treatment efficacy was assessed using changes in HbA1c, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h BG), and C-Peptide levels. Additional evaluations included changes in glycemic variability indicators such as standard deviation of blood glucose (SDBG), mean of daily differences (MODD), and mean amplitude of glycemic excursions (MAGE). The observation group showed significantly greater improvements in glycemic control and C-Peptide levels compared to the control group. Specifically, the observation group achieved a significant reduction in HbA1c from 70 mmol/mol to 53 mmol/mol, FBG from 10.91 mmol/l to 6.12 mmol/l, and increased C-Peptide levels in both fasting and postprandial states. Improvements in glycemic variability were also more pronounced in the observation group. There was no significant difference in the incidence of adverse events between the two groups. Semaglutide combined with metformin significantly enhances the efficacy of treatment in T2DM patients, with marked improvements in C-Peptide levels, glycemic control, and reduction in glycemic variability. This combination therapy not only offers superior glucose management but also appears to bolster pancreatic function. CI - Thieme. All rights reserved. FAU - Xie, Shuying AU - Xie S AD - Endocrinology, Ganzhou People's Hospital, Ganzhou, China. FAU - Ye, Lan AU - Ye L AD - Basic Medicine, Gannan Health Vocational College, Ganzhou, China. FAU - Yang, Anyuan AU - Yang A AD - Nursing, Gannan Health Vocational College, Ganzhou, China. FAU - Li, Xiaoyan AU - Li X AD - Endocrinology, Ganzhou People's Hospital, Ganzhou, China. FAU - Yin, Ying AU - Yin Y AD - Endocrinology, Ganzhou People's Hospital, Ganzhou, China. LA - eng PT - Journal Article DEP - 20250605 PL - Germany TA - Horm Metab Res JT - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JID - 0177722 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (C-Peptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - Middle Aged MH - *C-Peptide/blood MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Retrospective Studies MH - Blood Glucose/analysis MH - Glycated Hemoglobin/analysis/metabolism MH - Aged MH - Metformin/therapeutic use/administration & dosage MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- The authors declare that they have no conflict of interest. EDAT- 2025/06/06 00:27 MHDA- 2025/07/08 00:27 CRDT- 2025/06/05 20:13 PHST- 2025/07/08 00:27 [medline] PHST- 2025/06/06 00:27 [pubmed] PHST- 2025/06/05 20:13 [entrez] AID - 10.1055/a-2618-7509 [doi] PST - ppublish SO - Horm Metab Res. 2025 Jun;57(6):378-384. doi: 10.1055/a-2618-7509. Epub 2025 Jun 5. PMID- 40471293 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20250918 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 62 IP - 9 DP - 2025 Sep TI - Beyond GLP-1: efficacy and safety of dual and triple incretin agonists in personalized type 2 diabetes care-a systematic review and network meta-analysis. PG - 1359-1370 LID - 10.1007/s00592-025-02534-y [doi] AB - BACKGROUND: Dual and triple incretin-based agonists, targeting combinations of GLP-1, GIP, and glucagon receptors, represent an innovative approach in T2DM care. However, comparative efficacy and safety analyses tailored to receptor-specific strategies are limited. PURPOSE: This systematic review and network meta-analysis uniquely evaluates the efficacy and safety of dual and triple incretin agonists compared to standard therapies, offering insights into personalized, receptor-specific T2DM therapies. DATA SOURCES: Systematic searches in PubMed, Web of Science, Cochrane Library, and Embase (up to July 2024) identified RCTs. STUDY SELECTION: Trials assessing dual or triple incretin therapies in T2DM with outcomes on weight, HbA1c, FBG, AEs, and SAEs were included. DATA EXTRACTION: Data on efficacy and safety were extracted by independent reviewers and assessed for quality using the NIH Quality Assessment Tool. DATA SYNTHESIS: Retatrutide achieved the greatest weight reduction (MD: - 8.601; 95% CrI: - 11.20 to - 5.95) while Tirzepatide was most effective in lowering FBG (MD: - 57.30) and HbA1c ( - 1.88), with 95% CrIs of - 65.41 to - 48.9 and - 2.15 to - 1.64 respectively. Tirzepatide (RR 1.15) and Cotadutide (1.38) increased AEs, while Semaglutide reduced SAEs (0.35); 95% Crls: 1.04-1.33, 1.16-1.68, and 0.13-0.78, respectively. LIMITATIONS: Small sample sizes, short study durations, and reliance on indirect comparisons in some cases may limit the certainty of these findings. Direct head-to-head trials are needed to confirm these results. CONCLUSION: Receptor-specific targeting optimizes T2DM treatment, with Semaglutide supporting glycemic control, Tirzepatide enhancing weight loss and glucose regulation, and Retatrutide potentially offering broader metabolic benefits, advancing receptor-targeted, personalized therapy. PROSPERO REGISTRATION NUMBER: CRD42024532368. CI - (c) 2025. The Author(s). FAU - Yan, Kangling AU - Yan K AUID- ORCID: 0009-0009-8652-1395 AD - School of Medical Sciences - Faculty of Medicine and Health, University of Sydney, City Road, Sydney, NSW, 2006, Australia. katelinyan@gmail.com. FAU - Yu, Haichuan AU - Yu H AD - Wuhan University, Wuhan City, 430061, Hubei, China. FAU - Blaise, Benoit AU - Blaise B AD - Faculty of Pharmacy, Universite Paris-Saclay, 92290, Chatenay-Malabry, Paris, France. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250605 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1/agonists MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use MH - *Incretins/therapeutic use/agonists MH - *Precision Medicine/methods PMC - PMC12433336 OTO - NOTNLM OT - Adverse Events OT - Dual and Triple Agonists OT - Glycemic Control OT - Incretin-Based Agonists OT - Network Meta-Analysis OT - Type 2 Diabetes Mellitus COIS- Declarations. Conflict of interest: The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. EDAT- 2025/06/05 12:31 MHDA- 2025/09/16 06:35 PMCR- 2025/06/05 CRDT- 2025/06/05 11:14 PHST- 2024/12/04 00:00 [received] PHST- 2025/05/07 00:00 [accepted] PHST- 2025/09/16 06:35 [medline] PHST- 2025/06/05 12:31 [pubmed] PHST- 2025/06/05 11:14 [entrez] PHST- 2025/06/05 00:00 [pmc-release] AID - 10.1007/s00592-025-02534-y [pii] AID - 2534 [pii] AID - 10.1007/s00592-025-02534-y [doi] PST - ppublish SO - Acta Diabetol. 2025 Sep;62(9):1359-1370. doi: 10.1007/s00592-025-02534-y. Epub 2025 Jun 5. PMID- 40466625 OWN - NLM STAT- MEDLINE DCOM- 20250604 LR - 20260127 IS - 1932-7420 (Electronic) IS - 1550-4131 (Linking) VI - 37 IP - 6 DP - 2025 Jun 3 TI - GLP-1RAs for peripheral artery disease: A remarkable STRIDE in the right direction. PG - 1257-1259 LID - S1550-4131(25)00257-8 [pii] LID - 10.1016/j.cmet.2025.05.001 [doi] AB - With the rising prevalence of T2D worldwide, peripheral artery disease (PAD) now affects >230 million individuals globally. In the recent STRIDE trial, Bonaca et al.(1) demonstrated that semaglutide improved walking capacity and hemodynamic parameters and slowed PAD progression in patients with T2D. These results reveal an unanticipated vasculoprotective benefit of GLP-1RAs. CI - Published by Elsevier Inc. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery, Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. FAU - Hess, David A AU - Hess DA AD - Department of Physiology and Pharmacology, Western University, London, ON, Canada; Robarts Research Institute, London, ON, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital of Unity Health Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Electronic address: dhess3@uwo.ca. LA - eng PT - Journal Article PL - United States TA - Cell Metab JT - Cell metabolism JID - 101233170 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Peripheral Arterial Disease/drug therapy MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of interests S.V. reports receiving grants and/or research support and/or speaking honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Heart Research Center, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Humber River Health, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management Inc., Sanofi, and Sun Pharma. EDAT- 2025/06/05 00:28 MHDA- 2025/06/05 00:29 CRDT- 2025/06/04 18:24 PHST- 2025/05/07 00:00 [received] PHST- 2025/05/08 00:00 [accepted] PHST- 2025/06/05 00:29 [medline] PHST- 2025/06/05 00:28 [pubmed] PHST- 2025/06/04 18:24 [entrez] AID - S1550-4131(25)00257-8 [pii] AID - 10.1016/j.cmet.2025.05.001 [doi] PST - ppublish SO - Cell Metab. 2025 Jun 3;37(6):1257-1259. doi: 10.1016/j.cmet.2025.05.001. PMID- 40466271 OWN - NLM STAT- MEDLINE DCOM- 20250831 LR - 20260428 IS - 1578-8989 (Electronic) IS - 0025-7753 (Linking) VI - 165 IP - 3 DP - 2025 Sep TI - Efficacy of once-weekly semaglutide in patients with heart failure with preserved ejection fraction, obesity and type 2 diabetes. PG - 107019 LID - S0025-7753(25)00247-7 [pii] LID - 10.1016/j.medcli.2025.107019 [doi] AB - INTRODUCTION AND OBJECTIVES: There is still limited evidence on the role of glucagon-like peptide-1 receptor agonists in heart failure. We analyzed the efficacy in terms of health status, and the change in body weight of once-weekly semaglutide in patients with heart failure with preserved ejection fraction, obesity and type 2 diabetes. PATIENTS AND METHODS: This prospective, real-world study included patients with heart heart failure with preserved ejection fraction, obesity and type 2 diabetes treated with once-weekly 1.00mg semaglutide (Sema-Preserved Group) and patients not treated with glucagon-like peptide-1 receptor agonists (Control-Preserved Group). A 1:1 propensity score matching analysis was performed. The primary outcome was the heart failure status defined as the >/=5 point difference in the Spanish version of the Kansas City Cardiomyopathy Questionnaire total symptom score, and the change of body weight at 24 months. RESULTS: After matching, 203 patients were included in each group. A primary outcome event occurred in 123 patients (60.6%) in the Sema-Preserved Group and 36 (17.7%) in the Control-Preserved Group (odds ratio: 3.99; 95% confidence interval: 1.69-6.28; p<0.01), and the mean change in body weight was -12.9+/-4.2kg in patients with semaglutide and -2.5+/-1.1kg in control patients (p<0.01). There were also significant declines in the heart failure events, and in all-cause hospitalizations. CONCLUSIONS: Once-weekly 1.00mg semaglutide was associated with improved heart failure health status, and weight loss in patients with heart failure with preserved ejection fraction, obesity, and type 2 diabetes. Further research on glucagon-like peptide-1 receptor agonists in heart failure is needed. CI - Copyright (c) 2025 Elsevier Espana, S.L.U. All rights reserved. FAU - Perez-Velasco, Miguel A AU - Perez-Velasco MA AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. FAU - Bernal-Lopez, Maria-Rosa AU - Bernal-Lopez MR AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain; Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. FAU - Trenas, Alicia AU - Trenas A AD - Servicio de Medicina Interna, Area Sanitaria Norte de Malaga, Hospital de Antequera, Antequera, Spain. FAU - Ricci, Michele AU - Ricci M AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. FAU - Lopez-Carmona, Maria-Dolores AU - Lopez-Carmona MD AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. FAU - Garcia de Lucas, Maria-Dolores AU - Garcia de Lucas MD AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain. FAU - Gomez-Huelgas, Ricardo AU - Gomez-Huelgas R AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain; Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain. FAU - Perez-Belmonte, Luis M AU - Perez-Belmonte LM AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga, Malaga, Spain; Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain; Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: luismiguelpb1984@gmail.com. LA - eng LA - spa GR - CB06/03/0018/European Regional Development Fund (ERDF)/ PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20250603 PL - Spain TA - Med Clin (Barc) JT - Medicina clinica JID - 0376377 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Heart Failure/drug therapy/complications/physiopathology MH - Male MH - Female MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Aged MH - Prospective Studies MH - Middle Aged MH - *Obesity/complications MH - Stroke Volume MH - Treatment Outcome MH - Drug Administration Schedule MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Diabetes mellitus tipo 2 OT - Fraccion de eyeccion ventricular izquierda preservada OT - Heart failure OT - Insuficiencia cardiaca OT - Obesidad OT - Obesity OT - Preserved left ventricular ejection fraction OT - Semaglutida OT - Semaglutide OT - Type 2 diabetes EDAT- 2025/06/05 00:28 MHDA- 2025/09/01 00:44 CRDT- 2025/06/04 18:15 PHST- 2024/11/24 00:00 [received] PHST- 2025/03/06 00:00 [revised] PHST- 2025/03/07 00:00 [accepted] PHST- 2025/09/01 00:44 [medline] PHST- 2025/06/05 00:28 [pubmed] PHST- 2025/06/04 18:15 [entrez] AID - S0025-7753(25)00247-7 [pii] AID - 10.1016/j.medcli.2025.107019 [doi] PST - ppublish SO - Med Clin (Barc). 2025 Sep;165(3):107019. doi: 10.1016/j.medcli.2025.107019. Epub 2025 Jun 3. PMID- 40464480 OWN - NLM STAT- MEDLINE DCOM- 20250628 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 18 IP - 5 DP - 2025 May TI - COMBINE 2 is better than one: shaping the future of therapeutics in inadequately controlled type 2 diabetes. PG - 259-262 LID - 10.1080/17512433.2025.2516784 [doi] AB - During treatment intensification of injectable therapies among persons with type 2 diabetes mellitus (T2DM) without evidence of severe insulin deficiency, a glucagon-like peptide-1 agonist (GLP-1 RA) is preferred to insulin. However, due to its progressive nature, many individuals over the course of disease will ultimately require insulin treatment. The use of fixed-ratio combination of basal insulin and GLP-1 RA represents a practical and convenient method for treatment intensification. It has been shown to be more efficacious in improving glycemic control, compared with GLP-1 RA or basal insulin alone, and similarly effective with lower insulin dose in reducing glycated hemoglobin (HbA(1c)) levels, along with less weight gain, and a lower risk of hypoglycemia compared with basal/bolus insulin therapy. The recently published COMBINE 2 trial reported that switching to weekly combination therapy of basal insulin icodec and semaglutide (IcoSema), compared with semaglutide, results in greater HbA(1c) reduction, similar risk of clinically significant or severe hypoglycemia and comparable gastrointestinal tolerability, but unfavorable weight change among individuals with T2DM inadequately controlled with GLP-1 RA therapy, with or without additional oral glucose-lowering drugs. IcoSema represents an effective, safe, and convenient therapeutic choice for treatment intensification in individuals with T2DM inadequately controlled with GLP-1 RA therapy. FAU - Popovic, Djordje S AU - Popovic DS AD - Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Medical Faculty, University of Novi Sad, Novi Sad, Serbia. FAU - Patoulias, Dimitrios AU - Patoulias D AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AUID- ORCID: 0000-0002-5853-1352 AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Papanas, Nikolaos AU - Papanas N AD - Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20250609 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Drug Combinations) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/physiopathology MH - *Hypoglycemic Agents/administration & dosage/adverse effects/pharmacology/therapeutic use MH - Insulin/administration & dosage/adverse effects MH - Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Drug Combinations MH - Hypoglycemia/chemically induced MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Therapy, Combination MH - Blood Glucose/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 agonist OT - IcoSema OT - icodec OT - semaglutide OT - type 2 diabetes mellitus EDAT- 2025/06/04 12:29 MHDA- 2025/07/01 04:49 CRDT- 2025/06/04 08:43 PHST- 2025/07/01 04:49 [medline] PHST- 2025/06/04 12:29 [pubmed] PHST- 2025/06/04 08:43 [entrez] AID - 10.1080/17512433.2025.2516784 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2025 May;18(5):259-262. doi: 10.1080/17512433.2025.2516784. Epub 2025 Jun 9. PMID- 40450456 OWN - NLM STAT- MEDLINE DCOM- 20250613 LR - 20260127 IS - 2530-0180 (Electronic) IS - 2530-0180 (Linking) VI - 72 IP - 6 DP - 2025 Jun-Jul TI - Real-world evaluation of the efficacy and safety of switching from weekly dulaglutide to weekly semaglutide: The SEMA-SWITCH study. PG - 501574 LID - S2530-0180(25)00075-7 [pii] LID - 10.1016/j.endien.2025.501574 [doi] AB - INTRODUCTION: Dulaglutide and semaglutide are once-weekly administered GLP-1 receptor agonists (GLP-1 RAs) indicated for the treatment of hyperglycemia in individuals with type 2 diabetes mellitus (T2DM) and obesity (BMI >/= 30 kg/m(2)). OBJECTIVE: To evaluate the efficacy and safety of switching from subcutaneous (SC) dulaglutide to SC semaglutide, in real-world conditions. MATERIALS AND METHODS: A total of 123 individuals with T2DM on SC dulaglutide, either as monotherapy or with other antihyperglycemic drugs, who switched to SC semaglutide were included. This switch was motivated by insufficient reduction in glycated hemoglobin (HbA1C), the need for greater weight loss, or gastrointestinal intolerance associated with dulaglutide. Changes with semaglutide in HbA1C and weight at 6, 12, 18, and 24 mo, as well as any changes in associated adverse effects. Data are expressed as mean +/- standard deviation. RESULTS: Previous treatment with dulaglutide (duration 16.9 +/- 13.8 mo) reduced HbA1c by 0.38% (p = 0.003 vs. baseline) and weight by -1.3 kg (p = 0.003 vs. baseline). After switching to semaglutide, an additional reduction in HbA1C levels was observed at 6, 12, 18, and 24 mo (-0.43%, p = 0.000; -0.54%, p = 0.000; -0.38%, p = 0.021; -0.12%, p = 0.622, respectively) and in weight at 6, 12, 18, and 24 mo (-2.7 kg, p = 0.000; -3.7 kg, p = 0.000; -5.4 kg, p = 0.001; -4.2 kg, p = 0.000, respectively) With no significant differences in the frequency of adverse effects after switching to semaglutide. CONCLUSIONS: In real-world conditions, switching dulaglutide to semaglutide in obese patients with T2DM is associated with an additional reduction in HbA1C and weight, without notable changes in the frequency of adverse effects. CI - Copyright (c) 2025 SEEN and SED. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Pardo Lozano, Felipe AU - Pardo Lozano F AD - Endocrinologia y Nutricion, Hospital Universitario La Plana, Castellon, Spain. Electronic address: feparloz@gmail.com. FAU - Rubio Marcos, Arantxa AU - Rubio Marcos A AD - Departamento de Endocrinologia y Nutricion, Hospital IMED Valencia, Valencia, Spain. FAU - Casan Fernandez, Rosa AU - Casan Fernandez R AD - Servicio de Endocrinologia y Nutricion, Hospital Clinico Universitario de Valencia, Valencia, Spain. FAU - Bartual Rodrigo, Amparo AU - Bartual Rodrigo A AD - Servicio de Endocrinologia y Nutricion, Hospital Clinico Universitario de Valencia, Valencia, Spain. FAU - Martinez-Hervas, Sergio AU - Martinez-Hervas S AD - Servicio de Endocrinologia y Nutricion, Hospital Clinico Universitario de Valencia, Valencia, Spain; Instituto de Investigacion Sanitaria INCLIVA, Valencia, Spain; Departament de Medicina, Facultat de Medicina, Universitat de Valencia (UV), Valencia, Spain; CIBER de Diabetes y Enfermedades Metabolicas asociadas (CIBERDEM), Madrid, Spain. FAU - Ampudia-Blasco, Francisco Javier AU - Ampudia-Blasco FJ AD - Servicio de Endocrinologia y Nutricion, Hospital Clinico Universitario de Valencia, Valencia, Spain; Instituto de Investigacion Sanitaria INCLIVA, Valencia, Spain; Departament de Medicina, Facultat de Medicina, Universitat de Valencia (UV), Valencia, Spain. LA - eng PT - Journal Article DEP - 20250530 PL - Spain TA - Endocrinol Diabetes Nutr (Engl Ed) JT - Endocrinologia, diabetes y nutricion JID - 101717565 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/adverse effects/therapeutic use MH - *Recombinant Fusion Proteins/administration & dosage/adverse effects/therapeutic use MH - *Immunoglobulin Fc Fragments/administration & dosage/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Glycated Hemoglobin/analysis MH - Aged MH - Drug Administration Schedule MH - *Drug Substitution MH - Treatment Outcome MH - Obesity/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Injections, Subcutaneous MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Agonistas del receptor de GLP-1 OT - Diabetes tipo 2 OT - Dulaglutida OT - Dulaglutide OT - GLP-1 receptor agonists OT - Perdida de peso OT - Semaglutida OT - Semaglutide OT - Type 2 diabetes OT - Weight loss COIS- Declaration of competing interest The authors Felipe Pardo Lozano, Arantxa Rubio Marcos, Rosa Casan Fernandez, Amparo Bartual Rodrigo, and Francisco Javier Ampudia-Blasco have participated in presentations on drugs for the treatment of diabetes and for weight loss in obesity. Dr. Sergio Martinez-Hervas has not collaborated with any laboratory that has products for the treatment of obesity. EDAT- 2025/06/04 19:07 MHDA- 2025/06/14 16:44 CRDT- 2025/06/01 01:49 PHST- 2024/10/06 00:00 [received] PHST- 2024/12/03 00:00 [revised] PHST- 2025/01/09 00:00 [accepted] PHST- 2025/06/14 16:44 [medline] PHST- 2025/06/04 19:07 [pubmed] PHST- 2025/06/01 01:49 [entrez] AID - S2530-0180(25)00075-7 [pii] AID - 10.1016/j.endien.2025.501574 [doi] PST - ppublish SO - Endocrinol Diabetes Nutr (Engl Ed). 2025 Jun-Jul;72(6):501574. doi: 10.1016/j.endien.2025.501574. Epub 2025 May 30. PMID- 40458885 OWN - NLM STAT- MEDLINE DCOM- 20250711 LR - 20260529 IS - 1744-8298 (Electronic) IS - 1479-6678 (Print) IS - 1479-6678 (Linking) VI - 21 IP - 9 DP - 2025 Jul TI - Semaglutide: a key medication for managing cardiovascular-kidney-metabolic syndrome. PG - 663-683 LID - 10.1080/14796678.2025.2511412 [doi] AB - Recent trials underscore the cardiovascular (CV), renal, and metabolic benefits of semaglutide in individuals with and without type 2 diabetes (T2D). In T2D, semaglutide enhances glycemic control, reduces major adverse CV events (MACE), and slows chronic kidney disease (CKD) progression. The SUSTAIN-6 trial demonstrated a 26% MACE reduction (HR 0.74; 95% CI: 0.58-0.95; p = 0.02) in high CV-risk patients with T2D using semaglutide (0.5 or 1.0 mg weekly). Similarly, the FLOW trial showed a 24% reduction in major kidney disease events (HR 0.76; 95% CI: 0.66-0.88; p = 0.002) with weekly 1.0 mg semaglutide in individuals with T2D with CKD. Beyond T2D, the SELECT trial highlighted semaglutide's efficacy in reducing MACE by 20% (HR 0.80; 95% CI: 0.72-0.90; p < 0.001) and slowing kidney function loss in overweight or obese individuals with preexisting CV disease using 2.4 mg weekly. Additionally, semaglutide alleviates heart failure symptoms and reduces hospitalizations in obese individuals regardless of T2D status. These findings underscore semaglutide's role in improving kidney, CV, and survival outcomes among high-risk patients. This review highlights the cardio-kidney-metabolic benefits of semaglutide in individuals with and without T2D to inform cardiologists about its potential to enhance patient care. FAU - MacIsaac, Richard J AU - MacIsaac RJ AUID- ORCID: 0000-0001-8058-6977 AD - Director of Endocrinology & Diabetes, St Vincent's Hospital Melbourne & Professorial Fellow University of Melbourne, Victoria, Australia. AD - Australian Centre For Accelerating Diabetes Innovations, University of Melbourne, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PT - Review DEP - 20250603 PL - England TA - Future Cardiol JT - Future cardiology JID - 101239345 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Cardiovascular Diseases/prevention & control/drug therapy/etiology MH - *Metabolic Syndrome/drug therapy/complications MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use MH - *Renal Insufficiency, Chronic/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12258229 OAB - Semaglutide, a medication in the glucagon-like peptide-1 receptor agonist (GLP-1 RA) class, offers significant health benefits across cardiovascular (CV), kidney, and metabolic conditions, collectively known as cardiovascular-kidney-metabolic (CKM) syndrome. CKM syndrome encompasses interconnected issues such as obesity, type 2 diabetes (T2D), CV disease (CVD), and chronic kidney disease (CKD). These conditions are commonly seen together, increasing the risk of heart and kidney problems.Semaglutide has proven effective for weight loss, improved blood sugar control, and CV protection. Clinical trials have shown it reduces major heart events like heart attacks and strokes in individuals with and without diabetes. It also slows CKD progression and lowers hospitalization rates for heart failure, particularly in patients with obesity. Emerging evidence suggests semaglutide might have additional benefits, such as reducing inflammation, improving liver health, and lowering risks associated with atrial fibrillation and osteoarthritis.Semaglutide's real-world use supports clinical trial findings, demonstrating safety and effectiveness across diverse patient groups. Its safety profile is generally favorable, though gastrointestinal side effects can occur.By addressing multiple interconnected conditions, semaglutide is poised to transform care for patients at high risk of heart, kidney, and metabolic complications. Further research is exploring new dosing methods, combinations with other medications, and expanded use in non-diabetic populations to maximize its benefits. OABL- eng OTO - NOTNLM OT - Cardiovascular diseases OT - cardiovascular-kidney-metabolic syndrome OT - chronic kidney disease OT - diabetes, type 2 OT - glucagon-like peptide 1 receptor agonists OT - heart diseases OT - obesity OT - semaglutide COIS- R MacIsaac has received research grants from Novo Nordisk, Servier, Medtronic, The Rebecca Cooper Medical Research Foundation, St Vincent's Research Foundation, The Juvenile Diabetes Research Foundation, Grey Innovations, The Diabetes Australia Research Trust/Program and The National Health and Medical Research Council of Australia. He has also received honoraria for lectures from Eli Lilly, Novo Nordisk, Sanofi Aventis, Astra Zeneca, Merck Sharp & Dohme, Novartis and Boehringer Ingelheim. He is on the advisory boards for Novo Nordisk, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, Astra Zeneca, and Merck Shape and Dohme. Novo Nordisk, Sanofi, Boehringer Ingelheim and Astra Zeneca have supplied travel support. He has been a principal investigator for industry-sponsored clinical trials by Novo Nordisk, Sanofi, Bayer, Johnson-Cilag and AbbVie. He was an investigator for the semaglutide trials SUSTAIN-6 and FLOW and was on the global expert panel for the FLOW trial. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Brad Dalton of medScript Communications provided medical writing and editorial support for this article, which Novo Nordisk funded. EDAT- 2025/06/03 06:27 MHDA- 2025/07/11 12:31 PMCR- 2025/06/03 CRDT- 2025/06/03 05:13 PHST- 2025/07/11 12:31 [medline] PHST- 2025/06/03 06:27 [pubmed] PHST- 2025/06/03 05:13 [entrez] PHST- 2025/06/03 00:00 [pmc-release] AID - 2511412 [pii] AID - 10.1080/14796678.2025.2511412 [doi] PST - ppublish SO - Future Cardiol. 2025 Jul;21(9):663-683. doi: 10.1080/14796678.2025.2511412. Epub 2025 Jun 3. PMID- 40443145 OWN - NLM STAT- MEDLINE DCOM- 20250530 LR - 20260127 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 21 IP - 920 DP - 2025 May 28 TI - [Glucagon-like peptide 1 agonists : the fourth pillar of nephroprotection in type 2 diabetes]. PG - 1117-1120 LID - 10.53738/REVMED.2025.21.920.47251 [doi] AB - GLP1 agonists are the emerging fourth pillar of nephroprotection in type 2 diabetes (T2D), alongside renin-angiotensin system blockers, sodium-glucose cotransporter 2 inhibitors, and finerenone (a non-steroidal mineralocorticoid receptor antagonist). The FLOW study showed that semaglutide 1 mg weekly prescribed in T2D patients with moderate to severe renal disease resulted in a 24 % reduction in the risk of a major renal event (NNT: 20) after a median follow-up of 3.4 years and a 20 % reduction in the relative risk of all-cause mortality (NNT: 39). Tirzepatide (a dual GLP1-GIP agonist) shows promising potential, but further data are awaited. However, their use requires caution, especially with regard to gastrointestinal adverse effects and the risk of muscle loss. A multidisciplinary approach remains essential to optimize their efficacy and safety. FAU - Lamine, Faiza AU - Lamine F AUID- ORCID: 0000-0001-6299-714X AD - Unite d'endocrinologie-diabetologie, Service de medecine interne, Centre hospitalier de Rennaz, 1847 Rennaz. AD - Service d'endocrinologie, diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Chtioui, Haithem AU - Chtioui H AUID- ORCID: 0000-0003-3821-6942 AD - Service de pharmacologie medicale, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Zanchi, Anne AU - Zanchi A AUID- ORCID: 0000-0003-0987-9333 AD - Service d'endocrinologie, diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. AD - Service de nephrologie, Centre hospitalier universitaire vaudois, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article TT - Agonistes du GLP-1: quatrieme pilier de la nephroprotection dans le diabete de type 2. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies/prevention & control/etiology MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - *Glucagon-Like Peptide 1/agonists MH - Glucagon-Like Peptides/therapeutic use MH - Semaglutide COIS- A. Zanchi a ete consultante pour les entreprises Lilly et Novo Nordisk. Les autres auteurs n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2025/05/30 07:41 MHDA- 2025/05/30 07:42 CRDT- 2025/05/30 02:53 PHST- 2025/05/30 07:42 [medline] PHST- 2025/05/30 07:41 [pubmed] PHST- 2025/05/30 02:53 [entrez] AID - RMS0920-004 [pii] AID - 10.53738/REVMED.2025.21.920.47251 [doi] PST - ppublish SO - Rev Med Suisse. 2025 May 28;21(920):1117-1120. doi: 10.53738/REVMED.2025.21.920.47251. PMID- 40443143 OWN - NLM STAT- MEDLINE DCOM- 20250530 LR - 20260127 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 21 IP - 920 DP - 2025 May 28 TI - [Nutritional management of type 2 diabetes with GLP-1 and GLP-1/GIP agonists]. PG - 1106-1111 LID - 10.53738/REVMED.2025.21.920.47028 [doi] AB - In diabetic patients, treatment with GLP-1 (Glucagon-Like Peptide-1) and dual GLP-1/GIP (gastric inhibitory polypeptide) agonists, such as, respectively, semaglutide and tirzepatide, is effective in lowering blood sugar and reducing weight. However, their use requires dietary monitoring to prevent muscle loss which is often associated with rapid weight loss. The treatment should be accompanied by specific nutritional recommendations, including adequate hydration, quality carbohydrates, as well as a sufficient intake of high-quality proteins and fiber. Physical activity, particularly anaerobic and aerobic exercises, is strongly recommended to maintain muscle mass and support weight loss. Finally, special attention should be given to side effects such as nausea or constipation. FAU - Pabion, Celine AU - Pabion C AD - Dieteticienne diplomee HES, MSc, Service d'endocrinologie, de diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Pignolet-Marti, Anaelle AU - Pignolet-Marti A AD - Dieteticienne diplomee HES, Service d'endocrinologie, de diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Zanchi, Anne AU - Zanchi A AUID- ORCID: 0000-0003-0987-9333 AD - Service de nephrologie, Centre hospitalier universitaire vaudois, 1011 Lausanne. AD - Service d'endocrinologie, de diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. FAU - Borloz, Sylvie AU - Borloz S AUID- ORCID: 0000-0002-6199-1413 AD - Service d'endocrinologie, de diabetologie et metabolisme, Centre hospitalier universitaire vaudois, 1011 Lausanne. AD - Dieteticienne cheffe adjointe, MSc, Service d'endocrinologie, de diabetologie et metabolisme, nutrition clinique, Centre hospitalier universitaire vaudois, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article TT - Prise en charge nutritionnelle du diabete de type 2 avec les agonistes GLP-1 et du GLP-1/GIP. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy/therapy MH - *Glucagon-Like Peptide 1/agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Gastric Inhibitory Polypeptide/agonists MH - Glucagon-Like Peptides/therapeutic use MH - Exercise MH - Weight Loss/drug effects MH - Blood Glucose/drug effects MH - Semaglutide COIS- Les auteures n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2025/05/30 08:04 MHDA- 2025/05/30 08:05 CRDT- 2025/05/30 02:53 PHST- 2025/05/30 08:05 [medline] PHST- 2025/05/30 08:04 [pubmed] PHST- 2025/05/30 02:53 [entrez] AID - RMS0920-002 [pii] AID - 10.53738/REVMED.2025.21.920.47028 [doi] PST - ppublish SO - Rev Med Suisse. 2025 May 28;21(920):1106-1111. doi: 10.53738/REVMED.2025.21.920.47028. PMID- 40439835 OWN - NLM STAT- MEDLINE DCOM- 20261012 LR - 20261014 IS - 1556-3308 (Electronic) IS - 1094-3412 (Linking) VI - 53 IP - 4 DP - 2026 Oct TI - Glucagon-Like Peptide-1 Use and Healthcare Resource Utilization for Depression and Anxiety Among Adults with Type 2 Diabetes: 2019 to 2023. PG - 622-638 LID - 10.1007/s11414-025-09950-6 [doi] AB - Mental health disorders, including depression and anxiety, are common comorbidities in individuals with type 2 diabetes mellitus (T2DM), contributing to increased healthcare resource utilization (HCRU) and the financial burden of the disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are commonly used for T2DM management, and emerging evidence suggests they may help alleviate mental health symptoms. This study examined the association between GLP-1RA (versus DPP-4 inhibitor [DPP-4i]) initiation and mental health-related HCRU in T2DM patients. Using data from the Komodo Healthcare Map, a national database of pharmacy and medical claims, this study conducted a retrospective cohort analysis with 774,968 adults who initiated GLP-1RAs or DPP-4i between January 2019 and March 2022. Patients were followed for 12 months, and mental health-related HCRU (emergency department, inpatient, outpatient hospital, and office visits) for depression and anxiety was assessed. A difference-in-differences analysis compared HCRU before and after medication initiation, adjusting for sociodemographic and clinical variables. GLP-1RA use was associated with significant reductions in outpatient hospital visits (IRR: 0.96; 95% CI: 0.95-0.98) for depression, and office visits for depression (IRR: 0.87; 95% CI: 0.82-0.92) and anxiety (IRR: 0.85; 95% CI: 0.81-0.90) compared to DPP-4i. However, no significant changes were observed in emergency or inpatient visits. Reductions were more pronounced with semaglutide, liraglutide, and dulaglutide. These findings suggest that GLP-1RAs may help reduce depression- and anxiety-related HCRU in patients with T2DM, indicating potential benefits beyond glycemic control. Further research is needed to explore long-term outcomes and the cost-effectiveness of GLP-1RAs for managing mental health comorbidities. CI - (c) 2025. National Council for Mental Wellbeing. FAU - Do, Duy AU - Do D AUID- ORCID: 0000-0001-9919-6848 AD - Evernorth Research Institute, 1 Express Way, St. Louis, MO, 63121, USA. duy.do@evernorth.com. FAU - Lee, Tiffany AU - Lee T AD - Evernorth Research Institute, 1 Express Way, St. Louis, MO, 63121, USA. FAU - Inneh, Angela AU - Inneh A AD - Evernorth Research Institute, 1 Express Way, St. Louis, MO, 63121, USA. FAU - Patel, Urvashi AU - Patel U AD - Evernorth Research Institute, 1 Express Way, St. Louis, MO, 63121, USA. LA - eng PT - Journal Article DEP - 20250529 PL - United States TA - J Behav Health Serv Res JT - The journal of behavioral health services & research JID - 9803531 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/psychology MH - Female MH - Retrospective Studies MH - Male MH - *Depression/drug therapy MH - Middle Aged MH - *Patient Acceptance of Health Care/statistics & numerical data MH - *Anxiety/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptide 1/therapeutic use MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Semaglutide COIS- Declarations. Ethical approval and consent to participate: Not applicable. Reporting guidelines: This study was conducted in accordance with the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for observational research. Conflict of interest: The authors declare no competing interests. EDAT- 2025/05/29 12:56 MHDA- 2026/10/12 17:30 CRDT- 2025/05/29 11:07 PHST- 2025/04/25 00:00 [accepted] PHST- 2026/10/12 17:30 [medline] PHST- 2025/05/29 12:56 [pubmed] PHST- 2025/05/29 11:07 [entrez] AID - 10.1007/s11414-025-09950-6 [pii] AID - 10.1007/s11414-025-09950-6 [doi] PST - ppublish SO - J Behav Health Serv Res. 2026 Oct;53(4):622-638. doi: 10.1007/s11414-025-09950-6. Epub 2025 May 29. PMID- 40437949 OWN - NLM STAT- MEDLINE DCOM- 20250704 LR - 20260822 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 8 DP - 2025 Aug TI - GLP-1 receptor agonists and the risk for cancer: A meta-analysis of randomized controlled trials. PG - 4454-4468 LID - 10.1111/dom.16489 [doi] AB - AIMS: To assess if there is a difference in the oncogenic risk between GLP-1 RA and comparators in randomized controlled trials. MATERIALS AND METHODS: A meta-analysis of randomized controlled trials comparing GLP-1RA to any comparators for diabetes and/or obesity, lasting at least 52 weeks. The endpoints included the incidence of overall cancers and single malignancies. RESULTS: Fifty trials were included. GLP-1RA treatment was not associated with a significant difference in risk for overall cancer (MH-OR 1.05, 95% confidence interval [CI] [0.98, 1.13]). Uterine cancer was significantly reduced in the GLP-1RA arm in trials performed in subjects with obesity (MH-OR 0.24, 95% CI [0.06, 0.94]), but not in those aimed at diabetes treatment (MH-OR 0.92, [0.58, 1.47]). We detected an increase in the risk for thyroid cancer (MH-OR 1.55, [1.05, 2.27]), more evident in longer-term trials, and in the risk for colorectal cancer (MH-OR 1.27 [1.03, 1.57]), which, conversely, was significant only in shorter-term trials. No significant difference in the risk was detected for any other cancer. CONCLUSIONS: GLP-1 RA do not appear to produce an effect on most malignancies in clinical trials. A reduction of very close obesity-associated cancers seems possible, whereas a risk signal for thyroid cancer was observed, prompting the need for further specific studies. On the other hand, the small increase observed in colorectal cancer in shorter-term trials may be the effect of a disproportionate increase in diagnostic procedures in the GLP-1 RA arm, because of the suspicion raised by common side effects of GLP-1 RA. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Silverii, Giovanni Antonio AU - Silverii GA AUID- ORCID: 0000-0002-6695-3213 AD - AOU Careggi, Diabetology Unit - Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy. FAU - Marinelli, Christian AU - Marinelli C AD - AOU Careggi, Diabetology Unit - Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy. FAU - Bettarini, Costanza AU - Bettarini C AD - AOU Careggi, Diabetology Unit - Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy. FAU - Del Vescovo, Gloria Giovanna AU - Del Vescovo GG AD - AOU Careggi, Diabetology Unit - Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy. FAU - Monami, Matteo AU - Monami M AUID- ORCID: 0000-0001-9349-828X AD - Diabetology Unit, AOU Careggi, Florence, Italy. FAU - Mannucci, Edoardo AU - Mannucci E AUID- ORCID: 0000-0001-9759-9408 AD - AOU Careggi, Diabetology Unit - Experimental and Clinical Biomedical Sciences "Mario Serio" Department, University of Florence, Florence, Italy. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20250529 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Randomized Controlled Trials as Topic MH - *Neoplasms/epidemiology/chemically induced MH - *Obesity/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Risk Factors MH - Colorectal Neoplasms/epidemiology/chemically induced MH - Incidence PMC - PMC12232360 OTO - NOTNLM OT - GLP-1 RA OT - cancer OT - dulaglutide OT - exenatide OT - glucagon-like peptide-1 receptor agonists OT - liraglutide OT - meta-analysis OT - obesity OT - semaglutide OT - type 2 diabetes mellitus COIS- GAS has received speaking or consultancy fees from Astra Zeneca, Eli-Lilly and Novo Nordisk, outside the submitted work. MM has received speaking fees from Astra Zeneca, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk and Sanofi, outside the submitted work. The unit directed by EM has received research grants from Abbott, Eli-Lilly and Novo Nordisk, outside the submitted work. EM has received consultancy fees or speaking fees from Astra Zeneca, Bayer, Boehringer-Ingelheim, Coresearch, Dexcom, Eli-Lilly, Molteni, Novo Nordisk, Pidkare and Sanofi, outside the submitted work. C.M., G.G.D.V. and C.B. do not have any competing interests to disclose. EDAT- 2025/05/29 06:26 MHDA- 2025/07/04 12:43 PMCR- 2025/07/07 CRDT- 2025/05/29 04:03 PHST- 2025/05/14 00:00 [revised] PHST- 2025/01/13 00:00 [received] PHST- 2025/05/14 00:00 [accepted] PHST- 2025/07/04 12:43 [medline] PHST- 2025/05/29 06:26 [pubmed] PHST- 2025/05/29 04:03 [entrez] PHST- 2025/07/07 00:00 [pmc-release] AID - DOM16489 [pii] AID - 10.1111/dom.16489 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27(8):4454-4468. doi: 10.1111/dom.16489. Epub 2025 May 29. PMID- 40434727 OWN - NLM STAT- MEDLINE DCOM- 20250718 LR - 20260127 IS - 1743-9159 (Electronic) IS - 1743-9159 (Linking) VI - 111 IP - 7 DP - 2025 Jul 1 TI - The impact of semaglutide on fusion rates following posterior lumbar fusion surgery in patients with type 2 diabetes. PG - 4898-4900 LID - 10.1097/JS9.0000000000002492 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist used in managing type 2 diabetes mellitus (T2DM), has demonstrated cardiovascular and glycemic benefits. However, its influence on surgical outcomes, particularly spinal fusion, remains unclear. This study aims to evaluate the association between semaglutide use and pseudarthrosis rates following posterior lumbar fusion surgery in patients with T2DM. METHODS: Data were retrieved from the TriNetX Global Collaborative Network, which includes de-identified records from 117 healthcare systems. T2DM patients who underwent posterior lumbar fusion were identified using CPT codes, and semaglutide exposure was determined preoperatively. Patients were divided into semaglutide and non-semaglutide groups, with 1:1 propensity score matching applied. Pseudarthrosis was identified using ICD-10 code M96.0. RESULTS: After matching, baseline characteristics were well-balanced between groups with 884 patients in each group. Semaglutide users had significantly lower rates of pseudarthrosis at 6 months (8.0% vs. 13.1%, OR: 0.58; 95% CI: 0.42-0.79), 1 year (8.9% vs. 14.0%, OR: 0.60; 95% CI: 0.45-0.81), and two years (10.1% vs. 15.7%, OR: 0.60; 95% CI: 0.45-0.80) compared to non-users. CONCLUSIONS: Semaglutide use is associated with a reduced risk of pseudarthrosis following posterior lumbar fusion in patients with T2DM. Further studies are warranted to elucidate the mechanisms underlying this potential benefit and to assess its implications in broader patient populations. CI - Copyright (c) 2025 The Author(s). Published by Wolters Kluwer Health, Inc. FAU - Chang, Yu AU - Chang Y AD - Section of Neurosurgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. FAU - Lin, Hong-Min AU - Lin HM AD - Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA. FAU - Chi, Kuan-Yu AU - Chi KY AD - Department of Family Medicine, Chi-Mei Medical Center, Tainan, Taiwan. FAU - Song, Junmin AU - Song J AD - Department of Family Medicine, Chi-Mei Medical Center, Tainan, Taiwan. FAU - Atwan, Hany AU - Atwan H AD - Faculty of Medicine, Assiut University, Assiut, Egypt. LA - eng PT - Journal Article DEP - 20250528 PL - United States TA - Int J Surg JT - International journal of surgery (London, England) JID - 101228232 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Spinal Fusion/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Lumbar Vertebrae/surgery MH - Aged MH - *Pseudarthrosis/epidemiology/etiology/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - *Postoperative Complications/epidemiology/prevention & control MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - lumbar fusion surgery OT - pseudoarthrosis OT - semaglutide EDAT- 2025/05/28 12:28 MHDA- 2025/07/18 06:26 CRDT- 2025/05/28 11:23 PHST- 2025/04/22 00:00 [received] PHST- 2025/04/24 00:00 [accepted] PHST- 2025/07/18 06:26 [medline] PHST- 2025/05/28 12:28 [pubmed] PHST- 2025/05/28 11:23 [entrez] AID - 01279778-202507000-00069 [pii] AID - 10.1097/JS9.0000000000002492 [doi] PST - ppublish SO - Int J Surg. 2025 Jul 1;111(7):4898-4900. doi: 10.1097/JS9.0000000000002492. Epub 2025 May 28. PMID- 40409279 OWN - NLM STAT- MEDLINE DCOM- 20250603 LR - 20260127 IS - 1439-4286 (Electronic) IS - 0018-5043 (Linking) VI - 57 IP - 5 DP - 2025 May TI - Efficacy, Safety, and Future of GLP-1 Receptor Agonists: A Systematic Literature Review and Meta-Analysis. PG - 326-337 LID - 10.1055/a-2569-7315 [doi] AB - GLP-1 receptor agonists have emerged as important therapeutic agents for type 2 diabetes mellitus (T2DM), but their comparative efficacy and broader applications remain subjects of ongoing research. The aim of the study was to evaluate and compare the efficacy, safety, and clinical applications of three GLP-1 receptor agonists - Semaglutide, Dulaglutide, and Exenatide - through systematic review and meta-analysis. A comprehensive search of PubMed/MEDLINE, Embase, Cochrane Library, Scopus, and Web of Science (2015-2023) identified 20 randomized controlled trials and observational studies. Primary outcomes included changes in HbA1c and body weight. Risk of bias was assessed using the Cochrane Collaboration's Risk of Bias tool. Semaglutide demonstrated superior efficacy with mean HbA1c reduction of 1.45% and weight loss of 1.44 kg. Dulaglutide showed consistent reductions in HbA1c (1.1%) and weight (1.2 kg). while Exenatide exhibited moderate effects. Meta-analysis revealed a significant pooled effect estimate favoring GLP-1 receptor agonists. with a mean HbA1c difference of -0.81 (95% CI: -0.92 to -0.70). Gastrointestinal side effects were most common, with Semaglutide showing the highest incidence. This meta-analysis establishes Semaglutide as the most effective GLP-1 receptor agonist for glycemic control and weight reduction, while Dulaglutide and Exenatide offer viable alternatives with fewer side effects. These findings support evidence-based decision-making in T2DM management and highlight the potential broader therapeutic applications of GLP-1 receptor agonists beyond diabetes care. CI - Thieme. All rights reserved. FAU - Katz, Griffin AU - Katz G AUID- ORCID: 0009-0005-4153-2913 AD - Edith Neumann School of Health and Human Services, Touro University California, Vallejo, United States. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250523 PL - Germany TA - Horm Metab Res JT - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JID - 0177722 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Exenatide/therapeutic use/adverse effects MH - Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - *Recombinant Fusion Proteins/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism MH - Treatment Outcome MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- The authors declare that they have no conflict of interest. EDAT- 2025/05/24 00:46 MHDA- 2025/06/04 00:29 CRDT- 2025/05/23 18:42 PHST- 2025/06/04 00:29 [medline] PHST- 2025/05/24 00:46 [pubmed] PHST- 2025/05/23 18:42 [entrez] AID - 10.1055/a-2569-7315 [doi] PST - ppublish SO - Horm Metab Res. 2025 May;57(5):326-337. doi: 10.1055/a-2569-7315. Epub 2025 May 23. PMID- 40404820 OWN - NLM STAT- MEDLINE DCOM- 20250710 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 68 IP - 8 DP - 2025 Aug TI - Heterogeneity in response to GLP-1 receptor agonists in type 2 diabetes in real-world clinical practice: insights from the DPV register - an IMI-SOPHIA study. PG - 1666-1673 LID - 10.1007/s00125-025-06448-w [doi] AB - AIMS/HYPOTHESIS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a cornerstone in type 2 diabetes management. In this study we evaluated heterogeneity in body weight and glycaemic responses to the initiation of liraglutide, semaglutide or dulaglutide in real-world clinical practice. METHODS: Data from 4467 adults with type 2 diabetes in the Diabetes Patient Follow-up (DPV) registry were analysed, focusing on changes in HbA(1c) and body weight over 6 months following initiation of a GLP-1 RA. We categorised participants based on their response: HbA(1c) reduction only, weight loss only, both or neither. This analysis was part of the IMI-Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (IMI-SOPHIA) project. RESULTS: At 6 months' follow-up the median absolute HbA(1c) reduction was 5.3 mmol/mol (IQR 13.9, -1.0) (0.49% [1.27, -0.09]) and relative body weight reduction was 1.43% (4.26, 0). Only 14% of participants achieved meaningful reductions in both HbA(1c) (absolute reduction >/=5.5 mmol/mol [0.5%]) and body weight (relative reduction >/=5%). Men and those with a higher baseline HbA(1c) were more likely to show an HbA(1c) only response (36% of participants; both p<0.001), while older individuals and those with a longer diabetes duration were more likely to experience a weight-only response (7% of participants; both p<0.001). Higher baseline body weight and lower eGFR (both p<0.05) correlated with greater weight reduction, whereas lower baseline HbA(1c) and longer diabetes duration were linked to smaller HbA(1c) reductions (both p<0.001). CONCLUSIONS/INTERPRETATION: There is significant heterogeneity in responses to GLP-1 RA therapy among individuals with type 2 diabetes in routine clinical practice. However, in our study a substantial proportion achieved a reduction in either body weight or HbA(1c). Future studies should explore why some individuals achieve either weight loss or HbA(1c) reduction but not both. CI - (c) 2025. The Author(s). FAU - Heni, Martin AU - Heni M AUID- ORCID: 0000-0002-8462-3832 AD - Division of Endocrinology and Diabetology, Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany. martin.heni@uniklinik-ulm.de. AD - Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tubingen, Tubingen, Germany. martin.heni@uniklinik-ulm.de. FAU - Fruhwald, Lisa AU - Fruhwald L AD - 5th Medical Department, Endocrinology, Rheumatology and Acute Geriatrics, Hospital Ottakring, Vienna, Austria. FAU - Karges, Wolfram AU - Karges W AD - Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany. FAU - Naudorf, Michael AU - Naudorf M AD - Diabetes Center Lindlar, Lindlar, Germany. FAU - Niemoller, Kathrin AU - Niemoller K AD - Knappschaftskrankenhaus Dortmund, Department of Internal Medicine V, Dortmund, Germany. FAU - Pagnia, Frank AU - Pagnia F AD - Specialised Diabetes Practice, Memmingen, Germany. FAU - Reindel, Jorg AU - Reindel J AD - Department of Diabetology, Metabolic Disorders and Nephrology, Hospital Karlsburg, Karlsburg, Germany. FAU - Seufert, Jochen AU - Seufert J AD - Division of Endocrinology and Diabetology, Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Ufer, Gisa AU - Ufer G AD - Division of Endocrinology and Diabetology, Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany. FAU - Wagner, Christian AU - Wagner C AD - Specialised Diabetes Practice, Saaldorf-Surheim, Germany. FAU - Holl, Reinhard W AU - Holl RW AD - Institute of Epidemiology and Medical Biometry, CAQM, University of Ulm, Ulm, Germany. AD - German Centre for Diabetes Research (DZD), Munich-Neuherberg, Germany. FAU - Prinz, Nicole AU - Prinz N AUID- ORCID: 0000-0002-7570-9095 AD - Institute of Epidemiology and Medical Biometry, CAQM, University of Ulm, Ulm, Germany. AD - German Centre for Diabetes Research (DZD), Munich-Neuherberg, Germany. LA - eng GR - 875534/the Innovative Medicines Initiative 2 Joint Undertaking/ GR - 82DZD14E1G/German Center for Diabetes Research (DZD)/ GR - 1368-1711/Robert Koch Institut/ PT - Journal Article DEP - 20250522 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Liraglutide/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Aged MH - Registries MH - Immunoglobulin Fc Fragments/therapeutic use MH - Weight Loss/drug effects MH - Recombinant Fusion Proteins/therapeutic use MH - Blood Glucose/drug effects/metabolism MH - Body Weight/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12245949 OTO - NOTNLM OT - Body weight OT - GLP-1 receptor agonists OT - HbA1c OT - Heterogeneity OT - Real life COIS- Acknowledgements: Special thanks to A. Hungele and R. Ranz for support and development of the DPV documentation software (both clinical data managers, Ulm University). The authors further wish to express their special gratitude to all DPV centres participating in the initiative. Centres contributing data to the present analysis were Aachen - Innere RWTH, Aidlingen Praxisgemeinschaft, Asbach Kamillus-Klinik Innere, Augsburg IV, Medizinische Uni-Klinik, Bad Aibling Internist, Praxis, Bad Aibling Internistische Praxis-2, Bad Oeynhausen Herz-und Diabeteszentrum NRW, Bad Reichenhall Kreisklinik Innere Medizin, Bayreuth Innere Medizin, Berchtesgaden CJD, Bergen Gemeinschaftspraxis, Berlin DRK-Kliniken Mitte Innere, Berlin Endokrinologikum, Berlin Klinik St. Hedwig Innere, Berlin Oskar Zieten Krankenhaus Innere, Berlin Schlosspark-Klinik Innere, Berlin Vivantes Hellersdorf Innere, Bodnegg - MVZ Wollmarshohe, Bonn Schwerpunktpraxis, Bottrop Knappschaftskrankenhaus Innere, Bremen - Mitte Innere, Bremerhaven Kinderklinik, Castrop-Rauxel Rochus-Hospital, Chemnitz-Hartmannsdorf Innere Medizin - DIAKOMED-1, Coburg Innere Medizin, Coesfeld/Dulmen Innere Medizin, Darmstadt Innere Medizin, Deggendorf Gemeinschaftspraxis, Dortmund Johannes Hospital, Dortmund Knappschaftskrankenhaus Innere, Dortmund Medizinische Kliniken Nord, Dortmund-St. Josefshospital Innere, Dortmund-West Innere, Duisburg Homberg Helios Rhein-Ruhr Kliniken GmbH, Duisburg St. Anna Innere Helios Rhein-Ruhr Kliniken GmbH, Duisburg-Huckingen, Eckernforde Gemeinschaftspraxis, Eisleben Lutherstadt Helios-Klinik, Erlangen Uni Innere Medizin, Essen Diabetes-SPP, Essen Diabetes-Schwerpunktpraxis, Forchheim Diabeteszentrum SPP, Frankfurt Diabeteszentrum Rhein-Main-Erwachsenendiabetologie (Burgerhospital), Frankfurt Uni-Klinik Innere, Frankfurt-Sachsenhausen Innere, Frankfurt-Sachsenhausen Innere MVZ, Freiburg Uni Innere, Geislingen Klinik Helfenstein Innere, Giessen Evangelisches Krankenhaus Mittelhessen, Gottingen Uni Gastroenterologie, Gustrow Innere, Halberstadt Innere Medizin AMEOS Klinik, Hanau diabetolologische Schwerpunktpraxis, Heide Westkustenklinikum Innere Medizin, Heidelberg St. Josefskrankenhaus, Heidenheim Arztpraxis Allgemeinmedizin, Heilbronn Innere Klinik, Herford Innere Med I, Herne Evanangelisches Krankenhaus Innere, Hildesheim GmbH - Innere, Idar Oberstein Schwerpunktpraxis, Jena diabetologische Schwerpunktpraxis, Kamen Klinikum Westfalen Hellmig Krankenhaus, Kamen MKK - Medizinisches Kompetenzkollegium, Karlsburg Klinik fur Diabetes und Stoffwechsel, Karlsruhe Schwerpunktpraxis, Kirchheim-Nurtingen Innere, Koblenz Kemperhof 1. Medizinische Klinik, Konstanz Innere Klinik, Krefeld-Uerdingen St. Josef Innere, Landau Innere, Lilienthal Diabeteszentrum, Limburg Innere Medizin, Lindlar DM-Zentrum, Linz Krankenhaus Barmherzige Schwestern Kardiologie Abt. Int. II, Ludwigshafen diabetol. SPP, Luxembourg - Centre Hospitalier, Lubeck Uni-Klinik Innere Medizin, Lunen Klinik am Park, Magdeburg Stadtisches Klinikum Innere, Manderscheid Rathauspraxis, Marktredwitz Innere Medizin, Memmingen Internistische Praxis, Murnau am Staffelsee - diabetol. SPP, Muhlheim an der Ruhr Evang. Krankenhaus Medizinische Klinik, Munchen Diabetes-Zentrum Sud, Munchen Schwerpunktpraxis, Munster Herz Jesu Innere, Munster Ludgerus-Kliniken GmbH, Neunkirchen Innere Medizin, Neuwied Marienhaus Klinikum St. Elisabeth Innere, Oberndorf Gastroenterologische Praxis Schwerpunkt Diabetologie, Pirmasens Stadtisches Krankenhaus Innere, Prenzlau Krankenhaus Innere, Prien am Chiemsee Innere, Rosenheim Innere Medizin, Rosenheim Schwerpunktpraxis, Rottweil Gemeinschaftspraxis fur Innere Medizin, Saaldorf-Surheim Diabetespraxis, Schwerin Innere Medizin, Spaichingen Innere, Stuttgart Sana Klinik Bethesda, Tettnang Innere Medizin, Traunstein diabetologische Schwerpunktpraxis, Trostberg Innere, Ulm Schwerpunktpraxis Bahnhofsplatz, Ulm Uni Innere Medizin, Ulm Uni-Kinderklinik, Viersen internist. Praxis, Villingen-Schwenningen Schwarzwald-Baar-Klinikum Innere, Wangen Oberschwabenklinik Innere Medizin, Weisswasser Kreiskrankenhaus, Wernberg-Koblitz SPP, Wien Uni Innere Medizin III, Wittlich DSP, Worms Schwerpunktpraxis. Data availability: The data are not publicly available because they contain information that could compromise research participant privacy/consent. Funding: Open Access funding enabled and organized by Projekt DEAL. The DPV initiative is funded by the German Center for Diabetes Research (DZD, grant no. 82DZD14E1G), the Robert Koch Institute (RKI, grant no. 1368-1711) and the German Diabetes Association (DDG). In addition, this study is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (SOPHIA) project ( www.imisophia.eu ). SOPHIA has received funding from the Innovative Medicines Initiative (IMI) 2 Joint Undertaking under grant agreement no. 875534. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA and the T1D Exchange, JDRF and Obesity Action Coalition. This article reflects the authors' views and neither the IMI nor the European Union, EFPIA or any associated partners are responsible for any use that may be made of the information contained therein. Authors' relationships and activities: Outside the current work, MH reports lecture fees from Chiesi/Amryt, AstraZeneca, Boehringer Ingelheim, Lilly, Novartis, Novo Nordisk and Sanofi. He has also served on advisory boards for Chiesi/Amryt, Boehringer Ingelheim and Sanofi. He is also currently a board member of the German Diabetes Association (DDG). Outside the current work, MN reports lecture fees from AstraZeneca and Dexcom. He is a member of the scientific committee of the Arbeitsgemeinschaft Diabetes & Technologie of the German Diabetes Association (DDG). Outside the current work, JR reports lecture fees from AstraZeneca and Sanofi. Outside the current work, JS has received honoraria for talks and/or consultancy and/or research funding from Apitope, AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Bristol-Meyers Squibb, Eli Lilly, GI Dynamics, GlaxoSmithKline, Intarcia, Ipsen, Janssen, LifeScan, MedScape, MSD, Novartis, Novo Nordisk, OmniaMed, Pfizer, Roche, Sanofi, Servier, Takeda and Ypsomed. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: MH and NP designed/performed the analyses, discussed the findings and drafted the manuscript. LF, WK, MN, KN, FP, JR, JS, GU and CW were responsible for acquisition of the data and reviewed the manuscript critically for important intellectual content. RWH made substantial contributions to the initial conception of the work and reviewed the manuscript critically for important intellectual content. All authors approved the final version of the manuscript prior to submission. NP and RWH are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. EDAT- 2025/05/23 00:27 MHDA- 2025/07/10 12:31 PMCR- 2025/05/22 CRDT- 2025/05/22 23:25 PHST- 2024/10/26 00:00 [received] PHST- 2025/03/25 00:00 [accepted] PHST- 2025/07/10 12:31 [medline] PHST- 2025/05/23 00:27 [pubmed] PHST- 2025/05/22 23:25 [entrez] PHST- 2025/05/22 00:00 [pmc-release] AID - 10.1007/s00125-025-06448-w [pii] AID - 6448 [pii] AID - 10.1007/s00125-025-06448-w [doi] PST - ppublish SO - Diabetologia. 2025 Aug;68(8):1666-1673. doi: 10.1007/s00125-025-06448-w. Epub 2025 May 22. PMID- 40392993 OWN - NLM STAT- MEDLINE DCOM- 20250521 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 6 DP - 2025 Jun 1 TI - Cost-effectiveness of Semaglutide Compared With Other Glucose-Lowering Medications in Treating Type 2 Diabetes: A Comprehensive Systematic Review and Meta-analysis. PG - 1032-1041 LID - 10.2337/dc24-2241 [doi] AB - BACKGROUND: Significant clinical efficacy has been shown for semaglutide in managing type 2 diabetes (T2D); however, its cost-effectiveness remains uncertain. PURPOSE: To systematically review existing evidence on cost-effectiveness of semaglutide versus other T2D medications. DATA SOURCES: PubMed, Embase, and the Cost-Effectiveness Analysis Registry (by 11 June 2024). STUDY SELECTION: A total of 45 articles (with 119 comparisons) from 2019 onward were included, representing Europe (n = 24), North America (n = 13), and Asia (all from China) (n = 8). DATA EXTRACTION: Study characteristics and model characteristics/inputs/results were extracted. Lifetime costs and quality-adjusted life-years were evaluated. Proportions for cost-effectiveness outcomes (dominant, cost-effective, not cost-effective) were calculated. Subgroup analyses by region, sponsor type, comparator type, and model assumptions were performed. In sensitivity analysis a standard willingness-to-pay threshold was applied. DATA SYNTHESIS: Of the articles included, 93.3% included adoption of a lifetime horizon and 84.4% a health care perspective and 68.9% were industry sponsored. For most studies reporting quality was high (86.7%). Overall, semaglutide was dominant/cost-effective in 73.9% of all comparisons. Notably, semaglutide was found to be dominant/cost-effective in all comparisons sponsored by Novo Nordisk versus in 50.0% of these funded by nonindustry sponsors and in none funded by other industry sponsors. Additionally, semaglutide was more cost-effective in high-income countries and in studies with adoption of a broader perspective, longer horizon, and lower discount rates. Results remained consistent with conversion with a common currency unit and willingness-to-pay threshold of US$50,000. LIMITATIONS: Less detailed demographic information for more granular analyses. CONCLUSIONS: Semaglutide is generally cost-effective compared with other glucose-lowering medications in evaluation against within-study willingness-to-pay thresholds; however, results varied by study sponsor type, region, and model assumptions, highlighting the need for transparent and context-sensitive economic evaluations. CI - (c) 2025 by the American Diabetes Association. FAU - Liu, Ziyun AU - Liu Z AUID- ORCID: 0009-0003-8364-3270 AD - Division of the Social Sciences, University of Chicago, Chicago, IL. FAU - Zeng, Baoqi AU - Zeng B AUID- ORCID: 0000-0003-4443-6183 AD - Central Laboratory, Peking University Binhai Hospital, Tianjin, China. AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. FAU - Sun, Feng AU - Sun F AUID- ORCID: 0000-0003-4334-6805 AD - Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China. AD - Key Laboratory of Epidemiology of Major Diseases, Peking University, Ministry of Health, Beijing, China. AD - Department of Ophthalmology, Peking University Third Hospital, Beijing, China. FAU - Xia, Qing AU - Xia Q AD - Australian Centre for Health Services Innovation and Centre for Healthcare Transformation, School of Public Health and Social Work, Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucagon-Like Peptides/therapeutic use/economics MH - Cost-Benefit Analysis MH - *Hypoglycemic Agents/therapeutic use/economics MH - Quality-Adjusted Life Years MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12094200 COIS- Duality of Interest. No potential conflicts of interest relevant to this article were reported. EDAT- 2025/05/20 18:29 MHDA- 2025/05/21 18:29 PMCR- 2025/05/20 CRDT- 2025/05/20 15:12 PHST- 2024/10/16 00:00 [received] PHST- 2025/03/01 00:00 [accepted] PHST- 2025/05/21 18:29 [medline] PHST- 2025/05/20 18:29 [pubmed] PHST- 2025/05/20 15:12 [entrez] PHST- 2025/05/20 00:00 [pmc-release] AID - 158296 [pii] AID - dc242241 [pii] AID - 10.2337/dc24-2241 [doi] PST - ppublish SO - Diabetes Care. 2025 Jun 1;48(6):1032-1041. doi: 10.2337/dc24-2241. PMID- 40388980 OWN - NLM STAT- MEDLINE DCOM- 20250519 LR - 20260512 IS - 1439-4413 (Electronic) IS - 0012-0472 (Linking) VI - 150 IP - 12 DP - 2025 Jun TI - [GLP-1 agonists - new kid on the block in nephrology]. PG - 696-702 LID - 10.1055/a-2420-6176 [doi] AB - GLP-1 receptor agonists (GLP-1-RA) are emerging as promising agents beyond their established role in type 2 diabetes mellitus (T2DM) and obesity treatment, showing significant nephroprotective effects. The FLOW study demonstrated that semaglutide significantly slows the progression of chronic kidney disease (CKD) in T2DM patients. The nephroprotective mechanisms are multifactorial, including improved glycemic control, blood pressure reduction, antifibrotic, and anti-inflammatory effects. Early studies suggest that GLP-1-RA may also benefit patients without T2DM. Additionally, their combination with SGLT2 inhibitors is gaining relevance. Current evidence suggests that GLP-1-RA could play a key role in CKD management. Future studies will determine whether they can be established as a standard therapy to optimize care for high-risk patients. CI - Thieme. All rights reserved. FAU - Kraft, Leonie AU - Kraft L AD - Allg. Innere Medizin u. Nephrologie, Robert-Bosch-Krankenhaus, Stuttgart, Deutschland. FAU - Schanz, Moritz AU - Schanz M AD - Allg. Innere Medizin u. Nephrologie, Robert-Bosch-Krankenhaus, Stuttgart, Deutschland. FAU - Latus, Jorg AU - Latus J AD - Allg. Innere Medizin u. Nephrologie, Robert-Bosch-Krankenhaus, Stuttgart, Deutschland. LA - ger PT - English Abstract PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review TT - GLP-1-RA - "New kid on the block" in der Nephrologie? DEP - 20250519 PL - Germany TA - Dtsch Med Wochenschr JT - Deutsche medizinische Wochenschrift (1946) JID - 0006723 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Renal Insufficiency, Chronic/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetic Nephropathies/drug therapy MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Leonie Kraft: Beratungsgremium: AstraZeneca Moritz Schanz: Vortragshonorare: AstraZeneca Jorg Latus: Beratungsgremien und Vortragshonorare von Boehringer Ingelheim, AstraZeneca, Lilly, Novo Nordisk EDAT- 2025/05/20 00:30 MHDA- 2025/05/20 00:31 CRDT- 2025/05/19 19:12 PHST- 2025/05/20 00:31 [medline] PHST- 2025/05/20 00:30 [pubmed] PHST- 2025/05/19 19:12 [entrez] AID - 10.1055/a-2420-6176 [doi] PST - ppublish SO - Dtsch Med Wochenschr. 2025 Jun;150(12):696-702. doi: 10.1055/a-2420-6176. Epub 2025 May 19. PMID- 40383371 OWN - NLM STAT- MEDLINE DCOM- 20250612 LR - 20260505 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 51 IP - 4 DP - 2025 Jul TI - What the diabetologist needs to know about the risk of non-arteritic anterior ischaemic optic neuropathy and GLP-1 receptor agonist use in patients with type 2 diabetes. PG - 101664 LID - S1262-3636(25)00058-8 [pii] LID - 10.1016/j.diabet.2025.101664 [doi] AB - AIM: Recent findings have raised concern about a potential association between semaglutide use and non-arteritic anterior ischaemic optic neuropathy (NAION), a rare form of permanent vision loss. This report provides a critical analysis of the current knowledge of GLP-1 receptor agonist (RA) use and risk of NAION in patients with type 2 diabetes (T2D). METHODS: A literature search strategy was conducted for all English-language literature with a systematic review of key references up to April 2025. RESULTS: Across studies including patients with T2D, the relative increase in NAION risk associated with the use of a GLP-1 RA, mainly semaglutide, ranged from nonsignificant to fourfold, while the absolute number of affected patients remained low. Given the retrospective design of the main studies, no causal link could be established between the use of GLP-1RAs and NAION. Some mechanistic hypotheses have been put forward without any being formally demonstrated to date. The profound metabolic and haemodynamic changes induced by GLP-1RAs might be the trigger of NAION in predisposed patients with an optic "disc-at-risk", a potent anatomical risk factor easily detected by ocular examination. CONCLUSION: Pending studies clarifying this risk, these findings call for cautious use of GLP-1 RAs, particularly in patients with ocular risk factors. Given the widespread use of GLP-1RAs, clinicians should be aware of this potential risk, without overshadowing the remarkable benefit of GLP-1RAs in patients with type 2 diabetes. CI - Copyright (c) 2025 Elsevier Masson SAS. All rights reserved. FAU - Feldman-Billard, Sylvie AU - Feldman-Billard S AD - Centre d'Investigation Clinique 1423, INSERM, Hopital de la vision des 15-20, 28 rue de Charenton, Paris 75571, France. Electronic address: sfeldman@15-20.fr. LA - eng PT - Journal Article PT - Systematic Review DEP - 20250516 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Disc-at-risk OT - GLP-1 receptor agonist OT - Non-arteritic anterior ischaemic optic neuropathy OT - Semaglutide OT - Type 2 diabetes COIS- Declaration of competing interest Sylvie Feldman-Billard declares that she has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/05/19 00:37 MHDA- 2025/06/13 00:27 CRDT- 2025/05/18 19:36 PHST- 2025/04/14 00:00 [received] PHST- 2025/04/17 00:00 [revised] PHST- 2025/04/18 00:00 [accepted] PHST- 2025/06/13 00:27 [medline] PHST- 2025/05/19 00:37 [pubmed] PHST- 2025/05/18 19:36 [entrez] AID - S1262-3636(25)00058-8 [pii] AID - 10.1016/j.diabet.2025.101664 [doi] PST - ppublish SO - Diabetes Metab. 2025 Jul;51(4):101664. doi: 10.1016/j.diabet.2025.101664. Epub 2025 May 16. PMID- 40383360 OWN - NLM STAT- MEDLINE DCOM- 20250826 LR - 20260127 IS - 1879-1891 (Electronic) IS - 0002-9394 (Linking) VI - 277 DP - 2025 Sep TI - Association of Glucagon-Like Peptide-1 Receptor Agonists With Optic Nerve and Retinal Adverse Events: A Population-Based Observational Study Across 180 Countries. PG - 148-168 LID - S0002-9394(25)00239-9 [pii] LID - 10.1016/j.ajo.2025.05.007 [doi] AB - PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are important therapeutic options for type 2 diabetes and obesity; however, concerns about ophthalmic safety persist. This study examined associations between GLP-1 RAs and ocular adverse events (AEs). DESIGN: Global observational pharmacovigilance study. METHODS: We searched the US FAERS database (via OpenVigil 2.1) and WHO's VigiBase (via VigiAccess) for optic nerve and retinal AEs associated with semaglutide and tirzepatide, covering the period from their respective approval dates-December 2017 for semaglutide and May 2022 for tirzepatide-through September 2024. In FAERS, all other drugs were compared, while in VigiBase, metformin, empagliflozin, dulaglutide, and insulin served as controls. Disproportionality metrics included reporting odds ratios (RORs) with 95% confidence intervals. RESULTS: Semaglutide and tirzepatide accounted for 76 444 cases (0.59%) in FAERS (n = 12 936 341) and 118 639 cases (0.34%) in VigiBase (n > 35 000 000). Semaglutide showed significantly higher odds of ischemic optic neuropathy (ION) (FAERS: ROR = 11.12, 95% CI = 8.15-15.16; VigiBase: ROR = 68.58, 95% CI = 16.75-280.67), diabetic retinopathy (DR) (FAERS: ROR = 17.28, 95% CI = 13.62-21.91; VigiBase: ROR = 7.81, 95% CI = 5.60-10.90), as well as retinal/vitreous detachment, retinal/vitreous hemorrhage, and retinal tear (FAERS: ROR = 2.44-5.89, 95% CI = 1.70-8.97, all P < .001, IC(025) = 0.49, compared to all other drugs. VigiBase: ROR = 5.49-20.91, 95% CI = 2.71-90.11, all P /= 0.53, compared to metformin). Unique to VigiBase were macular edema (ROR = 3.87, 95% CI = 1.89-7.92), macular hole (ROR = 20.90, 95% CI = 2.65-165.01), and papilledema (ROR = 6.97, 95% CI = 2.53-19.17) (all P /= 0.27, compared to metformin). Sensitivity analyses using empagliflozin and dulaglutide revealed significant associations with ION and DR, while vitreous detachment and hemorrhage were significant when compared to dulaglutide. Additionally, when insulin was used as a comparator, semaglutide showed a higher ROR for ION (ROR = 9.84, 95% CI = 4.25-22.81, P < .0001, IC(025) = 0.42). However, tirzepatide was only significantly associated with DR in FAERS. CONCLUSIONS: Given the widespread use of semaglutide, its association with ocular AEs highlight the need for global pharmacovigilance and post-marketing surveillance. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Lakhani, Moiz AU - Lakhani M AD - From the Faculty of Medicine (M.L., A.T.H.K.), University of Ottawa, Ottawa, Ontario, Canada; The University of Ottawa Eye Institute (M.L., A.T.H.K., B.H.), Department of Ophthalmology, Ottawa, Ontario, Canada. FAU - Kwan, Angela T H AU - Kwan ATH AD - From the Faculty of Medicine (M.L., A.T.H.K.), University of Ottawa, Ottawa, Ontario, Canada; The University of Ottawa Eye Institute (M.L., A.T.H.K., B.H.), Department of Ophthalmology, Ottawa, Ontario, Canada. FAU - Mihalache, Andrew AU - Mihalache A AD - Temerty Faculty of Medicine (A.M., R.H.M.), University of Toronto, Toronto, Ontario, Canada. FAU - Popovic, Marko M AU - Popovic MM AD - Department of Ophthalmology (M.M.P., A.F., S.S., D.S.), David Geffen School of Medicine at University of California - Los Angeles (UCLA), Los Angeles, California, USA; Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada. FAU - Nanji, Keean AU - Nanji K AD - Department of Surgery (K.N., V.C.), Division of Ophthalmology, McMaster University, Hamilton, Ontario, Canada. FAU - Xie, Jim S AU - Xie JS AD - Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada. FAU - Feo, Alessandro AU - Feo A AD - Department of Ophthalmology (M.M.P., A.F., S.S., D.S.), David Geffen School of Medicine at University of California - Los Angeles (UCLA), Los Angeles, California, USA. FAU - Rabinovitch, David AU - Rabinovitch D AD - Faculty of Medicine (D.R.), Tel Aviv University, Tel Aviv, Israel. FAU - Shor, Reut AU - Shor R AD - Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada; Department of Ophthalmology (R.S., R.H.M.), St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada. FAU - Sadda, SriniVas AU - Sadda S AD - Department of Ophthalmology (M.M.P., A.F., S.S., D.S.), David Geffen School of Medicine at University of California - Los Angeles (UCLA), Los Angeles, California, USA; Doheny Eye Institute (S.S.), University of California - Los Angeles (UCLA), Pasadena, California, USA. FAU - Sarraf, David AU - Sarraf D AD - Department of Ophthalmology (M.M.P., A.F., S.S., D.S.), David Geffen School of Medicine at University of California - Los Angeles (UCLA), Los Angeles, California, USA; Stein Eye Institute (D.S.), University of California - Los Angeles (UCLA), Los Angeles, California, USA. FAU - Hurley, Bernard AU - Hurley B AD - The University of Ottawa Eye Institute (M.L., A.T.H.K., B.H.), Department of Ophthalmology, Ottawa, Ontario, Canada. FAU - Margolin, Edward A AU - Margolin EA AD - Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada. FAU - Kertes, Peter J AU - Kertes PJ AD - Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada; John and Liz Tory Eye Centre (P.J.K.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada. FAU - Chaudhary, Varun AU - Chaudhary V AD - Department of Surgery (K.N., V.C.), Division of Ophthalmology, McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods (V.C.), Evidence and Impact, McMaster University, Hamilton, Ontario, Canada. FAU - Muni, Rajeev H AU - Muni RH AD - Temerty Faculty of Medicine (A.M., R.H.M.), University of Toronto, Toronto, Ontario, Canada; Department of Ophthalmology and Visual Sciences (M.M.P., J.S.X., R.S., E.A.M., P.J.K., R.H.M.), University of Toronto, Toronto, Ontario, Canada; Department of Ophthalmology (R.S., R.H.M.), St. Michael's Hospital, Unity Health Toronto, Toronto, Ontario, Canada; Kensington Eye Institute (R.H.M.), Kensington Vision and Research Centre, Toronto, Ontario, Canada. Electronic address: rajeev.muni@gmail.com. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250516 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - *Hypoglycemic Agents/adverse effects MH - Male MH - Female MH - Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Pharmacovigilance MH - *Retinal Diseases/chemically induced/epidemiology MH - Aged MH - Recombinant Fusion Proteins/adverse effects MH - *Optic Nerve Diseases/chemically induced/epidemiology MH - Databases, Factual MH - Immunoglobulin Fc Fragments MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/05/19 00:37 MHDA- 2025/09/08 07:58 CRDT- 2025/05/18 19:36 PHST- 2025/01/25 00:00 [received] PHST- 2025/04/25 00:00 [revised] PHST- 2025/05/08 00:00 [accepted] PHST- 2025/09/08 07:58 [medline] PHST- 2025/05/19 00:37 [pubmed] PHST- 2025/05/18 19:36 [entrez] AID - S0002-9394(25)00239-9 [pii] AID - 10.1016/j.ajo.2025.05.007 [doi] PST - ppublish SO - Am J Ophthalmol. 2025 Sep;277:148-168. doi: 10.1016/j.ajo.2025.05.007. Epub 2025 May 16. PMID- 40380806 OWN - NLM STAT- MEDLINE DCOM- 20250701 LR - 20250701 IS - 1746-045X (Electronic) IS - 1746-0441 (Linking) VI - 20 IP - 7 DP - 2025 Jul TI - Animal models for development of anti-obesity drugs in the age of GLP-1 agents. PG - 913-925 LID - 10.1080/17460441.2025.2507766 [doi] AB - INTRODUCTION: Obesity is a major health crisis globally, with prevalence escalating significantly in recent decades. Obesity is not merely excessive weight but is associated with myriad health complications. Ensuring the translational effectiveness of pre-clinical obesity models is paramount, and the success of GLP-1 therapies has highlighted important benchmarks for guiding drug development. AREAS COVERED: The authors discuss the status of various animal models used for the development of anti-obesity drugs, with particular emphasis on rodent models and their validity of preclinical-to-clinical translation. They also highlight innovative animal model integration opportunities between obesity and other associated pathology. The article is based on literature searches using PubMed for content (up until February 2025). EXPERT OPINION: The effectiveness of GLP-1 therapies in treating type 2 diabetes and obesity presents an opportunity to evaluate the translational relevance of animal models of obesity. Due to their compelling safety profiles, GLP-1(s) are being tested in a wide range of obesity-associated diseases. Optimization of the mechanistic qualities in this drug class requires the incorporation of new endpoints beyond body weight, including lean mass preservation, cardiovascular health, and anti-inflammatory activities. Finally, we are compelled by the intersection of non-obesity disease models into an obesogenic framework to understand the combinatorial effects of obesity on these other disease indications, including heart failure, neurodegenerative diseases, and cancer. FAU - Culver, Alexander AU - Culver A AD - Pelagos Pharmaceuticals, Inc, Houston, TX, USA. AD - Monument Biosciences, Indianapolis, IN, USA. FAU - Stayrook, Keith AU - Stayrook K AD - Pelagos Pharmaceuticals, Inc, Houston, TX, USA. FAU - Comerota, Michele AU - Comerota M AD - Pelagos Pharmaceuticals, Inc, Houston, TX, USA. FAU - Oblak, Adrian AU - Oblak A AD - Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA. FAU - Burris, Thomas AU - Burris T AD - College of Pharmacy, University of Florida, Gainesville, FL, USA. LA - eng PT - Journal Article PT - Review DEP - 20250521 PL - England TA - Expert Opin Drug Discov JT - Expert opinion on drug discovery JID - 101295755 RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Animals MH - *Obesity/drug therapy/physiopathology MH - Humans MH - *Anti-Obesity Agents/pharmacology/adverse effects MH - Disease Models, Animal MH - *Glucagon-Like Peptide 1/metabolism MH - Drug Development/methods MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - GLP-1 OT - Obesity OT - diabetes OT - drug discovery OT - mounjaro OT - ozempic OT - semaglutide OT - tirzepitide EDAT- 2025/05/17 17:01 MHDA- 2025/07/01 21:13 CRDT- 2025/05/17 04:12 PHST- 2025/07/01 21:13 [medline] PHST- 2025/05/17 17:01 [pubmed] PHST- 2025/05/17 04:12 [entrez] AID - 10.1080/17460441.2025.2507766 [doi] PST - ppublish SO - Expert Opin Drug Discov. 2025 Jul;20(7):913-925. doi: 10.1080/17460441.2025.2507766. Epub 2025 May 21. PMID- 40364515 OWN - NLM STAT- MEDLINE DCOM- 20250704 LR - 20260821 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 8 DP - 2025 Aug TI - Glucagon-like peptide-1 receptor agonists and alcohol use disorders: An emerging unexpected beneficial effect. PG - 4083-4091 LID - 10.1111/dom.16453 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for the management of people living with type 2 diabetes mellitus (T2DM) and/or obesity. Numerous concordant animal and human studies suggest that GLP-1RAs could reduce the risk of addiction, especially alcohol use disorders (AUD). This comprehensive review aims at summarising the known effects of GLP-1RAs on AUD. An extensive literature search detected clinical (either observational or controlled) studies that investigated the prevalence and severity of AUD in obese/T2DM patients treated with GLP-1RAs compared with a control group. In seven observational cohort studies (12 paired data for comparisons), the prevalence of AUD was reduced by 35% (hazard ratio 0.65; 95% confidence interval 0.56-0.74) with GLP-1RA therapy when compared to no-GLP-1 therapy. The protection by GLP-1RAs concerned both incidence and recurrence of AUD. These positive human findings confirm preclinical data in rodents and monkeys. Some genetic, experimental and functional neuroimaging human studies also supported a potential role of the GLP-1 system in the alcohol-related reward process. Only two randomised controlled trials are available yet with inconclusive results, but several are ongoing to confirm the protective effect of semaglutide on AUD. Different neuronal and psychological mechanisms involving the reward pathways are proposed to explain the favourable findings reported with GLP-1RAs. In conclusion, available data from observational cohort studies showed a concordant and significantly reduced risk of AUD and alcohol consumption habits with GLP-1RA therapy. However, further studies are required before considering any indication of GLP-1RAs for the prevention or management of AUD. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Scheen, Andre J AU - Scheen AJ AUID- ORCID: 0000-0001-9743-4371 AD - Division of Diabetes, Nutrition and Metabolic Disorders, CHU Liege, Liege, Belgium. AD - Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), Liege University, Liege, Belgium. LA - eng PT - Journal Article PT - Review DEP - 20250513 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Animals MH - *Obesity/drug therapy/complications MH - *Alcoholism/prevention & control/epidemiology/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - Observational Studies as Topic OTO - NOTNLM OT - GLP-1 receptor agonist OT - Semaglutide OT - addiction OT - alcohol OT - alcohol use disorder OT - obesity EDAT- 2025/05/14 11:42 MHDA- 2025/07/04 12:43 CRDT- 2025/05/14 01:33 PHST- 2025/04/29 00:00 [revised] PHST- 2025/03/03 00:00 [received] PHST- 2025/04/29 00:00 [accepted] PHST- 2025/07/04 12:43 [medline] PHST- 2025/05/14 11:42 [pubmed] PHST- 2025/05/14 01:33 [entrez] AID - 10.1111/dom.16453 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Aug;27(8):4083-4091. doi: 10.1111/dom.16453. Epub 2025 May 13. PMID- 40358430 OWN - NLM STAT- MEDLINE DCOM- 20260130 LR - 20260326 IS - 1572-0241 (Electronic) IS - 0002-9270 (Linking) VI - 121 IP - 2 DP - 2026 Feb 1 TI - Glucagon-Like Peptide-1 Receptor Agonists Use Does Not Increase the Risk for Acute Pancreatitis and Is Associated With Lower Complications in Patients With Type 2 Diabetes Who Develop Acute Pancreatitis: A Multicenter Analysis. PG - 424-431 LID - 10.14309/ajg.0000000000003525 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) can lead to structural pancreatic changes potentially predisposing to acute pancreatitis (AP), increasing morbidity and mortality. Scarce data exist on the outcomes of AP in patients with T2DM who are taking glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The study aim was to evaluate AP outcome and all-cause mortality in patients with T2DM using GLP-1 RAs. METHODS: A retrospective cohort study was performed using population-based data from the TriNetX platform. Patients with T2DM receiving GLP-1 RAs drugs (semaglutide, liraglutide, dulaglutide, and tirzepatide) between January 1, 2015, and October 31, 2023, were included. This patient cohort was matched with patients with T2DM who did not receive GLP-1 RAs according to age, demographics, comorbidities, and medication by using 1:1 propensity matching. To avoid confounding, etiologies of AP including alcohol-induced, trauma, biliary, class Ia drug-induced, hypertriglyceridemia, and postendoscopic retrograde cholangiopancreatography were excluded from both cohorts. Primary outcomes were risk of developing AP, need for parenteral nutrition, systemic complications (sepsis, systemic inflammatory response syndrome, shock, mechanical ventilation, acute kidney injury), and local pancreatic complications. The secondary outcome was all-cause mortality. Cox proportional hazards models were used to estimate hazard ratios (HRs). RESULTS: A total of 740,370 patients with T2DM were identified with 29,423 on GLP-1 RAs; 20,459 of those 29,423 (mean [SD] age, 58.1 [11.9] years; 10,190 [49.85%] female) were matched with 20,459 individuals (mean [SD] age, 57.5 [13.9] years; 10,301 [50.35%] female) who did not take GLP-1 RAs. The GLP-1 RAs group had lower risk of complicated pancreatitis (HR 0.32; 95% confidence interval [CI] 0.14-0.74), parenteral nutrition needs (HR 0.28; 95% CI 0.09-0.83), sepsis (HR 0.71; 95% CI 0.59-0.84), acute kidney injury (HR 0.54; 95% CI 0.49-0.60), shock (HR 0.52; 95% CI 0.36-0.75), and mechanical ventilation support during admission (HR 0.23; 95% CI 0.16-0.33) compared with the non-GLP-1 RAs group. In addition, all-cause mortality was decreased in the GLP-1 agonist group compared with the non-GLP-1 agonist group (HR 0.45; 95% CI 0.41-0.49). Important to note that the GLP-1 RAs group had a tendency of lower risk of uncomplicated pancreatitis (HR 0.71; 95% CI 0.49-1.01) but without statistically significant result. No difference was found between the groups in risk of developing systemic inflammatory response syndrome if it occurs. DISCUSSION: GLP-1 RAs use does not increase AP risk is associated with lower complications in those who developed AP and linked with lower all-cause mortality in patients with T2DM. Prospective studies are needed to determine the mechanisms behind these findings. CI - Copyright (c) 2025 by The American College of Gastroenterology. FAU - Nieto, Luis M AU - Nieto LM AUID- ORCID: 0000-0001-6504-9348 AD - Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. FAU - Martinez, John AU - Martinez J AD - Department of Medicine, Henry Ford Health, Grand Blanc, Michigan, USA. FAU - Narvaez, Sharon I AU - Narvaez SI AD - Department of Medicine, Piedmont Athens Regional Hospital, Athens, Georgia, USA. FAU - Ko, Donghyun AU - Ko D AUID- ORCID: 0000-0003-0592-490 AD - Department of Medicine, Bridgeport Hospital, Yale New Haven Health, Bridgeport, Connecticut, USA. FAU - Kim, Do Han AU - Kim DH AUID- ORCID: 0000-0002-2815-1105 AD - Department of Medicine, Mount Sinai Morningside and West, Icahn School of Medicine at Mount Sinai, New York, New York, USA. FAU - Vega, Kenneth J AU - Vega KJ AUID- ORCID: 0000-0002-2432-6123 AD - Division of Gastroenterology and Hepatology, Prisma Health, Columbia, South Carolina, USA. FAU - Chawla, Saurabh AU - Chawla S AUID- ORCID: 0000-0001-6841-4929 AD - Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20250513 PL - United States TA - Am J Gastroenterol JT - The American journal of gastroenterology JID - 0421030 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - *Pancreatitis/epidemiology/etiology MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Liraglutide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Acute Disease MH - Risk Factors MH - Immunoglobulin Fc Fragments/therapeutic use OTO - NOTNLM OT - GLP-1 receptor agonists OT - acute pancreatitis OT - mortality OT - type 2 diabetes mellitus EDAT- 2025/05/13 13:50 MHDA- 2026/01/30 13:19 CRDT- 2025/05/13 09:52 PHST- 2025/02/05 00:00 [received] PHST- 2025/04/29 00:00 [accepted] PHST- 2026/01/30 13:19 [medline] PHST- 2025/05/13 13:50 [pubmed] PHST- 2025/05/13 09:52 [entrez] AID - 00000434-202602000-00027 [pii] AID - 10.14309/ajg.0000000000003525 [doi] PST - ppublish SO - Am J Gastroenterol. 2026 Feb 1;121(2):424-431. doi: 10.14309/ajg.0000000000003525. Epub 2025 May 13. PMID- 40349689 OWN - NLM STAT- MEDLINE DCOM- 20250618 LR - 20260720 IS - 1664-5502 (Electronic) IS - 1664-5502 (Linking) VI - 15 IP - 1 DP - 2025 TI - The Cardiac and Renal Safety of Semaglutide in Patients with Type 2 Diabetes: A Real-World Study Based on FAERS. PG - 413-422 LID - 10.1159/000546238 [doi] AB - BACKGROUND: Recently, a large clinical trial found that treatment with semaglutide significantly reduced the risk of renal damage and cardiovascular death in patients with type 2 diabetes (T2D). To validate these findings and ensure the suitability of the drug, it is necessary to address the renal and cardiac safety of semaglutide in patients with T2D through real-world safety evidence. METHODS: We examined post-marketing data on the use of semaglutide in patients with T2D using disproportionality analysis based on the FDA Adverse Event Reporting System database. We focused on the detection of positive signals for acute and chronic renal injury and cardiac adverse events associated with semaglutide therapy. RESULTS: A total of 2,380 patients were enrolled in semaglutide therapy in T2D patients with no renal or cardiac positive signals in four algorithmic thresholds, including disproportionality analysis. CONCLUSIONS: In the current study, we observed no significant cardiac or renal safety signals in patients with T2D treated with semaglutide. Our results provide further support for its use as initial and combination therapy in relevant populations. CI - (c) 2025 The Author(s). Published by S. Karger AG, Basel. FAU - Wang, Jingyu AU - Wang J AD - Renal Division, Peking University First Hospital, Beijing, China. AD - Peking University Institute of Nephrology, Beijing, China. AD - Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China. AD - Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Xie, Tong AU - Xie T AD - Renal Division, Peking University First Hospital, Beijing, China, xietong710@163.com. AD - Peking University Institute of Nephrology, Beijing, China, xietong710@163.com. AD - Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China, xietong710@163.com. AD - Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China, xietong710@163.com. AD - Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China, xietong710@163.com. FAU - Zhang, Yuemiao AU - Zhang Y AD - Renal Division, Peking University First Hospital, Beijing, China. AD - Peking University Institute of Nephrology, Beijing, China. AD - Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China. AD - Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. FAU - Zhang, Hong AU - Zhang H AD - Renal Division, Peking University First Hospital, Beijing, China. AD - Peking University Institute of Nephrology, Beijing, China. AD - Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China. AD - Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China. AD - Research Units of Diagnosis and Treatment of Immune-mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250511 PL - Switzerland TA - Cardiorenal Med JT - Cardiorenal medicine JID - 101554863 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Female MH - Male MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Middle Aged MH - Aged MH - Product Surveillance, Postmarketing MH - United States/epidemiology MH - Adverse Drug Reaction Reporting Systems MH - *Acute Kidney Injury/chemically induced/epidemiology MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adverse event OT - Cardiac disorders OT - Kidney injury OT - Pharmacovigilance OT - Semaglutide OT - Type 2 diabetes EDAT- 2025/05/12 05:12 MHDA- 2025/06/19 00:25 CRDT- 2025/05/11 18:23 PHST- 2024/12/24 00:00 [received] PHST- 2025/04/30 00:00 [accepted] PHST- 2025/06/19 00:25 [medline] PHST- 2025/05/12 05:12 [pubmed] PHST- 2025/05/11 18:23 [entrez] AID - 000546238 [pii] AID - 10.1159/000546238 [doi] PST - ppublish SO - Cardiorenal Med. 2025;15(1):413-422. doi: 10.1159/000546238. Epub 2025 May 11. PMID- 40345413 OWN - NLM STAT- MEDLINE DCOM- 20250730 LR - 20260723 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 289 DP - 2025 Nov TI - Effect of once-weekly subcutaneous semaglutide on arterial inflammation in people with type 2 diabetes and cardiovascular disease using PET-MRI: Primary results of a randomized, double-blind, placebo-controlled trial. PG - 17-27 LID - S0002-8703(25)00156-5 [pii] LID - 10.1016/j.ahj.2025.05.001 [doi] AB - BACKGROUND: Semaglutide has demonstrated cardiovascular benefits in people with type 2 diabetes (T2D) with cardiovascular disease (CVD). Inflammation plays a well-documented role in atherosclerosis and glucagon-like peptide-1 receptor agonists, like semaglutide, have shown anti-inflammatory effects in animal and clinical studies. This trial investigated the effect of semaglutide on atherosclerotic inflammation in the carotid arteries using positron emission tomography (PET)-magnetic resonance imaging (MRI). METHODS: Patients with T2D and CVD were randomized to double-blinded once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary and key secondary endpoints used PET-MRI with [(18)F]FDG and [(68)Ga]DOTATATE tracers to assess change from baseline to week 26 in plaque inflammation in the segments of the carotid arteries that were determined to be the most diseased and where plaque inflammation was quantified by the maximum target-to-background ratio (TBR(max)) of the tracers. Additional secondary endpoints assessed plaque morphology and burden using MRI at week 52, including total wall volume, lipid-rich necrotic core volume, and fibrous cap thickness. RESULTS: Of 101 patients, 87.1% were male, mean age was 66 years and they were well-treated according to guidelines. No significant treatment differences were observed between semaglutide and placebo for change in plaque inflammation at week 26 with either tracer; TBR(max) of FDG (estimated treatment difference [ETD]: 0.033, 95% confidence interval [CI]: -0.118;0.184) and [(68)Ga]DOTATATE (ETD: 0.045, 95% CI: -0.314;0.404). CONCLUSIONS: This trial explored the feasibility of following plaque inflammation with PET-MRI using [(18)F]FDG and [(68)Ga]DOTATATE. A significant effect of semaglutide versus placebo on carotid plaque inflammation could not be detected through the methodology used in this trial, likely due to minimal baseline inflammation. However, this does not exclude an effect of semaglutide on inflammation seen in previous preclinical and clinical studies. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04032197. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - James, Stefan AU - James S AD - Department of Medical Sciences, Uppsala University, Uppsala, Sweden. Electronic address: stefan.james@ucr.uu.se. FAU - Christoffersen, Andreas Dyreborg AU - Christoffersen AD AD - Novo Nordisk A/S, Aalborg, Denmark. FAU - David, Jens-Peter AU - David JP AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hacker, Marcus AU - Hacker M AD - Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria. FAU - Jensen, Maria D Radu Juul AU - Jensen MDRJ AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mellbin, Linda AU - Mellbin L AD - Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden. FAU - Pieber, Thomas R AU - Pieber TR AD - Division for Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. FAU - Ripa, Rasmus Sejersten AU - Ripa RS AD - Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen Denmark. FAU - Rossing, Peter AU - Rossing P AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen Denmark; Complications Research, Steno Diabetes Center, Copenhagen, Denmark. FAU - Svehlikova, Eva AU - Svehlikova E AD - Division for Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria. FAU - Kjaer, Andreas AU - Kjaer A AD - Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital-Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Cluster for Molecular Imaging, Department of Biomedical Sciences, University of Copenhagen, Denmark. LA - eng SI - ClinicalTrials.gov/NCT04032197 PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250507 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Organometallic Compounds) RN - 0 (Radiopharmaceuticals) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/complications MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Double-Blind Method MH - Drug Administration Schedule MH - Fluorodeoxyglucose F18 MH - *Glucagon-Like Peptides/administration & dosage MH - Injections, Subcutaneous MH - Magnetic Resonance Imaging/methods MH - Organometallic Compounds MH - Plaque, Atherosclerotic/drug therapy/diagnostic imaging MH - Positron-Emission Tomography/methods MH - Radiopharmaceuticals MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Conflict of interest SJ has received grants to his institution from Novo Nordisk, AstraZeneca, Amgen, Merck, and Novartis. ADC, J-PD and MDRJJ are employees and stockholders of Novo Nordisk A/S. MH has acted as consultant for ITM, Telix, Evomics and has received grants from Siemens Healthineers, Eli Lilly, Roche, Novartis, BMS, Ibsen, ITM, EZAG, Novo Nordisk, and has received payments for lectures from Siemens and Janssen. LM has received consulting and speaker fees for participation in advisory board, lectures and clinical trials supported and funded by Amgen, AstraZeneca, Bayer AG, Boehringer-Ingelheim, Janssen, Novartis, Novo Nordisk, and Sanofi, and received research grants from Amgen and Bayer AG. TRP has received research support from AstraZeneca, Novo Nordisk, and Sanofi and has served on advisory panels for Arecor Limited, Eli Lilly and Company, Novo Nordisk, and Roche Diabetes Care. RSR has received consultancy fees and holds stocks from Novo Nordisk A/S. PR has received grants to Steno Diabetes Center Copenhagen from AstraZeneca, Bayer AG, Lexicon, and Novo Nordisk and has received honoraria (paid to institution) from AstraZeneca, Abbott, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Gilead, Sanofi. ES has no conflicts of interest. AK is a consultant for Novo Nordisk A/S and has received research funding from EU H2020, the Lundbeck Foundation, the Novo Nordisk Foundation, the Innovation Fund Denmark, the Sygeforsikringen danmark, the Research Foundation of Rigshospitalet, the Danish National Research Foundation (grant 126) - PERSIMUNE, and Research Council for Independent Research. Andreas Kjaer is a Lundbeck Foundation Professor. EDAT- 2025/05/10 00:48 MHDA- 2025/07/30 06:30 CRDT- 2025/05/09 19:36 PHST- 2025/02/06 00:00 [received] PHST- 2025/05/02 00:00 [revised] PHST- 2025/05/03 00:00 [accepted] PHST- 2025/07/30 06:30 [medline] PHST- 2025/05/10 00:48 [pubmed] PHST- 2025/05/09 19:36 [entrez] AID - S0002-8703(25)00156-5 [pii] AID - 10.1016/j.ahj.2025.05.001 [doi] PST - ppublish SO - Am Heart J. 2025 Nov;289:17-27. doi: 10.1016/j.ahj.2025.05.001. Epub 2025 May 7. PMID- 40344607 OWN - NLM STAT- MEDLINE DCOM- 20250827 LR - 20260127 IS - 1365-2125 (Electronic) IS - 0306-5251 (Linking) VI - 91 IP - 9 DP - 2025 Sep TI - Pharmacokinetic-pharmacodynamic (PK/PD) modelling of cotadutide effect in patients with chronic kidney disease and type 2 diabetes mellitus. PG - 2672-2683 LID - 10.1002/bcp.70093 [doi] AB - AIMS: Cotadutide is a dual glucagon-like peptide-1/glucagon receptor agonist. The objective of the analysis was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model to describe the relationship between cotadutide exposure and response on urine albumin-to-creatinine ratio (UACR), urinary albumin (UALB), and body weight in participants with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) using data from a Phase2b study (NCT04515849). METHODS: A total of 247 participants with CKD and T2DM were randomized and titrated to either 100, 300 or 600 mug cotadutide, 1 mg semaglutide or placebo. UACR was measured biweekly from either morning void (Weeks 14 and 26) or spot urine (other visits). The analysis was implemented using a longitudinal non-linear mixed-effect model. The potential impact of covariates on efficacy in participants was quantified. RESULTS: PK/PD models were developed, and a significant relationship was identified between cotadutide exposure and PD biomarkers of UACR, UALB and body weight. The models described the data adequately; greater changes in PD responses were observed with higher cotadutide doses. Baseline mean blood pressure and baseline UALB were found to affect the reductions in UACR and UALB, respectively. Model-predicted relative change from placebo in UACR, UALB and body weight after 26 weeks of 600 mug cotadutide treatment were -45.6% (-52.4%, -38.7%), -47.2% (-56.0%, -39.9%) and -5.3% (-7.6%, -4.1%), respectively. CONCLUSIONS: This modelling assessment was successfully applied for cotadutide to understand the relationship between cotadutide dosing regimen and the response in UACR, UALB and body weight. These models have general application in analysing and interpreting data from CKD/diabetic kidney disease (DKD) studies. CI - (c) 2025 British Pharmacological Society. FAU - Yu, Hongtao AU - Yu H AUID- ORCID: 0000-0003-2278-4478 AD - Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Parker, Victoria AU - Parker V AD - Early Clinical Development, R&D, AstraZeneca, Cambridge, UK. FAU - Selvarajah, Viknesh AU - Selvarajah V AD - Early Clinical Development, R&D, AstraZeneca, Cambridge, UK. FAU - Hansen, Lars AU - Hansen L AD - Early Clinical Development, R&D, AstraZeneca, Gaithersburg, UK. FAU - Robertson, Darren AU - Robertson D AD - Early Clinical Development, R&D, AstraZeneca, Cambridge, UK. FAU - Hamren, Bengt AU - Hamren B AD - Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden. FAU - Khan, Anis AU - Khan A AUID- ORCID: 0000-0001-8262-3022 AD - Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Parkinson, Joanna AU - Parkinson J AUID- ORCID: 0000-0003-4492-5243 AD - Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Gothenburg, Sweden. LA - eng SI - ClinicalTrials.gov/NCT04515849 GR - AstraZeneca/ PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20250509 PL - England TA - Br J Clin Pharmacol JT - British journal of clinical pharmacology JID - 7503323 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - AYI8EX34EU (Creatinine) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/urine MH - Male MH - Female MH - Middle Aged MH - *Renal Insufficiency, Chronic/drug therapy/complications/urine MH - *Models, Biological MH - *Hypoglycemic Agents/pharmacokinetics/pharmacology/administration & dosage MH - Aged MH - Double-Blind Method MH - Dose-Response Relationship, Drug MH - Albuminuria/urine MH - *Glucagon-Like Peptides/pharmacology/pharmacokinetics/administration & dosage MH - Adult MH - Body Weight/drug effects MH - Creatinine/urine MH - Glucagon-Like Peptide 1/agonists MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - chronic kidney disease OT - modelling and simulation OT - pharmacokinetic-pharmacodynamic EDAT- 2025/05/09 18:31 MHDA- 2025/08/31 19:57 CRDT- 2025/05/09 16:24 PHST- 2025/04/15 00:00 [revised] PHST- 2024/11/13 00:00 [received] PHST- 2025/04/22 00:00 [accepted] PHST- 2025/08/31 19:57 [medline] PHST- 2025/05/09 18:31 [pubmed] PHST- 2025/05/09 16:24 [entrez] AID - 10.1002/bcp.70093 [doi] PST - ppublish SO - Br J Clin Pharmacol. 2025 Sep;91(9):2672-2683. doi: 10.1002/bcp.70093. Epub 2025 May 9. PMID- 40337971 OWN - NLM STAT- MEDLINE DCOM- 20260914 LR - 20260914 IS - 2212-3911 (Electronic) IS - 1574-8863 (Linking) VI - 21 IP - 3 DP - 2026 TI - A Descriptive Analysis from VigiAccess on Drug-related Problems Associated with the Glucagon-like Peptide-1 Receptor Agonists. PG - e15748863367086 LID - 10.2174/0115748863367086250420011411 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely accepted for managing Type 2 Diabetes Mellitus. However, numerous drug-related problems (DRPs) have recently been reported about GLP-1 RAs. The present descriptive study aims to compile and report the DRPs of various GLP-1 RAs. METHODS: The DRPs reported for all the GLP-1 RAs, including exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and trazeptide, were extracted from the category of injury, poisoning, and procedural complications of VigiAccess. The Pharmaceutical Care Network Europe Association (PCNE) classification for drug-related problems (version 9.1) was used to categorize the DRPs into patient-related, healthcare practice-related, and patient- or healthcare practice- related. RESULTS: Overall, 315952 potential side effects (PSEs) were reported regarding GLP-1 RAs in VigiAccess under injury, poisoning, and procedural complications. Out of 315952 PSE reports, 84187 were DRPs of GLP-1 RAs. Among the patient-related DRPs, the administered incorrect dose (17797; 48.37%) was predominant, and most of the reports were documented for tirzepatide (9993; 23.82%). Off-label use (13600; 48.37%) was a predominant healthcare practicerelated DRP, most of which were from Tirzepatide (4945; 17.59%). DISCUSSION: The alarming DRP reports in this descriptive analysis regarding the dosing and offlabel use of GLP-1 Ras need further investigation to establish the contribution of underlying factors. CONCLUSION: Qualified healthcare practitioners must educate the patients administering the GLP- 1 RAs to minimize preventable DRPs. Also, careful and frequent monitoring of GLP-1 RAs improves therapeutic outcomes by ruling out DRPs. Healthcare practitioners should comply with approved therapeutic guidelines to enhance the treatment quality of GLP-1 RAs. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Amirthalingam, Palanisamy AU - Amirthalingam P AUID- ORCID: 0000-0002-5803-1227 AD - Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. LA - eng PT - Journal Article PL - United Arab Emirates TA - Curr Drug Saf JT - Current drug safety JID - 101270895 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Adverse Drug Reaction Reporting Systems MH - Semaglutide MH - *Drug-Related Side Effects and Adverse Reactions/epidemiology/diagnosis MH - Tirzepatide OTO - NOTNLM OT - Drug-related problems OT - VigiAccess OT - glucagon-like peptide-1 receptor agonists OT - off-label use OT - potential side effects OT - type-2 diabetes mellitus EDAT- 2025/05/08 12:24 MHDA- 2026/09/14 11:41 CRDT- 2025/05/08 07:23 PHST- 2024/10/27 00:00 [received] PHST- 2025/02/10 00:00 [revised] PHST- 2025/02/18 00:00 [accepted] PHST- 2026/09/14 11:41 [medline] PHST- 2025/05/08 12:24 [pubmed] PHST- 2025/05/08 07:23 [entrez] AID - CDS-EPUB-148210 [pii] AID - 10.2174/0115748863367086250420011411 [doi] PST - ppublish SO - Curr Drug Saf. 2026;21(3):e15748863367086. doi: 10.2174/0115748863367086250420011411. PMID- 40330819 OWN - NLM STAT- MEDLINE DCOM- 20250507 LR - 20260127 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 19 DP - 2025 TI - A Comprehensive Review on the Pharmacokinetics and Drug-Drug Interactions of Approved GLP-1 Receptor Agonists and a Dual GLP-1/GIP Receptor Agonist. PG - 3509-3537 LID - 10.2147/DDDT.S506957 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are peptide-derived analogs that were initially investigated to treat type 2 diabetes. Recently, a drug targeting the receptors of both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) (tirzepatide) has been introduced to the market, and its indications have expanded to include treating obesity. Here, we review the pharmacokinetics, pharmacokinetic drug-drug interactions (DDIs), and pharmacokinetic modeling approaches of four currently available GLP-1 RAs (exenatide, liraglutide, dulaglutide, and semaglutide) and tirzepatide. To address the extremely short half-life (2 min) of native human GLP-1, structural modifications have been applied to GLP-1 RAs and a dual GLP-1/GIP RA. These include amino acid sequence substitutions, fatty acid conjugation using a linker, and fusion with albumin or the IgG fragment crystallizable (Fc) region, resulting in minimal metabolism and renal excretion. Due to their diverse structures, the pharmacokinetic profiles vary, and a prolonged half-life may be associated with an increased risk of adverse events. Clinically significant drug-metabolizing enzyme- and transporter-mediated DDIs are yet to be reported. Mechanism-of-action-mediated DDIs are currently limited to those involving delayed gastric emptying, and most studies have found them to be clinically insignificant. However, significant changes in exposure were observed for oral contraceptives and levothyroxine following the administration of tirzepatide and oral semaglutide, respectively, indicating the need for close monitoring in these instances. Thirty models have been developed to predict pharmacokinetics and physiologically based pharmacokinetic modeling can be useful for assessing mechanism-of-action-mediated DDIs. Alterations in the volume of distribution and clearance resulting from other mechanisms of action (eg, reduced fat mass, changes in cytochrome P450 activity, and glomerular filtration rate) are key factors in determining pharmacokinetics. However, the DDIs mediated by these factors remain poorly understood and require further investigation to ensure that GLP-1 RAs can be safely used with concomitant medications. CI - (c) 2025 Min et al. FAU - Min, Jee Sun AU - Min JS AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. FAU - Jo, Seong Jun AU - Jo SJ AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. AD - Department of Pharmaceutical Sciences, State University of New York, Buffalo, NY, 14214, USA. FAU - Lee, Sangyoung AU - Lee S AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. FAU - Kim, Duk Yeon AU - Kim DY AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. FAU - Kim, Da Hyun AU - Kim DH AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. FAU - Lee, Chae Bin AU - Lee CB AUID- ORCID: 0000-0003-4551-9191 AD - Johns Hopkins Drug Discovery, Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. FAU - Bae, Soo Kyung AU - Bae SK AUID- ORCID: 0000-0001-7258-7187 AD - College of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, The Catholic University of Korea, Bucheon, 14662, Republic of Korea. LA - eng PT - Journal Article PT - Review DEP - 20250430 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Interactions MH - *Hypoglycemic Agents/pharmacokinetics MH - Glucagon-Like Peptides/pharmacokinetics/analogs & derivatives MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy MH - Receptors, Gastrointestinal Hormone PMC - PMC12052016 OTO - NOTNLM OT - GIP OT - GLP-1 OT - drug-drug interactions OT - pharmacokinetics OT - physiologically based pharmacokinetic model COIS- The authors report no conflicts of interest in this work. EDAT- 2025/05/07 06:28 MHDA- 2025/05/07 12:32 PMCR- 2025/04/30 CRDT- 2025/05/07 05:26 PHST- 2024/11/17 00:00 [received] PHST- 2025/04/14 00:00 [accepted] PHST- 2025/05/07 12:32 [medline] PHST- 2025/05/07 06:28 [pubmed] PHST- 2025/05/07 05:26 [entrez] PHST- 2025/04/30 00:00 [pmc-release] AID - 506957 [pii] AID - 10.2147/DDDT.S506957 [doi] PST - epublish SO - Drug Des Devel Ther. 2025 Apr 30;19:3509-3537. doi: 10.2147/DDDT.S506957. eCollection 2025. PMID- 40321113 OWN - NLM STAT- MEDLINE DCOM- 20250609 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 7 DP - 2025 Jul TI - Tirzepatide 10 and 15 mg versus semaglutide 2.4 mg in people with obesity or overweight with type 2 diabetes: An indirect treatment comparison. PG - 3757-3765 LID - 10.1111/dom.16401 [doi] AB - AIMS: Tirzepatide and semaglutide demonstrated clinically meaningful weight reduction in people with obesity or overweight and type 2 diabetes (T2D) in SURMOUNT-2 and STEP 2 clinical trials, respectively. In the absence of head-to-head trials, this study compared the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. MATERIALS AND METHODS: Mean percent change in weight from baseline, weight reduction >/=5% and mean change in glycated haemoglobin (HbA1c [%]) were compared between tirzepatide 10/15 mg (week 72, SURMOUNT-2) and semaglutide 2.4 mg (week 68, STEP 2) applying the Bucher method to the efficacy estimand. Sensitivity analyses included the use of matching-adjusted indirect comparison, treatment regimen estimand and comparing study outcomes at 68 weeks. RESULTS: Tirzepatide 10 and 15 mg were associated with significantly greater mean percent weight reductions versus semaglutide (mean difference, 10 mg: 2.57%; 15 mg: 4.79%, p < 0.01). Tirzepatide 15 mg had significantly higher odds of achieving >/=5% weight reduction (odds ratio 15 mg: 1.76, 95% CI 1.04-2.97, p = 0.035; odds ratio 10 mg: 1.24, 95% CI 0.75-2.04, p = 0.407), and both tirzepatide doses were associated with significantly greater reductions in HbA1c (%) levels (mean difference, 10 mg: 0.47%; 15 mg: 0.56%, p < 0.001) than semaglutide. Sensitivity analyses were generally consistent with the primary analysis, exceptions including when power was reduced in the matching-adjusted indirect comparison analyses and in the categorical weight reduction outcome. CONCLUSIONS: This analysis suggested greater reductions in bodyweight and HbA1c (%) levels associated with tirzepatide 10 and 15 mg than with semaglutide 2.4 mg in people with obesity or overweight and T2D. CI - (c) 2025 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hankosky, Emily R AU - Hankosky ER AUID- ORCID: 0000-0001-9934-584X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - He, Xuanyao AU - He X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Malik, Raleigh AU - Malik R AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Fraseur Brumm, Julia AU - Fraseur Brumm J AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Wang, Fangyu AU - Wang F AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Niemeyer, Anthony AU - Niemeyer A AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Zhang, Xiaotian M AU - Zhang XM AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Garvey, W Timothy AU - Garvey WT AUID- ORCID: 0000-0003-0822-0860 AD - University of Alabama at Birmingham, Birmingham, Alabama, USA. LA - eng GR - P30 DK056336/DK/NIDDK NIH HHS/United States GR - Eli Lilly and Company/ PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250505 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Obesity/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Overweight/drug therapy/complications MH - Glycated Hemoglobin/analysis MH - Weight Loss/drug effects MH - *Tirzepatide/administration & dosage MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Treatment Outcome MH - Adult MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12146454 OTO - NOTNLM OT - indirect treatment comparison OT - obesity OT - semaglutide OT - tirzepatide OT - type 2 diabetes OT - weight reduction COIS- Emily R. Hankosky, Xuanyao He, Julia Fraseur Brumm, Fangyu Wang, Anthony Niemeyer and Xiaotian Michelle Zhang are employees and stockholders of Eli Lilly and Company, Indianapolis, United States. Raleigh Malik was an employee of Eli Lilly and Company at the time of the study. W. Timothy Garvey has served as a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand, Carmot/Roche, Regeneron and Merck, and as a site principal investigator for multi-centred clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly and Company, Epitomee, Neurovalens and Pfizer. EDAT- 2025/05/05 06:27 MHDA- 2025/06/09 06:26 PMCR- 2025/06/09 CRDT- 2025/05/05 04:53 PHST- 2025/03/18 00:00 [revised] PHST- 2025/01/03 00:00 [received] PHST- 2025/03/28 00:00 [accepted] PHST- 2025/06/09 06:26 [medline] PHST- 2025/05/05 06:27 [pubmed] PHST- 2025/05/05 04:53 [entrez] PHST- 2025/06/09 00:00 [pmc-release] AID - DOM16401 [pii] AID - 10.1111/dom.16401 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jul;27(7):3757-3765. doi: 10.1111/dom.16401. Epub 2025 May 5. PMID- 40309769 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260127 IS - 1558-8238 (Electronic) IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 135 IP - 9 DP - 2025 May 1 TI - GLP-1 receptor agonists for the treatment of alcohol use disorder. LID - 10.1172/JCI192414 [doi] LID - e192414 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, are widely used in the treatment of metabolic disorders, including type 2 diabetes (T2D) and obesity. These medications primarily function by enhancing insulin secretion; however, emerging evidence suggests that the effects extend beyond metabolic regulation. In this issue of the JCI, Farokhnia et al. evaluated the effects of GLP-1RAs alongside another T2D treatment, dipeptidyl peptidase-4 inhibitors (DPP-4Is), on alcohol consumption in humans and preclinical models. In humans, GLP1-RAs, but not DPP-4Is, were associated with reductions in alcohol consumption. Similarly, DPP-4 inhibition had no effect on alcohol intake in rodents. These findings invite further exploration of the mechanisms by which GLP-1RAs reduce alcohol consumption and redefine our pharmacotherapy approach to alcohol use disorder (AUD) by opening the possibility for application as an early harm-reduction tool. FAU - Petrie, Gavin N AU - Petrie GN AD - Department of Psychiatry. AD - Mathison Centre for Mental Health Education and Research, and. AD - Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada. FAU - Mayo, Leah M AU - Mayo LM AD - Department of Psychiatry. AD - Mathison Centre for Mental Health Education and Research, and. AD - Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada. LA - eng PT - Comment PT - Journal Article DEP - 20250501 PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) SB - IM CON - Glucagon-like peptide-1 receptor agonists, but not dipeptidyl peptidase-4 inhibitors, reduce alcohol intake MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Animals MH - *Alcoholism/drug therapy/metabolism MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Glucagon-Like Peptides/therapeutic use MH - Mice MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12043078 COIS- Conflict of interest: The authors have declared that no conflict of interest exists. EDAT- 2025/05/01 12:29 MHDA- 2025/05/01 12:30 PMCR- 2025/05/01 CRDT- 2025/05/01 06:03 PHST- 2025/05/01 12:30 [medline] PHST- 2025/05/01 12:29 [pubmed] PHST- 2025/05/01 06:03 [entrez] PHST- 2025/05/01 00:00 [pmc-release] AID - 192414 [pii] AID - 10.1172/JCI192414 [doi] PST - epublish SO - J Clin Invest. 2025 May 1;135(9):e192414. doi: 10.1172/JCI192414. eCollection 2025 May 1. PMID- 40301134 OWN - NLM STAT- MEDLINE DCOM- 20260222 LR - 20261009 IS - 1573-501X (Electronic) IS - 1381-1991 (Linking) VI - 30 IP - 1 DP - 2026 Feb TI - GLP-1R agonists: recent advances, current gaps, and future challenges. PG - 101-112 LID - 10.1007/s11030-025-11195-6 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) emerged as a promising class of drugs and have been shown to be effective as a key regulator in managing glucose metabolism-associated diseases such as type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), cardiovascular effects, nephrological complications, diabetes, non-alcoholic fatty liver (NAFLD), as well as to control obesity. A few drugs included in GLP-1RA class are liraglutide, exenatide, and semaglutide. Most recent drug that is available in both oral and subcutaneous forms is semaglutide. Available, withdrawn, and investigational GLP-RAs are listed in this paper. This review article will also explore common side effects and safety profiles of both long-acting and short-acting GLP-1 RAs. Additionally, it will highlight the recent advances and ongoing challenges in the field of drug discovery related to GLP-1 receptor agonists. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Saran, Anukriti AU - Saran A AD - Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India. anukritisaransingh@gmail.com. FAU - Raisinghani, Riya AU - Raisinghani R AD - Department of Bioscience and Biotechnology, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India. FAU - Paliwal, Sarvesh AU - Paliwal S AD - Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India. FAU - Sharma, Swapnil AU - Sharma S AD - Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, 304022, India. LA - eng PT - Journal Article PT - Review DEP - 20250429 PL - Netherlands TA - Mol Divers JT - Molecular diversity JID - 9516534 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Animals MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/therapeutic use/pharmacology MH - Liraglutide/therapeutic use OTO - NOTNLM OT - Glucagon-like peptide-1 OT - Glucagon-like peptide-1 receptor OT - Glucagon-like peptide-1 receptor agonists OT - Semaglutide COIS- Declarations. Conflict of interest: The authors declared that they have no conflict of interest. Ethical approval: As this submission is a review article ,it does not involve humans and animals, and no ethical approval was required for this publication. EDAT- 2025/04/30 00:31 MHDA- 2026/02/22 15:52 CRDT- 2025/04/29 23:13 PHST- 2025/02/06 00:00 [received] PHST- 2025/04/11 00:00 [accepted] PHST- 2026/02/22 15:52 [medline] PHST- 2025/04/30 00:31 [pubmed] PHST- 2025/04/29 23:13 [entrez] AID - 10.1007/s11030-025-11195-6 [pii] AID - 10.1007/s11030-025-11195-6 [doi] PST - ppublish SO - Mol Divers. 2026 Feb;30(1):101-112. doi: 10.1007/s11030-025-11195-6. Epub 2025 Apr 29. PMID- 40287313 OWN - NLM STAT- MEDLINE DCOM- 20250727 LR - 20260127 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 35 IP - 9 DP - 2025 Sep TI - The impact of semaglutide on liver fat assessed by serial cardiac CT scans in patients with type 2 diabetes: Results from STOP trial. PG - 104036 LID - S0939-4753(25)00190-5 [pii] LID - 10.1016/j.numecd.2025.104036 [doi] AB - BACKGROUND AND AIM: The prevalence of hepatic steatosis continues to increase worldwide. Hepatic steatosis is increasingly recognized as an independent risk factor for cardiovascular mortality. However, there are limited options for the treatment of fatty liver. In this study, we evaluated the effect of semaglutide on liver fat as measured by non-contrast cardiac CT scans. METHODS AND RESULTS: STOP is a randomized controlled trial that evaluated the semaglutide treatment effect on coronary atherosclerosis progression (STOP) in type 2 diabetes. We utilized unenhanced cardiac CT scans to quantify liver fat based on the CT Hounsfield attenuation method. Of the 140 subjects who were originally randomized, a total of 114 individuals qualified for this study. 59 participants were in the semaglutide group and 55 were in the placebo group, and these subjects were followed for 12 months. The secondary outcome (liver fat attenuation) was quantified using non-contrast cardiac computed tomography (CT) images at both the baseline and 12-month follow-up time points. Multivariate regression models were then used to evaluate the change in liver fat content overtime. One hundred and fourteen subjects were included in the study: 61 % male, mean age of 57.8 +/- 8.1 years, and mean BMI of 32.0 +/- 6.7. The average of three liver measures over 12 months showed an improvement in the semaglutide group of 1.4 +/- 9.0 mean HU, versus a worsening in the placebo group of 1.9 +/- 9.5 mean HU. The multivariable linear regression models (after adjusting for age, gender, BMI, hypertension, hyperlipidemia, past smoking and baseline liver attenuation) showed that average liver attenuation measures improved by 4.4 HU in the semaglutide group when compared to the placebo group (p = 0.002). This result demonstrated improvement in the liver fat content within the treatment group. CONCLUSION: In type 2 diabetes patients with hepatic steatosis, treatment with semaglutide resulted in a significant improvement in fatty liver reduction when compared to placebo. CI - Published by Elsevier B.V. FAU - Golub, Ilana S AU - Golub IS AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Manubolu, Venkat S AU - Manubolu VS AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Aldana-Bitar, Jairo AU - Aldana-Bitar J AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Dahal, Suraj AU - Dahal S AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Verghese, Dhiran AU - Verghese D AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Alalawi, Luay AU - Alalawi L AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Krishnan, Srikanth AU - Krishnan S AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Kianoush, Sina AU - Kianoush S AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Benzing, Travis AU - Benzing T AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Ichikawa, Keishi AU - Ichikawa K AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Kinninger, April AU - Kinninger A AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Fazlalizadeh, Hooman AU - Fazlalizadeh H AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Pourafkari, Leili AU - Pourafkari L AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Ahmad, Khadije AU - Ahmad K AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Susarla, Shriraj AU - Susarla S AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Mangaoang, Czarina AU - Mangaoang C AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Ghanem, Ahmed K AU - Ghanem AK AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Javier, Denise Alison AU - Javier DA AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Hamal, Sajad AU - Hamal S AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Roy, Sion K AU - Roy SK AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. FAU - Budoff, Matthew J AU - Budoff MJ AD - Harbor-UCLA Medical Center Lundquist Institute, Torrance, CA, USA. Electronic address: mbudoff@lundquist.org. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20250405 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/complications/blood MH - Male MH - Middle Aged MH - Female MH - Treatment Outcome MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Tomography, X-Ray Computed MH - *Liver/drug effects/diagnostic imaging MH - Time Factors MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Predictive Value of Tests MH - *Adiposity/drug effects MH - Double-Blind Method MH - *Coronary Artery Disease/diagnostic imaging/etiology/prevention & control MH - *Fatty Liver/diagnostic imaging/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Atherosclerotic cardiovascular disease (ASCVD) OT - Cardiovascular disease (CVD) OT - Computed tomography angiography (CTA) OT - Coronary artery calcium (CAC) OT - GLP1 receptor agonists OT - Hepatocellular carcinoma (HCC) OT - Metabolic dysfunction-associated steatohepatitis (MASH) OT - Metabolic dysfunction-associated steatotic liver disease (MASLD) OT - Randomized trial OT - Semaglutide EDAT- 2025/04/27 03:14 MHDA- 2025/07/28 08:45 CRDT- 2025/04/26 21:57 PHST- 2024/12/18 00:00 [received] PHST- 2025/03/27 00:00 [revised] PHST- 2025/04/03 00:00 [accepted] PHST- 2025/07/28 08:45 [medline] PHST- 2025/04/27 03:14 [pubmed] PHST- 2025/04/26 21:57 [entrez] AID - S0939-4753(25)00190-5 [pii] AID - 10.1016/j.numecd.2025.104036 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2025 Sep;35(9):104036. doi: 10.1016/j.numecd.2025.104036. Epub 2025 Apr 5. PMID- 40282858 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20260127 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 61 IP - 4 DP - 2025 Mar 22 TI - Subclinical Changes in Type 2 Diabetes Patients with Heart Failure Stage A and B Treated with Oral Semaglutide. LID - 10.3390/medicina61040567 [doi] LID - 567 AB - Background and Objectives: Heart failure (HF) among patients with type 2 diabetes (T2DM) is linked to significant morbidity and mortality, despite the increased availability of new drug therapy. This study aims to investigate subclinical changes in patients with HF stage A (at risk for HF) and B (Pre-HF) and T2DM treated with oral semaglutide. Materials and Methods: In a prospective, observational, single-center study, 50 T2DM patients were assessed at baseline and one-year follow-up for changes in spectral Doppler, tissue Doppler, and speckle-tracking (2DST) and metabolic parameters. Results: Correlation and regression analyses identified predictors of Delta GLS. In correlation analysis, Delta GLS showed a negative correlation with Delta VAI (rho = -0.3, p = 0.02), Delta LAP (rho = -0.3, p = 0.04), Delta FPG (rho = -0.3, p = 0.009), Delta TG (rho = -0.4, p = 0.004), and Delta TyG (rho = -0.3, p = 0.02). In linear stepwise regression analysis, the most accurate model, with a p-value < 0.001, was M(3), explaining 70% of the variance in Delta GLS (adjusted R(2) = 0.7); this model included Delta FPG (beta -0.4, p = 0.001), Delta CRR (beta -1.3, p < 0.001), and Delta LDLc (beta 0.6, p = 0.01). Conclusions: These findings show that improved subclinical left ventricular systolic dysfunction is associated with improved glycemic control, visceral adiposity, and reduced insulin resistance, respectively, with improved lipid profiling. FAU - Daniluc, Larissa AU - Daniluc L AD - Doctoral School, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. AD - Department of Cardiology, Pius Brinzeu Clinical Emergency County Hospital Timisoara, 300736 Timisoara, Romania. AD - Department VII, Internal Medicine II, Discipline of Cardiology, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. FAU - Braha, Adina AU - Braha A AUID- ORCID: 0000-0002-7904-6073 AD - Department of Second Internal Medicine Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases Clinic, "Pius Brinzeu" Emergency Clinical County University Hospital, 300723 Timisoara, Romania. AD - Centre for Molecular Research in Nephrology and Vascular Disease/MOL-NEPHRO-VASC, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. FAU - Sandu, Oana Elena AU - Sandu OE AD - Doctoral School, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. AD - Department of Cardiology, Pius Brinzeu Clinical Emergency County Hospital Timisoara, 300736 Timisoara, Romania. AD - Department VII, Internal Medicine II, Discipline of Cardiology, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. FAU - Bogdan, Carina AU - Bogdan C AUID- ORCID: 0009-0000-0204-6932 AD - Doctoral School, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. AD - Department of Cardiology, Pius Brinzeu Clinical Emergency County Hospital Timisoara, 300736 Timisoara, Romania. AD - Department VII, Internal Medicine II, Discipline of Cardiology, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. FAU - Suhov, Loredana AU - Suhov L AUID- ORCID: 0009-0008-9586-6080 AD - Doctoral School, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. AD - Department of Cardiology, Pius Brinzeu Clinical Emergency County Hospital Timisoara, 300736 Timisoara, Romania. FAU - Haj Ali, Lina AU - Haj Ali L AD - Doctoral School, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. AD - Department of Cardiology, Pius Brinzeu Clinical Emergency County Hospital Timisoara, 300736 Timisoara, Romania. FAU - Lazar-Hocher, Alexandra-Iulia AU - Lazar-Hocher AI AUID- ORCID: 0009-0004-1330-8191 AD - Doctoral School, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. AD - Institute of Cardiovascular Diseases Timisoara, 300310 Timisoara, Romania. FAU - Sima, Alexandra AU - Sima A AUID- ORCID: 0000-0001-9042-9924 AD - Department of Second Internal Medicine Diabetes, Nutrition, Metabolic Diseases, and Systemic Rheumatology, "Victor Babes" University of Medicine and Pharmacy, 300041 Timisoara, Romania. AD - Department of Diabetes, Nutrition and Metabolic Diseases Clinic, "Pius Brinzeu" Emergency Clinical County University Hospital, 300723 Timisoara, Romania. FAU - Apostol, Adrian AU - Apostol A AUID- ORCID: 0000-0001-6684-1759 AD - Department of Cardiology, Pius Brinzeu Clinical Emergency County Hospital Timisoara, 300736 Timisoara, Romania. AD - Department VII, Internal Medicine II, Discipline of Cardiology, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. FAU - Ivan, Mihaela Viviana AU - Ivan MV AUID- ORCID: 0000-0003-4304-4911 AD - Department of Cardiology, Pius Brinzeu Clinical Emergency County Hospital Timisoara, 300736 Timisoara, Romania. AD - Department VII, Internal Medicine II, Discipline of Cardiology, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timisoara, Romania. LA - eng PT - Journal Article PT - Observational Study DEP - 20250322 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - Female MH - Male MH - *Heart Failure/drug therapy/physiopathology/complications MH - Middle Aged MH - Prospective Studies MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Administration, Oral MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12028782 OTO - NOTNLM OT - GLP-1 receptor agonists OT - metabolic control OT - speckle-tracking echocardiography OT - visceral adiposity COIS- The authors declare no conflicts of interest. EDAT- 2025/04/26 16:04 MHDA- 2025/04/26 16:46 PMCR- 2025/03/22 CRDT- 2025/04/26 01:09 PHST- 2025/02/21 00:00 [received] PHST- 2025/03/16 00:00 [revised] PHST- 2025/03/21 00:00 [accepted] PHST- 2025/04/26 16:46 [medline] PHST- 2025/04/26 16:04 [pubmed] PHST- 2025/04/26 01:09 [entrez] PHST- 2025/03/22 00:00 [pmc-release] AID - medicina61040567 [pii] AID - medicina-61-00567 [pii] AID - 10.3390/medicina61040567 [doi] PST - epublish SO - Medicina (Kaunas). 2025 Mar 22;61(4):567. doi: 10.3390/medicina61040567. PMID- 40281304 OWN - NLM STAT- MEDLINE DCOM- 20250801 LR - 20260311 IS - 1474-1784 (Electronic) IS - 1474-1776 (Linking) VI - 24 IP - 8 DP - 2025 Aug TI - GLP-1-based therapies for diabetes, obesity and beyond. PG - 631-650 LID - 10.1038/s41573-025-01183-8 [doi] AB - Glucagon-like peptide 1 (GLP-1)-based therapies, such as semaglutide and tirzepatide, represent highly effective treatment options for people with type 2 diabetes and obesity, enabling effective control of glucose and weight loss, while reducing cardiovascular and renal morbidity and mortality. The success of these medicines has spurred development of next-generation GLP-1-based drugs, promising greater weight loss, improved tolerability and additional options for the route and frequency of dosing. This Review profiles established and emerging GLP-1-based medicines, discussing optimization of pharmacokinetics and tolerability, engagement of new therapeutically useful pathways and safety aspects. Structurally unique GLP-1-based medicines that achieve substantially greater and rapid weight loss may impact musculoskeletal health, providing a rationale for therapeutics that more selectively target adipose tissue loss while preserving muscle mass and strength. Ongoing clinical trials in peripheral vascular disease, neuropsychiatric and substance use disorders, metabolic liver disease, arthritis, hypertension and neurodegenerative disorders may broaden indications for GLP-1-based therapeutics. CI - (c) 2025. Springer Nature Limited. FAU - Drucker, Daniel J AU - Drucker DJ AUID- ORCID: 0000-0001-6688-8127 AD - Department of Medicine and Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. drucker@lunenfeld.ca. LA - eng PT - Journal Article PT - Review DEP - 20250425 PL - England TA - Nat Rev Drug Discov JT - Nature reviews. Drug discovery JID - 101124171 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Nat Rev Drug Discov. 2025 Jul;24(7):570. doi: 10.1038/s41573-025-01231-3. PMID: 40437221 MH - Humans MH - *Obesity/drug therapy/metabolism MH - *Glucagon-Like Peptide 1/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Hypoglycemic Agents/therapeutic use/pharmacology/adverse effects MH - Animals MH - Weight Loss/drug effects MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - Semaglutide COIS- Competing interests: D.J.D. has received consulting fees from Amgen, AstraZeneca Inc., Insulet, Kallyope and Pfizer Inc. and speaking fees from Boehringer Ingelheim and Novo Nordisk Inc. Mount Sinai Hospital has received investigator-initiated grant support from Amgen, Eli Lilly Inc., Novo Nordisk, Pfizer and Zealand Pharmaceuticals Inc. to support preclinical studies in the Drucker laboratory. EDAT- 2025/04/26 16:17 MHDA- 2025/08/02 10:43 CRDT- 2025/04/25 23:33 PHST- 2025/03/13 00:00 [accepted] PHST- 2025/08/02 10:43 [medline] PHST- 2025/04/26 16:17 [pubmed] PHST- 2025/04/25 23:33 [entrez] AID - 10.1038/s41573-025-01183-8 [pii] AID - 10.1038/s41573-025-01183-8 [doi] PST - ppublish SO - Nat Rev Drug Discov. 2025 Aug;24(8):631-650. doi: 10.1038/s41573-025-01183-8. Epub 2025 Apr 25. PMID- 40279144 OWN - NLM STAT- MEDLINE DCOM- 20250521 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 48 IP - 6 DP - 2025 Jun 1 TI - High-Dose Semaglutide (Up to 16 mg) in People With Type 2 Diabetes and Overweight or Obesity: A Randomized, Placebo-Controlled, Phase 2 Trial. PG - 905-913 LID - 10.2337/dc24-2425 [doi] AB - OBJECTIVE: Studies have demonstrated dose-dependent efficacy of glucagon-like peptide 1 receptor agonists for glycemic control and body weight. The aim of this trial was to characterize the dose-dependent effects of semaglutide (up to 16 mg/week) in people with type 2 diabetes and overweight or obesity. RESEARCH DESIGN AND METHODS: In this parallel-group, participant- and investigator-blinded, phase 2 trial, 245 individuals with type 2 diabetes and BMI >/=27 kg/m2 on metformin were randomized to weekly semaglutide (2, 8, or 16 mg s.c.) or placebo for 40 weeks. Doses were escalated every 4 weeks, followed by a maintenance period. Dose modifications were not allowed. Primary and secondary efficacy end points included change from baseline to week 40 in HbA1c and body weight, respectively. RESULTS: Estimated treatment difference between 16 and 2 mg was -0.3 percentage points (%-points) (95% CI -0.7 to 0.2; P = 0.245) for HbA1c change and -3.4 kg (-6.0 to -0.8; P = 0.011) for weight change for the treatment policy estimand and -0.5%-points (-1.0 to -0.1; P = 0.015) and -4.5 kg (-7.6 to -1.4; P = 0.004), respectively, for the hypothetical estimand. Dose-response modeling confirmed these findings. Treatment-emergent adverse events (AEs) and treatment discontinuations due to AEs, primarily gastrointestinal, were more frequent in the semaglutide 8 and 16 mg groups than in the 2 mg group. No severe hypoglycemic episodes were reported. CONCLUSIONS: Higher semaglutide doses for type 2 diabetes and overweight or obesity provide modest additional glucose-lowering effect, with additional weight loss, at the expense of more AEs and treatment discontinuations. A study for evaluating high-dose semaglutide in obesity is currently underway. CI - (c) 2025 by the American Diabetes Association. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. FAU - Jorgensen, Nils B AU - Jorgensen NB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kumar, Bharath AU - Kumar B AD - Biostatistics, Novo Nordisk Service Centre India Private Ltd., Bangalore, India. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX. FAU - Laulund, Anne Sofie AU - Laulund AS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - Division of Endocrinology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. CN - trial investigators LA - eng GR - P30 DK124723/DK/NIDDK NIH HHS/United States GR - UM1 TR004406/TR/NCATS NIH HHS/United States GR - Novo Nordisk/ PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - Female MH - Male MH - *Obesity/drug therapy MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Overweight/drug therapy MH - Aged MH - Glycated Hemoglobin/metabolism MH - Adult MH - Metformin/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12094194 COIS- Funding and Duality of Interest. The trial was funded by Novo Nordisk A/S. Representatives of the sponsor (Novo Nordisk A/S) were involved in the study design; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript; those who meet authorship criteria are included in the author group, and other contributors are acknowledged. A medical writer (employed by the sponsor) assisted with editing the manuscript, under the direction of the authors. As noted below, all authors received some form of compensation from Novo Nordisk A/S during the design and execution phases of the trial. N.B.J. and A.S.L. are employees of Novo Nordisk A/S, and B.K. is an employee at Novo Nordisk Service Centre India Private Ltd. N.B.J. is a stockholder of Novo Nordisk A/S and Eli Lilly. A.S.L. is a stockholder of Novo Nordisk A/S. J.B.B. was supported by grants from the National Institutes of Health (National Center for Advancing Translational Sciences Clinical and Translational Science Award UM1TR004406 and National Institute of Diabetes and Digestive and Kidney Diseases Diabetes Research Center Award P30DK124723). V.R.A. reports institutional contracts with or grants from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Corcept Therapeutics, Eli Lilly, Fractyl Health, Novo Nordisk, Pfizer, Rhythm Pharmaceuticals, and Servier and consultant contracts with Fractyl Health, Mediflix, Novo Nordisk, Pfizer, and Sanofi. J.B.B. reports that fees for contracted activities are paid to the University of North Carolina at Chapel Hill by Novo Nordisk for efforts of J.B.B. as an investigator, consultant, and expert witness; reports grant support from Bayer, Boehringer Ingelheim, Carmot Therapeutics, Corcept Therapeutics, Dexcom, Eli Lilly, Fractyl Health, Insulet, MannKind, and vTv Therapeutics; reports consulting fees from Alkahest, Altimmune, American Diabetes Association, Anji Pharmaceuticals, Aqua Medical, AstraZeneca, Boehringer Ingelheim, CeQur, Corcept Therapeutics, Eli Lilly, embecta, GentiBio, Glyscend, Insulet, Mediflix, Medscape, Medtronic MiniMed, Mellitus Health, Metsera, Moderna, Pendulum Therapeutics, Praetego, ReachMD, Stability Health, Tandem Diabetes Care, Terns Pharmaceuticals, and Vertex Pharmaceuticals; reports payment for presentations from Boehringer Ingelheim; reports payment for expert testimony from Medtronic MiniMed; reports stock options from Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Praetego, and Stability Health; and reports serving on the scientific advisory board for Dasman Diabetes Center, Kuwait City, Kuwait. I.L. received research funding (paid to institution) from Novo Nordisk, Sanofi, and Boehringer Ingelheim; received research-related consulting fees (paid to institution) from Novo Nordisk; and received advisory/consulting fees and/or other support from AbbVie, Altimmune, AstraZeneca, Bayer, Betagenon AB, BIOIO, Biomea Fusion, Boehringer Ingelheim, Carmot Therapeutics, Cytoki Pharma, Eli Lilly, Intercept, Janssen/Johnson & Johnson, Juvena Therapeutics, Keros Therapeutics, Mediflix, Merck, Metsera, Novo Nordisk, PharmaVentures, Pfizer, Regeneron Pharmaceuticals, Sanofi, Shionogi, Structure Therapeutics, Target RWE, Terns Pharmaceuticals, The Comm Group, WebMD, and Zealand Pharma. No other potential conflicts of interest relevant to this article were reported. EDAT- 2025/04/25 13:47 MHDA- 2025/05/21 18:29 PMCR- 2025/04/25 CRDT- 2025/04/25 11:42 PHST- 2024/11/05 00:00 [received] PHST- 2025/02/20 00:00 [accepted] PHST- 2025/05/21 18:29 [medline] PHST- 2025/04/25 13:47 [pubmed] PHST- 2025/04/25 11:42 [entrez] PHST- 2025/04/25 00:00 [pmc-release] AID - 158206 [pii] AID - dc242425 [pii] AID - 10.2337/dc24-2425 [doi] PST - ppublish SO - Diabetes Care. 2025 Jun 1;48(6):905-913. doi: 10.2337/dc24-2425. PMID- 40277315 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260918 IS - 1520-7560 (Electronic) IS - 1520-7552 (Print) IS - 1520-7552 (Linking) VI - 41 IP - 4 DP - 2025 May TI - Long-Term Effectiveness of Once-Weekly Semaglutide in Patients With Type 2 Diabetes Previously Treated With Insulin. A Multicentre Real-World Study. PG - e70045 LID - 10.1002/dmrr.70045 [doi] LID - e70045 AB - BACKGROUND: The introduction of glucagon-like peptide 1 receptor agonists (GLP-1RAs) has provided new avenues for managing type 2 diabetes (T2D), aiming to achieve optimal glycaemic control while minimising treatment burden. We conducted a multicentre retrospective real-world study to assess the effectiveness of semaglutide once-weekly (OW) in patients previously treated with insulin. METHODS: We included individuals with T2D who were on insulin (basal and/or bolus) and initiated OW semaglutide at 18 specialist care centres. We collected retrospective data on baseline clinical characteristics and updated values of HbA1c and body weight. The primary outcome was the change in HbA1c analysed using the mixed model for repeated measures. Secondary outcomes included the changes in body weight, insulin discontinuation and the change in insulin doses. RESULTS: The study included 674 individuals. At baseline, participants were 61.7 years old, with a mean diabetes duration of 11.5 years and an HbA1c of 8.2%. During a median follow-up of 18 months, OW semaglutide initiation led to a significant reduction in HbA1c (-0.9%) and body weight (-4.3 kg), with 60% of patients achieving HbA1c < 7%. 32.8% of patients discontinued insulin therapy, 72.5% of whom achieved an HbA1c < 7%. Among patients on basal-bolus insulin, 75% completely discontinued bolus, 62% of whom achieved an HbA1c < 7%. Predictors of insulin discontinuation included shorter diabetes duration, lower baseline HbA1c, and lower insulin doses. Among patients who remained on insulin, initiation of OW semaglutide was associated with a decrease in total daily insulin requirement. CONCLUSION: Our study highlights OW semaglutide as a valuable addition to a T2D regimen based on insulin, offering effective glycaemic and weight control with the potential for insulin deintensification or discontinuation. CI - (c) 2025 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd. FAU - Bonora, Benedetta Maria AU - Bonora BM AUID- ORCID: 0000-0002-6770-2723 AD - Department of Medicine, University of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine, Padua, Italy. FAU - Giaccari, Andrea AU - Giaccari A AUID- ORCID: 0000-0002-7462-7792 AD - Endocrine and Metabolic Center, Fondazione Policlinico Universitario A. Gemelli IRCCS and Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Consoli, Agostino AU - Consoli A AUID- ORCID: 0000-0002-1885-451X AD - Endocrinology and Metabolism Unit, ASL, Pescara, Italy. AD - Department of Medicine and Aging Sciences DMSI and Center for Advanced Studies and Technology CAST, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy. FAU - Broglio, Fabio AU - Broglio F AD - Division of Endocrinology, Department of Medical Sciences, University of Turin, Turin, Italy. FAU - Avogaro, Angelo AU - Avogaro A AUID- ORCID: 0000-0002-1177-0516 AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Fadini, Gian Paolo AU - Fadini GP AD - Department of Medicine, University of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine, Padua, Italy. CN - GLIMPLES Study Investigators LA - eng GR - Societa italiana di diabetologia/ PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Biomarkers/analysis MH - Blood Glucose/analysis MH - *Diabetes Mellitus, Type 2/drug therapy/pathology MH - Drug Administration Schedule MH - Follow-Up Studies MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Insulin/therapeutic use MH - Prognosis MH - Retrospective Studies MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12023824 OTO - NOTNLM OT - body weight OT - glucose control OT - real-world effectiveness OT - retrospective study OT - semaglutide OT - type 2 diabetes COIS- B.M.B. received lecture or advisory board fees from AstraZeneca, Boehringer-Ingelheim, Lilly, MSD, Sanofi, Servier and Novo-Nordisk. A.G. has received lecture fees from AstraZeneca, Lilly and Novo Nordisk. A.C. received grants from AstraZeneca, Lilly, Novo-Nordisk. He also received speaker fees, and provided advisory board services for Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Lilly, Merck Sharp & Dhome, Menarini, Novo-Nordisk, Sanofi, Sigma-Tau and Takeda. F.B. received lecture fees from Lilly and Novo-Nordisk. A.A. received research grants and lecture or advisory board fees from MSD, AstraZeneca, Novartis, Boehringer Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier and Takeda. G.P.F. received advisory board grants, honoraria or lecture fees from Abbott, AstraZeneca, Boehringer, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, Servier and Takeda. EDAT- 2025/04/25 13:45 MHDA- 2025/04/25 13:46 PMCR- 2025/04/25 CRDT- 2025/04/25 08:33 PHST- 2025/02/10 00:00 [revised] PHST- 2024/06/11 00:00 [received] PHST- 2025/03/11 00:00 [accepted] PHST- 2025/04/25 13:46 [medline] PHST- 2025/04/25 13:45 [pubmed] PHST- 2025/04/25 08:33 [entrez] PHST- 2025/04/25 00:00 [pmc-release] AID - DMRR70045 [pii] AID - 10.1002/dmrr.70045 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2025 May;41(4):e70045. doi: 10.1002/dmrr.70045. PMID- 40275332 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260802 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 24 IP - 1 DP - 2025 Apr 24 TI - Real-world effectiveness of adding newer generation GLP-1RA to SGLT2i in type 2 diabetes. PG - 177 LID - 10.1186/s12933-025-02737-1 [doi] LID - 177 AB - BACKGROUND: Guidelines recommend combination therapy with glucagonlike peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) for cardiorenal risk reduction in people with type 2 diabetes (T2D); however, there is limited real-world evidence on the long-term effects of combination therapy on cardiometabolic and renal outcomes. The objective of this study was to assess cardiovascular (CV), metabolic, and renal effects of combination therapy with newer generation GLP-1RA (including once-weekly GLP-1RAs, once-daily oral semaglutide, and dual GLP-1/glucose-dependent insulinotropic polypeptide [GIP] agonists) and SGLT2i compared with SGLT2i alone. METHODS: This retrospective cohort study included data on US adults with T2D receiving SGLT2i from Komodo's Healthcare Map from January 1, 2017, to June 30, 2023. The study included 100,455 people in the combination GLP-1RA and SGLT2i group and 339,540 people in the comparison SGLT2i group across 3 cohorts: T2D with atherosclerotic cardiovascular disease (ASCVD), T2D, and T2D with chronic kidney disease (CKD). Entropy balancing was used to balance patient characteristics. Time to first event of ischemic stroke, myocardial infarction (MI), 3-point major adverse cardiovascular event (MACE), and 5-point MACE in T2D with ASCVD cohort were measured. In the T2D cohort, follow-up and change in glycated hemoglobin (HbA(1c)) and weight, odds of achieving HbA(1c) < 7% and HbA(1c) < 8%, and odds of achieving 5%, 10%, and 15% decrease in weight were also measured. RESULTS: The combination and comparison groups included 34,690 and 130,220 people, respectively, in the T2D with ASCVD cohort; 8,220 and 22,891 people, respectively, in the T2D cohort; and 8,783 and 35,532 people, respectively, in the T2D with CKD cohort. Compared with SGLT2i alone, combination therapy was significantly associated with 42% lower risk of ischemic stroke, 37% lower risk of MI, 46% lower risk of 3-point MACE, and 45% lower risk of 5-point MACE among people with T2D and ASCVD. Among the individual GLP-1RAs assessed, the largest reductions in CV risk, HbA(1c), and weight outcomes were observed with combination therapy with SGLT2i and once weekly semaglutide for T2D. CONCLUSIONS: Combination of SGLT2i and GLP-1RA achieved significantly better cardiometabolic outcomes compared with SGLT2i alone; this supports the hypothesis that the cardioprotective benefits of GLP-1RA and SGLT2i may be additive. CI - (c) 2025. The Author(s). FAU - Chaiyakunapruk, Nathorn AU - Chaiyakunapruk N AD - Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, UT, USA. AD - IDEAS Center, Veterans Affairs Salt Lake City Healthcare System, Salt Lake City, UT, USA. FAU - Tan, Xi AU - Tan X AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Liang, Yuanjie AU - Liang Y AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Guevarra, Mico AU - Guevarra M AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Cheng, Alice Y Y AU - Cheng AYY AD - Department of Medicine, University of Toronto, 507-2300 Eglinton Avenue West, Mississauga, ON, L5M 2V8, Canada. Alice.Cheng@unityhealth.to. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250424 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Incretins) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/epidemiology/mortality MH - Retrospective Studies MH - Male MH - Female MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use/administration & dosage MH - Treatment Outcome MH - Middle Aged MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Time Factors MH - *Incretins/adverse effects/administration & dosage/therapeutic use MH - Drug Therapy, Combination MH - *Blood Glucose/metabolism/drug effects MH - Biomarkers/blood MH - *Cardiovascular Diseases/prevention & control/diagnosis/epidemiology MH - United States/epidemiology MH - Risk Assessment MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor MH - Glycated Hemoglobin MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12023599 OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Chronic kidney disease OT - Combination therapy OT - Glucagonlike peptide-1 receptor agonist OT - Major adverse cardiovascular event OT - Sodium-glucose cotransporter 2 inhibitor OT - Type 2 diabetes COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: NC has nothing to disclose. XT, YL, MG, and LX are employees of Novo Nordisk Inc. AYYC received consulting/speaking honoraria from Abbott, AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, GSK, HLS Therapeutics, Insulet, Janssen, Medtronic, Novo Nordisk, Pfizer, Sanofi, and Vertex. EDAT- 2025/04/25 01:21 MHDA- 2025/04/25 13:45 PMCR- 2025/04/24 CRDT- 2025/04/24 23:50 PHST- 2025/02/03 00:00 [received] PHST- 2025/04/09 00:00 [accepted] PHST- 2025/04/25 13:45 [medline] PHST- 2025/04/25 01:21 [pubmed] PHST- 2025/04/24 23:50 [entrez] PHST- 2025/04/24 00:00 [pmc-release] AID - 10.1186/s12933-025-02737-1 [pii] AID - 2737 [pii] AID - 10.1186/s12933-025-02737-1 [doi] PST - epublish SO - Cardiovasc Diabetol. 2025 Apr 24;24(1):177. doi: 10.1186/s12933-025-02737-1. PMID- 40265328 OWN - NLM STAT- MEDLINE DCOM- 20250724 LR - 20250729 IS - 1758-8111 (Electronic) IS - 1758-8103 (Print) IS - 1758-8103 (Linking) VI - 15 IP - 4 DP - 2025 Aug TI - Effect of glucagon-like peptide 1 receptor agonists on systolic blood pressure in patients with obesity, with or without diabetes: A systematic review and network meta-analysis. PG - e70012 LID - 10.1111/cob.70012 [doi] LID - e70012 AB - The effect of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on systolic blood pressure (SBP) in patients with obesity with or without diabetes remains unclear. The aim was to compare the effect of different drug-dose combinations of GLP-1RAs on SBP. The secondary aim was to assess whether changes in SBP with GLP-1RAs are associated with weight change. MEDLINE and Cochrane were searched until January 2022 for randomized control trials (RCTs) on patients with obesity, evaluating the impact of semaglutide, liraglutide, efpeglenatide, or exenatide on SBP. Separate analyses were done for trials with and without diabetes. Multivariate meta-regression assessed if SBP changes with GLP-1RA varied based on weight change or follow-up duration. Thirty-five RCTs were included. Follow-up duration ranged from 12 to 68 weeks for T2DM and 12-56 weeks for non-T2DM patients. GLP-1RAs significantly lowered SBP for all patients (MD = -3.14 [-3.60; -2.68]). Subgroup analysis showed a significantly greater difference in SBP reduction for patients without diabetes (-3.80 [-4.24; -3.37]) when compared with patients with diabetes (-2.13 [-3.27; -1.00]). Among patients with diabetes, liraglutide < 2 mg OD showed the greatest reduction in SBP (-3.78 [-6.27; -1.28]), while efpeglenatide /=18 years) with type 2 diabetes (T2D) and without diabetes with dispensations for GLMs and WLMs. Any use was defined as medication dispensation regardless of prior use. Incident use was defined as dispensation without use in the preceding year. MEASUREMENTS: Monthly trends in medication dispensations before and after tirzepatide market entry. Tirzepatide uptake was additionally compared with initial postapproval uptake of other GLMs and WLMs. RESULTS: Tirzepatide dispensations increased markedly among adults with T2D prescribed GLMs, reaching 12.3% of all GLM dispensations by December 2023. Similar patterns were observed for sodium-glucose cotransporter-2 inhibitors (14.5% to 24.4%) and GLP-1 RAs (19.5% to 28.5%). Dispensations of other GLMs, including metformin, declined. Among adults without diabetes but prescribed WLMs, tirzepatide (0.0% to 40.6%) and semaglutide (2.4 mg) (0.0% to 32.2%) dispensations increased sharply, but semaglutide (2.0 mg) was the most frequently dispensed WLM, increasing from 37.8% to 45.7%. Dispensations of other WLMs declined. Similar trends were observed among incident users. Tirzepatide uptake was more rapid and sustained compared with initial postapproval periods for other medications. LIMITATION: Generalizability to U.S. adults without commercial health insurance is uncertain. CONCLUSION: These findings highlight the sharp uptake of tirzepatide after U.S. market entry and enhance understanding of the rapidly shifting landscape of prescribing patterns for GLMs and WLMs. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases. FAU - Ostrominski, John W AU - Ostrominski JW AUID- ORCID: 0000-0002-2866-9414 AD - Cardiovascular Division, Division of Endocrinology, Diabetes and Hypertension, and Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.W.O.). FAU - Ortega-Montiel, Janinne AU - Ortega-Montiel J AUID- ORCID: 0000-0001-8196-6648 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.O.-M., H.T., C.A., E.D., E.P.). FAU - Tesfaye, Helen AU - Tesfaye H AUID- ORCID: 0000-0002-6264-2813 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.O.-M., H.T., C.A., E.D., E.P.). FAU - Alix, Caroline AU - Alix C AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.O.-M., H.T., C.A., E.D., E.P.). FAU - DiCesare, Elyse AU - DiCesare E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.O.-M., H.T., C.A., E.D., E.P.). FAU - Cromer, Sara J AU - Cromer SJ AUID- ORCID: 0000-0002-4924-2049 AD - Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (S.J.C., D.J.W.). FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (S.J.C., D.J.W.). FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics and Division of Renal Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.M.P.). FAU - Patorno, Elisabetta AU - Patorno E AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (J.O.-M., H.T., C.A., E.D., E.P.). LA - eng GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States GR - T32 HL007604/HL/NHLBI NIH HHS/United States GR - U01 FD007213/FD/FDA HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20250415 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - United States MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Male MH - Female MH - *Tirzepatide/therapeutic use MH - Adult MH - Aged MH - Cohort Studies MH - *Drug Utilization/trends MH - Drug Approval PMC - PMC12718076 MID - NIHMS2124627 COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2025/04/14 18:24 MHDA- 2025/05/19 18:34 PMCR- 2025/12/20 CRDT- 2025/04/14 17:02 PHST- 2025/05/19 18:34 [medline] PHST- 2025/04/14 18:24 [pubmed] PHST- 2025/04/14 17:02 [entrez] PHST- 2025/12/20 00:00 [pmc-release] AID - 10.7326/ANNALS-24-02870 [doi] PST - ppublish SO - Ann Intern Med. 2025 May;178(5):620-633. doi: 10.7326/ANNALS-24-02870. Epub 2025 Apr 15. PMID- 40227520 OWN - NLM STAT- MEDLINE DCOM- 20251125 LR - 20261010 IS - 1573-6709 (Electronic) IS - 0033-2720 (Linking) VI - 96 IP - 4 DP - 2025 Dec TI - Semaglutide Plus Metformin Versus Metformin Alone For Antipsychotic-Induced Weight Gain In Patients With Type 2 Diabetes Mellitus. PG - 819-827 LID - 10.1007/s11126-025-10137-7 [doi] AB - To determine whether combination therapy (semaglutide + metformin) is more efficacious than monotherapy (metformin alone) in reducing the risk of antipsychotic-induced weight gain (AIWG) in patients with Type 2 Diabetes Mellitus (T2DM). This was a single-center, retrospective study evaluating patients >/= 18 years of age receiving care at Michael E. DeBakey Veterans Affairs Medical Center (MEDVAMC) from January 2021 to December 2022. Subjects were identified by use of antipsychotic (quetiapine, risperidone, paliperidone, olanzapine, clozapine) with concomitant use of monotherapy or combination therapy. Key exclusion criteria included other medications impacting weight, unstable medical illness, active substance use disorder, and dual antipsychotic use. The primary endpoint was defined as weight loss >/= 5% from baseline. Secondary outcomes included BMI % difference and HbA1c difference from baseline. Data was analyzed using descriptive statistics. 31 patients were evaluated in each group for the final analysis. 38.7% (12/31) of patients in the monotherapy group achieved the primary outcome of weight loss >/= 5% from baseline vs. 61.29% (19/31) in the combination group (p = 0.04). For secondary outcomes, the BMI % difference from baseline in the monotherapy group was -3.88% vs. -5.58% in the combination group (p = 0.129). The monotherapy group had a difference in HbA1c % from baseline of 0.14% vs -0.9% in the combination group (p = 0.007). Among T2DM patients on antipsychotics, more patients in the combination group achieved weight loss >/= 5% within the study period compared to metformin monotherapy. Future research should account for non-diabetic patients, assess lifestyle factors, and exclude other psychotropic medications that may affect weight. CI - (c) 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. FAU - Vu, Catherine AU - Vu C AD - Pharmacy Department, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA. cthrnvu@gmail.com. FAU - Thai, Raymond AU - Thai R AD - Pharmacy Department, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA. FAU - Dike, Dozie AU - Dike D AD - Psychiatry & Behavioral Sciences Department, Baylor College of Medicine, Houston, TX, USA. FAU - Sydner, Bria AU - Sydner B AD - Pharmacy Department, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20250414 PL - United States TA - Psychiatr Q JT - The Psychiatric quarterly JID - 0376465 RN - 9100L32L2N (Metformin) RN - 0 (Antipsychotic Agents) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Metformin/pharmacology/administration & dosage MH - *Antipsychotic Agents/adverse effects MH - Male MH - Middle Aged MH - Female MH - *Weight Gain/drug effects MH - Retrospective Studies MH - Drug Therapy, Combination MH - *Hypoglycemic Agents/pharmacology/administration & dosage MH - Aged MH - *Glucagon-Like Peptides/administration & dosage/pharmacology/therapeutic use MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Antipsychotics OT - Diabetes OT - Metformin OT - Semaglutide OT - Veterans OT - Weight gain COIS- Declarations. All authors of this article do not have any financial or non-financial interests directly or indirectly related to the work submitted. Human Ethics and Consent to Participate: This study was approved by the Baylor College of Medicine Institutional Review Board (IRB) and was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. EDAT- 2025/04/14 12:25 MHDA- 2025/11/25 13:55 CRDT- 2025/04/14 11:18 PHST- 2025/03/18 00:00 [accepted] PHST- 2025/11/25 13:55 [medline] PHST- 2025/04/14 12:25 [pubmed] PHST- 2025/04/14 11:18 [entrez] AID - 10.1007/s11126-025-10137-7 [pii] AID - 10.1007/s11126-025-10137-7 [doi] PST - ppublish SO - Psychiatr Q. 2025 Dec;96(4):819-827. doi: 10.1007/s11126-025-10137-7. Epub 2025 Apr 14. PMID- 40227398 OWN - NLM STAT- MEDLINE DCOM- 20250414 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 31 IP - 4 DP - 2025 Apr TI - Combined effect of continuous glucose monitoring and semaglutide: analysis of administrative claims. PG - 183-188 LID - 10.37765/ajmc.2025.89719 [doi] AB - OBJECTIVES: This study evaluated whether the combined use of continuous glucose monitoring (CGM) and semaglutide, a glucagon-like peptide-1 receptor agonist, was associated with larger hemoglobin A1c (HbA1c) improvements compared with use of semaglutide alone. STUDY DESIGN: Using US health care claims data from the Optum Clinformatics database, this retrospective analysis identified adults with type 2 diabetes (T2D) using semaglutide. METHODS: The CGM cohort had at least 1 CGM-related claim between January 1, 2019, and September 30, 2022. Random index dates were used in the control (non-CGM) cohort. At least 1 laboratory HbA1c value was required during baseline and follow-up periods. Outcomes included change in HbA1c and the proportion of people who reached American Diabetes Association (ADA) or Healthcare Effectiveness Data and Information Set (HEDIS) HbA1c targets of less than 7.0% or less than 8.0%, respectively. RESULTS: A total of 21,247 people with T2D were identified, with 18,488 in the control group and 2759 using CGM. Overall, a significantly greater reduction in HbA1c was observed in the CGM cohort compared with the control group (difference-in-differences, -0.55%; 95% CI, -0.64% to -0.47%; P < .0001). Among CGM users, the proportion meeting the ADA target of HbA1c less than 7.0% nearly doubled, and the proportion achieving the HEDIS target of HbA1c less than 8.0% increased by more than 50%. CONCLUSIONS: The results suggest that CGM provides an additive benefit to semaglutide, leading to greater decreases in HbA1c. Expanded use of these complementary therapies in the primary care setting could enable more people with T2D to achieve their glycemic goals. FAU - Nemlekar, Poorva M AU - Nemlekar PM FAU - Hannah, Katia L AU - Hannah KL FAU - Green, Courtney R AU - Green CR FAU - Grace, Thomas AU - Grace T FAU - Lynch, Peter M AU - Lynch PM FAU - Castle, Jessica R AU - Castle JR FAU - Norman, Gregory J AU - Norman GJ AD - Dexcom, Inc, 6340 Sequence Dr, San Diego, CA 92121. Email: greg.norman@dexcom.com. LA - eng PT - Journal Article PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - Glycated Hemoglobin/analysis MH - Female MH - Middle Aged MH - Male MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Blood Glucose Self-Monitoring/methods MH - Aged MH - Blood Glucose/analysis MH - United States MH - Adult MH - Continuous Glucose Monitoring MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/04/14 12:25 MHDA- 2025/04/14 12:26 CRDT- 2025/04/14 11:12 PHST- 2025/04/14 12:26 [medline] PHST- 2025/04/14 12:25 [pubmed] PHST- 2025/04/14 11:12 [entrez] AID - 89719 [pii] AID - 10.37765/ajmc.2025.89719 [doi] PST - ppublish SO - Am J Manag Care. 2025 Apr;31(4):183-188. doi: 10.37765/ajmc.2025.89719. PMID- 40221226 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20250811 IS - 1873-3735 (Electronic) IS - 0165-6147 (Linking) VI - 46 IP - 5 DP - 2025 May TI - Structural pharmacology and mechanisms of GLP-1R signaling. PG - 422-436 LID - S0165-6147(25)00043-4 [pii] LID - 10.1016/j.tips.2025.03.003 [doi] AB - Glucagon-like peptide-1 receptor (GLP-1R), a class B1 G protein-coupled receptor, plays critical roles in glucose homeostasis. Recent structural pharmacology studies using cryogenic electron microscopy, X-ray crystallography, mass spectrometry, and functional analyses, have provided valuable insights into its activation by endogenous hormones and mono- or dual agonists like semaglutide and tirzepatide, highly effective in treating type 2 diabetes and obesity. They highlight significant conformational changes in the extracellular and transmembrane domains of GLP-1R that drive receptor activation and downstream signal transduction. Additionally, allosteric modulators, supported by emerging structural information, show great promises as an alternative strategy. Future research investigating unexplored effector interactions, biased signaling, weight rebound mechanisms, and personalized therapy strategies will be critical for developing better therapeutic agents targeting GLP-1R. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved. FAU - Zhou, Qingtong AU - Zhou Q AD - Research Center for Medicinal Structural Biology, National Research Center for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Research Center for Deepsea Bioresources, Sanya, Hainan 572025, China. FAU - Zhao, Fenghui AU - Zhao F AD - The National Center for Drug Screening, Shanghai 201203, China. FAU - Zhang, Yao AU - Zhang Y AD - Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China. FAU - Yang, Dehua AU - Yang D AD - Research Center for Deepsea Bioresources, Sanya, Hainan 572025, China; The National Center for Drug Screening, Shanghai 201203, China. FAU - Wang, Ming-Wei AU - Wang MW AD - Research Center for Medicinal Structural Biology, National Research Center for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Research Center for Deepsea Bioresources, Sanya, Hainan 572025, China; Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, School of Pharmacy, Hainan Medical University, Haikou 570228, China; Department of Chemistry, School of Science, The University of Tokyo, Tokyo 113-0033, Japan. Electronic address: mwwang@simm.ac.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20250411 PL - England TA - Trends Pharmacol Sci JT - Trends in pharmacological sciences JID - 7906158 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor/metabolism/chemistry MH - Signal Transduction/drug effects MH - Animals MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Hypoglycemic Agents/pharmacology OTO - NOTNLM OT - GLP-1R OT - GLP-1RA OT - allosteric modulation OT - conformational dynamics OT - diabetes OT - obesity OT - structural pharmacology COIS- Declaration of interests The authors declare no competing conflict of interest. EDAT- 2025/04/13 00:44 MHDA- 2025/05/04 15:35 CRDT- 2025/04/12 21:56 PHST- 2025/02/11 00:00 [received] PHST- 2025/03/13 00:00 [revised] PHST- 2025/03/13 00:00 [accepted] PHST- 2025/05/04 15:35 [medline] PHST- 2025/04/13 00:44 [pubmed] PHST- 2025/04/12 21:56 [entrez] AID - S0165-6147(25)00043-4 [pii] AID - 10.1016/j.tips.2025.03.003 [doi] PST - ppublish SO - Trends Pharmacol Sci. 2025 May;46(5):422-436. doi: 10.1016/j.tips.2025.03.003. Epub 2025 Apr 11. PMID- 40221023 OWN - NLM STAT- MEDLINE DCOM- 20250929 LR - 20260122 IS - 0210-5705 (Print) IS - 0210-5705 (Linking) VI - 48 IP - 8 DP - 2025 Oct TI - Multidisciplinary clinical practice guideline on the management of metabolic hepatic steatosis. PG - 502442 LID - S0210-5705(25)00118-9 [pii] LID - 10.1016/j.gastrohep.2025.502442 [doi] AB - Metabolic hepatic steatosis (MetHS) is a clinically heterogeneous, multisystemic, dynamic, and complex disease, whose progression is one of the main causes of cirrhosis and hepatocarcinoma. This clinical practice guideline aims to respond to its main challenges, both in terms of disease burden and complexity. To this end, recommendations have been proposed to experts through the Delphi method. The consensus was optimal in recommendations regarding type 2 diabetes as a risk factor (1.5.1, 4.5.1), in which cases early detection of MetHS should be carried out (4.5.2). Its results also emphasize the importance of the use of non-invasive tests (FIB-4, NFS, HFS) for the exclusion of significant fibrosis in patients with suspected MetHS (2.3.1, 2.3.3). Diagnosis should be carried out through the sequential combination of non-invasive indices and transient elastography by FibroScan(R) for its risk stratification (2.3.3). A nearly unanimous consensus was reached regarding the role of early prevention in the impact on the quality of life and survival of patients (5.1.2), as well as on the effectiveness of the Mediterranean diet and physical exercise in relation to the improvement of steatosis, steatohepatitis and fibrosis in MetHS patients (5.2.2) and on the positive results offered by resmiterom and semaglutide in promoting fibrosis regression (5.4.1). Finally, a great consensus has been reached regarding the importance of multidisciplinary management in MetHS, for which it is essential to agree on multidisciplinary protocols for referral between levels in each health area (6.2.1), as well as ensuring that referrals to Hepatology/Digestive and Endocrinology or Internal Medicine services are effective and beneficial to prevent the risk of disease progression (6.2.3, 6.3.1). CI - Copyright (c) 2025 Elsevier Espana, S.L.U. All rights reserved. FAU - Romero-Gomez, Manuel AU - Romero-Gomez M AD - UGC Aparato Digestivo, Hospital Universitario Virgen del Rocio, Sevilla, Espana; Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Madrid, Espana; Instituto de Biomedicina de Sevilla (HUVR/CSIC/US), Departamento de Medicina, Universidad de Sevilla, Sevilla, Espana; Asociacion Espanola para el Estudio del Higado, Espana. Electronic address: mromerogomez@us.es. FAU - Escalada, Javier AU - Escalada J AD - Sociedad Espanola de Endocrinologia y Nutricion. Clinica Universidad de Navarra, Pamplona, Espana; Sociedad Espanola de Endocrinologia y Nutricion, Madrid, Espana; CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERObn), Instituto de Salud Carlos III, Madrid, Espana; Instituto de Investigacion en la Salud de Navarra (IdiSNA), Pamplona, Espana. Electronic address: fjavier.escalada@gmail.com. FAU - Noguerol, Mar AU - Noguerol M AD - Centro de Salud Universitario Cuzco de Fuenlabrada, Madrid, Espana; Sociedad Espanola de Medicina de Familia y Comunitaria, Madrid, Espana. FAU - Perez, Antonio AU - Perez A AD - Servicio de Endocrinologia y Nutricion, Hospital de la Santa Creu i Sant Pau, Barcelona, Espana; CIBER de Diabetes y Enfermedades Metabolicas (CIBERDEM), Madrid, Espana; Sociedad Espanola de Diabetes, Madrid, Espana. FAU - Carretero, Juana AU - Carretero J AD - Hospital Universitario de Badajoz, Badajoz, Espana; Sociedad Espanola de Medicina Interna (SEMI), Madrid, Espana. FAU - Crespo, Javier AU - Crespo J AD - Hospital Universitario Marques de Valdecilla, Santander, Espana; Sociedad Espanola de Patologia Digestiva, Madrid, Espana; Grupo de Investigacion Clinica y Traslacional en Enfermedades Digestivas, Santander, Espana; Instituto de Investigacion Valdecilla (IDIVAL), Santander, Espana. FAU - Mascort, Juan J AU - Mascort JJ AD - Sociedad Espanola de Medicina de Familia y Comunitaria, Madrid, Espana; Centro de Salud Florida Sud, Institut Catala de la Salut, Hospitalet de Llobregat, Espana. FAU - Aguilar, Ignacio AU - Aguilar I AD - Centro de Salud Roquetas Norte, Roquetas de Mar, Almeria, Espana. FAU - Tinahones, Francisco AU - Tinahones F AD - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERObn), Instituto de Salud Carlos III, Madrid, Espana; Departamento de Endocrinologia y Nutricion, Hospital Virgen de la Victoria, Malaga, Espana; Sociedad Espanola de Obesidad, Madrid, Espana; Instituto de Investigacion Biomedica de Malaga (IBIMA)-Plataforma Bionard, Universidad de Malaga, Malaga, Espana. FAU - Canones, Pedro AU - Canones P AD - Sociedad Espanola de Medicos Generales y de Familia, Madrid, Espana. FAU - Gomez-Huelgas, Ricardo AU - Gomez-Huelgas R AD - Sociedad Espanola de Medicina Interna (SEMI), Madrid, Espana; Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Malaga, Espana; Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Espana. FAU - de Luis, Daniel AU - de Luis D AD - Sociedad Espanola de Endocrinologia y Nutricion, Madrid, Espana; Servicio de Endocrinologia y Nutricion, Hospital Clinico Universitario de Valladolid, Valladolid, Espana; Centro de Investigacion de Endocrinologia y Nutricion, Universidad de Valladolid, Valladolid, Espana. FAU - Genua Trullos, Idoia AU - Genua Trullos I AD - Servicio de Endocrinologia y Nutricion, Hospital de la Santa Creu i Sant Pau, Barcelona, Espana; Sociedad Espanola de Diabetes, Madrid, Espana. FAU - Aller, Rocio AU - Aller R AD - Asociacion Espanola para el Estudio del Higado, Espana; Servicio de Endocrinologia y Nutricion, Hospital de la Santa Creu i Sant Pau, Barcelona, Espana; Sociedad Espanola de Diabetes, Madrid, Espana; Servicio de Aparato Digestivo, Hospital Clinico Universitario de Valladolid, Universidad de Valladolid, Valladolid, Espana; Ciber Enfermedades infecciosas (CIBERINFEC), Madrid, Espana. FAU - Rubio, Miguel A AU - Rubio MA AD - Sociedad Espanola de Endocrinologia y Nutricion, Madrid, Espana; Hospital Clinico San Carlos, Madrid, Espana. LA - eng LA - spa PT - Journal Article PT - Practice Guideline TT - Guia de practica clinica multidisciplinar de manejo de la esteatosis hepatica metabolica. DEP - 20250411 PL - Spain TA - Gastroenterol Hepatol JT - Gastroenterologia y hepatologia JID - 8406671 SB - IM EIN - Gastroenterol Hepatol. 2026 Jan 21:502639. doi: 10.1016/j.gastrohep.2025.502639. PMID: 41571546 MH - Humans MH - *Fatty Liver/therapy/diagnosis MH - *Non-alcoholic Fatty Liver Disease/therapy/diagnosis MH - Liver Cirrhosis/etiology MH - Risk Factors MH - Diabetes Mellitus, Type 2/complications MH - Delphi Technique MH - Patient Care Team OTO - NOTNLM OT - Derivacion OT - Deteccion OT - Detection OT - Esteatohepatitis OT - Esteatosis hepatica metabolica OT - Fibrosis OT - Metabolic hepatic steatosis OT - Referral OT - Steatohepatitis EDAT- 2025/04/13 00:44 MHDA- 2025/09/30 05:17 CRDT- 2025/04/12 19:36 PHST- 2025/02/25 00:00 [received] PHST- 2025/03/26 00:00 [revised] PHST- 2025/03/31 00:00 [accepted] PHST- 2025/09/30 05:17 [medline] PHST- 2025/04/13 00:44 [pubmed] PHST- 2025/04/12 19:36 [entrez] AID - S0210-5705(25)00118-9 [pii] AID - 10.1016/j.gastrohep.2025.502442 [doi] PST - ppublish SO - Gastroenterol Hepatol. 2025 Oct;48(8):502442. doi: 10.1016/j.gastrohep.2025.502442. Epub 2025 Apr 11. PMID- 40212008 OWN - NLM STAT- MEDLINE DCOM- 20250608 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 7 DP - 2025 Jul TI - Comparative efficacy and tolerability of currently approved incretin mimetics: A systematic analysis of placebo-controlled clinical trials. PG - 3736-3746 LID - 10.1111/dom.16398 [doi] AB - AIMS: This study compares the therapeutic efficacy, gastrointestinal (GI) adverse event (AE) rates and the relationship between the therapeutic efficacy and GI AEs in randomized, placebo-controlled clinical trials (RCTs) of GLP-1 RAs and the dual GLP-1/GIP agonist tirzepatide. MATERIALS AND METHODS: A systematic PubMed search identified 38 phase 3 or 4 placebo-controlled RCTs of exenatide (b.i.d. and q.w.), lixisenatide, liraglutide, dulaglutide, albiglutide, semaglutide (s.c. and oral) and tirzepatide with a total of 16 660 individuals with type 2 diabetes (T2D) across 104 study arms. Changes in HbA1c, fasting plasma glucose and body weight and the proportion of GI AEs (nausea, vomiting or diarrhoea) were calculated by agent, preparation and dose. The correlation between odds ratios (ORs) for GI AEs and the magnitude of therapeutic efficacy was assessed in a linear regression analysis. RESULTS: Baseline characteristics were similar across studies: mean age 57 +/- 10 years, diabetes duration 8 +/- 6 years, body mass index (BMI) 31.9 +/- 5.8 kg/m(2) and HbA1c 8.2% +/- 0.9%. HbA1c reductions ranged from -0.63% +/- 0.03% (lixisenatide, 20 mug q.d.) to -1.79% +/- 0.09% (tirzepatide, 15 mg q.w.; p < 0.0001). Weight reductions ranged from -0.75 +/- 0.10 kg to -9.65 +/- 0.56 kg. Despite the high variability in therapeutic efficacy, ORs for GI AEs were similar across compounds/preparations. CONCLUSIONS: The magnitude of efficacy for intended therapeutic actions (HbA1c and body weight reduction) varied widely between incretin mimetic glucose-lowering agents. However, larger therapeutic efficacy was not systematically associated with higher GI AE or drug discontinuation rates, indicating better tolerability of the more effective agents/preparations. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kang, Yu Mi AU - Kang YM AUID- ORCID: 0000-0002-6272-0666 AD - Division of Endocrinology, Diabetes and Hypertension and TIMI Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Punov, Viktoria AU - Punov V AD - Diabetes, Endocrinology, Metabolism Section Medical Department I, Josef-Hospital, Ruhr University Bochum, Bochum, Germany. FAU - Lim, Soo AU - Lim S AUID- ORCID: 0000-0002-4137-1671 AD - Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes, Endocrinology, Metabolism Section Medical Department I, Josef-Hospital, Ruhr University Bochum, Bochum, Germany. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. LA - eng GR - T32 DK007529/DK/NIDDK NIH HHS/United States GR - 5T32DK007529/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250411 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 9P1872D4OL (Exenatide) RN - 0 (Glycated Hemoglobin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 5E7U48495E (rGLP-1 protein) RN - 0 (hemoglobin A1c protein, human) RN - 74O62BB01U (lixisenatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Incretins/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - Liraglutide/therapeutic use/adverse effects MH - Exenatide/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism/analysis MH - Middle Aged MH - Treatment Outcome MH - Tirzepatide MH - Blood Glucose/drug effects/metabolism MH - Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - Peptides/therapeutic use/adverse effects MH - Male MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1/analogs & derivatives MH - Female MH - Recombinant Fusion Proteins/therapeutic use/adverse effects MH - Clinical Trials, Phase III as Topic MH - Vomiting/chemically induced MH - Nausea/chemically induced MH - Diarrhea/chemically induced MH - Glucagon-Like Peptide-2 Receptor MH - Semaglutide PMC - PMC12146062 MID - NIHMS2070980 OTO - NOTNLM OT - GLP-1 analogue OT - incretin therapy OT - systematic review OT - type 2 diabetes OT - weight management COIS- YMK and VP have nothing to disclose. SL is an advisory board member for Novo Nordisk and AstraZeneca and has served on the speakers' bureau of Novo Nordisk, Sanofi, Boehringer Ingelheim, AstraZeneca and MSD. He has received research funding from CKD and Daewoong Pharma. MAN has been member on advisory boards or has consulted with Boehringer Ingelheim, Eli Lilly & Co., Medtronic, Merck, Sharp & Dohme, Novo Nordisk, Pfizer, Regor, Sun Pharma and Structure Therapeutics (ShouTi, Gasherbrum). He has received grant support from Merck, Sharp & Dohme. He has also served on the speakers' bureau of Eli Lilly & Co., Menarini/Berlin Chemie, Merck, Sharp & Dohme, Medscape, Medical Learning Institute and Novo Nordisk. SL is an advisory board member for Novo Nordisk and AstraZeneca and has served on the speakers' bureau of Novo Nordisk, Sanofi, Boehringer Ingelheim, AstraZeneca and MSD. He has received research funding from Chong Kun Dang and Daewoong Pharma. EDAT- 2025/04/11 06:25 MHDA- 2025/06/09 00:28 PMCR- 2025/06/09 CRDT- 2025/04/11 05:24 PHST- 2025/03/26 00:00 [revised] PHST- 2025/02/25 00:00 [received] PHST- 2025/03/28 00:00 [accepted] PHST- 2025/06/09 00:28 [medline] PHST- 2025/04/11 06:25 [pubmed] PHST- 2025/04/11 05:24 [entrez] PHST- 2025/06/09 00:00 [pmc-release] AID - DOM16398 [pii] AID - 10.1111/dom.16398 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jul;27(7):3736-3746. doi: 10.1111/dom.16398. Epub 2025 Apr 11. PMID- 40196945 OWN - NLM STAT- MEDLINE DCOM- 20250408 LR - 20250409 IS - 1545-9616 (Print) IS - 1545-9616 (Linking) VI - 24 IP - 4 DP - 2025 Apr 1 TI - A Retrospective Comparative Analysis of Cutaneous Adverse Reactions in GLP-1 Agonist Therapies. PG - 413-415 LID - 10.36849/JDD.8605 [doi] AB - Glucagon-like peptide-1 (GLP-1) agonists are used to treat type 2 diabetes mellitus (T2DM) and have recently gained approval and popularity for treating obesity and weight loss. There is a lack of data evaluating the types of reactions associated with this medication class, and this study aimed to characterize the types of cutaneous reactions seen across different GLP-1 agonists, and whether differences exist in reactions based on the reason for medication use. Through a retrospective review of cutaneous adverse events associated with semaglutide, dulaglutide, tirzepatide, lixisenatide, liraglutide, and exenatide in the FDA Adverse Event Reporting System, it was found that the 5 most common cutaneous reactions associated with GLP-1 agonists were eczematous, pruritus, drug eruptions, hyperhidrosis, and alopecia. Life-threatening cutaneous adverse events accounted for 2.17% of all cutaneous reactions, with no statistically significant differences observed between drug types. It was also found that GLP-1 agonist use for T2DM exhibited significantly higher rates of alopecia (P=0.000) and hyperhidrosis (P=0.000) in comparison to use for weight management. J Drugs Dermatol. 2025;24(4):413-415. doi:10.36849/JDD.8605. FAU - Daniel, Sophia AU - Daniel S FAU - Waggett, Stephanie AU - Waggett S FAU - Lyles, Elliott AU - Lyles E FAU - Sagut, Pelin AU - Sagut P FAU - Shamaei Zadeh, Parisa AU - Shamaei Zadeh P FAU - Marcelletti, Anthony AU - Marcelletti A FAU - Stegura, Carol AU - Stegura C FAU - Wine Lee, Lara AU - Wine Lee L LA - eng PT - Comparative Study PT - Journal Article PL - United States TA - J Drugs Dermatol JT - Journal of drugs in dermatology : JDD JID - 101160020 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 9P1872D4OL (Exenatide) SB - IM MH - Humans MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - *Drug Eruptions/etiology/epidemiology/diagnosis MH - Male MH - Female MH - *Glucagon-Like Peptide 1/agonists MH - Middle Aged MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Liraglutide/adverse effects MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Exenatide/adverse effects MH - Aged EDAT- 2025/04/08 13:55 MHDA- 2025/04/08 13:56 CRDT- 2025/04/08 09:58 PHST- 2025/04/08 13:56 [medline] PHST- 2025/04/08 13:55 [pubmed] PHST- 2025/04/08 09:58 [entrez] AID - S1545961625P8605X [pii] AID - 10.36849/JDD.8605 [doi] PST - ppublish SO - J Drugs Dermatol. 2025 Apr 1;24(4):413-415. doi: 10.36849/JDD.8605. PMID- 40196933 OWN - NLM STAT- MEDLINE DCOM- 20250416 LR - 20260526 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 Suppl 2 IP - Suppl 2 DP - 2025 Apr TI - Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies. PG - 66-88 LID - 10.1111/dom.16364 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as key agents for weight management, based on their marked efficacy as observed in randomized controlled trials. While still limited, real-world studies on GLP-1RA use in populations with obesity are increasingly available. This narrative review discusses contemporary real-world evidence demonstrating the utilization, clinical and comparative effectiveness, and adverse effects of the currently approved GLP-1RA-based weight-loss therapies, that is, liraglutide, semaglutide and tirzepatide. The observed weight reduction in clinical practice overall tends to be lower than in randomized controlled trials; however, outcomes approach those seen in trials when focusing on highly adherent patients. Real-world studies demonstrate high discontinuation rates of GLP-1RAs (20%-50%) within the first year, and the use of much lower doses than those evaluated in clinical trials. Evidence from observational studies within type 2 diabetes or obesity populations suggests frequent gastrointestinal disturbances in GLP-1RA users, as also observed in trials, but no clear increase in risks of severe events like pancreatitis or pancreatic cancer, thyroid disorders, or depression and self-harm. Further evidence is needed to understand possible real-world associations of GLP-1RAs with eye disease and other rare outcomes. We provide 10 areas of particular importance for further research on GLP-1RA within the real-world space, including improved understanding of the exact drivers of early discontinuation and suboptimal dosing, studies of the effects of stopping GLP-1RA treatment, and investigations of clinical and cost-effectiveness for hard clinical outcomes in real-world settings, including not only cardio-reno-metabolic outcomes but also obesity-induced diseases like neuropsychiatric disease, cancer, musculoskeletal disease, and infections. PLAIN LANGUAGE SUMMARY: Recent advancements in weight-loss medications have sparked a lot of interest. The so-called GLP-1 receptor agonist medications (GLP-1RAs) have gained a lot of attention, because they have shown to be very effective, leading to significant weight loss in patients participating in clinical trials. GLP-1RAs, like liraglutide, semaglutide, and tirzepatide, help manage weight by mimicking hormones that control blood sugar and appetite. However, how these medications perform in real life can be different from the controlled settings of clinical trials, in which patients are carefully selected and their treatment plans closely followed. This literature review looks at how these medications are used and their effectiveness and safety in real-world settings. In real-life practice, GLP-1RAs are often less effective than in clinical trial conditions. This is usually because patients don't follow their medication plans as strictly as in trials. Real-world data shows that many patients use lower doses and do not stick to their treatment as strictly as participants in a controlled trial might, leading to less weight loss. However, those who do follow their plans closely can achieve results similar to those in trials. A major issue with GLP-1RAs is that many patients stop using them within the first year due to side effects or high costs of the medications, especially if not covered by insurance. Common side effects include nausea and digestive problems, which are the main reasons patients stop taking these treatments. These side effects are often manageable and decrease over time, and this reviews found no strong real-world evidence that GLP-1RAs cause severe side effects in many users. Despite these challenges, when GLP-1RAs are used effectively and consistently, they show substantial benefits in weight loss, most so the newest medications semaglutide and tirzepatide. These medications are also likely to help manage and prevent weight-related health conditions like type 2 diabetes and cardiovascular disease, but evidence for these beneficial outcomes is still scarce in real-world settings. The review emphasizes the need for more research to understand why many patients stop using these medications and how to improve dosing. It also calls for studies on the long-term effects of these therapies on various health outcomes, including mental health, cardiometabolic health, cancer, and rare conditions like eye diseases. Overall, while GLP-1RAs are a valuable tool for weight management, their real-world use requires careful consideration of individual patient factors, such as the ability to stick to treatment plans, manage side effects, and afford the medications. Further research will help make these treatments more effective for a wider range of people that need them. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Thomsen, Reimar W AU - Thomsen RW AUID- ORCID: 0000-0001-9135-3474 AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Mailhac, Aurelie AU - Mailhac A AD - Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark. FAU - Lohde, Julie B AU - Lohde JB AD - Department of Biomedicine, Aarhus University, Aarhus, Denmark. AD - Steno Diabetes Center Aarhus, Aarhus, Denmark. FAU - Pottegard, Anton AU - Pottegard A AUID- ORCID: 0000-0001-9314-5679 AD - Department of Public Health, Clinical Pharmacology, Pharmacy, and Environmental Medicine, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article PT - Review DEP - 20250408 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Liraglutide/therapeutic use/adverse effects MH - *Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use/adverse effects/analogs & derivatives MH - *Weight Loss/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Tirzepatide/therapeutic use MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12000858 OTO - NOTNLM OT - drug safety OT - drug utilization OT - epidemiology OT - glucagon-like peptide-1 receptor agonists OT - medications for obesity OT - real-world evidence OT - treatment adherence OT - treatment outcomes OT - weight loss COIS- Anton Pottegard reports participation in research projects funded by Alcon, Almirall, Astellas, AstraZeneca, Boehringer-Ingelheim, Novo Nordisk, Servier and LEO Pharma(all regulator-mandated phase IV-studies), and an unrestricted research grant from Novo Nordisk, all with funds paid to the institution where he was employed (no personal fees) and with no relation to the work reported in this article. Reimar W. Thomsen reports that he has given single scientific presentations on medical research (both with and without financial compensation) for companies, including Astra-Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi. The Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of these studies have any relation to the current study. Julie B. Lohdes PhD project is financed by the Novo Nordisk Foundation. Aurelie Mailhac reports no conflicts of interest. EDAT- 2025/04/08 06:24 MHDA- 2025/04/16 06:19 PMCR- 2025/04/16 CRDT- 2025/04/08 05:02 PHST- 2025/03/05 00:00 [revised] PHST- 2025/01/28 00:00 [received] PHST- 2025/03/13 00:00 [accepted] PHST- 2025/04/16 06:19 [medline] PHST- 2025/04/08 06:24 [pubmed] PHST- 2025/04/08 05:02 [entrez] PHST- 2025/04/16 00:00 [pmc-release] AID - DOM16364 [pii] AID - 10.1111/dom.16364 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27 Suppl 2(Suppl 2):66-88. doi: 10.1111/dom.16364. Epub 2025 Apr 8. PMID- 40189538 OWN - NLM STAT- MEDLINE DCOM- 20250516 LR - 20260127 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 23 IP - 1 DP - 2025 Apr 7 TI - Increased vision impairment reports linked to semaglutide: analysis of FDA adverse event data. PG - 203 LID - 10.1186/s12916-025-04031-z [doi] LID - 203 AB - BACKGROUND: Semaglutide, a GLP-1 receptor agonist widely prescribed for type 2 diabetes and obesity, has recently raised concerns about its ocular safety. This study aimed to investigate the association between semaglutide use and vision impairment using data from the FDA Adverse Event Reporting System (FAERS). METHODS: We conducted an analysis of FAERS data, comparing reports of vision impairment associated with semaglutide to those associated with other antidiabetic and weight loss medications. The main outcome measure was the reporting odds ratio (rOR) for vision impairment linked to semaglutide use compared to other medications. RESULTS: Semaglutide showed significantly higher reporting of vision impairment compared to other GLP-1 receptor agonists (rOR 1.95, 95% CI 1.75-2.17, p < 0.0001), DPP-4 inhibitors (rOR 2.46, 95% CI 2.12-2.86, p < 0.0001), SGLT2 inhibitors (rOR 3.89, 95% CI 3.35-4.51, p < 0.0001), and metformin (rOR 2.23, 95% CI 1.90-2.62, p < 0.0001). Similar findings were observed when compared to phentermine (rOR 1.57, 95% CI 1.07-2.31, p = 0.026) and orlistat (rOR 3.77, 95% CI 2.96-4.81, p < 0.0001). Topiramate was the sole exception, showing higher vision impairment reporting than semaglutide (rOR 0.30, 95% CI 0.20-0.45, p < 0.0001). CONCLUSIONS: These findings suggest a potentially elevated risk of vision impairment with semaglutide use compared to other diabetes and weight loss medications, warranting further investigation and vigilant post-marketing surveillance. Future studies should assess the clinical impact of this potential increased risk on an absolute scale to better inform treatment decisions. CI - (c) 2025. The Author(s). FAU - Massy, Marine AU - Massy M AUID- ORCID: 0009-0006-4282-8609 AD - Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Rosenbuhlgasse 25, Bern, CH-3010, Switzerland. AD - Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland. AD - Department of Biomedical Research, University of Bern, Bern, Switzerland. FAU - Marti, Stefanie AU - Marti S AUID- ORCID: 0000-0001-8237-6965 AD - Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Rosenbuhlgasse 25, Bern, CH-3010, Switzerland. FAU - Hammer, Helly AU - Hammer H AD - Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Rosenbuhlgasse 25, Bern, CH-3010, Switzerland. FAU - Hoepner, Robert AU - Hoepner R AUID- ORCID: 0000-0002-0115-7021 AD - Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Rosenbuhlgasse 25, Bern, CH-3010, Switzerland. robert.hoepner@insel.ch. LA - eng PT - Journal Article DEP - 20250407 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - United States/epidemiology MH - *Glucagon-Like Peptides/adverse effects MH - United States Food and Drug Administration MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - *Vision Disorders/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - Female MH - Male MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11974072 OTO - NOTNLM OT - Diabetes OT - Obesity OT - Semaglutide OT - Vision impairment COIS- Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Massy M reports no competing interests. Marti S reports no competing interests. Hammer H received research support and travel grants within the last 5 years from Biogen, Merck, Roche & Bristol Myers Squibb, Teva, Johnson&Johnson, Novartis. All not related to that work. Hoepner R received speaker/advisor honorary from Merck, Novartis, Roche, Biogen, Alexion, Sanofi, Janssen, Bristol-Myers Squibb, Teva/Mepha and Almirall. He received research support within the last 5 years from Roche, Merck, Sanofi, Biogen, Chiesi, and Bristol-Myers Squibb. He also received research grants from the Swiss MS Society, the SITEM Insel Support Fund and is a member of the Advisory Board of the Swiss and International MS Society. He also serves as deputy editor in chief for Journal of Central Nervous System disease and is part of the ECTRIMS Young Investigator Committee. EDAT- 2025/04/07 02:02 MHDA- 2025/04/07 02:03 PMCR- 2025/04/07 CRDT- 2025/04/06 23:14 PHST- 2024/08/22 00:00 [received] PHST- 2025/03/21 00:00 [accepted] PHST- 2025/04/07 02:03 [medline] PHST- 2025/04/07 02:02 [pubmed] PHST- 2025/04/06 23:14 [entrez] PHST- 2025/04/07 00:00 [pmc-release] AID - 10.1186/s12916-025-04031-z [pii] AID - 4031 [pii] AID - 10.1186/s12916-025-04031-z [doi] PST - epublish SO - BMC Med. 2025 Apr 7;23(1):203. doi: 10.1186/s12916-025-04031-z. PMID- 40184508 OWN - NLM STAT- MEDLINE DCOM- 20250404 LR - 20260620 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 8 IP - 3 DP - 2025 May TI - Tirzepatide Versus Semaglutide on Weight Loss in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis of Direct Comparative Studies. PG - e70045 LID - 10.1002/edm2.70045 [doi] LID - e70045 AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as an efficacious treatment for type 2 diabetes mellitus (T2DM) and have demonstrated substantial weight loss effects. This systematic review compares two prevalent GLP-1RAs, tirzepatide and semaglutide, with their weight loss effects and rates of adverse events (AEs). METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), a systematic search was performed in PubMed, Embase and Cochrane Library for direct comparative studies between tirzepatide and semaglutide. A meta-analysis was conducted via a random-effects model to analyse the differences in weight loss outcomes between study cohorts. RESULTS: Four studies, with 28,827 patients (14,870 tirzepatide/13,928 semaglutide), mean age of 55.7 years (52.0 to 63.7) and mean follow-up of 35.9 weeks (23.6 to 44.6), were included in this study. Mean weight change across four studies for tirzepatide and semaglutide was -11.4% (-15.3% to -8.27%) and -7.3% (-8.3% to -6.08%), respectively. The meta-analysis supports these findings with a mean difference of -4.84 kg (95% CI: -6.21 to -3.47), favouring tirzepatide. The most common AEs were minor and moderate-severity gastrointestinal (GI) AEs. CONCLUSION: Current literature supports tirzepatide demonstrating a higher impact on weight loss than semaglutide, with both demonstrating high rates of minimal- to moderate-severity AEs. Further research with comparative head-to-head trials will better elucidate these weight loss effects and safety profiles. CI - (c) 2025 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Wen, Jimmy AU - Wen J AUID- ORCID: 0009-0007-5412-8551 AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Syed, Burhaan AU - Syed B AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Nadora, Denise AU - Nadora D AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - How-Volkman, Christiane AU - How-Volkman C AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Bernstein, Ethan AU - Bernstein E AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Truong, Alina AU - Truong A AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Akhtar, Muzammil AU - Akhtar M AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Razick, Adam AU - Razick A AD - University of California, Los Angeles, Los Angeles, California, USA. FAU - Puglisi, Jose AU - Puglisi J AD - California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Frezza, Eldo AU - Frezza E AD - California Northstate University College of Medicine, Elk Grove, California, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - *Tirzepatide/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11970626 OTO - NOTNLM OT - diabetes OT - meta-analysis OT - semaglutide OT - tirzepatide OT - weight loss COIS- The authors declare no conflicts of interest. EDAT- 2025/04/04 18:25 MHDA- 2025/04/04 18:26 PMCR- 2025/04/04 CRDT- 2025/04/04 15:02 PHST- 2025/02/15 00:00 [revised] PHST- 2024/10/24 00:00 [received] PHST- 2025/03/06 00:00 [accepted] PHST- 2025/04/04 18:26 [medline] PHST- 2025/04/04 18:25 [pubmed] PHST- 2025/04/04 15:02 [entrez] PHST- 2025/04/04 00:00 [pmc-release] AID - EDM270045 [pii] AID - 10.1002/edm2.70045 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2025 May;8(3):e70045. doi: 10.1002/edm2.70045. PMID- 40183412 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260820 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Population-level impact of semaglutide 2.4 mg in patients with obesity or overweight and cardiovascular disease: A modelling study based on the SELECT trial. PG - 3442-3452 LID - 10.1111/dom.16370 [doi] AB - AIM: To estimate the impact of semaglutide 2.4 mg treatment on the risk of major adverse cardiovascular events (MACE) in adults with overweight/obesity in the United States based on the SELECT trial of patients with atherosclerotic cardiovascular disease. MATERIALS AND METHODS: Using 2023 census projections and National Health and Nutrition Examination Survey data, we developed Markov population-based predictive models for US adults meeting SELECT inclusion criteria and, separately, for adults eligible for semaglutide 2.4 mg for its MACE risk reduction indication. The 10-year rate of recurrent MACE and deaths was estimated based on the Secondary Manifestations of ARTerial disease 2 risk calculator and estimated semaglutide 2.4 mg treatment effect as per the SELECT MACE hazard ratio. RESULTS: Of 6 164 019 US adults meeting the SELECT criteria, 2 523 218 (40.9%) are estimated to have >/=1 new MACE in the next 10 years with no additional intervention. Semaglutide 2.4 mg may prevent 496 400 events, a 16% relative reduction. An estimated 2 103 630 deaths are predicted over the next 10 years, of which 332 597 deaths (any cause, 16% relative reduction) could be avoided with semaglutide 2.4 mg. Among the estimated 22 653 158 meeting the MACE risk reduction FDA label criteria, 42.7% could experience >/=1 new MACE; treatment could prevent 1 934 493 MACE and 1 231 295 deaths (16% relative reduction for both). CONCLUSION: Four in 10 individuals in the United States meeting the SELECT criteria are estimated to experience a recurrent CV event without additional intervention. Semaglutide 2.4 mg can potentially prevent between half a million and up to 2 million MACE over the next 10 years in the population meeting SELECT and MACE risk reduction eligibility. PLAIN LANGUAGE SUMMARY: What is the context and purpose of this research study? More than 7 in 10 US adults have overweight or obesity, which increases the risk of heart disease. Semaglutide is a medication used to treat type 2 diabetes and obesity. A clinical study called SELECT found that semaglutide reduces the risk of heart attack, stroke, or death by 20% in adults with overweight or obesity and heart disease. What was done? Our research estimated how many people in the United States would meet the criteria for participation in SELECT, how many heart disease events they might have with regular medical care over the next 10 years, and how many could be avoided with semaglutide 2.4 mg treatment in addition to regular medical care. We also estimated how many people would still be alive if they were treated with semaglutide. We estimated the same information for all people eligible for treatment with semaglutide based on the US Food and Drug Administration (FDA) indication of semaglutide 2.4 mg in patients with heart disease. These estimations were based on a large survey of US adults. What were the main results? We found that over 6 million people would meet the SELECT study criteria. Of these, 41% are estimated to have at least 1 new heart disease event in the next 10 years. If treated with semaglutide 2.4 mg, nearly 500 000 heart disease events and more than 300 000 deaths could be avoided. More than 22 million adults would qualify for semaglutide 2.4 mg, according to the FDA indication. If all of these people were treated with semaglutide 2.4 mg, nearly 2 million heart disease events and more than 1 million deaths might be prevented. What is the originality and relevance of this study? Treatment with semaglutide 2.4 mg can reduce the risk of new heart disease events and death in patients with existing heart disease, showing a substantial impact of semaglutide treatment in a real-world setting in the United States. Our study used different analyses to add to the existing research about reducing the risk of heart disease in people with overweight or obesity. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Nanna, Michael G AU - Nanna MG AUID- ORCID: 0000-0001-5745-1636 AD - Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Doan, Quan V AU - Doan QV AUID- ORCID: 0000-0003-1170-1120 AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Fabricatore, Anthony AU - Fabricatore A AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Faurby, Mads AU - Faurby M AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Henry, Alasdair D AU - Henry AD AUID- ORCID: 0009-0006-2122-8620 AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Houshmand-Oeregaard, Azadeh AU - Houshmand-Oeregaard A AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Levine, Alina AU - Levine A AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Navar, Ann Marie AU - Navar AM AUID- ORCID: 0000-0002-6197-9860 AD - Departments of Internal Medicine and Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas, USA. FAU - Scassellati Sforzolini, Thomas AU - Scassellati Sforzolini T AD - Genesis Research Group, Hoboken, New Jersey, USA. FAU - Toliver, Joshua C AU - Toliver JC AUID- ORCID: 0000-0002-9159-2587 AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. LA - eng GR - K76 AG088428/AG/NIA NIH HHS/United States GR - P30 AG021342/AG/NIA NIH HHS/United States GR - Novo Nordisk/ PT - Journal Article DEP - 20250404 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Female MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/prevention & control/epidemiology/etiology/complications/mortality MH - *Obesity/complications/drug therapy MH - Adult MH - *Overweight/complications/drug therapy MH - United States/epidemiology MH - Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Markov Chains MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12046440 OTO - NOTNLM OT - United States OT - cardiovascular disease OT - cardiovascular risk OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - overweight OT - semaglutide COIS- MGN is a consultant for Merck, Novo Nordisk and HeartFlow, Inc. He reports current research support from the American College of Cardiology Foundation supported by the George F. and Ann Harris Bellows Foundation, the Patient-Centered Outcomes Research Institute and the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342). AMN reports funding for research to her institution from Esperion and Amgen, and honoraria and consulting fees from Amgen, Eli Lilly, Esperion, Janssen, Merck, NewAmsterdam, Novo Nordisk, Novartis, Pfizer and Silence Therapeutics. Her spouse receives research funding to his institution from Amgen and Esperion, and consulting from Janssen and Amgen. MF, JCT, AF, ASH are employees and shareholders of Novo Nordisk Inc. ADH, TSS and AL are employed by Genesis Research Group, a consulting company that received funding from Novo Nordisk to carry out this research. QVD was employed by Genesis Research Group at the time the research was conducted. EDAT- 2025/04/04 12:29 MHDA- 2025/05/03 22:26 PMCR- 2025/05/02 CRDT- 2025/04/04 07:42 PHST- 2025/03/14 00:00 [revised] PHST- 2024/12/12 00:00 [received] PHST- 2025/03/14 00:00 [accepted] PHST- 2025/05/03 22:26 [medline] PHST- 2025/04/04 12:29 [pubmed] PHST- 2025/04/04 07:42 [entrez] PHST- 2025/05/02 00:00 [pmc-release] AID - DOM16370 [pii] AID - 10.1111/dom.16370 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jun;27(6):3442-3452. doi: 10.1111/dom.16370. Epub 2025 Apr 4. PMID- 40183385 OWN - NLM STAT- MEDLINE DCOM- 20250624 LR - 20260127 IS - 1724-6016 (Electronic) IS - 1120-6721 (Linking) VI - 35 IP - 4 DP - 2025 Jul TI - Non arteritic ischemic optic neuropathy in a patient taking semaglutide: Is there a relation? A case report and a review of the literature. PG - NP10-NP15 LID - 10.1177/11206721251331655 [doi] AB - IntroductionThe glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as Semaglutide, have revolutionized the treatment of type 2 diabetes mellitus and obesity.Case desciptionThe aim of the present study was to report a case of Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) occurring in a diabetic patient taking Semaglutide and to review the literature in order to find a possible relation between the ophthalmological event and the drug intake.DiscussionAlthough the clinical trials of Semaglutide did not report any significant increase in the risk of NAION, a recent retrospective cohort study suggested a possible association between NAION and GLP-1 RAs. After this publication, the association between NAION and Semaglutide became an hot topic and several studies were published, presenting conflicting results.Conclusion and ImportanceAlbeit the association between the use of GLP-1 RAs and NAION, to date, remain controversial, clinicians and ophthalmologists should be aware of such possible association to analyze for each patient the risk-benefit ratio. FAU - Maceroni, Martina AU - Maceroni M AUID- ORCID: 0000-0002-3754-7486 AD - Istituto di Oftalmologia, Universita Cattolica del Sacro Cuore, 00168 Roma, Italia. RINGGOLD: 96983 AD - UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Roma, Italia. FAU - Sasso, Paola AU - Sasso P AD - UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Roma, Italia. FAU - Giarletti, Matteo AU - Giarletti M AD - UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Roma, Italia. FAU - Bruno, Valentina AU - Bruno V AD - UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Roma, Italia. FAU - Minnella, Angelo Maria AU - Minnella AM AD - Istituto di Oftalmologia, Universita Cattolica del Sacro Cuore, 00168 Roma, Italia. RINGGOLD: 96983 AD - UOC Oculistica, Fondazione Policlinico Universitario A. Gemelli - IRCCS, 00168 Roma, Italia. LA - eng PT - Case Reports PT - Journal Article PT - Review DEP - 20250404 PL - United States TA - Eur J Ophthalmol JT - European journal of ophthalmology JID - 9110772 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - Visual Acuity MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) OT - case report NAION OT - non-artehritic anterior ischemic optic neuropathy (NAION) OT - semaglutide COIS- Conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/04/04 12:30 MHDA- 2025/06/24 13:14 CRDT- 2025/04/04 07:33 PHST- 2025/06/24 13:14 [medline] PHST- 2025/04/04 12:30 [pubmed] PHST- 2025/04/04 07:33 [entrez] AID - 10.1177/11206721251331655 [doi] PST - ppublish SO - Eur J Ophthalmol. 2025 Jul;35(4):NP10-NP15. doi: 10.1177/11206721251331655. Epub 2025 Apr 4. PMID- 40182628 OWN - NLM STAT- MEDLINE DCOM- 20250404 LR - 20250604 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - A meta-analysis on the risk of esophageal cancer in type 2 diabetes patients treated with GLP-1 receptor agonists. PG - 1532587 LID - 10.3389/fendo.2025.1532587 [doi] LID - 1532587 AB - OBJECTIVE: To evaluate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) treatment and the risk of esophageal cancer in adults with type 2 diabetes mellitus (T2DM) or obesity through a comprehensive meta-analysis. METHODS: A systematic computerized searches and collection of eligible randomized controlled trials (RCTs) was performed to compare the risk of esophageal cancer between GLP-1 RA and control agents. The bias risks and quality of the studies were evaluated, and a meta-analysis was conducted using Stata 18.0 and R 4.0.2 statistical software. RESULTS: The meta-analysis included data from six studies involving 13,391 participants. The pooled relative risk (RR) of esophageal cancer in patients using GLP-1 RAs compared to control agents was 0.46 (95% CI 0.13-1.59; p=0.725; I(2)=0%). Subgroup analyses stratified by age groups, intervention durations, BMI categories, and indications for T2DM or obesity treatment more often indicated no association between GLP-1 RAs use and increased risk of esophageal cancer. CONCLUSIONS: GLP-1 RAs did not increase the incidence of esophageal neoplasms, and there were not probably significant within-class differences in T2DM or obesity treatment. This finding supports the safety of GLP-1 RAs as a therapeutic option for the clinical management of T2DM. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024543945. CI - Copyright (c) 2025 Wu, Zeng, Liu, Teng, Zhou, Guo, Jiang and Xu. FAU - Wu, Qi AU - Wu Q AD - Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. AD - Precision Pathology Diagnosis for Serious Diseases Key Laboratory of LuZhou, Luzhou, Sichuan, China. AD - Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao SAR, China. FAU - Zeng, Yan AU - Zeng Y AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. AD - Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao SAR, China. FAU - Liu, Yong AU - Liu Y AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. AD - Department of Intensive Care Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, China. AD - Department of Intensive Care Unit, Wangcang People's Hospital, Guangyuan, China. FAU - Teng, Fangyuan AU - Teng F AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. FAU - Zhou, Tiejun AU - Zhou T AD - Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Precision Pathology Diagnosis for Serious Diseases Key Laboratory of LuZhou, Luzhou, Sichuan, China. FAU - Guo, Man AU - Guo M AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. FAU - Jiang, Zongzhe AU - Jiang Z AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. FAU - Xu, Yong AU - Xu Y AD - Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. AD - Metabolic Vascular Disease Key Laboratory of Sichuan Province, and Sichuan-Chongqing Joint Key Laboratory of Metabolic Vascular Diseases, Luzhou, Sichuan, China. AD - Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao SAR, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250320 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Esophageal Neoplasms/epidemiology/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Obesity/drug therapy/complications MH - Risk Factors MH - Randomized Controlled Trials as Topic PMC - PMC11966957 OTO - NOTNLM OT - esophageal cancer OT - glucagon-like peptide-1 receptor agonist OT - meta-analysis OT - semaglutide OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2025/04/04 06:26 MHDA- 2025/04/04 06:27 PMCR- 2025/01/01 CRDT- 2025/04/04 05:13 PHST- 2024/11/26 00:00 [received] PHST- 2025/02/28 00:00 [accepted] PHST- 2025/04/04 06:27 [medline] PHST- 2025/04/04 06:26 [pubmed] PHST- 2025/04/04 05:13 [entrez] PHST- 2025/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2025.1532587 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Mar 20;16:1532587. doi: 10.3389/fendo.2025.1532587. eCollection 2025. PMID- 40169145 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 405 IP - 10489 DP - 2025 May 3 TI - Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial. PG - 1580-1593 LID - S0140-6736(25)00509-4 [pii] LID - 10.1016/S0140-6736(25)00509-4 [doi] AB - BACKGROUND: Peripheral artery disease is a highly morbid type of atherosclerotic vascular disease involving the legs and is estimated to affect over 230 million individuals globally. Few therapies improve functional capacity and health-related quality of life in people with lower limb peripheral artery disease. We aimed to evaluate whether semaglutide improves function as measured by walking ability as well as symptoms, quality of life, and outcomes in people with peripheral artery disease and type 2 diabetes. METHODS: STRIDE was a double-blind, randomised, placebo-controlled trial done at 112 outpatient clinical trial sites in 20 countries in North America, Asia, and Europe. Participants were aged 18 years and older, with type 2 diabetes and peripheral artery disease with intermittent claudication (Fontaine stage IIa, able to walk >200 m) and an ankle-brachial index of less than or equal to 0.90 or toe-brachial index of less than or equal to 0.70. Participants were randomly assigned (1:1) using an interactive web response system to receive subcutaneous semaglutide 1.0 mg once per week for 52 weeks or placebo. The primary endpoint was the ratio to baseline of the maximum walking distance at week 52 measured on a constant load treadmill in the full analysis set. Safety was evaluated in the safety analysis set. This trial is registered with ClinicalTrials.gov, NCT04560998 and is now completed. FINDINGS: From Oct 1, 2020, to July 12, 2024, 1363 patients were screened for eligibility, of whom 792 were randomly assigned to semaglutide (n=396) or placebo (n=396). 195 (25%) participants were female and 597 (75%) were male. Median age was 68.0 years (IQR 61.0-73.0). The estimated median ratio to baseline in maximum walking distance at week 52 was significantly greater in the semaglutide group than the placebo group (1.21 [IQR 0.95-1.55] vs 1.08 [0.86-1.36]; estimated treatment ratio 1.13 [95% CI 1.06-1.21]; p=0.0004). Six serious adverse events in five (1%) participants in the semaglutide group and nine serious adverse events in six (2%) participants in the placebo group were possibly or probably treatment related, with the most frequent being serious gastrointestinal events (two events reports by two [1%] in the semaglutide group and five events reported by three [1%] in the placebo group). There were no treatment-related deaths. INTERPRETATION: Semaglutide increased walking distance in patients with symptomatic peripheral artery disease and type 2 diabetes. Research implications include the need for future studies to further elucidate mechanisms of benefit and to assess the efficacy and safety in patients with peripheral artery disease who do not have type 2 diabetes. FUNDING: Novo Nordisk. CI - Copyright (c) 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Bonaca, Marc P AU - Bonaca MP AD - CPC Clinical Research, Cardiovascular Division, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: marc.bonaca@cpcmed.org. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk, Soborg, Denmark. FAU - Houlind, Kim AU - Houlind K AD - Department of Vascular Surgery, Lillebaelt Hospital, Kolding, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. FAU - Ludvik, Bernhard AU - Ludvik B AD - 1st Medical Department and Karl Landsteiner Institute for Obesity and Metabolic Disorders, Landstrasse Clinic, Vienna, Austria. FAU - Nordanstig, Joakim AU - Nordanstig J AD - Institute of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Ramesh, Chethana Kalmady AU - Ramesh CK AD - Novo Nordisk India, Bangalore, India. FAU - Rasouli, Neda AU - Rasouli N AD - Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, Aurora, CO, USA. FAU - Sourij, Harald AU - Sourij H AD - Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. FAU - Videmark, Alex AU - Videmark A AD - Novo Nordisk, Soborg, Denmark. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiovascular Surgery, St Michael's Hospital, University of Toronto, Toronto, ON, Canada. CN - STRIDE Trial Investigators LA - eng SI - ClinicalTrials.gov/NCT04560998 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250329 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet. 2025 May 3;405(10489):1556-1557. doi: 10.1016/S0140-6736(25)00574-4. PMID: 40169146 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Ankle Brachial Index MH - *Diabetes Mellitus, Type 2/complications/drug therapy/physiopathology MH - Double-Blind Method MH - Intermittent Claudication/drug therapy/etiology MH - *Peripheral Arterial Disease/drug therapy/complications/physiopathology MH - Quality of Life MH - Treatment Outcome MH - *Walking MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declaration of interests MPB is the Executive Director of the Colorado Prevention Center, a non-profit academic research organisation affiliated with the University of Colorado, that receives or has received research grant or consulting funding between August, 2021 and the present from: Abbott Laboratories, Agios Pharmaceuticals, Alexion Pharma, Alnylam Pharmaceuticals, Amgen, Angionetics, Anthos Therapeutics, Array BioPharma, AstraZeneca and Affiliates, Atentiv, Audentes Therapeutics, Bayer and Affiliates, Bristol Myers Squibb, Cambrian Biopharma, Cardiol Therapeutics, CellResearch, Cleerly, Cook Regentec, CSL Behring, Eidos Therapeutics, EP Trading, Epizon Pharma, Esperion Therapeutics, Everly Well, Exicon Consulting, Faraday Pharmaceuticals, Foresee Pharmaceuticals, Fortress Biotech, HDL Therapeutics, HeartFlow, Hummingbird Bioscience, Insmed, Ionis Pharmaceuticals, Janssen and Affiliates, Kowa Research Institute, Lexicon Pharmaceuticals, Medimmune, Merck and Affiliates, Nectero Medical, Novartis Pharmaceuticals, Novo Nordisk, Osiris Therapeutics, Pfizer, PhaseBio Pharmaceuticals, Prairie Education and Research Cooperative, Prothena Biosciences, Regeneron Pharmaceuticals, Regio Biosciences, Sanofi-Aventis Group, Silence Therapeutics, Smith & Nephew, Stealth BioTherapeutics, VarmX, and Virta Health Corporation. A-MC is an employee of and owns shares in Novo Nordisk. KH has received payment or honoraria, along with travel support, to give a presentation at a workshop organised by LeMaitre. BL has received consulting fees, payment, or honoraria from Amgen, Bayer, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; has received travel support from Novo Nordisk, with unpaid roles as a National Leader for the Novo Nordisk ESSENCE trial, a National Leader for the Eli Lilly Triumph-Outcome Study, and an advisor for an advisory board for the Austrian Obesity Society. JN has received payment or honoraria from Novo Nordisk; has received travel support from Philips Medical and Abbott; has served on advisory boards for AstraZeneca, Novo Nordisk, and iThera Medical; and has a research grant from the Swedish Heart and Lung Foundation 2021-26, with unpaid roles as President of the Swedish Society for Vascular Surgery and the Swedish Councillor for the European Society for Vascular Surgery 2020-23. CKR is an employee of and owns shares in Novo Nordisk. NR has served on advisory boards for Eli Lilly and Novo Nordisk, and has received research grants from Eli Lilly, Novo Nordisk, and Soma Scan. HS has received payment or honoraria from Amarin, Amgen, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, and Novo Nordisk; has received travel support from Boehringer Ingelheim, Daiichi Sankyo, and Novo Nordisk; and has served on advisory boards for Eli Lilly and Novo Nordisk, with unpaid roles as a board member of the Austrian Diabetes Association. AV is an employee of Novo Nordisk. SV has received payment or honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Humber River Health, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management, Sanofi, and Sun Pharmaceuticals; has served on advisory boards for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, and Sanofi; and his institution has received research grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, and Sanofi. EDAT- 2025/04/02 00:25 MHDA- 2025/05/04 15:35 CRDT- 2025/04/01 19:53 PHST- 2025/02/27 00:00 [received] PHST- 2025/03/13 00:00 [revised] PHST- 2025/03/13 00:00 [accepted] PHST- 2025/05/04 15:35 [medline] PHST- 2025/04/02 00:25 [pubmed] PHST- 2025/04/01 19:53 [entrez] AID - S0140-6736(25)00509-4 [pii] AID - 10.1016/S0140-6736(25)00509-4 [doi] PST - ppublish SO - Lancet. 2025 May 3;405(10489):1580-1593. doi: 10.1016/S0140-6736(25)00509-4. Epub 2025 Mar 29. PMID- 40163257 OWN - NLM STAT- MEDLINE DCOM- 20250613 LR - 20261010 IS - 1573-7322 (Electronic) IS - 1382-4147 (Linking) VI - 30 IP - 4 DP - 2025 Jul TI - Semaglutide in heart failure and atherosclerotic cardiovascular disease: the current state-of-the-art. PG - 801-816 LID - 10.1007/s10741-025-10506-1 [doi] AB - Cardiovascular disease mortality rates, which had steadily declined over decades, are now plateauing or reversing due to the global rise in type 2 diabetes mellitus (T2DM) and obesity. These cardiometabolic conditions contribute significantly to atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease. Among emerging pharmacological treatments, glucagon-like peptide-1 receptor agonists, particularly semaglutide, have shown benefits beyond diabetes and obesity management, including cardioprotective and renoprotective effects. This state-of-the-art review comprehensively analyzes current evidence from clinical trials, identifies critical insights, and outlines research directions regarding semaglutide use in HF, ASCVD, and diabetic nephropathy. In ASCVD, semaglutide has demonstrated significant reductions in major adverse cardiovascular events, supported by findings from meta-analyses of trials in patients with T2DM and the SELECT trial for patients without T2DM. In a prespecified analysis of the SELECT trial, semaglutide demonstrated significant reductions in cardiovascular mortality and HF hospitalizations for patients with HF and ASCVD. In HF with preserved ejection fraction and mildly reduced ejection fraction, semaglutide improved symptoms, physical function, natriuretic peptide levels, echocardiographic parameters, and HF hospitalizations, as shown in the STEP-HFpEF program and a pooled analysis of trials. Furthermore, evidence from the FLOW trial underscores semaglutide's renal and cardiovascular benefits in diabetic nephropathy, irrespective of body mass index. While these findings suggest semaglutide's efficacy in cardiorenal diseases, gaps in evidence remain, including the need for event-driven trials in HF populations without ASCVD and irrespective of obesity. Future research should address these gaps, which could potentially update guideline recommendations. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Theodorakis, Nikolaos AU - Theodorakis N AD - Department of Cardiology & Heart Failure Outpatient Clinic, Sismanogleio-Amalia Fleming General Hospital, 14, 25th Martiou Str., 15127, Melissia, Greece. m.nikolaou@flemig-hospital.gr. AD - School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527, Athens, Greece. m.nikolaou@flemig-hospital.gr. FAU - Kreouzi, Magdalini AU - Kreouzi M AD - Department of Internal Medicine, Sismanogleio-Amalia Fleming General Hospital, 14, 25th Martiou Str., 15127, Melissia, Greece. FAU - Nikolaou, Maria AU - Nikolaou M AD - Department of Cardiology & Heart Failure Outpatient Clinic, Sismanogleio-Amalia Fleming General Hospital, 14, 25th Martiou Str., 15127, Melissia, Greece. LA - eng PT - Journal Article PT - Review DEP - 20250331 PL - United States TA - Heart Fail Rev JT - Heart failure reviews JID - 9612481 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Heart Failure/drug therapy/physiopathology MH - *Atherosclerosis/drug therapy MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular disease OT - Coronary artery disease OT - Diabetic nephropathy OT - Glucagon-like peptide-1 receptor agonists OT - Heart failure OT - Semaglutide COIS- Declarations. Competing interests: The authors declare no competing interests. EDAT- 2025/03/31 21:17 MHDA- 2025/06/13 12:32 CRDT- 2025/03/31 11:56 PHST- 2025/03/06 00:00 [accepted] PHST- 2025/06/13 12:32 [medline] PHST- 2025/03/31 21:17 [pubmed] PHST- 2025/03/31 11:56 [entrez] AID - 10.1007/s10741-025-10506-1 [pii] AID - 10.1007/s10741-025-10506-1 [doi] PST - ppublish SO - Heart Fail Rev. 2025 Jul;30(4):801-816. doi: 10.1007/s10741-025-10506-1. Epub 2025 Mar 31. PMID- 40162642 OWN - NLM STAT- MEDLINE DCOM- 20250528 LR - 20260202 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 392 IP - 20 DP - 2025 May 29 TI - Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes. PG - 2001-2012 LID - 10.1056/NEJMoa2501006 [doi] AB - BACKGROUND: The cardiovascular safety of oral semaglutide, a glucagon-like peptide 1 receptor agonist, has been established in persons with type 2 diabetes and high cardiovascular risk. An assessment of the cardiovascular efficacy of oral semaglutide in persons with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both is needed. METHODS: In this double-blind, placebo-controlled, event-driven, superiority trial, we randomly assigned participants who were 50 years of age or older, had type 2 diabetes with a glycated hemoglobin level of 6.5 to 10.0%, and had known atherosclerotic cardiovascular disease, chronic kidney disease, or both to receive either once-daily oral semaglutide (maximal dose, 14 mg) or placebo, in addition to standard care. The primary outcome was major adverse cardiovascular events (a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke), assessed in a time-to-first-event analysis. The confirmatory secondary outcomes included major kidney disease events (a five-point composite outcome). RESULTS: Among the 9650 participants who had undergone randomization, the mean (+/-SD) follow-up was 47.5+/-10.9 months, and the median follow-up was 49.5 months. A primary-outcome event occurred in 579 of the 4825 participants (12.0%; incidence, 3.1 events per 100 person-years) in the oral semaglutide group, as compared with 668 of the 4825 participants (13.8%; incidence, 3.7 events per 100 person-years) in the placebo group (hazard ratio, 0.86; 95% confidence interval, 0.77 to 0.96; P = 0.006). The results for the confirmatory secondary outcomes did not differ significantly between the two groups. The incidence of serious adverse events was 47.9% in the oral semaglutide group and 50.3% in the placebo group; the incidence of gastrointestinal disorders was 5.0% and 4.4%, respectively. CONCLUSIONS: Among persons with type 2 diabetes and atherosclerotic cardiovascular disease, chronic kidney disease, or both, the use of oral semaglutide was associated with a significantly lower risk of major adverse cardiovascular events than placebo, without an increase in the incidence of serious adverse events. (Funded by Novo Nordisk; SOUL ClinicalTrials.gov number, NCT03914326.). CI - Copyright (c) 2025 Massachusetts Medical Society. FAU - McGuire, Darren K AU - McGuire DK AD - University of Texas Southwestern Medical Center, Dallas. AD - Parkland Health System, Dallas. FAU - Marx, Nikolaus AU - Marx N AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, Rheinisch-Westfalische Technische Hochschule Aachen University, University Hospital Aachen, Aachen, Germany. FAU - Mulvagh, Sharon L AU - Mulvagh SL AD - Department of Medicine, Division of Cardiology, Dalhousie University, Halifax, NS, Canada. FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Sciences, University College London, London. FAU - Inzucchi, Silvio E AU - Inzucchi SE AD - Section of Endocrinology, Yale University School of Medicine, New Haven, CT. FAU - Pop-Busui, Rodica AU - Pop-Busui R AD - Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland. FAU - Mann, Johannes F E AU - Mann JFE AD - Kuratorium fur Heimdialyse Kidney Center, Munich, Germany. AD - Friedrich Alexander University of Erlangen, Erlangen, Germany. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle. FAU - Poulter, Neil R AU - Poulter NR AD - Imperial Clinical Trials Unit, Imperial College London, London. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk, Soborg, Denmark. FAU - Ripa, Maria Sejersten AU - Ripa MS AD - Novo Nordisk, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk, Soborg, Denmark. FAU - Brown-Frandsen, Kirstine AU - Brown-Frandsen K AD - Novo Nordisk, Soborg, Denmark. FAU - Bain, Stephen C AU - Bain SC AD - Swansea University Medical School, Swansea, United Kingdom. FAU - Cavender, Matthew A AU - Cavender MA AUID- ORCID: 0000-0002-4466-4760 AD - University of North Carolina School of Medicine, Chapel Hill. FAU - Gislum, Mette AU - Gislum M AD - Novo Nordisk, Soborg, Denmark. FAU - David, Jens-Peter AU - David JP AD - Novo Nordisk, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill. CN - SOUL Study Group LA - eng SI - ClinicalTrials.gov/NCT03914326 GR - n/a/Novo Nordisk/ PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250329 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - N Engl J Med. 2025 Aug 14;393(7):724-725. doi: 10.1056/NEJMc2508958. PMID: 40802952 CIN - N Engl J Med. 2025 Aug 14;393(7):725. doi: 10.1056/NEJMc2508958. PMID: 40802953 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Atherosclerosis/complications/drug therapy MH - *Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/blood/complications/drug therapy MH - Double-Blind Method MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Follow-Up Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide FIR - Perez Manghi, F IR - Perez Manghi F FIR - Pozzi, J M IR - Pozzi JM FIR - Lorenzatti, A J IR - Lorenzatti AJ FIR - Visco, V E IR - Visco VE FIR - Piskorz, D IR - Piskorz D FIR - Nardone, L IR - Nardone L FIR - Chahin, M I IR - Chahin MI FIR - Bustamante Labarta, M IR - Bustamante Labarta M FIR - Luquez, C IR - Luquez C FIR - MacKinnon, I J IR - MacKinnon IJ FIR - Pieber, T IR - Pieber T FIR - Prager, R IR - Prager R FIR - Fliesser-Gorzer, E IR - Fliesser-Gorzer E FIR - Ebenbichler, C IR - Ebenbichler C FIR - Fasching, P IR - Fasching P FIR - Mathieu, C IR - Mathieu C FIR - De Block, C IR - De Block C FIR - Duyck, F IR - Duyck F FIR - Heyns, E IR - Heyns E FIR - Lapauw, B IR - Lapauw B FIR - Vercammen, C IR - Vercammen C FIR - Turatti, L A A IR - Turatti LAA FIR - Franco, D R IR - Franco DR FIR - Rea, R R IR - Rea RR FIR - Kurtz Lisboa, H R IR - Kurtz Lisboa HR FIR - Salles, J E IR - Salles JE FIR - Saraiva, J F K IR - Saraiva JFK FIR - Fonseca, A G T IR - Fonseca AGT FIR - Vidotti, M H IR - Vidotti MH FIR - Leite, S O IR - Leite SO FIR - Aggarwal, N IR - Aggarwal N FIR - Bajaj, H IR - Bajaj H FIR - Schlosser, R IR - Schlosser R FIR - Noronha, L IR - Noronha L FIR - Pedersen, S IR - Pedersen S FIR - Peterson, S IR - Peterson S FIR - Tellier, G IR - Tellier G FIR - Weisnagel, J IR - Weisnagel J FIR - Beca, S IR - Beca S FIR - Alasaad, H IR - Alasaad H FIR - Punthakee, Z IR - Punthakee Z FIR - Mancini, J G B IR - Mancini JGB FIR - Tytus, R IR - Tytus R FIR - Ransom, T P P IR - Ransom TPP FIR - Connelly, K IR - Connelly K FIR - Husain, M IR - Husain M FIR - Tsoukas, M IR - Tsoukas M FIR - Ji, L IR - Ji L FIR - Liu, J IR - Liu J FIR - Yuan, G IR - Yuan G FIR - Ye, X IR - Ye X FIR - Dong, X IR - Dong X FIR - Bian, F IR - Bian F FIR - Angelo, A A IR - Angelo AA FIR - Sanchez Garcia, R IR - Sanchez Garcia R FIR - Hernandez Erazo, I D IR - Hernandez Erazo ID FIR - Hernandez Ruiz, E A IR - Hernandez Ruiz EA FIR - Gomez Mesa, J E IR - Gomez Mesa JE FIR - Canecki Varzic, S IR - Canecki Varzic S FIR - Vucak Loncar, J IR - Vucak Loncar J FIR - Simegi-Djekic, V IR - Simegi-Djekic V FIR - Ticinovic Kurir, T IR - Ticinovic Kurir T FIR - Tusek, S IR - Tusek S FIR - Rahelic, D IR - Rahelic D FIR - Marusic, S IR - Marusic S FIR - Kruljac, I IR - Kruljac I FIR - Fabris Vitkovic, D IR - Fabris Vitkovic D FIR - Oznerova, M IR - Oznerova M FIR - Vrkoc, J IR - Vrkoc J FIR - Dolezalova, B IR - Dolezalova B FIR - Haluzik, M IR - Haluzik M FIR - Jankovec, Z IR - Jankovec Z FIR - Olsovsky, J IR - Olsovsky J FIR - Zemanova, J IR - Zemanova J FIR - Kyselova, P IR - Kyselova P FIR - Smahelova, A IR - Smahelova A FIR - Gregersen, S IR - Gregersen S FIR - Olsen, A-M Z IR - Olsen AZ FIR - Mikkelsen, D IR - Mikkelsen D FIR - Egstrup, K IR - Egstrup K FIR - Pedersen-Bjergaard, U IR - Pedersen-Bjergaard U FIR - Potier, L IR - Potier L FIR - Borot, S IR - Borot S FIR - Gaborit, B IR - Gaborit B FIR - Monier, A IR - Monier A FIR - Pradignac, A IR - Pradignac A FIR - Verges, B IR - Verges B FIR - Larroumet, A IR - Larroumet A FIR - Thuan, J-F IR - Thuan JF FIR - Birkenfeld, A IR - Birkenfeld A FIR - Kellerer, M IR - Kellerer M FIR - Ludemann, J IR - Ludemann J FIR - Esser, M IR - Esser M FIR - Kahrmann, G IR - Kahrmann G FIR - Kempe, H-P IR - Kempe HP FIR - Koch, T IR - Koch T FIR - Axthelm, C IR - Axthelm C FIR - Paschen, B IR - Paschen B FIR - Rose, L IR - Rose L FIR - Schaum, T IR - Schaum T FIR - Schulze, J IR - Schulze J FIR - Staudenmeyer, A IR - Staudenmeyer A FIR - Wenzl-Bauer, V IR - Wenzl-Bauer V FIR - Ma, R C W IR - Ma RCW FIR - Thomas, N IR - Thomas N FIR - Reddy, V S IR - Reddy VS FIR - Rao, P V IR - Rao PV FIR - Sahay, R IR - Sahay R FIR - Singh, J IR - Singh J FIR - Prakash, A IR - Prakash A FIR - Tandon, N IR - Tandon N FIR - Marwah, T IR - Marwah T FIR - Chaudhury, T IR - Chaudhury T FIR - Ghosh, S IR - Ghosh S FIR - Kanungo, A K IR - Kanungo AK FIR - Mittal, N IR - Mittal N FIR - Jacob, J J IR - Jacob JJ FIR - Chadha, M IR - Chadha M FIR - Chawla, M IR - Chawla M FIR - Bhagwat, N M IR - Bhagwat NM FIR - Jain, S M IR - Jain SM FIR - Thulaseedharan, N K IR - Thulaseedharan NK FIR - Girithara, G IR - Girithara G FIR - Desai, A IR - Desai A FIR - Sharma, S K IR - Sharma SK FIR - Murthy, S IR - Murthy S FIR - Sethi, B K IR - Sethi BK FIR - Kadam, Y IR - Kadam Y FIR - Kesavadev, J IR - Kesavadev J FIR - Daxini, B IR - Daxini B FIR - Chawla, R IR - Chawla R FIR - Gopalakrishnan, U A IR - Gopalakrishnan UA FIR - Baruah, M P IR - Baruah MP FIR - Reddy, S P IR - Reddy SP FIR - Suryanarayana, K M IR - Suryanarayana KM FIR - Singh, K P IR - Singh KP FIR - Saboo, B IR - Saboo B FIR - Aharon-Hananel, G IR - Aharon-Hananel G FIR - Hochberg, I IR - Hochberg I FIR - Sofer, Y IR - Sofer Y FIR - Tirosh, A IR - Tirosh A FIR - Shimon, I IR - Shimon I FIR - Vishlitzky, V IR - Vishlitzky V FIR - Bashkin, A IR - Bashkin A FIR - Tsur, A IR - Tsur A FIR - Shechter, M IR - Shechter M FIR - Andreozzi, F IR - Andreozzi F FIR - Setola, E IR - Setola E FIR - Consoli, A IR - Consoli A FIR - Lupoli, R IR - Lupoli R FIR - Genovese, S IR - Genovese S FIR - Maranghi, M IR - Maranghi M FIR - Lauro, D IR - Lauro D FIR - Citarrella, R IR - Citarrella R FIR - Fadini, G P IR - Fadini GP FIR - Murdolo, G IR - Murdolo G FIR - Di Carlo, A IR - Di Carlo A FIR - Giorgino, F IR - Giorgino F FIR - Buscemi, S IR - Buscemi S FIR - Hanaoka, K IR - Hanaoka K FIR - Osonoi, T IR - Osonoi T FIR - Ohashi, H IR - Ohashi H FIR - Ezaki, H IR - Ezaki H FIR - Yuki, H IR - Yuki H FIR - Kiyosue, A IR - Kiyosue A FIR - Hata, Y IR - Hata Y FIR - Sugawara, M IR - Sugawara M FIR - Domae, H IR - Domae H FIR - Iwata, H IR - Iwata H FIR - Nishida, Y IR - Nishida Y FIR - Igarashi, M IR - Igarashi M FIR - Fujino, S IR - Fujino S FIR - Oiwa, A IR - Oiwa A FIR - Oh, F IR - Oh F FIR - Sueyoshi, A IR - Sueyoshi A FIR - Murakami, T IR - Murakami T FIR - Tanaka, M IR - Tanaka M FIR - Idogaki, A IR - Idogaki A FIR - Onaka, H IR - Onaka H FIR - Mizote, I IR - Mizote I FIR - Doi, M IR - Doi M FIR - Ebisui, O IR - Ebisui O FIR - Tanabe, M IR - Tanabe M FIR - Natsuaki, M IR - Natsuaki M FIR - Jinnouchi, H IR - Jinnouchi H FIR - Nakamura, S IR - Nakamura S FIR - Wan Mohamed, W M I IR - Wan Mohamed WMI FIR - Yahaya, N IR - Yahaya N FIR - Ratnasingam, J IR - Ratnasingam J FIR - Ong, T K IR - Ong TK FIR - Mohamad, M IR - Mohamad M FIR - Yusoff Azmi Merican, N S IR - Yusoff Azmi Merican NS FIR - Abdul Ghani, R IR - Abdul Ghani R FIR - Adam, N L IR - Adam NL FIR - Fam, T L IR - Fam TL FIR - Tan, F H S IR - Tan FHS FIR - Morales Villegas, E C IR - Morales Villegas EC FIR - Gonzalez-Galvez, G IR - Gonzalez-Galvez G FIR - Espinoza Peralta, D IR - Espinoza Peralta D FIR - Medina Pech, C E IR - Medina Pech CE FIR - Arechavaleta-Granell, M IR - Arechavaleta-Granell M FIR - Garcia Ulloa, A C IR - Garcia Ulloa AC FIR - Laviada Molina, H A IR - Laviada Molina HA FIR - Banda Elizondo, R G IR - Banda Elizondo RG FIR - Garza Ruiz, J A IR - Garza Ruiz JA FIR - Garcia Cantu, E A IR - Garcia Cantu EA FIR - van Bemmel, T IR - van Bemmel T FIR - de Valk, H W IR - de Valk HW FIR - Kooy, A IR - Kooy A FIR - Lieverse, L IR - Lieverse L FIR - Landewe-Cleuren, S A N T IR - Landewe-Cleuren SANT FIR - Hoogenberg, K IR - Hoogenberg K FIR - van Raalte, D IR - van Raalte D FIR - Jebbink, M IR - Jebbink M FIR - Oldenburg-Ligtenberg, C IR - Oldenburg-Ligtenberg C FIR - Abbink-Zandbergen, E IR - Abbink-Zandbergen E FIR - Mihai, B IR - Mihai B FIR - Crisan, C IR - Crisan C FIR - Filip, I IR - Filip I FIR - Busegeanu, M M IR - Busegeanu MM FIR - Roman, G IR - Roman G FIR - Mot, A C IR - Mot AC FIR - Nicoara, A IR - Nicoara A FIR - Anghel, V IR - Anghel V FIR - Pletea, N N IR - Pletea NN FIR - Suciu, M IR - Suciu M FIR - Strajer, D IR - Strajer D FIR - Cernea, S IR - Cernea S FIR - Zilov, A IR - Zilov A FIR - Kobalava, Z IR - Kobalava Z FIR - Ruyatkina, L A IR - Ruyatkina LA FIR - Suplotova, L A IR - Suplotova LA FIR - Sergeeva-Kondrachenko, M Y IR - Sergeeva-Kondrachenko MY FIR - Yanovskaya, M E IR - Yanovskaya ME FIR - Kargina, L IR - Kargina L FIR - Ignatyeva, A IR - Ignatyeva A FIR - Astamirova, K IR - Astamirova K FIR - Zalevskaya, A IR - Zalevskaya A FIR - Zagrebelnaya, O IR - Zagrebelnaya O FIR - Frolova, E V IR - Frolova EV FIR - Peskov, A B IR - Peskov AB FIR - Mishchenko, O IR - Mishchenko O FIR - Otroshchenko, O IR - Otroshchenko O FIR - Gaysina, L IR - Gaysina L FIR - Shabelnikova, O Y IR - Shabelnikova OY FIR - Saprina, T V IR - Saprina TV FIR - Lysenko, T A IR - Lysenko TA FIR - Kunitsyna, M IR - Kunitsyna M FIR - Zyangirova, S T IR - Zyangirova ST FIR - Lalic, N IR - Lalic N FIR - Lalic, K IR - Lalic K FIR - Beljic Zivkovic, T IR - Beljic Zivkovic T FIR - Kikovic, S IR - Kikovic S FIR - Djukic, A IR - Djukic A FIR - Pesic, M IR - Pesic M FIR - Dimic, D IR - Dimic D FIR - Stokic, E IR - Stokic E FIR - Mitrovic, M IR - Mitrovic M FIR - Polovina, S IR - Polovina S FIR - Djordjevic, M IR - Djordjevic M FIR - Sosovec, D IR - Sosovec D FIR - Pella, D IR - Pella D FIR - Donicova, V IR - Donicova V FIR - Hanackova Prasekova, S IR - Hanackova Prasekova S FIR - Koleny, D IR - Koleny D FIR - Culak, J IR - Culak J FIR - Cerna, K IR - Cerna K FIR - Hundza, V IR - Hundza V FIR - Gmitrov, J IR - Gmitrov J FIR - Lacka, J IR - Lacka J FIR - Plasil, R IR - Plasil R FIR - Amod, A IR - Amod A FIR - Bacus, H B IR - Bacus HB FIR - Bhorat, Q E IR - Bhorat QE FIR - Joshi, P IR - Joshi P FIR - Lakha, D R IR - Lakha DR FIR - Makan, V IR - Makan V FIR - Ntusi, N IR - Ntusi N FIR - Padayachee, T IR - Padayachee T FIR - Seeber, M E IR - Seeber ME FIR - Pillay, D IR - Pillay D FIR - Joshi, M IR - Joshi M FIR - Mayet, L IR - Mayet L FIR - Lee, J IR - Lee J FIR - Kim, S G IR - Kim SG FIR - Min, K W IR - Min KW FIR - Kang, E S IR - Kang ES FIR - Lee, W J IR - Lee WJ FIR - Choi, S H IR - Choi SH FIR - Lee, C B IR - Lee CB FIR - Lopez Suarez, A IR - Lopez Suarez A FIR - Garcia Ordonez, M A IR - Garcia Ordonez MA FIR - Garcia Quintana, A IR - Garcia Quintana A FIR - Mazon Ramos, P IR - Mazon Ramos P FIR - Cigarran, S IR - Cigarran S FIR - Barrios, C IR - Barrios C FIR - Soto Gonzalez, A IR - Soto Gonzalez A FIR - Jodar, E IR - Jodar E FIR - Delgado Lista, J IR - Delgado Lista J FIR - Morales Portillo, C IR - Morales Portillo C FIR - Montalban Carrasco, C IR - Montalban Carrasco C FIR - Gorgojo Martinez, J J IR - Gorgojo Martinez JJ FIR - Tinahones, F IR - Tinahones F FIR - Tu, S-T IR - Tu ST FIR - Huang, C-N IR - Huang CN FIR - Chen, S-T IR - Chen ST FIR - Buranasupkajorn, P IR - Buranasupkajorn P FIR - Sriwijitkamol, A IR - Sriwijitkamol A FIR - Buranapin, S IR - Buranapin S FIR - Suwanagool, A IR - Suwanagool A FIR - Tantiwong, P IR - Tantiwong P FIR - Boonyavarakul, A IR - Boonyavarakul A FIR - Benjachareonwong, S IR - Benjachareonwong S FIR - Leelawattana, R IR - Leelawattana R FIR - Vathesatogkit, P IR - Vathesatogkit P FIR - Deerochanawong, C IR - Deerochanawong C FIR - Sonmez, Y A IR - Sonmez YA FIR - Oguz, A IR - Oguz A FIR - Tabak, O IR - Tabak O FIR - Kocak, M IR - Kocak M FIR - Sariakcali, B IR - Sariakcali B FIR - Bayram, F IR - Bayram F FIR - Guclu, M IR - Guclu M FIR - Gurkan, E IR - Gurkan E FIR - Kebapci, N IR - Kebapci N FIR - Comlekci, A IR - Comlekci A FIR - Acibucu, F IR - Acibucu F FIR - Ahbab, S IR - Ahbab S FIR - Bilen, H IR - Bilen H FIR - Mankovskyy, B IR - Mankovskyy B FIR - Urbanovych, A IR - Urbanovych A FIR - Kuskalo, P IR - Kuskalo P FIR - Bondarets, I IR - Bondarets I FIR - Petrosyan, O IR - Petrosyan O FIR - Pashkovska, N IR - Pashkovska N FIR - Oleksyk, O IR - Oleksyk O FIR - Kaydashev, I IR - Kaydashev I FIR - Maliar, K IR - Maliar K FIR - Myshanych, G IR - Myshanych G FIR - Bain, S C IR - Bain SC FIR - Black, D IR - Black D FIR - Johnston, P IR - Johnston P FIR - Dang, C IR - Dang C FIR - Dhatariya, K IR - Dhatariya K FIR - English, P IR - English P FIR - Field, B IR - Field B FIR - Grimmer, P IR - Grimmer P FIR - Gunstone, A IR - Gunstone A FIR - Ray, S IR - Ray S FIR - Tatovic, D IR - Tatovic D FIR - Kernohan, A IR - Kernohan A FIR - Lindsay, R IR - Lindsay R FIR - Mcknight, J A IR - Mcknight JA FIR - Park, A IR - Park A FIR - Patel, D IR - Patel D FIR - Philip, S IR - Philip S FIR - Randeva, H IR - Randeva H FIR - Sathyapalan, T IR - Sathyapalan T FIR - Turner, W IR - Turner W FIR - Wyatt, N IR - Wyatt N FIR - Allison, D C IR - Allison DC FIR - Awasty, V IR - Awasty V FIR - Ayele, E IR - Ayele E FIR - Bajaj, C IR - Bajaj C FIR - Budoff, M J IR - Budoff MJ FIR - Busch, R IR - Busch R FIR - Buse, J B IR - Buse JB FIR - Casaubon, L IR - Casaubon L FIR - Austin, P A IR - Austin PA FIR - Chaidarun, S S IR - Chaidarun SS FIR - Chochinov, R H IR - Chochinov RH FIR - Chu, J W IR - Chu JW FIR - Daboul, N Y IR - Daboul NY FIR - Dang, A H IR - Dang AH FIR - Desouza, C V IR - Desouza CV FIR - Everhart, B G IR - Everhart BG FIR - Arambasick, J IR - Arambasick J FIR - Fink, R I IR - Fink RI FIR - Fitz-Patrick, D IR - Fitz-Patrick D FIR - Fogarty, C M IR - Fogarty CM FIR - Gilbert, M P IR - Gilbert MP FIR - Johnson, D M IR - Johnson DM FIR - Krishnasamy, S S IR - Krishnasamy SS FIR - Lane, W S IR - Lane WS FIR - Nakhle, S N IR - Nakhle SN FIR - Levenson, D IR - Levenson D FIR - O'Donnell, P IR - O'Donnell P FIR - Weiss, D IR - Weiss D FIR - Risser, J A IR - Risser JA FIR - Wierum, C IR - Wierum C FIR - Sivalingam, K IR - Sivalingam K FIR - Gupta, D IR - Gupta D FIR - Philis-Tsimikas, A IR - Philis-Tsimikas A FIR - Pratley, R E IR - Pratley RE FIR - Mirza, L IR - Mirza L FIR - Snyder, B IR - Snyder B FIR - Rasouli, N IR - Rasouli N FIR - Porter, J IR - Porter J FIR - Ledesma, G N IR - Ledesma GN FIR - Powell, T IR - Powell T FIR - Tandron, I J IR - Tandron IJ FIR - Lingvay, I IR - Lingvay I FIR - Reed Iii, J C H IR - Reed Iii JCH FIR - Patel, M B IR - Patel MB FIR - Lovre, D IR - Lovre D FIR - Chaicha-Brom, T IR - Chaicha-Brom T FIR - Jantzi, C IR - Jantzi C FIR - Brautigam, D IR - Brautigam D FIR - Bao, S IR - Bao S FIR - Mbogua, C N IR - Mbogua CN FIR - Zemel, L R IR - Zemel LR FIR - Hasan, S IR - Hasan S FIR - Rosenstock, J IR - Rosenstock J FIR - Tran, H IR - Tran H FIR - Poremba, J IR - Poremba J FIR - Baker, C IR - Baker C FIR - Prier, K IR - Prier K FIR - Chilka, S IR - Chilka S FIR - Agaiby, J M IR - Agaiby JM FIR - Condit, J IR - Condit J FIR - Eagerton, D C IR - Eagerton DC FIR - Huffman, D IR - Huffman D FIR - Cornett, G M IR - Cornett GM FIR - Traylor, H IR - Traylor H FIR - Brinson, C IR - Brinson C FIR - Bays, H E IR - Bays HE FIR - Jerkins, T IR - Jerkins T FIR - Nicol, P R IR - Nicol PR FIR - Siddiqui, I A IR - Siddiqui IA FIR - Hewitt, M IR - Hewitt M FIR - Odugbesan, A O IR - Odugbesan AO FIR - Lillestol, M J IR - Lillestol MJ FIR - Thrasher, J R IR - Thrasher JR FIR - Gandy, W H Jr IR - Gandy WH Jr FIR - Pant, N IR - Pant N FIR - Nagelberg, S IR - Nagelberg S FIR - Cannon, K IR - Cannon K FIR - Anderson, M W IR - Anderson MW FIR - Bhargava, A IR - Bhargava A FIR - Doshi, A IR - Doshi A FIR - Jardula, M F IR - Jardula MF FIR - Montero, M IR - Montero M FIR - Purighalla, R S IR - Purighalla RS FIR - Warren, M L IR - Warren ML FIR - Harris, K IR - Harris K FIR - Jackson, R A IR - Jackson RA FIR - Khaira, A S IR - Khaira AS FIR - Gonzalez-Orozco, L IR - Gonzalez-Orozco L FIR - Gagianas, P J IR - Gagianas PJ FIR - Pantalone, K IR - Pantalone K FIR - Murray, A V IR - Murray AV FIR - McGuire, Darren K IR - McGuire DK FIR - Buse, John B IR - Buse JB FIR - Deanfield, John IR - Deanfield J FIR - Mann, Johannes F E IR - Mann JFE FIR - Poulter, Neil IR - Poulter N FIR - Marx, Nikolaus IR - Marx N FIR - Pop-Busui, Rodica IR - Pop-Busui R FIR - Emerson, Scott IR - Emerson S FIR - Mulvagh, Sharon L IR - Mulvagh SL FIR - Inzucchi, Silvio E IR - Inzucchi SE FIR - Brown-Frandsen, Kirstine IR - Brown-Frandsen K FIR - Hovingh, G Kees IR - Hovingh GK FIR - Engelmann, Mads D IR - Engelmann MD FIR - Billeskov Schelde, Peter IR - Billeskov Schelde P FIR - Rasmussen, Mads Frederik IR - Rasmussen MF FIR - Bain, Stephen C IR - Bain SC FIR - Cavender, Matthew A IR - Cavender MA FIR - Jhund Singh, Pardeep IR - Jhund Singh P FIR - Lorenzatti, Alberto IR - Lorenzatti A FIR - Pieber, Thomas IR - Pieber T FIR - Mathieu, Chantal IR - Mathieu C FIR - Kerr Saraiva, Jose Francisco IR - Kerr Saraiva JF FIR - Rea, Rosangela IR - Rea R FIR - Bajaj, Harpreet IR - Bajaj H FIR - Connelly, Kim IR - Connelly K FIR - Ji, Linong IR - Ji L FIR - Sanchez Garcia, Robinson IR - Sanchez Garcia R FIR - Canecki-Varzic, Silvija IR - Canecki-Varzic S FIR - Haluzik, Martin IR - Haluzik M FIR - Gregersen, Soren IR - Gregersen S FIR - Kellerer, Monika IR - Kellerer M FIR - Birkenfeld, Andreas IR - Birkenfeld A FIR - Chow, Francis Chun Chung IR - Chow FCC FIR - Mohan, V IR - Mohan V FIR - Nadu, Tamil IR - Nadu T FIR - Shechter, Michael IR - Shechter M FIR - Consoli, Agostino IR - Consoli A FIR - Watada, Hirotaka IR - Watada H FIR - Abdul Ghani, Rohana IR - Abdul Ghani R FIR - Arechavaleta Granell, Rosario IR - Arechavaleta Granell R FIR - van Bemmel, Thomas IR - van Bemmel T FIR - Roman, Gabriela IR - Roman G FIR - Zilov, Alexey IR - Zilov A FIR - Kobalava, Zhanna IR - Kobalava Z FIR - Lalic, Nebojsa IR - Lalic N FIR - Cerna, Katarina IR - Cerna K FIR - Amod, Aslam IR - Amod A FIR - Kim, Sin Gon IR - Kim SG FIR - Gorgojo Martinez, Juan Jose IR - Gorgojo Martinez JJ FIR - Mazon Ramos, Pilar IR - Mazon Ramos P FIR - Tu, Shih-Te IR - Tu ST FIR - Deerochanawong, Chaicharn IR - Deerochanawong C FIR - Oguz, Aytekin IR - Oguz A FIR - Mankovskyy, Boris IR - Mankovskyy B FIR - DeSouza, Cyrus IR - DeSouza C FIR - Allison, Dale IR - Allison D FIR - de Lemos, James A IR - de Lemos JA FIR - Saver, Jeffrey L IR - Saver JL FIR - Wexler, Deborah J IR - Wexler DJ FIR - Fried, Linda IR - Fried L FIR - Floege, Jurgen IR - Floege J FIR - Goodman, Shaun IR - Goodman S FIR - Ferris, Frederick L 3rd IR - Ferris FL 3rd FIR - Gillen, Daniel L IR - Gillen DL FIR - Nuno, Michelle IR - Nuno M FIR - Roe, Matthew T IR - Roe MT FIR - Wiviott, Stephen IR - Wiviott S FIR - Ducrocq, Gregory IR - Ducrocq G FIR - Povsic, Thomas IR - Povsic T FIR - Rodriguez, Fatima IR - Rodriguez F FIR - Mehta, Rajendra IR - Mehta R FIR - Kong, David IR - Kong D FIR - Kontos, Christopher IR - Kontos C FIR - Phillips, Lawrence IR - Phillips L FIR - Leonardi, Sergio IR - Leonardi S FIR - Becker, Kyra J IR - Becker KJ FIR - Jordan, J Dedrick IR - Jordan JD FIR - Sung, Gene IR - Sung G FIR - Dombrowski, Keith IR - Dombrowski K FIR - Fisher, Deborah IR - Fisher D FIR - Gellad, Ziad IR - Gellad Z FIR - Wilder, Julius IR - Wilder J FIR - Leiman, David IR - Leiman D FIR - Dwyer, Jamie IR - Dwyer J FIR - Middleton, John IR - Middleton J FIR - Umanath, Kausik IR - Umanath K FIR - Chang, Tara IR - Chang T FIR - Diamond, Matthew J IR - Diamond MJ EDAT- 2025/03/31 21:17 MHDA- 2025/05/28 18:27 CRDT- 2025/03/31 07:53 PHST- 2025/05/28 18:27 [medline] PHST- 2025/03/31 21:17 [pubmed] PHST- 2025/03/31 07:53 [entrez] AID - 10.1056/NEJMoa2501006 [doi] PST - ppublish SO - N Engl J Med. 2025 May 29;392(20):2001-2012. doi: 10.1056/NEJMoa2501006. Epub 2025 Mar 29. PMID- 40156846 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 48 IP - 5 DP - 2025 May 1 TI - Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral Glucagon-Like Peptide 1 Receptor Agonists in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Trials. PG - 846-859 LID - 10.2337/dc25-0241 [doi] AB - BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce the incidence of major adverse cardiovascular events (MACE) in type 2 diabetes (T2D), although whether benefits extend to both subcutaneous and oral formulations remains unclear. PURPOSE: In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinetics sufficient to provide 24-h activity) GLP-1RA in T2D. DATA SOURCES: A systematic review of PubMed was conducted (to 7 February 2025). STUDY SELECTION: Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with >/=500 individuals with T2D were included. DATA EXTRACTION: A random-effects model was used to estimate hazard ratios (HRs) for MACE, its components, all-cause mortality, hospitalization for heart failure (HHF), a composite kidney outcome (kidney failure [kidney replacement therapy or persistent estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2], sustained >/=50% eGFR decline or nearest equivalent, or kidney-related death), worsening kidney function, and safety outcomes. DATA SYNTHESIS: Across 10 trials (n = 71,351), long-acting GLP-1RA reduced incidence rate of MACE by 14% (HR 0.86 [95% CI 0.81, 0.90]; I2 = 27.6%), HHF by 14% (0.86 [0.79, 0.93]; I2 = 2.1%), and the composite kidney outcome by 17% (0.83 [0.75, 0.92]; I2 = 20.4%) and all-cause mortality by 12% (0.88 [0.82, 0.93]; I2 = 17.5%). A consistent 14% reduction was seen for all MACE components. There was no significant heterogeneity by GLP-1RA administration route (subcutaneous vs. oral). There were no increased risks of severe hypoglycemia, retinopathy, or pancreatic events. LIMITATIONS: Trial-level meta-analyses preclude detailed subgroup analyses and may introduce ecological bias. CONCLUSIONS: As a group, long-acting GLP-1RA, including both injectable and oral formulations, reduce incidence of MACE, HHF, and kidney events and all-cause mortality in T2D. CI - (c) 2025 by the American Diabetes Association. FAU - Lee, Matthew M Y AU - Lee MMY AUID- ORCID: 0000-0001-9213-2067 AD - School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, U.K. FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, U.K. FAU - Pop-Busui, Rodica AU - Pop-Busui R AUID- ORCID: 0000-0002-2042-1350 AD - Department of Medicine, Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, Portland, OR. FAU - Deanfield, John AU - Deanfield J AUID- ORCID: 0000-0001-8806-6052 AD - Institute of Cardiovascular Sciences, University College London, London, U.K. FAU - Emerson, Scott S AU - Emerson SS AUID- ORCID: 0000-0002-2695-0165 AD - Department of Biostatistics, University of Washington, Seattle, WA. FAU - Inzucchi, Silvio E AU - Inzucchi SE AUID- ORCID: 0000-0003-1254-6636 AD - Section of Endocrinology, Yale School of Medicine, New Haven, CT. FAU - Mann, Johannes F E AU - Mann JFE AUID- ORCID: 0000-0002-3154-5332 AD - KfH Kidney Center, Munich, Germany. AD - Friedrich Alexander University, Erlangen, Germany. FAU - Marx, Nikolaus AU - Marx N AUID- ORCID: 0000-0001-6141-634X AD - Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Aachen, Germany. FAU - Mulvagh, Sharon L AU - Mulvagh SL AUID- ORCID: 0000-0002-7377-4053 AD - Division of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada. FAU - Poulter, Neil R AU - Poulter NR AUID- ORCID: 0000-0002-6292-997X AD - Imperial Clinical Trials Unit, Imperial College London, London, U.K. FAU - Badve, Sunil V AU - Badve SV AUID- ORCID: 0000-0003-2269-312X AD - St George Hospital, Sydney, New South Wales, Australia. AD - Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia. AD - Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia. FAU - Pratley, Richard E AU - Pratley RE AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, FL. FAU - Perkovic, Vlado AU - Perkovic V AUID- ORCID: 0000-0002-4257-7620 AD - Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia. AD - Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia. FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - University of North Carolina School of Medicine, Chapel Hill, NC. FAU - McGuire, Darren K AU - McGuire DK AUID- ORCID: 0000-0002-6412-7989 AD - University of Texas Southwestern Medical Center and Parkland Health, Dallas, TX. CN - SOUL Trial Investigators LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/mortality MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cardiovascular Diseases/mortality/epidemiology MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glucagon-Like Peptides/therapeutic use MH - Administration, Oral MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/03/30 23:01 MHDA- 2025/04/25 06:28 CRDT- 2025/03/29 14:32 PHST- 2025/01/29 00:00 [received] PHST- 2025/02/20 00:00 [accepted] PHST- 2025/04/25 06:28 [medline] PHST- 2025/03/30 23:01 [pubmed] PHST- 2025/03/29 14:32 [entrez] AID - 158048 [pii] AID - 10.2337/dc25-0241 [doi] PST - ppublish SO - Diabetes Care. 2025 May 1;48(5):846-859. doi: 10.2337/dc25-0241. PMID- 40156843 OWN - NLM STAT- MEDLINE DCOM- 20250609 LR - 20260307 IS - 1524-4539 (Electronic) IS - 0009-7322 (Print) IS - 0009-7322 (Linking) VI - 151 IP - 23 DP - 2025 Jun 10 TI - Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial. PG - 1639-1650 LID - 10.1161/CIRCULATIONAHA.125.074545 [doi] AB - BACKGROUND: Both GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter-2) inhibitors (SGLT2i) improve cardiovascular outcomes in people with type 2 diabetes and cardiovascular or chronic kidney disease. However, there are limited data about the effect of combining these agents on cardiovascular and safety outcomes. METHODS: The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo. As prespecified, participants were analyzed according to baseline use of SGLT2i (yes, n=2596; no, n=7054), and subsequently for any use of SGLT2i during the trial (yes, n=4718; no, n=4932). The primary outcome was time to first major adverse cardiovascular event, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Safety was evaluated by comparing the incidence of serious adverse events. RESULTS: Over a mean follow-up of 47.5+/-10.9 months, the risk of the primary outcome in the overall trial population was 14% lower for oral semaglutide versus placebo (hazard ratio, 0.86; 95% CI, 0.77-0.96). In those taking SGLT2i at baseline, there were 143 of 1296 (semaglutide) versus 158 of 1300 (placebo) primary outcome events (hazard ratio, 0.89; 95% CI, 0.71-1.11); and 436 of 3529 versus 510 of 3525, respectively, in participants not taking SGLT2i at baseline (hazard ratio, 0.84; 95% CI, 0.74-0.95; P-interaction, 0.66). An analysis of major adverse cardiovascular events by any in-trial SGLT2i use versus no use also showed no evidence of heterogeneity in the effects of oral semaglutide. The adverse event profiles of oral semaglutide with or without concomitant SGLT2i were similar. CONCLUSIONS: Oral semaglutide reduced major adverse cardiovascular event outcomes independently of concomitant SGLT2i treatment, and this combination appeared to be safe. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03914326. FAU - Marx, Nikolaus AU - Marx N AUID- ORCID: 0000-0001-6141-634X AD - Department of Internal Medicine I, Rheinisch-Westfalische Technische Hochschule Aachen University, University Hospital Aachen, Germany (N.M.). FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Sciences, University College London, United Kingdom (J.E.D.). FAU - Mann, Johannes F E AU - Mann JFE AD - Kuratorium fur Heimdialyse Kidney Center, Munich, Germany (J.F.E.M.). AD - Friedrich Alexander University of Erlangen, Germany (J.F.E.M.). FAU - Arechavaleta, Rosario AU - Arechavaleta R AD - Department of Endocrinology, Universidad Autonoma de Guadalajara, Jalisco, Mexico (R.A.). FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - School of Medicine, Swansea University, United Kingdom (S.C.B.). FAU - Bajaj, Harpreet S AU - Bajaj HS AUID- ORCID: 0000-0002-1461-1465 AD - LMC Diabetes and Endocrinology, Brampton, Canada (H.S.B.). FAU - Bayer Tanggaard, Katrine AU - Bayer Tanggaard K AD - Novo Nordisk A/S, Soborg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.). FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AUID- ORCID: 0000-0003-1407-9023 AD - Department of Diabetology, Endocrinology and Nephrology, University Hospital Tubingen, Germany (A.L.B.). AD - Institute for Diabetes Research and Metabolic Diseases, Helmholtz Munich, German Center for Diabetes Research (A.L.B.). FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - University of North Carolina School of Medicine, Chapel Hill (J.B.B.). FAU - Davicevic-Elez, Zaklina AU - Davicevic-Elez Z AD - Novo Nordisk A/S, Soborg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.). FAU - Desouza, Cyrus AU - Desouza C AUID- ORCID: 0000-0001-6660-0568 AD - Division of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha (C.D.). FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle (S.S.E.). FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk A/S, Soborg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.). FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk A/S, Soborg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.). FAU - Inzucchi, Silvio E AU - Inzucchi SE AUID- ORCID: 0000-0003-1254-6636 AD - Section of Endocrinology, Yale University School of Medicine, New Haven, CT (S.E.I.). FAU - Jhund, Pardeep S AU - Jhund PS AUID- ORCID: 0000-0003-4306-5317 AD - British Heart Foundation, Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, United Kingdom (P.S.J.). FAU - Mulvagh, Sharon L AU - Mulvagh SL AUID- ORCID: 0000-0002-7377-4053 AD - Department of Medicine, Division of Cardiology, Dalhousie University, Halifax, Nova Scotia, Canada (S.L.M.). FAU - Pop-Busui, Rodica AU - Pop-Busui R AUID- ORCID: 0000-0002-2042-1350 AD - Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health and Science University, Portland (R.P.-B.). FAU - Poulter, Neil R AU - Poulter NR AUID- ORCID: 0000-0002-6292-997X AD - Imperial Clinical Trials Unit, Imperial College London, United Kingdom (N.R.P.). FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark (K.B.-T., Z.D.-E., M.D.M.E., G.K.H., S.R.). FAU - Tu, Shih-Te AU - Tu ST AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Taiwan (S.-T.T.). FAU - McGuire, Darren K AU - McGuire DK AUID- ORCID: 0000-0002-6412-7989 AD - Clinic for Cardiology, Angiology, and Intensive Care Medicine, University of Texas Southwestern Medical Center, and Parkland Health and Hospital System, Dallas (D.K.M.). CN - SOUL Study Group LA - eng SI - ClinicalTrials.gov/NCT03914326 GR - P30 DK045735/DK/NIDDK NIH HHS/United States GR - U01 DK119083/DK/NIDDK NIH HHS/United States PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250329 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - *Cardiovascular Diseases/mortality/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/mortality MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/administration & dosage/adverse effects/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12144549 OTO - NOTNLM OT - cardiovascular diseases OT - cardiovascular system OT - diabetes mellitus, type 2 OT - glucagon-like peptide-1 receptor agonists OT - renal insufficiency, chronic OT - semaglutide OT - sodium-glucose transporter 2 inhibitors COIS- Dr Marx is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TRR 219; project ID, 322900939 [M03, M05]); has given lectures for Bayer, Boehringer Ingelheim, Sanofi-Aventis, MSD, BMS, AstraZeneca, Lilly, and Novo Nordisk; has received unrestricted research grants from Boehringer Ingelheim; and has served as an advisor for Bayer, Boehringer Ingelheim, Sanofi-Aventis, MSD, BMS, AstraZeneca, and Novo Nordisk. In addition, Dr Marx served in trial leadership for Boehringer Ingelheim and Novo Nordisk. Dr Marx declines all personal compensation from pharma or device companies. Dr Deanfield reports grants or contracts from 2022 to 2025 from Alzheimer's Research UK and from 2019 to 2022 from the British Heart Foundation. He received consulting fees/honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer. Dr Mann reports grants from Novo Nordisk, the European Union, and McMaster University, Hamilton, Canada; consulting fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; and honoraria from Novo Nordisk, AstraZeneca, Bayer, and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi, and Boehringer Ingelheim. He is an author for UpToDate and has a leadership role in the KDIGO group. Dr Arechavaleta has given lectures for Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, and Sanofi. She has received advisory board fees and honoraria for clinical trials from Novo Nordisk and Eli Lilly. Dr Bain reports grants and honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Menarini, and Novo Nordisk. He has provided expert advice to the All-Wales Medicines Strategy Group and the National Institute for Health and Care Excellence (United Kingdom). Dr Bajaj reports trial fees paid to his institution by Abbott, Amgen, Anji Pharmaceuticals, Arrowhead Pharmaceuticals, AstraZeneca, Biomea, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Ionis Pharmaceuticals, Kowa Pharmaceuticals, Novartis, Novo Nordisk, and Pfizer. Dr Tanggaard is an employee at Novo Nordisk. Dr Birkenfeld is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; GRK2816; BI1292/12-1; 10-1; 9-1) and the German Federal Ministry for Education and Research (01GI0925) through the German Center for Diabetes Research (DZD e.V.). Dr Birkenfeld has given lectures for Novo Nordisk and Daiichi Sankyo, has received unrestricted research grants from Boehringer Ingelheim and AstraZeneca, and has served as an advisor for Bayer and Novo Nordisk. In addition, Dr Birkenfeld served in trial leadership for Boehringer Ingelheim, Novo Nordisk, and Eli Lilly. Dr Birkenfeld declines all personal compensation from pharma or device companies. Dr Buse reports research support from Corcept, Dexcom, and Novo Nordisk; consulting fees from Altimmune, Antag, Amgen, ApStem, Aqua Medical, AstraZeneca, Boehringer Ingelheim, CeQur, Corcept Therapeutics, Dexcom, Eli Lilly, embecta, GentiBio, Glyscend, Insulet, Medtronic MiniMed, Mellitus Health, Metsera, Novo Nordisk, Pendulum Therapeutics, Praetego, Stability Health, Tandem, Terns Inc, Vertex, and Zealand; and stock options from Glyscend, Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, and Stability Health. Dr Davicevic-Elez is an employee of and holds shares in Novo Nordisk. Dr Desouza reports Novo Nordisk research grants (payments to institution) and has personally received consulting fees from Eli Lilly and consulting fees and support for attending meetings or travel from Novo Nordisk. Dr Emerson declares consulting fees from Novo Nordisk for steering committee participation and from Boehringer Ingelheim for consulting regarding veterinary congestive heart failure; received support for attending meetings or travel from Novo Nordisk for attendance at steering committee and scientific meetings; and declares participation on an advisory board for Novo Nordisk, AstraZeneca, Daiichi Sankyo, Vertex, Roche, GlaxoSmithKline, Lilly, Novartis, Bristol Myers, and Sanofi. Dr Engelmann is a full-time employee of Novo Nordisk and has stocks in the company. Dr Hovingh has received funding from the Klinkerpadfonds, paid to his former academic institute (Amsterdam UMC, The Netherlands). He is also an employee and shareholder of Novo Nordisk. Dr Inzucchi has served as a consultant or on advisory boards for Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, and Bayer. He has given lectures sponsored by AstraZeneca and Boehringer Ingelheim/Lilly. He declares royalties from McGraw Hill and Wolters Kluwer Health and support for attending meetings or travel from Novo Nordisk, AstraZeneca, Boehringer Ingelheim/Lilly, and Bayer. Dr Jhund reports speaker fees from AstraZeneca, Novartis, and ProAdWise Communications; advisory board fees from AstraZeneca; research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc, and Roche Diagnostics. Dr Jhund reports other financial interests, including as Director of GCTP Ltd. His employer, the University of Glasgow, has been remunerated for his time working on clinical trials by AstraZeneca, Novartis, Novo Nordisk, and Bayer AG. Dr Mulvagh has served as a consultant or on advisory boards for Novo Nordisk and Merck. Dr Pop-Busui received research grant support to her institutions from NIDDK, Breakthrough T1D (formerly JDRF), Bayer, Lexicon Pharmaceuticals, and Novo Nordisk, and consulting fees from Averitas Pharma, Biogen, Lexicon Pharmaceuticals, Nevro Inc, Novo Nordisk, and Roche Diagnostic; received support for attending meetings or travel from Roche; participated on an advisory board for Biogen/Reata; and is a member of the board of directors of the American Diabetes Association. Dr Poulter received financial support from several pharmaceutical companies that manufacture blood pressure-lowering, lipid-lowering, and glucose-lowering agents for consultancy fees, research projects, and staff and for arranging and speaking at educational meetings including Servier, Pfizer, AstraZeneca, Amgen, Sanofi, and Novo Nordisk. He holds no stocks or shares in any such companies. Dr Rasmussen is an employee and shareholder in Novo Nordisk. Dr Tu has given lectures for Novo Nordisk, Eli Lilly, AstraZeneca, Boehringer Ingelheim, and Sanofi; received advisory board fees from Novo Nordisk and Eli Lilly; and received honoraria for clinical trials from Novo Nordisk, Eli Lilly, and Boehringer Ingelheim. Dr McGuire has received consulting fees from Novo Nordisk, AstraZeneca, Pfizer, Altimmune, Ventyx Pharmaceuticals, Bayer, Lexicon, Applied Therapeutics, Intercept Pharmaceuticals, Esperion, Lilly USA, Boehringer Ingelheim, New Amsterdam, CSL Behring, Amgen, Neurotronics, Metsera, Kailera, and Alveus Pharma. EDAT- 2025/03/30 23:01 MHDA- 2025/06/09 18:28 PMCR- 2025/06/07 CRDT- 2025/03/29 14:32 PHST- 2025/06/09 18:28 [medline] PHST- 2025/03/30 23:01 [pubmed] PHST- 2025/03/29 14:32 [entrez] PHST- 2025/06/07 00:00 [pmc-release] AID - CIRCULATIONAHA-2025-074545 [pii] AID - 10.1161/CIRCULATIONAHA.125.074545 [doi] PST - ppublish SO - Circulation. 2025 Jun 10;151(23):1639-1650. doi: 10.1161/CIRCULATIONAHA.125.074545. Epub 2025 Mar 29. PMID- 40146102 OWN - NLM STAT- MEDLINE DCOM- 20250515 LR - 20260908 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 143 IP - 5 DP - 2025 May 1 TI - Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy Risk Among Patients With Diabetes. PG - 400-407 LID - 10.1001/jamaophthalmol.2025.0349 [doi] AB - IMPORTANCE: Recent studies have suggested an association between nonarteritic anterior ischemic optic neuropathy (NAION) with semaglutide usage. However, the limitations of those analyses warrant further investigation, given the frequency of use of these medications in people with and without diabetes. OBJECTIVE: To investigate the association between semaglutide use and the risk of NAION among patients with diabetes. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the TriNetX database between October 1, 2019, and December 31, 2023, to identify patients with diabetes with no history of NAION who were prescribed semaglutide. The semaglutide cohort was compared with a control group of randomly selected patients with diabetes who were prescribed non-glucagonlike peptide 1 (non-GLP-1) receptor agonist (RA) antidiabetic medications. The data analysis for this study was performed on September 1, 2024. EXPOSURES: Semaglutide history, identified using diagnostic codes. MAIN OUTCOMES AND MEASURES: Cumulative incidence and (HR) hazard ratio of NAION. RESULTS: A total of 3 344 205 patients with diabetes were included in this study. Regarding the diabetes cohort, a total of 174 584 patients with diabetes who received semaglutide (mean [SD] age, 58.3 [12.5] years; 90 427 female [51.8%]; 71 739 male [41.1%]) and 174 584 patients with diabetes who received non-GLP-1 RA medications (mean [SD] age, 58.2 [14.3] years; 90 475 female [51.82%]; 71 989 male [41.24%]) were recruited. Patients with diabetes taking semaglutide exhibited an absence of NAION risk at the 1-month (HR, 2.99; 95% CI, 0.31-28.75), 3-month (HR, 1.33; 95% CI, 0.30-5.93), 6-month (HR, 1.79; 95% CI, 0.60-5.35), and 1-year (HR, 1.94; 95% CI: 0.93-4.02) time points after the index date. However, those taking semaglutide were found to have an increased risk for NAION at the 2-year (HR, 2.39; 95% CI, 1.37-4.18), 3-year (HR, 2.44; 95% CI, 1.44-4.12), and 4-year (HR, 2.05; 95% CI, 1.26-3.34) time points from the index date. Increased risk for NAION was also noted in patients with diabetes and concomitant hypertension who were taking semaglutide (HR, 2.42; 95% CI, 1.19-4.92). An increased NAION risk was also observed among patients with diabetes who had a history of Ozempic (Novo Nordisk) use or stand-alone Ozempic (Novo Nordisk) prescription history. CONCLUSIONS AND RELEVANCE: Results of this cohort study suggest that semaglutide use was associated with an increased risk of NAION in patients with diabetes. However, the study's retrospective design presents limitations, as it can only infer associations rather than establish causality; further studies are needed. FAU - Hsu, Alan Y AU - Hsu AY AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. FAU - Kuo, Hou-Ting AU - Kuo HT AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - Department of General Medicine, China Medical University Hospital, Taichung, Taiwan. FAU - Wang, Yu-Hsun AU - Wang YH AD - Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. FAU - Lin, Chun-Ju AU - Lin CJ AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Optometry, Asia University, Taichung, Taiwan. FAU - Shao, Yi-Ching AU - Shao YC AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan. FAU - Chiang, Chun-Chi AU - Chiang CC AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Optometry, Asia University, Taichung, Taiwan. FAU - Hsia, Ning-Yi AU - Hsia NY AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Optometry, Asia University, Taichung, Taiwan. FAU - Lai, Chun-Ting AU - Lai CT AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Optometry, Asia University, Taichung, Taiwan. FAU - Tseng, Hsin AU - Tseng H AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. FAU - Wu, Bing-Qi AU - Wu BQ AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - Department of General Medicine, China Medical University Hospital, Taichung, Taiwan. FAU - Chen, Huan-Sheng AU - Chen HS AD - An-Shin Dialysis Center, Excelsior Renal Service Co Ltd, Taiwan Branch, Taichung, Taiwan. FAU - Tsai, Yi-Yu AU - Tsai YY AD - Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan. AD - School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan. AD - Department of Optometry, Asia University, Taichung, Taiwan. FAU - Hsu, Min-Yen AU - Hsu MY AD - Department of Ophthalmology, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - School of Medicine, Chung Shan Medical University, Taichung, Taiwan. FAU - Wei, James Cheng-Chung AU - Wei JC AD - Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan. AD - Institute of Medicine/Department of Nursing, Chung Shan Medical University, Taichung, Taiwan. AD - Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. AD - Office of Research and Development, Asia University, Taichung, Taiwan. LA - eng PT - Journal Article PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA Ophthalmol. 2025 May 1;143(5):408-409. doi: 10.1001/jamaophthalmol.2025.0350. PMID: 40146117 MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Female MH - Male MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced/diagnosis MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Incidence MH - Aged MH - Risk Factors MH - Retrospective Studies MH - *Diabetes Mellitus/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Databases, Factual MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11950975 COIS- Conflict of Interest Disclosures: None reported. EDAT- 2025/03/27 13:16 MHDA- 2025/05/15 12:36 PMCR- 2026/03/27 CRDT- 2025/03/27 11:32 PHST- 2025/05/15 12:36 [medline] PHST- 2025/03/27 13:16 [pubmed] PHST- 2025/03/27 11:32 [entrez] PHST- 2026/03/27 00:00 [pmc-release] AID - 2831924 [pii] AID - eoi250007 [pii] AID - 10.1001/jamaophthalmol.2025.0349 [doi] PST - ppublish SO - JAMA Ophthalmol. 2025 May 1;143(5):400-407. doi: 10.1001/jamaophthalmol.2025.0349. PMID- 40128152 OWN - NLM STAT- MEDLINE DCOM- 20250821 LR - 20260127 IS - 1534-6080 (Electronic) IS - 0041-1337 (Linking) VI - 109 IP - 9 DP - 2025 Sep 1 TI - Impact of Glucagon-like Peptide-1 Receptor Agonists on Metabolic Health in Liver Transplant Recipients. PG - e501-e507 LID - 10.1097/TP.0000000000005361 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), initially approved for the management of diabetes, have demonstrated a wide range of metabolic benefits. However, their benefit and safety profile in liver transplant (LT) recipients remain poorly defined. METHODS: This study retrospectively analyzed adults who had undergone LT and had concomitant type 2 diabetes mellitus. Thirty-eight post-LT recipients treated with GLP-1RA for type 2 diabetes mellitus were matched with patients treated with insulin therapy 1:1 using propensity scoring for age, sex, ethnicity, cause of cirrhosis, and immunosuppression. This matching aimed to assess the metabolic effects and safety profile of GLP-1RA after LT. RESULTS: The 2 groups were similar at baseline with regard to clinical characteristics, except that time from LT was greater in patients who were on GLP-1RA. Semaglutide was the most commonly used GLP-1RA. LT recipients who received GLP-1RA lost approximately 8% of body weight during 12 mo, whereas patients on insulin therapy gained approximately 10% of body weight during the same period. Patients on GLP-1RA were less likely to have hepatic steatosis compared with patients on insulin therapy post-LT. Both GLP-1 and insulin were well tolerated, with no significant impact on renal function, immunosuppression, or rejection. GLP-1RA was stopped in only 1 patient due to persistent nausea. CONCLUSIONS: GLP-1RA therapy is safe after LT and is well tolerated. Aside from glycemic control, metabolic benefits of GLP-1RA included weight loss and lower prevalence of steatosis in LT recipients. The study findings provide much-needed safety data for GLP-1RA in LT patients and foundational data to design prospective trials to evaluate metabolic benefits of GLP-1RA. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Yakubu, Idris AU - Yakubu I AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Spengler, Joseph AU - Spengler J AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA. FAU - Taylor, Perry AU - Taylor P AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - LaPorte, Michael AU - LaPorte M AD - Virginia Commonwealth University School of Pharmacy, Richmond, VA. FAU - Brown, Andrew AU - Brown A AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Sterling, Sara AU - Sterling S AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Agegnehu, Bem AU - Agegnehu B AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Iaria, Aoife AU - Iaria A AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Marks, Ryan AU - Marks R AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Sprague, Taylor AU - Sprague T AD - Department of Pharmacy, Virginia Commonwealth University, Richmond, VA. FAU - Pontinha, Vasco AU - Pontinha V AD - Virginia Commonwealth University School of Pharmacy, Richmond, VA. FAU - Patel, Vaishali AU - Patel V AD - Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA. FAU - Patidar, Kavish R AU - Patidar KR AD - Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX. AD - Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX. FAU - Siddiqui, Mohammad Shadab AU - Siddiqui MS AD - Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA. LA - eng PT - Journal Article DEP - 20250325 PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Female MH - *Liver Transplantation/adverse effects MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood/diagnosis MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - Aged MH - Insulin/therapeutic use MH - Adult MH - Blood Glucose/metabolism/drug effects MH - Glucagon-Like Peptides/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Time Factors MH - Weight Loss/drug effects MH - *End Stage Liver Disease/complications/surgery MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/03/25 06:25 MHDA- 2025/08/31 19:52 CRDT- 2025/03/25 00:02 PHST- 2025/08/31 19:52 [medline] PHST- 2025/03/25 06:25 [pubmed] PHST- 2025/03/25 00:02 [entrez] AID - 00007890-990000000-01034 [pii] AID - 10.1097/TP.0000000000005361 [doi] PST - ppublish SO - Transplantation. 2025 Sep 1;109(9):e501-e507. doi: 10.1097/TP.0000000000005361. Epub 2025 Mar 25. PMID- 40108854 OWN - NLM STAT- MEDLINE DCOM- 20250415 LR - 20260524 IS - 1875-9114 (Electronic) IS - 0277-0008 (Linking) VI - 45 IP - 4 DP - 2025 Apr TI - Insulin requirements after switching from GLP-1 receptor agonist to dual GIP/GLP-1 receptor agonist in patients with type 2 diabetes mellitus. PG - 220-226 LID - 10.1002/phar.70009 [doi] AB - INTRODUCTION: With recent clinical implementation of tirzepatide, patients with type 2 diabetes mellitus (T2DM) are transitioning from glucagon-like peptide 1 receptor agonists (GLP-1 RA) to a dual gastric inhibitory polypeptide (GIP)/GLP-1 RA-like tirzepatide. Limited literature is available for insulin dose adjustments for patients concurrently using insulin during this transition. In clinical trials, tirzepatide has shown greater glycated hemoglobin (A1c) reduction and glucose-lowering effects compared to GLP-1 RAs, such as semaglutide, suggesting a potential elevated risk of hypoglycemia without proactive insulin adjustments. OBJECTIVES: The primary objective of this study was to assess the percent change in daily insulin requirements 6 months after transitioning patients from GLP-1 RAs to tirzepatide. METHODS: This retrospective cohort study includes patients with T2DM who transitioned from a GLP-1 RA to tirzepatide while concurrently using insulin therapy. Patient-reported doses of insulin and study medications were collected by chart review by investigators, along with baseline demographics and adverse effects as additional endpoints. RESULTS: Sixty-six patients were included. The median insulin dose reduced from 101 units at baseline to 71 units after 6 months, with a median decrease of 9.5 units (p < 0.001). The median percent change in insulin dose was -9.2%. Patients with a baseline A1c of 8.0% or lower required a larger decrease in insulin compared to patients with a higher baseline A1c (-22.6% vs. 0%, p = 0.018). The intensity of GLP-1 RA and tirzepatide, determined by agent and dose, did not show a difference in insulin requirements (p = 0.279 and p = 0.317, respectively). Hypoglycemia occurred in eight patients (12.1%). CONCLUSION: Patients require a reduction in insulin when transitioning from GLP-1 RAs to tirzepatide, especially if baseline A1c is less than or equal to 8.0%. Larger, comparative studies need to be performed to provide specific recommendations for various doses and product types of incretin receptor agonists. CI - (c) 2025 ACCP Foundation, Ltd. FAU - Lahey, Alexa M AU - Lahey AM AUID- ORCID: 0009-0001-2554-7200 AD - Department of Pharmacy, University of Kentucky HealthCare, Lexington, Kentucky, USA. FAU - Duprey, Karolyn AU - Duprey K AUID- ORCID: 0009-0002-4925-5453 AD - Department of Pharmacy, University of Kentucky HealthCare, Lexington, Kentucky, USA. FAU - Montague, Riley C AU - Montague RC AD - College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA. FAU - Schadler, Aric D AU - Schadler AD AUID- ORCID: 0000-0001-8814-5834 AD - College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA. AD - University of Kentucky Children's Hospital - Pediatrics, Lexington, Kentucky, USA. FAU - Naseman, Kristina W AU - Naseman KW AUID- ORCID: 0000-0003-4738-3785 AD - Department of Pharmacy, University of Kentucky HealthCare, Lexington, Kentucky, USA. LA - eng PT - Journal Article DEP - 20250319 PL - United States TA - Pharmacotherapy JT - Pharmacotherapy JID - 8111305 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glycated Hemoglobin) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Insulin/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Aged MH - Tirzepatide/administration & dosage MH - Glycated Hemoglobin MH - *Gastric Inhibitory Polypeptide/agonists MH - Blood Glucose/drug effects MH - Drug Substitution MH - Cohort Studies OTO - NOTNLM OT - diabetes mellitus, type 2 OT - glucagon-like peptide 1 OT - hypoglycemia OT - insulin OT - tirzepatide EDAT- 2025/03/20 06:24 MHDA- 2025/04/15 12:29 CRDT- 2025/03/20 02:03 PHST- 2025/01/18 00:00 [revised] PHST- 2024/08/10 00:00 [received] PHST- 2025/02/06 00:00 [accepted] PHST- 2025/04/15 12:29 [medline] PHST- 2025/03/20 06:24 [pubmed] PHST- 2025/03/20 02:03 [entrez] AID - 10.1002/phar.70009 [doi] PST - ppublish SO - Pharmacotherapy. 2025 Apr;45(4):220-226. doi: 10.1002/phar.70009. Epub 2025 Mar 19. PMID- 40107359 OWN - NLM STAT- MEDLINE DCOM- 20250516 LR - 20260127 IS - 2405-4577 (Electronic) IS - 2405-4577 (Linking) VI - 67 DP - 2025 Jun TI - Exploring beyond numeric weight loss: The metabolic effects of semaglutide. PG - 435-440 LID - S2405-4577(25)00101-9 [pii] LID - 10.1016/j.clnesp.2025.03.010 [doi] AB - The global burden of overweight and obesity has increased by threefold since the 1970s, which led to increased incidences of cardiovascular disease and type 2 diabetes. This review aimed to explore the metabolic impacts of semaglutide, including its effects on hunger and satiety, weight loss maintenance and regain, body composition, lipid profile, and glycemic control. Studies have shown that semaglutide reduced fat mass, particularly visceral fat, while preserving lean muscle mass, as the proportion relative to total body mass decreased by 3.5 % and 2.0 % for total and visceral fat mass, respectively, while it increased by 3.0 % for lean body mass. Also, it enhanced glycemic control, as evidenced by significant reductions in hemoglobin A1C (HbA1c) with the 0.5 mg and 1.0 mg doses. From a baseline range of 8.1-8.7 %, 0.5 mg dose lowered HbA1c by 1.2-1.5 %, while the 1.0 mg dose reduced it by 1.4-1.8 %. Furthermore, semaglutide was the only effective Glucagon Like Peptide-1 Receptor Agonist in reducing Low-Density Lipoprotein and total cholesterol levels, with mean differences of -0.16 mmol/L and -0.48 mmol/L, respectively. Evidence shows that withdrawing semaglutide led to weight regain, while continued treatment resulted in further weight loss. Semaglutide also slowed weight regain and promoted weight loss after failed bariatric surgery. It also significantly reduced ad libitum energy intake, decreased hunger, and increased satiety in multiple trials. Overall, these findings underscore the potential of semaglutide as a comprehensive treatment for obesity and type 2 diabetes. CI - Copyright (c) 2025 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Sokary, Sara AU - Sokary S AD - Department of Nutrition Sciences, College of Health Science, QU-Health, Qatar University, Doha, Qatar. FAU - Bawadi, Hiba AU - Bawadi H AD - Department of Nutrition Sciences, College of Health Science, QU-Health, Qatar University, Doha, Qatar. Electronic address: hbawadi@qu.edu.qa. LA - eng PT - Journal Article PT - Review DEP - 20250317 PL - England TA - Clin Nutr ESPEN JT - Clinical nutrition ESPEN JID - 101654592 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Weight Loss/drug effects MH - *Obesity/drug therapy MH - Glycated Hemoglobin/metabolism MH - Body Composition/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Blood Glucose/metabolism/drug effects MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Body composition OT - Glucagon-like Peptide-1 receptor agonist OT - Glycemic control OT - Hunger and satiety OT - Lipid profile OT - Semaglutide OT - Weight maintenance COIS- Declaration of competing interest All authors declare no conflict of interest. EDAT- 2025/03/20 00:33 MHDA- 2025/05/17 17:02 CRDT- 2025/03/19 20:35 PHST- 2024/10/26 00:00 [received] PHST- 2025/03/06 00:00 [revised] PHST- 2025/03/10 00:00 [accepted] PHST- 2025/05/17 17:02 [medline] PHST- 2025/03/20 00:33 [pubmed] PHST- 2025/03/19 20:35 [entrez] AID - S2405-4577(25)00101-9 [pii] AID - 10.1016/j.clnesp.2025.03.010 [doi] PST - ppublish SO - Clin Nutr ESPEN. 2025 Jun;67:435-440. doi: 10.1016/j.clnesp.2025.03.010. Epub 2025 Mar 17. PMID- 40106161 OWN - NLM STAT- MEDLINE DCOM- 20250705 LR - 20260127 IS - 1179-187X (Electronic) IS - 1175-3277 (Linking) VI - 25 IP - 4 DP - 2025 Jul TI - Cardiovascular Safety Profile of Semaglutide and Variations by Sex, Race, and Kidney Function: A Systematic Review and Meta-analysis. PG - 479-489 LID - 10.1007/s40256-025-00727-y [doi] AB - BACKGROUND: Patients with diabetes mellitus and its complications are at increased risk for cardiovascular diseases. Semaglutide is efficacious for glycemic control and reducing the risk of major adverse cardiovascular outcomes. Although trials have provided data about cardiovascular outcomes with this agent, a meta-analysis regarding its cardiovascular safety and variations in outcomes according to sex, race and estimated glomerular filtration rate was necessary. MATERIALS AND METHODS: We searched the PubMed, Cochrane Library, and Clinicaltrials.gov databases and included randomized controlled trials (RCTs) where semaglutide was the intervention and major adverse cardiovascular events (MACE) or expanded MACE was the outcome. We assessed the quality of the RCTs using the Cochrane Risk of Bias tool and used the statistical software RevMan 5.4. The protocol for this review was registered on PROSPERO (CRD42024580784). RESULTS: Of 5387 articles, four RCTs were included. The risk of MACE with semaglutide was significantly lower in patients with established or a risk of cardiovascular disease (risk ratio [RR] 0.81; 95% confidence interval [CI] 0.74-0.88; p < 0.00001). The risk of expanded MACE also reduced significantly with semaglutide (RR 0.80; 95% CI 0.75-0.86; p < 0.00001). MACE risk reduction was significant in males (RR 0.78; 95% CI 0.70-0.87; p < 0.00001) and in Asian (RR 0.61; 95% CI 0.44-0.83; p = 0.002) and white (RR 0.82; 95% CI 0.73-0.90; p = 0.0001) populations. CONCLUSION: Semaglutide provides significant advantages in terms of lowering the risk of MACE and expanded MACE and could possibly be used as a crucial component of cardiovascular risk management, particularly in populations that respond well, such as men and Asian and white populations. REGISTRATION: PROSPERO identifier number CRD42024580784. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Hamayal, Muhammad AU - Hamayal M AUID- ORCID: 0009-0005-4908-4844 AD - Al-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan. FAU - Akhtar, Chaudhary Humayun AU - Akhtar CH AD - Al-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan. FAU - Ahmad, Naveed AU - Ahmad N AD - Al-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan. FAU - Awwab, Muhammad AU - Awwab M AD - Quaid-e-Azam Medical College, Circular Road, Bahawalpur, 06318, Pakistan. FAU - Shahid, Warda AU - Shahid W AUID- ORCID: 0009-0009-5954-8461 AD - Al-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan. wardashahid198@gmail.com. FAU - Abbasi, Hasan Shaukat AU - Abbasi HS AD - Al-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan. FAU - Nadeem, Esha AU - Nadeem E AD - Al-Farabi Center, Federal Medical and Dental College, Hanna Road, G-8/4, Islamabad, 44080, Pakistan. FAU - Siddiqui, Erum AU - Siddiqui E AD - Jinnah Sindh Medical University, Rafiqui H.J, Iqbal Shaheed Rd, Karachi Cantonment, Karachi, 75510, Pakistan. FAU - Zafar, Wadana AU - Zafar W AD - Khyber Medical College, University of Peshawar, Road No. 2, Peshawar, 25120, Pakistan. FAU - Hussain, Saima AU - Hussain S AD - University of Regina Saskatoon, The Concourse, Innovation Place, Saskatoon, SK, S7N 3R3, Canada. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250319 PL - New Zealand TA - Am J Cardiovasc Drugs JT - American journal of cardiovascular drugs : drugs, devices, and other interventions JID - 100967755 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Randomized Controlled Trials as Topic MH - Sex Factors MH - Male MH - Glomerular Filtration Rate MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy MH - Racial Groups MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declarations. Funding: No external funding was used in the preparation of this manuscript. Conflict of Interest: Muhammad Hamayal, Chaudhary Humayun Akhtar, Naveed Ahmad, Muhammad Awwab, Warda Shahid, Hasan Shaukat Abbasi, Esha Nadeem, Erum Siddiqui, Wadana Zafar, and Saima Hussain have no potential conflicts of interest that might be relevant to the contents of this manuscript. Data Availability Statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics Approval: Not applicable. Code Availability: Not applicable. Consent To Participate: Not applicable. Consent For Publication: Not applicable. Authors' Contributions: Muhammad Hamayal: Conceptualization, formal analysis, investigation, methodology, writing - original draft, writing - review and editing, project administration. Chaudhary Humayun Akhtar: Conceptualization, investigation, methodology, writing - original draft. Naveed Ahmad: Conceptualization, investigation, methodology, writing - original draft. Muhammad Awwab: Conceptualization, investigation, methodology, writing - original draft. Warda Shahid: Conceptualization, formal analysis, writing - original draft, writing - review and editing. Hasan Shaukat Abbasi: Methodology, investigation, writing - original draft. Esha Nadeem: Conceptualization, investigation, writing - original draft. Erum Siddiqui: Investigation, writing - original draft, writing - review and editing. Wadana Zafar: Conceptualization, methodology, writing - original draft. Saima Hussain: Methodology, writing - review and editing, supervision. EDAT- 2025/03/19 18:23 MHDA- 2025/07/05 20:46 CRDT- 2025/03/19 12:24 PHST- 2025/02/26 00:00 [accepted] PHST- 2025/07/05 20:46 [medline] PHST- 2025/03/19 18:23 [pubmed] PHST- 2025/03/19 12:24 [entrez] AID - 10.1007/s40256-025-00727-y [pii] AID - 10.1007/s40256-025-00727-y [doi] PST - ppublish SO - Am J Cardiovasc Drugs. 2025 Jul;25(4):479-489. doi: 10.1007/s40256-025-00727-y. Epub 2025 Mar 19. PMID- 40100584 OWN - NLM STAT- MEDLINE DCOM- 20250416 LR - 20261010 IS - 1535-1645 (Electronic) IS - 1523-3812 (Linking) VI - 27 IP - 5 DP - 2025 May TI - Sex Differences in Obesity and Its Treatment. PG - 278-285 LID - 10.1007/s11920-025-01601-z [doi] AB - PURPOSE OF REVIEW: Researchers and clinicians have increasingly recognized the importance of investigating and considering sex differences in obesity treatment. In this narrative review, we first summarized sex differences in select obesity-related conditions that have been the focus of studies of second-generation anti-obesity medications (i.e., semaglutide and tirzepatide) including type 2 diabetes, obstructive sleep apnea, knee osteoarthritis, and heart failure. We next described sex differences related to obesity treatments with a focus on the second-generation anti-obesity medications, semaglutide and tirzepatide. RECENT FINDINGS: Type 2 diabetes, obstructive sleep apnea, knee osteoarthritis, and heart failure demonstrated sex-specific pathways influenced by factors such as hormones and body composition. Lifestyle modification, on average, resulted in larger weight losses in males. In contrast, second-generation AOMs produced higher mean weight losses among females. Females reported more adverse events (e.g., nausea, vomiting) with second-generation anti-obesity medications. The few studies that have performed analyses of changes in obesity-related comorbidities stratified by sex have shown consistent improvements between males and females in heart failure and cardiovascular outcomes. Studies are needed to evaluate the effect of sex on the efficacy of anti-obesity medications including on mental health, investigate the mechanisms underlying these effects, and develop interventions to improve the availability and access of these medications. CI - (c) 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Ghanta, Aleena AU - Ghanta A AD - Johns Hopkins University School of Nursing, Baltimore, MD, USA. AD - University of Pennsylvania School of Nursing, Philadelphia, PA, USA. FAU - Wilson, Elizabeth AU - Wilson E AD - Johns Hopkins University School of Nursing, Baltimore, MD, USA. FAU - Chao, Ariana M AU - Chao AM AD - Johns Hopkins University School of Nursing, Baltimore, MD, USA. Ariana.Chao@jhu.edu. AD - University of Pennsylvania School of Nursing, Philadelphia, PA, USA. Ariana.Chao@jhu.edu. LA - eng GR - R56NR020466/NR/NINR NIH HHS/United States GR - R56NR020466/NR/NINR NIH HHS/United States PT - Journal Article PT - Review DEP - 20250318 PL - United States TA - Curr Psychiatry Rep JT - Current psychiatry reports JID - 100888960 RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Obesity/drug therapy/therapy MH - Female MH - Male MH - *Anti-Obesity Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Sex Factors MH - *Sex Characteristics MH - Sleep Apnea, Obstructive/drug therapy OTO - NOTNLM OT - Anti-obesity medication OT - GLP-1 receptor agonists OT - Obesity treatment OT - Sex differences OT - Weight loss COIS- Declarations. Competing Interests: AMC has served on advisory boards for Eli Lilly and Company and Boehringer Ingelheim and received grant support, on behalf of the University of Pennsylvania, from Eli Lilly and Company. Disclosures: AMC has served on advisory boards for Eli Lilly and Company and Boehringer Ingelheim and received grant support, on behalf of the University of Pennsylvania, from Eli Lilly and Company. EDAT- 2025/03/18 18:22 MHDA- 2025/04/16 18:24 CRDT- 2025/03/18 12:21 PHST- 2025/03/04 00:00 [accepted] PHST- 2025/04/16 18:24 [medline] PHST- 2025/03/18 18:22 [pubmed] PHST- 2025/03/18 12:21 [entrez] AID - 10.1007/s11920-025-01601-z [pii] AID - 10.1007/s11920-025-01601-z [doi] PST - ppublish SO - Curr Psychiatry Rep. 2025 May;27(5):278-285. doi: 10.1007/s11920-025-01601-z. Epub 2025 Mar 18. PMID- 40098249 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260818 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: A Danish-Norwegian cohort study. PG - 3094-3103 LID - 10.1111/dom.16316 [doi] AB - AIMS: To investigate the putative association between semaglutide and non-arteritic anterior ischaemic optic neuropathy (NAION). MATERIALS AND METHODS: Data from national health registries in Denmark (2018-2024) and Norway (2018-2022) were used to compare NAION risk in individuals with type 2 diabetes initiating semaglutide versus sodium-glucose co-transporter 2 inhibitors (SGLT-2is). A supplementary self-controlled analysis examined NAION risk among all semaglutide users. National estimates were pooled using a fixed-effects model. RESULTS: We identified 44 517 users of semaglutide for the management of type 2 diabetes in Denmark and 16 860 in Norway, with a total of 32 NAION events observed. The unadjusted incidence rate of NAION was 2.19/10 000 person-years among Danish semaglutide initiators, compared to 1.18 among SGLT-2i initiators. In Norway, the corresponding rates were 2.90 and 0.92, respectively. After adjustment, the pooled hazard ratio (HR) was 2.81 (95% confidence interval [CI] 1.67-4.75), and the incidence rate difference (IRD) was +1.41 (95% CI +0.53 to +2.29) per 10 000 person-years. Estimates were consistent across both countries but higher and less precise in Norway (HR 7.25; 95% CI 2.34-22.4) compared to Denmark (HR 2.17; 95% CI 1.20-3.92). Results remained consistent across sensitivity and supplementary analyses, with a stronger association observed in a post hoc per-protocol analysis (HR 6.35; 95% CI 2.88-14.0). In the supplementary self-controlled study, symmetry ratios (SRs) for NAION were 1.14 (95% CI 0.55-2.36) in Denmark and 2.67 (95% CI 0.91-8.99) in Norway. CONCLUSIONS: The use of semaglutide for managing type 2 diabetes is associated with an increased risk of NAION compared with the use of SGLT-2is. However, the absolute risk remains low. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Simonsen, Emma AU - Simonsen E AUID- ORCID: 0000-0002-0254-0479 AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Lund, Lars Christian AU - Lund LC AUID- ORCID: 0000-0001-8651-6072 AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Ernst, Martin Thomsen AU - Ernst MT AUID- ORCID: 0000-0001-9003-3823 AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Hjellvik, Vidar AU - Hjellvik V AUID- ORCID: 0000-0002-2379-9906 AD - Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. FAU - Hegedus, Laszlo AU - Hegedus L AD - Department of Endocrinology, Odense University Hospital, Odense, Denmark. AD - Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. FAU - Hamann, Steffen AU - Hamann S AUID- ORCID: 0000-0003-4318-2716 AD - Department of Ophthalmology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Jorstad, Oystein Kalsnes AU - Jorstad OK AUID- ORCID: 0000-0003-1259-0653 AD - Department of Ophthalmology, Oslo University Hospital, Oslo, Norway. AD - Faculty of Medicine, University of Oslo, Oslo, Norway. FAU - Gulseth, Hanne Lovdal AU - Gulseth HL AUID- ORCID: 0000-0001-5057-4449 AD - Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. FAU - Karlstad, Oystein AU - Karlstad O AUID- ORCID: 0000-0003-1204-787X AD - Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. FAU - Pottegard, Anton AU - Pottegard A AUID- ORCID: 0000-0001-9314-5679 AD - Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. LA - eng GR - 2025-00052B/Danmarks Frie Forskningsfond/ PT - Journal Article DEP - 20250317 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Denmark/epidemiology MH - Female MH - Male MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - Middle Aged MH - Norway/epidemiology MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced MH - Aged MH - Incidence MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Cohort Studies MH - Registries MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12046482 OTO - NOTNLM OT - SGLT2 inhibitor OT - antidiabetic drug OT - antiobesity drug OT - pharmaco-epidemiology OT - semaglutide OT - type 2 diabetes COIS- Lars Christian Lund has taught a full-day course in epidemiological methods in drug safety surveillance at Novo Nordisk, with funds paid to the University of Southern Denmark (no personal fees). Vidar Hjellvik reports participation in research projects funded by Novo Nordisk and LEO Pharma, all regulator-mandated phase IV studies with funds paid to the institution where he is employed (no personal fees), and with no relation to the work reported in this paper. Steffen Hamann has received grants from Rigshospitalet and the VELUX Foundation. None of these grants has any relation to the work reported in this paper. Oystein Kalsnes Jorstad has received a grant from Roche for developing an educational application. He receives royalties from SJJ Solutions for a syringe used in intravitreal injections. He has received consulting fees from SJJ Solutions and Oslo Economics. He has also received lecture fees from Allergan, Bayer, and Chiesi Farmaceutici, as well as support for meetings, travel, and attendance from SJJ Solutions. He holds patents for a needle for intravitreal injections and a glaucoma stent. Jorstad is also a member of the advisory boards for Allergan, Bayer, and Roche. None of these relationships has any relation to the work reported in this paper. Oystein Karlstad reports participation in research projects funded by Sanofi, Bristol Myers Squibb, Novo Nordisk, and LEO Pharma, all regulator-mandated phase IV studies with funds paid to the institution where he is employed (no personal fees) and with no relation to the work reported in this paper. Anton Pottegard reports participation in research projects funded by Alcon, Almirall, Astellas, AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Servier, and LEO Pharma, all regulator-mandated phase IV studies with funds paid to the institution where he is employed (no personal fees). Further, his research group has received one unrestricted grant from Novo Nordisk. None of these grants has any relation to the work reported in this paper. The remaining authors report no conflicts of interest. EDAT- 2025/03/18 06:22 MHDA- 2025/05/03 22:26 PMCR- 2025/05/02 CRDT- 2025/03/18 01:22 PHST- 2025/02/21 00:00 [revised] PHST- 2025/01/12 00:00 [received] PHST- 2025/02/23 00:00 [accepted] PHST- 2025/05/03 22:26 [medline] PHST- 2025/03/18 06:22 [pubmed] PHST- 2025/03/18 01:22 [entrez] PHST- 2025/05/02 00:00 [pmc-release] AID - DOM16316 [pii] AID - 10.1111/dom.16316 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jun;27(6):3094-3103. doi: 10.1111/dom.16316. Epub 2025 Mar 17. PMID- 40088335 OWN - NLM STAT- MEDLINE DCOM- 20250920 LR - 20260127 IS - 1432-1912 (Electronic) IS - 0028-1298 (Print) IS - 0028-1298 (Linking) VI - 398 IP - 9 DP - 2025 Sep TI - Neuroprotective effects of semaglutide and metformin against rotenone-induced neurobehavioral changes in male diabetic rats. PG - 11919-11931 LID - 10.1007/s00210-025-03920-7 [doi] AB - Pre-existing diabetes raises the likelihood of Parkinson's disease (PD), according to epidemiological and animal research. Our study aimed to investigating the likely neuroprotective effect of metformin (Met) and/or semaglutide (Sem) in model of PD in male diabetic rats and the possible underlying mechanism. Type 2 diabetes (T2DM) was induced by giving high-fat diet (HFD) for 3 weeks followed by a single streptozotocin (STZ) injection (40 mg/kg, i.p., once dose) followed by injection of 9 doses of rotenone every 48 +/- 2 h for induction of PD. Met and/or Sema were administered to DM+PD via gastric gavage once daily for 4 weeks. In comparison with the DM+PD group, Met and/or Sem significantly lowered blood glucose levels, HOMA-IR, HbA1C, cholesterol, triglycerides, and LDL with significantly increased insulin and HDL levels. In addition, there was enhanced brain antioxidant status with lower oxidative-inflammatory stress biomarkers associated with improved rat cognitive, locomotor, and olfactory functions. A significant downregulation of caspase 3 and GFAP with concomitant upregulation of NRF2 protein expressions were observed in treated groups. Overall, co-treatment with Met and Sem elicited more efficacy than that of the individual regimen. When combined, the results of this study have demonstrated for the first time that Met and Sem work in concert to create neuroprotection in PD model of male diabetic rats compared to when taken separately. The study's findings indicate that Met and/or Sem have a restorative effect on T2DM and PD-induced changes in neurobehavioral and biochemical/molecular indices ascribed to the improvement of endogenous antioxidant systems, decreased lipid peroxidation, suppression of oxidative/inflammatory stress, and-most importantly-regulation of Nrf2 and caspase 3. CI - (c) 2025. The Author(s). FAU - Salem, Esraa A AU - Salem EA AD - Department of Medical Physiology, Faculty of Medicine, Menoufia University, Shebeen ElKom, 32511, Egypt. FAU - Alqahtani, Saad Misfer AU - Alqahtani SM AD - Department of Pathology, College of Medicine, The University Hospital, Najran University, Najran, Saudi Arabia. FAU - El-Shoura, Ehab A M AU - El-Shoura EAM AUID- ORCID: 0000-0003-2448-7549 AD - Department of Clinical Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt. ehabel-shoura@azhar.edu.eg. FAU - Zaghlool, Sameh S AU - Zaghlool SS AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University of Technology and Information (MTI), Mokattam, Cairo, 11571, Egypt. FAU - Abdelzaher, Lobna A AU - Abdelzaher LA AD - Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt. FAU - Mohamed, Sally A M AU - Mohamed SAM AD - Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt. FAU - Alalhareth, Ibrahim S AU - Alalhareth IS AD - College of Pharmacy, The University Hospital, Najran University, Najran, Saudi Arabia. FAU - Sheref, Alzahraa A M AU - Sheref AAM AD - Department of Medical Physiology, Faculty of Medicine, Menoufia University, Shebeen ElKom, 32511, Egypt. LA - eng PT - Journal Article DEP - 20250315 PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 9100L32L2N (Metformin) RN - 0 (Neuroprotective Agents) RN - 03L9OT429T (Rotenone) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (NF-E2-Related Factor 2) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Nfe2l2 protein, rat) SB - IM MH - Animals MH - Male MH - *Metformin/pharmacology/therapeutic use MH - *Neuroprotective Agents/pharmacology/therapeutic use MH - *Rotenone/toxicity MH - *Diabetes Mellitus, Experimental/drug therapy/metabolism/blood MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/blood MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Rats MH - Oxidative Stress/drug effects MH - *Behavior, Animal/drug effects MH - Blood Glucose/drug effects MH - Hypoglycemic Agents/pharmacology MH - Brain/drug effects/metabolism MH - Rats, Wistar MH - Diet, High-Fat MH - NF-E2-Related Factor 2 MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12449337 OTO - NOTNLM OT - CX3Cl1, Nrf2 OT - Diabetes OT - GFAP OT - Metformin OT - Parkinson OT - Semaglutide COIS- Declarations. Competing interest: The authors declare no competing interests. EDAT- 2025/03/16 11:18 MHDA- 2025/09/20 06:31 PMCR- 2025/03/15 CRDT- 2025/03/15 12:15 PHST- 2024/11/02 00:00 [received] PHST- 2025/02/11 00:00 [accepted] PHST- 2025/09/20 06:31 [medline] PHST- 2025/03/16 11:18 [pubmed] PHST- 2025/03/15 12:15 [entrez] PHST- 2025/03/15 00:00 [pmc-release] AID - 10.1007/s00210-025-03920-7 [pii] AID - 3920 [pii] AID - 10.1007/s00210-025-03920-7 [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 2025 Sep;398(9):11919-11931. doi: 10.1007/s00210-025-03920-7. Epub 2025 Mar 15. PMID- 40087651 OWN - NLM STAT- MEDLINE DCOM- 20250315 LR - 20260924 IS - 1471-2415 (Electronic) IS - 1471-2415 (Linking) VI - 25 IP - 1 DP - 2025 Mar 14 TI - Anterior ischemic optic neuropathy in patients treated with semaglutide: report of four cases with a possible association. PG - 132 LID - 10.1186/s12886-025-03958-4 [doi] LID - 132 AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is increasingly used worldwide for its cardiometabolic benefits. However, it has recently been associated with nonarteritic anterior ischemic optic neuropathy (NAION). This report presents four clinical cases and explores a possible association. CASE PRESENTATION: Four male patients were diagnosed with NAION during semaglutide treatment, with treatment durations of less than one year in three cases. All presented with significant optic disc edema and intraretinal fluid on optical coherence tomography, along with crowded optic disc and small Bruch's membrane opening diameters (< 1.4 mm in three cases). One patient exhibited optic disc drusen. Visual field defects corresponded with ganglion cell layer atrophy on optical coherence tomography. Systemic risk factors varied; two patients had only obesity. CONCLUSIONS: Our observation suggests that individuals with small Bruch's membrane opening diameter may be at risk of developing NAION during semaglutide treatment. CI - (c) 2025. The Author(s). FAU - Ahmadi, Hamid AU - Ahmadi H AD - Department of Ophthalmology, Copenhagen University Hospital Rigshospitalet, Valdemar Hansens vej, 13, 2600, Glostrup, Denmark. hamid.ahmadi.01@regionh.dk. FAU - Hamann, Steffen AU - Hamann S AD - Department of Ophthalmology, Copenhagen University Hospital Rigshospitalet, Valdemar Hansens vej, 13, 2600, Glostrup, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen N, Denmark. LA - eng PT - Case Reports PT - Journal Article DEP - 20250314 PL - England TA - BMC Ophthalmol JT - BMC ophthalmology JID - 100967802 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Phenylpropionates) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - *Glucagon-Like Peptides/adverse effects MH - Middle Aged MH - Aged MH - Tomography, Optical Coherence MH - *Hypoglycemic Agents/adverse effects MH - Visual Fields MH - *Phenylpropionates/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Visual Acuity MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11908077 OTO - NOTNLM OT - Semaglutide OT - case-series. OT - nonarteritic anterior ischemic optic neuropathy COIS- Declarations. Ethics approval and consent to participate: Ethics committee approval was not required as the study utilized data obtained through standard patient care practices. The authors declare that they adhered to the CARE guidelines/methodology. Consent for publication: Informed written consent for publication was obtained from the patients. Competing interests: The authors declare no competing interests. EDAT- 2025/03/16 11:16 MHDA- 2025/03/16 11:17 PMCR- 2025/03/14 CRDT- 2025/03/15 00:40 PHST- 2025/01/20 00:00 [received] PHST- 2025/03/04 00:00 [accepted] PHST- 2025/03/16 11:17 [medline] PHST- 2025/03/16 11:16 [pubmed] PHST- 2025/03/15 00:40 [entrez] PHST- 2025/03/14 00:00 [pmc-release] AID - 10.1186/s12886-025-03958-4 [pii] AID - 3958 [pii] AID - 10.1186/s12886-025-03958-4 [doi] PST - epublish SO - BMC Ophthalmol. 2025 Mar 14;25(1):132. doi: 10.1186/s12886-025-03958-4. PMID- 40086043 OWN - NLM STAT- MEDLINE DCOM- 20250521 LR - 20260127 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 19 IP - 3 DP - 2025 Mar TI - Comparative efficacy and safety of semaglutide 2.4 mg and tirzepatide 5-15 mg in obesity with or without type 2 diabetes: A systematic review of Phase 3 clinical trials. PG - 103212 LID - S1871-4021(25)00029-3 [pii] LID - 10.1016/j.dsx.2025.103212 [doi] AB - BACKGROUND AND AIMS: Both semaglutide 2.4 mg and tirzepatide have been recently approved for chronic use in obesity. There is a lack of literature comparing the efficacy and safety of both these agents in people with obesity/overweight with or without type 2 diabetes (T2D). We systematically reviewed Phase 3 randomized controlled trials (RCTs) conducted with two agents to synthesize the comparative efficacy and safety outcomes. METHODS: We systematically searched PubMed electronic databases until December 15, 2024, using selected keywords and Boolean "AND." Subsequently, we compared the most closely matched trials conducted with semaglutide 2.4 mg and tirzepatide through an adjusted (if baseline imbalance in treatment outcome modifiers present) or unadjusted (in the absence of baseline imbalance) indirect treatment comparison method. RESULTS: We identified one trial each of semaglutide 2.4 mg (STEP-1) and tirzepatide 5, 10, and 15 mg (SURMOUNT-1) in obese or overweight people without T2D and one trial each of semaglutide 2.4 mg (STEP-2) and tirzepatide 10 and 15 mg (SURMOUNT-2) in overweight people with T2D that were almost entirely comparable concerning baseline outcome modifier characteristics. Our unadjusted analysis without individual patients' data found relatively higher (4 and 5.4 % additional) weight loss, HbA1c (-0.4 % additional) reduction, and fewer gastrointestinal side effects (GI S/E) with tirzepatide 10 and 15 mg, respectively, than with semaglutide 2.4 mg, in the intention-to-treat analysis. CONCLUSION: Tirzepatide 10 and 15 mg are more effective and have fewer GI S/E than semaglutide 2.4 mg. A well-powered head-to-head RCT is currently needed to confirm these findings. CI - Copyright (c) 2025 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Singh, Akriti AU - Singh A AD - KPC Medical College & Hospital, Jadavpur, Kolkata, West Bengal, India. FAU - Singh, Awadhesh Kumar AU - Singh AK AD - G. D Hospital & Diabetes Institute, Kolkata, West Bengal, India; Sun Valley Hospital & Diabetes Research Center, Guwahati, Assam, India; Horizon Life Line Multispecialty Hospital, Kolkata, West Bengal, India; Institute of Medical Science & SUM Hospital, Bhubaneswar, Odisha, India. Electronic address: drawadheshkumarsingh@gmail.com. FAU - Singh, Ritu AU - Singh R AD - Horizon Life Line Multispecialty Hospital, Kolkata, West Bengal, India. FAU - Misra, Anoop AU - Misra A AD - Diabetes Foundation (India), New Delhi, India; National Diabetes, Obesity and Cholesterol Foundation, New Delhi, India; Fortis C-DOC Hospital for Diabetes & Allied Sciences, New Delhi, India. LA - eng PT - Comparative Study PT - Journal Article PT - Systematic Review DEP - 20250308 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Obesity/drug therapy/complications MH - Clinical Trials, Phase III as Topic MH - *Tirzepatide/therapeutic use/administration & dosage MH - Randomized Controlled Trials as Topic MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Efficacy OT - Obesity OT - Safety OT - Semaglutide OT - Tirzepatide OT - Type 2 diabetes COIS- Declaration of competing interest Akriti Singh and Ritu Singh has no competing interests. Awadhesh Kumar Singh and Anoop Misra have received speaker's honoraria from Novo Nordisk and Eli Lilly. EDAT- 2025/03/15 00:38 MHDA- 2025/05/22 00:28 CRDT- 2025/03/14 19:02 PHST- 2025/01/27 00:00 [received] PHST- 2025/02/27 00:00 [revised] PHST- 2025/03/01 00:00 [accepted] PHST- 2025/05/22 00:28 [medline] PHST- 2025/03/15 00:38 [pubmed] PHST- 2025/03/14 19:02 [entrez] AID - S1871-4021(25)00029-3 [pii] AID - 10.1016/j.dsx.2025.103212 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2025 Mar;19(3):103212. doi: 10.1016/j.dsx.2025.103212. Epub 2025 Mar 8. PMID- 40083081 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260819 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Time spent in glycaemic control with sustained body weight reduction with tirzepatide: A post hoc analysis of the SURPASS clinical trial programme. PG - 3223-3232 LID - 10.1111/dom.16337 [doi] AB - AIMS: This participant-level exploratory analysis assessed the continuous time spent in glycaemic control and/or with sustained weight reductions with tirzepatide treatment in participants with type 2 diabetes (T2D) from the SURPASS programme. MATERIALS AND METHODS: Participants (N = 6246) from SURPASS 1-5 were randomized to once weekly tirzepatide (5, 10 or 15 mg) or comparator (once weekly placebo, once weekly semaglutide 1 mg, insulin degludec or insulin glargine). Continuous time spent with HbA1c < 7.0% (53 mmol/mol), /=5% body weight reduction and combined HbA1c /=5% body weight reduction were assessed through 40 weeks (SURPASS-1, -2, and -5) or 52 weeks (SURPASS-3 and -4). The non-parametric Wilcoxon rank sum test was used to compare the median duration of continuous time spent in control, and logistic regression was used to analyse the proportion of participants achieving glycaemic control and body weight reduction at any time points or at the end of the primary study period. RESULTS: Median time spent with HbA1c < 7.0% (53 mmol/mol) was 80% (tirzepatide) versus 70% (semaglutide) and 0% (placebo) of the treatment duration in 40-week studies, and 77%-85% (tirzepatide) versus 62% (insulin degludec) and 23% (insulin glargine) of the treatment duration in 52-week studies (p < 0.001). Time spent with HbA1c < 7.0% (53 mmol/mol) was generally similar across all tirzepatide doses in each study. Dose-dependent increases in time spent with >/=5% body weight reduction were observed with tirzepatide (median time spent: 20%-77% with tirzepatide versus 25% with semaglutide 1 mg) (p < 0.001). Tirzepatide-treated participants experienced longer time spent with HbA1c /=5% body weight reduction versus semaglutide (median: 35%-60% vs. 7%) (p < 0.001). CONCLUSIONS: In this post hoc analysis, people with T2D experienced substantially longer continuous time in glycaemic control and more sustained body weight reductions with tirzepatide versus placebo and active comparators. CI - (c) 2025 Eli Lilly and Company and The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Bergman, Brandon K AU - Bergman BK AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Velocity Clinical Research at Medical City, Dallas, Texas, USA. FAU - Garvey, W Timothy AU - Garvey WT AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA. FAU - Batterham, Rachel L AU - Batterham RL AD - Eli Lilly and Company, Indianapolis, Indiana, USA. AD - Centre for Obesity Research, Department of Medicine, University College London, London, UK. FAU - Chen, Yanyun AU - Chen Y AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Liu, Minzhi AU - Liu M AD - Tigermed-BDM Inc., Somerset, New Jersey, USA. FAU - Sharma, Palash AU - Sharma P AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Karanikas, Chrisanthi A AU - Karanikas CA AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Thieu, Vivian T AU - Thieu VT AUID- ORCID: 0000-0001-9803-4134 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20250313 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin, Long-Acting) RN - OYN3CCI6QE (Tirzepatide) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - 54Q18076QB (insulin degludec) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Female MH - *Weight Loss/drug effects MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Glycemic Control MH - Glycated Hemoglobin/analysis/metabolism MH - Insulin, Long-Acting/administration & dosage/therapeutic use MH - Tirzepatide MH - Insulin Glargine/administration & dosage/therapeutic use MH - Blood Glucose/drug effects/metabolism MH - Aged MH - Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Time Factors MH - Drug Administration Schedule MH - Double-Blind Method MH - Treatment Outcome MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12046485 OTO - NOTNLM OT - body weight control OT - glycaemic control OT - tirzepatide OT - type 2 diabetes COIS- JR reports clinical research grants from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Merck, Novartis, Novo Nordisk, Oramed, Pfizer and Sanofi; served on scientific advisory boards; received honorarium or consulting fees from Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Eli Lilly and Company, Hanmi, Novo Nordisk, Oramed, Sanofi, Scholar Rock, Structure Therapeutics, Terns Pharma and Zealand; and received honoraria for lectures from Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk and Sanofi during the conduct of the study. WTG has served as a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand and Merck and as a site principal investigator for multicentred clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly and Company, Epitomee, Neurovalens and Pfizer. RLB is an employee and shareholder of Eli Lilly and Company and reports research grant support from Novo Nordisk, consultancy with Boehringer Ingelheim, Eli Lilly and Company, Gila Therapeutics Inc., GSK, Novo Nordisk, Pfizer and Rhythm Pharmaceuticals. ML was a contracted employee of Eli Lilly and Company at the time of this analysis. BKB, YC, PS, CAK and VTT are employees and shareholders of Eli Lilly and Company. EDAT- 2025/03/14 11:16 MHDA- 2025/05/03 22:26 PMCR- 2025/05/02 CRDT- 2025/03/14 01:23 PHST- 2025/03/03 00:00 [revised] PHST- 2024/12/20 00:00 [received] PHST- 2025/03/05 00:00 [accepted] PHST- 2025/05/03 22:26 [medline] PHST- 2025/03/14 11:16 [pubmed] PHST- 2025/03/14 01:23 [entrez] PHST- 2025/05/02 00:00 [pmc-release] AID - DOM16337 [pii] AID - 10.1111/dom.16337 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Jun;27(6):3223-3232. doi: 10.1111/dom.16337. Epub 2025 Mar 13. PMID- 40081498 OWN - NLM STAT- MEDLINE DCOM- 20250404 LR - 20260529 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 187 DP - 2025 May TI - Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities. PG - 171380 LID - S0196-9781(25)00041-5 [pii] LID - 10.1016/j.peptides.2025.171380 [doi] AB - Recent studies with peptide-based incretin therapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). Randomised clinical trials and 'real-world' studies have confirmed the marked glucose-lowering and weight-lowering efficacy of these agents across diverse populations. These include different ethnic groups, young and elderly individuals with and without diabetes and/or overweight or obesity. Recent studies have also confirmed protections against the development and progression of cardiovascular and renal diseases that are additive to the benefits conferred by improved control of blood glucose and body weight. Emerging evidence suggests that incretin therapies could additionally ameliorate fatty liver disease, chronic inflammation, sleep apnea and possibly degenerative bone disorders and cognitive decline. New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The aim of the review is to acquaint the reader with developments in the field from 2023 to the present (February 2025). CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Bailey, Clifford J AU - Bailey CJ AD - Life and Health Sciences, Aston University, Birmingham B4 7ET, UK. FAU - Flatt, Peter R AU - Flatt PR AD - Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland BT52 1SA, UK. FAU - Conlon, J Michael AU - Conlon JM AD - Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland BT52 1SA, UK. Electronic address: jmconlon1@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20250311 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Obesity/drug therapy/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Incretins/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Comorbidity MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Hypoglycemic Agents/therapeutic use MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular OT - Incretin OT - Multiagonist OT - Obesity OT - Renal OT - Type 2 diabetes COIS- Conflict of Interest CJB has served on steering committees for clinical trials and advisory boards for several pharmaceutical companies. PRF and JMC are named on patents held by Ulster University for peptide therapeutics and have served as advisor to several pharmaceutical companies. EDAT- 2025/03/14 11:19 MHDA- 2025/04/05 15:58 CRDT- 2025/03/13 20:13 PHST- 2025/01/27 00:00 [received] PHST- 2025/03/03 00:00 [revised] PHST- 2025/03/05 00:00 [accepted] PHST- 2025/04/05 15:58 [medline] PHST- 2025/03/14 11:19 [pubmed] PHST- 2025/03/13 20:13 [entrez] AID - S0196-9781(25)00041-5 [pii] AID - 10.1016/j.peptides.2025.171380 [doi] PST - ppublish SO - Peptides. 2025 May;187:171380. doi: 10.1016/j.peptides.2025.171380. Epub 2025 Mar 11. PMID- 40080656 OWN - NLM STAT- MEDLINE DCOM- 20250313 LR - 20260916 IS - 1752-8984 (Electronic) IS - 1479-1641 (Print) IS - 1479-1641 (Linking) VI - 22 IP - 2 DP - 2025 Mar-Apr TI - The impact of semaglutide on wound healing in diabetes related foot ulcer patients: A TriNetX database study. PG - 14791641251322909 LID - 10.1177/14791641251322909 [doi] LID - 14791641251322909 AB - IntroductionDiabetes related foot ulcers (DFUs) are common complications of type 2 diabetes mellitus (T2DM), affecting 15-25% of individuals living with diabetes and significantly contributing to healthcare costs ($9-13 billion annually in the U.S.). Without effective management, these wounds often lead to severe outcomes like amputations. This study aims to examine the association of semaglutide on DFU management.MethodsThis retrospective cohort study utilized TriNetX US Research Network data to assess the impact of semaglutide, a GLP-1 receptor agonist, on DFU outcomes between 2013 and 2023. The study compared outcomes between semaglutide users with DFU (Cohort A, N = 6329) and non-users with DFU (Cohort B, N = 118,821) across 64 healthcare organizations. We matched participants by age, gender, race, and ethnicity; however, we excluded patients with certain co-morbidities. Statistical analysis, such as chi-square analysis and risk ratio, using TriNetX software evaluated different complication outcomes.ResultsSemaglutide users with DFU demonstrated lower relative risks for complications compared to non-users. Within 1 year, semaglutide users were associated with lower relative risks for wound healing complications (0.19% vs 0.38%), chronic non-healing wounds (0.75% vs 1.23%), chronic pain (4.44% vs 8.06%), wound care (2.42% vs 4.86%), wound dehiscence (0.26% vs 0.56%), and amputation (2.34% vs 5.21%) (p < .05). Similar trends persisted over 5 years. While these findings highlight potential benefits of semaglutide with patients with DFU, causation cannot be inferred due to the study's observational design.ConclusionSemaglutide use was associated with favorable outcomes in patients with diabetes-related foot ulcers, including reductions in wound-related complications. While these findings suggest potential benefits of semaglutide as an adjunct in DFU management, further research is needed to confirm these associations and to better understand the mechanisms involved. FAU - Lewis, Joshua E AU - Lewis JE AUID- ORCID: 0009-0001-4785-2011 AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Omenge, Diana K AU - Omenge DK AUID- ORCID: 0009-0000-8116-4290 AD - Tilman J. Fertitta College of Medicine, University of Houston School of Medicine, Houston, TX, USA. FAU - Patterson, Amani R AU - Patterson AR AUID- ORCID: 0009-0006-3082-8986 AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Anwaegbu, Ogechukwu AU - Anwaegbu O AUID- ORCID: 0009-0008-8776-5941 AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Tabukum, Nangah N AU - Tabukum NN AD - John Sealy School of Medicine, University of Texas Medical Branch, Galveston, TX, USA. FAU - Lewis, Jimmie E 3rd AU - Lewis JE 3rd AD - School of Podiatric Medicine, Barry University, Miami, FL, USA. FAU - Lee, Wei-Chen AU - Lee WC AD - Department of Family Medicine, University of Texas Medical Branch, Galveston, TX, USA. LA - eng GR - UL1 TR001439/TR/NCATS NIH HHS/United States GR - D34HP49234/HRSA/HRSA HHS/United States PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, P.H.S. DEP - 20250313 PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Female MH - Male MH - *Wound Healing/drug effects MH - *Diabetic Foot/diagnosis/drug therapy/physiopathology/epidemiology MH - Retrospective Studies MH - Middle Aged MH - Treatment Outcome MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/epidemiology/complications MH - Aged MH - Databases, Factual MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Time Factors MH - United States/epidemiology MH - Risk Factors MH - Risk Assessment MH - Amputation, Surgical MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11907515 OTO - NOTNLM OT - Diabetes related foot ulcers OT - GLP-1 receptor agonists OT - diabetes complications OT - semaglutide OT - wound healing COIS- Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/03/14 11:17 MHDA- 2025/03/14 11:18 PMCR- 2025/03/13 CRDT- 2025/03/13 14:52 PHST- 2025/03/14 11:18 [medline] PHST- 2025/03/14 11:17 [pubmed] PHST- 2025/03/13 14:52 [entrez] PHST- 2025/03/13 00:00 [pmc-release] AID - 10.1177_14791641251322909 [pii] AID - 10.1177/14791641251322909 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2025 Mar-Apr;22(2):14791641251322909. doi: 10.1177/14791641251322909. Epub 2025 Mar 13. PMID- 40069849 OWN - NLM STAT- MEDLINE DCOM- 20250403 LR - 20260814 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 5 DP - 2025 May TI - Efficacy and safety of once-weekly semaglutide 2.4 mg for weight management in participants from China: A prespecified analysis of the STEP 7 randomized clinical trial. PG - 2540-2551 LID - 10.1111/dom.16253 [doi] AB - AIM: To evaluate the efficacy and safety of semaglutide 2.4 mg versus placebo for weight management in a population of Chinese adults with overweight or obesity. MATERIALS AND METHODS: In STEP 7 (NCT04251156), a double-blind, phase 3a trial, adults from a predominantly East Asian population with overweight or obesity, with or without type 2 diabetes, were randomized 2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 44 weeks as an adjunct to a reduced-calorie diet and increased physical activity. This prespecified analysis evaluated Chinese participants in STEP 7. The primary endpoints were percentage change in body weight from baseline to Week 44 and the proportion of participants who achieved >/=5% reduction in body weight from baseline. RESULTS: Overall, 195 Chinese participants were randomized to semaglutide 2.4 mg and 105 to placebo. Estimated change in mean body weight from baseline to Week 44 was -11.8% with semaglutide 2.4 mg versus -3.5% with placebo (estimated treatment difference -8.3%; 95% confidence interval [CI] -10.2, -6.4; p < 0.0001). At Week 44, a greater proportion of participants treated with semaglutide 2.4 mg achieved >/=5% body weight loss versus placebo (85.4% vs. 26.8%): odds ratio 16.1; 95% CI 8.4, 30.9; p < 0.0001. Adverse events were reported by 92.3% of semaglutide-treated participants and 82.9% of placebo-treated participants, the most common of which were gastrointestinal disorders (126/195, 64.6% vs. 35/105, 33.3%). CONCLUSIONS: These data demonstrate beneficial effects of semaglutide 2.4 mg versus placebo, supporting its use in an adult Chinese population with overweight or obesity. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gu, Weijun AU - Gu W AUID- ORCID: 0000-0001-8690-645X AD - Department of Endocrinology, The First Medical Center of Chinese PLA General Hospital, Beijing, China. FAU - Lu, Yibing AU - Lu Y AD - Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Ye, Xinhua AU - Ye X AD - Department of Endocrinology, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China. FAU - Yuan, Guoyue AU - Yuan G AUID- ORCID: 0000-0003-0822-6066 AD - Department of Endocrinology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China. FAU - Liu, Dongmei AU - Liu D AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd., Beijing, China. FAU - Shen, Zewei AU - Shen Z AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd., Beijing, China. FAU - Zu, Ning AU - Zu N AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd., Beijing, China. FAU - Mu, Yiming AU - Mu Y AUID- ORCID: 0000-0002-3344-3540 AD - Department of Endocrinology, The First Medical Center of Chinese PLA General Hospital, Beijing, China. LA - eng GR - Novo Nordisk A/S/ PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250311 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Double-Blind Method MH - China/epidemiology MH - *Obesity/drug therapy/complications/therapy MH - Adult MH - Weight Loss/drug effects MH - *Overweight/drug therapy/complications/therapy MH - Treatment Outcome MH - Diabetes Mellitus, Type 2/complications MH - Drug Administration Schedule MH - *Anti-Obesity Agents/administration & dosage/adverse effects/therapeutic use MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11964988 OTO - NOTNLM OT - GLP-1 analogue OT - antiobesity drug OT - clinical trial OT - phase III study OT - semaglutide OT - weight management COIS- Dongmei Lui, Ning Zu and Zewei Shen are employees of Novo Nordisk and own Novo Nordisk stock. Yiming Mu has received speaker honorarium or consultancy fees in advisory boards from Eli Lilly, Novo Nordisk and Sanofi. Weijun Gu, Yibing Lu, Xinhua Ye and Guoyue Yuan have no conflicts of interest to disclose. EDAT- 2025/03/12 11:34 MHDA- 2025/04/04 00:25 PMCR- 2025/04/03 CRDT- 2025/03/12 00:49 PHST- 2025/01/23 00:00 [revised] PHST- 2024/10/31 00:00 [received] PHST- 2025/01/29 00:00 [accepted] PHST- 2025/04/04 00:25 [medline] PHST- 2025/03/12 11:34 [pubmed] PHST- 2025/03/12 00:49 [entrez] PHST- 2025/04/03 00:00 [pmc-release] AID - DOM16253 [pii] AID - 10.1111/dom.16253 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 May;27(5):2540-2551. doi: 10.1111/dom.16253. Epub 2025 Mar 11. PMID- 40064382 OWN - NLM STAT- MEDLINE DCOM- 20250417 LR - 20260127 IS - 1873-3476 (Electronic) IS - 0378-5173 (Linking) VI - 674 DP - 2025 Apr 15 TI - Regulation of nanoparticle exocytosis direction via receptors transfer: A novel strategy to enhance therapeutic efficacy of semaglutide. PG - 125439 LID - S0378-5173(25)00275-3 [pii] LID - 10.1016/j.ijpharm.2025.125439 [doi] AB - Coumaric acid (CA) is a typical nutrient required in relatively high quantities by the body. It has been proved CA could specifically bind to monocarboxylate Transporter-1 (MCT-1) receptors, a transporter protein expressed on the surface of intestinal epithelial cells, to facilitate its cellular uptake. Although our preliminary research demonstrated semaglutide (SEM) loaded CA modified nanoparticles (SEM@CNP) could improve the absorption of SEM to some extent, the oral bioavailability still remained suboptimal owing to the lysosomal degradation. To address this issue, INF-7 (peptide chain GLFEAIEGFIENGWEGMIDGWYG) and chloroquine (CQ), two lysosomal escape agents (LEAs) with different mechanisms of action, were incorporated with SEM@CNP for oral delivery (SEM@CNP + INF-7, SEM@CNP + CQ). In type II diabetes mice models, SEM@CNP + CQ effectively inhibited postprandial glucose rise with a relative pharmacological bioavailability of 20.63 +/- 2.99 %, 1.73 times higher than SEM@CNP (11.90 +/- 4.56 %). Mechanistic studies revealed that: 1) after adding LEAs, the exocytosis preference of nanoparticles was altered, tending towards basolateral exocytosis apparently. Regulated exocytosis directionality was linked to the spatial redistribution of MCT-1 receptors. 2) among the two LEAs, CQ demonstrated superior efficacy compared to INF-7. This superiority was attributed to the earlier onset of action and more pronounced degree of membrane disruption induced by CQ. This research provided new insights for the design of oral delivery systems for peptidic drugs. CI - Copyright (c) 2025 Elsevier B.V. All rights reserved. FAU - Wang, Yating AU - Wang Y AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Ni, Mingjie AU - Ni M AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Huang, Minyi AU - Huang M AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Xing, Liyun AU - Xing L AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Liu, Xi AU - Liu X AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Jia, Fuya AU - Jia F AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. FAU - Huang, Yuan AU - Huang Y AD - Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: huangyuan0@163.com. LA - eng PT - Journal Article DEP - 20250308 PL - Netherlands TA - Int J Pharm JT - International journal of pharmaceutics JID - 7804127 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Monocarboxylic Acid Transporters) RN - 886U3H6UFF (Chloroquine) RN - 0 (Symporters) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (Monocarboxylate Transport Protein 1) SB - IM MH - Animals MH - *Nanoparticles/chemistry/administration & dosage MH - Mice MH - *Glucagon-Like Peptides/administration & dosage/pharmacokinetics/chemistry/pharmacology MH - Male MH - *Exocytosis/drug effects MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics/chemistry/pharmacology MH - Biological Availability MH - Monocarboxylic Acid Transporters/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Administration, Oral MH - Diabetes Mellitus, Experimental/drug therapy/blood MH - Humans MH - Chloroquine/administration & dosage/chemistry MH - Symporters/metabolism MH - Blood Glucose/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide MH - Monocarboxylate Transport Protein 1 OTO - NOTNLM OT - Basolateral exocytosis OT - Coumaric acid OT - Lysosomal escape agents OT - Oral OT - Semaglutide OT - Type II diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/03/11 00:25 MHDA- 2025/04/18 00:25 CRDT- 2025/03/10 20:15 PHST- 2024/12/22 00:00 [received] PHST- 2025/02/15 00:00 [revised] PHST- 2025/03/06 00:00 [accepted] PHST- 2025/04/18 00:25 [medline] PHST- 2025/03/11 00:25 [pubmed] PHST- 2025/03/10 20:15 [entrez] AID - S0378-5173(25)00275-3 [pii] AID - 10.1016/j.ijpharm.2025.125439 [doi] PST - ppublish SO - Int J Pharm. 2025 Apr 15;674:125439. doi: 10.1016/j.ijpharm.2025.125439. Epub 2025 Mar 8. PMID- 40058653 OWN - NLM STAT- MEDLINE DCOM- 20250512 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 222 DP - 2025 Apr TI - Drug adherence, glycemic control, and weight reduction with subcutaneous semaglutide in real-world management of type 2 diabetes. PG - 112086 LID - S0168-8227(25)00100-7 [pii] LID - 10.1016/j.diabres.2025.112086 [doi] AB - BACKGROUND: We describe changes in HbA1c and body-weight and the relationship between drug adherence and clinical response in a large real-world cohort of patients with type 2 diabetes (T2D) treated with subcutaneous semaglutide for up to three years. METHODS: We included adults with T2D registered at Maccabi Healthcare Services, Israel, who initiated subcutaneous semaglutide (August 2019 - June 2022). Adherence, assessed as Proportion of Days Covered (PDC), was based on drug's dispensation. We assessed the absolute change in HbA1c and the relative change in body-weight from baseline. RESULTS: The 23,442 participants (11,513 women) had a mean age of 62.2 years, HbA1c of 7.6 %, and BMI of 33.7 kg/m(2). Compared to baseline, the mean reductions in HbA1c were 0.77 [95 %CI 0.75-0.78], 0.57 [0.53-0.61], and 0.35 [0.27-0.44] %-points at 6 months, 2 years, and 3 years, respectively. The respective body-weight reductions were 4.9 % [4.8-5.0], 5.3% [5.1-5.5], and 4.5 % [3.7-5.2]. Among 6049 patients with >/=2 years of potential follow-up, median PDC between 0-6 months was 83.9 %, and remained relatively stable thereafter, reaching 74.6 % between 18-24 months. Higher PDC was associated with more pronounced HbA1c and body-weight reductions. CONCLUSIONS: Long-term real-world adherence with semaglutide was relatively stable. Semaglutide use was associated with sustained glycemic control and weight reduction in patients with T2D and relatively good baseline glycemic control, especially among those with high adherence, supporting its use for long-term management of T2D. CI - Copyright (c) 2025 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Melzer Cohen, Cheli AU - Melzer Cohen C AD - Maccabi Institute for Research and Innovation, Tel-Aviv, Israel. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; Regeneron Pharmaceuticals Inc., New York, NY, USA. FAU - Aharonovich, Alona AU - Aharonovich A AD - Novo Nordisk, Israel. FAU - Karasik, Avraham AU - Karasik A AD - Maccabi Institute for Research and Innovation, Tel-Aviv, Israel; Tel Aviv University, Tel Aviv, Israel. FAU - Schechter, Meir AU - Schechter M AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. Electronic address: meir.schechter@mail.huji.ac.il. LA - eng PT - Journal Article DEP - 20250308 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Female MH - Middle Aged MH - Male MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Weight Loss/drug effects MH - *Glycemic Control/statistics & numerical data MH - Aged MH - Glycated Hemoglobin/analysis MH - Blood Glucose/analysis/drug effects MH - Injections, Subcutaneous MH - *Medication Adherence MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Glycemic control OT - Real-world evidence OT - Semaglutide OT - Type 2 diabetes OT - Weight management COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Avraham Karasik reports financial support for this study was provided by Novo Nordisk. Meir Schechter reports a relationship with Novo Nordisk that includes: travel reimbursement. Ofri Mosenzon reports a relationship with Novo Nordisk that includes: consulting or advisory, funding grants, and speaking and lecture fees. Ofri Mosenzon reports a relationship with Eli Lilly that includes: board membership, consulting or advisory, and speaking and lecture fees. Ofri Mosenzon reports a relationship with Sanofi that includes: consulting or advisory and speaking and lecture fees. Ofri Mosenzon reports a relationship with Merck Sharp & Dohme Corp that includes: consulting or advisory and speaking and lecture fees. Ofri Mosenzon reports a relationship with Boehringer Ingelheim that includes: consulting or advisory and speaking and lecture fees. Ofri Mosenzon reports a relationship with AstraZeneca that includes: consulting or advisory, funding grants, and speaking and lecture fees. Ofri Mosenzon reports a relationship with BoL Pharma that includes: consulting or advisory. Ofri Mosenzon reports a relationship with Regeneron Pharmaceuticals Inc that includes: employment. Alona Aharonovich reports a relationship with Novo Nordisk that includes: employment. Avraham Karasik reports a relationship with AstraZeneca that includes: funding grants and speaking and lecture fees. Avraham Karasik reports a relationship with Novo Nordisk that includes: funding grants and speaking and lecture fees. Avraham Karasik reports a relationship with Boehringer Ingelheim that includes: funding grants and speaking and lecture fees. Meir Schechter reports a relationship with AstraZeneca that includes: speaking and lecture fees and travel reimbursement. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/03/10 07:59 MHDA- 2025/03/29 16:15 CRDT- 2025/03/09 20:17 PHST- 2024/11/28 00:00 [received] PHST- 2025/02/14 00:00 [revised] PHST- 2025/03/04 00:00 [accepted] PHST- 2025/03/29 16:15 [medline] PHST- 2025/03/10 07:59 [pubmed] PHST- 2025/03/09 20:17 [entrez] AID - S0168-8227(25)00100-7 [pii] AID - 10.1016/j.diabres.2025.112086 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2025 Apr;222:112086. doi: 10.1016/j.diabres.2025.112086. Epub 2025 Mar 8. PMID- 40055951 OWN - NLM STAT- MEDLINE DCOM- 20250812 LR - 20260127 IS - 1755-3768 (Electronic) IS - 1755-375X (Print) IS - 1755-375X (Linking) VI - 103 IP - 6 DP - 2025 Sep TI - Semaglutide and non-arteritic anterior ischaemic optic neuropathy: Review and interpretation of reported association. PG - 615-621 LID - 10.1111/aos.17473 [doi] AB - This review covers a seminal study of the relation between exposure to the glucagon-like peptide 1 (GLP-1) agonist semaglutide and incident non-arteritic anterior ischaemic optic neuropathy (NAION) in a neuro-ophthalmology clinic setting, subsequent studies in unselected populations, a meta-analysis of clinical trials and pathophysiology studies of the optic disc and retina that may help elucidate the relation between semaglutide and NAION in patients with diabetes or obesity. In the matched cohort study of neuro-ophthalmology patients, those treated using agents other than semaglutide had NAION rates, orders of magnitude higher than a background population, presumably because referral patterns led to the enrichment of the study populations with patients at high risk of NAION. With semaglutide, the rates of NAION were 4.28 and 7.64 times higher for type 2 diabetes (T2D) and obesity, respectively, and onset of NAION was within 14 months of treatment initiation, whereas non-semaglutide NAION was evenly distributed over the 3 years of follow-up. Of four health care registry studies, each covering more than 100 000 patients, two found relative rates of NAION two to three times higher with semaglutide than without semaglutide, one found a trend towards semaglutide being associated with NAION in patients with type 2 diabetes only, and one found statistically insignificant imbalances between the two alternatives. The meta-analysis of various GLP-1 receptor agonists versus placebo or active comparator found no significant difference in rates of NAION. Prior reports of long-term glycaemia reduction being associated with early worsening of retinopathy and with NAION indicate that semaglutide may promote such events in proportion to its antihyperglycaemic potency. The association of NAION with small, crowded discs, optic disc oedema and peripapillary exudation suggests that semaglutide-related NAION may result from changes in perfusion that lead to venous dilation and, presumably, to venous congestion during relative hypoglycaemia. Given the retrospective nature of the epidemiological studies, causality cannot be inferred, but a cautious approach to the use of semaglutide and other powerful glycaemia-reducing agents seems warranted, particularly in patients with crowded optic discs, a characteristic that can be identified by proactive eye examination for disc-at-risk characteristics by the use of optical coherence tomography. CI - (c) 2025 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation. FAU - Amini, Abdullah AU - Amini A AUID- ORCID: 0009-0003-1345-364X AD - Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark. AD - Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark. FAU - Hamann, Steffen AU - Hamann S AD - Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark. AD - Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark. FAU - Larsen, Michael AU - Larsen M AD - Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark. AD - Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark. LA - eng GR - Grosserer Christian Andersen og hustru Ingeborg Ovidia Signe Andersen, fodt Schmidts Legat/ GR - Synoptik Foundation/ PT - Journal Article PT - Review DEP - 20250308 PL - England TA - Acta Ophthalmol JT - Acta ophthalmologica JID - 101468102 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Global Health MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12340176 OTO - NOTNLM OT - diabetic retinopathy OT - non-arteritic anterior ischemic optic neuropathy OT - semaglutide COIS- AA and SH declare no conflicts of interest. ML has consulted for Novo Nordisk, Bayer, Roche, Stoke, Janssen, Novartis. EDAT- 2025/03/09 15:10 MHDA- 2025/08/12 06:27 PMCR- 2025/08/12 CRDT- 2025/03/08 04:33 PHST- 2024/11/04 00:00 [received] PHST- 2025/02/25 00:00 [accepted] PHST- 2025/08/12 06:27 [medline] PHST- 2025/03/09 15:10 [pubmed] PHST- 2025/03/08 04:33 [entrez] PHST- 2025/08/12 00:00 [pmc-release] AID - AOS17473 [pii] AID - 10.1111/aos.17473 [doi] PST - ppublish SO - Acta Ophthalmol. 2025 Sep;103(6):615-621. doi: 10.1111/aos.17473. Epub 2025 Mar 8. PMID- 40050929 OWN - NLM STAT- MEDLINE DCOM- 20250307 LR - 20260127 IS - 1749-799X (Electronic) IS - 1749-799X (Linking) VI - 20 IP - 1 DP - 2025 Mar 6 TI - Effects of semaglutide in patients with chronic ankle instability: evidence from a prospective cohort. PG - 243 LID - 10.1186/s13018-025-05664-9 [doi] LID - 243 AB - BACKGROUND: Whether patients with chronic ankle instability (CAI) can benefit from weight loss yielded by using glucagon-like peptide-1 receptor agonists (GLP1-RAs) has remained unclear. METHODS: In this observational study, we recruited more than 2000 adults with CAI according to the selection criteria proposed by International Ankle Consortium with at least two-year follow up from three medical centers. The primary endpoint was the change from baseline of the Foot and Ankle Ability Measure (FAAM) sports subscale at the last follow up. Secondary endpoints included the change from baseline of Foot and Ankle Outcome Score (FAOS)/ Cumberland Ankle Instability Tool (CAIT)/ FAAM activities of daily living (ADL) subscale, number of ankle sprains during study period, incident ankle surgery in treatment of CAI. RESULTS: In this study, 71 out of 2018 patients who received semaglutide in purpose of treating type 2 diabetes (T2DM) and/or weight loss during the study period. After controlling baseline characteristics, the adjusted mean difference in change from baseline was 16.3 for FAAM sports subscale and 9.3 for FAAM ADL subscale. Likewise, the adjusted analysis of five subscales of FAOS showed similar results, all consistently favoring semaglutide group. For CAIT, patients in the semaglutide group had achieved statistically significant improvement compared with control group. The association of semaglutide exposure with improvement in FAAM sports and ADL subscales was mediated by the weight loss measured by BMI (mediation proportion: FAAM sports subscale, 31.2% [22.2-41.2%]; FHSQ ADL subscale, 34.1% [24.4-44.8%]). We also observed statistically significant decreases in number of recurrent ankle sprains during study period. For incident ankle surgery, 1 out of 71 patients (1.4%) and 151 out of 1947 patients (7.8%) received ankle surgeries in semaglutide and control groups, respectively (P = 0.047). CONCLUSIONS: Semaglutide may show potential benefits as a supplementary intervention in treatment of CAI by improving patient-reported outcomes and preventing recurrent ankle sprains. Further randomized trial is warranted by the current study to further confirm our findings. TRIAL REGISTRATION: researchregistry10716. CI - (c) 2025. The Author(s). FAU - Zhang, Jieyuan AU - Zhang J AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. FAU - Wang, Cheng AU - Wang C AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. FAU - Wang, Jiazheng AU - Wang J AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. FAU - Gu, Wenqi AU - Gu W AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital East Campus, Shanghai, 201306, China. FAU - Wang, Haiqing AU - Wang H AD - Department of Orthopedic Surgery, Ningbo No. 6 hospital, Ningbo, 315040, China. FAU - Zhu, Hongyi AU - Zhu H AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. 420308955@qq.com. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. 420308955@qq.com. FAU - Ma, Xin AU - Ma X AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. maxin@sjtu.edu.cn. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. maxin@sjtu.edu.cn. FAU - Shi, Zhongmin AU - Shi Z AD - National Center for Orthopaedics, Shanghai Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, China. szm1972@sjtu.edu.cn. AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China. szm1972@sjtu.edu.cn. LA - eng GR - 82402855/National Natural Science Foundation of China/ GR - YG2022ZD018/Medical Engineering Cross Research Fund of Shanghai Jiao Tong University/ GR - 23SHS03600/Application Demonstration Project of Innovative Medical Devices in Shanghai in 2023/ GR - 23015820500/Science and Technology Commission of Shanghai Municipality/ PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20250306 PL - England TA - J Orthop Surg Res JT - Journal of orthopaedic surgery and research JID - 101265112 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Joint Instability/drug therapy MH - Female MH - Male MH - Prospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use MH - Adult MH - *Ankle Joint/drug effects/physiopathology MH - Chronic Disease MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Treatment Outcome MH - Follow-Up Studies MH - Weight Loss/drug effects MH - Cohort Studies MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11884071 OTO - NOTNLM OT - Ankle sprain OT - Chronic ankle instability OT - GLP-1 receptor agonist OT - Semaglutide OT - Weight loss COIS- Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Ethics Committee of Shanghai Sixth People's Hospital (approval no. 2019-084). Moreover, this study complied with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for research involving humans. Written consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. EDAT- 2025/03/07 00:21 MHDA- 2025/03/07 06:21 PMCR- 2025/03/06 CRDT- 2025/03/06 23:44 PHST- 2025/01/14 00:00 [received] PHST- 2025/02/27 00:00 [accepted] PHST- 2025/03/07 06:21 [medline] PHST- 2025/03/07 00:21 [pubmed] PHST- 2025/03/06 23:44 [entrez] PHST- 2025/03/06 00:00 [pmc-release] AID - 10.1186/s13018-025-05664-9 [pii] AID - 5664 [pii] AID - 10.1186/s13018-025-05664-9 [doi] PST - epublish SO - J Orthop Surg Res. 2025 Mar 6;20(1):243. doi: 10.1186/s13018-025-05664-9. PMID- 40047207 OWN - NLM STAT- MEDLINE DCOM- 20250326 LR - 20260127 IS - 1473-6543 (Electronic) IS - 1062-4821 (Linking) VI - 34 IP - 3 DP - 2025 May 1 TI - Glucagon-like peptide-1 receptor agonists to improve cardiorenal outcomes: data from FLOW and beyond. PG - 232-240 LID - 10.1097/MNH.0000000000001066 [doi] AB - PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP1RA), initially approved for glycemic control in type 2 diabetes mellitus (T2DM), have emerged as agents for weight loss, cardiovascular and kidney protection. This review summarizes the evidence supporting the benefits of these therapies on cardiorenal outcomes. RECENT FINDINGS: Clinical trials have consistently demonstrated reductions in major adverse cardiovascular events with GLP1RA treatments. Recently, the FLOW trial revealed that semaglutide reduced the composite outcome of kidney failure, at least 50% decline in estimated glomerular filtration rate, kidney or cardiovascular mortality by 24% in patients with T2DM, thereby establishing GLP1RA as a pillar of therapy in this population. New evidence suggests favorable effects on kidney endpoints in nondiabetic individuals with overweight or obesity. Dedicated trials have also provided evidence for reduction in the risk for heart failure hospitalization and improvement in symptoms in individuals with heart failure with preserved ejection fraction. Subgroup analyses have suggested that GLP1RAs confer additive cardiorenal benefits irrespective of background medication use. SUMMARY: There is increasing evidence that GLP1RA reduces the risk for cardiovascular events, chronic kidney disease progression, and heart failure hospitalizations. Further data on the effect of dual and triple GLP1-based therapies on cardiorenal outcomes is required. CI - Copyright (c) 2025 Wolters Kluwer Health, Inc. All rights reserved. FAU - Faruque, Labib AU - Faruque L AD - Department of Medicine, Division of Nephrology, University Health Network. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Yau, Kevin AU - Yau K AD - Department of Medicine, Division of Nephrology, University Health Network. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Cherney, David Z I AU - Cherney DZI AD - Department of Medicine, Division of Nephrology, University Health Network. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. LA - eng PT - Journal Article PT - Review DEP - 20250306 PL - England TA - Curr Opin Nephrol Hypertens JT - Current opinion in nephrology and hypertension JID - 9303753 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/mortality/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Incretins/therapeutic use/adverse effects MH - *Kidney/drug effects/physiopathology MH - *Cardiovascular Diseases/prevention & control/mortality MH - *Heart Failure/prevention & control/physiopathology/mortality MH - Glucagon-Like Peptides/therapeutic use MH - *Renal Insufficiency, Chronic/physiopathology/prevention & control/mortality MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2025/03/06 12:32 MHDA- 2025/03/26 13:06 CRDT- 2025/03/06 06:33 PHST- 2025/03/26 13:06 [medline] PHST- 2025/03/06 12:32 [pubmed] PHST- 2025/03/06 06:33 [entrez] AID - 00041552-990000000-00218 [pii] AID - 10.1097/MNH.0000000000001066 [doi] PST - ppublish SO - Curr Opin Nephrol Hypertens. 2025 May 1;34(3):232-240. doi: 10.1097/MNH.0000000000001066. Epub 2025 Mar 6. PMID- 40045764 OWN - NLM STAT- MEDLINE DCOM- 20250503 LR - 20260818 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 6 DP - 2025 Jun TI - Effectiveness and safety of daily oral semaglutide in people with type 2 diabetes mellitus switching from sulfonylureas: A real-world retrospective study. PG - 3084-3093 LID - 10.1111/dom.16314 [doi] AB - BACKGROUND: Hypoglycaemia is a serious side effect in the treatment of type 2 diabetes mellitus (T2DM), especially when using insulin and insulin secretagogues such as sulfonylureas. Current guidelines recommend reducing or discontinuing these medications in high-risk populations. This study assessed the real-world effectiveness and safety of oral semaglutide in T2DM patients who suspended or reduced sulfonylurea dosages in favour of oral semaglutide. METHODS: In this retrospective, multicentre cohort study, the primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to an average follow-up period of 37 weeks. Secondary endpoints included changes in fasting blood glucose, body weight, the proportion of patients achieving HbA1c /=1%) and body weight (>/=5%). Safety and exploratory endpoints were also evaluated. RESULTS: The study included 104 patients (mean age: 68.9 +/- 9.9 years). Treatment discontinuation occurred in 9.6% of patients, and 12.5% reported adverse events, primarily gastrointestinal; no hypoglycaemic events were reported. HbA1c significantly decreased from 7.62% to 7.42% (p = 0.04, mean reduction of 0.22%) and the proportion of patients achieving HbA1c /=12 years old with type 2 diabetes (T2DM) and considered overweight or obese (high BMI), with at least one ophthalmology or neurology visit. Among T2DM patients, approximately 120,000 patients with a semaglutide prescription and 220,000 prescribed any GLP-1RA were compared to matched T2DM controls. Among high BMI patients, approximately 58,000 on semaglutide and 66,000 on any GLP-1RA were compared to matched controls. METHODS: Patients prescribed semaglutide or any GLP-1RA were compared with those on non-GLP-1RA medications. Populations were propensity matched (1:1) on various demographic and risk factors to balance baseline cohorts. MAIN OUTCOMES AND MEASURES: Cumulative incidence and risk of NAION and ION. Risk ratios (RR) with 95% confidence intervals (CI) were reported, with significance defined as CI <0.9 or > 1.1. RESULTS: In T2DM patients prescribed semaglutide, the risk of NAION (RR = 0.7, 95% CI: 0.523-0.937) and ION (RR = 0.788, 95% CI: 0.609-1.102) after 5 years was not significantly increased compared to matched T2DM controls. Similarly, T2DM patients on any GLP-1RA demonstrated no significant difference in the risk of NAION (RR = 0.887, 95% CI: 0.735-1.071) or ION (RR = 0.969, 95% CI: 0.813-1.154) compared to controls. Furthermore, no increased risk of either outcome was found in the high BMI groups prescribed semaglutide or any GLP-1RA. The cumulative 5-year risk of NAION and ION in T2DM patients on semaglutide was 0.065% and 0.08%, respectively. In those with high BMI prescribed semaglutide, the risk of NAION and ION after 2 years was 0.038% and 0.404%, respectively. CONCLUSIONS: There was no significant increase in risk of NAION or ION in patients taking semaglutide or GLP-1RAs compared to T2DM or high BMI controls. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Abbass, Nadia J AU - Abbass NJ AD - From the Case Western Reserve University School of Medicine (N.J.A., R.N., J.K.S.), Cleveland, Ohio, USA; Center for Ophthalmic Bioinformatics (N.J.A., R.N., J.K.S., K.E.T., R.P.S.), Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Nahlawi, Raya AU - Nahlawi R AD - From the Case Western Reserve University School of Medicine (N.J.A., R.N., J.K.S.), Cleveland, Ohio, USA; Center for Ophthalmic Bioinformatics (N.J.A., R.N., J.K.S., K.E.T., R.P.S.), Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Shaia, Jacqueline K AU - Shaia JK AD - From the Case Western Reserve University School of Medicine (N.J.A., R.N., J.K.S.), Cleveland, Ohio, USA; Center for Ophthalmic Bioinformatics (N.J.A., R.N., J.K.S., K.E.T., R.P.S.), Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Allan, Kevin C AU - Allan KC AD - Cleveland Clinic Cole Eye Institute (K.C.A., K.E.T., R.P.S.), Cleveland, Ohio, USA. FAU - Kaelber, David C AU - Kaelber DC AD - Departments of Internal Medicine, Pediatrics and Population and Quantitative Health Sciences, Case Western Reserve University (D.C.K.), Cleveland, Ohio, USA; The Center for Clinical Informatics Research and Education (D.C.K.), The MetroHealth System, Cleveland, Ohio, USA. FAU - Talcott, Katherine E AU - Talcott KE AD - Center for Ophthalmic Bioinformatics (N.J.A., R.N., J.K.S., K.E.T., R.P.S.), Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (K.E.T., R.P.S.), Cleveland, Ohio, USA; Cleveland Clinic Cole Eye Institute (K.C.A., K.E.T., R.P.S.), Cleveland, Ohio, USA. FAU - Singh, Rishi P AU - Singh RP AD - Center for Ophthalmic Bioinformatics (N.J.A., R.N., J.K.S., K.E.T., R.P.S.), Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA; Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (K.E.T., R.P.S.), Cleveland, Ohio, USA; Cleveland Clinic Cole Eye Institute (K.C.A., K.E.T., R.P.S.), Cleveland, Ohio, USA; Cleveland Clinic Martin Hospitals (R.P.S.), Cleveland Clinic Florida, Stuart, Florida, USA. Electronic address: singhr@ccf.org. LA - eng GR - UM1 TR004528/TR/NCATS NIH HHS/United States GR - UL1 TR002548/TR/NCATS NIH HHS/United States GR - P30 EY025585/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20250225 PL - United States TA - Am J Ophthalmol JT - American journal of ophthalmology JID - 0370500 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Retrospective Studies MH - Female MH - Male MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced/diagnosis MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Risk Factors MH - Incidence MH - Adult MH - Body Mass Index MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC13110070 MID - NIHMS2163178 EDAT- 2025/02/28 00:20 MHDA- 2025/05/01 12:31 PMCR- 2026/04/25 CRDT- 2025/02/27 19:35 PHST- 2025/01/14 00:00 [received] PHST- 2025/02/19 00:00 [revised] PHST- 2025/02/20 00:00 [accepted] PHST- 2025/05/01 12:31 [medline] PHST- 2025/02/28 00:20 [pubmed] PHST- 2025/02/27 19:35 [entrez] PHST- 2026/04/25 00:00 [pmc-release] AID - S0002-9394(25)00094-7 [pii] AID - 10.1016/j.ajo.2025.02.025 [doi] PST - ppublish SO - Am J Ophthalmol. 2025 Jun;274:24-31. doi: 10.1016/j.ajo.2025.02.025. Epub 2025 Feb 25. PMID- 40014091 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260127 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 9 DP - 2025 Sep TI - Long-term efficacy of daily oral semaglutide as add-on or switch therapy in adults with type 2 diabetes: a 12-month real-world retrospective study. PG - 1469-1478 LID - 10.1007/s00592-025-02475-6 [doi] AB - AIMS: To evaluate the efficacy of oral semaglutide, either as an add-on or replacement therapy, in improving glycemic control, body weight, and cardiovascular parameters in patients with type 2 diabetes mellitus (T2DM). METHODS: This real-world study evaluated changes in glycated hemoglobin (HbA1c), body weight, and parameters of cardiovascular risk from baseline to a 12-month follow-up visit. The primary endpoint was the change in HbA1c between baseline and follow-up. Secondary endpoints included changes in body weight, the proportion of patients achieving HbA1c /= 1%) and body weight (>/= 5%). Exploratory endpoints were evaluated as well. RESULTS: Data from 950 patients, predominantly female (63.7%) and with a mean age of 68.3 +/- 10.1 years, were included in the study. Prior to starting semaglutide, most patients were on sulfonylureas, either as monotherapy or in combination with metformin or basal insulin. At baseline, mean HbA1c was 8.0 +/- 1.3% (64.0 +/- 14.2 mmol/mol), and body weight was 82.5 kg. Following 12 months of oral semaglutide treatment, HbA1c decreased significantly of -0.84% (p < 0.001) and 53% of patients achieved HbA1c /= 1% reduction in HbA1c and >/= 5% in body weight. Diastolic blood pressure and LDL levels decreased significantly (p < 0.001), while systolic blood pressure and eGFR remained stable. CONCLUSIONS: When used as an add-on or replacement therapy, oral semaglutide significantly improves glycemic control, body weight, renal and cardiovascular risk factors in T2DM patients. CI - (c) 2025. Springer-Verlag Italia S.r.l., part of Springer Nature. FAU - Sansone, Daniela AU - Sansone D AUID- ORCID: 0009-0002-5494-9580 AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. daniela.sansone@aslcittaditorino.it. FAU - Garino, Francesca AU - Garino F AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Gottero, Cristina AU - Gottero C AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Gauna, Carlotta AU - Gauna C AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Clerico, Alessandra AU - Clerico A AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Corneli, Ginevra AU - Corneli G AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Di Noi, Fabiana AU - Di Noi F AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Mainolfi, Alessandra Rita AU - Mainolfi AR AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Rossi, Claudio AU - Rossi C AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Marafetti, Lisa AU - Marafetti L AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Matteoda, Cristina AU - Matteoda C AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Balbo, Marcella Libera AU - Balbo ML AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Petraroli, Giuliana AU - Petraroli G AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Bonelli, Nadia AU - Bonelli N AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Toscano, Claudia Chiara M AU - Toscano CCM AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Visconti, Licia AU - Visconti L AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. FAU - Oleandri, Salvatore AU - Oleandri S AD - Endocrinology and Metabolism Unit, ASL CITTA' di Torino, Via Juvarra 19, Turin, 10121, Italy. LA - eng PT - Journal Article DEP - 20250227 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 9100L32L2N (Metformin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Middle Aged MH - Retrospective Studies MH - Glycated Hemoglobin/metabolism/analysis MH - Administration, Oral MH - Blood Glucose/drug effects/metabolism MH - Drug Therapy, Combination MH - Body Weight/drug effects MH - Treatment Outcome MH - Metformin/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Body weight OT - Cardiovascular risk OT - GLP1-RA OT - HbA1c OT - Oral semaglutide OT - Real-word evidence OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of interest: All authors have nothing to declare. Ethical statement: The study was approved by the relevant ethics committee and adhered to the Good Clinical Practice guidelines concerning clinical investigations on human subjects and the Declaration of Helsinki. Informed consent: All participants provided written informed consent to participate in the study. EDAT- 2025/02/27 12:29 MHDA- 2025/09/16 13:03 CRDT- 2025/02/27 11:14 PHST- 2024/12/04 00:00 [received] PHST- 2025/02/13 00:00 [accepted] PHST- 2025/09/16 13:03 [medline] PHST- 2025/02/27 12:29 [pubmed] PHST- 2025/02/27 11:14 [entrez] AID - 10.1007/s00592-025-02475-6 [pii] AID - 10.1007/s00592-025-02475-6 [doi] PST - ppublish SO - Acta Diabetol. 2025 Sep;62(9):1469-1478. doi: 10.1007/s00592-025-02475-6. Epub 2025 Feb 27. PMID- 39996062 OWN - NLM STAT- MEDLINE DCOM- 20250225 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 16 DP - 2025 TI - Efficacy and safety of once-weekly semaglutide monotherapy in a young subject with Prader-Willi syndrome, obesity, and type 2 diabetes: a case report. PG - 1533209 LID - 10.3389/fendo.2025.1533209 [doi] LID - 1533209 AB - BACKGROUND: The treatment of obesity and type 2 diabetes (T2D) in Prader-Willi syndrome (PWS) is still a challenge. Glucagon-like peptide 1 receptor agonists (GLP-1 RA) are attractive options, since they effectively reduce weight and improve blood glucose, without increasing the risk of hypoglycemia. However, data on their use in PWS are scarce. CASE DESCRIPTION: In 2019, a 27-year-old male came to our Clinic because of first appearance of severe hyperglycemia (fasting plasma glucose 22.5 mmol/L). Based on clinical presentation, PWS was suspected, and diagnosis was confirmed by genetic tests. The patient was discharged on a basal-bolus insulin therapy managed by his parents due to his cognitive impairment. In spite of COVID-19 pandemic, the patient achieved tight glycemic control (HbA1c 41 mmol/mol) with non-severe hypoglycemic events in the face of significant body weight (BW) increase (+ 13 kg vs baseline). Insulin therapy was then discontinued, and once-weekly semaglutide (up to 0,5 mg weekly) was started. At 12-month follow-up, BW dropped from 79 to 73 kg while maintaining excellent glycemic control (HbA1c 40 mmol/mol). At 24-month follow-up, glycemic control remained optimal (HbA1c 38 mmol/mol) with further BW reduction (71 kg). Neither hypoglycemia nor gastro-intestinal or psychiatric adverse events were reported. CONCLUSION: This case supports the potential use of semaglutide for the treatment of subjects with PWS, obesity and T2D. Ad hoc trials are needed to evaluate the long-term efficacy and tolerability in these subjects. CI - Copyright (c) 2025 Dinoi, Daniele, Michelucci, Baldinotti, Campi, Marchetti, Del Prato and Dardano. FAU - Dinoi, Elisa AU - Dinoi E AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Daniele, Giuseppe AU - Daniele G AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. AD - Center for Instrument Sharing of the University of Pisa (CISUP), Pisa, Italy. FAU - Michelucci, Angela AU - Michelucci A AD - Laboratory of Molecular Genetics, University Hospital of Pisa, Pisa, Italy. FAU - Baldinotti, Fulvia AU - Baldinotti F AD - Laboratory of Molecular Genetics, University Hospital of Pisa, Pisa, Italy. FAU - Campi, Fabrizio AU - Campi F AD - Section of Diabetes and Metabolic Diseases, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy. FAU - Marchetti, Piero AU - Marchetti P AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Del Prato, Stefano AU - Del Prato S AD - Interdisciplinary Research Center "Health Science", Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - Dardano, Angela AU - Dardano A AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. AD - Center for Instrument Sharing of the University of Pisa (CISUP), Pisa, Italy. LA - eng PT - Case Reports PT - Journal Article DEP - 20250210 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Prader-Willi Syndrome/drug therapy/complications MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Adult MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - *Obesity/drug therapy/complications MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Treatment Outcome MH - Drug Administration Schedule MH - Blood Glucose MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11847660 OTO - NOTNLM OT - GLP-1 RA OT - Prader-Willi syndrome OT - case report OT - obesity OT - semaglutide OT - type 2 diabetes mellitus COIS- ED, AD, AM, FB, FC: no duality of interest. GD: Eli lilly Italia. PM: Eli lilly Italia, Novo Nordisk, Gruppo Menarini, Laboratori Guidotti. SDP: Abbott, Amarin Corporation, AstraZeneca, Berlin Chemie AG, Biomea Fusion, Boehringer Ingelheim, Laboratori Guidotti, Menarini International, Novartis Pharmaceuticals Co., Merck Sharpe & Dohme, Eli Lilly and Company, Novo Nordisk, Sanofi, Sun Pharmaceuticals. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2025/02/25 06:21 MHDA- 2025/02/25 06:22 PMCR- 2025/01/01 CRDT- 2025/02/25 04:44 PHST- 2024/11/23 00:00 [received] PHST- 2025/01/16 00:00 [accepted] PHST- 2025/02/25 06:22 [medline] PHST- 2025/02/25 06:21 [pubmed] PHST- 2025/02/25 04:44 [entrez] PHST- 2025/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2025.1533209 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2025 Feb 10;16:1533209. doi: 10.3389/fendo.2025.1533209. eCollection 2025. PMID- 39981788 OWN - NLM STAT- MEDLINE DCOM- 20250312 LR - 20260127 IS - 1445-5994 (Electronic) IS - 1444-0903 (Linking) VI - 55 IP - 3 DP - 2025 Mar TI - Treatment of obesity: will incretin agonists make bariatric surgery a thing of the past? PG - 369-375 LID - 10.1111/imj.16625 [doi] AB - The prevalence of obesity continues to increase worldwide. Obesity is associated with an increased risk of cardiometabolic and other diseases, reduced quality of life and shortened life expectancy. Highly effective therapies are required to achieve meaningful and sustained weight reduction to prevent, slow or reverse disease associated with obesity. Bariatric surgery is a highly effective intervention to induce weight loss, with observational data demonstrating durability of weight loss over 10 or more years. In addition, bariatric surgery improves cardiometabolic risk factors, including hyperglycaemia and type 2 diabetes, hypertension and dyslipidaemia. Observational data have shown a reduction in all-cause mortality, cardiovascular events and mortality and a reduction in cancer risk and mortality in patients who have undergone bariatric surgery compared to matched patients who did not have surgery. The emergence of newer incretin agonists, particularly semaglutide and tirzepatide, have demonstrated remarkable efficacy in inducing and maintaining weight loss with ongoing use. As for bariatric surgery, incretin agonist therapies also improve type 2 diabetes outcomes, cardiovascular mortality and other obesity-related complications, with new evidence emerging and long-term outcome data awaited. This perspective compares bariatric surgery and incretin agonist therapy, assessing their relative efficacies in weight reduction, impact on obesity-related complications, their respective risk profiles and considerations of cost-effectiveness and equity of access. These comparisons seek to evaluate whether these increasingly popular medications could make bariatric surgery a thing of the past. CI - (c) 2025 Royal Australasian College of Physicians. FAU - Lah, Siehoon AU - Lah S AUID- ORCID: 0000-0003-2834-2486 AD - Metabolism and Obesity Service, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. FAU - Hocking, Samantha L AU - Hocking SL AUID- ORCID: 0000-0002-2514-9392 AD - Metabolism and Obesity Service, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. AD - Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia. AD - Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia. LA - eng PT - Journal Article PT - Review DEP - 20250221 PL - Australia TA - Intern Med J JT - Internal medicine journal JID - 101092952 RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Bariatric Surgery/trends/methods MH - *Incretins/agonists/therapeutic use MH - *Obesity/drug therapy/surgery/therapy MH - Weight Loss/drug effects/physiology MH - Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Tirzepatide MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 agonist OT - bariatric surgery OT - incretin agonist OT - obesity OT - semaglutide OT - tirzepatide EDAT- 2025/02/21 12:22 MHDA- 2025/03/12 12:32 CRDT- 2025/02/21 07:13 PHST- 2024/09/01 00:00 [received] PHST- 2024/12/09 00:00 [accepted] PHST- 2025/03/12 12:32 [medline] PHST- 2025/02/21 12:22 [pubmed] PHST- 2025/02/21 07:13 [entrez] AID - 10.1111/imj.16625 [doi] PST - ppublish SO - Intern Med J. 2025 Mar;55(3):369-375. doi: 10.1111/imj.16625. Epub 2025 Feb 21. PMID- 39980227 OWN - NLM STAT- MEDLINE DCOM- 20250509 LR - 20260524 IS - 1875-9114 (Electronic) IS - 0277-0008 (Linking) VI - 45 IP - 3 DP - 2025 Mar TI - The potential role of GLP-1 receptor agonists in osteoarthritis. PG - 177-186 LID - 10.1002/phar.70005 [doi] AB - Osteoarthritis (OA) is the most common form of arthritis, affecting over 500 million people globally. Current treatments are primarily symptom-focused, with no approved therapies to halt disease progression. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), widely used in type 2 diabetes (T2D) and obesity, demonstrate significant weight loss and glucose-lowering effects and have been shown to possess anti-inflammatory properties. Given the central role of inflammation and metabolic dysfunction in OA, this review examines the potential utility of GLP-1 RAs in OA management, focusing on both indirect effects, such as weight reduction, and possible direct effects on inflammatory pathways and cartilage preservation. Clinical studies suggest that GLP-1 RAs may benefit people with OA by reducing weight, improving glycemic control, and modulating inflammatory markers relevant to OA progression. Notable findings include significant weight loss and pain reduction in people with knee OA (KOA) treated with semaglutide in the STEP-9 trial. In other studies, GLP-1 RAs have shown potential to lower oxidative stress and pro-inflammatory cytokines, such as tumor necrosis factor (TNF-alpha) and interleukin (IL)-6, with reductions in OA-related pain and functional impairment observed in some cohorts. However, results vary, with some studies showing limited effects, potentially linked to the degree of weight loss achieved. Although some studies report variability in pain relief, likely influenced by the degree of weight loss achieved, GLP-1 RAs have shown overall promise in reducing both OA symptoms and markers associated with disease progression. This emerging evidence supports the utility of GLP-1 RAs as a potential disease-modifying option for OA, offering a dual benefit in metabolic and joint health. Future research should focus on establishing the long-term efficacy and safety and elucidating the mechanism by which GLP-1 RAs influence OA pathology. CI - (c) 2025 Pharmacotherapy Publications, Inc. FAU - Ryan, Mackenzie AU - Ryan M AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA. FAU - Megyeri, Saige AU - Megyeri S AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA. FAU - Nuffer, Wes AU - Nuffer W AUID- ORCID: 0000-0002-3355-4582 AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA. FAU - Trujillo, Jennifer M AU - Trujillo JM AUID- ORCID: 0000-0001-7898-8029 AD - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA. LA - eng PT - Journal Article PT - Review DEP - 20250220 PL - United States TA - Pharmacotherapy JT - Pharmacotherapy JID - 8111305 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Osteoarthritis/drug therapy MH - Weight Loss/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Animals MH - Hypoglycemic Agents/therapeutic use/pharmacology OTO - NOTNLM OT - GLP-1 receptor agonists OT - inflammation OT - osteoarthritis EDAT- 2025/02/21 06:22 MHDA- 2025/03/13 14:06 CRDT- 2025/02/21 01:53 PHST- 2025/01/15 00:00 [revised] PHST- 2024/11/16 00:00 [received] PHST- 2025/01/18 00:00 [accepted] PHST- 2025/03/13 14:06 [medline] PHST- 2025/02/21 06:22 [pubmed] PHST- 2025/02/21 01:53 [entrez] AID - 10.1002/phar.70005 [doi] PST - ppublish SO - Pharmacotherapy. 2025 Mar;45(3):177-186. doi: 10.1002/phar.70005. Epub 2025 Feb 20. PMID- 39976940 OWN - NLM STAT- MEDLINE DCOM- 20250417 LR - 20260908 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 143 IP - 4 DP - 2025 Apr 1 TI - Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy. PG - 304-314 LID - 10.1001/jamaophthalmol.2024.6555 [doi] AB - IMPORTANCE: Semaglutide, a glucagonlike peptide-1 receptor agonist (GLP-1RA), has recently been implicated in cases of nonarteritic anterior ischemic optic neuropathy (NAION), raising safety concerns in the treatment of type 2 diabetes (T2D). OBJECTIVE: To investigate the potential association between semaglutide and NAION in the Observational Health Data Sciences and Informatics (OHDSI) network. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective study across 14 databases (6 administrative claims and 8 electronic health records). Included were adults with T2D taking semaglutide, other GLP-1RA (dulaglutide, exenatide), or non-GLP-1RA medications (empagliflozin, sitagliptin, glipizide) from December 1, 2017, to December 31, 2023. The incidence proportion and rate of NAION were calculated. Association between semaglutide and NAION was assessed using 2 approaches: an active-comparator cohort design comparing new users of semaglutide with those taking other GLP-1RAs and non-GLP-1RA drugs, and a self-controlled case-series (SCCS) analysis to compare individuals' risks during exposure and nonexposure periods for each drug. The cohort design used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). Network-wide HR and IRR estimates were generated using a random-effects meta-analysis model. EXPOSURES: GLP-1RA and non-GLP-1RAs. MAIN OUTCOMES AND MEASURES: NAION under 2 alternative definitions based on diagnosis codes: one more inclusive and sensitive, the other more restrictive and specific. RESULTS: The study included 37.1 million individuals with T2D, including 810 390 new semaglutide users. Of the 43 620 new users of semaglutide in the Optum's deidentified Clinformatics Data Mart Database, 24 473 (56%) were aged 50 to 69 years, and 26 699 (61%) were female. The incidence rate of NAION was 14.5 per 100 000 person-years among semaglutide users. The HR for NAION among new users of semaglutide was not different compared with that of the non-GLP-1RAs using the sensitive NAION definition-empagliflozin (HR, 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR, 1.30; 95% CI, 0.56-3.01; P = .27), and glipizide (HR, 1.23; 95% CI, 0.66-2.28; P = .25). The risk was higher only compared with patients taking empagliflozin (HR, 2.27; 95% CI, 1.16-4.46; P = .02) using the specific definition. SCCS analysis of semaglutide exposure showed an increased risk of NAION (meta-analysis IRR, 1.32; 95% CI, 1.14-1.54; P < .001). CONCLUSIONS AND RELEVANCE: Results of this study suggest a modest increase in the risk of NAION among individuals with T2D associated with semaglutide use, smaller than that previously reported, and warranting further investigation into the clinical implications of this association. FAU - Cai, Cindy X AU - Cai CX AD - Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland. AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Hribar, Michelle AU - Hribar M AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland. AD - Casey Eye Institute, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland. FAU - Baxter, Sally AU - Baxter S AD - Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla. AD - Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla. FAU - Goetz, Kerry AU - Goetz K AD - National Eye Institute, National Institutes of Health, Bethesda, Maryland. FAU - Swaminathan, Swarup S AU - Swaminathan SS AD - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. FAU - Flowers, Alexis AU - Flowers A AD - Vanderbilt Eye Institute, Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee. AD - Vanderbilt Eye Institute, Department of Ophthalmology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Brown, Eric N AU - Brown EN AD - Vanderbilt Eye Institute, Department of Ophthalmology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Toy, Brian AU - Toy B AD - Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California. FAU - Xu, Benjamin AU - Xu B AD - Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California. FAU - Chen, John AU - Chen J AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. AD - Department of Neurology, Mayo Clinic, Rochester, Minnesota. FAU - Chen, Aiyin AU - Chen A AD - Casey Eye Institute, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland. FAU - Wang, Sophia AU - Wang S AD - Byers Eye Institute, Department of Ophthalmology, Stanford University, Palo Alto, California. FAU - Lee, Cecilia AU - Lee C AD - Department of Ophthalmology, University of Washington, Seattle. AD - Karalis Johnson Retina Center, Seattle, Washington. FAU - Leng, Theodore AU - Leng T AD - Byers Eye Institute at Stanford, Stanford University School of Medicine, Palo Alto, California. FAU - Ehrlich, Joshua R AU - Ehrlich JR AD - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor. AD - Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor. FAU - Barkmeier, Andrew AU - Barkmeier A AD - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota. FAU - Armbrust, Karen R AU - Armbrust KR AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota. FAU - Boland, Michael V AU - Boland MV AD - Department of Ophthalmology, Mass Eye and Ear and Harvard Medical School, Boston, Massachusetts. FAU - Dorr, David AU - Dorr D AD - Department of Medical Informatics & Clinical Epidemiology, Portland, Oregon. FAU - Boyce, Danielle AU - Boyce D AD - Johns Hopkins University School of Medicine, Baltimore, Maryland. AD - Tufts University School of Medicine, Boston, Massachusetts. FAU - Alshammari, Thamir AU - Alshammari T AD - Department of Clinical Practice, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia. AD - Pharmacy Practice Research Unit, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia. FAU - Swerdel, Joel AU - Swerdel J AD - Janssen Research and Development, Titusville, New Jersey. FAU - Suchard, Marc A AU - Suchard MA AD - Department of Biostatistics, UCLA School of Public Health, University of California, Los Angeles, Los Angeles. AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah. FAU - Schuemie, Martijn AU - Schuemie M AD - Janssen Research and Development, Titusville, New Jersey. AD - Department of Biostatistics, UCLA School of Public Health, University of California, Los Angeles, Los Angeles. FAU - Bu, Fan AU - Bu F AD - Department of Biostatistics, University of Michigan, Ann Arbor. FAU - Sena, Anthony G AU - Sena AG AD - Janssen Research and Development, Titusville, New Jersey. AD - Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands. FAU - Hripcsak, George AU - Hripcsak G AD - Department of Biomedical Informatics, Columbia University, New York, New York. FAU - Nishimura, Akihiko AU - Nishimura A AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. FAU - Nagy, Paul AU - Nagy P AD - Department of Biomedical Informatics and Data Science, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland. FAU - Falconer, Thomas AU - Falconer T AD - Department of Biomedical Informatics, Columbia University, New York, New York. FAU - DuVall, Scott L AU - DuVall SL AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah. AD - Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City. FAU - Matheny, Michael AU - Matheny M AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Nashville, Tennessee. FAU - Viernes, Benjamin AU - Viernes B AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah. FAU - O'Brien, William AU - O'Brien W AD - VA Informatics and Computing Infrastructure, US Department of Veterans Affairs, Salt Lake City, Utah. FAU - Zhang, Linying AU - Zhang L AD - Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St Louis, St Louis, Missouri. FAU - Martin, Benjamin AU - Martin B AD - Biomedical Informatics and Data Science, Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Westlund, Erik AU - Westlund E AD - Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. FAU - Mathioudakis, Nestoras AU - Mathioudakis N AD - Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. FAU - Fan, Ruochong AU - Fan R AD - Institute for Informatics, Data Science and Biostatistics, Department of Medicine, Washington University in St Louis, St Louis, Missouri. FAU - Wilcox, Adam AU - Wilcox A AD - Department of Medicine, Washington University in St Louis, St Louis, Missouri. FAU - Lai, Albert AU - Lai A AD - Department of Medicine, Washington University in St Louis, St Louis, Missouri. FAU - Stocking, Jacqueline C AU - Stocking JC AD - Department of Internal Medicine, University of California Davis, Sacramento. FAU - Takkouche, Sahar AU - Takkouche S AD - Department of Medicine, Division of Diabetes and Endocrinology, Vanderbilt University, Nashville, Tennessee. FAU - Lee, Lok Hin AU - Lee LH AD - Vanderbilt University School of Medicine, Nashville, Tennessee. FAU - Xie, Yangyiran AU - Xie Y AD - Vanderbilt University School of Medicine, Nashville, Tennessee. FAU - Humes, Izabelle AU - Humes I AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland. FAU - McCoy, David B AU - McCoy DB AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland. FAU - Adibuzzaman, Mohammad AU - Adibuzzaman M AD - Oregon Clinical and Translational Research Institute, Oregon Health & Science University, Portland. FAU - Areaux, Raymond G Jr AU - Areaux RG Jr AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota. FAU - Rojas-Carabali, William AU - Rojas-Carabali W AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. FAU - Brash, James AU - Brash J AD - IQVIA, Real World Solutions, Brighton, United Kingdom. FAU - Lee, David A AU - Lee DA AD - Ruiz Department of Ophthalmology and Visual Science, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston. FAU - Weiskopf, Nicole G AU - Weiskopf NG AD - Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland. FAU - Mawn, Louise AU - Mawn L AD - Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Agrawal, Rupesh AU - Agrawal R AD - Tan Tock Seng Hospital, Singapore. FAU - Morgan-Cooper, Hannah AU - Morgan-Cooper H AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California. FAU - Desai, Priya AU - Desai P AD - Stanford School of Medicine and Stanford Health Care, Palo Alto, California. FAU - Ryan, Patrick B AU - Ryan PB AD - Columbia University Irving Medical Center, New York, New York. AD - Johnson & Johnson, Horsham, Pennsylvania. LA - eng GR - R01 HL169954/HL/NHLBI NIH HHS/United States GR - K23 EY033440/EY/NEI NIH HHS/United States GR - T15 LM011271/LM/NLM NIH HHS/United States GR - R01 LM013426/LM/NLM NIH HHS/United States GR - K12 EY027720/EY/NEI NIH HHS/United States GR - R01 LM013990/LM/NLM NIH HHS/United States GR - K01 HL168222/HL/NHLBI NIH HHS/United States GR - R01 AG060942/AG/NIA NIH HHS/United States GR - UL1 TR002369/TR/NCATS NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Observational Study PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA Ophthalmol. 2025 Apr 1;143(4):315-316. doi: 10.1001/jamaophthalmol.2025.0005. PMID: 39976950 MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Databases, Factual MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Incidence MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology/diagnosis MH - Retrospective Studies MH - Semaglutide PMC - PMC11843465 COIS- Conflict of Interest Disclosures: Dr Cai reported receiving grants from Regeneron Pharmaceuticals outside the submitted work. Dr Baxter reported receiving grants from National Institutes of Health (NIH) and Research to Prevent Blindess, personal fees from Topcon, and nonfinancial support from Optomed outside the submitted work. Dr Swaminathan reported receiving personal fees from AbbVie, Elios Vision, and Lumata Health and grants from Heidelberg Engineering outside the submitted work. Dr Toy reported receiving advisory board fees from Alimera Sciences, Bausch & Lomb, and Regeneron outside the submitted work. Dr C. Lee reported receiving grants from NIH, Centers for Disease Control and Prevention, and the Alzheimer's Disease Drug Foundation outside the submitted work. Dr Leng reported receiving grants from Astellas and personal fees from Topcon, Astellas, Alcon, Boehringer Ingelheim, Iridex, Nanoscope, Regeneron, Genentech/Roche, Virtual Field, Aptitude Medical, Protagonist Therapeutics, Apellis, and Graybug outside the submitted work. Dr Boland reported receiving personal fees from Carl Zeiss Meditec, Topcon Healthcare, Allergan, and Janssen during the conduct of the study. Dr Swerdel reported being an employee and shareholder of Johnson & Johnson outside the submitted work. Dr Suchard reported receiving grants from NIH, US Department of Veterans Affairs, and the US Food and Drug Administration and personal fees from Johnson & Johnson outside the submitted work. Drs Schuemie and Sena reported being and employee and shareholder of Johnson & Johnson outside the submitted work. Dr DuVall reported receiving grants from Alnylam Pharmaceuticals, Astellas Pharma, AstraZeneca, Biodesix, Celgene Corp, Cerner Enviza, GSK, IQVIA, Janssen Pharmaceuticals, Moderna, Novartis International AG, and Parexel International Corp outside the submitted work. Dr Lai reported being a shareholder of Johnson & Johnson outside the submitted work. Dr Brash reported being employed by IQVIA outside the submitted work. Dr Mawn reported receiving grants from Research to Prevent Blindness and consultant fees from Amgen and Genentech. Dr Ryan reported being an employee and shareholder of Johnson & Johnson. No other disclosures were reported. EDAT- 2025/02/20 12:24 MHDA- 2025/04/17 12:26 PMCR- 2025/02/20 CRDT- 2025/02/20 11:33 PHST- 2025/04/17 12:26 [medline] PHST- 2025/02/20 12:24 [pubmed] PHST- 2025/02/20 11:33 [entrez] PHST- 2025/02/20 00:00 [pmc-release] AID - 2830475 [pii] AID - eoi240096 [pii] AID - 10.1001/jamaophthalmol.2024.6555 [doi] PST - ppublish SO - JAMA Ophthalmol. 2025 Apr 1;143(4):304-314. doi: 10.1001/jamaophthalmol.2024.6555. PMID- 39964295 OWN - NLM STAT- MEDLINE DCOM- 20260601 LR - 20260605 IS - 1744-764X (Electronic) IS - 1474-0338 (Linking) VI - 25 IP - 6 DP - 2026 Jun TI - Evaluating bowel obstruction and ileus events in patients on GLP-1 receptor agonists: a systematic review and meta-analysis. PG - 1057-1065 LID - 10.1080/14740338.2025.2465870 [doi] AB - INTRODUCTION: This research evaluated the association between glucagon-like peptide-1 receptor agonists (GLP-1 RA) and bowel obstruction or ileus. METHODS: We searched databases, including Medline, Embase, and Cochrane, for studies on adult patients treated with GLP-1 RA. We included randomized control trials (RCT), cohort, case-control studies, and case reports. We used the Cochrane Risk of Bias tool to evaluate the quality of RCTs and the Newcastle-Ottawa Scale for cohort and case-control studies. RESULTS: Out of 317 records identified, 14 studies were included in the systematic review. The meta-analysis included 6 studies with a combined total of 550,426 participants. The use of GLP-1 RA did not show an incremental risk of bowel obstruction or ileus compared to controls (OR 1.95, 95% CI 0.43-8.79). However, the studies had high heterogeneity (I(2) = 94%). A subgroup analysis by specific medication revealed that liraglutide was associated with a significantly high risk of bowel obstruction or ileus (OR 3.0, 95% CI 2.03-4.45; I(2) = 0%). CONCLUSIONS: GLP-1 receptor agonists do not significantly increase the risk of bowel obstruction or ileus. However, liraglutide is associated with a higher risk compared to semaglutide. Clinicians should remain aware of these rare events while recognizing the benefits of GLP-1 receptor agonists for glycemic control and cardiovascular health. PROSPERO REGISTRATION: CRD42024585971. FAU - Alfehaid, Lama AU - Alfehaid L AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Alyami, Majed AU - Alyami M AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Almohareb, Sumaya AU - Almohareb S AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Alshaya, Omar AU - Alshaya O AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Almutairi, Abdulaali AU - Almutairi A AD - Drug Safety and Risk Management, Saudi Food and Drug Authority, Riyadh, Saudi Arabia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250222 PL - England TA - Expert Opin Drug Saf JT - Expert opinion on drug safety JID - 101163027 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - *Ileus/chemically induced/epidemiology MH - *Intestinal Obstruction/chemically induced/epidemiology MH - *Liraglutide/adverse effects/administration & dosage MH - Randomized Controlled Trials as Topic MH - Semaglutide/administration & dosage/adverse effects OTO - NOTNLM OT - Bowel obstruction OT - glucagon-like peptide-1 receptor agonists OT - ileus OT - liraglutide OT - semaglutide EDAT- 2025/02/18 12:25 MHDA- 2026/06/01 12:38 CRDT- 2025/02/18 10:13 PHST- 2026/06/01 12:38 [medline] PHST- 2025/02/18 12:25 [pubmed] PHST- 2025/02/18 10:13 [entrez] AID - 10.1080/14740338.2025.2465870 [doi] PST - ppublish SO - Expert Opin Drug Saf. 2026 Jun;25(6):1057-1065. doi: 10.1080/14740338.2025.2465870. Epub 2025 Feb 22. PMID- 39963363 OWN - NLM STAT- MEDLINE DCOM- 20250218 LR - 20260127 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2025 DP - 2025 TI - Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors Improve Renal Resistive Index in Patients With Type 2 Diabetes: A 26-Week Prospective Observational Real-Life Study. PG - 8182211 LID - 10.1155/jdr/8182211 [doi] LID - 8182211 AB - Diabetic kidney disease (DKD) is one of the most life-threatening complications of diabetes and a leading cause of chronic kidney disease. Glucagon-like peptide 1 receptor agonists (GLP1-RAs) or sodium-glucose cotransporter 2 inhibitors (SGLT2is) appear to improve renal outcome in patients with Type 2 diabetes (T2D). In this context, the renal resistive index (RRI) is a useful doppler measure to study DKD and predict its evolution. The aim of this work was to study the effect of treatment with GLP1-RA or SGLT2i on RRI and the relationship between RRI and glycometabolic parameters. One hundred forty-five patients with T2D were enrolled in the study and treated for 26 weeks with once-weekly GLP1-RA (38 patients with dulaglutide and 39 with semaglutide), SGLT2i (40 patients), or other therapies (28 control patients). Clinical, anthropometric, and hematochemical parameters and RRI were measured at baseline (T0) and after 6 months of treatment (T6). Changes at 6 months were studied and compared by treatment group. Patients were predominantly male (58.6%), overweight (93.0%) or frankly obese (60.0%), with hypertension (90.0%) and high (> 0.64) or pathological (> 0.7) RRI values (82.0% or 37.0%, respectively). At baseline, RRI correlated positively with age, fasting blood glucose, glycated hemoglobin (HbA1c), triglycerides, and albuminuria and negatively with estimated-glomerular filtration rate (e-GFR). At T6, patients treated with either GLP1-RA or SGLT2i showed a significant improvement in RRI but not in albuminuria or e-GFR, compared with homologous at baseline. In particular, RRI normalized in 32% and 30% of patients on therapy with GLP1-RA and SGLT2i, respectively, while remaining almost unchanged in controls. Notably, the RRI improvement was independent of age, gender, diabetes duration, and changes in BMI, waist circumference, HbA1c, and e-GFR. In conclusion, RRI can be used to detect early kidney damage and follow the evolution of DKD. GLP1-RA and SGLT2i improve RRI, demonstrating benefits on cardiovascular risk and renal outcomes. CI - Copyright (c) 2025 Alfredo Vozza et al. Journal of Diabetes Research published by John Wiley & Sons Ltd. FAU - Vozza, Alfredo AU - Vozza A AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Volpe, Sara AU - Volpe S AUID- ORCID: 0000-0002-6831-0457 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Custodero, Carlo AU - Custodero C AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Colaianni, Valentina AU - Colaianni V AUID- ORCID: 0009-0004-7322-7705 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Lavarra, Valentina AU - Lavarra V AUID- ORCID: 0009-0007-6995-4127 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Triggiani, Domenico AU - Triggiani D AUID- ORCID: 0009-0007-9619-8726 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Crudele, Lucilla AU - Crudele L AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Bergamasco, Alessandro AU - Bergamasco A AUID- ORCID: 0009-0008-6387-0560 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Antonica, Gianfranco AU - Antonica G AUID- ORCID: 0009-0009-0693-6751 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Tortorella, Cosimo AU - Tortorella C AUID- ORCID: 0000-0002-4504-9313 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. FAU - Piazzolla, Giuseppina AU - Piazzolla G AUID- ORCID: 0000-0003-3221-6562 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Bari, Italy. LA - eng PT - Journal Article PT - Observational Study DEP - 20250210 PL - United States TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 0 (Blood Glucose) RN - WTT295HSY5 (dulaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/blood/complications/drug therapy MH - *Diabetic Nephropathies/blood/drug therapy/etiology/physiopathology MH - Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Glycated Hemoglobin MH - *Kidney/blood supply/diagnostic imaging/drug effects/physiopathology MH - Prospective Studies MH - *Sodium-Glucose Transporter 2 Inhibitors/pharmacology/therapeutic use MH - Treatment Outcome MH - *Vascular Resistance/drug effects MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC11832268 OTO - NOTNLM OT - Type 2 diabetes OT - chronic kidney disease OT - diabetic kidney disease OT - glucagon-like peptide 1 receptor agonists OT - renal Doppler ultrasound OT - renal damage OT - renal hemodynamic OT - renal resistive index OT - sodium-glucose cotransporter 2 inhibitors COIS- The authors declare no conflicts of interest. EDAT- 2025/02/18 06:21 MHDA- 2025/02/18 06:22 PMCR- 2025/02/10 CRDT- 2025/02/18 04:18 PHST- 2024/05/23 00:00 [received] PHST- 2025/01/22 00:00 [accepted] PHST- 2025/02/18 06:22 [medline] PHST- 2025/02/18 06:21 [pubmed] PHST- 2025/02/18 04:18 [entrez] PHST- 2025/02/10 00:00 [pmc-release] AID - 10.1155/jdr/8182211 [doi] PST - epublish SO - J Diabetes Res. 2025 Feb 10;2025:8182211. doi: 10.1155/jdr/8182211. eCollection 2025. PMID- 39954057 OWN - NLM STAT- MEDLINE DCOM- 20250916 LR - 20260127 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 9 DP - 2025 Sep TI - Different formulations of semaglutide and oxidative stress in subjects with type 2 diabetes and MASLD: an open-label, real-life study. PG - 1429-1437 LID - 10.1007/s00592-025-02466-7 [doi] AB - AIM: Semaglutide exerts metabolic effects and cardiovascular protection in type 2 diabetes (T2D), also acting on hepatic steatosis and inflammation. No data are, so far, available on the effect of semaglutide on oxidative stress, neither a comparison of injective (InjS) and oral (OrS) formulations has been performed in subjects with T2D and liver steatosis. METHODS: In a real-life, open label, prospective study we compared standard doses of InjS and OrS in targeting liver inflammation and fibrosis and systemic markers of inflammation and oxidative stress by consecutively prescribing InjS or OrS formulation in a 2:1 ratio to sixty T2D + MASLD subjects (T0), observing them for 6 months (T1). Anthropometry, biochemistry and transient elastography (TE) data were collected; hormones, inflammatory cytokines and peroxidation products were measured. RESULTS: At baseline, InjS and OrS subjects were similar, except for waist circumference, liver enzymes and Controlled Attenuation Parameter (CAP), a measure of liver steatosis (InjS > OrS, all p < 0.05). Differences emerged in T0-T1 variation between the formulations in HbA1c, lipid profile, blood pressure. CAP significantly decreased only in InjS. GLP-1 quite similarly increased; insulin, glucagon and GIP did not vary. InjS and OrS did not modify TNFalpha, IL-10 (an anti-inflammatory cytokine) and MCP-1, while IL-18 was reduced only by InjS. When exploring oxidative stress, AGEs were unaffected, Thiobarbituric acid reactive substances decreased in InjS, 4-Hydroxynonenal was reduced in OrS. CONCLUSION: In T2D + MASLD subjects, InjS, better than OrS, improves metabolic control; a significant reduction of IL-18 by InjS, and a mild anti-oxidative effect of both formulations are reported for the first time. CI - (c) 2025. Springer-Verlag Italia S.r.l., part of Springer Nature. FAU - Petralli, Giovanni AU - Petralli G AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Zoppo, Alice Del AU - Zoppo AD AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Rovera, Chiara AU - Rovera C AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Raggi, Francesco AU - Raggi F AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Salvati, Antonio AU - Salvati A AD - Hepatology Unit, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. FAU - Moriconi, Diego AU - Moriconi D AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Distaso, Mariarosaria AU - Distaso M AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. FAU - Brunetto, Maurizia Rossana AU - Brunetto MR AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Solini, Anna AU - Solini A AUID- ORCID: 0000-0002-7855-8253 AD - Department of Surgical Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy. anna.solini@unipi.it. AD - Department of Surgical Medical Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, Pisa, 56126, Italy. anna.solini@unipi.it. LA - eng PT - Journal Article DEP - 20250215 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Acta Diabetol. 2025 Oct;62(10):1829. doi: 10.1007/s00592-025-02482-7. PMID: 40105914 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism/complications MH - *Oxidative Stress/drug effects MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Prospective Studies MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Adult MH - Administration, Oral MH - *Fatty Liver/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Injective semaglutide OT - MASLD OT - Oral semaglutide OT - Oxidative stress COIS- Declarations. Conflict of interest: The authors declare no competing financial interest related to the present manuscript. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. EDAT- 2025/02/16 01:30 MHDA- 2025/09/16 06:36 CRDT- 2025/02/15 11:13 PHST- 2024/11/12 00:00 [received] PHST- 2025/02/01 00:00 [accepted] PHST- 2025/09/16 06:36 [medline] PHST- 2025/02/16 01:30 [pubmed] PHST- 2025/02/15 11:13 [entrez] AID - 10.1007/s00592-025-02466-7 [pii] AID - 10.1007/s00592-025-02466-7 [doi] PST - ppublish SO - Acta Diabetol. 2025 Sep;62(9):1429-1437. doi: 10.1007/s00592-025-02466-7. Epub 2025 Feb 15. PMID- 39950222 OWN - NLM STAT- MEDLINE DCOM- 20250507 LR - 20260924 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Alternative dosing regimens of GLP-1 receptor agonists may reduce costs and maintain weight loss efficacy. PG - 2251-2258 LID - 10.1111/dom.16229 [doi] AB - AIMS: To discover alternative dosing regimens of incretin mimetics that simultaneously reduce costs and maintain weight loss efficacy. As a secondary objective, we used our results to explore how allocating a limited incretin mimetics budget could affect public health on a national scale. MATERIALS AND METHODS: We used mathematical modelling and simulation of semaglutide and tirzepatide to investigate dosing regimens which have not yet been studied clinically. For semaglutide, we used a recent pharmacokinetic (PK) and pharmacodynamic (PD) model. For tirzepatide, we used a recent PK model and modelled PD by reparameterizing the semaglutide PD model to fit tirzepatide clinical data. RESULTS: Reducing dose frequency does not commensurately reduce weight loss. For example, merely switching from one dose per week (q1wk) to one dose every 2 weeks (q2wk) maintains roughly 75% of the weight loss. Furthermore, if the decrease in dose frequency involves an appropriate increase in dose size, then approximately 100% of the weight loss is maintained. In addition, we compared offering incretin mimetics to (1) a fraction of obese US adults with q1wk dosing versus (2) twice as many obese US adults with q2wk dosing. Though scenarios (1) and (2) require the same budget, our analysis suggests that (2) reduces national obesity and mortality to a much greater degree. CONCLUSION: Our study highlights the potential utility of alternative dosing regimens of incretin mimetics. Compared with standard once-weekly dosing, costs can be halved and weight loss maintained. These cost-saving results have implications for patients, physicians, insurers, and governments. CI - (c) 2025 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Cengiz, Anil AU - Cengiz A AUID- ORCID: 0009-0000-3165-7329 AD - Department of Mathematics, University of Utah, Salt Lake City, Utah, USA. FAU - Wu, Calvin C AU - Wu CC AUID- ORCID: 0000-0001-7758-1366 AD - Tono Health, Brooklyn, New York, USA. FAU - Lawley, Sean D AU - Lawley SD AUID- ORCID: 0000-0003-2208-026X AD - Department of Mathematics, University of Utah, Salt Lake City, Utah, USA. LA - eng GR - DMS-1944574/National Science Foundation/ GR - DMS-2325258/National Science Foundation/ PT - Journal Article DEP - 20250214 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/economics/pharmacokinetics/analogs & derivatives MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - Tirzepatide/administration & dosage MH - *Obesity/drug therapy/economics MH - *Hypoglycemic Agents/administration & dosage/economics MH - *Incretins/administration & dosage/economics MH - Drug Administration Schedule MH - Drug Costs MH - Cost-Benefit Analysis MH - *Anti-Obesity Agents/administration & dosage/economics MH - Treatment Outcome MH - Dose-Response Relationship, Drug MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11885104 OTO - NOTNLM OT - GIP OT - GLP-1 OT - cost-effectiveness OT - pharmacodynamics OT - pharmacokinetics OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2025/02/14 06:20 MHDA- 2025/03/07 00:21 PMCR- 2025/03/07 CRDT- 2025/02/14 04:33 PHST- 2025/01/23 00:00 [revised] PHST- 2024/11/27 00:00 [received] PHST- 2025/01/23 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/02/14 06:20 [pubmed] PHST- 2025/02/14 04:33 [entrez] PHST- 2025/03/07 00:00 [pmc-release] AID - DOM16229 [pii] AID - 10.1111/dom.16229 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):2251-2258. doi: 10.1111/dom.16229. Epub 2025 Feb 14. PMID- 39947393 OWN - NLM STAT- MEDLINE DCOM- 20250509 LR - 20260127 IS - 1524-4733 (Electronic) IS - 1098-3015 (Linking) VI - 28 IP - 5 DP - 2025 May TI - Newer Glucagon-Like Peptide-1 Receptor Agonists Are Associated With Improved Glycemic Control in US Adults With Type 2 Diabetes: A Population-Level Time Series Analysis. PG - 712-719 LID - S1098-3015(25)00059-2 [pii] LID - 10.1016/j.jval.2025.01.018 [doi] AB - OBJECTIVES: The population-level impact of newer glucagon-like peptide-1 receptor agonist (GLP-1 RA) treatments on patients with type 2 diabetes remains unclear. Therefore, this study investigated the association of newer GLP-1 RAs with population-level diabetes-related outcomes in US adults with type 2 diabetes. METHODS: This was a noninterventional, retrospective analysis of administrative insurance claims data obtained from Optum's deidentified Clinformatics(R) Data Mart Database between January 2004 and December 2022. Individual patient data were aggregated into monthly time series at the population level. Associations between the proportion of patients on newer GLP-1 RAs of interest (dulaglutide, once-weekly or oral semaglutide, and tirzepatide) and average hemoglobin A1c (HbA1c), HbA1c <7.0%, and HbA1c <8.0% were assessed using time series regressions. Time-based trends in population-level outcomes were assessed using interrupted time series analyses. All analyses were adjusted for potential confounders. RESULTS: Time series regression analyses demonstrated that a higher proportion of patients taking newer GLP-1 RAs was associated with a lower average HbA1c and a higher proportion of patients with HbA1c <7.0% (after 5 months of treatment) and <8.0% (after 2 months of treatment). Results from the interrupted time series analyses demonstrated that population-level glycemic control has been improving since the first newer GLP-1 RA (dulaglutide) was approved. This trend has persisted, even after the COVID-19 emergency declaration. CONCLUSIONS: A higher percentage of patients receiving newer GLP-1 RAs was associated with significantly improved population-level glycemic control. The newer GLP-1 RA period displayed improved population-level glycemic control compared with the older GLP-1 RA period. CI - Copyright (c) 2025. Published by Elsevier Inc. FAU - Lv, Lei AU - Lv L AD - Novo Nordisk Inc, Plainsboro, NJ, USA. Electronic address: lzlv@novonordisk.com. FAU - Wang, Yan AU - Wang Y AD - Analysis Group, Inc, Los Angeles, CA, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Noone, Josh AU - Noone J AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Alvarez, Sara AU - Alvarez S AD - Novo Nordisk Inc, Plainsboro, NJ, USA. FAU - Zhang, Yuehan AU - Zhang Y AD - Analysis Group, Inc, New York, NY, USA. FAU - Song, Yan AU - Song Y AD - Analysis Group, Inc, Boston, MA, USA. FAU - Rotroff, Daniel M AU - Rotroff DM AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, OH, USA; Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250211 PL - United States TA - Value Health JT - Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research JID - 100883818 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - United States/epidemiology MH - Glycated Hemoglobin/analysis MH - *Glycemic Control/methods MH - Aged MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/administration & dosage MH - Adult MH - Blood Glucose/drug effects MH - Tirzepatide/therapeutic use/administration & dosage MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - glycemic control OT - interrupted time series OT - time series analysis OT - type 2 diabetes COIS- Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section. EDAT- 2025/02/14 00:23 MHDA- 2025/05/09 12:37 CRDT- 2025/02/13 19:31 PHST- 2024/07/10 00:00 [received] PHST- 2025/01/15 00:00 [revised] PHST- 2025/01/24 00:00 [accepted] PHST- 2025/05/09 12:37 [medline] PHST- 2025/02/14 00:23 [pubmed] PHST- 2025/02/13 19:31 [entrez] AID - S1098-3015(25)00059-2 [pii] AID - 10.1016/j.jval.2025.01.018 [doi] PST - ppublish SO - Value Health. 2025 May;28(5):712-719. doi: 10.1016/j.jval.2025.01.018. Epub 2025 Feb 11. PMID- 39930946 OWN - NLM STAT- MEDLINE DCOM- 20250211 LR - 20260810 IS - 1752-8062 (Electronic) IS - 1752-8054 (Print) IS - 1752-8054 (Linking) VI - 18 IP - 2 DP - 2025 Feb TI - Once-Weekly Semaglutide Versus Once-Daily Liraglutide for Weight Loss in Adults: A Meta-Analysis of Randomized Controlled Trials. PG - e70127 LID - 10.1111/cts.70127 [doi] LID - e70127 AB - The effectiveness of glucagon-like peptide-1 receptor agonists in facilitating weight loss among patients with diabetes is widely recognized. However, there are limited data available on the relative effectiveness and safety of once-weekly semaglutide versus once-daily liraglutide. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) identified through a comprehensive search of the Cochrane Library, PubMed, and ScienceDirect databases from inception until July 2024. Statistical analysis was conducted using R version 4.4.1 with the "meta" package, employing a random effects model. Three RCTs with a total of 922 patients were included in our meta-analysis. The results indicated that OW semaglutide significantly reduced body weight (WMD: -4.55; 95% CI: -6.43, -2.67, p < 0.01), HbA1c (WMD: -0.46; 95% CI: -0.84, -0.08; p = 0.02), and fasting plasma glucose levels (WMD: -1.23; 95% CI: -1.51, -0.95; p < 0.01) in comparison to OD liraglutide. The risk of severe adverse effects (OR, 1.66; 95% CI, 0.53-5.16; p = 0.38) and gastrointestinal adverse effects (OR, 1.84; 95% CI, 0.82-4.14; p = 0.14) was comparable between both groups. Once-weekly semaglutide therapy results in a more pronounced loss in body weight, HbA1c, and fasting glucose levels compared to once-daily liraglutide. CI - (c) 2025 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Hashmi, Tallal Mushtaq AU - Hashmi TM AUID- ORCID: 0009-0006-6355-3907 AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Ahmed, Mushood AU - Ahmed M AUID- ORCID: 0000-0001-9872-8224 AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Haider, Ali AU - Haider A AUID- ORCID: 0000-0002-3464-4889 AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Naseem, Salman AU - Naseem S AUID- ORCID: 0009-0003-8755-6799 AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Jafar, Uzair AU - Jafar U AUID- ORCID: 0000-0003-0737-7444 AD - Department of Cardiology, King Edward Medical University, Lahore, Pakistan. FAU - Hussain, Munir AU - Hussain M AUID- ORCID: 0009-0001-8883-3810 AD - Department of Medicine, Rawalpindi Medical University, Rawalpindi, Pakistan. FAU - Iqbal, Javed AU - Iqbal J AUID- ORCID: 0000-0003-2627-685X AD - Hamad Medical Corporation, Doha, Qatar. FAU - Ali, Waqar AU - Ali W AUID- ORCID: 0009-0008-6727-3819 AD - Department of Endocrinology, King Edward Medical University, Lahore, Pakistan. FAU - Ahmed, Raheel AU - Ahmed R AUID- ORCID: 0000-0003-2814-7314 AD - Department of Cardiology, Royal Brompton Hospital, London, UK. AD - National Heart and Lung Institute, Imperial College London, London, UK. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review PL - United States TA - Clin Transl Sci JT - Clinical and translational science JID - 101474067 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - *Liraglutide/administration & dosage/adverse effects MH - Randomized Controlled Trials as Topic MH - *Weight Loss/drug effects MH - Drug Administration Schedule MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Glycated Hemoglobin/analysis MH - Blood Glucose/drug effects/analysis MH - Treatment Outcome MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11811509 OTO - NOTNLM OT - diabetes OT - metabolism OT - meta-analysis OT - obesity OT - weight loss COIS- The authors declare no conflicts of interest. EDAT- 2025/02/11 06:21 MHDA- 2025/02/11 06:22 PMCR- 2025/02/11 CRDT- 2025/02/11 03:44 PHST- 2024/12/05 00:00 [revised] PHST- 2024/11/03 00:00 [received] PHST- 2024/12/17 00:00 [accepted] PHST- 2025/02/11 06:22 [medline] PHST- 2025/02/11 06:21 [pubmed] PHST- 2025/02/11 03:44 [entrez] PHST- 2025/02/11 00:00 [pmc-release] AID - CTS70127 [pii] AID - 10.1111/cts.70127 [doi] PST - ppublish SO - Clin Transl Sci. 2025 Feb;18(2):e70127. doi: 10.1111/cts.70127. PMID- 39922760 OWN - NLM STAT- MEDLINE DCOM- 20250222 LR - 20260518 IS - 1871-403X (Print) IS - 1871-403X (Linking) VI - 19 IP - 1 DP - 2025 Jan-Feb TI - Semaglutide: Nonarteritic Anterior Ischemic Optic Neuropathy in the FDA adverse event reporting system - A disproportionality analysis. PG - 77-79 LID - S1871-403X(25)00017-1 [pii] LID - 10.1016/j.orcp.2025.01.011 [doi] AB - Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used for type 2 diabetes (T2D) and approved for obesity by the FDA in 2022 and in Europe in 2023. Its increasing use has raised concerns about access for T2D patients and potential adverse events (AE), such as Nonarteritic Anterior Ischemic Optic Neuropathy (NAION). This study investigates the association between semaglutide and these AE using the FDA Adverse Event Reporting System (FAERS). We conducted a disproportionality analysis using FAERS data. AE were identified using MedDRA Preferred Terms (PTs) and related terms. OpenVigil 2.1 was used for data extraction and analysis. This system is a spontaneous safety surveillance database for drugs. The participants are patients who reported AE related to GLP-1 receptor agonists in the FAERS database from January 1, 2004, to September 30, 2024. Reporting Odds Ratios (ROR) and Proportional Reporting Ratios (PRR) were calculated to assess the association between GLP-1 receptor agonists and the AE. Semaglutide showed a significant ROR and PRR for NAION, suggesting a stronger association compared to other GLP-1 receptor agonists. The findings suggest a disproportionate reporting signal for semaglutide and NAION. The mechanisms behind these associations are not fully understood but may involve effects on the hypothalamus and vascular health. Further research is necessary to confirm these findings ensure the safe use of semaglutide, given the potential risk associated with this rare but severe adverse event. CI - Copyright (c) 2025 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved. FAU - Azab, Marina AU - Azab M AD - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, Milan 20156, Italy. Electronic address: marina.azab@marionegri.it. FAU - Pasina, Luca AU - Pasina L AD - Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, Milan 20156, Italy. LA - eng PT - Journal Article DEP - 20250207 PL - Netherlands TA - Obes Res Clin Pract JT - Obesity research & clinical practice JID - 101303911 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Databases, Factual MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects MH - *Optic Neuropathy, Ischemic/chemically induced/epidemiology MH - United States MH - United States Food and Drug Administration MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Nonarteritic Anterior Ischemic Optic Neuropathy OT - Obesity OT - Semaglutide COIS- Declaration of Competing Interest The authors have no conflicts of interest that are directly relevant to the content of this article. EDAT- 2025/02/09 06:20 MHDA- 2025/02/23 00:42 CRDT- 2025/02/08 21:57 PHST- 2025/01/30 00:00 [received] PHST- 2025/01/31 00:00 [accepted] PHST- 2025/02/23 00:42 [medline] PHST- 2025/02/09 06:20 [pubmed] PHST- 2025/02/08 21:57 [entrez] AID - S1871-403X(25)00017-1 [pii] AID - 10.1016/j.orcp.2025.01.011 [doi] PST - ppublish SO - Obes Res Clin Pract. 2025 Jan-Feb;19(1):77-79. doi: 10.1016/j.orcp.2025.01.011. Epub 2025 Feb 7. PMID- 39921267 OWN - NLM STAT- MEDLINE DCOM- 20250228 LR - 20260917 IS - 1744-8417 (Electronic) IS - 1744-6651 (Linking) VI - 20 IP - 2 DP - 2025 Mar TI - Oral versus subcutaneous semaglutide weight loss outcomes after two years among patients with type 2 diabetes in a real-world database. PG - 163-168 LID - 10.1080/17446651.2025.2462100 [doi] AB - BACKGROUND: Interest has grown in glucagon-like peptide-1 receptor-agonist (GLP-1 RA) semaglutide long-term outcomes. This retrospective cohort study compared effectiveness of oral and subcutaneous semaglutide for weight loss outcomes in adults with type 2 diabetes (T2D) over a 2-year treatment period. RESEARCH DESIGN AND METHODS: Weight loss was evaluated through mean percentage change from baseline, proportion achieving at least 5% weight loss and at least 10% weight loss comparing subcutaneous (n = 310) versus oral users (n = 57) and by age group. RESULTS: Subcutaneous users experienced a mean percentage weight loss of 7.5% (16.7 pounds) with 58.7% and 32.9% achieving >/=5% and >/=10% loss, respectively. Oral users lost 4.4% (8.7 pounds) with 50.9% and 17.5% achieving >/=5% and >/=10% loss, respectively. Significant differences existed between formulations in mean percentage weight change (p-value <0.01) and proportion achieving >/=10% loss (p-value = 0.03), but not in proportion achieving >/=5% loss (p-value = 0.34). Outcomes differed by age within oral semaglutide (p-value = 0.02). Regression analyses adjusted for confounders yielded similar findings. CONCLUSION: Subcutaneous users achieved superior weight loss compared to oral users. Older oral users experienced better weight loss compared to younger users. However, no differences were observed between subcutaneous users. FAU - Kwon, Jimmy AU - Kwon J AD - Department of Statistics, UC Irvine Donald Bren School of Information and Computer Sciences, Irvine, USA. FAU - Thiara, Diana AU - Thiara D AD - Department of Medicine, UCSF School of Medicine, San Francisco, CA, USA. FAU - Watanabe, Jonathan H AU - Watanabe JH AD - Department of Clinical Pharmacy, UCSF School of Pharmacy, San Francisco, CA, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250207 PL - England TA - Expert Rev Endocrinol Metab JT - Expert review of endocrinology & metabolism JID - 101278293 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Weight Loss/drug effects MH - Retrospective Studies MH - Administration, Oral MH - Injections, Subcutaneous MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Treatment Outcome MH - Databases, Factual MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP OT - Type 2 diabetes OT - long-term OT - semaglutide OT - weight loss EDAT- 2025/02/08 19:52 MHDA- 2025/02/28 18:22 CRDT- 2025/02/08 01:52 PHST- 2025/02/28 18:22 [medline] PHST- 2025/02/08 19:52 [pubmed] PHST- 2025/02/08 01:52 [entrez] AID - 10.1080/17446651.2025.2462100 [doi] PST - ppublish SO - Expert Rev Endocrinol Metab. 2025 Mar;20(2):163-168. doi: 10.1080/17446651.2025.2462100. Epub 2025 Feb 7. PMID- 39919872 OWN - NLM STAT- MEDLINE DCOM- 20250506 LR - 20260614 IS - 1558-4410 (Electronic) IS - 0889-8529 (Linking) VI - 54 IP - 1 DP - 2025 Mar TI - Treatment of Type 2 Diabetes in Patients with Obesity: A Review. PG - 163-173 LID - S0889-8529(24)00084-7 [pii] LID - 10.1016/j.ecl.2024.10.004 [doi] AB - Type 2 diabetes and obesity have some overlapping pathophysiology. This has allowed for the creation of therapies which are highly effective in treating both conditions. Weekly subcutaneous incretin agonists are preferred agents as they provide significant improvement in glycemic parameters, weight, and other comorbidities, like heart failure and reduce major adverse cardiovascular event. Bariatric surgery continues to show the most durable benefits for patients with both type 2 diabetes mellitus and obesity and should be considered in patients who are unable to meet goals with pharmacotherapy and lifestyle. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Guzman, Heidi AU - Guzman H AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Columbia University College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA. FAU - Hasan, Leen Z AU - Hasan LZ AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Columbia University College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA. FAU - Reid, Tirissa J AU - Reid TJ AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Columbia University College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA. Electronic address: tjr2122@cumc.columbia.edu. LA - eng PT - Journal Article PT - Review DEP - 20241112 PL - United States TA - Endocrinol Metab Clin North Am JT - Endocrinology and metabolism clinics of North America JID - 8800104 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/therapy/drug therapy MH - *Obesity/complications/therapy/surgery MH - Bariatric Surgery MH - *Hypoglycemic Agents/therapeutic use MH - Incretins/therapeutic use OTO - NOTNLM OT - Obesity OT - Pharmacotherapy OT - Semaglutide OT - Tirzepatide OT - Treatment OT - Type 2 diabetes mellitus COIS- Disclosure None of the authors have any commercial or financial conflicts of interest or funding sources to disclose. EDAT- 2025/02/08 00:30 MHDA- 2025/02/08 00:31 CRDT- 2025/02/07 21:20 PHST- 2025/02/08 00:31 [medline] PHST- 2025/02/08 00:30 [pubmed] PHST- 2025/02/07 21:20 [entrez] AID - S0889-8529(24)00084-7 [pii] AID - 10.1016/j.ecl.2024.10.004 [doi] PST - ppublish SO - Endocrinol Metab Clin North Am. 2025 Mar;54(1):163-173. doi: 10.1016/j.ecl.2024.10.004. Epub 2024 Nov 12. PMID- 39910752 OWN - NLM STAT- MEDLINE DCOM- 20250306 LR - 20260810 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Comparison of the efficacy and safety of GLP-1 receptor agonists on cardiovascular events and risk factors: A review and network meta-analysis. PG - 1735-1751 LID - 10.1111/dom.16228 [doi] AB - OBJECTIVE: This study aims to systematically evaluate and perform a systematic review and network meta-analysis comparing the comprehensive cardiovascular protective effects of various glucagon-like peptide-1 receptor agonists (GLP-1RAs), focusing on cardiovascular events and risk factors. METHODS: We searched PubMed, Embase, Cochrane Library and Web of Science from inception to December 15, 2024. Included studies were published randomized controlled trials (RCTs) comparing GLP-1RAs to placebo or other GLP-1RAs. Missing data were standardized, and network meta-analysis was performed using Stata 17.0. Study heterogeneity, publication bias and evidence quality were assessed using the Cochrane Risk of Bias tool and Confidence in Network Meta-Analysis (CINeMA). RESULTS: As of December 15, 2024, a total of 18 313 articles were retrieved. Based on the inclusion and exclusion criteria, 156 high-quality studies were included, incorporating 144 782 patients and 14 different GLP-1RAs. The network meta-analysis demonstrated low heterogeneity, ensuring the reliability of the results. Comprehensive analysis revealed the following: Efpeglenatide was the most effective in reducing major adverse cardiovascular events. Oral semaglutide shows more significant advantages in reducing all-cause mortality and cardiovascular mortality. Orforglipron excelled in glycaemic control and weight reduction. SC-Semaglutide showed the greatest efficacy in lowering both systolic blood pressure and diastolic blood pressure, Liraglutide showed the greatest efficacy in lowering total cholesterol, Noiiglutide in triglycerides and Taspoglutide in low-density lipoprotein cholesterol, but no GLP-1RAs in high-density lipoprotein cholesterol. GLP-1RAs did not significantly increase the incidence of adverse events, but Orforglipron and Taspoglutide significantly increased the incidence of gastrointestinal adverse events compared with placebo. CONCLUSION: This study compared the cardiovascular benefits of different GLP-1RAs, including reductions in cardiovascular events and improvements in multiple cardiovascular risk factors. However, due to limitations in the quantity and quality of the included studies, the conclusions should be interpreted with caution. Future large-scale, high-quality clinical trials are needed to validate these findings and further optimize comprehensive cardiovascular management strategies for patients. CI - (c) 2025 John Wiley & Sons Ltd. FAU - An, Xuedong AU - An X AUID- ORCID: 0000-0002-2787-1645 AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Sun, WenJie AU - Sun W AUID- ORCID: 0009-0009-0861-2443 AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Wen, Zhige AU - Wen Z AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Duan, LiYun AU - Duan L AD - Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Zhang, YueHong AU - Zhang Y AD - Fangshan Hospital Beijing University of Chinese Medicine, Beijing, China. FAU - Kang, Xiaomin AU - Kang X AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Ji, Hangyu AU - Ji H AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Sun, Yuting AU - Sun Y AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Jiang, Linlin AU - Jiang L AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Zhao, Xuefei AU - Zhao X AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Gao, Qing AU - Gao Q AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. FAU - Lian, Fengmei AU - Lian F AUID- ORCID: 0000-0003-2222-7487 AD - Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China. LA - eng GR - 82305205/National Natural Science Foundation of China/ GR - CACM-2023-QNRC2-A05/Young Elite Scientists Sponsorship Program by CACM/ GR - HLCMHPP2023084/High Level Chinese Medical Hospital Promotion Project/ GR - GAMHH9324001/Escort Project of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine/ PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20250205 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Heart Disease Risk Factors MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - Treatment Outcome OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular events OT - cardiovascular risk factors OT - network meta-analysis OT - systematic review EDAT- 2025/02/06 06:20 MHDA- 2025/03/07 00:21 CRDT- 2025/02/06 00:42 PHST- 2025/01/07 00:00 [revised] PHST- 2024/09/11 00:00 [received] PHST- 2025/01/21 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/02/06 06:20 [pubmed] PHST- 2025/02/06 00:42 [entrez] AID - 10.1111/dom.16228 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):1735-1751. doi: 10.1111/dom.16228. Epub 2025 Feb 5. PMID- 39908666 OWN - NLM STAT- MEDLINE DCOM- 20250505 LR - 20260127 IS - 1748-605X (Electronic) IS - 1748-6041 (Linking) VI - 20 IP - 3 DP - 2025 Mar 18 TI - Chitosan hydrochloride coated and nonionic surfactant modified niosomes: a better way for oral administration of semaglutide. LID - 10.1088/1748-605X/adb2cf [doi] AB - Diabetes is now a global chronic disease, with the number of people with diabetes expected to reach 643 million by the end of 2030. Semaglutide, a human glucagon-like peptide-1 (GLP-1) analogue with 94% similarity to human GLP-1, can promote insulin secretion and repress glucagon secretion in a glucose concentration-dependent manner, resulting in substantial improvement of blood glucose levels and reducing the risk of hypoglycemia in patients with type 2 diabetes. To improve the absorption efficiency of semaglutide in oral delivery, we developed chitosan hydrochloride-coated and nonionic surfactant-modified niosomes (CS.HCL-NSPEs-NIO) as a new way to encapsulate it. The results showed that CS.HCL-NSPEs-NIO could efficiently penetrate the cell junctions in the intestinal endothelium and therefore promote drug absorbance. In addition, gastrointestinal distribution studies revealed that CS. HCL-NSPEs-NIO could stay in the intestine for more than 4 h, thus allowing for long-term glucose regulation. Effective reduction of blood glucose levels and weight loss were observed in db/db mice while no toxicity was detected in major organs. On the whole, our recommendation is that CS.HCL-NSPEs-NIO shows promise as an oral delivery tool for enhancing the hypoglycemic effects of semaglutide. CI - (c) 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved. FAU - Wang, Ben AU - Wang B AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Su, Zhengxing AU - Su Z AD - Sichuan Kelun Pharmaceutical Research Institute Co., Ltd, Chengdu 611138, Sichuan, People's Republic of China. AD - Hunan Kelun Pharmaceutical Research Co. Ltd, Yueyang 414000, Hunan, People's Republic of China. FAU - Kuang, Meiyan AU - Kuang M AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Luo, Yi AU - Luo Y AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Xu, Minhao AU - Xu M AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Sun, Meng AU - Sun M AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Liu, Xingyou AU - Liu X AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Guo, Yue AU - Guo Y AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Bai, Lu AU - Bai L AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Wang, Yu AU - Wang Y AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Yan, Xinlei AU - Yan X AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Xie, Jing AU - Xie J AUID- ORCID: 0000-0001-8517-3549 AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. FAU - Tang, Yaqin AU - Tang Y AUID- ORCID: 0009-0003-6395-9235 AD - School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 401135, People's Republic of China. LA - eng PT - Journal Article DEP - 20250318 PL - England TA - Biomed Mater JT - Biomedical materials (Bristol, England) JID - 101285195 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9012-76-4 (Chitosan) RN - 0 (Surface-Active Agents) RN - 0 (Liposomes) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Glucagon-Like Peptides/administration & dosage/chemistry/pharmacokinetics MH - Administration, Oral MH - *Chitosan/chemistry MH - Mice MH - *Surface-Active Agents/chemistry MH - Humans MH - *Liposomes/chemistry MH - Blood Glucose MH - Hypoglycemic Agents/administration & dosage/chemistry MH - Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Mice, Inbred C57BL MH - Diabetes Mellitus, Experimental/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - diabetes OT - oral delivery OT - penetration enhancers OT - semaglutide EDAT- 2025/02/06 00:20 MHDA- 2025/03/18 06:22 CRDT- 2025/02/05 18:03 PHST- 2024/07/26 00:00 [received] PHST- 2025/02/05 00:00 [accepted] PHST- 2025/03/18 06:22 [medline] PHST- 2025/02/06 00:20 [pubmed] PHST- 2025/02/05 18:03 [entrez] AID - 10.1088/1748-605X/adb2cf [doi] PST - epublish SO - Biomed Mater. 2025 Mar 18;20(3). doi: 10.1088/1748-605X/adb2cf. PMID- 39907981 OWN - NLM STAT- MEDLINE DCOM- 20250705 LR - 20260127 IS - 1179-187X (Electronic) IS - 1175-3277 (Linking) VI - 25 IP - 4 DP - 2025 Jul TI - Cardiovascular Effects of Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis. PG - 461-467 LID - 10.1007/s40256-025-00721-4 [doi] AB - BACKGROUND: Semaglutide has emerged as an effective medication for treating type 2 diabetes mellitus (DM). However, the cardiovascular effects and safety of this agent in patients with heart failure with preserved ejection fraction (HFpEF) are unclear. OBJECTIVE: This systematic review and meta-analysis aimed to assess the clinical and laboratory effects of semaglutide compared to placebo in patients with HFpEF. METHODS: We systematically searched EMBASE, PubMed, and Cochrane databases for randomized controlled trials (RCTs) and non-randomized cohorts, from inception to July 2024, comparing semaglutide versus placebo in patients with HFpEF. Statistical analyses were performed using R Studio 4.3.2. Mean difference (MD) and odds ratio (OR) with 95% confidence intervals (CIs) were pooled across trials. RESULTS: This meta-analysis included three studies, two RCTs and one non-randomized cohort, reporting data on 1463 patients. The follow-up time of the studies was 52 weeks. Compared to placebo, the use of semaglutide was associated with a significant increase in the 6-min walk distance (MD 16.20; 95% CI 10.19-22.21; p < 0.01; I(2) = 0%). Additionally, reductions were observed in systolic blood pressure (MD -2.22; 95% CI -3.60 to -0.83; p < 0.01; I(2) = 0%), C-reactive protein level (MD 0.59; 95% CI 0.49-0.70; p < 0.01; I(2) = 51%), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels (MD 0.81; 95% CI 0.74-0.89; p < 0.01; I(2) = 0%). CONCLUSION: These findings suggest that the use of semaglutide is associated with clinical and laboratory benefits in patients with HFpEF. CI - (c) 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Sobral, Milene Vitoria Sampaio AU - Sobral MVS AUID- ORCID: 0009-0001-5754-6472 AD - University of Western Sao Paulo, Presidente Prudente, Brazil. FAU - Rodrigues, Livia Kneipp AU - Rodrigues LK AD - Federal University of Minas Gerais, Belo Horizonte, Brazil. FAU - Barbosa, Abner Macola Pacheco AU - Barbosa AMP AD - Sao Paulo State University, Botucatu, Brazil. FAU - da Rocha, Naila Camila AU - da Rocha NC AD - Sao Paulo State University, Botucatu, Brazil. FAU - Moulaz, Isac Ribeiro AU - Moulaz IR AD - Federal University of Espirito Santo, Vitoria, Brazil. FAU - Dos Santos, Joao Pedro Pereira AU - Dos Santos JPP AD - University of Western Sao Paulo, Presidente Prudente, Brazil. FAU - Oliveira, Bruno Henrique Couto AU - Oliveira BHC AD - University of Western Sao Paulo, Presidente Prudente, Brazil. FAU - Moreira, Joao Lucas de Magalhaes Leal AU - Moreira JLML AD - State University of Feira de Santana, Feira de Santana, Brazil. FAU - Pacagnelli, Francis Lopes AU - Pacagnelli FL AD - University of Western Sao Paulo, Presidente Prudente, Brazil. FAU - Guida, Camila Mota AU - Guida CM AD - Dante Pazzanese Institute of Cardiology, Av. Dante Pazzanese, Sao Paulo, 500, Brazil. camila.mguida@hotmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250205 PL - New Zealand TA - Am J Cardiovasc Drugs JT - American journal of cardiovascular drugs : drugs, devices, and other interventions JID - 100967755 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology MH - *Glucagon-Like Peptides/therapeutic use/pharmacology/adverse effects MH - *Stroke Volume/drug effects MH - Randomized Controlled Trials as Topic MH - Diabetes Mellitus, Type 2/drug therapy MH - Natriuretic Peptide, Brain/blood MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declarations. Funding: None. Conflict of interest: All authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and materials: As this is a systematic review with meta-analysis, there is no database; for data extracted from other articles, see Table 1. Code availability: Not applicable. Author contributions: MS carried out the idealization of the work as well as the screening, risk-of-bias assessments, writing of the article, and coordination and supervision of the work. LR, carried out the idealization of the work as well the risk-of-bias assessments and writing the article. AB carried out the collection of outcomes and was involved in writing the article. NR carried out the collection of outcomes and was involved in writing the article. IM took part in writing the article. JS produced Table 1 and wrote the article. BO carried out the screening and was involved in writing the article. JM took part in writing the article. FP was involved in the supervision and coordination of the research group. CG participated in the writing of the article and supervision and coordination of the research group. EDAT- 2025/02/05 12:24 MHDA- 2025/07/05 20:46 CRDT- 2025/02/05 11:24 PHST- 2025/01/19 00:00 [accepted] PHST- 2025/07/05 20:46 [medline] PHST- 2025/02/05 12:24 [pubmed] PHST- 2025/02/05 11:24 [entrez] AID - 10.1007/s40256-025-00721-4 [pii] AID - 10.1007/s40256-025-00721-4 [doi] PST - ppublish SO - Am J Cardiovasc Drugs. 2025 Jul;25(4):461-467. doi: 10.1007/s40256-025-00721-4. Epub 2025 Feb 5. PMID- 39892787 OWN - NLM STAT- MEDLINE DCOM- 20250316 LR - 20260127 IS - 2405-4577 (Electronic) IS - 2405-4577 (Linking) VI - 66 DP - 2025 Apr TI - Efficacy and safety of combination of semaglutide and basal insulin in patients with of type 2 diabetes mellitus: A systematic review and meta-analysis. PG - 564-572 LID - S2405-4577(25)00057-9 [pii] LID - 10.1016/j.clnesp.2025.01.056 [doi] AB - BACKGROUND & AIMS: Semaglutide has demonstrated efficacy in both glycemic control and weight loss. This systematic review and meta-analysis aimed to assess the efficacy and safety of the combined use of semaglutide and basal insulin in individuals diagnosed with type 2 diabetes mellitus (T2DM). METHODS: PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) were searched to identify relevant publications. The primary outcome measure was the change in HbA1c levels. Secondary outcome measures encompassed change in body weight, fluctuations in FPG levels, occurrence of adverse events, serious adverse events, hypoglycemic episodes, and gastrointestinal reactions including nausea, vomiting, and diarrhea. Mean differences (MDs) and relative risk (RR) with confidence intervals (CI) of 95 % were used to analyze the deference. RESULTS: 7 RCTs with 2354 patients were incorporated into the study. Compared to placebo or other active treatment, the addition of semaglutide to basal insulin demonstrated significant reductions in hemoglobin A1c (HbA1c) [mean differences (MD): -1.17 %, P < 0.00001], body weight [MD -5.99 kg, P < 0.00001], and fasting blood glucose (FPG) [MD -1.08 %, P < 0.00001]. No evidence indicated a higher risk of adverse events [RR 1.46, P = 0.13]. However, it did result in increased rates of gastrointestinal adverse events, including nausea, vomiting and diarrhea. CONCLUSIONS: The combination treatment of semaglutide and basal insulin demonstrates significant improvements in glycemic control and reduction in body weight, without an increased risk of hypoglycemia. Our findings provided support for the utilization of a combination therapy involving semaglutide and basal insulin in T2DM. CI - Copyright (c) 2025. Published by Elsevier Ltd. FAU - Chen, Binbin AU - Chen B AD - Department of Gastroenterology, Xijing Hospital,Air Force Medical University, Xi'an 710032, China. Electronic address: 2407633730@qq.com. FAU - Tao, Lanqiu AU - Tao L AD - Department of Thyroid and Breast, Division of General Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, PR China. Electronic address: 2359367759@qq.com. FAU - Tian, Min AU - Tian M AD - State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, Air Force Medical University, Chang Le Road & 169, Xi'an City, Shaanxi, 710032, PR China. Electronic address: epidemiology@fmmu.edu.cn. FAU - Ji, Zhaohua AU - Ji Z AD - Department of Epidemiology, School of Public Health, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Air Force Medical University, Chang Le Road & 169, Xi'an City, Shaanxi, 710032, PR China. Electronic address: epidemiology@fmmu.edu.cn. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20250130 PL - England TA - Clin Nutr ESPEN JT - Clinical nutrition ESPEN JID - 101654592 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/adverse effects/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Glycated Hemoglobin/analysis/metabolism MH - Drug Therapy, Combination MH - Blood Glucose/drug effects MH - *Insulin/therapeutic use/adverse effects/administration & dosage MH - Treatment Outcome MH - Body Weight/drug effects MH - Randomized Controlled Trials as Topic MH - *Insulin Glargine/therapeutic use MH - Hypoglycemia/chemically induced MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - HbA1c OT - Insulin OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare no competing interests. EDAT- 2025/02/02 05:11 MHDA- 2025/03/17 00:42 CRDT- 2025/02/01 19:20 PHST- 2024/01/13 00:00 [received] PHST- 2025/01/16 00:00 [revised] PHST- 2025/01/27 00:00 [accepted] PHST- 2025/03/17 00:42 [medline] PHST- 2025/02/02 05:11 [pubmed] PHST- 2025/02/01 19:20 [entrez] AID - S2405-4577(25)00057-9 [pii] AID - 10.1016/j.clnesp.2025.01.056 [doi] PST - ppublish SO - Clin Nutr ESPEN. 2025 Apr;66:564-572. doi: 10.1016/j.clnesp.2025.01.056. Epub 2025 Jan 30. PMID- 39892489 OWN - NLM STAT- MEDLINE DCOM- 20250520 LR - 20250520 IS - 1555-7162 (Electronic) IS - 0002-9343 (Linking) VI - 138 IP - 6 DP - 2025 Jun TI - Mechanisms of GLP-1 Receptor Agonist-Induced Weight Loss: A Review of Central and Peripheral Pathways in Appetite and Energy Regulation. PG - 934-940 LID - S0002-9343(25)00059-2 [pii] LID - 10.1016/j.amjmed.2025.01.021 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have become central in managing obesity and type 2 diabetes, primarily through appetite suppression and metabolic regulation. This review explores the mechanisms underlying GLP-1 RA-induced weight loss, focusing on central and peripheral pathways. Centrally, GLP-1 RAs modulate brain regions controlling appetite, influencing neurotransmitter and peptide release to regulate hunger and energy expenditure. Peripherally, GLP-1 RAs improve glycemic control by enhancing insulin secretion, reducing glucagon release, delaying gastric emptying, and regulating gut hormones. They also reduce triglycerides and low-density lipoprotein cholesterol, mitigate adipose tissue inflammation, and minimize ectopic fat deposition, promoting overall metabolic health. Emerging dual and triple co-agonists, targeting GLP-1 alongside glucose-dependent insulinotropic polypeptide, and glucagon pathways, may enhance weight loss and metabolic flexibility. Understanding these mechanisms is crucial as the therapeutic landscape evolves, offering clinicians and researchers insights to optimize the efficacy of current and future obesity treatments. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Moiz, Areesha AU - Moiz A AD - Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Division of Experimental Medicine, McGill University, Montreal, Canada. FAU - Filion, Kristian B AU - Filion KB AD - Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada. FAU - Tsoukas, Michael A AU - Tsoukas MA AD - Department of Medicine, McGill University, Montreal, Canada; Division of Endocrinology and Metabolism, McGill University, Montreal, Canada. FAU - Yu, Oriana Hy AU - Yu OH AD - Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada; Division of Endocrinology and Metabolism, McGill University, Montreal, Canada. FAU - Peters, Tricia M AU - Peters TM AD - Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Division of Experimental Medicine, McGill University, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada; Division of Endocrinology and Metabolism, McGill University, Montreal, Canada. FAU - Eisenberg, Mark J AU - Eisenberg MJ AD - Centre of Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Division of Experimental Medicine, McGill University, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada; Division of Cardiology, Jewish General Hospital/McGill University, Canada. Electronic address: mark.eisenberg@ladydavis.ca. LA - eng PT - Journal Article PT - Review DEP - 20250131 PL - United States TA - Am J Med JT - The American journal of medicine JID - 0267200 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Energy Metabolism/drug effects MH - *Obesity/drug therapy/metabolism MH - *Appetite/drug effects MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Appetite OT - Glucagon-like peptide-1 receptor agonist OT - Metabolism OT - Obesity OT - Semaglutide OT - Tirzepatide OT - Weight loss EDAT- 2025/02/02 05:11 MHDA- 2025/05/20 06:28 CRDT- 2025/02/01 19:14 PHST- 2025/01/23 00:00 [received] PHST- 2025/01/24 00:00 [accepted] PHST- 2025/05/20 06:28 [medline] PHST- 2025/02/02 05:11 [pubmed] PHST- 2025/02/01 19:14 [entrez] AID - S0002-9343(25)00059-2 [pii] AID - 10.1016/j.amjmed.2025.01.021 [doi] PST - ppublish SO - Am J Med. 2025 Jun;138(6):934-940. doi: 10.1016/j.amjmed.2025.01.021. Epub 2025 Jan 31. PMID- 39888616 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20260127 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 8 IP - 1 DP - 2025 Jan 2 TI - Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. PG - e2457349 LID - 10.1001/jamanetworkopen.2024.57349 [doi] LID - e2457349 AB - IMPORTANCE: Adherence to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is important for their effectiveness. Discontinuation and reinitiation patterns are not well understood. OBJECTIVE: To describe rates of and factors associated with discontinuation and subsequent reinitiation of GLP-1 RAs among adults with overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort study, 125 474 adults with overweight or obesity newly initiated treatment with a dual-labeled GLP-1 RA (liraglutide, semaglutide, or tirzepatide) between January 1, 2018, and December 31, 2023, with a baseline body mass index of 27 or more, an available weight measurement within 60 days before initiation, and regular care in the year before initiation were identified using electronic health record data from a collective of US health care systems. Patients were followed up for up to 2 years to assess discontinuation and for 2 additional years to assess reinitiation. EXPOSURE: Patients were stratified by presence of type 2 diabetes at baseline. MAIN OUTCOMES AND MEASURES: Proportions of patients discontinuing and reinitiating GLP-1 RA were estimated from Kaplan-Meier models. Associations of sociodemographic characteristics, health factors, weight changes, and gastrointestinal adverse events with discontinuation and reinitiation outcomes were modeled using time-varying Cox proportional hazards regression models. All analyses were conducted separately for patients with and patients without type 2 diabetes. RESULTS: In this cohort study of 125 474 adults (mean [SD] age, 54.4 [13.1] years; 82 063 women [65.4%]), 76 524 (61.0%) had type 2 diabetes. One-year discontinuation was significantly higher for patients without type 2 diabetes (64.8% [95% CI, 64.4%-65.2%]) compared with those with type 2 diabetes (46.5% [95% CI, 46.2%-46.9%]). Higher weight loss (1% reduction in weight from baseline was associated with a 3.1% [95% CI, 2.9%-3.2%] lower hazard of discontinuation for patients with type 2 diabetes and a 3.3% [95% CI, 3.2%-3.5%] lower hazard of discontinuation for patients without type 2 diabetes) and higher income (type 2 diabetes only; >$80 000: hazard ratio [HR], 0.72 [95% CI, 0.69-0.76]) were significantly associated with lower rates of discontinuation, while moderate or severe incident gastrointestinal adverse events were associated with a higher hazard of discontinuation (with type 2 diabetes: HR, 1.38 [95% CI, 1.31-1.45]; without type 2 diabetes: HR, 1.19 [95% CI, 1.12-1.27]). Of 41 792 patients who discontinued and had a discontinuation weight measurement available, 1-year reinitiation was lower for those without type 2 diabetes (36.3% [95% CI, 35.6%-37.0%]) compared with those with type 2 diabetes (47.3% [95% CI, 46.6%-48.0%]). Weight regain of 1% from discontinuation was significantly associated with increased hazards of reinitiation of 2.3% (95% CI, 1.9%-2.8%) for patients with type 2 diabetes and 2.8% (95% CI, 2.4%-3.2%) for patients without type 2 diabetes. CONCLUSIONS AND RELEVANCE: In this cohort study, most patients with overweight or obesity discontinued GLP-1 RA therapy within 1 year, but those without type 2 diabetes had higher discontinuation rates and lower reinitiation rates. Inequities in access and adherence to effective treatments have the potential to exacerbate disparities in obesity. FAU - Rodriguez, Patricia J AU - Rodriguez PJ AD - Truveta Inc, Bellevue, Washington. FAU - Zhang, Vincent AU - Zhang V AD - Healthcare Transformation Institute, Department of Medical Ethics and Health Policy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. FAU - Gratzl, Samuel AU - Gratzl S AD - Truveta Inc, Bellevue, Washington. FAU - Do, Duy AU - Do D AD - Truveta Inc, Bellevue, Washington. FAU - Goodwin Cartwright, Brianna AU - Goodwin Cartwright B AD - Truveta Inc, Bellevue, Washington. FAU - Baker, Charlotte AU - Baker C AD - Truveta Inc, Bellevue, Washington. FAU - Gluckman, Ty J AU - Gluckman TJ AD - Center for Cardiovascular Analytics, Research and Data Science (CARDS), Providence Heart Institute, Providence Health System, Portland, Oregon. FAU - Stucky, Nicholas AU - Stucky N AD - Truveta Inc, Bellevue, Washington. FAU - Emanuel, Ezekiel J AU - Emanuel EJ AD - Healthcare Transformation Institute, Department of Medical Ethics and Health Policy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250102 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Adult MH - United States MH - *Hypoglycemic Agents/therapeutic use MH - *Overweight/drug therapy MH - Liraglutide/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11786232 COIS- Conflict of Interest Disclosures: Dr Emanuel reported receiving personal fees from the University of California San Francisco, Advocate Aurora Health, Cain Brothers, Bowdoin College, The Suntory Foundation, Ontario Hospital Association, University of Oklahoma, Sanford Health, Health Plan Alliance, Emory Health Care, and Employer Direct Health Care; nonfinancial support from Galien Foundation, Hlth Inc, National University of Singapore, Hawaii Medical Services Association, Tel Aviv University, The Quadrangle, Lazard, University of Bergen, University of Virginia, New York Historical Society, Amangiri, Forerunner Conference, BCEPS International Symposium, Future of Science, Cell and Gene Therapy, and Arendalsuka Meeting during the conduct of the study; and serving as a member of the Board of Advisors for Cellares Corp, advisor for Clarify Health Solutions, advisor for Notable Health, member of the Advisory Board for JSL Health, member of the Advisory Board for Peterson Center of Healthcare, special advisor to the Director General of the World Health Organization (WHO), member of the Expert Advisory Group WHO COVID-19 committee, member of the Advisory Board of the HIEx Health Innovation Exchange Partnership sponsored by the United Nations, member of the WHO Expert Group on Ethics & Governance of Outbreaks/Emergencies, member of the WHO Guideline Development Group on the Use and Indications of GLP-1s for Adults Living With Obesity, member of the Internal Advisory Board of The Penn Parity Center, advisor for Link Health Technologies, advisor for Nuna Health, member of the Board of Advisors of Alto Pharmacy, consultant for Korro/Coach AI, consultant for Aberdeen Inc, member of the Advisory Board of FeelBetter Inc, member of the Advisory Board of Biden's Transition COVID-19 Committee, and member of the JAMA Editorial Board. No other disclosures were reported. EDAT- 2025/01/31 12:24 MHDA- 2025/01/31 12:25 PMCR- 2025/01/31 CRDT- 2025/01/31 11:35 PHST- 2025/01/31 12:25 [medline] PHST- 2025/01/31 12:24 [pubmed] PHST- 2025/01/31 11:35 [entrez] PHST- 2025/01/31 00:00 [pmc-release] AID - 2829779 [pii] AID - zoi241605 [pii] AID - 10.1001/jamanetworkopen.2024.57349 [doi] PST - epublish SO - JAMA Netw Open. 2025 Jan 2;8(1):e2457349. doi: 10.1001/jamanetworkopen.2024.57349. PMID- 39886945 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20260127 IS - 1791-244X (Electronic) IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 55 IP - 4 DP - 2025 Apr TI - Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment. LID - 56 [pii] LID - 10.3892/ijmm.2025.5497 [doi] AB - The aim of the present study was to investigate the neuroprotective effects of semaglutide in diabetes‑associated cognitive decline (DACD), while also exploring the underlying mechanisms targeting anti‑oxidative effects. The present study evaluated the antioxidant properties of semaglutide using a DACD model of inflammation. To investigate the underlying mechanisms, omics technologies were employed. Comprehensive transcriptomic and proteomic analysis of the cells was conducted to identify the pathways responsible for the observed antioxidant effects. Semaglutide demonstrated the potential to enhance learning and memory functions while mitigating hippocampal pathological damage. RNA‑sequencing and data‑independent acquisition proteomics analyses identified 13,511 differentially expressed genes and 588 differentially expressed proteins between the control and type 2 diabetes mellitus (T2DM) groups. In addition, 1,378 genes and 2,394 proteins exhibited a differential expression between the T2DM and semaglutide (10 microg/kg) treatment groups. A combined transcriptomic and proteomic analysis unveiled 40 common pathways. Acyl‑CoA oxidase 1 (ACOX1) was observed to be activated during oxidative stress and subsequently suppressed by semaglutide. Of note, the antioxidant and anti‑apoptotic properties of semaglutide in high glucose (HG) conditions were partially reversed upon ACOX1 overexpression. Overall, the present data provided molecular evidence to elucidate the physiological connections between semaglutide and neuronal function, and contribute to clarifying the role of semaglutide in combating oxidative stress and HG‑induced cognitive impairment. FAU - Yang, Ying AU - Yang Y AD - Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China. FAU - Song, Lulu AU - Song L AD - Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China. FAU - Yu, Liping AU - Yu L AD - Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China. FAU - Zhang, Jinping AU - Zhang J AD - Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China. FAU - Zhang, Bo AU - Zhang B AD - Department of Endocrinology, China‑Japan Friendship Hospital, Beijing 100029, P.R. China. LA - eng PT - Journal Article DEP - 20250131 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Antioxidants) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Proteomics/methods MH - *Antioxidants/pharmacology/therapeutic use MH - *Cognitive Dysfunction/drug therapy/metabolism/genetics/etiology MH - Mice MH - Male MH - *Diabetes Mellitus, Experimental/complications/genetics/metabolism/drug therapy MH - *Transcriptome/drug effects MH - Oxidative Stress/drug effects MH - Hippocampus/drug effects/metabolism/pathology MH - Gene Expression Profiling MH - Mice, Inbred C57BL MH - *Diabetes Mellitus, Type 2/complications/genetics/metabolism MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11819768 OTO - NOTNLM OT - cognitive OT - diabetes OT - oxidative stress OT - proteomic OT - transcriptomic COIS- The authors declare that they have no competing interests. EDAT- 2025/01/31 12:23 MHDA- 2025/01/31 12:24 PMCR- 2025/01/30 CRDT- 2025/01/31 07:12 PHST- 2024/10/16 00:00 [received] PHST- 2025/01/16 00:00 [accepted] PHST- 2025/01/31 12:24 [medline] PHST- 2025/01/31 12:23 [pubmed] PHST- 2025/01/31 07:12 [entrez] PHST- 2025/01/30 00:00 [pmc-release] AID - 56 [pii] AID - ijmm-55-04-05497 [pii] AID - 10.3892/ijmm.2025.5497 [doi] PST - ppublish SO - Int J Mol Med. 2025 Apr;55(4):56. doi: 10.3892/ijmm.2025.5497. Epub 2025 Jan 31. PMID- 39883468 OWN - NLM STAT- MEDLINE DCOM- 20250320 LR - 20260908 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 143 IP - 3 DP - 2025 Mar 1 TI - Ophthalmic Complications Associated With the Antidiabetic Drugs Semaglutide and Tirzepatide. PG - 215-220 LID - 10.1001/jamaophthalmol.2024.6058 [doi] AB - IMPORTANCE: Nearly 2% of the US population received a prescription for semaglutide in 2023. There has been a recent concern that this drug and other similar medications may be associated with ophthalmic complications. OBJECTIVE: To report ophthalmic complications associated with the use of semaglutide or tirzepatide. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective case series. All patients were initially seen in a community setting. Patients experiencing an ophthalmic complication in association with the use of semaglutide or tirzepatide were included in this analysis. EXPOSURES: Patients described were using either semaglutide or tirzepatide. MAIN OUTCOMES AND MEASURES: Visual acuity and visual field defects. RESULTS: A total of 9 patients (mean [SD] age, 57.4 [11.6] years; age range, 37-77 years; 5 female [56%]; 4 male [44%]) were included in this study. Seven patients with nonarteritic ischemic anterior optic neuropathy, 1 patient with bilateral papillitis, and 1 patient with paracentral acute middle maculopathy were reported. Atypical features included sequential ischemic optic neuropathy, bilateral disc swelling at presentation, and progressive vision loss. CONCLUSIONS AND RELEVANCE: In this case series study, it was not possible to determine if there is a causal link between these drugs and the ophthalmic complications reported. In some cases, it is hypothesized that rapid correction of hyperglycemia induced by these drugs, rather than a toxic effect of the drugs, could be associated with the ophthalmic complications reported. FAU - Katz, Bradley J AU - Katz BJ AD - John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, Department of Neurology, University of Utah Health, Salt Lake City. FAU - Lee, Michael S AU - Lee MS AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis. FAU - Lincoff, Norah S AU - Lincoff NS AD - Department of Neurology, Jacobs School of Medicine & Biological Sciences, The State University of New York at Buffalo, Buffalo. FAU - Abel, Anne S AU - Abel AS AD - Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis. FAU - Chowdhary, Somya AU - Chowdhary S AD - Department of Ophthalmology, West Virginia University Hospitals, Morgantown. FAU - Ellis, Brian D AU - Ellis BD AD - Department of Ophthalmology, West Virginia University Hospitals, Morgantown. FAU - Najafi, Ahmad AU - Najafi A AD - Spectrum Eye Care Inc, Findlay, Ohio. FAU - Nguyen, John AU - Nguyen J AD - Department of Ophthalmology, West Virginia University Hospitals, Morgantown. FAU - Seay, Meagan D AU - Seay MD AD - John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, Department of Neurology, University of Utah Health, Salt Lake City. FAU - Warner, Judith E A AU - Warner JEA AD - John A. Moran Eye Center, Department of Ophthalmology & Visual Sciences, Department of Neurology, University of Utah Health, Salt Lake City. AD - George E. Whalen Department of Veteran's Affairs Medical Center, Salt Lake City, Utah. LA - eng PT - Journal Article PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA Ophthalmol. 2025 Mar 1;143(3):220-221. doi: 10.1001/jamaophthalmol.2024.6181. PMID: 39883452 EIN - JAMA Ophthalmol. 2026 Sep 1;144(9):882. doi: 10.1001/jamaophthalmol.2026.2772. PMID: 42424048 MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptides/adverse effects MH - Aged MH - *Hypoglycemic Agents/adverse effects MH - Adult MH - Visual Acuity/drug effects MH - Visual Fields/drug effects MH - *Optic Neuropathy, Ischemic/chemically induced/diagnosis MH - *Vision Disorders/chemically induced/physiopathology/diagnosis MH - Diabetes Mellitus, Type 2/drug therapy MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11783245 COIS- Conflict of Interest Disclosures: Dr Katz reported having an equity interest in and is a consultant for Avulux. Dr Lee reported receiving consultant fees from Eli Lilly and Panbela, grants from Invex, advisory board fees from Viridian, and personal fees from Horizon outside the submitted work. Dr Najafi reported previously being affiliated with Spectrum Eye Care Inc, where the information for this study was gathered, but has since left that institution and is currently a cornea and external disease fellow at University of Minnesota. No other disclosures were reported. EDAT- 2025/01/30 12:36 MHDA- 2025/03/20 12:34 PMCR- 2026/01/30 CRDT- 2025/01/30 11:33 PHST- 2025/03/20 12:34 [medline] PHST- 2025/01/30 12:36 [pubmed] PHST- 2025/01/30 11:33 [entrez] PHST- 2026/01/30 00:00 [pmc-release] AID - 2829326 [pii] AID - eoi240088 [pii] AID - 10.1001/jamaophthalmol.2024.6058 [doi] PST - ppublish SO - JAMA Ophthalmol. 2025 Mar 1;143(3):215-220. doi: 10.1001/jamaophthalmol.2024.6058. PMID- 39882599 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20260127 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 28 IP - 1 DP - 2025 Dec TI - Cost-effectiveness of semaglutide in people with obesity and cardiovascular disease without diabetes. PG - 268-278 LID - 10.1080/13696998.2025.2459529 [doi] AB - AIMS: The cardioprotective effects of semaglutide 2.4 mg reported in the SELECT cardiovascular (CV) outcomes trial (ClinicalTrials.gov NCT03574597) provide clinical benefit for subjects with overweight or obesity and established CV disease without type 2 diabetes (T2D). We assessed cost-effectiveness of semaglutide 2.4 mg in this population against the American College of Cardiology/American Heart Association value framework. MATERIALS AND METHODS: A cohort-level Markov-state cost-effectiveness model using trial-derived data with outcomes from a healthcare sector perspective measured over a lifetime horizon was developed. Treatment costs were based on US list prices; scenario analyses used literature-reported estimated rebates. Healthcare costs and benefits were discounted at 3.0%. A simulated cohort of 100,000 subjects was aligned to the SELECT trial population baseline characteristics and time-on-treatment. Subjects received either semaglutide 2.4 mg or placebo in addition to standard of care (SoC). Modelled outcomes included clinical events (CV events, progression to T2D, chronic kidney disease [CKD]) and health economic measures, including direct costs and quality-adjusted life years (QALYs). RESULTS: Mean semaglutide 2.4 mg treatment duration was 2.79 years. Per 100,000 subjects, treatment avoided 2,791 non-fatal myocardial infarctions, 3,000 coronary revascularizations, 487 non-fatal strokes, and 115 CV deaths over the modeled lifetime horizon. Average per-subject lifetime treatment costs were $47,353; savings arose from avoided T2D ($14,431), CKD ($2,074), and CV events ($1,512). Semaglutide 2.4 mg was associated with increased lifetime costs ($29,767), additional QALYs gained (0.218) and an incremental cost-effectiveness ratio of $136,271/QALY at list price; a scenario using an empirically estimated 48% rebate predicted $32,219/QALY. LIMITATIONS: The generalizability of observations from SELECT to a broader US population is unknown. Our model does not capture all outcomes nor costs that may be affected by weight loss. Modeling assumptions may present limitations. CONCLUSIONS: Semaglutide 2.4 mg use as in SELECT is cost-effective at list price, using a $150,000/QALY willingness-to-pay threshold. FAU - McEwan, Phil AU - McEwan P AUID- ORCID: 0000-0001-7488-9058 AD - Health Economics, Health Economics and Outcomes Research Ltd, Cardiff, UK. FAU - Bog, Martin AU - Bog M AUID- ORCID: 0000-0001-6431-8307 AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Faurby, Mads AU - Faurby M AUID- ORCID: 0000-0001-6464-9958 AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Foos, Volker AU - Foos V AD - Health Economics, Health Economics and Outcomes Research Ltd, Cardiff, UK. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine (Endocrinology Division) and Peter O'Donnel Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, Texas, USA. FAU - Lubker, Christopher AU - Lubker C AUID- ORCID: 0000-0003-3220-801X AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Miller, Ryan AU - Miller R AD - Health Economics, Health Economics and Outcomes Research Ltd, Cardiff, UK. FAU - Toliver, Joshua C AU - Toliver JC AUID- ORCID: 0000-0002-9159-2587 AD - Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Yeates, Florian AU - Yeates F AD - Health Economics, Health Economics and Outcomes Research Ltd, Cardiff, UK. FAU - Lincoff, A Michael AU - Lincoff AM AUID- ORCID: 0000-0001-8175-2121 AD - Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. LA - eng SI - ClinicalTrials.gov/NCT03574597 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study DEP - 20250212 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/prevention & control/drug therapy/complications MH - Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2 MH - *Glucagon-Like Peptides/economics/therapeutic use/administration & dosage MH - Markov Chains MH - *Obesity/drug therapy/complications MH - Quality-Adjusted Life Years MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Cardiovascular disease OT - I00 OT - I10 OT - cost-effectiveness analysis OT - glucagon-like peptide-1 receptor agonists OT - obesity OT - overweight EDAT- 2025/01/30 11:06 MHDA- 2025/02/12 12:27 CRDT- 2025/01/30 04:52 PHST- 2025/02/12 12:27 [medline] PHST- 2025/01/30 11:06 [pubmed] PHST- 2025/01/30 04:52 [entrez] AID - 10.1080/13696998.2025.2459529 [doi] PST - ppublish SO - J Med Econ. 2025 Dec;28(1):268-278. doi: 10.1080/13696998.2025.2459529. Epub 2025 Feb 12. PMID- 39878627 OWN - NLM STAT- MEDLINE DCOM- 20250129 LR - 20260127 IS - 1752-8984 (Electronic) IS - 1479-1641 (Print) IS - 1479-1641 (Linking) VI - 22 IP - 1 DP - 2025 Jan-Feb TI - Changes in food preferences after oral semaglutide administration in Japanese patients with type 2 diabetes: KAMOGAWA-DM cohort. PG - 14791641251318309 LID - 10.1177/14791641251318309 [doi] LID - 14791641251318309 AB - BACKGROUND: This study aimed to investigate the effects of oral semaglutide on the changes in food preference of Japanese patients with type 2 diabetes. METHODS: This retrospective multicenter study included 75 patients with type 2 diabetes who received oral semaglutide. The primary outcome was the change in the score of brief-type self-administered diet history questionnaire (BDHQ) score 3 months after the initiation of oral semaglutide treatment. The secondary outcome was the change in the Control of Eating Questionnaire (CoEQ), HbA1c, and body mass index (BMI) after 3 months. RESULTS: The median age, BMI, and HbA1c of the 23 participants were 64.0 years, 26.9 kg/m(2), and 7.6% (59 mmol/mol). The BDHQ results showed total energy was significantly reduced. Among the individual nutrients, carbohydrates most decreased. The CoEQ results particularly showed declines in cravings for something sweet, chocolate or chocolate flavored foods, and starchy foods, satisfaction at meals, frequency and intensity of food craving, difficulty of resisting the craving for food, and frequency of eating in response to cravings for food were significantly lower after 3 months. The mean HbA1c and BMI significantly decreased. CONCLUSIONS: In Japanese patients with type 2 diabetes, oral semaglutide treatment decreased total energy intake and changed food preferences. FAU - Hironaka, Junya AU - Hironaka J AUID- ORCID: 0000-0002-2970-5333 AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Ushigome, Emi AU - Ushigome E AUID- ORCID: 0000-0003-1031-4380 AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Kondo, Yuriko AU - Kondo Y AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Hashimoto, Yoshitaka AU - Hashimoto Y AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Osaka, Takafumi AU - Osaka T AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Majima, Saori AU - Majima S AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Nakanishi, Naoko AU - Nakanishi N AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Okada, Hiroshi AU - Okada H AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Senmaru, Takafumi AU - Senmaru T AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Hamaguchi, Masahide AU - Hamaguchi M AD - Department of Diabetology, Kameoka Municipal Hospital, Kyoto, Japan. FAU - Yamazaki, Masahiro AU - Yamazaki M AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. FAU - Fukui, Michiaki AU - Fukui M AD - Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. LA - eng PT - Journal Article PT - Multicenter Study PL - England TA - Diab Vasc Dis Res JT - Diabetes & vascular disease research JID - 101234011 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - Japanese people SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/psychology/physiopathology MH - Middle Aged MH - Male MH - Female MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - Aged MH - Retrospective Studies MH - Japan MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/adverse effects MH - Glycated Hemoglobin/metabolism MH - Treatment Outcome MH - *Food Preferences/drug effects MH - Time Factors MH - Blood Glucose/drug effects/metabolism MH - Biomarkers/blood MH - Body Mass Index MH - Energy Intake/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide MH - East Asian People PMC - PMC11780656 OTO - NOTNLM OT - Appetite depressants OT - glucagon-like peptide 1 OT - type 2 diabetes mellitus COIS- Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Hironaka J received personal fees from Novo Nordisk Pharma Ltd., Kowa Pharmaceutical Co., Ltd., outside the submitted work, and received personal fees from Nippon Boehringer Ingelheim Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Daiichi Sankyo Co., Ltd, MSD K.K., Kyowa Hakko Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharmaceutical Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., and Sanofi K.K., outside the submitted work. Donated Fund Laboratory of Diabetes therapeutics is an endowment department, supported with an unrestricted grant from Ono Pharmaceutical Co., Ltd., Taiyo Kagaku Co. Ltd. and Taisho Pharmaceutical Co., Ltd. Nakanishi N received personal fees from Kowa Pharmaceutical Co. Ltd., and Novo Nordisk Pharma Ltd., Nippon Boehringer Ingelheim Co. Ltd., TERUMO CORPORATION. Okada H received personal fees from Mochida Pharma Co. Ltd., Teijin Pharma Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corporation, AstraZeneca K.K., Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk Pharma Ltd., Daiichi Sankyo Co., Ltd, Eli Lilly Japan K.K, Kyowa Hakko Kirin Company Ltd, Kissei Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Kowa Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd., and Sanofi K.K. Senmaru T received personal fees from Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co, Daiichi Sankyo Co. Ltd., Kowa Pharma Co., Ltd., Astellas Pharma Inc., Takeda Pharma Co., Ltd., Sanofi K.K., Taisho Toyama Pharma Co., Ltd., Kyowa Kirin Co., Ltd., Kissei Pharma Co., Ltd., MSD K.K., Novo Nordisk Pharma Ltd., Ono Pharma Co., Ltd., AstraZeneca K.K., Mochida Pharma Co. Ltd., TERUMO CORPORATION, Abbott Japan Co. Ltd., outside the submitted work. Hashimoto Y received personal fees from Novo Nordisk Pharma Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Nippon Boehringer Ingelheim Co., Mitsubishi Tanabe Pharma Corp., Kowa Company, Ltd., Taisho Pharma Co., Eli Lilly Japan K.K. and Daiichi Sankyo Co. Yamazaki M received grants from AstraZeneca K.K., Ono Pharma Co. Ltd.,; and received personal fees from MSD K.K., Sumitomo Dainippon Pharma Co., Ltd., Kowa Company, Limited, AstraZeneca PLC, Takeda Pharmaceutical Company Limited, Kyowa Hakko Kirin Co., Ltd., Daiichi Sankyo Co., Ltd, Kowa Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd., outside the submitted work. Hamaguchi M received grants from AstraZeneca K.K., Ono Pharma Co. Ltd., Kowa Pharma Co. Ltd.; and received personal fees from AstraZeneca K.K., Ono Pharma Co. Ltd., Eli Lilly, Japan, Sumitomo Dainippon Pharma Co., Ltd., Daiichi Sankyo Co. Ltd., Mitsubishi Tanabe Pharma Corp., Sanofi K.K., K.K., and Kowa Pharma Co. Ltd. outside of the submitted work. Fukui M received grants from Ono Pharma Co. Ltd., Oishi Kenko inc., Yamada Bee Farm, Nippon Boehringer Ingelheim Co. Ltd., Kissei Pharma Co. Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co. Ltd., Sanofi K.K., Takeda Pharma Co. Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Kowa Pharma Co. Ltd., Novo Nordisk Pharma Ltd., Sanwa Kagagu Kenkyusho CO., Ltd., Eli Lilly, Japan, K.K., Taisho Pharma Co., Ltd., Terumo Corp., Tejin Pharma Ltd., Nippon Chemiphar Co., Ltd., Abbott Japan Co. Ltd., and Johnson & Johnson K.K. Medical Co., TERUMO CORPORATION, and received personal fees from Nippon Boehringer Ingelheim Co., Ltd., Kissei Pharma Co., Ltd., Mitsubishi Tanabe Pharma Corp., Daiichi Sankyo Co. Ltd., Sanofi K.K., Takeda Pharma Co. Ltd., Astellas Pharma Inc., MSD K.K., Kyowa Kirin Co. Ltd., Sumitomo Dainippon Pharma Co. Ltd., Kowa Pharma Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharma Co. Ltd., Sanwa Kagaku Kenkyusho Co. Ltd., Eli Lilly Japan K.K., Taisho Pharma Co., Ltd., Bayer Yakuhin, Ltd., AstraZeneca K.K., Mochida Pharma Co. Ltd., Abbott Japan Co. Ltd., Teijin Pharma Ltd., Arkray Inc., Medtronic Japan Co. Ltd., and Nipro Corp., TERUMO CORPORATION, outside the submitted work. EDAT- 2025/01/29 12:26 MHDA- 2025/01/29 12:27 PMCR- 2025/01/29 CRDT- 2025/01/29 10:04 PHST- 2025/01/29 12:27 [medline] PHST- 2025/01/29 12:26 [pubmed] PHST- 2025/01/29 10:04 [entrez] PHST- 2025/01/29 00:00 [pmc-release] AID - 10.1177_14791641251318309 [pii] AID - 10.1177/14791641251318309 [doi] PST - ppublish SO - Diab Vasc Dis Res. 2025 Jan-Feb;22(1):14791641251318309. doi: 10.1177/14791641251318309. PMID- 39873334 OWN - NLM STAT- MEDLINE DCOM- 20250504 LR - 20260917 IS - 1744-8417 (Electronic) IS - 1744-6651 (Linking) VI - 20 IP - 2 DP - 2025 Mar TI - Association between glucagon-like peptide-1 agonists and risk of diabetic retinopathy: a disproportionality analysis using FDA adverse event reporting system data. PG - 147-152 LID - 10.1080/17446651.2025.2459720 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) agonists are commonly prescribed for type 2 diabetes mellitus (T2DM). Concerns have emerged regarding their potential link to diabetic retinopathy (DR). METHODS: To evaluate the association between GLP-1 agonists and DR, a disproportionality analysis was conducted using FDA Adverse Event Reporting System (FAERS) data from Q4/2003 to Q2/2024 via OpenVigil 2.1 software. We focused on GLP-1 agonists and glucose-dependent insulinotropic polypeptide (GIP) agonist: Semaglutide, liraglutide, dulaglutide, lixisenatide, and tirzepatide, as primary suspect drugs. 'Diabetic retinopathy' was the key search term mapped to Medical Dictionary for Regulatory Activities (MedDRA) Lower-Level Terms (LLTs). We calculated Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), with 95% confidence intervals (CI) and the Evans' criteria were applied to check the significant associations. RESULTS: Semaglutide (PRR: 19.43, 95% CI: 15.17-24.88; ROR: 19.48, 95% CI: 15.20-24.96; Chi-square: 1078.08) and dulaglutide (PRR: 9.01, 95% CI: 7.11-11.42; ROR: 9.02, 95% CI: 7.11-11.44; Chi-square: 478.31) showed a strong association with DR. Tirzepatide and liraglutide showed a weaker but significant association while lixisenatide showed no significant association. CONCLUSION: GLP-1 agonists (except lixisenatide) were found to be associated with DR. These findings emphasize the need for close monitoring and further research to clarify these associations. FAU - Singh, Harmanjit AU - Singh H AD - Department of Pharmacology, Government Medical College & Hospital, Chandigarh, India. FAU - Natt, Navreet Kaur AU - Natt NK AD - Department of Health and Family Welfare, CHC Manawala, Amritsar, India. FAU - Nim, Dwividendra Kumar AU - Nim DK AUID- ORCID: 0009-0003-7823-7665 AD - Department of Pharmacology, Moti Lal Nehru Medical College, Allahabad, India. LA - eng PT - Journal Article DEP - 20250128 PL - England TA - Expert Rev Endocrinol Metab JT - Expert review of endocrinology & metabolism JID - 101278293 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 74O62BB01U (lixisenatide) SB - IM MH - Humans MH - United States/epidemiology MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - United States Food and Drug Administration MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - *Diabetic Retinopathy/chemically induced/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1/agonists MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Liraglutide/adverse effects MH - Recombinant Fusion Proteins/adverse effects MH - Immunoglobulin Fc Fragments/adverse effects MH - Peptides/adverse effects MH - Tirzepatide/adverse effects MH - Glucagon-Like Peptide-2 Receptor MH - Semaglutide OTO - NOTNLM OT - FAERS OT - GLP-1 agonists OT - diabetic retinopathy OT - disproportionality analysis OT - liraglutide OT - semaglutide EDAT- 2025/01/28 12:34 MHDA- 2025/02/28 18:22 CRDT- 2025/01/28 07:13 PHST- 2025/02/28 18:22 [medline] PHST- 2025/01/28 12:34 [pubmed] PHST- 2025/01/28 07:13 [entrez] AID - 10.1080/17446651.2025.2459720 [doi] PST - ppublish SO - Expert Rev Endocrinol Metab. 2025 Mar;20(2):147-152. doi: 10.1080/17446651.2025.2459720. Epub 2025 Jan 28. PMID- 39862389 OWN - NLM STAT- MEDLINE DCOM- 20250429 LR - 20260127 IS - 1535-2900 (Electronic) IS - 1079-2082 (Linking) VI - 82 IP - 9 DP - 2025 Apr 29 TI - Allodynia (skin tenderness) associated with semaglutide: A case series. PG - e426-e430 LID - 10.1093/ajhp/zxaf008 [doi] AB - PURPOSE: The glucagon-like peptide-1 receptor agonist (GLP-1RA) class of medications are widely prescribed for management of diabetes mellitus as well as obesity or weight management. Although there have been rare reports of skin hypersensitivity associated with GLP-1RA medications, no published reports have documented allodynia or skin pain to the touch. SUMMARY: We report 4 cases of allodynia associated with dose escalation of the GLP-1RA medication semaglutide. Each patient was prescribed semaglutide for management of obesity and developed symptoms of allodynia with the 2.4-mg subcutaneous once-weekly dose. Therapy was stopped in 2 patients, both of whom had resolution of symptoms. Two patients opted to continue semaglutide despite the adverse effect, with one experiencing resolution after 4 months. No pharmacological mechanism was identified for this unique adverse drug reaction. There was a clear temporal and dose-response relationship in each of the 4 cases. CONCLUSION: The 4 cases presented had scores of 5 or 6 (probable) on the Naranjo scale. It is not known whether this is a class effect of the GLP-1RA medications or if the adverse effect will consistently resolve or improve with continuation. CI - Published by Oxford University Press on behalf of the American Society of Health-System Pharmacists 2025. FAU - Stark, Jennifer AU - Stark J AD - Veterans Health Care System of the Ozarks, Fayetteville, AR, USA. FAU - Klass, Marian J AU - Klass MJ AD - Veterans Health Care System of the Ozarks, Springfield, MO, USA. FAU - Owen, Lauren AU - Owen L AD - Veterans Health Care System of the Ozarks, Fayetteville, AR, USA. LA - eng PT - Case Reports PT - Journal Article PL - England TA - Am J Health Syst Pharm JT - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists JID - 9503023 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - Dose-Response Relationship, Drug MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Hyperalgesia/chemically induced/diagnosis MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - Obesity/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - adverse drug reaction OT - allodynia OT - glucagon-like peptide-1 receptor agonists OT - semaglutide EDAT- 2025/01/26 00:10 MHDA- 2025/04/29 18:31 CRDT- 2025/01/25 11:33 PHST- 2025/04/29 18:31 [medline] PHST- 2025/01/26 00:10 [pubmed] PHST- 2025/01/25 11:33 [entrez] AID - 7979230 [pii] AID - 10.1093/ajhp/zxaf008 [doi] PST - ppublish SO - Am J Health Syst Pharm. 2025 Apr 29;82(9):e426-e430. doi: 10.1093/ajhp/zxaf008. PMID- 39858442 OWN - NLM STAT- MEDLINE DCOM- 20250125 LR - 20260407 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 15 IP - 1 DP - 2025 Jan 1 TI - Effects of Semaglutide Treatment on Psoriatic Lesions in Obese Patients with Type 2 Diabetes Mellitus: An Open-Label, Randomized Clinical Trial. LID - 10.3390/biom15010046 [doi] LID - 46 AB - Psoriasis is a chronic inflammatory skin disease with relapsing nature. Estimates are that approximately 2-3% of the world's population suffers from this disease. More severe forms of psoriasis are conditions of high inflammation, which is confirmed by the clinical picture and numerous inflammatory parameters such as C-reactive protein (CRP), cytokines and homocysteine, which vary with disease activity. The objective of this clinical study was to investigate the effect of GLP-1 receptor agonist semaglutide therapy on pro-inflammatory factors in the serum and the severity of the clinical picture of psoriasis in obese patients with type 2 diabetes mellitus (T2DM) on chronic metformin therapy. This randomized clinical study was conducted on 31 psoriatic patients with T2DM that were randomized into two groups: one that received semaglutide during the 12-week trial (n = 15), while the second was control (n = 16). The results demonstrated that the severity of the clinical picture of psoriasis, determined by the Psoriasis Area and Severity Index (PASI) score, was significantly better after the administration of semaglutide (the median baseline PASI score in patients treated with semaglutide was 21 (IQR = 19.8), while after 12 weeks of therapy the score was 10 (IQR = 6; p = 0.002). Also, the quality of life in the group of patients who received the drug, measured by the Dermatology Life Quality Index (DLQI), improved significantly after 3 months (a median baseline DLQI score in the semaglutide group was 14 (IQR = 5) at the beginning of the study, and after 12 weeks of treatment the median DLQI score was 4 (IQR = 4; p = 0.002)). The use of semaglutide led to a significant decrease in pro-inflammatory cytokines in the serum (IL6), as well as a significant decrease in CRP values (p < 0.05). A significant decrease in the body mass index (BMI) value in the semaglutide-treated group was also identified, as well as a significant decrease in the level of low-density cholesterol (LDL) (p < 0.05). In conclusion, semaglutide, based on its systemic anti-inflammatory characteristics, could contribute to the treatment of psoriatic obese patients with T2DM. FAU - Petkovic-Dabic, Jelena AU - Petkovic-Dabic J AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Clinic of Skin and Venereal Diseases, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Binic, Ivana AU - Binic I AD - Faculty of Medicine, University of Nis, 18000 Nis, Serbia. FAU - Caric, Bojana AU - Caric B AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Department of Internal Medicine, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Bozic, Ljiljana AU - Bozic L AUID- ORCID: 0000-0003-1564-2391 AD - Department of Microbiology and Immunology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Umicevic-Sipka, Sanja AU - Umicevic-Sipka S AUID- ORCID: 0009-0009-5460-8568 AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Clinic of Skin and Venereal Diseases, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Bednarcuk, Natasa AU - Bednarcuk N AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Dabic, Sasa AU - Dabic S AD - Faculty of Medicine Foca, University of East Sarajevo, 71123 Istocno Sarajevo, Bosnia and Herzegovina. FAU - Situm, Mirna AU - Situm M AD - Department of Dermatology and Venerology, University Hospital Center "Sestre Milosrdnice", University of Zagreb, 10000 Zagreb, Croatia. AD - Croatian Academy of Science and Arts, 10000 Zagreb, Croatia. FAU - Popovic-Pejicic, Snjezana AU - Popovic-Pejicic S AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Department of Internal Medicine, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Academy of Science and Arts of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Stojiljkovic, Milos P AU - Stojiljkovic MP AUID- ORCID: 0000-0001-9431-0736 AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. FAU - Skrbic, Ranko AU - Skrbic R AUID- ORCID: 0000-0002-6643-1781 AD - Center for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Academy of Science and Arts of the Republic of Srpska, 78000 Banja Luka, Bosnia and Herzegovina. AD - Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, Bosnia and Herzegovina. AD - Department of Pathologic Physiology, First Moscow State Medical University I.M. Sechenov, 119435 Moscow, Russia. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20250101 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9100L32L2N (Metformin) RN - 9007-41-4 (C-Reactive Protein) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Psoriasis/drug therapy/complications/pathology/blood MH - *Obesity/complications/drug therapy MH - Adult MH - Metformin/therapeutic use MH - C-Reactive Protein/metabolism MH - Aged MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11763288 OTO - NOTNLM OT - DLQI OT - PASI OT - T2DM OT - cytokine OT - psoriasis OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2025/01/25 13:53 MHDA- 2025/01/25 13:54 PMCR- 2025/01/01 CRDT- 2025/01/25 01:11 PHST- 2024/12/02 00:00 [received] PHST- 2024/12/25 00:00 [revised] PHST- 2024/12/30 00:00 [accepted] PHST- 2025/01/25 13:54 [medline] PHST- 2025/01/25 13:53 [pubmed] PHST- 2025/01/25 01:11 [entrez] PHST- 2025/01/01 00:00 [pmc-release] AID - biom15010046 [pii] AID - biomolecules-15-00046 [pii] AID - 10.3390/biom15010046 [doi] PST - epublish SO - Biomolecules. 2025 Jan 1;15(1):46. doi: 10.3390/biom15010046. PMID- 39856432 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20260813 IS - 1745-7254 (Electronic) IS - 1671-4083 (Print) IS - 1671-4083 (Linking) VI - 46 IP - 5 DP - 2025 May TI - Semaglutide administration protects cardiomyocytes in db/db mice via energetic improvement and mitochondrial quality control. PG - 1250-1261 LID - 10.1038/s41401-024-01448-9 [doi] AB - Diabetic cardiomyopathy causes end-stage heart failure, resulting in high morbidity and mortality in type 2 diabetes mellitus (T2DM) patients. Long-term treatment targeting metabolism is an emerging field in the treatment of diabetic cardiomyopathy. Semaglutide, an agonist of the glucagon-like peptide 1 receptor, is clinically approved for the treatment of T2DM and provides cardiac benefits in patients. However, the cardioprotective mechanism of semaglutide, especially its direct effects on cardiomyocytes (CMs), is not fully understood. Here, we used 8-week diabetic and obese db/db mice treated with semaglutide (200 mug.kg.d(-1), i.p.) to study its direct effect on CMs and the underlying mechanisms. Our results revealed that the consecutive application of semaglutide improved cardiac function. Increased AMPK and ULK1 phosphorylation levels were detected, accompanied by elevated [Ca(2+)](mito). Seahorse analysis revealed that semaglutide increases ATP production via elevated basal and maximum respiration rates as well as spare respiration capacity in CMs. Transmission electron microscopy revealed improved mitochondrial morphology in the cardiomyocytes of db/db mice. On the other hand, Western blot analysis revealed increased Parkin and LC3 protein expression, indicating mitophagy in CMs. Collectively, our findings demonstrate that semaglutide directly protects CMs from high-glucose damage by promoting AMPK-dependent ATP production as well as ULK1-mediated mitophagy in db/db mice. CI - (c) 2025. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society. FAU - Tian, Meng-Yun AU - Tian MY AD - Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. FAU - Yang, Ji-Qin AU - Yang JQ AD - Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. FAU - Hu, Jin-Chuan AU - Hu JC AD - Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. FAU - Lu, Shan AU - Lu S AD - Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. shnlu@njmu.edu.cn. FAU - Ji, Yong AU - Ji Y AD - Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, 211166, China. yongji@njmu.edu.cn. AD - State Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin Medical University, Harbin, 150081, China. yongji@njmu.edu.cn. LA - eng PT - Journal Article DEP - 20250124 PL - United States TA - Acta Pharmacol Sin JT - Acta pharmacologica Sinica JID - 100956087 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Cardiotonic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Myocytes, Cardiac/drug effects/metabolism MH - *Glucagon-Like Peptides/pharmacology/therapeutic use/administration & dosage MH - Mice MH - Male MH - Mice, Inbred C57BL MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Cardiotonic Agents/pharmacology/therapeutic use MH - *Diabetic Cardiomyopathies/drug therapy/metabolism/prevention & control MH - *Diabetes Mellitus, Experimental/drug therapy/metabolism MH - *Mitochondria/drug effects/metabolism MH - Energy Metabolism/drug effects MH - *Mitochondria, Heart/drug effects/metabolism MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC12032422 OTO - NOTNLM OT - db/db mice OT - diabetic cardiomyopathy OT - mitochondrial calcium OT - mitophagy OT - semaglutide COIS- Competing interests: The authors declare no competing interests. EDAT- 2025/01/25 13:52 MHDA- 2025/04/26 16:18 PMCR- 2026/05/01 CRDT- 2025/01/24 23:28 PHST- 2024/08/20 00:00 [received] PHST- 2024/11/27 00:00 [accepted] PHST- 2025/04/26 16:18 [medline] PHST- 2025/01/25 13:52 [pubmed] PHST- 2025/01/24 23:28 [entrez] PHST- 2026/05/01 00:00 [pmc-release] AID - 10.1038/s41401-024-01448-9 [pii] AID - 1448 [pii] AID - 10.1038/s41401-024-01448-9 [doi] PST - ppublish SO - Acta Pharmacol Sin. 2025 May;46(5):1250-1261. doi: 10.1038/s41401-024-01448-9. Epub 2025 Jan 24. PMID- 39853913 OWN - NLM STAT- MEDLINE DCOM- 20250502 LR - 20260307 IS - 1753-0407 (Electronic) IS - 1753-0393 (Print) IS - 1753-0407 (Linking) VI - 17 IP - 1 DP - 2025 Jan TI - Is Weight Loss the Main Driver for A1C Improvement by Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists? A 2.5-Year Analysis in Real-World Clinical Practice. PG - e70054 LID - 10.1111/1753-0407.70054 [doi] LID - e70054 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established treatment options for type 2 diabetes (T2D). In addition to their glycemic benefit, GLP-1 RAs also induce weight loss by suppressing appetite via hypothalamic pathways. However, it remains unclear whether weight reduction is the primary driver of glycemic improvement. METHODS: We retrospectively evaluated 256 patients with T2D who were treated with exenatide (n = 84), dulaglutide (n = 99), or semaglutide (n = 73) for 2.5 years without interruption in real-world clinical practice. Body weight and A1C were measured every 6 months. Baseline characteristics included an average age of 61.8 +/- 11.9 years, 51.5% female, diabetes duration of 12.9 +/- 8.3 years, weight of 103.1 +/- 20.7 kg, BMI of 35.7 +/- 7.5 kg/m(2), and A1C of 8.2% +/- 1.5%. Patients were stratified into tertiles based on percentage weight change at 2.5 years within the overall cohort and for each GLP-1 RA group. RESULTS: The first tertile experienced an average weight loss of -12.2% +/- 5.7% (p < 0.0001), the second tertile lost -3.5% +/- 1.4% (p < 0.0001), and the third tertile gained +2.8% +/- 3.4% (p < 0.0001). The average changes in A1C were - 0.98 +/- 1.8% (p < 0.0001), -0.56% +/- 1.4% (p < 0.001), and -0.19% +/- 1.9% (p = 0.4), respectively. A1C strongly correlated with weight change (p < 0.001). The same observations were reproducible in each medication group. CONCLUSIONS: These findings suggest that the long-term improvement in glycemic control associated with GLP-1 RA therapy is primarily driven by weight loss rather than any other intrinsic effect of GLP-1 RA. This highlights the importance of weight reduction as a key therapeutic target for optimizing glycemic outcomes in patients with T2D receiving GLP-1 RAs. CI - (c) 2025 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Al-Badri, Marwa AU - Al-Badri M AUID- ORCID: 0000-0002-4998-9708 AD - Joslin Diabetes Center, Affiliated With Harvard Medical School, Boston, Massachusetts, USA. AD - Harvard Medical School, Boston, Massachusetts, USA. FAU - Dhaver, Shilton AU - Dhaver S AUID- ORCID: 0000-0002-5281-6728 AD - Joslin Diabetes Center, Affiliated With Harvard Medical School, Boston, Massachusetts, USA. AD - Harvard Medical School, Boston, Massachusetts, USA. FAU - Hamdy, Osama AU - Hamdy O AD - Joslin Diabetes Center, Affiliated With Harvard Medical School, Boston, Massachusetts, USA. AD - Harvard Medical School, Boston, Massachusetts, USA. LA - eng GR - P30 DK036836/DK/NIDDK NIH HHS/United States PT - Journal Article PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Blood Glucose) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Female MH - *Weight Loss/drug effects MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Exenatide/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Aged MH - Blood Glucose/metabolism/analysis MH - Recombinant Fusion Proteins/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11757277 OTO - NOTNLM OT - GLP-1 receptor agonists OT - glycemic control OT - real-world clinical practice OT - type 2 diabetes OT - weight loss COIS- O.H. receives research support from Eli Lilly and Novo Nordisk and serves on an advisory board for Abbott Nutrition. M.A. and S.D. have no disclosures relevant to this work. EDAT- 2025/01/24 17:38 MHDA- 2025/01/24 18:25 PMCR- 2025/01/23 CRDT- 2025/01/24 11:42 PHST- 2024/12/16 00:00 [received] PHST- 2025/01/10 00:00 [accepted] PHST- 2025/01/24 18:25 [medline] PHST- 2025/01/24 17:38 [pubmed] PHST- 2025/01/24 11:42 [entrez] PHST- 2025/01/23 00:00 [pmc-release] AID - JDB70054 [pii] AID - 10.1111/1753-0407.70054 [doi] PST - ppublish SO - J Diabetes. 2025 Jan;17(1):e70054. doi: 10.1111/1753-0407.70054. PMID- 39848681 OWN - NLM STAT- MEDLINE DCOM- 20260306 LR - 20260813 IS - 1473-4257 (Electronic) IS - 0306-6800 (Print) IS - 0306-6800 (Linking) VI - 52 IP - 3 DP - 2026 Feb 27 TI - The Ethics of Ozempic and Wegovy. PG - 185-193 LID - 10.1136/jme-2024-110374 [doi] LID - e110374 AB - Semaglutide, sold under the brand names of Ozempic, Rybelsus and Wegovy, is one of the most popular drugs on the market. Manufactured by Novo Nordisk, semaglutide is the newest in a family of glucagon-like peptide-1 receptor agonists used most commonly to treat type II diabetes. To date, the results of semaglutide for the treatment of type II diabetes have been overwhelmingly positive. It is for the drug's effects on appetite suppression and weight loss, however, that have led its surge in popularity, with many hailing semaglutide as the new 'miracle drug for weight loss'. Despite its popularity, both the governmental and popular reception to the drug has largely been mixed. In this paper, we address a range of ethical concerns and argue that while many are legitimate, they do not provide conclusive reason not to prescribe semaglutide for weight loss. CI - (c) Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY. Published by BMJ Group. FAU - Ryan, Nanette AU - Ryan N AUID- ORCID: 0009-0007-7540-149X AD - National University of Singapore Centre for Biomedical Ethics, Singapore. FAU - Savulescu, Julian AU - Savulescu J AUID- ORCID: 0000-0003-1691-6403 AD - Centre for Biomedical Ethics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore julian.savulescu@philosophy.ox.ac.uk. AD - Uehiro Oxford Institute, University of Oxford, Oxford, UK. LA - eng PT - Journal Article DEP - 20260227 PL - England TA - J Med Ethics JT - Journal of medical ethics JID - 7513619 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use PMC - PMC13018845 OTO - NOTNLM OT - Ethics OT - Ozempic OT - Semaglutide OT - Weight loss COIS- Competing interests: Julian Savulescu is a Bioethics Committee consultant for Bayer. EDAT- 2025/01/24 00:25 MHDA- 2026/03/06 13:46 PMCR- 2026/03/26 CRDT- 2025/01/23 21:03 PHST- 2024/08/12 00:00 [received] PHST- 2024/11/28 00:00 [accepted] PHST- 2026/03/06 13:46 [medline] PHST- 2025/01/24 00:25 [pubmed] PHST- 2025/01/23 21:03 [entrez] PHST- 2026/03/26 00:00 [pmc-release] AID - jme-2024-110374 [pii] AID - 10.1136/jme-2024-110374 [doi] PST - epublish SO - J Med Ethics. 2026 Feb 27;52(3):185-193. doi: 10.1136/jme-2024-110374. PMID- 39848268 OWN - NLM STAT- MEDLINE DCOM- 20250227 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 13 IP - 3 DP - 2025 Mar TI - Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA(1c) levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial. PG - 196-209 LID - S2213-8587(24)00304-8 [pii] LID - 10.1016/S2213-8587(24)00304-8 [doi] AB - BACKGROUND: About half of patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) have type 2 diabetes. In the STEP-HFpEF DM trial of adults with obesity-related HFpEF and type 2 diabetes, subcutaneous once weekly semaglutide 2.4 mg conferred improvements in heart failure-related symptoms and physical limitations, bodyweight, and other heart failure outcomes. We aimed to determine whether these effects of semaglutide differ according to baseline HbA(1c). METHODS: STEP-HFpEF DM, a double-blind, randomised, placebo-controlled trial conducted at 108 clinical research sites across 16 countries in Asia, Europe, and North and South America, included individuals aged 18 years or older with documented HFpEF (left ventricular ejection fraction >/=45%), type 2 diabetes, and obesity (BMI >/=30 kg/m(2)). Participants were randomly assigned (1:1), with a block size of four within each stratum using an interactive web response system, stratified by baseline BMI (<35 kg/m(2)vs >/=35 kg/m(2)), to receive either semaglutide 2.4 mg or placebo subcutaneously. The effects of semaglutide versus placebo on the efficacy endpoints were evaluated by HbA(1c) categories at baseline: low (<6.5%; <48 mmol/mol), medium (6.5% to <7.5%; 48 mmol/mol to <58 mmol/mol), and high (>/=7.5%; >/=58 mmol/mol). The dual primary endpoints were change in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and bodyweight percentage from baseline to 52 weeks and were assessed in all randomly assigned participants by intention to treat. Hypoglycaemia events were also analysed to assess safety in all randomly assigned participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04916470. FINDINGS: Between June 27, 2021 and Sept 2, 2022, 616 participants were enrolled and randomly assigned (mean age 68.4 years [SD 8.9]; 273 [44%] were female, 343 [56%] were male, and 519 [84%] were White). The low baseline HbA(1c) group included 227 participants (112 assigned to semaglutide and 115 to placebo), the medium baseline HbA(1c) group included 226 participants (124 assigned to semaglutide and 102 to placebo), and the high baseline HbA(1c) group included 163 participants (74 assigned to semaglutide and 89 to placebo). The median duration of follow-up in the overall trial was 401 days (IQR 400-405). The change in KCCQ-CSS from baseline to 52 weeks was 12.4 points (95% CI 8.8 to 16.0) with semaglutide versus 5.7 points (2.1 to 9.2) with placebo (mean difference 6.7 points [1.6 to 11.8]) in the low baseline HbA(1c) group, 14.5 points (11.0 to 17.9) versus 8.5 points (4.8 to 12.2; 6.0 points [0.9 to 11.1]) in the medium baseline HbA(1c) group, and 14.5 points (10.0 to 19.0) versus 4.8 points (0.7 to 8.9; 9.6 points [3.5 to 15.7]) in the high baseline HbA(1c) group (p(interaction)=0.64; p(trend)=0.46). The change in bodyweight percentage from baseline to 52 weeks was -10.8 (95% CI -12.1 to -9.5) with semaglutide versus -3.3% (-4.6 to -2.0) with placebo (mean difference -7.5% [-9.4 to -5.6]) in the low baseline HbA(1c) group, -9.6% (-10.8 to -8.3) versus -3.3% (-4.7 to -1.9; -6.3 [-8.2 to -4.4]) in the medium baseline HbA(1c) group, and -8.6% (-10.2 to -7.0) versus -3.6% (-5.2 to -2.1; -5.0 [-7.2 to -2.7]) in the high baseline HbA(1c) group (p(interaction)=0.22; p(trend)=0.083). Hypoglycaemia events occurred in 30 (10%) of 310 participants (70 events; 22.9 events per 100 person-years) in the semaglutide group compared with 21 (7%) of 306 participants in the placebo group (90 events; 29.5 events per 100 person-years). INTERPRETATION: Semaglutide 2.4 mg improved heart failure-related symptoms and physical limitations, and reduced bodyweight in patients with obesity-related HFpEF and type 2 diabetes, all independently of baseline HbA(1c), and resulted in lower rates of hypoglycaemia than placebo, despite a well controlled baseline HbA(1c) and broad use of concomitant glucose-lowering medications. FUNDING: Novo Nordisk. CI - Copyright (c) 2025 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, UK; NIHR Leicester Biomedical Research Centre, Leicester, UK. FAU - van der Meer, Peter AU - van der Meer P AD - Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada. FAU - Patel, Shachi AU - Patel S AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. FAU - Chinnakondepalli, Khaja M AU - Chinnakondepalli KM AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. FAU - Borlaug, Barry A AU - Borlaug BA AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA. FAU - Butler, Javed AU - Butler J AD - Baylor Scott and White Research Institute, Dallas, TX, USA; Department of Medicine, University of Mississippi, Jackson, MS, USA. FAU - Kitzman, Dalane W AU - Kitzman DW AD - Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC, USA. FAU - Shah, Sanjiv J AU - Shah SJ AD - Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. FAU - Harring, Signe AU - Harring S AD - Novo Nordisk, Soborg, Denmark. FAU - Salsali, Afshin AU - Salsali A AD - Novo Nordisk, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk, Soborg, Denmark. FAU - von Lewinski, Dirk AU - von Lewinski D AD - Medical University of Graz, Graz, Austria. FAU - Abhayaratna, Walter AU - Abhayaratna W AD - College of Health and Medicine, The Australian National University, Canberra, ACT, Australia. FAU - Petrie, Mark C AU - Petrie MC AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. Electronic address: mkosiborod@saint-lukes.org. CN - STEP-HFpEF Trials Committees and Investigators LA - eng SI - ClinicalTrials.gov/NCT04916470 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250120 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM CIN - Lancet Diabetes Endocrinol. 2025 Mar;13(3):169-170. doi: 10.1016/S2213-8587(24)00335-8. PMID: 39848269 MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - *Heart Failure/drug therapy/etiology/metabolism/physiopathology MH - Double-Blind Method MH - Aged MH - Middle Aged MH - *Obesity/complications MH - *Glycated Hemoglobin/analysis/metabolism MH - *Stroke Volume/drug effects MH - Treatment Outcome MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Declarations of interests MJD has been a consultant, advisory board member, and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi; has been an advisory board member for Lexicon, Pfizer, ShouTi Pharma, AstraZeneca, Zealand Pharma, and Medtronic; has been a speaker for AstraZeneca, Napp Pharmaceuticals, Novartis, and Amgen; and has received grants from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Janssen, Sanofi-Aventis, and Eli Lilly. PvdM reports institutional payments for consultancy fees or grants from AstraZeneca, Boehringer Ingelheim, BridgeBio, Ionis, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharma Nord, and Vifor. SV reports speaking honoraria or consulting fees from Abbott, Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, and TIMI. BAB receives research support from the US National Institutes of Health (NIH) and the US Department of Defense, as well as research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, Rivus, and Tenax Therapeutics; has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, NGM, Novo Nordisk, NXT, and VADovations; and is named inventor (US patent number 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. JB is a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, Cardiocell, Cardior, CSL Behring, CVRx, Cytokinetics, Daxor, Edwards, Element Science, Faraday, Foundry, G3P, Innolife, Impulse Dynamics, Imbria, Inventiva, Ionis, Levator, Lexicon, Eli Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Prolaio, Pulnovo, Regeneron, Renibus, Roche, Salamandra, Salubris, Sanofi, SC Pharma, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. DWK reports receiving honoraria as a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, Corvia Medical, Ketyo, Novartis, Novo Nordisk, Pfizer, and Rivus, grant funding from AstraZeneca, Bayer, Novartis, Novo Nordisk, Pfizer, and Rivus, and has stock ownership in Gilead Sciences. SJS has received research grants from AstraZeneca, Corvia, and Pfizer, and consulting fees from Abbott, Alleviant, Amgen, Aria CV, AstraZeneca, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Recor, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics. SH, AS, and SR are employees of and shareholders in Novo Nordisk. DvL reports honoraria or consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, MSD, Novartis, Novo Nordisk, Recardio, Sanofi, Sanova, and Vaxxinity. WA reports honoraria or consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, and Novo Nordisk. MCP has received research funding from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Medtronic, Novo Nordisk, Novartis, Pharmacosmos, Roche, and SQ Innovations, and served on committees or consulted for AbbVie, Akero, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Cardiorentis, Corvia, Eli Lilly, Horizon Therapeutics, LIB Therapeutics, Moderna, New Amsterdam, Novartis, Novo Nordisk, Pharmacosmos, Siemens, SQ Innovations, Takeda, Teikoku, and Vifor. MNK served as a consultant or on an advisory board for 35Pharma, Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pfizer, Pharmacosmos, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; has received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer; holds stocks in Artera Health and Saghmos Therapeutics; has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and has received other research support from AstraZeneca. All other authors declare no competing interests. EDAT- 2025/01/24 00:26 MHDA- 2025/02/28 00:20 CRDT- 2025/01/23 18:52 PHST- 2024/06/06 00:00 [received] PHST- 2024/09/09 00:00 [revised] PHST- 2024/09/16 00:00 [accepted] PHST- 2025/02/28 00:20 [medline] PHST- 2025/01/24 00:26 [pubmed] PHST- 2025/01/23 18:52 [entrez] AID - S2213-8587(24)00304-8 [pii] AID - 10.1016/S2213-8587(24)00304-8 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2025 Mar;13(3):196-209. doi: 10.1016/S2213-8587(24)00304-8. Epub 2025 Jan 20. PMID- 39827023 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260127 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 47 IP - 4 DP - 2025 Apr TI - Real-World Treatment Patterns Among US Patients With Type 2 Diabetes Mellitus Initiating Treatment With Once Weekly Semaglutide for Diabetes. PG - 277-283 LID - S0149-2918(24)00418-1 [pii] LID - 10.1016/j.clinthera.2024.12.014 [doi] AB - PURPOSE: Injectable once weekly semaglutide for diabetes (OW sema) is a medication approved in 2017 for the treatment of patients with type 2 diabetes (T2DM). In clinical trials, OW sema has been shown to be effective at helping patients achieve glycemic targets. However, more data are needed to understand how patients who initiate treatment with OW sema are treated in the real world and to aid prescribers in making treatment decisions. This study characterized noninsulin antidiabetic medication use patterns among US patients with T2DM initiating treatment with OW sema. METHODS: In this retrospective, claims-based study, patients (15,588) were included if they had at least 1 claim for OW sema between January 1, 2018 and December 31, 2019, were at least 18 years old, were continuously enrolled in the health plan, and had at least 1 claim indicating a diagnosis of T2DM. All patients had at least 1 line of therapy (LOT) that started on the date of the first fill for OW sema. Data related to pre-index date demographics and clinical characteristics were collected, as were data on patient regimens and LOTs. The length of the LOT was calculated, and the top 10 noninsulin treatment regimens were reported in each LOT. FINDINGS: In the first LOT, OW sema monotherapy was the most common regimen. More than one third (36.5%) of patients had 1 LOT until the end of follow-up and most patients who had a second (52.1%) or third (72.0%) LOT continued it to the end of the study. Among the top 10 regimens, 42.2% of patients with a second LOT and 45.8% of patients with a third LOT had an LOT that included OW sema. IMPLICATIONS: This study describes medication regimens within the first year of OW sema use. Among patients initiating OW sema, monotherapy was the most common regimen. These results provide insight into real-world usage patterns of this medication. CI - Copyright (c) 2025 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk Inc, Plainsboro, New Jersey. FAU - Frazer, Monica AU - Frazer M AD - QualityMetric, Johnston, Rhode Island; Optum, Eden Prairie, Minnesota. FAU - Sargent, Andrew AU - Sargent A AD - Optum, Eden Prairie, Minnesota. FAU - Leszko, Michael AU - Leszko M AD - Optum, Eden Prairie, Minnesota. FAU - Buysman, Erin AU - Buysman E AD - Optum, Eden Prairie, Minnesota. FAU - Gronroos, Noelle N AU - Gronroos NN AD - Optum, Eden Prairie, Minnesota. Electronic address: Noelle.gronroos@optum.com. FAU - Alvarez, Sara AU - Alvarez S AD - Novo Nordisk Inc, Plainsboro, New Jersey. FAU - Dunn, Tyler J AU - Dunn TJ AD - Novo Nordisk Inc, Plainsboro, New Jersey. FAU - Noone, Josh AU - Noone J AD - Novo Nordisk Inc, Plainsboro, New Jersey. LA - eng PT - Journal Article DEP - 20250117 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Retrospective Studies MH - Female MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - United States MH - Aged MH - Drug Administration Schedule MH - Adult MH - *Practice Patterns, Physicians'/statistics & numerical data MH - Blood Glucose/drug effects MH - Glycated Hemoglobin MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Diabetes mellitus OT - Real-world evidence OT - Semaglutide OT - Treatment patterns COIS- Declaration of competing interest Caroline Swift, Sara Alvarez, Tyler J. Dunn, and Josh Noone are employees of Novo Nordisk. Monica Frazer was an employee of Optum at the time the study was conducted and is currently employed at QualityMetric. Andrew Sargent, Michael Leszko, Noelle N. Gronroos, and Erin Buysman are employees of Optum. EDAT- 2025/01/20 22:53 MHDA- 2025/03/14 11:18 CRDT- 2025/01/18 21:53 PHST- 2024/03/06 00:00 [received] PHST- 2024/12/02 00:00 [revised] PHST- 2024/12/25 00:00 [accepted] PHST- 2025/03/14 11:18 [medline] PHST- 2025/01/20 22:53 [pubmed] PHST- 2025/01/18 21:53 [entrez] AID - S0149-2918(24)00418-1 [pii] AID - 10.1016/j.clinthera.2024.12.014 [doi] PST - ppublish SO - Clin Ther. 2025 Apr;47(4):277-283. doi: 10.1016/j.clinthera.2024.12.014. Epub 2025 Jan 17. PMID- 39824696 OWN - NLM STAT- MEDLINE DCOM- 20250129 LR - 20260417 IS - 1871-403X (Print) IS - 1871-403X (Linking) VI - 18 IP - 6 DP - 2024 Nov-Dec TI - Clinical characteristics affecting weight loss in an East Asian population receiving semaglutide: A STEP 6 subgroup analysis. PG - 457-464 LID - S1871-403X(25)00003-1 [pii] LID - 10.1016/j.orcp.2025.01.002 [doi] AB - OBJECTIVE: To explore the effects of semaglutide versus placebo on body weight (BW) by subgroups of baseline characteristics. METHODS: In STEP 6, Japanese and Korean adults with overweight or obesity were randomized to subcutaneous semaglutide 2.4 mg, semaglutide 1.7 mg, or placebo for 68 weeks. A subset of Japanese participants with type 2 diabetes (T2D) was also included. In this post-hoc analysis, change from baseline in BW (%) was assessed by subgroups of baseline characteristics including baseline BW, body mass index, age, sex, glycemic status, dyslipidemia, and hypertension. RESULTS: Of 401 participants (148 female and 253 male) included, the estimated mean change in BW was clinically relevant across all subgroups for semaglutide 2.4 mg, ranging from -9.40 % to -16.42 %. Estimated treatment differences also favored both semaglutide doses versus placebo. Significant treatment-by-subgroup interactions were observed for sex with semaglutide 1.7 mg and 2.4 mg versus placebo at week 68 (p = 0.0008 and p = 0.0005, respectively). Significant treatment-by-subgroup interactions were also observed for presence of T2D and dyslipidemia at baseline, for semaglutide 2.4 mg versus placebo only (p = 0.0381 and p = 0.0181, respectively). CONCLUSIONS: Semaglutide reduces BW in a wide demographic of people with a range of weight-related comorbidities in an East Asian population. CI - Copyright (c) 2025. Published by Elsevier Ltd. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Toranomon Hospital, Tokyo, Japan. Electronic address: kadowaki@toranomon.kkr.or.jp. FAU - Lee, Sang Yeoup AU - Lee SY AD - Family Medicine Clinic and Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan, South Korea; Department of Medical Education, Pusan National University School of Medicine, Yangsan, South Korea. FAU - Ogawa, Wataru AU - Ogawa W AD - Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Nishida, Tomoyuki AU - Nishida T AD - Novo Nordisk Pharma Ltd., Tokyo, Japan. FAU - Overvad, Maria AU - Overvad M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Tobe, Kazuyuki AU - Tobe K AD - First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, Japan. FAU - Yamauchi, Toshimasa AU - Yamauchi T AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. FAU - Lim, Soo AU - Lim S AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea. Electronic address: limsoo@snu.ac.kr. CN - STEP 6 investigators LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20250116 PL - Netherlands TA - Obes Res Clin Pract JT - Obesity research & clinical practice JID - 101303911 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Body Mass Index MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - East Asian People MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use MH - Japan MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy MH - Republic of Korea MH - Treatment Outcome MH - *Weight Loss/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Clinical characteristics OT - GLP-1 OT - Obesity OT - Type 2 diabetes OT - Weight management COIS- Declaration of Competing Interest TK reports honoraria for lectures from Astellas Pharma Inc., AstraZeneca K.K., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., FUJIFILM Toyama Chemical Co., Ltd., Kowa Pharmaceutical Co. Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd.; research grant funding from Asahi Mutual Life Insurance Company, Astellas Pharma Inc., Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD Corporation, Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., and Takeda Pharmaceutical Co., Ltd.; and advisory board consulting fees from Abbott Japan LLC., Medtronic Japan Co., Ltd., and Novo Nordisk Pharma Ltd. SYL reports honoraria for lectures from Novo Nordisk. WO has received lecture fees from Abbott Japan LLC, Nippon Boehringer Ingelheim, Novo Nordisk Pharma Ltd., and Sumitomo Pharma; research funding from Abbott Diabetes Care UK Ltd., Nippon Boehringer Ingelheim, Nippon Eli Lilly Japan K.K., Noster, Novo Nordisk Pharma Ltd., Sumitomo Pharma, and Teijin Pharma; and subsidies or donations from Kowa Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Sumitomo Pharma, Takeda Pharmaceutical, and Teijin Pharma. TN is an employee and shareholder of Novo Nordisk. MO is an employee of Novo Nordisk. KT received lecture fees from Kowa Pharmaceutical Co. Ltd, MSD K.K., and Novo Nordisk Pharma Ltd., and grants from Asahi Kasei Pharma Corporation, Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., Heiseikai Medical corporation association Sakurai Hospital, Japan Diabetes Foundation Kuwayamakai Medical corporation association Tanbo Hospital, Medical corporation association Shichitokukai, Medical corporation association Shikinokai, Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co. Ltd., Suntory Global Innovation Center Ltd., Takeda, Pharmaceutical Co. Ltd., Teijin Pharma Limited, and The Mitsubishi Foundation. TY has received lecture fees from Abbott Japan LLC, Arkray Marketing, Inc., Astellas Pharma Inc, AstraZeneca K.K., Bayer Holding, Ltd., Boehringer Ingelheim, Cosmic Corporation, Covidien Japan Inc. (Medtronic Japan Co., Ltd.), Dojindo Laboratories, Daiichi Sankyo Co., Ltd., Eli Lilly Japan K.K., FUJIFILM Toyama Chemical Co., Ltd., Kissei, Kowa Pharmaceutical Co. Ltd., Kyorin Pharmaceutical, Kyowa Kirin, LifeScan Japan, Inc., Mitsubishi Tanabe Pharma Corporation, MSD, Musashino Foods Corporation, Nippon Becton Dickinson, Novartis Pharma K.K., Novo Nordisk, Ono, Roche DC Japan, Sanofi, Sanwa Chemistry Laboratory, Sumitomo Dainippon, Taisho, Takeda, Teijin Healthcare, and Terumo; grants and endowments from Aero Switch Therapeutics, Inc., Asahi Mutual Life Insurance Company, Astellas Pharma Inc., Bayer Holding, Ltd., Daiichi Sankyo Co., Ltd., EA Pharma, Eli Lilly Japan K.K., Kowa Pharmaceutical Co. Ltd., Kyowa Kirin, Minophagen, Mitsubishi Corporation Life Sciences, Mitsubishi Tanabe Pharma Corporation, MSD, Nippon Boehringer Ingelheim Co., Ltd., Nipro Corporation, Nitto Boseki Co., Ltd., Novartis Pharma K.K., Novo Nordisk, Ono, Sanofi, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda, and Tosoh Corporation; and consulting fees from Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Sanofi K.K., and Viatris Pharmaceutical Japan Inc. SL is an advisory board member for AstraZeneca K.K. and Novo Nordisk Pharma Ltd.; reports honoraria for lectures from AstraZeneca K.K., Boehringer Ingelheim, MSD, Novo Nordisk Pharma Ltd., and Sanofi; and has received research funding from CKD and Eli Lilly Japan K.K. EDAT- 2025/01/18 15:10 MHDA- 2025/01/30 00:19 CRDT- 2025/01/17 21:53 PHST- 2024/07/08 00:00 [received] PHST- 2024/12/19 00:00 [revised] PHST- 2025/01/03 00:00 [accepted] PHST- 2025/01/30 00:19 [medline] PHST- 2025/01/18 15:10 [pubmed] PHST- 2025/01/17 21:53 [entrez] AID - S1871-403X(25)00003-1 [pii] AID - 10.1016/j.orcp.2025.01.002 [doi] PST - ppublish SO - Obes Res Clin Pract. 2024 Nov-Dec;18(6):457-464. doi: 10.1016/j.orcp.2025.01.002. Epub 2025 Jan 16. PMID- 39820580 OWN - NLM STAT- MEDLINE DCOM- 20250327 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 68 IP - 4 DP - 2025 Apr TI - Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial. PG - 739-751 LID - 10.1007/s00125-024-06348-5 [doi] AB - AIMS/HYPOTHESIS: COMBINE 2 assessed the efficacy and safety of once-weekly IcoSema (a combination therapy of basal insulin icodec and semaglutide) vs once-weekly semaglutide (a glucagon-like peptide-1 analogue) 1.0 mg in individuals with type 2 diabetes inadequately managed with GLP-1 receptor agonist (GLP-1 RA) therapy, with or without additional oral glucose-lowering medications. METHODS: This 52 week, randomised, multicentre, open-label, parallel group, Phase IIIa trial was conducted across 121 sites in 13 countries/regions. Adults with type 2 diabetes (HbA(1c) 53.0-85.8 mmol/mol [7.0-10.0%]) receiving GLP-1 RA therapy with or without additional oral glucose-lowering medications were randomly assigned 1:1 to once-weekly IcoSema or once-weekly semaglutide 1.0 mg. The primary endpoint was change in HbA(1c) from baseline to week 52; superiority of IcoSema to semaglutide 1.0 mg was assessed. Secondary endpoints included change in fasting plasma glucose and body weight (baseline to week 52), and combined clinically significant (level 2; <3.0 mmol/l) or severe (level 3; associated with severe cognitive impairment requiring external assistance for recovery) hypoglycaemia (baseline to week 57). RESULTS: Overall, 683 participants were randomised using a Randomisation and Trial Supply Management system to IcoSema (n=342) or semaglutide 1.0 mg (n=341). Mean +/- SD baseline characteristics were as follows: HbA(1c) 64.0+/-8.2 mmol/mol (8.0+/-0.7%); diabetes duration 12.6+/-6.9 years; and BMI 31.1+/-4.7 kg/m(2). From baseline to week 52, mean change in HbA(1c) was -14.7 mmol/mol (-1.35%-points) in the IcoSema group and -9.88 mmol/mol (-0.90%-points) in the semaglutide group; the estimated treatment difference (ETD) was -4.85 (95% CI -6.13, -3.57) mmol/mol (-0.44 [95% CI -0.56, -0.33]%-points), confirming superiority of IcoSema to semaglutide (p<0.0001). The estimated mean change in fasting plasma glucose from baseline to week 52 was statistically significantly reduced with IcoSema vs semaglutide (-2.48 mmol/l vs -1.43 mmol/l, respectively; ETD -1.05 [95% CI -1.36, -0.75] mmol; p<0.0001). Mean change in body weight from baseline to week 52 was statistically significantly different between groups: +0.84 kg for IcoSema vs -3.70 kg for semaglutide (ETD 4.54 kg [95% CI 3.84, 5.23]; p<0.0001). There was no statistically significant difference in the rate of combined clinically significant or severe hypoglycaemia between IcoSema and semaglutide (0.042 vs 0.036 episodes per person-year of exposure; estimated rate ratio 1.20 [95% CI 0.53, 2.69]; p=0.66). The proportion of participants experiencing gastrointestinal adverse events was similar between treatment groups (IcoSema 31.4%; semaglutide 34.4%). CONCLUSIONS/INTERPRETATION: In people living with type 2 diabetes inadequately managed with GLP-1 RA therapy, with or without additional oral glucose-lowering medications, switching to once-weekly IcoSema in comparison with once-weekly semaglutide 1.0 mg demonstrated superiority in HbA(1c) reduction, similar rates of clinically significant or severe hypoglycaemia, and similar frequency of gastrointestinal adverse events. However, weight change from baseline to week 52 was statistically significantly in favour of semaglutide 1.0 mg. TRIAL REGISTRATION: ClinicalTrials.gov NCT05259033 FUNDING: This trial was funded by Novo Nordisk. CI - (c) 2025. The Author(s). FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Endocrinology Division, Department of Internal Medicine and Peter O'Donnell Jr School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. Ildiko.Lingvay@UTSouthwestern.edu. FAU - Benamar, Malik AU - Benamar M AUID- ORCID: 0009-0001-1820-1527 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Chen, Liming AU - Chen L AUID- ORCID: 0000-0002-5682-2340 AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Fu, Ariel AU - Fu A AUID- ORCID: 0009-0007-0220-5877 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jodar, Esteban AU - Jodar E AUID- ORCID: 0000-0002-1234-8560 AD - Universitary Hospital QuironSalud Madrid, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid, Spain. FAU - Nishida, Tomoyuki AU - Nishida T AUID- ORCID: 0009-0004-5812-7167 AD - Novo Nordisk Pharma Ltd, Tokyo, Japan. FAU - Riveline, Jean-Pierre AU - Riveline JP AUID- ORCID: 0000-0001-7991-0741 AD - Department of Endocrinology and Diabetology, Lariboisiere Hospital, APHP, Paris-Cite University Paris, Paris, France. AD - Institut Necker Enfants Malades, Inserm U1151, CNRS UMR 8253, IMMEDIAB Laboratory, Paris, France. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. FAU - Zueger, Thomas AU - Zueger T AUID- ORCID: 0000-0001-6190-7405 AD - Department of Endocrinology, Diabetes and Metabolic Diseases, Kantonsspital Olten, Olten, Switzerland. AD - Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. FAU - Rea, Rosangela AU - Rea R AUID- ORCID: 0000-0002-2102-0495 AD - Internal Medicine Department, Endocrine Division (SEMPR), Universidade Federal do Parana, Curitiba, Brazil. LA - eng SI - ClinicalTrials.gov/NCT05259033 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20250117 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Diabetologia. 2025 Jul;68(7):1586-1588. doi: 10.1007/s00125-025-06435-1. PMID: 40323333 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Aged MH - Blood Glucose/drug effects/metabolism MH - Glycated Hemoglobin/metabolism MH - Adult MH - Drug Administration Schedule MH - Treatment Outcome MH - Drug Therapy, Combination MH - Insulin Glargine/therapeutic use/administration & dosage MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11950020 OTO - NOTNLM OT - Fixed-ratio combination OT - GLP-1 RA OT - Glycaemic control OT - Hypoglycaemia OT - IcoSema OT - Insulin icodec OT - Once-weekly OT - Safety OT - Semaglutide OT - Type 2 diabetes COIS- Acknowledgements: The authors thank all trial participants and staff. Medical writing support was provided by G. Rogers and J. Geatrell of Oxford PharmaGenesis, Oxford, UK, funded by Novo Nordisk A/S. Data availability: Individual participant data will be shared in data sets in a de-identified/anonymised format. Shared data will include data sets from Novo Nordisk-sponsored clinical research completed after 2001 for product indications approved in both the EU and the USA. The trial protocol and redacted clinical trial report will be made available according to Novo Nordisk data sharing commitments. These data will be available after research completion and approval of product and product use in both the EU and the USA (no end date). Data will be shared with bona fide researchers submitting a research proposal requesting access to data, for use as approved by the Independent Review Board (IRB) according to the IRB charter (see novonordisk-trials.com). These data can be accessed via an access request proposal form; the access criteria can be found at novonordisk-trials.com. The data will be made available on a specialised SAS data platform. The results tables will be made available according to US and EU law, via Clinicaltrials.gov and EU Clinical Trials Register. Clinical trials synopsis will be uploaded to novonordisk-trials.com for clinical projects that have been discontinued. Funding: This trial was funded by Novo Nordisk A/S. Representatives of Novo Nordisk A/S were involved in the design and conduct of the trial; collection, management, analysis and interpretation of the data; and preparation, review and approval of the manuscript. Investigators were responsible for trial-related medical decisions and data collection; Novo Nordisk undertook site monitoring, data collation and analysis. Medical writers (G. Rogers and J. Geatrell from Oxford PharmaGenesis, Oxford, UK), funded by Novo Nordisk, assisted with drafting the manuscript under direction of the authors. Novo Nordisk did not have the right to veto publication or to control the decision regarding the journal to which the manuscript was submitted; these decisions were made by the authors. Authors' relationships and activities: IL has received research funding (paid to the institution they are affiliated with) from Boehringer Ingelheim, Merck, Mylan, Novo Nordisk, Pfizer and Sanofi, and has received advisory/consulting fees and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GI Dynamics, Intarcia Therapeutics, Intercept Pharmaceuticals, Johnson & Johnson, MannKind, Merck, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, Shionogi, Structure Therapeutics, Target Pharma, Valeritas and Zealand Pharma. MB and AF are employees of Novo Nordisk A/S. LC has received research funding (paid to the institution they are affiliated with) from AstraZeneca and Eli Lilly. EJ has received research funding (paid to the institution they are affiliated with) from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Faes Farma, MSD, Novartis and Novo Nordisk, and has received advisory/consulting fees and/or other support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, MSD, Novo Nordisk, Technofarma, UCB and Viatris. TN is an employee of Novo Nordisk Pharma Ltd. J-PR is an advisory panel member for Abbott, Air Liquide International, Alphadiab, AstraZeneca, Dexcom, Eli Lilly, Medtronic, MSD, Novo Nordisk and Sanofi, and has received research funding from and provided research support to Abbott, Air Liquide International, Medtronic, Novo Nordisk and Sanofi. DY has received consulting or speaker fees from Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma, MSD K.K., Nippon Boehringer Ingelheim, Novo Nordisk Pharma Ltd and Sumitomo Pharma, and clinically commissioned/received joint research grants from Arklay, Nippon Boehringer Ingelheim, Novo Nordisk Pharma Ltd and Taisho Pharmaceutical. TZ has received research funding (paid to the institution they are affiliated with) from Akero Therapeutics, Novartis and Novo Nordisk, and has received advisory/consulting fees and/or other support (paid to the institution they are affiliated with) from AstraZeneca, Eli Lilly, Novo Nordisk, and Sanofi. RR is an advisory panel member for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Novo Nordisk, has participated in speakers' bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD and Novo Nordisk, and has received research grants from Boehringer Ingelheim, Eli Lilly and Novo Nordisk. Contribution statement: All authors had full access to the data associated with this trial and contributed to interpreting the data and drafting the manuscript. The authors jointly decided to submit the manuscript, approved it before submission and take full responsibility for its content. IL is the guarantor of this work. EDAT- 2025/01/17 18:22 MHDA- 2025/03/27 18:26 PMCR- 2025/01/17 CRDT- 2025/01/17 13:22 PHST- 2024/08/16 00:00 [received] PHST- 2024/11/08 00:00 [accepted] PHST- 2025/03/27 18:26 [medline] PHST- 2025/01/17 18:22 [pubmed] PHST- 2025/01/17 13:22 [entrez] PHST- 2025/01/17 00:00 [pmc-release] AID - 10.1007/s00125-024-06348-5 [pii] AID - 6348 [pii] AID - 10.1007/s00125-024-06348-5 [doi] PST - ppublish SO - Diabetologia. 2025 Apr;68(4):739-751. doi: 10.1007/s00125-024-06348-5. Epub 2025 Jan 17. PMID- 39815707 OWN - NLM STAT- MEDLINE DCOM- 20250116 LR - 20250527 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 80 IP - 1 DP - 2025 Jan TI - [Patient with type 2 diabetes and progressive chronic kidney disease]. PG - 63-68 AB - Chronic kidney disease (CKD) is a common and severe complication in patients with type 2 diabetes (T2D). While inhibitors of the renin-angiotensin system remained for a long time the only medications that had proven nephroprotective effects, several other pharmacological classes also recently showed such a benefit : sodium-glucose cotransporter type 2 (SGLT2) inhibitors (gliflozins), glucagon-like peptide-1 receptor agonists (semaglutide), and mineralocorticoid receptor antagonists (MRA, finerenone). This clinical vignette aims at explaining the pharmacotherapy strategy for a patient with T2D who presents a progressive CKD. The interest of prescribing a combination of several medications with complementary actions that had proven a nephroprotection is emphasized. FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. FAU - Delanaye, Pierre AU - Delanaye P AD - Service de Nephrologie, Dialyse, Transplantation, CHU Liege, Belgique. LA - fre PT - Case Reports PT - English Abstract PT - Journal Article TT - Vignette therapeutique de l'etudiant. Patient avec un diabete de type 2 et une maladie renale chronique progressive. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 0 (Hypoglycemic Agents) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Diabetic Nephropathies/drug therapy MH - Disease Progression MH - Hypoglycemic Agents/therapeutic use MH - Mineralocorticoid Receptor Antagonists/therapeutic use MH - *Renal Insufficiency, Chronic/drug therapy/etiology/complications MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use OTO - NOTNLM OT - Chronic kidney disease OT - Finerenone OT - Gliflozin OT - Renal Insufficiency OT - SGLT2 inhibitor OT - Type 2 diabetes OT - angiotensin blocker EDAT- 2025/01/16 06:21 MHDA- 2025/01/16 06:22 CRDT- 2025/01/16 02:34 PHST- 2025/01/16 06:22 [medline] PHST- 2025/01/16 06:21 [pubmed] PHST- 2025/01/16 02:34 [entrez] PST - ppublish SO - Rev Med Liege. 2025 Jan;80(1):63-68. PMID- 39812288 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20250521 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 21 IP - 900-1 DP - 2025 Jan 15 TI - [Nephrology: what's new in 2024 (I)]. PG - 56-58 LID - 10.53738/REVMED.2025.21.900-1.56 [doi] AB - From immunoglobulin A nephropathy to primary focal segmental glomerulosclerosis, sparsentan expands its indications. Complement inhibitors offer new hope for patients with certain poor-prognosis glomerulonephritides. Semaglutide enjoys great success, promising nephro- and cardioprotection for type 2 diabetics. The renal safety of proton pump inhibitors is questioned. Quality of life benefits of hemodiafiltration are confirmed. Vadadustat represents an oral alternative for the treatment of renal anemia. Xenotransplantation offers a glimpse of a future without organ shortages. FAU - Nanchen, Giliane AU - Nanchen G AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. FAU - Pruijm, Menno AU - Pruijm M AUID- ORCID: 0000-0003-1027-1851 AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. FAU - Golshayan, Dela AU - Golshayan D AUID- ORCID: 0000-0001-5631-6096 AD - Centre de transplantation d'organes, Departement de medecine, CHUV et Universite de Lausanne, 1011 Lausanne. FAU - Fakhouri, Fadi AU - Fakhouri F AUID- ORCID: 0000-0001-5390-8002 AD - Service de nephrologie et d'hypertension, Centre hospitalier universitaire vaudois et Universite de Lausanne, 1011 Lausanne. LA - fre PT - English Abstract PT - Journal Article TT - Nephrologie : ce qui a change en 2024 (I). PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Complement Inactivating Agents) SB - IM MH - Humans MH - Quality of Life MH - *Kidney Diseases/therapy MH - *Nephrology/trends MH - Complement Inactivating Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Transplantation, Heterologous/methods COIS- les auteurs n'ont declare aucun conflit d'interets en relation avec cet article. EDAT- 2025/01/15 12:23 MHDA- 2025/01/15 12:24 CRDT- 2025/01/15 07:12 PHST- 2025/01/15 12:24 [medline] PHST- 2025/01/15 12:23 [pubmed] PHST- 2025/01/15 07:12 [entrez] AID - RMS0900-1-013 [pii] AID - 10.53738/REVMED.2025.21.900-1.56 [doi] PST - ppublish SO - Rev Med Suisse. 2025 Jan 15;21(900-1):56-58. doi: 10.53738/REVMED.2025.21.900-1.56. PMID- 39803696 OWN - NLM STAT- MEDLINE DCOM- 20250501 LR - 20260127 IS - 1556-9519 (Electronic) IS - 1556-3650 (Linking) VI - 63 IP - 2 DP - 2025 Feb TI - Characterization of glucagon-like peptide-1 (GLP-1) agonist exposures reported to a single United States poison center. PG - 133-136 LID - 10.1080/15563650.2024.2444642 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 agonists have gained attention in recent years due to their efficacy in managing type II diabetes mellitus and their emerging role in weight management. The purpose of this study was to characterize glucagon-like peptide-1 agonist exposures reported to a single United States regional poison center over nine years, including causes of exposure, associated clinical effects, and potential areas for improving patient education and safety. METHODS: This retrospective cohort study analyzed all poison center calls involving glucagon-like peptide-1 agonists submitted to a single United States regional poison center from 14 January 2014 to 1 May 2023. Data were abstracted from the electronic medical record of the poison center, including demographics, call volume, drug involved, type of exposure, frequency of hypoglycemia, and other side effects. RESULTS: Two hundred and thirty-seven cases involving glucagon-like peptide-1 agonists were reported to the poison center. The annual number of cases increased sharply over this period. Most patients (n = 166, 70.0%) were females. Most calls (n = 164, 69.2%) were due to unintentional therapeutic errors. Semaglutide was the most frequently involved medication (n = 72, 36.0%). Hypoglycemia was identified in eight patients (3.4%). The lowest mean (+/-SD) blood glucose concentration in these hypoglycemic patients was 49.6 +/- 23.7 mg/dL (2.76 +/- 1.3 mmol/L). DISCUSSION: Unintentional therapeutic errors were involved in 164 (69.2%) cases. Despite the generally mild clinical effects observed in this study, the occurrence of hypoglycemia in a subset of patients, often requiring hospitalization, is of concern. With reports of the acquisition of these medications through online platforms and poorly regulated compounding sources, this trend may pose public health risks. CONCLUSIONS: This study demonstrates the increasing incidence of glucagon-like peptide-1 agonist exposures reported to a United States regional poison center, predominantly due to unintentional overdoses, which highlights the need for ongoing patient education. FAU - Muschler, Karen AU - Muschler K AD - Rocky Mountain Poison and Drug Safety Center, Denver, CO, USA. FAU - Muschalek, Rachael AU - Muschalek R AD - Denver Health Residency in Emergency Medicine, Denver, CO, USA. FAU - Hoyte, Christopher AU - Hoyte C AD - Rocky Mountain Poison and Drug Safety Center, Denver, CO, USA. AD - Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA. LA - eng PT - Journal Article DEP - 20250113 PL - England TA - Clin Toxicol (Phila) JT - Clinical toxicology (Philadelphia, Pa.) JID - 101241654 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Poison Control Centers/statistics & numerical data MH - Female MH - Retrospective Studies MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide 1/agonists MH - Adult MH - United States/epidemiology MH - *Hypoglycemic Agents/poisoning MH - Aged MH - Hypoglycemia/chemically induced/epidemiology MH - Young Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Adolescent MH - Glucagon-Like Peptides MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 agonists OT - hypoglycemia OT - liraglutide OT - overdose OT - semaglutide EDAT- 2025/01/13 06:16 MHDA- 2025/02/18 12:26 CRDT- 2025/01/13 05:49 PHST- 2025/02/18 12:26 [medline] PHST- 2025/01/13 06:16 [pubmed] PHST- 2025/01/13 05:49 [entrez] AID - 10.1080/15563650.2024.2444642 [doi] PST - ppublish SO - Clin Toxicol (Phila). 2025 Feb;63(2):133-136. doi: 10.1080/15563650.2024.2444642. Epub 2025 Jan 13. PMID- 39796271 OWN - NLM STAT- MEDLINE DCOM- 20250111 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 26 IP - 1 DP - 2025 Jan 6 TI - Single and Combined Impact of Semaglutide, Tirzepatide, and Metformin on beta-Cell Maintenance and Function Under High-Glucose-High-Lipid Conditions: A Comparative Study. LID - 10.3390/ijms26010421 [doi] LID - 421 AB - Type 2 diabetes (T2D), the most common form, is marked by insulin resistance and beta-cell failure. beta-cell dysfunction under high-glucose-high-lipid (HG-HL) conditions is a key contributor to the progression of T2D. This study evaluates the comparative effects of 10 nM semaglutide, 10 nM tirzepatide, and 1 mM metformin, both alone and in combination, on INS-1 beta-cell maintenance and function under HG-HL conditions. INS-1 cells were pretreated for 2 h with single doses of metformin (1 mM), semaglutide (10 nM), tirzepatide (10 nM), or combinations of 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide, followed by 48 h of HG-HL stimulation. The results indicate that combining 1 mM metformin with either 10 nM semaglutide or 10 nM tirzepatide significantly enhances the effects of 10 nM semaglutide and 10 nM tirzepatide on HG-HL-induced apoptosis and dysregulated cell cycle. Specifically, the combination treatments demonstrated superior restoration of glucose-stimulated insulin secretion (GSIS) functionality compared to 1 mM metformin, 10 nM semaglutide, and 10 nM tirzepatide. FAU - Gojani, Esmaeel Ghasemi AU - Gojani EG AUID- ORCID: 0009-0003-3168-0379 AD - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. FAU - Wang, Bo AU - Wang B AUID- ORCID: 0000-0001-7260-1938 AD - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. FAU - Li, Dongping AU - Li D AD - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. FAU - Kovalchuk, Olga AU - Kovalchuk O AD - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. FAU - Kovalchuk, Igor AU - Kovalchuk I AUID- ORCID: 0000-0002-8137-6928 AD - Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada. LA - eng GR - IT28033/Mitacs/ PT - Comparative Study PT - Journal Article DEP - 20250106 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 9100L32L2N (Metformin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - IY9XDZ35W2 (Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Lipids) RN - OYN3CCI6QE (Tirzepatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Metformin/pharmacology MH - *Glucagon-Like Peptides/pharmacology MH - *Insulin-Secreting Cells/drug effects/metabolism MH - *Glucose/metabolism/pharmacology MH - Animals MH - Rats MH - *Hypoglycemic Agents/pharmacology MH - Apoptosis/drug effects MH - Diabetes Mellitus, Type 2/metabolism/drug therapy MH - Insulin Secretion/drug effects MH - Cell Line MH - Lipids MH - Tirzepatide MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11720205 OTO - NOTNLM OT - HG-HL conditions OT - metformin OT - semaglutide OT - tirzepatide OT - beta-cells COIS- The authors declare no conflicts of interest. EDAT- 2025/01/11 14:03 MHDA- 2025/01/11 14:04 PMCR- 2025/01/06 CRDT- 2025/01/11 01:09 PHST- 2024/12/02 00:00 [received] PHST- 2024/12/31 00:00 [revised] PHST- 2025/01/04 00:00 [accepted] PHST- 2025/01/11 14:04 [medline] PHST- 2025/01/11 14:03 [pubmed] PHST- 2025/01/11 01:09 [entrez] PHST- 2025/01/06 00:00 [pmc-release] AID - ijms26010421 [pii] AID - ijms-26-00421 [pii] AID - 10.3390/ijms26010421 [doi] PST - epublish SO - Int J Mol Sci. 2025 Jan 6;26(1):421. doi: 10.3390/ijms26010421. PMID- 39789997 OWN - NLM STAT- MEDLINE DCOM- 20250430 LR - 20260810 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 4 DP - 2025 Apr TI - Real-world retrospective study in elderly patients aged 65 years and older with type 2 diabetes mellitus treated with daily oral semaglutide (SEMA-elderly). PG - 1805-1814 LID - 10.1111/dom.16174 [doi] AB - AIM: This real-world, retrospective cohort study aimed to assess the efficacy, safety and tolerability of oral semaglutide-the first GLP-1 receptor agonist available in oral form-in patients aged 65 years and older with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline (V1) to six months (V3). Secondary endpoints included change in body weight, proportion of patients achieving HbA1c <7%, proportion of patients achieving both an HbA1c reduction of >/=1% and a body weight reduction of >/=5%. Exploratory endpoints were also assessed, including evaluations at three months (V2). RESULTS: One hundred and one patients (mean age 74.7 +/- 6.1 years) started oral semaglutide treatment. Mean HbA1c decreased significantly from V1 to V3 (change: -0.44%, p < 0.001), with reductions already evident at V2. The proportion of patients achieving an HbA1c /=1% and a weight loss of >/=5%. Body weight decreased from a baseline mean of 76.8-73.7 kg at V3 (p < 0.001). Body mass index, waist circumference, total cholesterol, low-density lipoprotein cholesterol and systolic blood pressure decreased significantly from V1 to V3, with changes already evident at V2. Eleven patients (10.9%) reported adverse events. Seven patients (6.9%) discontinued treatment. CONCLUSION: Oral semaglutide effectively improves glycaemic control and weight management in elderly patients with T2DM while improving lipid and cardiovascular parameters and proving to be safe and well tolerated. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Fiore, Vincenzo AU - Fiore V AD - UOSD Diabetologia Endocrinologia, ASL RM5, Rome, Italy. FAU - Carbotta, Giovanni AU - Carbotta G AUID- ORCID: 0000-0003-1348-3489 AD - UOSD Diabetologia Endocrinologia, ASL RM5, Rome, Italy. FAU - Barraco, Sonia AU - Barraco S AD - UOSD Diabetologia Endocrinologia, ASL RM5, Rome, Italy. FAU - Falasca, Paolo AU - Falasca P AD - Unit of Internal Medicine, RM6 Hospital, Rome, Italy. FAU - Arico, Concetta Nadia AU - Arico CN AD - U.O.C Diabetologia ed Endocrinologia Grande Ospedale Metropolitano - Reggio Calabria, Italy. FAU - Barucca, Alessandra AU - Barucca A AD - UOSD Diabetologia Endocrinologia, ASL RM5, Rome, Italy. LA - eng PT - Journal Article DEP - 20250110 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Female MH - Aged MH - Male MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Glycated Hemoglobin/analysis/metabolism MH - Administration, Oral MH - Aged, 80 and over MH - Blood Glucose/metabolism/drug effects MH - Treatment Outcome MH - Weight Loss/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Body Weight/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - HbA1c OT - glycaemic control OT - real-world evidence OT - semaglutide OT - type 2 diabetes EDAT- 2025/01/10 06:20 MHDA- 2025/03/07 00:21 CRDT- 2025/01/10 03:43 PHST- 2024/12/17 00:00 [revised] PHST- 2024/10/23 00:00 [received] PHST- 2024/12/24 00:00 [accepted] PHST- 2025/03/07 00:21 [medline] PHST- 2025/01/10 06:20 [pubmed] PHST- 2025/01/10 03:43 [entrez] AID - 10.1111/dom.16174 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Apr;27(4):1805-1814. doi: 10.1111/dom.16174. Epub 2025 Jan 10. PMID- 39786599 OWN - NLM STAT- MEDLINE DCOM- 20250109 LR - 20260127 IS - 1590-1262 (Electronic) IS - 1124-4909 (Print) IS - 1124-4909 (Linking) VI - 30 IP - 1 DP - 2025 Jan 9 TI - Real-world effectiveness of Semaglutide treatment on weight loss maintenance after weight loss in patients with obesity or overweight and diabetes. PG - 2 LID - 10.1007/s40519-024-01711-2 [doi] LID - 2 AB - PURPOSE: To report data on the real-world effectiveness and safety of injectable (IS) and oral (OS) therapies in obese or overweight diabetes (T2DM) patients on glycometabolic control, weight loss (WL) and weight maintenance after the use of semaglutide. METHODS: 175 subjects with obesity or overweight and T2DM were retrospectively assessed. Of these, 129 (75F, 54 M; mean age 61.2 +/- 9.8 years) patients were treated with IS and 46 (24F, 22 M; mean age 65.7 +/- 12.8 years) with OS for T2DM and WL. At baseline, mean weight (mW) was 101.8 +/- 24.6 kg and 95.2 +/- 15.0 kg; mean body mass index (mBMI) was 36.7 +/- 8.7 kg/m(2) and 34.3 +/- 5.3 kg/m(2). RESULTS: After 6 months, in the IS group, 127 patients had a mW and mBMI reduction of - 10.4 +/- 8.1 kg and - 3.9 +/- 3.0 kg/m(2). 46 patients in the OS group had a mW and mBMI reduction of - 6.7 +/- 5.3 kg and - 2.6 +/- 2.1 kg/m(2). After 12 months, 102 patients in the IS group achieved a mW and mBMI reduction of - 9.3 +/- 7.5 kg and - 3.4 +/- 2.6 kg/m(2). 44 patients in the OS group of treatment had a mW and mBMI reduction of - 10.7 +/- 6.5 kg and - 3.9 +/- 2.4 kg/m(2). After 24 months, 92 patients in the IS group of therapy achieved a mW and mBMI reduction of - 15.9 +/- 11.4 kg and - 5.8 +/- 3.7 kg/m(2). There was a mean percentage reduction of glycated hemoglobin (HBA1C) of - 1.9 +/- 1.4%, - 1.5 +/- 1.9%, and - 1.5 +/- 1.7% after 6, 12 and 24 months in the IS group. In the OS group there was a mean reduction of - 1.5 +/- 1.6% after 6 months and of - 0.8 +/- 0.6% after 12 months of therapy. CONCLUSIONS: Semaglutide induces WL maintenance after 12 and 24 months of treatment. Our results show a comparable effectiveness of IS and OS in T2DM patients with obesity or overweight. IS and OS treatment provide significant WL that allows reaching the glycometabolic therapeutic goal in a short time. Level of Evidence Level II. CI - (c) 2024. The Author(s). FAU - Del Prete, Michela AU - Del Prete M AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. michela.delprete@asst-lariana.it. FAU - Gavazzi, Lidia AU - Gavazzi L AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. FAU - Disoteo, Olga Eugenia AU - Disoteo OE AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. FAU - Vignati, Federico AU - Vignati F AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. FAU - Di Sacco, Gianleone AU - Di Sacco G AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. FAU - Muratori, Fabrizio AU - Muratori F AD - Division of Endocrinology, Diabetology and Clinical Nutrition, Sant'Anna Hospital - ASST Lariana, Como, Italy. LA - eng PT - Journal Article DEP - 20250109 PL - Germany TA - Eat Weight Disord JT - Eating and weight disorders : EWD JID - 9707113 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - Aged MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Retrospective Studies MH - Treatment Outcome MH - Hypoglycemic Agents/therapeutic use MH - Body Mass Index MH - Body Weight Maintenance MH - Semaglutide PMC - PMC11717789 OTO - NOTNLM OT - Continuing weight loss OT - Diabetes OT - Obesity OT - Overweight OT - Semaglutide COIS- Declarations. Ethics approval and consent to participate: This is a retrospective observational study, and no ethical approval is required. Informed consent was obtained from all the participants of the study. Competing interests: The authors declare no competing interests. EDAT- 2025/01/09 16:59 MHDA- 2025/01/09 18:21 PMCR- 2025/01/09 CRDT- 2025/01/09 11:16 PHST- 2024/11/18 00:00 [received] PHST- 2024/12/23 00:00 [accepted] PHST- 2025/01/09 18:21 [medline] PHST- 2025/01/09 16:59 [pubmed] PHST- 2025/01/09 11:16 [entrez] PHST- 2025/01/09 00:00 [pmc-release] AID - 10.1007/s40519-024-01711-2 [pii] AID - 1711 [pii] AID - 10.1007/s40519-024-01711-2 [doi] PST - epublish SO - Eat Weight Disord. 2025 Jan 9;30(1):2. doi: 10.1007/s40519-024-01711-2. PMID- 39777709 OWN - NLM STAT- MEDLINE DCOM- 20250625 LR - 20260515 IS - 2509-2723 (Electronic) IS - 2509-2715 (Print) IS - 2509-2723 (Linking) VI - 47 IP - 3 DP - 2025 Jun TI - Prognostic impact of glucagon-like peptide-1 receptor (GLP1R) expression on cancer survival and its implications for GLP-1R agonist therapy: an integrative analysis across multiple tumor types. PG - 4413-4427 LID - 10.1007/s11357-024-01494-5 [doi] AB - Glucagon-like peptide-1 receptor (GLP-1R) agonists, such as exenatide (Byetta, Bydureon), liraglutide (Victoza, Saxenda), albiglutide (Tanzeum), dulaglutide (Trulicity), lixisenatide (Lyxumia, Adlyxin), semaglutide (Ozempic, Rybelsus, Wegovy), and tirzepatide (Mounjaro, Zepbound), are widely used for the treatment of type 2 diabetes mellitus (T2DM) and obesity. While these agents are well known for their metabolic benefits, there is growing interest in their potential effects on cancer biology. However, the role of GLP-1R agonists in cancer remains complex and not fully understood, particularly across different tumor types. This study aimed to evaluate the prognostic significance of GLP1R expression on overall survival across various cancer types. Using a comprehensive analysis of gene expression data and survival outcomes a large cohorts of different tumor types, we employed Cox proportional hazards survival analyses, coupled with false discovery rate determinations, to explore correlations between GLP1R expression and survival. The integrated database included thousands of cancer specimens with available overall survival time and event data from numerous independent cohorts, providing a robust platform for survival analysis. Our findings reveal that increased GLP1R expression is associated with improved overall survival in cancers such as bladder cancer, breast cancer, esophageal adenocarcinoma, renal clear cell carcinoma, and thyroid carcinoma. Conversely, higher GLP1R expression is linked to poorer survival outcomes in cervical squamous cell carcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. Additionally, GLP1R expression showed no significant impact on overall survival in cancers such as esophageal squamous cell carcinoma, colon cancer, head-neck squamous cell carcinoma, renal papillary cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, ovarian cancer, and pancreatic cancer. In conclusion, GLP1R expression levels serve as an important biomarker with potential prognostic significance across multiple cancers, demonstrating both protective and adverse associations depending on the tumor type. These findings highlight the complex role of GLP-1R agonists in cancer risk and survival, suggesting that the therapeutic use of these agents should be carefully tailored to the individual patient's cancer risk profile. CI - (c) 2025. The Author(s). FAU - Ungvari, Zoltan AU - Ungvari Z AD - Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. AD - Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA. AD - Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. AD - Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. AD - International Training Program in Geroscience, Doctoral College/Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary. FAU - Bartha, Aron AU - Bartha A AD - Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary. FAU - Ungvari, Anna AU - Ungvari A AUID- ORCID: 0009-0001-5053-2828 AD - Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary. Ungann2004@gmail.com. FAU - Fekete, Monika AU - Fekete M AD - Institute of Preventive Medicine and Public Health, Semmelweis University, Budapest, Hungary. FAU - Bianchini, Giampaolo AU - Bianchini G AD - Department of Medical Oncology, IRCCS Ospedale San Raffaele, Milan, Italy. FAU - Gyorffy, Balazs AU - Gyorffy B AD - Dept. of Bioinformatics, Semmelweis University, 1094, Budapest, Hungary. AD - Dept. of Biophysics, Medical School, University of Pecs, H-7624, Pecs, Hungary. AD - Cancer Biomarker Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117, Budapest, Hungary. LA - eng GR - RRF-2.3.1-21-2022-00003/Nemzeti Kutatasi, Fejlesztesi es Innovacios Alap/ PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20250108 PL - Switzerland TA - Geroscience JT - GeroScience JID - 101686284 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (GLP1R protein, human) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Neoplasms/mortality/genetics/drug therapy MH - Prognosis MH - *Glucagon-Like Peptide-1 Receptor/genetics/metabolism MH - Female MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - Aged PMC - PMC12181560 OTO - NOTNLM OT - Cancer prognosis OT - GLP-1 receptor agonists OT - Gene expression OT - KM plotter OT - Survival analysis OT - Tumor biomarkers OT - Type 2 diabetes treatment COIS- Declarations. Competing interests: Dr. Balazs Gyorffy serves as Associate Editor for GeroScience. Dr. Zoltan Ungvari serves as Editor-in-Chief for GeroScience and has personal relationships with individuals involved in the submission of this paper. All other authors declare no competing interests. EDAT- 2025/01/09 00:23 MHDA- 2025/06/25 06:25 PMCR- 2025/01/08 CRDT- 2025/01/08 18:23 PHST- 2024/09/10 00:00 [received] PHST- 2024/12/17 00:00 [accepted] PHST- 2025/06/25 06:25 [medline] PHST- 2025/01/09 00:23 [pubmed] PHST- 2025/01/08 18:23 [entrez] PHST- 2025/01/08 00:00 [pmc-release] AID - 10.1007/s11357-024-01494-5 [pii] AID - 1494 [pii] AID - 10.1007/s11357-024-01494-5 [doi] PST - ppublish SO - Geroscience. 2025 Jun;47(3):4413-4427. doi: 10.1007/s11357-024-01494-5. Epub 2025 Jan 8. PMID- 39763481 OWN - NLM STAT- MEDLINE DCOM- 20250915 LR - 20250915 IS - 2396-9881 (Electronic) IS - 2396-9873 (Print) IS - 2396-9873 (Linking) VI - 10 IP - 3 DP - 2025 Sep TI - Prediabetes and diabetes mellitus type II after ischemic stroke. PG - 822-828 LID - 10.1177/23969873241304301 [doi] AB - INTRODUCTION: The progression of diabetes status in post-stroke patients remains under-investigated, particularly regarding new treatments for type II diabetes mellitus (DM II), like glucagon-like peptide 1 receptor agonists (GLP-1-RA) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, which have not been studied in the post-stroke setting. PATIENTS AND METHODS: Eight hundred eighty-four consecutive ischemic stroke patients recruited to our prospective STROKE-CARD Registry were assessed concerning their glycemic status at baseline (normoglycemia, prediabetes, DM II) and change over time within 1 year follow-up. Multivariate logistic regression was performed to identify factors associated with transitioning from normoglycemia to prediabetes or DM II. Additionally, we reviewed ongoing clinical trials for GLP-1-RA and SGLT-2 inhibitors in the context of acute ischemic stroke. RESULTS: At baseline, 44.6% (n = 394) of individuals had normoglycemia, 33.9% (n = 300) were prediabetic, and 21.5% had DM II (n = 190). After 1 year, normoglycemia decreased by 12.1 percentage points (n = 107), whereas prediabetes and DM II increased by 10.2 percentage (n = 90) points and 1.9 percentage points (n = 17), respectively. Statin therapy was the only significant risk factor for progression. 23.4% (n = 207) of our cohort would have met eligibility criteria for a recent trial on semaglutide in obese non-diabetics with prior cardiovascular disease. However, only one ongoing trial aims at evaluating short-term cardiovascular risk reduction in stroke patients. DISCUSSION: GPrediabetes and DM II are frequent in ischemic stroke patients. Even within an intensified post-stroke disease management setting, a considerable amount of stroke survivors convert to prediabetes or DM II within the first year. Our results demonstrate a notable proportion of patients qualifying inclusion in studies examining the efficacy of GLP-1-RA agonists and SGLT-2 inhibitors in secondary prevention. CONCLUSION: Given the high prevalence and progression of prediabetes and DM II in stroke survivors, there is a need for clinical trials evaluating the use of GLP-1-RA and SGLT-2 inhibitors in this population. FAU - Moelgg, Kurt AU - Moelgg K AUID- ORCID: 0009-0004-3508-3923 AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Karisik, Anel AU - Karisik A AUID- ORCID: 0009-0000-3075-5437 AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Scherer, Lukas AU - Scherer L AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Buergi, Lucie AU - Buergi L AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Dejakum, Benjamin AU - Dejakum B AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Komarek, Silvia AU - Komarek S AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Granna, Julian AU - Granna J AUID- ORCID: 0000-0003-2645-5129 AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Boehme, Christian AU - Boehme C AUID- ORCID: 0000-0003-1369-418X AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Pechlaner, Raimund AU - Pechlaner R AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Toell, Thomas AU - Toell T AUID- ORCID: 0000-0002-8168-2837 AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. FAU - Knoflach, Michael AU - Knoflach M AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Kiechl, Stefan AU - Kiechl S AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. AD - VASCage, Centre on Clinical Stroke Research, Innsbruck, Austria. FAU - Kaser, Susanne AU - Kaser S AD - Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria. FAU - Egger, Alexander AU - Egger A AD - Central Institute of Clinical Chemistry and Laboratory Medicine, Medical University of Innsbruck, Innsbruck, Austria. FAU - Griesmacher, Andrea AU - Griesmacher A AD - Central Institute of Clinical Chemistry and Laboratory Medicine, Medical University of Innsbruck, Innsbruck, Austria. FAU - Mayer-Suess, Lukas AU - Mayer-Suess L AUID- ORCID: 0000-0002-2856-0101 AD - Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria. LA - eng PT - Journal Article DEP - 20250107 PL - England TA - Eur Stroke J JT - European stroke journal JID - 101688446 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) SB - IM MH - Humans MH - Male MH - Female MH - Aged MH - *Diabetes Mellitus, Type 2/epidemiology/drug therapy MH - *Prediabetic State/epidemiology/drug therapy MH - *Ischemic Stroke/complications/epidemiology MH - Middle Aged MH - Prospective Studies MH - Registries MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Blood Glucose/metabolism MH - Aged, 80 and over MH - Disease Progression PMC - PMC11705302 OTO - NOTNLM OT - Prediabetes OT - antidiabetic therapy OT - cardiovascular risk factors OT - ischemic stroke OT - secondary prevention OT - type II diabetes mellitus COIS- Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2025/01/07 06:22 MHDA- 2025/09/16 00:33 PMCR- 2025/01/07 CRDT- 2025/01/07 04:23 PHST- 2025/09/16 00:33 [medline] PHST- 2025/01/07 06:22 [pubmed] PHST- 2025/01/07 04:23 [entrez] PHST- 2025/01/07 00:00 [pmc-release] AID - 10.1177_23969873241304301 [pii] AID - 10.1177/23969873241304301 [doi] PST - ppublish SO - Eur Stroke J. 2025 Sep;10(3):822-828. doi: 10.1177/23969873241304301. Epub 2025 Jan 7. PMID- 39762971 OWN - NLM STAT- MEDLINE DCOM- 20250206 LR - 20260808 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 3 DP - 2025 Mar TI - Greater improvement in insulin sensitivity per unit weight loss associated with tirzepatide versus semaglutide: An exploratory analysis. PG - 1507-1514 LID - 10.1111/dom.16159 [doi] AB - AIMS: To explore the relationship between weight loss and insulin sensitivity in response to tirzepatide or semaglutide. MATERIALS AND METHODS: We conducted a post hoc exploratory analysis of a 28-week, double-blind, randomized trial in people with type 2 diabetes treated with metformin, randomized to tirzepatide 15 mg, semaglutide 1 mg or placebo. We evaluated the relationship between change in body weight and change in insulin sensitivity determined from hyperinsulinemic euglycemic clamp (M value), or from mixed-meal tolerance testing (Matsuda index). RESULTS: Tirzepatide was associated with a greater improvement than semaglutide in insulin sensitivity assessed using hyperinsulinemic euglycemic clamps (p < 0.001). With tirzepatide, improvements in insulin sensitivity were associated with percent change in weight (R = -0.656, p < 0.0001). With semaglutide, change in insulin sensitivity was less strongly correlated with percent change in weight (R = -0.268, p = 0.0820; p = 0.0242 vs. tirzepatide). In regression analyses, the slope of the relationship between change in M value and change in weight was statistically different between semaglutide and tirzepatide (p = 0.0461). These relationships were also assessed using the Matsuda index as the metric of insulin sensitivity, and using change in fat mass as the determinant of change in insulin sensitivity. CONCLUSIONS: Improvement in insulin sensitivity was proportional to weight and fat loss, with greater strength of association with tirzepatide. In regression analysis, tirzepatide was associated with greater improvement in insulin sensitivity per unit weight loss than semaglutide. The greater improvement in insulin sensitivity following treatment with tirzepatide was not simply attributable to greater weight or fat loss. CI - (c) 2025 John Wiley & Sons Ltd. FAU - Mather, Kieren J AU - Mather KJ AUID- ORCID: 0000-0001-8696-7500 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Mari, Andrea AU - Mari A AD - Institute of Neuroscience, National Research Council, Padova, Italy. FAU - Weerakkody, Govinda AU - Weerakkody G AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Heise, Tim AU - Heise T AUID- ORCID: 0000-0002-8346-2037 AD - Profil, Neuss, Germany. FAU - DeVries, J Hans AU - DeVries JH AUID- ORCID: 0000-0001-9196-9906 AD - Profil, Neuss, Germany. FAU - Urva, Shweta AU - Urva S AUID- ORCID: 0000-0002-3681-479X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Coskun, Tamer AU - Coskun T AUID- ORCID: 0000-0002-2481-133X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Milicevic, Zvonko AU - Milicevic Z AUID- ORCID: 0000-0002-6746-901X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Haupt, Axel AU - Haupt A AUID- ORCID: 0000-0003-4502-0470 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Thomas, Melissa K AU - Thomas MK AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng GR - Eli Lilly and Company/ PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial DEP - 20250106 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 9100L32L2N (Metformin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Insulin Resistance MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Double-Blind Method MH - *Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - Glucose Clamp Technique MH - Metformin/therapeutic use MH - Blood Glucose/metabolism/drug effects MH - Aged MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GIP OT - GLP-1 OT - insulin sensitivity OT - tirzepatide OT - weight loss EDAT- 2025/01/07 00:21 MHDA- 2025/02/07 00:20 CRDT- 2025/01/06 23:52 PHST- 2024/12/06 00:00 [revised] PHST- 2024/08/26 00:00 [received] PHST- 2024/12/16 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2025/01/07 00:21 [pubmed] PHST- 2025/01/06 23:52 [entrez] AID - 10.1111/dom.16159 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Mar;27(3):1507-1514. doi: 10.1111/dom.16159. Epub 2025 Jan 6. PMID- 39757501 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260127 IS - 1941-5923 (Electronic) IS - 1941-5923 (Linking) VI - 26 DP - 2025 Jan 6 TI - Severe Hypomagnesemia and Hypocalcemia Linked to Semaglutide in Type 2 Diabetes: A Case Report. PG - e946539 LID - 10.12659/AJCR.946539 [doi] LID - e946539 AB - BACKGROUND Although hypomagnesemia is common in type 2 diabetes, clinical presentations with severe hypomagnesemia are rare. A number of oral blood glucose-lowering medications can reduce serum magnesium concentrations, and several severe cases have been reported in the presence of marked glucagon-like peptide-1 receptor agonist (GLP-1RA)-associated gastrointestinal adverse effects. In the present case, an acute presentation with severe hypomagnesemia was likely due to polypharmacy including semaglutide, albeit with a delayed relationship to discontinuation of this GLP-1RA, due to nausea and vomiting. CASE REPORT A 73-year-old woman with type 2 diabetes treated with several oral medications known to reduce serum magnesium (metformin, gliclazide, sitagliptin, esomeprazole) presented after an unwitnessed collapse at home without premonitory symptoms. She had discontinued low-dose semaglutide (0.25 mg subcutaneous weekly) 2 weeks beforehand, and her gastrointestinal adverse effects had largely resolved. She was found to have an undetectable serum magnesium (<0.3 mmol/L) and hypocalcemia. She responded to electrolyte replacement and was discharged well 2 days later. Three weeks after discharge, her serum magnesium and calcium concentrations were within the reference range, on regular oral supplements of both minerals. She spontaneously reported her longstanding muscle cramps had resolved after discharge. Her clinical features and course suggested she had chronic unrecognized hypomagnesemia associated with polypharmacy that progressed to a clinically severe level, with a likely contribution from recent antecedent semaglutide use. CONCLUSIONS Periodic monitoring of serum magnesium concentrations in at-risk individuals with type 2 diabetes is recommended, since the clinical presentation of severe hypomagnesemia can be sudden and without indicative warning symptoms. FAU - Davis, Timothy Mark Earls AU - Davis TME AD - Medical School, University of Western Australia, Fremantle, Western Australia, Australia. AD - Department of Endocrinology and Diabetes, Fiona Stanley and Fremantle Hospitals, Murdoch, Western Australia, Australia. LA - eng PT - Case Reports PT - Journal Article DEP - 20250106 PL - United States TA - Am J Case Rep JT - The American journal of case reports JID - 101489566 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - I38ZP9992A (Magnesium) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Aged MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypocalcemia/chemically induced MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Magnesium Deficiency/chemically induced MH - Magnesium/blood MH - Semaglutide PMC - PMC11717150 COIS- Conflict of interest: The author has received lecture fees from NovoNordisk Australia, manufacturers of semaglutide EDAT- 2025/01/06 10:08 MHDA- 2025/01/07 00:21 PMCR- 2025/01/06 CRDT- 2025/01/06 01:23 PHST- 2025/01/07 00:21 [medline] PHST- 2025/01/06 10:08 [pubmed] PHST- 2025/01/06 01:23 [entrez] PHST- 2025/01/06 00:00 [pmc-release] AID - 946539 [pii] AID - 10.12659/AJCR.946539 [doi] PST - epublish SO - Am J Case Rep. 2025 Jan 6;26:e946539. doi: 10.12659/AJCR.946539. PMID- 39756397 OWN - NLM STAT- MEDLINE DCOM- 20250128 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 33 IP - 2 DP - 2025 Feb TI - Effect of semaglutide 2.4 mg on use of antihypertensive and lipid-lowering treatment in five randomized controlled STEP trials. PG - 267-277 LID - 10.1002/oby.24202 [doi] AB - OBJECTIVE: The objective of this study was to assess antihypertensive and lipid-lowering treatment changes in participants receiving semaglutide 2.4 mg versus placebo across pooled populations from five Semaglutide Treatment Effect in People with Obesity (STEP) trials. METHODS: Efficacy and safety of semaglutide 2.4 mg were evaluated in the STEP clinical trials. In this post hoc analysis, STEP 1, 3, 6, and 8 (which included people with overweight or obesity) and, separately, STEP 2 and 6 (which included people with overweight or obesity and type 2 diabetes) were pooled for analysis. Changes in antihypertensive or lipid-lowering treatment intensity from randomization to end of treatment were evaluated. RESULTS: In both pooled samples, a higher proportion of participants in the semaglutide 2.4 mg group versus placebo underwent antihypertensive or lipid-lowering treatment intensity reduction by end of treatment. A smaller proportion underwent antihypertensive or lipid-lowering treatment intensification by end of treatment in the semaglutide 2.4 mg group of both samples versus placebo. In participants receiving antihypertensive or lipid-lowering medications in both samples, greater numeric reductions in body weight were observed in the semaglutide 2.4 mg group versus placebo. CONCLUSIONS: These results support a relationship between semaglutide 2.4 mg treatment of overweight and obesity and reduced need for antihypertensive and lipid-lowering treatment, facilitating treatment intensity reduction/discontinuation and abating treatment intensification. CI - (c) 2025 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Tchang, Beverly G AU - Tchang BG AUID- ORCID: 0000-0002-2955-8089 AD - Weill Cornell Medicine, New York, New York, USA. FAU - Knight, Michael G AU - Knight MG AD - The George Washington University, Washington, DC, USA. FAU - Adelborg, Kasper AU - Adelborg K AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Clements, Jennifer N AU - Clements JN AD - University of South Carolina College of Pharmacy, Columbia, South Carolina, USA. FAU - Iversen, Aske Thorn AU - Iversen AT AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Traina, Andrea AU - Traina A AD - Novo Nordisk Inc., Plainsboro, New Jersey, USA. LA - eng GR - Novo Nordisk/ GR - Novo Nordisk Inc./ PT - Journal Article PT - Randomized Controlled Trial DEP - 20250105 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Antihypertensive Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypolipidemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Antihypertensive Agents/administration & dosage MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - *Glucagon-Like Peptides/administration & dosage MH - *Hypertension/drug therapy/complications MH - *Hypolipidemic Agents/administration & dosage MH - *Obesity/drug therapy/complications MH - Overweight/drug therapy MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11774009 COIS- Michael G. Knight has participated in advisory boards and received payment for consulting from Novo Nordisk Inc.; has received support from Novo Nordisk for medical writing; has received payment for educational event participation from Gilead Sciences, Inc.; and is a member of the National Medical Association Board of Trustees (unpaid). Kasper Adelborg is an employee and shareholder of Novo Nordisk A/S and has received support from Novo Nordisk for research, medical writing, fees associated with article publication and travel, and registration fees for conferences/meetings. Jennifer N. Clements is a member and has received payment from the Novo Nordisk Cardiometabolic Speakers Bureau and the Eli Lilly Speakers Bureau. Aske Thorn Iversen is an employee and shareholder of Novo Nordisk A/S and has received support from Novo Nordisk for travel and registration fees for conferences/meetings. Beverly G. Tchang is a shareholder of Novo Nordisk Inc. and an advisor to Novo Nordisk and Palatin Technologies, Inc. Andrea Traina is an employee and shareholder of Novo Nordisk Inc. and has received support from Novo Nordisk for research, medical writing, fees associated with article publication and travel, and registration fees for conferences/meetings. EDAT- 2025/01/06 10:07 MHDA- 2025/01/28 12:35 PMCR- 2025/01/28 CRDT- 2025/01/05 18:33 PHST- 2024/09/26 00:00 [revised] PHST- 2024/05/29 00:00 [received] PHST- 2024/10/20 00:00 [accepted] PHST- 2025/01/28 12:35 [medline] PHST- 2025/01/06 10:07 [pubmed] PHST- 2025/01/05 18:33 [entrez] PHST- 2025/01/28 00:00 [pmc-release] AID - OBY24202 [pii] AID - 10.1002/oby.24202 [doi] PST - ppublish SO - Obesity (Silver Spring). 2025 Feb;33(2):267-277. doi: 10.1002/oby.24202. Epub 2025 Jan 5. PMID- 39753963 OWN - NLM STAT- MEDLINE DCOM- 20250121 LR - 20260717 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 31 IP - 1 DP - 2025 Jan TI - Proteomic changes upon treatment with semaglutide in individuals with obesity. PG - 267-277 LID - 10.1038/s41591-024-03355-2 [doi] AB - Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA(1c) at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering. A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities. This study showcases the potential of proteomics data gathered from randomized trials for providing insights into disease mechanisms and drug repurposing opportunities. These data also highlight the unmet need for, and importance of, examining proteomic changes in response to weight loss pharmacotherapy in future trials. CI - (c) 2025. The Author(s). FAU - Maretty, Lasse AU - Maretty L AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. AD - QIAGEN A/S, Aarhus, Denmark. FAU - Gill, Dipender AU - Gill D AUID- ORCID: 0000-0001-7312-7078 AD - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. AD - Sequoia Genetics, London, UK. FAU - Simonsen, Lotte AU - Simonsen L AUID- ORCID: 0000-0001-6914-0069 AD - Obesity Research, Novo Nordisk A/S, Malov, Denmark. FAU - Soh, Keng AU - Soh K AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Zagkos, Loukas AU - Zagkos L AUID- ORCID: 0000-0002-7700-8102 AD - Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. FAU - Galanakis, Michael AU - Galanakis M AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. AD - Center for Statistics and Data Science Institute, Hasselt University, Hasselt, Belgium. FAU - Sibbesen, Jonas AU - Sibbesen J AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Iglesias, Miquel Triana AU - Iglesias MT AUID- ORCID: 0000-0003-2161-8355 AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Secher, Anna AU - Secher A AUID- ORCID: 0000-0002-6276-5389 AD - Brain and Adipose Biology, Novo Nordisk A/S, Malov, Denmark. FAU - Valkenborg, Dirk AU - Valkenborg D AD - Center for Statistics and Data Science Institute, Hasselt University, Hasselt, Belgium. FAU - Purnell, Jonathan Q AU - Purnell JQ AUID- ORCID: 0000-0001-5505-6333 AD - Oregon Health & Science University (OHSU), Portland, OR, USA. FAU - Knudsen, Lotte Bjerre AU - Knudsen LB AUID- ORCID: 0000-0002-2439-7116 AD - Chief Scientific Advisor Office, Novo Nordisk A/S, Malov, Denmark. FAU - Tahrani, Abd A AU - Tahrani AA AUID- ORCID: 0000-0001-9037-1937 AD - Medical & Science, Novo Nordisk A/S, Soborg, Denmark. a.a.tahrani@bham.ac.uk. AD - Department of Metabolism and Systems Science, University of Birmingham, Birmingham, UK. a.a.tahrani@bham.ac.uk. FAU - Geybels, Milan AU - Geybels M AD - Data Science, Novo Nordisk A/S, Soborg, Denmark. AD - Genmab A/S, Valby, Denmark. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20250103 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Proteome) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism/complications MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Glycated Hemoglobin/metabolism MH - *Obesity/drug therapy/blood/metabolism MH - *Proteome/drug effects/metabolism MH - *Proteomics/methods MH - Weight Loss/drug effects MH - Clinical Trials, Phase III as Topic MH - Randomized Controlled Trials as Topic MH - Observational Studies as Topic MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11750704 COIS- Competing interests: L.S., K.S., M. Galanakis, M.T.I., J.S., A.S., L.B.K. and A.A.T. are employees and shareholders of Novo Nordisk. D.G., L.M. and M. Geybels were employees and shareholders of Novo Nordisk at the time of the analysis. M. Galanakis, M. Geybels and D.V. have received a grant from the Danish Innovation Fund (204000005B). J.Q.P. has received consulting fees from Boehringer Ingelheim and Novo Nordisk. L.Z. declares no competing interests. EDAT- 2025/01/04 00:20 MHDA- 2025/01/22 05:33 PMCR- 2025/01/03 CRDT- 2025/01/03 23:49 PHST- 2024/03/22 00:00 [received] PHST- 2024/10/14 00:00 [accepted] PHST- 2025/01/22 05:33 [medline] PHST- 2025/01/04 00:20 [pubmed] PHST- 2025/01/03 23:49 [entrez] PHST- 2025/01/03 00:00 [pmc-release] AID - 10.1038/s41591-024-03355-2 [pii] AID - 3355 [pii] AID - 10.1038/s41591-024-03355-2 [doi] PST - ppublish SO - Nat Med. 2025 Jan;31(1):267-277. doi: 10.1038/s41591-024-03355-2. Epub 2025 Jan 3. PMID- 39752752 OWN - NLM STAT- MEDLINE DCOM- 20250429 LR - 20250520 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 147 DP - 2025 Feb 6 TI - Dual GIP and GLP-1 receptor agonist tirzepatide alleviates hepatic steatosis and modulates gut microbiota and bile acid metabolism in diabetic mice. PG - 113937 LID - S1567-5769(24)02459-7 [pii] LID - 10.1016/j.intimp.2024.113937 [doi] AB - Tirzepatide is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors and is a promising therapeutic option for type 2 diabetes mellitus (T2DM). Nevertheless, its effect and underlying mechanism on hepatic steatosis remain ambiguous. Herein, we explored the impact of tirzepatide on improving hepatic steatosis in diabetic mice, with a particular focus on the gut microbiota and bile acids (BAs) using animal models. The tirzepatide effectively reduced body weight, improved insulin resistance, decreased serum and hepatic lipid levels, and mitigated liver injury. Compared to semaglutide, tirzepatide exhibited superior efficacy in reducing hepatic lipid accumulation. 16S rRNA gene sequencing and targeted metabolomics of BAs revealed that tirzepatide ameliorated gut microbiota dysbiosis and BAs metabolism in diabetic mice. Notably, tirzepatide observably increased the abundance of beneficial genera such as Akkermansia, elevated the ratio of farnesoid X receptor (FXR) antagonists (glycoursodeoxycholic acid: GUDCA, beta-muricholic acid: beta-MCA, hyodeoxycholic acid: HDCA, ursodeoxycholic acid: UDCA) to natural agonists (cholic acid: CA, lithocholic acid: LCA, chenodeoxycholic acid: CDCA, glycocholic acid: GCA, taurodeoxycholic acid: TDCA), and reduced FXR expression in intestinal tissues. In conclusion, tirzepatide attenuated hepatic steatosis in diabetic mice and regulated the gut microbiota and BAs metabolism, which may help to provide a novel therapeutic approach and therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD). CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Hu, Weiting AU - Hu W AD - Department of Clinical Medicine, The Second Clinical Medical College, Shanxi Medical University, Taiyuan 030000, China; Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. FAU - Gong, Wenyu AU - Gong W AD - Department of Clinical Medicine, The Second Clinical Medical College, Shanxi Medical University, Taiyuan 030000, China. FAU - Yang, Fan AU - Yang F AD - The First Clinical Medical College, Shanxi Medical University, Taiyuan 030000, China. FAU - Cheng, Rui AU - Cheng R AD - Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. FAU - Zhang, Gerong AU - Zhang G AD - Department of Clinical Medicine, The Second Clinical Medical College, Shanxi Medical University, Taiyuan 030000, China. FAU - Gan, Lu AU - Gan L AD - Department of Emergency Medicine and National Clinical Research Center for Geriatrics, Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu 610000, China. FAU - Zhu, Yikun AU - Zhu Y AD - Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. FAU - Qin, Weiwei AU - Qin W AD - Department of Cardiology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. FAU - Gao, Ying AU - Gao Y AD - Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. FAU - Li, Xing AU - Li X AD - Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. Electronic address: 13503504180@163.com. FAU - Liu, Jing AU - Liu J AD - Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. Electronic address: jingliu@sxmu.edu.cn. LA - eng PT - Journal Article DEP - 20250102 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Bile Acids and Salts) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - OYN3CCI6QE (Tirzepatide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) SB - IM MH - Animals MH - *Gastrointestinal Microbiome/drug effects MH - *Bile Acids and Salts/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Fatty Liver/drug therapy/metabolism MH - *Diabetes Mellitus, Experimental/drug therapy/metabolism MH - *Tirzepatide/therapeutic use/pharmacology MH - Liver/drug effects/pathology/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide/agonists MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Humans OTO - NOTNLM OT - Bile acids OT - GIP/GLP-1 receptor agonist OT - Gut microbiota OT - Hepatic steatosis OT - Tirzepatide COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2025/01/04 00:20 MHDA- 2025/01/28 11:26 CRDT- 2025/01/03 18:01 PHST- 2024/10/29 00:00 [received] PHST- 2024/12/14 00:00 [revised] PHST- 2024/12/21 00:00 [accepted] PHST- 2025/01/28 11:26 [medline] PHST- 2025/01/04 00:20 [pubmed] PHST- 2025/01/03 18:01 [entrez] AID - S1567-5769(24)02459-7 [pii] AID - 10.1016/j.intimp.2024.113937 [doi] PST - ppublish SO - Int Immunopharmacol. 2025 Feb 6;147:113937. doi: 10.1016/j.intimp.2024.113937. Epub 2025 Jan 2. PMID- 39719165 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260127 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 361 DP - 2025 Jan 15 TI - Semaglutide alleviates the pancreatic beta cell function via the METTL14 signaling and modulating gut microbiota in type 2 diabetes mellitus mice. PG - 123328 LID - S0024-3205(24)00918-4 [pii] LID - 10.1016/j.lfs.2024.123328 [doi] AB - AIMS: Semaglutide, a novel long-acting GLP-1RA, stimulates insulin and suppresses islet-secreted glucagon to reduce glucose levels. It has been unveiled that m6A mRNA modification plays a pivotal role in regulating beta cell function. However, it remains unclear whether semaglutide can elicit protective effects through manipulating m6A modification and the underlying mechanism. We aimed to elucidate the role played by semaglutide in m6A modification, and to explore its specific regulatory targets. Furthermore, we also delve into its effects on gut microbiota. MAIN METHODS: Five-week-old male C57BL/6 mice were assigned to two dietary groups and fed a control or high-fat diet for 4 weeks. Then T2DM was induced in high-fat diet-fed mice via streptozotocin (STZ), the main groups were resampled to include treatment with semaglutide (SEM, 40 mug/kg) for another 4 weeks, totaling three groups: Control, Model (T2DM), T2DM + SEM. Additionally, we elucidated specific regulatory targets and signaling pathways in palmitic acid (PA)-stimulated beta-TC-6 cells. Immunofluorescence, Western blot, and RT-qPCR were used in the study. KEY FINDINGS: Semaglutide mitigated pancreatic damage, enhanced islet cell proliferation, and restored islet size and alpha- and beta-cell masses. It also improved the expression of METTL14, pancreatic duodenal homeobox 1 (PDX-1), and protecting mitochondria, and modulated the PDX1 expression in an m6A-dependent manner. Concurrently, semaglutide significantly decreases the abundance of Firmicutes, Actinobacteriota, and Lactobacillus, while increasing the Bacteroides and norank_f_Muribaculaceae content, and the production of short-chain fatty acids (SCFA). SIGNIFICANCE: Semaglutide positively influences by regulating m6A modifications to alleviate pancreatic beta cell dysfunction and modulate the gut microbiome. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Luo, Yunfei AU - Luo Y AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China. FAU - Li, Jin-E AU - Li JE AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China. FAU - Zeng, Haixia AU - Zeng H AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China. FAU - Zhang, Yuying AU - Zhang Y AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China. FAU - Yang, Shiqi AU - Yang S AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China. FAU - Liu, Jianping AU - Liu J AD - Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, Jiangxi Province, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang City, Jiangxi Province, China; Branch of National Clinical Research Center for Metabolic Diseases, Nanchang City, Jiangxi Province, China. Electronic address: ndefy14105@ncu.edu.cn. LA - eng PT - Journal Article DEP - 20241222 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 62340-29-8 (Glucagon-Like Peptides) RN - EC 2.1.1.- (Methyltransferases) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Insulin-Secreting Cells/drug effects/metabolism MH - Male MH - *Glucagon-Like Peptides/pharmacology MH - Mice MH - *Gastrointestinal Microbiome/drug effects MH - *Mice, Inbred C57BL MH - *Diabetes Mellitus, Type 2/metabolism/drug therapy MH - *Signal Transduction/drug effects MH - *Diabetes Mellitus, Experimental/metabolism/drug therapy MH - Methyltransferases/metabolism MH - Diet, High-Fat/adverse effects MH - Hypoglycemic Agents/pharmacology MH - Semaglutide OTO - NOTNLM OT - Gut microbiota OT - METTL3/14 OT - Mitochondrial function OT - Pancreatic beta-cell function OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest No competing financial interests exist. EDAT- 2024/12/25 00:20 MHDA- 2025/01/07 00:21 CRDT- 2024/12/24 19:10 PHST- 2024/10/25 00:00 [received] PHST- 2024/12/09 00:00 [revised] PHST- 2024/12/19 00:00 [accepted] PHST- 2025/01/07 00:21 [medline] PHST- 2024/12/25 00:20 [pubmed] PHST- 2024/12/24 19:10 [entrez] AID - S0024-3205(24)00918-4 [pii] AID - 10.1016/j.lfs.2024.123328 [doi] PST - ppublish SO - Life Sci. 2025 Jan 15;361:123328. doi: 10.1016/j.lfs.2024.123328. Epub 2024 Dec 22. PMID- 39710901 OWN - NLM STAT- MEDLINE DCOM- 20241223 LR - 20260611 IS - 1536-9617 (Electronic) IS - 0020-8167 (Linking) VI - 65 IP - 1 DP - 2025 Jan 1 TI - Glucagon-like Peptide-1 Receptor Agonists in the Management of Diabetic Retinopathy. PG - 23-26 LID - 10.1097/IIO.0000000000000541 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists are a family of drugs, most well known by the third-generation once-weekly subcutaneous semaglutide, that act on the incretin pathway of metabolic, hormonal signaling to modulate pancreatic insulin release, gastric emptying, energy intake, and subjective feelings of satiety. This class of drugs' efficacy and safety in the treatment of type 2 diabetes and obesity have been demonstrated across multiple large randomized controlled trials. These data have propelled GLP-1 receptor agonists to ubiquity in diabetic management and weight loss therapy, leading them to be frequently encountered in ophthalmic practice. The effect of GLP-1 receptor agonists like semaglutide on diabetic retinopathy (DR) is at this point unclear; some studies indicate a worsening of DR with the initiation of GLP-1 agonists, especially semaglutide. Overall, the macrovascular reduction of cardiovascular and stroke risks from GLP-1 receptor agonists should be prioritized over the potential microvascular progression of DR, as long as the patient is regularly followed by ophthalmology. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Samanta, Anindya AU - Samanta A AD - Cullen Eye Institute, Baylor College of Medicine, Houston, TX. FAU - Bordbar, Darius D AU - Bordbar DD FAU - Weng, Christina Y AU - Weng CY FAU - Chancellor, John R AU - Chancellor JR LA - eng PT - Journal Article PT - Review DEP - 20241223 PL - United States TA - Int Ophthalmol Clin JT - International ophthalmology clinics JID - 0374731 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetic Retinopathy/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- C.Y.W. discloses the following relationships outside of the submitted work: Allergan/AbbVie, Alcon, Apellis Pharmaceuticals, Alimera Sciences, DORC, Novartis, Genentech, Regeneron, REGENXBIO, Astellas/Iveric Bio, EyePoint (consultant); DRCR Retina Network, Alimera Sciences, AGTC (research); Springer Publishers (royalties). The remaining authors declare that they have no conflicts of interest to disclose. EDAT- 2024/12/23 06:21 MHDA- 2024/12/23 06:22 CRDT- 2024/12/23 00:33 PHST- 2024/12/23 06:22 [medline] PHST- 2024/12/23 06:21 [pubmed] PHST- 2024/12/23 00:33 [entrez] AID - 00004397-202506510-00005 [pii] AID - 10.1097/IIO.0000000000000541 [doi] PST - ppublish SO - Int Ophthalmol Clin. 2025 Jan 1;65(1):23-26. doi: 10.1097/IIO.0000000000000541. Epub 2024 Dec 23. PMID- 39707717 OWN - NLM STAT- MEDLINE DCOM- 20250428 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 16 IP - 4 DP - 2025 Apr TI - Effectiveness for adding or switching from other incretin-related drugs to oral semaglutide in type 2 diabetes. PG - 608-614 LID - 10.1111/jdi.14391 [doi] AB - AIMS/INTRODUCTION: This study aimed to evaluate and compare the effectiveness of oral semaglutide after adding to or switching from incretin-related drugs by assessing the changes in HbA1c and body weight (BW) in participants with type 2 diabetes in clinical settings. MATERIALS AND METHODS: A total of 368 participants were divided into groups according to antidiabetic medications before oral semaglutide treatment; incretin-related drug-naive (naive), switching from dipeptidyl peptide-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonist (GLP-1 RA) groups. Adjusted mean changes in HbA1c and BW at 6 months after oral semaglutide administration were compared among the three groups. Similar analyses were performed in the GLP-1 RAs group between GLP-1RAs before switching. RESULTS: Mean change of HbA1c in DPP-4i and GLP-1 RA groups was -0.67% (95% confidence interval [CI]: -0.79 to -0.54) and -0.13% (95% CI: -0.40 to 0.15), respectively, which were significantly smaller than incretin-related drug-naive group; -0.85% (95% CI: -1.08 to -0.62). Mean change in BW between the naive and DPP-4i groups had no differences; however, these changes were lower in the GLP-1 RA group than in the naive group. Mean change in HbA1c between pretreatment with GLP-1 RAs had no differences; however, the mean change in BW in the dulaglutide group was significantly higher than that in the injectable semaglutide group. CONCLUSION: Oral semaglutide reduced HbA1c levels and BW after adding or switching from other incretin-related drugs in Japanese participants with type 2 diabetes. CI - (c) 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Oya, Junko AU - Oya J AUID- ORCID: 0000-0002-6413-2606 AD - Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. FAU - Shimizu, Mika AU - Shimizu M AUID- ORCID: 0009-0003-8614-4776 AD - Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. FAU - Kubota, Ryo AU - Kubota R AD - Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. FAU - Suda, Rika AU - Suda R AD - Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. FAU - Nagkagami, Tomoko AU - Nagkagami T AUID- ORCID: 0000-0003-4376-7212 AD - Division of Diabetology and Metabolism, Department of Internal Medicine, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20241220 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glycated Hemoglobin) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/analogs & derivatives MH - Female MH - Male MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Middle Aged MH - *Incretins/therapeutic use/administration & dosage MH - Administration, Oral MH - Glycated Hemoglobin/analysis MH - Aged MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Drug Therapy, Combination MH - *Drug Substitution MH - Blood Glucose/analysis MH - Treatment Outcome MH - Follow-Up Studies MH - Body Weight/drug effects MH - *Biomarkers/analysis MH - Prognosis MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11970300 OTO - NOTNLM OT - Dipeptidyl peptidase-4 inhibitor OT - Oral semaglutide OT - Real-world clinical setting COIS- Nakagami received personal fees from Sanwa Kagaku Kenkyusho Co. Ltd., Novo Nordisk Pharma Ltd., Japan; Eli Lily Japan KK, Sanofi K.K., Sumitomo Pharma, and Boehringer Ingelheim Japan Inc. The authors declare no conflicts of interest. Approval of the research protocol: N/A. Informed consent: Informed consent was obtained from all study participants. Registry and registration no. of the study/trial: N/A. Animal studies: N/A. EDAT- 2024/12/21 16:42 MHDA- 2025/04/04 12:29 PMCR- 2024/12/20 CRDT- 2024/12/21 02:43 PHST- 2024/11/21 00:00 [revised] PHST- 2024/08/20 00:00 [received] PHST- 2024/12/10 00:00 [accepted] PHST- 2025/04/04 12:29 [medline] PHST- 2024/12/21 16:42 [pubmed] PHST- 2024/12/21 02:43 [entrez] PHST- 2024/12/20 00:00 [pmc-release] AID - JDI14391 [pii] AID - 10.1111/jdi.14391 [doi] PST - ppublish SO - J Diabetes Investig. 2025 Apr;16(4):608-614. doi: 10.1111/jdi.14391. Epub 2024 Dec 20. PMID- 39700591 OWN - NLM STAT- MEDLINE DCOM- 20250428 LR - 20260818 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 39 IP - 2 DP - 2025 Feb TI - The effect of semaglutide combined with metformin on liver inflammation and pancreatic beta-cell function in patients with type 2 diabetes and non-alcoholic fatty liver disease. PG - 108932 LID - S1056-8727(24)00258-7 [pii] LID - 10.1016/j.jdiacomp.2024.108932 [doi] AB - BACKGROUND: Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) were often coexistent conditions driven by insulin resistance and systemic inflammation. Effective management strategies that address both metabolic disorders were urgently needed. This study investigates the effect of combining semaglutide, a glucagon-like peptide-1 receptor agonist, with metformin on liver inflammation and pancreatic beta-cell function in patients with T2DM and NAFLD. METHODS: This retrospective study analyzed 261 patients with T2DM and NAFLD treated at our institution from January 2021 to December 2023. Patients were divided into two groups: 127 received metformin alone (M group), and 134 received a combination of semaglutide and metformin (SAM group). Liver inflammation and fibrosis were assessed using alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (gamma-GTP), and the FIB-4 index. Pancreatic beta-cell function and insulin sensitivity were evaluated using the Matsuda index, HbA1c, fasting glucose, and the oral disposition index (DIo). RESULTS: Post-treatment, the SAM group showed significantly greater improvements in liver inflammation markers (ALT: 23.59 +/- 5.67 U/L in SAM vs. 25.56 +/- 5.46 U/L in M; AST: 18.97 +/- 3.94 U/L in SAM vs. 20.15 +/- 3.95 U/L in M), reduced fibrosis (FIB-4 index: 1.05 +/- 0.44 in SAM vs. 1.16 +/- 0.51 in M), and enhanced beta-cell function (Matsuda index: 5.18 +/- 1.09 in SAM vs. 4.84 +/- 1.15 in M; DIo: 0.18 +/- 0.06 in SAM vs. 0.16 +/- 0.05 in M). Glycemic control, as indicated by reduced HbA1c, was also superior in the SAM group. CONCLUSION: The combination of semaglutide and metformin significantly improves liver inflammation, fibrosis, and beta-cell function in patients with T2DM and NAFLD compared to metformin alone. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Ren, Rong AU - Ren R AD - Ward 1, Department of Endocrinology, Shanxi Provincial Integrated TCM And WM Hospital, Taiyuan 030013, China. Electronic address: RenYang_111@163.com. FAU - Pei, Yanxia AU - Pei Y AD - Department of Third Clinical College, Shanxi University of Chinese Medicine, Jinzhong 030619, China. FAU - Kong, Lufei AU - Kong L AD - Department of Third Clinical College, Shanxi University of Chinese Medicine, Jinzhong 030619, China. FAU - Shi, Yixin AU - Shi Y AD - Department of Third Clinical College, Shanxi University of Chinese Medicine, Jinzhong 030619, China. LA - eng PT - Journal Article DEP - 20241209 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 9100L32L2N (Metformin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Metformin/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - *Insulin-Secreting Cells/drug effects/physiology MH - Female MH - *Non-alcoholic Fatty Liver Disease/drug therapy/complications/physiopathology MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Hypoglycemic Agents/therapeutic use MH - Drug Therapy, Combination MH - Aged MH - Insulin Resistance MH - Liver/drug effects/pathology MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Insulin sensitivity OT - Liver inflammation OT - Metformin OT - Non-alcoholic fatty liver disease OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/12/20 00:23 MHDA- 2025/02/11 00:18 CRDT- 2024/12/19 18:01 PHST- 2024/11/04 00:00 [received] PHST- 2024/11/29 00:00 [revised] PHST- 2024/12/05 00:00 [accepted] PHST- 2025/02/11 00:18 [medline] PHST- 2024/12/20 00:23 [pubmed] PHST- 2024/12/19 18:01 [entrez] AID - S1056-8727(24)00258-7 [pii] AID - 10.1016/j.jdiacomp.2024.108932 [doi] PST - ppublish SO - J Diabetes Complications. 2025 Feb;39(2):108932. doi: 10.1016/j.jdiacomp.2024.108932. Epub 2024 Dec 9. PMID- 39697128 OWN - NLM STAT- MEDLINE DCOM- 20241219 LR - 20250121 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 79 IP - 12 DP - 2024 Dec TI - [Tirzepatide : overview of clinical studies SURPASS in type 2 diabetes and SURMOUNT in obesity]. PG - 812-820 AB - Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, which has been developed as once-weekly injection first for the treatment of type 2 diabetes (T2DM), then for the treatment of obesity. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, semaglutide 1 mg, basal insulin and preprandial boluses of insulin lispro in six studies of the SURPASS programme. In the SURMOUNT programme, tirzepatide showed a marked reduction in body weight, never reached before with a drug, among people with obesity or overweight associated with complications linked to excess weight. Such weight loss was accompanied by an improvement of comorbidities (as sleep apnea syndrome) and cardiovascular risk factors. Two large cardiovascular outcome trials are ongoing in patients with T2DM (SURPASS-CVOT) and in patients with obesity (SURMOUNT-MMO). FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. AD - Unite de Pharmacologie clinique, Centre Interdisciplinaire de Recherche sur le Medicament (CIRM), ULiege, Belgique. LA - fre PT - English Abstract PT - Journal Article PT - Review TT - Le medicament du mois. Le tirzepatide : resume des etudes cliniques SURPASS dans le diabete de type 2 et SURMOUNT dans l'obesite. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Clinical Trials as Topic MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide OTO - NOTNLM OT - Dual agonist OT - GIP/GLP-1 co-agonist OT - Obesity OT - Tirzepatide OT - Type 2 diabetes EDAT- 2024/12/19 06:22 MHDA- 2024/12/19 06:23 CRDT- 2024/12/19 04:22 PHST- 2024/12/19 06:23 [medline] PHST- 2024/12/19 06:22 [pubmed] PHST- 2024/12/19 04:22 [entrez] PST - ppublish SO - Rev Med Liege. 2024 Dec;79(12):812-820. PMID- 39688041 OWN - NLM STAT- MEDLINE DCOM- 20241217 LR - 20260127 IS - 2038-1840 (Electronic) IS - 0034-1193 (Linking) VI - 115 IP - 12 DP - 2024 Dec TI - [Impact of Elon Musk's statements on the use of semaglutide in the Lazio Region: a time series analysis study.]. PG - 593-598 LID - 10.1701/4392.43917 [doi] AB - INTRODUCTION: In recent times, TikTok 'weight loss influencers' have been promoting the use of GLP-1 receptor agonist drugs, with particular emphasis on semaglutide. The popularity of this class of drugs has been amplified by the statements of Elon Musk, who publicly declared in October 2022 that he had lost weight thanks to Wegovy, a semaglutide-based medication launched in the US. In Italy, GLP-1 receptor agonists are mainly indicated for the treatment of type 2 diabetes, but in certain cases they can be prescribed off-label for obesity and overweight. The aim of this study is to assess the impact of Elon Musk's statements on the use of semaglutide within Regional Health Service of the Lazio Region. METHODS: Dispensations of GLP-1 receptor agonist drugs (ATC: A10BJ) within Regional Health Service in the Lazio Region between January 2022 and March 2023 were analysed, identifying those related to semaglutide (ATC: A10BJ06). Monthly time series data on new users (with a 1-year washout period) of semaglutide and other GLP-1 drugs were compared to identify any changes after October 2022. In addition, the proportion of patients for whom it was possible to verify the indication of diabetes through health administrative data was examined. RESULTS: Analysis of the monthly trends for the entire class of GLP-1 receptor agonist drugs showed no difference in the monthly average of incident users between the pre and post Elon Musk statements. However, an increase in incident users was observed for semaglutide (monthly average: from 872 pre to 1,380 post) at the expense of the use of other drugs in the same class (monthly average: from 711 pre to 208 post). The proportion of semaglutide users for whom diabetes could not be confirmed remained stable over time at approximately 9.5%. CONCLUSIONS: Elon Musk's statements seem to have had an impact on the use of semaglutide among patients in the Lazio region. Further analyses are necessary to carefully assess the presence of possible other factors influencing the preference for semaglutide over other GLP-1 receptor agonists. FAU - Belleudi, Valeria AU - Belleudi V AD - Dipartimento di epidemiologia Asl Roma 1, Ssr Lazio. FAU - Lopes, Sara AU - Lopes S AD - Dipartimento di epidemiologia Asl Roma 1, Ssr Lazio. FAU - Addis, Antonio AU - Addis A AD - Dipartimento di epidemiologia Asl Roma 1, Ssr Lazio. LA - ita PT - English Abstract PT - Journal Article TT - Impatto delle dichiarazioni di Elon Musk sull'uso della semaglutide nella Regione Lazio: uno studio di analisi delle serie temporali. PL - Italy TA - Recenti Prog Med JT - Recenti progressi in medicina JID - 0401271 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Humans MH - Italy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use/administration & dosage MH - Obesity/drug therapy MH - Weight Loss/drug effects MH - Overweight/drug therapy MH - Practice Patterns, Physicians'/statistics & numerical data MH - Time Factors MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2024/12/17 11:49 MHDA- 2024/12/17 12:30 CRDT- 2024/12/17 05:33 PHST- 2024/12/17 12:30 [medline] PHST- 2024/12/17 11:49 [pubmed] PHST- 2024/12/17 05:33 [entrez] AID - 10.1701/4392.43917 [doi] PST - ppublish SO - Recenti Prog Med. 2024 Dec;115(12):593-598. doi: 10.1701/4392.43917. PMID- 39684653 OWN - NLM STAT- MEDLINE DCOM- 20241217 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 23 DP - 2024 Dec 2 TI - Pharmacological Nephroprotection in Chronic Kidney Disease Patients with Type 2 Diabetes Mellitus-Clinical Practice Position Statement of the Polish Society of Nephrology. LID - 10.3390/ijms252312941 [doi] LID - 12941 AB - Both chronic kidney disease (CKD) and type 2 diabetes (T2D) are modern epidemics worldwide and have become a severe public health problem. Chronic kidney disease progression in T2D patients is linked to the need for dialysis or kidney transplantation and represents the risk factor predisposing to serious cardiovascular complications. In recent years, important progress has occurred in nephroprotective pharmacotherapy in CKD patients with T2D. In the current position paper, we described a nephroprotective approach in CKD patients with T2D based on the five following pillars: effective antihyperglycemic treatment, SGLT2 inhibitor or semaglutide, antihypertensive therapy, use of RASi (ARB or ACEi), and in selected patients, finerenone, as well as sodium bicarbonate in patients with metabolic acidosis. We thought that the current statement is comprehensive and up-to-date and addresses multiple pathways of nephroprotection in patients with CKD and T2D. FAU - Adamczak, Marcin AU - Adamczak M AD - Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, 40-027 Katowice, Poland. FAU - Kurnatowska, Ilona AU - Kurnatowska I AUID- ORCID: 0000-0003-3448-0682 AD - Department of Internal Diseases and Transplant Nephrology, Medical University of Lodz, 90-153 Lodz, Poland. FAU - Naumnik, Beata AU - Naumnik B AUID- ORCID: 0000-0001-7090-8856 AD - 1st Department of Nephrology, Transplantation and Internal Medicine with Dialysis Unit, Medical University of Bialystok, 15-540 Bialystok, Poland. FAU - Stompor, Tomasz AU - Stompor T AD - Department of Nephrology, Hypertension and Internal Medicine, University of Warmia and Mazury in Olsztyn, 10-516 Olsztyn, Poland. FAU - Tylicki, Leszek AU - Tylicki L AD - Department of Nephrology, Transplantology and Internal Medicine, Medical University of Gdansk, 80-952 Gdansk, Poland. FAU - Krajewska, Magdalena AU - Krajewska M AUID- ORCID: 0000-0002-2632-2409 AD - Department of Non-Surgical Clinical Sciences, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland. LA - eng GR - Publication cost covering/Polish Society of Nephrology/ PT - Journal Article PT - Practice Guideline PT - Review DEP - 20241202 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Antihypertensive Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (finerenone) RN - 0 (Naphthyridines) SB - IM MH - Humans MH - Angiotensin Receptor Antagonists/therapeutic use/pharmacology MH - Angiotensin-Converting Enzyme Inhibitors/therapeutic use MH - Antihypertensive Agents/therapeutic use/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Diabetic Nephropathies/drug therapy/prevention & control MH - Hypoglycemic Agents/therapeutic use MH - Nephrology/standards/methods MH - Poland MH - *Renal Insufficiency, Chronic/drug therapy MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Naphthyridines PMC - PMC11641270 OTO - NOTNLM OT - blood pressure control OT - chronic kidney disease OT - diabetes mellitus type 2 OT - metabolic acidosis OT - nephroprotection OT - renin-angiotensin system OT - sodium-glucose co-transporter type 2 inhibitors COIS- Marcin Adamczak receives speaker's fees from AstraZeneca, Boehringer Ingelheim, Bayer, and Sanprobi, travel grants from AstraZeneca, Sandoz, and Chiesi, and participates in the advisory board for AstraZeneca and Boehringer Ingelheim. Ilona Kurnatowska receives speaker's fees from AstraZeneca, Boehringer Ingelheim, and Bayer and travel grants from AstraZeneca, Boehringer Ingelheim, and Chiesi. Beata Naumnik receives speaker's fees from AstraZeneca, Bayer, Boehringer Ingelheim, Baxter, Sandoz, travel grants from AstraZeneca, participates in advisory boards for AstraZeneca, Boehringer Ingelheim, and FreseniusCabi, and participates in clinical trials sponsored by AstraZeneca, Boehringer Ingelheim, Novartis, and Alexion. Tomasz Stompor receives speaker's fees from AstraZeneca, Berlin-Chemie/Menarini, Boehringer Ingelheim, Bayer, and Novo Nordisk, participates in advisory boards for AstraZeneca and Boehringer Ingelheim, and participates in clinical trials sponsored by AstraZeneca and Bayer. Leszek Tylicki declares no conflict of interest. Magdalena Krajewska receives speaker's fees from AstraZeneca, Boehringer Ingelheim, Bayer, Takeda, Amicus, Astellas, Chiesi, Fresenius Kabi and Swixx Pharma; travel grants from AstraZeneca, Sandoz, Chiesi and Boehringer Ingelheim; and participates in the advisory board for AstraZeneca and Boehringer Ingelheim. EDAT- 2024/12/17 11:48 MHDA- 2024/12/17 11:49 PMCR- 2024/12/02 CRDT- 2024/12/17 01:14 PHST- 2024/10/17 00:00 [received] PHST- 2024/11/20 00:00 [revised] PHST- 2024/11/26 00:00 [accepted] PHST- 2024/12/17 11:49 [medline] PHST- 2024/12/17 11:48 [pubmed] PHST- 2024/12/17 01:14 [entrez] PHST- 2024/12/02 00:00 [pmc-release] AID - ijms252312941 [pii] AID - ijms-25-12941 [pii] AID - 10.3390/ijms252312941 [doi] PST - epublish SO - Int J Mol Sci. 2024 Dec 2;25(23):12941. doi: 10.3390/ijms252312941. PMID- 39680313 OWN - NLM STAT- MEDLINE DCOM- 20250427 LR - 20260817 IS - 1865-8652 (Electronic) IS - 0741-238X (Linking) VI - 42 IP - 2 DP - 2025 Feb TI - Long-Term Clinical and Economic Effects of Switching to Once-Weekly Semaglutide from Other GLP-1 RAs Among Patients with Type 2 Diabetes in China: A Modeling Projection Study. PG - 904-917 LID - 10.1007/s12325-024-03082-7 [doi] AB - INTRODUCTION: Previous studies, using clinical trial data, demonstrated that once-weekly (OW) semaglutide is dominant versus other glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in China. This study aims to evaluate the long-term clinical and economic effects of switching to OW semaglutide from other GLP-1 RAs among patients with type 2 diabetes mellitus (T2DM) in China. METHODS: The Institute of Health Economics Diabetes Cohort Model (IHE-DCM) was used to project life expectancy, quality-adjusted life years (QALYs), and total direct medical cost over 40 years from a Chinese healthcare system perspective. Baseline characteristics, clinical effectiveness, and the treatment dose of OW semaglutide were derived from previously real-world studies. Patients were assumed to switch to semaglutide or continue previous GLP-1 RAs for 3 years and change to intensive therapy. Drug prices were based on the median bidding price in January 2024 in China. Costs of other GLP-1 RAs were calculated on the basis of their market share in China. All costs were accounted as 2023 Chinese yuan (CNY). A discount of 5% was applied. One-way sensitivity analyses and probabilistic sensitivity analyses were used to test the robustness of the base-case result. RESULTS: The results show that switching to OW semaglutide from other GLP-1 RAs among patients with T2DM in China can improve life expectancy by 0.02 years and afford an additional 0.12 QALYs per patient. Meanwhile, switching to OW semaglutide is associated with decreased total lifetime direct medical costs of 4204 CNY per patient, mainly resulting from savings in microvascular costs (2214 CNY) and macrovascular costs (1228 CNY). Sensitivity analyses show the robustness of modeling projection findings. CONCLUSION: Based on real-world data from China, this modeling projection study demonstrates that switching to OW semaglutide from other GLP-1 RAs can have better clinical and economic effects for patients with T2DM in China, indicating it as a dominant treatment choice. CI - (c) 2024. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature. FAU - Hu, Ying AU - Hu Y AD - Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army General Hospital, 28 Fu Xing Road, Haidian District, Beijing, China. FAU - Chen, Xianwen AU - Chen X AUID- ORCID: 0009-0008-5903-8368 AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Room 1050, E12 Research Building, Macau, SAR, China. FAU - Zou, Huimin AU - Zou H AUID- ORCID: 0000-0002-6239-3335 AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Room 1050, E12 Research Building, Macau, SAR, China. FAU - Zhang, Hao AU - Zhang H AUID- ORCID: 0000-0003-2180-0122 AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd, Beijing, China. FAU - Ni, Qi AU - Ni Q AD - Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army General Hospital, 28 Fu Xing Road, Haidian District, Beijing, China. FAU - Li, Yijun AU - Li Y AD - Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army General Hospital, 28 Fu Xing Road, Haidian District, Beijing, China. FAU - Ung, Carolina Oi Lam AU - Ung COL AUID- ORCID: 0000-0003-1915-5099 AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Room 1050, E12 Research Building, Macau, SAR, China. AD - Centre for Pharmaceutical Regulatory Sciences, University of Macau, Macao, China. AD - Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao, China. FAU - Hu, Hao AU - Hu H AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Room 1050, E12 Research Building, Macau, SAR, China. haohu@um.edu.mo. AD - Centre for Pharmaceutical Regulatory Sciences, University of Macau, Macao, China. haohu@um.edu.mo. AD - Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao, China. haohu@um.edu.mo. FAU - Mu, Yiming AU - Mu Y AUID- ORCID: 0000-0002-3344-3540 AD - Department of Endocrinology, The First Medical Center, Chinese People's Liberation Army General Hospital, 28 Fu Xing Road, Haidian District, Beijing, China. muyiming@301hospital.com.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241216 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucagon-Like Peptides/administration & dosage/economics/therapeutic use MH - China MH - *Hypoglycemic Agents/economics/administration & dosage/therapeutic use MH - Female MH - Male MH - Middle Aged MH - Quality-Adjusted Life Years MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Aged MH - Drug Administration Schedule MH - Cost-Benefit Analysis MH - Life Expectancy MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - China OT - Modeling OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of Interest: Hao Zhang is an employee of Novo Nordisk. Ying Hu, Xianwen Chen, Huimin Zou, Hao Zhang, Qi Ni, Yijun Li, Carolina Oi Lam Ung, and Yiming Mu declare that they have no competing interests. Ethics Approval: This article is based on previously conducted clinical trials and does not contain any studies with human participants or animals performed by any authors. EDAT- 2024/12/16 12:27 MHDA- 2025/02/01 20:43 CRDT- 2024/12/16 11:33 PHST- 2024/10/30 00:00 [received] PHST- 2024/11/22 00:00 [accepted] PHST- 2025/02/01 20:43 [medline] PHST- 2024/12/16 12:27 [pubmed] PHST- 2024/12/16 11:33 [entrez] AID - 10.1007/s12325-024-03082-7 [pii] AID - 10.1007/s12325-024-03082-7 [doi] PST - ppublish SO - Adv Ther. 2025 Feb;42(2):904-917. doi: 10.1007/s12325-024-03082-7. Epub 2024 Dec 16. PMID- 39680131 OWN - NLM STAT- MEDLINE DCOM- 20250722 LR - 20260127 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 62 IP - 7 DP - 2025 Jul TI - Comparing medication persistence with oral and subcutaneous semaglutide in a real-world setting. PG - 1065-1072 LID - 10.1007/s00592-024-02424-9 [doi] AB - AIMS: To compare medication persistence and efficacy of oral and subcutaneous semaglutide, in a real-world setting. MATERIALS AND METHODS: This is a single-center, retrospective observational cohort study. Patients with type 2 diabetes mellitus (T2DM) starting treatment with either formulation of semaglutide between January 1 2019 and July 31 2023 and with at least one follow-up visit were included. The primary endpoint was the difference in the proportion of patients that continued treatment after 6, 12 and 18 months. Main secondary endpoints were change in HbA1c and body weight. RESULTS: We included 242 patients on oral (n = 121) and subcutaneous (n = 121) semaglutide. At baseline, patients in the oral semaglutide group were significantly older (mean age: 67 +/- 11 vs. 63 +/- 11 years, p = 0.002) and had a lower body mass index (BMI: 30.5 +/- 5.6 vs. 33.9 +/- 7.1 kg/m(2), p < 0.001). The proportion of patients persistent to treatment was significantly lower in the oral group at 6 (85.3% vs. 94.8%; p < 0.001), 12 (72.3% vs. 92.4%, p < 0.001) and 18 (46.0% vs. 83.8%; p < 0.001) months. Most common reasons for discontinuation were gastro-intestinal side effects. When adjusted for age and BMI, body weight and HbA1c reduction were not significantly different between the two formulations, as the proportion of patients achieving the composite outcome of weight loss >/= 5% and HbA1c < 7.0%. CONCLUSIONS: The present real-world study suggests that persistence is significantly lower when semaglutide is administered as a once-daily tablet compared with a weekly injection, while there are no differences in efficacy between the two formulations. CI - (c) 2024. Springer-Verlag Italia S.r.l., part of Springer Nature. FAU - Conti, Matteo AU - Conti M AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. AD - Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. FAU - Pontiggia, Lorenzo AU - Pontiggia L AD - Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. FAU - Vergani, Michela AU - Vergani M AD - Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. FAU - Muraca, Emanuele AU - Muraca E AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. FAU - Cannistraci, Rosa AU - Cannistraci R AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. FAU - Perra, Silvia AU - Perra S AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. FAU - Lattuada, Guido AU - Lattuada G AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. FAU - Perseghin, Gianluca AU - Perseghin G AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. AD - Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. FAU - Ciardullo, Stefano AU - Ciardullo S AUID- ORCID: 0000-0003-2422-3041 AD - Department of Medicine and Rehabilitation, Policlinico di Monza, Monza, Italy. stefano.ciardullo@policlinicodimonza.it. AD - Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy. stefano.ciardullo@policlinicodimonza.it. AD - Department of Medicine and Surgery, Department of Medicine and Rehabilitation, Universita degli Studi di Milano Bicocca, Policlinico di Monza, Via Modigliani 10, 20900, Monza, MB, Italy. stefano.ciardullo@policlinicodimonza.it. LA - eng PT - Comparative Study PT - Journal Article PT - Observational Study DEP - 20241216 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - Retrospective Studies MH - Aged MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Glycated Hemoglobin/analysis/metabolism MH - Injections, Subcutaneous MH - Blood Glucose MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adherence OT - Diabetes OT - Persistence OT - Real-world OT - Semaglutide COIS- Declarations. Conflict of interest: The authors have no conflicts of interest to report. EDAT- 2024/12/16 12:28 MHDA- 2025/07/23 10:54 CRDT- 2024/12/16 11:15 PHST- 2024/10/07 00:00 [received] PHST- 2024/11/23 00:00 [accepted] PHST- 2025/07/23 10:54 [medline] PHST- 2024/12/16 12:28 [pubmed] PHST- 2024/12/16 11:15 [entrez] AID - 10.1007/s00592-024-02424-9 [pii] AID - 10.1007/s00592-024-02424-9 [doi] PST - ppublish SO - Acta Diabetol. 2025 Jul;62(7):1065-1072. doi: 10.1007/s00592-024-02424-9. Epub 2024 Dec 16. PMID- 39666879 OWN - NLM STAT- MEDLINE DCOM- 20250205 LR - 20260818 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 41 IP - 1 DP - 2025 Jan TI - Glucagon-like peptide 1 receptor agonists modestly reduced low-density lipoprotein cholesterol and total cholesterol levels independent of weight reduction: a meta-analysis and meta-regression of placebo controlled randomized controlled trials. PG - 185-197 LID - 10.1080/03007995.2024.2442027 [doi] AB - BACKGROUND: The effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on lipid components are unclear. We aim to quantify the lipid lowering effects of GLP1-RAs. METHODS: A comprehensive database search for placebo-controlled randomized controlled trials (RCTs) on GLP-1RA treatment was conducted until January 2023. Data extraction and quality assessment were performed, and outcomes were analyzed using a random-effects model to calculate weighted mean differences (MDs) in milligrams per deciliter (mg/dl) and 95% confidence intervals (CIs). The primary endpoint was the mean difference in low-density lipoprotein cholesterol (LDL-C). Secondary endpoints included total cholesterol (TC), triglycerides, high density lipoprotein-C (HLD-C), and very low-density lipoprotein-C (VLDL-C). Subgroup analyses and meta-regression accounted for covariates. RESULTS: GLP-1RAs modestly reduced LDL-C (MD -2.93, 95% CI (-5.01, -0.85), p = 0.01), consistent across treatment durations: 12 weeks (MD: -2.39, 95% CI (-4.70, -0.007), p = 0.04). GLP-1RA reduced TC by approximately 7 mg/dl. There was no significant reduction in triglycerides (MD = -7.19, 95% CI (-15.01, 0.62), p = 0.07) or VLDL-C (MD = -3.99, 95%, CI (-8.73, 0.75), p = 0.10). GLP-1RA did not increase HDL-C (MD = -0.12, 95% CI (-0.73, 0.49), p = 0.69). Weight change did not influence LDL-C (tau2 = 28.38, I2 = 99.83, R2 = 0.0, p = 0.67) or TC (tau2 = 93.6, I2 = 99.86, R2 = 0.0, p = 0.92). CONCLUSION: GLP-1RA treatment modestly decreased LDL-C and TC but did not significantly affect triglycerides, VLDL-C, or HDL-C. FAU - Rivera, Frederick Berro AU - Rivera FB AD - Lincoln Medical Center, Bronx, NY, USA. FAU - Chin, Marielle Nicole Cabusas AU - Chin MNC AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Pine, Polyn Luz S AU - Pine PLS AD - Ateneo School of Medicine and Public Health, Pasig, Philippines. FAU - Ruyeras, Monica Marie Jadena AU - Ruyeras MMJ AUID- ORCID: 0009-0009-9795-7979 AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Galang, Danica Janine Cabahug AU - Galang DJC AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Gandionco, Keshia Marice AU - Gandionco KM AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Morales, Benna Lynn Faye D AU - Morales BLFD AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Climaco, Zackaree Michael V AU - Climaco ZMV AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Bantayan, Nathan Ross Baoy AU - Bantayan NRB AD - College of Medicine, University of the Philippines, Manila, Philippines. FAU - Magalong, John Vincent AU - Magalong JV AD - College of Medicine, University of the Philippines, Manila, Philippines. FAU - Mangubat, Gerard Francis AU - Mangubat GF AD - Department of Medicine, Southern Philippines Medical Center, Davao, Philippines. FAU - Ong, Kenneth AU - Ong K AD - Department of Cardiology, Lincoln Medical Center, Bronx, NY, USA. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20241218 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Cholesterol, LDL) RN - 97C5T2UQ7J (Cholesterol) RN - 0 (Triglycerides) SB - IM MH - Humans MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Cholesterol, LDL/blood MH - Weight Loss/drug effects MH - *Cholesterol/blood MH - Triglycerides/blood MH - *Diabetes Mellitus, Type 2/drug therapy/blood OTO - NOTNLM OT - Dulaglutide OT - Glp-1RA OT - Semaglutide OT - lipids OT - liraglutide EDAT- 2024/12/12 18:23 MHDA- 2025/02/05 06:20 CRDT- 2024/12/12 14:53 PHST- 2025/02/05 06:20 [medline] PHST- 2024/12/12 18:23 [pubmed] PHST- 2024/12/12 14:53 [entrez] AID - 10.1080/03007995.2024.2442027 [doi] PST - ppublish SO - Curr Med Res Opin. 2025 Jan;41(1):185-197. doi: 10.1080/03007995.2024.2442027. Epub 2024 Dec 18. PMID- 39654073 OWN - NLM STAT- MEDLINE DCOM- 20250427 LR - 20260806 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 3 DP - 2025 Mar TI - An exploratory analysis of glucagon-like peptide-1 (GLP-1) agonists and biosimilars: A literature review. PG - 1113-1122 LID - 10.1111/dom.16110 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are at the forefront of treating the global health crisis of diabetes mellitus (DM) and obesity. However, the demand for GLP-1 RAs has far outstripped its supply and comes with a high monthly cost. Thus, the development of GLP-1 RA biosimilars can potentially address these barriers by providing greater access to medications that provide clinical outcomes similar to those of the reference products. A narrative review was conducted to examine the current and future developments for GLP-1 RA biosimilars. Liraglutide and semaglutide are the predominant GLP-1 RAs being investigated for the development of biosimilars. Preliminary liraglutide biosimilar comparisons to reference liraglutide have demonstrated similar clinical efficacy and safety profiles. Semaglutide and beinaglutide biosimilars are currently under investigation as well. With the growing popularity of GLP-1 RAs, accessibility and affordability remain a challenge as monthly costs without insurance for liraglutide, semaglutide and tirzepatide are $1418, $892, and $974 respectively. This trend negatively impacts patients with obesity and DM as well as patients who can utilize it for off-label indications for conditions that benefit from weight loss such as obstructive sleep apnoea and non-alcoholic fatty liver disease. A substantial number of pharmaceutical and healthcare companies worldwide are conducting clinical trials on their GLP-1 RA biosimilars. Preliminary results from liraglutide biosimilars are promising, and several semaglutide biosimilars are currently being investigated. Future research should focus on conducting comparative head-to-head trials to determine the clinical outcomes between biosimilars and reference products. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Wen, Jimmy AU - Wen J AUID- ORCID: 0009-0007-5412-8551 AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Razick, Adam AU - Razick A AD - Department of Psychology, University of California, Los Angeles, California, USA. FAU - How-Volkman, Christiane AU - How-Volkman C AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Bernstein, Ethan AU - Bernstein E AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Nadora, Denise AU - Nadora D AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Truong, Alina AU - Truong A AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Razick, Daniel AU - Razick D AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Akhtar, Muzammil AU - Akhtar M AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Karabala, Muhammad AU - Karabala M AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. FAU - Frezza, Eldo AU - Frezza E AD - College of Medicine, California Northstate University College of Medicine, Elk Grove, California, USA. LA - eng PT - Journal Article PT - Review DEP - 20241209 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Biosimilar Pharmaceuticals) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Biosimilar Pharmaceuticals/therapeutic use/economics MH - Humans MH - *Hypoglycemic Agents/therapeutic use/economics MH - Glucagon-Like Peptides/therapeutic use/economics MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Liraglutide/therapeutic use/economics MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1/agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - GLP-1 analogue OT - health economics OT - liraglutide OT - obesity care OT - semaglutide EDAT- 2024/12/10 00:22 MHDA- 2025/02/07 00:20 CRDT- 2024/12/09 23:34 PHST- 2024/11/08 00:00 [revised] PHST- 2024/09/22 00:00 [received] PHST- 2024/11/21 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2024/12/10 00:22 [pubmed] PHST- 2024/12/09 23:34 [entrez] AID - 10.1111/dom.16110 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Mar;27(3):1113-1122. doi: 10.1111/dom.16110. Epub 2024 Dec 9. PMID- 39651921 OWN - NLM STAT- MEDLINE DCOM- 20241209 LR - 20260127 IS - 0975-4466 (Electronic) IS - 0256-4947 (Print) IS - 0256-4947 (Linking) VI - 44 IP - 6 DP - 2024 Nov-Dec TI - Efficacy and safety of semaglutide: real-world tertiary care experience from Saudi Arabia. PG - 361-368 LID - 10.5144/0256-4947.2024.361 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1, is an effective antidiabetic drug promoting weight loss and providing cardiovascular protection. The original trials did not include participants from Saudi Arabia; hence, the study's findings are expected to be useful. OBJECTIVES: Explore the efficacy, safety, and favorable effects of once-weekly subcutaneous semaglutide (1 mg) in patients with type 2 diabetes and those who received it as an off-license prescription without having diabetes. DESIGN: Retrospective review of medical records. SETTING: Department of medicine at our institution. PATIENTS AND METHODS: This retrospective observational study evaluated patients receiving the glucagon-like peptide-1 analog semaglutide, with the trade name Ozempic. The weight, height, body mass index, blood pressure, and laboratory data, including serum creatinine and hemoglobin A1c (HbA1c) levels and urine albumin/creatinine ratio, were recorded. Moreover, any history of medical comorbidities, such as cardiovascular diseases, cerebrovascular diseases, and heart failure, was documented before and after drug administration. MAIN OUTCOME MEASURES: Glycemic and weight loss efficacy. SAMPLE SIZE: 1007 patients. RESULTS: The median age of the patients was 57.0 years, comprising 60.28% females. Among them, 955 and 442 patients received the medication for at least 3 and 6 months, respectively. Our results show a 4.4% weight loss and 0.4% improvement in HBA1c in patients with diabetes. Similar results were observed in the patients without diabetes in terms of weight along with a significant decrease in diastolic blood pressure. Our results also show stability in the serum creatinine and urine albumin creatinine ratio. The drug was equally effective in males and females. CONCLUSION: Treatment with once-weekly subcutaneous semaglutide (1 mg) led to clinically significant weight loss and improved HbA1c level and cardiometabolic risk factors such as blood pressure. LIMITATIONS: Retrospective design. FAU - Butt, Muhammad Imran AU - Butt MI AUID- ORCID: 0000-0002-2143-7303 AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Alkhalifah, Khalid Mania AU - Alkhalifah KM AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Riazuddin, Muhammad AU - Riazuddin M AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Almuammar, Saud Mohammed AU - Almuammar SM AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Almuammar, Salman Mohammed AU - Almuammar SM AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Alhifthi, Ghayda Abdulkader AU - Alhifthi GA AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Ahmed, Fahad Wali AU - Ahmed FW AD - From the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Al Hashim, Samia Mohamed AU - Al Hashim SM AD - From the Department of Biostatistics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. FAU - Waheed, Najeeb AU - Waheed N AD - From the Department of Endocrinology, Imperial College London Diabetes Centre, Al Ain, Abu Dhabi, United Arab Emirates. LA - eng PT - Journal Article PT - Observational Study DEP - 20241205 PL - Saudi Arabia TA - Ann Saudi Med JT - Annals of Saudi medicine JID - 8507355 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - Female MH - Male MH - Retrospective Studies MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Saudi Arabia MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - *Glycated Hemoglobin/drug effects MH - Aged MH - *Weight Loss/drug effects MH - Adult MH - Treatment Outcome MH - Tertiary Health Care MH - Blood Pressure/drug effects MH - Blood Glucose/drug effects MH - Injections, Subcutaneous MH - Semaglutide PMC - PMC11627033 COIS- None. EDAT- 2024/12/09 17:33 MHDA- 2024/12/09 17:34 PMCR- 2024/11/01 CRDT- 2024/12/09 09:14 PHST- 2024/12/09 17:34 [medline] PHST- 2024/12/09 17:33 [pubmed] PHST- 2024/12/09 09:14 [entrez] PHST- 2024/11/01 00:00 [pmc-release] AID - 0256-4947.2024.361 [pii] AID - 10.5144/0256-4947.2024.361 [doi] PST - ppublish SO - Ann Saudi Med. 2024 Nov-Dec;44(6):361-368. doi: 10.5144/0256-4947.2024.361. Epub 2024 Dec 5. PMID- 39647240 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260127 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 44 DP - 2025 Jan TI - Beyond fat: Does semaglutide affect lean mass? PG - 104-108 LID - S0261-5614(24)00445-X [pii] LID - 10.1016/j.clnu.2024.12.004 [doi] AB - This opinion paper aims to discuss the influence of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on lean mass beyond its impact on weight loss. Although significant weight loss is achieved with semaglutide, the impact of this drug on lean mass remains controversial. Several investigations have demonstrated that semaglutide-induced weight loss is linked to decreases in lean mass as well as fat mass; on the other hand, the ratio of lean mass to total body mass rises. Nevertheless, larger clinical trials have reported converse findings and significant reductions in lean mass following treatment with semaglutide. This disparity in research findings emphasizes the necessity for additional studies on this subject because semaglutide use is rising quickly. CI - Copyright (c) 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. FAU - Jamialahmadi, Tannaz AU - Jamialahmadi T AD - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Eid, Ali H AU - Eid AH AD - Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar. FAU - Gadde, Kishore M AU - Gadde KM AD - Department of Surgery, University of California Irvine Medical Center, Orange, CA, USA. FAU - Almahmeed, Wael AU - Almahmeed W AD - Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates. FAU - Kroh, Matthew AU - Kroh M AD - Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA. FAU - Al Zein, Mohammad AU - Al Zein M AD - Faculty of Medical Sciences, Lebanese University, Hadath, Beirut, Lebanon. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: amir_saheb2000@yahoo.com. LA - eng PT - Journal Article PT - Review DEP - 20241204 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/pharmacology MH - Humans MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/pharmacology MH - *Body Composition/drug effects MH - Adipose Tissue/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Body composition OT - Glucagon-like peptide-1 receptor agonist OT - Lean mass OT - Semaglutide COIS- Conflict of interest The authors have no competing interests to disclose. EDAT- 2024/12/09 00:22 MHDA- 2025/01/07 00:21 CRDT- 2024/12/08 18:02 PHST- 2024/08/19 00:00 [received] PHST- 2024/11/28 00:00 [revised] PHST- 2024/12/02 00:00 [accepted] PHST- 2025/01/07 00:21 [medline] PHST- 2024/12/09 00:22 [pubmed] PHST- 2024/12/08 18:02 [entrez] AID - S0261-5614(24)00445-X [pii] AID - 10.1016/j.clnu.2024.12.004 [doi] PST - ppublish SO - Clin Nutr. 2025 Jan;44:104-108. doi: 10.1016/j.clnu.2024.12.004. Epub 2024 Dec 4. PMID- 39636564 OWN - NLM STAT- MEDLINE DCOM- 20250427 LR - 20260814 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 42 IP - 2 DP - 2025 Feb TI - Glucagon-Like Peptide-1 Receptor Agonist-Experienced Adults with Type 2 Diabetes Switching to Once-Weekly Semaglutide in a Real-World Setting: SURE Program Post Hoc Analysis. PG - 788-800 LID - 10.1007/s12325-024-03000-x [doi] AB - INTRODUCTION: To investigate outcomes in adults with type 2 diabetes who switched to once-weekly (OW) semaglutide from another glucagon-like peptide-1 receptor agonist (GLP-1RA) in clinical practice. METHODS: This post hoc analysis used data from the SemaglUtide Real-world Evidence (SURE) program, which included nine observational studies investigating the initiation of OW semaglutide in people with type 2 diabetes in routine clinical practice. Using a random coefficient-adjusted mixed model for repeated measurements, changes in glycosylated hemoglobin (HbA(1c)), body weight, and body mass index were analyzed for GLP-1RA-experienced patients who had at least one documented HbA(1c) value within the 12 weeks before switching to OW semaglutide. In addition, descriptive statistics were used for HbA(1c), body weight target achievement, and safety data. RESULTS: Of the 3,505 patients included in the nine SURE studies, 651 switched to OW semaglutide from another GLP-1RA. GLP-1RA-experienced patients who switched to OW semaglutide demonstrated a 0.67%-point [95% confidence interval (CI) - 0.74; - 0.60, p < 0.0001] reduction in HbA(1c), and a 3.69-kg [95% CI - 3.98; - 3.41, p < 0.0001] reduction in body weight over 30 weeks. A body weight reduction of >/= 5% was achieved by 27.6% of patients, and 33.3% of patients with baseline HbA(1c) >/= 7% achieved HbA(1c) < 7% at end of study. No new safety concerns were identified. CONCLUSIONS: Data from this post hoc analysis suggest that, for those not adequately responding to treatment with other GLP-1RAs, switching to OW semaglutide could provide additional glycemic and weight benefits with the convenience of an OW dosing regimen. CI - (c) 2024. The Author(s). FAU - Rudofsky, Gottfried AU - Rudofsky G AUID- ORCID: 0000-0002-2576-7190 AD - Praxis fur Endokrinologie, Diabetes und Adipositas, Olten, Solothurn, Switzerland. Gottfried.rudofsky@hin.ch. FAU - Menzen, Markus AU - Menzen M AD - Gemeinschaftskrankenhaus, Bonn, Germany. FAU - Potier, Louis AU - Potier L AD - Universite Paris Cite, AP-HP, Bichat Hospital, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades, Paris, France. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Clark, Alice AU - Clark A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Priyadarshini, Prachi AU - Priyadarshini P AD - Novo Nordisk GBS, Bengaluru, India. FAU - Abreu, Cristina AU - Abreu C AD - Endocrinology and Nutrition Unit, Segovia General Hospital, Segovia, Spain. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20241205 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Male MH - Middle Aged MH - Female MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Glycated Hemoglobin/metabolism/analysis MH - Aged MH - Drug Administration Schedule MH - Body Weight/drug effects MH - Adult MH - Body Mass Index MH - Blood Glucose MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11787244 OTO - NOTNLM OT - Body weight OT - GLP-1RA OT - Glucagon-like peptide-1 receptor agonist OT - Glycated hemoglobin OT - Post hoc analysis OT - Real-world OT - Semaglutide OT - Type 2 diabetes COIS- Declarations. Conflict of Interest: Gottfried Rudofsky has received support, funding, consulting fees and honoraria from Novo Nordisk, and holds stock in Novo Nordisk. Markus Menzen has received consulting fees from Novo Nordisk, Lilly Deutschland, Ascensia, Boehringer Ingelheim, Bayer AG and Novartis; honoraria from AstraZeneca, Bayer AG, Santis, Boehringer Ingelheim, Novo Nordisk, Lilly Deutschland, Lilly Swiss and Abbott; and support for attending meetings from AstraZeneca, Novo Nordisk and Lilly Deutschland. Louis Potier has received research support from Novo Nordisk; consulting fees from Novo Nordisk, Lilly, Sanofi, Bayer, Boehringer Ingelheim and AstraZeneca; and honoraria from Novo Nordisk, Lilly, Sanofi, Bayer and AstraZeneca. Andrei-Mircea Catarig, Alice Clark and Prachi Priyadarshini are full-time employees of Novo Nordisk A/S. Andrei-Mircea Catarig and Prachi Priyadarshini hold stock in Novo Nordisk A/S. Cristina Abreu has no conflicts of interest. Ethical Approval: The SURE study protocols were conducted in accordance with the Declaration of Helsinki and approved by the institutional review board and ethics committee at each participating center. All participants provided written informed consent. EDAT- 2024/12/05 17:32 MHDA- 2025/02/01 20:41 PMCR- 2024/12/05 CRDT- 2024/12/05 11:20 PHST- 2024/07/25 00:00 [received] PHST- 2024/09/13 00:00 [accepted] PHST- 2025/02/01 20:41 [medline] PHST- 2024/12/05 17:32 [pubmed] PHST- 2024/12/05 11:20 [entrez] PHST- 2024/12/05 00:00 [pmc-release] AID - 10.1007/s12325-024-03000-x [pii] AID - 3000 [pii] AID - 10.1007/s12325-024-03000-x [doi] PST - ppublish SO - Adv Ther. 2025 Feb;42(2):788-800. doi: 10.1007/s12325-024-03000-x. Epub 2024 Dec 5. PMID- 39629799 OWN - NLM STAT- MEDLINE DCOM- 20241231 LR - 20260127 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 26 IP - 1 DP - 2025 Jan TI - Evaluating semaglutide + LAI-287 (IcoSema) for the treatment of diabetes mellitus type II. PG - 1-7 LID - 10.1080/14656566.2024.2436593 [doi] AB - INTRODUCTION: A stepwise coordinated multiple therapeutic targeted approach to the treatment of type 2 diabetes includes starting with lifestyle modification, oral antihyperglycemic agents, non-insulin injectables (Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and both short and long-acting insulins. Ultra-long-acting insulins offer more convenient administration. As in any chronic disease, the introduction of a novel medication must balance safety, efficacy, financial cost, as well as improved patient convenience and adherence. AREAS COVERED: This manuscript describes IcoSema - a new investigational fixed-ratio combination of basal insulin icodec and the GLP-1 RA semaglutide. The key trials from the clinical development process of insulin icodec, semaglutide, and IcoSema are reviewed with important endpoints highlighted. EXPERT OPINION: Once-weekly IcoSema offers glycemic efficacy that is non-inferior to glargine+aspart, similar risk of hypoglycemia, significant reduction in body weight, the convenience of use, and favorable safety profile with most adverse events being gastrointestinal. FAU - Siamashvili, Maka AU - Siamashvili M AD - Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. FAU - Davis, Stephen N AU - Davis SN AD - Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20241204 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Drug Combinations) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects/analogs & derivatives MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - *Drug Combinations MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - IcoSema OT - diabetes OT - icodec OT - insulin OT - semaglutide EDAT- 2024/12/04 12:29 MHDA- 2025/01/01 12:41 CRDT- 2024/12/04 07:53 PHST- 2025/01/01 12:41 [medline] PHST- 2024/12/04 12:29 [pubmed] PHST- 2024/12/04 07:53 [entrez] AID - 10.1080/14656566.2024.2436593 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2025 Jan;26(1):1-7. doi: 10.1080/14656566.2024.2436593. Epub 2024 Dec 4. PMID- 39616020 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20260127 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 47 IP - 1 DP - 2025 Jan TI - Real-world Evidence on Oral Semaglutide for the Management of Type 2 Diabetes. A Narrative Review for Clinical Practice. PG - 102-110 LID - S0149-2918(24)00330-8 [pii] LID - 10.1016/j.clinthera.2024.11.005 [doi] AB - PURPOSE: Oral semaglutide is the first oral glucagon-like peptide-1 receptor agonist (GLP-1RA) available for type 2 diabetes mellitus (T2DM) management, whose effectiveness and tolerability have extensively been demonstrated in the PIONEER clinical trial program. Nevertheless, data from real-world are crucial to evaluate treatment performance under routine care. The aim of this narrative review is to summarize available evidence regarding real-world utilization patterns of oral semaglutide, and discuss efficacy, safety, and dosing regimen data in routine scenarios. METHODS: We searched PubMed for real-world studies evaluating oral semaglutide up to August 2024, and specific search terms were: "oral semaglutide," and "real-world studies" or "observational studies" or "retrospective studies". FINDINGS: 19 real-world studies were included in the narrative review. In real-world settings, oral semaglutide provided significant glycemic (median HbA1c reduction at 6 months of 1%) and weight (median body weight reduction of 2 to 3 kg) benefits across the spectrum of T2DM, aligning with pre-clinical evidence from the PIONEER program. No new tolerability and safety issue has emerged from oral semaglutide administration in routine clinical practice. IMPLICATIONS: Oral semaglutide constitutes an effective and safe option for T2DM management, and its increased acceptance has the potential to favor the early introduction of GLP-1RAs along the disease course. Nevertheless, continuous evaluation of real-world data is critical to better define the optimal positioning of oral semaglutide along T2DM trajectory and fully exploit its potential in everyday clinical practice. CI - Copyright (c) 2024 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Marassi, M AU - Marassi M AD - Department of Medicine, University of Padova, Padua, Italy. Electronic address: mare.marassi@gmail.com. FAU - Fadini, G P AU - Fadini GP AD - Department of Medicine, University of Padova, Padua, Italy; Veneto Institute of Molecular Medicine, Padua, Italy. LA - eng PT - Journal Article PT - Review DEP - 20241129 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Administration, Oral MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Blood Glucose/drug effects MH - Glycated Hemoglobin/analysis MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Effectiveness OT - Narrative review OT - Oral semaglutide OT - Real-world OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gian Paolo Fadini reports a relationship with Abbott, AstraZeneca, Boehringer, Lilly, MSD, Novo Nordisk, Novaartis, Sanofi, Servier, Takeda that includes: funding grants and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/12/01 15:22 MHDA- 2025/01/11 13:59 CRDT- 2024/11/30 21:57 PHST- 2024/06/05 00:00 [received] PHST- 2024/09/30 00:00 [revised] PHST- 2024/11/02 00:00 [accepted] PHST- 2025/01/11 13:59 [medline] PHST- 2024/12/01 15:22 [pubmed] PHST- 2024/11/30 21:57 [entrez] AID - S0149-2918(24)00330-8 [pii] AID - 10.1016/j.clinthera.2024.11.005 [doi] PST - ppublish SO - Clin Ther. 2025 Jan;47(1):102-110. doi: 10.1016/j.clinthera.2024.11.005. Epub 2024 Nov 29. PMID- 39609879 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260730 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 2 DP - 2025 Feb TI - Similar weight loss with semaglutide regardless of diabetes and cardiometabolic risk parameters in individuals with metabolic dysfunction-associated steatotic liver disease: Post hoc analysis of three randomised controlled trials. PG - 710-718 LID - 10.1111/dom.16065 [doi] AB - AIMS: Weight loss mediated by glucagon-like peptide-1 (GLP-1) analogues is lower in patients with type 2 diabetes versus those without. Type 2 diabetes and obesity are risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD) and associated steatohepatitis (MASH). We evaluated weight changes in adults with MASLD/MASH with or without type 2 diabetes receiving the GLP-1 analogue semaglutide. MATERIALS AND METHODS: This was a post hoc analysis of data from three 48-72-week randomised trials investigating the effect of semaglutide versus placebo in adults with MASLD (NCT03357380) or biopsy-confirmed MASH (NCT02970942 and NCT03987451). Pooled data for semaglutide (0.4 mg once daily and 2.4 mg once weekly [n = 163]) and placebo (n = 137) were analysed at 1 year. Weight changes were analysed by type 2 diabetes status (type 2 diabetes [n = 209], pre-type 2 diabetes [n = 51] and no diabetes [n = 40]) and by other cardiometabolic risk parameters using analysis of covariance and Spearman's rank correlations. RESULTS: The overall mean weight change was -11.1 kg (-11.7%) and -0.7 kg (-0.6%) with semaglutide and placebo, respectively. While numerically higher for people without type 2 diabetes, estimated treatment differences with semaglutide versus placebo were similar overall for people with type 2 diabetes (-10.2 kg; -10.8%), pre-type 2 diabetes (-9.8 kg; -10.2%) and no diabetes (-11.6 kg; -13.1%). Differences between groups were not statistically significant (p > 0.50 for all). Baseline fasting plasma glucose, glycated haemoglobin, insulin levels, insulin resistance and lipids did not correlate with weight change. CONCLUSIONS: People with MASLD/MASH had similar semaglutide-mediated weight loss regardless of type 2 diabetes status and other cardiometabolic risk parameters. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Armstrong, Matthew J AU - Armstrong MJ AD - Liver Unit, Queen Elizabeth University Hospital, Birmingham, UK. AD - National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. AD - Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. FAU - Okanoue, Takeshi AU - Okanoue T AD - Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan. FAU - Sundby Palle, Mads AU - Sundby Palle M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sejling, Anne-Sophie AU - Sejling AS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Tawfik, Mohamed AU - Tawfik M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Roden, Michael AU - Roden M AD - Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Dusseldorf, Heinrich-Heine University Dusseldorf, Dusseldorf, Germany. AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Dusseldorf, Germany. AD - German Center for Diabetes Research, Partner Dusseldorf, Munchen-Neuherberg, Germany. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20241128 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Middle Aged MH - *Weight Loss/drug effects MH - Female MH - Male MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiometabolic Risk Factors MH - Fatty Liver/complications/drug therapy MH - Aged MH - Adult MH - Non-alcoholic Fatty Liver Disease/drug therapy/complications MH - Obesity/complications/drug therapy MH - Semaglutide PMC - PMC11701178 OTO - NOTNLM OT - GLP-1 analogue OT - semaglutide OT - type 2 diabetes OT - weight control COIS- MJA: consultancy and sponsored lectures for Norgine and Novo Nordisk. TO: no conflicts of interest to declare. MSP: employee and shareholder of Novo Nordisk. A-SS: employee and shareholder of Novo Nordisk. MT: employee and shareholder of Novo Nordisk. MR: research grants from Boehringer Ingelheim and Novo Nordisk; consulting or advisory boards for AstraZeneca, Boehringer Ingelheim, Echosens, Eli Lilly, MSD and Novo Nordisk; speaker fees from AstraZeneca, Madrigal, MSD and Novo Nordisk. EDAT- 2024/11/29 05:20 MHDA- 2025/01/07 04:51 PMCR- 2025/01/06 CRDT- 2024/11/28 23:59 PHST- 2024/10/24 00:00 [revised] PHST- 2024/08/22 00:00 [received] PHST- 2024/10/31 00:00 [accepted] PHST- 2025/01/07 04:51 [medline] PHST- 2024/11/29 05:20 [pubmed] PHST- 2024/11/28 23:59 [entrez] PHST- 2025/01/06 00:00 [pmc-release] AID - DOM16065 [pii] AID - 10.1111/dom.16065 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Feb;27(2):710-718. doi: 10.1111/dom.16065. Epub 2024 Nov 28. PMID- 39606869 OWN - NLM STAT- MEDLINE DCOM- 20241128 LR - 20260127 IS - 1876-8784 (Electronic) IS - 0028-2162 (Linking) VI - 168 DP - 2024 Nov 21 TI - [Prescribing semaglutide for overweight: is it allowed?]. LID - D8347 [pii] AB - Semaglutide is registered in the Netherlands as a treatment for type 2 diabetes. If semaglutide is prescribed off-label as slimming agent, in principle, patient's costs are not reimbursed by health insurers. With the entry of the Geneesmiddelenwet (Gnw), regulations were provided for off-label prescription of medication. Based on article 68, paragraph 1 Gnw, off-label prescribing is allowed when protocols or standards have been developed. So far, this has not been the case in the Netherlands regarding semaglutide. When protocols and standards are under development, consultation must take place between doctor and pharmacist. The term "protocols or standards under development" is open to multiple interpretations, as shown by case law. Regardless of the chosen interpretation, the scientific evidence for semaglutide as slimming agent seems insufficient. In conclusion does off-label prescribing of semaglutide as slimming agent not meet the requirements of article 68, paragraph 1 Gnw and is therefore not permitted. FAU - Rijk, Paul C AU - Rijk PC AD - Medisch Centrum Leeuwarden, afd. Orthopedie, Leeuwarden. AD - Contact: p.rijk@mcl.nl. LA - dut PT - English Abstract PT - Journal Article TT - Semaglutide voorschrijven als afslankmiddel: mag dat? DEP - 20241121 PL - Netherlands TA - Ned Tijdschr Geneeskd JT - Nederlands tijdschrift voor geneeskunde JID - 0400770 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - Netherlands MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Off-Label Use MH - Hypoglycemic Agents/therapeutic use MH - Overweight/drug therapy MH - Semaglutide EDAT- 2024/11/28 06:35 MHDA- 2024/11/28 12:20 CRDT- 2024/11/28 05:53 PHST- 2024/11/28 12:20 [medline] PHST- 2024/11/28 06:35 [pubmed] PHST- 2024/11/28 05:53 [entrez] AID - D8347 [pii] PST - epublish SO - Ned Tijdschr Geneeskd. 2024 Nov 21;168:D8347. PMID- 39602049 OWN - NLM STAT- MEDLINE DCOM- 20250416 LR - 20261010 IS - 1936-0541 (Electronic) IS - 1936-0533 (Linking) VI - 19 IP - 2 DP - 2025 Apr TI - Semaglutide and the risk of adverse liver outcomes in patients with nonalcoholic fatty liver disease and type 2 diabetes: a multi-institutional cohort study. PG - 395-404 LID - 10.1007/s12072-024-10752-9 [doi] AB - BACKGROUND: Semaglutide has shown potential liver benefits in patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). However, no direct comparisons have been made between semaglutide and other antidiabetic medications, including sodium-glucose cotransporter-2 inhibitors (SGLT2i), thiazolidinediones (TZD), and dipeptidyl peptidase-4 inhibitors (DPP-4i), regarding liver outcomes in patients with both NAFLD and T2D. METHODS: This retrospective cohort study utilized the TriNetX electronic health record database, a multinational and multi-institutional database. Adults with NAFLD and T2D who received their first prescription for either semaglutide or other antidiabetic medications were included. New users of semaglutide were matched 1:1 via propensity score matching with users of SGLT2i, DPP-4i, and TZD. The primary outcome was major adverse liver outcome (MALO), a composite end point consisting of decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. Secondary outcomes included the individual components of MALO and all-cause mortality. RESULTS: A total of 648,070 adult patients with T2D and NAFLD were identified, and patients were categorized into three different comparison groups based on their drug of interest. Semaglutide was associated with a lower risk of MALO compared to SGLT2i (adjusted hazard ratio [aHR], 0.73; 95% CI 0.60-0.88), DPP-4i (aHR, 0.72; 95% CI 0.56-0.86), and TZD (aHR, 0.76; 95% CI 0.56-0.99). Additionally, semaglutide was linked to a lower risk of all-cause mortality compared to SGLT2i (aHR, 0.62; 95% CI 0.53-0.72), DPP-4i (aHR, 0.42; 95% CI 0.36-0.49), and TZD (aHR, 0.67; 95% CI 0.54-0.83). CONCLUSION: Semaglutide is associated with better liver outcomes and a lower risk of all-cause mortality compared to SGLT2i, DPP-4i, and TZD in patients with NAFLD and T2D. CI - (c) 2024. Asian Pacific Association for the Study of the Liver. FAU - Kuo, Chia-Chih AU - Kuo CC AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Chuang, Min-Hsiang AU - Chuang MH AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Li, Chun-Hsien AU - Li CH AD - Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, Tainan, Taiwan. FAU - Huang, Po-Yu AU - Huang PY AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. FAU - Kuo, Hsing-Tao AU - Kuo HT AD - Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan. kht@mail.chimei.org.tw. AD - School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. kht@mail.chimei.org.tw. FAU - Lai, Chih-Cheng AU - Lai CC AUID- ORCID: 0000-0002-6334-2388 AD - Department of Intensive Care Medicine, Chi Mei Medical Center, Tainan, Taiwan. dtmed141@gmail.com. AD - School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan. dtmed141@gmail.com. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20241127 PL - United States TA - Hepatol Int JT - Hepatology international JID - 101304009 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Thiazolidinediones) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Non-alcoholic Fatty Liver Disease/complications/drug therapy MH - Female MH - Male MH - Middle Aged MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Adult MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/adverse effects MH - Thiazolidinediones/therapeutic use MH - Liver Transplantation/statistics & numerical data MH - Carcinoma, Hepatocellular/epidemiology MH - Liver Neoplasms/epidemiology MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Diabetes mellitus OT - Major adverse liver outcomes OT - Nonalcoholic fatty liver disease OT - Semaglutide COIS- Declarations. Competing interests: The authors state that they have no conflicts of interest. Ethics approval and consent to participate: The Institutional Review Board of the Chi Mei Medical Center approved the study protocol. Written informed consent was not required because TriNetX contains anonymized data. Consent for publication: All authors consent to the publishing of this article. EDAT- 2024/11/27 12:34 MHDA- 2025/04/16 14:35 CRDT- 2024/11/27 11:22 PHST- 2024/09/30 00:00 [received] PHST- 2024/11/09 00:00 [accepted] PHST- 2025/04/16 14:35 [medline] PHST- 2024/11/27 12:34 [pubmed] PHST- 2024/11/27 11:22 [entrez] AID - 10.1007/s12072-024-10752-9 [pii] AID - 10.1007/s12072-024-10752-9 [doi] PST - ppublish SO - Hepatol Int. 2025 Apr;19(2):395-404. doi: 10.1007/s12072-024-10752-9. Epub 2024 Nov 27. PMID- 39596946 OWN - NLM STAT- MEDLINE DCOM- 20241127 LR - 20260127 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 60 IP - 11 DP - 2024 Oct 27 TI - The Influence of GLP1 on Body Weight and Glycemic Management in Patients with Diabetes-A Scientometric Investigation and Visualization Study. LID - 10.3390/medicina60111761 [doi] LID - 1761 AB - Diabetes medications can affect weight and cardiovascular health. Some medications can aid in weight management, while others may lead to weight gain. Patients must be monitored and receive appropriate care to manage weight and prevent cardiovascular complications. Despite advancements in diabetes treatments that can influence weight and cardiovascular outcomes, ongoing research is necessary in this intricate field. Long-term effects, individual variations, and combination therapies are still subjects of uncertainty and ongoing investigation. The major objective of the research is to evaluate the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on body weight in diabetic patients through a scientometric assessment. Methodology: Research data were gathered from the Web of Science Core Collection (WoSCC) database by searching for the keywords "Body Weight", dulaglutide, and semaglutide, identifying 60 relevant articles in the field. While there are advantages in managing diseases in which the cardiovascular system is implicated, there are also clinical considerations for personalized medicine and shared decision-making. The scientometric analysis of the articles revealed important insights into how dulaglutide and semaglutide impact weight management and their potential benefits for managing cardiovascular diseases in individuals with diabetes. Conclusions: Semaglutide shows superior outcomes compared to other commercially available GLP-1RAs, particularly in improving blood sugar control, lowering body weight, and addressing other cardio-metabolic risk factors in individuals with type 2 diabetes (T2DM). The findings suggest that GLP-1 RAs have the potential to provide cardiovascular protection by influencing various physiological factors such as blood pressure, pulse rate, glycated hemoglobin (HbA1c) levels, and the urinary albumin-to-creatinine ratio (RAC). The development and validation of the 4GI model provides a sophisticated tool for evaluating the complex interactions involved in diabetes treatments, offering insights into the mechanisms of action of various medications. FAU - Pantea, Ileana AU - Pantea I AD - Department of Basic, Preventive and Clinical Sciences, Transilvania University, 500036 Brasov, Romania. FAU - Repanovici, Angela AU - Repanovici A AUID- ORCID: 0000-0002-8748-5332 AD - Faculty of Product Design and Environment, Transilvania University, 500036 Brasov, Romania. FAU - Andreescu, Oana AU - Andreescu O AD - Department of Basic, Preventive and Clinical Sciences, Transilvania University, 500036 Brasov, Romania. LA - eng PT - Journal Article PT - Review DEP - 20241027 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology/analogs & derivatives MH - *Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Glycemic Control/methods MH - Glucagon-Like Peptide 1 MH - Blood Glucose/analysis MH - Semaglutide PMC - PMC11596011 OTO - NOTNLM OT - body weight OT - diabetes OT - dulaglutide OT - scientometric analyses OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2024/11/27 06:20 MHDA- 2024/11/27 06:21 PMCR- 2024/10/27 CRDT- 2024/11/27 01:26 PHST- 2024/07/26 00:00 [received] PHST- 2024/10/19 00:00 [revised] PHST- 2024/10/23 00:00 [accepted] PHST- 2024/11/27 06:21 [medline] PHST- 2024/11/27 06:20 [pubmed] PHST- 2024/11/27 01:26 [entrez] PHST- 2024/10/27 00:00 [pmc-release] AID - medicina60111761 [pii] AID - medicina-60-01761 [pii] AID - 10.3390/medicina60111761 [doi] PST - epublish SO - Medicina (Kaunas). 2024 Oct 27;60(11):1761. doi: 10.3390/medicina60111761. PMID- 39592891 OWN - NLM STAT- MEDLINE DCOM- 20250426 LR - 20260806 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 27 IP - 3 DP - 2025 Mar TI - Why does GLP-1 agonist combined with GIP and/or GCG agonist have greater weight loss effect than GLP-1 agonist alone in obese adults without type 2 diabetes? PG - 1079-1095 LID - 10.1111/dom.16106 [doi] AB - Obesity is a chronic condition demanding effective treatment strategies, among which pharmacotherapy plays a critical role. As glucagon-like peptide-1 (GLP-1) agonist approved by the Food and Drug Administration (FDA) for long-term weight management in adults with obesity, liraglutide and semaglutide have great weight loss effect through reducing food intake and delaying gastric emptying. The emergence of unimolecular polypharmacology, which utilizes single molecules to simultaneously target multiple receptors or pathways, marked a revolutionary improvement in GLP-1-based obesity pharmacotherapy. The dual agonist tirzepatide activates both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors and has shown enhanced potency for weight loss compared to conventional GLP-1 mono agonist. Furthermore, emerging data suggests that unimolecular GLP-1/glucagon (GCG) dual agonist, as well as GLP-1/GIP/GCG triple agonist, may offer superior weight loss efficacy over GLP-1 agonist. This review summarizes the comprehensive mechanisms underlying the pronounced advantages of GLP-1/GIP dual agonist, GLP-1/GCG dual agonist and GLP-1/GIP/GCG triple agonist over GLP-1 mono agonist in weight reduction in obese adults without type 2 diabetes. A deeper understanding of these unimolecular multitargeting GLP-1-based agonists will provide insights for their clinical application and guide the development of new drugs for obesity treatment. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Jiang, Yuchen AU - Jiang Y AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. FAU - Zhu, Huijuan AU - Zhu H AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. FAU - Gong, Fengying AU - Gong F AUID- ORCID: 0000-0002-6361-3811 AD - Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China. LA - eng GR - 2022-I2M-2-002/the CAMS Innovation Fund for Medical Sciences (CIFMS)/ GR - 82270913/the National Natural Science Foundation of China/ GR - 7222137/the Beijing Natural Science Foundation/ GR - the National Key Clinical Specialty Capacity Improvement Project/ GR - 2023-PT320-10/the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ GR - pumch-2013-020/the PUMCH Foundation/ PT - Journal Article PT - Review DEP - 20241126 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) SB - IM MH - Humans MH - *Obesity/drug therapy/metabolism MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptide 1/agonists MH - *Gastric Inhibitory Polypeptide/agonists MH - Liraglutide/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides/therapeutic use MH - Drug Therapy, Combination MH - Tirzepatide MH - Receptors, Gastrointestinal Hormone/agonists MH - *Anti-Obesity Agents/therapeutic use MH - Adult MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide OTO - NOTNLM OT - GIP OT - GLP-1 OT - antiobesity drug OT - drug mechanism OT - glucagon OT - weight management EDAT- 2024/11/27 00:21 MHDA- 2025/02/07 00:20 CRDT- 2024/11/26 23:50 PHST- 2024/10/21 00:00 [revised] PHST- 2024/08/23 00:00 [received] PHST- 2024/10/29 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2024/11/27 00:21 [pubmed] PHST- 2024/11/26 23:50 [entrez] AID - 10.1111/dom.16106 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Mar;27(3):1079-1095. doi: 10.1111/dom.16106. Epub 2024 Nov 26. PMID- 39592207 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20250517 IS - 1468-3288 (Electronic) IS - 0017-5749 (Linking) VI - 74 IP - 3 DP - 2025 Feb 6 TI - Recent advances in incretin-based therapy for MASLD: from single to dual or triple incretin receptor agonists. PG - 487-497 LID - 10.1136/gutjnl-2024-334023 [doi] AB - Clinically effective pharmacological treatment(s) for metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form metabolic dysfunction-associated steatohepatitis (MASH) represent a largely unmet need in medicine. Since glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been licensed for the treatment of type 2 diabetes mellitus and obesity, they were one of the first drug classes to be examined in individuals with MASLD/MASH. Successful phase 2 randomised clinical trials with these agents have resulted in progression to phase 3 clinical trials (principally testing the long-term efficacy of subcutaneous semaglutide). Over the last few years, in addition to GLP-1RAs, newer agents with glucose-dependent insulinotropic peptide and/or glucagon receptor agonist functions have been tested, with increasing evidence from phase 2 randomised clinical trials of histological improvements in MASLD/MASH, as well as benefits on MASLD-related extrahepatic complications. Based on this background of evidence, single, dual or triple incretin receptor agonists are becoming an attractive and promising treatment option for MASLD or MASH, particularly in individuals with coexisting obesity or type 2 diabetes mellitus. In this narrative review, we examine the rapidly expanding body of clinical evidence supporting a role of incretin-based pharmacotherapies in delaying or reversing MASH progression. We also discuss the biology of incretins and the putative hepatoprotective mechanisms of incretin-based pharmacotherapies for managing MASLD or MASH. CI - (c) Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group. FAU - Targher, Giovanni AU - Targher G AUID- ORCID: 0000-0002-4325-3900 AD - Metabolic Diseases Research Unit, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy giovanni.targher@univr.it. FAU - Mantovani, Alessandro AU - Mantovani A AUID- ORCID: 0000-0002-7271-6329 AD - Endocrinology and Metabolism, University of Verona Faculty of Medicine and Surgery, Verona, Italy. FAU - Byrne, Christopher D AU - Byrne CD AUID- ORCID: 0000-0001-6322-7753 AD - Southampton General Hospital, Southampton, UK. FAU - Tilg, Herbert AU - Tilg H AUID- ORCID: 0000-0002-4235-2579 AD - Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria. LA - eng PT - Journal Article PT - Review DEP - 20250206 PL - England TA - Gut JT - Gut JID - 2985108R RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - *Fatty Liver/drug therapy MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - LIVER OT - NONALCOHOLIC STEATOHEPATITIS OT - PHARMACOTHERAPY COIS- Competing interests: HT is an associate editor of the journal, and GT is an editorial board member of the journal. The authors do not have other potential conflicts of interest to disclose. EDAT- 2024/11/27 00:21 MHDA- 2025/02/07 00:20 CRDT- 2024/11/26 21:03 PHST- 2024/10/03 00:00 [received] PHST- 2024/11/03 00:00 [accepted] PHST- 2025/02/07 00:20 [medline] PHST- 2024/11/27 00:21 [pubmed] PHST- 2024/11/26 21:03 [entrez] AID - gutjnl-2024-334023 [pii] AID - 10.1136/gutjnl-2024-334023 [doi] PST - epublish SO - Gut. 2025 Feb 6;74(3):487-497. doi: 10.1136/gutjnl-2024-334023. PMID- 39588627 OWN - NLM STAT- MEDLINE DCOM- 20241126 LR - 20260127 IS - 1972-6481 (Electronic) IS - 1827-6806 (Linking) VI - 25 IP - 12 DP - 2024 Dec TI - [ANMCO Statement: semaglutide in cardio-nephro-metabolic disorders]. PG - 891-899 LID - 10.1714/4372.43702 [doi] AB - Semaglutide, a glucagon-like peptide-1 receptor agonist, has emerged as a pivotal therapeutic agent in the management of the cardio-renal-metabolic continuum. Initially developed for glycemic control in type 2 diabetes mellitus, its benefits extend far beyond glucose regulation. Clinical trials have demonstrated semaglutide's potential to reduce major adverse cardiovascular events, particularly in overweight/obese patients with high cardiovascular risk, as well as improving functional capacity in patients suffering from heart failure with preserved left ventricular function. Additionally, it has shown promise in improving renal outcomes, such as slowing the progression of albuminuria and reducing the risk of chronic kidney disease in diabetic populations. These effects are likely due to its multifaceted mechanisms, including anti-inflammatory properties, weight reduction, blood pressure lowering, and direct renal protection. This review synthesizes current evidence on semaglutide's role in the interrelated domains of cardiovascular, renal, and metabolic health. FAU - De Luca, Leonardo AU - De Luca L AD - S.C. Cardiologia, Dipartimento Cardio-Toraco-Vascolare, Fondazione IRCCS Policlinico San Matteo, Pavia. FAU - Bilato, Claudio AU - Bilato C AD - U.O.C. Cardiologia, Ospedali dell'Ovest Vicentino, Azienda ULSS 8 Berica, Vicenza. FAU - Navazio, Alessandro AU - Navazio A AD - S.O.C. Cardiologia Ospedaliera, Presidio Ospedaliero Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia - IRCCS, Reggio Emilia. FAU - Corda, Marco AU - Corda M AD - S.C. Cardiologia, Azienda Ospedaliera "G. Brotzu", Cagliari. FAU - Milli, Massimo AU - Milli M AD - Cardiologia Firenze 1, Ospedali S. Maria Nuova e Nuovo San Giovanni di Dio, Azienda USL Toscana Centro, Firenze. FAU - Scicchitano, Pietro AU - Scicchitano P AD - U.O. Cardiologia-UTIC, Ospedale "F. Perinei", Altamura (BA). FAU - Di Marco, Massimo AU - Di Marco M AD - U.O.C. Cardiologia-UTIC, Ospedale Santo Spirito, Pescara. FAU - Riccio, Carmine AU - Riccio C AD - U.O.S.D. Follow-up del Paziente Post-Acuto, Dipartimento Cardio-Vascolare, AORN Sant'Anna e San Sebastiano, Caserta. FAU - Geraci, Giovanna AU - Geraci G AD - U.O.C. Cardiologia, Ospedale Sant'Antonio Abate, Trapani. FAU - Iacovoni, Attilio AU - Iacovoni A AD - SSD Chirurgia dei Trapianti e del Trattamento Chirurgico dello Scompenso, Dipartimento Cardiovascolare, ASST Papa Giovanni XXIII, Bergamo. FAU - Pascale, Vittorio AU - Pascale V AD - UTIC-Emodinamica e Cardiologia Interventistica, Ospedale Civile Pugliese, Catanzaro. FAU - Tizzani, Emanuele AU - Tizzani E AD - Dipartimento di Cardiologia, Ospedale degli Infermi, Rivoli (TO). FAU - Gabrielli, Domenico AU - Gabrielli D AD - U.O.C. Cardiologia, Dipartimento di Scienza Cardio-Toraco-Vascolari, Azienda Ospedaliera San Camillo Forlanini, Roma. FAU - Grimaldi, Massimo AU - Grimaldi M AD - U.O.C. Cardiologia-UTIC, Ospedale Miulli, Acquaviva delle Fonti (BA). FAU - Colivicchi, Furio AU - Colivicchi F AD - U.O.C. Cardiologia Clinica e Riabilitativa, Presidio Ospedaliero San Filippo Neri - ASL Roma 1, Roma. FAU - Oliva, Fabrizio AU - Oliva F AD - Cardiologia 1-Emodinamica, Dipartimento Cardio-Toraco-Vascolare "A. De Gasperis", ASST Grande Ospedale Metropolitano Niguarda, Milano. LA - ita PT - English Abstract PT - Journal Article PT - Review TT - Statement ANMCO: la semaglutide nel continuum cardio-nefro-metabolico. PL - Italy TA - G Ital Cardiol (Rome) JT - Giornale italiano di cardiologia (2006) JID - 101263411 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use MH - Metabolic Diseases/prevention & control/drug therapy MH - Obesity/complications/drug therapy MH - Kidney Diseases/prevention & control MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2024/11/26 06:35 MHDA- 2024/11/26 06:36 CRDT- 2024/11/26 04:53 PHST- 2024/11/26 06:36 [medline] PHST- 2024/11/26 06:35 [pubmed] PHST- 2024/11/26 04:53 [entrez] AID - 10.1714/4372.43702 [doi] PST - ppublish SO - G Ital Cardiol (Rome). 2024 Dec;25(12):891-899. doi: 10.1714/4372.43702. PMID- 39584713 OWN - NLM STAT- MEDLINE DCOM- 20241223 LR - 20260919 IS - 1522-1598 (Electronic) IS - 0022-3077 (Linking) VI - 133 IP - 1 DP - 2025 Jan 1 TI - Impact of glucagon-like peptide-1 receptor agonists on axonal function in diabetic peripheral neuropathy. PG - 14-21 LID - 10.1152/jn.00228.2024 [doi] AB - Diabetic peripheral neuropathy (DPN) affects approximately half of the 500 million people with type 2 diabetes worldwide. Previous studies have suggested that glucagon-like peptide-1 (GLP-1) receptors in the peripheral nervous system may be a suitable target for DPN treatment. Fourteen participants were consecutively recruited after being prescribed either semaglutide or dulaglutide as part of standard clinical care for type 2 diabetes. Participants underwent clinical assessment, nerve conduction studies, and axonal excitability assessment at baseline and at 3 mo following commencement of GLP-1 receptor agonist (GLP-1RA) therapy. These data were combined with 10 participants who had previously received exenatide therapy, and mathematical modeling of excitability data was undertaken. Clinical neuropathy scores improved at 3 mo following commencement of GLP-1 (baseline TNS 3.7 +/- 4.5, posttreatment TNS 2.3 +/- 3.4, P = 0.005). Nerve conduction studies demonstrated an improvement in sural amplitude at 3 mo (baseline 11.9 +/- 8.5 muV, posttreatment 14.2 +/- 9.2 muV; P = 0.013). Axonal excitability studies revealed changes consistent with improvements in Na(+)/K(+)-ATPase pump function and Na(+) permeability, and this was supported by mathematical modeling. GLP-1RA therapy improves clinical and neurophysiological outcomes in DPN. Treatment with GLP-1RA may reverse axonal dysfunction by improving Na(+)/K(+)-ATPase pump function.NEW & NOTEWORTHY Diabetic peripheral neuropathy is known to be relentlessly progressive and irreversible. Prospective studies in 24 participants with diabetic peripheral neuropathy (DPN) treated with glucagon-like peptide-1 receptor agonists (GLP-1RA) demonstrated improvements in clinical neuropathy scores, nerve conduction studies, and axonal excitability recordings. Analysis of axonal excitability recordings revealed the mechanism for GLP-1RA improvement in DPN were changed consistent with improvements in Na(+)/K(+)-ATPase pump function, and this was supported by mathematical modeling. CI - Copyright (c) 2025 The Authors. FAU - Dhanapalaratnam, Roshan AU - Dhanapalaratnam R AUID- ORCID: 0000-0002-7684-0976 AD - School of Clinical Medicine, UNSW Sydney, Sydney, New South Wales, Australia. AD - Department of Neurology, Prince of Wales Hospital, Sydney, New South Wales, Australia. FAU - Issar, Tushar AU - Issar T AD - School of Clinical Medicine, UNSW Sydney, Sydney, New South Wales, Australia. FAU - Poynten, Ann M AU - Poynten AM AD - Department of Endocrinology, Prince of Wales Hospital, Sydney, New South Wales, Australia. FAU - Milner, Kerry-Lee AU - Milner KL AD - Department of Endocrinology, Prince of Wales Hospital, Sydney, New South Wales, Australia. FAU - Kwai, Natalie C G AU - Kwai NCG AD - School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, New South Wales, Australia. FAU - Krishnan, Arun V AU - Krishnan AV AUID- ORCID: 0000-0001-8883-8825 AD - School of Clinical Medicine, UNSW Sydney, Sydney, New South Wales, Australia. AD - Department of Neurology, Prince of Wales Hospital, Sydney, New South Wales, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241125 PL - United States TA - J Neurophysiol JT - Journal of neurophysiology JID - 0375404 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetic Neuropathies/drug therapy/physiopathology MH - Male MH - Female MH - Middle Aged MH - *Axons/drug effects/physiology MH - Aged MH - *Neural Conduction/drug effects MH - *Glucagon-Like Peptides/pharmacology/administration & dosage/analogs & derivatives MH - Immunoglobulin Fc Fragments/pharmacology/administration & dosage MH - Recombinant Fusion Proteins/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy/complications/physiopathology MH - Hypoglycemic Agents/pharmacology MH - Sodium-Potassium-Exchanging ATPase/metabolism MH - Exenatide/pharmacology/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - axonal excitability OT - diabetes OT - glucagon-like peptide-1 OT - glucagon-like peptide-1 receptor agonist OT - peripheral nerve OT - peripheral neuropathy EDAT- 2024/11/25 12:31 MHDA- 2024/12/23 12:21 CRDT- 2024/11/25 08:13 PHST- 2024/12/23 12:21 [medline] PHST- 2024/11/25 12:31 [pubmed] PHST- 2024/11/25 08:13 [entrez] AID - 10.1152/jn.00228.2024 [doi] PST - ppublish SO - J Neurophysiol. 2025 Jan 1;133(1):14-21. doi: 10.1152/jn.00228.2024. Epub 2024 Nov 25. PMID- 39583077 OWN - NLM STAT- MEDLINE DCOM- 20241125 LR - 20261022 IS - 2296-2565 (Electronic) IS - 2296-2565 (Linking) VI - 12 DP - 2024 TI - Benchmarking the medication efficiency and technological progress of diabetes drugs. PG - 1396832 LID - 10.3389/fpubh.2024.1396832 [doi] LID - 1396832 AB - BACKGROUND: Diabetes poses a serious global challenge, given its increasing prevalence, detrimental effects on public health, and substantial economic burden. Since 1950s, tens of drugs have been approved by the United States (US) Food and Drug Administration (FDA). In the past decade, the medical community and regulatory agencies have moved away from the glucose-centric paradigm and increasingly call for a holistic approach to assess different treatments' benefits and harms. OBJECTIVE: This study aimed to assess the medication efficiency and technological progress of Type 2 Diabetes (T2D) drugs, by considering their physiological outcomes, including both benefits (i.e., glucose lowering and weight loss) and adverse effects (mortality), relative to dosing frequency. METHODS: To derive medication efficiency, this study utilized data from the US FDA and prominent meta-analyses. Given that both the benefits and adverse effects of medications are multidimensional, this study employed a nonparametric frontier method, the data envelopment analysis (DEA) model, to integrate these factors into a measure of medication efficiency. Physiological outcomes could assume both positive and negative values. Adverse effects were regarded undesirable outputs. The DEA model was built under the framework of directional distance function and was able to handle negative and undesirable values which naturally arose in the case of T2D medications. RESULTS: The paper presented a ranking of 20 T2D drugs in terms of medication efficiency. Three of them were able to attain the highest medication efficiency, all of which were in the GLP-1 class, including oral Semaglutide, subcutaneous Semaglutide and Dulaglutide. However, the other two GLP-1 drugs, Lixisenatide and Liraglutide, were less efficient. The average medication efficiency of drugs approved post-2010 was significantly higher than pre-2010 drugs. High dose frequency, low HbA1c reduction and insignificant weight loss were the main driving factors behind inefficiencies. Overall, medication efficiency provided an alternative perspective on treatment effectiveness other than conventional measures such as cost-effectiveness. CI - Copyright (c) 2024 Zhang, Wang, Xu, Liu, Ban, Liu, Yan and Han. FAU - Zhang, Hongwei AU - Zhang H AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Chen AU - Wang C AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Xu, Ting AU - Xu T AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Liu, Lin AU - Liu L AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ban, Xuyan AU - Ban X AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Liu, Weijie AU - Liu W AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Yan, Chenli AU - Yan C AD - Technological Economics and Management, School of Business Administration, Capital University of Economics and Business, Beijing, China. FAU - Han, Xiaodong AU - Han X AD - Department of Metabolic and Bariatric Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article DEP - 20241108 PL - Switzerland TA - Front Public Health JT - Frontiers in public health JID - 101616579 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Benchmarking MH - United States MH - United States Food and Drug Administration PMC - PMC11582034 OTO - NOTNLM OT - DEA OT - diabetes OT - directional distance model OT - efficiency change OT - frontier OT - medication efficiency OT - technological progress COIS- The author(s) declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/11/25 11:34 MHDA- 2024/11/25 11:35 PMCR- 2024/11/08 CRDT- 2024/11/25 05:06 PHST- 2024/03/06 00:00 [received] PHST- 2024/10/23 00:00 [accepted] PHST- 2024/11/25 11:35 [medline] PHST- 2024/11/25 11:34 [pubmed] PHST- 2024/11/25 05:06 [entrez] PHST- 2024/11/08 00:00 [pmc-release] AID - 10.3389/fpubh.2024.1396832 [doi] PST - epublish SO - Front Public Health. 2024 Nov 8;12:1396832. doi: 10.3389/fpubh.2024.1396832. eCollection 2024. PMID- 39580054 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260127 IS - 1544-3450 (Electronic) IS - 1086-5802 (Linking) VI - 65 IP - 1 DP - 2025 Jan-Feb TI - An analysis of national news coverage of semaglutide for weight loss. PG - 102297 LID - S1544-3191(24)00328-5 [pii] LID - 10.1016/j.japh.2024.102297 [doi] AB - BACKGROUND: Glucagon-like peptide 1 (GLP-1) agonists like semaglutide have risen significantly in use in recent years as a therapeutic option for the management of obesity. Popular media serves as an information source for many patients, and depending on the content, may influence how a patient views a particular therapy. OBJECTIVE: To describe the content of online/print news articles published about semaglutide for weight loss. METHODS: Online websites and databases were used to access 8 major U.S. online/print news outlets, including the New York Times, Wall Street Journal, Washington Post, USA Today, Fox News, CNN, ABC News, and CBS News. Sources were searched for articles focusing on semaglutide and weight loss published in 2023. Articles were excluded if they focused on: (1) type 2 diabetes, (2) company press releases, or were (3) videos or transcripts of oral broadcasts/podcasts. A random sample of articles was chosen with equitable distribution across sources. Articles were assessed for the presence of data across 9 domains and 30 different content codes, stratified by news source. RESULTS: A total of 127 articles were analyzed, split almost equally between print (n = 63) and online (n = 64) sources. The vast majority of articles were news articles/analyses (122; 96.1%). The most popular primary focus of articles were social/popular aspects of GLP-1 agonists (22; 17.3%), followed by basic medication information (20; 15.8%), harms of the medication (20; 15.8%), and benefits of the medication (17; 13.4%). Print sources were more likely to report on the cash price (55.6% Vs. 28.1%, P = 0.002), lack of insurance (61.9% Vs. 21.9%, P < 0.001), and cost-effectiveness (11.1% Vs. 1.6%, P = 0.027) of the medication compared to online sources. CONCLUSION: Online/print news articles regarding semaglutide for weight loss provide a variety of information about the medication, commonly focusing on social aspects of treatment. CI - Copyright (c) 2024 American Pharmacists Association(R). Published by Elsevier Inc. All rights reserved. FAU - Gionfriddo, Michael R AU - Gionfriddo MR FAU - Owens, Katelyn M AU - Owens KM FAU - Banks, Hannah AU - Banks H FAU - Sherigar, Anwitha AU - Sherigar A FAU - Covvey, Jordan R AU - Covvey JR LA - eng PT - Journal Article DEP - 20241122 PL - United States TA - J Am Pharm Assoc (2003) JT - Journal of the American Pharmacists Association : JAPhA JID - 101176252 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Weight Loss/drug effects MH - *Obesity/drug therapy MH - *Anti-Obesity Agents/therapeutic use MH - United States MH - *Mass Media/statistics & numerical data MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosure The authors declare no relevant conflicts of interest or financial relationships. EDAT- 2024/11/24 00:44 MHDA- 2025/02/20 00:21 CRDT- 2024/11/23 19:16 PHST- 2024/09/13 00:00 [received] PHST- 2024/11/07 00:00 [revised] PHST- 2024/11/14 00:00 [accepted] PHST- 2025/02/20 00:21 [medline] PHST- 2024/11/24 00:44 [pubmed] PHST- 2024/11/23 19:16 [entrez] AID - S1544-3191(24)00328-5 [pii] AID - 10.1016/j.japh.2024.102297 [doi] PST - ppublish SO - J Am Pharm Assoc (2003). 2025 Jan-Feb;65(1):102297. doi: 10.1016/j.japh.2024.102297. Epub 2024 Nov 22. PMID- 39549371 OWN - NLM STAT- MEDLINE DCOM- 20241124 LR - 20260627 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 38 IP - 12 DP - 2024 Dec TI - Exploring the antioxidant properties of semaglutide: A comprehensive review. PG - 108906 LID - S1056-8727(24)00232-0 [pii] LID - 10.1016/j.jdiacomp.2024.108906 [doi] AB - Patients with diabetes commonly experience an aberrant production of free radicals and weakened antioxidative defenses, making them highly susceptible to oxidative stress development. This, in turn, can induce and promote diabetic complications. Therefore, utilizing antidiabetic agents with antioxidative properties can offer dual benefits by addressing hyperglycemia and reducing oxidative damage. Semaglutide, a recently approved oral form of glucagon-like peptide-1 (GLP-1) analogues, has shown potent antidiabetic effects. Additionally, recent studies have suggested that it possesses antioxidative properties. However, the exact effects and the molecular pathways involved are not well understood. In this review, we present the latest findings on the antioxidative impacts of semaglutide and draw conclusions about the mechanisms involved. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Yaribeygi, Habib AU - Yaribeygi H AD - Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran. Electronic address: habib.yari@yahoo.com. FAU - Maleki, Mina AU - Maleki M AD - Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Forouzanmehr, Behina AU - Forouzanmehr B AD - Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran. FAU - Kesharwani, Prashant AU - Kesharwani P AD - Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India. FAU - Jamialahmadi, Tannaz AU - Jamialahmadi T AD - Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Karav, Sercan AU - Karav S AD - Department of Molecular Biology and Genetics, Canakkale Onsekiz Mart University, Canakkale 17100, Turkey. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: amir_saheb2000@yahoo.com. LA - eng PT - Journal Article PT - Review DEP - 20241112 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Antioxidants) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Humans MH - *Antioxidants/therapeutic use/pharmacology MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Oxidative Stress/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Animals MH - Semaglutide OTO - NOTNLM OT - Diabetes mellitus OT - GLP-1 agonist OT - NRF2 OT - Oxidative stress OT - Semaglutide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/11/17 04:19 MHDA- 2024/11/25 01:26 CRDT- 2024/11/16 18:02 PHST- 2024/07/27 00:00 [received] PHST- 2024/10/02 00:00 [revised] PHST- 2024/11/09 00:00 [accepted] PHST- 2024/11/25 01:26 [medline] PHST- 2024/11/17 04:19 [pubmed] PHST- 2024/11/16 18:02 [entrez] AID - S1056-8727(24)00232-0 [pii] AID - 10.1016/j.jdiacomp.2024.108906 [doi] PST - ppublish SO - J Diabetes Complications. 2024 Dec;38(12):108906. doi: 10.1016/j.jdiacomp.2024.108906. Epub 2024 Nov 12. PMID- 39549228 OWN - NLM STAT- MEDLINE DCOM- 20241216 LR - 20261010 IS - 1179-1926 (Electronic) IS - 0312-5963 (Linking) VI - 63 IP - 12 DP - 2024 Dec TI - Time-Efficacy Relationship of Semaglutide in the Treatment of Type 2 Diabetes Mellitus: A Model-Based Meta-Analysis. PG - 1679-1688 LID - 10.1007/s40262-024-01449-1 [doi] AB - OBJECTIVE: Our objective was to quantify the efficacy of subcutaneous once-weekly semaglutide in treating type 2 diabetes mellitus (T2DM) over time. METHODS: Based on a literature search of the PubMed, Embase, Cochrane, and Web of Science databases, a modified maximum effect (E(max)) model including rebound effects was built using model-based meta-analysis with change from baseline in glycated hemoglobin as the efficacy endpoint. This was combined with the covariate model to form a final model, and then theoretical values of E(max) and time to reach 50% of E(max) (ET(50)) were obtained for each dose. Model fit and prediction were assessed using goodness-of-fit plots and visual prediction checking. RESULTS: E(max) and ET(50) were influenced by the proportion of males and the baseline values, respectively. There was no evidence of a placebo effect with semaglutide. The efficacy of other doses became more significant over time, and a rebound effect was observed after maximum efficacy, at a rate of 0.018. Simulation of the typical efficacy at the different doses yielded a maximum efficacy of -1.58% with 0.5 mg and a maximum efficacy of -1.87% with 1 mg. In addition, the six simulated doses (0, 0.1, 0.2, 0.5, 1, and 2 mg) showed a dose-dependent relationship between dose and efficacy except for 0.4 mg and 0.8 mg. A higher dose would result in greater efficacy and a faster onset of action. CONCLUSION: The efficacy of semaglutide in glucose control was investigated using the model-based meta-analysis method, which yields new insights into the treatment of T2DM with semaglutide. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Zhang, Ke AU - Zhang K AD - School of Mathematics and Computing Science, Guangxi Colleges and Universities Key Laboratory of Data Analysis and Computation, Guilin University of Electronic Technology, Jinji Road No 1, Qixing District, Guilin, 541004, China. AD - Center for Applied Mathematics of Guangxi (GUET), Jinji Road No 1, Qixing District, Guilin, 541004, China. FAU - Zhao, Aiping AU - Zhao A AD - School of Mathematics and Computing Science, Guangxi Colleges and Universities Key Laboratory of Data Analysis and Computation, Guilin University of Electronic Technology, Jinji Road No 1, Qixing District, Guilin, 541004, China. AD - Center for Applied Mathematics of Guangxi (GUET), Jinji Road No 1, Qixing District, Guilin, 541004, China. AD - Department of Biostatistics, Guangzhou Jeeyor Medical Research Co., Ltd,, Room 536, Building 4, Ground 7, Guangzhou International Airport Center, Yingbin Avenue, Huadu District, Guangzhou, 510000, China. FAU - Wang, Zhen AU - Wang Z AD - School of Mathematics and Computing Science, Guangxi Colleges and Universities Key Laboratory of Data Analysis and Computation, Guilin University of Electronic Technology, Jinji Road No 1, Qixing District, Guilin, 541004, China. AD - Center for Applied Mathematics of Guangxi (GUET), Jinji Road No 1, Qixing District, Guilin, 541004, China. FAU - Ye, Kaihe AU - Ye K AD - Department of Biostatistics, Guangzhou Jeeyor Medical Research Co., Ltd,, Room 536, Building 4, Ground 7, Guangzhou International Airport Center, Yingbin Avenue, Huadu District, Guangzhou, 510000, China. FAU - Xu, Zhaosi AU - Xu Z AD - Department of Biostatistics, Guangzhou Jeeyor Medical Research Co., Ltd,, Room 536, Building 4, Ground 7, Guangzhou International Airport Center, Yingbin Avenue, Huadu District, Guangzhou, 510000, China. FAU - Gong, Xiao AU - Gong X AD - Department of Biostatistics, Guangzhou Jeeyor Medical Research Co., Ltd,, Room 536, Building 4, Ground 7, Guangzhou International Airport Center, Yingbin Avenue, Huadu District, Guangzhou, 510000, China. x.gong@foxmail.com. FAU - Zhu, Guanghu AU - Zhu G AUID- ORCID: 0000-0002-1416-1476 AD - School of Mathematics and Computing Science, Guangxi Colleges and Universities Key Laboratory of Data Analysis and Computation, Guilin University of Electronic Technology, Jinji Road No 1, Qixing District, Guilin, 541004, China. ghzhu@guet.edu.cn. AD - Center for Applied Mathematics of Guangxi (GUET), Jinji Road No 1, Qixing District, Guilin, 541004, China. ghzhu@guet.edu.cn. LA - eng GR - 2024GXNSFAA010475/Natural Science Foundation of Guangxi Province/ GR - CRKL210106/Director Fund Project of the Ministry of Education Key Laboratory of Cognitive Radio and Information Processing/ GR - Guike AD23023002/Science and Technology Project of Guangxi/ PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20241116 PL - Switzerland TA - Clin Pharmacokinet JT - Clinical pharmacokinetics JID - 7606849 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Female MH - Humans MH - Male MH - Blood Glucose/drug effects/analysis MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Dose-Response Relationship, Drug MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/pharmacology MH - Glycated Hemoglobin/drug effects/analysis MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/pharmacology MH - Models, Biological MH - Treatment Outcome MH - Semaglutide COIS- Declarations. Funding: The work was jointly supported by Guangxi Natural Science Foundation (2024GXNSFAA010475), the Science and Technology Project of Guangxi (Guike AD23023002), and the Director Fund Project of the Ministry of Education Key Laboratory of Cognitive Radio and Information Processing (CRKL210106). Conflict of Interest Statement: All authors declare that they have no conflicts of interest to disclose. Ethics Approval: Not applicable. Data Availability: Data availability is not applicable to this article as no new data were created in this study. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Code Availability: Not applicable. Authors' Contributions: KZ, XG, and GZ wrote the original draft. KZ, AZ, and ZW extracted the data and assessed the quality of the literature. KZ and AZ performed the pharmacodynamic analyses. KY, ZX, and XG provided resources and software. All authors reviewed the manuscript and approved the final version. EDAT- 2024/11/16 22:29 MHDA- 2024/12/16 18:18 CRDT- 2024/11/16 11:21 PHST- 2024/10/24 00:00 [accepted] PHST- 2024/12/16 18:18 [medline] PHST- 2024/11/16 22:29 [pubmed] PHST- 2024/11/16 11:21 [entrez] AID - 10.1007/s40262-024-01449-1 [pii] AID - 10.1007/s40262-024-01449-1 [doi] PST - ppublish SO - Clin Pharmacokinet. 2024 Dec;63(12):1679-1688. doi: 10.1007/s40262-024-01449-1. Epub 2024 Nov 16. PMID- 39536977 OWN - NLM STAT- MEDLINE DCOM- 20241212 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 218 DP - 2024 Dec TI - Real world effectiveness of oral semaglutide: Focus on patients with type 2 diabetes older than 75 years. PG - 111928 LID - S0168-8227(24)00838-6 [pii] LID - 10.1016/j.diabres.2024.111928 [doi] AB - AIM: Data on the efficacy of oral semaglutide (OS) in elderly patients with type 2 diabetes are still lacking. This study evaluates the effectiveness of OS in a real world setting with a large >/=75 year old population. METHODS: This study includes all type 2 diabetic patients who started OS between October 2021 and December 2023 in seven diabetes centers. Data were collected at baseline, 6 (T6) and 12 (T12) months. Effectiveness measures were assessed on the total sample and by patient age (<65, 65-75, >75 years). RESULTS: Overall 1824 patients started OS, of those 18.7 % were over 75 years (>75 yr). OS resulted in a significant reduction in rate of patients using sulphonylureas, rapid and basal insulin therapy, HbA1c reduced by 0.87 % at T6 and at T12 (both p < 0.0001), body weight by 2.78 Kg (p < 0.0001) at T6 and 3.89 Kg (p < 0.0001) at T12. Similarly, >75 yr showed HbA1c reduction at T6 (p < 0.0001) and T12 (p = 0.0003), body weight significantly reduced (p for interaction 0.005) both at T6 (-1.57 Kg; p = 0.0003) and T12 (-2.74 Kg; p < 0.0001). CONCLUSION: In our study, OS results efficacy in non-elderly and elderly patients, making it an effective treatment option also for very elderly type 2 diabetic patients. CI - Copyright (c) 2024. Published by Elsevier B.V. FAU - Baronti, Walter AU - Baronti W AD - Diabetic and Metabolic Diseases Unit, Health Local Unit South-East Tuscany, Grosseto Hospital, Italy. Electronic address: walter.baronti@uslsudest.toscana.it. FAU - Lencioni, Cristina AU - Lencioni C AD - Diabetic and Metabolic Diseases Unit, Health Local Nord-West Tuscany, Lucca, Versilia and Livorno Hospitals, Italy. FAU - Occhipinti, Margherita AU - Occhipinti M AD - Diabetic and Metabolic Diseases Unit, Health Local Nord-West Tuscany, Lucca, Versilia and Livorno Hospitals, Italy. FAU - Nicolucci, Antonio AU - Nicolucci A AD - Coresearch-Centre for Outcome Research and Clinical Epidemiology, Pescara, Italy. FAU - Cianni, Graziano Di AU - Cianni GD AD - Diabetic and Metabolic Diseases Unit, Health Local Nord-West Tuscany, Lucca, Versilia and Livorno Hospitals, Italy. CN - Tuscany Study Group- Italian Diabetologists Association AMD LA - eng PT - Journal Article PT - Multicenter Study DEP - 20241112 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Aged MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Male MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Female MH - Aged, 80 and over MH - *Glycated Hemoglobin/metabolism/analysis MH - Administration, Oral MH - Treatment Outcome MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - Semaglutide OTO - NOTNLM OT - BMI OT - Elderly Type 2 diabetic patients OT - HbA1c OT - Oral-semaglutide OT - Real world COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/11/14 03:56 MHDA- 2024/12/13 00:23 CRDT- 2024/11/13 19:26 PHST- 2024/09/09 00:00 [received] PHST- 2024/11/05 00:00 [revised] PHST- 2024/11/08 00:00 [accepted] PHST- 2024/12/13 00:23 [medline] PHST- 2024/11/14 03:56 [pubmed] PHST- 2024/11/13 19:26 [entrez] AID - S0168-8227(24)00838-6 [pii] AID - 10.1016/j.diabres.2024.111928 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2024 Dec;218:111928. doi: 10.1016/j.diabres.2024.111928. Epub 2024 Nov 12. PMID- 39532398 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260918 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 2 DP - 2025 Feb TI - De-intensification of basal-bolus therapy by replacing prandial insulin with once-weekly subcutaneous semaglutide in individuals with well-controlled type 2 diabetes: A single-centre, open-label randomised trial (TRANSITION-T2D). PG - 642-651 LID - 10.1111/dom.16057 [doi] AB - AIMS: The study aims to examine the outcome of replacement of prandial insulin with once-weekly subcutaneous semaglutide in people with type 2 diabetes reasonably controlled on multiple daily insulin injections (MDI). MATERIALS AND METHODS: This single-centre, randomised, open-label trial enrolled a statistically predetermined sample of 60 adults with HbA1c 50%, 97.5% stopped prandial insulin and 45% lost >10% body weight. Participant treatment satisfaction scores trended higher with semaglutide. Hypoglycaemia frequency was similar between groups. CONCLUSIONS: In people with type 2 diabetes well controlled (HbA(1c) /=6 weeks experienced significantly greater weight loss compared to those using it for shorter periods (6.3 +/- 6.43 vs 1.65 +/- 1.69; P < .001). GI-related adverse events were reported in 57.8% of patients. Over 95% of patients discontinued G1RA due to insufficient weight loss and/or adverse effects. Patients reaching the maximal recommended dose exhibited significantly greater weight loss versus patients who did not reach it for both Liraglutide (5.9 +/- 4.98 kg vs. 3.9 +/- 5.53 kg; P = .03) and Semaglutide (6.5 +/- 7.8 kg vs. 2.5 +/- 3.8 kg; P = .016). CONCLUSION: Pre-MBS G1RA utilization and failure are prevalent among MBS candidates. Our study underscores the need for further research to understand the role of G1RA therapy in obesity management and the development of guidelines for its appropriate use in MBS candidates. CI - Copyright (c) 2025 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved. FAU - Rayman, Shlomi AU - Rayman S AD - Department of General Surgery, Assuta Ashdod Public Hospital, Affiliated with Faculty of Health and Science and Ben-Gurion University, Ashdod, Israel. Electronic address: shlomir@assuta.co.il. FAU - Morduch, Evyatar AU - Morduch E AD - Faculty of Health and Science, Ben-Gurion University, Be'er-Sheva, Israel. FAU - Reiner-Benaim, Anat AU - Reiner-Benaim A AD - Department of Epidemiology, Biostatistics and Community Health Sciences, School of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva, Israel. FAU - Catzman, Netta-Lee AU - Catzman NL AD - Department of Epidemiology, Biostatistics and Community Health Sciences, School of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva, Israel. FAU - Carmeli, Idan AU - Carmeli I AD - Department of General Surgery, Assuta Ashdod Public Hospital, Affiliated with Faculty of Health and Science and Ben-Gurion University, Ashdod, Israel. FAU - Froylich, Dvir AU - Froylich D AD - Surgery department, Carmel Medical Center, The Ruth and Bruce Rappaport Faculty of Medicine, Technion Institute of Technology, Haifa, Israel. FAU - Goitein, David AU - Goitein D AD - Department of General Surgery, Chaim Sheba Medical Center, Ramat Gan, Israel; Affiliated with the School of Medicine, Tel Aviv University, Tel Aviv, Israel. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20241009 PL - United States TA - Surg Obes Relat Dis JT - Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery JID - 101233161 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Bariatric Surgery/statistics & numerical data MH - Female MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Liraglutide/therapeutic use MH - Weight Loss/drug effects MH - Glucagon-Like Peptides/therapeutic use MH - Israel MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Bariatric surgery OT - GLP-1 receptor agonists OT - Semaglutide OT - Weight loss OT - liraglutide COIS- Disclosure The authors have no commercial associations that might be a conflict of interest in relation to this article. EDAT- 2024/11/13 13:48 MHDA- 2025/01/20 22:54 CRDT- 2024/11/08 21:58 PHST- 2024/02/28 00:00 [received] PHST- 2024/08/15 00:00 [revised] PHST- 2024/09/21 00:00 [accepted] PHST- 2025/01/20 22:54 [medline] PHST- 2024/11/13 13:48 [pubmed] PHST- 2024/11/08 21:58 [entrez] AID - S1550-7289(24)00815-3 [pii] AID - 10.1016/j.soard.2024.09.010 [doi] PST - ppublish SO - Surg Obes Relat Dis. 2025 Feb;21(2):121-126. doi: 10.1016/j.soard.2024.09.010. Epub 2024 Oct 9. PMID- 39514688 OWN - NLM STAT- MEDLINE DCOM- 20241108 LR - 20260127 IS - 2175-8239 (Electronic) IS - 0101-2800 (Print) IS - 0101-2800 (Linking) VI - 46 IP - 4 DP - 2024 Oct-Dec TI - Kidney effects of Glucagon-Like Peptide 1 (GLP1): from molecular foundations to a pharmacophysiological perspective. PG - e20240101 LID - S0101-28002024000400405 [pii] LID - 10.1590/2175-8239-JBN-2024-0101en [doi] LID - e20240101 AB - GLP1 receptor agonists (GLP1-RAs) are drugs that mimic the effects of the incretin hormone GLP1 and were initially introduced in medicine for the treatment of diabetes in 2005 and for obesity in 2014. Over time, data from secondary and exploratory objectives of large randomized controlled-trials suggested that GLP1-RAs could also exert renal action by slowing the progression of kidney disease in patients with and without diabetes. Based on this rationale, the Flow study (1 mg semaglutide vs placebo) was designed and recruitment began in 2019 until May 2021. The recently published results confirmed the effect of semaglutide in reducing the composite renal outcome. However, similar to SGLT2 inhibitors, the potential mechanisms behind the renal effects of GLP1-RAs still need to be elucidated. The aim of this review is to address the different physiological mechanisms of GLP1-RAs at the renal level, using evidence from experimental studies and current scientific literature. FAU - Rico-Fontalvo, Jorge AU - Rico-Fontalvo J AUID- ORCID: 0000-0002-2852-1241 AD - Asociacion Colombiana de Nefrologia e HTA, Comite de Rinon, Diabetes y Metabolismo, Bogota, Colombia. AD - Universidad Simon Bolivar, Facultad de Ciencias de la Salud, Departamento de Nefrologia, Barranquilla, Colombia. FAU - Reina, Maricely AU - Reina M AUID- ORCID: 0000-0002-1262-1555 AD - Fundacion Universitaria de Ciencias de la Salud, Hospital San Jose, Departamento de Nefrologia, Bogota, Colombia. FAU - Soler, Maria Jose AU - Soler MJ AUID- ORCID: 0000-0003-3621-0766 AD - Hospital Universitario Vall de Hebron, Servicio de Nefrologia, Barcelona, Espana. AD - Nephrology and Transplantation Research Group, Vall d'Hebron Institut de Recerca (VHIR), Nephrology Department, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain. Centro de Referencia en Enfermedad Glomerular Compleja del Sistema Nacional de Salud de Espana (CSUR), Barcelona, Espana. AD - Redes de Investigacion Cooperativa Orientadas a Resultados en Salud (RICORS), Instituto de Salud Carlos III (RD21/0005/0031), Spain. FAU - Unigarro-Palacios, Mario AU - Unigarro-Palacios M AUID- ORCID: 0000-0002-7753-6079 AD - Fundacion Universitaria de Ciencias de la Salud, Hospital San Jose, Departamento de Endocrinologia, Bogota, Colombia. FAU - Castaneda-Gonzalez, Juan Pablo AU - Castaneda-Gonzalez JP AUID- ORCID: 0000-0001-5400-9068 AD - Fundacion Universitaria de Ciencias de la Salud, Instituto de Investigaciones, Bogota, Colombia. FAU - Quintero, Javier Jimenez AU - Quintero JJ AUID- ORCID: 0009-0007-5150-7580 AD - Universidad Militar Nueva Granada, Bogota, Colombia. FAU - Raad-Sarabia, Maria AU - Raad-Sarabia M AUID- ORCID: 0000-0002-7080-7024 AD - Universidad del Sinu, Departamento de Medicina Interna, Cartagena, Colombia. FAU - Moraes, Thyago Proenca de AU - Moraes TP AUID- ORCID: 0000-0002-2983-3968 AD - Pontificia Universidade de Catolica do Parana (PUCPR), Curitiba, PR, Brazil. FAU - Daza-Arnedo, Rodrigo AU - Daza-Arnedo R AUID- ORCID: 0000-0002-6295-4972 AD - Asociacion Colombiana de Nefrologia e HTA, Comite de Rinon, Diabetes y Metabolismo, Bogota, Colombia. LA - eng LA - por PT - Journal Article PT - Review PL - Brazil TA - J Bras Nefrol JT - Jornal brasileiro de nefrologia JID - 9426946 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Glucagon-Like Peptide 1 MH - Kidney/drug effects/metabolism/physiology MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Diabetic Nephropathies/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Animals MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC11548866 COIS- Conflict of Interest The authors declare that they have no conflict of interest related to the publication of this manuscript. Jorge Rico Fontalvo declares that he has received honoraria for conferences from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, Lilly, Sanofi, Novartis, Abbvie, Merck y Bayer. And participated on Advisory Board for AZ, Boehringer Ingelheim, Bayer y Novo Nordisk. Maria Jose Soler declares that she has received honoraria for conferences and consulting fees from Novo Nordisk, Jansen, Mundipharma, AstraZeneca, Esteve, Fresenius, Eli Lilly, Boehringer-Ingelheim, Vifor, ICU, Pfizer, Bayer, Travere Therapeutics, GE Healthcare, GSK and Otsuka. She is also one of the former Editors-in-Chief of CKJ. Current editorial board of American Society of Nephrology (ASN) journals. Thyago Moraes declares that he has received honoraria for conferences from AstraZeneca, Baxter, Bayer, Boehringer, Lilly, Novo Nordisk and Takeda; and participated on advisory board for AstraZeneca, Baxter, Bayer, Boehringer and Lilly. Rodrigo Daza Arnedo declares that he has received honoraria for conferences from Astra Zeneca, Boehringer Ingelheim, Novo Nordisk y Bayer. Participated in Advisory Board for AZ, Boehringer Ingelheim, Bayer y Novo Nordisk. The other authors declare no conflict of interest. EDAT- 2024/11/13 13:55 MHDA- 2024/11/14 03:56 PMCR- 2024/11/08 CRDT- 2024/11/08 14:22 PHST- 2024/06/02 00:00 [received] PHST- 2024/08/08 00:00 [accepted] PHST- 2024/11/14 03:56 [medline] PHST- 2024/11/13 13:55 [pubmed] PHST- 2024/11/08 14:22 [entrez] PHST- 2024/11/08 00:00 [pmc-release] AID - S0101-28002024000400405 [pii] AID - 10.1590/2175-8239-JBN-2024-0101en [doi] PST - ppublish SO - J Bras Nefrol. 2024 Oct-Dec;46(4):e20240101. doi: 10.1590/2175-8239-JBN-2024-0101en. PMID- 39511836 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260721 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 27 IP - 2 DP - 2025 Feb TI - Semaglutide improved sperm morphology in obese men with type 2 diabetes mellitus and functional hypogonadism. PG - 519-528 LID - 10.1111/dom.16042 [doi] AB - AIMS: To compare the effects of semaglutide and testosterone replacement therapy (TRT) on semen quality and parameters of functional hypogonadism (FH) in men with type 2 diabetes mellitus and obesity. MATERIALS AND METHODS: We designed a randomised open-label trial in 25 men with type 2 diabetes (aged 50 [46-60] years, BMI 35.9 [32.8-38.7] kg/m(2)) and FH randomised to semaglutide (SEMA) 1 mg/week or intramuscular testosterone undecanoate (TRT) 1000 mg/10-12 weeks for 24 weeks. Semen analysis and parameters of FH were measured at baseline and after 24 weeks of treatment. Participants completed questionnaires of the International Index of Erectile Function-15 (IIEF-15) and the Aging Symptoms in Men (AMS). RESULTS: The quality of baseline sperm parameters of our study cohort was poor, below the 5th percentile of reference values. In the SEMA group, there was a significant increase in morphologically normal sperm from baseline to the end of the study (2% [2; 3.5] vs. 4% [2; 5.5]; p = 0.012), whereas sperm concentration and total number decreased significantly in the TRT group. Compared to TRT, the SEMA group had a significantly higher number of morphologically normal sperm, sperm concentration and total number. Both groups experienced an increase in total testosterone and improvement in the AMS score, whereas the IIEF-15 score significantly improved only in the TRT group. CONCLUSION: Semaglutide markedly improved sperm morphology, total testosterone levels and symptoms of hypogonadism. These findings highlight semaglutide's potential as a therapeutic approach for men with obesity-related FH who desire fertility. CLINICAL TRIAL REGISTRATION NUMBER: NCT06489457, www. CLINICALTRIALS: gov. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gregoric, Nadan AU - Gregoric N AUID- ORCID: 0000-0001-5511-0934 AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Sikonja, Jaka AU - Sikonja J AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Janez, Andrej AU - Janez A AUID- ORCID: 0000-0002-6594-5254 AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Jensterle, Mojca AU - Jensterle M AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. LA - eng SI - ClinicalTrials.gov/NCT06489457 GR - P3-0298/Javna Agencija za Raziskovalno Dejavnost RS/ GR - P3-0343/Javna Agencija za Raziskovalno Dejavnost RS/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20241107 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 3XMK78S47O (Testosterone) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - H16A5VCT9C (testosterone undecanoate) SB - IM MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives/pharmacology/administration & dosage MH - *Testosterone/therapeutic use/administration & dosage/analogs & derivatives MH - *Obesity/complications/drug therapy MH - *Hypogonadism/drug therapy/complications MH - Spermatozoa/drug effects MH - Semen Analysis MH - Hormone Replacement Therapy/methods MH - Hypoglycemic Agents/therapeutic use MH - Sperm Count MH - Semaglutide PMC - PMC11701185 OTO - NOTNLM OT - functional hypogonadism OT - obesity OT - semaglutide OT - sperm OT - type 2 diabetes COIS- NG has received lecture honoraria from Novo Nordisk, Eli Lilly, BioMarin, Genesis Pharm and Boehringer Ingelheim. AJ has served as a consultant and is on speaker bureaus for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Abbott, Novo Nordisk, Medtronic and Sanofi. MJ has received lecture honoraria from Novo Nordisk, Eli Lilly, Pfizer, Amgen, Novartis and Sanofi, and is an advisory board member of Novo Nordisk, Eli Lilly, Amgen and Pfizer. JS declares no conflict of interest. EDAT- 2024/11/13 13:59 MHDA- 2025/01/07 04:51 PMCR- 2025/01/06 CRDT- 2024/11/08 01:13 PHST- 2024/10/13 00:00 [revised] PHST- 2024/08/31 00:00 [received] PHST- 2024/10/16 00:00 [accepted] PHST- 2025/01/07 04:51 [medline] PHST- 2024/11/13 13:59 [pubmed] PHST- 2024/11/08 01:13 [entrez] PHST- 2025/01/06 00:00 [pmc-release] AID - DOM16042 [pii] AID - 10.1111/dom.16042 [doi] PST - ppublish SO - Diabetes Obes Metab. 2025 Feb;27(2):519-528. doi: 10.1111/dom.16042. Epub 2024 Nov 7. PMID- 39496023 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20260127 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 103 IP - 44 DP - 2024 Nov 1 TI - Effect of GLP-1 receptor agonists on weight and cardiovascular outcomes: A review. PG - e40364 LID - 10.1097/MD.0000000000040364 [doi] LID - e40364 AB - Diet and lifestyle modifications remain the foundation of obesity treatment, but they have historically proven insufficient for significant, long-term weight loss. As a result, there is a high demand for new pharmacologic treatments to promote weight loss and prevent life-threatening diseases associated with obesity. Researchers are particularly interested in 1 type of drug, glucagon-like peptide 1 receptor agonists (GLP-1 RAs), because of its promising potential in addressing the limitations of non-pharmacologic treatments. In addition to their role in weight loss, these drugs have shown promising early evidence of cardiovascular benefits in obese patients, further enhancing their clinical relevance. Semaglutide and liraglutide, which were initially approved for the treatment of type 2 diabetes, have since been approved by the Food and Drug Administration as weight loss medications due to their effectiveness in promoting significant and sustained weight loss. In this narrative review, we will explore the mechanism of GLP-1 RAs, their effects on weight loss, cardiovascular risk factors and outcomes, common adverse effects, and strategies for managing these effects. CI - Copyright (c) 2024 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Raza, Fatima Ali AU - Raza FA AUID- ORCID: 0000-0001-6889-2197 AD - Department of Medicine, Karachi Medical and Dental College, Karachi, Pakistan. FAU - Altaf, Rafiya AU - Altaf R AD - Department of Surgery, Dow International Medical College, Dow University of Health Sciences, Karachi, Pakistan. FAU - Bashir, Talha AU - Bashir T AD - Department of Medicine, Karachi Institute of Medical Sciences, Combined Military Hospital Malir, Karachi City, Pakistan. FAU - Asghar, Fatima AU - Asghar F AD - Department of Medicine, Ras Al Khaimah College of Medical Sciences, Ras Al Khaimah Medical and Health Sciences University, Ras Al Khaimah, United Arab Emirates. FAU - Altaf, Rabiya AU - Altaf R AD - Department of Medicine, Mersey and West Lancashire Teaching Hospitals NHS Trust, Prescot, United Kingdom. FAU - Tousif, Sohaib AU - Tousif S AD - Department of Medicine, Ziauddin University, Karachi City, Pakistan. FAU - Goyal, Aman AU - Goyal A AD - Department of Medicine, Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai, India. FAU - Mohammed, Aisha AU - Mohammed A AD - Department of Medicine, Comanche County Memorial Hospital, Lawton, OK. FAU - Mohammad, Mahnoor Faisal AU - Mohammad MF AD - Department of Medicine, Liaquat National Hospital and Medical College, Karachi, Pakistan. FAU - Anan, Mahfuza AU - Anan M AUID- ORCID: 0009-0004-9176-4782 AD - Department of Medicine, Bangladesh Medical College, Dhaka, Bangladesh. FAU - Ali, Sajjad AU - Ali S AUID- ORCID: 0000-0002-8024-5942 AD - Department of Medicine, Ziauddin University, Karachi City, Pakistan. LA - eng PT - Journal Article PT - Review PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - *Obesity/drug therapy/complications MH - *Liraglutide/therapeutic use/pharmacology MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Heart Disease Risk Factors MH - Hypoglycemic Agents/therapeutic use MH - Anti-Obesity Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC11537668 COIS- The authors have no funding and conflicts of interest to disclose. EDAT- 2024/11/04 22:24 MHDA- 2024/11/04 22:25 PMCR- 2024/11/01 CRDT- 2024/11/04 15:33 PHST- 2024/11/04 22:25 [medline] PHST- 2024/11/04 22:24 [pubmed] PHST- 2024/11/04 15:33 [entrez] PHST- 2024/11/01 00:00 [pmc-release] AID - 00005792-202411010-00056 [pii] AID - MD-D-24-09777 [pii] AID - 10.1097/MD.0000000000040364 [doi] PST - ppublish SO - Medicine (Baltimore). 2024 Nov 1;103(44):e40364. doi: 10.1097/MD.0000000000040364. PMID- 39491755 OWN - NLM STAT- MEDLINE DCOM- 20250322 LR - 20260608 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 132 IP - 4 DP - 2025 Apr TI - Association between Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Study. PG - 381-388 LID - S0161-6420(24)00685-7 [pii] LID - 10.1016/j.ophtha.2024.10.030 [doi] AB - PURPOSE: To investigate whether semaglutide increases the risk of nonarteritic anterior ischemic optic neuropathy (NAION) in the general population. DESIGN: This retrospective cohort study used a deidentified global electronic medical records database. The enrollment period was extended from January 2017 to August 2023, with observations concluding in August 2024. PARTICIPANTS: This study included individuals with type 2 diabetes mellitus (T2DM) or obesity. They were further categorized into T2DM-only, obesity-only, and T2DM with obesity groups to assess the differences among these subgroups. The effects of semaglutide were compared with those of glucose-lowering or weight-loss medications other than glucagon-like peptide receptor agonists. METHODS: Patient data were obtained from 160 health care organizations across 21 countries. Outcomes were evaluated at 1, 2, and 3 years of follow-up. A 1:1 propensity score matching was performed to balance age, sex, body mass index, hemoglobin A1C, medications, and underlying comorbidities. Cox regression models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: The occurrence of NAION. RESULTS: The final analysis included 37 314 participants with T2DM only, 129 690 participants with obesity only, and 130 216 participants with both T2DM and obesity. The results indicated that the administration of semaglutide was not associated with the development of NAION in the T2DM-only group (1-year follow-up: HR, 2.32; 95% CI, 0.60-8.97; 2 years: HR, 2.31; 95% CI, 0.86-6.17; 3 years: HR, 1.51; 95% CI, 0.71-3.25), the obesity-only group (1-year follow-up: HR, 0.41; 95% CI, 0.08-2.09; 2 years: HR, 0.67; 95% CI, 0.20-2.24; 3 years: HR, 0.72; 95% CI, 0.24-2.16), and the T2DM with obesity group (1 year follow-up: HR, 0.81; 95% CI, 0.42-1.57; 2 years: HR, 1.2; 95% CI, 0.74-1.94; 3 years: HR, 1.19; 95% CI, 0.78-1.82). CONCLUSIONS: The findings suggest that semaglutide may not be associated with an increased risk of NAION in the general population. Therefore, avoidance of semaglutide based solely on concerns regarding the risk of NAION may not be warranted because its potential benefits for blood glucose control and cardiovascular health likely outweigh its potential risks. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. CI - Copyright (c) 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Chou, Chien-Chih AU - Chou CC AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan. FAU - Pan, Ssu-Yu AU - Pan SY AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Sheen, Yi-Jing AU - Sheen YJ AD - School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; Center for Quantitative Imaging in Medicine, Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Lin, Jun-Fu AU - Lin JF AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan. FAU - Lin, Ching-Heng AU - Lin CH AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan; Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan. FAU - Lin, Hui-Ju AU - Lin HJ AD - Eye Center, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan. FAU - Wang, I-Jong AU - Wang IJ AD - Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. FAU - Weng, Chien-Hsiang AU - Weng CH AD - Department of Family Medicine, Brown University Warren Alpert Medical School, Providence, Rhode Island; Coastal Medical Lifespan, Providence, Rhode Island. Electronic address: chien-hsiang_weng@brown.edu. LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20241102 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Female MH - *Glucagon-Like Peptides/adverse effects MH - Retrospective Studies MH - *Optic Neuropathy, Ischemic/epidemiology/chemically induced/diagnosis MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology MH - Aged MH - Obesity/complications/drug therapy/epidemiology MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Follow-Up Studies MH - Incidence MH - Glycated Hemoglobin/metabolism MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Nonarteritic anterior ischemic optic neuropathy OT - Semaglutide OT - Stroke EDAT- 2024/11/04 06:23 MHDA- 2025/03/23 16:51 CRDT- 2024/11/04 01:23 PHST- 2024/09/12 00:00 [received] PHST- 2024/10/16 00:00 [revised] PHST- 2024/10/24 00:00 [accepted] PHST- 2025/03/23 16:51 [medline] PHST- 2024/11/04 06:23 [pubmed] PHST- 2024/11/04 01:23 [entrez] AID - S0161-6420(24)00685-7 [pii] AID - 10.1016/j.ophtha.2024.10.030 [doi] PST - ppublish SO - Ophthalmology. 2025 Apr;132(4):381-388. doi: 10.1016/j.ophtha.2024.10.030. Epub 2024 Nov 2. PMID- 39491749 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260127 IS - 1878-1632 (Electronic) IS - 1529-9430 (Linking) VI - 25 IP - 3 DP - 2025 Mar TI - Semaglutide utilization associated with reduced 90-day postoperative complications following single-level posterior lumbar fusion for patients with type II diabetes. PG - 485-493 LID - S1529-9430(24)01093-3 [pii] LID - 10.1016/j.spinee.2024.10.011 [doi] AB - BACKGROUND CONTEXT: Semaglutide (the active agent in medications such as Ozempic) has emerged as an increasingly popular medication in the management of diabetes due to its superior clinical efficacy compared with other medications. Patients undergoing surgery, such as posterior lumbar fusion (PLF), may be on these medications for type II diabetes mellitus (T2DM). While the correlation of T2DM with inferior PLF outcomes is known, considering the potential impact of semaglutide on the odds of postoperative complications has not previously been characterized. PURPOSE: To investigate the potential correlation of semaglutide on 90-day postoperative adverse events following single-level PLF for those with T2DM who are or are not concurrently taking insulin. STUDY DESIGN/SETTING: A retrospective cohort study utilizing the 2010 to Q2 2022 M161Ortho PearlDiver Mariner Patient Claims Database. PATIENT SAMPLE: T2DM patients (with or without concurrent insulin use) undergoing single-level PLF (with or without interbody fusion) were identified using Current Procedural Terminology (CPT) codes. Exclusion criteria included: patients less than 18 years of age, those undergoing concurrent cervical, thoracic, anterior, or multilevel fusion procedures, and those with trauma, neoplasm, or infection diagnosed within three months of surgery. OUTCOME MEASURES: Incidence of 90-day aggregated any, severe, and minor adverse events (AAE, SAE, and MAE, respectively), emergency department (ED) visits, and hospital readmissions. METHODS: Patients with a prior diagnosis of T2DM not using insulin (T2DM-insulin) and T2DM concurrently using insulin (T2DM+insulin) undergoing PLF were identified. Patients within each group who utilized semaglutide in the year prior to surgery were identified and matched 1:4 with nonsemaglutide T2DM-insulin and nonsemaglutide T2DM+insulin patients, respectively, based on age, sex, Elixhauser Comorbidity Index (ECI), obesity, tobacco use, metformin use, and sodium-glucose transport protein 2 inhibitor (SGLT2i) use. The incidence of 90-day adverse events between groups was compared by univariate and multivariate analyses. Bonferroni correction was utilized to reduce the risk of type I error. RESULTS: Of all T2DM patients undergoing PLF, semaglutide use was noted for 227 (0.73%) of T2DM-insulin patients, and 244 (2.17%) of T2DM+insulin patients. Once matched, there were 191 and 148 in the semaglutide groups, respectively. For the PLF T2DM-insulin analysis, those using semaglutide were at significantly lower odds of AAE (odds ratio [OR] 0.43), MAE (OR 0.45), and ED visits (OR 0.34) (p<.001 for all), but not of SAEs or readmissions. For the PLF T2DM+insulin analysis, those using semaglutide were at significantly lower odds of AAE (OR 0.40, p<.001), SAE (OR 0.43, p=.004), MAE (OR 0.34, p<.001), and ED visits (OR 0.26, p<.001), but not readmissions. CONCLUSIONS: The current study found consistent reductions in aggregated 90-day adverse events, but similar odds of hospital readmission for T2DM patients undergoing PLF taking semaglutide preoperatively. These encouraging findings of reduced postoperative complications suggest further prospective analysis, as the observed findings suggest clinical benefit to semaglutide being utilized by the studied patient population. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Seddio, Anthony E AU - Seddio AE AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Gouzoulis, Michael J AU - Gouzoulis MJ AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Vasudevan, Rajiv S AU - Vasudevan RS AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Dhodapkar, Meera M AU - Dhodapkar MM AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Jabbouri, Sahir S AU - Jabbouri SS AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Varthi, Arya G AU - Varthi AG AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Rubio, Daniel R AU - Rubio DR AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. FAU - Grauer, Jonathan N AU - Grauer JN AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, CT. Electronic address: jonathan.grauer@yale.edu. LA - eng PT - Journal Article DEP - 20241102 PL - United States TA - Spine J JT - The spine journal : official journal of the North American Spine Society JID - 101130732 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Spinal Fusion/adverse effects/methods MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Postoperative Complications/epidemiology/prevention & control MH - *Lumbar Vertebrae/surgery MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - Adverse events OT - Ozempic OT - Posterior lumbar fusion OT - Semaglutide OT - Spine surgery OT - Type II diabetes COIS- Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms. EDAT- 2024/11/04 06:24 MHDA- 2025/02/16 01:32 CRDT- 2024/11/04 01:22 PHST- 2024/02/29 00:00 [received] PHST- 2024/09/09 00:00 [revised] PHST- 2024/10/27 00:00 [accepted] PHST- 2025/02/16 01:32 [medline] PHST- 2024/11/04 06:24 [pubmed] PHST- 2024/11/04 01:22 [entrez] AID - S1529-9430(24)01093-3 [pii] AID - 10.1016/j.spinee.2024.10.011 [doi] PST - ppublish SO - Spine J. 2025 Mar;25(3):485-493. doi: 10.1016/j.spinee.2024.10.011. Epub 2024 Nov 2. PMID- 39490542 OWN - NLM STAT- MEDLINE DCOM- 20250425 LR - 20260901 IS - 1526-3231 (Electronic) IS - 0749-8063 (Linking) VI - 41 IP - 2 DP - 2025 Feb TI - Lower Risk of Postoperative Complications and Rotator Cuff Retear Associated With Semaglutide Use in Patients with Type II Diabetes Mellitus Undergoing Arthroscopic Rotator Cuff Repair. PG - 199-206 LID - S0749-8063(24)00838-7 [pii] LID - 10.1016/j.arthro.2024.09.057 [doi] AB - PURPOSE: To investigate the potential impact of preoperative semaglutide use (the active agent in Ozempic and Wegovy) on 90-day postoperative outcomes and 2-year rotator cuff retear after arthroscopic rotator cuff repair (ARCR) in patients with type II diabetes mellitus (T2DM). METHODS: Patients with T2DM undergoing primary ARCR were identified from the PearlDiver database using administrative billing codes. Exclusion criteria included patients <18 years old; previous RCR; concurrent nonrotator cuff-related arthroscopic shoulder procedures; any traumatic, neoplastic, or infectious diagnoses within 90 days before surgery; and <90-days follow-up. Patients with T2DM using semaglutide within 1 year of ARCR ([+]semaglutide) were matched 1:4 with patients with T2DM who did not ([-]semaglutide) by age, sex, Elixhauser Comorbidity Index, diabetes complications, obesity, tobacco, insulin, and metformin use. Occurrence of any adverse events (AAE), severe adverse events (SAE), and minor adverse events (MAE) within 90 days were compared by multivariable logistic regression. The 2-year retear was assessed by Kaplan-Meier survival analysis and compared by log-rank test. RESULTS: There were 1,094 ARCR (+)semaglutide and 4,110 ARCR (-)semaglutide patients meeting inclusion criteria after matching. The incidence of AAE for the ARCR (-)semaglutide versus ARCR (+)semaglutide patients was 27.4% versus 11.0%, SAE was 10.5% versus 3.5%, and MAE was 22.0% versus 8.5%, respectively (P < .001 for all). ARCR (-)semaglutide patients had a greater odds ratio of AAE (3.65, P < .001) and SAE (3.62, P < .001), including surgical-site infection (2.22, P = .049), venous thromboembolism (3.10, P < .001), sepsis (3.87, P < .001), and cardiac events (3.96, P < .001), as well as greater odds of MAE (3.59, P < .001), including urinary tract infection (3.27), pneumonia (3.88), acute kidney injury (3.91), and emergency department visits (2.51) (P < .001 for all). In addition, (-)semaglutide patients revealed greater 2-year retear vs (+)semaglutide patients (18.3% vs 12.5%, respectively) (P < .001). CONCLUSIONS: Preoperative semaglutide use for patients with T2DM undergoing ARCR was associated with decreased odds of minor and serious 90-day adverse events and lower 2-year rotator cuff retear. LEVEL OF EVIDENCE: Level III, retrospective comparative study. CI - Copyright (c) 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved. FAU - Seddio, Anthony E AU - Seddio AE AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, Connecticut, U.S.A. FAU - Moran, Jay AU - Moran J AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, Connecticut, U.S.A. FAU - Gouzoulis, Michael J AU - Gouzoulis MJ AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, Connecticut, U.S.A. FAU - Garbis, Nickolas G AU - Garbis NG AD - Department of Orthopaedic Surgery and Rehabilitation, Loyola University Chicago, Maywood, Illinois, U.S.A. FAU - Salazar, Dane H AU - Salazar DH AD - Department of Orthopaedic Surgery and Rehabilitation, Loyola University Chicago, Maywood, Illinois, U.S.A. FAU - Grauer, Jonathan N AU - Grauer JN AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, Connecticut, U.S.A. FAU - Jimenez, Andrew E AU - Jimenez AE AD - Department of Orthopaedics & Rehabilitation, Yale School of Medicine, New Haven, Connecticut, U.S.A.. Electronic address: andrew.jimenez@yale.edu. LA - eng PT - Journal Article DEP - 20241026 PL - United States TA - Arthroscopy JT - Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association JID - 8506498 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Arthroscopy/adverse effects/methods MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Middle Aged MH - *Postoperative Complications/epidemiology/prevention & control/etiology MH - *Rotator Cuff Injuries/surgery/complications MH - Aged MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.E.J. reports consulting or advisory for Arthrex and member of the editorial board of The Journal Arthroscopy. D.H.S. reports consulting or advisory for Zimmer, Arthrex, and Stryker; and board membership, American Shoulder and Elbow Surgeons and American Orthopaedic Association that includes. J.N.G. reports board membership, North American Spine Society and Editor-in-Chief, North American Spine Society Journal. N.G.G. reports consulting or advisory for Medacta USA; speaking and lecture fees from Enovis Corporation and Arthrex; and equity or stocks from Additive Implants and Aevumed. All other authors (A.E.S., J.M., M.J.G.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/11/04 00:31 MHDA- 2025/01/24 00:26 CRDT- 2024/11/03 23:53 PHST- 2024/07/17 00:00 [received] PHST- 2024/09/11 00:00 [revised] PHST- 2024/09/23 00:00 [accepted] PHST- 2025/01/24 00:26 [medline] PHST- 2024/11/04 00:31 [pubmed] PHST- 2024/11/03 23:53 [entrez] AID - S0749-8063(24)00838-7 [pii] AID - 10.1016/j.arthro.2024.09.057 [doi] PST - ppublish SO - Arthroscopy. 2025 Feb;41(2):199-206. doi: 10.1016/j.arthro.2024.09.057. Epub 2024 Oct 26. PMID- 39488821 OWN - NLM STAT- MEDLINE DCOM- 20241114 LR - 20260127 IS - 1179-1918 (Electronic) IS - 1173-2563 (Print) IS - 1173-2563 (Linking) VI - 44 IP - 11 DP - 2024 Nov TI - Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus. PG - 849-861 LID - 10.1007/s40261-024-01405-8 [doi] AB - BACKGROUND AND OBJECTIVE: IcoSema is being developed as a subcutaneous once-weekly fixed-ratio combination of the once-weekly basal insulin icodec and the once-weekly glucagon-like peptide-1 receptor agonist semaglutide. This study investigated the pharmacokinetics of icodec and semaglutide in IcoSema versus separate administration of each component in individuals with type 2 diabetes mellitus (T2DM). METHODS: In a randomised, double-blind, three-period crossover study, 31 individuals with T2DM (18-64 years, body weight 80-120 kg, glycosylated haemoglobin 6.0-8.5%) received single subcutaneous injections of IcoSema (175 U icodec, 0.5 mg semaglutide), icodec (175 U) or semaglutide (0.5 mg) with 6-9 weeks' washout. Pharmacokinetic blood samples were drawn up to 840 h post-dose. RESULTS: Icodec pharmacokinetics were unaffected by combining icodec with semaglutide. The 90% confidence interval (CI) of IcoSema/icodec was within 0.80-1.25 for total exposure (area under the curve from zero to last quantifiable observation; AUC(0-t): ratio [90% CI] 1.06 [1.01; 1.12]) and maximum concentration (C(max)): 1.12 [1.06; 1.18]. Semaglutide AUC(0-t) was also unaffected by combination with icodec (IcoSema/semaglutide 1.11 [1.05; 1.17]). However, semaglutide C(max) was higher for IcoSema versus semaglutide alone (IcoSema/semaglutide 1.99 [1.84; 2.15]) and occurred earlier for IcoSema (12 versus 84 h). Results of in vitro albumin binding studies and animal pharmacokinetic studies supported that the change in semaglutide absorption pharmacokinetics in IcoSema is owing to competition for albumin binding locally at the injection site with icodec outcompeting semaglutide. IcoSema, icodec and semaglutide were well-tolerated, although more gastrointestinal related adverse events occurred with IcoSema versus icodec or semaglutide alone. CONCLUSION: The combination of icodec and semaglutide in IcoSema leads to a higher and earlier maximum semaglutide concentration, which will guide the dose recommendations for IcoSema. CLINICAL TRIAL: ClinicalTrials.gov identifier: NCT03789578. CI - (c) 2024. The Author(s). FAU - Westergaard, Lisbet AU - Westergaard L AD - Novo Nordisk, Development, Soborg, Denmark. FAU - Alifrangis, Lene AU - Alifrangis L AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Buckley, Stephen T AU - Buckley ST AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Coester, Hans Veit AU - Coester HV AD - Profil, Neuss, Germany. FAU - Klitgaard, Thomas AU - Klitgaard T AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Kristensen, Niels R AU - Kristensen NR AD - Novo Nordisk, Development, Soborg, Denmark. FAU - Nishimura, Erica AU - Nishimura E AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Norgreen, Lea AU - Norgreen L AD - Novo Nordisk, Development, Aalborg, Denmark. FAU - Rocha, Thais M P AU - Rocha TMP AD - Novo Nordisk, Development, Soborg, Denmark. FAU - Steensgaard, Dorte B AU - Steensgaard DB AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Vegge, Andreas AU - Vegge A AD - Novo Nordisk, Research and Early Development, Malov, Denmark. FAU - Plum-Morschel, Leona AU - Plum-Morschel L AD - Profil, Neuss, Germany. leona.plum-moerschel@profil.com. LA - eng SI - ClinicalTrials.gov/NCT03789578 PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial DEP - 20241103 PL - New Zealand TA - Clin Drug Investig JT - Clinical drug investigation JID - 9504817 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Drug Combinations) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/pharmacokinetics/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Middle Aged MH - *Cross-Over Studies MH - Male MH - Adult MH - Female MH - *Hypoglycemic Agents/administration & dosage/pharmacokinetics MH - Double-Blind Method MH - Young Adult MH - Adolescent MH - Drug Combinations MH - Injections, Subcutaneous MH - Drug Administration Schedule MH - Insulin/administration & dosage/pharmacokinetics MH - Semaglutide PMC - PMC11564230 COIS- Declarations Funding This study was funded by Novo Nordisk. Conflicts of interest L.W., L.A., S.T.B., T.K., N.R.K., E.N., L.N., T.M.P.R., D.B.S. and A.V. are employees and shareholders of Novo Nordisk. H.V.C. has no conflicts of interest to disclose. L.P.-M. is an employee and shareholder of Profil. Profil received research funds from Adocia, AstraZeneca, Betagenon, Biocon, Bioton, Crinetics, Eli Lilly, Genova, Nanexa, NeoDyne, Novo Nordisk, Sanofi, Spiden and Zealand Pharma. L.P.-M. received speaker honoraria from Eli Lilly, Gan and Lee Pharmaceuticals and Novo Nordisk. Availability of data and material Individual participant data will be shared in data sets in a de-identified/anonymised format. Datasets from Novo Nordisk sponsored clinical research completed after 2001 for product indications approved in both the EU and USA will be shared. Study protocol and redacted clinical study report will be available according to Novo Nordisk data sharing commitments. The data will be available permanently after research completion and approval of product and product use in both EU and USA. There is no end date. Data will be shared with bona fide researchers submitting a research proposal requesting access to data for use as approved by the independent review board according to the independent review board charter (see novonordisk-trials.com). The data will be made available on a specialised SAS data platform. Individual data from animal studies and in vitro studies will be shared upon reasonable request. Ethics approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The clinical study was approved by an independent ethics committee (Arztekammer Nordrhein, Dusseldorf, Germany; approval ID 2018242; approval date 12 November 2018). Animal studies were performed according to the Danish Act on Experiments on Animals, the Appendix A of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS 123), and European Union Directive 2010/63. The animal studies were performed under licenses granted by the Danish national Animal Experiments Inspectorate (no. 2010/561-1786 and no. 2015-15-0201-00540). Consent to participate Informed consent was obtained from all individual participants included in the clinical study. Consent for publication Not applicable. Code availability Not applicable. Author contributions L.W., N.R.K., L.N. and T.M.P.R. contributed to clinical study data analysis, critical manuscript revision and final manuscript approval; L.A., S.T.B., T.K., E.N., D.B.S. and A.V. contributed to animal and in vitro study design, data analysis, critical manuscript revision and final manuscript approval; H.V.C. and L.P.-M. contributed to clinical study data collection, critical manuscript revision and final manuscript approval. EDAT- 2024/11/03 12:23 MHDA- 2024/11/14 18:30 PMCR- 2024/11/03 CRDT- 2024/11/03 11:04 PHST- 2024/10/14 00:00 [accepted] PHST- 2024/11/14 18:30 [medline] PHST- 2024/11/03 12:23 [pubmed] PHST- 2024/11/03 11:04 [entrez] PHST- 2024/11/03 00:00 [pmc-release] AID - 10.1007/s40261-024-01405-8 [pii] AID - 1405 [pii] AID - 10.1007/s40261-024-01405-8 [doi] PST - ppublish SO - Clin Drug Investig. 2024 Nov;44(11):849-861. doi: 10.1007/s40261-024-01405-8. Epub 2024 Nov 3. PMID- 39487881 OWN - NLM STAT- MEDLINE DCOM- 20250130 LR - 20260623 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 42 IP - 1 DP - 2025 Jan TI - Dosing Patterns of Dulaglutide and Semaglutide in Patients with Type 2 Diabetes Mellitus in France and Italy: A Retrospective Cohort Study. PG - 174-192 LID - 10.1007/s12325-024-03002-9 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease with several treatment options. Some glucagon-like peptide 1 receptor agonists (GLP-1 RAs) approved by the European Medicines Agency include dulaglutide, subcutaneous (s.c.) semaglutide, and oral semaglutide. This study examines dulaglutide and semaglutide dosing patterns for T2DM in France and Italy. METHODS: IQVIA Longitudinal Prescription Data identified adults with T2DM prescribed dulaglutide or semaglutide between August 1, 2020 and December 31, 2022. Cohort 1 (incident) and cohort 2 (prevalent) users were followed for 12 months. RESULTS: In France and Italy, 255,571 and 350,853 patients, respectively, received at least one study GLP-1 RA. Most dulaglutide-naive patients in France (62%) and approximately half in Italy (49%) started on 1.5 mg and remained on this dose for up to 12 months (France: 66% cohort 1, 88% cohort 2; Italy: 73% cohort 1, 87% cohort 2). In cohort 1, s.c. semaglutide users mostly started on 0.25 mg (France, 78%; Italy, 61%). At 12 months, s.c. semaglutide 1.0 mg was most prescribed (France: 58% cohort 1, 75% cohort 2; Italy: 59% cohort 2), with cohort 1 in Italy mostly receiving 0.5 mg (57%). Most oral semaglutide users in Italy started on 3.0 mg (78% cohort 1; 68% cohort 2), which was increased to 7.0 mg (62% cohort 1) and 14.0 mg (48% cohort 2) at 12 months. CONCLUSIONS: GLP-1 RA dosing patterns, although similar between France and Italy, were heterogeneous over time. As oral semaglutide and higher dulaglutide doses are recent to the market, additional real-world evidence is required to evaluate utilization patterns. Graphical abstract available for this article. CI - (c) 2024. The Author(s). FAU - Khare, Swarna AU - Khare S AD - Eli Lilly and Company, 8 Arlington Square West, Bracknell, RG12 1PU, UK. FAU - Osumili, Beatrice AU - Osumili B AUID- ORCID: 0000-0002-5862-9325 AD - Eli Lilly and Company, Indianapolis, IN, USA. osumili_beatrice@lilly.com. FAU - Debackere, Nele AU - Debackere N AD - Eli Lilly and Company, Brussels, Belgium. FAU - Keapoletswe, Karabo AU - Keapoletswe K AD - IQVIA Inc., London, UK. FAU - Falato, Serena AU - Falato S AD - IQVIA Inc., Milan, Italy. FAU - Raoul, Thomas AU - Raoul T AD - IQVIA Inc., Paris, France. FAU - Coles, Briana AU - Coles B AD - IQVIA Inc., London, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241102 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Recombinant Fusion Proteins/administration & dosage MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage MH - France MH - Italy MH - Retrospective Studies MH - Aged MH - *Immunoglobulin Fc Fragments/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Adult MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11782337 OTO - NOTNLM OT - Dulaglutide OT - Observational study OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declarations. Conflict of Interest: Swarna Khare, Beatrice Osumili, and Nele Debackere are employees and shareholders of Eli Lilly and Company. Briana Coles, Karabo Keapoletswe, Serena Falato, and Thomas Raoul are employees of IQVIA, which was contracted by Eli Lilly and Company to conduct the study. Briana Coles is the Vice Chair of the trial steering committee for the United Kingdom Early Detection Initiative (UK-EDI). Ethical Approval: The authors had permission to access and use the data from both the IQVIA LRx databases, and ethical approval was not required for secondary use of the data. This study was conducted in accordance with all relevant regulatory requirements, including, where applicable, the Declaration of Helsinki (and its amendments) and the Guidelines for Good Pharmacoepidemiology Practices (ISPE). EDAT- 2024/11/03 00:06 MHDA- 2025/01/30 18:21 PMCR- 2024/11/02 CRDT- 2024/11/02 12:14 PHST- 2024/07/08 00:00 [received] PHST- 2024/09/16 00:00 [accepted] PHST- 2025/01/30 18:21 [medline] PHST- 2024/11/03 00:06 [pubmed] PHST- 2024/11/02 12:14 [entrez] PHST- 2024/11/02 00:00 [pmc-release] AID - 10.1007/s12325-024-03002-9 [pii] AID - 3002 [pii] AID - 10.1007/s12325-024-03002-9 [doi] PST - ppublish SO - Adv Ther. 2025 Jan;42(1):174-192. doi: 10.1007/s12325-024-03002-9. Epub 2024 Nov 2. PMID- 39486172 OWN - NLM STAT- MEDLINE DCOM- 20241207 LR - 20250103 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 143 IP - Pt 3 DP - 2024 Dec 25 TI - Neuroprotective effects of GLP-1 receptor agonists in neurodegenerative Disorders: A Large-Scale Propensity-Matched cohort study. PG - 113537 LID - S1567-5769(24)02059-9 [pii] LID - 10.1016/j.intimp.2024.113537 [doi] AB - BACKGROUND: GLP-1 receptor agonists, traditionally used for treating type 2 diabetes mellitus and obesity, have demonstrated anti-inflammatory properties. However, their potential neuroprotective effects in neurodegenerative disorders remain unclear. OBJECTIVE: To evaluate the impact of GLP-1 receptor agonists on the risk of developing various neurodegenerative conditions in obese patients. METHODS: This comprehensive retrospective cohort study analyzed data from 5,307,845 obese adult patients across 73 healthcare organizations in 17 countries. Propensity score matching was performed, resulting in 102,935 patients in each cohort. We compared the risk of developing neurodegenerative disorders between obese patients receiving GLP-1 receptor agonist therapy and those who were not. RESULTS: Obese patients treated with GLP-1 receptor agonists showed significantly lower risks of developing Alzheimer's disease (RR = 0.627, 95 %CI = 0.481-0.817), Lewy body dementia (RR = 0.590, 95 %CI = 0.462-0.753), and vascular dementia (RR = 0.438, 95 %CI = 0.327-0.588). The risk reduction for Parkinson's disease was not statistically significant overall (RR = 0.784, 95 %CI = 0.580-1.058) but was significant for semaglutide users (RR = 0.574, 95 %CI = 0.369-0.893). Semaglutide consistently showed the most pronounced protective effects across all disorders. Additionally, a significant reduction in all-cause mortality was observed (HR = 0.525, 95 %CI = 0.493-0.558). CONCLUSION: This study provides evidence that the effects of GLP-1 receptor agonists may extend beyond their known metabolic and cardioprotective benefits to include neuroprotection, associated with a decreased risk of developing various neurodegenerative disorders. These findings suggest the potential for expanding the therapeutic applications of GLP-1 receptor agonists to improve neurocognitive outcomes. Further research is warranted to elucidate the mechanisms underlying these neuroprotective effects and to explore their clinical applications in neurodegenerative disease prevention and treatment. CI - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Siddeeque, Nabeela AU - Siddeeque N AD - Tulane University School of Medicine, New Orleans, LA, 70112, USA. FAU - Hussein, Mohammad H AU - Hussein MH AD - Ochsner Clinic Foundation, New Orleans, LA 70112, USA. FAU - Abdelmaksoud, Ahmed AU - Abdelmaksoud A AD - Department of Internal Medicine, University of California, Riverside, CA 92521, USA. FAU - Bishop, Julia AU - Bishop J AD - Tulane University School of Medicine, New Orleans, LA, 70112, USA. FAU - Attia, Abdallah S AU - Attia AS AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA. FAU - Elshazli, Rami M AU - Elshazli RM AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA; Biochemistry and Molecular Genetic Unit, Department of Basic Sciences, Faculty of Physical Therapy, Horus University - Egypt, New Damietta 34517, Egypt; Department of Biological Sciences, Faculty of Science, New Mansoura University, New Mansoura City 35742, Egypt. FAU - Fawzy, Manal S AU - Fawzy MS AD - Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia; Center for Health Research, Northern Border University, Arar 1321, Saudi Arabia. FAU - Toraih, Eman A AU - Toraih EA AD - Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA; Medical Genetics Unit, Department of Histology and Cell Biology, Suez Canal University, Ismailia 41522, Egypt. Electronic address: etoraih@tulane.edu. LA - eng PT - Journal Article DEP - 20241031 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Neuroprotective Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Neurodegenerative Diseases/drug therapy MH - Male MH - *Neuroprotective Agents/therapeutic use/pharmacology MH - Female MH - Retrospective Studies MH - Middle Aged MH - Aged MH - Obesity/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy MH - Cohort Studies MH - Propensity Score MH - Adult MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Alzheimer's disease OT - GLP-1 receptor agonists OT - Neurodegenerative disorders OT - Neuroprotection OT - Obesity OT - Parkinson's disease COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/11/02 23:13 MHDA- 2024/12/07 14:47 CRDT- 2024/11/01 19:04 PHST- 2024/09/04 00:00 [received] PHST- 2024/10/27 00:00 [revised] PHST- 2024/10/28 00:00 [accepted] PHST- 2024/12/07 14:47 [medline] PHST- 2024/11/02 23:13 [pubmed] PHST- 2024/11/01 19:04 [entrez] AID - S1567-5769(24)02059-9 [pii] AID - 10.1016/j.intimp.2024.113537 [doi] PST - ppublish SO - Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113537. doi: 10.1016/j.intimp.2024.113537. Epub 2024 Oct 31. PMID- 39471057 OWN - NLM STAT- MEDLINE DCOM- 20241112 LR - 20250507 IS - 1936-086X (Electronic) IS - 1936-0851 (Linking) VI - 18 IP - 45 DP - 2024 Nov 12 TI - Engineering Supramolecular Nanofiber Depots from a Glucagon-Like Peptide-1 Therapeutic. PG - 31274-31285 LID - 10.1021/acsnano.4c10248 [doi] AB - Diabetes and obesity have emerged as major global health concerns. Glucagon-like peptide-1 (GLP-1), a natural incretin hormone, stimulates insulin production and suppresses glucagon secretion to stabilize and reduce blood glucose levels and control appetite. The therapeutic use of GLP-1 receptor agonists (e.g., semaglutide) has transformed the standard of care in recent years for treating type 2 diabetes and reversing obesity. The native GLP-1 sequence has a very short half-life, and therapeutic advances have come from molecular engineering to alter the pharmacokinetic profile of synthetic GLP-1 receptor agonists to enable once-weekly administration, reduce the frequency of injection, and improve adherence. Efforts to further extend this profile would offer additional convenience or enable entirely different treatment modalities. Here, an injectable GLP-1 receptor agonist depot is engineered through integration of a prosthetic self-assembling peptide motif to enable supramolecular nanofiber formation and hydrogelation. This supramolecular GLP-1 receptor agonistic (PA-GLP1) offers sustained release in vitro for multiple weeks, supporting long-lasting therapy. Moreover, in a rat model of type 2 diabetes, a single injection of the supramolecular PA-GLP1 formulation achieved sustained serum concentrations for at least 40 days, with an overall reduction in blood glucose levels and reduced weight gain, comparing favorably to daily injections of semaglutide. The general and modular approach is also extensible to other next-generation peptide therapies. Accordingly, the formation of supramolecular nanofiber depots offers a more convenient and long-lasting therapeutic option to manage diabetes and treat metabolic disorders. FAU - Chen, Weike AU - Chen W AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Xian, Sijie AU - Xian S AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Webber, Bernice AU - Webber B AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - DeWolf, Emily L AU - DeWolf EL AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Schmidt, Connor R AU - Schmidt CR AUID- ORCID: 0000-0002-6514-8757 AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Kilmer, Rory AU - Kilmer R AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Liu, Dongping AU - Liu D AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Power, Elizabeth M AU - Power EM AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. FAU - Webber, Matthew J AU - Webber MJ AUID- ORCID: 0000-0003-3111-6228 AD - Department of Chemical & Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana 46556, United States. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20241029 PL - United States TA - ACS Nano JT - ACS nano JID - 101313589 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - *Glucagon-Like Peptide 1/chemistry/metabolism MH - *Nanofibers/chemistry MH - Rats MH - *Glucagon-Like Peptide-1 Receptor/metabolism/chemistry MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - Male MH - Hypoglycemic Agents/chemistry/administration & dosage/pharmacology/pharmacokinetics MH - Rats, Sprague-Dawley MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - drug delivery OT - hydrogels OT - nanotechnology OT - self-assembly OT - supramolecular chemistry EDAT- 2024/10/29 18:22 MHDA- 2024/11/13 13:55 CRDT- 2024/10/29 12:43 PHST- 2024/11/13 13:55 [medline] PHST- 2024/10/29 18:22 [pubmed] PHST- 2024/10/29 12:43 [entrez] AID - 10.1021/acsnano.4c10248 [doi] PST - ppublish SO - ACS Nano. 2024 Nov 12;18(45):31274-31285. doi: 10.1021/acsnano.4c10248. Epub 2024 Oct 29. PMID- 39455729 OWN - NLM STAT- MEDLINE DCOM- 20250122 LR - 20261010 IS - 1546-170X (Electronic) IS - 1078-8956 (Linking) VI - 31 IP - 1 DP - 2025 Jan TI - Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial. PG - 278-285 LID - 10.1038/s41591-024-03327-6 [doi] AB - Semaglutide reduces albuminuria and the risk of kidney disease progression in patients with type 2 diabetes and chronic kidney disease (CKD). We conducted a randomized placebo-controlled double-blind clinical trial in adults with CKD (estimated glomerular filtration rate (eGFR) >/=25 ml min(-1) 1.73 m(-)(2) and urine albumin-to-creatinine ratio (UACR) >/=30 and <3,500 mg g(-1)) and body mass index >/=27 kg m(-)(2). Participants were randomized to semaglutide 2.4 mg per week or placebo. The primary endpoint was percentage change from baseline in UACR at week 24. Safety was monitored throughout. Overall, 125 participants were screened, of whom 101 were randomized to semaglutide (n = 51) or placebo (n = 50). Mean age was 55.8 (s.d. 12) years; 40 participants (39.6%) were female; median UACR was 251 mg g(-1) (interquartile range 100, 584); mean eGFR was 65.0 (s.d. 25) ml min(-1) 1.73 m(-)(2); and mean body mass index was 36.2 (s.d. 5.6) kg m(-)(2). Chronic glomerulonephritis (n = 25) and hypertensive CKD (n = 27) were the most common CKD etiologies. Treatment for 24 weeks with semaglutide compared to placebo reduced UACR by -52.1% (95% confidence interval -65.5, -33.4; P < 0.0001). Gastrointestinal adverse events were more often reported with semaglutide (n = 30) than with placebo (n = 15). Semaglutide treatment for 24 weeks resulted in a clinically meaningful reduction in albuminuria in patients with overweight/obesity and non-diabetic CKD. ClinicalTrials.gov registration: NCT04889183 . CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature America, Inc. FAU - Apperloo, Ellen M AU - Apperloo EM AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Gorriz, Jose L AU - Gorriz JL AD - Department of Nephrology, University Clinical Hospital, INCLIVA, University of Valencia, Valencia, Spain. FAU - Soler, Maria Jose AU - Soler MJ AD - Department of Nephrology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, Barcelona, Spain. FAU - Cigarran Guldris, Secundino AU - Cigarran Guldris S AUID- ORCID: 0000-0001-9043-992X AD - Nephrology Service Hospital Ribera-Polusa Lugo, Lugo, Spain. FAU - Cruzado, Josep M AU - Cruzado JM AUID- ORCID: 0000-0003-1388-8558 AD - Department of Nephrology, Hospital Universitari Bellvitge, Bellvitge Biomedical Research Institute, University of Barcelona, Barcelona, Spain. FAU - Puchades, Maria Jesus AU - Puchades MJ AD - Department of Nephrology, University Clinical Hospital, INCLIVA, University of Valencia, Valencia, Spain. FAU - Lopez-Martinez, Marina AU - Lopez-Martinez M AD - Department of Nephrology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, Barcelona, Spain. FAU - Waanders, Femke AU - Waanders F AUID- ORCID: 0000-0003-4417-7732 AD - Department of Internal Medicine, Isala, Zwolle, The Netherlands. FAU - Laverman, Gozewijn D AU - Laverman GD AUID- ORCID: 0000-0002-8716-7115 AD - Department of Internal Medicine, ZiekenhuisGroep Twente, Almelo, The Netherlands. FAU - van der Aart-van der Beek, Annemarie AU - van der Aart-van der Beek A AD - Department of Internal Medicine, Martini Hospital, Groningen, The Netherlands. FAU - Hoogenberg, Klaas AU - Hoogenberg K AD - Department of Internal Medicine, Martini Hospital, Groningen, The Netherlands. FAU - van Beek, Andre P AU - van Beek AP AUID- ORCID: 0000-0002-0335-8177 AD - Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Verhave, Jacobien AU - Verhave J AD - Department Internal Medicine, Rijnstate Ziekenhuis, Arnhem, The Netherlands. FAU - Ahmed, Sofia B AU - Ahmed SB AUID- ORCID: 0000-0003-3000-2229 AD - Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada. AD - Women and Children's Health Research Institute, University of Alberta, Edmonton, AB, Canada. FAU - Schmieder, Roland E AU - Schmieder RE AUID- ORCID: 0000-0003-2356-5883 AD - Department of Nephrology and Hypertension, University Hospital Erlangen Friedrich-Alexander University Erlangen-Nurnberg (FAU), Erlangen, Germany. FAU - Wanner, Christoph AU - Wanner C AUID- ORCID: 0000-0001-9507-5301 AD - Division of Nephrology, Department of Medicine, University Hospital Wurzburg, Wurzburg, Germany. FAU - Cherney, David Z I AU - Cherney DZI AUID- ORCID: 0000-0003-4164-0429 AD - Division of Nephrology, Department of Medicine, Toronto General Hospital, University of Toronto, Toronto, ON, Canada. FAU - Jongs, Niels AU - Jongs N AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AUID- ORCID: 0000-0002-3126-3730 AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. h.j.lambers.heerspink@umcg.nl. LA - eng SI - ClinicalTrials.gov/NCT04889183 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20241025 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Female MH - Male MH - *Renal Insufficiency, Chronic/drug therapy/complications/physiopathology MH - Middle Aged MH - Double-Blind Method MH - *Obesity/drug therapy/complications MH - *Overweight/drug therapy/complications MH - Glomerular Filtration Rate/drug effects MH - Albuminuria/drug therapy MH - Aged MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Body Mass Index MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- Competing interests: E.M., F.W., J.M.C., M.L.-M., J.V., K.H. and A.v.d.A. report no conflicts of interest. J.L.G. declares funding to conduct clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim and Novo Nordisk (all to the INCLIVA Research Institute); consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim and Novo Nordisk; and payment of honoraria for lectures from AstraZeneca, Novo Nordisk, Bayer, Menarini, Boehringer Ingelheim and Eli Lilly. N.J. received travel support from AstraZeneca. S.C.G. declares funding to conduct clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim and Novo Nordisk (all to the FIDES Research Foundation) and payment of honoraria for lectures from AstraZeneca, Novo Nordisk, Baxter, Chiesi, ChemoCentrix, Clarion and Boehringer Ingelheim. M.J.P. received board speaker fees and travel expenses from AstraZeneca, NovoNordisk, Boehringer Ingelheim, Eli Lilly, Bayer and Menarini. G.D.L. received lecture fees from Sanofi, AstraZeneca and Janssen and has served as a consultant for AbbVie, Sanofi, Novo Nordisk, AstraZeneca, Boehringer Ingelheim and Merck Sharp & Dohme. A.v.B. declares being contracted via the University of Groningen (no personal payment) to undertake consultancy for Novo Nordisk, Eli Lilly and Boehringer Ingelheim. D.Z.I.C. has received honoraria from Boehringer Ingelheim, Eli Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, AbbVie, Janssen, Bayer, Prometic, Bristol Myers Squibb, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene and Novo Nordisk and has received operational funding for clinical trials from Boehringer Ingelheim, Eli Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo Nordisk. S.B.A. reports no conflicts of interest. She receives research support from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada. R.E.S. received grants to the institution from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim and NovoNordisk and speaker and advisor honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Servier and TAD. C.W. has received grants and served on steering committees for Boehringer Ingelheim; served on advisory boards for Boehringer Ingelheim, Merck Sharp & Dohme and Bayer; and received lecture fees from Boehringer Ingelheim, Eli Lilly, AstraZeneca, Merck Sharp & Dohme, Novo Nordisk and Bayer. H.J.L.H. is a consultant for AstraZeneca, Alexion, Bayer, Boehringer Ingelheim, CSL-Behring, DIMERIX, Eli Lilly, Gilead, Janssen, Novartis, Novo Nordisk, Roche, Travere Pharmaceuticals and VIFOR Pharma. He received research support through his institution from AstraZeneca, Boehringer Ingelheim, Janssen and Novo Nordisk. He received lecture fees from AstraZeneca, Bayer and Novo Nordisk. EDAT- 2024/10/26 19:24 MHDA- 2025/01/22 06:27 CRDT- 2024/10/25 23:41 PHST- 2024/09/03 00:00 [received] PHST- 2024/09/30 00:00 [accepted] PHST- 2025/01/22 06:27 [medline] PHST- 2024/10/26 19:24 [pubmed] PHST- 2024/10/25 23:41 [entrez] AID - 10.1038/s41591-024-03327-6 [pii] AID - 10.1038/s41591-024-03327-6 [doi] PST - ppublish SO - Nat Med. 2025 Jan;31(1):278-285. doi: 10.1038/s41591-024-03327-6. Epub 2024 Oct 25. PMID- 39445596 OWN - NLM STAT- MEDLINE DCOM- 20241224 LR - 20260414 IS - 1552-5279 (Electronic) IS - 1552-5260 (Print) IS - 1552-5260 (Linking) VI - 20 IP - 12 DP - 2024 Dec TI - Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. PG - 8661-8672 LID - 10.1002/alz.14313 [doi] AB - INTRODUCTION: Emerging preclinical evidence suggests that semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration and neuroinflammation. However, real-world evidence for its ability to protect against Alzheimer's disease (AD) is lacking. METHODS: We conducted emulation target trials based on a nationwide database of electronic health records (EHRs) of 116 million US patients. Seven target trials were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide with seven other antidiabetic medications. First-ever diagnosis of AD occurred within a 3-year follow-up period and was examined using Cox proportional hazards and Kaplan-Meier survival analyses. RESULTS: Semaglutide was associated with significantly reduced risk for first-time AD diagnosis, most strongly compared with insulin (hazard ratio [HR], 0.33 [95% CI: 0.21 to 0.51]) and most weakly compared with other GLP-1RAs (HR, 0.59 [95% CI: 0.37 to 0.95]). Similar results were seen across obesity status, gender, and age groups. DISCUSSION: These findings support further studies to assess semaglutide's potential in preventing AD. HIGHLIGHTS: Semaglutide was associated with 40% to 70% reduced risks of first-time AD diagnosis in T2DM patients compared to other antidiabetic medications, including other GLP-1RAs. Semaglutide was associated with significantly lower AD-related medication prescriptions. Similar reductions were seen across obesity status, gender, and age groups. Our findings provide real-world evidence supporting the potential clinical benefits of semaglutide in mitigating AD initiation and development in patients with T2DM. These findings support further clinical trials to assess semaglutide's potential in delaying or preventing AD. CI - (c) 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. FAU - Wang, William AU - Wang W AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Wang, QuangQiu AU - Wang Q AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Qi, Xin AU - Qi X AD - Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Gurney, Mark AU - Gurney M AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Perry, George AU - Perry G AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. AD - Department of Neuroscience, Development and Regenerative Biology, College of Sciences, The University of Texas at San Antonio, San Antonio, Texas, USA. FAU - Volkow, Nora D AU - Volkow ND AD - National Institute on Drug Abuse, National Institutes of Health, Maryland, USA. FAU - Davis, Pamela B AU - Davis PB AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. FAU - Kaelber, David C AU - Kaelber DC AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Ohio, USA. FAU - Xu, Rong AU - Xu R AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. LA - eng GR - R01 AG057557/AG/NIA NIH HHS/United States GR - R01 AG076051/AG/NIA NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States GR - RF1 AG074346/AG/NIA NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States GR - AG057557 AG061388 AG062272 AG076649/AG/NIA NIH HHS/United States GR - R01 AG065240/AG/NIA NIH HHS/United States GR - UM1 TR004528/TR/NCATS NIH HHS/United States GR - RF1 AG076649/AG/NIA NIH HHS/United States GR - TR004528/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20241024 PL - United States TA - Alzheimers Dement JT - Alzheimer's & dementia : the journal of the Alzheimer's Association JID - 101231978 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Alzheimer Disease/drug therapy MH - Female MH - Male MH - Aged MH - *Hypoglycemic Agents/therapeutic use MH - United States MH - Middle Aged MH - Aged, 80 and over MH - Semaglutide PMC - PMC11667504 OTO - NOTNLM OT - Alzheimer's disease OT - emulation target trial OT - patient electronic health records OT - prevention OT - real-world data OT - semaglutide OT - type 2 diabetes COIS- All authors declare no competing interests. Author disclosures are available in the Supporting Information. EDAT- 2024/10/24 16:21 MHDA- 2024/12/24 12:21 PMCR- 2024/10/24 CRDT- 2024/10/24 07:03 PHST- 2024/09/10 00:00 [revised] PHST- 2024/07/29 00:00 [received] PHST- 2024/09/12 00:00 [accepted] PHST- 2024/12/24 12:21 [medline] PHST- 2024/10/24 16:21 [pubmed] PHST- 2024/10/24 07:03 [entrez] PHST- 2024/10/24 00:00 [pmc-release] AID - ALZ14313 [pii] AID - 10.1002/alz.14313 [doi] PST - ppublish SO - Alzheimers Dement. 2024 Dec;20(12):8661-8672. doi: 10.1002/alz.14313. Epub 2024 Oct 24. PMID- 39442257 OWN - NLM STAT- MEDLINE DCOM- 20241124 LR - 20260627 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 38 IP - 12 DP - 2024 Dec TI - REAL life study of subcutaneous SEMaglutide in patients with type 2 diabetes in SPain: Ambispective, multicenter clinical study. Results in the GLP1-experienced cohort. PG - 108874 LID - S1056-8727(24)00200-9 [pii] LID - 10.1016/j.jdiacomp.2024.108874 [doi] AB - OBJECTIVE: To evaluate the efficacy of switching to once-weekly subcutaneous semaglutide in patients with type 2 diabetes mellitus (T2DM) who were previously treated with other glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in a real-world setting in Spain. METHODS: The REAL Life study of SEMaglutide in Patients with Type 2 diabetes in Spain (REALSEM-SP) was conducted in four endocrinology departments in Madrid, Spain. Adult patients with T2DM who were prescribed once-weekly (OW) subcutaneous semaglutide and had been previously treated with other GLP-1 RAs were included. Baseline characteristics, including demographic, anthropometric, and laboratory variables, were recorded at baseline and at 6 +/- 3 and 12 +/- 3 months of follow-up. The primary outcome was the change in HbA(1c) at 12 +/- 3 months of follow-up, with secondary outcomes including changes in weight, BMI, and other glycemic parameters. RESULTS: A total of 267 patients were included in the analysis, with a mean age of 61.6 years and a mean T2DM duration of 11.3 years. The majority of patients had grade 1 or 2 obesity at baseline. Switching to OW-semaglutide was associated with a significant reduction in HbA(1c) from baseline to 13 months (-0.35 % +/- 0.81). Patients who reached the 1.0 mg OW-dose showed a significant reduction in HbA(1c) compared to those on the /=18 years without previous stroke or acute myocardial infarction (AMI) were included. Cox regression was utilized to investigate MACE risk factors and compare MACE risk reduction associated with early use of MACE-preventive GLMs. RESULTS: A total of 19 685 subjects were included, with 5431 having MACE, including 4453 strokes, 977 AMI, and 1 death. There were 11 123 subjects with good baseline GC. Subjects with good baseline GC had 0.837 (confidence interval [CI]: 0.782-0.895) times lower MACE risk than their counterpart. Subjects with a single MACE-preventive GLM at baseline with continuous use >365 days showed a decreased MACE hazard ratio (0.681; CI: 0.635-0.731). Among all MACE-preventive GLMs, semaglutide provided a more significant MACE-preventive effect. CONCLUSIONS: This study identified that GLM, early GC, and HVS are MACE determinants among patients with T2DM. Novel GLM, adequate GC, and reduction of HVS can benefit MACE outcomes. CI - (c) 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Hsu, Haowen AU - Hsu H AUID- ORCID: 0009-0007-7422-9544 AD - Department of Clinical Pharmacy, School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. AD - Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, USA. FAU - Kocis, Paul Thomas AU - Kocis PT AD - Department of Pharmacy, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. AD - Department of Pharmacology, College of Medicine, Penn State University, Hershey, Pennsylvania, USA. FAU - Pichardo-Lowden, Ariana AU - Pichardo-Lowden A AD - Department of Medicine, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, USA. FAU - Hwang, Wenke AU - Hwang W AD - Department of Public Health Sciences, College of Medicine, Penn State University, Hershey, Pennsylvania, USA. LA - eng GR - UL1 TR002014/TR/NCATS NIH HHS/United States GR - Patient-Centered Outcomes Research Institute through PCORnet Clinical Research Network Infrastructure 1259/ PT - Journal Article PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Female MH - Retrospective Studies MH - Male MH - *Electronic Health Records/statistics & numerical data MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/prevention & control/etiology/mortality MH - *Glycemic Control MH - Aged MH - *Blood Glucose/analysis/metabolism MH - Longitudinal Studies MH - Glycated Hemoglobin/analysis/metabolism MH - Risk Factors PMC - PMC11492400 OTO - NOTNLM OT - glucose-lowering medications OT - glycemic control OT - major adverse cardiovascular events OT - primary prevention OT - type 2 diabetes COIS- The authors declare no conflicts of interest. EDAT- 2024/10/21 16:17 MHDA- 2024/10/21 16:18 PMCR- 2024/10/21 CRDT- 2024/10/21 09:14 PHST- 2024/06/16 00:00 [revised] PHST- 2024/04/20 00:00 [received] PHST- 2024/06/30 00:00 [accepted] PHST- 2024/10/21 16:18 [medline] PHST- 2024/10/21 16:17 [pubmed] PHST- 2024/10/21 09:14 [entrez] PHST- 2024/10/21 00:00 [pmc-release] AID - JDB13604 [pii] AID - 10.1111/1753-0407.13604 [doi] PST - ppublish SO - J Diabetes. 2024 Oct;16(10):e13604. doi: 10.1111/1753-0407.13604. PMID- 39429118 OWN - NLM STAT- MEDLINE DCOM- 20241118 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 17 IP - 11 DP - 2024 Nov TI - Semaglutide and smoking cessation in individuals with type 2 diabetes mellitus: there is no smoke without fire! PG - 1009-1012 LID - 10.1080/17512433.2024.2418398 [doi] AB - Tobacco use represents the leading preventable risk factor for premature deaths worldwide. A meta-analysis of 74 epidemiological studies, including 3.2 million individuals with type 2 diabetes mellitus (T2DM) from 33 countries, reported a pooled prevalence of smoking of 20.8% among individuals with T2DM. Cigarette smoking further aggravates existing deleterious vascular effects of T2DM. Namely, chronic hyperglycemia and exposure to cigarette smoke cause additive injurious effect on the endothelium, leading to an acceleration of vascular complications seen in persons with T2DM and tobacco use disorders (TUD). In a recent study, Wang and colleagues found that semaglutide use was associated with a significantly lower risk for medical encounters for TUD, when compared to other antidiabetic drug classes; indeed, this effect was strongest compared with insulins and weakest compared with other glucagon-like peptide-1 receptor agonists. Semaglutide was associated with reduced smoking cessation medication prescriptions and counseling. Similar findings were observed irrespective of the presence of obesity. Therefore, semaglutide use might be useful in terms of smoking cessation among individuals with T2DM, thus offering an additional benefit for this constantly growing population. However, those interesting findings should be confirmed through dedicated, large-scale randomized controlled trials. FAU - Popovic, Djordje S AU - Popovic DS AD - Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Centre of Vojvodina, Medical Faculty, University of Novi Sad, Novi Sad, Serbia. FAU - Patoulias, Dimitrios AU - Patoulias D AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AUID- ORCID: 0000-0002-5853-1352 AD - Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Karakasis, Paschalis AU - Karakasis P AUID- ORCID: 0000-0002-3561-5713 AD - Second Department of Cardiology, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece. FAU - Ruza, Ieva AU - Ruza I AUID- ORCID: 0000-0002-3998-3548 AD - Department of Endocrinology, Riga Eastern Clinical University Hospital, Riga, Latvia. FAU - Papanas, Nikolaos AU - Papanas N AD - Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. LA - eng PT - Journal Article DEP - 20241021 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/pharmacology/administration & dosage/adverse effects MH - *Hypoglycemic Agents/pharmacology/administration & dosage/adverse effects MH - Risk Factors MH - Smoking/adverse effects/epidemiology MH - *Smoking Cessation/methods MH - Tobacco Use Disorder/complications MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - semaglutide OT - smoking cessation OT - tobacco use disorders OT - type 2 diabetes mellitus EDAT- 2024/10/21 10:51 MHDA- 2024/11/18 06:22 CRDT- 2024/10/21 04:54 PHST- 2024/11/18 06:22 [medline] PHST- 2024/10/21 10:51 [pubmed] PHST- 2024/10/21 04:54 [entrez] AID - 10.1080/17512433.2024.2418398 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2024 Nov;17(11):1009-1012. doi: 10.1080/17512433.2024.2418398. Epub 2024 Oct 21. PMID- 39424598 OWN - NLM STAT- MEDLINE DCOM- 20250111 LR - 20260611 IS - 2055-6845 (Electronic) IS - 2055-6837 (Print) VI - 10 IP - 8 DP - 2025 Jan 11 TI - Design and baseline characteristics of the STRIDE trial: evaluating semaglutide in people with symptomatic peripheral artery disease and type 2 diabetes. PG - 728-737 LID - 10.1093/ehjcvp/pvae071 [doi] AB - BACKGROUND: People with lower extremity peripheral artery disease (PAD) suffer from a high burden of symptoms and significant functional impairment. There are few therapies that improve function and reduce symptoms in this population. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to improve glycaemic control, reduce body weight, and reduce the risk of major adverse cardiovascular events in people with atherosclerotic cardiovascular disease and type 2 diabetes (T2D). METHODS AND RESULTS: STRIDE (NCT04560998) is a randomized, placebo-controlled, double-blind phase 3b trial evaluating 1 mg once-weekly subcutaneous semaglutide (GLP-1 RA) vs. placebo, in people with symptomatic PAD (Fontaine IIa claudication) and T2D. Eligible participants were >/=18 years, had haemodynamically stable PAD, had no planned intervention, and were not receiving a GLP-1 RA. The primary endpoint is change in maximum walking distance on a constant-load treadmill (CLT). Secondary endpoints include quality of life and cardiometabolic assessments. A total of 792 participants were randomized in 20 countries. Participants' median age was 68 and median T2D duration 12 years. Risk factors included 25.6% current smokers, 87.9% with hypertension, and 42.7% with coronary heart disease. The mean BMI was 29.6 kg/m2 and the mean HbA1C was 7.3%. Participants exhibited baseline functional impairment with a median maximum walking distance of 186 m on a CLT. CONCLUSION: STRIDE has enrolled participants with symptomatic PAD and T2D, frequent risk factors and comorbidities, and functional impairment. The trial will provide evidence for the functional outcomes with semaglutide in people with PAD and T2D. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Bonaca, Marc P AU - Bonaca MP AUID- ORCID: 0000-0002-9860-3584 AD - CPC Clinical Research, Cardiovascular Division, University of Colorado School of Medicine, Aurora, CO, USA. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hansen, Yasemin AU - Hansen Y AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Houlind, Kim AU - Houlind K AUID- ORCID: 0000-0002-1600-4415 AD - Department of Vascular Surgery, Lillebaelt Hospital. AD - Department of Regional Health Research, University of Southern Denmark, Denmark. FAU - Ramesh, Chethana Kalmady AU - Ramesh CK AD - Novo Nordisk GBS India, Bangalore, India. FAU - Ludvik, Bernhard AU - Ludvik B AD - 1st Medical Department and Karl Landsteiner Institute for Obesity and Metabolic Disorders Landstrasse Clinic, Vienna, Austria. FAU - Nordanstig, Joakim AU - Nordanstig J AUID- ORCID: 0000-0002-2670-2268 AD - Institute of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden. FAU - Rasouli, Neda AU - Rasouli N AUID- ORCID: 0000-0003-1269-3580 AD - School of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado, Aurora, CO, USA. FAU - Sourij, Harald AU - Sourij H AUID- ORCID: 0000-0003-3510-9594 AD - Interdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. FAU - Verma, Subodh AU - Verma S AUID- ORCID: 0000-0002-4018-8533 AD - Division of Cardiovascular Surgery, St. Michael's Hospital, University of Toronto, Toronto, Canada. LA - eng GR - Novo Nordisk/ PT - Clinical Trial Protocol PT - Journal Article PL - England TA - Eur Heart J Cardiovasc Pharmacother JT - European heart journal. Cardiovascular pharmacotherapy JID - 101669491 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Biomarkers/blood MH - *Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood/epidemiology/physiopathology MH - Double-Blind Method MH - Exercise Tolerance/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Glucagon-Like Peptides/adverse effects/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/adverse effects/administration & dosage MH - *Incretins/adverse effects/administration & dosage MH - Injections, Subcutaneous MH - *Intermittent Claudication/drug therapy/physiopathology/diagnosis MH - *Peripheral Arterial Disease/drug therapy/diagnosis/physiopathology/epidemiology MH - Quality of Life MH - Recovery of Function MH - Risk Factors MH - Time Factors MH - Treatment Outcome MH - Walk Test MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11724141 OTO - NOTNLM OT - GLP1 agonist OT - Maximal walking distance OT - PAD OT - Peripheral artery disease OT - Semaglutide EDAT- 2024/10/19 16:23 MHDA- 2025/01/12 04:19 PMCR- 2025/10/18 CRDT- 2024/10/18 22:23 PHST- 2024/08/06 00:00 [received] PHST- 2024/09/08 00:00 [revised] PHST- 2025/01/12 04:19 [medline] PHST- 2024/10/19 16:23 [pubmed] PHST- 2024/10/18 22:23 [entrez] PHST- 2025/10/18 00:00 [pmc-release] AID - 7826783 [pii] AID - pvae071 [pii] AID - 10.1093/ehjcvp/pvae071 [doi] PST - ppublish SO - Eur Heart J Cardiovasc Pharmacother. 2025 Jan 11;10(8):728-737. doi: 10.1093/ehjcvp/pvae071. PMID- 39421913 OWN - NLM STAT- MEDLINE DCOM- 20260922 LR - 20260923 IS - 1130-0108 (Print) IS - 1130-0108 (Linking) VI - 118 IP - 9 DP - 2026 Sep TI - Pulmonary aspiration during upper endoscopy in a patient prescribed semaglutide. PG - 532-533 LID - 10.17235/reed.2024.10844/2024 [doi] AB - The past decade has witnessed an increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) owing to robust evidence of its benefits in type 2 diabetes and obesity. However, delay gastric emptying effect of GLP-1RAs has raised concerns for risk of gastric food retention and pneumonia aspiration during upper endoscopy. There have been observation studies reporting an increased incidence of gastric food retention among patients on GLP-1RAs, especially long-acting one like semaglutide. But the association between GLP-1RAs use and pneumonia aspiration during EGD remains unclear due to lack of high-level evidence. We report a case of pulmonary aspiration during EGD in a patient prescribed semaglutide. FAU - Dong, Tao AU - Dong T AD - Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine. FAU - Wang, Lan AU - Wang L AD - Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine. FAU - Wang, Hanying AU - Wang H AD - Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine. FAU - Xiao, Jun AU - Xiao J AD - Digestive Endoscopy Center, Affiliated Hospital of Nanjing University of Chinese Medicine, China. LA - eng PT - Case Reports PT - Letter PL - Spain TA - Rev Esp Enferm Dig JT - Revista espanola de enfermedades digestivas JID - 9007566 RN - 53AXN4NNHX (Semaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - Semaglutide MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - *Pneumonia, Aspiration/etiology/diagnostic imaging EDAT- 2024/10/18 06:23 MHDA- 2026/09/22 12:41 CRDT- 2024/10/18 04:53 PHST- 2026/09/22 12:41 [medline] PHST- 2024/10/18 06:23 [pubmed] PHST- 2024/10/18 04:53 [entrez] AID - 10.17235/reed.2024.10844/2024 [doi] PST - ppublish SO - Rev Esp Enferm Dig. 2026 Sep;118(9):532-533. doi: 10.17235/reed.2024.10844/2024. PMID- 39415416 OWN - NLM STAT- MEDLINE DCOM- 20250108 LR - 20260610 IS - 1360-0443 (Electronic) IS - 0965-2140 (Print) IS - 0965-2140 (Linking) VI - 120 IP - 2 DP - 2025 Feb TI - The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis. PG - 236-250 LID - 10.1111/add.16679 [doi] AB - AIMS: This study aimed to estimate the strength of association between prescriptions of glucose-dependent insulinotropic polypeptide (GIP) and/or glucagon-like peptide-1 receptor agonists (GLP-1 RA) and the incidence of opioid overdose and alcohol intoxication in patients with opioid use disorder (OUD) and alcohol use disorder (AUD), respectively. This study also aimed to compare the strength of the GIP/GLP-1 RA and substance use-outcome association among patients with comorbid type 2 diabetes and obesity. DESIGN: A retrospective cohort study analyzing de-identified electronic health record data from the Oracle Cerner Real-World Data. SETTING: About 136 United States of America health systems, covering over 100 million patients, spanning January 2014 to September 2022. PARTICIPANTS: The study included 503 747 patients with a history of OUD and 817 309 patients with a history of AUD, aged 18 years or older. MEASUREMENTS: The exposure indicated the presence (one or more) or absence of GIP/GLP-1 RA prescriptions. The outcomes were the incidence rates of opioid overdose in the OUD cohort and alcohol intoxication in the AUD cohort. Potential confounders included comorbidities and demographic factors. FINDINGS: Patients with GIP/GLP-1 RA prescriptions demonstrated statistically significantly lower rates of opioid overdose [adjusted incidence rate ratio (aIRR) in OUD patients: 0.60; 95% confidence interval (CI) = 0.43-0.83] and alcohol intoxication (aIRR in AUD patients: 0.50; 95% CI = 0.40-0.63) compared to those without such prescriptions. When stratified by comorbid conditions, the rate of incident opioid overdose and alcohol intoxication remained similarly protective for those prescribed GIP/GLP-1 RA among patients with OUD and AUD. CONCLUSIONS: Prescriptions of glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonists appear to be associated with lower rates of opioid overdose and alcohol intoxication in patients with opioid use disorder and alcohol use disorder. The protective effects are consistent across various subgroups, including patients with comorbid type 2 diabetes and obesity. CI - (c) 2024 The Author(s). Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction. FAU - Qeadan, Fares AU - Qeadan F AUID- ORCID: 0000-0002-3376-220X AD - Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA. FAU - McCunn, Ashlie AU - McCunn A AD - Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA. FAU - Tingey, Benjamin AU - Tingey B AD - Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL, USA. LA - eng PT - Journal Article DEP - 20241016 PL - England TA - Addiction JT - Addiction (Abingdon, England) JID - 9304118 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - Adult MH - Middle Aged MH - *Diabetes Mellitus, Type 2/epidemiology/drug therapy MH - *Opioid-Related Disorders/epidemiology MH - *Alcoholism/epidemiology MH - *Gastric Inhibitory Polypeptide MH - United States/epidemiology MH - Opiate Overdose/epidemiology MH - Alcoholic Intoxication/epidemiology MH - Obesity/epidemiology MH - Comorbidity MH - Incidence MH - Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11707322 OTO - NOTNLM OT - AUD OT - GIP/GLP-1 RA OT - OUD OT - dulaglutide OT - intoxication OT - overdose OT - semaglutide COIS- None. EDAT- 2024/10/17 10:05 MHDA- 2025/01/09 04:53 PMCR- 2025/01/08 CRDT- 2024/10/17 01:04 PHST- 2023/12/30 00:00 [received] PHST- 2024/08/29 00:00 [accepted] PHST- 2025/01/09 04:53 [medline] PHST- 2024/10/17 10:05 [pubmed] PHST- 2024/10/17 01:04 [entrez] PHST- 2025/01/08 00:00 [pmc-release] AID - ADD16679 [pii] AID - 10.1111/add.16679 [doi] PST - ppublish SO - Addiction. 2025 Feb;120(2):236-250. doi: 10.1111/add.16679. Epub 2024 Oct 16. PMID- 39400314 OWN - NLM STAT- MEDLINE DCOM- 20250424 LR - 20260127 IS - 1365-2362 (Electronic) IS - 0014-2972 (Linking) VI - 55 IP - 2 DP - 2025 Feb TI - Exploring omics signature in the cardiovascular response to semaglutide: Mechanistic insights and clinical implications. PG - e14334 LID - 10.1111/eci.14334 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is a widely used drug for the treatment of type 2 diabetes that offers significant cardiovascular benefits. RESULTS: This review systematically examines the proteomic and metabolomic indicators associated with the cardiovascular effects of semaglutide. A comprehensive literature search was conducted to identify relevant studies. The review utilizes advanced analytical technologies such as mass spectrometry and nuclear magnetic resonance (NMR) to investigate the molecular mechanisms underlying the effects of semaglutide on insulin secretion, weight control, anti-inflammatory activities and lipid metabolism. These "omics" approaches offer critical insights into metabolic changes associated with cardiovascular health. However, challenges remain such as individual variability in expression, the need for comprehensive validation and the integration of these data with clinical parameters. These issues need to be addressed through further research to refine these indicators and increase their clinical utility. CONCLUSION: Future integration of proteomic and metabolomic data with artificial intelligence (AI) promises to improve prediction and monitoring of cardiovascular outcomes and may enable more accurate and effective management of cardiovascular health in patients with type 2 diabetes. This review highlights the transformative potential of integrating proteomics, metabolomics and AI to advance cardiovascular medicine and improve patient outcomes. CI - (c) 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd. FAU - Vitorino, Rui AU - Vitorino R AUID- ORCID: 0000-0003-3636-5805 AD - Department of Medical Sciences, Institute of Biomedicine iBiMED, University of Aveiro, Aveiro, Portugal. AD - Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. LA - eng GR - UIDB/04501/2020/European Union, QREN, FEDER, and COMPETE for funding Institute of Biomedicine (iBiMED)/ GR - POCI-01-0145-FEDER-007628/European Union, QREN, FEDER, and COMPETE for funding Institute of Biomedicine (iBiMED)/ GR - UIDP/00051/2020/Cardiovascular R&D Centre-UnIC@RISE/ GR - Fundacao para a Ciencia e a Tecnologia/ PT - Journal Article PT - Review DEP - 20241014 PL - England TA - Eur J Clin Invest JT - European journal of clinical investigation JID - 0245331 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Metabolomics MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Proteomics MH - *Cardiovascular Diseases/prevention & control/metabolism MH - Lipid Metabolism/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - cardiovascular diseases OT - endothelial function OT - inflammation pathways OT - lipid metabolism OT - molecular mechanisms OT - personalized medicine OT - proteomic biomarkers OT - semaglutide OT - therapeutic strategies EDAT- 2024/10/14 12:23 MHDA- 2025/01/20 22:54 CRDT- 2024/10/14 10:43 PHST- 2024/05/05 00:00 [received] PHST- 2024/10/01 00:00 [accepted] PHST- 2025/01/20 22:54 [medline] PHST- 2024/10/14 12:23 [pubmed] PHST- 2024/10/14 10:43 [entrez] AID - 10.1111/eci.14334 [doi] PST - ppublish SO - Eur J Clin Invest. 2025 Feb;55(2):e14334. doi: 10.1111/eci.14334. Epub 2024 Oct 14. PMID- 39397557 OWN - NLM STAT- MEDLINE DCOM- 20241014 LR - 20260127 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 79 IP - 10 DP - 2024 Oct TI - [New outcome studies with injectable semaglutide in different at risk populations]. PG - 676-682 AB - Injectable semaglutide at a dose of 1 mg once weekly has been shown to be the most efficacious glucagon-like peptide-1 receptor agonist when considering both the improvement in blood glucose control and the reduction in body weight in patients with type 2 diabetes (T2D). After the SUSTAIN-6 study, published in 2016, which demonstrated not only the good safety but also already the cardiovascular (CV) efficacy of semaglutide in patients with T2D and high CV risk, several large placebo-controlled randomised trials have confirmed improved prognosis with semaglutide in different at risk populations : patients with T2D and chronic kidney disease (FLOW trial), subjects with obesity and heart failure with preserved ejection fraction, with or without T2D (STEP-HFpEF trial) and people with overweight or obesity (but without T2D) and a confirmed atheromatous cardiovascular disease (SELECT trial). Studies performed in patients with obesity used a higher dose of 2.4 mg/week. These positive results, based upon major clinically relevant outcomes, extend the therapeutic possibilities with semaglutide among at high risk patients of cardiovascular and/or renal diseases. FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques et Unite de Pharmacologie clinique, CHU Liege, ULiege, Belgique. FAU - Delanaye, Pierre AU - Delanaye P AD - Service de Nephrologie, Dialyse et Transplantation, CHU Liege, Belgique. FAU - Lancellotti, Patrizio AU - Lancellotti P AD - Service de Cardiologie, CHU Liege, Belgique. LA - fre PT - English Abstract PT - Journal Article PT - Review TT - L'etude clinique du mois. Nouvelles etudes cliniques avec le semaglutide injectable dans differentes populations a risque. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Cardiovascular Diseases/prevention & control MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Obesity/drug therapy/complications MH - Treatment Outcome MH - Injections MH - Semaglutide OTO - NOTNLM OT - Cardiovascular disease OT - Chronic kidney disease OT - GLP-1 OT - Obesity OT - Semaglutide OT - Type 2 diabetes EDAT- 2024/10/14 10:17 MHDA- 2024/10/14 10:18 CRDT- 2024/10/14 04:13 PHST- 2024/10/14 10:18 [medline] PHST- 2024/10/14 10:17 [pubmed] PHST- 2024/10/14 04:13 [entrez] PST - ppublish SO - Rev Med Liege. 2024 Oct;79(10):676-682. PMID- 39396098 OWN - NLM STAT- MEDLINE DCOM- 20241231 LR - 20261010 IS - 1476-5497 (Electronic) IS - 0307-0565 (Linking) VI - 49 IP - 1 DP - 2025 Jan TI - Semaglutide effects on safety and cardiovascular outcomes in patients with overweight or obesity: a systematic review and meta-analysis. PG - 21-30 LID - 10.1038/s41366-024-01646-9 [doi] AB - BACKGROUND: Semaglutide is a GLP-1 receptor agonist that provides a reduction in glycated hemoglobin and weight. The objective was to evaluate whether the use of semaglutide, in individuals with overweight or obesity, reduces cardiovascular outcomes and adverse effects (AE). METHODS: The data bases Pubmed, Lilacs, Scielo, Scopus, Web of Science and Cochrane Library were surveyed. RESULTS: Initially, 3333 articles were found, of which 19 articles were included. An additional search included 19 studies, totaling 38 articles. Relative risk (RR) values were significant for hospitalization due to heart failure (HF) 0.24 95% CI 0.12-0.57 (n = 2; 1045 participants; I(2) = 0.18), death due to cardiovascular causes 0.83 95% CI 0.71-0.98 (n = 3; 24 084 participants; I(2) = 0.21), death from any cause 0.79 95% CI 0.70-0.89 (n = 3; 24 084 participants; I(2) = 0.07), coronary revascularization 0.76 95% CI 0.69-0.85 (n = 2;20 951 participants; I(2) = 0.41), and non-fatal myocardial infarction 0.76 95%CI 0.66-0.88 (n = 3; 24 084 participants; I(2) = 0.21), with a difference between the subgroups (p = 0.05), favoring the subcutaneous administration route. The RR of stroke was 0.65 95% CI 0.44-0.97 for patients with diabetes (n = 2; 6480 participants; I(2) = 0.66). There was no difference between the frequency of constipation and routes of administration, as well as between doses of oral semaglutide. The RR of adverse effects was only not significant for discontinuation of treatment for oral semaglutide. CONCLUSION: The use of semaglutide reduced 76% in hospitalization due to HF, 17% deaths due to cardiovascular causes, 21% deaths due to any cause, 24% non-fatal myocardial infarction, 24% coronary revascularization and 35% stroke (in patients with diabetes). The use of semaglutide was associated with a higher relative risk and frequency of most adverse effects evaluated. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Cleto, Andre Saad AU - Cleto AS AUID- ORCID: 0009-0008-7272-9083 AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. andresaad8@gmail.com. FAU - Schirlo, Joao Matheus AU - Schirlo JM AUID- ORCID: 0009-0005-2886-7700 AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Beltrame, Mayara AU - Beltrame M AUID- ORCID: 0009-0008-8359-1657 AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Gomes, Victor Hugo Oliveira AU - Gomes VHO AUID- ORCID: 0009-0008-9307-3108 AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Acras, Isabela Hellmann AU - Acras IH AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Neiverth, Guinter Sponholz AU - Neiverth GS AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Silva, Breno Bach AU - Silva BB AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Juliatto, Beatriz Moreira Salles AU - Juliatto BMS AUID- ORCID: 0000-0002-1442-5646 AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Machozeki, Janete AU - Machozeki J AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. FAU - Martins, Camila Marinelli AU - Martins CM AD - State University of Ponta Grossa, Department of Medicine, Parana, Brazil. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20241012 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/complications/drug therapy MH - *Cardiovascular Diseases/prevention & control MH - *Hypoglycemic Agents/therapeutic use MH - Overweight/complications/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Treatment Outcome MH - Semaglutide COIS- Competing interests: The authors declare no competing interests. EDAT- 2024/10/13 00:30 MHDA- 2025/01/01 12:42 CRDT- 2024/10/12 23:27 PHST- 2024/06/09 00:00 [received] PHST- 2024/09/27 00:00 [accepted] PHST- 2024/09/24 00:00 [revised] PHST- 2025/01/01 12:42 [medline] PHST- 2024/10/13 00:30 [pubmed] PHST- 2024/10/12 23:27 [entrez] AID - 10.1038/s41366-024-01646-9 [pii] AID - 10.1038/s41366-024-01646-9 [doi] PST - ppublish SO - Int J Obes (Lond). 2025 Jan;49(1):21-30. doi: 10.1038/s41366-024-01646-9. Epub 2024 Oct 12. PMID- 39367214 OWN - NLM STAT- MEDLINE DCOM- 20241014 LR - 20260127 IS - 2731-0590 (Electronic) IS - 2731-0590 (Linking) VI - 3 IP - 10 DP - 2024 Oct TI - Semaglutide may reduce cardiovascular disease and heart failure. PG - 1180 LID - 10.1038/s44161-024-00556-3 [doi] FAU - Korda, Michelle AU - Korda M AD - Nature Cardiovascular Research, . michelle.korda@nature.com. LA - eng PT - News PL - England TA - Nat Cardiovasc Res JT - Nature cardiovascular research JID - 9918284280206676 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Heart Failure/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Cardiovascular Diseases/prevention & control MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - Treatment Outcome MH - Semaglutide EDAT- 2024/10/05 11:43 MHDA- 2024/10/15 00:20 CRDT- 2024/10/04 23:33 PHST- 2024/10/15 00:20 [medline] PHST- 2024/10/05 11:43 [pubmed] PHST- 2024/10/04 23:33 [entrez] AID - 10.1038/s44161-024-00556-3 [pii] AID - 10.1038/s44161-024-00556-3 [doi] PST - ppublish SO - Nat Cardiovasc Res. 2024 Oct;3(10):1180. doi: 10.1038/s44161-024-00556-3. PMID- 39366019 OWN - NLM STAT- MEDLINE DCOM- 20250101 LR - 20260815 IS - 1547-5646 (Electronic) IS - 1547-5646 (Linking) VI - 42 IP - 1 DP - 2025 Jan 1 TI - Semaglutide exposure and its association with adverse outcomes in diabetic patients undergoing transforaminal lumbar interbody fusion for lumbar degenerative disc disease. PG - 1-8 LID - 10.3171/2024.6.SPINE24141 [doi] AB - OBJECTIVE: Semaglutide, a novel glucagon-like peptide-1 receptor agonist, has transformed the therapeutic landscape for type 2 diabetes mellitus. However, its effect on osteoclast activity and its potential to induce weight-related muscle loss raises concerns about its impact on spine surgery outcomes. As such, evaluating semaglutide's influence on transforaminal lumbar interbody fusion (TLIF) is imperative, given the procedure's reliance on successful bony fusion to prevent postoperative instability and further interventions. METHODS: Using an all-payer database (MARINER), the authors analyzed data from patients with type 2 diabetes mellitus who were 18-74 years of age and who underwent short-segment fusion (/= 1%-point HbA(1C) reduction and body weight reduction of >/= 3% or >/= 5% at EOS. Treatment satisfaction was assessed by Diabetes Treatment Satisfaction Questionnaire (DTSQ) status and change. RESULTS: Of 333 participants, 299 completed the study and 227 were on treatment at EOS. People treated with oral semaglutide experienced significantly reduced HbA(1C) by an estimated change of - 1.1%-points (95% CI - 1.27 to - 0.96; P < 0.0001) or - 12.2 mmol/mol (CI - 13.87 to - 10.47; P < 0.0001). Estimated change in body weight was - 4.8 kg (CI - 5.47 to - 4.12; P < 0.0001). At EOS, an HbA(1C) level < 7% (53 mmol/mol) was recorded in 46.3% of participants. A >/= 1%-point reduction in HbA(1C) combined with a >/= 3% reduction in body weight was observed in 36.4% of participants, and 27.1% had a >/= 1%-point reduction in HbA(1C) and a >/= 5% body weight reduction. Treatment satisfaction improved significantly during the study. No new safety concerns or cases of severe hypoglycaemia were reported. CONCLUSION: People living with T2D in the UK experienced a meaningful decrease in HbA(1C) and body weight after initiation of oral semaglutide treatment. No new safety issues were observed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04862923. Graphical plain language summary available for this article. CI - (c) 2024. The Author(s). FAU - Saravanan, Ponnusamy AU - Saravanan P AUID- ORCID: 0000-0002-9566-2626 AD - Warwick Applied Health, Warwick Medical School, University of Warwick, Coventry, UK. P.Saravanan@warwick.ac.uk. AD - Department of Diabetes, Endocrinology and Metabolism, George Eliot Hospital NHS Trust, Nuneaton, UK. P.Saravanan@warwick.ac.uk. AD - Warwick Centre for Global Health, University of Warwick, Coventry, UK. P.Saravanan@warwick.ac.uk. FAU - Bell, Heather AU - Bell H AD - Old School Surgery, Greenisland, Northern Ireland, UK. FAU - Braae, Uffe Christian AU - Braae UC AUID- ORCID: 0000-0002-2743-4584 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Collins, Edward AU - Collins E AD - Novo Nordisk Ltd, Gatwick, UK. FAU - Deinega, Alisa AU - Deinega A AUID- ORCID: 0000-0001-6314-0471 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Dhatariya, Ketan AU - Dhatariya K AUID- ORCID: 0000-0003-3619-9579 AD - Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK. AD - Norwich Medical School, University of East Anglia, Norwich, UK. FAU - Machell, Alena AU - Machell A AUID- ORCID: 0009-0007-1962-6061 AD - Egremont Medical Centre, Wallasey, UK. FAU - Trent, Antonia AU - Trent A AD - Novo Nordisk Ltd, Gatwick, UK. FAU - Strzelecka, Anna AU - Strzelecka A AD - Diabetic Services, Whiteabbey Hospital, Northern Health and Social Care Trust, Newtownabbey, UK. LA - eng SI - ClinicalTrials.gov/NCT04862923 PT - Clinical Trial, Phase IV PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20240924 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Drug Administration Schedule MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Glycated Hemoglobin/analysis/drug effects MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Patient Satisfaction MH - Prospective Studies MH - Treatment Outcome MH - United Kingdom MH - Weight Loss/drug effects MH - Semaglutide PMC - PMC11480173 OAB - PIONEER REAL UK investigated the use of a tablet form of the medicine semaglutide in people living with type 2 diabetes in the UK. The purpose was to determine how well the tablet works for blood sugar control and weight loss in everyday clinical practice. The study followed 333 participants whose doctors had given them semaglutide tablets. Their blood sugar levels and body weight were measured before and after taking the semaglutide tablet for 34-44 weeks. The participants were also asked to fill out questionnaires about their treatment satisfaction and how it changed when taking the semaglutide tablet. The participants' blood sugar levels dropped a lot, and body weight was lowered by an average of 4.8 kg during the 34-44 weeks of the study. The participants were also more satisfied with their treatment at the end of the study than before taking the semaglutide tablet. Doctors treating the participants found the treatment to be a success in more than two-thirds of participants. The study also found that the semaglutide tablet was not associated with cases of too low blood sugar and was generally well tolerated. In summary, the semaglutide tablet is a good option for people living with type 2 diabetes who need better blood sugar control and would benefit from weight loss. The treatment is generally well tolerated, and people are very satisfied with it. OABL- eng OTO - NOTNLM OT - Body weight OT - GLP-1 receptor agonist OT - Glucose-lowering medication OT - Glycaemic control OT - HbA1C OT - Incretin therapy OT - Real-world evidence OT - Semaglutide OT - Type 2 diabetes COIS- The authors disclose the following competing interests: Ponnusamy Saravanan: honoraria or travel support from Novo Nordisk and Abbott, UK; an unrestricted educational grant from Novo Nordisk A/S to set up an international Doctoral Training Partnership. Heather Bell: honoraria, travel support or fees for advisory boards from Abbott, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Menarini, Novo Nordisk, PCDS, Roche. Uffe Christian Braae: employee and shareholder of Novo Nordisk A/S. Edward Collins: employee and shareholder of Novo Nordisk A/S. Alisa Deinega: employee of Novo Nordisk A/S. Ketan Dhatariya: honoraria, travel support or fees for advisory boards from AstraZeneca, Novo Nordisk, Boehringer-Ingelheim, Eli Lilly, Abbott Diabetes, Menarini, Sanofi. Alena Machell: honoraria, travel support or fees for advisory boards from Novo Nordisk, Abbott. Antonia Trent: employee of Novo Nordisk A/S. Anna Strzelecka: honoraria from Astra Zeneca, Boehringer Ingelheim, Janssen, Lilly, MSD, Novo Nordisk, NAPP. EDAT- 2024/09/24 12:44 MHDA- 2024/10/15 12:24 PMCR- 2024/09/24 CRDT- 2024/09/24 11:23 PHST- 2024/07/17 00:00 [received] PHST- 2024/08/14 00:00 [accepted] PHST- 2024/10/15 12:24 [medline] PHST- 2024/09/24 12:44 [pubmed] PHST- 2024/09/24 11:23 [entrez] PHST- 2024/09/24 00:00 [pmc-release] AID - 10.1007/s12325-024-02973-z [pii] AID - 2973 [pii] AID - 10.1007/s12325-024-02973-z [doi] PST - ppublish SO - Adv Ther. 2024 Nov;41(11):4266-4281. doi: 10.1007/s12325-024-02973-z. Epub 2024 Sep 24. PMID- 39309109 OWN - NLM STAT- MEDLINE DCOM- 20240923 LR - 20261019 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Non-functional alpha-cell hyperplasia with glucagon-producing NET: a case report. PG - 1405835 LID - 10.3389/fendo.2024.1405835 [doi] LID - 1405835 AB - INTRODUCTION: Alpha-cell hyperplasia (ACH) is a rare pancreatic endocrine condition. Three types of ACH have been described: functional or nonglucagonoma hyperglucagonemic glucagonoma syndrome, reactive or secondary to defective glucagon signaling, and non-functional. Few cases of ACH with concomitant pancreatic neuroendocrine tumors (pNETs) have been reported and its etiology remains poorly understood. A case report of non-functional ACH with glucagon-producing NET is herein presented. CASE REPORT: A 72-year-old male was referred to our institution for a 2 cm single pNET incidentally found during imaging for acute cholecystitis. The patient's past medical history included type 2 diabetes (T2D) diagnosed 12 years earlier, for which he was prescribed metformin, dapagliflozin, and semaglutide. The pNET was clinically and biochemically non-functioning, apart from mildly elevated glucagon 217 pg/ml (<209), and (68)Ga-SSTR PET/CT positive uptake was only found at the pancreatic tail (SUVmax 11.45). The patient underwent a caudal pancreatectomy and the post-operative (68)Ga-SSTR PET/CT was negative. A multifocal well-differentiated NET G1, pT1N0M0R0 (mf) strongly staining for glucagon on a background neuroendocrine alpha-cell hyperplasia with some degree of acinar fibrosis was identified on pathology analysis. DISCUSSION AND CONCLUSION: This case reports the incidental finding of a clinically non-functioning pNET in a patient with T2D and elevated glucagon levels, unexpectedly diagnosed as glucagon-producing NET and ACH. A high level of suspicion was required to conduct the glucagon immunostaining, which is not part of the pathology routine for a clinically non-functioning pNET, and was key for the diagnosis that otherwise would have been missed. This case highlights the need to consider the diagnosis of glucagon-producing pNET on an ACH background even in the absence of glucagonoma syndrome. CI - Copyright (c) 2024 Cidade-Rodrigues, Santos, Calheiros, Santos, Matos, Moreira, Inacio, Souteiro, Oliveira, Jacome, Pereira, Henrique, Torres and Monteiro. FAU - Cidade-Rodrigues, Catarina AU - Cidade-Rodrigues C AD - Hospital Padre Americo, Unidade Local de Saude do Tamega e Sousa, Penafiel, Portugal. FAU - Santos, Ana Paula AU - Santos AP AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. AD - Research Center of IPO Porto (CI-IPOP), RISE@CI-IPO (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), Porto, Portugal. FAU - Calheiros, Raquel AU - Calheiros R AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Santos, Sara AU - Santos S AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Matos, Catarina AU - Matos C AD - Hospital de Braga, Unidade Local de Saude de Braga, Braga, Portugal. FAU - Moreira, Ana Paula AU - Moreira AP AD - Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra, Coimbra, Portugal. FAU - Inacio, Isabel AU - Inacio I AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Souteiro, Pedro AU - Souteiro P AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Oliveira, Joana AU - Oliveira J AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Jacome, Manuel AU - Jacome M AD - Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Pereira, Sofia S AU - Pereira SS AD - Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal. AD - Laboratory of Integrative and Translocation Research in Population Health (ITR), Porto, Portugal. FAU - Henrique, Rui AU - Henrique R AD - Research Center of IPO Porto (CI-IPOP), RISE@CI-IPO (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto Comprehensive Cancer Centre (P.CCC), Porto, Portugal. AD - Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. AD - Department of Pathology and Molecular Immunology, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal. FAU - Torres, Isabel AU - Torres I AD - Department of Endocrinology, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal. FAU - Monteiro, Mariana P AU - Monteiro MP AD - Unit for Multidisciplinary Research in Biomedicine (UMIB), School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal. AD - Laboratory of Integrative and Translocation Research in Population Health (ITR), Porto, Portugal. LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240906 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 9007-92-5 (Glucagon) SB - IM MH - Humans MH - Male MH - Aged MH - *Hyperplasia/metabolism/pathology MH - *Glucagon-Secreting Cells/metabolism/pathology MH - *Glucagon/metabolism MH - *Neuroendocrine Tumors/metabolism/pathology/diagnosis MH - *Pancreatic Neoplasms/metabolism/pathology/diagnosis MH - Diabetes Mellitus, Type 2/metabolism/complications PMC - PMC11412808 OTO - NOTNLM OT - alpha-cell OT - glucagon-producing NET OT - hyperplasia OT - neuroendocrine tumors OT - pancreas COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2024/09/23 07:29 MHDA- 2024/09/23 12:48 PMCR- 2024/01/01 CRDT- 2024/09/23 05:43 PHST- 2024/03/23 00:00 [received] PHST- 2024/08/08 00:00 [accepted] PHST- 2024/09/23 12:48 [medline] PHST- 2024/09/23 07:29 [pubmed] PHST- 2024/09/23 05:43 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1405835 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Sep 6;15:1405835. doi: 10.3389/fendo.2024.1405835. eCollection 2024. PMID- 39295084 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 12 DP - 2024 Dec TI - Glycaemic and weight effects of metabolic surgery or semaglutide in diabetes dosage for patients with type 2 diabetes. PG - 5812-5818 LID - 10.1111/dom.15952 [doi] AB - AIM: To compare weight and glucometabolic outcomes of semaglutide and metabolic and bariatric surgery (MBS) for patients with type 2 diabetes and obesity. MATERIALS AND METHODS: Patients treated with either semaglutide for a duration of >/=2 years or MBS in Sweden were identified within the Scandinavian Obesity Surgery Registry and the National Diabetes Registry and matched in a 1:1-2 ratio using a propensity score matching with a generalized linear model, including age, sex, glycated haemoglobin before treatment, duration of type 2 diabetes, use of insulin, presence of comorbidities and history of cancer, with good matching results but with a remaining imbalance for glomerular filtration rate and body mass index, which were then adjusted for in the following analyses. Main outcomes were weight loss and glycaemic control. RESULTS: The study included 606 patients in the surgical group matched to 997 controls who started their treatment from 2018 until 2020. Both groups improved in weight and glucometabolic control. At 2 years after the intervention, mean glycated haemoglobin was 42.3 +/- 11.18 after MBS compared with 50.7 +/- 12.48 after semaglutide treatment (p < 0.001) with 382 patients (63.0%) and 139 (13.9%), respectively, reaching complete remission without other treatment than the intervention (p < 0.001). Mean total weight loss reached 26.4% +/- 8.83% after MBS compared with 5.2% +/- 7.87% after semaglutide (p < 0.001). CONCLUSION: Semaglutide and MBS were both associated with improvements in weight and improved glycaemic control at 2 years after the start of the intervention, but MBS was associated with better weight loss and glucometabolic control. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Stenberg, Erik AU - Stenberg E AUID- ORCID: 0000-0001-9189-0093 AD - Department of Surgery, Faculty of Medicine and Health, Orebro University, Orebro, Sweden. FAU - Cao, Yang AU - Cao Y AUID- ORCID: 0000-0002-3552-9153 AD - Department of Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health, Orebro University, Orebro, Sweden. AD - Unit of Integrative Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Ottosson, Johan AU - Ottosson J AD - Department of Surgery, Faculty of Medicine and Health, Orebro University, Orebro, Sweden. FAU - Hedberg, Suzanne AU - Hedberg S AD - Department of Surgery (Ostra Sjukhuset), Sahlgrenska University Hospital, Gothenburg, Sweden. AD - Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. FAU - Naslund, Erik AU - Naslund E AD - Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. LA - eng GR - Stockholm Lans Landsting/ GR - Strategic Research Programme in Diabetes/ GR - OLL-939106/Region Orebro Lan/ PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240918 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - Male MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Weight Loss/drug effects MH - *Bariatric Surgery MH - *Glycated Hemoglobin/analysis/metabolism MH - *Hypoglycemic Agents/therapeutic use MH - *Blood Glucose/metabolism/drug effects MH - Adult MH - Sweden/epidemiology MH - Glycemic Control/methods MH - Obesity/surgery/complications MH - Registries MH - Treatment Outcome MH - Aged MH - Semaglutide OTO - NOTNLM OT - antidiabetic drug OT - bariatric surgery OT - cohort study OT - glucagon-like peptide-1 OT - glycaemic control OT - weight management EDAT- 2024/09/19 06:42 MHDA- 2024/11/04 12:23 CRDT- 2024/09/19 01:03 PHST- 2024/08/22 00:00 [revised] PHST- 2024/07/22 00:00 [received] PHST- 2024/08/31 00:00 [accepted] PHST- 2024/11/04 12:23 [medline] PHST- 2024/09/19 06:42 [pubmed] PHST- 2024/09/19 01:03 [entrez] AID - 10.1111/dom.15952 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Dec;26(12):5812-5818. doi: 10.1111/dom.15952. Epub 2024 Sep 18. PMID- 39293069 OWN - NLM STAT- MEDLINE DCOM- 20241212 LR - 20260429 IS - 1536-3708 (Electronic) IS - 0148-7043 (Linking) VI - 94 IP - 1 DP - 2025 Jan 1 TI - Glucagon-Like Peptide-1 Agonists: A Practical Overview for Plastic and Reconstructive Surgeons. PG - 121-127 LID - 10.1097/SAP.0000000000004089 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) agonists, such as exenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide, effectively manage type 2 diabetes by promoting insulin release, suppressing glucagon secretion, and enhancing glucose metabolism. They also aid weight reduction and cardiovascular health, potentially broadening their therapeutic scope. In plastic surgery, they hold promise for perioperative weight management and glycemic control, potentially impacting surgical outcomes. METHODS: A comprehensive review was conducted to assess GLP-1 agonists' utilization in plastic surgery. We analyzed relevant studies, meta-analyses, and trials to evaluate their benefits and limitations across surgical contexts, focusing on weight reduction, glycemic control, cardiovascular risk factors, and potential complications. RESULTS: Studies demonstrate GLP-1 agonists' versatility, spanning weight management, cardiovascular health, neurological disorders, and metabolic dysfunction-associated liver diseases. Comparative analyses highlight variations in glycemic control, weight loss, and cardiometabolic risk. Meta-analyses reveal significant reductions in hemoglobin A1C levels, especially with high-dose semaglutide (2 mg) and tirzepatide (15 mg). However, increased dosing may lead to gastrointestinal side effects and serious complications like pancreatitis and bowel obstruction. Notably, GLP-1 agonists' efficacy in weight reduction and glycemic control may impact perioperative management in plastic surgery, potentially expanding surgical candidacy for procedures like autologous flap-based breast reconstruction and influencing outcomes related to lymphedema. Concerns persist regarding venous thromboembolism and delayed gastric emptying, necessitating further investigation into bleeding and aspiration risk with anesthesia. CONCLUSIONS: GLP-1 agonists offer advantages in perioperative weight management and glycemic control in plastic surgery patients. They may broaden surgical candidacy and mitigate lymphedema risk but require careful consideration of complications, particularly perioperative aspiration risk. Future research should focus on their specific impacts on surgical outcomes to optimize their integration into perioperative protocols effectively. Despite challenges, GLP-1 agonists promise to enhance surgical outcomes and patient care in plastic surgery. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Stanton, Eloise W AU - Stanton EW AUID- ORCID: 0000-0003-0063-8584 FAU - Manasyan, Artur AU - Manasyan A AD - From the Keck School of Medicine, University of Southern California, Los Angeles, CA. FAU - Banerjee, Rakhi AU - Banerjee R AD - From the Keck School of Medicine, University of Southern California, Los Angeles, CA. FAU - Hong, Kurt AU - Hong K AD - Division of Internal Medicine, Keck School of Medicine of USC, Los Angeles, CA. FAU - Koesters, Emma AU - Koesters E FAU - Daar, David A AU - Daar DA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240904 PL - United States TA - Ann Plast Surg JT - Annals of plastic surgery JID - 7805336 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1/agonists MH - Plastic Surgery Procedures/methods MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Weight Loss COIS- Conflicts of interest and sources of funding: none declared. EDAT- 2024/09/18 18:45 MHDA- 2024/12/12 12:28 CRDT- 2024/09/18 17:03 PHST- 2024/12/12 12:28 [medline] PHST- 2024/09/18 18:45 [pubmed] PHST- 2024/09/18 17:03 [entrez] AID - 00000637-990000000-00551 [pii] AID - 10.1097/SAP.0000000000004089 [doi] PST - ppublish SO - Ann Plast Surg. 2025 Jan 1;94(1):121-127. doi: 10.1097/SAP.0000000000004089. Epub 2024 Sep 4. PMID- 39279647 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Impact of baseline characteristics on the efficacy of once-weekly subcutaneous semaglutide among participants with type 2 diabetes: A post hoc analysis of SUSTAIN China. PG - 5312-5324 LID - 10.1111/dom.15888 [doi] AB - AIMS: To investigate the impact of baseline characteristics on the efficacy of once-weekly subcutaneous semaglutide 0.5 and 1.0 mg in participants with type 2 diabetes (T2D) from the SUSTAIN China trial. METHODS: In this post hoc analysis, data for semaglutide 0.5 and 1.0 mg versus sitagliptin 100 mg were analysed in the total (n = 868) and Chinese-only (n = 605) populations. Changes from baseline to end of treatment (EOT) in glycated haemoglobin (HbA1c) and body weight were analysed by baseline age, sex, body mass index, HbA1c, diabetes duration, and homeostatic model assessment of beta-cell function (HOMA-beta) tertile. Proportions of participants achieving HbA1c <7.0% (53 mmol/mol) by baseline HbA1c, change from baseline to EOT in standard deviation of seven-point self-monitored plasma glucose (SMPG), derived time-in-range (dTIR) of seven-point SMPG at Week 30, and HOMA-beta ratio to baseline at Week 30 were assessed for both populations. RESULTS: In both populations the efficacy of once-weekly subcutaneous semaglutide 0.5 and 1.0 mg versus sitagliptin was not significantly affected by most of the baseline characteristics studied. The proportion of participants achieving the target HbA1c <7% was not affected by baseline HbA1c (p(interaction) > 0.05). SMPG fluctuation and dTIR indicated less glucose variability in participants treated with semaglutide 0.5 and 1.0 mg versus sitagliptin, and the HOMA-beta ratios to baseline at EOT were greater with semaglutide 0.5 and 1.0 mg versus sitagliptin (p < 0.05). CONCLUSIONS: These results support the effectiveness of once-weekly subcutaneous semaglutide 0.5 and 1.0 mg across a broad range of baseline characteristics, in participants with T2D from SUSTAIN China. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Peking University People's Hospital, Beijing, China. FAU - Lu, Yibing AU - Lu Y AD - The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Shen, Zewei AU - Shen Z AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Shanghai, China. FAU - Hu, Ping AU - Hu P AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Shanghai, China. FAU - Liu, Wenyan AU - Liu W AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Shanghai, China. FAU - Zhang, Qiu AU - Zhang Q AUID- ORCID: 0000-0002-0204-3528 AD - First Affiliated Hospital of Anhui Medical University, Hefei, China. FAU - Shi, Bimin AU - Shi B AD - The First Affiliated Hospital of Soochow University, Jiangsu, China. LA - eng GR - Novo Nordisk Shanghai Ltd./ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240916 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - Male MH - Female MH - Middle Aged MH - *Sitagliptin Phosphate/administration & dosage/therapeutic use MH - *Glycated Hemoglobin/analysis/drug effects MH - China/epidemiology MH - Injections, Subcutaneous MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Blood Glucose/drug effects MH - Treatment Outcome MH - Aged MH - Drug Administration Schedule MH - Double-Blind Method MH - Semaglutide OTO - NOTNLM OT - GLP-1 analogue OT - clinical trial OT - glycaemic control OT - incretin therapy OT - type 2 diabetes EDAT- 2024/09/16 06:22 MHDA- 2024/10/04 12:42 CRDT- 2024/09/16 05:03 PHST- 2024/07/30 00:00 [revised] PHST- 2024/05/13 00:00 [received] PHST- 2024/08/04 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/09/16 06:22 [pubmed] PHST- 2024/09/16 05:03 [entrez] AID - 10.1111/dom.15888 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5312-5324. doi: 10.1111/dom.15888. Epub 2024 Sep 16. PMID- 39279639 OWN - NLM STAT- MEDLINE DCOM- 20241104 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 12 DP - 2024 Dec TI - Cagrilintide is not associated with clinically relevant QTc prolongation: A thorough QT study in healthy participants. PG - 5805-5811 LID - 10.1111/dom.15951 [doi] AB - AIMS: The combination of cagrilintide and semaglutide (CagriSema) is being developed for the treatment of obesity and type 2 diabetes. The objective of this thorough QT study was to confirm that cagrilintide does not result in a clinically relevant prolongation in cardiac repolarization compared with placebo. MATERIALS AND METHODS: This was a double-blind study (NCT05804162) in which healthy participants were randomized to cagrilintide, administered as a once-weekly subcutaneous injection dose escalated to 4.5 mg, or a placebo. The primary end point was the time-matched change from baseline in Fridericia heart rate-corrected QT interval (QTcF) at 12-, 24-, 48- and 72 h after the last cagrilintide 4.5-mg dose. To conclude that cagrilintide does not induce a clinically relevant prolongation, the upper limit of the two-sided 90% confidence interval (CI) for the treatment difference at each of the four time points must fall below 10 ms. To establish QT assay sensitivity, participants in the placebo arms received a single 400-mg oral moxifloxacin dose as a positive control and moxifloxacin placebo in a nested cross-over fashion. RESULTS: A total of 105 participants received cagrilintide (n = 53) or placebo (n = 52). No clinically relevant QTcF prolongation occurred after the last cagrilintide 4.5-mg dose; the upper limits of the two-sided 90% CIs of the placebo-adjusted QTcF changes from baseline were below 10 ms at all time points. QT assay sensitivity was demonstrated with moxifloxacin as a positive control. CONCLUSIONS: Cagrilintide did not result in clinically relevant QTcF prolongation, indicating no increased risk of ventricular tachyarrhythmias. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gabe, Maria B N AU - Gabe MBN AUID- ORCID: 0000-0003-2559-862X AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Fuhr, Rainard AU - Fuhr R AD - Parexel International GmbH, Berlin, Germany. FAU - Sinn, Angela AU - Sinn A AD - Parexel International GmbH, Berlin, Germany. FAU - Eliasen, Astrid AU - Eliasen A AUID- ORCID: 0000-0002-2261-0323 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Berthelsen, Kasper K AU - Berthelsen KK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kuhlman, Anja B AU - Kuhlman AB AUID- ORCID: 0000-0001-8893-8498 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Baekdal, Tine A AU - Baekdal TA AUID- ORCID: 0000-0002-1348-0352 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Nejad, Ayna B AU - Nejad AB AUID- ORCID: 0000-0003-4688-7877 AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT05804162 GR - Novo Nordisk A/S/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240916 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - U188XYD42P (Moxifloxacin) RN - 0 (Islet Amyloid Polypeptide) RN - 53AXN4NNHX (Semaglutide) RN - AO43BIF1U8 (cagrilintide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Middle Aged MH - Young Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - *Electrocardiography/drug effects MH - Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Healthy Volunteers MH - Heart Rate/drug effects MH - Hypoglycemic Agents/adverse effects/administration & dosage MH - Long QT Syndrome/chemically induced MH - Moxifloxacin/adverse effects/administration & dosage MH - *Islet Amyloid Polypeptide/adverse effects MH - Semaglutide OTO - NOTNLM OT - antidiabetic drug OT - antiobesity drug OT - clinical trial OT - drug development OT - randomized trial EDAT- 2024/09/16 06:22 MHDA- 2024/11/04 12:25 CRDT- 2024/09/16 05:03 PHST- 2024/08/27 00:00 [revised] PHST- 2024/07/30 00:00 [received] PHST- 2024/08/29 00:00 [accepted] PHST- 2024/11/04 12:25 [medline] PHST- 2024/09/16 06:22 [pubmed] PHST- 2024/09/16 05:03 [entrez] AID - 10.1111/dom.15951 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Dec;26(12):5805-5811. doi: 10.1111/dom.15951. Epub 2024 Sep 16. PMID- 39269759 OWN - NLM STAT- MEDLINE DCOM- 20240913 LR - 20260923 IS - 1929-0748 (Electronic) IS - 1929-0748 (Linking) VI - 13 DP - 2024 Sep 13 TI - Effect of Semaglutide on Physical Function, Body Composition, and Biomarkers of Aging in Older Adults With Overweight and Insulin Resistance: Protocol for an Open-Labeled Randomized Controlled Trial. PG - e62667 LID - 10.2196/62667 [doi] LID - e62667 AB - BACKGROUND: Older adults with type 2 diabetes mellitus (T2DM) or prediabetes are at increased risk of adverse changes in body composition, physical function, and aging-related biomarkers compared to those with normal glucose tolerance. Semaglutide is a glucagon-like peptide 1 receptor agonist that has been approved for T2DM and chronic weight management. Although semaglutide is effective for weight loss and T2DM management, its effects on lean body mass, physical function, and biomarkers of aging are understudied in older adults. OBJECTIVE: This study aims to compare the effects of lifestyle counseling with and that without semaglutide on body composition, physical function, and biomarkers of aging in older adults. METHODS: This is an open-label randomized controlled trial. A total of 20 adults (aged 65 years and older) with elevated BMI (27-40 kg/m(2)) and prediabetes or well-controlled T2DM (hemoglobin A(1c) 5.7%-7.5%) are recruited, stratified by sex, and randomized 1:1 to one of 2 groups (semaglutide plus lifestyle counseling vs lifestyle counseling alone) and followed up for 5 months. Those in the semaglutide group are titrated to 1 mg weekly, as tolerated, for 12 weeks. Lifestyle counseling is given by registered dietitians and based on the Diabetes Prevention Program Lifestyle Change Program. Our primary outcomes include changes in lean mass, physical function, and biomarkers of aging. Body composition is measured by dual-energy x-ray absorptiometry and includes total fat mass and lean mass. Physical function is measured by 6-minute walk distance, grip strength, and short physical performance battery. Biomarkers of aging are measured in blood, skeletal muscle, and abdominal adipose tissue to include C-reactive protein, interleukin-6, tumor necrosis factors alpha, and beta galactosidase staining. RESULTS: The study was funded in December 2021 with a projected data collection period from spring 2023 through summer 2024. CONCLUSIONS: Despite the elevated risk of adverse changes in body composition, physical function, and biomarkers of aging among older adults with glucose intolerance and elevated adiposity, the benefits and risks of commonly prescribed antihyperglycemic or weight loss medications such as semaglutide are understudied. This study aims to fill this knowledge gap to inform clinicians about the potential for additional clinically meaningful, nonglycemic effects of semaglutide. TRIAL REGISTRATION: ClinicalTrials.gov NCT05786521; https://clinicaltrials.gov/study/NCT05786521. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/62667. CI - (c)Tiffany M Cortes, Libia Vasquez, Monica C Serra, Ronna Robbins, Allison Stepanenko, Kevin Brown, Hannah Barrus, Annalisa Campos, Sara E Espinoza, Nicolas Musi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.09.2024. FAU - Cortes, Tiffany M AU - Cortes TM AUID- ORCID: 0000-0002-8971-9542 AD - Division of Endocrinology, Department of Medicine, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. AD - San Antonio Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, United States. FAU - Vasquez, Libia AU - Vasquez L AUID- ORCID: 0009-0005-2857-4852 AD - Texas Diabetes Institute, University Health System, San Antonio, TX, United States. FAU - Serra, Monica C AU - Serra MC AUID- ORCID: 0000-0002-2466-4675 AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. AD - San Antonio Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, United States. AD - Division of Geriatrics, Gerontology & Palliative Medicine, Department of Medicine, University of Texas Health Science San Antonio, San Antonio, TX, United States. FAU - Robbins, Ronna AU - Robbins R AUID- ORCID: 0000-0002-2787-9727 AD - Department of Nutrition and Food Science, Texas Woman's University, Denton, TX, United States. FAU - Stepanenko, Allison AU - Stepanenko A AUID- ORCID: 0009-0009-0350-7716 AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. FAU - Brown, Kevin AU - Brown K AUID- ORCID: 0000-0003-4327-5090 AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. FAU - Barrus, Hannah AU - Barrus H AUID- ORCID: 0009-0006-2454-5656 AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. FAU - Campos, Annalisa AU - Campos A AUID- ORCID: 0009-0007-9443-0122 AD - Sam & Ann Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States. FAU - Espinoza, Sara E AU - Espinoza SE AUID- ORCID: 0000-0002-1116-302X AD - Division of Geriatrics, Gerontology & Palliative Medicine, Department of Medicine, University of Texas Health Science San Antonio, San Antonio, TX, United States. AD - Center for Translational Geroscience, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States. AD - Diabetes and Aging Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States. FAU - Musi, Nicolas AU - Musi N AUID- ORCID: 0000-0003-4242-2888 AD - Center for Translational Geroscience, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States. AD - Diabetes and Aging Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, United States. LA - eng SI - ClinicalTrials.gov/NCT05786521 GR - P30 AG021332/AG/NIA NIH HHS/United States GR - P30 AG044271/AG/NIA NIH HHS/United States GR - R01 AG052697/AG/NIA NIH HHS/United States PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240913 PL - Canada TA - JMIR Res Protoc JT - JMIR research protocols JID - 101599504 RN - 0 (Biomarkers) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Aging/drug effects MH - *Biomarkers/blood MH - *Body Composition/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - *Insulin Resistance MH - *Overweight/drug therapy MH - Physical Functional Performance MH - Prediabetic State/drug therapy/blood MH - Non-Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC11437224 OTO - NOTNLM OT - biomarkers of aging OT - glucagon-like peptide OT - lean body mass OT - physical function OT - semaglutide COIS- Conflicts of Interest: None declared. EDAT- 2024/09/13 14:45 MHDA- 2024/09/13 18:44 PMCR- 2024/09/13 CRDT- 2024/09/13 11:54 PHST- 2024/05/28 00:00 [received] PHST- 2024/07/11 00:00 [accepted] PHST- 2024/07/01 00:00 [revised] PHST- 2024/09/13 18:44 [medline] PHST- 2024/09/13 14:45 [pubmed] PHST- 2024/09/13 11:54 [entrez] PHST- 2024/09/13 00:00 [pmc-release] AID - v13i1e62667 [pii] AID - 10.2196/62667 [doi] PST - epublish SO - JMIR Res Protoc. 2024 Sep 13;13:e62667. doi: 10.2196/62667. PMID- 39269703 OWN - NLM STAT- MEDLINE DCOM- 20240913 LR - 20260127 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 7 IP - 9 DP - 2024 Sep 3 TI - One-Year Weight Reduction With Semaglutide or Liraglutide in Clinical Practice. PG - e2433326 LID - 10.1001/jamanetworkopen.2024.33326 [doi] LID - e2433326 AB - IMPORTANCE: Limited data are available on long-term weight loss achieved with semaglutide or liraglutide for type 2 diabetes (T2D) or obesity in clinical practice. OBJECTIVE: To document weight loss achieved with injectable forms of semaglutide or liraglutide and identify factors associated with weight reduction of 10% or greater at 1 year. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used electronic health records from a large, integrated health system in Ohio and Florida. Participants included adults with a body mass index (calculated as the weight in kilograms divided by the height in meters squared) of at least 30.0 who initiated treatment with semaglutide or liraglutide between July 1, 2015, and June 30, 2022. Follow-up was completed July 28, 2023. EXPOSURE: Injectable forms of semaglutide or liraglutide approved for T2D or obesity. MAIN OUTCOMES AND MEASURES: Percentage weight change and categorical weight reduction of 10% or greater at 1 year. RESULTS: A total of 3389 patients (mean [SD] age, 50.4 [12.2] years; 1835 [54.7%] female) were identified. Of these, 1341 patients received semaglutide for T2D; 1444, liraglutide for T2D; 227, liraglutide for obesity; and 377, semaglutide for obesity. Mean (SD) percentage weight change at 1 year was -5.1% (7.8%) with semaglutide vs -2.2% (6.4%) with liraglutide (P < .001); -3.2% (6.8%) for T2D as a treatment indication vs -5.9% (9.0%) for obesity (P < .001); and -5.5% (7.5%) with persistent medication coverage (ie, a cumulative gap of less than 90 days) at 1 year vs -2.8% (7.0%) with 90 to 275 medication coverage days and -1.8% (6.7%) with fewer than 90 medication coverage days (P < .001). In the multivariable model, semaglutide vs liraglutide (adjusted odds ratio [AOR], 2.19 [95% CI, 1.77-2.72]), obesity as a treatment indication vs T2D (AOR, 2.46 [95% CI, 1.83-3.30]), persistent medication coverage vs 90 medication coverage days (AOR, 3.36 [95% CI, 2.52-4.54]) or 90 to 275 medication coverage days within the first year (AOR, 1.50 [95% CI, 1.10-2.06]), high dosage of the medication vs low (AOR, 1.58 [95% CI, 1.11-2.25]), and female sex (AOR, 1.57 [95% CI, 1.27-1.94]) were associated with achieving a 10% or greater weight reduction at year 1. CONCLUSIONS AND RELEVANCE: In this retrospective cohort study of 3389 patients with obesity, weight reduction at 1 year was associated with the medication's active agent, its dosage, treatment indication, persistent medication coverage, and patient sex. Future research should focus on identifying the reasons for discontinuation of medication use and interventions aimed at improving long-term persistent coverage. FAU - Gasoyan, Hamlet AU - Gasoyan H AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. FAU - Pfoh, Elizabeth R AU - Pfoh ER AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. FAU - Schulte, Rebecca AU - Schulte R AD - Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio. FAU - Le, Phuc AU - Le P AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. FAU - Butsch, W Scott AU - Butsch WS AD - Department of Surgery, Bariatric and Metabolic Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio. FAU - Rothberg, Michael B AU - Rothberg MB AD - Center for Value-Based Care Research, Department of Internal Medicine and Geriatrics, Primary Care Institute, Cleveland Clinic, Cleveland, Ohio. AD - Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240903 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Liraglutide/therapeutic use MH - Female MH - Male MH - Middle Aged MH - *Weight Loss/drug effects MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Aged MH - Ohio MH - Body Mass Index MH - Florida MH - Semaglutide PMC - PMC11400221 COIS- Conflict of Interest Disclosures: Dr Gasoyan reported receiving grant funding from the National Cancer Institute outside the submitted work. Dr Butsch reported advisory board fees from Novo Nordisk A/S and research funding from Eli Lilly and Co during the conduct of the study. Dr Rothberg reported receiving personal fees from the Blue Cross Blue Shield Association outside the submitted work. No other disclosures were reported. EDAT- 2024/09/13 14:44 MHDA- 2024/09/13 14:45 PMCR- 2024/09/13 CRDT- 2024/09/13 11:33 PHST- 2024/09/13 14:45 [medline] PHST- 2024/09/13 14:44 [pubmed] PHST- 2024/09/13 11:33 [entrez] PHST- 2024/09/13 00:00 [pmc-release] AID - 2823644 [pii] AID - zoi241001 [pii] AID - 10.1001/jamanetworkopen.2024.33326 [doi] PST - epublish SO - JAMA Netw Open. 2024 Sep 3;7(9):e2433326. doi: 10.1001/jamanetworkopen.2024.33326. PMID- 39265294 OWN - NLM STAT- MEDLINE DCOM- 20240929 LR - 20260127 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 43 IP - 10 DP - 2024 Oct TI - Very-low calorie diet and Semaglutide: Synergy and long-term impact on type 2 diabetes management. PG - 2350-2351 LID - S0261-5614(24)00319-4 [pii] LID - 10.1016/j.clnu.2024.09.008 [doi] FAU - Zheng, Ziwei AU - Zheng Z AD - Shanghai Eighth People's Hospital, Xu Hui District, Shanghai, China. FAU - Zhao, Kun AU - Zhao K AD - Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, China. FAU - Yang, Shaoling AU - Yang S AD - Shanghai Eighth People's Hospital, Xu Hui District, Shanghai, China. Electronic address: drysl@163.com. LA - eng PT - Letter DEP - 20240906 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Caloric Restriction/methods MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Semaglutide OTO - NOTNLM OT - Beta cell function OT - Digital health technology OT - Personalized treatment OT - Synergistic effect COIS- Conflict of interest This statement follows the International Committee of Medical Journal Editors (ICMJE) guidelines. All authors disclose no conflict of interest for this work. EDAT- 2024/09/13 00:46 MHDA- 2024/09/30 00:42 CRDT- 2024/09/12 18:04 PHST- 2024/07/24 00:00 [received] PHST- 2024/09/04 00:00 [accepted] PHST- 2024/09/30 00:42 [medline] PHST- 2024/09/13 00:46 [pubmed] PHST- 2024/09/12 18:04 [entrez] AID - S0261-5614(24)00319-4 [pii] AID - 10.1016/j.clnu.2024.09.008 [doi] PST - ppublish SO - Clin Nutr. 2024 Oct;43(10):2350-2351. doi: 10.1016/j.clnu.2024.09.008. Epub 2024 Sep 6. PMID- 39259460 OWN - NLM STAT- MEDLINE DCOM- 20241128 LR - 20261010 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 84 IP - 11 DP - 2024 Nov TI - Slowing the Progression of Chronic Kidney Disease in Patients with Type 2 Diabetes Using Four Pillars of Therapy: The Time to Act is Now. PG - 1337-1346 LID - 10.1007/s40265-024-02091-8 [doi] AB - Chronic kidney disease (CKD) is the most common co-morbidity in patients with type 2 diabetes (T2D) and its presence substantially amplifies the risk for premature death, adverse cardiovascular events, and faster progression of kidney injury to kidney failure. For nearly two decades, the pharmacological blockade of the renin-angiotensin-system (RAS) was the only pillar of therapy to afford cardiorenal protection in these patients. During the last 5 years, newer novel therapies have been added to our therapeutic armamentarium, offering promise for more effective management of diabetic kidney disease in the future. Large phase 3 clinical trials have demonstrated additive cardiorenal protective benefits of sodium-glucose co-transporter type 2 (SGLT-2) inhibitors, the non-steroidal mineralocorticoid-receptor-antagonist (MRA) finerenone, and glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide relative to placebo in patients with albuminuric CKD and T2D who are receiving standard-of-care treatment with a RAS-blocker. These therapies are likely much more effective when administered in a combined therapeutic algorithm, but the potential additive effects of combination therapy remain to be established in ongoing clinical trials. In this article, we assemble four pillars of therapy for the attenuation of residual cardiorenal risk in patients with CKD associated with T2D. We provide evidence from recent randomized trials and we discuss the concept of combined treatment for maximal cardiorenal protection in this high-risk patient population. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Georgianos, Panagiotis I AU - Georgianos PI AUID- ORCID: 0000-0001-7065-2096 AD - Second Department of Nephrology, School of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, St. Kyriakidi 1, 54636, Thessaloniki, Greece. pangeorgi@yahoo.gr. FAU - Vaios, Vasilios AU - Vaios V AD - Second Department of Nephrology, School of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, St. Kyriakidi 1, 54636, Thessaloniki, Greece. FAU - Koufakis, Theocharis AU - Koufakis T AD - Second Propedeutic Department of Internal Medicine, School of Medicine, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Liakopoulos, Vassilios AU - Liakopoulos V AD - Second Department of Nephrology, School of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, St. Kyriakidi 1, 54636, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20240911 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Naphthyridines) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (finerenone) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Renal Insufficiency, Chronic/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - *Disease Progression MH - *Mineralocorticoid Receptor Antagonists/therapeutic use MH - Diabetic Nephropathies/drug therapy MH - Naphthyridines/therapeutic use/pharmacology MH - Renin-Angiotensin System/drug effects MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptides MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- Declarations. Conflicts of Interest: The authors (P.I.G., V.V., T.K., V.L.) report no conflicts of interest relevant to this work. Funding: No external funds were used in the preparation of this article. Author Contributions: P.I.G. reviewed the literature and drafted the initial version of the manuscript. V.V., T.K., and V.L. reviewed the literature and edited the manuscript. All authors read and approved the final version of the manuscript. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Availability of Data and Material: Not applicable because this is a review article. Code Availability: Not applicable. EDAT- 2024/09/11 12:45 MHDA- 2024/11/28 06:36 CRDT- 2024/09/11 11:21 PHST- 2024/08/26 00:00 [accepted] PHST- 2024/11/28 06:36 [medline] PHST- 2024/09/11 12:45 [pubmed] PHST- 2024/09/11 11:21 [entrez] AID - 10.1007/s40265-024-02091-8 [pii] AID - 10.1007/s40265-024-02091-8 [doi] PST - ppublish SO - Drugs. 2024 Nov;84(11):1337-1346. doi: 10.1007/s40265-024-02091-8. Epub 2024 Sep 11. PMID- 39248157 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Semaglutide use in people with obesity and type 2 diabetes from real-world utilization data: An analysis of the All of US Program. PG - 4989-4995 LID - 10.1111/dom.15911 [doi] AB - AIM: To analyse data from the All of Us Research Program to evaluate the real-world application and long-term effectiveness of semaglutide in treating type 2 diabetes and obesity patients in a large population. MATERIALS AND METHODS: We identified patients prescribed semaglutide and analysed differences in route of administration and the time on semaglutide. For individuals diagnosed with obesity, we measured changes in body mass index (BMI) and weight from baseline, while measured changes in HbA1c for those patients with type 2 diabetes. We also examined the occurrence of newly diagnosed common adverse events from taking semaglutide. RESULTS: For 3739 semaglutide patients, those on injectable semaglutide (3364 patients) averaged 301.54 days on the medication, with 20.36% having no end date, while those on oral semaglutide (435 patients) averaged 172.48 days, with 24.60% having no end date. We found average decreases of 1.54 kg/m(2) in BMI, 4.65 kg in weight and 0.75% in HbA1c for semaglutide users. The decreases were larger in participants taking injectable formulation, probably because of higher starting values. Over time, improvements in these outcomes diminished, but the values remained significantly lower than baseline levels. Approximately only 1.0% of patients reported newly diagnosed common adverse events. CONCLUSIONS: Consistent with clinical trial findings, this real-world data analysis showed that semaglutide was well tolerated and that, for a large population, it effectively reduced BMI, body weight and HbA1c, albeit to smaller magnitudes than observed in clinical trials. These findings provide valuable insights into real-world experience and the long-term effectiveness of semaglutide. CI - Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Mayer, Craig S AU - Mayer CS AUID- ORCID: 0000-0002-2705-9550 AD - Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA. FAU - Fontelo, Paul AU - Fontelo P AD - Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA. LA - eng GR - Z99 LM999999/ImNIH/Intramural NIH HHS/United States GR - Lister Hill National Center for Biomedical Communications of the National Library of Medicine (NLM), National Institutes of Health/ PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240909 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Female MH - Male MH - Middle Aged MH - *Obesity/drug therapy/complications MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Glycated Hemoglobin/analysis/drug effects/metabolism MH - *Body Mass Index MH - Aged MH - United States/epidemiology MH - Adult MH - Weight Loss/drug effects MH - Treatment Outcome MH - Administration, Oral MH - Semaglutide PMC - PMC11462475 MID - NIHMS2018147 OTO - NOTNLM OT - obesity care OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- CONFLICT OF INTEREST STATEMENT The authors have no conflicts of interest to report. EDAT- 2024/09/09 12:43 MHDA- 2024/10/04 12:43 PMCR- 2025/11/01 CRDT- 2024/09/09 06:23 PHST- 2024/08/12 00:00 [revised] PHST- 2024/06/06 00:00 [received] PHST- 2024/08/13 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/09/09 12:43 [pubmed] PHST- 2024/09/09 06:23 [entrez] PHST- 2025/11/01 00:00 [pmc-release] AID - 10.1111/dom.15911 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):4989-4995. doi: 10.1111/dom.15911. Epub 2024 Sep 9. PMID- 39243175 OWN - NLM STAT- MEDLINE DCOM- 20241101 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 15 IP - 11 DP - 2024 Nov TI - Adherence and treatment discontinuation of oral semaglutide and once-weekly semaglutide injection at 12 month follow-up: Japanese real-world data. PG - 1578-1584 LID - 10.1111/jdi.14265 [doi] AB - Adherence and treatment continuation rates of the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide for both oral (O-SEMA) and subcutaneous injection (SEMA-SC) remain unknown in real-world clinical practice. This retrospective observational study compared the 12 month adherence and treatment discontinuation of O-SEMA and once-weekly SEMA-SC in patients with type 2 diabetes using a real-world claims database. SEMA-SC initiators were 1:1 propensity score-matched to O-SEMA initiators. Non-adherence was defined as <0.8 of the proportion of days covered. SEMA-SC had a significantly higher odds ratio (OR) for non-adherence than O-SEMA (OR: 1.39). The hazard ratio for treatment discontinuation, using O-SEMA as the reference, was 1.45 for SEMA-SC, although the discontinuation rate of O-SEMA was higher during the early stage. O-SEMA initiators showed significantly higher adherence and greater persistence in therapy than SEMA-SC initiators at 12 months, which could lead to earlier initiation of GLP-1RA treatment. CI - (c) 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Horii, Takeshi AU - Horii T AUID- ORCID: 0000-0002-5465-4531 AD - Department of Pharmacy, Faculty of Pharmacy, Musashino University, Tokyo, Japan. AD - Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan. FAU - Masudo, Chikako AU - Masudo C AD - Department of Pharmacy, Faculty of Pharmacy, Musashino University, Tokyo, Japan. FAU - Takayanagi, Yui AU - Takayanagi Y AD - Department of Pharmacy, Faculty of Pharmacy, Musashino University, Tokyo, Japan. FAU - Oikawa, Yoichi AU - Oikawa Y AUID- ORCID: 0000-0003-1524-6751 AD - Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan. FAU - Shimada, Akira AU - Shimada A AUID- ORCID: 0000-0002-3954-4983 AD - Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan. FAU - Mihara, Kiyoshi AU - Mihara K AD - Department of Pharmacy, Faculty of Pharmacy, Musashino University, Tokyo, Japan. LA - eng PT - Journal Article PT - Observational Study DEP - 20240907 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - Retrospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Follow-Up Studies MH - Administration, Oral MH - Aged MH - Injections, Subcutaneous MH - Japan MH - Withholding Treatment/statistics & numerical data MH - East Asian People MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Drug Monitoring MH - Semaglutide PMC - PMC11527826 OTO - NOTNLM OT - Injection OT - Oral OT - Semaglutide COIS- A.S. received lecture fees from Astellas Pharma, Inc., Eli Lilly Japan K.K., Novo Nordisk Pharma, Inc., and Sanofi K.K. The authors declare no conflicts of interest. Approval of the research protocol: The Ethics Board of Musashino University waived the requirement for ethical approval for this study because all available data were completely anonymous with no personal information, which is characteristic of DPC-based clinical databases. This study was conducted in accordance with the Declaration of Helsinki (revised in Fortaleza, Brazil, October 2013) and the Ethical Guidelines for Medical and Health Research Involving Human Subjects. Informed consent: All patient data were anonymized and did not contain personal data; therefore, informed consent was not required. Registry and the registration no. of the study/trial: N/A. Animal studies: N/A. EDAT- 2024/09/07 14:42 MHDA- 2024/11/01 06:22 PMCR- 2024/09/07 CRDT- 2024/09/07 05:42 PHST- 2024/06/07 00:00 [revised] PHST- 2024/04/26 00:00 [received] PHST- 2024/06/27 00:00 [accepted] PHST- 2024/11/01 06:22 [medline] PHST- 2024/09/07 14:42 [pubmed] PHST- 2024/09/07 05:42 [entrez] PHST- 2024/09/07 00:00 [pmc-release] AID - JDI14265 [pii] AID - 10.1111/jdi.14265 [doi] PST - ppublish SO - J Diabetes Investig. 2024 Nov;15(11):1578-1584. doi: 10.1111/jdi.14265. Epub 2024 Sep 7. PMID- 39230989 OWN - NLM STAT- MEDLINE DCOM- 20250106 LR - 20260410 IS - 1546-3141 (Electronic) IS - 0361-803X (Linking) VI - 223 IP - 6 DP - 2024 Dec TI - Intrapatient Changes in CT-Based Body Composition After Initiation of Semaglutide (Glucagon-Like Peptide-1 Receptor Agonist) Therapy. PG - e2431805 LID - 10.2214/AJR.24.31805 [doi] AB - BACKGROUND. The long-acting glucagon-like peptide-1 receptor agonist semaglutide is used to treat type 2 diabetes or obesity in adults. Clinical trials have observed associations of semaglutide with weight loss, improved control of diabetes, and cardiovascular risk reduction. OBJECTIVE. The purpose of this study was to evaluate intrapatient changes in body composition after initiation of semaglutide therapy by applying an automated suite of CT-based artificial intelligence (AI) body composition tools. METHODS. This retrospective study included adult patients who were receiving semaglutide treatment and who, between January 2016 and November 2023, underwent abdominopelvic CT within both 5 years before and 5 years after initiation of semaglutide. An automated suite of previously validated CT-based AI body composition tools was applied to scans obtained before semaglutide initiation (hereafter, presemaglutide scans) and scans obtained after semaglutide initiation (hereafter, postsemaglutide scans) to quantify visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) area, skeletal muscle area and attenuation, intermuscular adipose tissue (IMAT) area, liver volume and attenuation, and trabecular bone mineral density (BMD). Patients with weight loss of 5 kg or more and those with weight gain of 5 kg or more between the scans were compared. RESULTS. The study included 241 patients (151 women and 90 men; mean age, 60.4 +/- 12.4 [SD] years). In the weight-loss group (n = 67), the postsemaglutide scan, compared with the presemaglutide scan, showed a decrease in VAT area (309.4 vs 341.1 cm(2), p < .001), SAT area (371.4 vs 410.7 cm(2), p < .001), muscle area (179.2 vs 193.0, p < .001), and liver volume (2379.0 vs 2578 HU, p = .009) and an increase in liver attenuation (74.5 vs 67.6 HU, p = .03). In the weight-gain group (n = 48), the postsemaglutide scan, compared with the presemaglutide scan, showed an increase in VAT area (334.0 vs 312.8, p = .002), SAT area (485.8 vs 448.8 cm(2), p = .01), and IMAT area (48.4 vs 37.6, p = .009) and a decrease in muscle attenuation (5.9 vs 13.1, p < .001). Other comparisons were not statistically significant (p > .05). CONCLUSION. Patients using semaglutide who lost versus gained weight showed distinct patterns of changes in CT-based body composition measures. Those with weight loss had overall favorable shifts in measures related to cardiometabolic risk. A decrease in muscle attenuation in those with weight gain is consistent with decreased muscle quality. CLINICAL IMPACT. Among patients using semaglutide, automated CT-based AI tools provide biomarkers of changes in body composition beyond those that are evident by standard clinical measures. FAU - Nelson, Leslie W AU - Nelson LW AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. FAU - Lee, Matthew H AU - Lee MH AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. FAU - Garrett, John W AU - Garrett JW AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. AD - Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI. AD - Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, WI. FAU - Pickhardt, Silas G AU - Pickhardt SG AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. FAU - Warner, Joshua D AU - Warner JD AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. FAU - Summers, Ronald M AU - Summers RM AD - Imaging Biomarkers and Computer-Aided Diagnosis Laboratory, Radiology and Imaging Sciences, NIH Clinical Center, Bethesda, MD. FAU - Pickhardt, Perry J AU - Pickhardt PJ AD - Department of Radiology, University of Wisconsin School of Medicine and Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252. AD - Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI. LA - eng PT - Journal Article DEP - 20240904 PL - United States TA - AJR Am J Roentgenol JT - AJR. American journal of roentgenology JID - 7708173 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - AJR Am J Roentgenol. 2024 Dec;223(6):e2432045. doi: 10.2214/AJR.24.32045. PMID: 39291948 CIN - AJR Am J Roentgenol. 2024 Dec;223(6):e2432063. doi: 10.2214/AJR.24.32063. PMID: 39320356 MH - Humans MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Middle Aged MH - Retrospective Studies MH - *Body Composition/drug effects MH - *Tomography, X-Ray Computed/methods MH - *Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/agonists MH - Obesity/drug therapy MH - Adult MH - Semaglutide OTO - NOTNLM OT - CT OT - artificial intelligence OT - diabetes OT - glucagon-like peptide-1 receptor agonist OT - semaglutide EDAT- 2024/09/04 18:42 MHDA- 2025/01/07 00:21 CRDT- 2024/09/04 12:22 PHST- 2025/01/07 00:21 [medline] PHST- 2024/09/04 18:42 [pubmed] PHST- 2024/09/04 12:22 [entrez] AID - 10.2214/AJR.24.31805 [doi] PST - ppublish SO - AJR Am J Roentgenol. 2024 Dec;223(6):e2431805. doi: 10.2214/AJR.24.31805. Epub 2024 Sep 4. PMID- 39223865 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Beneficial effect of oral semaglutide for type 2 diabetes mellitus in patients with metabolic dysfunction-associated steatotic liver disease: A prospective, multicentre, observational study. PG - 4958-4965 LID - 10.1111/dom.15898 [doi] AB - AIMS: To evaluate the efficacy and safety of oral semaglutide for type 2 diabetes mellitus (T2DM) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). MATERIALS AND METHODS: This was a single-arm, multicentre, prospective study. Among 80 consecutive patients with MASLD and T2DM who newly received oral semaglutide, 70 completed 48-week oral semaglutide treatment as scheduled and were included in an efficacy analysis. Dose adjustments of oral semaglutide were determined by each physician while monitoring efficacy and adverse events. RESULTS: Significant improvements in body weight, liver enzymes, lipid profile, and glycaemic control were found at 48 weeks compared with baseline values (all p < 0.01). Controlled attenuation parameter values significantly decreased from baseline to 48 weeks (p < 0.01). Changes in alanine aminotransferase concentrations (r = 0.37, p < 0.01) and controlled attenuation parameter values (r = 0.44, p < 0.01) were significantly correlated with changes in body weight. Liver fibrosis markers, such as type IV collagen 7S, Wisteria floribunda agglutinin-positive Mac-2-binding protein, fibrosis-4 index, and liver stiffness measurement, significantly decreased from baseline to 48 weeks (all p < 0.01). The most common adverse events were Grades 1-2 transient gastrointestinal symptoms, such as nausea (23 patients, 28.8%), dyspepsia (12, 15.0%) and appetite loss (4, 5.0%). CONCLUSIONS: Oral semaglutide treatment for T2DM in patients with MASLD leads to an improvement in liver steatosis and injury, surrogate markers of fibrosis, diabetic status, and lipid profile, and reduces body weight. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Arai, Taeang AU - Arai T AD - Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan. FAU - Atsukawa, Masanori AU - Atsukawa M AUID- ORCID: 0000-0003-3374-7111 AD - Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan. FAU - Tsubota, Akihito AU - Tsubota A AD - Core Research Facilities for Basic Science, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan. FAU - Oikawa, Tsunekazu AU - Oikawa T AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. FAU - Tada, Toshifumi AU - Tada T AD - Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan. FAU - Matsuura, Kentaro AU - Matsuura K AD - Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. FAU - Ishikawa, Toru AU - Ishikawa T AD - Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan. FAU - Abe, Hiroshi AU - Abe H AD - Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba, Japan. FAU - Kato, Keizo AU - Kato K AD - Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba, Japan. FAU - Morishita, Asahiro AU - Morishita A AD - Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan. FAU - Tani, Joji AU - Tani J AD - Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, Japan. FAU - Okubo, Tomomi AU - Okubo T AD - Division of Gastroenterology, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan. FAU - Nagao, Mototsugu AU - Nagao M AD - Division of Endocrinology, Diabetes and Metabolism, Nippon Medical School, Tokyo, Japan. FAU - Iwabu, Masato AU - Iwabu M AD - Division of Endocrinology, Diabetes and Metabolism, Nippon Medical School, Tokyo, Japan. FAU - Iwakiri, Katsuhiko AU - Iwakiri K AD - Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20240902 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - Male MH - Female MH - Middle Aged MH - Prospective Studies MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - Fatty Liver/drug therapy/complications MH - Treatment Outcome MH - Non-alcoholic Fatty Liver Disease/drug therapy/complications MH - Adult MH - Blood Glucose/drug effects/metabolism MH - Glycated Hemoglobin/analysis/drug effects/metabolism MH - Semaglutide OTO - NOTNLM OT - clinical trial OT - diabetes complications OT - effectiveness OT - liver EDAT- 2024/09/03 06:43 MHDA- 2024/10/04 12:43 CRDT- 2024/09/03 02:03 PHST- 2024/08/04 00:00 [revised] PHST- 2024/06/17 00:00 [received] PHST- 2024/08/08 00:00 [accepted] PHST- 2024/10/04 12:43 [medline] PHST- 2024/09/03 06:43 [pubmed] PHST- 2024/09/03 02:03 [entrez] AID - 10.1111/dom.15898 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):4958-4965. doi: 10.1111/dom.15898. Epub 2024 Sep 2. PMID- 39222642 OWN - NLM STAT- MEDLINE DCOM- 20240907 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 404 IP - 10456 DP - 2024 Sep 7 TI - Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. PG - 949-961 LID - S0140-6736(24)01643-X [pii] LID - 10.1016/S0140-6736(24)01643-X [doi] AB - BACKGROUND: Heart failure with mildly reduced or preserved ejection fraction (hereafter referred to as HFpEF) is the most common type of heart failure and is associated with a high risk of hospitalisation and death, especially in patients with overweight, obesity, or type 2 diabetes. In the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide improved heart failure-related symptoms and physical limitations in participants with HFpEF. Whether semaglutide also reduces clinical heart failure events in this group remains to be established. METHODS: We conducted a post-hoc pooled, participant-level analysis of four randomised, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) to examine the effects of once-weekly subcutaneous semaglutide (2.4 mg in SELECT, STEP-HFpEF, and STEP-HFpEF DM; 1.0 mg in FLOW) on heart failure events. The STEP-HFpEF and STEP-HFpF DM trials enrolled participants with obesity-related HFpEF, the SELECT trial enrolled participants with atherosclerotic cardiovascular disease and overweight or obesity, and the FLOW trial enrolled participants with type 2 diabetes and chronic kidney disease. Hence, for this analysis, we include all participants from the STEP-HFpEF trials and those with an investigator-reported history of HFpEF from SELECT and FLOW. The main outcomes for this analysis were the composite endpoint of time to cardiovascular death or first worsening heart failure event (defined as hospitalisation or urgent visit due to heart failure), time to first worsening heart failure event, and time to cardiovascular death. Efficacy and safety endpoints were analysed with the full analysis set (ie, all participants randomly assigned to treatment, according to the intention-to-treat principle). The SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM trials are registered at ClinicalTrials.gov, NCT03574597, NCT03819153, NCT04788511, and NCT04916470, respectively, and all are complete. FINDINGS: Across the four trials, 3743 (16.8%) of 22 282 participants had a history of HFpEF (1914 assigned to semaglutide and 1829 assigned to placebo). In this group of participants with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or heart failure events (103 [5.4%] of 1914 in the semaglutide group had events vs 138 [7.5%] of 1829 in the placebo group; hazard ratio [HR] 0.69 [95% CI 0.53-0.89]; p=0.0045). Semaglutide also reduced the risk of worsening heart failure events (54 [2.8%] vs 86 [4.7%]; HR 0.59 [0.41-0.82]; p=0.0019). No significant effect on cardiovascular death alone was seen (59 [3.1%] vs 67 [3.7%]; HR 0.82 [0.57-1.16]; p=0.25). A lower proportion of patients treated with semaglutide had serious adverse events than did those who were treated with placebo (572 [29.9%] vs 708 [38.7%]). INTERPRETATION: In patients with HFpEF, semaglutide reduced the risk of the combined endpoint of cardiovascular death or worsening heart failure events, and worsening heart failure events alone, whereas its effect on cardiovascular death alone was not significant. These data support the use of semaglutide as an efficacious therapy to reduce the risk of clinical heart failure events in patients with HFpEF, for whom few treatment options are currently available. FUNDING: Novo Nordisk. CI - Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. Electronic address: mkosiborod@saint-lukes.org. FAU - Deanfield, John AU - Deanfield J AD - Institute of Cardiovascular Science, University College London, London, UK. FAU - Pratley, Richard AU - Pratley R AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Borlaug, Barry A AU - Borlaug BA AD - Mayo Clinic, Rochester, MN, USA. FAU - Butler, Javed AU - Butler J AD - Baylor Scott & White Research Institute, Dallas, TX, USA; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, UK; National Institute for Health Research Leicester Biomedical Research Centre, Leicester, UK. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle, WA, USA. FAU - Kahn, Steven E AU - Kahn SE AD - Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA; University of Washington, Seattle, WA, USA. FAU - Kitzman, Dalane W AU - Kitzman DW AD - Wake Forest University School of Medicine, Winston-Salem, NC, USA. FAU - Lingvay, Ildiko AU - Lingvay I AD - University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Stanford School of Medicine, Palo Alto, CA, USA. FAU - Petrie, Mark C AU - Petrie MC AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Plutzky, Jorge AU - Plutzky J AD - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk, Soborg, Denmark. FAU - Ronnback, Cecilia AU - Ronnback C AD - Novo Nordisk, Soborg, Denmark. FAU - Shah, Sanjiv J AU - Shah SJ AD - Northwestern University Feinberg School of Medicine, Chicago, IL, USA. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada. FAU - Weeke, Peter E AU - Weeke PE AD - Novo Nordisk, Soborg, Denmark. FAU - Lincoff, A Michael AU - Lincoff AM AD - Department of Cardiovascular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA. CN - SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM Trial Committees and Investigators LA - eng SI - ClinicalTrials.gov/NCT04916470 SI - ClinicalTrials.gov/NCT03574597 SI - ClinicalTrials.gov/NCT03819153 SI - ClinicalTrials.gov/NCT04788511 GR - U01 AG076928/AG/NIA NIH HHS/United States GR - P30 AG021332/AG/NIA NIH HHS/United States GR - U01 HL160272/HL/NHLBI NIH HHS/United States GR - R01 AG018915/AG/NIA NIH HHS/United States GR - R01 AG078153/AG/NIA NIH HHS/United States GR - U24 AG059624/AG/NIA NIH HHS/United States GR - R01 AG045551/AG/NIA NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20240830 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet. 2024 Sep 7;404(10456):909-911. doi: 10.1016/S0140-6736(24)01763-X. PMID: 39222643 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - *Heart Failure/drug therapy/mortality MH - Hospitalization/statistics & numerical data MH - Obesity/drug therapy MH - *Stroke Volume MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Semaglutide COIS- Declaration of interests MNK has served as a consultant for 35Pharma, Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Corcept Therapeutics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, Regeneron, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; has served on a data monitoring board for Applied Therapeutics; has served on an advisory board for Alnylam, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Eli Lilly, Esperion Therapeutics, Merck (Diabetes and Cardiovascular), Novo Nordisk, and Sanofi; has received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer; holds stocks in Artera Health and Saghmos Therapeutics; has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and has received support for data analyses from AstraZeneca and Vifor. JD has received consulting honoraria from Aegerion, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda and research grants from Aegerion, British Heart Foundation, Colgate, UK Medical Research Council, MSD, National Institute for Health and Care Research, Pfizer, Public Health England, and Roche. RP reports speaker fees from Eli Lilly, Lilly USA, and Novo Nordisk; consulting fees from AbbVie, AstraZeneca, Bayer, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui (USA), Intas Pharmaceuticals, Eli Lilly, Lilly USA, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock, and Sun Pharmaceutical Industries; and grants from Biomea Fusion, Carmot Therapeutics, Dompe, Endogenex, Fractyl, Eli Lilly, Novo Nordisk, and Sanofi. All grants are directed to RP's institution. Up to Dec 31, 2023, payment for RP's consultant and speaker services was made directly to his employer, AdventHealth, a nonprofit entity; as of Jan 1, 2024, payment was directed to RP personally. BAB receives research support from the US National Institutes of Health and the US Department of Defense, as well as research grant funding from AstraZeneca, Axon Therapies, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, Rivus, and Tenax Therapeutics; he has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, NGM, Novo Nordisk, NXT, and VADovations; and is named inventor (US patent number 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. JB is a consultant to Abbott, American Regent, Amgen, Applied Therapeutics, AskBio, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiac Dimension, CardioCell, Cardior, CSL Behring, CVRx, Cytokinetics, Daxor, Edwards Lifesciences, Element Science, Faraday, Foundry, G3P, Imbria, Impulse Dynamics, Innolife, Inventiva, Ionis, Levator, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Owkin, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, PharmaIN, Prolaio, Pulnovo, Regeneron, Renibus, Roche, Salamandra, Salubris, Sanofi, scPharmaceuticals, Secretome, Sequana, SQ Innovation, Tenex, Tricog, Ultromics, Vifor, and Zoll. MJD has acted as a consultant, advisory board member, and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi; an advisory board member for AstraZeneca, Carmot/Roche, Medtronic, Pfizer, and Zealand Pharma; and a speaker for Amgen and AstraZeneca; and has received grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, and Sanofi-Aventis. SSE has received consulting fees from Amylyx, AstraZeneca, Avillion, Ayala, Bayer, BeiGene, Boehringer Ingelheim, 89 Bio, BioAge, BioAtla, Bristol Meyer Squibb, BridgeBio, Daiichi Sankyo, Denovo, Fore Therapeutics, GlaxoSmithKline, Inovio, Insmed, Ipsen, Karuna, Lilly, Lundbeck, Mirati, Moderna, Novartis, Novavax, Novo Nordisk, National Surgical Adjuvant Breast and Bowel Project, Pfizer, Principia, Reata, Rebiotx, Roche, Sanofi, solvd, Sutro Biopharma, and TG Therapeutics. SEK received consulting fees from Casma Therapeutics, Oramed, and Third Rock Ventures; and served on an advisory board for AltPep, Anji Pharmaceuticals, Bayer, Boehringer Ingelheim, Eli Lilly, Intarcia, Merck, and Novo Nordisk. He has received stock options from AltPep. DK was supported in part by the Kermit Glenn Phillips II Chair in Cardiovascular Medicine and US National Institutes of Health grants U01AG076928, R01AG078153, R01AG045551, R01AG18915, P30AG021332, U24AG059624, and U01HL160272; and received honoraria as a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, Corvia Medical, Ketyo, Novartis, Novo Nordisk, Pfizer, and Rivus; grant funding from AstraZeneca, Bayer, Novartis, Novo Nordisk, Pfizer, and Rivus; and has stock ownership in Gilead Sciences. IL has received research grants from Boehringer Ingelheim, Merck, Mylan Pharmaceuticals, Novo Nordisk, Pfizer, and Sanofi; served as a consultant for AstraZeneca, Bayer Healthcare Pharmaceuticals, Biomea, Boehringer Ingelheim, Carmot, Eli Lilly, Intarcia, Intercept Pharmaceuticals, Janssen Global Services, Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, MannKind, Merck, Novo Nordisk, Pfizer, Sanofi, Shionogi, Structure Therapeutics, Target Pharma, Valeritas, and Zealand Pharma; and received travel expenses from Boehringer Ingelheim, Eli Lilly, Johnson & Johnson Medical Devices & Diagnostics Group-Latin America, Novo Nordisk, Sanofi, and Zealand Pharma. KWM has received grants from AHA, Apple, Bayer, California Institute for Regenerative Medicine, CSL Behring, Eidos, Ferring, Gilead, Google, Idorsia, Johnson & Johnson, Luitpold, Novartis, PAC-12, Precordior, and Sanifit; and consulting fees from Applied Therapeutics, Bayer, BMS, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, Phasebio, Portola, Quidel, and Theravance; and holds stock options for Human, Medeloop, Precordior, and Regencor. MCP was supported by the British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217; has received research funding from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Medtronic, Novartis, Novo Nordisk, Pharmacosmos, Roche, and SQ Innovations; and served on committees or consulted for AbbVie, Akero, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Cardiorentis, Corvia, Eli Lilly, Horizon Therapeutics, LIB Therapeutics, Moderna, New Amsterdam, Novartis, Novo Nordisk, Pharmacosmos, Siemens, SQ Innovations, Takeda, Teikoku, and Vifor. JP has received consulting fees from Altimmune, Amgen, Esperion Therapeutics, Merck, MJH Life Sciences, Novartis, and Novo Nordisk and received a grant, paid to his institution, from Boehringer Ingelheim. CR, SR, and PEW are employees and SR and PEW are shareholders of Novo Nordisk. SJS has received research grants from AstraZeneca, Corvia, and Pfizer; and consulting fees from Abbott, Alleviant, Amgen, Aria CV, AstraZeneca, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, ReCor, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics. SV reports speaking honoraria or consulting fees from Abbott, Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, and TIMI. AML has received research grants from AbbVie, AstraZeneca, CSL Behring, Eli Lilly, Esperion Therapeutics, and Novartis, paid to his institution; and consulting fees from Akebia Therapeutics, Alnylam Pharmaceuticals, Ardelyx, Eli Lilly, FibroGen, GlaxoSmithKline, Intarcia, Medtronic Vascular, Novartis, Novo Nordisk, Provention Bio, Amgen, and ReCor Medical. All other authors declare no competing interests. EDAT- 2024/09/03 01:42 MHDA- 2024/09/08 13:49 CRDT- 2024/09/02 18:53 PHST- 2024/07/18 00:00 [received] PHST- 2024/08/05 00:00 [revised] PHST- 2024/08/06 00:00 [accepted] PHST- 2024/09/08 13:49 [medline] PHST- 2024/09/03 01:42 [pubmed] PHST- 2024/09/02 18:53 [entrez] AID - S0140-6736(24)01643-X [pii] AID - 10.1016/S0140-6736(24)01643-X [doi] PST - ppublish SO - Lancet. 2024 Sep 7;404(10456):949-961. doi: 10.1016/S0140-6736(24)01643-X. Epub 2024 Aug 30. PMID- 39219442 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Diabetic kidney disease: The fourth pharmacological pillar may be semaglutide. PG - 4813-4815 LID - 10.1111/dom.15892 [doi] FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Endocrine and Metabolic Unit, Department of Advanced Medical and Surgical Sciences, Universita della Campania Luigi Vanvitelli, Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AUID- ORCID: 0000-0002-3652-5154 AD - Endocrine and Metabolic Unit, Department of Advanced Medical and Surgical Sciences, Universita della Campania Luigi Vanvitelli, Naples, Italy. FAU - De Nicola, Luca AU - De Nicola L AD - Nephrologic Unit, Department of Advanced Medical and Surgical Sciences, Universita della Campania Luigi Vanvitelli, Naples, Italy. LA - eng PT - Journal Article DEP - 20240902 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Diabetic Nephropathies/drug therapy MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2024/09/02 08:45 MHDA- 2024/10/04 12:42 CRDT- 2024/09/02 04:03 PHST- 2024/08/01 00:00 [revised] PHST- 2024/07/11 00:00 [received] PHST- 2024/08/05 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/09/02 08:45 [pubmed] PHST- 2024/09/02 04:03 [entrez] AID - 10.1111/dom.15892 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):4813-4815. doi: 10.1111/dom.15892. Epub 2024 Sep 2. PMID- 39219391 OWN - NLM STAT- MEDLINE DCOM- 20240902 LR - 20260127 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 20 IP - 884 DP - 2024 Aug 28 TI - [GLP-1 receptor agonists : impact on diabetic kidney disease]. PG - 1488-1491 LID - 10.53738/REVMED.2024.20.884.1488 [doi] AB - In addition to optimal glycemic control and management of other factors aggravating the pathology (hypertension, dyslipidemia, -obesity), the cornerstone of treatment of diabetic kidney disease (DKD) includes blockers of the renin-angiotensin system, sodium-glucose cotransporter 2 inhibitors or nonsteroidal antagonists of the mineralocorticoid receptor (finerenone). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended in the treatment of high-risk patients with type 2 diabetes (T2DM) to reduce cardiovascular (CV) risk. Data from CV studies indicate a nephroprotective effect of certain GLP-1 RAs in T2DM patients with DKD. The FLOW study published in May 2024, analyzing the impact of semaglutide vs placebo on renal events as primary outcome, confirms this renal protection of GLP-1 RAs. FAU - Wera, Madeleine AU - Wera M AD - Service de diabetologie, nutrition et maladies metaboliques, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. FAU - Paquot, Nicolas AU - Paquot N AUID- ORCID: 0000-0001-7923-2098 AD - Service de diabetologie, nutrition et maladies metaboliques, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. LA - fre PT - English Abstract PT - Journal Article TT - Agonistes des recepteurs du GLP-1 : -impact sur la maladie renale diabetique. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetic Nephropathies/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptides/therapeutic use/pharmacology MH - Cardiovascular Diseases/prevention & control MH - Renin-Angiotensin System/drug effects/physiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- N. Paquot est coinvestigateur principal pour le CHU de Liege dans l'essai SURPASS-CVOT et declare avoir recu des honoraires comme orateur et/ou membre d'un conseil scientifique de la part des firmes AstraZeneca, Boehringer Ingelheim, Lilly, NovoNordisk, Fresenius et Sanofi. EDAT- 2024/09/02 08:46 MHDA- 2024/09/02 08:47 CRDT- 2024/09/02 03:52 PHST- 2024/09/02 08:47 [medline] PHST- 2024/09/02 08:46 [pubmed] PHST- 2024/09/02 03:52 [entrez] AID - RMS0884-009 [pii] AID - 10.53738/REVMED.2024.20.884.1488 [doi] PST - ppublish SO - Rev Med Suisse. 2024 Aug 28;20(884):1488-1491. doi: 10.53738/REVMED.2024.20.884.1488. PMID- 39218393 OWN - NLM STAT- MEDLINE DCOM- 20241122 LR - 20260312 IS - 1523-1755 (Electronic) IS - 0085-2538 (Linking) VI - 106 IP - 6 DP - 2024 Dec TI - A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease. PG - 1170-1180 LID - S0085-2538(24)00629-X [pii] LID - 10.1016/j.kint.2024.08.023 [doi] AB - Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m(2) and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 mug, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).The co-primary endpoints were absolute and percentage change versus placebo in UACR from baseline to the end of week 14. Among 248 randomized patients, mean age 67.1 years, 19% were female, mean eGFR was 55.3 mL/min per 1.73 m(2), geometric mean was UACR 205.5 mg/g (coefficient of variation 270.0), and 46.8% were receiving concomitant sodium-glucose co-transporter 2 inhibitors. Cotadutide dose-dependently reduced UACR from baseline to the end of week 14, reaching significance at 300 mug (-43.9% [95% confidence interval -54.7 to -30.6]) and 600 mug (-49.9% [-59.3 to -38.4]) versus placebo; with effects sustained at week 26. Serious adverse events were balanced across arms. Safety and tolerability of cotadutide 600 mug were comparable to semaglutide. Thus, our study shows that in patients with T2D and CKD, cotadutide significantly reduced UACR on top of standard of care with an acceptable tolerability profile, suggesting kidney protective benefits that need confirmation in a larger study. CI - Copyright (c) 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. FAU - Selvarajah, Viknesh AU - Selvarajah V AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Robertson, Darren AU - Robertson D AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Hansen, Lars AU - Hansen L AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Jermutus, Lutz AU - Jermutus L AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Smith, Kirsten AU - Smith K AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Coggi, Angela AU - Coggi A AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Sanchez, Jose AU - Sanchez J AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Chang, Yi-Ting AU - Chang YT AD - Oncology Biometrics, late Oncology R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Yu, Hongtao AU - Yu H AD - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Parkinson, Joanna AU - Parkinson J AD - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. FAU - Khan, Anis AU - Khan A AD - Clinical Pharmacology & Quantitative Pharmacology, Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Chung, H Sophia AU - Chung HS AD - Dynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Hess, Sonja AU - Hess S AD - Dynamic Omics, Centre for Genomics Research, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, USA. FAU - Dumas, Richard AU - Dumas R AD - CISSS Laval, Medecine Department, Endocrinology Division, Laval, Quebec, Canada; Centre de recherches cliniques de Laval, Laval, Quebec, Canada. FAU - Duck, Tabbatha AU - Duck T AD - Division of Nephrology, Clinical Research Solutions, Waterloo, Ontario, Canada. FAU - Jolly, Simran AU - Jolly S AD - Department of Arts and Science, McMaster University, Hamilton, Ontario, Canada. FAU - Elliott, Tom G AU - Elliott TG AD - BC Diabetes, Vancouver, British Columbia, Canada. FAU - Baker, John AU - Baker J AD - Aoteoroa Clinical Trials, Middlemore Hospital, Auckland, New Zealand. FAU - Lecube, Albert AU - Lecube A AD - Endocrinology and Nutrition Department, Arnau de Vilanova University Hospital and Obesity, Diabetes and Metabolism (ODIM) Research Group, Institut de Recerca Biomedica de Lleida, University of Lleida, Lleida, Catalonia, Spain. FAU - Derwahl, Karl-Michael AU - Derwahl KM AD - Institute for Clinical Research and Development, Practise of Endocrinology, Berlin, Germany. FAU - Scott, Russell AU - Scott R AD - Clinical Research Ltd., Christchurch, New Zealand. FAU - Morales, Cristobal AU - Morales C AD - CardioRenalMetabolic Health Unit, Vithas Hospital, Seville, Spain. FAU - Peters, Carl AU - Peters C AD - Diabetes Services, Te Whatu Ora Waitemata, Auckland, New Zealand. FAU - Goldenberg, Ronald AU - Goldenberg R AD - LMC Diabetes & Endocrinology, Vaughan, Ontario, Canada. FAU - Parker, Victoria E R AU - Parker VER AD - Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AD - Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; The George Institute for Global Health, Sydney, Australia. Electronic address: h.j.lambers.heerspink@umcg.nl. CN - study investigators LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240831 PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Glucagon) RN - AYI8EX34EU (Creatinine) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - QL6A9B13HW (cotadutide) SB - IM MH - Humans MH - Female MH - Male MH - Aged MH - *Diabetic Nephropathies/drug therapy/diagnosis MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - *Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/adverse effects MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - Treatment Outcome MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Albuminuria/drug therapy/urine/diagnosis MH - Kidney/drug effects/physiopathology MH - Glucagon-Like Peptide 1/agonists/analogs & derivatives MH - Receptors, Glucagon/agonists MH - Creatinine/urine/blood MH - Peptides MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - chronic kidney disease OT - cotadutide OT - diabetic kidney disease OT - type 2 diabetes mellitus EDAT- 2024/09/02 08:44 MHDA- 2024/11/23 11:12 CRDT- 2024/09/01 19:30 PHST- 2024/04/19 00:00 [received] PHST- 2024/08/05 00:00 [revised] PHST- 2024/08/15 00:00 [accepted] PHST- 2024/11/23 11:12 [medline] PHST- 2024/09/02 08:44 [pubmed] PHST- 2024/09/01 19:30 [entrez] AID - S0085-2538(24)00629-X [pii] AID - 10.1016/j.kint.2024.08.023 [doi] PST - ppublish SO - Kidney Int. 2024 Dec;106(6):1170-1180. doi: 10.1016/j.kint.2024.08.023. Epub 2024 Aug 31. PMID- 39217553 OWN - NLM STAT- MEDLINE DCOM- 20241017 LR - 20260127 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 84 IP - 17 DP - 2024 Oct 22 TI - Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial. PG - 1615-1628 LID - S0735-1097(24)08116-6 [pii] LID - 10.1016/j.jacc.2024.08.004 [doi] AB - BACKGROUND: People with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent >/=50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m(2), kidney replacement therapy, and kidney or CV death) by 24%. OBJECTIVES: This prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population. METHODS: Participants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee. RESULTS: A total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV death (HR: 0.73; 95% CI: 0.62-0.87; P = 0.0005), HF events alone (HR: 0.73; 95% CI: 0.58-0.92; P = 0.0068), and CV death alone (HR: 0.71; 95% CI: 0.56-0.89; P = 0.0036). The risk reduction for the composite HF outcome was similar in those with (HR: 0.73; 95% CI: 0.54-0.98; P = 0.0338) and without (HR: 0.72; 95% CI: 0.58-0.89; P = 0.0028) HF at baseline. The risk of HF outcomes (HF events or CV death) was generally higher in participants categorized as NYHA functional class III and those with the HF reduced ejection fraction subtype, regardless of treatment. CONCLUSIONS: Semaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV death alone, in a high-risk population with T2D and CKD. These effects were consistent regardless of history of HF. (A Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153). CI - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. Electronic address: Richard.pratley.md@adventhealth.com. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Providence Inland Northwest Health, Spokane, Washington, USA; University of Washington School of Medicine, Seattle, Washington, USA. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Perkovic, Vlado AU - Perkovic V AD - University of New South Wales, Sydney, New South Wales, Australia. FAU - Nielsen, Olav Wendelboe AU - Nielsen OW AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Centre, Munich, Germany; University Hospital, Friedrich-Alexander University, Erlangen, Germany. FAU - MacIsaac, Richard J AU - MacIsaac RJ AD - Department of Endocrinology and Diabetes, St Vincent's Hospital Melbourne, Melbourne, Victoria, Australia; Department of Medicine, Fitzroy, Victoria and Australian Centre for Accelerating Diabetes Innovations, University of Melbourne, Parkville, Victoria, Australia. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. FAU - Kamenov, Zdravko AU - Kamenov Z AD - Alexandrovska University Hospital, Medical University of Sofia, Sofia, Bulgaria. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hansen, Marco Bo AU - Hansen MB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hadjadj, Samy AU - Hadjadj S AD - l'Institut du Thorax, Nantes Universite, Centre Hospitalier Universitaire Nantes, Centre National de la Recherche Scientifique, Institut National de la Sante et de la Recherche Medicale, Nantes, France. FAU - Bakris, George AU - Bakris G AD - Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, Illinois, USA. FAU - Baeres, Florian M M AU - Baeres FMM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, California, USA. CN - FLOW Trial Committees and Investigators LA - eng SI - ClinicalTrials.gov/NCT03819153 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20240830 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - *Heart Failure/drug therapy/mortality MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Female MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Middle Aged MH - Aged MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Double-Blind Method MH - Semaglutide OTO - NOTNLM OT - chronic kidney disease OT - heart failure OT - outcomes OT - semaglutide OT - type 2 diabetes COIS- Funding Support and Author Disclosures The FLOW trial was funded by Novo Nordisk A/S. Dr Pratley has received speaker fees paid to his employer, AdventHealth (through December 31, 2023) from Eli Lilly, Lilly USA LLC, and Novo Nordisk; has received consulting fees directed to his institution from AbbVie, AstraZeneca, Bayer AG, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui (USA) Ltd, Intas Pharmaceuticals, Eli Lilly, Lilly USA LLC, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock, and Sun Pharmaceutical Industries; has received grants directed to his institution from Biomea Fusion, Carmot Therapeutics, Dompe, Endogenex, Fractyl, Eli Lilly, Novo Nordisk, and Sanofi; and has received personal fees (from January 1, 2024) from AdventHealth, a nonprofit entity. Dr Tuttle has received support from National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, and OT2OD032581, and from Centers for Disease Control and Prevention project numbers 75D301-21-P-12254 and 75D301-23-C-18264; has received investigator-initiated grant support from Travere, Bayer, and the Doris Duke Foundation outside of the submitted work; has received consulting fees from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; and has received speaker fees from Novo Nordisk. Dr Rossing has received grants from Bayer, AstraZeneca, and Novo Nordisk; has received honoraria paid to the Steno Diabetes Centre Copenhagen from AstraZeneca, Astellas, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi, and Bayer; and has received consulting fees from AstraZeneca, Astellas, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi, and Bayer. Dr Perkovic has received honoraria for steering committee, data monitoring committee, or advisory board roles or for scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, GSK, Janssen, Novo Nordisk, Novartis, Otsuka, Travere, Tricida, and UptoDate; and is Board Director for George Clinical, St Vincent's Health Australia and several independent medical research institutes. Dr Mann has received grants from Novo Nordisk, the European Union, and McMaster University, Hamilton, Canada; has received consulting fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; has received honoraria from Novo Nordisk, AstraZeneca, Bayer, and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi, and Boehringer Ingelheim, as well as a leadership role in the Kidney Disease: Improving Global Outcomes group. Dr MacIsaac was a FLOW trial investigator and member of the FLOW global expert panel; has received research grants from Novo Nordisk, Servier, Medtronic, The Rebecca Cooper Medical Research Foundation, St Vincent's Research Foundation, The Juvenile Diabetes Research Foundation, Grey Innovations, The Diabetes Australia Research Trust/Program, and The National Health and Medical Research Council of Australia; has received honoraria for lectures from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, MSD, Novartis, and Boehringer Ingelheim; has been on the advisory boards for Novo Nordisk, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, AstraZeneca, and MSD; has received travel support from Novo Nordisk, Sanofi, Boehringer Ingelheim, and AstraZeneca; and has been a principal investigator for industry-sponsored clinical trials run by Novo Nordisk, Sanofi, Bayer, Johnson-Cilag, and AbbVie. Dr Kosiborod has received research grant support from AstraZeneca and Boehringer Ingelheim; has served as a consultant or on an advisory board for Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, and Vifor Pharma; has received other research support from AstraZeneca; and has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Kamenov has received speaker fees from Actavis, AstraZeneca, Bayer-Schering, Berlin Chemie, Boehringer Ingelheim, Eli Lilly, KRKA, Merck, MLD, MSD (Merck), Mundipharma, Mylan, Novartis, Novo Nordisk, Pfizer, Sandoz, Sanofi, Servier, TEVA Pharmaceuticals, Valentis, Vedra, and Viatris. Dr Hadjadj has received grants from Asdia, Asten, AstraZeneca, Homeperf, LVL, Nestle Home Care, Pierre Fabre, and VitalAire; has received consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi, Servier, and Valbiotis; has received speaker fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bayer, Dino Sante, Eli Lilly, Novartis, Novo Nordisk, Pierre Fabre, Sanofi, Servier, and Valbiotis; and has received meeting invitations from AstraZeneca, Abbott, Dino Sante, Eli Lilly, and Novo Nordisk. Dr Bakris has received consulting fees from Bayer, KBP Biosciences, Ionis, Alnylam, AstraZeneca, Quantum Genomics, Novo Nordisk, and Dia Medica Therapeutics. Dr Mahaffey has received grants from the American Heart Association, Apple, Bayer, California Institute Regenerative Medicine, CSL Behring, Eidos, Ferring, Gilead, Google (Verify), Idorsia, Johnson and Johnson, Luitpold, Novartis, PAC-12, Precordior, and Sanifit; and has received consulting fees from Applied Therapeutics, Bayer, Bristol Myers Squibb, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson and Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, PhaseBio, Portola, Quidel, and Theravance; and holds equity in Human, Medeloop, Precordior and Regencor. Drs Rasmussen, Nielsen, Idorn, Hansen, and Baeres are employees of and shareholders in Novo Nordisk. EDAT- 2024/09/01 16:19 MHDA- 2024/10/17 10:20 CRDT- 2024/09/01 10:33 PHST- 2024/07/13 00:00 [received] PHST- 2024/08/05 00:00 [revised] PHST- 2024/08/09 00:00 [accepted] PHST- 2024/10/17 10:20 [medline] PHST- 2024/09/01 16:19 [pubmed] PHST- 2024/09/01 10:33 [entrez] AID - S0735-1097(24)08116-6 [pii] AID - 10.1016/j.jacc.2024.08.004 [doi] PST - ppublish SO - J Am Coll Cardiol. 2024 Oct 22;84(17):1615-1628. doi: 10.1016/j.jacc.2024.08.004. Epub 2024 Aug 30. PMID- 39211948 OWN - NLM STAT- MEDLINE DCOM- 20250324 LR - 20260127 IS - 1522-9645 (Electronic) IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 46 IP - 12 DP - 2025 Mar 24 TI - Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial. PG - 1096-1108 LID - 10.1093/eurheartj/ehae613 [doi] AB - BACKGROUND AND AIMS: In the FLOW trial, semaglutide reduced the risks of kidney and cardiovascular (CV) outcomes and death in participants with type 2 diabetes and chronic kidney disease (CKD). These prespecified analyses assessed the effects of semaglutide on CV outcomes and death by CKD severity. METHODS: Participants were randomized to subcutaneous semaglutide 1 mg or placebo weekly. The main outcome was a composite of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke (CV death/MI/stroke) as well as death due to any cause by baseline CKD severity. CKD was categorized by estimated glomerular filtration rate < or >/=60 mL/min/1.73 m2, urine albumin-to-creatinine ratio < or >/=300 mg/g, or Kidney Disease Improving Global Outcomes (KDIGO) risk classification. RESULTS: Three thousand, five hundred and thirty-three participants were randomized with a median follow-up of 3.4 years. Low/moderate KDIGO risk was present in 242 (6.8%), while 878 (24.9%) had high and 2412 (68.3%) had very high KDIGO risk. Semaglutide reduced CV death/MI/stroke by 18% [hazard ratio (HR) 0.82 (95% confidence interval 0.68-0.98); P = .03], with consistency across estimated glomerular filtration rate categories, urine albumin-to-creatinine ratio levels, and KDIGO risk classification (all P-interaction > .13). Death due to any cause was reduced by 20% [HR 0.80 (0.67-0.95); P = .01], with consistency across estimated glomerular filtration rate categories and KDIGO risk class (P-interaction .21 and .23, respectively). The P-interaction treatment effect for death due to any cause by urine albumin-to-creatinine ratio was .01 [<300 mg/g HR 1.17 (0.83-1.65); >/=300 mg/g HR 0.70 (0.57-0.85)]. CONCLUSIONS: Semaglutide significantly reduced the risk of CV death/MI/stroke regardless of baseline CKD severity in participants with type 2 diabetes. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, 300 Pasteur Drive, Grant S-102, Stanford, Palo Alto, CA 94305, USA. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Division of Nephrology, University of Washington School of Medicine, Seattle, WA, USA. AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA. FAU - Arici, Mustafa AU - Arici M AD - Department of Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey. FAU - Baeres, Florian M M AU - Baeres FMM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bakris, George AU - Bakris G FAU - Charytan, David M AU - Charytan DM AD - Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA. FAU - Cherney, David Z I AU - Cherney DZI AD - Division of Nephrology, University of Toronto, Toronto, ON, Canada. FAU - Chernin, Gil AU - Chernin G AD - Kaplan Medical Center, Hebrew University of Jerusalem, Rehovot, Israel. FAU - Correa-Rotter, Ricardo AU - Correa-Rotter R AD - National Institute of Medical Sciences and Nutrition, Salvador Zubiran, Mexico City, Mexico. FAU - Gumprecht, Janusz AU - Gumprecht J AD - Department of Clinical and Molecular Medicine, Medical University of Silesia, Katowice, Poland. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Pugliese, Giuseppe AU - Pugliese G AUID- ORCID: 0000-0003-1574-0397 AD - Department of Clinical and Molecular Medicine, La Sapienza University, Rome, Italy. FAU - Rasmussen, Ida Kirstine Bull AU - Rasmussen IKB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Sokareva, Ekaterina AU - Sokareva E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Centre, Munich, Germany. AD - Department of Nephrology, Hypertension and Rheumatology, University Hospital, Friedrich-Alexander University, Erlangen, Germany. FAU - Perkovic, Vlado AU - Perkovic V AD - Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. FAU - Pratley, Richard AU - Pratley R AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, FL, USA. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - doi: 10.1093/eurheartj/ehae744 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications/mortality MH - Male MH - *Renal Insufficiency, Chronic/complications/mortality/drug therapy MH - Female MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Aged MH - *Cardiovascular Diseases/mortality/prevention & control MH - Glomerular Filtration Rate MH - Double-Blind Method MH - *Diabetic Nephropathies/drug therapy/mortality MH - Treatment Outcome MH - Stroke/mortality/prevention & control MH - Myocardial Infarction/mortality/prevention & control MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11931213 OTO - NOTNLM OT - Cardiovascular outcomes OT - Chronic kidney disease OT - Semaglutide OT - Type 2 diabetes EDAT- 2024/08/31 09:46 MHDA- 2025/03/24 06:30 PMCR- 2024/08/30 CRDT- 2024/08/30 04:32 PHST- 2024/07/01 00:00 [received] PHST- 2024/08/09 00:00 [revised] PHST- 2024/08/22 00:00 [accepted] PHST- 2025/03/24 06:30 [medline] PHST- 2024/08/31 09:46 [pubmed] PHST- 2024/08/30 04:32 [entrez] PHST- 2024/08/30 00:00 [pmc-release] AID - 7745056 [pii] AID - ehae613 [pii] AID - 10.1093/eurheartj/ehae613 [doi] PST - ppublish SO - Eur Heart J. 2025 Mar 24;46(12):1096-1108. doi: 10.1093/eurheartj/ehae613. PMID- 39205685 OWN - NLM STAT- MEDLINE DCOM- 20240829 LR - 20261019 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - The effectiveness of 0.5 mg and 1mg of semaglutide in patients with type two diabetes and predictors of response: a retrospective cohort study. PG - 1395651 LID - 10.3389/fendo.2024.1395651 [doi] LID - 1395651 AB - BACKGROUND: Semaglutide is a glucagon-like peptide-1 receptor agonists (GLP-1-RAs) approved for the treatment of type 2 diabetes mellitus (T2DM) at doses up to 1 mg. The results from randomized control trials and real-world studies revealed that weekly semaglutide was associated with significant improvements in HbA1c and body weight. To our knowledge, no study assessed the effectiveness of using semaglutide for patients with T2DM in the Saudi population. We aim to assess the effectiveness of once weekly SC 0.5 and 1 mg of semaglutide on HbA1c and weight reduction in patients with T2DM in the Saudi population within 12 months of use, evaluate the predictors of response, and compare the effect of the two doses. METHOD: This is a retrospective cohort study conducted at Security Force Hospital in Riyadh, Saudi Arabia. Using electronic medical records of patients with type two diabetes who received semaglutide 0.5 or 1 mg for a total duration of at least 12 months of use. RESULTS: Within the study period of semaglutide use, HbA1c significantly decreased from baseline by -2.1% (-2.3 to -1.91, 95% CI) (P <0.001). While the mean change in weight was -6.19 kg (-6.66 to -5.72, 95% CI) (P<0.001). Moreover, BMI, FBG, total cholesterol, LDL, and TG all decreased significantly from baseline (p<0.001). When comparing the sub-groups of 0.5 and 1 mg doses, although results were numerically favorable of 1 mg, there were no statistically significant differences in HbA1c % (-2.1 +/- 1.8 vs. -2.1 +/- 1.9, p-value= 0.934, respectively), and weight (-6.1 +/- 5 vs. -6.2 +/- 4.4 kg, p-value=0.837, respectively). Significant predictors of HbA1c reduction were the duration of DM, baseline HbA1c, and insulin therapy. While the significant predictor for weight reduction was insulin therapy. CONCLUSION: This study is document the effectiveness of once-weekly SC semaglutide on glycemic control and weight loss in real-world practice. We recommend a starting goal dose of 0.5 mg and gradual increase of dose based individual patient response. further studies are needed to assess the effectiveness and tolerability of various semagltude doses. CI - Copyright (c) 2024 Alenzi, Alzahrani, Aljaloud, Alanazi and Alarfaj. FAU - Alenzi, Sara AU - Alenzi S AD - Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia. FAU - Alzahrani, Abdullah AU - Alzahrani A AD - Department of Pharmaceutical Services, Security Forces Hospital Program, Riyadh, Saudi Arabia. FAU - Aljaloud, Afnan AU - Aljaloud A AD - Department of Pharmaceutical Services, Security Forces Hospital Program, Riyadh, Saudi Arabia. FAU - Alanazi, Kamayel AU - Alanazi K AD - Department of Pharmaceutical Services, Security Forces Hospital Program, Riyadh, Saudi Arabia. FAU - Alarfaj, Sumaiah J AU - Alarfaj SJ AD - Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240814 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Glycated Hemoglobin/analysis MH - Saudi Arabia/epidemiology MH - Adult MH - Aged MH - Treatment Outcome MH - Blood Glucose/drug effects/analysis MH - Cohort Studies MH - Dose-Response Relationship, Drug MH - Weight Loss/drug effects MH - Semaglutide PMC - PMC11349510 OTO - NOTNLM OT - Saudi OT - diabetes mellitus OT - glucagon-like peptide 1 analog OT - obesity OT - ozempic OT - semaglutide COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/08/31 09:49 MHDA- 2024/09/01 16:18 PMCR- 2024/01/01 CRDT- 2024/08/29 04:07 PHST- 2024/03/17 00:00 [received] PHST- 2024/07/08 00:00 [accepted] PHST- 2024/09/01 16:18 [medline] PHST- 2024/08/31 09:49 [pubmed] PHST- 2024/08/29 04:07 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1395651 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Aug 14;15:1395651. doi: 10.3389/fendo.2024.1395651. eCollection 2024. PMID- 39197936 OWN - NLM STAT- MEDLINE DCOM- 20240828 LR - 20260127 IS - 1756-1833 (Electronic) IS - 0959-8138 (Linking) VI - 386 DP - 2024 Aug 28 TI - Semaglutide's CVD indication could cost US Medicare $145bn extra a year. PG - q1878 LID - 10.1136/bmj.q1878 [doi] FAU - Mahase, Elisabeth AU - Mahase E AD - The BMJ. LA - eng PT - News DEP - 20240828 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - United States MH - Humans MH - *Glucagon-Like Peptides/economics/therapeutic use MH - *Medicare/economics MH - *Cardiovascular Diseases/economics/prevention & control/drug therapy MH - Hypoglycemic Agents/economics/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/economics MH - Drug Costs MH - Semaglutide EDAT- 2024/08/31 09:50 MHDA- 2024/08/31 09:51 CRDT- 2024/08/28 20:43 PHST- 2024/08/31 09:51 [medline] PHST- 2024/08/31 09:50 [pubmed] PHST- 2024/08/28 20:43 [entrez] AID - 10.1136/bmj.q1878 [doi] PST - epublish SO - BMJ. 2024 Aug 28;386:q1878. doi: 10.1136/bmj.q1878. PMID- 39188242 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Effect of semaglutide on primary prevention of diabetic kidney disease in people with type 2 diabetes: A post hoc analysis of the SUSTAIN 6 randomized controlled trial. PG - 5157-5166 LID - 10.1111/dom.15860 [doi] AB - AIM: Efficient primary prevention of diabetic kidney disease (DKD) is currently lacking. The identification of people at high DKD risk and timely intervention are key to preventing DKD. Therefore, a model to classify people according to their risk for developing DKD was developed previously and used in the current analysis to assess the effect of semaglutide versus placebo on primary DKD prevention. METHODS: Participants with type 2 diabetes from the randomized, double-blind, placebo-controlled SUSTAIN 6 trial without DKD at baseline who received 0.5/1.0 mg semaglutide or placebo were grouped by baseline DKD risk, calculated using a validated model. The main post hoc outcome was the effect of semaglutide versus placebo on the proportion of participants who developed DKD [urinary albumin/creatinine ratio (UACR) >/=30 mg/g and/or estimated glomerular filtration rate <60 mL/min/1.73 m(2)]. Additional post hoc outcomes included changes in DKD risk score, UACR and estimated glomerular filtration rate over time. RESULTS: Of the total 1139 participants included in the analysis, 28.7% developed DKD; more participants with a high DKD risk (952/1139) developed DKD. Semaglutide significantly reduced the risk of developing DKD in both the total [odds ratio 0.56 (95% confidence interval: 0.42; 0.74; p < 0.0001)], and high DKD risk population [odds ratio 0.51 (95% confidence interval: 0.38; 0.69; p < 0.0001)] and significantly delayed DKD development versus placebo. The beneficial effects of semaglutide were largely driven by UACR changes. The number needed to treat for semaglutide in the high DKD risk population was 7. CONCLUSIONS: This post hoc study indicates that semaglutide may have beneficial effects on primary DKD prevention in people with T2D. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Wang, Jingyu AU - Wang J AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Yang, Juhong AU - Yang J AD - Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-communicable Diseases, Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang, Institute of Nephrology, Endocrinology Department of Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Jiang, Wenhui AU - Jiang W AUID- ORCID: 0000-0001-9629-6878 AD - Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine of Hebei Province, Cangzhou, China. FAU - Liu, Wenyan AU - Liu W AD - Novo Nordisk (China) Pharmaceutical Company, Beijing, China. FAU - Shen, Zewei AU - Shen Z AD - Novo Nordisk (China) Pharmaceutical Company, Beijing, China. FAU - Gao, Zhongai AU - Gao Z AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. FAU - Chang, Baocheng AU - Chang B AUID- ORCID: 0000-0002-6674-6644 AD - NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240827 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Diabetic Nephropathies/prevention & control MH - Double-Blind Method MH - Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Primary Prevention/methods MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - diabetic kidney disease OT - prediction model OT - primary prevention OT - semaglutide OT - type 2 diabetes EDAT- 2024/08/27 09:48 MHDA- 2024/10/04 12:42 CRDT- 2024/08/27 04:03 PHST- 2024/07/03 00:00 [revised] PHST- 2024/04/16 00:00 [received] PHST- 2024/07/12 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/08/27 09:48 [pubmed] PHST- 2024/08/27 04:03 [entrez] AID - 10.1111/dom.15860 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5157-5166. doi: 10.1111/dom.15860. Epub 2024 Aug 27. PMID- 39186788 OWN - NLM STAT- MEDLINE DCOM- 20241014 LR - 20260703 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 177 IP - 10 DP - 2024 Oct TI - Estimating New Eligibility and Maximum Costs of Expanded Medicare Coverage of Semaglutide for Cardiovascular Risk Prevention. PG - 1440-1442 LID - 10.7326/ANNALS-24-00308 [doi] FAU - Chaitoff, Alexander AU - Chaitoff A AD - Center for Healthcare Delivery Sciences, Division of Pharmacoepidemiology, Department of Medicine, Brigham and Women's Hospital, Boston; and Harvard Medical School, Boston, Massachusetts. FAU - Bendicksen, Liam AU - Bendicksen L AD - Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Feldman, William B AU - Feldman WB AD - Harvard Medical School, Boston; Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston; and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Zheutlin, Alexander R AU - Zheutlin AR AD - Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. FAU - Lalani, Hussain S AU - Lalani HS AUID- ORCID: 0000-0002-5972-3997 AD - Harvard Medical School, Boston; and Division of General Internal Medicine and Primary Care, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. LA - eng PT - Letter DEP - 20240827 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - United States MH - *Glucagon-Like Peptides/therapeutic use/economics/adverse effects MH - *Cardiovascular Diseases/prevention & control/economics MH - Hypoglycemic Agents/economics/therapeutic use MH - Medicare/economics MH - Eligibility Determination MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy/prevention & control/economics MH - Heart Disease Risk Factors MH - Semaglutide COIS- Disclosures: Disclosure forms are available with the article online. EDAT- 2024/08/26 19:50 MHDA- 2024/10/14 19:00 CRDT- 2024/08/26 17:02 PHST- 2024/10/14 19:00 [medline] PHST- 2024/08/26 19:50 [pubmed] PHST- 2024/08/26 17:02 [entrez] AID - 10.7326/ANNALS-24-00308 [doi] PST - ppublish SO - Ann Intern Med. 2024 Oct;177(10):1440-1442. doi: 10.7326/ANNALS-24-00308. Epub 2024 Aug 27. PMID- 39181497 OWN - NLM STAT- MEDLINE DCOM- 20241226 LR - 20260825 IS - 1097-6868 (Electronic) IS - 0002-9378 (Linking) VI - 232 IP - 1 DP - 2025 Jan TI - Glucagon-like peptide-1 receptor agonist use in pregnancy: a review. PG - 17-25 LID - S0002-9378(24)00864-0 [pii] LID - 10.1016/j.ajog.2024.08.024 [doi] AB - Glucagon-like peptide-1 receptor agonists are peptide analogues that are used to treat type 2 diabetes mellitus and obesity. The first medication in this class, exenatide, was approved in 2005, and these medications, specifically semaglutide, have become more popular in recent years due to their pronounced effects on glycemic control, weight reduction, and cardiovascular health. Due to successful weight loss from these medications, many women previously diagnosed with oligomenorrhea and unable to conceive have experienced unplanned pregnancies while taking the medications. However, there are currently little data for clinicians to use in counseling patients in cases of accidental periconceptional exposure. In some studies examining small animals exposed to glucagon-like peptide-1 receptor agonists in pregnancy, there has been evidence of adverse outcomes in the offspring, including decreased fetal growth, skeletal and visceral anomalies, and embryonic death. Although there are no prospective studies in humans, case reports, cohort studies, and population-based studies have not shown a pattern of congenital anomalies in infants. A recent large, observational, population-based cohort study examined 938 pregnancies affected by type 2 diabetes mellitus and compared outcomes from periconceptional exposure to glucagon-like peptide-1 receptor agonists and insulin. The authors concluded there was not a significantly increased risk of major congenital malformations in patients taking glucagon-like peptide-1 receptor agonists, although there was no information on maternal glycemic control or diabetic fetopathy. As diabetic embryopathy is directly related to the degree of maternal hyperglycemia and not the diagnosis of diabetes itself, it is not possible to make this conclusion without this information. Furthermore, there is little evidence available regarding fetal growth restriction, embryonic or fetal death, or other potential complications. At this time, patients should be counseled there is not enough evidence to predict any adverse effects, or the lack thereof, of periconceptional exposure of glucagon-like peptide-1 receptor agonists during pregnancy. We recommend that all patients use contraception to prevent unintended pregnancy while taking glucagon-like peptide-1 receptor agonists. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Drummond, Rosa F AU - Drummond RF AD - Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine and Medical Center, Baltimore, MD. Electronic address: rosa.drummond@umm.edu. FAU - Seif, Karl E AU - Seif KE AD - Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine and Medical Center, Baltimore, MD. FAU - Reece, E Albert AU - Reece EA AD - Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine and Medical Center, Baltimore, MD. LA - eng PT - Journal Article PT - Review DEP - 20240823 PL - United States TA - Am J Obstet Gynecol JT - American journal of obstetrics and gynecology JID - 0370476 RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - Female MH - Humans MH - Pregnancy MH - *Abnormalities, Drug-Induced/epidemiology/etiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Exenatide/therapeutic use MH - *Obesity/drug therapy MH - *Pregnancy in Diabetics/drug therapy MH - Pregnancy Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Semaglutide OTO - NOTNLM OT - PCOS OT - abortion OT - diabetic fetopathy OT - dulaglutide OT - embryonic death OT - exenatide OT - fetal anomalies OT - fetal death OT - fetal growth restriction OT - glucagon-like peptide-1 receptor agonists OT - glycemic control OT - hyperglycemia OT - insulin resistance OT - liraglutide OT - lixisenatide OT - major congenital malformations OT - miscarriage OT - obesity OT - periconceptional use OT - semaglutide OT - teratogenicity OT - tirzepatide OT - type 2 diabetes OT - unplanned pregnancy OT - weight loss EDAT- 2024/08/26 12:39 MHDA- 2024/12/27 00:20 CRDT- 2024/08/24 19:29 PHST- 2024/05/08 00:00 [received] PHST- 2024/07/28 00:00 [revised] PHST- 2024/08/14 00:00 [accepted] PHST- 2024/12/27 00:20 [medline] PHST- 2024/08/26 12:39 [pubmed] PHST- 2024/08/24 19:29 [entrez] AID - S0002-9378(24)00864-0 [pii] AID - 10.1016/j.ajog.2024.08.024 [doi] PST - ppublish SO - Am J Obstet Gynecol. 2025 Jan;232(1):17-25. doi: 10.1016/j.ajog.2024.08.024. Epub 2024 Aug 23. PMID- 39175005 OWN - NLM STAT- MEDLINE DCOM- 20240823 LR - 20260127 IS - 1745-6215 (Electronic) IS - 1745-6215 (Linking) VI - 25 IP - 1 DP - 2024 Aug 22 TI - Patient and public involvement and engagement in the ASCEND PLUS trial: reflections from the design of a streamlined and decentralised clinical trial. PG - 554 LID - 10.1186/s13063-024-08393-2 [doi] LID - 554 AB - INTRODUCTION: ASCEND PLUS is a randomised controlled trial assessing the effects of oral semaglutide on the primary prevention of cardiovascular events in around 20,000 individuals with type 2 diabetes in the UK. The trial's innovative design includes a decentralised direct-to-participant invitation, recruitment, and follow-up model, relying on self-completion of online forms or telephone or video calls with research nurses, with no physical sites. Extensive patient and public involvement and engagement (PPIE) was essential to the design and conduct of ASCEND PLUS. AIM: To report the process and conduct of PPIE activity in ASCEND PLUS, evaluate effects on trial design, reflect critically on successes and aspects that could have been improved, and identify themes and learning relevant to implementation of PPIE in future trials. METHODS: PPIE activity was coordinated centrally and included six PPIE focus groups and creation of an ASCEND PLUS public advisory group (PAG) during the design phase. Recruitment to these groups was carefully considered to ensure diversity and inclusion, largely consisting of adults living with type 2 diabetes from across the UK. Two members of the PAG also joined the trial Steering Committee. Steering Committee meetings, focus groups, and PAG meetings were conducted online, with two hybrid workshops to discuss PPIE activity and aspects of the trial. RESULTS: PPIE activity was critical to shaping the design and conduct of ASCEND PLUS. Key examples included supporting choice for participants to either complete the screening/consent process independently online, or during a telephone or video call interview with a research nurse. A concise 'initial information leaflet' was developed to be sent with the initial invitations, with the 'full' information leaflet sent later to those interested in joining the trial. The PAG reviewed the content and format of participant- and public-facing materials, including written documents, online screening forms, animated videos, and the trial website, to aid clarity and accessibility, and provided input into the choice of instruments to assess quality of life. CONCLUSIONS: PPIE is integral in ASCEND PLUS and will continue throughout the trial. This involvement has been critical to optimising the trial design, successfully obtaining regulatory and ethical approval, and conducting the trial. CI - (c) 2024. The Author(s). FAU - El-Nayir, Muram AU - El-Nayir M AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Wijesurendra, Rohan AU - Wijesurendra R AUID- ORCID: 0000-0002-8261-8343 AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. rohan.wijesurendra@ndph.ox.ac.uk. FAU - Preiss, David AU - Preiss D AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Mafham, Marion AU - Mafham M AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Tsiotos, Leandros AU - Tsiotos L AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Islam, Sadman AU - Islam S AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Whitehouse, Anne AU - Whitehouse A AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Wilkinson, Sophia AU - Wilkinson S AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Freeman, Hannah AU - Freeman H AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Lee, Ryonfa AU - Lee R AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Brudlo, Wojciech AU - Brudlo W AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Bobby, Genna AU - Bobby G AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Jenkins, Bryony AU - Jenkins B AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Humphrey, Robert AU - Humphrey R AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Mallorie, Amy AU - Mallorie A AD - Clinical Trial Service and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Toal, Andrew AU - Toal A AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Barker, Elnora C AU - Barker EC AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Moylan, Dianna AU - Moylan D AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Thomson, Graeme AU - Thomson G AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Davies, Firoza AU - Davies F AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Khan, Hameed AU - Khan H AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Allotey, Ian AU - Allotey I AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Dickie, Susan AU - Dickie S AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. FAU - Roberts, John AU - Roberts J AD - Public Advisory Group; ASCEND PLUS Clinical Trial, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20240822 PL - England TA - Trials JT - Trials JID - 101263253 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Patient Participation MH - *Research Design MH - Cardiovascular Diseases/prevention & control MH - Hypoglycemic Agents/therapeutic use MH - Treatment Outcome MH - Patient Selection MH - Community Participation MH - Administration, Oral MH - United Kingdom MH - Stakeholder Participation MH - Glucagon-Like Peptides MH - Semaglutide PMC - PMC11340079 OTO - NOTNLM OT - Clinical trial OT - Diabetes OT - PPIE OT - Patient and public involvement and engagement COIS- The authors declare that they have no competing interests. EDAT- 2024/08/23 00:43 MHDA- 2024/08/23 06:41 PMCR- 2024/08/22 CRDT- 2024/08/22 23:45 PHST- 2024/04/14 00:00 [received] PHST- 2024/08/08 00:00 [accepted] PHST- 2024/08/23 06:41 [medline] PHST- 2024/08/23 00:43 [pubmed] PHST- 2024/08/22 23:45 [entrez] PHST- 2024/08/22 00:00 [pmc-release] AID - 10.1186/s13063-024-08393-2 [pii] AID - 8393 [pii] AID - 10.1186/s13063-024-08393-2 [doi] PST - epublish SO - Trials. 2024 Aug 22;25(1):554. doi: 10.1186/s13063-024-08393-2. PMID- 39172634 OWN - NLM STAT- MEDLINE DCOM- 20241101 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 15 IP - 11 DP - 2024 Nov TI - PIONEER REAL Japan: Primary results from a multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice. PG - 1566-1577 LID - 10.1111/jdi.14291 [doi] AB - AIMS/INTRODUCTION: PIONEER REAL Japan was a non-interventional prospective study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice. MATERIALS AND METHODS: Adults naive to injectable glucose-lowering therapies initiated oral semaglutide in routine clinical practice and were followed for 34-44 weeks. The primary endpoint was change in glycated hemoglobin (HbA(1c)) from baseline to end of study; the co-primary endpoint was number of adverse events (AEs). Secondary endpoints included change in bodyweight from baseline to end of study. Analyses were also carried out for subgroups aged <75 and >/=75 years. RESULTS: A total of 624 participants initiated oral semaglutide; 578 completed the study. Mean baseline HbA(1c) and bodyweight were 7.7% and 72.4 kg, respectively. At end of study, estimated change (95% confidence interval [CI]) in HbA(1c) from baseline was -0.7 percentage points (-0.77, -0.61) overall, -0.8 percentage points (-0.86, -0.67) in the <75 years subgroup and -0.5 percentage points (-0.68, -0.41) in the >/=75 years subgroup (all P < 0.0001). Estimated change (95% CI) in bodyweight was -2.8 (-3.19, -2.50) kg overall, -2.9 (-3.38, -2.49) kg in the <75 years subgroup and - 2.7 (-3.18, -2.14) kg in the >/=75 years subgroup (all P < 0.0001). AEs occurred in 161 (25.8%) participants: 99 of 423 (23.4%) and 62 of 201 (30.8%) participants in the <75 and >/=75 years subgroups, respectively. Gastrointestinal AEs were the AEs most frequently leading to oral semaglutide discontinuation. CONCLUSIONS: In routine clinical practice, HbA(1c) and bodyweight were significantly reduced from baseline in adults initiating oral semaglutide, including those aged >/=75 years, with no new safety concerns. CI - (c) 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. AD - Department of Diabetes, Endocrinology and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, Japan. AD - Center for One Medicine Innovative Translational Research, Gifu University, Gifu, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. FAU - Hamamoto, Yoshiyuki AU - Hamamoto Y AUID- ORCID: 0000-0002-1938-7394 AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. FAU - Kawanami, Daiji AU - Kawanami D AUID- ORCID: 0000-0002-8926-4701 AD - Department of Endocrinology and Diabetes, Fukuoka University School of Medicine, Fukuoka, Japan. FAU - Nishimura, Rimei AU - Nishimura R AD - Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. FAU - Amadid, Hanan AU - Amadid H AD - Global Clinical Drug Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Braae, Uffe Christian AU - Braae UC AD - Real-World Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Major-Pedersen, Atheline AU - Major-Pedersen A AD - Global Safety, Novo Nordisk A/S, Soborg, Denmark. FAU - Suzuki, Ryo AU - Suzuki R AUID- ORCID: 0000-0002-2965-6906 AD - Department of Diabetes, Metabolism and Endocrinology, Tokyo Medical University, Tokyo, Japan. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Multicenter Study DEP - 20240822 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Male MH - Female MH - Prospective Studies MH - Aged MH - Japan/epidemiology MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - *Glycated Hemoglobin/analysis MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/analysis MH - Body Weight/drug effects MH - Adult MH - Treatment Outcome MH - East Asian People MH - Semaglutide PMC - PMC11527839 OTO - NOTNLM OT - Diabetes mellitus, type 2 OT - Oral semaglutide OT - Prospective studies COIS- Daisuke Yabe received consulting/lecture fees from Eli Lilly Japan K.K., Kyowa Kirin Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Sanofi K.K. and Sumitomo Pharma Co., Ltd.; and research funding/grants from Arkray Inc., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Taisho Pharmaceutical Co., Ltd. and Terumo Corporation. Professor Yabe is an Editorial Board member of Journal of Diabetes Investigation and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication. Yoshiyuki Hamamoto received consulting/lecture fees from Novo Nordisk Pharma Ltd. and Sumitomo Pharma Co., Ltd.; and research funding from Nippon Boehringer Ingelheim Co., Ltd. and Sumitomo Pharma Co., Ltd. Dr Hamamoto is an Editorial Board member of Journal of Diabetes Investigation and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication. Daiji Kawanami received consulting/lecture fees from Bayer Yakuhin Ltd., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Sanofi K.K. and Sumitomo Pharma Co., Ltd.; and grants from Bayer Yakuhin Ltd., Nippon Boehringer Ingelheim Co., Ltd., Nipro Corporation and Sumitomo Pharma Co., Ltd. Rimei Nishimura received consulting/lecture fees from Abbott Japan LLC, Astellas Pharma Inc., AstraZeneca K.K., Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company Ltd., Medtronic Japan Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Pharma Co., Ltd. and Teijin Pharma Ltd.; and research funding/grants from Abbott Japan LLC, Mitsubishi Electric Corporation, Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd. and Taisho Pharmaceutical Co., Ltd. Yasuo Terauchi received consulting/lecture fees from Novo Nordisk Pharma Ltd., Astellas Pharma Inc., AstraZeneca K.K., Eli Lilly Japan K.K., Kowa Company Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Sanofi K.K. and Sumitomo Pharma Co., Ltd.; and grants from Nippon Boehringer Ingelheim Co., Ltd. and Sumitomo Pharma Co., Ltd. Hanan Amadid is employed by, and a shareholder in, Novo Nordisk. Uffe Christian Braae is employed by, and a shareholder in, Novo Nordisk. Atheline Major-Pedersen is employed by, and a shareholder in, Novo Nordisk. Ryo Suzuki received lecture fees from Astellas Pharma Inc., Eli Lilly Japan K.K., Kowa Company Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novo Nordisk Pharma Ltd., Sanofi K.K., Sumitomo Pharma Co., Ltd. and Teijin Healthcare Ltd; and grants from Nippon Boehringer Ingelheim Co., Ltd. Approval of the research protocol: The protocol for this research project has been approved by suitably constituted ethics committees or institutional review boards of the institutions, and it conforms to the provisions of the Declaration of Helsinki. Ethics committees, institutional review boards and approval numbers are listed in the Supporting Information. Informed consent: All informed consent was obtained from the participants and/or their guardians. Approval date of registry and the registration no. of the study/trial: This study is registered with ClinicalTrials.gov (NCT04878393; first submitted 5 May 2021). Animal studies: N/A. EDAT- 2024/08/22 18:42 MHDA- 2024/11/01 06:21 PMCR- 2024/08/22 CRDT- 2024/08/22 12:43 PHST- 2024/08/14 00:00 [revised] PHST- 2024/04/12 00:00 [received] PHST- 2024/07/29 00:00 [accepted] PHST- 2024/11/01 06:21 [medline] PHST- 2024/08/22 18:42 [pubmed] PHST- 2024/08/22 12:43 [entrez] PHST- 2024/08/22 00:00 [pmc-release] AID - JDI14291 [pii] AID - 10.1111/jdi.14291 [doi] PST - ppublish SO - J Diabetes Investig. 2024 Nov;15(11):1566-1577. doi: 10.1111/jdi.14291. Epub 2024 Aug 22. PMID- 39171608 OWN - NLM STAT- MEDLINE DCOM- 20241101 LR - 20241105 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 15 IP - 11 DP - 2024 Nov TI - Application of the integrated data platform combined with dietary management for adults with diabetes: A prospective randomized controlled trial. PG - 1548-1555 LID - 10.1111/jdi.14296 [doi] AB - AIMS: To investigate the efficacy of the integrated data platform of cloud hospital combined with dietary management for adults with type 2 diabetes. MATERIALS AND METHODS: We conducted a randomized controlled clinical trial. One hundred eighty patients with type 2 diabetes were randomly allocated into a control group (Group A) and an experimental group (Group B). Routine standard diabetes care was applied to the patients in Group A. The integrated data platform with dietary management was applied to Group B. Individualized diabetes education videos were sent to the patients through the platform. The primary endpoint was the change in HbA1c and change in body weight from baseline to Week 12 during the follow-up. RESULTS: At Week 12, HbA1c was 7.4 +/- 0.7%, 6.9 +/- 0.9% in Groups A and B, P < 0.01. The rate of fasting blood glucose <7 mmol/L, and glycosylated hemoglobin <7% was higher in Group B than in Group A. At Week 12, there was a significant weight loss and body mass index decrease in the overweight or obese patients of the experimental group. Those overweight or obese patients in the experimental group utilizing the appetite suppressant semaglutide achieved the most significant weight loss, with a 13.4% reduction after 12 weeks. CONCLUSIONS: The integrated data platform combined with personalized diabetes education video delivery was verified to be a more effective management mode for diabetes. For overweight or obese adults with diabetes, the use of semaglutide in conjunction with dietary management and the integrated data platform led to greater weight loss. CI - (c) 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Liu, Xiyu AU - Liu X AUID- ORCID: 0000-0003-2315-3221 AD - Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China. FAU - Wang, Xiaohong AU - Wang X AD - Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China. FAU - Xie, Mengxun AU - Xie M AD - Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China. FAU - Cao, Lulu AU - Cao L AD - Dongyang Hospital of Wenzhou Medical University, Dongyang, Zhejiang, China. LA - eng GR - 2022-03-029/Grant from the project of Science and Technology of Jinhua/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20240822 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/diet therapy/therapy MH - Male MH - Female MH - Middle Aged MH - Prospective Studies MH - *Glycated Hemoglobin/analysis MH - Blood Glucose/analysis MH - Adult MH - Follow-Up Studies MH - Weight Loss MH - Patient Education as Topic MH - Aged MH - Body Mass Index PMC - PMC11527811 OTO - NOTNLM OT - Dietary intervention OT - Digital platform OT - Type 2 diabetes COIS- The authors declare no conflict of interest. Approval of the research protocol: This study conformed to the provisions of the Declaration of Helsinki. It was approved by the Ethics Committee of Dongyang People's Hospital. Informed consent: All participants signed written informed consent before eligibility screening. Registry and the registration no. of the study/trial: The approval date of registry was 30/01/2024, and the registration no. was ChiCTR2400080460. Animal studies: N/A. EDAT- 2024/08/22 12:42 MHDA- 2024/11/01 06:21 PMCR- 2024/08/22 CRDT- 2024/08/22 06:33 PHST- 2024/07/20 00:00 [revised] PHST- 2024/05/14 00:00 [received] PHST- 2024/07/31 00:00 [accepted] PHST- 2024/11/01 06:21 [medline] PHST- 2024/08/22 12:42 [pubmed] PHST- 2024/08/22 06:33 [entrez] PHST- 2024/08/22 00:00 [pmc-release] AID - JDI14296 [pii] AID - 10.1111/jdi.14296 [doi] PST - ppublish SO - J Diabetes Investig. 2024 Nov;15(11):1548-1555. doi: 10.1111/jdi.14296. Epub 2024 Aug 22. PMID- 39168573 OWN - NLM STAT- MEDLINE DCOM- 20240821 LR - 20260127 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 84 IP - 9 DP - 2024 Aug 27 TI - Effect of Semaglutide on Epicardial Adipose Tissue in Type 2 Diabetes: Insights From the STOP (Semaglutide Treatment effect On coronary atherosclerosis Progression) Randomized Trial. PG - 865-867 LID - S0735-1097(24)07684-8 [pii] LID - 10.1016/j.jacc.2024.05.065 [doi] FAU - Manubolu, Venkat Sanjay AU - Manubolu VS AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Lakshmanan, Suvasini AU - Lakshmanan S AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Kinninger, April AU - Kinninger A AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Ahmad, Khadije AU - Ahmad K AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Susarla, Shriraj AU - Susarla S AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Seok, Hoon J AU - Seok HJ AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Hamal, Sajad AU - Hamal S AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Dahal, Suraj AU - Dahal S AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Roy, Sion K AU - Roy SK AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. FAU - Budoff, Matthew J AU - Budoff MJ AD - Lundquist Institute, Harbor UCLA, Torrance, California, USA. Electronic address: mbudoff@lundquist.org. LA - eng PT - Letter PT - Randomized Controlled Trial PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Adipose Tissue/drug effects MH - *Coronary Artery Disease/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Disease Progression MH - Epicardial Adipose Tissue MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Pericardium/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Semaglutide EDAT- 2024/08/22 00:42 MHDA- 2024/08/22 00:43 CRDT- 2024/08/21 20:57 PHST- 2024/02/09 00:00 [received] PHST- 2024/05/14 00:00 [revised] PHST- 2024/05/16 00:00 [accepted] PHST- 2024/08/22 00:43 [medline] PHST- 2024/08/22 00:42 [pubmed] PHST- 2024/08/21 20:57 [entrez] AID - S0735-1097(24)07684-8 [pii] AID - 10.1016/j.jacc.2024.05.065 [doi] PST - ppublish SO - J Am Coll Cardiol. 2024 Aug 27;84(9):865-867. doi: 10.1016/j.jacc.2024.05.065. PMID- 39164856 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 11 DP - 2024 Nov TI - Early uptake of semaglutide for type 2 diabetes in Scandinavia and characteristics of initiators in Denmark: A register-based drug utilization study. PG - 5479-5482 LID - 10.1111/dom.15876 [doi] FAU - Rasmussen, Lotte AU - Rasmussen L AUID- ORCID: 0000-0001-5962-6647 AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Andersen, Jacob Harbo AU - Andersen JH AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. FAU - Karlstad, Oystein AU - Karlstad O AD - Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. FAU - Giunta, Diego Hernan AU - Giunta DH AD - Centre for Pharmacoepidemiology, Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Linder, Marie AU - Linder M AD - Centre for Pharmacoepidemiology, Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. FAU - Furu, Kari AU - Furu K AD - Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. FAU - Pottegard, Anton AU - Pottegard A AUID- ORCID: 0000-0001-9314-5679 AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense, Denmark. LA - eng PT - Letter DEP - 20240820 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Denmark/epidemiology MH - *Glucagon-Like Peptides/therapeutic use MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - *Registries MH - Middle Aged MH - Drug Utilization/statistics & numerical data MH - Aged MH - Scandinavian and Nordic Countries/epidemiology MH - Adult MH - Semaglutide OTO - NOTNLM OT - antidiabetic drug OT - database research OT - liraglutide OT - pharmaco-epidemiology OT - semaglutide EDAT- 2024/08/21 11:41 MHDA- 2024/10/04 12:42 CRDT- 2024/08/21 00:42 PHST- 2024/07/04 00:00 [revised] PHST- 2024/04/29 00:00 [received] PHST- 2024/07/07 00:00 [accepted] PHST- 2024/10/04 12:42 [medline] PHST- 2024/08/21 11:41 [pubmed] PHST- 2024/08/21 00:42 [entrez] AID - 10.1111/dom.15876 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Nov;26(11):5479-5482. doi: 10.1111/dom.15876. Epub 2024 Aug 20. PMID- 39163055 OWN - NLM STAT- MEDLINE DCOM- 20240820 LR - 20260127 IS - 0004-5772 (Print) IS - 0004-5772 (Linking) VI - 72 IP - 8 DP - 2024 Aug TI - Nonarteritic Anterior Ischemic Optic Neuropathy and Semaglutide: What is This All About? PG - 11-12 LID - 10.59556/japi.72.0621 [doi] AB - Nonarteritic anterior ischemic optic neuropathy (NAION) was first documented by a French physician Jean-Pierre Saint-Yves in 1817 (19th century). The clinical description of NAION was not known until 1935 when C. Miller Fischer thoroughly described it. Briefly, NAION is a rare (2.5-11.8 per 1,00,000 cases in men above 50 years) but serious condition that causes sudden painless loss of vision due to ischemia of the optic nerve.(1) It is more common in Caucasians compared with Asians and is associated with various risk factors such as hypertension, type 2 diabetes (T2D), smoking, hyperlipidemia, obesity, obstructive sleep apnea, small optic nerve cup ("disk at risk"), optic nerve drusen, and certain drugs, especially phosphodiesterase type 5 inhibitors (PDE-5I), amiodarone, and cabergoline.(2) Although the clinical development programs and real-world studies of semaglutide [a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for the treatment of T2D and obesity] did not report any significant increase in the risk of NAION, a recent retrospective cohort study suggested a possible link between NAION and semaglutide.(3) This editorial briefly summarizes the current knowledge about NAION and its relation to metabolic disorders, cardiovascular, and antidiabetes drugs and puts a perspective concerning semaglutide. CI - (c) Journal of the Association of Physicians of India 2024. FAU - Singh, Awadhesh Kumar AU - Singh AK AD - Consultant Endocrinologist, Department of Diabetes & Endocrinology, G. D. Hospital & Diabetes Institute, Kolkata, West Bengal, India, Corresponding Author. FAU - Kesavadev, Jothydev AU - Kesavadev J AD - Consultant Physician and Diabetes Specialist, Department of Diabetes & Endocrinology, Jothydev's Diabetes and Research Centre, Trivandrum, Kerala, India. FAU - Tiwaskar, Mangesh AU - Tiwaskar M AD - Consultant Physician and Diabetes Specialist, Department of Diabetes & Endocrinology, Shilpa Medical Research Centre, Mumbai, Maharashtra, India. LA - eng PT - Editorial PL - India TA - J Assoc Physicians India JT - The Journal of the Association of Physicians of India JID - 7505585 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Optic Neuropathy, Ischemic/drug therapy MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Risk Factors MH - Semaglutide EDAT- 2024/08/20 12:43 MHDA- 2024/08/20 12:44 CRDT- 2024/08/20 11:39 PHST- 2024/08/20 12:44 [medline] PHST- 2024/08/20 12:43 [pubmed] PHST- 2024/08/20 11:39 [entrez] AID - 10.59556/japi.72.0621 [doi] PST - ppublish SO - J Assoc Physicians India. 2024 Aug;72(8):11-12. doi: 10.59556/japi.72.0621. PMID- 39160334 OWN - NLM STAT- MEDLINE DCOM- 20241023 LR - 20250103 IS - 2522-5812 (Electronic) IS - 2522-5812 (Linking) VI - 6 IP - 10 DP - 2024 Oct TI - GLP-1 physiology in obesity and development of incretin-based drugs for chronic weight management. PG - 1866-1885 LID - 10.1038/s42255-024-01113-9 [doi] AB - The introduction of the highly potent incretin receptor agonists semaglutide and tirzepatide has marked a new era in the treatment of type 2 diabetes and obesity. With normalisation of glycated haemoglobin levels and weight losses around 15-25%, therapeutic goals that were previously unrealistic are now within reach, and clinical trials have documented that these effects are associated with reduced risk of cardiovascular events and premature mortality. Here, I review this remarkable development from the earliest observations of glucose lowering and modest weight losses with native glucagon-like peptide (GLP)-1 and short acting compounds, to the recent development of highly active formulations and new molecules. I will classify these agents as GLP-1-based therapies in the understanding that these compounds or combinations may have actions on other receptors as well. The physiology of GLP-1 is discussed as well as its mechanisms of actions in obesity, in particular, the role of sensory afferents and GLP-1 receptors in the brain. I provide details regarding the development of GLP-1 receptor agonists for anti-obesity therapy and discuss the possible mechanism behind their beneficial effects on adverse cardiovascular events. Finally, I highlight new pharmacological developments, including oral agents, and discuss important questions regarding maintenance therapy. CI - (c) 2024. Springer Nature Limited. FAU - Holst, Jens Juul AU - Holst JJ AUID- ORCID: 0000-0001-6853-3805 AD - Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences. Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. jjholst@sund.ku.dk. LA - eng PT - Journal Article PT - Review DEP - 20240819 PL - Germany TA - Nat Metab JT - Nature metabolism JID - 101736592 RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Obesity/drug therapy MH - *Incretins/therapeutic use MH - *Glucagon-Like Peptide 1/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy MH - Anti-Obesity Agents/therapeutic use/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/08/20 00:42 MHDA- 2024/10/23 06:22 CRDT- 2024/08/19 23:26 PHST- 2024/01/30 00:00 [received] PHST- 2024/07/17 00:00 [accepted] PHST- 2024/10/23 06:22 [medline] PHST- 2024/08/20 00:42 [pubmed] PHST- 2024/08/19 23:26 [entrez] AID - 10.1038/s42255-024-01113-9 [pii] AID - 10.1038/s42255-024-01113-9 [doi] PST - ppublish SO - Nat Metab. 2024 Oct;6(10):1866-1885. doi: 10.1038/s42255-024-01113-9. Epub 2024 Aug 19. PMID- 39151204 OWN - NLM STAT- MEDLINE DCOM- 20241022 LR - 20260127 IS - 1539-2864 (Electronic) IS - 0275-004X (Linking) VI - 44 IP - 11 DP - 2024 Nov 1 TI - NOVEL AGENTS IN THE MANAGEMENT OF DIABETES AND RISK OF WORSENING DIABETIC RETINOPATHY. PG - 1851-1859 LID - 10.1097/IAE.0000000000004252 [doi] AB - PURPOSE: Novel therapies for diabetes have potent effects on glycemic control, obesity, and cardiovascular risk reduction, but some, including the popular drug semaglutide, have also been implicated in worsening of diabetic retinopathy (DR). Given the ubiquity of these new agents, understanding the risks to vision is important. Here, we review the data for several newly available agents in terms of systemic efficacy and retinal safety. METHODS: Literature review. RESULTS: Novel antihyperglycemic treatments include incretin mimetics and enhancers, sodium-glucose cotransporter inhibitors, long-acting insulins, and insulin delivery systems. All improve glycemic control, and some have been shown to reduce major cardiovascular outcomes. In a pivotal trial, semaglutide was associated with approximately 75% increased risk of DR worsening. The novel long-acting insulin icodec, formulated for once weekly dosing, showed increased risk of DR worsening over a once daily insulin. No other recent antihyperglycemic agent was associated with DR worsening, although following the semaglutide trials, nearly all studies excluded patients with preexisting DR. Cases of DR worsening were rare in all instances. Dedicated safety studies for semaglutide in DR are currently underway. CONCLUSION: For most patients being considered for treatment with a novel antihyperglycemic agent, benefits on systemic metabolic and cardiovascular health are very likely to outweigh potential retinal harms. Although the true risks of the new agents on DR are unclear because their safety data come from secondary end points, the most vulnerable patients are those with preexisting high-risk DR, poor baseline glycemic control, and using insulin. CI - Copyright (c) 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc. FAU - Rajagopal, Rithwick AU - Rajagopal R AUID- ORCID: 0000-0002-3036-2665 AD - Department of Ophthalmology and Visual Sciences, and. FAU - McGill, Janet B AU - McGill JB AD - Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, Saint Louis, Missouri. LA - eng GR - EY034172/National Eye Institute, Horncrest Foundation/ PT - Journal Article PT - Review PL - United States TA - Retina JT - Retina (Philadelphia, Pa.) JID - 8309919 RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetic Retinopathy/drug therapy MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Blood Glucose/metabolism/drug effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use/administration & dosage/adverse effects MH - Risk Factors MH - Disease Progression MH - Semaglutide EDAT- 2024/08/16 18:42 MHDA- 2024/10/22 18:22 CRDT- 2024/08/16 17:53 PHST- 2024/10/22 18:22 [medline] PHST- 2024/08/16 18:42 [pubmed] PHST- 2024/08/16 17:53 [entrez] AID - 00006982-990000000-00774 [pii] AID - 10.1097/IAE.0000000000004252 [doi] PST - ppublish SO - Retina. 2024 Nov 1;44(11):1851-1859. doi: 10.1097/IAE.0000000000004252. PMID- 39137181 OWN - NLM STAT- MEDLINE DCOM- 20240813 LR - 20260127 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 66 IP - 1708 DP - 2024 Aug 5 TI - Table: GLP-1 and GIP/GLP-1 receptor agonists for type 2 diabetes. PG - e1-e3 LID - 10.58347/tml.2024.1708c [doi] LA - eng PT - Journal Article PT - Review DEP - 20240805 PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1/agonists MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage/pharmacology MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - Receptors, Gastrointestinal Hormone/agonists MH - Animals MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Bydureon BCise OT - Byetta OT - Mounjaro OT - Ozempic OT - Rybelsus OT - Trulicity OT - Victoza OT - adverse effects OT - dosage OT - drug interactions OT - dulaglutide OT - exenatide OT - lactation OT - liraglutide OT - pregnancy OT - safety OT - semaglutide OT - tirzepatide OT - type 2 diabetes EDAT- 2024/08/13 18:41 MHDA- 2024/08/13 18:42 CRDT- 2024/08/13 13:23 PHST- 2024/08/13 18:42 [medline] PHST- 2024/08/13 18:41 [pubmed] PHST- 2024/08/13 13:23 [entrez] AID - 10.58347/tml.2024.1708c [doi] PST - epublish SO - Med Lett Drugs Ther. 2024 Aug 5;66(1708):e1-e3. doi: 10.58347/tml.2024.1708c. PMID- 39127152 OWN - NLM STAT- MEDLINE DCOM- 20241025 LR - 20260127 IS - 1873-2968 (Electronic) IS - 0006-2952 (Linking) VI - 229 DP - 2024 Nov TI - Peptide GLP-1 receptor agonists: From injection to oral delivery strategies. PG - 116471 LID - S0006-2952(24)00454-4 [pii] LID - 10.1016/j.bcp.2024.116471 [doi] AB - Peptide glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective drugs for treating type 2 diabetes (T2DM) and have been proven to benefit the heart and kidney. Apart from oral semaglutide, which does not require injection, other peptide GLP-1RAs need to be subcutaneously administered. However, oral semaglutide also faces significant challenges, such as low bioavailability and frequent gastrointestinal discomfort. Thus, it is imperative that advanced oral strategies for peptide GLP-1RAs need to be explored. This review mainly compares the current advantages and disadvantages of various oral delivery strategies for peptide GLP-1RAs in the developmental stage and discusses the latest research progress of peptide GLP-1RAs, providing a useful guide for the development of new oral peptide GLP-1RA drugs. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Ke, Zhiqiang AU - Ke Z AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China; Hubei Key Laboratory of Diabetes and Angiopathy, National Demonstration Center for Experimental General Medicine Education, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei 437100, China. FAU - Ma, Qianqian AU - Ma Q AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China; School of Pharmaceutical Sciences and Institute of Materia Medica, Xinjiang University, Urumqi 830017, China. FAU - Ye, Xiaonan AU - Ye X AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China. FAU - Wang, Yanlin AU - Wang Y AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China. FAU - Jin, Yan AU - Jin Y AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China. FAU - Zhao, Xinyuan AU - Zhao X AD - Hubei Key Laboratory of Diabetes and Angiopathy, National Demonstration Center for Experimental General Medicine Education, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei 437100, China. Electronic address: zhaoxinyuan@hbust.edu.cn. FAU - Su, Zhengding AU - Su Z AD - Protein Engineering and Biopharmaceuticals Science, Hubei University of Technology, Wuhan 430068, China; School of Pharmaceutical Sciences and Institute of Materia Medica, Xinjiang University, Urumqi 830017, China. Electronic address: james_su@xju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240808 PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage MH - Animals MH - Drug Delivery Systems/methods MH - Glucagon-Like Peptides/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Advanced microbiome delivery OT - Cell penetrating peptides OT - Oral delivery OT - Peptide GLP-1 receptor agonists OT - Pharmaceutical Technology OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/08/11 04:43 MHDA- 2024/10/26 19:25 CRDT- 2024/08/10 19:17 PHST- 2024/04/19 00:00 [received] PHST- 2024/07/20 00:00 [revised] PHST- 2024/08/06 00:00 [accepted] PHST- 2024/10/26 19:25 [medline] PHST- 2024/08/11 04:43 [pubmed] PHST- 2024/08/10 19:17 [entrez] AID - S0006-2952(24)00454-4 [pii] AID - 10.1016/j.bcp.2024.116471 [doi] PST - ppublish SO - Biochem Pharmacol. 2024 Nov;229:116471. doi: 10.1016/j.bcp.2024.116471. Epub 2024 Aug 8. PMID- 39127032 OWN - NLM STAT- MEDLINE DCOM- 20240810 LR - 20260603 IS - 2666-6340 (Electronic) IS - 2666-6340 (Linking) VI - 5 IP - 8 DP - 2024 Aug 9 TI - Therapy for HFpEF: A step forward brings new hope for people with obesity and diabetes. PG - 848-851 LID - S2666-6340(24)00257-5 [pii] LID - 10.1016/j.medj.2024.06.011 [doi] AB - The STEP-HFpEF DM trial(1) showed that semaglutide improved body weight, systemic inflammation, and heart failure symptoms in people with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. By addressing both metabolic and cardiovascular risk, semaglutide is a promising therapeutic option for HFpEF in addition to SGLT2i. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Lim, Lee-Ling AU - Lim LL AD - Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; Asia Diabetes Foundation, Hong Kong SAR, China. Electronic address: leeling.lim@ummc.edu.my. FAU - Khunti, Kamlesh AU - Khunti K AD - Diabetes Research Centre, University of Leicester, Leicester, UK. LA - eng GR - NIHR, NHS, and Department of Health and Social Care/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Obesity/drug therapy/physiopathology MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Heart Failure/drug therapy/physiopathology MH - *Stroke Volume/drug effects MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - Semaglutide COIS- Declaration of interests L.-L.L. has acted as a consultant, speaker, or received research grants via her institution from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, Roche, Servier, Viatris, and Zuellig Pharma Therapeutics. K.K. has acted as a consultant, speaker, or received grants for investigator-initiated studies for AstraZeneca, Bayer, Novo Nordisk, Sanofi-Aventis, Servier, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Oramed Pharmaceuticals, Pfizer, Roche, Daiichi-Sankyo, Applied Therapeutics, Embecta, and Nestle Health Science. EDAT- 2024/08/11 04:43 MHDA- 2024/08/11 04:44 CRDT- 2024/08/10 18:18 PHST- 2024/06/20 00:00 [received] PHST- 2024/06/20 00:00 [revised] PHST- 2024/06/20 00:00 [accepted] PHST- 2024/08/11 04:44 [medline] PHST- 2024/08/11 04:43 [pubmed] PHST- 2024/08/10 18:18 [entrez] AID - S2666-6340(24)00257-5 [pii] AID - 10.1016/j.medj.2024.06.011 [doi] PST - ppublish SO - Med. 2024 Aug 9;5(8):848-851. doi: 10.1016/j.medj.2024.06.011. PMID- 39127031 OWN - NLM STAT- MEDLINE DCOM- 20240810 LR - 20260603 IS - 2666-6340 (Electronic) IS - 2666-6340 (Linking) VI - 5 IP - 8 DP - 2024 Aug 9 TI - Glucagon-like peptide receptor-1 receptor agonists: The emerging fourth pillar in type 2 diabetes and chronic kidney disease? PG - 845-847 LID - S2666-6340(24)00256-3 [pii] LID - 10.1016/j.medj.2024.06.010 [doi] AB - Previously, no randomized controlled trials investigated the renoprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) as the primary endpoint in patients with diabetes and chronic kidney disease. In the FLOW trial, Perkovic et al. showed that once-weekly semaglutide reduced kidney failure, kidney-related death, and cardiovascular death by 24% as compared with placebo in patients with type 2 diabetes at high risk of renal progression.(1). CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Ling, James AU - Ling J AD - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR. FAU - Chow, Elaine AU - Chow E AD - Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR; Phase 1 Clinical Trial Centre, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR. Electronic address: e.chow@cuhk.edu.hk. LA - eng PT - Journal Article PL - United States TA - Med JT - Med (New York, N.Y.) JID - 101769215 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Renal Insufficiency, Chronic/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/pharmacology/administration & dosage MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Diabetic Nephropathies/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- Declaration of interests The authors declare no competing interests. EDAT- 2024/08/11 04:43 MHDA- 2024/08/11 04:44 CRDT- 2024/08/10 18:18 PHST- 2024/06/19 00:00 [received] PHST- 2024/06/20 00:00 [revised] PHST- 2024/06/20 00:00 [accepted] PHST- 2024/08/11 04:44 [medline] PHST- 2024/08/11 04:43 [pubmed] PHST- 2024/08/10 18:18 [entrez] AID - S2666-6340(24)00256-3 [pii] AID - 10.1016/j.medj.2024.06.010 [doi] PST - ppublish SO - Med. 2024 Aug 9;5(8):845-847. doi: 10.1016/j.medj.2024.06.010. PMID- 39125772 OWN - NLM STAT- MEDLINE DCOM- 20240810 LR - 20250103 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 15 DP - 2024 Jul 27 TI - Molecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy. LID - 10.3390/ijms25158202 [doi] LID - 8202 AB - Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the development of type 2 diabetes mellitus, leading to reduced life expectancy. In this review, we would like to present the molecular pathomechanisms underlying obesity, which constitute the target points for the action of anti-obesity medications. These include the central nervous system, brain-gut-microbiome axis, gastrointestinal motility, and energy expenditure. A significant part of this article is dedicated to incretin-based drugs such as GLP-1 receptor agonists (e.g., liraglutide and semaglutide), as well as the brand new dual GLP-1 and GIP receptor agonist tirzepatide, all of which have become "block-buster" drugs due to their effectiveness in reducing body weight and beneficial effects on the patient's metabolic profile. Finally, this review article highlights newly designed molecules with the potential for future obesity management that are the subject of ongoing clinical trials. FAU - Nicze, Michal AU - Nicze M AUID- ORCID: 0000-0003-2181-4356 AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Dec, Adrianna AU - Dec A AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Borowka, Maciej AU - Borowka M AUID- ORCID: 0000-0002-2714-208X AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Krzyzak, Damian AU - Krzyzak D AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Boldys, Aleksandra AU - Boldys A AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Buldak, Lukasz AU - Buldak L AUID- ORCID: 0000-0002-2017-5516 AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. FAU - Okopien, Boguslaw AU - Okopien B AUID- ORCID: 0000-0001-7228-2906 AD - Department of Internal Medicine and Clinical Pharmacology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Medykow 18, 40-752 Katowice, Poland. LA - eng GR - BNW-1-03/N/3/O/Medical University of Silesia/ GR - 2023/07/X/NZ7/01190/National Science Center/ PT - Journal Article PT - Review DEP - 20240727 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Obesity/drug therapy/metabolism MH - *Anti-Obesity Agents/therapeutic use/pharmacology MH - Animals MH - Energy Metabolism/drug effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Gastrointestinal Microbiome/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11311839 OTO - NOTNLM OT - appetite OT - energy expenditure OT - gastrointestinal tract hormones OT - gut-brain axis OT - incretins OT - microbiome OT - obesity OT - retatrutide OT - semaglutide OT - tirzepatide COIS- The authors declare no conflicts of interest. EDAT- 2024/08/10 15:47 MHDA- 2024/08/10 15:48 PMCR- 2024/07/27 CRDT- 2024/08/10 01:15 PHST- 2024/06/28 00:00 [received] PHST- 2024/07/22 00:00 [revised] PHST- 2024/07/25 00:00 [accepted] PHST- 2024/08/10 15:48 [medline] PHST- 2024/08/10 15:47 [pubmed] PHST- 2024/08/10 01:15 [entrez] PHST- 2024/07/27 00:00 [pmc-release] AID - ijms25158202 [pii] AID - ijms-25-08202 [pii] AID - 10.3390/ijms25158202 [doi] PST - epublish SO - Int J Mol Sci. 2024 Jul 27;25(15):8202. doi: 10.3390/ijms25158202. PMID- 39125424 OWN - NLM STAT- MEDLINE DCOM- 20240810 LR - 20260127 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 16 IP - 15 DP - 2024 Aug 3 TI - Real-World Evaluation of Once-Weekly Subcutaneous Semaglutide in Patients with Type 2 Diabetes Mellitus in Spain (SEMA-RW Study). LID - 10.3390/nu16152545 [doi] LID - 2545 AB - Although, in randomized clinical trials, once-weekly subcutaneous semaglutide (OW s.c.) has demonstrated superior efficacy in comparison with placebo and active controls in terms of glycemic control and body weight reduction in patients with type 2 diabetes mellitus (T2DM), these results need to be confirmed in a real-world (RW) setting. An RW ambispective study (6 months retrospective and 6 months prospective) was conducted in 10 tertiary hospitals in Spain. We evaluated changes in HbA1c and body weight in patients with T2DM treated with semaglutide OW s.c. Additionally, we analyzed different subgroups of patients treated with semaglutide OW s.c. as an add-on to glucose-lowering therapy. A total of 752 patients with a mean age of 60.2 years, a mean HbA1c level of 8.5%, a mean body weight of 101.6 kg, and a mean T2DM duration of 10 years were included. At 12 months, compared with baseline, there was a mean difference of -2.1% in HbA1c levels (p < 0.001) and a mean difference of 9.2 kg in body weight (p < 0.001). Moreover, there were statistically significant differences (p < 0.001) between baseline and month 12 in both HbA1c and body weight in the four subgroups receiving semaglutide OW s.c. as an add-on to glucose-lowering therapy. Semaglutide OW s.c. was well tolerated, with gastrointestinal disorders being the most commonly reported side effects. In this RW study, 12 months of treatment with semaglutide OW s.c. in patients with T2DM was associated with significant and clinically relevant improvements in glycemic control and weight loss, regardless of the glucose-lowering therapy received, and the overall safety profile was positive. FAU - Caballero Mateos, Irene AU - Caballero Mateos I AUID- ORCID: 0000-0002-2041-1013 AD - Endocrinology and Nutrition Department, Virgen Macarena University Hospital and Vithas Hospital, 41009 Sevilla, Spain. FAU - Garcia de Lucas, Maria Dolores AU - Garcia de Lucas MD AD - Internal Medicine Department, Hospital Costa del Sol, 29603 Marbella, Spain. FAU - Doulatram-Gamgaram, Viyey Kishore AU - Doulatram-Gamgaram VK AD - Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Biomedical Research Institute of Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29016 Malaga, Spain. FAU - Moreno-Moreno, Paloma AU - Moreno-Moreno P AD - Endocrinology and Nutrition Department, Reina Sofia University Hospital, 14004 Cordoba, Spain. FAU - Jimenez-Millan, Ana Isabel AU - Jimenez-Millan AI AD - Endocrinology and Nutrition Department, University Hospital, 11510 Puerto Real, Spain. FAU - Botana-Lopez, Manuel AU - Botana-Lopez M AD - Endocrinology and Nutrition Department, Lucus Augusti University Hospital, 27003 Lugo, Spain. FAU - Merino-Torres, Juan Francisco AU - Merino-Torres JF AUID- ORCID: 0000-0002-0191-4504 AD - Endocrinology and Nutrition Department, La Fe University Hospital, 46026 Valencia, Spain. FAU - Soto-Gonzalez, Alfonso AU - Soto-Gonzalez A AD - Endocrinology and Nutrition Department, A Coruna University Hospital Complex, 15006 A Coruna, Spain. FAU - Fernandez-Garcia, Jose Carlos AU - Fernandez-Garcia JC AD - Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Biomedical Research Institute of Malaga (IBIMA), Faculty of Medicine, University of Malaga, 29016 Malaga, Spain. FAU - Morales-Portillo, Cristobal AU - Morales-Portillo C AUID- ORCID: 0000-0003-0348-826X AD - Endocrinology and Nutrition Department, Virgen Macarena University Hospital and Vithas Hospital, 41009 Sevilla, Spain. LA - eng GR - INT21/00078/Instituto de Salud Carlos III/ PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20240803 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Administration Schedule MH - *Glucagon-Like Peptides/administration & dosage/adverse effects MH - *Glycated Hemoglobin/analysis MH - Glycemic Control/methods MH - *Hypoglycemic Agents/administration & dosage MH - Injections, Subcutaneous MH - Prospective Studies MH - Retrospective Studies MH - Spain MH - Treatment Outcome MH - Weight Loss/drug effects MH - Semaglutide PMC - PMC11314012 OTO - NOTNLM OT - body weight OT - glucagon-like peptide-1 receptor agonist OT - glycemic control OT - once weekly semaglutide OT - type 2 diabetes mellitus COIS- J.C.F.-G. has received speaker honoraria from Novo Nordisk, Lilly, Boehringer-Ingelheim, Esteve, Menarini, and AstraZeneca. The rest of the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/08/10 15:43 MHDA- 2024/08/10 15:44 PMCR- 2024/08/03 CRDT- 2024/08/10 01:13 PHST- 2024/07/04 00:00 [received] PHST- 2024/07/24 00:00 [revised] PHST- 2024/08/01 00:00 [accepted] PHST- 2024/08/10 15:44 [medline] PHST- 2024/08/10 15:43 [pubmed] PHST- 2024/08/10 01:13 [entrez] PHST- 2024/08/03 00:00 [pmc-release] AID - nu16152545 [pii] AID - nutrients-16-02545 [pii] AID - 10.3390/nu16152545 [doi] PST - epublish SO - Nutrients. 2024 Aug 3;16(15):2545. doi: 10.3390/nu16152545. PMID- 39121301 OWN - NLM STAT- MEDLINE DCOM- 20240809 LR - 20260127 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 103 IP - 32 DP - 2024 Aug 9 TI - Real world study of GLP-1 receptor agonists in overweight or obese type 2 diabetes by using repeated measurement analysis of variance. PG - e38879 LID - 10.1097/MD.0000000000038879 [doi] LID - e38879 AB - To investigate the safety and efficacy of long-acting glucagon like peptide-1 receptor agonists in overweight or obese patients with type 2 diabetes. Overweight or obese patients with type 2 diabetes from July 2021 to June 2022 were randomly divided into control group (metformin) and experimental group (metformin + dulaglitide or semaglutide). Repeated measures analysis of variance was used to compare Hemoglobin A1c, fasting plasma glucose and body mass index (BMI) of patients before treatment, 6 months and 12 months after treatment. The adverse reactions of patients before treatment and 12 months after treatment were analyzed. The time effect of Hemoglobin A1c, fasting plasma glucose and BMI in the control group (n = 35) and the experimental group (n = 32) were statistically significant (P < .001), and the intergroup effect of BMI was statistically significant (P < .05). The interaction effect of BMI was statistically significant (P < .001). The BMI level of the experimental group was lower than that of the control group at 6 and 12 months after treatment (P < .001). There was no significant difference in the incidence of adverse reactions between the 2 groups (P > .05). Long-acting glucagon like peptide-1 receptor agonists, such as dulaglitide and semaglutide, not only reduce glycosylated hemoglobin levels, but also significantly improve BMI in overweight or obese patients with type 2 diabetes. CI - Copyright (c) 2024 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Yang, Wanying AU - Yang W AUID- ORCID: 0009-0004-7197-2867 AD - Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Zhou, Xiangming AU - Zhou X AD - Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Miao, Yuanyuan AU - Miao Y AD - Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Wang, Lu AU - Wang L AD - Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Zhao, Yunhui AU - Zhao Y AD - Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Ke, Tingyu AU - Ke T AD - Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. FAU - Ban, Lili AU - Ban L AD - Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. LA - eng GR - YNWR-MY-2020-022/Yunnan provincial Talent Work Leading group office/ PT - Journal Article PT - Randomized Controlled Trial PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 0 (Blood Glucose) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Middle Aged MH - Female MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/analogs & derivatives MH - *Glycated Hemoglobin/drug effects/analysis MH - *Obesity/drug therapy/complications MH - *Body Mass Index MH - *Metformin/therapeutic use MH - *Overweight/drug therapy/complications MH - *Blood Glucose/drug effects/analysis MH - Aged MH - Immunoglobulin Fc Fragments/therapeutic use/adverse effects MH - Analysis of Variance MH - Adult MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Recombinant Fusion Proteins MH - Semaglutide PMC - PMC11315522 COIS- The authors have no conflicts of interest to disclose. EDAT- 2024/08/09 18:42 MHDA- 2024/08/09 18:43 PMCR- 2024/08/09 CRDT- 2024/08/09 14:13 PHST- 2024/08/09 18:43 [medline] PHST- 2024/08/09 18:42 [pubmed] PHST- 2024/08/09 14:13 [entrez] PHST- 2024/08/09 00:00 [pmc-release] AID - 00005792-202408090-00058 [pii] AID - MD-D-24-00002 [pii] AID - 10.1097/MD.0000000000038879 [doi] PST - ppublish SO - Medicine (Baltimore). 2024 Aug 9;103(32):e38879. doi: 10.1097/MD.0000000000038879. PMID- 39118222 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260604 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Real-world safety profile of once-weekly semaglutide in people with type 2 diabetes: Analysis of pooled data from the SemaglUtide Real-world Evidence (SURE) programme. PG - 4429-4440 LID - 10.1111/dom.15794 [doi] AB - AIM: To investigate, through post hoc analysis of nine studies from the SemaglUtide Real-world Evidence (SURE) programme, the safety of once-weekly (OW) semaglutide in adults with type 2 diabetes (T2D) and in subpopulations in routine clinical practice, complementing findings from the phase 3 randomized clinical trial (RCT) SUSTAIN programme. METHODS: The SURE studies had a duration of ~30 weeks and included adults with diagnosed T2D treated with OW semaglutide. Safety information, including hypoglycaemic events, were collected and analysed for the total study population and for patient subgroups based on baseline patient characteristics, baseline co-medication and prescriber specialty. RESULTS: Of the total 3505 patients, 24.3% reported adverse events (AEs), with most patients reporting non-serious (22.3%) and mild (17.1%) AEs. AEs mainly belonged to the gastrointestinal disorders system organ class (16.3% of patients). In total, 5.1% of patients reported AEs that led to treatment discontinuation, 0.5% reported serious adverse drug reactions and 0.2% had an AE with a fatal outcome, reported as unrelated to treatment. Overall, 1.1% and 0.1% of patients reported level 2 and 3 hypoglycaemic events, respectively. A higher rate of level 2 hypoglycaemia was observed in patients with baseline microvascular complications treated with insulin versus those on insulin without these complications. CONCLUSIONS: Safety data reported in the real-world SURE studies were generally consistent with observations in phase 3 OW semaglutide RCTs. No new safety concerns were identified, highlighting that OW semaglutide is well tolerated by adults with T2D and in subpopulations in routine clinical practice. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Yale, Jean-Francois AU - Yale JF AUID- ORCID: 0000-0002-7833-9050 AD - McGill University Health Centre, Montreal, Quebec, Canada. FAU - Major-Pedersen, Atheline AU - Major-Pedersen A AUID- ORCID: 0000-0002-1755-630X AD - Global Safety, Novo Nordisk A/S, Soborg, Denmark. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jain, Rashmi AU - Jain R AD - Novo Nordisk Service Centre India Private Ltd., Bengaluru, India. FAU - Menzen, Markus AU - Menzen M AD - Gemeinschaftskrankenhaus Bonn, Bonn, Germany. FAU - Holmes, Patrick AU - Holmes P AD - St. George's Medical Practice, Darlington, UK. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240808 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Female MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Male MH - Middle Aged MH - Aged MH - *Hypoglycemia/chemically induced/epidemiology MH - Drug Administration Schedule MH - Adult MH - Clinical Trials, Phase III as Topic MH - Randomized Controlled Trials as Topic MH - Semaglutide OTO - NOTNLM OT - SURE studies OT - glucagon-like peptide-1 receptor agonist OT - real-world data OT - safety OT - semaglutide OT - type 2 diabetes EDAT- 2024/08/09 06:42 MHDA- 2024/09/18 12:51 CRDT- 2024/08/09 00:04 PHST- 2024/06/28 00:00 [revised] PHST- 2024/02/01 00:00 [received] PHST- 2024/06/28 00:00 [accepted] PHST- 2024/09/18 12:51 [medline] PHST- 2024/08/09 06:42 [pubmed] PHST- 2024/08/09 00:04 [entrez] AID - 10.1111/dom.15794 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4429-4440. doi: 10.1111/dom.15794. Epub 2024 Aug 8. PMID- 39109559 OWN - NLM STAT- MEDLINE DCOM- 20241212 LR - 20260127 IS - 1531-1937 (Electronic) IS - 0897-1900 (Linking) VI - 38 IP - 1 DP - 2025 Feb TI - Problematic Pharmacokinetics: A Case of Recurrent Pancreatitis Post Discontinuation of a Glucagon-Like Peptide 1 Receptor Agonists. PG - 187-192 LID - 10.1177/08971900241273188 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP-1RA) are guideline recommended agents for the treatment of type 2 diabetes mellitus (T2DM) and select agents (liraglutide and semaglutide) are FDA approved as anti-obesity pharmacotherapy options. These drugs act on the incretin hormone system within the body to revive insulin excretion, delay gastric emptying, and inhibit the production of glucagon from pancreatic alpha cells. Acute pancreatitis is a serious condition that may have a fatal outcome. It has been shown, and is now part of the prescribing information label, that GLP-1RA agents can cause changes in the pancreas that may ultimately lead to pancreatitis. We describe the case of a 53-year-old female patient with uncontrolled type II diabetes mellitus, who experienced multiple episodes of pancreatitis, from what we suspect was due to repeated exposure to the GLP-1 RA agent, semaglutide. After discontinuation of semaglutide, our patient experienced another episode of pancreatitis roughly 15-week later; which we believe may be due to the patient experiencing the effects of a smoldering pancreas brought on by repeated injury and prolonged circulation of semaglutide post-discontinuation. FAU - Morehouse, Zachary P AU - Morehouse ZP AUID- ORCID: 0000-0002-5719-0947 AD - Department of Family Medicine, Atrium Health Carolinas Medical Center, Charlotte, NC, USA. RINGGOLD: 2351 FAU - Ledford, Jack D AU - Ledford JD AUID- ORCID: 0000-0002-1033-1327 AD - Division of Pharmacy, Atrium Health Carolinas Medical Center, Charlotte, NC, USA. AD - Department of Family and Community Medicine, Wake Forest School of Medicine, Charlotte NC, USA. LA - eng PT - Case Reports PT - Journal Article DEP - 20240807 PL - United States TA - J Pharm Pract JT - Journal of pharmacy practice JID - 8900945 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Middle Aged MH - *Pancreatitis/chemically induced MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use/pharmacokinetics MH - Recurrence MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - diabetes OT - pancreatitis OT - semaglutide COIS- Declaration of Conflicting InterestsZPM and JDL are full time employees of Atrium Health Carolinas Medical Center and neither have any relevant financial disclosures or potential conflicts of interest which may have impacted the production or description of this manuscript in any way. EDAT- 2024/08/07 12:42 MHDA- 2024/12/12 12:28 CRDT- 2024/08/07 06:44 PHST- 2024/12/12 12:28 [medline] PHST- 2024/08/07 12:42 [pubmed] PHST- 2024/08/07 06:44 [entrez] AID - 10.1177/08971900241273188 [doi] PST - ppublish SO - J Pharm Pract. 2025 Feb;38(1):187-192. doi: 10.1177/08971900241273188. Epub 2024 Aug 7. PMID- 39109455 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260604 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Efficacy, adherence and persistence of various glucagon-like peptide-1 agonists: nationwide real-life data. PG - 4646-4652 LID - 10.1111/dom.15828 [doi] AB - AIM: The management of type 2 diabetes mellitus has advanced in the last two decades since the introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, multiple factors may interfere with achieving better glycaemic control. This study evaluated the differences between various GLP-1RAs in efficacy, adherence and persistence. MATERIALS AND METHODS: We conducted a retrospective cohort study using the electronic medical database from Clalit Health Services. Adults with type 2 diabetes mellitus who purchased any GLP-1RA between 2009 and 2021 were included. The Index Date was defined as the date of the first purchase of any GLP-1RA. We evaluated the adherence, persistence and glycaemic control after GLP-1RAs initiation. Baseline glycaemic and post-treatment glycaemic controls were analysed. RESULTS: In total, 70 654 patients were included. The mean age was 11.7 +/- 60.4, and 51% were females. A significant reduction in glycated haemoglobin (HbA1c) was observed in all patients who received GLP-1RAs. However, the percentage of changes in the HbA1c was higher among weekly GLP-1RA than daily initiators (14.6% vs. 10.2%, p < 0.001). The proportion of subjects with any decrease in HbA1c was higher among the once-weekly compared with the daily dose (82.4% vs. 74.7%) and mainly patients initiated semaglutide or dulaglutide, with 16.0% and 14.7% reduction. The frequency of good adherence (the proportion of days covered >/=80%) was significantly higher among the weekly group odds ratio = 1.25 (95% confidence interval 1.21-1.28). Good adherence was reported in older age, female gender, Jewish ethnicity and high socio-economic status (p < 0.001). CONCLUSIONS: Weekly GLP-1RAs initiators were more adherent, persistent to therapy and achieved better glycaemic control. Epidemiological variables might play a role in achieving this goal. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kassem, Sameer AU - Kassem S AD - Department of Internal Medicine, Carmel Medical Center, Haifa, Israel. AD - Department of Internal Medicine, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel. FAU - Khalaila, Buthaina AU - Khalaila B AD - Department of Internal Medicine, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel. AD - Department of Clinical Pharmacology and Regulatory Management, Carmel Medical Center, Haifa, Israel. FAU - Stein, Nili AU - Stein N AD - Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel. AD - Department of Community Medicine and Epidemiology, Statistical Unit, Lady Davis Carmel Medical Center, Haifa, Israel. FAU - Saliba, Walid AU - Saliba W AD - Department of Internal Medicine, Ruth and Bruce Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel. AD - Department of Community Medicine and Epidemiology, Carmel Medical Center, Haifa, Israel. AD - Translational Epidemiology Unit and Research Authority, Lady Davis Carmel Medical Center, Haifa, Israel. FAU - Zaina, Adnan AU - Zaina A AUID- ORCID: 0000-0001-7482-3104 AD - Division of Endocrinology and Metabolism, Clalit Medical Health Care Services, Haifa, Israel. AD - Division of Endocrinology and Metabolism, Bar-Ilan University, The Azrieli Faculty of Medicine, Safed, Israel. LA - eng PT - Journal Article DEP - 20240807 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Blood Glucose/drug effects/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Exenatide/therapeutic use/administration & dosage MH - Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/administration & dosage MH - Glycated Hemoglobin/analysis/metabolism MH - Glycemic Control/statistics & numerical data MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Immunoglobulin Fc Fragments/therapeutic use/administration & dosage MH - Liraglutide/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use/administration & dosage MH - Retrospective Studies MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Drug Monitoring MH - Semaglutide OTO - NOTNLM OT - database research OT - glucagon-like peptide-1 analogue OT - glycaemic control OT - real-world evidence OT - type 2 diabetes EDAT- 2024/08/07 06:42 MHDA- 2024/09/18 12:52 CRDT- 2024/08/07 05:32 PHST- 2024/07/04 00:00 [revised] PHST- 2024/05/30 00:00 [received] PHST- 2024/07/07 00:00 [accepted] PHST- 2024/09/18 12:52 [medline] PHST- 2024/08/07 06:42 [pubmed] PHST- 2024/08/07 05:32 [entrez] AID - 10.1111/dom.15828 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4646-4652. doi: 10.1111/dom.15828. Epub 2024 Aug 7. PMID- 39103719 OWN - NLM STAT- MEDLINE DCOM- 20241028 LR - 20250103 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 67 IP - 11 DP - 2024 Nov TI - Association of glucagon-like peptide-1 receptor agonists with suicidal ideation and self-injury in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study. PG - 2471-2480 LID - 10.1007/s00125-024-06243-z [doi] AB - AIMS/HYPOTHESIS: Regulators worldwide are reviewing safety data on glucagon-like peptide-1 receptor agonists (GLP-1RA), following reports by the Icelandic Medicines Agency in July 2023 of suicidal ideation and self-injury (SIS) in individuals taking liraglutide and semaglutide. We aimed to assess the risk of SIS in new users of GLP-1RA when compared with sodium-glucose cotransporter 2 inhibitors (SGLT-2i) users, prescribed to treat type 2 diabetes in individuals with obesity. METHODS: This is a cohort study combining several population-wide databases and covering a Spanish population of five million inhabitants, including all adults with obesity who initiated treatment with either GLP-1RA or SGLT-2i for type 2 diabetes from 2015 to 2021. To estimate the comparative effect of GLP-1RA on the risk of SIS, we employed a new user, active comparator design and we carried out multivariable Cox regression modelling with inverse probability of treatment weighting (IPTW) based on propensity scores. We performed several stratified and sensitivity analyses. RESULTS: We included 3040 patients initiating treatment with GLP-1RA and 11,627 with SGLT-2i. When compared with patients treated with SGLT-2i, those in the GLP-1RA group were younger (55 vs 60 years old, p<0.001), had more anxiety (49.4% vs 41.5%, p<0.001), sleep disorders (43.2% vs 34.1%, p<0.001) and depression (24.4% vs 19.0%, p<0.001), and were more obese (35.1% of individuals with BMI >/=40 vs 15.1%, p<0.001). After propensity score weighting, standardised mean differences between groups were <0.1 for all covariates, showing adequate balance between groups at baseline after adjustment. In the main per-protocol analyses we found no evidence that GLP-1RA increased the incidence of SIS (HR 1.04; 95% CI 0.35, 3.14). Intention-to-treat analyses resulted in an HR of 1.36 (95% CI 0.51, 3.61). In analyses excluding individuals with no BMI information and using imputation for BMI missing values, respective HRs were 0.89 (95% CI 0.26, 3.14) and 1.29 (95% CI 0.42, 3.92). Stratified analyses showed no differences between subgroups. CONCLUSIONS/INTERPRETATION: Our findings do not support an increased risk of SIS when taking GLP-1RA in individuals with type 2 diabetes and obesity; however, the rarity of SIS events and the wide uncertainty of effect size (although null, effect may be compatible with a risk as high as threefold) calls for a cautious interpretation of our results. Further studies, including final evaluations from regulatory bodies, are called for to discard a causal link between GLP-1RA and suicidality. CI - (c) 2024. The Author(s). FAU - Hurtado, Isabel AU - Hurtado I AD - Health Services Research & Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Fisabio, Valencia, Spain. AD - Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Robles, Celia AU - Robles C AD - Health Services Research & Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Fisabio, Valencia, Spain. AD - Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Peiro, Salvador AU - Peiro S AD - Health Services Research & Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Fisabio, Valencia, Spain. AD - Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. FAU - Garcia-Sempere, Anibal AU - Garcia-Sempere A AUID- ORCID: 0000-0002-4313-3976 AD - Health Services Research & Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Fisabio, Valencia, Spain. anibal.garcia@fisabio.es. AD - Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. anibal.garcia@fisabio.es. FAU - Sanfelix-Gimeno, Gabriel AU - Sanfelix-Gimeno G AD - Health Services Research & Pharmacoepidemiology Unit, Foundation for the Promotion of Health and Biomedical Research of Valencia Region, Fisabio, Valencia, Spain. AD - Spanish Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS), Valencia, Spain. LA - eng PT - Journal Article DEP - 20240806 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Obesity/complications/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Cohort Studies MH - Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Self-Injurious Behavior/drug therapy/epidemiology MH - *Suicidal Ideation MH - Adult MH - Liraglutide/therapeutic use MH - Propensity Score MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11519213 OTO - NOTNLM OT - Cohort study OT - Diabetes OT - GLP-1RA OT - Glucose-lowering drugs OT - Obesity OT - SGLT-2i OT - Self-injury OT - Suicidal ideation EDAT- 2024/08/06 00:41 MHDA- 2024/10/28 18:23 PMCR- 2024/08/06 CRDT- 2024/08/05 23:33 PHST- 2024/02/08 00:00 [received] PHST- 2024/06/17 00:00 [accepted] PHST- 2024/10/28 18:23 [medline] PHST- 2024/08/06 00:41 [pubmed] PHST- 2024/08/05 23:33 [entrez] PHST- 2024/08/06 00:00 [pmc-release] AID - 10.1007/s00125-024-06243-z [pii] AID - 6243 [pii] AID - 10.1007/s00125-024-06243-z [doi] PST - ppublish SO - Diabetologia. 2024 Nov;67(11):2471-2480. doi: 10.1007/s00125-024-06243-z. Epub 2024 Aug 6. PMID- 39096914 OWN - NLM STAT- MEDLINE DCOM- 20240907 LR - 20260127 IS - 2468-1253 (Electronic) VI - 9 IP - 10 DP - 2024 Oct TI - Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions. PG - 957-964 LID - S2468-1253(24)00188-2 [pii] LID - 10.1016/S2468-1253(24)00188-2 [doi] AB - The availability of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) such as liraglutide and semaglutide, and a GLP-1 and glucose dependent insulinotropic polypeptide coagonist (tirzepatide) represents a paradigm shift in the management of both type 2 diabetes and obesity. There is now considerable attention, including in the public media, on the effect of both long-acting and short-acting GLP-1RAs to delay gastric emptying. Although slowed gastric emptying is integral to reducing post-prandial blood glucose responses in type 2 diabetes, marked slowing of gastric emptying might also increase the propensity for longer intragastric retention of food, with a consequent increased risk of aspiration at the time of surgery or upper gastrointestinal endoscopy. This Personal View summarises current knowledge of the effects of GLP-1 and GLP-1RAs on gastrointestinal physiology, particularly gastric emptying, and discusses the implications for the development of sound pre-operative or pre-procedural guidelines. The development of pre-procedural guidelines is currently compromised by the poor evidence base, particularly in relation to the effect of long-acting GLP-1RAs on gastric emptying. We suggest pre-procedural management pathways for individuals on GLP-1RA-based therapy and discuss priorities for future research. CI - Copyright (c) 2024 Elsevier Ltd. All rights reserved. FAU - Jalleh, Ryan J AU - Jalleh RJ AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA, Australia. FAU - Rayner, Chris K AU - Rayner CK AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA, Australia. FAU - Hausken, Trygve AU - Hausken T AD - Department of Medicine, Haukeland University Hospital, Bergen, Norway. FAU - Jones, Karen L AU - Jones KL AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA, Australia. FAU - Camilleri, Michael AU - Camilleri M AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Horowitz, Michael AU - Horowitz M AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, SA, Australia. Electronic address: michael.horowitz@adelaide.edu.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240801 PL - Netherlands TA - Lancet Gastroenterol Hepatol JT - The lancet. Gastroenterology & hepatology JID - 101690683 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Gastric Emptying/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Obesity/drug therapy MH - Liraglutide/therapeutic use/pharmacology MH - Glucagon-Like Peptide 1/agonists MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- Declaration of interests CKR has participated on advisory boards for Glyscend Therapeutics, a company that owns orally administered, gut-targeted polymer therapies and has work underway related to type 2 diabetes and obesity. CKR has received honoraria for lectures from Eli Lilly and Boehringer Ingelheim. KLJ has previously received research funding from Sanofi-Aventis and AstraZeneca; participated on an advisory board for Glyscend Therapeutics (without receipt of payment); and declares stock options, but does not own any stock, in Glyscend Therapeutics. MH declares stocks in Mirum Pharmaceuticals, a company that owns Livmarli (maralixibat), which is approved in the USA and Europe for the treatment of cholestatic pruritus in Alagille syndrome (a genetic liver disorder). Mirum Pharmaceuticals has work underway related to rare liver diseases, but not diabetes or obesity. MH declares stock options, but does not own any stock, in Glyscend Therapeutics; and is a member of the scientific and clinical advisory board for Glyscend Therapeutics. All other authors declare no competing interests. EDAT- 2024/08/04 13:44 MHDA- 2024/09/08 13:50 CRDT- 2024/08/03 18:55 PHST- 2024/04/12 00:00 [received] PHST- 2024/05/28 00:00 [revised] PHST- 2024/05/29 00:00 [accepted] PHST- 2024/09/08 13:50 [medline] PHST- 2024/08/04 13:44 [pubmed] PHST- 2024/08/03 18:55 [entrez] AID - S2468-1253(24)00188-2 [pii] AID - 10.1016/S2468-1253(24)00188-2 [doi] PST - ppublish SO - Lancet Gastroenterol Hepatol. 2024 Oct;9(10):957-964. doi: 10.1016/S2468-1253(24)00188-2. Epub 2024 Aug 1. PMID- 39093590 OWN - NLM STAT- MEDLINE DCOM- 20240802 LR - 20260827 IS - 2689-0186 (Electronic) IS - 2689-0186 (Linking) VI - 5 IP - 8 DP - 2024 Aug 2 TI - Prescription Fills for Semaglutide Products by Payment Method. PG - e242026 LID - 10.1001/jamahealthforum.2024.2026 [doi] LID - e242026 FAU - Scannell, Christopher AU - Scannell C AD - Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles. AD - Los Angeles Area Health Service Research Training Program, Fielding School of Public Health, University of California, Los Angeles. FAU - Romley, John AU - Romley J AD - Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles. AD - Price School of Public Policy, University of Southern California, Los Angeles. AD - Program on Medicines and Public Health, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles. FAU - Myerson, Rebecca AU - Myerson R AD - Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles. AD - Department of Population Health Sciences, University of Wisconsin, Madison. FAU - Goldman, Dana AU - Goldman D AD - Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles. AD - Price School of Public Policy, University of Southern California, Los Angeles. FAU - Qato, Dima M AU - Qato DM AD - Schaeffer Center for Health Policy & Economics, University of Southern California, Los Angeles. AD - Program on Medicines and Public Health, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles. LA - eng GR - T32 HS000046/HS/AHRQ HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240802 PL - United States TA - JAMA Health Forum JT - JAMA health forum JID - 101769500 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/economics MH - *Hypoglycemic Agents/economics/therapeutic use MH - United States MH - Diabetes Mellitus, Type 2/drug therapy/economics MH - Semaglutide PMC - PMC11297375 OAB - This cross-sectional study examines trends in US prescription fills for semaglutide products by payment method between January 2021 and December 2023. OABL- eng COIS- Conflict of Interest Disclosures: Dr Scannell reported receiving a postdoctoral training grant from the Agency for Healthcare Research and Quality during the conduct of the study. Dr Goldman reported receiving grants from the National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study; grants from the American Heart Association, Amgen, Blue Cross Blue Shield of Arizona, Bristol Myers Squibb, the California Hospital Association, Cedars-Sinai Health System, Charles Koch Foundation, Edwards Lifesciences, Gates Ventures, Genentech, Gilead Sciences, Incyte, Johnson & Johnson, Lilly, the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, Novartis, and Pfizer, receiving personal fees from Biogen, the National Railway Labor Conference, and GRAIL, and being a cofounder with equity from EntityRisk outside the submitted work. Dr Qato reported receiving personal fees from Public Citizens Health Research Group and grants from the National Institutes of Health outside the submitted work. No other disclosures were reported. EDAT- 2024/08/02 12:42 MHDA- 2024/08/02 12:43 PMCR- 2024/08/02 CRDT- 2024/08/02 11:33 PHST- 2024/08/02 12:43 [medline] PHST- 2024/08/02 12:42 [pubmed] PHST- 2024/08/02 11:33 [entrez] PHST- 2024/08/02 00:00 [pmc-release] AID - 2821688 [pii] AID - ald240016 [pii] AID - 10.1001/jamahealthforum.2024.2026 [doi] PST - epublish SO - JAMA Health Forum. 2024 Aug 2;5(8):e242026. doi: 10.1001/jamahealthforum.2024.2026. PMID- 39093567 OWN - NLM STAT- MEDLINE DCOM- 20240802 LR - 20260127 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 7 IP - 8 DP - 2024 Aug 1 TI - Safety and Risk Assessment of No-Prescription Online Semaglutide Purchases. PG - e2428280 LID - 10.1001/jamanetworkopen.2024.28280 [doi] LID - e2428280 FAU - Ashraf, Amir Reza AU - Ashraf AR AD - Department of Pharmaceutics, Faculty of Pharmacy, University of Pecs, Pecs, Hungary. FAU - Mackey, Tim K AU - Mackey TK AD - Global Health Program, Department of Anthropology, University of California San Diego, La Jolla. AD - Global Health Policy and Data Institute, San Diego, California. AD - S-3 Research, San Diego, California. FAU - Schmidt, Janos AU - Schmidt J AD - Institute of Biochemistry and Medical Chemistry, Medical School, University of Pecs, Pecs, Hungary. FAU - Kulcsar, Gyozo AU - Kulcsar G AD - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Pecs, Pecs, Hungary. FAU - Vida, Robert Gyorgy AU - Vida RG AD - Department of Pharmaceutics, Faculty of Pharmacy, University of Pecs, Pecs, Hungary. FAU - Li, Jiawei AU - Li J AD - S-3 Research, San Diego, California. FAU - Fittler, Andras AU - Fittler A AD - Department of Pharmaceutics, Faculty of Pharmacy, University of Pecs, Pecs, Hungary. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240801 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Female MH - Male MH - Risk Assessment MH - Middle Aged MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Semaglutide PMC - PMC11297364 OAB - This qualitative study assesses the quality, amount of active ingredient, and characteristics associated with counterfeiting of semaglutide purchased from illegal online pharmacies without a prescription. OABL- eng COIS- Conflict of Interest Disclosures: Mr Schmidt reported receiving grant TKP2021-EGA-17 from the Hungarian National Research, Development and Innovation Office outside the submitted work. No other disclosures were reported. EDAT- 2024/08/02 12:44 MHDA- 2024/08/02 18:42 PMCR- 2024/08/02 CRDT- 2024/08/02 11:32 PHST- 2024/08/02 18:42 [medline] PHST- 2024/08/02 12:44 [pubmed] PHST- 2024/08/02 11:32 [entrez] PHST- 2024/08/02 00:00 [pmc-release] AID - 2821882 [pii] AID - zld240127 [pii] AID - 10.1001/jamanetworkopen.2024.28280 [doi] PST - epublish SO - JAMA Netw Open. 2024 Aug 1;7(8):e2428280. doi: 10.1001/jamanetworkopen.2024.28280. PMID- 39091271 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260604 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Semaglutide improves treatment satisfaction and eating behaviour in Japanese patients with type 2 diabetes mellitus. PG - 4787-4790 LID - 10.1111/dom.15823 [doi] FAU - Baba, Yusuke AU - Baba Y AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Watanabe, Suzuka AU - Watanabe S AD - Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan. FAU - Hayashi, Saho AU - Hayashi S AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Sakai, Toshiki AU - Sakai T AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Naka, Masamitsu AU - Naka M AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Kami, Saori AU - Kami S AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Hirayama, Kiichi AU - Hirayama K AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Koizumi, Kazuko AU - Koizumi K AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Takahashi, Ai AU - Takahashi A AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Meguro, Miwako AU - Meguro M AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Iga, Ryo AU - Iga R AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Yamanaka, Yoshitaka AU - Yamanaka Y AD - Department of Rehabilitation, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Kataoka, Masaaki AU - Kataoka M AD - Department of Surgery, Kimitsu Chuo Hospital, Chiba, Japan. FAU - Uchida, Daigaku AU - Uchida D AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. AD - Department of Internal Medicine, Hotaruno Central Naika, Chiba, Japan. FAU - Ishibashi, Ryoichi AU - Ishibashi R AUID- ORCID: 0000-0003-2535-5396 AD - Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Kimitsu Chuo Hospital, Chiba, Japan. AD - Department of Endocrinology, Hematology and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan. LA - eng PT - Journal Article DEP - 20240802 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - East Asian People MH - Feeding Behavior MH - *Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin/analysis/metabolism/drug effects MH - *Hypoglycemic Agents/therapeutic use MH - Japan/epidemiology MH - *Patient Satisfaction MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - antiobesity drug OT - appetite control OT - attitudes OT - semaglutide EDAT- 2024/08/02 06:41 MHDA- 2024/09/18 12:45 CRDT- 2024/08/02 04:23 PHST- 2024/07/09 00:00 [revised] PHST- 2024/05/16 00:00 [received] PHST- 2024/07/09 00:00 [accepted] PHST- 2024/09/18 12:45 [medline] PHST- 2024/08/02 06:41 [pubmed] PHST- 2024/08/02 04:23 [entrez] AID - 10.1111/dom.15823 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4787-4790. doi: 10.1111/dom.15823. Epub 2024 Aug 2. PMID- 39079728 OWN - NLM STAT- MEDLINE DCOM- 20240730 LR - 20260127 IS - 1756-1833 (Electronic) IS - 0959-8138 (Linking) VI - 386 DP - 2024 Jul 30 TI - Semaglutide: FDA publishes warning amid reports of patients overdosing. PG - q1696 LID - 10.1136/bmj.q1696 [doi] FAU - Mahase, Elisabeth AU - Mahase E AD - The BMJ. LA - eng PT - News DEP - 20240730 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - United States MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - *United States Food and Drug Administration MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Medical Overuse/prevention & control MH - Semaglutide EDAT- 2024/07/31 00:42 MHDA- 2024/07/31 00:43 CRDT- 2024/07/30 20:43 PHST- 2024/07/31 00:43 [medline] PHST- 2024/07/31 00:42 [pubmed] PHST- 2024/07/30 20:43 [entrez] AID - 10.1136/bmj.q1696 [doi] PST - epublish SO - BMJ. 2024 Jul 30;386:q1696. doi: 10.1136/bmj.q1696. PMID- 39078489 OWN - NLM STAT- MEDLINE DCOM- 20241002 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 67 IP - 10 DP - 2024 Oct TI - Effects of semaglutide, empagliflozin and their combination on renal diffusion-weighted MRI and total kidney volume in patients with type 2 diabetes: a post hoc analysis from a 32 week randomised trial. PG - 2175-2187 LID - 10.1007/s00125-024-06228-y [doi] AB - AIMS/HYPOTHESIS: The apparent diffusion coefficient (ADC) derived from diffusion-weighted MRI (DWI-MRI) has been proposed as a measure of changes in kidney microstructure, including kidney fibrosis. In advanced kidney disease, the kidneys often become atrophic; however, in the initial phase of type 2 diabetes, there is an increase in renal size. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors both provide protection against progression of kidney disease in diabetes. However, the mechanisms are incompletely understood. To explore this, we examined the effects of semaglutide, empagliflozin and their combination on renal ADC and total kidney volume (TKV). METHODS: This was a substudy of a randomised clinical trial on the effects of semaglutide and empagliflozin alone or in combination. Eighty patients with type 2 diabetes and high risk of CVD were randomised into four groups (n=20 in each) receiving either tablet placebo, empagliflozin, a combination of semaglutide and tablet placebo (herein referred to as the 'semaglutide' group), or the combination of semaglutide and empagliflozin (referred to as the 'combination-therapy' group). The semaglutide and the combination-therapy group had semaglutide treatment for 16 weeks and then had either tablet placebo or empagliflozin added to the treatment, respectively, for a further 16 weeks; the placebo and empagliflozin groups were treated with the respective monotherapy for 32 weeks. We analysed the effects of treatment on changes in ADC (cortical, medullary and the cortico-medullary difference [DeltaADC; medullary ADC subtracted from cortical ADC]), as well as TKV measured by MRI. RESULTS: Both semaglutide and empagliflozin decreased cortical ADC significantly compared with placebo (semaglutide: -0.20x10(-3) mm(2)/s [95% CI -0.30, -0.10], p<0.001; empagliflozin: -0.15x10(-3) mm(2)/s [95% CI -0.26, -0.04], p=0.01). No significant change was observed in the combination-therapy group (-0.05x10(-3) mm(2)/s [95%CI -0.15, 0.05]; p=0.29 vs placebo). The changes in cortical ADC were not associated with changes in GFR, albuminuria, TKV or markers of inflammation. Further, there were no changes in medullary ADC in any of the groups compared with placebo. Only treatment with semaglutide changed DeltaADC significantly from placebo, showing a decrease of -0.13x10(-3) mm(2)/s (95% CI -0.22, -0.04; p=0.01). Compared with placebo, TKV decreased by -3% (95% CI -5%, -0.3%; p=0.04), -3% (95% CI -5%, -0.4%; p=0.02) and -5% (95% CI -8%, -2%; p<0.001) in the semaglutide, empagliflozin and combination-therapy group, respectively. The changes in TKV were associated with changes in GFR, albuminuria and HbA(1c). CONCLUSIONS/INTERPRETATION: In a population with type 2 diabetes and high risk of CVD, semaglutide and empagliflozin significantly reduced cortical ADC compared with placebo, indicating microstructural changes in the kidneys. These changes were not associated with changes in GFR, albuminuria or inflammation. Further, we found a decrease in TKV in all active treatment groups, which was possibly mediated by a reduction in hyperfiltration. Our findings suggest that DWI-MRI may serve as a promising tool for investigating the underlying mechanisms of medical interventions in individuals with type 2 diabetes but may reflect effects not related to fibrosis. TRIAL REGISTRATION: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2019-000781-38. CI - (c) 2024. The Author(s). FAU - Vernstrom, Liv AU - Vernstrom L AUID- ORCID: 0000-0003-2875-435X AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. lvh@clin.au.dk. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. lvh@clin.au.dk. AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. lvh@clin.au.dk. FAU - Gullaksen, Soren AU - Gullaksen S AUID- ORCID: 0000-0001-8275-1278 AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Regional Hospital Horsens, Horsens, Denmark. FAU - Sorensen, Steffen S AU - Sorensen SS AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. FAU - Ringgaard, Steffen AU - Ringgaard S AUID- ORCID: 0000-0001-5353-7379 AD - The MR Research Centre, Aarhus University, Aarhus, Denmark. FAU - Laustsen, Christoffer AU - Laustsen C AUID- ORCID: 0000-0002-0317-2911 AD - The MR Research Centre, Aarhus University, Aarhus, Denmark. FAU - Birn, Henrik AU - Birn H AUID- ORCID: 0000-0003-3715-7266 AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Biomedicine, Aarhus University, Aarhus, Denmark. FAU - Funck, Kristian L AU - Funck KL AUID- ORCID: 0000-0003-0213-5550 AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. FAU - Laugesen, Esben AU - Laugesen E AUID- ORCID: 0000-0003-1782-1596 AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. AD - Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark. FAU - Poulsen, Per L AU - Poulsen PL AUID- ORCID: 0000-0001-6468-2715 AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. LA - eng GR - 2019-3780/41/Laegeforeningen/ GR - NNF170C0029064/Novo Nordisk Fonden/ GR - A3192/Health Research Fund of Central Denmark Region/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20240730 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Glucosides) RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Humans MH - *Glucosides/therapeutic use MH - *Benzhydryl Compounds/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/diagnostic imaging MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use MH - Middle Aged MH - *Kidney/drug effects/diagnostic imaging/pathology MH - Aged MH - Diffusion Magnetic Resonance Imaging MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Drug Therapy, Combination MH - Diabetic Nephropathies/drug therapy/diagnostic imaging MH - Semaglutide PMC - PMC11447057 OTO - NOTNLM OT - Apparent diffusion coefficient OT - Diffusion-weighted magnetic resonance imaging OT - Glucagon-like peptide-1 receptor agonist OT - Magnetic resonance imaging OT - Sodium-glucose cotransporter 2 inhibitors OT - Total kidney volume OT - Type 2 diabetes EDAT- 2024/07/30 12:42 MHDA- 2024/10/02 12:42 PMCR- 2024/07/30 CRDT- 2024/07/30 11:13 PHST- 2024/02/28 00:00 [received] PHST- 2024/05/07 00:00 [accepted] PHST- 2024/10/02 12:42 [medline] PHST- 2024/07/30 12:42 [pubmed] PHST- 2024/07/30 11:13 [entrez] PHST- 2024/07/30 00:00 [pmc-release] AID - 10.1007/s00125-024-06228-y [pii] AID - 6228 [pii] AID - 10.1007/s00125-024-06228-y [doi] PST - ppublish SO - Diabetologia. 2024 Oct;67(10):2175-2187. doi: 10.1007/s00125-024-06228-y. Epub 2024 Jul 30. PMID- 39074369 OWN - NLM STAT- MEDLINE DCOM- 20240819 LR - 20260919 IS - 1539-3704 (Electronic) IS - 0003-4819 (Print) IS - 0003-4819 (Linking) VI - 177 IP - 8 DP - 2024 Aug TI - Association of Semaglutide With Tobacco Use Disorder in Patients With Type 2 Diabetes : Target Trial Emulation Using Real-World Data. PG - 1016-1027 LID - 10.7326/M23-2718 [doi] AB - BACKGROUND: Reports of reduced desire to smoke in patients treated with semaglutide, a glucagon-like peptide receptor agonist (GLP-1RA) medication for type 2 diabetes mellitus (T2DM) and obesity, have raised interest about its potential benefit for tobacco use disorders (TUDs). OBJECTIVE: To examine the association of semaglutide with TUD-related health care measures in patients with comorbid T2DM and TUD. DESIGN: Emulation target trial based on a nationwide population-based database of patient electronic health records. SETTING: United States, 1 December 2017 to 31 March 2023. PARTICIPANTS: Seven target trials were emulated among eligible patients with comorbid T2DM and TUD by comparing the new use of semaglutide versus 7 other antidiabetes medications (insulins, metformin, dipeptidyl-peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, sulfonylureas, thiazolidinediones, and other GLP-1RAs). MEASUREMENTS: The TUD-related health care measures (medical encounter for diagnosis of TUD, smoking cessation medication prescriptions, and smoking cessation counseling) that occurred within a 12-month follow-up were examined using Cox proportional hazards and Kaplan-Meier survival analyses. RESULTS: The study compared 222 942 new users of antidiabetes medications including 5967 of semaglutide. Semaglutide was associated with a significantly lower risk for medical encounters for TUD diagnosis compared with other antidiabetes medications, and was strongest compared with insulins (hazard ratio [HR], 0.68 [95% CI, 0.63 to 0.74]) and weakest but statistically significant compared with other GLP-1RAs (HR, 0.88 [CI, 0.81 to 0.96]). Semaglutide was associated with reduced smoking cessation medication prescriptions and counseling. Similar findings were observed in patients with and without a diagnosis of obesity. For most of the group comparisons, the differences occurred within 30 days of prescription initiation. LIMITATION: Documentation bias, residual confounding, missing data on current smoking behavior, body mass index, and medication adherence. CONCLUSION: Semaglutide was associated with lower risks for TUD-related health care measures in patients with comorbid T2DM and TUD compared with other antidiabetes medications including other GLP-1Ras, primarily within 30 days of prescription. These findings suggest the need for clinical trials to evaluate semaglutide's potential for TUD treatment. PRIMARY FUNDING SOURCE: National Institutes of Health. FAU - Wang, William AU - Wang W AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio (W.W., N.A.B.). FAU - Volkow, Nora D AU - Volkow ND AUID- ORCID: 0000-0001-6668-0908 AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland (N.D.V.). FAU - Berger, Nathan A AU - Berger NA AUID- ORCID: 0000-0001-7086-9885 AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, Ohio (W.W., N.A.B.). FAU - Davis, Pamela B AU - Davis PB AUID- ORCID: 0000-0002-7113-5338 AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, Ohio (P.B.D.). FAU - Kaelber, David C AU - Kaelber DC AUID- ORCID: 0000-0001-7855-9515 AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, Ohio (D.C.K.). FAU - Xu, Rong AU - Xu R AUID- ORCID: 0000-0003-3127-4795 AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio (R.X.). LA - eng GR - R01 AG057557/AG/NIA NIH HHS/United States GR - R01 AG076649/AG/NIA NIH HHS/United States GR - R01 AA029831/AA/NIAAA NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States GR - RF1 AG076649/AG/NIA NIH HHS/United States GR - UM1 TR004528/TR/NCATS NIH HHS/United States GR - R25 CA221718/CA/NCI NIH HHS/United States GR - P30 CA043703/CA/NCI NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240730 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Female MH - Male MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - *Tobacco Use Disorder/drug therapy/complications MH - Aged MH - United States/epidemiology MH - Smoking Cessation MH - Obesity/complications/drug therapy MH - Semaglutide PMC - PMC12721465 MID - NIHMS2123689 COIS- Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-2718. EDAT- 2024/07/29 18:42 MHDA- 2024/08/19 18:42 PMCR- 2025/12/23 CRDT- 2024/07/29 17:03 PHST- 2024/08/19 18:42 [medline] PHST- 2024/07/29 18:42 [pubmed] PHST- 2024/07/29 17:03 [entrez] PHST- 2025/12/23 00:00 [pmc-release] AID - 10.7326/M23-2718 [doi] PST - ppublish SO - Ann Intern Med. 2024 Aug;177(8):1016-1027. doi: 10.7326/M23-2718. Epub 2024 Jul 30. PMID- 39072877 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260604 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - The role of incretin receptor agonists in the treatment of obesity. PG - 4178-4196 LID - 10.1111/dom.15796 [doi] AB - INTRODRODUCTION: Obesity and its associated metabolic conditions have become a significant global health problem in recent years, with many people living with obesity fulfilling criteria for pharmacological treatment. The development of the glucagon-like peptide-1 receptor agonists for chronic weight management has triggered new interest in the incretins and other hormones as targets for obesity, and investigations into dual and triple co-agonists. METHODS: The objective of this narrative review was to summarize the available data on approved and emerging incretin-based agents for the treatment of obesity. RESULTS: In clinical trials of currently available agents in people with overweight or obesity, weight loss of between 6% and 21% of baseline body weight has been observed, with between 23% and 94% of participants achieving 10% or higher weight loss, depending on the study and the agent used. Favourable outcomes have also been seen with regard to cardiovascular risk and outcomes, diabetes prevention, metabolic dysfunction-associated steatotic liver disease/steatohepatitis and prevention of weight regain after metabolic surgery. Limitations associated with these agents include high costs, the potential for weight regain once treatment is stopped, the potential loss of lean body mass and gastrointestinal adverse events; potential issues with respect to gallbladder and biliary diseases require further investigation. CONCLUSIONS: Many dual and triple co-agonists are still in development, and more data are needed to assess the efficacy, safety and tolerability of these emerging therapies versus the established incretin-based therapies; however, data are promising, and further results are eagerly awaited. CI - (c) 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Forst, Thomas AU - Forst T AUID- ORCID: 0000-0003-2132-5691 AD - CRS Clinical Research Services GmbH, Mannheim, Germany. FAU - De Block, Christophe AU - De Block C AUID- ORCID: 0000-0002-0679-3203 AD - Antwerp University Hospital and University of Antwerp, Antwerp, Belgium. FAU - Del Prato, Stefano AU - Del Prato S AUID- ORCID: 0000-0002-5388-0270 AD - Interdisciplinary Research Center "Health Science," Sant'Anna School of Advanced Studies, Pisa, Italy. FAU - Armani, Sara AU - Armani S AUID- ORCID: 0009-0009-5209-6474 AD - CRS Clinical Research Services GmbH, Mannheim, Germany. FAU - Frias, Juan AU - Frias J AUID- ORCID: 0000-0001-9486-1255 AD - Biomea Fusion, Redwood City, California, USA. FAU - Lautenbach, Anne AU - Lautenbach A AUID- ORCID: 0000-0002-7763-1527 AD - University Medical-Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Ludvik, Bernhard AU - Ludvik B AUID- ORCID: 0009-0003-8717-8396 AD - Landstrasse Clinic and Karl Landsteiner Institute for Obesity and Metabolic Disorders, Vienna, Austria. FAU - Marinez, Marina AU - Marinez M AD - CRS Clinical Research Services GmbH, Mannheim, Germany. FAU - Mathieu, Chantal AU - Mathieu C AUID- ORCID: 0000-0002-4055-5233 AD - Department of Endocrinology, KU Leuven, Leuven, Belgium. FAU - Muller, Timo D AU - Muller TD AUID- ORCID: 0000-0002-0624-9339 AD - Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Munich, Neuherberg, Germany. AD - German Center for Diabetes Research (DZD), Neuherberg, Germany. AD - Walther-Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universitat Munchen (LMU), Munich, Germany. FAU - Schnell, Oliver AU - Schnell O AUID- ORCID: 0000-0003-1713-2766 AD - Forschergruppe Diabetes e.V. at the Helmholtz Center Munich, Munich, Germany. LA - eng GR - Clinical Research Services, Grenadiesrstrasse 1, 68167 Mannheim, Germany/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240729 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Anti-Obesity Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Anti-Obesity Agents/therapeutic use/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Incretins/therapeutic use MH - *Obesity/drug therapy/complications MH - Weight Loss/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use OTO - NOTNLM OT - dual co-agonists OT - incretins OT - obesity OT - semaglutide OT - tirzepatide EDAT- 2024/07/29 12:44 MHDA- 2024/09/18 12:44 CRDT- 2024/07/29 09:52 PHST- 2024/06/28 00:00 [revised] PHST- 2024/05/03 00:00 [received] PHST- 2024/06/29 00:00 [accepted] PHST- 2024/09/18 12:44 [medline] PHST- 2024/07/29 12:44 [pubmed] PHST- 2024/07/29 09:52 [entrez] AID - 10.1111/dom.15796 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4178-4196. doi: 10.1111/dom.15796. Epub 2024 Jul 29. PMID- 39072425 OWN - NLM STAT- MEDLINE DCOM- 20240830 LR - 20260127 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 40 IP - 9 DP - 2024 Sep TI - The first report of leukocytoclastic vasculitis induced by once-weekly subcutaneous semaglutide. PG - 1525-1531 LID - 10.1080/03007995.2024.2386047 [doi] AB - INTRODUCTION: Leukocytoclastic vasculitis (LCV) is a small vessel vasculitis involving arterioles, capillaries and postcapillary venules. LCV is generally confined to the skin, with extracutaneous manifestations occurring less frequently. LCV has multiple potential etiologies. Indeed, histological LCV can be found in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, immune complex vasculitis, vasculitis associated with systemic diseases (i.e. sarcoidosis, Sjogren's syndrome, rheumatoid arthritis, and systemic lupus erythematosus), or in vasculitis associated with cancer, infections, sepsis and use of certain medications. LCV can also be idiopathic in up to 50% of cases. CASE REPORT: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist used for management of type 2 diabetes mellitus (T2DM), obesity and overweight associated with one or more weight-related comorbidities. A case of drug-induced LCV has already been described with the use of once-daily oral semaglutide. Herein, we describe the first case of skin-limited LCV induced by once-weekly subcutaneous semaglutide in a 73-year-old man with T2DM, who experienced the complete resolution of the skin lesions shortly after the discontinuation of semaglutide therapy. CONCLUSION: Future prospective studies, adverse event reporting and post-marketing surveillance will certainly contribute to establishing if LCV represents a less rare than expected side effect of both oral and subcutaneous semaglutide formulations. FAU - Pinheiro, Marcelo Maia AU - Pinheiro MM AD - UNIVAG, Centro Universitario de Varzea Grande, Varzea Grande, MT, Brazil. FAU - de Souza, Luciana Gasques AU - de Souza LG AD - UFMT, Universidade Federal de Mato Grosso, Cuiaba, MT, Brazil. FAU - Nunes, Guilherme Pavini AU - Nunes GP AD - UNIVAG, Centro Universitario de Varzea Grande, Varzea Grande, MT, Brazil. FAU - Martin, Isis Franco AU - Martin IF AD - UNIVAG, Centro Universitario de Varzea Grande, Varzea Grande, MT, Brazil. FAU - de Oliveira, Yasmin Utuari AU - de Oliveira YU AD - UNIVAG, Centro Universitario de Varzea Grande, Varzea Grande, MT, Brazil. FAU - Pinheiro, Felipe Moura Maia AU - Pinheiro FMM AD - Hospital das Clinicas, Faculdade de Medicina de Sao Paulo, Universidade de Sao Paulo-USP, Sao Paulo, SP, Brazil. FAU - Costa, Lygia Nazario AU - Costa LN AD - LAPAT Anatomia Patologica e Citopatologia, Cuiaba, MT, Brazil. FAU - Caprio, Massimiliano AU - Caprio M AD - Department of Human Sciences and Promotion of the Quality of Life & Laboratory of Cardiovascular Endocrinology, San Raffaele Open University & San Raffaele Research Institute-IRCCS San Raffaele, Rome, Italy. FAU - Della-Morte, David AU - Della-Morte D AD - Department of Biomedicine and Prevention, Section of Clinical Nutrition and Nutrigenomics, University of Rome Tor Vergata, Rome, Italy. FAU - Infante, Marco AU - Infante M AUID- ORCID: 0000-0003-2032-8735 AD - Section of Diabetes & Metabolic Disorders, UniCamillus, Saint Camillus International University of Health Sciences, Rome, Italy. LA - eng PT - Case Reports PT - Journal Article DEP - 20240802 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Vasculitis, Leukocytoclastic, Cutaneous/chemically induced/drug therapy/pathology MH - Injections, Subcutaneous MH - Hypoglycemic Agents/adverse effects/administration & dosage MH - Semaglutide OTO - NOTNLM OT - glp-1 OT - glp-1ra OT - glucagon-like peptide 1 receptor agonist OT - leukocytoclastic vasculitis OT - once-weekly semaglutide OT - subcutaneous semaglutide OT - type 2 diabetes mellitus EDAT- 2024/07/29 12:45 MHDA- 2024/08/31 09:53 CRDT- 2024/07/29 06:43 PHST- 2024/08/31 09:53 [medline] PHST- 2024/07/29 12:45 [pubmed] PHST- 2024/07/29 06:43 [entrez] AID - 10.1080/03007995.2024.2386047 [doi] PST - ppublish SO - Curr Med Res Opin. 2024 Sep;40(9):1525-1531. doi: 10.1080/03007995.2024.2386047. Epub 2024 Aug 2. PMID- 39058274 OWN - NLM STAT- MEDLINE DCOM- 20241119 LR - 20260127 IS - 1365-2362 (Electronic) IS - 0014-2972 (Linking) VI - 54 IP - 12 DP - 2024 Dec TI - Glucagon-like peptide-1 receptor agonist semaglutide reduces atrial fibrillation incidence: A systematic review and meta-analysis. PG - e14292 LID - 10.1111/eci.14292 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are new anti-hyperglycaemic drugs with proven cardiovascular (CV) benefit in diabetic and non-diabetic patients at high CV risk. Despite a neutral class effect on arrhythmia risk, data on semaglutide suggest a possible drug-specific benefit in reducing atrial fibrillation (AF) occurrence. OBJECTIVE: To perform a meta-analysis of randomized clinical trials (RCTs) to assess the risk of incident AF in patients treated with semaglutide compared to placebo. METHODS AND RESULTS: Ten RCTs were included in the analysis. Study population encompassed 12,651 patients (7285 in semaglutide and 5366 in placebo arms), with median follow-up of 68 months. A random effect meta-analytic model was adopted to pool relative risk (RR) of incident AF. Semaglutide reduces the risk of AF by 42% (RR .58, 95% CI .40-.85), with low heterogeneity across the studies (I(2) 0%). At subgroup analysis, no differences emerged between oral and subcutaneous administration (oral: RR .53, 95% CI .23-1.24, I(2) 0%; subcutaneous: RR .59, 95% CI .39-.91, I(2) 0%; p-value .83). In addition, meta-regression analyses did not show any potential influence of baseline study covariates, in particular the proportion of diabetic patients (p-value .14) and body mass index (BMI) (p-value .60). CONCLUSIONS: Semaglutide significantly reduces the occurrence of incident AF by 42% as compared to placebo in individuals at high CV risk, mainly affected by type 2 diabetes mellitus. This effect appears to be consistent independently of the route of administration of the drug (oral or subcutaneous), the presence of underlying diabetes and BMI. CI - (c) 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation. FAU - Saglietto, Andrea AU - Saglietto A AUID- ORCID: 0000-0001-9475-1507 AD - Division of Cardiology, Cardiovascular and Thoracic Department, "Citta della Salute e della Scienza" Hospital, Turin, Italy. AD - Department of Medical Sciences, University of Turin, Turin, Italy. AD - Heart Institute, Teknon Medical Centre, Barcelona, Spain. FAU - Falasconi, Giulio AU - Falasconi G AD - Heart Institute, Teknon Medical Centre, Barcelona, Spain. AD - Campus Clinic, University of Barcelona, Barcelona, Spain. AD - Arrhythmology Department, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Penela, Diego AU - Penela D AD - Heart Institute, Teknon Medical Centre, Barcelona, Spain. AD - Arrhythmology Department, IRCCS Humanitas Research Hospital, Rozzano, Italy. FAU - Francia, Pietro AU - Francia P AD - Heart Institute, Teknon Medical Centre, Barcelona, Spain. AD - Division of Cardiology, Department of Clinical and Molecular Medicine, St. Andrea Hospital, Sapienza University. FAU - Sau, Arunashis AU - Sau A AD - National Heart and Lung Institute, Hammersmith Campus, Imperial College London, London, UK. AD - Department of Cardiology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK. FAU - Ng, Fu Siong AU - Ng FS AD - National Heart and Lung Institute, Hammersmith Campus, Imperial College London, London, UK. AD - Department of Cardiology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK. AD - Department of Cardiology, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK. FAU - Dusi, Veronica AU - Dusi V AD - Division of Cardiology, Cardiovascular and Thoracic Department, "Citta della Salute e della Scienza" Hospital, Turin, Italy. AD - Department of Medical Sciences, University of Turin, Turin, Italy. FAU - Castagno, Davide AU - Castagno D AD - Division of Cardiology, Cardiovascular and Thoracic Department, "Citta della Salute e della Scienza" Hospital, Turin, Italy. AD - Department of Medical Sciences, University of Turin, Turin, Italy. FAU - Gaita, Fiorenzo AU - Gaita F AD - Department of Medical Sciences, University of Turin, Turin, Italy. AD - Cardiology Unit, J Medical, Turin, Italy. FAU - Berruezo, Antonio AU - Berruezo A AD - Heart Institute, Teknon Medical Centre, Barcelona, Spain. FAU - De Ferrari, Gaetano Maria AU - De Ferrari GM AD - Division of Cardiology, Cardiovascular and Thoracic Department, "Citta della Salute e della Scienza" Hospital, Turin, Italy. AD - Department of Medical Sciences, University of Turin, Turin, Italy. FAU - Anselmino, Matteo AU - Anselmino M AD - Division of Cardiology, Cardiovascular and Thoracic Department, "Citta della Salute e della Scienza" Hospital, Turin, Italy. AD - Department of Medical Sciences, University of Turin, Turin, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240726 PL - England TA - Eur J Clin Invest JT - European journal of clinical investigation JID - 0245331 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Administration, Oral MH - *Atrial Fibrillation/epidemiology/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptides/administration & dosage MH - Incidence MH - Injections, Subcutaneous MH - *Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage MH - Semaglutide OTO - NOTNLM OT - atrial fibrillation OT - glucagon-like peptide-1 receptor agonists OT - overweight OT - semaglutide EDAT- 2024/07/26 12:47 MHDA- 2024/11/19 11:00 CRDT- 2024/07/26 09:33 PHST- 2024/05/20 00:00 [received] PHST- 2024/07/16 00:00 [accepted] PHST- 2024/11/19 11:00 [medline] PHST- 2024/07/26 12:47 [pubmed] PHST- 2024/07/26 09:33 [entrez] AID - 10.1111/eci.14292 [doi] PST - ppublish SO - Eur J Clin Invest. 2024 Dec;54(12):e14292. doi: 10.1111/eci.14292. Epub 2024 Jul 26. PMID- 39049060 OWN - NLM STAT- MEDLINE DCOM- 20240725 LR - 20260127 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 24 IP - 1 DP - 2024 Jul 24 TI - Efficacy and safety of oral semaglutide in older patients with type 2 diabetes: a retrospective observational study (the OTARU-SEMA study). PG - 124 LID - 10.1186/s12902-024-01658-6 [doi] LID - 124 AB - BACKGROUND: Oral semaglutide in older subjects with type 2 diabetes was as effective as in younger subjects, according to phase 3 clinical trials. However, its efficacy can be limited in very aged population, due to the presence of impaired cognitive function and the complex instructions for its use. Here, we investigated its efficacy and safety by further age bracket in older subjects in real-world. METHODS: We retrospectively studied subjects > 65 years of age with type 2 diabetes who started oral semaglutide treatment. The primary outcome was the change in glycated hemoglobin (HbA1c) over 6 months. Adverse events and cognitive function were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and the Hasegawa Dementia Rating Scale-revised (HDS-R). The achievement rate of glycemic targets was evaluated based on the age, health status of subjects and their use of anti-diabetic agents which can cause hypoglycemia, with additional analysis between two subgroups; early (65-74) versus late (>/= 75) older. Furthermore, we evaluated the relationships between their improvements in HbA1c and the baseline characteristics of the subjects, including their cognitive function and insulin secretory capacity. RESULTS: We studied the efficacy of the drug in 24 subjects. Their HbA1c and body weight significantly decreased (- 13.1 +/- 7.5 mmol/mol and - 3.0 +/- 2.4 kg, respectively; P < 0.01). Although cognitive function was lower in the late older group (r = -0.57, P < 0.01), changes in HbA1c showed no difference between the two subgroups (P = 0.66) and it correlated with the insulin secretory capacity rather than cognitive function (r = -0.49, P < 0.05). Glycemic targets were more likely to be achieved (P < 0.01), but HbA1c excessively decreased in late older subjects who were also using insulin or an insulin secretagogue. The frequency of adverse events was similar to that in the clinical trial, whereas discontinuation of medication were more frequent among the late older subjects (Early; n = 2, Late; n = 4). CONCLUSIONS: Oral semaglutide improves the glycemic control of older subjects, but it might be a risk for potential hypoglycemia and discontinuation because of adverse events in subjects of >/= 75 years. Attention should be paid to insulin secretory capacity and concomitant medications rather than concern about adherence. CI - (c) 2024. The Author(s). FAU - Oe, Yuki AU - Oe Y AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. AD - Department of Diabetes, Otaru General Hospital, Wakamatsu-1-1-1, Otaru, Hokkaido, 047-0017, Japan. FAU - Nomoto, Hiroshi AU - Nomoto H AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. hnomoto@med.hokudai.ac.jp. AD - Division of Endocrinology, Metabolism, and Rheumatology, Department of Internal Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka-Higashi, Asahikawa-City, Hokkaido, 078-8510, Japan. hnomoto@med.hokudai.ac.jp. FAU - Cho, Kyu Yong AU - Cho KY AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. FAU - Yokozeki, Kei AU - Yokozeki K AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. AD - Department of Diabetes, Otaru General Hospital, Wakamatsu-1-1-1, Otaru, Hokkaido, 047-0017, Japan. FAU - Ono, Tsubasa AU - Ono T AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. AD - Department of Diabetes, Otaru General Hospital, Wakamatsu-1-1-1, Otaru, Hokkaido, 047-0017, Japan. FAU - Miya, Aika AU - Miya A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. FAU - Kameda, Hiraku AU - Kameda H AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. FAU - Nakamura, Akinobu AU - Nakamura A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. FAU - Arimura, Yoshiaki AU - Arimura Y AD - Department of Gastroenterology, Otaru General Hospital, Wakamatsu-1-1-1, Otaru, Hokkaido, 047-0017, Japan. FAU - Atsumi, Tatsuya AU - Atsumi T AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, North-15, West-7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. LA - eng PT - Journal Article PT - Observational Study DEP - 20240724 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Male MH - Female MH - Retrospective Studies MH - Aged MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - *Glycated Hemoglobin/analysis MH - Aged, 80 and over MH - Administration, Oral MH - Blood Glucose/analysis/drug effects MH - Treatment Outcome MH - Hypoglycemia/chemically induced MH - Follow-Up Studies MH - Cognition/drug effects MH - Semaglutide PMC - PMC11267784 OTO - NOTNLM OT - Aged OT - Cognitive test OT - Glucagon-like peptide 1 receptor OT - Oral medicine OT - Type 2 diabetes COIS- YO has received honoraria for lectures from Novo Nordisk Pharma Ltd.. HN has received honoraria for lectures from Novo Nordisk Pharma Ltd. and Sumitomo Pharma Co., Ltd; and has obtained research support from Kowa Pharmaceutical Co.. AN has received honoraria for lectures from Mitsubishi Tanabe Pharma and has obtained research support from Kowa Co., Ltd. TA has received honoraria for lectures from GlaxoSmithKline plc., Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd. Eisai Co. Ltd., AbbVie Inc., UCB Japan Co. Ltd., Novartis Pharma K.K., Pfizer Inc. Gilead Sciences, Inc., Daiichi Sankyo Co., Ltd., Gilead Sciences, Inc., Daiichi Sankyo Co., Ltd., AstraZeneca plc., Asahi Kasei Pharma Co., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd.; and research grants from Eli Lilly Japan K.K., AbbVie Inc., Bristol-Myers Squibb Co., Daiichi Sankyo Co., Ltd., Asahi Kasei Pharma Co., Eisai Co. Ltd., Chugai Pharmaceutical Co., Ltd., AstraZeneca plc., Novartis Pharma K.K., Pfizer Inc. and UCB Japan Co., Ltd.; and consultancy fees from GlaxoSmithKline plc., Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd., Boehringer Ingelheim., Bristol-Myers Squibb Co., Amgen K.K., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Gilead Sciences, Inc. and Daiichi Sankyo Co., Ltd.. KYC, KY, TO, AM, HK, and YA have no conflicts of interest to declare. EDAT- 2024/07/26 12:40 MHDA- 2024/07/26 12:41 PMCR- 2024/07/24 CRDT- 2024/07/25 00:09 PHST- 2024/02/04 00:00 [received] PHST- 2024/07/16 00:00 [accepted] PHST- 2024/07/26 12:41 [medline] PHST- 2024/07/26 12:40 [pubmed] PHST- 2024/07/25 00:09 [entrez] PHST- 2024/07/24 00:00 [pmc-release] AID - 10.1186/s12902-024-01658-6 [pii] AID - 1658 [pii] AID - 10.1186/s12902-024-01658-6 [doi] PST - epublish SO - BMC Endocr Disord. 2024 Jul 24;24(1):124. doi: 10.1186/s12902-024-01658-6. PMID- 39047254 OWN - NLM STAT- MEDLINE DCOM- 20240724 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 391 IP - 4 DP - 2024 Jul 25 TI - Semaglutide, Obesity-Related Heart Failure, and Type 2 Diabetes. Reply. PG - 381-382 LID - 10.1056/NEJMc2406233#sa4 [pii] LID - 10.1056/NEJMc2406233 [doi] FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Saint Luke's Mid America Heart Institute, Kansas City, MO mkosiborod@saint-lukes.org. FAU - Petrie, Mark C AU - Petrie MC AD - University of Glasgow, Glasgow, United Kingdom. FAU - Borlaug, Barry A AU - Borlaug BA AD - Mayo Clinic, Rochester, MN. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2024 Apr 18;390(15):1394-1407. doi: 10.1056/NEJMoa2313917. PMID: 38587233 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/etiology MH - Glucagon-Like Peptides/therapeutic use MH - *Heart Failure/drug therapy/etiology MH - Hypoglycemic Agents/therapeutic use MH - *Obesity/complications/drug therapy/surgery MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Bariatric Surgery MH - Weight Loss/drug effects/physiology MH - Semaglutide EDAT- 2024/07/26 12:40 MHDA- 2024/07/26 12:41 CRDT- 2024/07/24 16:22 PHST- 2024/07/26 12:41 [medline] PHST- 2024/07/26 12:40 [pubmed] PHST- 2024/07/24 16:22 [entrez] AID - 10.1056/NEJMc2406233#sa4 [pii] AID - 10.1056/NEJMc2406233 [doi] PST - ppublish SO - N Engl J Med. 2024 Jul 25;391(4):381-382. doi: 10.1056/NEJMc2406233. PMID- 39047253 OWN - NLM STAT- MEDLINE DCOM- 20240725 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 391 IP - 4 DP - 2024 Jul 25 TI - Semaglutide, Obesity-Related Heart Failure, and Type 2 Diabetes. PG - 381 LID - 10.1056/NEJMc2406233#sa3 [pii] LID - 10.1056/NEJMc2406233 [doi] FAU - Ammon, Jessica P AU - Ammon JP AD - University of Tennessee Health Science Center, Memphis, TN klh742@uthsc.edu. FAU - Jackson, Christopher D AU - Jackson CD AD - University of Tennessee Health Science Center, Memphis, TN klh742@uthsc.edu. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2024 Apr 18;390(15):1394-1407. doi: 10.1056/NEJMoa2313917. PMID: 38587233 MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Heart Failure/etiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Obesity/complications/drug therapy/surgery MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - Bariatric Surgery MH - Semaglutide EDAT- 2024/07/26 12:39 MHDA- 2024/07/26 12:40 CRDT- 2024/07/24 16:22 PHST- 2024/07/26 12:40 [medline] PHST- 2024/07/26 12:39 [pubmed] PHST- 2024/07/24 16:22 [entrez] AID - 10.1056/NEJMc2406233#sa3 [pii] AID - 10.1056/NEJMc2406233 [doi] PST - ppublish SO - N Engl J Med. 2024 Jul 25;391(4):381. doi: 10.1056/NEJMc2406233. PMID- 39047252 OWN - NLM STAT- MEDLINE DCOM- 20240725 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 391 IP - 4 DP - 2024 Jul 25 TI - Semaglutide, Obesity-Related Heart Failure, and Type 2 Diabetes. PG - 380-381 LID - 10.1056/NEJMc2406233#sa2 [pii] LID - 10.1056/NEJMc2406233 [doi] FAU - Wagner, Jeffrey AU - Wagner J AD - University of Colorado Anschutz Medical Campus, Aurora, CO jeffrey.wagner@cuanschutz.edu. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2024 Apr 18;390(15):1394-1407. doi: 10.1056/NEJMoa2313917. PMID: 38587233 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/etiology MH - Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Heart Failure/drug therapy/etiology MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - *Obesity/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Semaglutide EDAT- 2024/07/26 12:39 MHDA- 2024/07/26 12:40 CRDT- 2024/07/24 16:22 PHST- 2024/07/26 12:40 [medline] PHST- 2024/07/26 12:39 [pubmed] PHST- 2024/07/24 16:22 [entrez] AID - 10.1056/NEJMc2406233#sa2 [pii] AID - 10.1056/NEJMc2406233 [doi] PST - ppublish SO - N Engl J Med. 2024 Jul 25;391(4):380-381. doi: 10.1056/NEJMc2406233. PMID- 39047251 OWN - NLM STAT- MEDLINE DCOM- 20240724 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 391 IP - 4 DP - 2024 Jul 25 TI - Semaglutide, Obesity-Related Heart Failure, and Type 2 Diabetes. PG - 380 LID - 10.1056/NEJMc2406233#sa1 [pii] LID - 10.1056/NEJMc2406233 [doi] FAU - Cohen, Charlotte AU - Cohen C AD - Hopital Bichat, Paris, France. FAU - Cohen, Regis AU - Cohen R AD - Centre Hospitalier de Saint-Denis, Saint-Denis, France cohen.regis93@gmail.com. FAU - Sabouret, Pierre AU - Sabouret P AD - Pitie-Salpetriere Hospital, Paris, France. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2024 Apr 18;390(15):1394-1407. doi: 10.1056/NEJMoa2313917. PMID: 38587233 MH - Humans MH - Bariatric Surgery MH - *Diabetes Mellitus, Type 2/drug therapy/etiology MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - *Heart Failure/drug therapy/etiology MH - Hypoglycemic Agents/therapeutic use MH - *Obesity/complications/drug therapy MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Weight Loss/drug effects/physiology MH - Semaglutide EDAT- 2024/07/26 12:40 MHDA- 2024/07/26 12:41 CRDT- 2024/07/24 16:22 PHST- 2024/07/26 12:41 [medline] PHST- 2024/07/26 12:40 [pubmed] PHST- 2024/07/24 16:22 [entrez] AID - 10.1056/NEJMc2406233#sa1 [pii] AID - 10.1056/NEJMc2406233 [doi] PST - ppublish SO - N Engl J Med. 2024 Jul 25;391(4):380. doi: 10.1056/NEJMc2406233. PMID- 39046272 OWN - NLM STAT- MEDLINE DCOM- 20240830 LR - 20260127 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 40 IP - 9 DP - 2024 Sep TI - Evaluating the safety profile of semaglutide: an updated meta-analysis. PG - 1495-1514 LID - 10.1080/03007995.2024.2383731 [doi] AB - BACKGROUND: Semaglutide is increasingly used in the management of type 2 diabetes mellitus and obesity. Ensuring the safety of this medication is crucial for its clinical use. This meta-analysis evaluates the safety profile of semaglutide across patient populations and treatment durations. METHODS: Randomized controlled trials assessing the safety of semaglutide vs. placebo, with specified treatment durations were identified. The primary outcome was occurrence of any cardiovascular adverse events. Secondary outcomes included sudden cardiac death, adverse events leading to death, adverse events, gastrointestinal side effects, occurrence of hypoglycemia, and new-onset neoplasm. RESULTS: A total of 23 studies met the inclusion criteria with a combined sample size of 57,911 participants. The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups. CONCLUSION: Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity. It is generally well-tolerated, with a low incidence of adverse events. Clinicians should be aware of these findings and monitor patients accordingly. Further long-term studies are warranted to assess the safety of semaglutide in clinical practice. FAU - Rivera, Frederick Berro AU - Rivera FB AUID- ORCID: 0000-0001-9100-0724 AD - Department of Medicine, Lincoln Medical Center, New York, NY, USA. FAU - Arias-Aguirre, Eloise AU - Arias-Aguirre E AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Aguirre, Zedrick AU - Aguirre Z AUID- ORCID: 0009-0003-3227-6052 AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Ybanez, Mc John C AU - Ybanez MJC AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Rubia, Janos Marc M AU - Rubia JMM AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Galang, Danica Janine AU - Galang DJ AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Lumbang, Grace Nooriza AU - Lumbang GN AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Ruyeras, Jade Monica Marie J AU - Ruyeras JMMJ AUID- ORCID: 0009-0009-9795-7979 AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Magalong, John Vincent AU - Magalong JV AD - College of Medicine, San Beda University, Manila, Philippines. FAU - Pine, Polyn Luz AU - Pine PL AD - Ateneo School of Medicine and Public Health, Manila, Philippines. FAU - Amigo, John Andrew C AU - Amigo JAC AD - Ateneo School of Medicine and Public Health, Manila, Philippines. FAU - Ansay, Marie Francesca M AU - Ansay MFM AD - Department of Family Medicine, University of Pittsburgh Medical Center (UPMC) McKeesport, McKeesport, PA, USA. FAU - Zelenkov, Nenad AU - Zelenkov N AD - Department of Family Medicine, University of Pittsburgh Medical Center (UPMC) McKeesport, McKeesport, PA, USA. FAU - Thomas, Steve Samuel AU - Thomas SS AD - Arizona State University, Tempe, AZ, USA. FAU - Vijayaraghavan, Krishnaswami AU - Vijayaraghavan K AD - University of Arizona, Tucson, AZ, USA. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20240727 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Female MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Obesity/drug therapy MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - Semaglutide OTO - NOTNLM OT - Semaglutide OT - adverse events OT - glucagon-like peptide-1 receptor agonist OT - meta-analysis OT - obesity OT - safety profile OT - type 2 diabetes mellitus EDAT- 2024/07/24 12:43 MHDA- 2024/08/31 09:49 CRDT- 2024/07/24 09:23 PHST- 2024/08/31 09:49 [medline] PHST- 2024/07/24 12:43 [pubmed] PHST- 2024/07/24 09:23 [entrez] AID - 10.1080/03007995.2024.2383731 [doi] PST - ppublish SO - Curr Med Res Opin. 2024 Sep;40(9):1495-1514. doi: 10.1080/03007995.2024.2383731. Epub 2024 Jul 27. PMID- 39044308 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260615 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Medication adherence to sodium-glucose cotransporter-2 inhibitors versus glucagon-like peptide-1 receptor agonists: A meta-analysis. PG - 4544-4550 LID - 10.1111/dom.15809 [doi] AB - AIM: To perform a meta-analysis comparing real-world medication adherence to sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs). MATERIALS AND METHODS: A systematic search of Medline and Embase was conducted through October 2023. To meet inclusion criteria, articles had to be published in full text form and directly compare medication adherence to SGLT2is versus GLP-1RAs in adults. Only studies evaluating real-world data and utilizing the proportion of days covered (PDC) to measure adherence were included. Non-adherence, defined as the proportion of patients with a PDC <80%, was the primary outcome. A subgroup analysis evaluating results among studies conducted in the United States was performed. RESULTS: We identified eight studies evaluating 205 103 patients for inclusion. The most common country from which the data was derived was the United States (n = 5 studies). Upon meta-analysis, we observed no difference in non-adherence (i.e. PDC <80%) to SGLT2is versus GLP-1RAs (relative risk = 0.86; 95% confidence interval = 0.72-1.02). In the analysis, including only US studies, SGLT2i use was associated with a 23% lower risk of non-adherence compared with GLP-1RA use (relative risk = 0.77; 95% confidence interval = 0.72-0.82). CONCLUSIONS: In this meta-analysis of eight studies that included approximately 200 000 patients, there was no difference in adherence to SGLT2is versus GLP-1RAs. However, SGLT2i use was associated with higher adherence when the analysis was limited to US studies. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Johnson, Conner E AU - Johnson CE AD - University of South Carolina School of Medicine Greenville, Greenville, South Carolina, USA. FAU - Sussman, Whitney B AU - Sussman WB AD - University of South Carolina School of Medicine Greenville, Greenville, South Carolina, USA. FAU - Weeda, Erin R AU - Weeda ER AUID- ORCID: 0000-0001-7876-5802 AD - University of South Carolina School of Medicine Greenville, Greenville, South Carolina, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240723 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Drug Monitoring OTO - NOTNLM OT - canagliflozin OT - dapagliflozin OT - empagliflozin OT - exenatide OT - liraglutide OT - semaglutide EDAT- 2024/07/24 00:42 MHDA- 2024/09/18 12:51 CRDT- 2024/07/23 23:49 PHST- 2024/06/23 00:00 [revised] PHST- 2024/06/19 00:00 [received] PHST- 2024/07/04 00:00 [accepted] PHST- 2024/09/18 12:51 [medline] PHST- 2024/07/24 00:42 [pubmed] PHST- 2024/07/23 23:49 [entrez] AID - 10.1111/dom.15809 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4544-4550. doi: 10.1111/dom.15809. Epub 2024 Jul 23. PMID- 39044306 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260615 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Glucagon-like peptide-1 receptor agonists in adolescents with overweight or obesity with or without type 2 diabetes multimorbidity-a systematic review and network meta-analysis. PG - 4302-4317 LID - 10.1111/dom.15777 [doi] AB - AIM: To synthesize the evidence on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adolescents with overweight or obesity. MATERIALS AND METHODS: For this systematic review and network meta-analysis, we searched five databases and registries until 2 March 2024 for eligible randomized controlled trials (RCTs). The primary outcome was weight change. We did a pairwise meta-analysis to compare GLP-1RAs and placebo, followed by a drug-wise network meta-analysis (NMA) to compare GLP-1RAs against each other. RESULTS: We screened 770 records to include 12 RCTs with 883 participants. The evidence suggests that GLP-1RAs reduced weight (mean difference -4.21 kg, 95% confidence interval [CI] -7.08 to -1.35) and body mass index (BMI; mean difference -2.11 kg/m(2), 95% CI -3.60 to -0.62). The evidence on waist circumference, body fat percentage and adverse events (AEs) was very uncertain. The results remained consistent with subgroup analyses for coexisting type 2 diabetes. Longer therapy duration led to a greater reduction in weight and BMI. In the NMA, semaglutide led to the greatest weight reduction, followed by exenatide, liraglutide and lixisenatide. CONCLUSIONS: The evidence suggests that GLP-1RAs reduce most weight-related outcomes in adolescents, with semaglutide being the most efficacious. There is uncertain evidence on body fat and serious AEs, probably due to fewer studies and low incidence, respectively. Larger RCTs with head-to-head comparisons, pragmatic design, adiposity-related outcomes, and economic evaluation can further guide the use and choice of GLP-1RAs. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Shamim, Muhammad Aaqib AU - Shamim MA AUID- ORCID: 0000-0003-3418-8171 AD - Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India. FAU - Patil, Amol N AU - Patil AN AUID- ORCID: 0000-0001-8552-2796 AD - Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. FAU - Amin, Ulfat AU - Amin U AUID- ORCID: 0000-0002-1299-3279 AD - Syed Mantaquie Memorial College of Nursing and Medical Technology (SMMCNMT), Islamic University of Science and Technology (IUST), Awantipora, India. FAU - Roy, Tuli AU - Roy T AUID- ORCID: 0009-0006-8952-4872 AD - Department of Nursing, GitaRam College of Nursing, Berhampore, India. FAU - Tiwari, Krishna AU - Tiwari K AUID- ORCID: 0009-0001-2855-6006 AD - Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India. FAU - Husain, Noor AU - Husain N AD - Department of Pharmacology, Indira Gandhi Institute of Medical Sciences, Patna, India. FAU - Kumar, Jogender AU - Kumar J AUID- ORCID: 0000-0002-0464-9689 AD - Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India. FAU - Chenchula, Santenna AU - Chenchula S AUID- ORCID: 0000-0001-7466-1037 AD - Department of Pharmacology, All India Institute of Medical Sciences, Bhopal, India. FAU - Rao, Priyanka AU - Rao P AUID- ORCID: 0000-0002-5152-3771 AD - Indian Institute of Public Health Gandhinagar, Gandhinagar, India. FAU - Ganesh, Venkata AU - Ganesh V AUID- ORCID: 0000-0001-8265-5198 AD - Department of Anaesthesia and Intensive Care, Postgraduate Institute of Medical Education and Research, Chandigarh, India. FAU - Varthya, Shoban Babu AU - Varthya SB AUID- ORCID: 0000-0002-7163-0400 AD - Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India. FAU - Singh, Surjit AU - Singh S AUID- ORCID: 0000-0002-8990-3235 AD - Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India. FAU - Shukla, Ravindra AU - Shukla R AUID- ORCID: 0000-0002-5742-4096 AD - Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, Jodhpur, India. FAU - Rastogi, Ashu AU - Rastogi A AUID- ORCID: 0000-0002-9375-3102 AD - Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. FAU - Gandhi, Aravind P AU - Gandhi AP AUID- ORCID: 0000-0003-3898-5450 AD - Department of Community Medicine, All India Institute of Medical Sciences, Nagpur, India. FAU - Satapathy, Prakisini AU - Satapathy P AD - Center for Global Health Research, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India. AD - Medical Laboratories Techniques Department, AL-Mustaqbal University, Hillah, Iraq. FAU - Sah, Ranjit AU - Sah R AUID- ORCID: 0000-0002-5158-5550 AD - SR Sanjeevani Hospital, Kalyanpur, Siraha, Nepal. AD - Department of Microbiology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, India. AD - Department of Public Health Dentistry, Dr. D.Y. Patil Dental College and Hospital, Dr. D.Y. Patil Vidyapeeth, Pune, India. FAU - Padhi, Bijaya Kumar AU - Padhi BK AUID- ORCID: 0000-0002-2828-2375 AD - Department of Community Medicine and School of Public Health, Postgraduate Institute of Medical Education and Research, Chandigarh, India. FAU - Dwivedi, Pradeep AU - Dwivedi P AUID- ORCID: 0000-0001-6709-3780 AD - Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, India. AD - Centre of Excellence for Tribal Health, All India Institute of Medical Sciences, Jodhpur, India. FAU - Khunti, Kamlesh AU - Khunti K AUID- ORCID: 0000-0003-2343-7099 AD - Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK. AD - NIHR Applied Research Collaboration East Midlands, Leicester, UK. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20240723 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Adolescent MH - *Hypoglycemic Agents/therapeutic use MH - *Pediatric Obesity/drug therapy/complications MH - Randomized Controlled Trials as Topic MH - Exenatide/therapeutic use MH - Overweight/complications/drug therapy MH - Liraglutide/therapeutic use MH - Female MH - Weight Loss/drug effects MH - Male MH - Comorbidity MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - adolescent/teen OT - glucagon-like peptide-1 receptor agonists OT - metabolic control OT - overweight OT - weight loss EDAT- 2024/07/24 00:42 MHDA- 2024/09/18 12:43 CRDT- 2024/07/23 23:49 PHST- 2024/06/17 00:00 [revised] PHST- 2024/06/15 00:00 [received] PHST- 2024/06/25 00:00 [accepted] PHST- 2024/09/18 12:43 [medline] PHST- 2024/07/24 00:42 [pubmed] PHST- 2024/07/23 23:49 [entrez] AID - 10.1111/dom.15777 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4302-4317. doi: 10.1111/dom.15777. Epub 2024 Jul 23. PMID- 39042202 OWN - NLM STAT- MEDLINE DCOM- 20240723 LR - 20261010 IS - 1557-1904 (Electronic) IS - 1557-1890 (Linking) VI - 19 IP - 1 DP - 2024 Jul 23 TI - Semaglutide Attenuates Anxious and Depressive-Like Behaviors and Reverses the Cognitive Impairment in a Type 2 Diabetes Mellitus Mouse Model Via the Microbiota-Gut-Brain Axis. PG - 36 LID - 10.1007/s11481-024-10142-w [doi] AB - Newly conducted research suggests that metabolic disorders, like diabetes and obesity, play a significant role as risk factors for psychiatric disorders. This connection presents a potential avenue for creating novel antidepressant medications by repurposing drugs originally developed to address antidiabetic conditions. Earlier investigations have shown that GLP-1 (Glucagon-like Peptide-1) analogs exhibit neuroprotective qualities in various models of neurological diseases, encompassing conditions such as Alzheimer's disease, Parkinson's disease, and stroke. Moreover, GLP-1 analogs have demonstrated the capability to enhance neurogenesis, a process recognized for its significance in memory formation and the cognitive and emotional aspects of information processing. Nonetheless, whether semaglutide holds efficacy as both an antidepressant and anxiolytic agent remains uncertain. To address this, our study focused on a mouse model of depression linked to type 2 diabetes induced by a High Fat Diet (HFD). In this model, we administered semaglutide (0.05 mg/Kg intraperitoneally) on a weekly basis to evaluate its potential as a therapeutic option for depression and anxiety. Diabetic mice had higher blood glucose, lipidic profile, and insulin resistance. Moreover, mice fed HFD showed higher serum interleukin (IL)-1beta and lipopolysaccharide (LPS) associated with impaired humor and cognition. The analysis of behavioral responses revealed that the administration of semaglutide effectively mitigated depressive- and anxiety-like behaviors, concurrently demonstrating an enhancement in cognitive function. Additionally, semaglutide treatment protected synaptic plasticity and reversed the hippocampal neuroinflammation induced by HFD fed, improving activation of the insulin pathway, demonstrating the protective effects of semaglutide. We also found that semaglutide treatment decreased astrogliosis and microgliosis in the dentate gyrus region of the hippocampus. In addition, semaglutide prevented the DM2-induced impairments of pro-opiomelanocortin (POMC), and G-protein-coupled receptor 43 (GPR43) and simultaneously increased the NeuN + and Glucagon-like Peptide-1 receptor (GLP-1R+) neurons in the hippocampus. Our data also showed that semaglutide increased the serotonin (5-HT) and serotonin transporter (5-HTT) and glutamatergic receptors in the hippocampus. At last, semaglutide changed the gut microbiota profile (increasing Bacterioidetes, Bacteroides acidifaciens, and Blautia coccoides) and decreased leaky gut, improving the gut-brain axis. Taken together, semaglutide has the potential to act as a therapeutic tool for depression and anxiety. CI - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - de Paiva, Igor Henrique Rodrigues AU - de Paiva IHR AD - Laboratory of Ultrastructure, Aggeu Magalhaes Institute (IAM), Av. Moraes Rego s/n, Recife CEP, PE, 50670-420, Brazil. igorhenriqueigor231@gmail.com. AD - Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, Brazil. igorhenriqueigor231@gmail.com. FAU - da Silva, Rodrigo Soares AU - da Silva RS AD - Laboratory of Ultrastructure, Aggeu Magalhaes Institute (IAM), Av. Moraes Rego s/n, Recife CEP, PE, 50670-420, Brazil. AD - Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, Brazil. FAU - Mendonca, Ingrid Prata AU - Mendonca IP AD - Laboratory of Ultrastructure, Aggeu Magalhaes Institute (IAM), Av. Moraes Rego s/n, Recife CEP, PE, 50670-420, Brazil. AD - Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, Brazil. FAU - de Souza, Jose Roberto Botelho AU - de Souza JRB AD - Department of Zoology, Federal University of Pernambuco, Recife, PE, Brazil. FAU - Peixoto, Christina Alves AU - Peixoto CA AD - Laboratory of Ultrastructure, Aggeu Magalhaes Institute (IAM), Av. Moraes Rego s/n, Recife CEP, PE, 50670-420, Brazil. christina.peixoto@fiocruz.br. AD - Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Recife, Brazil. christina.peixoto@fiocruz.br. LA - eng GR - PROEP#400208/2019-9/Centro de Pesquisas Aggeu Magalhaes, Fundacao Oswaldo Cruz/ GR - VPPCB-007-FIO-18-2-17/Fundacao Oswaldo Cruz/ GR - #301777/2012-8/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240723 PL - United States TA - J Neuroimmune Pharmacol JT - Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology JID - 101256586 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Antidepressive Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Glucagon-Like Peptides/pharmacology MH - *Diabetes Mellitus, Type 2/complications/drug therapy/psychology/metabolism MH - Mice MH - *Cognitive Dysfunction/drug therapy/prevention & control/etiology/metabolism MH - *Depression/drug therapy/psychology/metabolism MH - Male MH - *Anxiety/drug therapy/psychology/etiology MH - *Gastrointestinal Microbiome/drug effects MH - *Mice, Inbred C57BL MH - *Brain-Gut Axis/drug effects MH - Diabetes Mellitus, Experimental/complications/drug therapy/psychology/metabolism MH - Disease Models, Animal MH - Antidepressive Agents/pharmacology/therapeutic use MH - Semaglutide OTO - NOTNLM OT - Anxiety OT - Cognition OT - Depression OT - Diabetes mellitus 2 OT - Gut microbiota OT - Semaglutide EDAT- 2024/07/23 12:42 MHDA- 2024/07/23 12:43 CRDT- 2024/07/23 11:05 PHST- 2023/08/09 00:00 [received] PHST- 2024/07/14 00:00 [accepted] PHST- 2024/07/23 12:43 [medline] PHST- 2024/07/23 12:42 [pubmed] PHST- 2024/07/23 11:05 [entrez] AID - 10.1007/s11481-024-10142-w [pii] AID - 10.1007/s11481-024-10142-w [doi] PST - epublish SO - J Neuroimmune Pharmacol. 2024 Jul 23;19(1):36. doi: 10.1007/s11481-024-10142-w. PMID- 39039725 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260615 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Effectiveness of switching from dipeptidyl peptidase-4 inhibitor to oral glucagon-like peptide-1 receptor agonist in Japanese participants with type 2 diabetes mellitus: Prospective observational study using propensity score matching. PG - 4366-4374 LID - 10.1111/dom.15784 [doi] AB - AIM: Recently, the development of the oral glucagon-like peptide-1 receptor agonist semaglutide has drawn a great deal of attention. This study aimed to compare the effectiveness of oral glucagon-like peptide-1 receptor agonist semaglutide and dipeptidyl peptidase-4 (DPP-4) inhibitors on glycaemic control and several metabolic parameters in patients with type 2 diabetes mellitus over a 6-month period. METHODS: Fifty-nine participants were included, and we compared various clinical parameters between before and after switching from DPP-4 inhibitors to oral semaglutide in 'study 1' (pre-post comparison) and set the control group using the propensity score matching method in 'study 2'. RESULTS: In 'study 1', 6 months after the switching, the glycated haemoglobin value was significantly reduced from 7.5% to 7.0%, and the body mass index was also decreased from 29.7 kg/m(2) to 28.8 kg/m(2). Such effects were more clearly observed in participants whose glycaemic control was poor. In 'study 2', after 1:1 propensity score matching, 51 participants from each group were matched, and glycaemic control as well as body weight management were improved in the switching group compared with the DPP-4 inhibitor continuation group over the 6-month observation period. CONCLUSION: In this study, including obese participants with poor glycaemic control, switching DPP-4 inhibitors to oral semaglutide showed more beneficial effects on both glycaemic and weight control, irrespective of age, body weight and diabetes duration. Therefore, we should bear in mind that it would be better to start using an oral semaglutide in clinical practice, particularly in obese participants with poor glycaemic control with DPP-4 inhibitors. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Iwamoto, Hideyuki AU - Iwamoto H AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Kimura, Tomohiko AU - Kimura T AUID- ORCID: 0000-0003-3986-9494 AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Fushimi, Yoshiro AU - Fushimi Y AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Iwamoto, Masahiro AU - Iwamoto M AD - Iwamoto Medical Clinic, Kagawa, Japan. FAU - Tatsumi, Fuminori AU - Tatsumi F AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Sanada, Junpei AU - Sanada J AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Iwamoto, Yuichiro AU - Iwamoto Y AUID- ORCID: 0000-0001-8162-359X AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Katakura, Yukino AU - Katakura Y AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Shimoda, Masashi AU - Shimoda M AUID- ORCID: 0000-0002-4223-9613 AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Nakanishi, Shuhei AU - Nakanishi S AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Mune, Tomoatsu AU - Mune T AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Kaku, Kohei AU - Kaku K AUID- ORCID: 0000-0003-1574-0565 AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Kaneto, Hideaki AU - Kaneto H AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20240722 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Female MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/administration & dosage MH - Middle Aged MH - *Propensity Score MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - Prospective Studies MH - Aged MH - *Glycated Hemoglobin/analysis/drug effects MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Japan MH - Drug Substitution MH - Treatment Outcome MH - Blood Glucose/drug effects MH - Glycemic Control/methods MH - Administration, Oral MH - East Asian People MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - body mass index OT - dipeptidyl peptidase-4 inhibitors OT - glucagon-like peptide-1 receptor agonist OT - glycated haemoglobin OT - oral semaglutide EDAT- 2024/07/23 06:42 MHDA- 2024/09/18 12:50 CRDT- 2024/07/23 00:53 PHST- 2024/06/24 00:00 [revised] PHST- 2024/05/25 00:00 [received] PHST- 2024/06/24 00:00 [accepted] PHST- 2024/09/18 12:50 [medline] PHST- 2024/07/23 06:42 [pubmed] PHST- 2024/07/23 00:53 [entrez] AID - 10.1111/dom.15784 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Oct;26(10):4366-4374. doi: 10.1111/dom.15784. Epub 2024 Jul 22. PMID- 39034750 OWN - NLM STAT- MEDLINE DCOM- 20250423 LR - 20260127 IS - 1528-1159 (Electronic) IS - 0362-2436 (Linking) VI - 50 IP - 8 DP - 2025 Apr 15 TI - No Difference in Short-term Surgical Outcomes From Semaglutide Treatment for Type 2 Diabetes Mellitus After Cervical Decompression and Fusion: A Propensity Score-matched Analysis. PG - 515-521 LID - 10.1097/BRS.0000000000005099 [doi] AB - STUDY DESIGN: Retrospective cohort. OBJECTIVE: To evaluate the impact of semaglutide treatment for Type 2 Diabetes Mellitus (T2DM) on the risk of short-term (<6 mo) postoperative complications in patients undergoing primary cervical spine decompression and fusion (CSDF). SUMMARY OF BACKGROUND DATA: Semaglutide, a GLP-1 receptor agonist, is gaining popularity as a weekly injectable medication for the treatment of T2DM and obesity. Existing research indicates that higher levels of HbA1c and obesity are linked to fewer positive results after undergoing spine surgery, particularly cervical decompression and fusion. Nevertheless, there is a scarcity of publications evaluating the influence of semaglutide therapy on surgical complications, including surgical site infection, wound complications, and reoperation within 6 months, which were aggregated into a composite measure. METHODS: The PearlDiver Database was queried from January 2010 to December 2021 for patients with a primary diagnosis of T2DM who underwent CSDF for degenerative pathology. Patients with semaglutide treatment within 6 months before index surgery were propensity score-matched to patients without the treatment, using age, sex, and Charlson comorbidity index (CCI) as matching covariates. A multivariate regression model was used to investigate the impact of semaglutide treatment on postoperative surgical complications. RESULTS: The propensity score-matched cohort included 596 patients (semaglutide cohort: 298 and control cohort: 298). There were no statistically significant differences between cohorts in the composite measure of postoperative surgical complications following index CSDF (OR 1.26, 95% CI 0.83-1.93, P =0.331). Similarly, both 30-day (OR 0.83, 95% CI 0.49-1.42, P =0.589) and 90-day readmission rate (OR 0.89, 95% CI 0.56-1.42, P =0.724) were similar between both cohorts. CONCLUSIONS: This study suggests that in patients with T2DM, semaglutide treatment is not associated with higher rates of short-term adverse events after CSDF. The effect of semaglutide use on long-term outcomes remains unknown. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Tao, Xu AU - Tao X AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Ranganathan, Sruthi AU - Ranganathan S AD - School of Clinical Medicine, University of Cambridge University, Cambridge UK. FAU - Van Halm-Lutterodt, Nicholas AU - Van Halm-Lutterodt N AD - Department of Orthopedics Surgery, Rhode Island Hospital, Brown University, Providence, RI. AD - School of Public Health and Professional Studies, Brown University, Providence, RI. FAU - Garcia-Vargas, Julia AU - Garcia-Vargas J AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Wu, Andrew AU - Wu A AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Karnati, Janesh AU - Karnati J AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Shankar, Sachin AU - Shankar S AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Agyeman, Nana AU - Agyeman N AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Ashraf, Ahmed AU - Ashraf A AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Barve, Parikshit AU - Barve P AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Childress, Kelly AU - Childress K AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Adogwa, Owoicho AU - Adogwa O AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. LA - eng PT - Journal Article DEP - 20240722 PL - United States TA - Spine (Phila Pa 1976) JT - Spine JID - 7610646 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Spinal Fusion/adverse effects MH - Female MH - Male MH - Propensity Score MH - Retrospective Studies MH - Aged MH - Middle Aged MH - *Decompression, Surgical/adverse effects/trends MH - Treatment Outcome MH - *Cervical Vertebrae/surgery MH - *Postoperative Complications/epidemiology MH - *Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Semaglutide COIS- The authors report no conflicts of interest. EDAT- 2024/07/22 06:43 MHDA- 2025/03/26 12:29 CRDT- 2024/07/22 03:23 PHST- 2024/05/21 00:00 [received] PHST- 2024/06/28 00:00 [accepted] PHST- 2025/03/26 12:29 [medline] PHST- 2024/07/22 06:43 [pubmed] PHST- 2024/07/22 03:23 [entrez] AID - 00007632-990000000-00733 [pii] AID - 10.1097/BRS.0000000000005099 [doi] PST - ppublish SO - Spine (Phila Pa 1976). 2025 Apr 15;50(8):515-521. doi: 10.1097/BRS.0000000000005099. Epub 2024 Jul 22. PMID- 39031282 OWN - NLM STAT- MEDLINE DCOM- 20240906 LR - 20261010 IS - 1534-3170 (Electronic) IS - 1523-3782 (Linking) VI - 26 IP - 9 DP - 2024 Sep TI - Curbing the Obesity Epidemic: Should GLP-1 Receptor Agonists Be the Standard of Care for Obesity? PG - 1011-1019 LID - 10.1007/s11886-024-02097-4 [doi] AB - PURPOSE OF REVIEW: This article summarizes the medical management of obesity with an emphasis on incretin-based therapeutics that target the neuro-hormonal basis of obesity. RECENT FINDINGS: Medications that mimic the effect of incretins, a group of peptide hormones released in response to nutrient intake that regulate appetite, result in potent and durable weight loss. Glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide (GIP) agonists such as semaglutide and tirzepatide are approved by the United States Food and Drug Administration (FDA) for the management of obesity. The SELECT trial demonstrated that semaglutide led to a reduction in major adverse cardiovascular events in patients without diabetes who were either overweight and had preexisting cardiovascular disease or obese. SUMMARY: The treatment of obesity is critical to prevent the progression of cardiovascular-kidney-metabolic syndrome. Incretin-based therapies offer remarkable weight loss and reduce major cardiovascular adverse events. CI - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Kaplan, Jennifer M AU - Kaplan JM AD - Department of Internal Medicine, Section of Endocrinology, Diabetes, and Metabolism, Baylor College of Medicine, One Baylor Plaza, R618, Houston, TX, 77030, USA. FAU - Zaman, Adnin AU - Zaman A AD - Department of Internal Medicine. Division of Endocrinology, Diabetes and Metabolism School of Medicine and Dentistry, University of Rochester, Box 693, 601 Elmwood Avenue, Rochester, NY, 14620, USA. FAU - Abushamat, Layla A AU - Abushamat LA AD - Department of Internal Medicine, Section of Cardiovascular Research, Baylor College of Medicine, One Baylor Plaza, MS BCM285, Houston, TX, 77030, USA. Layla.abushamat@bcm.edu. LA - eng GR - 4-23-CVD1-01/American Diabetes Association/ PT - Journal Article PT - Review DEP - 20240720 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 0 (Incretins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Obesity/drug therapy/complications MH - *Incretins/therapeutic use MH - *Glucagon-Like Peptides/therapeutic use MH - *Cardiovascular Diseases/prevention & control MH - Weight Loss/drug effects MH - Standard of Care MH - Anti-Obesity Agents/therapeutic use/adverse effects MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Cardiovascular kidney metabolic syndrome OT - Cardiovascular outcomes OT - Glucagon-like receptor 1 OT - Incretin OT - Obesity EDAT- 2024/07/20 20:46 MHDA- 2024/09/06 12:44 CRDT- 2024/07/20 11:08 PHST- 2024/07/05 00:00 [accepted] PHST- 2024/09/06 12:44 [medline] PHST- 2024/07/20 20:46 [pubmed] PHST- 2024/07/20 11:08 [entrez] AID - 10.1007/s11886-024-02097-4 [pii] AID - 10.1007/s11886-024-02097-4 [doi] PST - ppublish SO - Curr Cardiol Rep. 2024 Sep;26(9):1011-1019. doi: 10.1007/s11886-024-02097-4. Epub 2024 Jul 20. PMID- 39030739 OWN - NLM STAT- MEDLINE DCOM- 20240720 LR - 20260127 IS - 1440-1797 (Electronic) IS - 1320-5358 (Linking) VI - 29 IP - 8 DP - 2024 Aug TI - Potential kidney protective effects of glucagon-like peptide-1 receptor agonists. PG - 457-469 LID - 10.1111/nep.14336 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes (T2DM) with chronic kidney disease (CKD). This class of medication has demonstrated promising results in reducing albuminuria, preserving estimated glomerular filtration rate (eGFR), and mitigating cardiovascular (CV) risk, making them potential therapeutic options for individuals with CKD. The kidney protective effects of GLP-1RAs extend beyond glycaemic control, and are thought to be attributed to their anti-inflammatory, antioxidant, and natriuretic properties. Despite these promising findings, the use of GLP-RAs has yet to be definitively shown to slow progression to chronic kidney failure, or reduce CV and kidney related death in people with T2DM and CKD. The Research Study to See How Semaglutide (a once weekly subcutaneous administered GLP-1RA) Works Compared to Placebo in People with Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) was recently stopped because of efficacy. The primary end point for the FLOW trial consists of a composite endpoint of (i) onset of chronic kidney failure; (ii) death from kidney failure; (iii) cardiovascular death; and (iv) onset of a persistent >/=50% reduction in eGFR from baseline. It has also been reported by the sponsors of the trial that the primary end point of the trial was reduced by 24% with both CKD and CV outcomes contributing to risk reduction. In anticipation of the results of the FLOW trial being published, we review the current evidence surrounding kidney outcomes and proposed kidney protective pathways associated with GLP-1RA use. CI - (c) 2024 The Author(s). Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology. FAU - Trevella, Philippa AU - Trevella P AD - Department of Endocrinology & Diabetes, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia. FAU - Ekinci, Elif I AU - Ekinci EI AD - Department of Endocrinology, Austin Health, Melbourne, Vitoria, Australia. AD - Department of Medicine, Austin Health, Melbourne Medical School, Parkville, Victoria, Australia. AD - Australian Centre for Accelerating Diabetes Innovations, School of Medicine, University of Melbourne, Parkville, Victoria, Australia. FAU - MacIsaac, Richard J AU - MacIsaac RJ AUID- ORCID: 0000-0001-8058-6977 AD - Department of Endocrinology & Diabetes, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia. AD - Australian Centre for Accelerating Diabetes Innovations, School of Medicine, University of Melbourne, Parkville, Victoria, Australia. AD - Department of Medicine St Vincent's Hospital Melbourne, University of Melbourne, Fitzroy, Vitoria, Australia. LA - eng PT - Journal Article PT - Review DEP - 20240620 PL - Australia TA - Nephrology (Carlton) JT - Nephrology (Carlton, Vic.) JID - 9615568 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Renal Insufficiency, Chronic/drug therapy/physiopathology/complications/mortality MH - *Kidney/drug effects/physiopathology MH - *Diabetic Nephropathies/prevention & control/drug therapy MH - Treatment Outcome MH - Hypoglycemic Agents/therapeutic use MH - Glomerular Filtration Rate/drug effects MH - Incretins/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - albuminuria OT - diabetes OT - diabetic nephropathy OT - glucagon-like peptide-1 receptor agonists OT - kidney EDAT- 2024/07/20 20:46 MHDA- 2024/07/20 20:47 CRDT- 2024/07/20 06:03 PHST- 2024/05/08 00:00 [revised] PHST- 2024/02/25 00:00 [received] PHST- 2024/06/09 00:00 [accepted] PHST- 2024/07/20 20:47 [medline] PHST- 2024/07/20 20:46 [pubmed] PHST- 2024/07/20 06:03 [entrez] AID - 10.1111/nep.14336 [doi] PST - ppublish SO - Nephrology (Carlton). 2024 Aug;29(8):457-469. doi: 10.1111/nep.14336. Epub 2024 Jun 20. PMID- 39025300 OWN - NLM STAT- MEDLINE DCOM- 20241003 LR - 20260127 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 30 IP - 10 DP - 2024 Oct TI - The Use of Semaglutide in Patients With Renal Failure-A Retrospective Cohort Study. PG - 963-969 LID - S1530-891X(24)00606-2 [pii] LID - 10.1016/j.eprac.2024.07.008 [doi] AB - OBJECTIVE: Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m(2) (CKD stage 4), eGFR<15 mL/min/1.73 m(2) (CKD stage 5) or on dialysis. METHODS: This is a retrospective electronic medical record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between January 2018 and January 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher's exact test, paired t test, linear mixed effects models and Wilcoxon signed rank test. RESULTS: Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of type 2 diabetes mellitus (96.0%), and most were males (53.9%). The mean age was 66.8 y (SD 11.5) with the mean body mass index was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1 mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2 (SD 24.2) to 101.3 (SD 27.3) kg (P < .001). Eight patients (16%) with type 2 diabetes mellitus T2DM discontinued insulin after starting semaglutide. Mean hemoglobin A1c (HbA1c) decreased from 8.0% (SD 1.7) to 7.1% (SD 1.3) (P < .001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints. CONCLUSIONS: Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6% of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity. CI - Copyright (c) 2024 AACE. Published by Elsevier Inc. All rights reserved. FAU - Long, Jane J AU - Long JJ AD - Department of Surgery, Mayo Clinic, Rochester, Minnesota. FAU - Sahi, Sukhdeep S AU - Sahi SS AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Lemke, Adley I AU - Lemke AI AD - Department of Pharmacy, Mayo Clinic, Rochester, Minnesota. FAU - Na, Jie AU - Na J AD - Department of Biostatistics, Mayo Clinic, Rochester, Minnesota. FAU - Garcia Valencia, Oscar A AU - Garcia Valencia OA AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Budhiraja, Pooja AU - Budhiraja P AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Arizona. FAU - Wadei, Hani M AU - Wadei HM AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Jacksonville, Florida. FAU - Sudhindran, Vineeth AU - Sudhindran V AD - Department of Surgery, Mayo Clinic, Rochester, Minnesota. FAU - Benzo, Roberto AU - Benzo R AD - Department of Pulmonary Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Clark, Matthew M AU - Clark MM AD - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota. FAU - Shah, Meera AU - Shah M AD - Division of Endocrinology, Diabetes, Metabolism & Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Fipps, David AU - Fipps D AD - Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota. FAU - Navratil, Pavel AU - Navratil P AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota; Department of Urology, University Hospital Hradec Kralove, Hradec Kralove, Czechia; Faculty of Medicine in Hradec Kralove, Charles University, Hradec Kralove, Czechia. FAU - Abdelrheem, Ahmed A AU - Abdelrheem AA AD - Department of Surgery, Mayo Clinic, Rochester, Minnesota. FAU - Shaik, Afsana A AU - Shaik AA AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Duffy, Dustin J AU - Duffy DJ AD - Department of Biostatistics, Mayo Clinic, Rochester, Minnesota. FAU - Pencovich, Niv AU - Pencovich N AD - Department of Surgery, Mayo Clinic, Rochester, Minnesota. FAU - Shah, Pankaj AU - Shah P AD - Division of Endocrinology, Diabetes, Metabolism & Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Kudva, Yogish C AU - Kudva YC AD - Division of Endocrinology, Diabetes, Metabolism & Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Kukla, Aleksandra AU - Kukla A AD - Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Diwan, Tayyab S AU - Diwan TS AD - Department of Surgery, Mayo Clinic, Rochester, Minnesota. Electronic address: diwan.tayyab@mayo.edu. LA - eng PT - Journal Article DEP - 20240716 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Retrospective Studies MH - Male MH - Female MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Aged MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Glomerular Filtration Rate/drug effects MH - Cohort Studies MH - Renal Insufficiency MH - Aged, 80 and over MH - Renal Dialysis MH - Semaglutide OTO - NOTNLM OT - chronic kidney disease OT - end-stage renal disease OT - glucagon-like peptide-1 receptor agonist OT - semaglutide COIS- Disclosure Dr Aleksandra Kukla participated in NovoNordisk Advisory Board in 2020 but recieved no personal compensation. Dr Matthew M. Clark, Associate Editor, Obesity. Intellectual Property, Phenomix Science, Inc, Pheno-Diet: Individualized Lifestyle Intervention for Obesity Management Based on Obesity Phenotypes. EDAT- 2024/07/19 00:41 MHDA- 2024/10/04 00:42 CRDT- 2024/07/18 19:26 PHST- 2024/03/27 00:00 [received] PHST- 2024/07/07 00:00 [revised] PHST- 2024/07/08 00:00 [accepted] PHST- 2024/10/04 00:42 [medline] PHST- 2024/07/19 00:41 [pubmed] PHST- 2024/07/18 19:26 [entrez] AID - S1530-891X(24)00606-2 [pii] AID - 10.1016/j.eprac.2024.07.008 [doi] PST - ppublish SO - Endocr Pract. 2024 Oct;30(10):963-969. doi: 10.1016/j.eprac.2024.07.008. Epub 2024 Jul 16. PMID- 39023081 OWN - NLM STAT- MEDLINE DCOM- 20240718 LR - 20250828 IS - 1399-0012 (Electronic) IS - 0902-0063 (Print) IS - 0902-0063 (Linking) VI - 38 IP - 7 DP - 2024 Jul TI - Cardio-Renal-Metabolic Outcomes Associated With the Use of GLP-1 Receptor Agonists After Heart Transplantation. PG - e15401 LID - 10.1111/ctr.15401 [doi] AB - BACKGROUND: The use of glucagon-like-peptide 1 receptor agonists (GLP1-RA) has dramatically increased over the past 5 years for diabetes mellitus type 2 (T2DM) and obesity. These comorbidities are prevalent in adult heart transplant (HT) recipients. However, there are limited data evaluating the efficacy of this drug class in this population. The aim of the current study was to describe cardiometabolic changes in HT recipients prescribed GLP1-RA at a large-volume transplant center. METHODS: We retrospectively reviewed all adult HT recipients who received GLP1-RA after HT for a minimum of 1-month. Cardiometabolic parameters including body mass index (BMI), lipid panel, hemoglobin A1C, estimated glomerular filtration rate (eGFR), and NT-proBNP were compared prior to initiation of the drug and at most recent follow-up. We also evaluated for significant dose adjustments to immunosuppression after drug initiation and adverse effects leading to drug discontinuation. RESULTS: Seventy-four patients were included (28% female, 53% White, 20% Hispanic) and followed for a median of 383 days [IQR 209, 613] on a GLP1-RA. The majority of patients (n = 56, 76%) were prescribed semaglutide. The most common indication for prescription was T2DM alone (n = 33, 45%), followed by combined T2DM and obesity (n = 26, 35%). At most recent follow-up, mean BMI decreased from 33.3 to 31.5 kg/m(2) (p < 0.0001), HbA1C from 7.3% to 6.7% (p = 0.005), LDL from 78.6 to 70.3 mg/dL (p = 0.018) and basal insulin daily dose from 32.6 to 24.8 units (p = 0.0002). CONCLUSION: HT recipients prescribed GLP1-RA therapy showed improved glycemic control, weight loss, and cholesterol levels during the study follow-up period. GLP1-RA were well tolerated and were rarely associated with changes in immunosuppression dosing. CI - (c) 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Donald, Elena M AU - Donald EM AUID- ORCID: 0000-0002-2232-5688 AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Driggin, Elissa AU - Driggin E AUID- ORCID: 0000-0002-0070-381X AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Choe, Jason AU - Choe J AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Batra, Jaya AU - Batra J AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Vargas, Fabian AU - Vargas F AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Lindekens, Jordan AU - Lindekens J AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Fried, Justin A AU - Fried JA AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Raikhelkar, Jayant K AU - Raikhelkar JK AUID- ORCID: 0000-0002-8561-7899 AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Bae, David J AU - Bae DJ AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Oh, Kyung T AU - Oh KT AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Yuzefpolskaya, Melana AU - Yuzefpolskaya M AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Colombo, Paolo C AU - Colombo PC AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Latif, Farhana AU - Latif F AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Sayer, Gabriel AU - Sayer G AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Uriel, Nir AU - Uriel N AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - Clerkin, Kevin J AU - Clerkin KJ AUID- ORCID: 0000-0001-8351-9219 AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. FAU - DeFilippis, Ersilia M AU - DeFilippis EM AUID- ORCID: 0000-0002-0493-1326 AD - Department of Medicine, Division of Cardiology New York Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA. LA - eng GR - K23 HL148528/HL/NHLBI NIH HHS/United States GR - T32 HL007854/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - Denmark TA - Clin Transplant JT - Clinical transplantation JID - 8710240 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Male MH - Retrospective Studies MH - Middle Aged MH - *Heart Transplantation/adverse effects MH - Follow-Up Studies MH - Prognosis MH - Diabetes Mellitus, Type 2/drug therapy MH - Glomerular Filtration Rate MH - Hypoglycemic Agents/therapeutic use MH - Kidney Function Tests MH - Adult MH - Postoperative Complications/drug therapy MH - Graft Rejection/etiology/prevention & control/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11634378 MID - NIHMS2037290 OTO - NOTNLM OT - diabetes OT - glucagon-like peptide 1 OT - heart transplantation OT - obesity OT - weight loss COIS- Conflicts of Interest Dr. Sayer has received consulting fees and honoraria from Abbott, Dr. Uriel has received grants from Abbott. Dr. DeFilippis is a speaker for Astrazeneca and serves on a clinical trial committee for Abiomed. EDAT- 2024/07/18 12:42 MHDA- 2024/07/18 12:43 PMCR- 2025/01/01 CRDT- 2024/07/18 06:55 PHST- 2024/06/09 00:00 [revised] PHST- 2024/04/21 00:00 [received] PHST- 2024/06/24 00:00 [accepted] PHST- 2024/07/18 12:43 [medline] PHST- 2024/07/18 12:42 [pubmed] PHST- 2024/07/18 06:55 [entrez] PHST- 2025/01/01 00:00 [pmc-release] AID - 10.1111/ctr.15401 [doi] PST - ppublish SO - Clin Transplant. 2024 Jul;38(7):e15401. doi: 10.1111/ctr.15401. PMID- 39015186 OWN - NLM STAT- MEDLINE DCOM- 20240717 LR - 20261019 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Changes in body weight and composition, metabolic parameters, and quality of life in patients with type 2 diabetes treated with subcutaneous semaglutide in real-world clinical practice. PG - 1394506 LID - 10.3389/fendo.2024.1394506 [doi] LID - 1394506 AB - Subcutaneous once-weekly (ow) semaglutide is a recent treatment option for type 2 diabetes (T2D) and obesity, but real-world data on weight loss and associated changes in body composition, nutrients intake, and quality of life are still scarce. This observational, prospective clinical study involved all T2D patients starting ow semaglutide according to routine care between December 2021 and February 2022. Clinical information was collected after 6 months (T6) and 12 months (T12) from semaglutide initiation (T0). Bioelectrical Impedance Analysis (BIA) was performed to measure changes in body composition. Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the 36 - items Short Form Health Survey (SF-36) were administered as patient-reported outcomes (PROs). Changes in continuous endpoints (weight, body composition, nutrients intake, other clinical parameters, and PROs) were assessed using mixed models for repeated measurements. Overall, 90 patients (age 63.0 +/- 10.0 years; diabetes duration 7.6 +/- 5.9 years; 58.9% men; HbA1c 7.7 +/- 1.1%; weight 95.4 +/- 19.4 Kg, BMI 34.6 +/- 6.4 Kg/m(2); 36.7% naive to diabetes treatment, 43.3% on metformin, 10.0% on dual oral therapy, and 10.0% treated with schemes including insulin) were included in the study. After 6 months from semaglutide initiation, body weight significantly decrease by -4.69 Kg (95%CI -6.19;-3.19) (primary endpoint). After 12 months, body weight was further reduced (-5.38 Kg; 95%CI -7.79;-2.97). At BIA, fat mass was significantly reduced by 2.1 Kg after 6 months but only slightly reduced after 12 months vs. baseline; lean mass was also significantly reduced by over 3 Kg both at 6 and 12 months. Intake of all nutrients declined in the first 6 months of therapy, although only lipids reduction reached the statistical significance (-6.73 g; p=0.02). Statistically significant improvements in BMI, waist circumference, glycemic control, blood pressure and lipid profile were documented. Satisfaction with treatment (DTSQ questionnaire) and mental health (MCS score of SF-36 questionnaire) significantly increased during the follow-up. The study documented real-world benefits of semaglutide for treating obesity in T2D subjects, with important changes on clinical and patient-reported outcomes. Loss of lean mass associated with weight loss warrants attention; parallel strategies to preserve skeletal muscle and improve physical function, i.e. nutritional education and structured exercise, are of great importance. CI - Copyright (c) 2024 Pantanetti, Cangelosi, Alberti, Di Marco, Michetti, Cerasoli, Di Giacinti, Coacci, Francucci, Petrelli, Ambrosio and Grinta. FAU - Pantanetti, Paola AU - Pantanetti P AD - AST Fermo, Unit of Diabetology, Fermo, Italy. FAU - Cangelosi, Giovanni AU - Cangelosi G AD - AST Fermo, Unit of Diabetology, Fermo, Italy. FAU - Alberti, Sara AU - Alberti S AD - AUSL Romagna, "Infermi" Hospital, Rimini, Italy. FAU - Di Marco, Sandra AU - Di Marco S AD - AST Fermo, Unit of Diabetology, Fermo, Italy. FAU - Michetti, Grazia AU - Michetti G AD - AST Fermo, Unit of Diabetology, Fermo, Italy. FAU - Cerasoli, Gianluca AU - Cerasoli G AD - AST Fermo, Unit of Diabetology, Fermo, Italy. FAU - Di Giacinti, Marco AU - Di Giacinti M AD - AST Fermo, Unit of Diabetology, Fermo, Italy. FAU - Coacci, Silvia AU - Coacci S AD - AST Fermo, Unit of Diabetology, Fermo, Italy. FAU - Francucci, Nadia AU - Francucci N AD - AST Fermo, Unit of Diabetology, Fermo, Italy. FAU - Petrelli, Fabio AU - Petrelli F AD - School of Medicinal and Health Products Sciences, University of Camerino, Camerino, Italy. FAU - Ambrosio, Giuseppe AU - Ambrosio G AD - Cardiology University of Perugia, Perugia, Italy. FAU - Grinta, Roberto AU - Grinta R AD - AST Fermo, Fermo, Italy. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20240702 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Male MH - Middle Aged MH - *Quality of Life MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Body Composition/drug effects MH - Aged MH - *Body Weight/drug effects MH - Prospective Studies MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Injections, Subcutaneous MH - Weight Loss/drug effects MH - Blood Glucose/analysis/drug effects MH - Semaglutide PMC - PMC11250060 OTO - NOTNLM OT - body composition OT - obesity OT - real-world evidence OT - semaglutide OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/07/17 06:43 MHDA- 2024/07/17 06:44 PMCR- 2024/01/01 CRDT- 2024/07/17 04:15 PHST- 2024/03/01 00:00 [received] PHST- 2024/06/14 00:00 [accepted] PHST- 2024/07/17 06:44 [medline] PHST- 2024/07/17 06:43 [pubmed] PHST- 2024/07/17 04:15 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1394506 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Jul 2;15:1394506. doi: 10.3389/fendo.2024.1394506. eCollection 2024. PMID- 38996661 OWN - NLM STAT- MEDLINE DCOM- 20240727 LR - 20260127 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 43 IP - 8 DP - 2024 Aug TI - Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus. PG - 1907-1913 LID - S0261-5614(24)00226-7 [pii] LID - 10.1016/j.clnu.2024.06.034 [doi] AB - BACKGROUND & AIMS: Very-low calorie diets (VLCD) and the glucagon-like peptide-1 receptor agonist (GLP1RA) Semaglutide induce significant weight loss and improve glycaemic control in individuals with type 2 diabetes (T2D). This pilot study was conducted to explore the comparative short-term effects of these interventions individually, and in combination, on weight, body composition and metabolic outcomes. METHODS: Thirty individuals with T2D (age 18-75 years, BMI 27-50 kg m(-2)) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks. Measurement of weight and glycated haemoglobin (HbA1c), dual energy X-ray absorptiometry, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and post-intervention. Diet diaries were utilised to assess compliance. Insulin first phase response during IVGTT provided a marker of pancreatic beta-cell function, and insulin sensitivity was estimated using HOMA-IR. RESULTS: Significantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p < 0.01 v both). VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively. HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only. Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p < 0.01). CONCLUSION: VLCD elicited greater short-term losses of weight and fat mass than Semaglutide. Adding VLCD to Semaglutide stimulated further weight loss than Semaglutide alone. The combination did not yield any additive effects on weight and body composition above VLCD alone, but did provoke greater improvements in pancreatic beta-cell function. Thus, combination of Semaglutide and VLCD warrants further exploration as a novel approach to T2D management. CI - Copyright (c) 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Anyiam, Oluwaseun AU - Anyiam O AD - MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK; Department of Endocrinology and Diabetes, University Hospitals Derby and Burton NHS Foundation Trust, Derby, DE22 3NE, UK. FAU - Phillips, Bethan AU - Phillips B AD - MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK. FAU - Quinn, Katie AU - Quinn K AD - College of Agriculture, Food & Nutrition, University College Dublin, Ireland. FAU - Wilkinson, Daniel AU - Wilkinson D AD - MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK. FAU - Smith, Kenneth AU - Smith K AD - MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK. FAU - Atherton, Philip AU - Atherton P AD - MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK. Electronic address: philip.atherton@nottingham.ac.uk. FAU - Idris, Iskandar AU - Idris I AD - MRC/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre (BRC), School of Medicine, University of Nottingham, Derby, DE22 3DT, UK; Department of Endocrinology and Diabetes, University Hospitals Derby and Burton NHS Foundation Trust, Derby, DE22 3NE, UK. Electronic address: iskandar.idris@nottingham.ac.uk. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20240702 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diet therapy MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/pharmacology MH - Male MH - Female MH - Adult MH - Aged MH - *Caloric Restriction/methods MH - Pilot Projects MH - *Weight Loss/drug effects MH - *Glycated Hemoglobin MH - *Hypoglycemic Agents/administration & dosage/pharmacology MH - *Blood Glucose/drug effects/metabolism MH - Adolescent MH - Young Adult MH - Body Composition/drug effects MH - Insulin/blood MH - Insulin Resistance MH - Glucose Tolerance Test MH - Combined Modality Therapy MH - Semaglutide OTO - NOTNLM OT - Beta cell function OT - Body composition OT - Obesity OT - Semaglutide OT - Type 2 diabetes OT - Very-low calorie diet COIS- Conflict of interest The authors have no conflicts of interest to declare. EDAT- 2024/07/13 07:44 MHDA- 2024/07/28 14:46 CRDT- 2024/07/12 19:46 PHST- 2024/06/26 00:00 [received] PHST- 2024/06/26 00:00 [accepted] PHST- 2024/07/28 14:46 [medline] PHST- 2024/07/13 07:44 [pubmed] PHST- 2024/07/12 19:46 [entrez] AID - S0261-5614(24)00226-7 [pii] AID - 10.1016/j.clnu.2024.06.034 [doi] PST - ppublish SO - Clin Nutr. 2024 Aug;43(8):1907-1913. doi: 10.1016/j.clnu.2024.06.034. Epub 2024 Jul 2. PMID- 38991896 OWN - NLM STAT- MEDLINE DCOM- 20240920 LR - 20260127 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 18 IP - 5 DP - 2024 Oct TI - Adherence and persistence among people with type 2 diabetes newly initiating oral semaglutide versus DPP-4is in a US real-world setting. PG - 511-517 LID - S1751-9918(24)00126-8 [pii] LID - 10.1016/j.pcd.2024.06.013 [doi] AB - AIMS: To investigate real-world treatment adherence and persistence in people with type 2 diabetes newly initiating oral semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), or a dipeptidyl peptidase-4 inhibitor (DPP-4i). METHODS: This retrospective cohort study used the Merative MarketScan(R) Commercial and Medicare databases. Index date was the first fill for the cohort medication. Adherence was defined as proportion of days covered (PDC) over the 12-month post-index period ('adherent' = >/=0.8). Persistence was number of days until discontinuation, based on a 45-day gap. Results were compared between cohorts using inverse probability treatment weighting. RESULTS: Oral semaglutide (n=5485) and DPP-4i (n=4980) cohorts had similar percentages of people who were adherent (PDC >/=0.8; 41.6 % vs. 42.9 %; P = 0.182) and persistent for >/=9 months (45.0 % vs. 46.3 %; P = 0.185). The DPP-4i cohort used significantly more anti-diabetic medication (ADM) classes over the post-index period (mean+/-SD: 2.6+/-1.0 vs. 2.9+/-1.1, P < 0.001), with 23.2 % filling a GLP-1 RA in the post-period. CONCLUSIONS: Adherence and persistence were similar between cohorts. However, there are potential benefits to prescribing oral semaglutide over DPP-4is, including reduced need for additional ADM. CI - Copyright (c) 2024 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Lv, Lei AU - Lv L AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536, USA. Electronic address: lzlv@novonordisk.com. FAU - Brady, Brenna L AU - Brady BL AD - Merative, 100 Phoenix Dr Suite 200, Ann Arbor, MI 48108, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536, USA. FAU - Guevarra, Mico AU - Guevarra M AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ 08536, USA. FAU - Turchin, Alexander AU - Turchin A AD - Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240710 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Biomarkers) RN - EC 3.4.14.5 (Dipeptidyl Peptidase 4) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - EC 3.4.14.5 (DPP4 protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis/blood MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Retrospective Studies MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/administration & dosage/adverse effects MH - Male MH - Female MH - *Medication Adherence MH - Administration, Oral MH - Middle Aged MH - Treatment Outcome MH - Aged MH - Time Factors MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - United States MH - *Incretins/therapeutic use/adverse effects/administration & dosage MH - Databases, Factual MH - Biomarkers/blood MH - Adult MH - Dipeptidyl Peptidase 4 MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Adherence OT - DPP-4i OT - Oral semaglutide OT - Persistence OT - Type 2 diabetes EDAT- 2024/07/12 00:42 MHDA- 2024/09/21 13:19 CRDT- 2024/07/11 22:13 PHST- 2024/01/16 00:00 [received] PHST- 2024/06/26 00:00 [revised] PHST- 2024/06/29 00:00 [accepted] PHST- 2024/09/21 13:19 [medline] PHST- 2024/07/12 00:42 [pubmed] PHST- 2024/07/11 22:13 [entrez] AID - S1751-9918(24)00126-8 [pii] AID - 10.1016/j.pcd.2024.06.013 [doi] PST - ppublish SO - Prim Care Diabetes. 2024 Oct;18(5):511-517. doi: 10.1016/j.pcd.2024.06.013. Epub 2024 Jul 10. PMID- 38986062 OWN - NLM STAT- MEDLINE DCOM- 20240710 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 391 IP - 2 DP - 2024 Jul 11 TI - Diabetic Kidney Disease - Semaglutide Flows into the Mainstream. PG - 178-179 LID - 10.1056/NEJMe2406408 [doi] FAU - Herrington, William G AU - Herrington WG AUID- ORCID: 0000-0003-1172-8243 AD - From the Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. FAU - Haynes, Richard AU - Haynes R AD - From the Renal Studies Group, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. LA - eng PT - Editorial PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Diabetic Nephropathies/drug therapy/etiology/mortality/prevention & control MH - Drug Approval MH - Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - *Renal Insufficiency, Chronic/drug therapy/etiology/mortality/prevention & control MH - Cardiovascular Diseases/etiology/mortality/prevention & control MH - *Diabetic Cardiomyopathies/etiology/mortality/prevention & control MH - Injections, Subcutaneous MH - Randomized Controlled Trials as Topic MH - Semaglutide EDAT- 2024/07/10 18:42 MHDA- 2024/07/10 18:43 CRDT- 2024/07/10 16:32 PHST- 2024/07/10 18:43 [medline] PHST- 2024/07/10 18:42 [pubmed] PHST- 2024/07/10 16:32 [entrez] AID - 10.1056/NEJMe2406408 [doi] PST - ppublish SO - N Engl J Med. 2024 Jul 11;391(2):178-179. doi: 10.1056/NEJMe2406408. PMID- 38985162 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 67 IP - 9 DP - 2024 Sep TI - Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes (PIONEER 11): a double-blind, Phase IIIa, randomised trial. PG - 1783-1799 LID - 10.1007/s00125-024-06142-3 [doi] AB - AIMS/HYPOTHESIS: The aim of this study was to evaluate the efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly Chinese population with type 2 diabetes insufficiently controlled with diet and exercise alone. METHODS: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 11 trial was a double-blind, randomised, Phase IIIa trial conducted across 52 sites in the China region (mainland China and Taiwan), Hungary, Serbia and Ukraine. Eligible participants were >/=18 years (>/=20 years in Taiwan), had a diagnosis of type 2 diabetes with HbA(1c) 53-86 mmol/mol (7.0-10.0%) and were not receiving any glucose-lowering drugs. After a 4-week run-in period in which participants were treated with diet and exercise alone, those who fulfilled the randomisation criteria were randomised (1:1:1:1) using a web-based randomisation system to receive once-daily oral semaglutide 3 mg, 7 mg or 14 mg or placebo for 26 weeks (using a 4-week dose-escalation regimen for the higher doses). Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary and confirmatory secondary endpoints were change from baseline to week 26 in HbA(1c) and body weight (kg), respectively. Safety was assessed in all participants exposed to at least one dose of the trial product. RESULTS: Between October 2019 and October 2021, a total of 774 participants were screened and 521 participants were randomised to oral semaglutide 3 mg (n=130), 7 mg (n=130), 14 mg (n=130) or placebo (n=131); most participants (92.5%, n=482) completed the trial, with 39 participants prematurely discontinuing treatment. The number of participants contributing to the trial analyses was based on the total number of participants who were randomised at the beginning of the trial. The majority of participants were male (63.7%), and the mean age of participants was 52 years. At baseline, mean HbA(1c) and body weight were 63 mmol/mol (8.0%) and 79.6 kg, respectively. Oral semaglutide resulted in significantly greater reductions in HbA(1c) than placebo at week 26 (p<0.001 for all doses). The estimated treatment differences (ETDs [95% CIs]) for oral semaglutide 3 mg, 7 mg and 14 mg vs placebo were -11 (-13, -9) mmol/mol, -16 (-18, -13) mmol/mol and -17 (-19, -15) mmol/mol, respectively. The corresponding ETDs in percentage points (95% CI) vs placebo were -1.0 (-1.2, -0.8), -1.4 (-1.6, -1.2) and -1.5 (-1.8, -1.3), respectively. Significantly greater reductions in body weight were also observed for oral semaglutide 7 mg and 14 mg than for placebo at week 26 (ETD [95% CI] -1.2 kg [-2.0 kg, -0.4 kg; p<0.01] and -2.0 kg [-2.8 kg, -1.2 kg; p<0.001], respectively), but not for oral semaglutide 3 mg (ETD [95% CI] -0.0 kg [-0.9 kg, 0.8 kg; not significant]). Similar reductions in HbA(1c) and body weight were observed in the Chinese subpopulation, which represented 74.9% of participants in the overall population. Adverse events (AEs) occurred in between 65.4% and 72.3% of participants receiving oral semaglutide (for all doses) and 57.3% of participants with placebo. Most AEs were mild to moderate in severity, with few serious AEs reported; the most commonly reported AEs were gastrointestinal-related and were more frequent with semaglutide (all doses) than with placebo. The proportion of AEs was slightly higher in the Chinese subpopulation. CONCLUSIONS/INTERPRETATION: Oral semaglutide resulted in significantly greater reductions in HbA(1c) across all doses and in significant body weight reductions for the 7 mg and 14 mg doses when compared with placebo in predominantly Chinese participants with type 2 diabetes insufficiently controlled by diet and exercise alone. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04109547. FUNDING: Novo Nordisk A/S. CI - (c) 2024. The Author(s). FAU - Wang, Weiqing AU - Wang W AUID- ORCID: 0000-0001-6027-3084 AD - Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Diabetes Research Unit, University of Swansea, Swansea, UK. bainsc60@mail.com. FAU - Bian, Fang AU - Bian F AUID- ORCID: 0009-0005-1219-4345 AD - Department of Endocrinology, Cangzhou People's Hospital, Cangzhou, China. FAU - Chen, Rui AU - Chen R AUID- ORCID: 0009-0007-3128-3524 AD - Novo Nordisk (China) Pharmaceuticals Co. Ltd., Beijing, China. FAU - Gabery, Sanaz AU - Gabery S AUID- ORCID: 0000-0002-2243-7540 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Huang, Shan AU - Huang S AUID- ORCID: 0000-0001-8125-953X AD - Endocrinology Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Jensen, Thomas B AU - Jensen TB AUID- ORCID: 0000-0002-8920-9374 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Luo, Bifen AU - Luo B AUID- ORCID: 0000-0001-7166-278X AD - Novo Nordisk (China) Pharmaceuticals Co. Ltd., Beijing, China. FAU - Yuan, Guoyue AU - Yuan G AUID- ORCID: 0000-0003-0822-6066 AD - Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China. FAU - Ning, Guang AU - Ning G AUID- ORCID: 0000-0002-5754-7635 AD - Shanghai Jiaotong University School of Medicine, Shanghai, China. CN - PIONEER 11 investigators LA - eng SI - ClinicalTrials.gov/NCT04109547 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20240710 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects MH - China MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Double-Blind Method MH - East Asian People MH - Glucagon-Like Peptides/therapeutic use/administration & dosage/adverse effects MH - Glycated Hemoglobin/metabolism MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - Semaglutide PMC - PMC11410837 OTO - NOTNLM OT - China OT - GLP-1 analogue OT - Glycaemic control OT - Incretin therapy OT - Phase III OT - Semaglutide OT - Type 2 diabetes EDAT- 2024/07/10 12:43 MHDA- 2024/09/18 12:51 PMCR- 2024/07/10 CRDT- 2024/07/10 11:03 PHST- 2023/10/05 00:00 [received] PHST- 2024/01/15 00:00 [accepted] PHST- 2024/09/18 12:51 [medline] PHST- 2024/07/10 12:43 [pubmed] PHST- 2024/07/10 11:03 [entrez] PHST- 2024/07/10 00:00 [pmc-release] AID - 10.1007/s00125-024-06142-3 [pii] AID - 6142 [pii] AID - 10.1007/s00125-024-06142-3 [doi] PST - ppublish SO - Diabetologia. 2024 Sep;67(9):1783-1799. doi: 10.1007/s00125-024-06142-3. Epub 2024 Jul 10. PMID- 38985161 OWN - NLM STAT- MEDLINE DCOM- 20240918 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 67 IP - 9 DP - 2024 Sep TI - Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial. PG - 1800-1816 LID - 10.1007/s00125-024-06133-4 [doi] AB - AIMS/HYPOTHESIS: The aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. METHODS: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged >/=18 years (>/=20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA(1c) between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA(1c) from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS). RESULTS: Of 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA(1c) from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were -2 (-4, -1) mmol/mol, -8 (-9, -6) mmol/mol and -11 (-12, -9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were -0.2 (-0.3, -0.1), -0.7 (-0.8, -0.6) and -1.0 (-1.1, -0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] -0.9 [-1.4, -0.4] kg, -2.3 [-2.8, -1.8] kg and -3.3 [-3.8, -2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA(1c) and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity. CONCLUSIONS/INTERPRETATION: Significantly greater reductions in both HbA(1c) and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04017832. FUNDING: This trial was funded by Novo Nordisk A/S, Soborg, Denmark. CI - (c) 2024. The Author(s). FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Peking University People's Hospital, Beijing, China. FAU - Agesen, Rikke M AU - Agesen RM AUID- ORCID: 0000-0002-7649-7928 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Diabetes Research Unit, Swansea University, Swansea, UK. bainsc60@mail.com. FAU - Fu, Fangming AU - Fu F AUID- ORCID: 0000-0002-0874-7526 AD - Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China. FAU - Gabery, Sanaz AU - Gabery S AUID- ORCID: 0000-0002-2243-7540 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Geng, Jianlin AU - Geng J AUID- ORCID: 0009-0001-6844-9221 AD - Harrison International Peace Hospital, Hengshui, China. FAU - Li, Yiming AU - Li Y AUID- ORCID: 0000-0002-1828-8765 AD - Huashan Hospital, Fudan University, Shanghai, China. FAU - Lu, Yibing AU - Lu Y AD - Second Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Luo, Bifen AU - Luo B AUID- ORCID: 0000-0001-7166-278X AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd., Beijing, China. FAU - Pang, Wuyan AU - Pang W AD - Huaihe Hospital of Henan University, Kaifeng, Henan, China. FAU - Tao, Yi AU - Tao Y AUID- ORCID: 0009-0003-6453-5354 AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd., Beijing, China. CN - PIONEER 12 investigators LA - eng SI - ClinicalTrials.gov/NCT04017832 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20240710 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Triazoles) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/drug effects MH - China MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Double-Blind Method MH - East Asian People MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Glycated Hemoglobin/metabolism MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - *Metformin/therapeutic use/administration & dosage MH - *Sitagliptin Phosphate/therapeutic use/adverse effects/administration & dosage MH - Treatment Outcome MH - Triazoles/therapeutic use/adverse effects/administration & dosage MH - Semaglutide PMC - PMC11410852 OTO - NOTNLM OT - GLP-1 analogue OT - Glycaemic control OT - Incretin therapy OT - Phase III OT - Semaglutide OT - Type 2 diabetes EDAT- 2024/07/10 12:43 MHDA- 2024/09/18 12:51 PMCR- 2024/07/10 CRDT- 2024/07/10 11:03 PHST- 2023/10/05 00:00 [received] PHST- 2024/01/22 00:00 [accepted] PHST- 2024/09/18 12:51 [medline] PHST- 2024/07/10 12:43 [pubmed] PHST- 2024/07/10 11:03 [entrez] PHST- 2024/07/10 00:00 [pmc-release] AID - 10.1007/s00125-024-06133-4 [pii] AID - 6133 [pii] AID - 10.1007/s00125-024-06133-4 [doi] PST - ppublish SO - Diabetologia. 2024 Sep;67(9):1800-1816. doi: 10.1007/s00125-024-06133-4. Epub 2024 Jul 10. PMID- 38985093 OWN - NLM STAT- MEDLINE DCOM- 20241007 LR - 20260918 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 45 IP - 38 DP - 2024 Oct 7 TI - Weekly Journal Scan: improved renal outcomes by semaglutide in patients with chronic kidney disease and type 2 diabetes in FLOW trial. PG - 3910-3911 LID - 10.1093/eurheartj/ehae429 [doi] FAU - Pedicino, Daniela AU - Pedicino D AUID- ORCID: 0000-0002-4218-3066 AD - Department of Cardiovascular Medicine, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Largo A. Gemelli 8, Rome 00168, Italy. FAU - Volpe, Massimo AU - Volpe M AUID- ORCID: 0000-0002-9642-8380 AD - Department of Clinical and Molecular Medicine, Sapienza University of Rome, Via di Grottarossa 1035, Rome, Italy. AD - IRCCS San Raffaele Roma, Via di Valcannuta 250, Rome, Italy. LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Diabetic Nephropathies/drug therapy MH - Glomerular Filtration Rate/drug effects/physiology MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Renal Insufficiency, Chronic/complications MH - Treatment Outcome MH - Randomized Controlled Trials as Topic MH - Semaglutide EDAT- 2024/07/10 12:44 MHDA- 2024/10/08 04:18 CRDT- 2024/07/10 10:42 PHST- 2024/10/08 04:18 [medline] PHST- 2024/07/10 12:44 [pubmed] PHST- 2024/07/10 10:42 [entrez] AID - 7710527 [pii] AID - 10.1093/eurheartj/ehae429 [doi] PST - ppublish SO - Eur Heart J. 2024 Oct 7;45(38):3910-3911. doi: 10.1093/eurheartj/ehae429. PMID- 38982987 OWN - NLM STAT- MEDLINE DCOM- 20240710 LR - 20260620 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Effectiveness and safety of once-weekly semaglutide: findings from the SEMACOL-REAL retrospective multicentric observational study in Colombia. PG - 1372992 LID - 10.3389/fendo.2024.1372992 [doi] LID - 1372992 AB - INTRODUCTION: Diabetes stands as one of the leading causes of death worldwide. Glucagon-like peptide-1 receptor agonists rank among the most effective medications for lowering blood glucose and body weight, as well as reducing cardiovascular risk in individuals with diabetes. Observational studies complement experimental evidence in new settings, different populations, and real-world healthcare practices. METHODS: A multicentric observational study of adults with type 2 diabetes treated with once-weekly subcutaneous semaglutide in four health centers in Colombia was conducted. The protocol for the present study was not pre-registered. RESULTS: Data from 186 patients were included. Most patients were women (57%) with a mean age of 62.8 +/- 12.1 years. One year of once-weekly semaglutide usage was associated with a mean reduction in HbA1C of -1.47% (95% CI -1.76, -1.17), weight loss of -4.23 kg (95% CI -5.34, -3.12), and albumin/creatinine ratio of -18.6 mg/g (95% CI -60.2, -5.9). Approximately half the treated patients achieved a level of HbA1c /=8%; <64/>/=64 mmol/mol), systolic BP (<140/90/>/=140/90 mmHg) and BMI (<30/>/=30 kg/m2). SUSTAIN 6 data were analyzed by baseline urinary albumin:creatinine ratio (UACR; <30/30-300/>300 mg/g). RESULTS: The estimated absolute treatment differences overall in eGFR slope (95% confidence intervals) favored semaglutide versus placebo in the pooled analysis [0.59 (0.29; 0.89) mL/min/1.73 m2/year] and in SUSTAIN 6 [0.60 (0.24; 0.96) mL/min/1.73 m2/year]; the absolute benefit was consistent across all HbA1c, BP, BMI and UACR subgroups (all P-interaction >.5). CONCLUSION: A clinically meaningful reduction in risk of chronic kidney disease progression was observed with semaglutide versus placebo regardless of HbA1c, BP, BMI, and UACR levels. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the ERA. FAU - Apperloo, Ellen M AU - Apperloo EM AD - Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Cherney, David Z I AU - Cherney DZI AD - Division of Nephrology, Department of Medicine, University Health Network and University of Toronto, Toronto, ON, Canada. FAU - Kuhlman, Anja Birk AU - Kuhlman AB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Center, Munich, Germany. AD - Dept of Nephrology & Hypertension, Friedrich Alexander University of Erlangen, Erlangen, Germany. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Steno Diabetes Centre, Copenhagen, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Providence Inland Northwest Health, University of Washington School of Medicine, Spokane, USA. FAU - Vrhnjak, Blaz AU - Vrhnjak B AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AUID- ORCID: 0000-0002-3126-3730 AD - Department of Clinical Pharmacy & Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. AD - The George Institute for Global Health, Sydney, Australia. LA - eng GR - Novo Nordisk/ PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Albuminuria/drug therapy/etiology MH - *Blood Pressure/drug effects MH - Body Mass Index MH - *Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - Follow-Up Studies MH - Glomerular Filtration Rate/drug effects MH - *Glucagon-Like Peptides/therapeutic use MH - *Glycated Hemoglobin/metabolism/analysis MH - *Hypoglycemic Agents/therapeutic use MH - Prognosis MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11792646 OTO - NOTNLM OT - cardiovascular risk OT - diabetes OT - eGFR decline OT - semaglutide COIS- E.M.A. reports no conflicts of interest. D.Z.I.C. has received honoraria from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK and Novo Nordisk; and has received operational funding for clinical trials from Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo Nordisk. J.F.E.M. reports grants from Novo Nordisk, the European Union and McMaster University Hamilton, Canada; consulting fees from Novo Nordisk, AstraZeneca, Bayer and Boehringer Ingelheim; honoraria from Novo Nordisk, AstraZeneca, Bayer, Fresenius and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi and Boehringer Ingelheim as well as a leadership role in the KDIGO group. K.R.T. is supported by NIH research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568 and CDC project number 75D301-21-P-12254. She has also received investigator-initiated grant support from Travere and Bayer Pharmaceuticals outside of the submitted work. She reports consultancy fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk and Travere. H.J.L.H. is consultant for AstraZeneca, Bayer, Boehringer Ingelheim, CSL-Behring, Eli-Lilly and Company, Gilead, Janssen, Novartis, Novo Nordisk, and Travere Pharmaceuticals. He received research support from Abbvie, AstraZeneca, Boehringer Ingelheim, Janssen and Novo Nordisk. A.B.K., S.R. and B.V. are Novo Nordisk employees. Data included in this manuscript were presented as abstracts to the American Society of Nephrology Annual Meeting in 2022. EDAT- 2024/07/03 00:42 MHDA- 2025/02/04 17:03 PMCR- 2024/07/02 CRDT- 2024/07/02 20:33 PHST- 2024/02/23 00:00 [received] PHST- 2025/02/04 17:03 [medline] PHST- 2024/07/03 00:42 [pubmed] PHST- 2024/07/02 20:33 [entrez] PHST- 2024/07/02 00:00 [pmc-release] AID - 7704453 [pii] AID - gfae150 [pii] AID - 10.1093/ndt/gfae150 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2025 Feb 4;40(2):352-359. doi: 10.1093/ndt/gfae150. PMID- 38955095 OWN - NLM STAT- MEDLINE DCOM- 20240905 LR - 20260127 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 18 IP - 6 DP - 2024 Jun TI - Semaglutide for the prevention of atrial fibrillation: A systematic review and meta-analysis. PG - 103067 LID - S1871-4021(24)00128-0 [pii] LID - 10.1016/j.dsx.2024.103067 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is reported to have cardiac benefits, but its effects on preventing atrial fibrillation (AF) remain inconclusive. This study aimed to investigate whether semaglutide can prevent AF occurrence in patients with type 2 diabetes mellitus (T2DM), obesity, or overweight. METHODS: We searched MEDLINE, EMBASE, the Cochrane CENTRAL database, and clinicaltrials.gov from inception to December 29, 2023. Randomized controlled trials of semaglutide in patients with T2DM, obesity, or overweight were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for the overall population and subgroups. RESULTS: Twenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52-0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21-0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56-1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52-0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18-1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25-0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55-1.07). CONCLUSION: Semaglutide was associated with a reduced risk of AF occurrence in the overall analysis. Favorable outcomes were observed in subsets using other antihyperglycemic medications as controls, in patients with T2DM, and with oral semaglutide. CI - Copyright (c) 2024 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Zhang, Hong-Da AU - Zhang HD AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China. Electronic address: zhanghongda213@163.com. FAU - Ding, Lei AU - Ding L AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China. Electronic address: dingleifw@163.com. FAU - Liu, Ke AU - Liu K AD - School of Pharmacy, Henan University, Kaifeng, 475004, China. Electronic address: liukeup@139.com. FAU - Mi, Li-Jie AU - Mi LJ AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China. Electronic address: milijie0822@sina.com. FAU - Zhang, Ai-Kai AU - Zhang AK AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China. Electronic address: jeremyzkk@163.com. FAU - Yu, Feng-Yuan AU - Yu FY AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China. Electronic address: yufengyuan@fuwai.com. FAU - Yan, Xin-Xin AU - Yan XX AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China. Electronic address: yxx_fuwai@163.com. FAU - Peng, Fu-Hua AU - Peng FH AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China. Electronic address: ctpfh@163.com. FAU - Shen, Yu-Jing AU - Shen YJ AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China. Electronic address: shenyj0328@126.com. FAU - Tang, Min AU - Tang M AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China. Electronic address: doctortangmin@yeah.net. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240627 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Atrial Fibrillation/drug therapy/prevention & control MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Obesity/complications/drug therapy MH - Prognosis MH - Randomized Controlled Trials as Topic MH - Overweight/complications MH - Semaglutide OTO - NOTNLM OT - Atrial fibrillation OT - Diabetes mellitus OT - Glucagon-like peptide-1 receptor agonist OT - Meta-analysis OT - Semaglutide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/07/03 00:42 MHDA- 2024/09/06 01:02 CRDT- 2024/07/02 18:09 PHST- 2024/03/05 00:00 [received] PHST- 2024/06/22 00:00 [revised] PHST- 2024/06/25 00:00 [accepted] PHST- 2024/09/06 01:02 [medline] PHST- 2024/07/03 00:42 [pubmed] PHST- 2024/07/02 18:09 [entrez] AID - S1871-4021(24)00128-0 [pii] AID - 10.1016/j.dsx.2024.103067 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2024 Jun;18(6):103067. doi: 10.1016/j.dsx.2024.103067. Epub 2024 Jun 27. PMID- 38949006 OWN - NLM STAT- MEDLINE DCOM- 20240701 LR - 20260127 IS - 0030-9982 (Print) IS - 0030-9982 (Linking) VI - 74 IP - 6 DP - 2024 Jun TI - Semaglutide and weight loss - A concern for diabetics and pharmaceuticals. PG - 1204 LID - 10.47391/JPMA.10705 [doi] FAU - Admani, Bushra AU - Admani B AD - Department of Paediatrics, Dow University of Health Sciences, Karachi, Pakistan. FAU - Fahim, Mariam AU - Fahim M AD - Third Year MBBS Student, Jinnah Sindh Medical University, Karachi, Pakistan. FAU - Ahmed, Huda AU - Ahmed H AD - Second Year MBBS Student, Dow University of Health Sciences, Karachi, Pakistan. LA - eng PT - Letter PL - Pakistan TA - J Pak Med Assoc JT - JPMA. The Journal of the Pakistan Medical Association JID - 7501162 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Weight Loss/drug effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide EDAT- 2024/07/01 12:42 MHDA- 2024/07/01 12:43 CRDT- 2024/07/01 06:06 PHST- 2024/07/01 12:43 [medline] PHST- 2024/07/01 12:42 [pubmed] PHST- 2024/07/01 06:06 [entrez] AID - xxx [pii] AID - 10.47391/JPMA.10705 [doi] PST - ppublish SO - J Pak Med Assoc. 2024 Jun;74(6):1204. doi: 10.47391/JPMA.10705. PMID- 38943656 OWN - NLM STAT- MEDLINE DCOM- 20241001 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 15 IP - 10 DP - 2024 Oct TI - A real-world disproportionality analysis of semaglutide: Post-marketing pharmacovigilance data. PG - 1422-1433 LID - 10.1111/jdi.14229 [doi] AB - AIM/INTRODUCTION: The recent adverse reactions associated with semaglutide have led the Food and Drug Administration (FDA) to issue a "black box warning", and it is necessary to analyze all reports of adverse reactions to improve the safety of its clinical use. MATERIALS AND METHODS: Statistical analyses and signal mining were performed by obtaining the adverse event reports related to semaglutide in the FAERS database from the first quarter of 2018 to the fourth quarter of 2023. We used disproportionality and Bayesian analysis to examine clinical and demographic attributes, trends reported quarterly, and contrasts between two distinct indications (obesity and type 2 diabetes). RESULTS: We found 10 unexpected adverse signals related to "pancreatic cancer", "intestinal obstruction", "cholecystitis", and "polycystic ovary" and both the two different indications had the same serious adverse reaction events occurring. CONCLUSIONS: This study identified many unexpected signals of serious adverse reactions, suggesting the importance of continuous post-marketing surveillance of semaglutide to understand its potential risks. CI - (c) 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Du, Yikuan AU - Du Y AD - Central Laboratory, The Tenth Affiliated Hospital of Southern Medical University, Dongguan, China. FAU - Zhang, Mengting AU - Zhang M AD - Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China. FAU - Wang, Zhenjie AU - Wang Z AD - Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China. FAU - Hu, Mianda AU - Hu M AD - Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China. FAU - Xie, Dongxia AU - Xie D AD - Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China. FAU - Wang, Xiuzhu AU - Wang X AD - Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China. FAU - Guo, Zhuoming AU - Guo Z AD - Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China. FAU - Zhu, Jinfeng AU - Zhu J AD - Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China. FAU - Zhang, Weichui AU - Zhang W AD - Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China. FAU - Luo, Ziyi AU - Luo Z AD - Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China. FAU - Yang, Chun AU - Yang C AUID- ORCID: 0000-0001-5813-0914 AD - Dongguan Key Laboratory of Stem Cell and Regenerative Tissue Engineering, The First Dongguan Affiliated Hospital, School of Basic Medical Sciences, Guangdong Medical University, Dongguan, China. LA - eng GR - 2021B1515140012/Natural Science Foundation of Guangdong Province/ GR - 2023A1515010083/Natural Science Foundation of Guangdong Province/ GR - 20211800905342/Dongguan Science and Technology of Social Development Program/ GR - k202005/Research and Development Fund of Dongguan People's Hospital/ GR - 2021ZZDS006/Guangdong Medical University Students' Innovation Experiment Program/ GR - 2021ZCDS003/Guangdong Medical University Students' Innovation Experiment Program/ GR - 2022ZYDS003/Guangdong Medical University Students' Innovation Experiment Program/ GR - 2022FYDB009/Guangdong Medical University Students' Innovation Experiment Program/ GR - 2022FCDS003/Guangdong Medical University Students' Innovation Experiment Program/ GR - GDMU2021003/Guangdong Medical University Students' Innovation and Entrepreneurship Training Program/ GR - GDMU2021049/Guangdong Medical University Students' Innovation and Entrepreneurship Training Program/ GR - GDMU2022031/Guangdong Medical University Students' Innovation and Entrepreneurship Training Program/ GR - GDMU2022047/Guangdong Medical University Students' Innovation and Entrepreneurship Training Program/ GR - GDMU2022063/Guangdong Medical University Students' Innovation and Entrepreneurship Training Program/ GR - GDMU2022077/Guangdong Medical University Students' Innovation and Entrepreneurship Training Program/ GR - GDMU2022078/Guangdong Medical University Students' Innovation and Entrepreneurship Training Program/ GR - 202210571008/Provincial and National College Students' Innovation and Entrepreneurship Training Program/ GR - S202210571075/Provincial and National College Students' Innovation and Entrepreneurship Training Program/ GR - 202310571031/Provincial and National College Students' Innovation and Entrepreneurship Training Program/ GR - S202310571047/Provincial and National College Students' Innovation and Entrepreneurship Training Program/ GR - S202310571078/Provincial and National College Students' Innovation and Entrepreneurship Training Program/ GR - S202310571063/Provincial and National College Students' Innovation and Entrepreneurship Training Program/ GR - S202310571077/Provincial and National College Students' Innovation and Entrepreneurship Training Program/ GR - 4SG24028G/Guangdong Medical University-Southern Medical University Twinning Research Team Project/ GR - Cai Limin National Traditional Chinese Medicine Inheritance Studio/ PT - Journal Article DEP - 20240629 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects MH - *Pharmacovigilance MH - Female MH - *Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Product Surveillance, Postmarketing/statistics & numerical data MH - Male MH - Middle Aged MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Adult MH - United States/epidemiology MH - Aged MH - Databases, Factual MH - Bayes Theorem MH - Obesity/epidemiology/chemically induced MH - Semaglutide PMC - PMC11442840 OTO - NOTNLM OT - Diabetes mellitus OT - Pharmacovigilance OT - Semaglutide COIS- The authors have no relevant financial or non-financial interests to disclose. Approval of the research protocol: N/A. Informed consent: N/A. Registry and the registration no. of the study/trial: N/A. Animal studies: N/A. EDAT- 2024/06/29 23:43 MHDA- 2024/10/01 10:19 PMCR- 2024/06/29 CRDT- 2024/06/29 13:02 PHST- 2024/04/18 00:00 [revised] PHST- 2024/01/12 00:00 [received] PHST- 2024/04/24 00:00 [accepted] PHST- 2024/10/01 10:19 [medline] PHST- 2024/06/29 23:43 [pubmed] PHST- 2024/06/29 13:02 [entrez] PHST- 2024/06/29 00:00 [pmc-release] AID - JDI14229 [pii] AID - 10.1111/jdi.14229 [doi] PST - ppublish SO - J Diabetes Investig. 2024 Oct;15(10):1422-1433. doi: 10.1111/jdi.14229. Epub 2024 Jun 29. PMID- 38935106 OWN - NLM STAT- MEDLINE DCOM- 20250423 LR - 20260127 IS - 1743-9159 (Electronic) IS - 1743-9191 (Print) IS - 1743-9159 (Linking) VI - 111 IP - 1 DP - 2025 Jan 1 TI - Semaglutide outperforms insulin in restoring neutrophil function against implant-related infection in diabetic and obese mice: experimental research. PG - 273-282 LID - 10.1097/JS9.0000000000001896 [doi] AB - BACKGROUND: Bone and joint infections (BJI) are a significant complication after arthroplasty and fracture fixation, particularly challenging in patients with type 2 diabetes mellitus (T2DM) and obesity. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has shown efficacy in managing T2DM and obesity. However, its impact on BJI risk and neutrophil function remains unclear. To investigate whether preoperative semaglutide treatment (1) reduces the risk of BJI in diabetic and obese mice undergoing intra-articular implants, and (2) outperforms insulin in restoring neutrophil function to mitigate implant-related infection. METHODS: A C57BL/6 mouse model of T2DM/obesity was induced using a high-fat diet (HFD) for 12 weeks. Mice received preoperative insulin or semaglutide therapy for 1-28 days. BJI risk was assessed using an intra-articular-implant model challenged with Staphylococcus aureus or Escherichia coli . The neutrophil function was evaluated through bactericidal activity, superoxide production, and migration ability. RESULTS: Semaglutide treatment led to a significant and sustained reduction in body weight and improved glucose tolerance in HFD mice. Both insulin and semaglutide therapies significantly reduced BJI risk, with semaglutide showing a more pronounced effect over time. Semaglutide therapy also enhanced neutrophil bactericidal activity, superoxide production, and migration ability compared to insulin therapy. CONCLUSIONS: Preoperative semaglutide treatment effectively reduces BJI risk and improves neutrophil function in diabetic and obese mouse models. These findings suggest that semaglutide may be a promising pharmacological intervention to mitigate infection risk in orthopedic patients with T2DM or obesity. CI - Copyright (c) 2024 The Author(s). Published by Wolters Kluwer Health, Inc. FAU - Liu, Tiexin AU - Liu T AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. AD - National Center for Orthopedics, Shanghai, People's Republic of China. FAU - Zhou, Lenian AU - Zhou L AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. AD - National Center for Orthopedics, Shanghai, People's Republic of China. FAU - Chen, Yiwei AU - Chen Y AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. AD - National Center for Orthopedics, Shanghai, People's Republic of China. FAU - Lin, Junqing AU - Lin J AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. AD - National Center for Orthopedics, Shanghai, People's Republic of China. FAU - Zhu, Hongyi AU - Zhu H AD - Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. AD - National Center for Orthopedics, Shanghai, People's Republic of China. LA - eng PT - Journal Article DEP - 20250101 PL - United States TA - Int J Surg JT - International journal of surgery (London, England) JID - 101228232 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - Mice, Inbred C57BL MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Neutrophils/drug effects/physiology MH - Mice MH - *Insulin/therapeutic use/pharmacology MH - *Prosthesis-Related Infections/prevention & control MH - *Obesity/complications MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Male MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Disease Models, Animal MH - Diet, High-Fat MH - *Diabetes Mellitus, Experimental/complications MH - Mice, Obese MH - Glucagon-Like Peptide 1 MH - Semaglutide PMC - PMC11745711 COIS- The authors declare that they have no conflicts of interest. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. EDAT- 2024/06/27 12:42 MHDA- 2025/03/07 18:22 PMCR- 2025/01/20 CRDT- 2024/06/27 11:04 PHST- 2024/05/03 00:00 [received] PHST- 2024/06/18 00:00 [accepted] PHST- 2025/03/07 18:22 [medline] PHST- 2024/06/27 12:42 [pubmed] PHST- 2024/06/27 11:04 [entrez] PHST- 2025/01/20 00:00 [pmc-release] AID - 01279778-202501000-00027 [pii] AID - IJS-D-24-01845 [pii] AID - 10.1097/JS9.0000000000001896 [doi] PST - epublish SO - Int J Surg. 2025 Jan 1;111(1):273-282. doi: 10.1097/JS9.0000000000001896. PMID- 38929525 OWN - NLM STAT- MEDLINE DCOM- 20240627 LR - 20260127 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 60 IP - 6 DP - 2024 May 30 TI - Influence of Dulaglutide on Serum Biomarkers of Atherosclerotic Plaque Instability: An Interventional Analysis of Cytokine Profiles in Diabetic Subjects-A Pilot Study. LID - 10.3390/medicina60060908 [doi] LID - 908 AB - Background and Objectives: The rise in global diabetes cases, reaching a staggering 529 million in 2021 from 108 million in 1980, underscores the urgency of addressing its complications, notably macrovascular ones like coronary artery, cerebrovascular, and peripheral artery diseases, which contribute to over 50% of diabetes mortality. Atherosclerosis, linked to hyperglycemia-induced endothelial dysfunction, is pivotal in cardiovascular disease development. Cytokines, including pentraxin 3 (PTX3), copeptin, lipoprotein(a) [Lp(a)], and matrix metalloproteinase-9 (MMP-9), influence atherosclerosis progression and plaque vulnerability. Inhibiting atherosclerosis progression is crucial, especially in diabetic individuals. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), increasingly used for type 2 diabetes, show promise in reducing the cardiovascular risk, sparking interest in their effects on atherogenesis. This study sought to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on biomarkers that indicate the instability of atherosclerotic plaques. These biomarkers include pentraxin 3 (PTX3), copeptin (CPC), matrix metalloproteinase-9 (MMP-9), and lipoprotein(a) [Lp(a)]. Materials and Methods: A total of 34 participants, ranging in age from 41 to 81 years (with an average age of 61), who had been diagnosed with type 2 diabetes mellitus (with a median HbA1c level of 8.8%), dyslipidemia, and verified atherosclerosis using B-mode ultrasonography, were included in the study. All subjects were eligible to initiate treatment with a GLP-1 RA-dulaglutide. Results: Significant reductions in anthropometric parameters, blood pressure, fasting glucose levels, and HbA1c levels were observed posttreatment. Moreover, a notable decrease in biochemical markers associated with atherosclerotic plaque instability, particularly PTX3 and MMP-9 (p < 0.001), as well as Lp(a) (p < 0.05), was evident following the GLP-1 RA intervention. Conclusions: These findings underscore the potential of GLP-1 RAs in mitigating atherosclerosis progression and plaque vulnerability, thus enhancing cardiovascular outcomes in individuals with type 2 diabetes mellitus. FAU - Hachula, Marcin AU - Hachula M AUID- ORCID: 0000-0001-9023-676X AD - Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, 40-752 Katowice, Poland. FAU - Kosowski, Michal AU - Kosowski M AUID- ORCID: 0000-0003-2597-463X AD - Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, 40-752 Katowice, Poland. FAU - Basiak, Marcin AU - Basiak M AUID- ORCID: 0000-0003-0674-5612 AD - Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, 40-752 Katowice, Poland. FAU - Okopien, Boguslaw AU - Okopien B AUID- ORCID: 0000-0001-7228-2906 AD - Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, 40-752 Katowice, Poland. LA - eng GR - PCN-1-227/N/2/O/Medical University of Silesia/ PT - Journal Article DEP - 20240530 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Biomarkers) RN - 9007-41-4 (C-Reactive Protein) RN - 0 (Serum Amyloid P-Component) RN - 62340-29-8 (Glucagon-Like Peptides) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - 0 (Cytokines) RN - 0 (Hypoglycemic Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Lipoprotein(a)) RN - 0 (Glycopeptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Pentraxins) RN - WTT295HSY5 (dulaglutide) RN - 0 (copeptins) SB - IM MH - Humans MH - Pilot Projects MH - *Biomarkers/blood MH - Middle Aged MH - Male MH - *Diabetes Mellitus, Type 2/complications/drug therapy/blood MH - Female MH - *Plaque, Atherosclerotic/blood/drug therapy MH - *C-Reactive Protein/analysis MH - *Serum Amyloid P-Component/analysis MH - *Glucagon-Like Peptides/analogs & derivatives/therapeutic use/pharmacology MH - *Matrix Metalloproteinase 9/blood MH - Aged MH - *Cytokines/blood MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - *Recombinant Fusion Proteins/therapeutic use MH - Atherosclerosis/blood/drug therapy MH - Lipoprotein(a)/blood MH - Glycopeptides MH - Immunoglobulin Fc Fragments MH - Pentraxins PMC - PMC11205508 OTO - NOTNLM OT - GLP-1 receptor agonist OT - MMP-9 OT - copeptin OT - diabetes mellitus OT - dulaglutide OT - lipoprotein(a) OT - pentraxin 3 OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2024/06/27 06:43 MHDA- 2024/06/27 06:44 PMCR- 2024/05/30 CRDT- 2024/06/27 01:13 PHST- 2024/05/07 00:00 [received] PHST- 2024/05/23 00:00 [revised] PHST- 2024/05/28 00:00 [accepted] PHST- 2024/06/27 06:44 [medline] PHST- 2024/06/27 06:43 [pubmed] PHST- 2024/06/27 01:13 [entrez] PHST- 2024/05/30 00:00 [pmc-release] AID - medicina60060908 [pii] AID - medicina-60-00908 [pii] AID - 10.3390/medicina60060908 [doi] PST - epublish SO - Medicina (Kaunas). 2024 May 30;60(6):908. doi: 10.3390/medicina60060908. PMID- 38925801 OWN - NLM STAT- MEDLINE DCOM- 20240626 LR - 20250103 IS - 1756-1833 (Electronic) IS - 0959-8138 (Print) IS - 0959-8138 (Linking) VI - 385 DP - 2024 Jun 26 TI - SGLT-2 inhibitors, GLP-1 receptor agonists, and DPP-4 inhibitors and risk of hyperkalemia among people with type 2 diabetes in clinical practice: population based cohort study. PG - e078483 LID - 10.1136/bmj-2023-078483 [doi] LID - e078483 AB - OBJECTIVES: To evaluate the comparative effectiveness of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and dipeptidyl peptidase-4 (DPP-4) inhibitors in preventing hyperkalemia in people with type 2 diabetes in routine clinical practice. DESIGN: Population based cohort study with active-comparator, new user design. SETTING: Claims data from Medicare and two large commercial insurance databases in the United States from April 2013 to April 2022. PARTICIPANTS: 1:1 propensity score matched adults with type 2 diabetes newly starting SGLT-2 inhibitors versus DPP-4 inhibitors (n=778 908), GLP-1 receptor agonists versus DPP-4 inhibitors (n=729 820), and SGLT-2 inhibitors versus GLP-1 receptor agonists (n=873 460). MAIN OUTCOME MEASURES: Hyperkalemia diagnosis in the inpatient or outpatient setting. Secondary outcomes were hyperkalemia defined as serum potassium levels >/=5.5 mmol/L and hyperkalemia diagnosis in the inpatient or emergency department setting. RESULTS: Starting SGLT-2 inhibitor treatment was associated with a lower rate of hyperkalemia than DPP-4 inhibitor treatment (hazard ratio 0.75, 95% confidence interval (CI) 0.73 to 0.78) and a slight reduction in rate compared with GLP-1 receptor agonists (0.92, 0.89 to 0.95). Use of GLP-1 receptor agonists was associated with a lower rate of hyperkalemia than DPP-4 inhibitors (0.79, 0.77 to 0.82). The three year absolute risk was 2.4% (95% CI 2.1% to 2.7%) lower for SGLT-2 inhibitors than DPP-4 inhibitors (4.6% v 7.0%), 1.8% (1.4% to 2.1%) lower for GLP-1 receptor agonists than DPP-4 inhibitors (5.7% v 7.5%), and 1.2% (0.9% to 1.5%) lower for SGLT-2 inhibitors than GLP-1 receptor agonists (4.7% v 6.0%). Findings were consistent for the secondary outcomes and among subgroups defined by age, sex, race, medical conditions, other drug use, and hemoglobin A1c levels on the relative scale. Benefits for SGLT-2 inhibitors and GLP-1 receptor agonists on the absolute scale were largest for those with heart failure, chronic kidney disease, or those using mineralocorticoid receptor antagonists. Compared with DPP-4 inhibitors, the lower rate of hyperkalemia was consistently observed across individual agents in the SGLT-2 inhibitor (canagliflozin, dapagliflozin, empagliflozin) and GLP-1 receptor agonist (dulaglutide, exenatide, liraglutide, semaglutide) classes. CONCLUSIONS: In people with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists were associated with a lower risk of hyperkalemia than DPP-4 inhibitors in the overall population and across relevant subgroups. The consistency of associations among individual agents in the SGLT-2 inhibitor and GLP-1 receptor agonist classes suggests a class effect. These ancillary benefits of SGLT-2 inhibitors and GLP-1 receptor agonists further support their use in people with type 2 diabetes, especially in those at risk of hyperkalemia. CI - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Fu, Edouard L AU - Fu EL AUID- ORCID: 0000-0002-9698-6825 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. AD - Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. FAU - Wexler, Deborah J AU - Wexler DJ AD - Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. AD - Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. FAU - Cromer, Sara J AU - Cromer SJ AD - Diabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. AD - Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. FAU - Bykov, Katsiaryna AU - Bykov K AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. FAU - Paik, Julie M AU - Paik JM AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. AD - Division of Renal (Kidney) Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - New England Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, MA, USA. FAU - Patorno, Elisabetta AU - Patorno E AUID- ORCID: 0000-0002-8809-9898 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. LA - eng GR - K01 AG068365/AG/NIA NIH HHS/United States GR - R01 DK135706/DK/NIDDK NIH HHS/United States GR - R01 DK138036/DK/NIDDK NIH HHS/United States PT - Comparative Study PT - Journal Article DEP - 20240626 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Hyperkalemia/chemically induced/epidemiology MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Male MH - Female MH - Aged MH - Middle Aged MH - United States/epidemiology MH - Cohort Studies MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Propensity Score MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11200155 COIS- Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare the following: support from Brigham and Women's Hospital, Harvard Medical School, the Netherlands Organization for Scientific Research, Patient-Centered Outcomes Research Institute, Food and Drug Administration, National Institutes of Health, National Institute on Aging, American Diabetes Association for the submitted work. EP is principal investigator of an investigator initiated grant to the Brigham and Women's Hospital from Boehringer Ingelheim, not directly related to the topic of the submitted work; DJW reports serving on data monitoring committees for Novo Nordisk not related to the topic of this work; SJC reports serving on advisory boards for Alexion Pharmaceuticals and employment of a family member by a Johnson and Johnson company. No other potential conflicts of interest relevant to this article were reported. EDAT- 2024/06/27 00:42 MHDA- 2024/06/27 00:43 PMCR- 2024/06/26 CRDT- 2024/06/26 21:03 PHST- 2024/06/27 00:43 [medline] PHST- 2024/06/27 00:42 [pubmed] PHST- 2024/06/26 21:03 [entrez] PHST- 2024/06/26 00:00 [pmc-release] AID - bmj-2023-078483.R1 [pii] AID - fued078483 [pii] AID - 10.1136/bmj-2023-078483 [doi] PST - epublish SO - BMJ. 2024 Jun 26;385:e078483. doi: 10.1136/bmj-2023-078483. PMID- 38925293 OWN - NLM STAT- MEDLINE DCOM- 20240712 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 213 DP - 2024 Jul TI - Tirzepatide 5, 10 and 15 mg versus injectable semaglutide 0.5 mg for the treatment of type 2 diabetes: An adjusted indirect treatment comparison. PG - 111759 LID - S0168-8227(24)00669-7 [pii] LID - 10.1016/j.diabres.2024.111759 [doi] FAU - Zaheer, Hamza AU - Zaheer H AD - Services Institute of medical Sciences, Lahore, Punjab 54000, Pakistan. Electronic address: hamzazaheer583@gmail.com. FAU - Hammad Zaheer, Muhammad AU - Hammad Zaheer M AD - Allama Iqbal Medical College, Lahore, Punjab 54700, Pakistan. Electronic address: muhammadhammadzaheer6466@gmail.com. LA - eng PT - Comparative Study PT - Letter DEP - 20240624 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Glycated Hemoglobin/analysis/metabolism MH - Aged MH - Semaglutide COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/06/27 00:42 MHDA- 2024/07/13 07:42 CRDT- 2024/06/26 19:26 PHST- 2024/06/18 00:00 [received] PHST- 2024/06/21 00:00 [accepted] PHST- 2024/07/13 07:42 [medline] PHST- 2024/06/27 00:42 [pubmed] PHST- 2024/06/26 19:26 [entrez] AID - S0168-8227(24)00669-7 [pii] AID - 10.1016/j.diabres.2024.111759 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2024 Jul;213:111759. doi: 10.1016/j.diabres.2024.111759. Epub 2024 Jun 24. PMID- 38914124 OWN - NLM STAT- MEDLINE DCOM- 20241016 LR - 20260127 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 30 IP - 10 DP - 2024 Oct TI - Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial. PG - 2849-2856 LID - 10.1038/s41591-024-03133-0 [doi] AB - People with type 2 diabetes and chronic kidney disease have a high risk for kidney failure and cardiovascular (CV) complications. Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors (SGLT2i) independently reduce CV and kidney events. The effect of combining both is unclear. FLOW trial participants with type 2 diabetes and chronic kidney disease were stratified by baseline SGLT2i use (N = 550) or no use (N = 2,983) and randomized to semaglutide/placebo. The primary outcome was a composite of kidney failure, >/=50% estimated glomerular filtration rate reduction, kidney death or CV death. The risk of the primary outcome was 24% lower in all participants treated with semaglutide versus placebo (95% confidence interval: 34%, 12%). The primary outcome occurred in 41/277 (semaglutide) versus 38/273 (placebo) participants on SGLT2i at baseline (hazard ratio 1.07; 95% confidence interval: 0.69, 1.67; P = 0.755) and in 290/1,490 versus 372/1,493 participants not taking SGLT2i at baseline (hazard ratio 0.73; 0.63, 0.85; P < 0.001; P interaction 0.109). Three confirmatory secondary outcomes were predefined. Treatment differences favoring semaglutide for total estimated glomerular filtration rate slope (ml min(-1)/1.73 m(2)/year) were 0.75 (-0.01, 1.5) in the SGLT2i subgroup and 1.25 (0.91, 1.58) in the non-SGLT2i subgroup, P interaction 0.237. Semaglutide benefits on major CV events and all-cause death were similar regardless of SGLT2i use (P interaction 0.741 and 0.901, respectively). The benefits of semaglutide in reducing kidney outcomes were consistent in participants with/without baseline SGLT2i use; power was limited to detect smaller but clinically relevant effects. ClinicalTrials.gov identifier: NCT03819153 . CI - (c) 2024. The Author(s). FAU - Mann, Johannes F E AU - Mann JFE AUID- ORCID: 0000-0002-3154-5332 AD - KfH Kidney Centre, Munchen, Germany. johannes.mann@kms.mhn.de. AD - University Hospital Erlangen, Friedrich Alexander University, Erlangen, Germany. johannes.mann@kms.mhn.de. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Bakris, George AU - Bakris G AD - Department of Medicine, AHA Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, IL, USA. FAU - Belmar, Nicolas AU - Belmar N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bosch-Traberg, Heidrun AU - Bosch-Traberg H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Busch, Robert AU - Busch R AD - Albany Medical Center Division of Community Endocrinology, Albany, NY, USA. FAU - Charytan, David M AU - Charytan DM AUID- ORCID: 0000-0002-7695-3583 AD - Nephrology Division, Department of Medicine, New York University Grossman School of Medicine, and NYU Langone Health, New York, NY, USA. FAU - Hadjadj, Samy AU - Hadjadj S AD - L'Institut du Thorax, CHU Nantes, CNRS, INSERM, Nantes Universite, Nantes, France. FAU - Gillard, Pieter AU - Gillard P AD - Department of Endocrinology, University Hospitals Leuven - KU Leuven, Leuven, Belgium. FAU - Gorriz, Jose Luis AU - Gorriz JL AUID- ORCID: 0000-0002-1134-9051 AD - Department of Nephrology, Hospital Clinico Universitario de Valencia (INCLIVA), Valencia, Spain. AD - Department of Medicine, Universitat de Valencia, Valencia, Spain. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA, USA. FAU - Perkovic, Vlado AU - Perkovic V AD - Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Schmieder, Roland E AU - Schmieder RE AUID- ORCID: 0000-0003-2356-5883 AD - Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich Alexander University, Erlangen, Germany. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, FL, USA. FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - Division of Nephrology, University of Washington, Seattle, WA, USA. AD - Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA. LA - eng SI - ClinicalTrials.gov/NCT03819153 PT - Journal Article PT - Randomized Controlled Trial DEP - 20240624 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Female MH - Male MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - Middle Aged MH - Aged MH - *Glomerular Filtration Rate/drug effects MH - Treatment Outcome MH - Cardiovascular Diseases/drug therapy/prevention & control/mortality MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide PMC - PMC11485243 COIS- J.F.E.M. reports grants from Novo Nordisk, the European Union and McMaster University Hamilton, Canada; consulting fees from Novo Nordisk, AstraZeneca, Bayer and Boehringer Ingelheim; honoraria from Novo Nordisk, AstraZeneca, Bayer and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi and Boehringer Ingelheim, as well as a leadership role in the KDIGO group. P.R. has received consultancy and/or speaking fees (institutional) from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Novo Nordisk and Sanofi; and research grants from AstraZeneca, Bayer and Novo Nordisk. G.B. has been a consultant to or an executive committee member for a clinical trial: Bayer, KBP Biosciences, Ionis, Alnylam, AstraZeneca, Novo Nordisk and InREGEN; and is editor for the American Journal of Nephrology. N.B., H.B.-T., T.I. and S.R. are employees and shareholders of Novo Nordisk. R.B. has served on the speaker bureau for Novo Nordisk; and is a clinical investigator in several Novo Nordisk trials (for example, SUSTAIN6, SUSTAIN9, FLOW, SOUL and CagriSema). D.M.C. declares being a consultant for Allena Pharmaceuticals (DSMB), AstraZeneca, CSL Behring, Eli Lilly/Boehringer Ingelheim, Gilead, GSK, LG Chemical, Medtronic, Merck, Novo Nordisk, Renalytix and Zogenix; has received research funding from Amgen and Medtronic, and clinical trial support from Eli Lilly/Boehringer Ingelheim, Gilead and Novo Nordisk; has patents or royalties from UpToDate.com for authorship/editorials on reviews; has provided advisory or leadership roles for CJASN; and has received expert witness fees related to proton pump inhibitors. S.H. has received grants from Asdia, AstraZeneca, LVL, Nestle Homeperf, ISIS Diabete, Pierre Fabre and VitalAire; consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi, Servier and Valbiotis; payment or honoraria from Abbott, AstraZeneca, Boehringer Ingelheim, Bayer, Dino Sante, Eli Lilly, Novartis, Novo Nordisk, Pierre Fabre, Sanofi, Servier and Valbiotis; and support to attend meetings from AstraZeneca, Abbott, Dino Sante, Eli Lilly and Novo Nordisk. P.G. serves or has served on advisory panels for Abbott, Bayer, Boehringer Ingelheim, Janssen Pharmaceuticals, Medtronic, Novo Nordisk, Roche and Sanofi, with financial compensation for these activities received by KU Leuven; serves or has served on the speakers bureau for Abbott, Bayer, Boehringer Ingelheim, Dexcom, Insulet, Merck Sharp & Dohme, Medtronic, Novo Nordisk, Roche and VitalAire, with financial compensation for these activities received by KU Leuven; and KU Leuven has received nonfinancial support for P.G. for travel from A. Menarini Diagnostics, Medtronic, Novo Nordisk, Sanofi and Roche. J.L.G. declares funding to conduct clinical trials from AstraZeneca, Bayer, Boehringer Ingelheim and Novo Nordisk (all to the INCLIVA Research Institute); consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim and Novo Nordisk; and payment of honoraria for lectures from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Menarini and Novo Nordisk. L.J. has received consulting/lecture fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck, MSD, Novo Nordisk and Sanofi; and payment of honoraria for lectures from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck, MSD, Novo Nordisk and Sanofi; and support to attend meetings from Bayer, Eli Lilly, Merck, MSD and Novo Nordisk. K.W.M. has received grants from AHA, Apple, Bayer, California Institute for Regenerative Medicine, CSL Behring, Eidos, Ferring, Gilead, Google (Verify), Idorsia, Johnson & Johnson, Luitpold, Novartis, PAC-12, Precordior and Sanifit; and consulting fees from Applied Therapeutics, Bayer, BMS, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson & Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, Phasebio, Portola, Quidel, and Theravance; and has equity in Human, Medeloop, Precordior, and Regencor. V.P. has received honoraria for steering committee, data monitoring committee or advisory board roles or for scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, GlaxoSmithKline, Janssen, Novo Nordisk, Novartis, Otsuka, Travere, Tricida and UptoDate; and is a Board Director for George Clinical, St. Vincents Health Australia, and several independent medical research institutes. R.E.S. has received grants to the Institution from Amgen, Ablative Solution, Bayer, IPPmed, Medtronic, Novo Nordisk and Recor; and honoraria as a speaker and advisor from Ablative Solutions, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Medtronic, Merck, Novo Nordisk, Novartis, Recor, Servier and TAD. R.E.P. declares speaker fees from Lilly and Novo Nordisk; consulting fees from Bayer AG, Bayer HealthCare Pharmaceuticals, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Intas Pharmaceuticals, Lilly, Novo Nordisk, Pfizer and Sun Pharmaceutical Industries; and research grants from Biomea Fusion, Carmot Therapeutics, Dompe, Endogenex, Fractyl, Lilly, Novo Nordisk and Sanofi. K.R.T. has received grants from Bayer and Travere Therapeutics (institutional); consulting fees and honoraria for lectures, presentations, speakers bureaus and educational events from Bayer, Boehringer Ingelheim, Eli Lilly and Company and Novo Nordisk; provides unpaid participation as the Data Safety Monitoring Board Chair for the George Clinical Institute, and NIDDK/NIH; and is also the Diabetic Kidney Disease Collaborative Chair for the American Society of Nephrology. EDAT- 2024/06/25 00:42 MHDA- 2024/10/17 10:02 PMCR- 2024/06/24 CRDT- 2024/06/24 19:03 PHST- 2024/05/17 00:00 [received] PHST- 2024/06/13 00:00 [accepted] PHST- 2024/10/17 10:02 [medline] PHST- 2024/06/25 00:42 [pubmed] PHST- 2024/06/24 19:03 [entrez] PHST- 2024/06/24 00:00 [pmc-release] AID - 10.1038/s41591-024-03133-0 [pii] AID - 3133 [pii] AID - 10.1038/s41591-024-03133-0 [doi] PST - ppublish SO - Nat Med. 2024 Oct;30(10):2849-2856. doi: 10.1038/s41591-024-03133-0. Epub 2024 Jun 24. PMID- 38913778 OWN - NLM STAT- MEDLINE DCOM- 20241120 LR - 20260714 IS - 1532-4303 (Electronic) IS - 0277-0903 (Linking) VI - 61 IP - 12 DP - 2024 Dec TI - Can glucagon-like peptide-1 receptor agonists induce asthma? An analysis of the FAERS database. PG - 1638-1645 LID - 10.1080/02770903.2024.2372600 [doi] AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP1RAs), originally developed for the treatment of type 2 diabetes mellitus, have attracted attention for their potential therapeutic benefits in asthma due to their anti-inflammatory properties and effects on airway smooth muscle function. However, concerns have been raised about the possibility of GLP1RAs inducing or exacerbating asthma symptoms. METHODS: We reviewed data from the US Food and Drug Administration's (FDA) adverse event (AE) reporting system (FAERS) to examine reports of cases of asthma observed in the real-world during treatment with GLP1RAs. RESULTS: Analysis of the FAERS reporting system database has shown that certain GLP1RAs, particularly exenatide, semaglutide and liraglutide, were associated with a higher proportion of respiratory AEs, particularly asthma or asthma-like events. This association was statistically significant at least for semaglutide and liraglutide. Serious asthma-related events and deaths were also reported, with exenatide having the highest proportion of deaths. CONCLUSIONS: The reasons for the observed differences in the AE profiles of the GLP1RAs remain unclear and may involve various factors such as pharmacological properties, patient characteristics and reporting biases. The complex interplay between the therapeutic benefits of GLP1RAs and the potential respiratory risks requires careful monitoring by clinicians, underpinned by ongoing research efforts to improve patient care and safety. FAU - Cazzola, Mario AU - Cazzola M AUID- ORCID: 0000-0003-4895-9707 AD - Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome 'Tor Vergata', Rome, Italy. FAU - Matera, Maria Gabriella AU - Matera MG AD - Unit of Pharmacology, Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy. FAU - Calzetta, Luigino AU - Calzetta L AD - Unit of Respiratory Disease and Lung Function, Department of Medicine and Surgery, University of Parma, Parma, Italy. FAU - Lauro, Davide AU - Lauro D AD - Unit of Endocrinology and Metabolic Diseases, Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy. FAU - Rogliani, Paola AU - Rogliani P AUID- ORCID: 0000-0001-7801-5040 AD - Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome 'Tor Vergata', Rome, Italy. LA - eng PT - Journal Article DEP - 20240704 PL - England TA - J Asthma JT - The Journal of asthma : official journal of the Association for the Care of Asthma JID - 8106454 RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Asthma/drug therapy MH - *Exenatide/adverse effects/therapeutic use MH - *Glucagon-Like Peptides/adverse effects/therapeutic use/analogs & derivatives MH - *Liraglutide/therapeutic use/adverse effects MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - United States/epidemiology MH - Male MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - Female MH - Middle Aged MH - United States Food and Drug Administration MH - Adult MH - Diabetes Mellitus, Type 2/drug therapy MH - Aged MH - Databases, Factual MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Asthma OT - US Food and Drug Administration's adverse events reporting system OT - glucagon-like peptide-1 receptor agonists EDAT- 2024/06/24 18:42 MHDA- 2024/11/20 11:04 CRDT- 2024/06/24 14:03 PHST- 2024/11/20 11:04 [medline] PHST- 2024/06/24 18:42 [pubmed] PHST- 2024/06/24 14:03 [entrez] AID - 10.1080/02770903.2024.2372600 [doi] PST - ppublish SO - J Asthma. 2024 Dec;61(12):1638-1645. doi: 10.1080/02770903.2024.2372600. Epub 2024 Jul 4. PMID- 38913003 OWN - NLM STAT- MEDLINE DCOM- 20240821 LR - 20260127 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 84 IP - 9 DP - 2024 Aug 27 TI - Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials. PG - 773-785 LID - S0735-1097(24)07445-X [pii] LID - 10.1016/j.jacc.2024.06.001 [doi] AB - BACKGROUND: More women than men have heart failure with preserved ejection fraction (HFpEF). OBJECTIVES: The purpose of this study was to assess baseline characteristics and treatment effect of semaglutide by sex across the STEP-HFpEF (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity) program. METHODS: In a prespecified secondary analysis of pooled data from STEP-HFpEF and STEP-HFpEF DM (Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes), patients with heart failure (HF), left ventricular ejection fraction >/=45%, body mass index >/=30 kg/m(2), and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) <90 points were randomized 1:1 to once-weekly semaglutide 2.4 mg or matched placebo for 52 weeks. Dual primary endpoints (KCCQ-CSS change and percentage change in body weight) and confirmatory secondary endpoints (6-minute walking distance [6MWD] change; hierarchical composite endpoint comprising all-cause death, HF events, changes in KCCQ-CSS, and 6MWD; and C-reactive protein) were compared between sexes. RESULTS: Of 1,145 patients, 570 (49.7%) were women. Women had higher body mass index, left ventricular ejection fraction, C-reactive protein, and worse HF symptoms, and were less likely to have atrial fibrillation or coronary artery disease vs men. Semaglutide improved KCCQ-CSS regardless of sex (mean difference in women +7.6 points [95% CI: 4.5-10.7 points]; men +7.5 points [95% CI: 4.3-10.6 points]; P interaction = 0.94) but reduced body weight more in women (mean difference in women -9.6% [95% CI: -10.9% to -8.4%]; men -7.2% [95% CI: -8.4% to -6.0%]; P interaction = 0.006). Semaglutide improved 6MWD (P interaction = 0.21) and the hierarchical composite endpoint (P interaction = 0.66) in both sexes. Fewer serious adverse events were reported with semaglutide vs placebo. CONCLUSIONS: In patients with obesity-related HFpEF, semaglutide 2.4 mg reduced body weight to a greater extent in women, and produced similar improvements in HF-related symptoms, physical limitations, and exercise function, regardless of sex. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF]; NCT04788511; and Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP HFpEF DM]; NCT04916470). CI - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada. FAU - Butler, Javed AU - Butler J AD - Baylor Scott & White Research Institute, Dallas, Texas, USA. FAU - Borlaug, Barry A AU - Borlaug BA AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. FAU - Davies, Melanie AU - Davies M AD - Diabetes Research Centre, University of Leicester, Leicester, United Kingdom. FAU - Kitzman, Dalane W AU - Kitzman DW AD - Department of Internal Medicine, Sections on Cardiovascular Medicine and Geriatrics/Gerontology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. FAU - Shah, Sanjiv J AU - Shah SJ AD - Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. FAU - Petrie, Mark C AU - Petrie MC AD - School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, United Kingdom. FAU - Barros, Eric AU - Barros E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ronnback, Cecilia AU - Ronnback C AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Vestergaard, Lene Sommer AU - Vestergaard LS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Schou, Morten AU - Schou M AD - Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, Herlev, Denmark. FAU - Ezekowitz, Justin A AU - Ezekowitz JA AD - University of Alberta, Edmonton, Alberta, Canada. FAU - Sharma, Kavita AU - Sharma K AD - Division of Cardiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Patel, Shachi AU - Patel S AD - Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA. FAU - Chinnakondepalli, Khaja M AU - Chinnakondepalli KM AD - Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. Electronic address: mkosiborod@saint-lukes.org. CN - STEP-HFpEF Trial Committees and Investigators LA - eng SI - ClinicalTrials.gov/NCT04916470 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20240623 PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Heart Failure/drug therapy/physiopathology/complications MH - *Obesity/complications/drug therapy MH - Sex Factors MH - *Stroke Volume/drug effects MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - heart failure OT - obesity OT - semaglutide OT - sex COIS- Funding Support and Author Disclosures This trial was funded by Novo Nordisk A/S. Administrative support for manuscript development was funded by Novo Nordisk A/S. Dr Verma is supported by the Canadian Institutes of Health Research and Heart and Stroke Foundation of Canada; holds the Tier 1 Canada Research Chair in Cardiovascular Surgery; and has received speaking honoraria and/or consulting fees from Abbott, Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, and TIMI. Dr Butler has served as a consultant for Abbott, American Regent, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Daxor Edwards, Element Science, Imbria, Impulse Dynamics, Innolife, Inventiva, Janssen, Lexicon, Lilly, LivaNova, Medtronics, Merck, Novartis, Novo Nordisk, Occlutech, Owkin, Pfizer, Pharmacosmos, Pharmain, Prolaio, Roche, Secretome, Sequana, SQ Innovation, Tenex, and Vifor. Dr Borlaug is supported in part by the National Institutes of Health grants R01HL128526, R01HL162828, and U01HL160226, and by the U.S. Department of Defense grant W81XWH2210245; has received research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, Rivus, and Tenax Therapeutics; has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, Becton, Dickinson and Company, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, NGM, Novo Nordisk, NXT, and VADovations; and is named inventor (U.S. patent number 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. Dr Davies is supported by the Leicester National Institute for Health Research Biomedical Research Centre, Leicester General Hospital; has acted as a consultant, advisory board member, and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi; has served as an advisory board member and speaker for AstraZeneca; has served as an advisory board member for Medtronic, Pfizer, and ShouTi Pharma; has served as a speaker for Amgen, Novartis, and Sanofi; and has received grants as an investigator in support of investigator-initiated trials from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, and Sanofi. Dr Kitzman was supported in part by the Kermit Glenn Phillips II Chair in Cardiovascular Medicine and National Institutes of Health grants U01AG076928, R01AG078153, R01AG045551, R01AG18915, P30AG021332, U24AG059624, and U01HL160272; has received honoraria as a consultant for AstraZeneca, Bayer, Boehringer Ingelheim, Corvia Medical, Ketyo, Novartis, Novo Nordisk, Pfizer, and Rivus; has received grant funding from AstraZeneca, Bayer, Novartis, Novo Nordisk, Pfizer, and Rivus; and has stock ownership in Gilead Sciences. Dr Shah was supported by National Institutes of Health grants U54HL160273, R01HL107577, R01HL127028, R01HL140731, and R01HL149423; has received research grants from AstraZeneca, Corvia, and Pfizer; and has received consulting fees from Abbott, Alleviant, Amgen, Aria CV, AstraZeneca, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, ReCor, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and Ultromics. Dr Petrie is supported by the British Heart Foundation Centre of Research Excellence Award (RE/13/5/30177 and RE/18/6/34217+); has received research funding from AstraZeneca, Boehringer Ingelheim, Boston Scientific, Medtronic, Novartis, Novo Nordisk, Pharmacosmos, Roche, and SQ Innovations; and has served on committees or consulted for AbbVie, Akero, AnaCardio, Applied Therapeutics, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Cardiorentis, Corvia, Eli Lilly, Horizon Therapeutics, LIB Therapeutics, Moderna, New Amsterdam, Novartis, Novo Nordisk, Pharmacosmos, Siemens, SQ Innovations, Takeda, Teikoku, and Vifor. Drs Barros, Ronnback, and Vestergaard are employees and shareholders of Novo Nordisk A/S. Dr Schou has received speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, and Novo Nordisk. Dr Ezekowitz has received research support for trial leadership from American Regent, Applied Therapeutics, Bayer, Cytokinetics, Merck, and Novo Nordisk; has received honoraria for consultancy from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, and Otsuka; and has served as an adviser to US2.ai. Dr Sharma is an advisory board member and consultant for Alleviant, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Janssen, Novartis, Novo Nordisk, and Rivus; and received honoraria from these companies. Dr Kosiborod has served as a consultant or as an advisory board member for 35Pharma, Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pfizer, Pharmacosmos, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; has received research grants from AstraZeneca and Boehringer Ingelheim; holds stocks in Artera Health and Saghmos Therapeutics; has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and has received other research support from AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. EDAT- 2024/06/24 12:42 MHDA- 2024/08/22 00:42 CRDT- 2024/06/24 10:33 PHST- 2024/04/30 00:00 [received] PHST- 2024/05/29 00:00 [revised] PHST- 2024/06/02 00:00 [accepted] PHST- 2024/08/22 00:42 [medline] PHST- 2024/06/24 12:42 [pubmed] PHST- 2024/06/24 10:33 [entrez] AID - S0735-1097(24)07445-X [pii] AID - 10.1016/j.jacc.2024.06.001 [doi] PST - ppublish SO - J Am Coll Cardiol. 2024 Aug 27;84(9):773-785. doi: 10.1016/j.jacc.2024.06.001. Epub 2024 Jun 23. PMID- 38908837 OWN - NLM STAT- MEDLINE DCOM- 20240622 LR - 20260127 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 14 IP - 6 DP - 2024 Jun 21 TI - Adverse effects with semaglutide: a protocol for a systematic review with meta-analysis and trial sequential analysis. PG - e084190 LID - 10.1136/bmjopen-2024-084190 [doi] LID - e084190 AB - INTRODUCTION: Semaglutide is increasingly used for the treatment of type 2 diabetes mellitus, overweight and other conditions. It is well known that semaglutide lowers blood glucose levels and leads to significant weight loss. Still, a systematic review has yet to investigate the adverse effects with semaglutide for all patient groups. METHODS AND ANALYSIS: We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medline, Embase, Latin American and Caribbean Health Sciences Literature, Science Citation Index Expanded, Conference Proceedings Citation Index-Science) and clinical trial registries from their inception and onwards to identify relevant randomised clinical trials. We expect to conduct the literature search in July 2024. Two review authors will independently extract data and perform risk-of-bias assessments. We will include randomised clinical trials comparing oral or subcutaneous semaglutide versus placebo. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be myocardial infarction, stroke, all-cause hospitalisation and non-serious adverse events. Data will be synthesised by meta-analyses and trial sequential analysis; risk of bias will be assessed with Cochrane Risk of Bias tool-version 2, an eight-step procedure will be used to assess if the thresholds for statistical and clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations. ETHICS AND DISSEMINATION: This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals. PROSPERO REGISTRATION NUMBER: CRD42024499511. CI - (c) Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Sillassen, Christina Dam Bjerregaard AU - Sillassen CDB AUID- ORCID: 0009-0004-9247-5245 AD - Centre for Clinical Intervention Research, Rigshospitalet Copenhagen Trial Unit, Copenhagen, Denmark christina.sillassen@ctu.dk. AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Kamp, Caroline Barkholt AU - Kamp CB AUID- ORCID: 0000-0002-7756-4694 AD - Centre for Clinical Intervention Research, Rigshospitalet Copenhagen Trial Unit, Copenhagen, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Petersen, Johanne Juul AU - Petersen JJ AUID- ORCID: 0000-0001-9837-1958 AD - Centre for Clinical Intervention Research, Rigshospitalet Copenhagen Trial Unit, Copenhagen, Denmark. AD - Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Faltermeier, Pascal AU - Faltermeier P AD - Centre for Clinical Intervention Research, Rigshospitalet Copenhagen Trial Unit, Copenhagen, Denmark. AD - MSH Medical School Hamburg University of Applied Sciences and Medical University, Hamburg, Germany. FAU - Siddiqui, Faiza AU - Siddiqui F AUID- ORCID: 0000-0002-8358-6259 AD - Centre for Clinical Intervention Research, Rigshospitalet Copenhagen Trial Unit, Copenhagen, Denmark. FAU - Grand, Johannes AU - Grand J AUID- ORCID: 0000-0002-5511-4668 AD - Amager-Hvidovre Hospital, Department of Cardiology, Copenhagen University Hospital, Copenhagen, Denmark. FAU - Dominguez, Helena AU - Dominguez H AD - Bispebjerg and Frederiksberg Hospital, Department of Cardiology, Copenhagen University Hospital, Copenhagen, Denmark. AD - Department of Biomedicine, Health Faculty, University of Copenhagen, Copenhagen, Denmark. FAU - Frolich, Anne AU - Frolich A AD - Innovation and Research Centre for Multimorbidity, Slagelse Hospital, Slagelse, Denmark. AD - Section of General Practice, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark. FAU - Gaede, Peter Haulund AU - Gaede PH AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Gluud, Christian AU - Gluud C AD - Centre for Clinical Intervention Research, Rigshospitalet Copenhagen Trial Unit, Copenhagen, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Mathiesen, Ole AU - Mathiesen O AD - Department of Anaesthesiology, Zealand University Hospital Koge Centre for Anaesthesiological Research, Koge, Denmark. AD - Department of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark. FAU - Jakobsen, Janus AU - Jakobsen J AD - Centre for Clinical Intervention Research, Rigshospitalet Copenhagen Trial Unit, Copenhagen, Denmark. AD - Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article DEP - 20240621 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Systematic Reviews as Topic MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Meta-Analysis as Topic MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Research Design MH - Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC11331358 OTO - NOTNLM OT - meta-analysis OT - public health OT - safety OT - systematic review COIS- Competing interests: PG has received lecture fees for Novo Nordisk, AstraZeneca, Eli Lilly, Bayer, MSD and has served in Advisory Boards for Novo Nordisk, AstraZeneca, Bayer. EDAT- 2024/06/23 00:42 MHDA- 2024/06/23 00:43 PMCR- 2024/06/21 CRDT- 2024/06/22 20:43 PHST- 2024/06/23 00:43 [medline] PHST- 2024/06/23 00:42 [pubmed] PHST- 2024/06/22 20:43 [entrez] PHST- 2024/06/21 00:00 [pmc-release] AID - bmjopen-2024-084190 [pii] AID - 10.1136/bmjopen-2024-084190 [doi] PST - epublish SO - BMJ Open. 2024 Jun 21;14(6):e084190. doi: 10.1136/bmjopen-2024-084190. PMID- 38907681 OWN - NLM STAT- MEDLINE DCOM- 20240725 LR - 20260625 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 47 IP - 8 DP - 2024 Aug 1 TI - Deciphering the Effects of Semaglutide Across the Glycemic Spectrum. PG - 1322-1324 LID - 10.2337/dci24-0057 [doi] AB - CI - (c) 2024 by the American Diabetes Association. FAU - Misra, Shivani AU - Misra S AUID- ORCID: 0000-0003-2886-0726 AD - Division of Metabolism, Digestion and Reproduction, Imperial College London, London, U.K. AD - Department of Diabetes and Endocrinology, Imperial College Healthcare NHS Trust, London, U.K. LA - eng PT - Comment PT - Editorial PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - Diabetes Care. 2024 Aug 1;47(8):1350-1359. doi: 10.2337/dc24-0491. PMID: 38907683 CON - Diabetes Care. 2024 Aug 1;47(8):1360-1369. doi: 10.2337/dc24-0764. PMID: 38907684 MH - *Glucagon-Like Peptides/therapeutic use MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - *Blood Glucose/drug effects/metabolism MH - Diabetes Mellitus, Type 2/drug therapy/blood MH - Semaglutide EDAT- 2024/06/22 19:45 MHDA- 2024/07/26 12:43 CRDT- 2024/06/22 08:03 PHST- 2024/06/03 00:00 [received] PHST- 2024/06/04 00:00 [accepted] PHST- 2024/07/26 12:43 [medline] PHST- 2024/06/22 19:45 [pubmed] PHST- 2024/06/22 08:03 [entrez] AID - 156879 [pii] AID - 10.2337/dci24-0057 [doi] PST - ppublish SO - Diabetes Care. 2024 Aug 1;47(8):1322-1324. doi: 10.2337/dci24-0057. PMID- 38904969 OWN - NLM STAT- MEDLINE DCOM- 20240716 LR - 20260127 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 332 IP - 3 DP - 2024 Jul 16 TI - Study: Semaglutide Lowered Chronic Kidney Disease-Related Risks. PG - 188 LID - 10.1001/jama.2024.10349 [doi] FAU - Bock, Anna AU - Bock A LA - eng PT - News PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Cardiovascular Diseases/prevention & control MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Renal Insufficiency, Chronic/complications MH - Risk MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2024/06/21 12:42 MHDA- 2024/07/16 12:44 CRDT- 2024/06/21 11:33 PHST- 2024/07/16 12:44 [medline] PHST- 2024/06/21 12:42 [pubmed] PHST- 2024/06/21 11:33 [entrez] AID - 2820424 [pii] AID - 10.1001/jama.2024.10349 [doi] PST - ppublish SO - JAMA. 2024 Jul 16;332(3):188. doi: 10.1001/jama.2024.10349. PMID- 38894744 OWN - NLM STAT- MEDLINE DCOM- 20240619 LR - 20260920 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 15 DP - 2024 TI - Transforming body composition with semaglutide in adults with obesity and type 2 diabetes mellitus. PG - 1386542 LID - 10.3389/fendo.2024.1386542 [doi] LID - 1386542 AB - BACKGROUND: Glucagon-like peptide-1 receptor-agonists (GLP-1ra), such as semaglutide, have emerged as promising treatments, demonstrating sustained weight reduction and metabolic benefits. This study aims to assess the impact of oral and subcutaneous semaglutide on body composition and metabolic parameters in patients with T2DM and obesity. METHODS: A 24-week quasi-experimental retrospective study including adults with T2DM and obesity (BMI >/= 30 kg/m(2)) who were treated with either daily-oral or weekly-subcutaneous semaglutide. Body composition was measured using bioelectrical impedance analysis, evaluating fat mass, fat-free mass, total body water, skeletal muscle mass, and whole-body phase angle. Analytical parameters included lipid profile and glycaemic control. Statistical analyses were performed using SPSS v.26. RESULTS: Participants (n=88) experienced significant weight loss after treatment with semaglutide (9.5% in subcutaneous, 9.4% in oral, P<0.001). Weight reduction primarily resulted from fat mass reduction without substantial lean mass compromise. Visceral fat area decreased, whiles phase-angle remained stable. Improvements in lipid profiles and glycaemic control were observed, with a decrease in both HbA1c and insulin requirements. Multivariate analysis demonstrated comparable impacts of oral and subcutaneous semaglutide on body composition. CONCLUSION: Semaglutide, administered orally or subcutaneously, demonstrated positive effects on body composition, metabolic and glycaemic control in patients with T2DM and obesity. This real-world study highlights the potential of bioelectrical impedance analysis in assessing antidiabetic drugs' impact on body composition, providing valuable insights for future research and clinical applications. CI - Copyright (c) 2024 Rodriguez Jimenez, Rodriguez de Vera Gomez, Belmonte Lomas, Mesa Diaz, Caballero Mateos, Galan, Morales Portillo and Martinez-Brocca. FAU - Rodriguez Jimenez, Beatriz AU - Rodriguez Jimenez B AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Virgen Macarena, Seville, Spain. FAU - Rodriguez de Vera Gomez, Pablo AU - Rodriguez de Vera Gomez P AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Virgen Macarena, Seville, Spain. FAU - Belmonte Lomas, Samuel AU - Belmonte Lomas S AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Virgen Macarena, Seville, Spain. FAU - Mesa Diaz, Angel Manuel AU - Mesa Diaz AM AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Virgen Macarena, Seville, Spain. FAU - Caballero Mateos, Irene AU - Caballero Mateos I AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Virgen Macarena, Seville, Spain. FAU - Galan, Irene AU - Galan I AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Virgen Macarena, Seville, Spain. FAU - Morales Portillo, Cristobal AU - Morales Portillo C AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Virgen Macarena, Seville, Spain. FAU - Martinez-Brocca, Maria Asuncion AU - Martinez-Brocca MA AD - Servicio de Endocrinologia y Nutricion, Hospital Universitario Virgen Macarena, Seville, Spain. LA - eng PT - Journal Article DEP - 20240604 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Body Composition/drug effects MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - *Obesity/drug therapy MH - Adult MH - *Hypoglycemic Agents/therapeutic use MH - Aged MH - Weight Loss/drug effects MH - Blood Glucose/drug effects/metabolism MH - Semaglutide PMC - PMC11182984 OTO - NOTNLM OT - HbA1c OT - body composition OT - fat mass OT - lean body mass OT - obesity OT - phase angle OT - type 2 diabetes mellitus OT - visceral fat area COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/06/19 06:41 MHDA- 2024/06/19 06:42 PMCR- 2024/01/01 CRDT- 2024/06/19 04:15 PHST- 2024/02/15 00:00 [received] PHST- 2024/05/21 00:00 [accepted] PHST- 2024/06/19 06:42 [medline] PHST- 2024/06/19 06:41 [pubmed] PHST- 2024/06/19 04:15 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2024.1386542 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2024 Jun 4;15:1386542. doi: 10.3389/fendo.2024.1386542. eCollection 2024. PMID- 38889587 OWN - NLM STAT- MEDLINE DCOM- 20240801 LR - 20260127 IS - 1878-0539 (Electronic) IS - 1748-6815 (Linking) VI - 95 DP - 2024 Aug TI - Plastic surgery amid a semaglutide epidemic: Direction for future studies and service implications. PG - 104-105 LID - S1748-6815(24)00320-6 [pii] LID - 10.1016/j.bjps.2024.05.045 [doi] FAU - Ragsdale, Louisa B AU - Ragsdale LB AD - Division of Plastic and Reconstructive Surgery, Saint Louis University School of Medicine, Saint Louis, MO, USA. FAU - Badran, Saif AU - Badran S AD - Division Plastic and Reconstructive Surgery, Washington University School of Medicine, Saint Louis, MO, USA. Electronic address: Badran@wustl.edu. LA - eng PT - Letter DEP - 20240604 PL - Netherlands TA - J Plast Reconstr Aesthet Surg JT - Journal of plastic, reconstructive & aesthetic surgery : JPRAS JID - 101264239 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Diabetes Mellitus, Type 2/epidemiology MH - Plastic Surgery Procedures MH - Semaglutide OTO - NOTNLM OT - Body contouring OT - GLP1-RAs OT - Ozempic OT - Plastic surgery OT - Semaglutide OT - Weight loss EDAT- 2024/06/19 00:43 MHDA- 2024/08/02 00:47 CRDT- 2024/06/18 18:05 PHST- 2024/05/07 00:00 [received] PHST- 2024/05/17 00:00 [accepted] PHST- 2024/08/02 00:47 [medline] PHST- 2024/06/19 00:43 [pubmed] PHST- 2024/06/18 18:05 [entrez] AID - S1748-6815(24)00320-6 [pii] AID - 10.1016/j.bjps.2024.05.045 [doi] PST - ppublish SO - J Plast Reconstr Aesthet Surg. 2024 Aug;95:104-105. doi: 10.1016/j.bjps.2024.05.045. Epub 2024 Jun 4. PMID- 38874130 OWN - NLM STAT- MEDLINE DCOM- 20240927 LR - 20260602 IS - 1552-4604 (Electronic) IS - 0091-2700 (Linking) VI - 64 IP - 10 DP - 2024 Oct TI - Efficacy and Safety of Oral Semaglutide in the Treatment of Type 2 Diabetes: A Meta-Analysis. PG - 1312-1325 LID - 10.1002/jcph.2483 [doi] AB - This study aims to systematically review the efficacy and safety of oral semaglutide in the treatment of type 2 diabetes mellitus (T2DM) and provide a basis for the rational use of the drug in clinical practice. From the database's inception until February 2023, a systematic search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and China Science and Technology Journal Database to identify randomized controlled trials (RCTs) comparing the efficacy of oral semaglutide at dosages of 3, 7, and 14 mg (trial group) against placebo or other positive control drugs (control group) for the treatment of T2DM. Following literature screening and data extraction, the bias risk assessment tool in the Cochrane reviewer handbook 5.1.0 was used to evaluate the literature quality. Meta-analysis was carried out with RevMan 5.4 software. A total of 10 RCTs with 9541 patients were included. The meta-analysis results revealed that compared with placebo or positive control drugs (empagliflozin, sitagliptin, liraglutide, and dulaglutide), oral semaglutide significantly reduced the hemoglobin A1c (HbA1c) in patients (compared to placebo, 3 mg [MD = -0.61%, 95% CI (-0.89, -0.34)], 7 mg [MD = -1.12%, 95% CI (-1.45, -0.79)], 14 mg [MD = -1.08%, 95% CI (-1.32, -0.85)]; compared to positive control drugs (7 mg [MD = -0.26%, 95% CI (-0.38, -0.15)], 14 mg [MD = -0.37%, 95% CI (-0.52, -0.23)]). Oral semaglutide also showed certain advantages over placebo or positive control drugs in terms of weight loss, HbA1c reduction achievement rate, fasting plasma glucose level, and body mass index with overall dose-dependent efficacy. The incidence of nausea, diarrhea, and vomiting caused by oral semaglutide was higher than that of the placebo or positive control drugs, and the incidence of appetite decrease or constipation was higher than that of the placebo. Severe or symptomatic hypoglycemic episodes were reduced compared to positive control drugs. Oral semaglutide has definite clinical benefits of reducing blood glucose, body weight, reducing the risk of hypoglycemia, and with good safety. CI - (c) 2024, The American College of Clinical Pharmacology. FAU - Zhang, Lin AU - Zhang L AD - Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. FAU - Hua, Zixin AU - Hua Z AD - Department of Clinical Pharmacy, Capital Medical University, Beijing, China. FAU - Fang, Zhenwei AU - Fang Z AD - Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. FAU - Wei, Juanjuan AU - Wei J AUID- ORCID: 0000-0001-9620-6457 AD - Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. FAU - Lin, Yang AU - Lin Y AD - Department of Pharmacy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20240614 PL - England TA - J Clin Pharmacol JT - Journal of clinical pharmacology JID - 0366372 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Administration, Oral MH - Randomized Controlled Trials as Topic MH - Glycated Hemoglobin MH - Blood Glucose/drug effects MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - glycemic control OT - meta-analysis OT - oral semaglutide OT - type 2 diabetes EDAT- 2024/06/14 12:43 MHDA- 2024/09/27 07:06 CRDT- 2024/06/14 07:24 PHST- 2024/01/30 00:00 [received] PHST- 2024/05/22 00:00 [accepted] PHST- 2024/09/27 07:06 [medline] PHST- 2024/06/14 12:43 [pubmed] PHST- 2024/06/14 07:24 [entrez] AID - 10.1002/jcph.2483 [doi] PST - ppublish SO - J Clin Pharmacol. 2024 Oct;64(10):1312-1325. doi: 10.1002/jcph.2483. Epub 2024 Jun 14. PMID- 38869512 OWN - NLM STAT- MEDLINE DCOM- 20241028 LR - 20260518 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 67 IP - 11 DP - 2024 Nov TI - EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD): Executive Summary. PG - 2375-2392 LID - 10.1007/s00125-024-06196-3 [doi] AB - Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as the fibrosis-4 index [FIB-4]) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification-including weight loss, dietary changes, physical exercise and discouraging alcohol consumption-as well as optimal management of comorbidities-including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for type 2 diabetes or obesity, if indicated-is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage >/=2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis. CI - (c) 2024. The Author(s). CN - European Association for the Study of the Liver CN - European Association for the Study of Diabetes CN - European Association for the Study of Obesity LA - eng PT - Journal Article PT - Practice Guideline PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 SB - IM EIN - Diabetologia. 2024 Nov;67(11):2608. doi: 10.1007/s00125-024-06258-6. PMID: 39352523 MH - Humans MH - *Non-alcoholic Fatty Liver Disease/therapy/complications MH - Obesity/complications MH - Liver Cirrhosis/complications MH - Fatty Liver/therapy MH - Diabetes Mellitus, Type 2/complications PMC - PMC11519095 OTO - NOTNLM OT - Diabetes OT - Glucagon-like peptide OT - Hepatocellular carcinoma OT - Liver fibrosis OT - MASH OT - MASLD OT - NAFLD OT - NASH OT - Non-invasive tests OT - Resmetirom COIS- Luca Valenti has disclosed speaking engagements with Viatris, Novo Nordisk, and GSK; consulting roles with Novo Nordisk, Pfizer, Boehringer Ingelheim, Resalis, and MSD; and received unrestricted grant support from Gilead. Elisabetta Bugianesi serves as a consultant for Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Pfizer, Bristol-Myers Squibb, and MSD. Amalia Gastaldelli has acted as a consultant for Boehringer Ingelheim, Eli Lilly and Company, and Metadeq Diagnostics; participated in advisory boards for Boehringer Ingelheim, Merck Sharp & Dohme, Novo Nordisk, Metadeq Diagnostics, and Pfizer; and received speaker's honorarium or other fees from Eli Lilly and Company, Merck Sharp & Dohme, Novo Nordisk, and Pfizer. Frank Tacke's lab has received research funding from Gilead, AstraZeneca, and MSD (funding to the institution); he has received honoraria for consulting or lectures from AstraZeneca, Gilead, AbbVie, BMS, Boehringer, Intercept, Falk, Inventiva, MSD, GSK, Orphalan, Merz, Pfizer, Alnylam, Novo Nordisk, Sanofi, and Novartis. Michael Roden has participated in consulting for and/or scientific advisory boards of BMS, Boehringer Ingelheim Pharma, Echosens, Eli Lilly, Madrigal, MSD, Novo Nordisk, as well as in clinical trials supported by Boehringer Ingelheim, Novo Nordisk, and Nutricia/Danone. Paul Horn received grants from Novo Nordisk (through the University of Birmingham) and MSD (through Charite - Universitatsmedizin Berlin); speaking fees from Orphalan; and travel support from IPSEN. Hannele Yki-Jarvinen declares no conflicts of interest regarding the present work. Shira Zelber-Sagi received travel support for attending a conference and honoraria for a lecture presentation in this conference by AbbVie, a one-time consulting fee by SIEMENS, and holds an unpaid leadership role as Chair-elect of the EASL public health committee. Vincent Wong has served as a consultant or advisory board member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Novo Nordisk, Pfizer, Sagimet Biosciences, TARGET PharmaSolutions, and Visirna; a speaker for Abbott, AbbVie, Echosens, Gilead Sciences, Novo Nordisk, and Unilab; received a research grant from Gilead Sciences, and is a co-founder of Illuminatio Medical Technology. Gema Fruhbeck received payment of honoraria for attendance to Advisory Boards from Lilly, and Novo Nordisk as well as payment of honoraria for lectures as Member of the OPEN Spain Initiative. Sven Francque holds a senior clinical investigator fellowship from the Research Foundation Flanders (FWO) and has acted as consultant for Astellas, Falk Pharma, Genfit, Gilead Sciences, GlympsBio, Janssens Pharmaceutica, Inventiva, Merck Sharp & Dome, Pfizer, Roche. He has acted as consultant for Abbvie, Actelion, Aelin Therapeutics, AgomAb, Aligos Therapeutics, Allergan, Alnylam, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Bristoll-Meyers Squibb, CSL Behring, Coherus, Echosens, Dr. Falk Pharma, Eisai, Enyo, Galapagos, Galmed, Genetech, Genfit, Genflow Biosciences, Gilead Sciences, Intercept, Inventiva, Janssens Pharmaceutica, PRO.MED.CS Praha, Julius Clinical, Madrigal, Medimmune, Merck Sharp & Dome, Mursla Bio, NGM Bio, Novartis, Novo Nordisk, Promethera, Roche, Siemens Healthineers, and lectured for for Abbvie, Allergan, Bayer, Eisai, Genfit, Gilead Sciences, Janssens Cilag, Intercept, Inventiva, Merck Sharp & Dome, Novo Nordisk, Promethera, Siemens. Dror Dicker received grants, personal fees, and nonfinancial support from NovoNordisk and Eli Lilly, and personal fees and nonfinancial support from Boehringer Ingelheim outside the submitted work. Vlad Ratziu serves as a consultant for Novo-Nordisk, Madrigal, Boehringer-Ingelheim, GSK, and 89 Bio; and has a grant to institution from MSD. Fritz Schick declares no conflict of interest pertaining to this article. Roberto Vettor has received honoraria from Novo Nordisk, Eli Lilly and AstraZeneca, and has served on advisory boards for Novo Nordisk and Eli Lilly. FIR - Tacke, Frank IR - Tacke F FIR - Horn, Paul IR - Horn P FIR - Wong, Vincent Wai-Sun IR - Wong VW FIR - Ratziu, Vlad IR - Ratziu V FIR - Bugianesi, Elisabetta IR - Bugianesi E FIR - Francque, Sven IR - Francque S FIR - Zelber-Sagi, Shira IR - Zelber-Sagi S FIR - Valenti, Luca IR - Valenti L FIR - Roden, Michael IR - Roden M FIR - Schick, Fritz IR - Schick F FIR - Yki-Jarvinen, Hannele IR - Yki-Jarvinen H FIR - Gastaldelli, Amalia IR - Gastaldelli A FIR - Vettor, Roberto IR - Vettor R FIR - Fruhbeck, Gema IR - Fruhbeck G FIR - Dicker, Dror IR - Dicker D EDAT- 2024/06/13 12:43 MHDA- 2024/10/28 18:23 PMCR- 2024/06/13 CRDT- 2024/06/13 11:03 PHST- 2024/10/28 18:23 [medline] PHST- 2024/06/13 12:43 [pubmed] PHST- 2024/06/13 11:03 [entrez] PHST- 2024/06/13 00:00 [pmc-release] AID - 10.1007/s00125-024-06196-3 [pii] AID - 6196 [pii] AID - 10.1007/s00125-024-06196-3 [doi] PST - ppublish SO - Diabetologia. 2024 Nov;67(11):2375-2392. doi: 10.1007/s00125-024-06196-3. PMID- 38864922 OWN - NLM STAT- MEDLINE DCOM- 20240713 LR - 20260825 IS - 1432-0827 (Electronic) IS - 0171-967X (Print) IS - 0171-967X (Linking) VI - 115 IP - 2 DP - 2024 Aug TI - Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study. PG - 160-168 LID - 10.1007/s00223-024-01240-1 [doi] AB - Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis. CI - (c) 2024. The Author(s). FAU - Al Refaie, Antonella AU - Al Refaie A AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100, Siena, Italy. AD - Division of Internal Medicine I, San Giuseppe Hospital, 50053, Empoli, Italy. FAU - Baldassini, Leonardo AU - Baldassini L AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100, Siena, Italy. FAU - Mondillo, Caterina AU - Mondillo C AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100, Siena, Italy. FAU - Ceccarelli, Elena AU - Ceccarelli E AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100, Siena, Italy. FAU - Tarquini, Roberto AU - Tarquini R AD - Division of Internal Medicine I, San Giuseppe Hospital, 50053, Empoli, Italy. FAU - Gennari, Luigi AU - Gennari L AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100, Siena, Italy. FAU - Gonnelli, Stefano AU - Gonnelli S AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100, Siena, Italy. FAU - Caffarelli, Carla AU - Caffarelli C AUID- ORCID: 0000-0003-4163-7289 AD - Section of Internal Medicine, Department of Medicine, Surgery and Neuroscience, University of Siena, Policlinico Le Scotte, Viale Bracci 2, 53100, Siena, Italy. carla.caffarelli@unisi.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240612 PL - United States TA - Calcif Tissue Int JT - Calcified tissue international JID - 7905481 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Incretins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Longitudinal Studies MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/therapeutic use/analogs & derivatives/pharmacology MH - Male MH - *Bone Density/drug effects MH - *Hypoglycemic Agents/therapeutic use/pharmacology MH - Aged MH - *Immunoglobulin Fc Fragments/therapeutic use MH - *Incretins/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use/pharmacology MH - Bone Diseases, Metabolic/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC11246279 OTO - NOTNLM OT - Bone mineral density (BMD) OT - Bone turnover markers OT - Dual-energy X-ray absorptiometry (DXA) OT - Dulaglutide OT - Radiofrequency echographic multispectrometry (REMS) OT - Semaglutide OT - Trabecular bone score (TBS) OT - Type 2 diabetes mellitus (T2DM) COIS- Antonella Al Refaie, Leonardo Baldassini, Caterina Mondillo, Elena Ceccarelli, Roberto Tarquini, Luigi Gennari, Stefano Gonnelli, Carla Caffarelli declares that they have no conflict of interest to report. EDAT- 2024/06/12 12:43 MHDA- 2024/07/14 01:42 PMCR- 2024/06/12 CRDT- 2024/06/12 11:06 PHST- 2024/03/23 00:00 [received] PHST- 2024/05/22 00:00 [accepted] PHST- 2024/07/14 01:42 [medline] PHST- 2024/06/12 12:43 [pubmed] PHST- 2024/06/12 11:06 [entrez] PHST- 2024/06/12 00:00 [pmc-release] AID - 10.1007/s00223-024-01240-1 [pii] AID - 1240 [pii] AID - 10.1007/s00223-024-01240-1 [doi] PST - ppublish SO - Calcif Tissue Int. 2024 Aug;115(2):160-168. doi: 10.1007/s00223-024-01240-1. Epub 2024 Jun 12. PMID- 38864815 OWN - NLM STAT- MEDLINE DCOM- 20240722 LR - 20260513 IS - 1522-1555 (Electronic) IS - 0193-1849 (Linking) VI - 327 IP - 2 DP - 2024 Aug 1 TI - The enduring metabolic improvement of combining dual amylin and calcitonin receptor agonist and semaglutide treatments in a rat model of obesity and diabetes. PG - E145-E154 LID - 10.1152/ajpendo.00092.2024 [doi] AB - Long-acting dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for the treatment of type 2 diabetes and obesity due to their beneficial effects on body weight, glucose control, and insulin action. However, how the metabolic benefits are maintained after long-lasting treatment is unknown. This study investigates the long-term anti-obesity and anti-diabetic treatment efficacy of the DACRA KBP-336 alone and combined with the GLP-1 analog semaglutide. Zucker diabetic Sprague Dawley (ZDSD) rats with obesity and diabetes received KBP-336 (4.5 nmol/kg Q3D), semaglutide (50 nmol/kg Q3D), or the combination for 7 mo, and the treatment impact on body weight, food intake, glucose control, and insulin action was evaluated. Furthermore, serum levels of the cardiac fibrosis biomarker endotrophin were evaluated. KBP-336, semaglutide, and the combination lowered body weight significantly compared with the vehicle, with the combination inducing a larger and more sustained weight loss than either monotherapy. All treatments resulted in reduced fasting blood glucose levels and HbA1c levels and improved glucose tolerance compared with vehicle-treated rats. Furthermore, all treatments protected against lost insulin secretory capacity and improved insulin action. Serum levels of endotrophin were significantly lowered by KBP-336 compared with vehicle. This study shows the benefit of combining KBP-336 and semaglutide to obtain significant and sustained weight loss, as well as improved glucose control. Furthermore, KBP-336-driven reductions in circulating endotrophin indicate a clear reduction in the risk of complications. Altogether, KBP-336 is a promising candidate for the treatment of obesity and type 2 diabetes both alone and in combination with GLP-1 analogs.NEW & NOTEWORTHY These studies describe the benefit of combining dual amylin and calcitonin receptor agonists (DACRA) with semaglutide for long-term treatment of obesity and type 2 diabetes. Combination treatment induced sustained weight loss and improved glucose control. A DACRA-driven reduction in a serological biomarker of cardiac fibrosis indicated a reduced risk of complications. These results highlight DACRAs as a promising candidate for combination treatment of obesity and type 2 diabetes and related long-term complications. FAU - Larsen, Anna Thorso AU - Larsen AT AUID- ORCID: 0000-0002-3286-4319 AD - Nordic Bioscience, Herlev, Denmark. FAU - Mohamed, Khaled Elhady AU - Mohamed KE AD - Nordic Bioscience, Herlev, Denmark. FAU - Melander, Simone Anna AU - Melander SA AUID- ORCID: 0000-0002-1844-3294 AD - Nordic Bioscience, Herlev, Denmark. FAU - Karsdal, Morten Asser AU - Karsdal MA AD - Nordic Bioscience, Herlev, Denmark. AD - KeyBioscience AG, Stans, Switzerland. FAU - Henriksen, Kim AU - Henriksen K AD - Nordic Bioscience, Herlev, Denmark. AD - KeyBioscience AG, Stans, Switzerland. AD - Department of Science and Environment, Roskilde University, Roskilde, Denmark. LA - eng GR - NA/Innovation Fund Denmark/ GR - 814244/European Union's horizon 2020 research and innovation program under the Marie Sklodowske-Curie/ PT - Journal Article DEP - 20240612 PL - United States TA - Am J Physiol Endocrinol Metab JT - American journal of physiology. Endocrinology and metabolism JID - 100901226 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Receptors, Calcitonin) RN - 0 (Amylin Receptor Agonists) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - *Glucagon-Like Peptides/pharmacology/administration & dosage/therapeutic use MH - *Receptors, Calcitonin/agonists MH - Rats MH - *Obesity/drug therapy/metabolism MH - *Rats, Zucker MH - *Amylin Receptor Agonists/pharmacology/therapeutic use MH - *Rats, Sprague-Dawley MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Male MH - *Drug Therapy, Combination MH - *Blood Glucose/drug effects/metabolism MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Diabetes Mellitus, Experimental/drug therapy/metabolism MH - Weight Loss/drug effects MH - Disease Models, Animal MH - Body Weight/drug effects MH - Insulin/blood MH - Anti-Obesity Agents/pharmacology/therapeutic use MH - Semaglutide OTO - NOTNLM OT - DACRA OT - GLP-1 OT - obesity OT - type 2 diabetes OT - weight loss EDAT- 2024/06/12 12:42 MHDA- 2024/07/22 12:44 CRDT- 2024/06/12 10:34 PHST- 2024/07/22 12:44 [medline] PHST- 2024/06/12 12:42 [pubmed] PHST- 2024/06/12 10:34 [entrez] AID - 10.1152/ajpendo.00092.2024 [doi] PST - ppublish SO - Am J Physiol Endocrinol Metab. 2024 Aug 1;327(2):E145-E154. doi: 10.1152/ajpendo.00092.2024. Epub 2024 Jun 12. PMID- 38860419 OWN - NLM STAT- MEDLINE DCOM- 20240805 LR - 20260617 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 9 DP - 2024 Sep TI - No association between semaglutide and postoperative pneumonia in people with diabetes undergoing elective surgery. PG - 4105-4110 LID - 10.1111/dom.15711 [doi] FAU - Welk, Blayne AU - Welk B AUID- ORCID: 0000-0001-7093-558X AD - Department of Surgery, Western University, London, Ontario, Canada. AD - Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. AD - ICES, Toronto, Ontario, Canada. FAU - McClure, J Andrew AU - McClure JA AD - London Health Sciences Centre, London, Ontario, Canada. FAU - Carter, Brooke AU - Carter B AD - ICES, Toronto, Ontario, Canada. FAU - Clarke, Collin AU - Clarke C AD - Department of Anesthesia, Western University, London, Ontario, Canada. FAU - Dubois, Luc AU - Dubois L AD - Department of Surgery, Western University, London, Ontario, Canada. AD - Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. AD - ICES, Toronto, Ontario, Canada. FAU - Clemens, Kristin K AU - Clemens KK AUID- ORCID: 0000-0001-9636-5597 AD - Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada. AD - ICES, Toronto, Ontario, Canada. AD - Department of Medicine, Western University, London, Ontario, Canada. LA - eng PT - Letter PT - Research Support, Non-U.S. Gov't DEP - 20240611 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Elective Surgical Procedures/adverse effects MH - Female MH - Male MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Postoperative Complications/prevention & control/etiology MH - *Pneumonia/prevention & control MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - Aged MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - anaesthesia OT - aspiration OT - diabetes OT - surgery EDAT- 2024/06/11 06:42 MHDA- 2024/08/05 06:42 CRDT- 2024/06/11 05:23 PHST- 2024/05/24 00:00 [revised] PHST- 2024/04/19 00:00 [received] PHST- 2024/05/24 00:00 [accepted] PHST- 2024/08/05 06:42 [medline] PHST- 2024/06/11 06:42 [pubmed] PHST- 2024/06/11 05:23 [entrez] AID - 10.1111/dom.15711 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Sep;26(9):4105-4110. doi: 10.1111/dom.15711. Epub 2024 Jun 11. PMID- 38856001 OWN - NLM STAT- MEDLINE DCOM- 20241030 LR - 20260127 IS - 2191-0286 (Electronic) IS - 0792-6855 (Linking) VI - 35 IP - 4-5 DP - 2024 Jul 1 TI - IcoSema: unveiling the future of diabetes management from a clinical pharmacology perspective. PG - 213-224 LID - 10.1515/jbcpp-2024-0058 [doi] AB - IcoSema, a groundbreaking approach to diabetes management, combines insulin icodec and semaglutide to offer a transformative treatment option. Insulin icodec delivers consistent glucose-lowering effects with once-weekly dosing, while semaglutide, a GLP-1 agonist, stimulates insulin secretion and aids in weight loss. This comprehensive article evaluates the potential of IcoSema from a clinical pharmacology perspective, examining the pharmacokinetics, efficacy, safety, compliance and cost-effectiveness of its individual components, as well as considering comparable combination therapies like iGlarLixi and IDegLira. By analysing these crucial factors, the article aims to determine the potential of IcoSema in the field of diabetes management. The combination of insulin icodec and semaglutide has the potential to provide improved glycaemic control, weight management, and simplified treatment regimens, addressing common challenges faced in diabetes management. Safety, compliance and cost considerations are important aspects of evaluating this combination therapy. Ongoing trials investigating IcoSema are expected to provide valuable insights into its efficacy, safety and comparative effectiveness. By addressing concerns such as potential side effects, individual patient response and drug interactions, healthcare providers can optimize treatment outcomes and enhance the management of type 2 diabetes. CI - (c) 2024 Walter de Gruyter GmbH, Berlin/Boston. FAU - Seetharaman, Rajmohan AU - Seetharaman R AUID- ORCID: 0000-0002-4605-2805 AD - Department of Pharmacology and Therapeutics, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai, India. FAU - Monteiro, Rhea AU - Monteiro R AD - Department of Pharmacology and Therapeutics, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai, India. FAU - Maradia, Jay AU - Maradia J AUID- ORCID: 0009-0002-3617-1576 AD - Department of Pharmacology and Therapeutics, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai, India. FAU - Tripathi, Raakhi AU - Tripathi R AD - Department of Pharmacology and Therapeutics, Seth G.S. Medical College and KEM Hospital, Parel, Mumbai, India. LA - eng PT - Journal Article PT - Review DEP - 20240611 PL - Germany TA - J Basic Clin Physiol Pharmacol JT - Journal of basic and clinical physiology and pharmacology JID - 9101750 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Insulin) RN - 0 (Drug Combinations) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/pharmacology/therapeutic use/pharmacokinetics MH - *Glucagon-Like Peptides/pharmacology/therapeutic use MH - Insulin MH - Drug Combinations MH - Blood Glucose/drug effects MH - Cost-Benefit Analysis MH - Pharmacology, Clinical/methods MH - Semaglutide OTO - NOTNLM OT - cost effectiveness OT - efficacy OT - insulin icodec OT - pharmacokinetics OT - safety OT - semaglutide EDAT- 2024/06/10 13:21 MHDA- 2024/10/30 06:21 CRDT- 2024/06/10 07:33 PHST- 2024/04/15 00:00 [received] PHST- 2024/05/25 00:00 [accepted] PHST- 2024/10/30 06:21 [medline] PHST- 2024/06/10 13:21 [pubmed] PHST- 2024/06/10 07:33 [entrez] AID - jbcpp-2024-0058 [pii] AID - 10.1515/jbcpp-2024-0058 [doi] PST - epublish SO - J Basic Clin Physiol Pharmacol. 2024 Jun 11;35(4-5):213-224. doi: 10.1515/jbcpp-2024-0058. eCollection 2024 Jul 1. PMID- 38852625 OWN - NLM STAT- MEDLINE DCOM- 20240712 LR - 20250103 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 213 DP - 2024 Jul TI - The impact of GLP-1 receptor agonist shortages on glycaemic Control: Findings from an Australian specialist diabetes clinic. PG - 111740 LID - S0168-8227(24)00650-8 [pii] LID - 10.1016/j.diabres.2024.111740 [doi] AB - There have been shortages of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for type 2 diabetes (T2D) care. Analyses of data from 811 T2D adults at an Australian specialist diabetes clinic (1/2019-10/2023) who received >/= 2 GLP-1 RA prescriptions before and during the shortage showed median HbA1c levels significantly increased by 0.3 %. CI - Copyright (c) 2024. Published by Elsevier B.V. FAU - Nanayakkara, Natalie AU - Nanayakkara N AD - Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia; Baker Department of Diabetes Clinical Research, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. Electronic address: natalie.nanayakkara@unimelb.edu.au. FAU - Lh Huang, Michael AU - Lh Huang M AD - Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia; Baker Department of Diabetes Clinical Research, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia; Diabetes and Vascular Medicine Lab, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. FAU - Jenkins, Alicia J AU - Jenkins AJ AD - Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia; Baker Department of Diabetes Clinical Research, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia; Diabetes and Vascular Medicine Lab, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia. FAU - Cohen, Neale D AU - Cohen ND AD - Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, VIC, Australia; Baker Department of Diabetes Clinical Research, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia; School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. LA - eng PT - Journal Article DEP - 20240607 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Male MH - Australia/epidemiology MH - Middle Aged MH - *Glycemic Control/methods MH - Female MH - *Glycated Hemoglobin/metabolism/analysis MH - Aged MH - Blood Glucose/drug effects/metabolism/analysis MH - Adult MH - Liraglutide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Dulaglutide OT - GLP-1 receptor agonists OT - Glycaemic control, weight OT - Medication shortages OT - Semaglutide OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [These authors disclose the following: NN has received honoraria/participated a Data Safety Monitoring Board or Advisory Board from Lilly, MH has received Support for attending meetings and/or travel from JDRF Australia and is Associate Editor of Bioscience Reports, AJ is Chair Elect IDF Western Pacific Region, Insulin For Life Global and Australia Board Member NC has received honoraria for lectures from Lectures Novo Nordisk, Lilly, Astra Zeneca, participated a Data Safety Monitoring Board or Advisory Board for Lilly.]. EDAT- 2024/06/10 00:42 MHDA- 2024/07/13 07:47 CRDT- 2024/06/09 19:24 PHST- 2024/05/26 00:00 [received] PHST- 2024/06/05 00:00 [accepted] PHST- 2024/07/13 07:47 [medline] PHST- 2024/06/10 00:42 [pubmed] PHST- 2024/06/09 19:24 [entrez] AID - S0168-8227(24)00650-8 [pii] AID - 10.1016/j.diabres.2024.111740 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2024 Jul;213:111740. doi: 10.1016/j.diabres.2024.111740. Epub 2024 Jun 7. PMID- 38852583 OWN - NLM STAT- MEDLINE DCOM- 20240805 LR - 20260417 IS - 1662-4033 (Electronic) IS - 1662-4025 (Print) IS - 1662-4025 (Linking) VI - 17 IP - 4 DP - 2024 TI - EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). PG - 374-444 LID - 10.1159/000539371 [doi] AB - Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage >/=2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis. CI - (c) 2024 The Author(s). Published by Elsevier BV on behalf of European Association for the Study of the Liver (EASL) and by S Karger AG. CN - European Association for the Study of the Liver (EASL) CN - European Association for the Study of Diabetes (EASD) CN - European Association for the Study of Obesity (EASO) LA - eng PT - Journal Article PT - Practice Guideline DEP - 20240607 PL - Switzerland TA - Obes Facts JT - Obesity facts JID - 101469429 SB - IM EIN - Obes Facts. 2024;17(6):658. doi: 10.1159/000541386. PMID: 39284304 MH - Humans MH - *Non-alcoholic Fatty Liver Disease/therapy/complications/etiology MH - *Obesity/complications/therapy MH - Diabetes Mellitus, Type 2/complications/therapy MH - Risk Factors MH - Liver Cirrhosis/complications/therapy MH - Liver Neoplasms/therapy/etiology MH - Cardiometabolic Risk Factors PMC - PMC11299976 COIS- The authors would like to thank the members of the Delphi Panel of this Clinical Practice Guideline for their valuable contribution: Quentin Anstee, Marco Arrese, Heike Bantel, Giulia Besutti, Jerome Boursier, Christopher Byrne, Ali Canbay, Cyrielle Caussy, Helena Cortez-Pinto, Mattias Ekstedt, Mirto Foletto, Jacob George, Liana Gheorghe, Isabel Graupera, Hannes Hagstrom, Kate Hallsworth, Onno Holleboom, Achim Kautz, Marko Korenjak, Karoline Lackner, Christos Lionis, Giulio Marchesini, Juris J. Meier, Juan M. Mendive, Luca Miele, Geltrude Mingrone, J. Bernadette Moore, Philip Newsome, George Papatheodoridis, Valerie Paradis, Gianluca Perseghin, Ralph Peterli, Salvatore Petta, Manuel Romero-Gomez, Jorn M. Schattenberg, Silvia Sookoian, Wendy Spearman, Norbert Stefan, Maja Thiele, Dina Tiniakos, Emmanouil Tsochatzis, Bernard Van Beers, Jose Willemse, Yusuf Yilmaz, and Volkan Yumuk. The authors would also like to thank the external reviewers and the EASL, EASD and EASO Governing Boards for their valuable contribution to the review process. EDAT- 2024/06/10 00:42 MHDA- 2024/08/06 05:41 PMCR- 2024/06/07 CRDT- 2024/06/09 18:23 PHST- 2024/05/08 00:00 [received] PHST- 2024/05/15 00:00 [accepted] PHST- 2024/08/06 05:41 [medline] PHST- 2024/06/10 00:42 [pubmed] PHST- 2024/06/09 18:23 [entrez] PHST- 2024/06/07 00:00 [pmc-release] AID - 000539371 [pii] AID - 539371 [pii] AID - 10.1159/000539371 [doi] PST - ppublish SO - Obes Facts. 2024;17(4):374-444. doi: 10.1159/000539371. Epub 2024 Jun 7. PMID- 38847728 OWN - NLM STAT- MEDLINE DCOM- 20240607 LR - 20260127 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 103 IP - 23 DP - 2024 Jun 7 TI - Favorable liver and skeletal muscle changes in patients with MASLD and T2DM receiving glucagon-like peptide-1 receptor agonist: A prospective cohort study. PG - e38444 LID - 10.1097/MD.0000000000038444 [doi] LID - e38444 AB - To investigate changes in skeletal muscle mass and fat fraction in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) undergoing treatment with Semaglutide for 6months. This single-arm pilot study included 21 patients with MASLD who received semaglutide for T2DM. Body weight, metabolic parameters, liver enzymes, fibrosis markers, skeletal muscle index (cm2/m2), and fat fraction (%) at the L3 level using the two-point Dixon method on magnetic resonance imaging (MRI), as well as liver steatosis and liver stiffness assessed using MRI-based proton density fat fraction (MRI-PDFF) and MR elastography, respectively, were prospectively examined before and 6 months after semaglutide administration. The mean age of the patients was 53 years and 47.6% were females. The median liver steatosis-fraction (%) and skeletal muscle steatosis-fraction values (%) significantly decreased (22.0 vs 12.0; P = .0014) and (12.8 vs 9.9; P = .0416) at baseline and 6 months, respectively, while maintaining muscle mass during treatment. Semaglutide also dramatically reduced hemoglobin A1c (%) (6.8 vs 5.8, P = .0003), AST (IU/L) (54 vs 26, P < .0001), ALT (IU/L) (80 vs 34, P = .0004), and gamma-GTP (IU/L) levels (64 vs 34, P = .0007). Although not statistically significant, Body weight (kg) (79.9 vs 77.4), body mass index (BMI) (kg/m2) (28.9 vs 27.6), and liver stiffness (kPa) (28.9 vs 27.6) showed a decreasing trend. Fibrosis markers such as M2BPGi, type IV collagen, and skeletal muscle area did not differ. Semaglutide demonstrated favorable effects on liver and skeletal muscle steatosis, promoting improved liver function and diabetic status. CI - Copyright (c) 2024 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Kakegawa, Tatsuya AU - Kakegawa T AD - Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Japan. FAU - Sugimoto, Katsutoshi AU - Sugimoto K AUID- ORCID: 0000-0001-6271-7806 AD - Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Japan. FAU - Saito, Kazuhiro AU - Saito K AD - Department of Radiology, Tokyo Medical University, Shinjuku-ku, Japan. FAU - Yunaiyama, Daisuke AU - Yunaiyama D AD - Department of Radiology, Tokyo Medical University, Shinjuku-ku, Japan. FAU - Araki, Yoichi AU - Araki Y AD - Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Japan. FAU - Wada, Takuya AU - Wada T AD - Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Japan. FAU - Takahashi, Hiroshi AU - Takahashi H AD - Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Japan. FAU - Yoshimasu, Yu AU - Yoshimasu Y AD - Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Japan. FAU - Takeuchi, Hirohito AU - Takeuchi H AD - Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Japan. FAU - Itoi, Takao AU - Itoi T AD - Department of Gastroenterology and Hepatology, Tokyo Medical University, Shinjuku-ku, Japan. LA - eng PT - Journal Article PT - Observational Study PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Middle Aged MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - Prospective Studies MH - *Muscle, Skeletal/drug effects MH - *Glucagon-Like Peptides/therapeutic use/administration & dosage MH - Pilot Projects MH - *Liver/drug effects/diagnostic imaging/pathology MH - Hypoglycemic Agents/therapeutic use MH - Fatty Liver/drug therapy MH - Adult MH - Magnetic Resonance Imaging MH - Elasticity Imaging Techniques MH - Glycated Hemoglobin/drug effects/analysis MH - Aged MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC11155541 COIS- The authors have no funding and conflicts of interest to disclose. EDAT- 2024/06/07 12:54 MHDA- 2024/06/07 12:55 PMCR- 2024/06/07 CRDT- 2024/06/07 10:14 PHST- 2024/06/07 12:55 [medline] PHST- 2024/06/07 12:54 [pubmed] PHST- 2024/06/07 10:14 [entrez] PHST- 2024/06/07 00:00 [pmc-release] AID - 00005792-202406070-00072 [pii] AID - MD-D-24-00797 [pii] AID - 10.1097/MD.0000000000038444 [doi] PST - ppublish SO - Medicine (Baltimore). 2024 Jun 7;103(23):e38444. doi: 10.1097/MD.0000000000038444. PMID- 38838981 OWN - NLM STAT- MEDLINE DCOM- 20240920 LR - 20260409 IS - 1532-8414 (Electronic) IS - 1071-9164 (Linking) VI - 30 IP - 9 DP - 2024 Sep TI - Does Semaglutide Reduce Kidney Disease Events on Top of SGLT2 Inhibitors in Patients with CKD and T2D? PG - 1181-1182 LID - S1071-9164(24)00194-5 [pii] LID - 10.1016/j.cardfail.2024.05.006 [doi] FAU - Ferreira, Joao Pedro AU - Ferreira JP AD - Faculty of Medicine of the University of Porto, Porto, Portugal. Electronic address: jpferreira@med.up.pt. FAU - Mendonca, Luis AU - Mendonca L AD - Faculty of Medicine of the University of Porto, Porto, Portugal. FAU - Neves, Joao Sergio AU - Neves JS AD - Faculty of Medicine of the University of Porto, Porto, Portugal. LA - eng PT - Journal Article DEP - 20240604 PL - United States TA - J Card Fail JT - Journal of cardiac failure JID - 9442138 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Renal Insufficiency, Chronic/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Semaglutide OTO - NOTNLM OT - Semaglutide, SGLT2 inhibitor, type 2 diabetes OT - chronic kidney disease EDAT- 2024/06/06 01:14 MHDA- 2024/09/20 11:30 CRDT- 2024/06/05 19:26 PHST- 2024/05/27 00:00 [received] PHST- 2024/05/31 00:00 [revised] PHST- 2024/05/31 00:00 [accepted] PHST- 2024/09/20 11:30 [medline] PHST- 2024/06/06 01:14 [pubmed] PHST- 2024/06/05 19:26 [entrez] AID - S1071-9164(24)00194-5 [pii] AID - 10.1016/j.cardfail.2024.05.006 [doi] PST - ppublish SO - J Card Fail. 2024 Sep;30(9):1181-1182. doi: 10.1016/j.cardfail.2024.05.006. Epub 2024 Jun 4. PMID- 38825012 OWN - NLM STAT- MEDLINE DCOM- 20240728 LR - 20260527 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 179 DP - 2024 Sep TI - NPYR modulation: Potential for the next major advance in obesity and type 2 diabetes management? PG - 171256 LID - S0196-9781(24)00109-8 [pii] LID - 10.1016/j.peptides.2024.171256 [doi] AB - The approval of the glucagon-like peptide 1 (GLP-1) mimetics semaglutide and liraglutide for management of obesity, independent of type 2 diabetes (T2DM), has initiated a resurgence of interest in gut-hormone derived peptide therapies for the management of metabolic diseases, but side-effect profile is a concern for these medicines. However, the recent approval of tirzepatide for obesity and T2DM, a glucose-dependent insulinotropic polypeptide (GIP), GLP-1 receptor co-agonist peptide therapy, may provide a somewhat more tolerable option. Despite this, an increasing number of non-incretin alternative peptides are in development for obesity, and it stands to reason that other hormones will take to the limelight in the coming years, such as peptides from the neuropeptide Y family. This narrative review outlines the therapeutic promise of the neuropeptide Y family of peptides, comprising of the 36 amino acid polypeptides neuropeptide Y (NPY), peptide tyrosine-tyrosine (PYY) and pancreatic polypeptide (PP), as well as their derivatives. This family of peptides exerts a number of metabolically relevant effects such as appetite regulation and can influence pancreatic beta-cell survival. Although some of these actions still require full translation to the human setting, potential therapeutic application in obesity and type 2 diabetes is conceivable. However, like GLP-1 and GIP, the endogenous NPY, PYY and PP peptide forms are subject to rapid in vivo degradation and inactivation by the serine peptidase, dipeptidyl-peptidase 4 (DPP-4), and hence require structural modification to prolong circulating half-life. Numerous protective modification strategies are discussed in this regard herein, alongside related impact on biological activity profile and therapeutic promise. CI - Crown Copyright (c) 2024. Published by Elsevier Inc. All rights reserved. FAU - Lafferty, Ryan A AU - Lafferty RA AD - Diabetes Research Centre, Ulster University, Coleraine, Northern Ireland BT52 1SA, UK. Electronic address: r.lafferty@ulster.ac.uk. FAU - Flatt, Peter R AU - Flatt PR AD - Diabetes Research Centre, Ulster University, Coleraine, Northern Ireland BT52 1SA, UK. FAU - Irwin, Nigel AU - Irwin N AD - Diabetes Research Centre, Ulster University, Coleraine, Northern Ireland BT52 1SA, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240531 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Neuropeptide Y) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 59763-91-6 (Pancreatic Polypeptide) RN - 106388-42-5 (Peptide YY) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - *Obesity/drug therapy/metabolism MH - *Neuropeptide Y/metabolism MH - Animals MH - Glucagon-Like Peptides/therapeutic use MH - Liraglutide/therapeutic use/pharmacology MH - Pancreatic Polypeptide/metabolism MH - Peptide YY/metabolism/therapeutic use MH - Gastric Inhibitory Polypeptide/therapeutic use/metabolism MH - Glucagon-Like Peptide 1/metabolism/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptide-2 Receptor MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Diabetes OT - Obesity OT - Pancreatic polypeptide (PP) OT - Peptide YY (PYY) COIS- Declaration of Competing Interest PRF and NI are named on patents filed by Ulster University for the exploitation of peptide-based therapeutics for metabolic disease. All authors are shareholders in Dia Beta Labs Ltd., an Ulster University spinout developing peptide therapeutics for the management of metabolic disease. EDAT- 2024/06/03 00:42 MHDA- 2024/07/28 14:51 CRDT- 2024/06/02 19:13 PHST- 2024/03/15 00:00 [received] PHST- 2024/05/13 00:00 [revised] PHST- 2024/05/30 00:00 [accepted] PHST- 2024/07/28 14:51 [medline] PHST- 2024/06/03 00:42 [pubmed] PHST- 2024/06/02 19:13 [entrez] AID - S0196-9781(24)00109-8 [pii] AID - 10.1016/j.peptides.2024.171256 [doi] PST - ppublish SO - Peptides. 2024 Sep;179:171256. doi: 10.1016/j.peptides.2024.171256. Epub 2024 May 31. PMID- 38821845 OWN - NLM STAT- MEDLINE DCOM- 20240717 LR - 20250228 IS - 1532-8171 (Electronic) IS - 0735-6757 (Linking) VI - 82 DP - 2024 Aug TI - Implications of GLP-1 agonist use on airway management. PG - 190-191 LID - S0735-6757(24)00249-3 [pii] LID - 10.1016/j.ajem.2024.05.018 [doi] FAU - Mizubuti, Glenio B AU - Mizubuti GB AD - Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston General Hospital, 76 Stuart Street, Kingston, Ontario K7L 2V7, Canada. Electronic address: Gleniomizubuti@hotmail.com. FAU - Ho, Anthony M-H AU - Ho AM AD - Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston General Hospital, 76 Stuart Street, Kingston, Ontario K7L 2V7, Canada. FAU - da Silva, Leopoldo Muniz AU - da Silva LM AD - Department of Anesthesiology, Sao Luiz Hospital, Itaim / Rede D'Or - CMA Anesthesia Team, Sao Paulo, Brazil. LA - eng PT - Comment PT - Letter DEP - 20240524 PL - United States TA - Am J Emerg Med JT - The American journal of emergency medicine JID - 8309942 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) SB - IM CON - Am J Emerg Med. 2024 Apr;78:89-94. doi: 10.1016/j.ajem.2024.01.010. PMID: 38241775 MH - Humans MH - *Airway Management/methods MH - Glucagon-Like Peptide 1/agonists MH - Hypoglycemic Agents/therapeutic use MH - Male MH - Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Intubation, Intratracheal OTO - NOTNLM OT - Bronchoaspiration OT - Complications OT - GLP-1 agonists OT - Glucagon-like peptide-1 agonists OT - Pulmonary aspiration OT - Semaglutide COIS- Declaration of competing interest The authors declare no competing interests. EDAT- 2024/06/01 10:50 MHDA- 2024/07/18 00:42 CRDT- 2024/05/31 21:57 PHST- 2024/04/16 00:00 [received] PHST- 2024/05/24 00:00 [accepted] PHST- 2024/07/18 00:42 [medline] PHST- 2024/06/01 10:50 [pubmed] PHST- 2024/05/31 21:57 [entrez] AID - S0735-6757(24)00249-3 [pii] AID - 10.1016/j.ajem.2024.05.018 [doi] PST - ppublish SO - Am J Emerg Med. 2024 Aug;82:190-191. doi: 10.1016/j.ajem.2024.05.018. Epub 2024 May 24. PMID- 38813830 OWN - NLM STAT- MEDLINE DCOM- 20240530 LR - 20250103 IS - 1365-2036 (Electronic) IS - 0269-2813 (Linking) VI - 59 Suppl 1 DP - 2024 Jun TI - Role of lifestyle and glucagon-like peptide-1 receptor agonists for weight loss in obesity, type 2 diabetes and steatotic liver diseases. PG - S52-S75 LID - 10.1111/apt.17848 [doi] AB - BACKGROUND: The current obesity pandemic has given rise to associated comorbidities and complications, including type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). During the last decade, certain glucagon-like peptide 1 receptor agonists (GLP-1RA), originally developed as antihyperglycemic drugs, also demonstrated efficacy for weight loss. AIMS: To review shared pathophysiologic features of common metabolic diseases and compare therapeutic strategies to reduce body weight and related complications. METHODS: We performed an extensive literature research to describe the effects of lifestyle modification, first-generation anti-obesity drugs, and GLP-1RA on weight loss in humans with obesity, type 2 diabetes and MASLD. RESULTS: Until recently, treatment of obesity has been limited to lifestyle modification, which offer moderate degree and sustainability of weight loss. The few approved first-generation anti-obesity drugs are either limited to short term use or to certain forms of obesity. Some GLP-1RA significantly decrease caloric intake and body weight. Liraglutide and semaglutide have therefore been approved for treating people with obesity. They also lead to a reduction of hepatic fat content and inflammation in people with biopsy-confirmed MASLD. Possible limitations comprise adverse effects, treatment adherence and persistence. CONCLUSION: Certain GLP-1RA are superior to lifestyle modification and first-generation anti-obesity drugs in inducing weight loss. They have therefore markedly changed the portfolio of obesity treatment with additional beneficial effects on steatotic liver disease. CI - (c) 2024 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. FAU - Giannakogeorgou, Anna AU - Giannakogeorgou A AUID- ORCID: 0009-0009-7817-803X AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany. AD - German Center for Diabetes Research (DZD e.V.), Partner Dusseldorf, Neuherberg, Germany. FAU - Roden, Michael AU - Roden M AUID- ORCID: 0000-0001-8200-6382 AD - Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University, Dusseldorf, Germany. AD - German Center for Diabetes Research (DZD e.V.), Partner Dusseldorf, Neuherberg, Germany. AD - Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Dusseldorf, Heinrich Heine University Dusseldorf, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Obesity/drug therapy/complications MH - *Weight Loss/drug effects MH - *Life Style MH - *Fatty Liver/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Anti-Obesity Agents/therapeutic use MH - Liraglutide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2024/05/30 12:43 MHDA- 2024/05/30 12:44 CRDT- 2024/05/30 06:23 PHST- 2023/11/08 00:00 [revised] PHST- 2023/10/21 00:00 [received] PHST- 2023/12/15 00:00 [accepted] PHST- 2024/05/30 12:44 [medline] PHST- 2024/05/30 12:43 [pubmed] PHST- 2024/05/30 06:23 [entrez] AID - 10.1111/apt.17848 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2024 Jun;59 Suppl 1:S52-S75. doi: 10.1111/apt.17848. PMID- 38808476 OWN - NLM STAT- MEDLINE DCOM- 20240709 LR - 20260617 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 8 DP - 2024 Aug TI - A phase 1, randomized, double-blind, placebo-controlled trial investigating the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide in healthy Chinese subjects. PG - 3068-3077 LID - 10.1111/dom.15624 [doi] AB - AIM: The trial (NCT04016974) investigated the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide, the first orally administered glucagon-like peptide-1 analogue for type 2 diabetes, in healthy Chinese subjects. MATERIALS AND METHODS: This single-centre, multiple-dose, placebo-controlled trial randomized 32 healthy Chinese adults to once-daily oral semaglutide (3 mg escalating to 14 mg) or placebo for 12 weeks. Blood samples were collected regularly during treatment and follow-up. The primary endpoint was the area under the semaglutide concentration-time curve over a dosing interval (0-24 h) at steady state (AUC(0-24h,sema,SS)). Secondary pharmacokinetic endpoints included the maximum observed semaglutide plasma concentration at steady state (C(max,sema,SS)). Supportive secondary pharmacodynamics endpoints included changes in body weight and fasting plasma glucose. RESULTS: Treatment with all oral semaglutide doses showed dose-dependent increases in semaglutide exposure in healthy Chinese subjects at steady state, determined by AUC(0-24h,sema,SS) (233, 552 and 1288 h.nmol/L for 3, 7 and 14 mg of oral semaglutide, respectively) and C(max,sema,SS). Oral semaglutide treatment was associated with significant reductions in body weight (p = .0001) and fasting plasma glucose (p = .0011) versus placebo at the end of treatment. The safety and tolerability of oral semaglutide were consistent with the known profile of glucagon-like peptide-1 receptor agonists, with no severe or blood-glucose-confirmed symptomatic hypoglycaemic events, serious adverse events or deaths. The most frequent adverse events were gastrointestinal disorders. CONCLUSIONS: At steady state, oral semaglutide exposure was dose dependent and close to dose proportionality in healthy Chinese subjects. This is consistent with previous clinical pharmacology results for oral semaglutide. CI - (c) 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Xie, Panpan AU - Xie P AUID- ORCID: 0000-0001-6702-059X AD - Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. FAU - Abildlund, Morten T AU - Abildlund MT AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Baekdal, Tine A AU - Baekdal TA AUID- ORCID: 0000-0002-1348-0352 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - He, Xuemei AU - He X AD - Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. FAU - Lyauk, Yassine K AU - Lyauk YK AUID- ORCID: 0000-0003-1349-2801 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Patted, Usha Rani H AU - Patted URH AUID- ORCID: 0000-0002-4815-3300 AD - Novo Nordisk Service Centre India Private Ltd, Bangalore, India. FAU - Ning, Zu AU - Ning Z AUID- ORCID: 0000-0003-4208-1630 AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd, Beijing, China. FAU - Shi, Aixin AU - Shi A AUID- ORCID: 0000-0002-9106-7643 AD - Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China. LA - eng SI - ClinicalTrials.gov/NCT04016974 SI - ClinicalTrials.gov/NCT04016974 GR - Novo Nordisk A/S/ PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240529 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/pharmacokinetics/administration & dosage/adverse effects/pharmacology MH - Male MH - Double-Blind Method MH - Adult MH - Female MH - *Hypoglycemic Agents/pharmacokinetics/administration & dosage/adverse effects/pharmacology MH - Administration, Oral MH - *Blood Glucose/drug effects MH - China MH - Young Adult MH - Dose-Response Relationship, Drug MH - Healthy Volunteers MH - Middle Aged MH - Diabetes Mellitus, Type 2/drug therapy/blood MH - Area Under Curve MH - Body Weight/drug effects MH - East Asian People MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide-1 analogue OT - pharmacodynamics OT - pharmacokinetics OT - population study OT - randomized trial OT - semaglutide EDAT- 2024/05/29 06:42 MHDA- 2024/07/09 12:43 CRDT- 2024/05/29 04:33 PHST- 2024/04/10 00:00 [revised] PHST- 2023/12/18 00:00 [received] PHST- 2024/04/10 00:00 [accepted] PHST- 2024/07/09 12:43 [medline] PHST- 2024/05/29 06:42 [pubmed] PHST- 2024/05/29 04:33 [entrez] AID - 10.1111/dom.15624 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Aug;26(8):3068-3077. doi: 10.1111/dom.15624. Epub 2024 May 29. PMID- 38807009 OWN - NLM STAT- MEDLINE DCOM- 20240725 LR - 20260413 IS - 1496-8975 (Electronic) IS - 0832-610X (Linking) VI - 71 IP - 8 DP - 2024 Aug TI - A call to update anesthetic protocols: the hidden risks of semaglutide. PG - 1175-1176 LID - 10.1007/s12630-024-02774-6 [doi] FAU - Santos, Leonardo B AU - Santos LB AUID- ORCID: 0000-0002-3052-5452 AD - Department of Anesthesiology, Rede D'Or Villa Lobos Hospital-CMA Anesthesia Team, Sao Paulo, SP, Brazil. bs.leonardo@usp.br. FAU - Nersessian, Rafael S F AU - Nersessian RSF AD - Department of Anesthesiology, Rede D'Or Villa Lobos Hospital-CMA Anesthesia Team, Sao Paulo, SP, Brazil. FAU - Silveira, Saullo Q AU - Silveira SQ AD - Department of Anesthesiology, Rede D'Or Villa Lobos Hospital-CMA Anesthesia Team, Sao Paulo, SP, Brazil. FAU - Silva, Leopoldo M AU - Silva LM AD - Department of Anesthesiology, Rede D'Or Villa Lobos Hospital-CMA Anesthesia Team, Sao Paulo, SP, Brazil. FAU - Matheus, Giulia D AU - Matheus GD AD - Department of Medicine, Nove de Julho University, Sao Paulo, SP, Brazil. FAU - Buniotti, Bianca P AU - Buniotti BP AD - Department of Anesthesiology, Rede D'Or Villa Lobos Hospital-CMA Anesthesia Team, Sao Paulo, SP, Brazil. FAU - Vieira, Joaquim E AU - Vieira JE AD - Department of Anesthesiology, Faculty of Medicine, Sao Paulo University (FMUSP), Sao Paulo, SP, Brazil. FAU - Mizubuti, Glenio B AU - Mizubuti GB AD - Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, ON, Canada. LA - eng PT - Letter DEP - 20240528 PL - United States TA - Can J Anaesth JT - Canadian journal of anaesthesia = Journal canadien d'anesthesie JID - 8701709 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/administration & dosage MH - *Hypoglycemic Agents/adverse effects MH - Anesthesia/adverse effects/methods MH - Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - patient safety OT - respiratory aspiration OT - semaglutide EDAT- 2024/05/29 00:49 MHDA- 2024/07/26 12:39 CRDT- 2024/05/28 23:44 PHST- 2024/03/25 00:00 [received] PHST- 2024/05/01 00:00 [accepted] PHST- 2024/04/21 00:00 [revised] PHST- 2024/07/26 12:39 [medline] PHST- 2024/05/29 00:49 [pubmed] PHST- 2024/05/28 23:44 [entrez] AID - 10.1007/s12630-024-02774-6 [pii] AID - 10.1007/s12630-024-02774-6 [doi] PST - ppublish SO - Can J Anaesth. 2024 Aug;71(8):1175-1176. doi: 10.1007/s12630-024-02774-6. Epub 2024 May 28. PMID- 38806481 OWN - NLM STAT- MEDLINE DCOM- 20240528 LR - 20260127 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 15 IP - 1 DP - 2024 May 28 TI - Associations of semaglutide with incidence and recurrence of alcohol use disorder in real-world population. PG - 4548 LID - 10.1038/s41467-024-48780-6 [doi] LID - 4548 AB - Alcohol use disorders are among the top causes of the global burden of disease, yet therapeutic interventions are limited. Reduced desire to drink in patients treated with semaglutide has raised interest regarding its potential therapeutic benefits for alcohol use disorders. In this retrospective cohort study of electronic health records of 83,825 patients with obesity, we show that semaglutide compared with other anti-obesity medications is associated with a 50%-56% lower risk for both the incidence and recurrence of alcohol use disorder for a 12-month follow-up period. Consistent reductions were seen for patients stratified by gender, age group, race and in patients with and without type 2 diabetes. Similar findings are replicated in the study population with 598,803 patients with type 2 diabetes. These findings provide evidence of the potential benefit of semaglutide in AUD in real-world populations and call for further randomized clinicl trials. CI - (c) 2024. The Author(s). FAU - Wang, William AU - Wang W AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Volkow, Nora D AU - Volkow ND AUID- ORCID: 0000-0001-6668-0908 AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. nvolkow@nida.nih.gov. FAU - Berger, Nathan A AU - Berger NA AUID- ORCID: 0000-0001-7086-9885 AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Davis, Pamela B AU - Davis PB AUID- ORCID: 0000-0002-7113-5338 AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Kaelber, David C AU - Kaelber DC AUID- ORCID: 0000-0001-7855-9515 AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, OH, USA. FAU - Xu, Rong AU - Xu R AUID- ORCID: 0000-0003-3127-4795 AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA. rxx@case.edu. LA - eng GR - R01 AG057557/AG/NIA NIH HHS/United States GR - CA221718, CA043703, CA2332216/U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ GR - R01 AG076649/AG/NIA NIH HHS/United States GR - R01 AA029831/AA/NIAAA NIH HHS/United States GR - DP2 HD084068/HD/NICHD NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States GR - RF1 AG076649/AG/NIA NIH HHS/United States GR - AA029831/U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA)/ GR - R25 CA221718/CA/NCI NIH HHS/United States GR - P30 CA043703/CA/NCI NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20240528 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Nat Commun. 2024 Jun 18;15(1):5177. doi: 10.1038/s41467-024-49655-6. PMID: 38890337 MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - Male MH - Female MH - Middle Aged MH - Retrospective Studies MH - Incidence MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Adult MH - *Recurrence MH - *Obesity/drug therapy/epidemiology MH - Aged MH - Alcoholism/epidemiology/drug therapy MH - Anti-Obesity Agents/therapeutic use MH - Semaglutide PMC - PMC11133479 COIS- The authors declare no competing interests. EDAT- 2024/05/29 00:49 MHDA- 2024/05/29 00:50 PMCR- 2024/05/28 CRDT- 2024/05/28 23:16 PHST- 2023/11/08 00:00 [received] PHST- 2024/05/08 00:00 [accepted] PHST- 2024/05/29 00:50 [medline] PHST- 2024/05/29 00:49 [pubmed] PHST- 2024/05/28 23:16 [entrez] PHST- 2024/05/28 00:00 [pmc-release] AID - 10.1038/s41467-024-48780-6 [pii] AID - 48780 [pii] AID - 10.1038/s41467-024-48780-6 [doi] PST - epublish SO - Nat Commun. 2024 May 28;15(1):4548. doi: 10.1038/s41467-024-48780-6. PMID- 38801960 OWN - NLM STAT- MEDLINE DCOM- 20240614 LR - 20250103 IS - 1879-0720 (Electronic) IS - 0928-0987 (Linking) VI - 199 DP - 2024 Aug 1 TI - Discovery of novel glucagon-like peptide 1/cholecystokinin 1 receptor dual agonists. PG - 106818 LID - S0928-0987(24)00130-1 [pii] LID - 10.1016/j.ejps.2024.106818 [doi] AB - The combined use of gastrointestinal hormones for treating metabolic diseases is gaining increasing attention. The potential of developing novel dual agonists targeting both cholecystokinin 1 (CCK-1) receptor and glucagon-like peptide 1 (GLP-1) receptor to improve the treatment of type 2 diabetes and obesity have not been fully explored. In this investigation, we reported a series of novel GLP-1/CCK-1 receptor co-agonists constructed by linking the C-terminus of a GLP-1 receptor agonist (bullfrog GLP-1) to the N-terminus of a CCK-1 receptor selective agonist NN9056. In comprehensive in vitro assays, these co-agonists exhibited complete agonistic potency on GLP-1 and CCK-1 receptor. Remarkably, 1f displayed superior hypoglycemic and insulinotropic effects when compared to NN9056 and semaglutide. Evaluation in Kunming and diet-induced obesity (DIO) mice unveiled significant acute and enduring hypoglycemic effects of 1f. Administration of 1f to DIO mice resulted in substantial weight loss, normalized lipid metabolism, and enhanced glucose regulation. These preclinical observations strongly advocate for the therapeutic potential CCK-1 and GLP-1 pathways could be harnessed in a single fusion peptide, yielding a promising combination therapy strategy for treating metabolic disorders. CI - Copyright (c) 2024 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Chenxu, Zhou AU - Chenxu Z AD - College of Medicine, Jiaxing University, Jiaxing 314001, PR China. FAU - Lidan, Sun AU - Lidan S AD - College of Medicine, Jiaxing University, Jiaxing 314001, PR China; Taizhou Hospital, Zhejiang University, Taigzhou 317000, PR China. Electronic address: slidan89@zjxu.edu.cn. FAU - Guoqiang, Hu AU - Guoqiang H AD - Taizhou Hospital, Zhejiang University, Taigzhou 317000, PR China. FAU - Binbin, Gong AU - Binbin G AD - College of Medicine, Jiaxing University, Jiaxing 314001, PR China; College of Pharmacy, Zhejiang University of Technology, Hangzhou 310000, PR China. FAU - Ting, Wang AU - Ting W AD - College of Medicine, Jiaxing University, Jiaxing 314001, PR China; College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, PR China. FAU - Xiaoyi, Sun AU - Xiaoyi S AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Qian, Long AU - Qian L AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. LA - eng PT - Journal Article DEP - 20240526 PL - Netherlands TA - Eur J Pharm Sci JT - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JID - 9317982 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - *Obesity/drug therapy/metabolism MH - Male MH - *Glucagon-Like Peptide 1/agonists MH - Mice MH - *Hypoglycemic Agents/pharmacology/therapeutic use/chemistry MH - Humans MH - Blood Glucose/drug effects MH - Cricetulus MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cholecystokinin OT - Diabetes OT - Glucagon-like peptide-1 OT - Obesity COIS- Declaration of competing interest Authors have no conflict of interest concerning this study and have nothing to declare. EDAT- 2024/05/28 00:43 MHDA- 2024/06/15 10:44 CRDT- 2024/05/27 19:28 PHST- 2024/03/17 00:00 [received] PHST- 2024/05/05 00:00 [revised] PHST- 2024/05/25 00:00 [accepted] PHST- 2024/06/15 10:44 [medline] PHST- 2024/05/28 00:43 [pubmed] PHST- 2024/05/27 19:28 [entrez] AID - S0928-0987(24)00130-1 [pii] AID - 10.1016/j.ejps.2024.106818 [doi] PST - ppublish SO - Eur J Pharm Sci. 2024 Aug 1;199:106818. doi: 10.1016/j.ejps.2024.106818. Epub 2024 May 26. PMID- 38801466 OWN - NLM STAT- MEDLINE DCOM- 20241112 LR - 20260713 IS - 1573-7233 (Electronic) IS - 0167-7659 (Print) IS - 0167-7659 (Linking) VI - 43 IP - 4 DP - 2024 Dec TI - The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer. PG - 1297-1314 LID - 10.1007/s10555-024-10192-9 [doi] AB - Glucagon-like peptide-1 receptor (GLP-1R) agonists have garnered significant attention for their therapeutic potential in addressing the interconnected health challenges of diabetes, obesity, and cancer. The role of GLP-1R in type 2 diabetes mellitus (T2DM) is highlighted, emphasizing its pivotal contribution to glucose homeostasis, promoting beta-cell proliferation, and facilitating insulin release. GLP-1R agonists have effectively managed obesity by reducing hunger, moderating food intake, and regulating body weight. Beyond diabetes and obesity, GLP-1R agonists exhibit a multifaceted impact on cancer progression across various malignancies. The mechanisms underlying these effects involve the modulation of signaling pathways associated with cell growth, survival, and metabolism. However, the current literature reveals a lack of in vivo studies on specific GLP-1R agonists such as semaglutide, necessitating further research to elucidate its precise mechanisms and effects, particularly in cancer. While other GLP-1R agonists have shown promising outcomes in mitigating cancer progression, the association between some GLP-1R agonists and an increased risk of cancer remains a topic requiring more profound investigation. This calls for more extensive research to unravel the intricate relationships between the GLP-1R agonist and different cancers, providing valuable insights for clinicians and researchers alike. CI - (c) 2024. The Author(s). FAU - Ibrahim, Shahad Sabaawi AU - Ibrahim SS AD - Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, 24144, Qatar. FAU - Ibrahim, Raghad Sabaawi AU - Ibrahim RS AD - Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, 24144, Qatar. FAU - Arabi, Batoul AU - Arabi B AD - Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, 24144, Qatar. FAU - Brockmueller, Aranka AU - Brockmueller A AD - Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Pettenkoferstr. 11, D-80336, Munich, Germany. FAU - Shakibaei, Mehdi AU - Shakibaei M AD - Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, LMU Munich, Pettenkoferstr. 11, D-80336, Munich, Germany. FAU - Busselberg, Dietrich AU - Busselberg D AD - Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, 24144, Qatar. dib2015@qatar-med.cornell.edu. LA - eng GR - NPRP 14S-0311-210033/Qatar National Research Fund/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240527 PL - Netherlands TA - Cancer Metastasis Rev JT - Cancer metastasis reviews JID - 8605731 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Obesity/drug therapy/metabolism MH - *Neoplasms/drug therapy/pathology/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Animals MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11554930 OTO - NOTNLM OT - Cancer OT - Diabetes OT - GLP1RA OT - Obesity OT - Ozempic OT - Semaglutide COIS- Declarations Ethical approval and consent to participate Not applicable. Conflict of interest The authors declare no competing interests. EDAT- 2024/05/27 12:43 MHDA- 2024/11/13 14:00 PMCR- 2024/05/27 CRDT- 2024/05/27 11:06 PHST- 2024/01/01 00:00 [received] PHST- 2024/05/21 00:00 [accepted] PHST- 2024/11/13 14:00 [medline] PHST- 2024/05/27 12:43 [pubmed] PHST- 2024/05/27 11:06 [entrez] PHST- 2024/05/27 00:00 [pmc-release] AID - 10.1007/s10555-024-10192-9 [pii] AID - 10192 [pii] AID - 10.1007/s10555-024-10192-9 [doi] PST - ppublish SO - Cancer Metastasis Rev. 2024 Dec;43(4):1297-1314. doi: 10.1007/s10555-024-10192-9. Epub 2024 May 27. PMID- 38798184 OWN - NLM STAT- MEDLINE DCOM- 20240726 LR - 20241218 IS - 2042-8189 (Electronic) IS - 1478-2715 (Linking) VI - 54 IP - 2 DP - 2024 Jun TI - Newer treatments for diabetes mellitus: A caveat with rapid glycaemic improvement and caution regarding changes in retinopathy screening guidelines within the UK NHS programme. PG - 178-179 LID - 10.1177/14782715241257970 [doi] FAU - Varadhan, Lakshminarayanan AU - Varadhan L AUID- ORCID: 0000-0003-1976-8071 AD - Diabetes Department, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke on Trent, UK. FAU - Jose, Merin AU - Jose M AD - Diabetes Department, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke on Trent, UK. AD - King's College, London, UK. FAU - Humphreys, Tracy AU - Humphreys T AD - Opthalmology Department, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke on Trent, UK. FAU - Brown, Andrew AU - Brown A AD - Opthalmology Department, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke on Trent, UK. LA - eng PT - Comment PT - Letter DEP - 20240527 PL - England TA - J R Coll Physicians Edinb JT - The journal of the Royal College of Physicians of Edinburgh JID - 101144324 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) SB - IM CON - J R Coll Physicians Edinb. 2024 Jun;54(2):170-173. doi: 10.1177/14782715241244843. PMID: 38578067 MH - Humans MH - *Diabetic Retinopathy/diagnosis MH - United Kingdom MH - *Practice Guidelines as Topic MH - *Mass Screening/methods/standards MH - *State Medicine MH - Blood Glucose/analysis MH - Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Diabetes Mellitus/drug therapy/diagnosis OTO - NOTNLM OT - GLP-1 receptor agonists OT - diabetic retinopathy OT - glycaemic control OT - semaglutide OT - worsening COIS- Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2024/05/27 06:43 MHDA- 2024/07/26 12:48 CRDT- 2024/05/27 03:33 PHST- 2024/07/26 12:48 [medline] PHST- 2024/05/27 06:43 [pubmed] PHST- 2024/05/27 03:33 [entrez] AID - 10.1177/14782715241257970 [doi] PST - ppublish SO - J R Coll Physicians Edinb. 2024 Jun;54(2):178-179. doi: 10.1177/14782715241257970. Epub 2024 May 27. PMID- 38796654 OWN - NLM STAT- MEDLINE DCOM- 20240719 LR - 20261010 IS - 1546-170X (Electronic) IS - 1078-8956 (Linking) VI - 30 IP - 7 DP - 2024 Jul TI - What the SELECT trial of semaglutide means for clinicians. PG - 1830-1831 LID - 10.1038/s41591-024-03013-7 [doi] FAU - Sattar, Naveed AU - Sattar N AUID- ORCID: 0000-0002-1604-2593 AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. naveed.sattar@glasgow.ac.uk. FAU - Lee, Matthew M Y AU - Lee MMY AUID- ORCID: 0000-0001-9213-2067 AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - McGuire, Darren K AU - McGuire DK AD - Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Health, Dallas, TX, USA. LA - eng PT - Comment PT - News PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - Nat Med. 2024 Jul;30(7):2049-2057. doi: 10.1038/s41591-024-02996-7. PMID: 38740993 CON - Nat Med. 2024 Jul;30(7):2058-2066. doi: 10.1038/s41591-024-03015-5. PMID: 38796653 MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Clinical Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2024/05/26 18:11 MHDA- 2024/07/20 10:43 CRDT- 2024/05/25 23:31 PHST- 2024/07/20 10:43 [medline] PHST- 2024/05/26 18:11 [pubmed] PHST- 2024/05/25 23:31 [entrez] AID - 10.1038/s41591-024-03013-7 [pii] AID - 10.1038/s41591-024-03013-7 [doi] PST - ppublish SO - Nat Med. 2024 Jul;30(7):1830-1831. doi: 10.1038/s41591-024-03013-7. PMID- 38795393 OWN - NLM STAT- MEDLINE DCOM- 20241117 LR - 20260630 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 109 IP - 12 DP - 2024 Nov 18 TI - Effects of Tirzepatide vs Semaglutide on beta-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test. PG - 3046-3054 LID - 10.1210/clinem/dgae319 [doi] AB - CONTEXT: In a clinical study, tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA), provided superior glycemic control vs the GLP-1RA semaglutide. The physiologic mechanisms are incompletely understood. OBJECTIVE: This work aimed to evaluate treatment effects by model-based analyses of mixed-meal tolerance test (MMTT) data. METHODS: A 28-week double-blind, randomized, placebo-controlled trial of patients with type 2 diabetes treated with metformin was conducted at 2 clinical research centers in Germany. Interventions included tirzepatide 15 mg, semaglutide 1 mg, and placebo. Main outcome measures included glycemic control, model-derived beta-cell function indices including insulin secretion rate (ISR) at 7.2-mmol/L glucose (ISR7.2), beta-cell glucose sensitivity (beta-CGS), insulin sensitivity, and estimated hepatic insulin-to-glucagon ratio. RESULTS: Tirzepatide significantly reduced fasting glucose and MMTT total glucose area under the curve (AUC) vs semaglutide (P < .01). Incremental glucose AUC did not differ significantly between treatments; therefore, greater total glucose AUC reduction with tirzepatide was mainly attributable to greater suppression of fasting glucose. A greater reduction in total ISR AUC was achieved with tirzepatide vs semaglutide (P < .01), in the context of greater improvement in insulin sensitivity with tirzepatide (P < .01). ISR7.2 was significantly increased with tirzepatide vs semaglutide (P < .05), showing improved beta-CGS. MMTT-derived beta-CGS was increased but not significantly different between treatments. Both treatments reduced fasting glucagon and total glucagon AUC, with glucagon AUC significantly reduced with tirzepatide vs semaglutide (P < .01). The estimated hepatic insulin-to-glucagon ratio did not change substantially with either treatment. CONCLUSION: These results suggest that the greater glycemic control observed for tirzepatide manifests as improved fasting glucose and glucose excursion control, due to improvements in ISR, insulin sensitivity, and glucagon suppression. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. See the journal About page for additional terms. FAU - Mather, Kieren J AU - Mather KJ AUID- ORCID: 0000-0001-8696-7500 AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Mari, Andrea AU - Mari A AUID- ORCID: 0000-0002-1436-5591 AD - Institute of Neuroscience, National Research Council, 2-35122 Padua, Italy. FAU - Heise, Tim AU - Heise T AD - Profil Institute for Metabolic Research, 41460 Neuss, Germany. FAU - DeVries, J Hans AU - DeVries JH AUID- ORCID: 0000-0001-9196-9906 AD - Profil Institute for Metabolic Research, 41460 Neuss, Germany. FAU - Hua, Ming AU - Hua M AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Urva, Shweta AU - Urva S AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Coskun, Tamer AU - Coskun T AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Haupt, Axel AU - Haupt A AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Heine, Robert J AU - Heine RJ AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Pratt, Edward AU - Pratt E AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Thomas, Melissa K AU - Thomas MK AUID- ORCID: 0000-0001-9848-2834 AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Milicevic, Zvonko AU - Milicevic Z AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Insulin-Secreting Cells/drug effects/metabolism MH - *Glucagon-Like Peptides/pharmacology MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism MH - Middle Aged MH - Female MH - *Insulin Resistance MH - Double-Blind Method MH - *Blood Glucose/drug effects/metabolism MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Aged MH - Glycemic Control/methods MH - Insulin MH - Meals MH - Adult MH - Metformin/pharmacology MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide MH - Semaglutide OTO - NOTNLM OT - glucagon OT - glucose control OT - insulin sensitivity OT - meal tolerance test OT - tirzepatide OT - beta-cell function EDAT- 2024/05/25 20:50 MHDA- 2024/11/18 00:31 CRDT- 2024/05/25 16:03 PHST- 2024/01/24 00:00 [received] PHST- 2024/11/18 00:31 [medline] PHST- 2024/05/25 20:50 [pubmed] PHST- 2024/05/25 16:03 [entrez] AID - 7682337 [pii] AID - 10.1210/clinem/dgae319 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2024 Nov 18;109(12):3046-3054. doi: 10.1210/clinem/dgae319. PMID- 38795152 OWN - NLM STAT- MEDLINE DCOM- 20240525 LR - 20250103 IS - 1432-069X (Electronic) IS - 0340-3696 (Linking) VI - 316 IP - 6 DP - 2024 May 25 TI - Rare cutaneous adverse reactions associated with GLP-1 agonists: a review of the published literature. PG - 248 LID - 10.1007/s00403-024-02969-3 [doi] AB - Glucagon-like-peptide-1 (GLP-1) agonists are an emerging class of medications used to manage type 2 diabetes mellitus (T2DM) and weight loss, with demonstrated efficacy in reducing hemoglobin A1c levels, body mass index, and adverse cardiovascular events. While previous studies have reviewed notable cutaneous adverse effects with other antidiabetic medications, little is known about GLP-1 agonist-induced cutaneous reactions. Nevertheless, rare but significant cutaneous adverse reactions have been reported, including but not limited to dermal hypersensitivity reactions, eosinophilic panniculitis, bullous pemphigoid, and morbilliform drug eruptions. As GLP-1 induced cutaneous reactions are diverse, diagnosis requires clinical suspicion, thorough history-taking, and supportive histopathological findings when available. Management involves cessation of the offending agent with a tailored regimen to address inflammatory and/or immunogenic etiologies as well as irritative symptoms. This review aims to consolidate available information from case reports and case series regarding rare skin-related adverse outcomes due to GLP-1 use, aiming to provide a comprehensive overview of the presentation, pathogenesis, and management for dermatologists and other clinicians. CI - (c) 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Salazar, Carlos E AU - Salazar CE AD - Department of Dermatology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Patil, Mihir K AU - Patil MK AD - Department of Dermatology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA. AD - Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Champaign, IL, USA. FAU - Aihie, Osaigbokan AU - Aihie O AD - University of Missouri School of Medicine, Columbia, MO, USA. FAU - Cruz, Nicolas AU - Cruz N AD - Department of Dermatology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Nambudiri, Vinod E AU - Nambudiri VE AD - Department of Dermatology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA, 02115, USA. vnambudiri@bwh.harvard.edu. AD - Harvard Medical School, Boston, MA, USA. vnambudiri@bwh.harvard.edu. LA - eng PT - Journal Article PT - Review DEP - 20240525 PL - Germany TA - Arch Dermatol Res JT - Archives of dermatological research JID - 8000462 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1/adverse effects/agonists MH - *Hypoglycemic Agents/adverse effects MH - *Drug Eruptions/etiology/diagnosis/pathology MH - Skin/pathology/drug effects MH - Liraglutide/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cutaneous adverse effects OT - Dulaglutide OT - Exenatide OT - GLP-1 agonists OT - Glucagon-like-peptide-1 OT - Hemoglobin A1c OT - Liraglutide OT - Lixisenatide OT - Semaglutide OT - Tirzepatide OT - Type 2 diabetes mellitus OT - Weight loss EDAT- 2024/05/25 20:47 MHDA- 2024/05/25 20:48 CRDT- 2024/05/25 11:04 PHST- 2024/01/13 00:00 [received] PHST- 2024/04/26 00:00 [accepted] PHST- 2024/04/21 00:00 [revised] PHST- 2024/05/25 20:48 [medline] PHST- 2024/05/25 20:47 [pubmed] PHST- 2024/05/25 11:04 [entrez] AID - 10.1007/s00403-024-02969-3 [pii] AID - 10.1007/s00403-024-02969-3 [doi] PST - epublish SO - Arch Dermatol Res. 2024 May 25;316(6):248. doi: 10.1007/s00403-024-02969-3. PMID- 38787986 OWN - NLM STAT- MEDLINE DCOM- 20240524 LR - 20260127 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 103 IP - 21 DP - 2024 May 24 TI - Gastrointestinal safety evaluation of semaglutide for the treatment of type 2 diabetes mellitus: A meta-analysis. PG - e38236 LID - 10.1097/MD.0000000000038236 [doi] LID - e38236 AB - BACKGROUND: Semaglutide, as an innovative weekly formulation, has attracted much attention. Nevertheless, the predominant occurrence of gastrointestinal adverse events (GIAEs) poses a noteworthy challenge linked to the use of this medication, substantially affecting its clinical applicability and the overall well-being of patients. Therefore, this systematic review aims to comprehensively discuss the GIAEs, providing a basis for clinical therapeutic decisions. METHODS: We systematically searched 4 independent databases for randomized controlled trials investigating the application of semaglutide in managing type 2 diabetes mellitus. The search period spanned from the inception of the databases to December 2023. We conducted a comprehensive meta-analysis, employing Review Manager 5.4.1 software, to systematically analyze and evaluate potential biases. Our primary emphasis was on assessing the gastrointestinal safety profile of semaglutide. RESULTS: The outcomes unveiled a noteworthy rise in the collective occurrence of GIAEs across all dosage groups of semaglutide in comparison with the control group (P < .05). Upon further analysis, it was observed that semaglutide showed a heightened occurrence of GIAEs in contrast to the placebo. However, statistically significant distinction was not observed when compared to the reduction of conventional doses or the transition to other types of glucagon-like peptide-1 receptor agonist. Additionally, an extended treatment duration with semaglutide (>30 weeks) demonstrated an association with a certain degree of decrease in the incidence of gastrointestinal events. Funnel plot assessment for publication bias demonstrated high-quality inclusion of studies with no apparent publication bias. CONCLUSION: The frequency of GIAEs in using semaglutide was observed to be elevated in comparison to the control group. However, it was comparable to other glucagon-like peptide-1 receptor agonist or low-dose treatment regimens. Additionally, an extended treatment duration played a role in decreasing the frequency of GIAEs. These findings provide valuable insights for clinical practice. Nonetheless, further research is crucial to explore supplementary data indicators, informing clinical practices and better serving the interests of patients. CI - Copyright (c) 2024 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Huang, Xiaoyan AU - Huang X AUID- ORCID: 0009-0007-3487-9905 AD - Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Fujian, China. FAU - Wu, Miaohui AU - Wu M AD - School of Pharmacy, Fujian Medical University, Fujian, China. FAU - Lin, Jiaojiao AU - Lin J AD - Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Fujian, China. FAU - Mou, Lunpan AU - Mou L AD - Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Fujian, China. FAU - Zhang, Yaping AU - Zhang Y AD - Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Fujian, China. FAU - Jiang, Jianjia AU - Jiang J AD - Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Fujian, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - *Hypoglycemic Agents/therapeutic use/adverse effects MH - *Gastrointestinal Diseases/chemically induced MH - Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC11124640 COIS- The authors have no funding and conflicts of interest to disclose. EDAT- 2024/05/24 18:44 MHDA- 2024/05/24 18:45 PMCR- 2024/05/24 CRDT- 2024/05/24 14:13 PHST- 2024/05/24 18:45 [medline] PHST- 2024/05/24 18:44 [pubmed] PHST- 2024/05/24 14:13 [entrez] PHST- 2024/05/24 00:00 [pmc-release] AID - 00005792-202405240-00020 [pii] AID - MD-D-24-00580 [pii] AID - 10.1097/MD.0000000000038236 [doi] PST - ppublish SO - Medicine (Baltimore). 2024 May 24;103(21):e38236. doi: 10.1097/MD.0000000000038236. PMID- 38785209 OWN - NLM STAT- MEDLINE DCOM- 20240710 LR - 20260518 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 391 IP - 2 DP - 2024 Jul 11 TI - Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. PG - 109-121 LID - 10.1056/NEJMoa2403347 [doi] AB - BACKGROUND: Patients with type 2 diabetes and chronic kidney disease are at high risk for kidney failure, cardiovascular events, and death. Whether treatment with semaglutide would mitigate these risks is unknown. METHODS: We randomly assigned patients with type 2 diabetes and chronic kidney disease (defined by an estimated glomerular filtration rate [eGFR] of 50 to 75 ml per minute per 1.73 m(2) of body-surface area and a urinary albumin-to-creatinine ratio [with albumin measured in milligrams and creatinine measured in grams] of >300 and <5000 or an eGFR of 25 to <50 ml per minute per 1.73 m(2) and a urinary albumin-to-creatinine ratio of >100 and <5000) to receive subcutaneous semaglutide at a dose of 1.0 mg weekly or placebo. The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of <15 ml per minute per 1.73 m(2)), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes. Prespecified confirmatory secondary outcomes were tested hierarchically. RESULTS: Among the 3533 participants who underwent randomization (1767 in the semaglutide group and 1766 in the placebo group), median follow-up was 3.4 years, after early trial cessation was recommended at a prespecified interim analysis. The risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs. 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.88; P = 0.0003). Results were similar for a composite of the kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56 to 0.89). The results for all confirmatory secondary outcomes favored semaglutide: the mean annual eGFR slope was less steep (indicating a slower decrease) by 1.16 ml per minute per 1.73 m(2) in the semaglutide group (P<0.001), the risk of major cardiovascular events 18% lower (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = 0.029), and the risk of death from any cause 20% lower (hazard ratio, 0.80; 95% CI, 0.67 to 0.95, P = 0.01). Serious adverse events were reported in a lower percentage of participants in the semaglutide group than in the placebo group (49.6% vs. 53.8%). CONCLUSIONS: Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease. (Funded by Novo Nordisk; FLOW ClinicalTrials.gov number, NCT03819153.). CI - Copyright (c) 2024 Massachusetts Medical Society. FAU - Perkovic, Vlado AU - Perkovic V AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Tuttle, Katherine R AU - Tuttle KR AUID- ORCID: 0000-0002-2235-0103 AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Mann, Johannes F E AU - Mann JFE AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Bakris, George AU - Bakris G AUID- ORCID: 0000-0003-1183-1267 AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Baeres, Florian M M AU - Baeres FMM AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Idorn, Thomas AU - Idorn T AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Bosch-Traberg, Heidrun AU - Bosch-Traberg H AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Lausvig, Nanna Leonora AU - Lausvig NL AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). FAU - Pratley, Richard AU - Pratley R AD - From the University of New South Wales, Sydney (V.P.); the Division of Nephrology, University of Washington School of Medicine, Seattle, and Providence Medical Research Center, Providence Inland Northwest Health, Spokane - both in Washington (K.R.T.); Steno Diabetes Center Copenhagen, Herlev (P.R.), the Department of Clinical Medicine, University of Copenhagen, Copenhagen (P.R.), and Novo Nordisk, Soborg (F.M.M.B., T.I., H.B.-T., N.L.L.) - all in Denmark; Stanford Center for Clinical Research, Department of Medicine, Stanford School of Medicine, Palo Alto, CA (K.W.M.); KfH Kidney Center, Munich, and University Hospital, Friedrich-Alexander University, Erlangen - both in Germany (J.F.E.M.); the Department of Medicine, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, Chicago (G.B.); and AdventHealth Translational Research Institute, Orlando, FL (R.P.). CN - FLOW Trial Committees and Investigators LA - eng SI - ClinicalTrials.gov/NCT03819153 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural DEP - 20240524 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Ann Intern Med. 2024 Sep;177(9):JC98. doi: 10.7326/ANNALS-24-01579-JC. PMID: 39222509 CIN - N Engl J Med. 2024 Nov 7;391(18):1757. doi: 10.1056/NEJMc2410532. PMID: 39504528 CIN - N Engl J Med. 2024 Nov 7;391(18):1757. doi: 10.1056/NEJMc2410532. PMID: 39504529 CIN - MMW Fortschr Med. 2024 Nov;166(19):28-29. doi: 10.1007/s15006-024-4438-6. PMID: 39511083 MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Cardiovascular Diseases/prevention & control/mortality/etiology MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Diabetic Nephropathies/etiology/mortality MH - Double-Blind Method MH - Glomerular Filtration Rate/drug effects MH - Glucagon-Like Peptides/administration & dosage/adverse effects/pharmacology/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Injections, Subcutaneous MH - *Renal Insufficiency, Chronic/etiology/mortality MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - Semaglutide FIR - Porto, A IR - Porto A FIR - Oviedo, A IR - Oviedo A FIR - Elbert, A IR - Elbert A FIR - Gelersztein, E IR - Gelersztein E FIR - Wassermann, A IR - Wassermann A FIR - Quevedo, M A IR - Quevedo MA FIR - MacIsaac, R IR - MacIsaac R FIR - Roger, S IR - Roger S FIR - Phoon, R IR - Phoon R FIR - Kerr, P IR - Kerr P FIR - Ajani, A IR - Ajani A FIR - Tan, S IR - Tan S FIR - Colquhoun, D IR - Colquhoun D FIR - Mather, A IR - Mather A FIR - Gillard, P IR - Gillard P FIR - De Block, C IR - De Block C FIR - Debroye, C IR - Debroye C FIR - Duyck, F IR - Duyck F FIR - Krzesinski, J M IR - Krzesinski JM FIR - Lapauw, B IR - Lapauw B FIR - Preumont, V IR - Preumont V FIR - Vercammen, C IR - Vercammen C FIR - Kamenov, Z IR - Kamenov Z FIR - Bobeva, R IR - Bobeva R FIR - Levterov, G IR - Levterov G FIR - Gerilovska, S IR - Gerilovska S FIR - Yabrudi, N IR - Yabrudi N FIR - Stoyanovska-Elencheva, B IR - Stoyanovska-Elencheva B FIR - Nikitov, Z IR - Nikitov Z FIR - Franco, D IR - Franco D FIR - Akerman Augusto, G IR - Akerman Augusto G FIR - Salles, J IR - Salles J FIR - Canani, L IR - Canani L FIR - Krakauer, M IR - Krakauer M FIR - Cerqueira, M J IR - Cerqueira MJ FIR - Riella, M IR - Riella M FIR - Bajaj, H IR - Bajaj H FIR - Schlosser, R IR - Schlosser R FIR - Ajala, B IR - Ajala B FIR - Aggarwal, N IR - Aggarwal N FIR - Dumas, R IR - Dumas R FIR - O'Keefe, D IR - O'Keefe D FIR - Peterson, S IR - Peterson S FIR - Tsoukas, G IR - Tsoukas G FIR - Tailor, C IR - Tailor C FIR - Tytus, R IR - Tytus R FIR - Akhras, R IR - Akhras R FIR - Khandwala, H IR - Khandwala H FIR - Steen, O IR - Steen O FIR - Carbonneau, D IR - Carbonneau D FIR - Cha, J IR - Cha J FIR - Steele, A IR - Steele A FIR - Bailey, G IR - Bailey G FIR - Berlingieri, J IR - Berlingieri J FIR - Dzongowski, P IR - Dzongowski P FIR - Cherney, D IR - Cherney D FIR - Elliott, T IR - Elliott T FIR - Kovacs, C IR - Kovacs C FIR - Hamet, P IR - Hamet P FIR - Perkins, B IR - Perkins B FIR - Tennankore, K IR - Tennankore K FIR - Gupta, A IR - Gupta A FIR - Ji, L IR - Ji L FIR - Li, Y IR - Li Y FIR - Yuan, G IR - Yuan G FIR - Dong, X IR - Dong X FIR - Cariou, B IR - Cariou B FIR - Clavel, S IR - Clavel S FIR - Marchand, L IR - Marchand L FIR - Reznik, Y IR - Reznik Y FIR - Moulin, P IR - Moulin P FIR - Legrand, E IR - Legrand E FIR - Benoit Tricaud, I IR - Benoit Tricaud I FIR - Gourdy, P IR - Gourdy P FIR - Zaoui, P IR - Zaoui P FIR - Monier, A IR - Monier A FIR - Kazes, I IR - Kazes I FIR - Dahl, D IR - Dahl D FIR - Esser, M IR - Esser M FIR - Kruger, T IR - Kruger T FIR - Rose, L IR - Rose L FIR - Schmieder, R IR - Schmieder R FIR - Segner, A IR - Segner A FIR - Lee-Barkey, Y H IR - Lee-Barkey YH FIR - Vidal, S IR - Vidal S FIR - Schurholz, T IR - Schurholz T FIR - Boletis, I IR - Boletis I FIR - Raptis, A IR - Raptis A FIR - Lanaras, L IR - Lanaras L FIR - Pagkalos, E IR - Pagkalos E FIR - Doupis, J IR - Doupis J FIR - Bekiari, E IR - Bekiari E FIR - Goumenos, D IR - Goumenos D FIR - Papadopoulou, D IR - Papadopoulou D FIR - Tziomalos, K IR - Tziomalos K FIR - Karousos, G IR - Karousos G FIR - Somali, M IR - Somali M FIR - Markou, A IR - Markou A FIR - Zografou, I IR - Zografou I FIR - Wittmann, I IR - Wittmann I FIR - Brasnyo, P IR - Brasnyo P FIR - Korhaz, Siofoki IR - Korhaz S FIR - Balla, J IR - Balla J FIR - Petro, G IR - Petro G FIR - Baranyai, M IR - Baranyai M FIR - Dudas, M IR - Dudas M FIR - Vangel, S IR - Vangel S FIR - Konyves, L IR - Konyves L FIR - Vasas, S IR - Vasas S FIR - Tanczer, T IR - Tanczer T FIR - Shah, M IR - Shah M FIR - Anil, B T IR - Anil BT FIR - Bhalla, A IR - Bhalla A FIR - Gireesh, M S IR - Gireesh MS FIR - Prasad, N IR - Prasad N FIR - Sahay, M IR - Sahay M FIR - Jamale, T IR - Jamale T FIR - Jain, M IR - Jain M FIR - Magdum, M IR - Magdum M FIR - Dewan, D IR - Dewan D FIR - Dinesh, K IR - Dinesh K FIR - Kumar, H IR - Kumar H FIR - Jayakumar, K IR - Jayakumar K FIR - Murthy, S IR - Murthy S FIR - Srikanth, K IR - Srikanth K FIR - Gupta, S IR - Gupta S FIR - Aharon-Hananel, G IR - Aharon-Hananel G FIR - Wainstein, J IR - Wainstein J FIR - Chernin, G IR - Chernin G FIR - Kenis, I IR - Kenis I FIR - Trevisan, R IR - Trevisan R FIR - Bosi, E IR - Bosi E FIR - Setola, E IR - Setola E FIR - Fiorina, P IR - Fiorina P FIR - Penno, G IR - Penno G FIR - Pugliese, G IR - Pugliese G FIR - Giordano, C IR - Giordano C FIR - Orsi, E IR - Orsi E FIR - Cavallo, M G IR - Cavallo MG FIR - Tsuchida, K IR - Tsuchida K FIR - Sasaki, T IR - Sasaki T FIR - Seino, H IR - Seino H FIR - Kawada, T IR - Kawada T FIR - Osonoi, T IR - Osonoi T FIR - Ohashi, H IR - Ohashi H FIR - Shimizu, Y IR - Shimizu Y FIR - Mitomo, S IR - Mitomo S FIR - Nakamura, C IR - Nakamura C FIR - Takai, K IR - Takai K FIR - Maeda, H IR - Maeda H FIR - Nishi, H IR - Nishi H FIR - Nishida, Y IR - Nishida Y FIR - Yamada, M IR - Yamada M FIR - Fukushima, Y IR - Fukushima Y FIR - Kato, M IR - Kato M FIR - Sugawara, M IR - Sugawara M FIR - Araki, H IR - Araki H FIR - Nakagawa, A IR - Nakagawa A FIR - Onaka, H IR - Onaka H FIR - Sueyoshi, A IR - Sueyoshi A FIR - Kidokoro, K IR - Kidokoro K FIR - Tanabe, M IR - Tanabe M FIR - Jinnouchi, H IR - Jinnouchi H FIR - Nakamura, S IR - Nakamura S FIR - Hasumi, S IR - Hasumi S FIR - Gonzalez-Galvez, G IR - Gonzalez-Galvez G FIR - Aguilar Salinas, C IR - Aguilar Salinas C FIR - Morales de Teresa, M IR - Morales de Teresa M FIR - Violante Ortiz, R M IR - Violante Ortiz RM FIR - Correa Rotter, J IR - Correa Rotter J FIR - Irizar Santana, S IR - Irizar Santana S FIR - Lim, S K IR - Lim SK FIR - Yoon, C K IR - Yoon CK FIR - Tan, F IR - Tan F FIR - Goh, B L IR - Goh BL FIR - Loh, C L IR - Loh CL FIR - Yusoff Azmi Merican, N S IR - Yusoff Azmi Merican NS FIR - Bax, W A IR - Bax WA FIR - van Raalte, D IR - van Raalte D FIR - Luik, P T IR - Luik PT FIR - de Vries, P A M IR - de Vries PAM FIR - Dorresteijn, J IR - Dorresteijn J FIR - AlHakim, M IR - AlHakim M FIR - van Wissen, S IR - van Wissen S FIR - Kamphuisen, P IR - Kamphuisen P FIR - Verhave, J IR - Verhave J FIR - Gumprecht, J IR - Gumprecht J FIR - Majcher-Witczak, G IR - Majcher-Witczak G FIR - Mlodawska-Choluj, D IR - Mlodawska-Choluj D FIR - Stompor, T IR - Stompor T FIR - Ciechanowski, K IR - Ciechanowski K FIR - Malecki, R IR - Malecki R FIR - Wasilewska, K IR - Wasilewska K FIR - Shamkhalova, M IR - Shamkhalova M FIR - Ruyatkina, L IR - Ruyatkina L FIR - Vagapova, G IR - Vagapova G FIR - Sergeeva-Kondrachenko, M IR - Sergeeva-Kondrachenko M FIR - Kargina, L IR - Kargina L FIR - Peskov, A IR - Peskov A FIR - Zhdanova, E IR - Zhdanova E FIR - Lysenko, T IR - Lysenko T FIR - Frolova, E IR - Frolova E FIR - Mishchenko, O IR - Mishchenko O FIR - Belousova, L IR - Belousova L FIR - Astamirova, K IR - Astamirova K FIR - Antonova, E IR - Antonova E FIR - Pergaeva, Y IR - Pergaeva Y FIR - Palyutin, S IR - Palyutin S FIR - Sharkaeva, A IR - Sharkaeva A FIR - Krasnopeeva, N IR - Krasnopeeva N FIR - Tyugaeva, A IR - Tyugaeva A FIR - Krasilnikova, E IR - Krasilnikova E FIR - Romasheva, E IR - Romasheva E FIR - Sorokin, M IR - Sorokin M FIR - Martinka, E IR - Martinka E FIR - Ilavska, A IR - Ilavska A FIR - Tomasova, L IR - Tomasova L FIR - Porubska, K IR - Porubska K FIR - Skripova, D IR - Skripova D FIR - Buganova, I IR - Buganova I FIR - Rociakova, J IR - Rociakova J FIR - Rosenberger, J IR - Rosenberger J FIR - Pavelcikova, A IR - Pavelcikova A FIR - Smik, R IR - Smik R FIR - Gorriz, J IR - Gorriz J FIR - Castro, C IR - Castro C FIR - Cigarran, S IR - Cigarran S FIR - Barrios, C IR - Barrios C FIR - Soler, M IR - Soler M FIR - Martins, J IR - Martins J FIR - Sriwijitkamol, A IR - Sriwijitkamol A FIR - Phornphutkul, M IR - Phornphutkul M FIR - Supasyndh, O IR - Supasyndh O FIR - Kiattisunthorn, K IR - Kiattisunthorn K FIR - Buranasupkajorn, P IR - Buranasupkajorn P FIR - Susantitaphong, P IR - Susantitaphong P FIR - Helvaci, O IR - Helvaci O FIR - Ates, K IR - Ates K FIR - Arikan, I IR - Arikan I FIR - Arici, M IR - Arici M FIR - Suleymanlar, G IR - Suleymanlar G FIR - Yazici, H IR - Yazici H FIR - Alisir Ecder, S IR - Alisir Ecder S FIR - Gungor, O IR - Gungor O FIR - Ok, E IR - Ok E FIR - Seyahi, N IR - Seyahi N FIR - Eren, N IR - Eren N FIR - Yenicerioglu, Y IR - Yenicerioglu Y FIR - Chabanna, O IR - Chabanna O FIR - Panina, S IR - Panina S FIR - Semenovykh, P IR - Semenovykh P FIR - Leonidova, V IR - Leonidova V FIR - Zinych, O IR - Zinych O FIR - Legun, O IR - Legun O FIR - Kaydashev, I IR - Kaydashev I FIR - Bellary, S IR - Bellary S FIR - Boyle, J IR - Boyle J FIR - Chen, M IR - Chen M FIR - Mcknight, J IR - Mcknight J FIR - Pearson, E IR - Pearson E FIR - Philip, S IR - Philip S FIR - Sharma, S IR - Sharma S FIR - Viljoen, A IR - Viljoen A FIR - Wakeling, J IR - Wakeling J FIR - Tindall, H IR - Tindall H FIR - Yousseif, A IR - Yousseif A FIR - Aw, T IR - Aw T FIR - Guerrero, A IR - Guerrero A FIR - Arif, A IR - Arif A FIR - Betts, J IR - Betts J FIR - Busch, R IR - Busch R FIR - Desouza, C IR - Desouza C FIR - Gonzalez-Orozco, L IR - Gonzalez-Orozco L FIR - Dukes, C IR - Dukes C FIR - Hammoud, J IR - Hammoud J FIR - Houser, P IR - Houser P FIR - Jackson, T IR - Jackson T FIR - Kayali, Z IR - Kayali Z FIR - Young, L IR - Young L FIR - Klein, E IR - Klein E FIR - Lingvay, I IR - Lingvay I FIR - Nicol, P IR - Nicol P FIR - Smith, S IR - Smith S FIR - Snyder, B IR - Snyder B FIR - Soroka, E IR - Soroka E FIR - Wysham, C IR - Wysham C FIR - Akyea-Djamson, A IR - Akyea-Djamson A FIR - Arauz-Pacheco, C IR - Arauz-Pacheco C FIR - Horeish, A IR - Horeish A FIR - Chang, A IR - Chang A FIR - Connery, L IR - Connery L FIR - Gandy, W Jr IR - Gandy W Jr FIR - Gilbert, M IR - Gilbert M FIR - Hernandez, G IR - Hernandez G FIR - Hewitt, M IR - Hewitt M FIR - Huffman, D IR - Huffman D FIR - Lovell, C IR - Lovell C FIR - Masani, N IR - Masani N FIR - McGill, J IR - McGill J FIR - Siddiqui, I IR - Siddiqui I FIR - Perez, R IR - Perez R FIR - Reed, J 3rd IR - Reed J 3rd FIR - Sivalingam, K IR - Sivalingam K FIR - London, J IR - London J FIR - Saha, S IR - Saha S FIR - Awad, A IR - Awad A FIR - Billings, L IR - Billings L FIR - Blaze, K IR - Blaze K FIR - Stricklin, D IR - Stricklin D FIR - Brinson, C IR - Brinson C FIR - Bornfreund, J IR - Bornfreund J FIR - McCall, N IR - McCall N FIR - Buynak, R IR - Buynak R FIR - Cannon, K IR - Cannon K FIR - Daboul, N IR - Daboul N FIR - Acosta, I IR - Acosta I FIR - Diaz, J IR - Diaz J FIR - Greenwood, G IR - Greenwood G FIR - Hart, T IR - Hart T FIR - Hasan, S IR - Hasan S FIR - Iranmanesh, A IR - Iranmanesh A FIR - Koilpillai, R IR - Koilpillai R FIR - Latif, K IR - Latif K FIR - Lawrence, M IR - Lawrence M FIR - Chen, C IR - Chen C FIR - Marar, I IR - Marar I FIR - East, C IR - East C FIR - Patel, R IR - Patel R FIR - Rovner, S IR - Rovner S FIR - Seco, G IR - Seco G FIR - Shaikh, Z IR - Shaikh Z FIR - Traylor, H IR - Traylor H FIR - Zieve, F IR - Zieve F FIR - Aroda, V IR - Aroda V FIR - Ahmed, A IR - Ahmed A FIR - Biscoveanu, M IR - Biscoveanu M FIR - Budoff, M IR - Budoff M FIR - El-Shahawy, M IR - El-Shahawy M FIR - Garza, J IR - Garza J FIR - Hanson, L IR - Hanson L FIR - Reddy, J IR - Reddy J FIR - Rodriguez, H IR - Rodriguez H FIR - Shrestha, A IR - Shrestha A FIR - Bernardo, M IR - Bernardo M FIR - Christensen, T IR - Christensen T FIR - Denker, P IR - Denker P FIR - Dua, S IR - Dua S FIR - El Shahawy, M IR - El Shahawy M FIR - Farias, A IR - Farias A FIR - Fernando, R IR - Fernando R FIR - Jamal, A IR - Jamal A FIR - Jardula, M IR - Jardula M FIR - Moustafa, M IR - Moustafa M FIR - Posada, J IR - Posada J FIR - Sanchez, W IR - Sanchez W FIR - Vega, D IR - Vega D FIR - Kumar, J IR - Kumar J FIR - Sultan, S IR - Sultan S FIR - Bansal, S IR - Bansal S FIR - Benjamin, S IR - Benjamin S FIR - Brusco, O IR - Brusco O FIR - Wayne, J IR - Wayne J FIR - Gaona, R IR - Gaona R FIR - Degani, O IR - Degani O FIR - Figueroa, C IR - Figueroa C FIR - Montero, M IR - Montero M FIR - Rasouli, N IR - Rasouli N FIR - Zemel, L IR - Zemel L FIR - Fadda, G IR - Fadda G FIR - Shlesinger, Y IR - Shlesinger Y FIR - Charytan, D IR - Charytan D FIR - Butuk, D IR - Butuk D FIR - Stringam, S IR - Stringam S FIR - Espinosa, V IR - Espinosa V FIR - Brandon, D IR - Brandon D FIR - Shea, H IR - Shea H FIR - Cheung, D IR - Cheung D FIR - Sanchez, Y IR - Sanchez Y FIR - Kudva, Y IR - Kudva Y FIR - Beddhu, S IR - Beddhu S FIR - Rayner, B IR - Rayner B FIR - Bhorat, Q IR - Bhorat Q FIR - Badat, A IR - Badat A FIR - Makan, H IR - Makan H FIR - Joshi, M IR - Joshi M FIR - Basson, M IR - Basson M FIR - Naidoo, V IR - Naidoo V FIR - Amod, A IR - Amod A FIR - Perkovic, Vlado IR - Perkovic V FIR - Pratley, Richard IR - Pratley R FIR - Mann, Johannes IR - Mann J FIR - Bakris, George IR - Bakris G FIR - Tuttle, Katherine IR - Tuttle K FIR - Rossing, Peter IR - Rossing P FIR - Mahaffey, Kenneth IR - Mahaffey K FIR - Baeres, Florian M M IR - Baeres FMM FIR - Idorn, Thomas IR - Idorn T FIR - Schelde, Peter IR - Schelde P EDAT- 2024/05/24 12:43 MHDA- 2024/07/10 18:42 CRDT- 2024/05/24 06:33 PHST- 2024/07/10 18:42 [medline] PHST- 2024/05/24 12:43 [pubmed] PHST- 2024/05/24 06:33 [entrez] AID - 10.1056/NEJMoa2403347 [doi] PST - ppublish SO - N Engl J Med. 2024 Jul 11;391(2):109-121. doi: 10.1056/NEJMoa2403347. Epub 2024 May 24. PMID- 38778795 OWN - NLM STAT- MEDLINE DCOM- 20240711 LR - 20260127 IS - 1758-8111 (Electronic) IS - 1758-8103 (Linking) VI - 14 IP - 4 DP - 2024 Aug TI - Glucagon-like-peptide 1 receptor agonism and attempted suicide: A Mendelian randomisation study to assess a potential causal association. PG - e12676 LID - 10.1111/cob.12676 [doi] AB - Glucagon-like-peptide 1 receptor agonists (GLP-1RA) have transformed type 2 diabetes (T2D) and obesity management. Multiple regulatory agencies are investigating reported associations between GLP1-RA and increased suicide attempts (SA), but observational data may be prone to confounding. Randomised control trials (RCT) of GLP-1RA were largely undertaken in people at lower risk of SA. Real-world data suggest semaglutide use associates with reduced suicidal ideation and depression but was under-powered to statistically assess risk of SA. Mendelian randomisation (MR) leverages genetic instrument(s) to infer potential causal association between an exposure and an outcome. We undertook MR using missense variants in the gene encoding GLP1R that improve glycemia, lower T2D risk and/or lower BMI, to investigate potential causal association between GLP-1RA and SA. In people of European ancestry, MR did not find evidence genetically proxied GLP1RA increased SA in a general population cohort: (rs10305492, exposure: HbA1c, odds ratio [OR] and 95% confidence interval [CI]: 1.38, 0.41-4.62, p = .60), (rs10305492, exposure: FG, OR 1.27, 0.52-3.13, p = .60) and (rs1042044, exposure BMI, OR 0.30, 0.06-1.48) with concordant results in a multi-ancestry SA case-control cohort. In conclusion, we did not find MR evidence that increased GLP-1RA impacts SA. This awaits confirmation with RCT and real-world data. CI - (c) 2024 World Obesity Federation. FAU - Nguyen, Anthony AU - Nguyen A AD - Department of Medicine, University Health Network, Toronto, Toronto, Canada. FAU - Smith, Emily AU - Smith E AD - Centre for Addiction and Mental Health (CAMH), Toronto, Institute of Medical Science, Department of Psychiatry & Pharmacology, Banting and Best Diabetes Centre (BBDC), University of Toronto, Toronto, Canada. FAU - Hashemy, Habiba AU - Hashemy H AD - Department of Medicine, University Health Network, Toronto, Toronto, Canada. FAU - Agarwal, Sri Mahavir AU - Agarwal SM AD - Centre for Addiction and Mental Health (CAMH), Toronto, Institute of Medical Science, Department of Psychiatry & Pharmacology, Banting and Best Diabetes Centre (BBDC), University of Toronto, Toronto, Canada. FAU - Hahn, Margaret K AU - Hahn MK AD - Centre for Addiction and Mental Health (CAMH), Toronto, Institute of Medical Science, Department of Psychiatry & Pharmacology, Banting and Best Diabetes Centre (BBDC), University of Toronto, Toronto, Canada. FAU - Paterson, Andrew D AU - Paterson AD AD - Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada. AD - Divisions of Epidemiology and Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. FAU - Dash, Satya AU - Dash S AD - Department of Medicine, University Health Network, Toronto, Toronto, Canada. LA - eng GR - Heart and Stroke Foundation of Canada/ GR - PJT-153262/CAPMC/CIHR/Canada GR - PJT-153262/CAPMC/CIHR/Canada PT - Journal Article DEP - 20240523 PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Mendelian Randomization Analysis MH - *Glucagon-Like Peptide-1 Receptor/genetics MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - *Suicide, Attempted MH - Male MH - Female MH - Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Glucagon-Like Peptides MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Mendelian randomisation OT - glucagon like peptide 1 OT - obesity OT - suicide attempt OT - type 2 diabetes EDAT- 2024/05/23 06:43 MHDA- 2024/07/12 00:42 CRDT- 2024/05/23 03:35 PHST- 2024/04/25 00:00 [revised] PHST- 2024/04/09 00:00 [received] PHST- 2024/05/05 00:00 [accepted] PHST- 2024/07/12 00:42 [medline] PHST- 2024/05/23 06:43 [pubmed] PHST- 2024/05/23 03:35 [entrez] AID - 10.1111/cob.12676 [doi] PST - ppublish SO - Clin Obes. 2024 Aug;14(4):e12676. doi: 10.1111/cob.12676. Epub 2024 May 23. PMID- 38777128 OWN - NLM STAT- MEDLINE DCOM- 20240609 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 212 DP - 2024 Jun TI - Tirzepatide 5, 10 and 15 mg versus injectable semaglutide 0.5 mg for the treatment of type 2 diabetes: An adjusted indirect treatment comparison. PG - 111717 LID - S0168-8227(24)00627-2 [pii] LID - 10.1016/j.diabres.2024.111717 [doi] AB - AIMS: To compare the efficacy and safety of tirzepatide 5, 10 and 15 mg with subcutaneous semaglutide 0.5 mg as second-line treatment for adults with type 2 diabetes mellitus, after metformin monotherapy, using adjusted indirect treatment comparisons (aITCs). METHODS: The aITCs were performed using the Bucher method to compare the relative efficacy and safety of tirzepatide 5, 10 and 15 mg versus semaglutide 0.5 mg via a common comparator (subcutaneous semaglutide 1.0 mg) based on trial results from SURPASS-2 (NCT03987919) and SUSTAIN7 (NCT02648204). RESULTS: All tirzepatide doses showed statistically significantly greater reductions in glycated haemoglobin, body weight and body mass index from baseline to week 40, with a comparable adverse event (AE) profile and no statistically significant differences in the odds of gastrointestinal AEs versus semaglutide 0.5 mg. Furthermore, all tirzepatide doses showed greater odds of patients achieving HbA1c targets of /= 5 % and >/= 10 %, versus semaglutide 0.5 mg. CONCLUSIONS: In these aITCs, glycated haemoglobin and weight reductions were significantly greater for all tirzepatide doses versus semaglutide 0.5 mg with a comparable AE profile. These findings provide comparative effectiveness insights in the absence of a head-to-head clinical trial. CI - Copyright (c) 2024 Eli Lilly and Company. Published by Elsevier B.V. All rights reserved. FAU - Osumili, Beatrice AU - Osumili B AD - Eli Lilly and Company, 893 Delaware St, Indianapolis, IN 46225, USA. FAU - Fan, Ludi AU - Fan L AD - Eli Lilly and Company, 893 Delaware St, Indianapolis, IN 46225, USA. FAU - Paik, Jim S AU - Paik JS AD - Eli Lilly and Company, 893 Delaware St, Indianapolis, IN 46225, USA. FAU - Pantalone, Kevin M AU - Pantalone KM AD - Department of Endocrinology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, USA. FAU - Ranta, Kari AU - Ranta K AD - Eli Lilly and Company, 893 Delaware St, Indianapolis, IN 46225, USA. Electronic address: kari.ranta@lilly.com. FAU - Sapin, Helene AU - Sapin H AD - Eli Lilly and Company, 893 Delaware St, Indianapolis, IN 46225, USA. FAU - Tofe, Santiago AU - Tofe S AD - Department of Endocrinology and Nutrition, University Hospital Son Espases, Carretera de Valldemossa, 79 07120, Palma de Mallorca, Spain. LA - eng SI - ClinicalTrials.gov/NCT02648204 SI - ClinicalTrials.gov/NCT03987919 PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial DEP - 20240521 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - Male MH - Female MH - Middle Aged MH - *Glycated Hemoglobin/analysis/metabolism MH - Injections, Subcutaneous MH - Treatment Outcome MH - Adult MH - Aged MH - Blood Glucose/drug effects/analysis MH - Metformin/administration & dosage/therapeutic use MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide MH - Semaglutide OTO - NOTNLM OT - HbA1c OT - Indirect treatment comparison OT - Subcutaneous semaglutide OT - Tirzepatide OT - Type2 diabetes mellitus OT - Weight COIS- Declaration of competing interest Beatrice Osumili, Ludi Fan, Jim S. Paik, Kari Ranta, and Helene Sapin are employees and minor shareholders of Eli Lilly and Company. Kevin M. Pantalone, in the past 36 months, has received consulting honoraria from AstraZeneca, Bayer, Corcept Therapeutics, Eli Lilly and Company, Merck, and Novo Nordisk; speaker honoraria from AstraZeneca, Merck, and Novo Nordisk; and research support from Bayer, Merck, Novo Nordisk and Twin Health. Santiago Tofe, in the past 36 months, has received consulting honoraria from Eli Lilly and Company; speaker honoraria from AstraZeneca, and Novo Nordisk; and research support from Eli Lilly and Company, and Novo Nordisk. EDAT- 2024/05/23 00:42 MHDA- 2024/06/10 00:42 CRDT- 2024/05/22 19:27 PHST- 2024/03/13 00:00 [received] PHST- 2024/05/15 00:00 [revised] PHST- 2024/05/19 00:00 [accepted] PHST- 2024/06/10 00:42 [medline] PHST- 2024/05/23 00:42 [pubmed] PHST- 2024/05/22 19:27 [entrez] AID - S0168-8227(24)00627-2 [pii] AID - 10.1016/j.diabres.2024.111717 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2024 Jun;212:111717. doi: 10.1016/j.diabres.2024.111717. Epub 2024 May 21. PMID- 38766830 OWN - NLM STAT- MEDLINE DCOM- 20250604 LR - 20250604 IS - 2212-3911 (Electronic) IS - 1574-8863 (Linking) VI - 20 IP - 3 DP - 2025 TI - Suicidal Thoughts and Self-injurious Behavior Associated With Glucagon- Like Peptide-1 Receptor Agonists - A Review. PG - 253-257 LID - 10.2174/0115748863301925240507044637 [doi] AB - GLP-1 receptor agonists mimic the actions of GLP-1 and are used to manage type 2 diabetes and help with weight loss. In recent times, antidiabetic GLP-1 receptor agonists have been misused widely for weight loss. This review article focuses on some serious side effects of GLP-1 receptor agonists, notified by different regulatory agencies. We searched the literature in online databases such as Medline/Pubmed/PMC, Google Scholar, Science Direct, Ebsco, Scopus, Web of Science, Embase, and reference lists to identify publications relevant to the serious side effects associated with the use of GLP-1 receptor agonists. Various pharmacovigilance analyses and notifications from different regulatory agencies have documented the occurrence of suicidal thoughts and self-injurious behavior associated with the use of GLP-1 receptor agonists. Healthcare professionals should be aware of GLP-1 receptor agonistsassociated suicidal thoughts and self-injurious behavior. Patients should not misuse/abuse antidiabetic GLP-1 receptor agonists and should consult their physician before using any GLP-1 receptor agonists for weight loss. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Maideen, Naina Mohamed Pakkir AU - Maideen NMP AUID- ORCID: 0000-0002-6950-9783 AD - Pharmacologist, Dubai Academic Health Corporation, Dubai, UAE. FAU - Al Rashid, Sulthan AU - Al Rashid S AD - Department of Pharmacology, Saveetha Medical College and Hospital, Saveetha Institute of Medical & Technical Sciences (SIMATS), Chennai, Tamil Nadu, India. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Drug Saf JT - Current drug safety JID - 101270895 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - *Self-Injurious Behavior/chemically induced/psychology MH - *Suicidal Ideation MH - *Hypoglycemic Agents/adverse effects MH - Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - GLP-1 receptor agonists OT - depression OT - dulaglutide OT - self-injurious behavior OT - semaglutide OT - suicidal thoughts OT - tirzepatide EDAT- 2024/05/20 06:42 MHDA- 2025/06/04 06:27 CRDT- 2024/05/20 04:54 PHST- 2024/02/14 00:00 [received] PHST- 2024/04/15 00:00 [revised] PHST- 2024/04/25 00:00 [accepted] PHST- 2025/06/04 06:27 [medline] PHST- 2024/05/20 06:42 [pubmed] PHST- 2024/05/20 04:54 [entrez] AID - CDS-EPUB-140428 [pii] AID - 10.2174/0115748863301925240507044637 [doi] PST - ppublish SO - Curr Drug Saf. 2025;20(3):253-257. doi: 10.2174/0115748863301925240507044637. PMID- 38753454 OWN - NLM STAT- MEDLINE DCOM- 20240618 LR - 20250103 IS - 1744-7666 (Electronic) IS - 1465-6566 (Print) IS - 1465-6566 (Linking) VI - 25 IP - 7 DP - 2024 May TI - Oral glucagon-like peptide-1 receptor agonists and combinations of entero-pancreatic hormones as treatments for adults with type 2 diabetes: where are we now? PG - 801-818 LID - 10.1080/14656566.2024.2356254 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have changed the landscape of type 2 diabetes (T2D) management due to their cardio-renal benefits, their glucose-lowering efficacy and weight loss (WL) maintenance. However, the response to GLP-1 RA monotherapy is heterogeneous. Additionally, the majority of GLP-1 RAs are injectable treatments. Oral GLP-1 RAs and injectable combinations of GLP-1 with other entero-pancreatic hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon and amylin) are under development for T2D and obesity management. AREAS COVERED: Herein, we review the data on (i) oral GLP-1 RAs (oral semaglutide 25/50 mg and orforglipron) and (ii) dual/triple agonists (tirzepatide, cagrilintide 2.4 mg/semaglutide 2.4 mg, survodutide, mazdutide, retatrutide) that have recently completed phase 3 trials for T2D or are currently in phase 3 clinical trials. Tirzepatide is the first approved dual agonist (GLP-1/GIP) for T2D and obesity management. EXPERT OPINION: We are in a new era in T2D management where entero-pancreatic hormone-based treatments can result in >/=15% WL and euglycemia for many people with T2D. Multiple molecules with different mechanisms of action are under development for T2D, obesity and other metabolic complications. Data on their cardio-renal benefits, long-term efficacy and safety as well as their cost-effectiveness will better inform their position in treatment algorithms. FAU - Gogineni, Prathima AU - Gogineni P AD - Diabetes Research Centre, University of Leicester College of Life Sciences, Leicester, UK. FAU - Melson, Eka AU - Melson E AUID- ORCID: 0000-0003-0685-4819 AD - Diabetes Research Centre, University of Leicester College of Life Sciences, Leicester, UK. FAU - Papamargaritis, Dimitris AU - Papamargaritis D AD - Diabetes Research Centre, University of Leicester College of Life Sciences, Leicester, UK. FAU - Davies, Melanie AU - Davies M AD - Diabetes Research Centre, University of Leicester College of Life Sciences, Leicester, UK. LA - eng PT - Journal Article PT - Review DEP - 20240522 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/pharmacology MH - Adult MH - Administration, Oral MH - Glucagon-Like Peptides/therapeutic use/administration & dosage/pharmacology/analogs & derivatives MH - Animals MH - Obesity/drug therapy MH - Drug Therapy, Combination MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC11195668 OTO - NOTNLM OT - Cagrisema OT - obesity OT - orforglipron OT - retatrutide OT - semaglutide OT - survodutide OT - tirzepatide OT - type 2 diabetes COIS- D Papamargaritis has acted as a speaker for Novo Nordisk and has received grants from Novo Nordisk, Novo Nordisk UK Research Foundation, Academy of Medical Sciences/Diabetes UK, Health Education East Midlands and the National Institute for Health and Care Research (NIHR). M J Davies has acted as consultant, advisory board member and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi, an advisory board member Lexicon, Pfizer, ShouTi Pharma Inc, AstraZeneca, Zealand Pharma and Medtronic and as a speaker for AstraZeneca, Napp Pharmaceuticals, Novartis and Amgen. M J Davies has received grants from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Janssen, Sanofi-Aventis and Eli Lilly. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. EDAT- 2024/05/16 18:42 MHDA- 2024/06/18 17:41 PMCR- 2024/05/16 CRDT- 2024/05/16 12:12 PHST- 2024/06/18 17:41 [medline] PHST- 2024/05/16 18:42 [pubmed] PHST- 2024/05/16 12:12 [entrez] PHST- 2024/05/16 00:00 [pmc-release] AID - 2356254 [pii] AID - 10.1080/14656566.2024.2356254 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2024 May;25(7):801-818. doi: 10.1080/14656566.2024.2356254. Epub 2024 May 22. PMID- 38752974 OWN - NLM STAT- MEDLINE DCOM- 20240902 LR - 20241010 IS - 1879-8519 (Electronic) IS - 1879-8500 (Linking) VI - 14 IP - 5 DP - 2024 Sep-Oct TI - Exploring the Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Genitourinary Toxicities in Prostate Cancer Patients Undergoing Radiation Therapy: A Case Study and Discussion. PG - 373-376 LID - S1879-8500(24)00086-9 [pii] LID - 10.1016/j.prro.2024.04.006 [doi] AB - Radiation therapy is a common treatment modality offered to patients with localized prostate cancer. It can be associated with early radiation-induced toxicities including dysuria, nocturia, frequency, urgency, spasm, and, rarely, hematuria. Early toxicities usually resolve once the treatment period has ended. Chronic toxicities are less common, and rarely, patients may experience radiation-induced hemorrhagic cystitis and hematuria months or years after radiation. We herein describe the case of a 65-year-old man with a past medical history of type-2 diabetes mellitus who experienced hemorrhagic cystitis for months following his radiation therapy. The patient was on sodium-glucose cotransporter-2 inhibitor therapy (empagliflozin), which we highlight as a potential risk factor for hemorrhagic cystitis. After cessation of Jardiance and initiation of semaglutide (GLP-1 agonist), his urinary symptoms significantly improved. To the best of our knowledge, this is the first such case reported. CI - Copyright (c) 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. FAU - Andrianu, Kelly AU - Andrianu K AD - College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska. Electronic address: knisbet@unmc.edu. FAU - Works, Duncan AU - Works D AD - College of Medicine, University of Nebraska Medical Center, Omaha, Nebraska. FAU - Christiansen, Andrew AU - Christiansen A AD - Department of Urology, University of Nebraska Medical Center, Omaha, Nebraska. FAU - Enke, Charles AU - Enke C AD - Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska. FAU - Chaiken, Lisa AU - Chaiken L AD - Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska. FAU - Baine, Michael AU - Baine M AD - Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska. LA - eng PT - Case Reports PT - Journal Article DEP - 20240516 PL - United States TA - Pract Radiat Oncol JT - Practical radiation oncology JID - 101558279 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Humans MH - Male MH - Aged MH - *Prostatic Neoplasms/radiotherapy/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Radiation Injuries/etiology MH - Diabetes Mellitus, Type 2/complications MH - Cystitis/etiology/chemically induced COIS- Disclosures None. EDAT- 2024/05/16 12:43 MHDA- 2024/09/02 08:45 CRDT- 2024/05/16 10:37 PHST- 2023/11/21 00:00 [received] PHST- 2024/03/30 00:00 [revised] PHST- 2024/04/03 00:00 [accepted] PHST- 2024/09/02 08:45 [medline] PHST- 2024/05/16 12:43 [pubmed] PHST- 2024/05/16 10:37 [entrez] AID - S1879-8500(24)00086-9 [pii] AID - 10.1016/j.prro.2024.04.006 [doi] PST - ppublish SO - Pract Radiat Oncol. 2024 Sep-Oct;14(5):373-376. doi: 10.1016/j.prro.2024.04.006. Epub 2024 May 16. PMID- 38747140 OWN - NLM STAT- MEDLINE DCOM- 20240709 LR - 20260617 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 8 DP - 2024 Aug TI - Japan initiates market authorization of weight-loss drug semaglutide under universal health coverage, but with stringent prescription restrictions. PG - 3006-3008 LID - 10.1111/dom.15638 [doi] FAU - Hakariya, Hayase AU - Hakariya H AUID- ORCID: 0000-0002-9121-4551 AD - Interfaculty Institute of Biochemistry, University of Tuebingen, Tuebingen, Germany. AD - Institute for Pharmaceutical and Social Health Sciences, Kyoto, Japan. FAU - Ohnishi, Mutsuko AU - Ohnishi M AD - Medical Governance Research Institute, Tokyo, Japan. FAU - Tanimoto, Tetsuya AU - Tanimoto T AUID- ORCID: 0000-0002-9818-8587 AD - Navitas Clinic, Tokyo, Japan. LA - eng GR - Toyobo Biotechnology Foundation/ PT - Letter PT - Research Support, Non-U.S. Gov't DEP - 20240515 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - Japan MH - *Universal Health Insurance MH - Anti-Obesity Agents/therapeutic use MH - Drug Approval MH - Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - Semaglutide EDAT- 2024/05/15 06:43 MHDA- 2024/07/09 12:42 CRDT- 2024/05/15 04:54 PHST- 2024/04/11 00:00 [revised] PHST- 2024/03/09 00:00 [received] PHST- 2024/04/12 00:00 [accepted] PHST- 2024/07/09 12:42 [medline] PHST- 2024/05/15 06:43 [pubmed] PHST- 2024/05/15 04:54 [entrez] AID - 10.1111/dom.15638 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Aug;26(8):3006-3008. doi: 10.1111/dom.15638. Epub 2024 May 15. PMID- 38738340 OWN - NLM STAT- MEDLINE DCOM- 20240709 LR - 20260618 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 8 DP - 2024 Aug TI - Cost-utility analysis and drug pricing for tirzepatide for type 2 diabetes in the Chinese market compared with semaglutide. PG - 3176-3190 LID - 10.1111/dom.15645 [doi] AB - AIM: To investigate the most matchable price of tirzepatide (TIRZ) compared with semaglutide (SEMA) in the treatment of type 2 diabetes in China. METHODS: The patient cohort and clinical efficacy data were derived from the SURPASS-2 trial. Cost-utility analysis and a binary search were performed to identify the most matchable price of TIRZ from a Chinese healthcare provider's perspective. RESULTS: After lifetime simulation, the quality-adjusted life years of TIRZ 5, 10, 15 mg and SEMA 1 mg were 11.17, 11.21, 11.27 and 11.12 years, respectively. Despite an initial assumption that the annual cost of TIRZ equals that of SEMA, our analysis revealed that TIRZ is probably more cost-effective than SEMA. A thorough evaluation of pricing showed that the cost ranges for TIRZ at doses of 5, 10 and 15 mg were $1628.61-$1846.23, $1738.40-$2140.95 and $1800.30-$2430.81, respectively. After adjustment in the univariate sensitivity analysis, the cost ranges for TIRZ 5, 10 and 15 mg were $1542.68-$1757.57, $1573.00-$1967.16 and $1576.54-$2133.96, respectively. These cost intervals were validated through robust probabilistic sensitivity analysis and scenario analysis, except for the cost range for TIRZ 5 mg. CONCLUSIONS: This study shows that, using SEMA as a reference, the annual costs for TIRZ 10 and 15 mg are $1573.00-$1967.16 and $1576.54-$2133.96, respectively, for patients with type 2 diabetes in China. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Hu, Shanshan AU - Hu S AUID- ORCID: 0009-0004-5708-9744 AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Shi, Chenyang AU - Shi C AUID- ORCID: 0000-0002-0626-0781 AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Ma, Yuhang AU - Ma Y AUID- ORCID: 0000-0002-5931-5846 AD - Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Shuowen AU - Wang S AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Gu, Shengying AU - Gu S AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Qi, Chendong AU - Qi C AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Fan, Guorong AU - Fan G AUID- ORCID: 0000-0001-5141-5896 AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng GR - Z-2021-46-2101/Research Fund for Clinical Pharmacy of China International Medical Foundation/ GR - 81973289/National Natural Science Foundation of China/ PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240513 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/economics MH - *Glucagon-Like Peptides/therapeutic use/economics MH - *Cost-Benefit Analysis MH - China MH - *Quality-Adjusted Life Years MH - *Hypoglycemic Agents/economics/therapeutic use MH - *Drug Costs/statistics & numerical data MH - Male MH - Female MH - Middle Aged MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - cost-utility analysis OT - drug pricing OT - semaglutide OT - tirzepatide OT - type 2 diabetes EDAT- 2024/05/13 06:42 MHDA- 2024/07/09 12:42 CRDT- 2024/05/13 04:43 PHST- 2024/04/22 00:00 [revised] PHST- 2024/01/15 00:00 [received] PHST- 2024/04/22 00:00 [accepted] PHST- 2024/07/09 12:42 [medline] PHST- 2024/05/13 06:42 [pubmed] PHST- 2024/05/13 04:43 [entrez] AID - 10.1111/dom.15645 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Aug;26(8):3176-3190. doi: 10.1111/dom.15645. Epub 2024 May 13. PMID- 38723893 OWN - NLM STAT- MEDLINE DCOM- 20240803 LR - 20260127 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 30 IP - 8 DP - 2024 Aug TI - Switching to Tirzepatide 5 mg From Glucagon-Like Peptide-1 Receptor Agonists: Clinical Expectations in the First 12 Weeks of Treatment. PG - 701-709 LID - S1530-891X(24)00515-9 [pii] LID - 10.1016/j.eprac.2024.05.005 [doi] AB - OBJECTIVE: This prospective study aimed to describe the clinical course in terms of glycemic outcomes, body weight, and adverse events during the first 12 weeks following a switch from glucagon-like peptide-1 receptor agonists (GLP-1 RAs) directly to tirzepatide 5 mg. METHODS: Participants were >/=18 years with type 2 diabetes (T2D), glycated hemoglobin (HbA1c) >/=6.5% to /=25 kg/m(2) and were on a stable treatment dose of GLP-1 RAs (liraglutide every day [1.2, 1.8 mg], semaglutide once-weekly [0.5, 1.0, 2.0 mg], or dulaglutide once-weekly [0.75, 1.5, 3.0, and 4.5 mg]) for >/=3 months at baseline. The primary end point was HbA1c change from baseline at week 12. Secondary end points included change from baseline in fasting serum glucose, body weight, and glucose assessed by continuous glucose monitoring. Safety was also assessed. RESULTS: Participants were 58.3 years on average, with baseline HbA1c 7.39%, body mass index 35.18 kg/m(2), T2D duration around 12.4 years, and included 55% females. Semaglutide (55%) and dulaglutide (42%) were the most commonly used GLP-1 RAs at baseline with semaglutide 1.0 mg and dulaglutide 1.5 mg being the most common treatment doses. At week 12, mean HbA1c changed from baseline by -0.43%, fasting serum glucose by -7.83 mg/dL, and body weight by -2.15 kg (all P < .01). Glycemic outcomes and body weight improved in participants in all baseline GLP-1 RA subgroups. Twenty participants (13.2%) developed gastrointestinal events. Three (2%) participants discontinued tirzepatide due to adverse events. There were no severe hypoglycemic events or deaths. CONCLUSION: In this prospective study, when people with T2D on stable GLP-1 RA treatment were switched directly to tirzepatide 5 mg, they experienced improved glycemic outcomes and additional weight reduction with an acceptable risk of adverse gastrointestinal events over 12 weeks. CI - Copyright (c) 2024 AACE. Published by Elsevier Inc. All rights reserved. FAU - Jabbour, Serge AU - Jabbour S AD - Thomas Jefferson University, Philadelphia, Pennsylvania. FAU - Paik, Jim S AU - Paik JS AD - Eli Lilly and Company, Indianapolis, Indiana. Electronic address: paik_jim_s@lilly.com. FAU - Aleppo, Grazia AU - Aleppo G AD - Feinberg School of Medicine, Northwestern University, Chicago, Illinois. FAU - Sharma, Palash AU - Sharma P AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Gomez Valderas, Elisa AU - Gomez Valderas E AD - Eli Lilly and Company, Indianapolis, Indiana. FAU - Benneyworth, Brian D AU - Benneyworth BD AD - Eli Lilly and Company, Indianapolis, Indiana. LA - eng PT - Journal Article DEP - 20240508 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Blood Glucose) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Blood Glucose/drug effects/analysis MH - Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Drug Substitution MH - Gastric Inhibitory Polypeptide MH - *Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects MH - Glucagon-Like Peptide-2 Receptor MH - *Glucagon-Like Peptides/analogs & derivatives/administration & dosage/therapeutic use/adverse effects MH - Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/administration & dosage/therapeutic use/adverse effects MH - *Immunoglobulin Fc Fragments/administration & dosage/therapeutic use/adverse effects MH - Liraglutide/administration & dosage/therapeutic use/adverse effects MH - Prospective Studies MH - Recombinant Fusion Proteins/administration & dosage/therapeutic use/adverse effects MH - Tirzepatide MH - Semaglutide OTO - NOTNLM OT - GLP-1 RA OT - clinical considerations OT - gastrointestinal tolerability OT - glycemic levels OT - switching OT - tirzepatide COIS- Disclosure S.J. reports consultancy fees from Eli Lilly and Company and Sanofi. G.A. received consulting fees from Dexcom, Insulet, and Medscape. J.S.P., P.S., E.G.V., and B.D.B. are employees and shareholders of Eli Lilly and Company. EDAT- 2024/05/10 00:42 MHDA- 2024/08/04 13:44 CRDT- 2024/05/09 19:29 PHST- 2024/02/22 00:00 [received] PHST- 2024/05/03 00:00 [revised] PHST- 2024/05/03 00:00 [accepted] PHST- 2024/08/04 13:44 [medline] PHST- 2024/05/10 00:42 [pubmed] PHST- 2024/05/09 19:29 [entrez] AID - S1530-891X(24)00515-9 [pii] AID - 10.1016/j.eprac.2024.05.005 [doi] PST - ppublish SO - Endocr Pract. 2024 Aug;30(8):701-709. doi: 10.1016/j.eprac.2024.05.005. Epub 2024 May 8. PMID- 38718449 OWN - NLM STAT- MEDLINE DCOM- 20240713 LR - 20260127 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 18 IP - 5 DP - 2024 May TI - Efficacy and safety of oral semaglutide in type 2 diabetes: A systematic review of real-world evidence. PG - 103024 LID - S1871-4021(24)00085-7 [pii] LID - 10.1016/j.dsx.2024.103024 [doi] AB - BACKGROUND AND AIMS: Oral semaglutide has undergone global Phase 3 development programs named PIONEER and approved for therapeutic use in people with type 2 diabetes (T2D). We aim to systematically review the efficacy and safety of oral semaglutide in real-world settings. METHODS: We systematically searched the electronic databases of PubMed, Google Scholar, and ClinicalTrials.gov from inception until March 15, 2024, using several keywords with Boolean "AND". We retrieved all the available granular details of real-world studies (RWS). RESULTS: To date, results from four prospective and ten retrospective real-world studies of oral semaglutide in T2D are available. In prospective studies, the primary outcome of HbA1c reduction varied from -0.9 % to -1.6 %, weight loss varied from -4.7 kg to -8.2 kg and HbA1c target of <7 % was achieved in 30 %-64 % with oral semaglutide. In retrospective studies, HbA1c reduction varied from -0.4 % to -1.8 %, weight reduction varied from -1.4 to -9.0 kg, HbA1c target of <7 % was achieved in 32-64 %, and 30-41 % of people with T2D had >/=5 % weight loss with oral semaglutide. Gastrointestinal adverse events with oral semaglutide varied from 16 % to 50 % in prospective and 6 %-47 % in retrospective RWS. Overall, 0 %-18 % of patients had oral semaglutide discontinuation due to any cause. CONCLUSION: Oral semaglutide exhibited a reasonable reduction in HbA1c and weight in people with T2D, consistent with the findings from PIONEER trials. While no new safety issues emerged, the inherent limitations of RWS underscore the necessity of long-term investigations to comprehensively assess safety. CI - Copyright (c) 2024 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Singh, Awadhesh Kumar AU - Singh AK AD - G. D Hospital & Diabetes Institute, Kolkata, West Bengal, India; Horizon Multispecialty Hospital, Kolkata, West Bengal, India; Sun Valley Hospital & Diabetes Research Centre, Guwahati, Assam, India. Electronic address: drawadheshkumarsingh@gmail.com. FAU - Singh, Ritu AU - Singh R AD - Horizon Multispecialty Hospital, Kolkata, West Bengal, India. FAU - Singh, Akriti AU - Singh A AD - College of Medicine and JNM Hospital, Kalyani, Nadia, West Bengal, India. FAU - Misra, Anoop AU - Misra A AD - Fortis C-DOC Hospital for Diabetes & Allied Sciences, New Delhi, India; National Diabetes, Obesity and Cholesterol Foundation, New Delhi, India; Diabetes Foundation (India), New Delhi, India. LA - eng PT - Journal Article PT - Systematic Review DEP - 20240501 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Administration, Oral MH - Prognosis MH - Glycated Hemoglobin/analysis MH - Semaglutide OTO - NOTNLM OT - Oral semaglutide OT - Prospective studies OT - Real-world evidence OT - Retrospective studies COIS- Declaration of competing interest Although authors have no conflict of interest, related to this article titled "Efficacy and Safety of Oral Semaglutide in Type 2 Diabetes: A Systematic Review of Real-World Evidence" they declare the following financial interests/personal relationships which may be considered as potential competing interests. AKS has received speaker and consultant fees from Novo-Nordisk, Sanofi, Boehringer Ingelheim, Astra Zeneca, USV, Alkem Laboratory, Lupin, and Sun Pharma. AS and RS have nothing to declare. AM reports a relationship with Novo-Nordisk, Eli Lilly, Lupin, Boehringer Ingelheim, Janssen, Cipla, AstraZeneca, and Glenmark that includes: funding grants, speaking and lecture fees, and travel reimbursement. EDAT- 2024/05/09 00:47 MHDA- 2024/07/14 02:43 CRDT- 2024/05/08 18:01 PHST- 2024/03/25 00:00 [received] PHST- 2024/04/22 00:00 [revised] PHST- 2024/04/24 00:00 [accepted] PHST- 2024/07/14 02:43 [medline] PHST- 2024/05/09 00:47 [pubmed] PHST- 2024/05/08 18:01 [entrez] AID - S1871-4021(24)00085-7 [pii] AID - 10.1016/j.dsx.2024.103024 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2024 May;18(5):103024. doi: 10.1016/j.dsx.2024.103024. Epub 2024 May 1. PMID- 38711208 OWN - NLM STAT- MEDLINE DCOM- 20240801 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 15 IP - 8 DP - 2024 Aug TI - PIONEER REAL Japan: Baseline characteristics of a multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in clinical practice in Japan. PG - 1047-1056 LID - 10.1111/jdi.14219 [doi] AB - AIMS/INTRODUCTION: PIONEER REAL Japan was a non-interventional, multicenter, prospective study investigating oral semaglutide in adults with type 2 diabetes in routine clinical practice. We report baseline characteristics of participants enrolled in this study. MATERIALS AND METHODS: Adults aged >/=20 years with type 2 diabetes but no previous treatment with injectable glucose-lowering medication were enrolled. Participants initiated oral semaglutide at their treating physician's discretion and were followed for 34-44 weeks. Participants were stratified into <75-year-old and >/=75-year-old subgroups. RESULTS: A total of 624 participants initiated the study. The mean (standard deviation) age was 64.1 years (14.1), the mean (standard deviation) body weight was 72.4 kg (16.1), and the mean (standard deviation) body mass index was 27.5 kg/m(2) (5.0). Participants had a median (interquartile range) type 2 diabetes duration of 9.3 years (4.2, 15.2) and mean (standard deviation) glycated hemoglobin 7.7% (1.1). Most (75.6%) participants were taking glucose-lowering medications at baseline; the most common was metformin (51.9%). The main reasons for initiating oral semaglutide were glycemic control and weight loss. Most (86.0%) participants had an individualized target for glycemic control of glycated hemoglobin /=75-year-old subgroup. CONCLUSIONS: PIONEER REAL Japan describes the characteristics of individuals with type 2 diabetes prescribed oral semaglutide. The baseline characteristics provide insights into Japanese individuals with type 2 diabetes prescribed oral semaglutide in clinical practice. CI - (c) 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Suzuki, Ryo AU - Suzuki R AUID- ORCID: 0000-0002-2965-6906 AD - Department of Diabetes, Metabolism, and Endocrinology, Tokyo Medical University, Tokyo, Japan. FAU - Amadid, Hanan AU - Amadid H AD - Global Clinical Drug Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Major-Pedersen, Atheline AU - Major-Pedersen A AD - Global Safety, Novo Nordisk A/S, Soborg, Denmark. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology, and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, Japan. AD - Center for One Medicine Innovative Translational Research, Gifu University, Gifu, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kyoto, Japan. LA - eng GR - Novo Nordisk/ PT - Journal Article PT - Multicenter Study DEP - 20240506 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Prospective Studies MH - Female MH - Japan/epidemiology MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Middle Aged MH - Aged MH - Administration, Oral MH - Blood Glucose/analysis MH - Glycated Hemoglobin/analysis MH - Adult MH - Semaglutide PMC - PMC11292382 OTO - NOTNLM OT - Prospective studies OT - Semaglutide OT - Type 2 diabetes COIS- RS received lecture fees from Novo Nordisk. HA and AM-P report employment with, and being shareholders in, Novo Nordisk. DY received consulting/lecture fees from Novo Nordisk Pharma Ltd, Nippon Boehringer Ingelheim, Eli Lilly Japan K.K., and Kyowa Kirin Co. Ltd; and grants from Arkray Inc., Novo Nordisk Pharma Ltd, Nippon Boehringer Ingelheim, Taisho Pharmaceutical Co. Ltd, and Terumo Corporation. DY is an Editorial Board member of the Journal of Diabetes Investigation and a co-author of this article. To minimize bias, they were excluded from all editorial decision-making related to the acceptance of this article for publication. Approval of the research protocol: The protocol for this research project has been approved by suitably constituted Ethics Committees or Institutional Review Boards of the institutions and it conforms to the provisions of the Declaration of Helsinki. Ethics Committees, Institutional Review Boards and approval numbers are listed in the Supporting Information. Informed consent: All informed consent was obtained from the participants and/or guardians. Registration no. of the study/trial: This study is registered with ClinicalTrials.gov (NCT04878393; first submitted May 5, 2021). Animal studies: Not applicable. EDAT- 2024/05/07 06:42 MHDA- 2024/08/01 12:42 PMCR- 2024/05/06 CRDT- 2024/05/07 00:42 PHST- 2024/03/18 00:00 [revised] PHST- 2023/12/13 00:00 [received] PHST- 2024/04/08 00:00 [accepted] PHST- 2024/08/01 12:42 [medline] PHST- 2024/05/07 06:42 [pubmed] PHST- 2024/05/07 00:42 [entrez] PHST- 2024/05/06 00:00 [pmc-release] AID - JDI14219 [pii] AID - 10.1111/jdi.14219 [doi] PST - ppublish SO - J Diabetes Investig. 2024 Aug;15(8):1047-1056. doi: 10.1111/jdi.14219. Epub 2024 May 6. PMID- 38706431 OWN - NLM STAT- MEDLINE DCOM- 20240627 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 32 IP - 7 DP - 2024 Jul TI - The association between weight loss medications and cardiovascular complications. PG - 1401-1409 LID - 10.1002/oby.24037 [doi] AB - OBJECTIVE: Obesity and its cardiovascular complications are major causes of morbidity and mortality. Little is known in real-world settings about the effect of newly approved antiobesity medications (AOMs) on cardiovascular complications among patients with obesity. METHODS: This retrospective cohort study examined the association between newly approved AOM use and cardiovascular events among Medicare patients with obesity using data from 2020 to 2022. Patient age, gender, comorbidity scores, socioeconomic status, and baseline cardiovascular comorbidities were compared descriptively. Subgroup analysis compared variables by medication type. Relative risk and absolute risk of cardiovascular disease (CVD) events were estimated using Cox and Aalen regression models. RESULTS: The analysis included 5926 patients treated with semaglutide and tirzepatide, including Ozempic (5404 patients), Wegovy (375 patients), or Mounjaro (147 patients). Hypertension, type 2 diabetes, and hyperlipidemia were the most common comorbidities. For patients with AOMs, less incidence of heart failure (4.89% vs. 6.13%, p < 0.0001), atrial fibrillation (3.83% vs. 5.17%, p < 0.0001), arrhythmia (3.59% vs. 4.14%, p < 0.0153), and peripheral vascular disease (3.44% vs. 2.94%, p < 0.0395) was found versus patients without AOMs. Patients receiving AOMs showed an 8% risk reduction in any CVD. Protective effect on CVD was apparent over the first 375 days. CONCLUSIONS: Results suggest that utilization of AOMs effectively alleviates the high prevalence of CVD. CI - (c) 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Baser, Onur AU - Baser O AUID- ORCID: 0000-0001-7447-5672 AD - Department of Economics, Bogazici University, Istanbul, Turkey. AD - Graduate School of Public Health, City University of New York, New York, New York, USA. AD - Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA. FAU - Samayoa, Gabriela AU - Samayoa G AD - Columbia Data Analytics, New York, New York, USA. FAU - Rodchenko, Katarzyna AU - Rodchenko K AD - Columbia Data Analytics, New York, New York, USA. FAU - Isenman, Lauren AU - Isenman L AD - Columbia Data Analytics, Ann Arbor, Michigan, USA. FAU - Baser, Erdem AU - Baser E AD - Columbia Data Analytics, New York, New York, USA. FAU - Yapar, Nehir AU - Yapar N AD - Columbia Data Analytics, New York, New York, USA. LA - eng PT - Journal Article DEP - 20240506 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Anti-Obesity Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Male MH - Female MH - Retrospective Studies MH - *Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - Aged MH - *Obesity/complications/epidemiology MH - *Anti-Obesity Agents/therapeutic use/adverse effects MH - United States/epidemiology MH - Comorbidity MH - Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Aged, 80 and over MH - Medicare/statistics & numerical data MH - Middle Aged MH - Weight Loss/drug effects MH - Incidence MH - Hypertension/drug therapy/epidemiology MH - Risk Factors MH - Hyperlipidemias/drug therapy/epidemiology MH - Glucagon-Like Peptides MH - Semaglutide EDAT- 2024/05/06 06:44 MHDA- 2024/06/27 06:43 CRDT- 2024/05/06 03:53 PHST- 2024/03/11 00:00 [revised] PHST- 2023/12/12 00:00 [received] PHST- 2024/03/19 00:00 [accepted] PHST- 2024/06/27 06:43 [medline] PHST- 2024/05/06 06:44 [pubmed] PHST- 2024/05/06 03:53 [entrez] AID - 10.1002/oby.24037 [doi] PST - ppublish SO - Obesity (Silver Spring). 2024 Jul;32(7):1401-1409. doi: 10.1002/oby.24037. Epub 2024 May 6. PMID- 38701096 OWN - NLM STAT- MEDLINE DCOM- 20240503 LR - 20260901 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 19 IP - 5 DP - 2024 TI - Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial. PG - e0302155 LID - 10.1371/journal.pone.0302155 [doi] LID - e0302155 AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674). CI - Copyright: (c) 2024 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Lin, Yu-Hao AU - Lin YH AUID- ORCID: 0000-0002-8244-8495 AD - Department of Endocrinology, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian, China. FAU - Zhang, Zhi-Jun AU - Zhang ZJ AD - Department of Endocrinology, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian, China. FAU - Zhong, Jin-Qing AU - Zhong JQ AD - Department of Laboratory Medicine, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian, China. FAU - Wang, Zhi-Yi AU - Wang ZY AD - Department of Endocrinology, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian, China. FAU - Peng, Yi-Ting AU - Peng YT AD - Department of Endocrinology, Zhongshan Hospital Xiamen University, Xiamen, Fujian, China. FAU - Lin, Yan-Mei AU - Lin YM AD - Department of Endocrinology, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian, China. FAU - Zhang, Huo-Ping AU - Zhang HP AD - Department of Ultrasound, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian, China. FAU - Tian, Jian-Qing AU - Tian JQ AD - Department of Endocrinology, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian, China. LA - eng PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240503 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Benzhydryl Compounds) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Benzhydryl Compounds/therapeutic use/adverse effects MH - Blood Glucose/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Double-Blind Method MH - Drug Therapy, Combination MH - *Glucagon-Like Peptides/therapeutic use MH - *Glucosides/therapeutic use/adverse effects MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - *Non-alcoholic Fatty Liver Disease/drug therapy/complications MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Treatment Outcome MH - Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC11068176 COIS- The authors have declared that no competing interests exist. EDAT- 2024/05/03 18:47 MHDA- 2024/05/03 18:48 PMCR- 2024/05/03 CRDT- 2024/05/03 13:35 PHST- 2024/01/03 00:00 [received] PHST- 2024/03/23 00:00 [accepted] PHST- 2024/05/03 18:48 [medline] PHST- 2024/05/03 18:47 [pubmed] PHST- 2024/05/03 13:35 [entrez] PHST- 2024/05/03 00:00 [pmc-release] AID - PONE-D-23-41958 [pii] AID - 10.1371/journal.pone.0302155 [doi] PST - epublish SO - PLoS One. 2024 May 3;19(5):e0302155. doi: 10.1371/journal.pone.0302155. eCollection 2024. PMID- 38700282 OWN - NLM STAT- MEDLINE DCOM- 20240830 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 15 IP - 9 DP - 2024 Sep TI - Efficacy and tolerability of oral semaglutide in Japanese patients with type 2 diabetes mellitus: Analysis report from diabetes specialist clinics. PG - 1202-1210 LID - 10.1111/jdi.14225 [doi] AB - INTRODUCTION: Glucagon-like peptide 1 receptor agonists (GLP1Ras) have emerged as pivotal agents in diabetes management and organ protection. However, their use is limited due to the necessity for injectable administration. The advent of the first oral GLP1Ra (oral semaglutide) in Japan since 2021 is expected to expand its usage. The aim of this study is to survey the efficacy and tolerability of oral semaglutide in clinical practice. MATERIALS AND METHODS: We retrospectively analyzed 120 outpatients diagnosed with type 2 diabetes mellitus who had received oral semaglutide for >6 months. Changes in clinical parameters during oral semaglutide treatment from baseline to 12 months were analyzed. The inverse probability weighting method using the propensity score was used to evaluate the differences in clinical parameters at 6 months after treatment, based on the patients' obesity levels. RESULTS: Body weight (BW), glycated hemoglobin A(1c) (HbA(1c)), and alanine aminotransferase (ALT) levels at baseline decreased significantly after treatment compared with those at 12 months (P < 0.001, P < 0.001, and P = 0.03, respectively). The patients were divided into two groups using a cutoff baseline body mass index (BMI) of 30.3 kg/m(2). Although no significant difference was observed, changes in body weight and HbA(1c) indicated a potentially greater decrease in the BMI >== 30.3 group than that in the BMI < 30.3 group (P = 0.07 and 0.13, respectively). Among 206 registered patients, 25 (12.1%) discontinued oral-semaglutide treatment owing to adverse effects, including gastrointestinal symptoms. CONCLUSIONS: Oral semaglutide treatment demonstrates efficacy and tolerability for managing type 2 diabetes mellitus in Japan. Significant improvements in metabolic factors induced by oral semaglutide are anticipated, particularly in obese patients. CI - (c) 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Inokuchi, Tetsuaki AU - Inokuchi T AUID- ORCID: 0009-0000-2893-4436 AD - Inokuchi Medical Clinic, Fukuoka, Japan. AD - Department of Auditors, Japan Physicians Association, Tokyo, Japan. FAU - Fukumoto, Yoshihide AU - Fukumoto Y AD - Fukumoto Clinic, Kagoshima, Japan. FAU - Lee, Gendai AU - Lee G AD - Diabetes and Endocrinology, Diabetes and Kidney Medical Corporation Gendai Clinic, Fukuoka, Japan. FAU - Yokomizo, Yoshifumi AU - Yokomizo Y AD - Yokomizo Clinic, Fukuoka, Japan. FAU - Tanaka, Kokichi AU - Tanaka K AD - Tanaka Medical Clinic, Fukuoka, Japan. FAU - Chosa, Michiko AU - Chosa M AD - Wakamatsu Memorial Hospital, Kagoshima, Japan. FAU - Doi, Masaru AU - Doi M AD - Doi Clinic, Kumamoto, Japan. FAU - Tamaki, Noboru AU - Tamaki N AD - Tamaki Clinic, Miyazaki, Japan. FAU - Goto, Seiichi AU - Goto S AD - Goto Clinic, Fukuoka, Japan. FAU - Ichikawa, Kojiro AU - Ichikawa K AD - Fukutsu Clinic, Fukuoka, Japan. FAU - Kobayashi, Kazuo AU - Kobayashi K AD - Department of Clinical Research Support Center, Japan Physicians Association, Tokyo, Japan. AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. LA - eng PT - Journal Article DEP - 20240503 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - Administration, Oral MH - Blood Glucose/analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - East Asian People MH - Glucagon-Like Peptides/therapeutic use MH - *Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/therapeutic use MH - Japan MH - Retrospective Studies MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Semaglutide PMC - PMC11363112 OTO - NOTNLM OT - Glucagon-like peptide 1 receptor agonist OT - Oral semaglutide OT - Tolerability COIS- The authors declare no conflict of interest. Approval of the research protocol: This research protocol was approved by the Ethics Committee of Diabetes and Endocrinology, Diabetes and Kidney Medical Corporation Gendai Clinic (No. 220705-0603-22). Informed consent: This study was conducted in accordance with the Declaration of Helsinki. Registry and the registration no. of the study/trial: Approval on July 5, 2022 and (No. 220705-0603-22). Animal studies: N/A. EDAT- 2024/05/03 12:52 MHDA- 2024/08/31 09:51 PMCR- 2024/05/03 CRDT- 2024/05/03 08:53 PHST- 2024/03/28 00:00 [revised] PHST- 2024/02/16 00:00 [received] PHST- 2024/04/14 00:00 [accepted] PHST- 2024/08/31 09:51 [medline] PHST- 2024/05/03 12:52 [pubmed] PHST- 2024/05/03 08:53 [entrez] PHST- 2024/05/03 00:00 [pmc-release] AID - JDI14225 [pii] AID - 10.1111/jdi.14225 [doi] PST - ppublish SO - J Diabetes Investig. 2024 Sep;15(9):1202-1210. doi: 10.1111/jdi.14225. Epub 2024 May 3. PMID- 38695547 OWN - NLM STAT- MEDLINE DCOM- 20250218 LR - 20260127 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 110 IP - 3 DP - 2025 Feb 18 TI - Improvement of beta-Cell Function After Switching From DPP-4 Inhibitors to Oral Semaglutide: SWITCH-SEMA2 Post Hoc Analysis. PG - e583-e591 LID - 10.1210/clinem/dgae213 [doi] AB - CONTEXT: Whether continuation of dipeptidyl peptidase-4 inhibitors (DPP-4is) or switching to oral semaglutide is more beneficial for beta-cell function is unclear. OBJECTIVE: To assess the efficacy of switching from DPP-4is to oral semaglutide for beta-cell function compared with DPP-4i continuation. METHODS: Post hoc analysis of SWITCH-SEMA 2, a multicenter prospective randomized controlled trial on the switch to oral semaglutide vs DPP-4i continuation without dose adjustment for 24 weeks in subjects with type 2 diabetes treated with DPP-4is, was conducted. Changes in markers for glucose metabolism, including homeostatic model assessment (HOMA2) scores and disposition index (DI), were compared between the groups. RESULTS: A total of 146 subjects (semaglutide group, 69; DPP-4i group, 77) were analyzed. In the semaglutide group, glycemic control, liver enzyme deviations, and lipid profiles improved after 24 weeks. Regarding indices for beta-cell function, changes in HOMA2-beta as well as DI, reflecting the ability of beta-cells to compensate for insulin resistance, were significantly higher in the semaglutide group compared with the DPP-4i group (mean change, +10.4 vs +0.6 in HOMA2-beta [P = .001] and +0.09 vs 0.0 in DI [P < .001]). Improvement in DI in the semaglutide group was correlated significantly to changes in body mass index (BMI), HbA1c, and fatty liver index reflecting liver steatosis. Multiple linear regression analysis revealed that dose of semaglutide (>/= 7 mg/day), reduction in fatty liver index, and metformin nonuse were independently associated with improvement of DI. CONCLUSION: Switching to oral semaglutide ameliorated beta-cell function compared with DPP-4is, presumably via tissue-to-tissue crosstalk between liver and beta-cells. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site-for further information please contact journals.permissions@oup.com. FAU - Nomoto, Hiroshi AU - Nomoto H AUID- ORCID: 0000-0003-0713-221X AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Furusawa, Sho AU - Furusawa S AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Yokoyama, Hiroki AU - Yokoyama H AD - Jiyugaoka Medical Clinic, Obihiro 080-0016, Japan. FAU - Suzuki, Yuka AU - Suzuki Y AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Izumihara, Rimi AU - Izumihara R AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Oe, Yuki AU - Oe Y AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Takahashi, Kiyohiko AU - Takahashi K AD - Division of Diabetes and Endocrinology, Department of Medicine, Hakodate Central General Hospital, Hakodate 040-8585, Japan. FAU - Miya, Aika AU - Miya A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Kameda, Hiraku AU - Kameda H AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Cho, Kyu Yong AU - Cho KY AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Takeuchi, Jun AU - Takeuchi J AD - Sapporo Diabetes and Thyroid Clinic, Sapporo 060-0807, Japan. FAU - Kurihara, Yoshio AU - Kurihara Y AD - Kurihara Clinic, Sapporo 004-0053, Japan. FAU - Nakamura, Akinobu AU - Nakamura A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Atsumi, Tatsuya AU - Atsumi T AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Insulin-Secreting Cells/drug effects/physiology/metabolism MH - *Dipeptidyl-Peptidase IV Inhibitors/administration & dosage/therapeutic use MH - Male MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Administration, Oral MH - Aged MH - Prospective Studies MH - Blood Glucose MH - *Drug Substitution MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Insulin Resistance MH - Glycated Hemoglobin/analysis MH - Glucagon-Like Peptide 1 MH - Semaglutide OTO - NOTNLM OT - dipeptidyl peptidase-4 inhibitor OT - semaglutide OT - type 2 diabetes OT - beta-cell function EDAT- 2024/05/02 13:00 MHDA- 2025/02/18 18:20 CRDT- 2024/05/02 08:43 PHST- 2024/01/04 00:00 [received] PHST- 2025/02/18 18:20 [medline] PHST- 2024/05/02 13:00 [pubmed] PHST- 2024/05/02 08:43 [entrez] AID - 7662554 [pii] AID - 10.1210/clinem/dgae213 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2025 Feb 18;110(3):e583-e591. doi: 10.1210/clinem/dgae213. PMID- 38692517 OWN - NLM STAT- MEDLINE DCOM- 20241108 LR - 20260415 IS - 1097-6779 (Electronic) IS - 0016-5107 (Linking) VI - 100 IP - 5 DP - 2024 Nov TI - Recellularization via electroporation therapy of the duodenum combined with glucagon-like peptide-1 receptor agonist to replace insulin therapy in patients with type 2 diabetes: 12-month results of a first-in-human study. PG - 896-904 LID - S0016-5107(24)03163-8 [pii] LID - 10.1016/j.gie.2024.04.2904 [doi] AB - BACKGROUND AND AIMS: Studies have shown that hydrothermal duodenal mucosal ablation results in improved glycemic control. Recellularization via electroporation therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization. In this study, we aimed to eliminate exogenous insulin treatment in type 2 diabetes (T2D) patients through a single ReCET procedure combined with a glucagon-like peptide-1 receptor agonist. Feasibility, safety, and (dose) efficacy of ReCET were assessed. METHODS: This first-in-human study included patients with T2D on basal insulin (age, 28-75 years; body mass index, 24-40 kg/m(2); glycosylated hemoglobin, /=0.2 nmol/L). The electroporation dose was optimized during the study, starting with single 600 V and ending with double 750 V treatments. All patients underwent ReCET, after which insulin was discontinued and semaglutide (glucagon-like peptide-1 receptor agonist) was initiated. The primary endpoints were feasibility (procedure time [from catheter in to catheter out], technical success rate), safety, and efficacy (patients off insulin at 6 months; HbA1c, /=30 kg/m(2). Compared with placebo, the use of semaglutide was associated with substantial decreases in long-term relative (WMD -12.1%, 95% CI -13.5 to -10.7) and absolute body weight (WMD -12.3 kg, 95% CI -13.6 to -11.0). At the longest follow-up, 33.4% of participants randomized to semaglutide achieved >/=20% weight loss compared with 2.2% with placebo (RR 15.08, 95% CI 9.31 to 24.43). The risk of gastrointestinal adverse events was higher in participants who took semaglutide than placebo (RR 1:47, 95% CI 1.28 to 1.68); however, the majority of these events were transient and mild-to-moderate in severity and did not require treatment discontinuation. In conclusion, semaglutide is efficacious for sustained weight loss in patients with overweight/obesity and without diabetes. CI - Copyright (c) 2024 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Moiz, Areesha AU - Moiz A AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Division of Experimental Medicine, McGill University, Montreal, Canada. FAU - Levett, Jeremy Y AU - Levett JY AD - Division of Cardiac Surgery, Department of Surgery, McGill University, Montreal, Canada. FAU - Filion, Kristian B AU - Filion KB AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada. FAU - Peri, Katya AU - Peri K AD - Department of Medicine, McGill University, Montreal, Canada. FAU - Reynier, Pauline AU - Reynier P AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. FAU - Eisenberg, Mark J AU - Eisenberg MJ AD - Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada; Division of Experimental Medicine, McGill University, Montreal, Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada; Department of Medicine, McGill University, Montreal, Canada; Division of Cardiology, Jewish General Hospital/McGill University, Montreal, Canada. Electronic address: mark.eisenberg@mcgill.ca. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20240426 PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Humans MH - *Weight Loss/drug effects MH - *Randomized Controlled Trials as Topic MH - Obesity/drug therapy/complications MH - Treatment Outcome MH - Drug Administration Schedule MH - Hypoglycemic Agents/therapeutic use/administration & dosage MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Injections, Subcutaneous MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - obesity OT - semaglutide OT - weight loss COIS- Declaration of competing interest The authors have no competing interests to declare. EDAT- 2024/04/29 01:00 MHDA- 2024/06/14 00:42 CRDT- 2024/04/28 19:25 PHST- 2024/03/13 00:00 [received] PHST- 2024/04/15 00:00 [revised] PHST- 2024/04/19 00:00 [accepted] PHST- 2024/06/14 00:42 [medline] PHST- 2024/04/29 01:00 [pubmed] PHST- 2024/04/28 19:25 [entrez] AID - S0002-9149(24)00319-9 [pii] AID - 10.1016/j.amjcard.2024.04.041 [doi] PST - ppublish SO - Am J Cardiol. 2024 Jul 1;222:121-130. doi: 10.1016/j.amjcard.2024.04.041. Epub 2024 Apr 26. PMID- 38673931 OWN - NLM STAT- MEDLINE DCOM- 20240427 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 8 DP - 2024 Apr 15 TI - Assessment of Thyroid Carcinogenic Risk and Safety Profile of GLP1-RA Semaglutide (Ozempic) Therapy for Diabetes Mellitus and Obesity: A Systematic Literature Review. LID - 10.3390/ijms25084346 [doi] LID - 4346 AB - The broadening application of glucagon-like peptide (GLP)-1 receptor agonists, specifically semaglutide (Ozempic) for the management of diabetes and obesity brings a critical need to evaluate its safety profile, considering estimates of up to 20 million prescriptions per year in the US until 2035. This systematic review aims to assess the incidence of thyroid cancer and detail the spectrum of adverse events associated with semaglutide, focusing on its implications for patient care. Through a systematic search of PubMed, Scopus, and Embase databases up to December 2023, ten randomized controlled trials (RCTs) involving 14,550 participants, with 7830 receiving semaglutide, were analyzed, with an additional number of 18 studies that were separately discussed because they reported data from the same RCTs. The review focused on thyroid cancer incidence, gastrointestinal symptoms, and other significant adverse events attributed to semaglutide. The incidence of thyroid cancer in semaglutide-treated patients was less than 1%, suggesting no significant risk. Adverse events were predominantly gastrointestinal, including nausea (2.05% to 19.95%) and diarrhea (1.4% to 13%). Nasopharyngitis and vomiting were also notable, with mean prevalences of 8.23% and 5.97%, respectively. Other adverse events included increased lipase levels (mean of 6.5%), headaches (mean prevalence of 7.92%), decreased appetite (reported consistently at 7%), influenza symptoms (mean prevalence of 5.23%), dyspepsia (mean prevalence of 5.18%), and constipation (mean prevalence of 6.91%). Serious adverse events varied from 7% to 25.2%, highlighting the need for vigilant patient monitoring. These findings underscore the gastrointestinal nature of semaglutide's adverse events, which, while prevalent, did not significantly deter from its clinical benefits in the treatment landscape. This systematic review provides a comprehensive assessment of semaglutide's safety profile, with a focus on gastrointestinal adverse events and a low incidence of thyroid cancer. Despite the prevalence of gastrointestinal symptoms, semaglutide remains an efficacious option for managing diabetes and obesity. The detailed characterization of adverse events underscores the importance of monitoring and managing these effects in clinical practice, excluding the hypothesis of carcinogenesis. FAU - Feier, Catalin Vladut Ionut AU - Feier CVI AD - First Discipline of Surgery, Department X-Surgery, "Victor Babes" University of Medicine and Pharmacy, 2 E. Murgu Sq., 300041 Timisoara, Romania. AD - First Surgery Clinic, "Pius Brinzeu" Clinical Emergency Hospital, 300723 Timisoara, Romania. FAU - Vonica, Razvan Constantin AU - Vonica RC AD - Preclinical Department, Discipline of Physiology, Faculty of General Medicine, "Lucian Blaga" University of Sibiu, 550169 Sibiu, Romania. FAU - Faur, Alaviana Monique AU - Faur AM AD - Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy, 2 E. Murgu Sq., 300041 Timisoara, Romania. FAU - Streinu, Diana Raluca AU - Streinu DR AUID- ORCID: 0009-0001-5118-2989 AD - Department of Doctoral Studies, "Victor Babes" University of Medicine and Pharmacy, 2 E. Murgu Sq., 300041 Timisoara, Romania. FAU - Muntean, Calin AU - Muntean C AUID- ORCID: 0000-0002-0497-0405 AD - Medical Informatics and Biostatistics, Department III-Functional Sciences, "Victor Babes" University of Medicine and Pharmacy, 2 E. Murgu Sq., 300041 Timisoara, Romania. LA - eng PT - Journal Article PT - Systematic Review DEP - 20240415 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Diabetes Mellitus/drug therapy/epidemiology MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Incidence MH - *Obesity/drug therapy MH - *Thyroid Neoplasms/chemically induced/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC11050669 OTO - NOTNLM OT - Ozempic OT - cancer risk OT - oncology OT - semaglutide OT - thyroid cancer COIS- The authors declare no conflicts of interest. EDAT- 2024/04/27 09:53 MHDA- 2024/04/27 09:54 PMCR- 2024/04/15 CRDT- 2024/04/27 01:14 PHST- 2024/03/22 00:00 [received] PHST- 2024/04/09 00:00 [revised] PHST- 2024/04/13 00:00 [accepted] PHST- 2024/04/27 09:54 [medline] PHST- 2024/04/27 09:53 [pubmed] PHST- 2024/04/27 01:14 [entrez] PHST- 2024/04/15 00:00 [pmc-release] AID - ijms25084346 [pii] AID - ijms-25-04346 [pii] AID - 10.3390/ijms25084346 [doi] PST - epublish SO - Int J Mol Sci. 2024 Apr 15;25(8):4346. doi: 10.3390/ijms25084346. PMID- 38669474 OWN - NLM STAT- MEDLINE DCOM- 20241004 LR - 20260401 IS - 1557-8593 (Electronic) IS - 1520-9156 (Linking) VI - 26 IP - 10 DP - 2024 Oct TI - Initiating GLP-1 Therapy in Combination with FreeStyle Libre Provides Greater Benefit Compared with GLP-1 Therapy Alone. PG - 754-762 LID - 10.1089/dia.2024.0015 [doi] AB - Background and Aim: Glucagon-like peptide-1 receptor agonists (GLP-1 RA) therapy provides glycemic benefits to individuals with type 2 diabetes (T2D). However, the effects of GLP-1 RA therapy in combination with FreeStyle Libre systems (FSL) are unknown. This study aimed to compare changes in hemoglobin A1c (HbA1c) between people acquiring GLP-1 with FSL (GLP-1+FSL) versus GLP-1 without FSL (GLP-1). Methods: This real-world study used Optum's de-identified Market Clarity Data, a linked electronic health records (EHR)-claims database, and included adults with T2D and HbA1c >/=8% who acquired their first GLP-1 RA medication between 2018 and 2022. GLP-1+FSL subjects acquired their first FSL within +/-30 days of their first GLP-1 acquisition. Cohorts were matched 1:5 on baseline insulin therapy, age, sex, baseline HbA1c, and GLP-1 type. Paired changes in HbA1c were compared between unmatched and matched groups at 6 months. Results: The study included 24,724 adults in the unmatched cohort (GLP-1+FSL, n = 478; GLP-1, n = 24,246). The matched cohort included 478 GLP-1+FSL users and 2,390 GLP-1 users: mean age 53.5 +/- 11.8 and 53.5 +/- 11.3 years, HbA1c 10.25 +/- 1.68% and 10.22 +/- 1.69%, respectively. HbA1c reduction was greater in the GLP-1+FSL group compared with the GLP-1 group in the unmatched cohort (-2.43% vs. -1.73%, difference 0.70%, P < 0.001, respectively) and in the matched cohort (-2.43% vs. -2.06%, difference 0.37%, P < 0.001). GLP-1+FSL vs. GLP-1 treatment was associated with greater HbA1c reduction in the intensive insulin (-2.32% vs. -1.50%), nonintensive insulin (-2.50% vs. -1.74%), and noninsulin group (-2.46% vs. -1.78%), as well as in patients using semaglutide (-2.73% vs. -1.92%) and dulaglutide (-2.45% vs. -1.71%) GLP-1 RA, all P < 0.001. Conclusions: Adults with suboptimally controlled T2D, initiating GLP-1 RA with FreeStyle Libre, had greater improvement in HbA1c compared with those treated with GLP-1 RA only. These results suggest an additional glycemic benefit of FSL when used with a GLP-1 RA in T2D treatment. FAU - Wright, Eugene E AU - Wright EE AD - South Piedmont AHEC, Charlotte, North Carolina, USA. FAU - Roberts, Gregory J AU - Roberts GJ AD - Abbott, Sylmar, California, USA. FAU - Chuang, Joyce S AU - Chuang JS AD - Abbott, Santa Clara, California, USA. FAU - Nabutovsky, Yelena AU - Nabutovsky Y AD - Abbott, Santa Clara, California, USA. FAU - Virdi, Naunihal AU - Virdi N AD - Abbott Diabetes Care, Alameda, California, USA. FAU - Miller, Eden AU - Miller E AD - Diabetes and Obesity Care LLC, Bend, Oregon, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20240531 PL - United States TA - Diabetes Technol Ther JT - Diabetes technology & therapeutics JID - 100889084 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (hemoglobin A1c protein, human) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Insulin) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Middle Aged MH - *Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - Blood Glucose/analysis/drug effects MH - Adult MH - Aged MH - Glucagon-Like Peptide 1/therapeutic use MH - Drug Therapy, Combination MH - Insulin/therapeutic use/administration & dosage MH - Exenatide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - CGM OT - GLP-1 OT - RWE OT - continuous glucose monitoring OT - real-world studies OT - type 2 diabetes EDAT- 2024/04/26 18:53 MHDA- 2024/10/04 18:59 CRDT- 2024/04/26 14:43 PHST- 2024/10/04 18:59 [medline] PHST- 2024/04/26 18:53 [pubmed] PHST- 2024/04/26 14:43 [entrez] AID - 10.1089/dia.2024.0015 [doi] PST - ppublish SO - Diabetes Technol Ther. 2024 Oct;26(10):754-762. doi: 10.1089/dia.2024.0015. Epub 2024 May 31. PMID- 38658349 OWN - NLM STAT- MEDLINE DCOM- 20240619 LR - 20260127 IS - 1348-4540 (Electronic) IS - 0918-8959 (Linking) VI - 71 IP - 6 DP - 2024 Jun 18 TI - Real-world clinical evidence of oral semaglutide on metabolic abnormalities in subjects with type 2 diabetes: a multicenter retrospective observational study (the Sapporo-Oral SEMA study). PG - 603-616 LID - 10.1507/endocrj.EJ23-0648 [doi] AB - Oral semaglutide has potent anti-hyperglycemic efficacy in phase III trials. However, the complicated dosing instructions hamper to use this drug; therefore, we evaluated the efficacy and safety of oral semaglutide in subjects with type 2 diabetes in a real-world clinical setting. In this multi-center retrospective observational study, we analyzed subjects with type 2 diabetes newly treated with an oral semaglutide for >6 months at four medical centers located in Sapporo, Japan. The changes in glycated hemoglobin, body weight, and other metabolic parameters were evaluated and any adverse event leading to semaglutide discontinuation were recorded from February 2021 to December 2022. This study was registered with the University Hospital Medical Information Network Center (UMIN000050583). Of 543 subjects who met the inclusion criteria, data for 434 subjects (age 55.5 +/- 12.6 years; body mass index 29.6 +/- 6.0 kg/m(2)) were analyzed. After a 6 months of observation period, semaglutide 3 mg, 7 mg, or 14 mg was used by 55 (12.7%), 241 (55.5%), and 138 (31.8%) of subjects, respectively. Both glycated hemoglobin and body weight significantly improved: 7.65 +/- 1.11% to 6.88 +/- 0.91% (p < 0.001) and 80.2 +/- 19.2 kg to 77.6 +/- 19.2 kg (p < 0.001), respectively. Efficacy was also confirmed in the subgroup switched from other anti-hyperglycemic agents, including dipeptidyl peptidase-4 inhibitors. In total, 154 subjects had symptomatic gastrointestinal symptoms and 39 (7.2%) were discontinued semaglutide due to the adverse events. None of the participants experienced severe hypoglycemic events. Oral semaglutide in subjects with type 2 diabetes improved glycemic control and body weight in a real-world clinical setting. FAU - Furusawa, Sho AU - Furusawa S AUID- ORCID: 0009-0008-9509-7170 AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Nomoto, Hiroshi AU - Nomoto H AUID- ORCID: 0000-0003-0713-221X AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Oba-Yamamoto, Chiho AU - Oba-Yamamoto C AD - Sapporo Diabetes and Thyroid Clinic, Sapporo 060-0807, Japan. FAU - Takeuchi, Jun AU - Takeuchi J AD - Sapporo Diabetes and Thyroid Clinic, Sapporo 060-0807, Japan. FAU - Ito, Miki AU - Ito M AD - Kurihara Clinic, Sapporo 004-0053, Japan. FAU - Kurihara, Hiroyoshi AU - Kurihara H AD - Kurihara Clinic, Sapporo 004-0053, Japan. FAU - Aoki, Shin AU - Aoki S AD - Aoki Clinic, Sapporo 003-0023, Japan. FAU - Miya, Aika AU - Miya A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Kameda, Hiraku AU - Kameda H AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Nakamura, Akinobu AU - Nakamura A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. FAU - Atsumi, Tatsuya AU - Atsumi T AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20240425 PL - Japan TA - Endocr J JT - Endocrine journal JID - 9313485 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Middle Aged MH - Male MH - Retrospective Studies MH - Female MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Glycated Hemoglobin/analysis/metabolism MH - Adult MH - Administration, Oral MH - Japan MH - Treatment Outcome MH - Blood Glucose/drug effects/metabolism/analysis MH - Body Weight/drug effects MH - Semaglutide OTO - NOTNLM OT - Clinical trial OT - Glucagon-like peptide-1 receptor agonist OT - Glycemic control OT - Type 2 diabetes EDAT- 2024/04/25 00:54 MHDA- 2024/06/20 00:42 CRDT- 2024/04/24 22:43 PHST- 2024/06/20 00:42 [medline] PHST- 2024/04/25 00:54 [pubmed] PHST- 2024/04/24 22:43 [entrez] AID - 10.1507/endocrj.EJ23-0648 [doi] PST - ppublish SO - Endocr J. 2024 Jun 18;71(6):603-616. doi: 10.1507/endocrj.EJ23-0648. Epub 2024 Apr 25. PMID- 38650544 OWN - NLM STAT- MEDLINE DCOM- 20240604 LR - 20260618 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 7 DP - 2024 Jul TI - Cross-sectional, case-control and longitudinal associations between exposure to glucagon-like peptide-1 receptor agonists and the dispensing of antidepressants. PG - 2925-2932 LID - 10.1111/dom.15616 [doi] AB - AIM: To determine if the dispensing of glucagon-like peptide (GLP)-1 receptor agonists is associated with increased dispensing of antidepressants. MATERIALS AND METHODS: We used cross-sectional, case-control and retrospective cohort study designs to examine the association between dispensed GLP-1 receptor agonists and antidepressants between 2012 and 2022 in the 10% random sample of the Australian Pharmaceutical Benefits Scheme (PBS) data. PBS-listed GLP-1 receptor agonists, exenatide, dulaglutide and semaglutide were the exposures. Outcomes were the odds ratio [ORs; 99% confidence interval (CI)] and hazard ratio (99% CI) of being dispensed any antidepressant. Analyses were adjusted for demographic measures and the dispensing of medicines to manage cardiovascular diseases or anxiety/insomnia. Statistical tests were two-sided at the 1% level of significance. RESULTS: In total, 358 075 of 1 746 391 individuals were dispensed antidepressants, and 8495 of the 24 783 dispensed a GLP-1 receptor agonist were also dispensed an antidepressant in 2022 (OR 1.44; 99% CI 1.38-1.50); 24 103 of the 1 746 391 participants had been dispensed a GLP-1 receptor agonist between 2012 and 2021, and of these 8083 were dispensed antidepressants in 2022 (OR 1.52; 99% CI 1.46-1.59). The 2012 cohort included 1 213 316 individuals who had not been dispensed antidepressants that year. The hazard ratio of being dispensed an antidepressant between 2013 and 2022 following the dispensing of a GLP-1 receptor agonist was 1.19 (99% CI 1.12-1.27). Additional analyses restricting the time of exposure confirmed these associations for all PBS-listed GLP-1 receptor agonists. CONCLUSIONS: Individuals exposed to GLP-1 receptor agonists are at greater risk of being dispensed antidepressants. The possible impact of GLP-1 receptor agonists on the mood of consumers requires ongoing vigilance and further research. CI - (c) 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Almeida, Osvaldo P AU - Almeida OP AUID- ORCID: 0000-0002-8689-6199 AD - Institute for Health Research, University of Notre Dame, Fremantle, Western Australia, Australia. AD - Medical School, University of Western Australia, Perth, Western Australia, Australia. FAU - Fong, Zheng AU - Fong Z AD - Royal Perth Hospital, Perth, Western Australia, Australia. FAU - Hill Almeida, Lydia M AU - Hill Almeida LM AD - Sir Charles Gairdner Hospital, Perth, Western Australia, Australia. FAU - Sanfilippo, Frank M AU - Sanfilippo FM AUID- ORCID: 0000-0003-3639-0787 AD - School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia. FAU - Page, Amy AU - Page A AUID- ORCID: 0000-0002-2084-8469 AD - School of Allied Health, University of Western Australia, Perth, Western Australia, Australia. FAU - Etherton-Beer, Christopher AU - Etherton-Beer C AUID- ORCID: 0000-0001-5148-0188 AD - Medical School, University of Western Australia, Perth, Western Australia, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240423 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Antidepressive Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9P1872D4OL (Exenatide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Male MH - Female MH - Cross-Sectional Studies MH - *Antidepressive Agents/therapeutic use MH - Middle Aged MH - Case-Control Studies MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/analogs & derivatives MH - Retrospective Studies MH - *Exenatide/therapeutic use MH - Australia/epidemiology MH - Aged MH - Longitudinal Studies MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Adult MH - Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - antidepressant OT - anxiety OT - depression OT - diabetes EDAT- 2024/04/23 15:04 MHDA- 2024/06/04 06:42 CRDT- 2024/04/23 03:33 PHST- 2024/04/09 00:00 [revised] PHST- 2024/01/14 00:00 [received] PHST- 2024/04/10 00:00 [accepted] PHST- 2024/06/04 06:42 [medline] PHST- 2024/04/23 15:04 [pubmed] PHST- 2024/04/23 03:33 [entrez] AID - 10.1111/dom.15616 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Jul;26(7):2925-2932. doi: 10.1111/dom.15616. Epub 2024 Apr 23. PMID- 38639997 OWN - NLM STAT- MEDLINE DCOM- 20240520 LR - 20260625 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 47 IP - 6 DP - 2024 Jun 1 TI - Early-Onset Type 2 Diabetes and Tirzepatide Treatment: A Post Hoc Analysis From the SURPASS Clinical Trial Program. PG - 1056-1064 LID - 10.2337/dc23-2356 [doi] AB - OBJECTIVE: We evaluated baseline characteristics of participants with early-onset type 2 diabetes (T2D) from the SURPASS program and tirzepatide's effects on glycemic control, body weight (BW), and cardiometabolic markers. RESEARCH DESIGN AND METHODS: This post hoc analysis compared baseline characteristics and changes in mean HbA1c, BW, waist circumference (WC), lipids, and blood pressure (BP) in 3,792 participants with early-onset versus later-onset T2D at week 40 (A Study of Tirzepatide [LY3298176] in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone [SURPASS-1] and A Study of Tirzepatide [LY3298176] Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes [SURPASS-2]) or week 52 (A Study of Tirzepatide [LY3298176] Versus Insulin Degludec in Participants With Type 2 Diabetes [SURPASS-3]). Analyses were performed by study on data from participants while on assigned treatment without rescue medication in case of persistent hyperglycemia. RESULTS: At baseline in SURPASS-2, participants with early-onset versus later-onset T2D were younger with longer diabetes duration (9 vs. 7 years, P < 0.001) higher glycemic levels (8.5% vs. 8.2%, P < 0.001), higher BW (97 vs. 93 kg, P < 0.001) and BMI (35 vs. 34 kg/m2, P < 0.001), and a similarly abnormal lipid profile (e.g., triglycerides 167 vs. 156 mg/dL). At week 40, similar improvements in HbA1c (-2.6% vs. -2.4%), BW (-14 vs. -13 kg), WC (-10 vs. -10 cm), triglycerides (-26% vs. -24%), HDL (7% vs. 7%), and systolic BP (-6 vs. -7 mmHg) were observed in both subgroups with tirzepatide. CONCLUSIONS: Despite younger age, participants with early-onset T2D from the SURPASS program had higher glycemic levels and worse overall metabolic health at baseline versus those with later-onset T2D. In this post hoc analysis, similar improvements in HbA1c, BW, and cardiometabolic markers were observed with tirzepatide, irrespective of age at T2D diagnosis. Future studies are needed to determine long-term outcomes of tirzepatide in early-onset T2D. CI - (c) 2024 by the American Diabetes Association. FAU - Zeitler, Philip AU - Zeitler P AD - Children's Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - University of Miami Miller School of Medicine, Miami, FL. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester and the Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, U.K. FAU - Bergman, Brandon K AU - Bergman BK AD - Eli Lilly and Company, Indianapolis, IN. FAU - Thieu, Vivian T AU - Thieu VT AD - Eli Lilly and Company, Indianapolis, IN. FAU - Nicolay, Claudia AU - Nicolay C AD - Eli Lilly and Company, Indianapolis, IN. FAU - Allen, Sheryl AU - Allen S AD - Eli Lilly and Company, Indianapolis, IN. FAU - Heine, Robert J AU - Heine RJ AD - Eli Lilly and Company, Indianapolis, IN. FAU - Lee, Clare J AU - Lee CJ AUID- ORCID: 0000-0002-0824-0207 AD - Eli Lilly and Company, Indianapolis, IN. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Female MH - Middle Aged MH - *Hypoglycemic Agents/therapeutic use MH - Adult MH - Glycated Hemoglobin/metabolism MH - Blood Glucose/drug effects/metabolism MH - Blood Pressure/drug effects MH - Body Weight/drug effects MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide PMC - PMC11116907 EDAT- 2024/04/19 12:43 MHDA- 2024/05/20 18:44 PMCR- 2024/04/19 CRDT- 2024/04/19 11:53 PHST- 2023/12/08 00:00 [received] PHST- 2024/03/21 00:00 [accepted] PHST- 2024/05/20 18:44 [medline] PHST- 2024/04/19 12:43 [pubmed] PHST- 2024/04/19 11:53 [entrez] PHST- 2024/04/19 00:00 [pmc-release] AID - 154513 [pii] AID - 232356 [pii] AID - 10.2337/dc23-2356 [doi] PST - ppublish SO - Diabetes Care. 2024 Jun 1;47(6):1056-1064. doi: 10.2337/dc23-2356. PMID- 38629387 OWN - NLM STAT- MEDLINE DCOM- 20240530 LR - 20260127 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 25 IP - 5 DP - 2024 Apr TI - A systematic review of the effect of semaglutide on lean mass: insights from clinical trials. PG - 611-619 LID - 10.1080/14656566.2024.2343092 [doi] AB - INTRODUCTION: Semaglutide, a glucagon-like peptide-1 receptor agonist, is associated with significant weight loss, yet its impact on lean body mass remains insufficiently understood. This review investigates the effect of semaglutide on lean mass in the context of obesity management. METHODOLOGY: This study investigates through different databases (PubMed, Elsevier, and Google Scholar) from 2016 for randomized control trials (RCTs) or observational studies that assessed the use of semaglutide in overweight or obese patients, regardless of whether they have type 2 diabetes or not. The studies compared semaglutide to a placebo or alternative medications. RESULTS: Six studies with 1,541 overweight or obese adults were included, and significant weight reductions were observed primarily due to fat mass loss. While the lean mass remained stable in some cases, notable reductions ranging from almost 0% to 40% of total weight reduction were observed in others. Noteworthy decreases in lean mass were particularly evident in larger trials, yet the proportion of lean mass relative to total body mass increased, suggesting a positive overall outcome. CONCLUSION: Semaglutide displays potential for weight loss primarily through fat mass reduction. However, concerns arise from notable reductions in lean mass, especially in trials with a larger number of patients. FAU - Bikou, Alexia AU - Bikou A AD - Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece. AD - Equally contributed. FAU - Dermiki-Gkana, Foteini AU - Dermiki-Gkana F AD - Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece. AD - Equally contributed. FAU - Penteris, Michail AU - Penteris M AD - Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece. AD - Equally contributed. FAU - Constantinides, Theodoros K AU - Constantinides TK AD - Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Kontogiorgis, Christos AU - Kontogiorgis C AD - Laboratory of Hygiene and Environmental Protection, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece. LA - eng PT - Journal Article PT - Systematic Review DEP - 20240418 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - *Weight Loss/drug effects MH - *Obesity/drug therapy MH - *Randomized Controlled Trials as Topic MH - *Overweight/drug therapy MH - Anti-Obesity Agents/therapeutic use/pharmacology MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Muscle loss OT - glucagon-like peptide-1 receptor agonist OT - lean mass loss OT - semaglutide OT - weight loss EDAT- 2024/04/17 06:42 MHDA- 2024/05/30 12:42 CRDT- 2024/04/17 05:54 PHST- 2024/05/30 12:42 [medline] PHST- 2024/04/17 06:42 [pubmed] PHST- 2024/04/17 05:54 [entrez] AID - 10.1080/14656566.2024.2343092 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2024 Apr;25(5):611-619. doi: 10.1080/14656566.2024.2343092. Epub 2024 Apr 18. PMID- 38613667 OWN - NLM STAT- MEDLINE DCOM- 20240605 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 67 IP - 7 DP - 2024 Jul TI - Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials. PG - 1206-1222 LID - 10.1007/s00125-024-06144-1 [doi] AB - AIMS/HYPOTHESIS: We conducted a systematic review and network meta-analysis to compare the efficacy and safety of s.c. administered tirzepatide vs s.c. administered semaglutide for adults of both sexes with type 2 diabetes mellitus. METHODS: We searched PubMed and Cochrane up to 11 November 2023 for RCTs with an intervention duration of at least 12 weeks assessing s.c. tirzepatide at maintenance doses of 5 mg, 10 mg or 15 mg once weekly, or s.c. semaglutide at maintenance doses of 0.5 mg, 1.0 mg or 2.0 mg once weekly, in adults with type 2 diabetes, regardless of background glucose-lowering treatment. Eligible trials compared any of the specified doses of tirzepatide and semaglutide against each other, placebo or other glucose-lowering drugs. Primary outcomes were changes in HbA(1c) and body weight from baseline. Secondary outcomes were achievement of HbA(1c) target of /= 5% weight loss, respectively. For the comparator analysis, the OW GLP-1RAs (N = 651) were significantly more effective (p < 0.001) in reducing HbA(1c) (- 1.5% vs. - 1.0%) and weight (- 3.2 kg vs. - 1.0 kg) than the DPP-4is (N = 431). Similarly, the semaglutide cohort (N = 251) also displayed more effectiveness (p < 0.001) in reducing HbA(1c) (- 1.7% vs. - 0.9%) and weight (- 4.1 kg vs. - 1.3 kg) than the respective DPP-4i cohort (N = 417). Patients initiating OW GLP-1RAs, including the semaglutide cohort, were at least twice as likely to achieve HbA(1c) and weight outcomes as well as composite outcomes compared with those initiating DPP-4is. CONCLUSION: The study reinforces that OW GLP-1RAs are more effective in glycemic control and weight reduction compared with DPP-4is in people with T2DM in the real-world setting. These findings align with the recommendation in the current guidelines for utilizing glucose-lowering treatment regimens that support weight-management goals in people with T2DM. CI - (c) 2024. The Author(s). FAU - Tan, Xi AU - Tan X AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. mxtz@novonordisk.com. FAU - Divino, Victoria AU - Divino V AD - IQVIA, Falls Church, VA, USA. FAU - Amamoo, James AU - Amamoo J AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - Xie, Lin AU - Xie L AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - Coyle, Katharine B AU - Coyle KB AD - IQVIA, Falls Church, VA, USA. FAU - Gamble, Cory L AU - Gamble CL AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - Guevarra, Mico AU - Guevarra M AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - Paprocki, Yurek AU - Paprocki Y AD - Novo Nordisk Inc., 800 Scudders Mill Road, Plainsboro, NJ, 08536, USA. FAU - King, Aaron A AU - King AA AD - Baptist Health System, San Antonio, TX, USA. LA - eng PT - Journal Article PT - Observational Study DEP - 20240320 PL - New Zealand TA - Clin Drug Investig JT - Clinical drug investigation JID - 9504817 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycemic Control MH - Weight Loss MH - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases PMC - PMC10980663 OAB - In type 2 diabetes mellitus (T2DM), glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for managing blood sugar levels and major adverse cardiovascular event risk reduction. In clinical trials, once-weekly (OW) GLP-1RAs showed better control of blood sugar levels and body weight than those administered daily, as well as another class of daily T2DM medications called dipeptidyl peptidase-4 inhibitors (DPP-4is). However, there is limited evidence of OW GLP-1RAs-based routine care to confirm these findings. This study gathered prescription and outcomes data for people with T2DM (January 2017-April 2022) from two linked US databases. Body weight measurements and glycated hemoglobin (HbA(1c)) test results (measuring average blood sugar levels) were used to evaluate the effectiveness of OW GLP-1RAs (exenatide, dulaglutide, and semaglutide) via a pre-post analysis, and compare OW GLP-1RAs with DPP-4is. We found that treatment with semaglutide lowered body weight and blood sugar levels to a greater extent than OW GLP-1RAs in the pre-post analysis. In the comparator analysis, people receiving OW GLP-1RAs, including semaglutide, were at least twice as likely to achieve reduced HbA(1c) levels and body weight compared with those receiving DPP-4is. People receiving OW GLP-1RAs were three times more likely than those on DPP-4is to achieve the recommended target of HbA(1c) < 7.0% and weight loss >/= 5%, while treatment with semaglutide increased this likelihood by > 4.6 times. This study shows clear benefits of OW GLP-1RAs, building on current evidence for integration of this treatment into overall management of T2DM. OABL- eng COIS- XT, JA, LX, CLG, MG, YP are employed by Novo Nordisk Inc. LX has been employed by Pfizer within the last 3 years. VD and KBC are employees of IQVIA, which received funding from Novo Nordisk Inc. for this study. AK is an employee of Baptist Medical Network MedFirst Primary Care - Quarry, and served as consultant/speaker for Abbott, Astellas, Dexcom, Eli Lilly, Mannkind, and Novo Nordisk Inc. EDAT- 2024/03/20 18:46 MHDA- 2024/04/01 06:42 PMCR- 2024/03/20 CRDT- 2024/03/20 12:21 PHST- 2024/02/28 00:00 [accepted] PHST- 2024/04/01 06:42 [medline] PHST- 2024/03/20 18:46 [pubmed] PHST- 2024/03/20 12:21 [entrez] PHST- 2024/03/20 00:00 [pmc-release] AID - 10.1007/s40261-024-01354-2 [pii] AID - 1354 [pii] AID - 10.1007/s40261-024-01354-2 [doi] PST - ppublish SO - Clin Drug Investig. 2024 Apr;44(4):271-284. doi: 10.1007/s40261-024-01354-2. Epub 2024 Mar 20. PMID- 38505997 OWN - NLM STAT- MEDLINE DCOM- 20240508 LR - 20260619 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 6 DP - 2024 Jun TI - Glucagon-like peptide-1 receptor agonists modestly reduced blood pressure among patients with and without diabetes mellitus: A meta-analysis and meta-regression. PG - 2209-2228 LID - 10.1111/dom.15529 [doi] AB - AIM: The cardiovascular benefits provided by glucagon-like peptide-1 receptor agonists (GLP-1RAs) extend beyond weight reduction and glycaemic control. One possible mechanism may relate to blood pressure (BP) reduction. We aim to quantify the BP-lowering effects of GLP1-RAs. METHODS: A comprehensive database search for placebo-controlled randomized controlled trials on GLP-1RA treatment was conducted until December 2023. Data extraction and quality assessment were carried out, employing a robust statistical analysis using a random effects model to determine outcomes with a mean difference (MD) in mmHg and 95% confidence intervals (CIs). The primary endpoint was the mean difference in systolic BP (SBP) and diastolic BP. Subgroup analyses and meta-regressions were done to account for covariates. RESULTS: Compared with placebo, GLP-1RAs modestly reduced SBP [semaglutide: MD -3.40 (95% CI -4.22 to -2.59, p < .001); liraglutide: MD -2.61 (95% CI -3.48 to -1.74, p < .001); dulaglutide: MD -1.46 (95% CI -2.20 to -0.72, p < .001); and exenatide: MD -3.36 (95% CI -3.63 to -3.10, p < .001)]. This benefit consistently increased with longer treatment durations. Diastolic BP reduction was only significant in the exenatide group [MD -0.94 (95% CI -1.78 to -0.1), p = .03]. Among semaglutide cohorts, mean changes in glycated haemoglobin and mean changes in body mass index were directly associated with SBP reduction. CONCLUSION: Patients on GLP-1RA experienced modest SBP lowering compared with placebo. This observed effect was associated with weight/body mass index reduction and better glycaemic control, which suggests that BP-lowering is an indirect effect of GLP-1RA and unlikely to be responsible for the benefits. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Rivera, Frederick Berro AU - Rivera FB AUID- ORCID: 0000-0001-9100-0724 AD - Department of Medicine, Lincoln Medical Center, New York, New York, USA. FAU - Lumbang, Grace Nooriza O AU - Lumbang GNO AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Gaid, Danielle Rose Magno AU - Gaid DRM AD - Cebu Institute of Medicine, Cebu City, Philippines. FAU - Cruz, Linnaeus Louisse A AU - Cruz LLA AD - University of the Philippines College of Medicine, Manila, Philippines. FAU - Magalong, John Vincent AU - Magalong JV AD - University of the Philippines College of Medicine, Manila, Philippines. FAU - Bantayan, Nathan Ross B AU - Bantayan NRB AD - University of the Philippines College of Medicine, Manila, Philippines. FAU - Lara-Breitinger, Kyla M AU - Lara-Breitinger KM AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. FAU - Gulati, Martha AU - Gulati M AD - Department of Cardiology, Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, California, USA. FAU - Bakris, George AU - Bakris G AUID- ORCID: 0000-0003-1183-1267 AD - Department of Medicine, University of Chicago, Chicago, Illinois, USA. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20240320 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Blood Pressure/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy/complications/blood MH - Exenatide/therapeutic use/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - *Hypoglycemic Agents/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Liraglutide/therapeutic use MH - Randomized Controlled Trials as Topic MH - Recombinant Fusion Proteins/therapeutic use MH - Semaglutide OTO - NOTNLM OT - blood pressure OT - dulaglutide OT - exenatide OT - glucagon-like peptide-1 receptor agonists OT - liraglutide OT - semaglutide EDAT- 2024/03/20 06:45 MHDA- 2024/05/08 06:45 CRDT- 2024/03/20 04:44 PHST- 2024/02/12 00:00 [revised] PHST- 2024/02/04 00:00 [received] PHST- 2024/02/13 00:00 [accepted] PHST- 2024/05/08 06:45 [medline] PHST- 2024/03/20 06:45 [pubmed] PHST- 2024/03/20 04:44 [entrez] AID - 10.1111/dom.15529 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Jun;26(6):2209-2228. doi: 10.1111/dom.15529. Epub 2024 Mar 20. PMID- 38504284 OWN - NLM STAT- MEDLINE DCOM- 20240321 LR - 20250110 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 23 IP - 1 DP - 2024 Mar 19 TI - CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes. PG - 104 LID - 10.1186/s12933-024-02180-8 [doi] LID - 104 AB - The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ). CI - (c) 2024. The Author(s). FAU - Schnell, Oliver AU - Schnell O AD - Forschergruppe Diabetes e. V, Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764, Neuherberg (Munich), Germany. oliver.schnell@lrz.uni-muenchen.de. FAU - Barnard-Kelly, Katharine AU - Barnard-Kelly K AD - Southern Health NHS Foundation Trust, Southampton, United Kingdom. FAU - Battelino, Tadej AU - Battelino T AD - University Medical Center, Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. FAU - Ceriello, Antonio AU - Ceriello A AD - IRCCS MultiMedica, Milan, Italy. FAU - Larsson, Helena Elding AU - Larsson HE AD - Department of Pediatrics, Skane University Hospital, Malmo/Lund, Sweden. AD - Department of Clinical Sciences Malmo, Lund University, Lund, Sweden. FAU - Fernandez-Fernandez, Beatriz AU - Fernandez-Fernandez B AD - Division of Nephrology and Hypertension, University Hospital Fundacion Jimenez Diaz, Madrid, Spain. FAU - Forst, Thomas AU - Forst T AD - CRS Clinical Research Services Mannheim GmbH, Mannheim, Germany. FAU - Frias, Juan-Pablo AU - Frias JP AD - Biomea Fusion, Redwood City, CA, United States of America. FAU - Gavin, James R 3rd AU - Gavin JR 3rd AD - Emory University School of Medicine, Atlanta, GA, United States of America. FAU - Giorgino, Francesco AU - Giorgino F AD - Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, Bari, Italy. FAU - Groop, Per-Henrik AU - Groop PH AD - Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. AD - Department of Diabetes, Central Medical School, Monash University, Melbourne, Australia. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AD - Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Herzig, Stephan AU - Herzig S AD - Division Diabetic Complications, Institute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany. FAU - Hummel, Michael AU - Hummel M AD - Forschergruppe Diabetes e. V, Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764, Neuherberg (Munich), Germany. FAU - Huntley, George AU - Huntley G AD - Diabetes Leadership Council, Indianapolis, IN, United States of America. FAU - Ibrahim, Mahmoud AU - Ibrahim M AD - Center for Diabetes Education, EDC, Charlotte, NC, United States of America. FAU - Itzhak, Baruch AU - Itzhak B AD - Clalit Health Services, Haifa, Israel. AD - Technion Faculty of Medicine, Haifa, Israel. FAU - Jacob, Stephan AU - Jacob S AD - Practice for Prevention and Therapy and Cardio-Metabolic Institute, Villingen-Schwenningen, Germany. FAU - Ji, Linong AU - Ji L AD - Peking University People's Hospital, Xicheng District, Beijing, China. FAU - Kosiborod, Mikhail AU - Kosiborod M AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States of America. FAU - Lalic, Nebosja AU - Lalic N AD - Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Belgrade, Serbia. AD - Faculty of Medicine, University of Belgrade, Belgrade, Serbia. FAU - Macieira, Sofia AU - Macieira S AD - Sciarc GmbH, Baierbrunn, Germany. FAU - Malik, Rayaz A AU - Malik RA AD - Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, Ar-Rayyan, Doha, Qatar. FAU - Mankovsky, Boris AU - Mankovsky B AD - Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine. FAU - Marx, Nikolaus AU - Marx N AD - Clinic for Cardiology, Pneumology, Angiology and Internal Intensive Care Medicine (Medical Clinic I), RWTH Aachen University Hospital, Aachen, Germany. FAU - Mathieu, Chantal AU - Mathieu C AD - Department of Endocrinology, Catholic University Leuven, Leuven, Belgium. FAU - Muller, Timo D AU - Muller TD AD - Institute for Diabetes and Obesity, Helmholtz Munich, Munich, Germany. AD - Walther-Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University Munich (LMU), Munich, Germany. FAU - Ray, Kausik AU - Ray K AD - School of Public Health, Imperial College London, London, United Kingdom. FAU - Rodbard, Helena W AU - Rodbard HW AD - Endocrine and Metabolic Consultants, Rockville, MD, United States of America. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Ryden, Lars AU - Ryden L AD - Department of Medicine K2, Karolinska Institute, Stockholm, Sweden. FAU - Schumm-Draeger, Petra-Maria AU - Schumm-Draeger PM AD - Center Internal Medicine Funf Hofe, Munich, Germany. FAU - Schwarz, Peter AU - Schwarz P AD - Medical Clinic III, University Hospital Carl Gustav Carus, Dresden, Germany. FAU - Skrha, Jan AU - Skrha J AD - Third Medical Department and Laboratory for Endocrinology and Metabolism, First Faculty of Medicine, Charles University, Prague, Czech Republic. FAU - Snoek, Frank AU - Snoek F AD - Amsterdam University Medical Centers, Amsterdam, The Netherlands. FAU - Tacke, Frank AU - Tacke F AD - Department of Hepatology and Gastroenterology, Charite Universitatsmedizin Berlin, Campus Virchow-Klinikum and Campus Charite Mitte, Berlin, Germany. FAU - Taylor, Bruce AU - Taylor B AD - Diabetes Patient Advocacy Coalition, Tampa, FL, United States of America. FAU - Jeppesen, Britta Tendal AU - Jeppesen BT AD - Future Evidence Foundation, Melbourne, Australia. FAU - Tesfaye, Solomon AU - Tesfaye S AD - Sheffield Teaching Hospitals, Sheffield, United Kingdom. AD - University of Sheffield, Sheffield, United Kingdom. FAU - Topsever, Pinar AU - Topsever P AD - Department of Family Medicine, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkiye. FAU - Vilsboll, Tina AU - Vilsboll T AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Yu, Xuefeng AU - Yu X AD - Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Standl, Eberhard AU - Standl E AD - Forschergruppe Diabetes e. V, Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764, Neuherberg (Munich), Germany. LA - eng PT - Letter DEP - 20240319 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Blood Glucose) SB - IM MH - Humans MH - *Heart Failure/complications MH - Blood Glucose Self-Monitoring MH - Stroke Volume MH - Blood Glucose MH - *Cardiovascular Diseases/diagnosis/epidemiology/prevention & control MH - Obesity/complications MH - *Renal Insufficiency, Chronic/diagnosis/epidemiology/therapy MH - *Diabetes Mellitus/drug therapy MH - Kidney MH - *Diabetes Mellitus, Type 2/drug therapy PMC - PMC10953147 OTO - NOTNLM OT - CGM OT - Cardiovascular disease OT - Chronic kidney disease OT - Diabetes OT - Finerenone OT - GLP-1 RA OT - Guidelines OT - Heart failure OT - MASLD OT - NAFLD OT - Obesity OT - SGLT2 inhibitor OT - Teplizumab COIS- OS (Oliver Schnell) is the founder and CEO of Sciarc and reports consulting, speaking, or serving on advisory boards for AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, MSD, Mundipharma, Novo Nordisk, Roche, Sanofi, and Worwag Pharma. KBK (Katharine Barnard-Kelly) is founder and shareholder at Spotlight-AQ Ltd. KBK has received research support from Dexcom, Embecta, JDRF, Novo Nordisk and Roche Diabetes Care, and honoraria from Sanofi. TB (Tadej Battelino) has served on the advisory boards of Abbott, Boehringer Ingelheim, Dreamed Diabetes, Eli Lilly and Company, Indigo Diabetes, Medtronic, Novo Nordisk, and Sanofi. TB has received speaker's bureau honoraria from Abbott, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche, and Sanofi. The University Medical Center has received research grant support from Abbott, GluSense, Medtronic, Novo Nordisk, Sandoz, Sanofi, and Zealand Pharma. AC (Antonio Ceriello) reports consulting and speaking for Bayer, Berlin-Chemie, Eli Lilly and Company, Guidotti, Merck, Novo Nordisk, Roche Diagnostics and Sanofi. HEL (Helena Elding Larsson) declares that she has no competing interests. BFF (Beatriz Fernandez-Fernandez) has received grants from AstraZeneca and Esteve and consultancy or speaker fees or travel support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Menarini, Novo Nordisk, and Mundipharma. JPF (Juan-Pablo Frias) is employee and stockholder of Biomea Fusion, Inc. JPF has received research support from Akero, Altimmune, Boehringer Ingelheim, 89bio, Eli Lilly and Company, Intercept, IONIS, Janssen, Madrigal, Merck, NorthSea Therapeutics, Novartis, Novo Nordisk, Oramed, Pfizer, Sanofi, and Shionogi. JPF has also served as a consultant and on the advisory boards of Akero, Altimmune, Biomea Fusion, Boehringer Ingelheim, Carmot Therapeutics, Echosens, 89bio, Eli Lilly and Company, Gilead, Intercept, Metacrine, Merck, Novo Nordisk, Pfizer, Sanofi, and on the speaker's bureau for Eli Lilly and Company. TF (Thomas Forst) has been a member of the speaker panel of Amarin, AstraZeneca, Boehringer Ingelheim, Berlin-Chemie, Cipla, Daiichi-Sankyo, Eli Lilly and Company, Fortbildungskolleg, MSD, Novartis, Novo Nordisk, Sanofi, Santis, and of the advisory panel of Atrogi, Bayer, Cipla, Diabetes-Akademie Bad Mergentheim e.V., Eli Lilly and Company, Eyesense, Fortbildungskolleg, Novo Nordisk, Pfizer, reMYND, Roche and Sanofi. JRG (James R. Gavin III) has served on the advisory boards of Abbott Diabetes Care and Embecta, and on the speaker's bureaus of Boehringer Ingelheim and Eli Lilly and Company. FG (Francesco Giorgino) has served on the advisory boards of AstraZeneca, Eli Lilly and Company, Novo Nordisk, Roche Diabetes Care, Sanofi and as a consultant to AstraZeneca, Boehringer Ingelheim, LifeScan, Medimmune, Medtronic, Merck Sharp & Dohme, Roche Diabetes Care and Sanofi. FG has also received research support from Eli Lilly and Company and Roche Diabetes Care. PHG (Per-Henrik Groop) has received lecture honoraria from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company, EloWater, Genzyme, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, Peer Voice, Sanofi and Sciarc. PHG also serves as an advisory board member for AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, and Sanofi. HJLH (Hiddo J.L. Heerspink) declares that he has no competing interests. SH (Stephan Herzig) declares that he has no competing interests. MH (Michael Hummel) declares that he has no competing interests. GH (George Huntley) declares that he has no competing interests. MI (Mahmoud Ibrahim) has consultancy agreement with and received speaker honoraria from Boehringer Ingelheim, Medtronic, Novo Nordisk, and Pfizer. BI (Baruch Itzhak) has received honoraria or consulting fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, and Novo Nordisk and speaking fees from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk, Roche, and Sanofi. SJ (Stephan Jacob) declares that he has no competing interests. LJ (Linong Ji) declares that he has no competing interests. MK (Mikhail Kosiborod) reports consulting or advisory board participation for 35Pharma, Alnylam Pharmaceuticals, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly and Company, Esperion Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, scPharmaceuticals, Sanofi, Structure Therapeutics, Vifor Pharma and Youngene Therapeutics. MK has also received honoraria from AstraZeneca, Boehringer Ingelheim and Novo Nordisk, and research grants from AstraZeneca, Boehringer Ingelheim and Pfizer. NL (Nebosja Lalic) declares that he has no competing interests. SM (Sofia Macieira) is employee of Sciarc. RM (Rayaz A. Malik) has served on the advisory panel and received honoraria for speaking for Eli Lilly and Company, Novo Nordisk, Proctor & Gamble, Sanofi Aventis, and Viatris. RM has also received research funding for studies from Novo Nordisk and Proctor & Gamble. BM (Boris Mankovsky) has served on advisory boards and received speaking fees from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, Sanofi, Servier, and Worwag Pharma. NM (Nikolaus Marx) has received research grants from Boehringer Ingelheim and MSD, speaking fees form Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Eli Lilly and Company, MSD, Novo Nordisk, and Sanofi-Aventis and has served or serves on the advisory board of Amgen, Bayer, BMS, Boehringer Ingelheim, MSD, Novo Nordisk, and Sanofi-Aventis. CM (Chantal Mathieu) serves or has served on the advisory panel for ActoBio Therapeutics, Avotres, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Imcyse, Insulet, Mannkind, Medtronic, Merck Sharp and Dohme Ltd., Novartis, Novo Nordisk, Pfizer, Sandoz, Sanofi, Roche, Vertex and Zealand Pharma. CM serves or has served on the speakers' bureau for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Novartis Novo Nordisk, and Sanofi. Financial compensation for these activities has been received by KU Leuven. KU Leuven has received research support for CM from ActoBio Therapeutics, Imcyse, Medtronic, Novo Nordisk, and Sanofi. TM (Timo Muller) reports having received honoraria or research support from AstraZeneca, Berlin-Chemie, Eli Lilly and Company, Merck, Mercodia, MSD, Novo Nordisk, and Sanofi Aventis in the past 3 years. KR (Kausik Ray) has served as a consultant for Abbott, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cargene Therapeutics, Cleerly Health, CRISPR Therapeutics, CSL Behring, Eli Lilly and Company, EmendoBio, Esperion Therapeutics, Kowa Pharmaceutics, New Amsterdam Pharma, Novartis, Novo Nordisk, Pfizer, Regeneron, Resverlogix, Sanofi, Scribe Thearapeutics, Silence Therapeutics, VAXXINITY, and Viatris. KR reports having received research grants from Amgen, Daiichi Sankyo, MSD, Pfizer, Regeneron, Sanofi and Ultragenix. HR (Helena W. Rodbard) declares that she has no competing interests. PR (Peter Rossing) has received honoraria for consultancy and/or speaking fees (to his institution) from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Gilead, MSD, Novo Nordisk, and Sanofi Aventis and research grants from AstraZeneca, Bayer, and Novo Nordisk. LR (Lars Ryden) declares that he has no competing interests. PMSD (Petra-Maria Schumm-Draeger) declares that she has no competing interests. PS (Peter Schwarz) declares that he has no competing interests. JS (Jan Skrha) declares that he has no competing interests. FS (Frank Snoek) has received research support from Sanofi, consulting fees from Abbott, LifeScan, Roche, and Sanofi, and has served on a speaker's bureau for Abbott and Sanofi. FT (Frank Tacke) declares that work in his lab has been supported by research grants from AstraZeneca, Gilead, and MSD. BT (Bruce Taylor) is employee of Dexcom. BTJ (Britta Tendal Jeppesen) declares that she has no competing interests. ST (Solomon Tesfaye) reports honoraria for educational meetings from Astellas Pharma, AstraZeneca, Berlin-Chemie, Eva Pharma, Grunenthal, Hikma, Merck, Nevro, Novo Nordisk, P&G Health, Viatris, and Worwag Pharma; consulting fees from Angelini, AstraZeneca, Bayer, Grunenthal, Mitsubishi Tanabe Pharma, Merz, NeuroPN, Nevro, Viatris and Worwag Pharma; unrestricted research grants from Proctor and Gamble, Viatris and Withings. PT (Pinar Topsever) has received honoraria or consulting fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, and LifeScan, and has served on the speaker's bureau for AstraZeneca. PT received grant/research support from PCDE, made possible by corporate sponsorship from AstraZeneca, Eli Lilly, Novo Nordisk, and Roche Diagnostics; the sponsors had no input into the study protocols. TV (Tina Vilsboll) has served on scientific advisory panels, been part of speaker's bureaus, and served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Gilead, GSK, Mundipharma, MSD/Merck, Novo Nordisk, Sanofi, and Sun Pharmaceuticals. XY (Xuefeng Yu) declares that he has no competing interests. ES (Eberhard Standl) declares that he has no competing interests. EDAT- 2024/03/20 06:45 MHDA- 2024/03/21 12:44 PMCR- 2024/03/19 CRDT- 2024/03/20 00:51 PHST- 2024/02/20 00:00 [received] PHST- 2024/02/26 00:00 [accepted] PHST- 2024/03/21 12:44 [medline] PHST- 2024/03/20 06:45 [pubmed] PHST- 2024/03/20 00:51 [entrez] PHST- 2024/03/19 00:00 [pmc-release] AID - 10.1186/s12933-024-02180-8 [pii] AID - 2180 [pii] AID - 10.1186/s12933-024-02180-8 [doi] PST - epublish SO - Cardiovasc Diabetol. 2024 Mar 19;23(1):104. doi: 10.1186/s12933-024-02180-8. PMID- 38503415 OWN - NLM STAT- MEDLINE DCOM- 20240321 LR - 20260127 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 14 IP - 3 DP - 2024 Mar 18 TI - Home-based Intervention with Semaglutide Treatment of Neuroleptic-Related Prediabetes (HISTORI): protocol describing a prospective, randomised, placebo controlled and double-blinded multicentre trial. PG - e077173 LID - 10.1136/bmjopen-2023-077173 [doi] LID - e077173 AB - INTRODUCTION: Subjects with schizophrenia have a 2-3 fold higher mortality rate than the general population and a reduced life expectancy of 10-20 years. Approximately one-third of this excess mortality has been attributed to obesity-related type 2 diabetes (T2D) and to cardiovascular disease. Glucagon-like peptide-1 (GLP-1) analogues increase satiety and delay gastric emptying, thereby reducing food intake and weight. GLP-1 analogues also exert beneficial effects on cardiovascular outcomes in high-risk patients with T2D.Our aim is to investigate whether 30 weeks add-on treatment with the GLP-1 analogue semaglutide can reduce HbA1c sufficiently to reverse pre-diabetes and the metabolic syndrome in overweight schizophrenic patients. METHODS AND ANALYSIS: We will perform a 30 week, two-armed, multicentre, superiority, double-blinded, randomised trial investigating the effect of weekly injections of semaglutide versus placebo in mental health facilities in Region of Southern Denmark and Region of Zealand, Denmark. In total, 154 adults with schizophrenia spectrum disease, aged 18-60 years treated with second generation antipsychotic treatment, HbA1c 39-47 mmol/mol and body mass index >27 kg/m(2) will be randomised to injections of 1.0 mg semaglutide or placebo. The primary outcome is changes in HbA1c. Secondary outcomes encompass metabolic measures, psychotic symptoms and quality of life. Exploratory outcomes encompass insulin sensitivity, cardiovascular risk profile, medication adherence, general well-being and physical activity. ETHICS AND DISSEMINATION: This study will be carried out in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. This research has obtained approval from both the Danish Medicines Agency and The Regional Committees on Health Research Ethics for Southern Denmark. TRIAL REGISTRATION NUMBER: NCT05193578 European Clinical Trials Database Number (EudraCT) 2020-004374-22, Regional Ethical Committee number S-20200182. CI - (c) Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. FAU - Ganeshalingam, Ashok Ainkaran AU - Ganeshalingam AA AUID- ORCID: 0000-0003-2218-5045 AD - Endocrine Research Unit, Department of Endocrinology, Odense University Hospital & Department of Clinical Research, Faculty of Health, Odense Universitetshospital, Odense, Denmark ashok.ganeshalingam@rsyd.dk. AD - Department of Internal Medicine, Lillebaelt Hospital - University Hospital of Southern Denmark, Kolding, Denmark. AD - Department of Endocrinology, Odense University Hospital, Odense, Denmark. FAU - Uhrenholt, Nicolai Gundtoft AU - Uhrenholt NG AD - Psychiatry West, Region Zealand, Research Unit West, Slagelse, Denmark, Slagelse, Denmark. AD - Department of Child and Adolescent Mental Health Odense, Mental Health Services, University of Southern Denmark, Odense, Denmark. FAU - Arnfred, Sidse AU - Arnfred S AD - University of Copenhagen, Kobenhavn, Denmark. FAU - Gaede, Peter Haulund AU - Gaede PH AD - Department of Cardiology and Endocrinology, Slagelse Hospital, Slagelse, Denmark. FAU - Bilenberg, Niels AU - Bilenberg N AD - Department of Child and Adolescent Mental Health Odense, Mental Health Services, University of Southern Denmark, Odense, Denmark. AD - Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. FAU - Frystyk, Jan AU - Frystyk J AD - Endocrine Research Unit, Department of Endocrinology, Odense University Hospital & Department of Clinical Research, Faculty of Health, Odense Universitetshospital, Odense, Denmark. LA - eng SI - ClinicalTrials.gov/NCT05193578 SI - EudraCT/2020-004374-22 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240318 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Antipsychotic Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - *Antipsychotic Agents/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - *Prediabetic State/complications MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - Glycated Hemoglobin MH - Quality of Life MH - Prospective Studies MH - Double-Blind Method MH - Glucagon-Like Peptide 1 MH - Treatment Outcome MH - Randomized Controlled Trials as Topic MH - Multicenter Studies as Topic MH - *Glucagon-Like Peptides MH - Equivalence Trials as Topic MH - Semaglutide PMC - PMC10953037 OTO - NOTNLM OT - General diabetes OT - Obesity OT - PREVENTIVE MEDICINE OT - Primary Prevention OT - Schizophrenia & psychotic disorders COIS- Competing interests: None declared. EDAT- 2024/03/20 00:42 MHDA- 2024/03/21 12:45 PMCR- 2024/03/18 CRDT- 2024/03/19 20:32 PHST- 2024/03/21 12:45 [medline] PHST- 2024/03/20 00:42 [pubmed] PHST- 2024/03/19 20:32 [entrez] PHST- 2024/03/18 00:00 [pmc-release] AID - bmjopen-2023-077173 [pii] AID - 10.1136/bmjopen-2023-077173 [doi] PST - epublish SO - BMJ Open. 2024 Mar 18;14(3):e077173. doi: 10.1136/bmjopen-2023-077173. PMID- 38502519 OWN - NLM STAT- MEDLINE DCOM- 20240422 LR - 20261010 IS - 1708-0428 (Electronic) IS - 0960-8923 (Linking) VI - 34 IP - 5 DP - 2024 May TI - Glucagon-Like Peptide-1 Receptor Agonists in Post-bariatric Surgery Patients: A Systematic Review and Meta-analysis. PG - 1653-1664 LID - 10.1007/s11695-024-07175-8 [doi] AB - BACKGROUND: A significant number of patients face the issue of weight gain (WG) or inadequate weight loss (IWL) post-bariatric surgery for obesity. Several studies have been published evaluating the role of glucagon-like peptide-1 receptor agonists (GLP1RA) for weight loss post-bariatric surgery. However, no systematic review and meta-analysis (SRM) till date has evaluated the efficacy, safety and tolerability of GLP1RA in this clinical scenario. Hence, this SRM aimed to address this knowledge gap. METHODS: Databases were searched for randomized controlled trials (RCTs), case-control, cohort and observational studies involving use of GLP1RA in the intervention arm post-bariatric surgery. Primary outcome was weight loss post at least 3 months of therapy. Secondary outcomes were evaluation of body composition parameters, total adverse events (TAEs) and severe adverse events (SAEs). RESULTS: From initially screened 1759 articles, 8 studies (557 individuals) were analysed. Compared to placebo, patients receiving liraglutide had significantly greater weight loss after 6-month therapy [MD - 6.0 kg (95% CI, - 8.66 to - 3.33); P < 0.001; I(2) = 79%]. Compared to liraglutide, semaglutide had significantly greater percent reduction in body weight after 6-month [MD - 2.57% (95% CI, - 3.91 to - 1.23); P < 0.001; I(2) = 0%] and 12-month [MD - 4.15% (95% CI, - 6.96 to - 1.34); P = 0.004] therapy. In study by Murvelashvili et al. (2023), after 12-month therapy, semaglutide had significantly higher rates of achieving > 15% [OR 2.15 (95% CI, 1.07-4.33); P = 0.03; n = 207] and > 10% [OR 2.10 (95% CI, 1.19-3.71); P = 0.01; n = 207] weight loss. A significant decrease in fat mass [MD - 4.78 kg (95% CI, - 7.11 to - 2.45); P < 0.001], lean mass [MD - 3.01 kg (95% CI, - 4.80 to - 1.22); P = 0.001] and whole-body bone mineral density [MD - 0.02 kg/m(2) (95% CI, - 0.04 to - 0.00); P = 0.03] was noted with liraglutide. CONCLUSION: Current data is encouraging regarding use of GLP1RAs for managing WG or IWL post-bariatric surgery. Deterioration of bone health and muscle mass remains a concern needing further evaluation. TRIAL REGISTRATION: The predefined protocol has been registered in PROSPERO having registration number of CRD42023473991. CI - (c) 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Dutta, Deep AU - Dutta D AUID- ORCID: 0000-0003-4915-8805 AD - Department of Endocrinology, Center for Endocrinology Diabetes Arthritis & Rheumatism (CEDAR) Superspeciality Healthcare, Dwarka, New Delhi, India. deepdutta2000@yahoo.com. FAU - Nagendra, Lakshmi AU - Nagendra L AUID- ORCID: 0000-0001-6865-5554 AD - Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, India. FAU - Joshi, Ameya AU - Joshi A AD - Department of Endocrinology, Bhaktivedanta Hospital, Mumbai, India. FAU - Krishnasamy, Suryashri AU - Krishnasamy S AD - Department of Pharmacy Practice, JSS College of Pharmacy, Mysuru, Karnataka, India. FAU - Sharma, Meha AU - Sharma M AD - Department of Rheumatology, CEDAR Superspeciality Healthcare, Dwarka, New Delhi, India. FAU - Parajuli, Naresh AU - Parajuli N AUID- ORCID: 0000-0002-6009-1552 AD - Department of Medicine/Endocrinology, Institute of Medicine, Maharajgunj Medical Campus, Tribhuvan University Teaching Hospital, Kathmandu, Nepal. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240319 PL - United States TA - Obes Surg JT - Obesity surgery JID - 9106714 RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) SB - IM CIN - Obes Surg. 2024 Jun;34(6):2259-2260. doi: 10.1007/s11695-024-07229-x. PMID: 38619774 MH - Humans MH - Liraglutide/pharmacology/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity, Morbid/surgery MH - *Bariatric Surgery MH - Weight Loss MH - Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/surgery OTO - NOTNLM OT - Bariatric surgery OT - Diabetes reversal OT - Liraglutide OT - Metabolic surgery OT - Semaglutide OT - Weight loss EDAT- 2024/03/19 18:42 MHDA- 2024/04/22 06:42 CRDT- 2024/03/19 12:21 PHST- 2024/01/13 00:00 [received] PHST- 2024/03/13 00:00 [accepted] PHST- 2024/03/12 00:00 [revised] PHST- 2024/04/22 06:42 [medline] PHST- 2024/03/19 18:42 [pubmed] PHST- 2024/03/19 12:21 [entrez] AID - 10.1007/s11695-024-07175-8 [pii] AID - 10.1007/s11695-024-07175-8 [doi] PST - ppublish SO - Obes Surg. 2024 May;34(5):1653-1664. doi: 10.1007/s11695-024-07175-8. Epub 2024 Mar 19. PMID- 38497231 OWN - NLM STAT- MEDLINE DCOM- 20240508 LR - 20260619 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 6 DP - 2024 Jun TI - Effectiveness and safety of once-weekly subcutaneous semaglutide versus other glucose-lowering agents in real-world patients with type 2 diabetes: A retrospective, observational post-marketing study. PG - 2513-2516 LID - 10.1111/dom.15552 [doi] FAU - Shi, Chenyang AU - Shi C AUID- ORCID: 0000-0002-0626-0781 AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Tan, Yijiong AU - Tan Y AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Hu, Shanshan AU - Hu S AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Qin, Yingyi AU - Qin Y AD - Department of Military Health Statistics, Naval Medical University, Shanghai, China. FAU - Tang, Yuanjun AU - Tang Y AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Wang, Yufan AU - Wang Y AD - Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. FAU - Fan, Guorong AU - Fan G AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China. LA - eng GR - SHYXH-ZP-2021-013/Shanghai Pharmaceutical Association of Clinical Comprehensive Evaluation of Drugs and Research Project on Drug Treatment Pathways/ PT - Comparative Study PT - Letter PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20240318 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/administration & dosage/adverse effects MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Female MH - Male MH - Injections, Subcutaneous MH - Middle Aged MH - Product Surveillance, Postmarketing MH - Aged MH - Treatment Outcome MH - Blood Glucose/drug effects/metabolism MH - Glycated Hemoglobin/analysis/drug effects/metabolism MH - Drug Administration Schedule MH - Semaglutide EDAT- 2024/03/18 06:44 MHDA- 2024/05/08 06:45 CRDT- 2024/03/18 05:12 PHST- 2024/02/27 00:00 [revised] PHST- 2024/01/21 00:00 [received] PHST- 2024/02/28 00:00 [accepted] PHST- 2024/05/08 06:45 [medline] PHST- 2024/03/18 06:44 [pubmed] PHST- 2024/03/18 05:12 [entrez] AID - 10.1111/dom.15552 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Jun;26(6):2513-2516. doi: 10.1111/dom.15552. Epub 2024 Mar 18. PMID- 38493915 OWN - NLM STAT- MEDLINE DCOM- 20240402 LR - 20260127 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 970 DP - 2024 May 5 TI - Semaglutide 6-months therapy of type 2 diabetes mellitus restores adipose progenitors potential to develop metabolically active adipocytes. PG - 176476 LID - S0014-2999(24)00164-X [pii] LID - 10.1016/j.ejphar.2024.176476 [doi] AB - BACKGROUND: Nowadays type 2 diabetes mellitus (T2DM) leads to population mortality growth. Today glucagon-like peptide type 1 receptor agonists (GLP-1 RA) are one of the most promising glucose-lowered drugs with anorexigenic and cardioprotective effects. The present study aims to determine the effects of GLP-1 RA semaglutide 6-month therapy on T2DM patient metabolic parameters and adipose progenitor cell health. METHODS: T2DM patients (N = 8) underwent clinical characterization and subcutaneous fat biopsy at start point and after semaglutide 6-month therapy. Adipose-derived stem cells (ADSC) were isolated by enzymatic method. Cell proliferation analysis was performed by MTT and immunocytochemistry. White and beige adipogenesis was analyzed by BODIPY493/503 staining and confocal microscopy. Adipocyte's metabolic properties were estimated by (3)H- and (14)C-based metabolic assays. Thermogenesis analysis was performed by ERthermAC staining and confocal microscopy. Protein markers were assessed by Western blotting. RESULTS: Semaglutide 6-month therapy demonstrated significant anorexigenic and glucose-lowering effects. However, insulin sensitivity (HOMA-IR and M-index) was unchanged after therapy. Semaglutide 6-month therapy increased ADSC proliferation and white and beige adipogenesis. Moreover, lipid droplets fragmentation was observed in beige adipocytes. Both white and beige adipocytes after semaglutide therapy demonstrated 2-3 fold growth of glucose uptake without changes in insulin sensitivity. Newly formed white adipocytes demonstrated glucose utilization for active ATP synthesis, whereas beige adipocytes for canonical thermogenesis. CONCLUSIONS: Our study has revealed that semaglutide 6-month therapy has not only systemic anorexigenic effects, but can markedly improve adipose tissue health. We have demonstrated critical restoration of ADSC renewal functions, which potentially can be involved in semaglutide based weight loss. CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Stafeev, I AU - Stafeev I AD - National Medical Research Centre of Cardiology Named After Academician E.I.Chazov, 121552, Moscow, Russia. Electronic address: yuristafeev@gmail.com. FAU - Agareva, M AU - Agareva M AD - National Medical Research Centre of Cardiology Named After Academician E.I.Chazov, 121552, Moscow, Russia; Lomonosov Moscow State University, 119991, Moscow, Russia. FAU - Michurina, S AU - Michurina S AD - National Medical Research Centre of Cardiology Named After Academician E.I.Chazov, 121552, Moscow, Russia; Lomonosov Moscow State University, 119991, Moscow, Russia. FAU - Tomilova, A AU - Tomilova A AD - Endocrinology Research Centre, 117292, Moscow, Russia. FAU - Shestakova, E AU - Shestakova E AD - Endocrinology Research Centre, 117292, Moscow, Russia. FAU - Zubkova, E AU - Zubkova E AD - National Medical Research Centre of Cardiology Named After Academician E.I.Chazov, 121552, Moscow, Russia. FAU - Sineokaya, M AU - Sineokaya M AD - Endocrinology Research Centre, 117292, Moscow, Russia. FAU - Ratner, E AU - Ratner E AD - National Medical Research Centre of Cardiology Named After Academician E.I.Chazov, 121552, Moscow, Russia. FAU - Menshikov, M AU - Menshikov M AD - National Medical Research Centre of Cardiology Named After Academician E.I.Chazov, 121552, Moscow, Russia. FAU - Parfyonova, Ye AU - Parfyonova Y AD - National Medical Research Centre of Cardiology Named After Academician E.I.Chazov, 121552, Moscow, Russia; Lomonosov Moscow State University, 119991, Moscow, Russia. FAU - Shestakova, M AU - Shestakova M AD - Lomonosov Moscow State University, 119991, Moscow, Russia; Endocrinology Research Centre, 117292, Moscow, Russia. LA - eng PT - Journal Article DEP - 20240315 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - IY9XDZ35W2 (Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Adipose Tissue, White/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Adipose Tissue, Brown/metabolism MH - *Insulin Resistance/physiology MH - Obesity/metabolism MH - Adipocytes, White/metabolism MH - Glucose/metabolism MH - Glucagon-Like Peptide 1/metabolism MH - *Glucagon-Like Peptides MH - Semaglutide OTO - NOTNLM OT - Adipocytes OT - Adipose-derived stem cells OT - GLP-1 analogues OT - Incretins OT - Obesity OT - Semaglutide OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was supported by Russian Science Foundation grant #22-15-00365. EDAT- 2024/03/18 00:42 MHDA- 2024/04/02 06:46 CRDT- 2024/03/17 20:27 PHST- 2023/12/11 00:00 [received] PHST- 2024/02/20 00:00 [revised] PHST- 2024/03/01 00:00 [accepted] PHST- 2024/04/02 06:46 [medline] PHST- 2024/03/18 00:42 [pubmed] PHST- 2024/03/17 20:27 [entrez] AID - S0014-2999(24)00164-X [pii] AID - 10.1016/j.ejphar.2024.176476 [doi] PST - ppublish SO - Eur J Pharmacol. 2024 May 5;970:176476. doi: 10.1016/j.ejphar.2024.176476. Epub 2024 Mar 15. PMID- 38486046 OWN - NLM STAT- MEDLINE DCOM- 20240920 LR - 20260617 IS - 1476-5578 (Electronic) IS - 1359-4184 (Print) IS - 1359-4184 (Linking) VI - 29 IP - 8 DP - 2024 Aug TI - Association of semaglutide with reduced incidence and relapse of cannabis use disorder in real-world populations: a retrospective cohort study. PG - 2587-2598 LID - 10.1038/s41380-024-02498-5 [doi] AB - Cannabis is the most frequently used illicit drug in the United States with more than 45 million users of whom one-third suffer from a cannabis use disorder (CUD). Despite its high prevalence, there are currently no FDA-approved medications for CUD. Patients treated with semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for treating type 2 diabetes (T2D) and for weight management have reported reduced desire to drink and smoke. Preclinical studies have shown that semaglutide decreased nicotine and alcohol consumption. Preclinical and preliminary clinical evidence of semaglutide's potential beneficial effects on various substance use disorders led us to evaluate if it pertained to CUD. In this retrospective cohort study of electronic health records (EHRs) from the TriNetX Analytics Network, a global federated health research network of approximately 105.3 million patients from 61 large healthcare organizations in the US, we aimed to assess the associations of semaglutide with both incident and recurrent CUD diagnosis compared to non-GLP-1RA anti-obesity or anti-diabetes medications. Hazard ratio (HR) and 95% confidence intervals (CI) of incident and recurrent CUD were calculated for 12-month follow-up by comparing propensity-score matched patient cohorts. The study population included 85,223 patients with obesity who were prescribed semaglutide or non-GLP-1RA anti-obesity medications, with the findings replicated in 596,045 patients with T2D. In patients with obesity (mean age 51.3 years, 65.6% women), semaglutide compared with non-GLP-1RA anti-obesity medications was associated with lower risk for incident CUD in patients with no prior history CUD (HR: 0.56, 95% CI: 0.42-0.75), and recurrent CUD diagnosis in patients with a prior history CUD (HR: 0.62, 95% CI: 0.46-0.84). Consistent reductions were seen for patients stratified by gender, age group, race and in patients with and without T2D. Similar findings were replicated in the study population with T2D when comparing semaglutide with non-GLP-1RA anti-diabetes medications for incident CUD (HR: 0.40, 95% CI: 0.29-0.56) and recurrent CUD (HR: 0.66, 95% CI: 0.42-1.03). While these findings provide preliminary evidence of the potential benefit of semaglutide in CUD in real-world populations, further preclinical studies are warranted to understand the underlying mechanism and randomized clinical trials are needed to support its use clinically for CUD. CI - (c) 2024. The Author(s). FAU - Wang, William AU - Wang W AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Volkow, Nora D AU - Volkow ND AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. nvolkow@nida.nih.gov. FAU - Berger, Nathan A AU - Berger NA AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Davis, Pamela B AU - Davis PB AUID- ORCID: 0000-0002-7113-5338 AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Kaelber, David C AU - Kaelber DC AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, OH, USA. FAU - Xu, Rong AU - Xu R AUID- ORCID: 0000-0003-3127-4795 AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA. rxx@case.edu. LA - eng GR - R01 AG057557/AG/NIA NIH HHS/United States GR - R01 AG076649/AG/NIA NIH HHS/United States GR - R01 AA029831/AA/NIAAA NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States GR - RF1 AG076649/AG/NIA NIH HHS/United States GR - UM1 TR004528/TR/NCATS NIH HHS/United States GR - R25 CA221718/CA/NCI NIH HHS/United States GR - P30 CA043703/CA/NCI NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240314 PL - England TA - Mol Psychiatry JT - Molecular psychiatry JID - 9607835 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Retrospective Studies MH - *Glucagon-Like Peptides/therapeutic use/pharmacology MH - Male MH - Middle Aged MH - Adult MH - Incidence MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Marijuana Abuse/epidemiology/drug therapy MH - *Recurrence MH - Hypoglycemic Agents/therapeutic use MH - Aged MH - United States/epidemiology MH - Cohort Studies MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC11412894 COIS- The authors declare no competing interests. EDAT- 2024/03/15 06:43 MHDA- 2024/09/21 13:19 PMCR- 2024/03/14 CRDT- 2024/03/15 00:35 PHST- 2023/10/23 00:00 [received] PHST- 2024/02/26 00:00 [accepted] PHST- 2024/02/22 00:00 [revised] PHST- 2024/09/21 13:19 [medline] PHST- 2024/03/15 06:43 [pubmed] PHST- 2024/03/15 00:35 [entrez] PHST- 2024/03/14 00:00 [pmc-release] AID - 10.1038/s41380-024-02498-5 [pii] AID - 2498 [pii] AID - 10.1038/s41380-024-02498-5 [doi] PST - ppublish SO - Mol Psychiatry. 2024 Aug;29(8):2587-2598. doi: 10.1038/s41380-024-02498-5. Epub 2024 Mar 14. PMID- 38477183 OWN - NLM STAT- MEDLINE DCOM- 20240508 LR - 20260622 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 6 DP - 2024 Jun TI - Oral or injectable semaglutide for the management of type 2 diabetes in routine care: A multicentre observational study comparing matched cohorts. PG - 2390-2400 LID - 10.1111/dom.15554 [doi] AB - AIM: To investigate the real-world utilization and comparative clinical outcomes of injectable and oral semaglutide in individuals with type 2 diabetes (T2D) with the aim of enhancing understanding of the practical implications associated with choosing between these formulations. METHODS: New users of oral or injectable semaglutide were selected from a cohort of 14 079 initiators of glucagon-like peptide-1 receptor agonists. Propensity-score matching (PSM) was employed to create balanced groups, ensuring comparability. The analysis encompassed dose exposure, drug persistence, and clinical outcomes, including changes in glycated haemoglobin (HbA1c) and body weight, with up to 18 months' follow-up. RESULTS: We analysed two matched groups of 107 participants each, who comprised on average 63.6% men, aged 64 years, with diabetes duration of approximately 10 years, body mass index of 29 kg/m(2) and HbA1c level of 7.7-7.8% (61-62 mmol/mol). The proportion of low, intermediate and high doses were similar with the oral and the injectable formulation. The change in HbA1c was similar between groups (-0.9% / -10 mmol/mol at 18 months) as was the proportion of individuals reaching HbA1c <6.5% (48 mmol/mol). The average change in body weight was similar in the two groups (-3.7 kg with injectable and -3.3 kg with oral at 18 months) but more new users of injectable semaglutide lost >/=5% body weight. Persistence on drug was longer with injectable than with oral semaglutide. CONCLUSION: In a real-world setting, improvements in HbA1c and body weight were similar after initiation of oral or injectable semaglutide. These results may be specific to the features of the matched cohorts under investigation, with limited generalizability to populations with different characteristics. CI - (c) 2024 John Wiley & Sons Ltd. FAU - Fadini, Gian Paolo AU - Fadini GP AUID- ORCID: 0000-0002-6510-2097 AD - Department of Medicine, University of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine (VIMM), Padua, Italy. FAU - Bonora, Benedetta Maria AU - Bonora BM AUID- ORCID: 0000-0002-6770-2723 AD - Department of Medicine, University of Padova, Padua, Italy. AD - Veneto Institute of Molecular Medicine (VIMM), Padua, Italy. FAU - Ghiani, Mariangela AU - Ghiani M AD - Diabetology Unit, Azienda Sanitaria Locale 8 Cagliari Quartu S. Elena, Cagliari, Italy. FAU - Anichini, Roberto AU - Anichini R AD - Diabetes Unit Area Pistoiese, USL Centro Toscana, Pistoia, Italy. FAU - Melchionda, Elena AU - Melchionda E AD - Diabetology and Metabolic Diseases, San Luigi Gonzaga Hospital, Orbassano, Italy. FAU - Fattor, Bruno AU - Fattor B AD - Diabetology Service, Azienda Sanitaria dell'Alto Adige, Bolzano, Italy. FAU - Fazion, Stefano AU - Fazion S AD - Diabetology and Metabolic Diseases, Ospedale C. Poma, Mantova, Italy. FAU - Meregalli, Giancarla AU - Meregalli G AD - Endocrine Disease Center and Regional Diabetes Center, ASST, Bergamo Ovest, Italy. FAU - Giaccari, Andrea AU - Giaccari A AUID- ORCID: 0000-0002-7462-7792 AD - Endocrine and Metabolic Center, Fondazione Policlinico Universitario A. Gemelli IRCCS and Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Avogaro, Angelo AU - Avogaro A AUID- ORCID: 0000-0002-1177-0516 AD - Department of Medicine, University of Padova, Padua, Italy. FAU - Consoli, Agostino AU - Consoli A AD - Endocrinology and Metabolism Unit, ASL, Pescara, Italy; Department of Medicine and Aging Sciences DMSI and Center for Advanced Studies and Technology CAST, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy. CN - GLIMPLES study investigators LA - eng GR - Italian Diabetes Society, GLIMPLES project/ PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20240313 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Middle Aged MH - Female MH - Administration, Oral MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - *Glycated Hemoglobin/analysis/drug effects MH - Cohort Studies MH - Body Weight/drug effects MH - Treatment Outcome MH - Injections MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - antiobesity drug OT - cohort study OT - glycaemic control OT - real-world OT - weight control FIR - Baldassarre, Maria Antonia Pompea IR - Baldassarre MAP FIR - Formoso, Gloria IR - Formoso G FIR - Consoli, Agostino IR - Consoli A FIR - Leto, Gaetano IR - Leto G FIR - Leonetti, Frida IR - Leonetti F FIR - Fazion, Stefano IR - Fazion S FIR - Meregalli, Giancarla IR - Meregalli G FIR - Zavattaro, Marco IR - Zavattaro M FIR - Aimaretti, Gianluca IR - Aimaretti G FIR - Melchionda, Elena IR - Melchionda E FIR - Barale, Cristina IR - Barale C FIR - Cau, Rosella IR - Cau R FIR - Ghiani, Mariangela IR - Ghiani M FIR - Muscara, Andrea IR - Muscara A FIR - Russo, Giuseppina IR - Russo G FIR - Anichini, Roberto IR - Anichini R FIR - Fattor, Bruno IR - Fattor B FIR - Fadini, Gian Paolo IR - Fadini GP FIR - Avogaro, Angelo IR - Avogaro A FIR - Nollino, Laura IR - Nollino L FIR - Paccagnella, Agostino IR - Paccagnella A FIR - Strazzabosco, Marco IR - Strazzabosco M EDAT- 2024/03/13 06:46 MHDA- 2024/05/08 06:45 CRDT- 2024/03/13 05:33 PHST- 2024/02/24 00:00 [revised] PHST- 2024/01/30 00:00 [received] PHST- 2024/02/28 00:00 [accepted] PHST- 2024/05/08 06:45 [medline] PHST- 2024/03/13 06:46 [pubmed] PHST- 2024/03/13 05:33 [entrez] AID - 10.1111/dom.15554 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Jun;26(6):2390-2400. doi: 10.1111/dom.15554. Epub 2024 Mar 13. PMID- 38474208 OWN - NLM STAT- MEDLINE DCOM- 20240314 LR - 20260922 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 5 DP - 2024 Mar 4 TI - Semaglutide Improves Liver Steatosis and De Novo Lipogenesis Markers in Obese and Type-2-Diabetic Mice with Metabolic-Dysfunction-Associated Steatotic Liver Disease. LID - 10.3390/ijms25052961 [doi] LID - 2961 AB - Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a prevalent clinical condition associated with elevated morbidity and mortality rates. Patients with MASLD treated with semaglutide, a glucagon-like peptide-1 receptor agonist, demonstrate improvement in terms of liver damage. However, the mechanisms underlaying this beneficial effect are not yet fully elucidated. We investigated the efficacy of semaglutide in halting MASLD progression using a genetic mouse model of diabesity. Leptin-receptor-deficient mice with obesity and diabetes (BKS db/db) were either untreated or administered with semaglutide for 11 weeks. Changes in food and water intake, body weight and glycemia were monitored throughout the study. Body fat composition was assessed by dual-energy X-ray absorptiometry. Upon sacrifice, serum biochemical parameters, liver morphology, lipidomic profile and liver-lipid-related pathways were evaluated. The semaglutide-treated mice exhibited lower levels of glycemia, body weight, serum markers of liver dysfunction and total and percentage of fat mass compared to untreated db/db mice without a significant reduction in food intake. Histologically, semaglutide reduced hepatic steatosis, hepatocellular ballooning and intrahepatic triglycerides. Furthermore, the treatment ameliorated the hepatic expression of de novo lipogenesis markers and modified lipid composition by increasing the amount of polyunsaturated fatty acids. The administration of semaglutide to leptin-receptor-deficient, hyperphagic and diabetic mice resulted in the amelioration of MASLD, likely independently of daily caloric intake, suggesting a direct effect of semaglutide on the liver through modulation of the lipid profile. FAU - Soto-Catalan, Manuel AU - Soto-Catalan M AD - Renal, Vascular and Diabetes Research Laboratory, IIS-Fundacion Jimenez Diaz, Spanish Biomedical Universidad Autonoma de Madrid, 28049 Madrid, Spain. AD - Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain. FAU - Opazo-Rios, Lucas AU - Opazo-Rios L AUID- ORCID: 0000-0003-3586-3319 AD - Renal, Vascular and Diabetes Research Laboratory, IIS-Fundacion Jimenez Diaz, Spanish Biomedical Universidad Autonoma de Madrid, 28049 Madrid, Spain. AD - Facultad de Ciencias de la Salud, Universidad de Las Americas, Concepcion-Talcahuano 4301099, Chile. FAU - Quiceno, Hernan AU - Quiceno H AD - Department of Pathology, Fundacion Jimenez Diaz, 28040 Madrid, Spain. FAU - Lazaro, Iolanda AU - Lazaro I AD - Cardiovascular Risk and Nutrition Research Group, Epidemiology and Public Health Program, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain. FAU - Moreno, Juan Antonio AU - Moreno JA AUID- ORCID: 0000-0002-7468-2871 AD - Department of Cell Biology, Physiology and Immunology, University of Cordoba, 140471 Cordoba, Spain. AD - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofia, 14004 Cordoba, Spain. FAU - Gomez-Guerrero, Carmen AU - Gomez-Guerrero C AUID- ORCID: 0000-0001-9001-5414 AD - Renal, Vascular and Diabetes Research Laboratory, IIS-Fundacion Jimenez Diaz, Spanish Biomedical Universidad Autonoma de Madrid, 28049 Madrid, Spain. AD - Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain. FAU - Egido, Jesus AU - Egido J AD - Renal, Vascular and Diabetes Research Laboratory, IIS-Fundacion Jimenez Diaz, Spanish Biomedical Universidad Autonoma de Madrid, 28049 Madrid, Spain. AD - Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain. FAU - Mas-Fontao, Sebastian AU - Mas-Fontao S AUID- ORCID: 0000-0001-6604-3327 AD - Renal, Vascular and Diabetes Research Laboratory, IIS-Fundacion Jimenez Diaz, Spanish Biomedical Universidad Autonoma de Madrid, 28049 Madrid, Spain. AD - Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain. AD - Faculty of Medicine and Biomedicine, Universidad Alfonso X el Sabio (UAX), 28691 Madrid, Spain. LA - eng GR - PI20/00375/Instituto de Salud Carlos III/ GR - PI23/00119/Instituto de Salud Carlos III/ PT - Journal Article DEP - 20240304 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Leptin) RN - 0 (Triglycerides) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Animals MH - Mice MH - Lipogenesis MH - Leptin/metabolism MH - *Diabetes Mellitus, Experimental/metabolism MH - *Fatty Liver/metabolism MH - Obesity/metabolism MH - Liver/metabolism MH - Body Weight MH - Triglycerides/metabolism MH - *Diabetes Mellitus, Type 2/metabolism MH - *Non-alcoholic Fatty Liver Disease/metabolism MH - Mice, Obese MH - *Glucagon-Like Peptides MH - Semaglutide PMC - PMC10932050 OTO - NOTNLM OT - GLP1 receptor agonists OT - diabetes OT - insulin resistance OT - obesity OT - semaglutide OT - steatosis COIS- The authors declare no conflicts of interest. EDAT- 2024/03/13 06:47 MHDA- 2024/03/14 06:46 PMCR- 2024/03/04 CRDT- 2024/03/13 01:24 PHST- 2024/02/03 00:00 [received] PHST- 2024/02/26 00:00 [revised] PHST- 2024/02/28 00:00 [accepted] PHST- 2024/03/14 06:46 [medline] PHST- 2024/03/13 06:47 [pubmed] PHST- 2024/03/13 01:24 [entrez] PHST- 2024/03/04 00:00 [pmc-release] AID - ijms25052961 [pii] AID - ijms-25-02961 [pii] AID - 10.3390/ijms25052961 [doi] PST - epublish SO - Int J Mol Sci. 2024 Mar 4;25(5):2961. doi: 10.3390/ijms25052961. PMID- 38470137 OWN - NLM STAT- MEDLINE DCOM- 20240322 LR - 20260127 IS - 1556-9519 (Electronic) IS - 1556-3650 (Linking) VI - 62 IP - 2 DP - 2024 Feb TI - Challenges with glucagon-like peptide-1 (GLP-1) agonist initiation: a case series of semaglutide overdose administration errors. PG - 131-133 LID - 10.1080/15563650.2024.2322049 [doi] AB - BACKGROUND: Prescriptions of semaglutide, a glucagon-like peptide-1 receptor agonist administered weekly for Type 2 diabetes mellitus and obesity, are increasing. Adverse effects from semaglutide overdose are poorly described. We report adverse effects from three unintentional semaglutide overdoses upon initiation. CASE REPORTS: Case 1: A 53-year-old man unintentionally injected semaglutide 2 mg instead of the recommended 0.1 mg. Case 2: A 45-year-old woman unintentionally injected semaglutide 2.4 mg instead of 0.25 mg. Case 3: A 33-year-old woman injected semaglutide 1.7 mg. All three of these patients developed nonspecific gastrointestinal symptoms. No patient experienced hypoglycemia. DISCUSSION: These unintentional semaglutide overdoses occurred due to deficits in patient and prescriber knowledge, and evasion of regulated access to pharmaceuticals. Nonspecific gastrointestinal symptoms predominated. The potential for hypoglycemia following glucagon-like peptide-1 agonist overdose is unclear, though it did not occur in our patients. It is thought that glucagon-like peptide-1 agonists are unlikely to cause hypoglycemia because their effects are glucose-dependent and diminish as serum glucose concentrations approach euglycemia. There is, however, an increase in hypoglycemia when glucagon-like peptide-1 agonists are combined with sulfonylureas. CONCLUSIONS: This case series highlights the critical role of patient education and training upon initiation of semaglutide therapy to minimize administration errors and adverse effects from injection of glucagon-like peptide-1 receptor agonists. FAU - Wiener, Brian G AU - Wiener BG AD - Division of Medical Toxicology, NewYork-Presbyterian Department of Emergency Medicine, Weill Cornell School of Medicine, New York, NY, USA. FAU - Gnirke, Marlis AU - Gnirke M AD - Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University Grossman School of Medicine, New York, NY, USA. AD - Department of Health & Mental Hygiene, New York City Poison Control Center, New York, NY, USA. FAU - Vassallo, Susi AU - Vassallo S AD - Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University Grossman School of Medicine, New York, NY, USA. AD - Department of Health & Mental Hygiene, New York City Poison Control Center, New York, NY, USA. FAU - Smith, Silas W AU - Smith SW AD - Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University Grossman School of Medicine, New York, NY, USA. AD - Department of Health & Mental Hygiene, New York City Poison Control Center, New York, NY, USA. AD - Institute for Innovations in Medical Education, New York University Grossman School of Medicine, NYU Langone Health, New York, NY, USA. FAU - Su, Mark K AU - Su MK AD - Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, New York University Grossman School of Medicine, New York, NY, USA. AD - Department of Health & Mental Hygiene, New York City Poison Control Center, New York, NY, USA. LA - eng PT - Case Reports PT - Journal Article DEP - 20240312 PL - England TA - Clin Toxicol (Phila) JT - Clinical toxicology (Philadelphia, Pa.) JID - 101241654 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - IY9XDZ35W2 (Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Male MH - Female MH - Humans MH - Middle Aged MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/toxicity MH - Glucagon-Like Peptide 1/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - *Hypoglycemia/chemically induced/drug therapy MH - Glucose/therapeutic use MH - *Glucagon-Like Peptides MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Semaglutide overdose; GLP-1 overdose; glucagon-like peptide-1 overdose; semaglutide administration error EDAT- 2024/03/12 12:44 MHDA- 2024/03/22 06:44 CRDT- 2024/03/12 09:04 PHST- 2024/03/22 06:44 [medline] PHST- 2024/03/12 12:44 [pubmed] PHST- 2024/03/12 09:04 [entrez] AID - 10.1080/15563650.2024.2322049 [doi] PST - ppublish SO - Clin Toxicol (Phila). 2024 Feb;62(2):131-133. doi: 10.1080/15563650.2024.2322049. Epub 2024 Mar 12. PMID- 38468125 OWN - NLM STAT- MEDLINE DCOM- 20240409 LR - 20260622 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 5 DP - 2024 May TI - Use of once-daily oral semaglutide and associated clinical outcomes among adults with type 2 diabetes in routine clinical practice in Canada: A multicentre, prospective real-world study (PIONEER REAL Canada). PG - 1799-1807 LID - 10.1111/dom.15493 [doi] AB - AIM: PIONEER REAL Canada examined real-world clinical outcomes associated with the use of once-daily oral semaglutide in adults with type 2 diabetes. MATERIALS AND METHODS: This was a 34- to 44-week, multicentre, prospective, open-label, non-interventional study in adults who were treatment-naive to injectable glucose-lowering medication and initiated oral semaglutide in routine clinical practice. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to the end of the study (EoS). Secondary endpoints assessed at EoS were change from baseline in body weight (BW); the proportion of participants reaching HbA1c levels <7% and the composite endpoints, HbA1c reduction >/=1% point with BW reduction >/=3% and >/=5%; and treatment satisfaction measured using Diabetes Treatment Satisfaction Questionnaires (DTSQ) status and change. Primary analyses were based on the in-study observation period. RESULTS: In total, 182 participants initiated oral semaglutide (mean age, 58.6 years; HbA1c, 8.0%; BW, 93.7 kg). The estimated changes (95% confidence interval) from baseline to EoS in HbA1c and BW were -1.09% points (-1.24, -0.94; p < .0001) and -7.17% (-8.24, -6.11; p < .0001), respectively. At EoS, 53.7% of participants had HbA1c levels <7%; 39.3% and 31.6% reached HbA1c reduction >/=1% point plus BW reduction >/=3% and >/=5%, respectively. Treatment satisfaction significantly increased (DTSQ status, +4.47 points; DTSQ change, 11.83 points; both p < .0001). At EoS, 75.3% of participants remained on oral semaglutide (55.5% received oral semaglutide 14 mg). No new safety signals were identified for oral semaglutide. CONCLUSIONS: In PIONEER REAL Canada, participants treated with oral semaglutide in routine clinical practice experienced clinically relevant reductions in HbA1c and BW and increased treatment satisfaction. CI - (c) 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Jain, Akshay B AU - Jain AB AUID- ORCID: 0000-0001-8515-5359 AD - TLC Diabetes and Endocrinology, Surrey, Canada. AD - Division of Endocrinology and Metabolism, University of British Columbia, Vancouver, Canada. FAU - Reichert, Sonja M AU - Reichert SM AD - Department of Family Medicine and Centre for Studies in Family Medicine, Schulich School of Medicine & Dentistry, Western University, London, Canada. FAU - Amadid, Hanan AU - Amadid H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Braae, Uffe C AU - Braae UC AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bradley, Ryan M AU - Bradley RM AD - Novo Nordisk Inc., Mississauga, Canada. FAU - Kim, James W AU - Kim JW AD - Department of Family Medicine, University of Calgary, Calgary, Canada. FAU - Soo, Victoria AU - Soo V AD - Department of Family Medicine, Western University, London, Canada. FAU - Yale, Jean-Francois AU - Yale JF AUID- ORCID: 0000-0002-7833-9050 AD - Division of Endocrinology and Metabolism, Department of Medicine, McGill University, Montreal, Canada. LA - eng SI - ClinicalTrials.gov/NCT04559815 GR - Novo Nordisk Pharma Ltd/ PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20240311 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Glycated Hemoglobin MH - Prospective Studies MH - Glucagon-Like Peptides/adverse effects MH - Body Weight MH - Canada/epidemiology MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide-1 analogue OT - real-world evidence OT - semaglutide OT - type 2 diabetes EDAT- 2024/03/12 06:43 MHDA- 2024/04/09 06:45 CRDT- 2024/03/12 00:46 PHST- 2024/01/19 00:00 [revised] PHST- 2023/11/10 00:00 [received] PHST- 2024/01/27 00:00 [accepted] PHST- 2024/04/09 06:45 [medline] PHST- 2024/03/12 06:43 [pubmed] PHST- 2024/03/12 00:46 [entrez] AID - 10.1111/dom.15493 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 May;26(5):1799-1807. doi: 10.1111/dom.15493. Epub 2024 Mar 11. PMID- 38447814 OWN - NLM STAT- MEDLINE DCOM- 20241222 LR - 20260914 IS - 1542-7714 (Electronic) IS - 1542-3565 (Linking) VI - 23 IP - 1 DP - 2025 Jan TI - Safety and Efficacy of Efruxifermin in Combination With a GLP-1 Receptor Agonist in Patients With NASH/MASH and Type 2 Diabetes in a Randomized Phase 2 Study. PG - 103-113 LID - S1542-3565(24)00226-X [pii] LID - 10.1016/j.cgh.2024.02.022 [doi] AB - BACKGROUND & AIMS: In phase 2 studies, efruxifermin, an Fc-FGF21 analog, significantly reduced steatohepatitis and fibrosis in patients with non-alcoholic steatohepatitis, now called metabolic dysfunction-associated steatohepatitis (MASH), for which there is no approved treatment. Type 2 diabetes (T2D) and obesity are prevalent among patients with MASH and increasingly treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). This study evaluated the safety and efficacy of efruxifermin in patients with MASH, fibrosis, and T2D taking a GLP-1RA. METHODS: Cohort D was a double-blind, placebo-controlled, phase 2b study in adults with T2D and MASH with fibrosis (F1-F3) on stable GLP-1RA therapy randomized (2:1) to receive efruxifermin 50 mg or placebo, once weekly for 12 weeks. The primary endpoint was safety and tolerability of efruxifermin added to a stable dose of GLP-1RA. Secondary endpoints included changes in hepatic fat fraction (HFF), markers of liver injury and fibrosis, and metabolic parameters. RESULTS: Adults (N = 31) with T2D and MASH fibrosis (F1-F3) on a stable GLP-1RA (semaglutide, 48.4%; dulaglutide, 45.2%; liraglutide, 6.5%) received efruxifermin 50 mg (n = 21) or placebo (n = 10) for 12 weeks. The addition of efruxifermin to a GLP-1RA appeared safe and well-tolerated. The most frequent efruxifermin-related adverse events were mild to moderate gastrointestinal events. One patient receiving efruxifermin discontinued due to nausea, and another withdrew consent. There were no treatment-related serious adverse events. After 12 weeks, efruxifermin reduced HFF by 65% (P < .0001 vs placebo) compared with a 10% reduction for placebo (GLP-1RA alone). Efruxifermin also improved noninvasive markers of liver injury, fibrosis, glucose, and lipid metabolism while maintaining GLP-1RA-mediated weight loss. CONCLUSIONS: The tolerability profile of efruxifermin added to GLP-1RA appeared comparable to that of either drug alone, while also significantly reducing HFF and noninvasive markers of fibrosis in patients with MASH and T2D. Liver health in patients already on a GLP-1RA may be further improved by addition of efruxifermin. CLINICALTRIALS: gov, Number: NCT05039450. CI - Copyright (c) 2025 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Harrison, Stephen A AU - Harrison SA AD - University of Oxford, Oxford, United Kingdom; Pinnacle Clinical Research, San Antonio, Texas. FAU - Frias, Juan P AU - Frias JP AD - Velocity Clinical Research, Los Angeles, California. FAU - Lucas, K Jean AU - Lucas KJ AD - Lucas Research, Morehead, North Carolina. FAU - Reiss, Gary AU - Reiss G AD - Tandem Clinical Research, Marrero, Louisiana. FAU - Neff, Guy AU - Neff G AD - Covenant Metabolic Specialists, LLC, Sarasota, Florida; Covenant Research and Clinics LLC, Ft. Myers, Florida. FAU - Bollepalli, Sureka AU - Bollepalli S AD - Tampa Bay Medical Research, Clearwater, Florida. FAU - Su, Yan AU - Su Y AD - Medpace, Cincinnati, Ohio. FAU - Chan, Doreen AU - Chan D AD - Akero Therapeutics Inc, South San Francisco, California. FAU - Tillman, Erik J AU - Tillman EJ AD - Akero Therapeutics Inc, South San Francisco, California. FAU - Moulton, Ali AU - Moulton A AD - Akero Therapeutics Inc, South San Francisco, California. FAU - de Temple, Brittany AU - de Temple B AD - Akero Therapeutics Inc, South San Francisco, California. FAU - Zari, Arian AU - Zari A AD - Akero Therapeutics Inc, South San Francisco, California. FAU - Shringarpure, Reshma AU - Shringarpure R AD - Akero Therapeutics Inc, South San Francisco, California. Electronic address: reshma@akerotx.com. FAU - Rolph, Timothy AU - Rolph T AD - Akero Therapeutics Inc, South San Francisco, California. FAU - Cheng, Andrew AU - Cheng A AD - Akero Therapeutics Inc, South San Francisco, California. FAU - Yale, Kitty AU - Yale K AD - Akero Therapeutics Inc, South San Francisco, California. LA - eng SI - ClinicalTrials.gov/NCT05039450 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240304 PL - United States TA - Clin Gastroenterol Hepatol JT - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JID - 101160775 RN - 0 (Placebos) RN - 0 (Immunoglobulin Fc Fragments) RN - 62031-54-3 (Fibroblast Growth Factors) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Male MH - Female MH - Middle Aged MH - Double-Blind Method MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Adult MH - Treatment Outcome MH - Aged MH - Placebos/administration & dosage MH - Drug Therapy, Combination MH - Immunoglobulin Fc Fragments/therapeutic use/adverse effects/administration & dosage MH - Fibroblast Growth Factors/therapeutic use MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Drug-Related Side Effects and Adverse Reactions/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Fibroblast Growth Factor 21 OT - GLP-1 Analog OT - Hispanic/Latinx OT - NAFLD EDAT- 2024/03/07 00:42 MHDA- 2024/12/23 00:19 CRDT- 2024/03/06 19:17 PHST- 2023/11/09 00:00 [received] PHST- 2024/02/02 00:00 [revised] PHST- 2024/02/16 00:00 [accepted] PHST- 2024/12/23 00:19 [medline] PHST- 2024/03/07 00:42 [pubmed] PHST- 2024/03/06 19:17 [entrez] AID - S1542-3565(24)00226-X [pii] AID - 10.1016/j.cgh.2024.02.022 [doi] PST - ppublish SO - Clin Gastroenterol Hepatol. 2025 Jan;23(1):103-113. doi: 10.1016/j.cgh.2024.02.022. Epub 2024 Mar 4. PMID- 38444317 OWN - NLM STAT- MEDLINE DCOM- 20240307 LR - 20260312 IS - 1557-8593 (Electronic) IS - 1520-9156 (Linking) VI - 26 IP - 3 DP - 2024 Mar TI - Efficacy of Semaglutide in Overweight and Obese Patients with Type 1 Diabetes. PG - 184-189 LID - 10.1089/dia.2023.0490 [doi] AB - Introduction: More than two-thirds of patients with type 1 diabetes (T1D) are overweight (OW) and/or obese (OB) in the USA and Western Europe, resulting in insulin resistance as in type 2 diabetes. None of the currently available glucagon like polypeptide 1 (GLP-1) analogs are approved for patients with T1D. A higher dose of semaglutide has been approved by the Food and Drug Administration (FDA) for subjects with body mass index (BMI) >27 kg/m(2). We evaluated the real-world use of semaglutide in patients with T1D. Methods: This was a retrospective chart review study of 50 OW or OB patients with T1D who were initiated on semaglutide and followed for 1 year. The control group comprised of 50 computer-matched patients (for sex, race, weight, BMI, and diabetes duration) during a similar time period and were not on any weight loss medications. Results: Most patients (92%) were non-Hispanic white in both arms. Mean +/- standard deviation (SD) age and duration of diabetes were 42 +/- 11 and 27 +/- 12 years, respectively. The continuous glucose monitors (CGM), insulin pump use, baseline BMI and body weight were also similar in the two groups. Baseline glycosylated hemoglobin (HbA1c) was insignificantly lower in the semaglutide group (7.6% vs. 8.2%, respectively; P = non-significant [NS]). Total daily insulin dose (TDD) and insulin dose per kg body weight were higher in the semaglutide group at baseline with no difference in basal or prandial insulin dose. There were significantly greater declines in mean (+/-SD), BMI (7.9% +/- 2.6%), body weight (15.9 lbs +/- 5.4 lbs), HbA1c, CGM glucose SD and coefficient of variation (CV), and increase in CGM time in range (TIR) in the semaglutide group compared to the control group with no difference in insulin dose changes, time above range (TAR), or time below range (TBR). Conclusions: We conclude that use of semaglutide in patients who are OW and/or OB with T1D was effective in lowering body weight and BMI, and improving glycemic metrics in this pilot real-world study. We strongly recommend performing prospective, large-randomized clinical trials with newer GLP-1 analogs like semaglutide and tirzepatide (twin-cretin) for subjects with T1D associated with OW and/or OB. FAU - Garg, Satish K AU - Garg SK AD - Barbara Davis Center for Diabetes, Department of Medicine and Pediatrics, University of Colorado Denver, Aurora, Colorado, USA. FAU - Kaur, Gurleen AU - Kaur G AD - Barbara Davis Center for Diabetes, Department of Medicine and Pediatrics, University of Colorado Denver, Aurora, Colorado, USA. FAU - Haider, Zehra AU - Haider Z AD - Barbara Davis Center for Diabetes, Department of Medicine and Pediatrics, University of Colorado Denver, Aurora, Colorado, USA. FAU - Rodriquez, Erika AU - Rodriquez E AD - Barbara Davis Center for Diabetes, Department of Medicine and Pediatrics, University of Colorado Denver, Aurora, Colorado, USA. FAU - Beatson, Christie AU - Beatson C AD - Barbara Davis Center for Diabetes, Department of Medicine and Pediatrics, University of Colorado Denver, Aurora, Colorado, USA. FAU - Snell-Bergeon, Janet AU - Snell-Bergeon J AD - Barbara Davis Center for Diabetes, Department of Medicine and Pediatrics, University of Colorado Denver, Aurora, Colorado, USA. LA - eng PT - Journal Article PL - United States TA - Diabetes Technol Ther JT - Diabetes technology & therapeutics JID - 100889084 RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Insulin, Regular, Human) RN - 0 (Insulin) RN - IY9XDZ35W2 (Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - United States MH - Humans MH - Overweight/complications/drug therapy MH - *Diabetes Mellitus, Type 1/complications/drug therapy MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glycated Hemoglobin MH - Prospective Studies MH - Retrospective Studies MH - Obesity/complications/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Insulin, Regular, Human MH - Insulin MH - Glucose MH - Semaglutide OTO - NOTNLM OT - BMI OT - CGM OT - CV OT - HbA1c OT - Obesity OT - Overweight OT - SD OT - TIR OT - Type 1 diabetes EDAT- 2024/03/06 06:43 MHDA- 2024/03/07 06:42 CRDT- 2024/03/06 03:09 PHST- 2024/03/07 06:42 [medline] PHST- 2024/03/06 06:43 [pubmed] PHST- 2024/03/06 03:09 [entrez] AID - 10.1089/dia.2023.0490 [doi] PST - ppublish SO - Diabetes Technol Ther. 2024 Mar;26(3):184-189. doi: 10.1089/dia.2023.0490. PMID- 38437690 OWN - NLM STAT- MEDLINE DCOM- 20240320 LR - 20260127 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 177 IP - 3 DP - 2024 Mar TI - In adults with overweight or obesity and CVD, but without diabetes, semaglutide reduced MACE at a mean 40 mo. PG - JC31 LID - 10.7326/J24-0008 [doi] AB - Lincoff AM, Brown-Frandsen K, Colhoun HM, et al; SELECT Trial Investigators. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389:2221-2232. 37952131. FAU - Koutroumpakis, Efstratios AU - Koutroumpakis E AD - University of Texas MD Anderson Cancer Center, Houston, Texas, USA (E.K., A.D.). FAU - Deswal, Anita AU - Deswal A AD - University of Texas MD Anderson Cancer Center, Houston, Texas, USA (E.K., A.D.). LA - eng PT - Comment PT - Journal Article DEP - 20240305 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. PMID: 37952131 MH - Adult MH - Humans MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptides MH - Hypoglycemic Agents/therapeutic use MH - Obesity/complications/drug therapy MH - Overweight/complications/drug therapy MH - Clinical Trials as Topic MH - Semaglutide COIS- Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J24-0008. EDAT- 2024/03/04 18:42 MHDA- 2024/03/20 06:45 CRDT- 2024/03/04 17:02 PHST- 2024/03/20 06:45 [medline] PHST- 2024/03/04 18:42 [pubmed] PHST- 2024/03/04 17:02 [entrez] AID - 10.7326/J24-0008 [doi] PST - ppublish SO - Ann Intern Med. 2024 Mar;177(3):JC31. doi: 10.7326/J24-0008. Epub 2024 Mar 5. PMID- 38426245 OWN - NLM STAT- MEDLINE DCOM- 20240422 LR - 20260426 IS - 1469-7793 (Electronic) IS - 0022-3751 (Linking) VI - 602 IP - 8 DP - 2024 Apr TI - Turning fat into muscle: can this be an alternative to anti-obesity drugs such as semaglutide? PG - 1655-1658 LID - 10.1113/JP286430 [doi] FAU - Wackerhage, Henning AU - Wackerhage H AUID- ORCID: 0000-0001-5920-5842 AD - School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany. FAU - Hinrichs, Arne AU - Hinrichs A AUID- ORCID: 0000-0003-3022-5983 AD - Center for Innovative Medical Models (CiMM), LMU Munich, Munich, Germany. FAU - Wolf, Eckhard AU - Wolf E AD - Center for Innovative Medical Models (CiMM), LMU Munich, Munich, Germany. AD - German Center for Diabetes Research (DZD), Neuherberg, Germany. FAU - Hrabe de Angelis, Martin AU - Hrabe de Angelis M AUID- ORCID: 0000-0002-7898-2353 AD - German Center for Diabetes Research (DZD), Neuherberg, Germany. AD - Institute of Experimental Genetics, Helmholtz Zentrum Munchen, Neuherberg, Germany. AD - Chair of Experimental Genetics, School of Life Science Weihenstephan, Technische Universitat Munchen, Freising, Germany. LA - eng GR - 450149205/Deutsche Forschungsgemeinschaft (DFG)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240301 PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 0 (Anti-Obesity Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Anti-Obesity Agents/pharmacology/therapeutic use MH - Muscles MH - Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptide-1 Receptor MH - Hypoglycemic Agents MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonists OT - diabetes mellitus OT - hypertrophy OT - muscle atrophy OT - obesity OT - skeletal muscle EDAT- 2024/03/01 06:44 MHDA- 2024/04/22 06:42 CRDT- 2024/03/01 04:23 PHST- 2024/02/15 00:00 [received] PHST- 2024/02/15 00:00 [accepted] PHST- 2024/04/22 06:42 [medline] PHST- 2024/03/01 06:44 [pubmed] PHST- 2024/03/01 04:23 [entrez] AID - 10.1113/JP286430 [doi] PST - ppublish SO - J Physiol. 2024 Apr;602(8):1655-1658. doi: 10.1113/JP286430. Epub 2024 Mar 1. PMID- 38421490 OWN - NLM STAT- MEDLINE DCOM- 20240325 LR - 20260905 IS - 1937-6995 (Electronic) IS - 1556-9039 (Print) IS - 1556-9039 (Linking) VI - 20 IP - 2 DP - 2024 Apr TI - Glucagon-Like Peptide-1 Receptor Agonist Cases Reported to United States Poison Centers, 2017-2022. PG - 193-204 LID - 10.1007/s13181-024-00999-x [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of medications for management of diabetes and obesity. The objective of this study is to characterize the epidemiology of GLP-1RA cases reported to US poison centers. METHODS: We analyzed cases involving a GLP-1RA reported to the National Poison Data System during 2017-2022. RESULTS: There were 5,713 single-substance exposure cases reported to US poison centers involving a GLP-1RA. Most cases were among females (71.3%) and attributable to therapeutic errors (79.9%). More than one-fifth (22.4%) of cases were evaluated in a healthcare facility, including 0.9% admitted to a critical care unit and 4.1% admitted to a non-critical care unit. Serious medical outcomes were described in 6.2% of cases, including one fatality. The rate of cases per one million US population increased from 1.16 in 2017 to 3.49 in 2021, followed by a rapid increase of 80.9% to 6.32 in 2022. Trends for rates of serious medical outcomes and admissions to a healthcare facility showed similar patterns with 129.9% and 95.8% increases, respectively, from 2021 to 2022. CONCLUSIONS: Most GLP-1RA cases reported to US poison centers were associated with no or minimal effects and did not require referral for medical treatment; however, a notable minority of individuals experienced a serious medical outcome or healthcare facility admission. The rate of reported cases increased during the study period, including an 80.9% increase from 2021 to 2022. Opportunities exist to improve provider and patient awareness of the adverse effects of these medications. CI - (c) 2024. The Author(s). FAU - Gaw, Christopher E AU - Gaw CE AD - Center for Injury Research and Policy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, 43205, Columbus, OH, USA. AD - Division of Emergency Medicine, Nationwide Children's Hospital, Columbus, OH, USA. AD - Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA. FAU - Hays, Hannah L AU - Hays HL AD - Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA. AD - Section of Toxicology, Nationwide Children's Hospital, Columbus, OH, USA. AD - Central Ohio Poison Center, Nationwide Children's Hospital, Columbus, OH, USA. FAU - Kemp, Cydney A AU - Kemp CA AD - Center for Injury Research and Policy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, 43205, Columbus, OH, USA. AD - Campbell University School of Osteopathic Medicine, Lillington, NC, USA. FAU - Kistamgari, Sandhya AU - Kistamgari S AD - Center for Injury Research and Policy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, 43205, Columbus, OH, USA. FAU - Spiller, Henry A AU - Spiller HA AD - Central Ohio Poison Center, Nationwide Children's Hospital, Columbus, OH, USA. FAU - Rine, Natalie I AU - Rine NI AD - Central Ohio Poison Center, Nationwide Children's Hospital, Columbus, OH, USA. FAU - Rhodes, Allison L AU - Rhodes AL AD - Division of General Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA. FAU - Zhu, Motao AU - Zhu M AD - Center for Injury Research and Policy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, 43205, Columbus, OH, USA. AD - Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA. FAU - Smith, Gary A AU - Smith GA AUID- ORCID: 0000-0001-5838-8982 AD - Center for Injury Research and Policy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 700 Children's Drive, 43205, Columbus, OH, USA. gary.smith@nationwidechildrens.org. AD - Division of Emergency Medicine, Nationwide Children's Hospital, Columbus, OH, USA. gary.smith@nationwidechildrens.org. AD - Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA. gary.smith@nationwidechildrens.org. AD - Child Injury Prevention Alliance, Columbus, OH, USA. gary.smith@nationwidechildrens.org. LA - eng GR - N/A/Child Injury Prevention Alliance/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240229 PL - United States TA - J Med Toxicol JT - Journal of medical toxicology : official journal of the American College of Medical Toxicology JID - 101284598 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Poisons) SB - IM MH - Female MH - Humans MH - United States/epidemiology MH - Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Liraglutide/toxicity/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Poisons/therapeutic use PMC - PMC10959851 OTO - NOTNLM OT - Adverse drug events OT - GLP-1 receptor agonist OT - Liraglutide OT - Semaglutide OT - Toxicity COIS- The authors declare that they have no conflicts of interest. EDAT- 2024/02/29 12:46 MHDA- 2024/03/25 06:42 PMCR- 2024/02/29 CRDT- 2024/02/29 11:10 PHST- 2023/11/28 00:00 [received] PHST- 2024/02/14 00:00 [accepted] PHST- 2024/02/12 00:00 [revised] PHST- 2024/03/25 06:42 [medline] PHST- 2024/02/29 12:46 [pubmed] PHST- 2024/02/29 11:10 [entrez] PHST- 2024/02/29 00:00 [pmc-release] AID - 10.1007/s13181-024-00999-x [pii] AID - 999 [pii] AID - 10.1007/s13181-024-00999-x [doi] PST - ppublish SO - J Med Toxicol. 2024 Apr;20(2):193-204. doi: 10.1007/s13181-024-00999-x. Epub 2024 Feb 29. PMID- 38420695 OWN - NLM STAT- MEDLINE DCOM- 20240312 LR - 20240312 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 27 IP - 1 DP - 2024 Jan-Dec TI - Budget impact analysis for three glucagon-like peptide-1 receptor agonist-based therapies for type 2 diabetes mellitus management in Saudi Arabia. PG - 418-429 LID - 10.1080/13696998.2024.2319458 [doi] AB - BACKGROUND AND OBJECTIVES: This study presents a budget impact analysis (BIA) conducted in Saudi Arabia, evaluating the cost implications of adopting semaglutide, tirzepatide, or dulaglutide in the management of type 2 diabetes mellitus (T2DM) patients. The analysis aims to assess the individual budgetary impact of these treatment options on healthcare budgets and provide insights for decision-makers. METHODS: A prevalence-based BIA was developed using real-world and clinical trials data. The model considered disease epidemiology, medication prices, diabetes management expenses, cardiovascular (CV) complications costs, and weight reduction savings over a 5-year time horizon. One-way and probabilistic sensitivity analyses (OWSA, PSA) were performed to assess the robustness of the results. RESULTS: Over a 5-year period, the cumulative budget impact for semaglutide, tirzepatide, and dulaglutide were 85,923,089 USD, 169,790,195 USD, and 94,558,356 USD, respectively. Hypothetical scenarios considering price parity between semaglutide and tirzepatide are associated with financial impacts of 85,923,091 USD and 86,475,335 USD, respectively. In the public sector, semaglutide showed the lowest incidence of 3-point major adverse CV events (3P-MACE), with tirzepatide leading in weight loss and HbA1c reduction, and dulaglutide presenting the highest 3P-MACE rates and least improvements in HbA1c and weight. A breakeven analysis suggested that tirzepatide's list price would need to be $199.91 lower than its current list price to achieve budget impact parity with semaglutide based on currently available evidence. Results from the OWSA suggested that risk reductions for CV events were key drivers of budget impact. PSA results were confirmatory of base-case analyses. CONCLUSIONS: CV cost-offsets and drug acquisition considerations may make semaglutide a favorable use of resources for Saudi budget planners and decision-makers. These results were robust to assumptions regarding the list price of tirzepatide. FAU - Al-Omar, Hussain A AU - Al-Omar HA AUID- ORCID: 0000-0002-0765-0466 AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. AD - Health Technology Assessment Unit, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Almodaimegh, Hind S AU - Almodaimegh HS AUID- ORCID: 0000-0001-7620-6054 AD - College of Pharmacy, King Saud bin Abdul-Aziz University for Health Sciences, Riyadh, Saudi Arabia. AD - Pharmaceutical Care Department, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia. AD - King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. FAU - Omaer, Abubker AU - Omaer A AUID- ORCID: 0000-0002-1452-4652 AD - Department of Clinical Pharmacy, King Saud Medical City, Riyadh, Saudi Arabia. FAU - Alzubaidi, Lamya M AU - Alzubaidi LM AUID- ORCID: 0009-0007-1516-7304 AD - Therapeutic Deputyship, Ministry of Health, Riyadh, Saudi Arabia. FAU - Al-Harbi, Bandar AU - Al-Harbi B AD - Department of Pharmacy, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. FAU - Al-Harbi, Ibtisam AU - Al-Harbi I AD - Department of Pharmacy, Jeddah Military Hospital, Jeddah, Saudi Arabia. FAU - Hassan, Mohamed AU - Hassan M AD - Novo Nordisk, Riyadh, Saudi Arabia. FAU - Akhtar, Omar AU - Akhtar O AUID- ORCID: 0000-0001-6435-501X AD - Poa Alpina Research, Seoul, South Korea. LA - eng PT - Journal Article DEP - 20240311 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - EC 3.4.21.77 (Prostate-Specific Antigen) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Male MH - Humans MH - *Diabetes Mellitus, Type 2 MH - Hypoglycemic Agents/therapeutic use MH - Saudi Arabia MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - Prostate-Specific Antigen/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - I OT - I1 OT - I18 OT - I19 OT - Saudi Arabia OT - budget impact analysis OT - semaglutide OT - tirzepatide OT - type 2 diabetes mellitus EDAT- 2024/02/29 06:42 MHDA- 2024/03/12 06:42 CRDT- 2024/02/29 04:18 PHST- 2024/03/12 06:42 [medline] PHST- 2024/02/29 06:42 [pubmed] PHST- 2024/02/29 04:18 [entrez] AID - 10.1080/13696998.2024.2319458 [doi] PST - ppublish SO - J Med Econ. 2024 Jan-Dec;27(1):418-429. doi: 10.1080/13696998.2024.2319458. Epub 2024 Mar 11. PMID- 38418411 OWN - NLM STAT- MEDLINE DCOM- 20240508 LR - 20260622 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 6 DP - 2024 Jun TI - Real-world glycated haemoglobin changes among type 2 diabetes mellitus patients treated with a maintenance dose of 7 mg or 14 mg of oral semaglutide. PG - 2111-2118 LID - 10.1111/dom.15516 [doi] AB - AIM: To describe the change in glycated haemoglobin (HbA1c) among patients with type 2 diabetes following treatment with a 7 or 14 mg maintenance dose of oral semaglutide. MATERIALS AND METHODS: This retrospective, claims-based study included adult patients with type 2 diabetes with a pre-index HbA1c of >/=7%, initiating treatment with oral semaglutide between 1 November 2019 and 30 June 2020; the patients had continuous health plan enrolment for >/=12 months before (pre-index) and >/=6 months following (post-index) the date of the first oral semaglutide claim (index). Patients were required to have a maintenance dose of 7 or 14 mg. Pre-index demographic and clinical characteristics were captured, as were doses at initiation and prescriber specialty. The change in HbA1c between the latest post-index and pre-index HbA1c measurements was calculated among all patients and among those with >/=90 days of continuous treatment (persistent patients). RESULTS: This study included 520 patients, most of whom had a complex medical history, experienced a range of comorbidities and received an average of 11.5 different classes of medications during the pre-index period. The mean HbA1c reduction during the 6-month post-initiation period was 1.2% (p < .001) for all patients and 1.4% (p < .001) for persistent patients. CONCLUSIONS: In this real-world study, patients with a pre-index HbA1c >/=7% who initiated treatment with oral semaglutide with a 7 or 14 mg maintenance dose had significantly lower HbA1c levels following treatment. CI - (c) 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk, Inc., Plainsboro, New Jersey, USA. FAU - Frazer, Monica AU - Frazer M AD - QualityMetric, Johnston, RI, formerly Optum, Eden Prairie, Minnesota, USA. FAU - Gronroos, Noelle N AU - Gronroos NN AD - Optum, Eden Prairie, Minnesota, USA. FAU - Sargent, Andrew AU - Sargent A AD - Optum, Eden Prairie, Minnesota, USA. FAU - Leszko, Michael AU - Leszko M AD - Optum, Eden Prairie, Minnesota, USA. FAU - Buysman, Erin AU - Buysman E AUID- ORCID: 0000-0003-0104-5836 AD - Optum, Eden Prairie, Minnesota, USA. FAU - Alvarez, Sara AU - Alvarez S AD - Novo Nordisk, Inc., Plainsboro, New Jersey, USA. FAU - Dunn, Tyler J AU - Dunn TJ AD - Novo Nordisk, Inc., Plainsboro, New Jersey, USA. FAU - Noone, Josh AU - Noone J AD - Novo Nordisk, Inc., Plainsboro, New Jersey, USA. FAU - Guevarra, Mico AU - Guevarra M AD - Novo Nordisk, Inc., Plainsboro, New Jersey, USA. LA - eng GR - Novo Nordisk, Inc. Sarah Hague, Optum/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240228 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Glycated Hemoglobin/analysis/drug effects/metabolism MH - Female MH - Male MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use/adverse effects MH - Retrospective Studies MH - Middle Aged MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - Aged MH - Administration, Oral MH - Adult MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - glycaemic control OT - real-world evidence OT - type 2 diabetes EDAT- 2024/02/29 00:43 MHDA- 2024/05/08 06:45 CRDT- 2024/02/28 22:33 PHST- 2024/02/05 00:00 [revised] PHST- 2023/12/22 00:00 [received] PHST- 2024/02/07 00:00 [accepted] PHST- 2024/05/08 06:45 [medline] PHST- 2024/02/29 00:43 [pubmed] PHST- 2024/02/28 22:33 [entrez] AID - 10.1111/dom.15516 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Jun;26(6):2111-2118. doi: 10.1111/dom.15516. Epub 2024 Feb 28. PMID- 38418010 OWN - NLM STAT- MEDLINE DCOM- 20240301 LR - 20260127 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 83 IP - 9 DP - 2024 Mar 5 TI - Eligibility for and Preventive Potential of Semaglutide in Overweight and Obese Patients With Myocardial Infarction. PG - 956-958 LID - S0735-1097(24)00003-2 [pii] LID - 10.1016/j.jacc.2023.12.029 [doi] FAU - Hansen, Malene K AU - Hansen MK AD - Aarhus University Hospital, Aarhus, Denmark; Aarhus University, Aarhus, Denmark. FAU - Olesen, Kevin K W AU - Olesen KKW AD - Aarhus University Hospital, Aarhus, Denmark. FAU - Gyldenkerne, Christine AU - Gyldenkerne C AD - Aarhus University Hospital, Aarhus, Denmark; Aarhus University, Aarhus, Denmark. FAU - Thrane, Pernille G AU - Thrane PG AD - Aarhus University Hospital, Aarhus, Denmark; Aarhus University, Aarhus, Denmark. FAU - Stodkilde-Jorgensen, Nina AU - Stodkilde-Jorgensen N AD - Aarhus University Hospital, Aarhus, Denmark; Aarhus University, Aarhus, Denmark. FAU - Mortensen, Martin B AU - Mortensen MB AD - Aarhus University Hospital, Aarhus, Denmark; Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Maeng, Michael AU - Maeng M AD - Aarhus University Hospital, Aarhus, Denmark; Aarhus University, Aarhus, Denmark. Electronic address: michael.maeng@clin.au.dk. LA - eng PT - Letter PT - Research Support, Non-U.S. Gov't PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Overweight/complications MH - Obesity/complications MH - Glucagon-Like Peptides/therapeutic use MH - *Myocardial Infarction/complications/prevention & control MH - Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Semaglutide EDAT- 2024/02/29 00:43 MHDA- 2024/03/01 06:44 CRDT- 2024/02/28 20:57 PHST- 2023/09/21 00:00 [received] PHST- 2023/11/27 00:00 [revised] PHST- 2023/12/18 00:00 [accepted] PHST- 2024/03/01 06:44 [medline] PHST- 2024/02/29 00:43 [pubmed] PHST- 2024/02/28 20:57 [entrez] AID - S0735-1097(24)00003-2 [pii] AID - 10.1016/j.jacc.2023.12.029 [doi] PST - ppublish SO - J Am Coll Cardiol. 2024 Mar 5;83(9):956-958. doi: 10.1016/j.jacc.2023.12.029. PMID- 38416593 OWN - NLM STAT- MEDLINE DCOM- 20240415 LR - 20260127 IS - 1522-9645 (Electronic) IS - 0195-668X (Print) IS - 0195-668X (Linking) VI - 45 IP - 15 DP - 2024 Apr 14 TI - Semaglutide and cardiovascular outcomes by baseline HbA1c in diabetes: the SUSTAIN 6 and PIONEER 6 trials. PG - 1371-1374 LID - 10.1093/eurheartj/ehae028 [doi] FAU - Mellbin, Linda G AU - Mellbin LG AUID- ORCID: 0000-0001-8655-4044 AD - Department of Medicine Solna, Karolinska Institutet, Eugeniavagen 27, 171 64 Solna, Stockholm, Sweden. AD - Heart Vascular and Neuro Theme, Karolinska University Hospital, K2 Medicin, K2 Kardio Pernow J, 171 77 Solna, Stockholm, Sweden. FAU - Bhatt, Deepak L AU - Bhatt DL AUID- ORCID: 0000-0002-1278-6245 AD - Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA. FAU - David, Jens-Peter AU - David JP AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ekstrom, Kathrine AU - Ekstrom K AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Petrie, Mark C AU - Petrie MC AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AUID- ORCID: 0000-0002-0456-6787 AD - Clinical Research, Steno Diabetes Center Copenhagen, University of Copenhagen, Copenhagen, Denmark. LA - eng GR - Region Stockholm/ GR - Swedish Heart-Lung Foundation/ PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Glycated Hemoglobin MH - Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Cardiovascular System MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide PMC - PMC11015952 OTO - NOTNLM OT - Post hoc analysis OT - Cardiovascular outcomes trial OT - Glucagon-like peptide-1 receptor agonist OT - HbA1c OT - Major adverse cardiovascular events OT - PIONEER 6 OT - SUSTAIN 6 OT - Semaglutide OT - Type 2 diabetes EDAT- 2024/02/28 18:43 MHDA- 2024/04/15 06:43 PMCR- 2024/02/28 CRDT- 2024/02/28 12:12 PHST- 2023/10/17 00:00 [received] PHST- 2024/01/08 00:00 [revised] PHST- 2024/01/10 00:00 [accepted] PHST- 2024/04/15 06:43 [medline] PHST- 2024/02/28 18:43 [pubmed] PHST- 2024/02/28 12:12 [entrez] PHST- 2024/02/28 00:00 [pmc-release] AID - 7615664 [pii] AID - ehae028 [pii] AID - 10.1093/eurheartj/ehae028 [doi] PST - ppublish SO - Eur Heart J. 2024 Apr 14;45(15):1371-1374. doi: 10.1093/eurheartj/ehae028. PMID- 38407177 OWN - NLM STAT- MEDLINE DCOM- 20240403 LR - 20260127 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 40 IP - 4 DP - 2024 Apr TI - Model-based simulation of glycaemic effect and body weight loss when switching from semaglutide or dulaglutide to once weekly tirzepatide. PG - 567-574 LID - 10.1080/03007995.2024.2322072 [doi] AB - OBJECTIVE: To evaluate the efficacy endpoints of HbA1c and body weight loss after switching from the GLP-1 receptor agonists, semaglutide or dulaglutide, to treatment with the GIP/GLP-1 receptor agonist (RA) tirzepatide. METHODS: Models were developed and validated to describe the HbA1c and weight loss time course for semaglutide (SUSTAIN 1-10), dulaglutide (AWARD-11) and tirzepatide (SURPASS 1-5, phase 3 global T2D program). The impact of switching from once weekly GLP-1 RAs to tirzepatide was described by simulating the efficacy time course. Semaglutide and dulaglutide doses were escalated in accordance with their respective labels. RESULTS: Model-predicted mean decreases from baseline in HbA1c and body weight for semaglutide 0.5 mg, 1 mg, and 2 mg were 1.22 to 1.79% and 3.62 to 6.87 kg respectively, at Week 26. Model-predicted mean decreases from baseline in HbA1c and body weight for dulaglutide 1.5 mg, 3 mg and 4.5 mg were 1.53 to 1.84% and 2.55 to 3.71 kg respectively, at Week 26. After switching to tirzepatide 5, 10 and 15 mg HbA1c reductions were predicted to range between 1.95 to 2.46% and body weight reductions between 6.50 to 12.1 kg by Week 66. CONCLUSION: In this model-based simulation, switching from approved maintenance doses of semaglutide or dulaglutide to tirzepatide, even at the lowest approved maintenance dose of 5 mg, showed the potential to further improve HbA1c and body weight reductions. FAU - Urva, Shweta AU - Urva S AUID- ORCID: 0000-0002-3681-479X AD - Global PK/PD & Pharmacometrics, Eli Lilly and Company, Indianapolis, IN, USA. FAU - Levine, Joshua A AU - Levine JA AUID- ORCID: 0000-0003-1112-2700 AD - Diabetes and Obesity Global Medical Affairs, Eli Lilly and Company, Indianapolis, IN, USA. FAU - Schneck, Karen AU - Schneck K AUID- ORCID: 0000-0002-9229-4987 AD - Pharmacometrics & QSP, Eli Lilly and Company, Indianapolis, IN, USA. FAU - Tang, Cheng Cai AU - Tang CC AUID- ORCID: 0000-0003-3052-393X AD - Clinical Pharmacology Modeling and Simulation (CPMS), Parexel International, Singapore. LA - eng PT - Journal Article DEP - 20240312 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - Body Weight MH - Weight Loss MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptides/*analogs & derivatives MH - *Gastric Inhibitory Polypeptide MH - *Immunoglobulin Fc Fragments MH - *Recombinant Fusion Proteins MH - *Glucagon-Like Peptide-2 Receptor MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OAB - Type 2 diabetes is a disease of elevated blood sugar levels. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a type of medication used to treat type 2 diabetes that work on GLP-1 receptors in the body. Semaglutide and dulaglutide are examples of GLP-1 RAs, which lower blood sugar and body weight. Tirzepatide is a newer medication, which works on both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. It reduces blood sugar and body weight in people living with type 2 diabetes. Healthcare professionals and patients are interested in how switching medication from semaglutide or dulaglutide to tirzepatide might change blood glucose levels and body weight. However, because tirzepatide is a newer medication, there is not much information available on this aspect. Data from clinical trials of these medications were used to predict the effects of switching from semaglutide or dulaglutide to tirzepatide. These model-based simulations showed that switching to tirzepatide may further reduce HbA1c (a measure of blood sugar) and body weight. This may provide useful information to healthcare professionals and patients when making decisions about treatment with these medications. OABL- eng OTO - NOTNLM OT - Type 2 diabetes OT - body weight OT - glucagon-like peptide-1 OT - glucose-dependent insulinotropic polypeptide OT - glycated hemoglobin OT - tirzepatide EDAT- 2024/02/26 12:43 MHDA- 2024/04/03 06:44 CRDT- 2024/02/26 11:02 PHST- 2024/04/03 06:44 [medline] PHST- 2024/02/26 12:43 [pubmed] PHST- 2024/02/26 11:02 [entrez] AID - 10.1080/03007995.2024.2322072 [doi] PST - ppublish SO - Curr Med Res Opin. 2024 Apr;40(4):567-574. doi: 10.1080/03007995.2024.2322072. Epub 2024 Mar 12. PMID- 38403174 OWN - NLM STAT- MEDLINE DCOM- 20240325 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 209 DP - 2024 Mar TI - Effect of low dose Semaglutide in people with Type 1 Diabetes and excess weight. PG - 111593 LID - S0168-8227(24)00077-9 [pii] LID - 10.1016/j.diabres.2024.111593 [doi] AB - Obesity is a prevalent problem in people living with T1D (PwT1D), and it has been linked to cardiovascular disease in this population. The use of low dose weekly Semaglutide (0,5 mg) was evaluated in a cohort of PwT1D and excess weight. CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Grassi, Bruno A AU - Grassi BA AD - Departamento de Nutricion, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Diagonal Paraguay 362, Santiago, Chile. Electronic address: bagrassi@gmail.com. FAU - Teresa Onetto, Maria AU - Teresa Onetto M AD - Departamento de Nutricion, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Diagonal Paraguay 362, Santiago, Chile. FAU - Sanchez, Camila AU - Sanchez C AD - Departamento de Nutricion, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Diagonal Paraguay 362, Santiago, Chile. FAU - Tapia, Nicole AU - Tapia N AD - Departamento de Nutricion, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Diagonal Paraguay 362, Santiago, Chile. FAU - Mena, Francisca AU - Mena F AD - Departamento de Nutricion, Diabetes y Metabolismo, Escuela de Medicina, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Diagonal Paraguay 362, Santiago, Chile. LA - eng PT - Journal Article DEP - 20240224 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/epidemiology MH - *Diabetes Mellitus, Type 1/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Weight Gain MH - Glucagon-Like Peptide-1 Receptor MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonists OT - Obesity OT - Type 1 Diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/02/26 00:42 MHDA- 2024/03/25 06:42 CRDT- 2024/02/25 19:17 PHST- 2023/10/13 00:00 [received] PHST- 2023/12/12 00:00 [revised] PHST- 2024/02/22 00:00 [accepted] PHST- 2024/03/25 06:42 [medline] PHST- 2024/02/26 00:42 [pubmed] PHST- 2024/02/25 19:17 [entrez] AID - S0168-8227(24)00077-9 [pii] AID - 10.1016/j.diabres.2024.111593 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2024 Mar;209:111593. doi: 10.1016/j.diabres.2024.111593. Epub 2024 Feb 24. PMID- 38388874 OWN - NLM STAT- MEDLINE DCOM- 20240401 LR - 20261010 IS - 1179-1950 (Electronic) IS - 0012-6667 (Linking) VI - 84 IP - 2 DP - 2024 Feb TI - Tirzepatide: A Review in Type 2 Diabetes. PG - 227-238 LID - 10.1007/s40265-023-01992-4 [doi] AB - Tirzepatide (Mounjaro((R))), a first-in-class dual incretin agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, is approved for use as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM) in the USA, EU, Japan and other countries. It comes as single-dose prefilled pens and single-dose vials. In phase III SURPASS trials, once-weekly subcutaneous tirzepatide, as monotherapy or add-on-therapy to oral glucose-lowering medications and insulin, was superior to the GLP-1 receptor agonists (RAs) dulaglutide 0.75 mg and semaglutide 1 mg as well as basal and prandial insulin for glycaemic control and weight loss in adults with inadequately controlled T2DM. Tirzepatide was generally well tolerated, with a safety profile consistent with that of GLP-1 RAs. Tirzepatide was associated with a low risk of clinically significant or severe hypoglycaemia and no increased risk of major adverse cardiovascular events. Adverse events were mostly mild to moderate in severity, with the most common being gastrointestinal events including nausea, diarrhoea, decreased appetite and vomiting. In conclusion, tirzepatide is a valuable addition to the treatment options for T2DM. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - France, Nicole L AU - France NL AD - Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. demail@springer.com. FAU - Syed, Yahiya Y AU - Syed YY AD - Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. LA - eng PT - Journal Article PT - Review DEP - 20240223 PL - New Zealand TA - Drugs JT - Drugs JID - 7600076 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - IY9XDZ35W2 (Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Adult MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Insulin MH - Glucagon-Like Peptide-1 Receptor MH - Glucose MH - Glucagon-Like Peptide 1/therapeutic use MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - *Glucagon-Like Peptide-2 Receptor MH - *Gastric Inhibitory Polypeptide MH - Tirzepatide OAB - Many people with type 2 diabetes mellitus (T2DM) do not achieve and maintain glycaemic and weight management goals using currently available treatments. Tirzepatide (Mounjaro((R))) is the first incretin-based glucose-lowering medication to be approved as an add-on to diet and exercise in adults with T2DM that targets both the glucose-dependent insulinotropic polypeptide receptor (GIP) and the glucagon-like peptide-1 (GLP-1) receptor. In patients with inadequately controlled T2DM, tirzepatide improved glycaemic control and body weight more so than dulaglutide 0.75 mg, semaglutide 1 mg and insulin when used on its own or in combination with other medications. Tirzepatide was generally well tolerated and had a low risk of hypoglycaemia. The most common adverse events were usually short-lived gastrointestinal-related events, which were generally mild to moderate in nature, including nausea, diarrhoea, decreased appetite and vomiting. Tirzepatide is a valuable addition to the treatment options for people with inadequately controlled T2DM. OABL- eng EDAT- 2024/02/23 00:42 MHDA- 2024/04/01 06:42 CRDT- 2024/02/22 23:58 PHST- 2023/12/20 00:00 [accepted] PHST- 2024/04/01 06:42 [medline] PHST- 2024/02/23 00:42 [pubmed] PHST- 2024/02/22 23:58 [entrez] AID - 10.1007/s40265-023-01992-4 [pii] AID - 10.1007/s40265-023-01992-4 [doi] PST - ppublish SO - Drugs. 2024 Feb;84(2):227-238. doi: 10.1007/s40265-023-01992-4. Epub 2024 Feb 23. PMID- 38381687 OWN - NLM STAT- MEDLINE DCOM- 20240223 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 390 IP - 8 DP - 2024 Feb 22 TI - Semaglutide and Cardiovascular Outcomes. Reply. PG - 768-769 LID - 10.1056/NEJMc2400414#sa6 [pii] LID - 10.1056/NEJMc2400414 [doi] FAU - Lincoff, A Michael AU - Lincoff AM AD - Cleveland Clinic, Cleveland, OH lincofa@ccf.org. FAU - Ryan, Donna H AU - Ryan DH AD - Pennington Biomedical Research Center, Baton Rouge, LA. FAU - Esbjerg, Sille AU - Esbjerg S AD - Novo Nordisk, Soborg, Denmark. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. PMID: 37952131 MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity MH - Semaglutide EDAT- 2024/02/21 18:42 MHDA- 2024/02/23 06:43 CRDT- 2024/02/21 13:03 PHST- 2024/02/23 06:43 [medline] PHST- 2024/02/21 18:42 [pubmed] PHST- 2024/02/21 13:03 [entrez] AID - 10.1056/NEJMc2400414#sa6 [pii] AID - 10.1056/NEJMc2400414 [doi] PST - ppublish SO - N Engl J Med. 2024 Feb 22;390(8):768-769. doi: 10.1056/NEJMc2400414. PMID- 38381686 OWN - NLM STAT- MEDLINE DCOM- 20240223 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 390 IP - 8 DP - 2024 Feb 22 TI - Semaglutide and Cardiovascular Outcomes. PG - 767-768 LID - 10.1056/NEJMc2400414#sa5 [pii] LID - 10.1056/NEJMc2400414 [doi] FAU - Neves, Joao Sergio AU - Neves JS AD - University of Porto, Porto, Portugal jsneves@med.up.pt. FAU - Leite, Ana Rita AU - Leite AR AD - University of Porto, Porto, Portugal jsneves@med.up.pt. FAU - Ferreira, Joao Pedro AU - Ferreira JP AD - University of Porto, Porto, Portugal jsneves@med.up.pt. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. PMID: 37952131 MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Obesity MH - Semaglutide EDAT- 2024/02/21 18:43 MHDA- 2024/02/23 06:44 CRDT- 2024/02/21 13:03 PHST- 2024/02/23 06:44 [medline] PHST- 2024/02/21 18:43 [pubmed] PHST- 2024/02/21 13:03 [entrez] AID - 10.1056/NEJMc2400414#sa5 [pii] AID - 10.1056/NEJMc2400414 [doi] PST - ppublish SO - N Engl J Med. 2024 Feb 22;390(8):767-768. doi: 10.1056/NEJMc2400414. PMID- 38381685 OWN - NLM STAT- MEDLINE DCOM- 20240223 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 390 IP - 8 DP - 2024 Feb 22 TI - Semaglutide and Cardiovascular Outcomes. PG - 767 LID - 10.1056/NEJMc2400414#sa4 [pii] LID - 10.1056/NEJMc2400414 [doi] FAU - Campbell, Laura A AU - Campbell LA AD - University of Tennessee Health Science Center, Memphis, TN lcampb55@uthsc.edu. FAU - Jenkins, Alexa V AU - Jenkins AV AD - Western Governors University of Salt Lake City, Salt Lake City, UT. FAU - Jackson, Christopher D AU - Jackson CD AD - University of Tennessee Health Science Center, Memphis, TN. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. PMID: 37952131 MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Obesity MH - Semaglutide EDAT- 2024/02/21 18:43 MHDA- 2024/02/23 06:43 CRDT- 2024/02/21 13:03 PHST- 2024/02/23 06:43 [medline] PHST- 2024/02/21 18:43 [pubmed] PHST- 2024/02/21 13:03 [entrez] AID - 10.1056/NEJMc2400414#sa4 [pii] AID - 10.1056/NEJMc2400414 [doi] PST - ppublish SO - N Engl J Med. 2024 Feb 22;390(8):767. doi: 10.1056/NEJMc2400414. PMID- 38381684 OWN - NLM STAT- MEDLINE DCOM- 20240223 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 390 IP - 8 DP - 2024 Feb 22 TI - Semaglutide and Cardiovascular Outcomes. PG - 767 LID - 10.1056/NEJMc2400414#sa3 [pii] LID - 10.1056/NEJMc2400414 [doi] FAU - Belkhouribchia, Jamal AU - Belkhouribchia J AD - Endocrinology Center, Hasselt, Belgium. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. PMID: 37952131 MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Obesity MH - Semaglutide EDAT- 2024/02/21 18:43 MHDA- 2024/02/23 06:44 CRDT- 2024/02/21 13:03 PHST- 2024/02/23 06:44 [medline] PHST- 2024/02/21 18:43 [pubmed] PHST- 2024/02/21 13:03 [entrez] AID - 10.1056/NEJMc2400414#sa3 [pii] AID - 10.1056/NEJMc2400414 [doi] PST - ppublish SO - N Engl J Med. 2024 Feb 22;390(8):767. doi: 10.1056/NEJMc2400414. PMID- 38381683 OWN - NLM STAT- MEDLINE DCOM- 20240223 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 390 IP - 8 DP - 2024 Feb 22 TI - Semaglutide and Cardiovascular Outcomes. PG - 766-767 LID - 10.1056/NEJMc2400414#sa2 [pii] LID - 10.1056/NEJMc2400414 [doi] FAU - Belalcazar, L Maria AU - Belalcazar LM AD - University of Texas Medical Branch, Galveston, TX lmbelalc@utmb.edu. FAU - Kuo, Yong-Fang AU - Kuo YF AD - University of Texas Medical Branch, Galveston, TX lmbelalc@utmb.edu. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. PMID: 37952131 MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Obesity MH - Semaglutide EDAT- 2024/02/21 18:42 MHDA- 2024/02/23 06:43 CRDT- 2024/02/21 13:03 PHST- 2024/02/23 06:43 [medline] PHST- 2024/02/21 18:42 [pubmed] PHST- 2024/02/21 13:03 [entrez] AID - 10.1056/NEJMc2400414#sa2 [pii] AID - 10.1056/NEJMc2400414 [doi] PST - ppublish SO - N Engl J Med. 2024 Feb 22;390(8):766-767. doi: 10.1056/NEJMc2400414. PMID- 38381682 OWN - NLM STAT- MEDLINE DCOM- 20240223 LR - 20260303 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 390 IP - 8 DP - 2024 Feb 22 TI - Semaglutide and Cardiovascular Outcomes. PG - 766 LID - 10.1056/NEJMc2400414#sa1 [pii] LID - 10.1056/NEJMc2400414 [doi] FAU - Taqueti, Viviany R AU - Taqueti VR AD - Brigham and Women's Hospital, Boston, MA vtaqueti@bwh.harvard.edu. FAU - Shaw, Leslee J AU - Shaw LJ AD - Icahn School of Medicine at Mount Sinai, New York, NY. LA - eng GR - K23 HL135438/HL/NHLBI NIH HHS/United States PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. PMID: 37952131 MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Obesity MH - Semaglutide EDAT- 2024/02/21 18:43 MHDA- 2024/02/23 06:43 CRDT- 2024/02/21 13:03 PHST- 2024/02/23 06:43 [medline] PHST- 2024/02/21 18:43 [pubmed] PHST- 2024/02/21 13:03 [entrez] AID - 10.1056/NEJMc2400414#sa1 [pii] AID - 10.1056/NEJMc2400414 [doi] PST - ppublish SO - N Engl J Med. 2024 Feb 22;390(8):766. doi: 10.1056/NEJMc2400414. PMID- 38369592 OWN - NLM STAT- MEDLINE DCOM- 20240601 LR - 20260127 IS - 1720-8386 (Electronic) IS - 0391-4097 (Print) IS - 0391-4097 (Linking) VI - 47 IP - 6 DP - 2024 Jun TI - Effectiveness of oral semaglutide on glucose control and body weight up to 18 months: a multicenter retrospective real-world study. PG - 1395-1403 LID - 10.1007/s40618-024-02309-2 [doi] AB - AIM: Oral semaglutide, an innovative orally administered GLP-1 receptor agonist for type 2 diabetes (T2D) management was herein evaluated for its effectiveness in a multi-center retrospective real-world study. METHODS: We included new-users of oral semaglutide from 18 specialist care centres and collected retrospective data on baseline clinical characteristics. Updated values of HbA1c and body weight were analyzed using the mixed model for repeated measures. RESULTS: The study included 166 individuals with T2D, predominantly men (64.5%), with a mean age of 64.4 years and a mean diabetes duration of 10.1 years. In the majority of patients (68.3%) oral semaglutide was used as a second-line drug, mostly with metformin. At baseline, mean BMI was 28.9 kg/m(2) and HbA1c was 7.5%. During the 18-month observation period, oral semaglutide demonstrated significant reductions in HbA1c, with a maximum change of - 0.9%, and 42.1% of patients achieved HbA1c values below 7.0%. Additionally, there was a substantial reduction in body weight, with an estimated change of - 3.4 kg at 18 months, and 30.3% of patients experienced a 5% or greater reduction in baseline body weight. Only 24.2% of patients reached the 14 mg dose. Subgroup analysis revealed that baseline HbA1c > 7%, persistence on drug, not being on a prior therapy with DPP-4 inhibitors, and loosing 5% or more the initial body weight were associated with greater HbA1c reductions. CONCLUSION: This study supports oral semaglutide as an effective option for T2D treatment, offering improved glucose control and weight management in a real-world setting. CI - (c) 2024. The Author(s). FAU - Bonora, B M AU - Bonora BM AD - Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy. AD - Veneto Institute of Molecular Medicine, Padua, Italy. FAU - Russo, G AU - Russo G AD - Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. FAU - Leonetti, F AU - Leonetti F AD - Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy. FAU - Strazzabosco, M AU - Strazzabosco M AD - Diabetology and Metabolic Diseases Unit, S. Bortolo Hospital, Vicenza, Italy. FAU - Nollino, L AU - Nollino L AD - Department of Medicine, Diabetology Service, Azienda ULSS 2 Marca Trevigiana, Treviso, Italy. FAU - Aimaretti, G AU - Aimaretti G AD - Endocrinology, Department of Translational Medicine, Universita del Piemonte Orientale, Novara, Italy. FAU - Giaccari, A AU - Giaccari A AD - Centro per le Malattie Endocrine e Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS and Universita Cattolica del Sacro Cuore, Rome, Italy. FAU - Broglio, F AU - Broglio F AD - Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy. FAU - Consoli, A AU - Consoli A AD - Endocrinology and Metabolism Unit, ASL, Pescara, Italy. AD - Department of Medicine and Aging Sciences DMSI and Center for Advanced Studies and Technology CAST, "G. D'Annunzio" University of Chieti-Pescara, Chieti, Italy. FAU - Avogaro, A AU - Avogaro A AD - Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy. FAU - Fadini, G P AU - Fadini GP AUID- ORCID: 0000-0002-6510-2097 AD - Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy. gianpaolo.fadini@unipd.it. AD - Veneto Institute of Molecular Medicine, Padua, Italy. gianpaolo.fadini@unipd.it. CN - GLIMPLES Study Investigators LA - eng PT - Journal Article PT - Multicenter Study DEP - 20240218 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Male MH - Female MH - Retrospective Studies MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - *Body Weight/drug effects MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Blood Glucose/drug effects/analysis/metabolism MH - Administration, Oral MH - Aged MH - Glycated Hemoglobin/analysis MH - Glycemic Control/methods MH - Treatment Outcome MH - Follow-Up Studies MH - Semaglutide PMC - PMC11142994 OTO - NOTNLM OT - Body weight OT - Glucose control OT - Oral semaglutide OT - Real-world effectiveness OT - Retrospective study OT - Type 2 diabetes COIS- BMB received lecture or advisory board fees from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Mundipharma, Novartis, Novo Nordisk and Sanofi. GR is on the advisory board and does consultancy and lectures for Novo Nordisk, Astra Zeneca, Sanofi, Boehringer, Lilly, Mundipharma, and Sanchio. AG received lecture fees from Novo Nordisk. AC received grants from Astra Zeneca, Lilly, Novo-Nordisk. He also received speaker fees, and provided advisory board services for Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Lilly, Merck Sharp & Dhome, Menarini, Novo-Nordisk, Sanofi, Sigma-Tau. AA received research grants and lecture or advisory board fees from MSD, AstraZeneca, Novartis, Boehringer Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Lilly, Servier and Takeda. GPF received grants, lecture or advisory board fees from Abbott, AstraZeneca, Boehringer, Lilly, Novo Nordisk, Novartis, Sanofi, Servier. FL, MS, LN, GA, FB have nothing to disclose EDAT- 2024/02/19 00:42 MHDA- 2024/06/01 20:42 PMCR- 2024/02/18 CRDT- 2024/02/18 23:47 PHST- 2023/11/15 00:00 [received] PHST- 2024/01/11 00:00 [accepted] PHST- 2024/06/01 20:42 [medline] PHST- 2024/02/19 00:42 [pubmed] PHST- 2024/02/18 23:47 [entrez] PHST- 2024/02/18 00:00 [pmc-release] AID - 10.1007/s40618-024-02309-2 [pii] AID - 2309 [pii] AID - 10.1007/s40618-024-02309-2 [doi] PST - ppublish SO - J Endocrinol Invest. 2024 Jun;47(6):1395-1403. doi: 10.1007/s40618-024-02309-2. Epub 2024 Feb 18. PMID- 38363873 OWN - NLM STAT- MEDLINE DCOM- 20240327 LR - 20250103 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 47 IP - 4 DP - 2024 Apr 1 TI - Risk of Anaphylaxis Among New Users of GLP-1 Receptor Agonists: A Cohort Study. PG - 712-719 LID - 10.2337/dc23-1911 [doi] AB - OBJECTIVE: To assess risk of anaphylaxis among patients with type 2 diabetes mellitus who are initiating therapy with a glucagon-like peptide 1 receptor agonist (GLP-1 RA), with a focus on those starting lixisenatide therapy. RESEARCH DESIGN AND METHODS: A cohort study was conducted in three large, U.S. claims databases (2017-2021). Adult (aged >/=18 years) new users of a GLP-1 RA who had type 2 diabetes mellitus and >/=6 months enrollment in the database before GLP-1 RA initiation (start of follow-up) were included. GLP-1 RAs evaluated were lixisenatide, an insulin glargine/lixisenatide fixed-ratio combination (FRC), exenatide, liraglutide or insulin degludec/liraglutide FRC, dulaglutide, and semaglutide (injectable and oral). The first anaphylaxis event during follow-up was identified using a validated algorithm. Incidence rates (IRs) and 95% CIs were calculated within each medication cohort. The unadjusted IR ratio (IRR) comparing anaphylaxis rates in the lixisenatide cohort with all other GLP-1 RAs combined was analyzed post hoc. RESULTS: There were 696,089 new users with 456,612 person-years of exposure to GLP-1 RAs. Baseline demographics, comorbidities, and use of other prescription medications in the 6 months before the index date were similar across medication cohorts. IRs (95% CIs) per 10,000 person-years were 1.0 (0.0-5.6) for lixisenatide, 6.0 (3.6-9.4) for exenatide, 5.1 (3.7-7.0) for liraglutide, 3.9 (3.1-4.8) for dulaglutide, and 3.6 (2.6-4.9) for semaglutide. The IRR (95% CI) for the anaphylaxis rate for the lixisenatide cohort compared with the pooled other GLP-1 RA cohort was 0.24 (0.01-1.35). CONCLUSIONS: Anaphylaxis is rare with GLP-1 RAs. Lixisenatide is unlikely to confer higher risk of anaphylaxis than other GLP-1 RAs. CI - (c) 2024 by the American Diabetes Association. FAU - Anthony, Mary S AU - Anthony MS AUID- ORCID: 0000-0002-5201-1794 AD - RTI Health Solutions, Research Triangle Park, NC. FAU - Aroda, Vanita R AU - Aroda VR AD - Brigham and Women's Hospital, Boston, MA. FAU - Parlett, Lauren E AU - Parlett LE AD - Carelon Research, Wilmington, DE. FAU - Djebarri, Leila AU - Djebarri L AD - Sanofi, Chilly-Mazarin, France. FAU - Berreghis, Sofia AU - Berreghis S AD - Sanofi, Chilly-Mazarin, France. FAU - Calingaert, Brian AU - Calingaert B AD - RTI Health Solutions, Research Triangle Park, NC. FAU - Beachler, Daniel C AU - Beachler DC AD - Carelon Research, Wilmington, DE. FAU - Crowe, Christopher L AU - Crowe CL AD - Carelon Research, Wilmington, DE. FAU - Johannes, Catherine B AU - Johannes CB AD - RTI Health Solutions, Waltham, MA. FAU - Juhaeri, Juhaeri AU - Juhaeri J AD - Sanofi, Inc., Bridgewater, NJ. FAU - Lanes, Stephan AU - Lanes S AD - Carelon Research, Wilmington, DE. FAU - Pan, Chunshen AU - Pan C AD - Sanofi, Inc., Bridgewater, NJ. FAU - Rothman, Kenneth J AU - Rothman KJ AD - RTI Health Solutions, Waltham, MA. FAU - Saltus, Catherine W AU - Saltus CW AD - RTI Health Solutions, Waltham, MA. FAU - Walsh, Kathleen E AU - Walsh KE AD - Boston Children's Hospital, Boston, MA. LA - eng GR - Sanofi/ PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 9P1872D4OL (Exenatide) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Adult MH - Humans MH - Adolescent MH - Exenatide/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Liraglutide/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Cohort Studies MH - *Anaphylaxis/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide 1/therapeutic use PMC - PMC10973896 COIS- Duality of Interest. M.S.A., C.B.J., K.J.R., C.W.S., and B.C. are employees of RTI Health Solutions. C.L.C., D.C.B., L.E.P., and S.L. are employees of Elevance Health. S.B., L.D., J.J., and C.P. are employees of Sanofi. V.R.A. has served as a consultant for Applied Therapeutics, Fractyl, Novo Nordisk, Pfizer, and Sanofi, conducting this work as a paid consultant to Sanofi, and is publishing in that capacity. V.R.A. has received research contracts (payable to institution) from Applied Therapeutics, Eli Lilly, Fractyl, Novo Nordisk, and Sanofi. No other potential conflicts of interest relevant to this article were reported. EDAT- 2024/02/16 18:43 MHDA- 2024/03/27 06:43 PMCR- 2024/02/16 CRDT- 2024/02/16 14:12 PHST- 2023/10/10 00:00 [received] PHST- 2024/01/18 00:00 [accepted] PHST- 2024/03/27 06:43 [medline] PHST- 2024/02/16 18:43 [pubmed] PHST- 2024/02/16 14:12 [entrez] PHST- 2024/02/16 00:00 [pmc-release] AID - 154237 [pii] AID - 231911 [pii] AID - 10.2337/dc23-1911 [doi] PST - ppublish SO - Diabetes Care. 2024 Apr 1;47(4):712-719. doi: 10.2337/dc23-1911. PMID- 38355513 OWN - NLM STAT- MEDLINE DCOM- 20240216 LR - 20241115 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 22 IP - 1 DP - 2024 Feb 14 TI - Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database. PG - 65 LID - 10.1186/s12916-024-03274-6 [doi] LID - 65 AB - BACKGROUND: Establishing whether there is a potential relationship between glucagon-like peptide 1 receptor agonists (GLP-1RAs) and suicidal or self-injurious behaviors (SSIBs) is crucial for public safety. This study investigated the potential association between GLP-1RAs and SSIBs by exploring the FDA Adverse Event Reporting System (FAERS) database. METHODS: A disproportionality analysis was conducted using post-marketing data from the FAERS repository (2018 Q1 to 2022 Q4). SSIB cases associated with GLP-1RAs were identified and analyzed through disproportionality analysis using the information component. The parametric distribution with a goodness-of-fit test was employed to analyze the time-to-onset, and the Omega shrinkage was used to evaluate the potential effect of co-medication on the occurrence of SSIBs. RESULTS: In total, 204 cases of SSIBs associated with GLP-1RAs, including semaglutide, liraglutide, dulaglutide, exenatide, and albiglutide, were identified in the FAERS database. Time-of-onset analysis revealed no consistent mechanism for the latency of SSIBs in patients receiving GLP-1RAs. The disproportionality analysis did not indicate an association between GLP-1RAs and SSIBs. Co-medication analysis revealed 81 cases with antidepressants, antipsychotics, and benzodiazepines, which may be proxies of mental health comorbidities. CONCLUSIONS: We found no signal of disproportionate reporting of an association between GLP-1RA use and SSIBs. Clinicians need to maintain heightened vigilance on patients premedicated with neuropsychotropic drugs. This contributes to the greater acceptance of GLP-1RAs in patients with type 2 diabetes mellitus or obesity. CI - (c) 2024. The Author(s). FAU - Zhou, Jianxing AU - Zhou J AD - Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. AD - School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China. FAU - Zheng, You AU - Zheng Y AD - Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. AD - School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China. FAU - Xu, Baohua AU - Xu B AD - Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. AD - School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China. FAU - Long, Songjun AU - Long S AD - School of Medical Imaging, Fujian Medical University, Fuzhou, Fujian, China. FAU - Zhu, Li-E AU - Zhu LE AD - Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. FAU - Liu, Yunhui AU - Liu Y AD - Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. FAU - Li, Chengliang AU - Li C AD - Department of Respiratory, Shanghai Electric Power Hospital, Shanghai, China. FAU - Zhang, Yifan AU - Zhang Y AD - Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. FAU - Liu, Maobai AU - Liu M AD - Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. liumb0591@fjmu.edu.cn. FAU - Wu, Xuemei AU - Wu X AUID- ORCID: 0000-0003-1640-7385 AD - Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China. wuxuemei@fjmu.edu.cn. AD - School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China. wuxuemei@fjmu.edu.cn. LA - eng PT - Journal Article DEP - 20240214 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Pharmacovigilance MH - Suicidal Ideation PMC - PMC10865629 OTO - NOTNLM OT - FAERS database OT - GLP-1RAs OT - Obesity OT - Pharmacovigilance OT - Suicidal or self-injurious behaviors OT - Type 2 diabetes COIS- The authors declare that they have no competing interests. EDAT- 2024/02/15 00:42 MHDA- 2024/02/16 06:42 PMCR- 2024/02/14 CRDT- 2024/02/14 23:37 PHST- 2023/08/18 00:00 [received] PHST- 2024/01/25 00:00 [accepted] PHST- 2024/02/16 06:42 [medline] PHST- 2024/02/15 00:42 [pubmed] PHST- 2024/02/14 23:37 [entrez] PHST- 2024/02/14 00:00 [pmc-release] AID - 10.1186/s12916-024-03274-6 [pii] AID - 3274 [pii] AID - 10.1186/s12916-024-03274-6 [doi] PST - epublish SO - BMC Med. 2024 Feb 14;22(1):65. doi: 10.1186/s12916-024-03274-6. PMID- 38344772 OWN - NLM STAT- MEDLINE DCOM- 20240424 LR - 20240425 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 136 IP - 2 DP - 2024 Mar TI - Non-steroidal mineralocorticoid antagonists and hyperkalemia monitoring in chronic kidney disease patients associated with type II diabetes: a narrative review. PG - 111-119 LID - 10.1080/00325481.2024.2316572 [doi] AB - Chronic kidney disease (CKD) is a prevalent complication of Type II diabetes (T2D). The coexistence of CKD with T2D is comparable to cardiovascular disease (CVD) when the estimated glomerular filtration rate declines below 60 ml/min/1.73 m(2). Screening and early detection of people with high risk for CKD would be beneficial in managing CKD progress and the associated complications such as CV complications. Renin-angiotensin-aldosterone system inhibitors (RAASi) have demonstrated beneficial effects in delaying CKD progression, but they carry the risk of hyperkalemia. Nonsteroidal mineralocorticoid antagonists (nsMRA), such as finerenone, exhibit considerable efficacy in their anti-inflammatory, antifibrotic, and renal protective effects with demonstrable reductions in CV complications. In addition, nsMRAs do not cause significant changes in serum potassium levels compared to traditional steroidal MRA. Ongoing research explores the capacity of the sodium-glucose transport protein 2 inhibitors (SGLT-2i), combined with nsMRA, to produce synergistic renal protective effects and reduce the risk of hyperkalemia. Also, a dedicated renal outcomes study (FLOW study) involving a once-weekly injectable Glucagon-like peptide-1 receptor agonist, semaglutide, was halted early by the data monitoring committee due to having achieved the predefined efficacy endpoint and considerations related to renal disease. In CKD patients with T2D on nsMRA, hyperkalemia management requires a comprehensive approach involving lifestyle adjustments, dietary modifications, regular serum potassium level monitoring, and potassium binders, if necessary. Withholding or down-titration of nsMRAs with close monitoring of serum potassium levels may be required in patients with concerning potassium levels. In light of the current state of knowledge, this review article explores the perspectives and approaches that HCPs may consider when monitoring and managing hyperkalemia in CKD patients with T2D. FAU - Morales, Javier AU - Morales J AD - Medicine, Donald and Barbara Zucker School of Medicine at Hofstra Northwell, Hempstead, NY, USA. AD - Advanced Internal Medicine Group, P.C, East Hills, NY, USA. FAU - Palmer, Biff F AU - Palmer BF AD - Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX, USA. LA - eng PT - Journal Article PT - Review DEP - 20240216 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Mineralocorticoid Receptor Antagonists) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Naphthyridines) RN - 0 (finerenone) SB - IM MH - Humans MH - *Hyperkalemia/etiology MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - *Mineralocorticoid Receptor Antagonists/therapeutic use/administration & dosage MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/administration & dosage MH - Naphthyridines/therapeutic use/administration & dosage OAB - Chronic Kidney Disease (CKD) is a common and serious problem among people with Type II Diabetes (T2D). People who have CKD with T2D are at a higher risk for heart disease after normal kidney function declines below certain levels. Renin-angiotensin-aldosterone system inhibitors are a group of medications that can help delay CKD progression but may cause a rise in circulating potassium levels. Nonsteroidal mineralocorticoid antagonist (nsMRA), such as finerenone, can reduce kidney inflammation and damage, with noted cardiovascular benefits, and with less effect on serum potassium levels as compared to their steroid-based counterparts. Researchers are studying whether combining blood sugar medications such as sodium-glucose transport protein-2 inhibitors (SGLT-2i) and finerenone can help protect the kidneys and heart. They also want to see if this combination can prevent high potassium levels. This article talks about ways to check and monitor potassium levels in CKD patients with T2D who may be taking nsMRA. To manage high potassium levels in people with CKD and T2D, doctors may suggest lifestyle changes, dietary adjustments, potassium-lowering medication, or adjustment of other medications with close monitoring of potassium levels. OABL- eng OTO - NOTNLM OT - Chronic kidney disease OT - finerenone OT - hyperkalemia OT - type II diabetes OT - urine albumin creatinine ratio EDAT- 2024/02/12 15:42 MHDA- 2024/04/24 19:06 CRDT- 2024/02/12 04:33 PHST- 2024/04/24 19:06 [medline] PHST- 2024/02/12 15:42 [pubmed] PHST- 2024/02/12 04:33 [entrez] AID - 10.1080/00325481.2024.2316572 [doi] PST - ppublish SO - Postgrad Med. 2024 Mar;136(2):111-119. doi: 10.1080/00325481.2024.2316572. Epub 2024 Feb 16. PMID- 38343381 OWN - NLM STAT- MEDLINE DCOM- 20240410 LR - 20250716 IS - 1557-9077 (Electronic) IS - 1050-7256 (Print) IS - 1050-7256 (Linking) VI - 34 IP - 4 DP - 2024 Apr TI - Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review. PG - 403-418 LID - 10.1089/thy.2023.0530 [doi] AB - Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective medications for the treatment of type 2 diabetes and obesity. Pharmacological studies in rodents support an association between the use of GLP-1 RAs and the development of medullary thyroid cancer (MTC) resulting in a black box warning for these agents in patients at risk for this condition. Yet, the association between GLP-1 RAs and non-MTC remains controversial. Excessive worry about unproven thyroid cancer risk might lead to underutilizing GLP-1 RAs in patients who could otherwise experience substantial benefits. Unwarranted concerns about thyroid cancer could lead to unnecessary thyroid cancer screening and harms from overdiagnosis. Summary: The body of evidence assessing the association between GLP-1 RA use and thyroid cancer spans a wide range of methodologies, including basic and translational research investigating biological plausibility; randomized trials assessing clinical efficacy and providing the strongest evidence for causality; observational studies providing real-life outcome evaluation in larger populations but with limited evaluation of covariates or dependable outcome definitions; and pharmacovigilance studies that provide postmarketing assessments of a safety signal but do not address causality. There is biological plausibility supporting an association between GLP-1 RA and MTC in rodents, which is less clear for non-MTC in humans. Clinical evidence from randomized trials and associated meta-analysis suggest thyroid cancer as a rare event making effect estimates imprecise but without conclusive and consistent evidence of increase risk in those receiving GLP-1 RA. Observational studies at higher risk of bias also show low event rates for thyroid cancer, with effect estimates that are inconsistent among different studies. Pharmacovigilance studies consistently show a signal of increased reporting of thyroid cancer in patients treated with GLP-1 RA. Conclusions: Evidence from randomized controlled trials indicates occurrence of thyroid cancer is infrequent in individuals exposed to GLP-1 RA. Observational studies at higher risk of bias yield inconsistent results. Overall there is no conclusive evidence of elevated thyroid cancer risk. These findings can help clinicians when addressing patient's concerns about a potential yet unproven link between GLP-1 RA therapy and thyroid cancer. FAU - Espinosa De Ycaza, Ana E AU - Espinosa De Ycaza AE AD - Facultad de Medicina, Universidad de Panama, Panama City, Panama. FAU - Brito, Juan P AU - Brito JP AD - Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA. FAU - McCoy, Rozalina G AU - McCoy RG AD - Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA. AD - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. AD - University of Maryland Institute for Health Computing, Bethesda, Maryland, USA. FAU - Shao, Hui AU - Shao H AD - Emory Global Diabetes Research Center of Woodruff Health Sciences Center, Emory University, Atlanta, Georgia, USA. AD - Hubert Department of Global Health, Rollin School of Public Health, Emory University, Atlanta, Georgia, USA. FAU - Singh Ospina, Naykky AU - Singh Ospina N AD - Division of Endocrinology, Department of Medicine, University of Florida, Gainesville, Florida, USA. LA - eng GR - K08 CA248972/CA/NCI NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240326 PL - United States TA - Thyroid JT - Thyroid : official journal of the American Thyroid Association JID - 9104317 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - Thyroid cancer, medullary SB - IM MH - Humans MH - *Carcinoma, Neuroendocrine MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists/adverse effects/therapeutic use MH - *Thyroid Neoplasms/complications/drug therapy PMC - PMC10998705 OTO - NOTNLM OT - GLP-1 receptor agonist OT - medullary thyroid cancer OT - semaglutide OT - thyroid cancer COIS- None of the authors have any conflict of interest related to the article. EDAT- 2024/02/12 15:42 MHDA- 2024/04/10 06:42 PMCR- 2025/04/01 CRDT- 2024/02/12 03:54 PHST- 2024/04/10 06:42 [medline] PHST- 2024/02/12 15:42 [pubmed] PHST- 2024/02/12 03:54 [entrez] PHST- 2025/04/01 00:00 [pmc-release] AID - 10.1089/thy.2023.0530 [pii] AID - 10.1089/thy.2023.0530 [doi] PST - ppublish SO - Thyroid. 2024 Apr;34(4):403-418. doi: 10.1089/thy.2023.0530. Epub 2024 Mar 26. PMID- 38341541 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20250103 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 23 IP - 1 DP - 2024 Feb 10 TI - Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: a post hoc analysis from the SURPASS Clinical Trial Program. PG - 63 LID - 10.1186/s12933-024-02147-9 [doi] LID - 63 AB - BACKGROUND: Metabolic syndrome is characterized as the co-occurrence of interrelated cardiovascular risk factors, including insulin resistance, hyperinsulinemia, abdominal obesity, dyslipidemia and hypertension. Once weekly tirzepatide is approved in the US and EU for the treatment of type 2 diabetes (T2D) and obesity. In the SURPASS clinical trial program for T2D, tirzepatide demonstrated greater improvements in glycemic control, body weight reduction and other cardiometabolic risk factors versus placebo, subcutaneous semaglutide 1 mg, insulin degludec, and insulin glargine. This post hoc analysis assessed the effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome across SURPASS 1-5. METHODS: Metabolic syndrome was defined as having >/= 3 of 5 criteria according to the US National Cholesterol Education Program: Adult Treatment Panel III. Analyses were based on on-treatment data at the primary endpoint from patients adherent to treatment (taking >/= 75% study drug). A logistic regression model with metabolic syndrome status as the response variable, metabolic syndrome status at the baseline visit as an adjustment, and randomized treatment as fixed explanatory effect was used. The effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome by categorical weight loss, background medication and gender were assessed. RESULTS: In SURPASS, the prevalence of patients meeting the criteria for metabolic syndrome at baseline was 67-88% across treatment groups with reductions at the primary endpoint to 38-64% with tirzepatide versus 64-82% with comparators. Reductions in the prevalence of patients meeting the criteria for metabolic syndrome was significantly greater with all tirzepatide doses versus placebo, semaglutide 1 mg, insulin glargine, and insulin degludec (p < 0.001). Individual components of metabolic syndrome were also reduced to a greater extent with tirzepatide vs comparators. Greater reductions in body weight were associated with greater reductions in the prevalence of patients meeting the criteria for metabolic syndrome and its individual components. Background SGLT2i or sulfonylurea use or gender did not impact the change in prevalence of patients meeting the criteria for metabolic syndrome. CONCLUSIONS: In this post hoc analysis, tirzepatide at all doses studied was associated with a greater reduction in the prevalence of patients meeting the criteria for metabolic syndrome compared to placebo, semaglutide 1 mg, insulin degludec, and insulin glargine. Although more evidence is needed, these data would support greater potential improvement in cardiovascular risk factor profile with tirzepatide treatment in people across the continuum of T2D. CI - (c) 2024. The Author(s). FAU - Nicholls, Stephen J AU - Nicholls SJ AD - Victorian Heart Institute, Monash University, Clayton, VIC, Australia. FAU - Tofe, Santiago AU - Tofe S AD - Department of Endocrinology and Nutrition, University Hospital Son Espases, Palma, Spain. FAU - le Roux, Carel W AU - le Roux CW AD - Diabetes Complications Research Centre, Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland. AD - Diabetes Research Centre, Ulster University, Coleraine, UK. FAU - D'Alessio, David A AU - D'Alessio DA AD - Division of Endocrinology, Department of Medicine, Duke Molecular Physiology Institute, Duke University, Durham, NC, USA. FAU - Wiese, Russell J AU - Wiese RJ AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Pavo, Imre AU - Pavo I AD - Eli Lilly Regional Operations GmbH, Vienna, Austria. FAU - Brown, Katelyn AU - Brown K AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Weerakkody, Govinda J AU - Weerakkody GJ AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Zeytinoglu, Meltem AU - Zeytinoglu M AD - Eli Lilly and Company, Indianapolis, IN, USA. FAU - Romera, Irene C AU - Romera IC AD - Eli Lilly and Company, Avda. de La Industria 30, 28108, Alcobendas, Madrid, Spain. romera_irene@lilly.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240210 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - OYN3CCI6QE (Tirzepatide) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Adult MH - Humans MH - *Metabolic Syndrome/diagnosis/drug therapy/epidemiology MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy/epidemiology MH - Prevalence MH - Insulin Glargine MH - Gastric Inhibitory Polypeptide MH - Obesity MH - Body Weight MH - Hypoglycemic Agents/adverse effects MH - *Glucagon-Like Peptide-2 Receptor MH - Tirzepatide PMC - PMC10859014 OTO - NOTNLM OT - Incretin OT - Metabolic syndrome OT - Tirzepatide OT - Type 2 diabetes COIS- SJN has received research support from AstraZeneca, New Amsterdam Pharma, Amgen, Anthera, Eli Lilly and Company, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron and LipoScience and is a consultant for AstraZeneca, Amarin, Akcea, Eli Lilly and Company, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim and Vaxxinity. ST has served on advisory boards and received consulting fees from Boehringer Ingelheim, Eli Lilly and Company, Johnson and Johnson, Novo Nordisk, and Sanofi. CWlR serves on advisory boards of Novo Nordisk A/S, Herbalife, GI Dynamics, Eli Lilly and Company, Johnson & Johnson, Glia, and Boehringer Ingelheim and was gifted stockholdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. DAD receive research support from Eli Lilly and Company and participates on the Diabetes Advisory Board for Eli Lilly and Company and the steering committee for the tirzepatide CVOT. RJW, IP, KB, GJW, MZ and ICR are employees and shareholders of Eli Lilly and Company. EDAT- 2024/02/11 07:19 MHDA- 2024/02/11 07:20 PMCR- 2024/02/10 CRDT- 2024/02/10 23:24 PHST- 2023/11/07 00:00 [received] PHST- 2024/01/29 00:00 [accepted] PHST- 2024/02/11 07:20 [medline] PHST- 2024/02/11 07:19 [pubmed] PHST- 2024/02/10 23:24 [entrez] PHST- 2024/02/10 00:00 [pmc-release] AID - 10.1186/s12933-024-02147-9 [pii] AID - 2147 [pii] AID - 10.1186/s12933-024-02147-9 [doi] PST - epublish SO - Cardiovasc Diabetol. 2024 Feb 10;23(1):63. doi: 10.1186/s12933-024-02147-9. PMID- 38340253 OWN - NLM STAT- MEDLINE DCOM- 20240427 LR - 20260822 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 41 IP - 5 DP - 2024 May TI - Risk of Stroke in Real-World US Individuals with Type 2 Diabetes Receiving Semaglutide or a Dipeptidyl Peptidase 4 Inhibitor. PG - 1843-1859 LID - 10.1007/s12325-023-02750-4 [doi] AB - INTRODUCTION: People with type 2 diabetes (T2D) have a higher risk of stroke and worse outcomes than those without T2D. Pooled data from randomized controlled trials indicate that the glucagon-like peptide 1 receptor agonist semaglutide is associated with stroke risk reduction in people with T2D at high cardiovascular risk. We compared real-world stroke risk in people with T2D or T2D plus atherosclerotic cardiovascular disease (ASCVD) initiating either semaglutide or a dipeptidyl peptidase 4 inhibitor (DPP4i). METHODS: Adults (>/= 18 years old) in a US claims database with a claim indicating initiation of either semaglutide or a DPP4i (index date) during the index period (1 January 2018-30 September 2020), a diagnosis code for T2D on or before the index date and at least 12 months' continuous enrolment in the database pre-index were included and propensity score matched 1:1 on baseline demographic and clinical characteristics. The primary outcome was time to first stroke event during follow-up. Healthcare resource utilization was also compared between groups. RESULTS: The analysis included 17,920 matched pairs with T2D and 4234 matched pairs with T2D and ASCVD. The groups were well matched on baseline characteristics. People initiating semaglutide had a lower risk of stroke over short-term follow-up than those initiating a DPP4i (T2D: hazard ratio 0.63 [95% confidence interval 0.41-0.95], p = 0.029; T2D plus ASCVD: 0.45 [0.24-0.86], p = 0.015). Semaglutide was also associated with a lower rate of inpatient, outpatient and emergency room visits compared with a DPP4i. CONCLUSION: This proof-of-concept analysis indicates that semaglutide has the potential to reduce the risk of stroke in people with T2D when prescribed in clinical practice. CI - (c) 2024. The Author(s). FAU - Evans, Marc AU - Evans M AD - Diabetes Resource Centre, University Hospital Llandough, Penlan Road, Llandough, Cardiff, CF64 2XX, UK. marclyndon1@hotmail.com. FAU - Husain, Mansoor AU - Husain M AD - Ted Rogers Centre for Heart Research, Department of Medicine, University of Toronto, Toronto, ON, Canada. FAU - Srivastava, Ayush AU - Srivastava A AD - Novo Nordisk Service Centre (India) Private Limited, Bangalore, India. FAU - Mangla, Kamal Kant AU - Mangla KK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kuhlman, Anja Birk AU - Kuhlman AB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine and Peter O'Donnell Jr. School of Public Health, The University of Texas Southwestern Medical Center, Dallas, TX, USA. LA - eng GR - P30 DK127984/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240210 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use/adverse effects MH - Male MH - *Glucagon-Like Peptides/therapeutic use/adverse effects MH - Female MH - Middle Aged MH - *Stroke/prevention & control/epidemiology MH - Aged MH - United States/epidemiology MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Adult MH - Semaglutide PMC - PMC11052848 OTO - NOTNLM OT - Diabetes mellitus - Type 2 OT - Glucagon-like peptide 1 OT - Hospitalization OT - Stroke COIS- Marc Evans has received fees from AstraZeneca, Boehringer Ingelheim and Novo Nordisk. Mansoor Husain has received research grants from AstraZeneca, Merck and Novo Nordisk; consultancy fees for participation in advisory board meetings from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk and Roche; speaker fees from AstraZeneca, Boehringer Ingelheim, Janssen, Merck and Novo Nordisk; and payment for expert testimony from Novo Nordisk. He holds one patent relating to GLP-1 peptides and has one patent pending relating to methods for inhibiting platelet aggregation using GLP-1 peptides. Ayush Srivastava is an employee of Novo Nordisk Service Centre Pvt. Ltd. Kamal Kant Mangla and Anja Birk Kuhlman are employees of Novo Nordisk A/S. Ayush Srivastava, Kamal Kant Mangla and Anja Birk Kuhlman hold Novo Nordisk stocks. Ildiko Lingvay has received research funding (paid to institution) from Boehringer Ingelheim, Merck, Mylan, Novo Nordisk, Pfizer and Sanofi; and advisory/consulting fees and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GI Dynamics, Intarcia Therapeutics, Intercept Pharmaceuticals, Janssen, MannKind, Merck, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, Target Pharma, Valeritas and Zealand Pharma. EDAT- 2024/02/10 14:44 MHDA- 2024/04/27 09:53 PMCR- 2024/02/10 CRDT- 2024/02/10 11:18 PHST- 2023/10/06 00:00 [received] PHST- 2023/11/23 00:00 [accepted] PHST- 2024/04/27 09:53 [medline] PHST- 2024/02/10 14:44 [pubmed] PHST- 2024/02/10 11:18 [entrez] PHST- 2024/02/10 00:00 [pmc-release] AID - 10.1007/s12325-023-02750-4 [pii] AID - 2750 [pii] AID - 10.1007/s12325-023-02750-4 [doi] PST - ppublish SO - Adv Ther. 2024 May;41(5):1843-1859. doi: 10.1007/s12325-023-02750-4. Epub 2024 Feb 10. PMID- 38339133 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20250103 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 3 DP - 2024 Feb 3 TI - Impact of Glucagon-Like Peptide 1 Receptor Agonists on Biochemical Markers of the Initiation of Atherosclerotic Process. LID - 10.3390/ijms25031854 [doi] LID - 1854 AB - Atherosclerosis stands out as one of the leading causes of global mortality. The inflammatory response against vascular wall components plays a pivotal role in the atherogenic process. The initiation of this process is notably driven by oxidized low-density lipoprotein (oxLDL) and a range of pro-inflammatory cytokines, with interleukin-1beta (Il-1beta) and tumor necrosis factor alpha (TNFalpha) emerging as particularly significant in the early stages of atherosclerotic plaque formation. In recent years, researchers worldwide have been diligently exploring innovative therapeutic approaches for metabolic diseases, recognizing their impact on the atherogenesis process. Our study aimed to investigate the influence of glucagon-like peptide 1 receptor agonists (GLP-1RA) on cytokine concentrations associated with the initiation of atherosclerotic plaque formation in a group of patients with type 2 diabetes and dyslipidemia. The study encompassed 50 subjects aged 41-81 (mean: 60.7), all diagnosed with type 2 diabetes, dyslipidemia and confirmed atherosclerosis based on B-mode ultrasound. Following a 180-day treatment with dulaglutide or semaglutide, we observed a statistically significant reduction in biochemical markers (oxLDL, TNFalpha and Il-1beta) associated with the initiation of the atherosclerotic process (p < 0.001) within our study group. In addition to the already acknowledged positive effects of GLP-1RA on the metabolic parameters of treated patients, these drugs demonstrated a notable reduction in proinflammatory cytokine concentrations and may constitute an important element of therapy aimed at reducing cardiovascular risk. FAU - Hachula, Marcin AU - Hachula M AUID- ORCID: 0000-0001-9023-676X AD - Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, 40-752 Katowice, Poland. FAU - Kosowski, Michal AU - Kosowski M AUID- ORCID: 0000-0003-2597-463X AD - Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, 40-752 Katowice, Poland. FAU - Ryl, Sabina AU - Ryl S AD - Department of Anaesthesiology and Intensive Care, Municipal Hospital in Zabrze-Biskupice, Zamkowa 4, 41-803 Zabrze, Poland. FAU - Basiak, Marcin AU - Basiak M AUID- ORCID: 0000-0003-0674-5612 AD - Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, 40-752 Katowice, Poland. FAU - Okopien, Boguslaw AU - Okopien B AUID- ORCID: 0000-0001-7228-2906 AD - Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medykow 18, 40-752 Katowice, Poland. LA - eng PT - Journal Article DEP - 20240203 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Hypoglycemic Agents) RN - 0 (Interleukin-1beta) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Atherosclerosis/drug therapy/metabolism MH - Biomarkers MH - Cytokines/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Dyslipidemias/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Interleukin-1beta/therapeutic use MH - *Plaque, Atherosclerotic/drug therapy MH - Tumor Necrosis Factor-alpha/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use PMC - PMC10855444 OTO - NOTNLM OT - GLP-1 OT - Il-1 OT - TNFalpha OT - atherosclerosis OT - atherosclerotic plaque OT - dulaglutide OT - oxLDL OT - semaglutide COIS- The authors declare no conflicts of interest. EDAT- 2024/02/10 10:49 MHDA- 2024/02/10 14:43 PMCR- 2024/02/03 CRDT- 2024/02/10 01:13 PHST- 2023/12/21 00:00 [received] PHST- 2024/01/11 00:00 [revised] PHST- 2024/01/31 00:00 [accepted] PHST- 2024/02/10 14:43 [medline] PHST- 2024/02/10 10:49 [pubmed] PHST- 2024/02/10 01:13 [entrez] PHST- 2024/02/03 00:00 [pmc-release] AID - ijms25031854 [pii] AID - ijms-25-01854 [pii] AID - 10.3390/ijms25031854 [doi] PST - epublish SO - Int J Mol Sci. 2024 Feb 3;25(3):1854. doi: 10.3390/ijms25031854. PMID- 38338770 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 25 IP - 3 DP - 2024 Jan 25 TI - Semaglutide Modulates Extracellular Matrix Production of LX-2 Cells via Exosomes and Improves Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). LID - 10.3390/ijms25031493 [doi] LID - 1493 AB - Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to some metabolic disorders, such as central obesity and type 2 diabetes (T2D). Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide, may have therapeutic roles in MASLD associated with T2D. This study aims to investigate the molecular mechanisms underlying the effectiveness of semaglutide on MASLD in terms of progression from liver steatosis to fibrosis. We characterized exosomes from ten patients with type 2 diabetes (T2D) before (T0) and after 12 months (T12) of treatment with once-weekly subcutaneous semaglutide. Six of ten patients were considered responders to therapy (R) based on MASLD severity downgrading by at least one class according to a validated ultrasonographic (US) score. Normal hepatocytes (HEPA-RG) and stellate (LX-2) cells were challenged with exosomes from R and NR patients, isolated before and after 12 months of therapy. Exosomes from both R and NR patients isolated at T0 significantly affected LX-2 viability. After 12 months of treatment, only those isolated from R patients restored cell viability, whereas those from NR patients did not. No effects were observed on HEPA-RG cells. Exosomes at T12 from R but not from NR patients significantly decreased the production of alpha-SMA, a marker of LX-2 activation, a liver stellate cell model, and ph-SMAD2 and CTGF, involved in fibrosis processes. TGF-beta1 was not modulated by the exosomes of R and NR patients. As a downstream effect, Vimentin, Collagen 1A1, and Fibronectin extracellular matrix components were also downregulated, as measured by droplets digital PCR. In conclusion, these results shed light on the potential effectiveness of semaglutide in improving liver fibrosis in MASLD. FAU - Scavo, Maria Principia AU - Scavo MP AUID- ORCID: 0000-0002-0812-4441 AD - Laboratory of Personalized Medicine, National Institute of Gastroenterology, IRCCS DeBellis, 70013 Castellana Grotte, BA, Italy. FAU - Lisco, Giuseppe AU - Lisco G AUID- ORCID: 0000-0001-6521-8578 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, BA, Italy. FAU - Depalo, Nicoletta AU - Depalo N AUID- ORCID: 0000-0002-2107-2762 AD - Institute for Chemical-Physical Processes, Italian National Research Council (IPCF)-CNR SS Bari, Via Orabona 4, 70125 Bari, BA, Italy. FAU - Rizzi, Federica AU - Rizzi F AUID- ORCID: 0000-0001-8891-4218 AD - Institute for Chemical-Physical Processes, Italian National Research Council (IPCF)-CNR SS Bari, Via Orabona 4, 70125 Bari, BA, Italy. FAU - Volpe, Sara AU - Volpe S AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, BA, Italy. FAU - Arre, Valentina AU - Arre V AD - Laboratory of Personalized Medicine, National Institute of Gastroenterology, IRCCS DeBellis, 70013 Castellana Grotte, BA, Italy. FAU - Carrieri, Livianna AU - Carrieri L AUID- ORCID: 0000-0001-6769-9520 AD - Laboratory of Personalized Medicine, National Institute of Gastroenterology, IRCCS DeBellis, 70013 Castellana Grotte, BA, Italy. FAU - Notarnicola, Maria AU - Notarnicola M AUID- ORCID: 0000-0003-2274-2198 AD - Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology, IRCCS "S. de Bellis" Research Hospital, 70013 Castellana Grotte, BA, Italy. FAU - De Nunzio, Valentina AU - De Nunzio V AUID- ORCID: 0000-0001-7912-9023 AD - Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology, IRCCS "S. de Bellis" Research Hospital, 70013 Castellana Grotte, BA, Italy. FAU - Curri, Maria Lucia AU - Curri ML AD - Dipartimento di Chimica, Universita degli Studi di Bari Aldo Moro, Via Orabona 4, 70125 Bari, BA, Italy. FAU - De Pergola, Giovanni AU - De Pergola G AUID- ORCID: 0000-0003-0020-3273 AD - Center of Nutrition for the Research and the Care of Obesity and Metabolic Diseases, National Institute of Gastroenterology IRCCS "Saverio de Bellis", 70013 Castellana Grotte, BA, Italy. FAU - Piazzolla, Giuseppina AU - Piazzolla G AUID- ORCID: 0000-0003-3221-6562 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, BA, Italy. FAU - Giannelli, Gianluigi AU - Giannelli G AUID- ORCID: 0000-0002-5140-8060 AD - Scientific Direction, National Institute of Gastroenterology IRCCS "De Bellis," Via Turi 27, 70013 Castellana Grotte, BA, Italy. LA - eng GR - RC2022/Ministero della Salute/ PT - Journal Article DEP - 20240125 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Exosomes MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Metabolic Diseases MH - Extracellular Matrix MH - *Fatty Liver/drug therapy MH - Fibrosis MH - *Glucagon-Like Peptides MH - Semaglutide PMC - PMC10855465 OTO - NOTNLM OT - HEPA-REG OT - LX-2 cells OT - MASLD OT - exosomes OT - glucagon-like peptide 1 receptor agonist OT - metabolic dysfunction-associated steatotic liver disease OT - type 2 diabetes COIS- The authors declare no conflict of interest. EDAT- 2024/02/10 10:48 MHDA- 2024/02/11 07:43 PMCR- 2024/01/25 CRDT- 2024/02/10 01:11 PHST- 2023/12/18 00:00 [received] PHST- 2024/01/17 00:00 [revised] PHST- 2024/01/23 00:00 [accepted] PHST- 2024/02/11 07:43 [medline] PHST- 2024/02/10 10:48 [pubmed] PHST- 2024/02/10 01:11 [entrez] PHST- 2024/01/25 00:00 [pmc-release] AID - ijms25031493 [pii] AID - ijms-25-01493 [pii] AID - 10.3390/ijms25031493 [doi] PST - epublish SO - Int J Mol Sci. 2024 Jan 25;25(3):1493. doi: 10.3390/ijms25031493. PMID- 38330988 OWN - NLM STAT- MEDLINE DCOM- 20240226 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 12 IP - 3 DP - 2024 Mar TI - Efficacy and safety of once weekly semaglutide 2.4 mg for weight management in a predominantly east Asian population with overweight or obesity (STEP 7): a double-blind, multicentre, randomised controlled trial. PG - 184-195 LID - S2213-8587(23)00388-1 [pii] LID - 10.1016/S2213-8587(23)00388-1 [doi] AB - BACKGROUND: Data on the benefits of the once weekly GLP-1 receptor agonist semaglutide 2.4 mg for weight management in people from east Asia are insufficient. The objective of this study was to determine the efficacy and safety of once weekly semaglutide 2.4 mg versus placebo for weight management in a predominantly east Asian adult population. METHODS: This randomised phase 3a, double-blind multicentre controlled trial (STEP 7) recruited participants from 23 hospitals and trial centres in China, Hong Kong, Brazil, and South Korea. Adults with overweight or obesity, with or without type 2 diabetes, were randomly assigned (2:1) to receive a subcutaneous injection of either semaglutide 2.4 mg or placebo once a week for 44 weeks, plus a diet and physical activity intervention. Randomisation was done in blocks of six with an interactive web response system and was stratified by diagnosis of type 2 diabetes. Participants, investigators, and the trial sponsor were masked to treatment allocation until after database lock. Primary endpoints were percentage change in mean bodyweight and proportion of participants having reached a weight reduction of at least 5% of bodyweight from baseline to week 44. Safety was assessed in all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04251156, and is now complete. FINDINGS: From Dec 8, 2020, to Aug 23, 2022, 448 participants were screened, of whom 375 were randomly assigned to either the semaglutide 2.4 mg group (n=249) or the placebo group (n=126). Estimated mean percentage change in bodyweight from baseline to week 44 was -12.1% (SE 0.5) with semaglutide 2.4 mg versus -3.6% (0.7) with placebo (estimated treatment difference -8.5 percentage points [95% CI -10.2 to -6.8]; p<0.0001). At week 44, the proportion of participants who lost 5% or more of their bodyweight was higher in the semaglutide 2.4 mg group than in the placebo group (203/238 [85%] vs 36/116 [31%]); odds ratio 13.1 (95% CI 7.4-23.1; p<0.0001). Adverse events were reported by 231 (93%) of 249 participants in the semaglutide 2.4 mg group and 108 (86%) of 126 participants in the placebo group, the most common of which were gastrointestinal disorders (168/249, 67% vs 45/126, 36%). INTERPRETATION: The results of this study support the use of semaglutide 2.4 mg for weight management in people of east Asian ethnicity with overweight or obesity and with or without type 2 diabetes. FUNDING: Novo Nordisk. TRANSLATIONS: For the Mandarin, Portuguese and South Korean translations of the abstract see Supplementary Materials section. CI - Copyright (c) 2024 Elsevier Ltd. All rights reserved. FAU - Mu, Yiming AU - Mu Y AD - Department of Endocrinology, The First Medical Center of Chinese PLA General Hospital, Beijing, China. Electronic address: muyiming@301hospital.com.cn. FAU - Bao, Xiaolei AU - Bao X AD - Novo Nordisk (China) Pharmaceuticals Co, Ltd, Beijing, China. FAU - Eliaschewitz, Freddy G AU - Eliaschewitz FG AD - CpClin/DASA Clinical Research Center, Sao Paulo, Brazil. FAU - Hansen, Morten Rix AU - Hansen MR AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kim, Bom Taeck AU - Kim BT AD - Department of Family Practice and Community Health, Ajou University School of Medicine (AUSOM), Suwon, South Korea. FAU - Koroleva, Anna AU - Koroleva A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ma, Ronald C W AU - Ma RCW AD - Division of Endocrinology and Diabetes, Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China. FAU - Yang, Tao AU - Yang T AD - The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Zu, Ning AU - Zu N AD - Novo Nordisk (China) Pharmaceuticals Co, Ltd, Beijing, China. FAU - Liu, Ming AU - Liu M AD - Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China. CN - STEP 7 Study Group LA - eng SI - ClinicalTrials.gov/NCT04251156 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240205 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet Diabetes Endocrinol. 2024 Mar;12(3):153-154. doi: 10.1016/S2213-8587(24)00031-7. PMID: 38330985 MH - Adult MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - East Asian People MH - *Glucagon-Like Peptides/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - *Obesity/drug therapy MH - *Overweight/drug therapy MH - Treatment Outcome MH - Semaglutide COIS- Declaration of interests YM reports having received honoraria and personal fees from Eli Lilly Diabetes, Novo Nordisk, and Sanofi outside the submitted work. XB is a full-time employee of Novo Nordisk (China) Pharmaceuticals, Beijing, China, and is a shareholder in Novo Nordisk. FGE has received clinical research grants from Novo Nordisk, Eli Lilly, AstraZeneca, Novartis, Eurofarma, and Kowa; is on advisory boards for Novo Nordisk, Eli Lilly, AstraZeneca, and Pfizer; and has given lectures for AstraZeneca, Bayer, Novo Nordisk, Eli Lilly, Sanofi, Abbot, Merck, and Novartis. MRH is a full-time employee of Novo Nordisk and shareholder in Novo Nordisk and Eli Lilly; before his current employment MRH received speaking fees from Novartis outside the submitted work. BTK has received research funding from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk for carrying out clinical trials or studies; speaker honoraria from Alvogen Korea and Novo Nordisk; all proceeds have been donated to the Ajou University Hospital to support obesity research. AK is an employee of and shareholder in Novo Nordisk. RCWM has received research funding from AstraZeneca, Bayer, Novo Nordisk, Pfizer, Roche Diagnostics Hong Kong and Tricida for carrying out clinical trials, and has received speaker honorarium or consultancy in advisory boards from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Merck, and Kyowa Kirin; all proceeds have been donated to the Chinese University of Hong Kong to support diabetes research. NZ is an employee of and shareholder in Novo Nordisk. ML has received consulting fees from Novo Nordisk and Sanofi, and honoraria from Novo Nordisk, Sanofi, and Bayer, and is a committee member of the Chinese Society of Endocrinology. TY declares no competing interests. EDAT- 2024/02/09 00:42 MHDA- 2024/02/26 06:45 CRDT- 2024/02/08 18:53 PHST- 2023/09/20 00:00 [received] PHST- 2023/12/21 00:00 [revised] PHST- 2023/12/21 00:00 [accepted] PHST- 2024/02/26 06:45 [medline] PHST- 2024/02/09 00:42 [pubmed] PHST- 2024/02/08 18:53 [entrez] AID - S2213-8587(23)00388-1 [pii] AID - 10.1016/S2213-8587(23)00388-1 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2024 Mar;12(3):184-195. doi: 10.1016/S2213-8587(23)00388-1. Epub 2024 Feb 5. PMID- 38316483 OWN - NLM STAT- MEDLINE DCOM- 20240207 LR - 20260502 IS - 2208-7958 (Electronic) VI - 53 IP - 1-2 DP - 2024 Jan-Feb TI - Impact of semaglutide and dulaglutide shortages on Pharmaceutical Benefits Scheme prescriptions supplied for type 2 diabetes treatment. PG - 57-61 LID - 10.31128/AJGP/04-23-6814 [doi] AB - METHOD: A retrospective analysis was performed of actual and predicted (Holt-Winters modelling) semaglutide and dulaglutide prescriptions supplied by the Australian PBS and Repatriation PBS in 2021-22. RESULTS: Semaglutide prescriptions decreased by 17% in March - September 2022, whereas dulaglutide prescriptions increased by 53% in April - July 2022 before decreasing by 17% in August - September 2022. There were 119,069 fewer semaglutide and 31,953 more dulaglutide prescriptions supplied than predicted in April - July and June - July 2022, respectively. DISCUSSION: Changes in semaglutide and dulaglutide T2D prescription patterns in 2022 coincided with supply shortages. General practitioners are encouraged to continue to prescribe semaglutide and dulaglutide for their appropriate indication and support patients with alternative treatments during the shortage. FAU - Phakey, Sachin AU - Phakey S AD - MD, MPH, Hospital Medical Officer, Department of General Medicine, The Royal Melbourne Hospital, Melbourne, Vic. FAU - Shen, Angeline AU - Shen A AD - MBBS, FRACP, Consultant Endocrinologist, Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Melbourne, Vic; Consultant General Physician, Department of General Medicine, The Royal Melbourne Hospital, Melbourne, Vic. LA - eng PT - Journal Article PL - Australia TA - Aust J Gen Pract JT - Australian journal of general practice JID - 101718099 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - Australia MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Drug Prescriptions/statistics & numerical data MH - Glucagon-Like Peptides/analogs & derivatives MH - *Hypoglycemic Agents/supply & distribution/therapeutic use MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins MH - Retrospective Studies MH - Semaglutide EDAT- 2024/02/06 00:42 MHDA- 2024/02/07 06:43 CRDT- 2024/02/05 20:53 PHST- 2024/02/07 06:43 [medline] PHST- 2024/02/06 00:42 [pubmed] PHST- 2024/02/05 20:53 [entrez] AID - 10.31128/AJGP/04-23-6814 [doi] PST - ppublish SO - Aust J Gen Pract. 2024 Jan-Feb;53(1-2):57-61. doi: 10.31128/AJGP/04-23-6814. PMID- 38310052 OWN - NLM STAT- MEDLINE DCOM- 20240415 LR - 20260127 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 46 IP - 3 DP - 2024 Mar TI - Use of Dulaglutide, Semaglutide, and Tirzepatide in Diabetes and Weight Management. PG - 289-292 LID - S0149-2918(24)00008-0 [pii] LID - 10.1016/j.clinthera.2023.12.014 [doi] AB - PURPOSE: Glucagon-like peptide 1 receptor agonists (GLP1-RA) are effective therapies in lowering glycosylated hemoglobin (HbA(1c)), providing cardioprotective benefits, and lowering weight. The use of GLP1-RA solely for weight-loss has become commonplace in many practices, which in turn has made it difficult in some areas for those with type 2 diabetes (T2DM) to obtain these much-needed medications. METHODS: Using recent published literature, along with clinical experience, it has become apparent that many GLP1-RAs have become difficult to obtain for patients with diabetes. FINDINGS: Many clinicians started to prescribe the brand Ozempic(R) (semaglutide*) and dulaglutide for weight loss despite neither of them being Food and Drug Administration (FDA) approved for this indication. Ozempic, having outperformed dulaglutide in in both HbA(1c) reduction and weight loss, along with FDA approval of semaglutide for weight loss, has quickly become widely used off-label for weight loss. This off-label use may have increased, despite the approval of semaglutide,(dagger) because many insurances will not cover semaglutide solely for weight management. Most recently, Eli Lilly was able to develop tirzepatide,(double dagger) which was FDA approved in May of 2022, and they are seeking fast-track FDA approval for weight loss and are projected to gain this approval within 2023. IMPLICATIONS: Insurance coverage for weight management remains sparse, and obtaining these therapies for diabetes has now become more burdensome, with insurance companies requiring a prior authorization proving FDA-approved diagnosis of T2DM. Hopefully, should more GLP1-Ras receive approval for weight loss, along with an increase in insurance coverage, the burden on patients with diabetes will be lessened as they are able to quickly obtain this highly effective therapy. CI - Copyright (c) 2024 Elsevier Inc. All rights reserved. FAU - Powell, Jason AU - Powell J AD - University of Florida College of Pharmacy, Gainesville, FL. Electronic address: jpowell@cop.ufl.edu. FAU - Taylor, James AU - Taylor J AD - University of Florida College of Pharmacy, Gainesville, FL. LA - eng PT - Journal Article DEP - 20240202 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/adverse effects/*analogs & derivatives MH - Weight Loss MH - *Glucagon-Like Peptide-2 Receptor MH - *Gastric Inhibitory Polypeptide MH - *Immunoglobulin Fc Fragments MH - *Recombinant Fusion Proteins MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Diabetes OT - Dulaglutide OT - Semaglutide OT - Tirzepatide OT - Weight management COIS- Declaration of competing interest The authors have no conflicts to declare. EDAT- 2024/02/04 00:42 MHDA- 2024/04/15 06:42 CRDT- 2024/02/03 22:02 PHST- 2023/04/18 00:00 [received] PHST- 2023/11/21 00:00 [revised] PHST- 2023/12/23 00:00 [accepted] PHST- 2024/04/15 06:42 [medline] PHST- 2024/02/04 00:42 [pubmed] PHST- 2024/02/03 22:02 [entrez] AID - S0149-2918(24)00008-0 [pii] AID - 10.1016/j.clinthera.2023.12.014 [doi] PST - ppublish SO - Clin Ther. 2024 Mar;46(3):289-292. doi: 10.1016/j.clinthera.2023.12.014. Epub 2024 Feb 2. PMID- 38308628 OWN - NLM STAT- MEDLINE DCOM- 20240205 LR - 20260127 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 30 IP - 2 DP - 2024 Feb 3 TI - Tirzepatide 10 and 15 mg vs semaglutide 2.0 mg: A long-term cost-effectiveness analysis in patients with type 2 diabetes in the United States. PG - 153-162 LID - 10.18553/jmcp.2024.30.2.153 [doi] AB - BACKGROUND: Tirzepatide is a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes (T2D) treatment. OBJECTIVE: To compare the long-term cost-effectiveness of tirzepatide 10 mg and 15 mg vs semaglutide 2.0 mg, an injectable glucagon-like peptide-1 receptor agonist, in patients with T2D from a US health care payer perspective. METHODS: The PRIME T2D Model was used to project clinical and cost outcomes over a 50-year time horizon. Baseline cohort characteristics and treatment effects were sourced from a published adjusted indirect treatment comparison that used data from the SURPASS-2 and SUSTAIN FORTE trials. Patients were assumed to intensify to insulin therapy at a hemoglobin A1c of greater than 7.5%. Costs and health state utilities were derived from published sources. Future costs and clinical benefits were discounted at 3% annually. RESULTS: Tirzepatide 10 mg and 15 mg were associated with improved quality-adjusted life-expectancy (10 mg: 0.085 quality-adjusted life-years [QALYs], 15 mg: 0.121 QALYs), higher direct costs (10 mg: USD 5,990, 15 mg: USD 6,617), and incremental cost-effectiveness ratios of USD 70,147 and 54,699 per QALY gained, respectively, vs semaglutide 2.0 mg. Both doses of tirzepatide remained cost-effective vs semaglutide 2.0 mg over a range of sensitivity analyses. CONCLUSIONS: Long-term projections using the PRIME T2D model and based on treatment effects from an adjusted indirect treatment comparison indicate that tirzepatide 10 mg and 15 mg are likely to be cost-effective vs semaglutide 2.0 mg for the treatment of T2D in the United States. FAU - Mody, Reema AU - Mody R AD - Eli Lilly and Company, Indianapolis, IN. FAU - Valentine, William J AU - Valentine WJ AD - Ossian Health Economics and Communications GmbH, Basel, Switzerland. FAU - Hoog, Meredith AU - Hoog M AD - Eli Lilly and Company, Indianapolis, IN. FAU - Sharland, Helen AU - Sharland H AD - Ossian Health Economics and Communications GmbH, Basel, Switzerland. FAU - Belger, Mark AU - Belger M AD - Eli Lilly and Company Ltd, Bracknell, UK. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - United States MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents MH - Cost-Effectiveness Analysis MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Cost-Benefit Analysis MH - *Glucagon-Like Peptide-2 Receptor MH - *Glucagon-Like Peptides MH - *Gastric Inhibitory Polypeptide MH - Tirzepatide MH - Semaglutide PMC - PMC10839462 EDAT- 2024/02/03 21:42 MHDA- 2024/02/05 06:43 PMCR- 2024/02/01 CRDT- 2024/02/03 09:52 PHST- 2024/02/05 06:43 [medline] PHST- 2024/02/03 21:42 [pubmed] PHST- 2024/02/03 09:52 [entrez] PHST- 2024/02/01 00:00 [pmc-release] AID - 10.18553/jmcp.2024.30.2.153 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2024 Feb 3;30(2):153-162. doi: 10.18553/jmcp.2024.30.2.153. PMID- 38299476 OWN - NLM STAT- MEDLINE DCOM- 20240327 LR - 20240327 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 25 IP - 2 DP - 2024 Feb TI - Treatment of obesity with medications binding the glucagon-like peptide 1 receptor: what is the current state of play? PG - 131-138 LID - 10.1080/14656566.2024.2311731 [doi] AB - INTRODUCTION: Obesity, marked by abnormal fat accumulation, poses significant health risks, necessitating effective therapeutic interventions. The focus of this review is to elucidate the importance of glucagon-like peptide 1 (GLP-1) receptor-binding medications in addressing obesity-related health deteriorations. AREAS COVERED: Exploring the mechanisms, efficacy, and safety profiles, this review comprehensively assesses medications selectively or non-selectively binding the GLP-1 receptor for obesity treatment. A meticulous analysis of phase 2 and phase 3 data positions retatrutide, CagriSema, survudotide, tirzepatide, semaglutide, and liraglutide in order of effectiveness. While showcasing their efficacy and safety, the review acknowledges the ongoing phase 3 studies, highlighting the need for further exploration of contraindications, dosage, and potential adverse effects to inform personalized treatment decisions. EXPERT OPINION: The ongoing anticipation of long-term benefits, particularly sustained weight loss and cardiovascular outcomes, underscores the significance of future treatment algorithms for addressing the disease of obesity. FAU - Le Roux, Carel AU - Le Roux C AD - University College Dublin Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland. AD - Imperial College London Institute of Clinical Sciences, London, UK. FAU - Mondoh, Alvin AU - Mondoh A AD - University College Dublin Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland. LA - eng PT - Journal Article PT - Review DEP - 20240202 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Obesity/drug therapy MH - Liraglutide/adverse effects OTO - NOTNLM OT - GIP receptor agonist OT - GLP-1 receptor agonists OT - Obesity OT - adverse effects OT - pharmacological therapy EDAT- 2024/02/01 06:42 MHDA- 2024/03/27 06:43 CRDT- 2024/02/01 05:54 PHST- 2024/03/27 06:43 [medline] PHST- 2024/02/01 06:42 [pubmed] PHST- 2024/02/01 05:54 [entrez] AID - 10.1080/14656566.2024.2311731 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2024 Feb;25(2):131-138. doi: 10.1080/14656566.2024.2311731. Epub 2024 Feb 2. PMID- 38294187 OWN - NLM STAT- MEDLINE DCOM- 20240404 LR - 20250729 IS - 1531-7080 (Electronic) IS - 0268-4705 (Linking) VI - 39 IP - 3 DP - 2024 May 1 TI - Beyond Weight Loss: the Emerging Role of Incretin-Based Treatments in Cardiometabolic HFpEF. PG - 148-153 LID - 10.1097/HCO.0000000000001117 [doi] AB - PURPOSE OF REVIEW: Incretin-based drugs are potent weight-lowering agents, emerging as potential breakthrough therapy for the treatment of obesity-related phenotype of heart failure with preserved ejection fraction (HFpEF). In this review article, we will discuss the contribution of weight loss as part of the benefits of incretin-based medications in obese patients with HFpEF. Furthermore, we will describe the potential effects of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists on the heart, particularly in relation to HFpEF pathophysiology. RECENT FINDINGS: In the STEP-HFpEF trial, the GLP-1 receptor agonist semaglutide significantly improved quality of life outcomes in obese HFpEF patients. Whether the beneficial effects of semaglutide in obese patients with HFpEF are merely a consequence of body weight reduction is unclear. Considering the availability of other weight loss strategies (e.g., caloric restriction, exercise training, bariatric surgery) to be used in obese HFpEF patients, answering this question is crucial to provide tailored therapeutic options in these subjects. SUMMARY: Incretin-based drugs may represent a milestone in the treatment of obesity in HFpEF. Elucidating the contribution of weight loss in the overall benefit observed with these drugs is critical in the management of obese HFpEF patients, considering that other weight-lowering strategies are available and might represent potential alternative options for these patients. CI - Copyright (c) 2024 Wolters Kluwer Health, Inc. All rights reserved. FAU - Capone, Federico AU - Capone F AD - Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany. AD - Division of Internal Medicine, Department of Medicine, University of Padua, Padua, Italy. FAU - Nambiar, Natasha AU - Nambiar N AD - Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany. FAU - Schiattarella, Gabriele G AU - Schiattarella GG AD - Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbruck Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany. AD - Max Rubner Center for Cardiovascular Metabolic Renal Research (MRC), Deutsches Herzzentrum der Charite (DHZC), Charite -Universitatsmedizin Berlin, Berlin, Germany. AD - DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany. AD - Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy. LA - eng GR - ERC_/European Research Council/International PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240131 PL - United States TA - Curr Opin Cardiol JT - Current opinion in cardiology JID - 8608087 RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - Incretins/therapeutic use MH - *Heart Failure/drug therapy MH - Quality of Life MH - Stroke Volume/physiology MH - Weight Loss/physiology MH - Glucagon-Like Peptide 1/pharmacology/therapeutic use MH - Obesity/complications MH - *Diabetes Mellitus, Type 2/drug therapy EDAT- 2024/01/31 12:43 MHDA- 2024/04/04 06:44 CRDT- 2024/01/31 08:43 PHST- 2024/04/04 06:44 [medline] PHST- 2024/01/31 12:43 [pubmed] PHST- 2024/01/31 08:43 [entrez] AID - 00001573-202405000-00004 [pii] AID - 10.1097/HCO.0000000000001117 [doi] PST - ppublish SO - Curr Opin Cardiol. 2024 May 1;39(3):148-153. doi: 10.1097/HCO.0000000000001117. Epub 2024 Jan 31. PMID- 38291203 OWN - NLM STAT- MEDLINE DCOM- 20240429 LR - 20260127 IS - 1476-5497 (Electronic) IS - 0307-0565 (Print) IS - 0307-0565 (Linking) VI - 48 IP - 5 DP - 2024 May TI - Cost-effectiveness of weight-management pharmacotherapies in Canada: a societal perspective. PG - 683-693 LID - 10.1038/s41366-024-01467-w [doi] AB - OBJECTIVES: This study aimed to assess the cost-effectiveness of weight-management pharmacotherapies approved by Canada Health, i.e., orlistat, naltrexone 32 mg/bupropion 360 mg (NB-32), liraglutide 3.0 mg and semaglutide 2.4 mg as compared to the current standard of care (SoC). METHODS: Analyses were conducted using a cohort with a mean starting age 50 years, body mass index (BMI) 37.5 kg/m(2), and 27.6% having type 2 diabetes. Using treatment-specific changes in surrogate endpoints from the STEP trials (BMI, glycemic, blood pressure, lipids), besides a network meta-analysis, the occurrence of weight-related complications, costs, and quality-adjusted life-years (QALYs) were projected over lifetime. RESULTS: From a societal perspective, at a willingness-to-pay (WTP) threshold of CAD 50 000 per QALY, semaglutide 2.4 mg was the most cost-effective treatment, at an incremental cost-utility ratio (ICUR) of CAD 31 243 and CAD 29 014 per QALY gained versus the next best alternative, i.e., orlistat, and SoC, respectively. Semaglutide 2.4 mg extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg and remained cost-effective both under a public and private payer perspective. Results were robust to sensitivity analyses varying post-treatment catch-up rates, longer treatment durations and using real-world cohort characteristics. Semaglutide 2.4 mg was the preferred intervention, with a likelihood of 70% at a WTP threshold of CAD 50 000 per QALY gained. However, when the modeled benefits of weight-loss on cancer, mortality, cardiovascular disease (CVD) or osteoarthritis surgeries were removed simultaneously, orlistat emerged as the best value for money compared with SoC, with an ICUR of CAD 35 723 per QALY gained. CONCLUSION: Semaglutide 2.4 mg was the most cost-effective treatment alternative compared with D&E or orlistat alone, and extendedly dominated other pharmacotherapies such as NB-32 or liraglutide 3.0 mg. Results were sensitive to the inclusion of the combined benefits of mortality, cancer, CVD, and knee osteoarthritis. CI - (c) 2024. The Author(s). FAU - Olivieri, Anamaria-Vera AU - Olivieri AV AUID- ORCID: 0000-0002-0947-3002 AD - QVIA, Basel, Switzerland. FAU - Muratov, Sergey AU - Muratov S AD - QVIA Mississauga, Mississauga, ON, Canada. FAU - Larsen, Sara AU - Larsen S AD - Novo Nordisk A/S, Soborg, Bagsvaerd, Denmark. FAU - Luckevich, Maria AU - Luckevich M AUID- ORCID: 0000-0002-4308-2574 AD - Novo Nordisk Canada Inc, Mississauga, ON, Canada. MLVH@novonordisk.com. FAU - Chan, Katalina AU - Chan K AD - Novo Nordisk Canada Inc, Mississauga, ON, Canada. FAU - Lamotte, Mark AU - Lamotte M AD - QVIA, Zaventem, Zaventem, Belgium. FAU - Lau, David C W AU - Lau DCW AUID- ORCID: 0000-0002-1780-9039 AD - Department of Medicine, University of Calgary Cumming School of Medicine, Calgary, AB, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240131 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - 0 (Anti-Obesity Agents) RN - 95M8R751W8 (Orlistat) RN - 839I73S42A (Liraglutide) RN - 01ZG3TPX31 (Bupropion) RN - 5S6W795CQM (Naltrexone) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Cost-Benefit Analysis MH - Canada MH - Middle Aged MH - *Obesity/drug therapy/economics MH - Female MH - *Anti-Obesity Agents/therapeutic use/economics MH - Male MH - *Orlistat/therapeutic use MH - Quality-Adjusted Life Years MH - Liraglutide/therapeutic use/economics MH - Diabetes Mellitus, Type 2/drug therapy/economics MH - Bupropion/therapeutic use/economics MH - Naltrexone/therapeutic use/economics MH - Glucagon-Like Peptides/therapeutic use/economics MH - Semaglutide PMC - PMC11058048 COIS- IQVIA, the employer of AVO, SM, and MLa (at the moment of the project development) received consulting fees from Novo Nordisk for the development of the model and conducting the analyses reported in this manuscript. SL, MLu, and KC are full-time employees of Novo Nordisk. DCWL received consulting fees from Amgen, Bayer, Boehringer Ingelheim, HLS Therapeutics, Eli Lilly, Novartis, Novo Nordisk, Pfizer, and Viatris. EDAT- 2024/01/31 00:42 MHDA- 2024/04/30 00:43 PMCR- 2024/01/31 CRDT- 2024/01/30 23:28 PHST- 2022/10/05 00:00 [received] PHST- 2024/01/11 00:00 [accepted] PHST- 2024/01/09 00:00 [revised] PHST- 2024/04/30 00:43 [medline] PHST- 2024/01/31 00:42 [pubmed] PHST- 2024/01/30 23:28 [entrez] PHST- 2024/01/31 00:00 [pmc-release] AID - 10.1038/s41366-024-01467-w [pii] AID - 1467 [pii] AID - 10.1038/s41366-024-01467-w [doi] PST - ppublish SO - Int J Obes (Lond). 2024 May;48(5):683-693. doi: 10.1038/s41366-024-01467-w. Epub 2024 Jan 31. PMID- 38286487 OWN - NLM STAT- MEDLINE DCOM- 20240221 LR - 20250623 IS - 1756-1833 (Electronic) IS - 0959-8138 (Print) IS - 0959-8138 (Linking) VI - 384 DP - 2024 Jan 29 TI - Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: systematic review and network meta-analysis. PG - e076410 LID - 10.1136/bmj-2023-076410 [doi] LID - e076410 AB - OBJECTIVE: To evaluate the comparative efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycaemic control, body weight, and lipid profile in adults with type 2 diabetes. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from database inception to 19 August 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials enrolled adults with type 2 diabetes who received GLP-1RA treatments and compared effects with placebo or any GLP-1RA drug, with a follow-up duration of at least 12 weeks. Trials with a crossover design, non-inferiority studies comparing GLP-1RA and other drug classes without a placebo group, using withdrawn drugs, and non-English studies were deemed ineligible. RESULTS: 76 eligible trials involving 15 GLP-1RA drugs and 39 246 participants were included in this network meta-analysis; all subsequent estimates refer to the comparison with placebo. All 15 GLP-1RAs effectively lowered haemoglobin A(1c) and fasting plasma glucose concentrations. Tirzepatide induced the largest reduction of haemoglobin A(1c) concentrations (mean difference -2.10% (95% confidence interval -2.47% to -1.74%), surface under the cumulative ranking curve 94.2%; high confidence of evidence), and fasting plasma glucose concentrations (-3.12 mmol/L (-3.59 to -2.66), 97.2%; high confidence), and proved the most effective GLP-1RA drug for glycaemic control. Furthermore, GLP-1RAs were shown to have strong benefits to weight management for patients with type 2 diabetes. CagriSema (semaglutide with cagrilintide) resulted in the highest weight loss (mean difference -14.03 kg (95% confidence interval -17.05 to -11.00); high confidence of evidence), followed by tirzepatide (-8.47 kg (-9.68 to -7.26); high confidence). Semaglutide was effective in lowering the concentration of low density lipoprotein (-0.16 mmol/L (-0.30 to -0.02)) and total cholesterol (-0.48 mmol/L (-0.84 to -0.11)). Moreover, this study also raises awareness of gastrointestinal adverse events induced by GLP-1RAs, and concerns about safety are especially warranted for high dose administration. CONCLUSIONS: GLP-1RAs are efficacious in treating adults with type 2 diabetes. Compared with the placebo, tirzepatide was the most effective GLP-1RA drug for glycaemic control by reducing haemoglobin A(1c) and fasting plasma glucose concentrations. GLP-1RAs also significantly improved weight management for type 2 diabetes, with CagriSema performing the best for weight loss. The results prompt safety concerns for GLP-1RAs, especially with high dose administration, regarding gastrointestinal adverse events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022342845. CI - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Yao, Haiqiang AU - Yao H AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. AD - National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Zhang, Anqi AU - Zhang A AD - National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Li, Delong AU - Li D AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. AD - National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Wu, Yuqi AU - Wu Y AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. AD - National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Wang, Chong-Zhi AU - Wang CZ AD - Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL, USA. AD - Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA. FAU - Wan, Jin-Yi AU - Wan JY AUID- ORCID: 0000-0001-8830-2035 AD - School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China. AD - National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China. FAU - Yuan, Chun-Su AU - Yuan CS AD - Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL, USA. AD - Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL, USA. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20240129 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) SB - IM CIN - Ann Intern Med. 2024 May;177(5):JC55. doi: 10.7326/J24-0028. PMID: 38710089 MH - Adult MH - Humans MH - Blood Glucose MH - Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Glycated Hemoglobin MH - Glycemic Control/methods MH - Hypoglycemic Agents/adverse effects MH - Weight Loss MH - Lipid Metabolism/drug effects PMC - PMC10823535 COIS- Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, and Beijing University of Chinese Medicine High-level Talent Start-up Research Project; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. EDAT- 2024/01/30 00:42 MHDA- 2024/01/31 06:43 PMCR- 2024/01/29 CRDT- 2024/01/29 20:44 PHST- 2024/01/31 06:43 [medline] PHST- 2024/01/30 00:42 [pubmed] PHST- 2024/01/29 20:44 [entrez] PHST- 2024/01/29 00:00 [pmc-release] AID - yaoh076410 [pii] AID - 10.1136/bmj-2023-076410 [doi] PST - epublish SO - BMJ. 2024 Jan 29;384:e076410. doi: 10.1136/bmj-2023-076410. PMID- 38275036 OWN - NLM STAT- MEDLINE DCOM- 20240718 LR - 20250104 IS - 1875-6417 (Electronic) IS - 1573-3998 (Print) IS - 1573-3998 (Linking) VI - 20 IP - 8 DP - 2024 TI - Future is Brighter: New Potential Paradigm-Shifting Medications and Regimens for Diabetes and Obesity. PG - 84-97 LID - 10.2174/0115733998276832231124170324 [doi] AB - Diabetes is a chronic illness that can become debilitating owing to its microvascular and macrovascular complications. Its prevalence is increasing and so is its cost. Diabetes, particularly type 2, appears to have a very close relationship with obesity. While lifestyle modifications, exercises, and current therapeutics have substantially improved clinical outcomes, the need for new therapeutics and regimens continue to exist. Several new medications and regimens for diabetes, obesity, and diabesity are showing promising results in advanced clinical trials. For type 1 diabetes mellitus (T1DM), they include teplizumab, ustekinumab, jakinibs, and cell therapies, whereas for type 2 diabetes mellitus (T2DM), they include once-weakly insulin, tirzepatide, high oral dose of semaglutide, orforglipron, retatrutide, CagriSema, and survodutide. Given their structural and mechanistic diversity as well as their substantial efficacy and safety profiles, these medications and regimens are paradigm shifting and promise a brighter future. They will likely enable better disease prevention and management. This review will provide details about each of the above strategies to keep the scientific community up to date about progress in the fields of diabetes and obesity. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Al-Horani, Rami A AU - Al-Horani RA AUID- ORCID: 0000-0001-9146-2662 AD - Division of Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, Louisiana 70125, USA. FAU - Aliter, Kholoud F AU - Aliter KF AD - Department of Biology and Chemistry, School of STEM, Dillard University, New Orleans, Louisiana 70122, USA. FAU - Aliter, Hashem F AU - Aliter HF AD - Division of Cardiac Surgery, Department of Surgery, Dalhouise University, Halifax, NS B3H 3A6, Canada. LA - eng GR - R16 GM149412/GM/NIGMS NIH HHS/United States GR - SC3 GM131986/GM/NIGMS NIH HHS/United States GR - SC3GM131986, R16GM149412/National Institute of Health/ PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Diabetes Rev JT - Current diabetes reviews JID - 101253260 RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) SB - IM MH - Humans MH - *Obesity/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Diabetes Mellitus, Type 1/drug therapy MH - Anti-Obesity Agents/therapeutic use PMC - PMC11452264 MID - NIHMS2024777 OTO - NOTNLM OT - Diabetes OT - cagrisema OT - insulin OT - jakinibs. OT - obesity OT - orforglipron OT - retatrutide OT - semaglutide OT - survodutide OT - teplizumab OT - tirzepatide OT - ustekinumab COIS- CONFLICT OF INTEREST The authors declare no conflict of interest financial or otherwise. EDAT- 2024/01/26 06:43 MHDA- 2024/07/18 12:44 PMCR- 2025/01/01 CRDT- 2024/01/26 04:13 PHST- 2023/08/24 00:00 [received] PHST- 2023/10/15 00:00 [revised] PHST- 2023/10/24 00:00 [accepted] PHST- 2024/07/18 12:44 [medline] PHST- 2024/01/26 06:43 [pubmed] PHST- 2024/01/26 04:13 [entrez] PHST- 2025/01/01 00:00 [pmc-release] AID - CDR-EPUB-137718 [pii] AID - 10.2174/0115733998276832231124170324 [doi] PST - ppublish SO - Curr Diabetes Rev. 2024;20(8):84-97. doi: 10.2174/0115733998276832231124170324. PMID- 38265519 OWN - NLM STAT- MEDLINE DCOM- 20240325 LR - 20260127 IS - 2210-7711 (Electronic) IS - 2210-7703 (Print) VI - 46 IP - 2 DP - 2024 Apr TI - Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database. PG - 488-495 LID - 10.1007/s11096-023-01694-7 [doi] AB - BACKGROUND: Semaglutide, liraglutide and tirzepatide are glucagon-like peptide-1 (GLP-1) receptor agonists that are effective for weight reduction. Recent reports of patients experiencing suicidal thoughts and other psychiatric adverse events while using GLP-1 agonists have raised concerns about the potential risk of self-harm and led the European Medicines Agency to investigate these medications. AIM: To identify and analyse the psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide. METHOD: All individual case safety reports for semaglutide, liraglutide, and tirzepatide reported to the EudraVigilance database from 01/01/2021 to 30/05/2023 were analysed. Descriptive statistics were used to explore study population characteristics. RESULTS: During the study period, 31,444 adverse event reports were identified: semaglutide (n = 13,956; 44.4%), liraglutide (n = 16,748; 53.2%), and tirzepatide (n = 740; 2.3%). There were 372 reports with psychiatric adverse event reports (n = 372; 1.18%) with a total of 481 adverse events. Women accounted for 65% (n = 242) of these reports. Depression was the most commonly reported adverse event (n = 187; 50.3%), followed by anxiety (n = 144; 38.7%) and suicidal ideation (n = 73; 19.6%). Nine deaths (8 with liraglutide and 1 with semaglutide) and 11 life-threatening outcomes (4 associated with liraglutide and 7 with semaglutide) were reported. The fatal outcomes occurred primarily among men (8 out of 9) resulting from completed suicidal attempts and depression. CONCLUSION: Psychiatric adverse events comprised only 1.2% of the total reports for semaglutide, liraglutide, and tirzepatide. However, the severity and fatal outcomes of some of these reports warrant further investigation. CI - (c) 2024. The Author(s). FAU - Tobaiqy, Mansour AU - Tobaiqy M AUID- ORCID: 0000-0002-4292-0900 AD - Department of Pharmacology, College of Medicine, University of Jeddah, Jeddah, Saudi Arabia. mtobaiqy@uj.edu.sa. FAU - Elkout, Hajer AU - Elkout H AUID- ORCID: 0000-0003-3191-3868 AD - Department of Family and Community Medicine, Medical Faculty, University of Tripoli, Tripoli, 13275, Libya. LA - eng PT - Journal Article DEP - 20240124 PL - Netherlands TA - Int J Clin Pharm JT - International journal of clinical pharmacy JID - 101554912 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Male MH - Humans MH - Female MH - *Liraglutide/adverse effects MH - Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Pharmacovigilance MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - *Glucagon-Like Peptide-2 Receptor MH - *Glucagon-Like Peptides MH - *Gastric Inhibitory Polypeptide MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC10960895 OTO - NOTNLM OT - Liraglutide OT - Obesity OT - Psychiatric adverse events OT - Semaglutide OT - Suicide OT - Tirzepatide COIS- The authors have no conflicts of interest to declare. EDAT- 2024/01/24 12:42 MHDA- 2024/03/25 06:42 PMCR- 2024/01/24 CRDT- 2024/01/24 11:07 PHST- 2023/10/10 00:00 [received] PHST- 2023/12/18 00:00 [accepted] PHST- 2024/03/25 06:42 [medline] PHST- 2024/01/24 12:42 [pubmed] PHST- 2024/01/24 11:07 [entrez] PHST- 2024/01/24 00:00 [pmc-release] AID - 10.1007/s11096-023-01694-7 [pii] AID - 1694 [pii] AID - 10.1007/s11096-023-01694-7 [doi] PST - ppublish SO - Int J Clin Pharm. 2024 Apr;46(2):488-495. doi: 10.1007/s11096-023-01694-7. Epub 2024 Jan 24. PMID- 38265050 OWN - NLM STAT- MEDLINE DCOM- 20240221 LR - 20250103 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 17 IP - 3 DP - 2024 Mar TI - Revolutionizing diabetes care: unveiling tirzepatide's potential in glycemic control and beyond. PG - 235-246 LID - 10.1080/17512433.2024.2310070 [doi] AB - INTRODUCTION: Diabetes is a global public health challenge with rising prevalence. This review explores current diabetes understanding, diagnostic and management guidelines, economic impact, and lifestyle modifications as the primary approach. AREAS COVERED: Focusing on pharmacological interventions, we discuss the roles of GLP-1 agonists and GLP/GIP agonists in diabetes management and cardiovascular risk reduction. Tirzepatide, a novel medication, is highlighted for its unique mechanism of action. Clinical trials demonstrate its effectiveness in glucose control, weight reduction, and its potential impact on diabetes, obesity, NASH, and cardiovascular risks. EXPERT OPINION: Tirzepatide shows promise in diabetes treatment, offering glucose control and weight loss. It also holds potential for addressing comorbidities. However, cautious use is vital due to potential adverse effects and contraindications, including hypersensitivity reactions, pregnancy, and breastfeeding precautions. This review underscores tirzepatide as a valuable addition to diabetes therapies, with evolving prospects for enhanced patient outcomes as research advances. FAU - Sood, Aayushi AU - Sood A AD - Department of Medicine, The Wright Center for Graduate Medical Education, Scranton, PA, USA. FAU - Kaur, Purnoor AU - Kaur P AD - Department of Medicine, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, India. FAU - Syed, Omar AU - Syed O AD - Department of Medicine, The Wright Center for Graduate Medical Education, Scranton, PA, USA. FAU - Sood, Akshit AU - Sood A AD - Department of Medicine, Sri Venkateshwara Institute of Medical Sciences, Gajraula, India. FAU - Aronow, Wilbert S AU - Aronow WS AD - Department of Cardiology, Westchester Medical Center, Valhalla, NY, USA. FAU - Borokhovsky, Benjamin AU - Borokhovsky B AD - Department of Medicine, Lehigh Valley Health Network, Allentown, PA, USA. FAU - Bhatia, Vishal AU - Bhatia V AD - Department of Endocrinology, Department of Internal Medicine, St Vincent Medical Group, Evansville, IN, USA. FAU - Gupta, Rahul AU - Gupta R AD - Department of Cardiology, Lehigh Valley Health Network, Allentown, PA, USA. LA - eng PT - Journal Article PT - Review DEP - 20240131 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Blood Glucose) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Female MH - Pregnancy MH - Humans MH - Glycemic Control MH - Blood Glucose MH - *Diabetes Mellitus/drug therapy MH - Gastric Inhibitory Polypeptide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Hypoglycemic Agents/adverse effects MH - *Glucagon-Like Peptide-2 Receptor MH - Tirzepatide OTO - NOTNLM OT - Tirzepatide OT - diabetes OT - insulin OT - review OT - semaglutide EDAT- 2024/01/24 12:43 MHDA- 2024/02/21 11:15 CRDT- 2024/01/24 08:58 PHST- 2024/02/21 11:15 [medline] PHST- 2024/01/24 12:43 [pubmed] PHST- 2024/01/24 08:58 [entrez] AID - 10.1080/17512433.2024.2310070 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2024 Mar;17(3):235-246. doi: 10.1080/17512433.2024.2310070. Epub 2024 Jan 31. PMID- 38252888 OWN - NLM STAT- MEDLINE DCOM- 20240616 LR - 20260713 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 109 IP - 7 DP - 2024 Jun 17 TI - Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2). PG - 1745-1753 LID - 10.1210/clinem/dgae038 [doi] AB - CONTEXT: In previous SURPASS studies tirzepatide reduced hemoglobin glycated A1c (HbA1c) and body weight and improved markers of insulin sensitivity and beta-cell function to a greater extent than comparators. OBJECTIVE: Explore changes in biomarkers of beta-cell function and insulin sensitivity and in efficacy profiles in baseline biomarker quartile analyses with tirzepatide compared to semaglutide. DESIGN: Post hoc analysis of SURPASS-2 phase 3 trial (participants randomly assigned to receive weekly subcutaneous tirzepatide or semaglutide for 40 weeks). SETTING: Post hoc analysis of 128 sites in 8 countries. PARTICIPANTS: A total of 1879 participants with type 2 diabetes. INTERVENTIONS: Once-weekly tirzepatide (5, 10, 15 mg) or semaglutide 1 mg. MAIN OUTCOMES MEASURES: Change in homeostatic model assessment indices for pancreatic beta-cell function (HOMA2-B) and for insulin resistance (HOMA2-IR), fasting glucagon, fasting C-peptide, and fasting insulin. RESULTS: At week 40, a greater increase in HOMA2-B was seen with tirzepatide (5, 10, 15 mg) doses (96.9-120.4%) than with semaglutide 1 mg (84.0%) (P < .05). There was a greater reduction in HOMA2-IR with all doses of tirzepatide (15.5%-24.0%) than with semaglutide 1 mg (5.1%) (P < .05). Tirzepatide 10 and 15 mg resulted in a significant reduction in both fasting C-peptide (5.2%-6.0%) and fasting glucagon (53.0%-55.3%) compared with an increase of C-peptide (3.3%) and a reduction of glucagon (47.7%) with semaglutide 1 mg (P < .05). HbA1c and body weight reductions were greater with all tirzepatide doses than semaglutide within each HOMA2-B and HOMA2-IR baseline quartile. CONCLUSION: In this post hoc analysis, improvements in HbA1c and weight loss were consistent and significantly higher with tirzepatide, regardless of baseline beta-cell function and insulin resistance, compared with semaglutide. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Frias, Juan P AU - Frias JP AD - Velocity Clinical Research, Los Angeles, CA 90057, USA. FAU - De Block, Christophe AU - De Block C AD - Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, 2650 Edegem, Belgium. FAU - Brown, Katelyn AU - Brown K AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Wang, Hui AU - Wang H AD - TechData Service, King of Prussia, PA 19406, USA. FAU - Thomas, Melissa K AU - Thomas MK AUID- ORCID: 0000-0001-9848-2834 AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Zeytinoglu, Meltem AU - Zeytinoglu M AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Maldonado, Juan M AU - Maldonado JM AUID- ORCID: 0000-0002-1370-327X AD - Lilly Research Laboratories, Eli Lilly and Company, San Juan 00918, Puerto Rico. LA - eng GR - Eli Lilly and Company/ PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Biomarkers) RN - 0 (Glycated Hemoglobin) RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/blood/metabolism MH - *Insulin Resistance MH - Male MH - Female MH - Middle Aged MH - *Glucagon-Like Peptides/administration & dosage/pharmacology MH - *Hypoglycemic Agents/administration & dosage/pharmacology/therapeutic use MH - *Biomarkers/blood MH - Glycated Hemoglobin/analysis MH - Insulin-Secreting Cells/drug effects/metabolism MH - Blood Glucose/drug effects/metabolism MH - Aged MH - Adult MH - Double-Blind Method MH - Insulin/blood/metabolism MH - Islets of Langerhans/drug effects/metabolism MH - Treatment Outcome MH - Glucagon-Like Peptide-2 Receptor MH - Gastric Inhibitory Polypeptide MH - Tirzepatide MH - Semaglutide PMC - PMC11180500 OTO - NOTNLM OT - beta-cell function OT - incretin OT - insulin sensitivity OT - tirzepatide OT - type 2 diabetes EDAT- 2024/01/22 18:42 MHDA- 2024/06/17 05:42 PMCR- 2024/01/22 CRDT- 2024/01/22 15:42 PHST- 2023/10/25 00:00 [received] PHST- 2024/06/17 05:42 [medline] PHST- 2024/01/22 18:42 [pubmed] PHST- 2024/01/22 15:42 [entrez] PHST- 2024/01/22 00:00 [pmc-release] AID - 7585180 [pii] AID - dgae038 [pii] AID - 10.1210/clinem/dgae038 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2024 Jun 17;109(7):1745-1753. doi: 10.1210/clinem/dgae038. PMID- 38242040 OWN - NLM STAT- MEDLINE DCOM- 20240215 LR - 20250623 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 171 DP - 2024 Feb TI - Efficacy and safety of GLP-1RAs for people with obesity: A systematic review based on RCT and Bayesian network meta-analysis. PG - 116150 LID - S0753-3322(24)00031-3 [pii] LID - 10.1016/j.biopha.2024.116150 [doi] AB - BACKGROUND: GLP-1 receptor agonists (GLP-1RAs) reduce glucagon and glycogen secretion, inhibit appetite and slow gastric empties and have recently been approved to treat obesity. OBJECTIVE: To explore the safety and efficacy of GLP-1RAs in the treatment of obesity and clarify the optimal GLP-1RAs treatment regimen. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched for English randomized controlled trials (RCTs) on GLP-1RAs in the treatment and management of obesity published before July 18, 2023. Literature screening and data extraction were performed independently by three researchers. Bayesian random effect model was used to compare the effects of interventions. Continuous variables were expressed as mean difference with 95% CI, and dichotomous variables were reported as RR with 95% CI. RESULTS: A total of 29 studies with 10,333 participants were included in the present study. The combination of cagrilintide and semaglutide (short for cagrANDsema) was an optimal strategy for weight loss and glycosylated hemoglobin (HbA1c) reduction. Compared to placebo, cagrANDsema reduced weight by - 14.13 kg (95% CI: -16.49, -11.73) and HbA1c by - 0.33% (95% CI: -0.41, -0.25). Moreover, this study indicated that orforglipron and semaglutide also had relatively good effects on weight loss. Meta-regression results indicated that higher dose levels might have better effects on weight loss. CONCLUSIONS: CagrANDsema exerts the best effect for weight loss. In terms of current dose levels, a higher dose gets better weight-loss effects without increasing the risk of adverse events. CI - Copyright (c) 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Li, Hong AU - Li H AD - Chinese Medicinal Materials Products Quality Supervision and Inspection Center in Wuling Mountainous Area, Hubei Minzu University, Hubei, China. FAU - Yu, Guanzheng AU - Yu G AD - Chinese Medicinal Materials Products Quality Supervision and Inspection Center in Wuling Mountainous Area, Hubei Minzu University, Hubei, China; School of Medical, Hubei Minzu University, Hubei, China. FAU - Huang, Qi AU - Huang Q AD - School of Medical, Hubei Minzu University, Hubei, China. FAU - Yang, Bao AU - Yang B AD - Chinese Medicinal Materials Products Quality Supervision and Inspection Center in Wuling Mountainous Area, Hubei Minzu University, Hubei, China; School of Medical, Hubei Minzu University, Hubei, China. FAU - Nie, Juan AU - Nie J AD - Chinese Medicinal Materials Products Quality Supervision and Inspection Center in Wuling Mountainous Area, Hubei Minzu University, Hubei, China; School of Medical, Hubei Minzu University, Hubei, China. FAU - Liu, Yinbei AU - Liu Y AD - Chinese Medicinal Materials Products Quality Supervision and Inspection Center in Wuling Mountainous Area, Hubei Minzu University, Hubei, China; School of Medical, Hubei Minzu University, Hubei, China. FAU - Tu, Xing AU - Tu X AD - Chinese Medicinal Materials Products Quality Supervision and Inspection Center in Wuling Mountainous Area, Hubei Minzu University, Hubei, China; School of Medical, Hubei Minzu University, Hubei, China. Electronic address: 2015030@hbmzu.edu.cn. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20240118 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/therapeutic use MH - Obesity/drug therapy MH - Randomized Controlled Trials as Topic MH - Weight Loss OTO - NOTNLM OT - Bayesian network meta-analysis OT - GLP-1RAs OT - Obesity OT - Overweight OT - RCT COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/01/20 05:42 MHDA- 2024/02/08 06:43 CRDT- 2024/01/19 18:15 PHST- 2023/10/23 00:00 [received] PHST- 2024/01/03 00:00 [revised] PHST- 2024/01/10 00:00 [accepted] PHST- 2024/02/08 06:43 [medline] PHST- 2024/01/20 05:42 [pubmed] PHST- 2024/01/19 18:15 [entrez] AID - S0753-3322(24)00031-3 [pii] AID - 10.1016/j.biopha.2024.116150 [doi] PST - ppublish SO - Biomed Pharmacother. 2024 Feb;171:116150. doi: 10.1016/j.biopha.2024.116150. Epub 2024 Jan 18. PMID- 38241775 OWN - NLM STAT- MEDLINE DCOM- 20240325 LR - 20250228 IS - 1532-8171 (Electronic) IS - 0735-6757 (Linking) VI - 78 DP - 2024 Apr TI - GLP-1 agonists: A review for emergency clinicians. PG - 89-94 LID - S0735-6757(24)00011-1 [pii] LID - 10.1016/j.ajem.2024.01.010 [doi] AB - INTRODUCTION: Glucagon-like peptide 1 (GLP-1) based therapies, including GLP-1 agonists, are currently in use for treatment of diabetes and obesity. However, several complications may occur with their use. OBJECTIVE: This narrative review provides a focused evaluation of GLP-1 agonist therapy and associated complications for emergency clinicians. DISCUSSION: GLP-1 agonists potentiate insulin release and reduce gastric emptying and food intake. These agents have demonstrated significant improvements in glucose control in diabetics and weight loss in obese patients. The two most common agents include subcutaneous semaglutide (Ozempic, approved for type 2 diabetes, and Wegovy, approved for weight loss) and liraglutide (Saxenda, approved for weight loss, and Victoza, approved for type 2 diabetes), though an oral formulation of semaglutide is available (Rybelsus). While these drugs are associated with improved long-term outcomes, there are a variety of associated adverse events. The most common include gastrointestinal (GI) adverse events such as nausea, vomiting, diarrhea, and abdominal pain. Pancreatitis and biliary disease may also occur. Hypersensitivity including injection site reactions have been associated with use, with reports of anaphylaxis and other rashes. Renal adverse events are most commonly associated with severe GI losses. Hypoglycemia may occur when these agents are used with sulfonylureas or insulin. There is also an increased risk of diabetic retinopathy. Due to the current shortage and expense of these medications, many patients have attempted to obtain these medications from non-licensed and unregulated agents, which may be associated with increased risk of serious complications. CONCLUSIONS: An understanding of the indications for GLP-1 agonist use and associated adverse events can assist emergency clinicians. CI - Published by Elsevier Inc. FAU - Long, Brit AU - Long B AD - Department of Emergency Medicine, Brooke Army Medical Center, Fort Sam Houston, TX, USA. Electronic address: Brit.long@yahoo.com. FAU - Pelletier, Jessica AU - Pelletier J AD - Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA. FAU - Koyfman, Alex AU - Koyfman A AD - Department of Emergency Medicine, UT Southwestern, Dallas, TX, USA. FAU - Bridwell, Rachel E AU - Bridwell RE AD - Department of Emergency Medicine, Madigan Army Medical Center, Tacoma, WA, USA. LA - eng PT - Journal Article PT - Review DEP - 20240112 PL - United States TA - Am J Emerg Med JT - The American journal of emergency medicine JID - 8309942 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Insulin) SB - IM CIN - Am J Emerg Med. 2024 Jun;80:194-196. doi: 10.1016/j.ajem.2024.03.034. PMID: 38582620 CIN - Am J Emerg Med. 2024 Aug;82:190-191. doi: 10.1016/j.ajem.2024.05.018. PMID: 38821845 CIN - Am J Emerg Med. 2024 Aug;82:192-193. doi: 10.1016/j.ajem.2024.06.007. PMID: 38866625 MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide 1/therapeutic use MH - Obesity MH - Weight Loss MH - Insulin/therapeutic use OTO - NOTNLM OT - Adverse event OT - Complication OT - Compounding OT - Diabetes OT - Endocrine OT - GLP-1 agonist OT - Liraglutide OT - Semaglutide OT - Side effect OT - Weight loss COIS- Declaration of competing interest None. None of the authors have submitted a review on this topic or published previously on this topic. No AI program was utilized in the construction of this manuscript. EDAT- 2024/01/20 05:42 MHDA- 2024/03/25 06:43 CRDT- 2024/01/19 18:01 PHST- 2023/10/26 00:00 [received] PHST- 2024/01/07 00:00 [revised] PHST- 2024/01/08 00:00 [accepted] PHST- 2024/03/25 06:43 [medline] PHST- 2024/01/20 05:42 [pubmed] PHST- 2024/01/19 18:01 [entrez] AID - S0735-6757(24)00011-1 [pii] AID - 10.1016/j.ajem.2024.01.010 [doi] PST - ppublish SO - Am J Emerg Med. 2024 Apr;78:89-94. doi: 10.1016/j.ajem.2024.01.010. Epub 2024 Jan 12. PMID- 38240066 OWN - NLM STAT- MEDLINE DCOM- 20240409 LR - 20260808 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 5 DP - 2024 May TI - Separate and combined effects of empagliflozin and semaglutide on vascular function: A 32-week randomized trial. PG - 1624-1635 LID - 10.1111/dom.15464 [doi] AB - AIM: Despite the increasing use of combination treatment with sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, data are limited on the effects of combination treatment on markers of cardiovascular disease. This study aimed to investigate the effect of empagliflozin, semaglutide, and their combination on vascular function. MATERIALS AND METHODS: In total, 120 patients with type 2 diabetes were randomized into four groups (n = 30 in each) for 32 weeks: placebo, semaglutide, empagliflozin, and their combination. The study had two co-primary outcomes: change in arterial stiffness and kidney oxygenation. This paper reports on arterial stiffness assessed as carotid-femoral pulse wave velocity. Secondary outcomes included 24-h blood pressure (BP), 24-h central BP, urinary albumin to creatinine ratio and glycaemic control assessed by both continuous glucose monitoring and glycated haemoglobin. RESULTS: The carotid-femoral pulse wave velocity did not change significantly in any of the groups compared with placebo. Twenty-four-hour systolic BP was reduced by 10 mmHg (95% CI 6-14), p < .001 in the combination group, significantly superior to both placebo and monotherapy (p < .05). Combination treatment increased glycaemic time in range from 72% at baseline to 91% at week 32, p < .001, without increasing time below range. The urinary albumin to creatinine ratio decreased by 36% (95% CI 4-57), p = .03 in the combination group compared with placebo. CONCLUSIONS: Empagliflozin, semaglutide, or their combination did not reduce arterial stiffness. Combination treatment showed a substantial and clinically important reduction in 24-h systolic BP compared with either treatment alone. Combination treatment increased glycaemic time in range without increasing the risk of hypoglycaemia. CI - (c) 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Vernstrom, Liv AU - Vernstrom L AUID- ORCID: 0000-0003-2875-435X AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. FAU - Gullaksen, Soren AU - Gullaksen S AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Regional Hospital Horsens, Horsens, Denmark. FAU - Sorensen, Steffen S AU - Sorensen SS AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. FAU - Funck, Kristian L AU - Funck KL AUID- ORCID: 0000-0003-0213-5550 AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. FAU - Laugesen, Esben AU - Laugesen E AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. AD - Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark. FAU - Poulsen, Per L AU - Poulsen PL AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark. LA - eng GR - 2019-3780/41/Laegeforeningen/ GR - NNF170C0029064/Novo Nordisk Fonden/ GR - Sundhedsvidenskabelige Fakultet, Aarhus Universitet/ GR - A3192/the Central Denmark Region Research Fund/ GR - 2019-3780/41/Laegeforeningen/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20240119 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - AYI8EX34EU (Creatinine) RN - 0 (Blood Glucose) RN - 0 (Benzhydryl Compounds) RN - 0 (Albumins) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Creatinine MH - Blood Glucose Self-Monitoring MH - Pulse Wave Analysis MH - Blood Glucose MH - Benzhydryl Compounds/adverse effects MH - Albumins MH - Treatment Outcome MH - Double-Blind Method MH - *Glucagon-Like Peptides MH - *Glucosides MH - Semaglutide OTO - NOTNLM OT - continuous glucose monitoring OT - drug mechanism OT - glucagon-like peptide-1 analogue OT - macrovascular disease OT - sodium-glucose cotransporter 2 inhibitor OT - type 2 diabetes EDAT- 2024/01/19 06:42 MHDA- 2024/04/09 06:45 CRDT- 2024/01/19 04:13 PHST- 2024/01/04 00:00 [revised] PHST- 2023/12/13 00:00 [received] PHST- 2024/01/05 00:00 [accepted] PHST- 2024/04/09 06:45 [medline] PHST- 2024/01/19 06:42 [pubmed] PHST- 2024/01/19 04:13 [entrez] AID - 10.1111/dom.15464 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 May;26(5):1624-1635. doi: 10.1111/dom.15464. Epub 2024 Jan 19. PMID- 38237952 OWN - NLM STAT- MEDLINE DCOM- 20240301 LR - 20260127 IS - 1755-5248 (Electronic) IS - 0012-6543 (Linking) VI - 62 IP - 3 DP - 2024 Feb 28 TI - Effect of semaglutide on major cardiovascular events. PG - 35 LID - 10.1136/dtb.2024.000007 [doi] AB - Overview of: Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 2023;389:2221-32. CI - (c) BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ. LA - eng PT - Journal Article DEP - 20240228 PL - England TA - Drug Ther Bull JT - Drug and therapeutics bulletin JID - 0112037 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Glucagon-Like Peptides/adverse effects MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Obesity MH - *Cardiovascular Diseases/prevention & control MH - Hypoglycemic Agents/adverse effects MH - Semaglutide OTO - NOTNLM OT - Drug-Related Side Effects and Adverse Reactions OT - Health Care Quality, Access, and Evaluation EDAT- 2024/01/19 00:42 MHDA- 2024/03/01 06:44 CRDT- 2024/01/18 20:53 PHST- 2024/03/01 06:44 [medline] PHST- 2024/01/19 00:42 [pubmed] PHST- 2024/01/18 20:53 [entrez] AID - dtb.2024.000007 [pii] AID - 10.1136/dtb.2024.000007 [doi] PST - epublish SO - Drug Ther Bull. 2024 Feb 28;62(3):35. doi: 10.1136/dtb.2024.000007. PMID- 38237661 OWN - NLM STAT- MEDLINE DCOM- 20240629 LR - 20260127 IS - 1885-5857 (Electronic) IS - 1885-5857 (Linking) VI - 77 IP - 7 DP - 2024 Jul TI - Once weekly semaglutide and cardiovascular outcomes in patients with type 2 diabetes and heart failure with reduced left ventricular ejection fraction. PG - 583-587 LID - S1885-5857(24)00024-0 [pii] LID - 10.1016/j.rec.2023.12.008 [doi] FAU - Perez-Velasco, Miguel A AU - Perez-Velasco MA AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain. FAU - Trenas, Alicia AU - Trenas A AD - Servicio de Medicina Interna, Area Sanitaria Norte de Malaga, Hospital de Antequera, Antequera, Spain. FAU - Bernal-Lopez, M Rosa AU - Bernal-Lopez MR AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain; Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. FAU - Garcia de Lucas, Maria D AU - Garcia de Lucas MD AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain. FAU - Gomez-Huelgas, Ricardo AU - Gomez-Huelgas R AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain; Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain. FAU - Perez-Belmonte, Luis M AU - Perez-Belmonte LM AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain; Departamento de Medicina y Dermatologia, Facultad de Medicina, Universidad de Malaga (UMA), Instituto de Investigacion Biomedica de Malaga (IBIMA), Malaga, Spain; Servicio de Medicina Interna, Hospital Helicopteros Sanitarios, Marbella, Spain; Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: luismiguelpb1984@gmail.com. LA - eng LA - spa PT - Case Reports PT - Letter DEP - 20240116 PL - Spain TA - Rev Esp Cardiol (Engl Ed) JT - Revista espanola de cardiologia (English ed.) JID - 101587954 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Heart Failure/drug therapy/physiopathology/complications MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Stroke Volume/physiology/drug effects MH - Male MH - Female MH - *Hypoglycemic Agents/therapeutic use/administration & dosage MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/therapeutic use MH - Aged MH - Treatment Outcome MH - Ventricular Function, Left/physiology/drug effects MH - Drug Administration Schedule MH - Middle Aged MH - Semaglutide EDAT- 2024/01/19 00:42 MHDA- 2024/06/30 00:42 CRDT- 2024/01/18 19:12 PHST- 2023/11/08 00:00 [received] PHST- 2023/12/19 00:00 [accepted] PHST- 2024/06/30 00:42 [medline] PHST- 2024/01/19 00:42 [pubmed] PHST- 2024/01/18 19:12 [entrez] AID - S1885-5857(24)00024-0 [pii] AID - 10.1016/j.rec.2023.12.008 [doi] PST - ppublish SO - Rev Esp Cardiol (Engl Ed). 2024 Jul;77(7):583-587. doi: 10.1016/j.rec.2023.12.008. Epub 2024 Jan 16. PMID- 38228454 OWN - NLM STAT- MEDLINE DCOM- 20240315 LR - 20260127 IS - 1768-3122 (Electronic) IS - 0248-8663 (Linking) VI - 45 IP - 3 DP - 2024 Mar TI - [Among adults with cardiovascular disease and BMI>/=27kg/m(2) but no diabetes, does semaglutide lower risk of cardiovascular mortality, myocardial infarction, or stroke when compared with placebo, and is it safe?]. PG - 178-179 LID - S0248-8663(24)00007-9 [pii] LID - 10.1016/j.revmed.2024.01.006 [doi] FAU - Lanthier, L AU - Lanthier L AD - Departement de medecine specialise, service de medecine interne generale, universite de Sherbrooke, Sherbrooke, QC, Canada. Electronic address: luc.lanthier@usherbrooke.ca. FAU - Langlois, M-F AU - Langlois MF AD - Departement de medecine specialise, service d'endocrinologie, universite de Sherbrooke, Sherbrooke, QC, Canada. FAU - Plourde, M-E AU - Plourde ME AD - Departement de medecine nucleaire et radiobiologie, service de radio-oncologie, universite de Sherbrooke, Sherbrooke, QC, Canada. FAU - Cauchon, M AU - Cauchon M AD - Departement de medecine familiale et de medecine d'urgence, universite Laval, Quebec, QC, Canada. LA - fre PT - Letter TT - Chez les adultes avec maladie cardiovasculaire et IMC>/=27kg/m(2), mais sans diabete, est-ce que le semaglutide diminue le risque de mortalite cardiovasculaire, d'infarctus du myocarde ou d'AVC comparativement au placebo tout en etant securitaire ? DEP - 20240116 PL - France TA - Rev Med Interne JT - La Revue de medecine interne JID - 8101383 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - *Cardiovascular Diseases MH - Body Mass Index MH - *Myocardial Infarction/epidemiology/drug therapy MH - *Stroke/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptides MH - Semaglutide EDAT- 2024/01/17 00:42 MHDA- 2024/03/15 06:44 CRDT- 2024/01/16 21:57 PHST- 2023/12/21 00:00 [received] PHST- 2024/01/01 00:00 [accepted] PHST- 2024/03/15 06:44 [medline] PHST- 2024/01/17 00:42 [pubmed] PHST- 2024/01/16 21:57 [entrez] AID - S0248-8663(24)00007-9 [pii] AID - 10.1016/j.revmed.2024.01.006 [doi] PST - ppublish SO - Rev Med Interne. 2024 Mar;45(3):178-179. doi: 10.1016/j.revmed.2024.01.006. Epub 2024 Jan 16. PMID- 38227645 OWN - NLM STAT- MEDLINE DCOM- 20240118 LR - 20261017 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 121 IP - 5 DP - 2024 Jan 30 TI - Surface-mediated spontaneous emulsification of the acylated peptide, semaglutide. PG - e2305770121 LID - 10.1073/pnas.2305770121 [doi] LID - e2305770121 AB - Acylated peptides composed of glucagon-like peptide-1 receptor agonists modified with a fatty acid side chain are an important class of therapeutics for type 2 diabetes and obesity but are susceptible to an unusual physical instability in the presence of hydrophobic surfaces, i.e., spontaneous emulsification, also known as ouzo formation in practice. In this work, light scattering, small-angle X-ray scattering, and circular dichroism measurements are used to characterize the physical properties of the semaglutide colloidal phase, including size distribution, shape, secondary structure, internal structure, and internal composition, as a function of solution physico-chemical conditions. The existence and size of the colloids formed are successfully predicted by a classical Rayleigh model, which identifies the parameters controlling their size and formation. Colloid formation is found to be catalyzed by hydrophobic surfaces, and formation rates are modeled as an autocatalytic reaction, enabling the formation of a master curve for various surfaces that elucidates the mechanism. Surfaces differ due to differences in surface wettability, which can be correlated with Hansen solubility parameters. This work provides insights into this unusual colloidal phenomenon and guides the peptide synthesis process and drug product formulation in the pharmaceutical industry. FAU - Li, Qi AU - Li Q AD - Department of Chemical and Biomolecular Engineering, Center for Neutron Science, University of Delaware, Newark, DE 19716. FAU - Tangry, Vasudev AU - Tangry V AD - Department of Chemical and Biomolecular Engineering, Center for Neutron Science, University of Delaware, Newark, DE 19716. FAU - Allen, David P AU - Allen DP AD - Eli Lilly and Company, Indianapolis, IN 46225. FAU - Seibert, Kevin D AU - Seibert KD AUID- ORCID: 0000-0003-0626-0033 AD - Eli Lilly and Company, Indianapolis, IN 46225. FAU - Qian, Ken K AU - Qian KK AUID- ORCID: 0000-0002-1942-1943 AD - Eli Lilly and Company, Indianapolis, IN 46225. FAU - Wagner, Norman J AU - Wagner NJ AUID- ORCID: 0000-0001-9565-619X AD - Department of Chemical and Biomolecular Engineering, Center for Neutron Science, University of Delaware, Newark, DE 19716. LA - eng GR - P41 RR008630/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240116 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Peptides) RN - 0 (Colloids) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides MH - Wettability MH - Peptides MH - Colloids/chemistry MH - Hypoglycemic Agents MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC10835113 OTO - NOTNLM OT - acylated peptides OT - kinetics OT - semaglutide OT - spontaneous emulsification OT - stability COIS- Competing interests statement:The authors declare no competing interest. EDAT- 2024/01/16 18:42 MHDA- 2024/01/18 06:42 PMCR- 2024/01/16 CRDT- 2024/01/16 13:53 PHST- 2024/01/18 06:42 [medline] PHST- 2024/01/16 18:42 [pubmed] PHST- 2024/01/16 13:53 [entrez] PHST- 2024/01/16 00:00 [pmc-release] AID - 202305770 [pii] AID - 10.1073/pnas.2305770121 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2024 Jan 30;121(5):e2305770121. doi: 10.1073/pnas.2305770121. Epub 2024 Jan 16. PMID- 38226456 OWN - NLM STAT- MEDLINE DCOM- 20240229 LR - 20240724 IS - 1897-9483 (Electronic) IS - 0032-3772 (Linking) VI - 134 IP - 2 DP - 2024 Feb 28 TI - Role of glucagon-like peptide-1 receptor agonists in the treatment of obesity, cardiovascular disease, and cerebrovascular disease. LID - 16658 [pii] LID - 10.20452/pamw.16658 [doi] AB - Worldwide prevalence of obesity is increasing dramatically, imposing a significant economic burden on our society. Treatment of obesity is challenging, potentially due to different disease phenotypes. Taking into consideration "obesities" rather than "obesity," and thus aiming to understand different pathophysiologic mechanisms of individual phenotypes, might help identify more tailored treatment strategies. Glucagon‑like peptide‑1 receptor agonists (GLP‑1RAs), for example, dulaglutide and semaglutide, are routinely prescribed for the treatment of type 2 diabetes mellitus (T2DM) in patients with obesity or those at a high cardiovascular (CV) risk. Indeed, despite having been developed for T2DM, GLP‑1RAs are being increasingly often recognized as antiobesity medications due to their weight loss effects. Furthermore, recent evidence has shown that the extent of CV prevention offered by these drugs goes beyond that associated with their weight loss and pleiotropic effects. For instance, they exert anti‑inflammatory effects on vessels, enhance atherosclerotic plaque stability, reduce local advanced glycation end product receptor expression, lower monocyte‑macrophage adhesion, and antagonize the effect of angiotensin II. In the heart, GLP‑1RAs ameliorate cardiomyocyte survival and myocardial contractility, reduce cardiac hypertrophy, and are one of few drugs that can reduce epicardial fat thickness. In this review, we summarize recent evidence concerning the effects of GLP‑1RAs on obesity / dysmetabolism and on cardio- / cerebrovascular health. We further highlight the possible role of GLP‑1RAs in the treatment of obesity‑related CV diseases by describing the principal molecular mechanisms reported in the current literature. FAU - Tirandi, Amedeo AU - Tirandi A AD - First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy FAU - Montecucco, Fabrizio AU - Montecucco F AD - First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, Genoa, Italy. fabrizio.montecucco@unige.it FAU - Carbone, Federico AU - Carbone F AD - First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy AD - IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, Genoa, Italy FAU - Liberale, Luca AU - Liberale L AD - First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy AD - IRCCS Ospedale Policlinico San Martino, Genoa - Italian Cardiovascular Network, Genoa, Italy LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20240109 PL - Poland TA - Pol Arch Intern Med JT - Polish archives of internal medicine JID - 101700960 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/metabolism MH - *Cardiovascular Diseases/drug therapy/prevention & control MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Obesity/complications/drug therapy MH - *Cerebrovascular Disorders/drug therapy MH - Weight Loss EDAT- 2024/01/16 06:42 MHDA- 2024/02/29 06:43 CRDT- 2024/01/16 05:16 PHST- 2024/02/29 06:43 [medline] PHST- 2024/01/16 06:42 [pubmed] PHST- 2024/01/16 05:16 [entrez] AID - 16658 [pii] AID - 10.20452/pamw.16658 [doi] PST - ppublish SO - Pol Arch Intern Med. 2024 Feb 28;134(2):16658. doi: 10.20452/pamw.16658. Epub 2024 Jan 9. PMID- 38224977 OWN - NLM STAT- MEDLINE DCOM- 20240117 LR - 20260127 IS - 1756-1833 (Electronic) IS - 0959-8138 (Linking) VI - 384 DP - 2024 Jan 15 TI - Semaglutide reduces the absolute risk of major cardiovascular events by 1.5. PG - q53 LID - 10.1136/bmj.q53 [doi] FAU - Phizackerley, David AU - Phizackerley D AD - Drug and Therapeutics Bulletin, London, UK. LA - eng PT - Letter DEP - 20240115 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Cardiovascular Diseases/prevention & control MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - Semaglutide COIS- Competing interests: None declared. EDAT- 2024/01/16 00:42 MHDA- 2024/01/17 06:42 CRDT- 2024/01/15 20:33 PHST- 2024/01/17 06:42 [medline] PHST- 2024/01/16 00:42 [pubmed] PHST- 2024/01/15 20:33 [entrez] AID - 10.1136/bmj.q53 [doi] PST - epublish SO - BMJ. 2024 Jan 15;384:q53. doi: 10.1136/bmj.q53. PMID- 38223524 OWN - NLM STAT- MEDLINE DCOM- 20240116 LR - 20260127 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2024 DP - 2024 TI - Usefulness of Once-Weekly GLP-1 Receptor Agonist Semaglutide on Glycemic Control in Subjects with Type 2 Diabetes Mellitus: Switching from the Same Class Dulaglutide in a Retrospective Observation Study. PG - 5880589 LID - 10.1155/2024/5880589 [doi] LID - 5880589 AB - Recently, the development of once-weekly incretin-based injections dulaglutide and semaglutide has drawn a great deal of attention. This study is aimed at comparing the efficacy of once-weekly GLP-1 receptor activator (GLP-1RA) dulaglutide and semaglutide on glycemic control and several metabolic parameters in patients with type 2 diabetes mellitus. We compared various clinical parameters between before and after switching from dulaglutide to semaglutide in "study 1" (pre-post comparison) and set the control group using propensity score matching method in "study 2." In "study 1," six months after the switching, HbA1c was significantly reduced from 8.2% to 7.6% and body mass index was also decreased from 30.4 kg/m(2) to 30.0 kg/m(2). Such effects were more pronounced in subjects whose glycemic control was poor. In "study 2," after 1 : 1 propensity score matching, glycemic control and body weight management were improved in the switching group compared with the dulaglutide continuation group. In this study including obese subjects with poor glycemic control, switching dulaglutide to semaglutide showed more beneficial effects on both glycemic and weight control irrespective of age, body weight, and diabetes duration. Therefore, we should bear in mind that it would be better to start using a relatively new once-weekly GLP-1RA semaglutide in clinical practice, especially in obese subjects with poor glycemic control with other GLP-1RAs. CI - Copyright (c) 2024 Tomohiko Kimura et al. FAU - Kimura, Tomohiko AU - Kimura T AUID- ORCID: 0000-0003-3986-9494 AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Kubo, Masato AU - Kubo M AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Takahashi, Kaio AU - Takahashi K AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Wamata, Ryo AU - Wamata R AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Iwamoto, Yuichiro AU - Iwamoto Y AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Iwamoto, Hideyuki AU - Iwamoto H AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Katakura, Yukino AU - Katakura Y AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Sanada, Junpei AU - Sanada J AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Fushimi, Yoshiro AU - Fushimi Y AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Shimoda, Masashi AU - Shimoda M AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Tatsumi, Fuminori AU - Tatsumi F AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Nakanishi, Shuhei AU - Nakanishi S AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Mune, Tomoatsu AU - Mune T AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Kaku, Kohei AU - Kaku K AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Kaneto, Hideaki AU - Kaneto H AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. LA - eng PT - Journal Article PT - Observational Study DEP - 20240104 PL - United States TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycemic Control MH - Body Weight MH - Obesity MH - Glucagon-Like Peptides/*analogs & derivatives MH - *Immunoglobulin Fc Fragments MH - *Recombinant Fusion Proteins MH - Semaglutide PMC - PMC10783983 COIS- T.K. has received honoraria for lectures from Sumitomo Pharma. K.K. has been an advisor to, received honoraria for lectures from, and received scholarship grants from Takeda, Kowa, Sanwa Kagaku Kenkyusho, MSD, Novo Nordisk Pharma, Boehringer Ingelheim, Novartis, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Taisho Pharma, AstraZeneca, Daiichi Sankyo, Sanofi, and Chugai. H.K. has received honoraria for lectures, received scholarship grants, and received research grants from Eli Lilly, Novo Nordisk Pharma, Boehringer Ingelheim, Taisho Pharma, Sanofi, Ono Pharma, Sumitomo Pharma, Takeda Pharma, Mitsubishi Tanabe Pharma, Kissei Pharma, Daiichi Sankyo, MSD, Astellas, AstraZeneca, Kowa, Novartis, and Abbott. Other authors declare no competing interests. EDAT- 2024/01/15 06:42 MHDA- 2024/01/16 06:42 PMCR- 2024/01/04 CRDT- 2024/01/15 04:50 PHST- 2022/08/18 00:00 [received] PHST- 2023/12/16 00:00 [revised] PHST- 2023/12/19 00:00 [accepted] PHST- 2024/01/16 06:42 [medline] PHST- 2024/01/15 06:42 [pubmed] PHST- 2024/01/15 04:50 [entrez] PHST- 2024/01/04 00:00 [pmc-release] AID - 10.1155/2024/5880589 [doi] PST - epublish SO - J Diabetes Res. 2024 Jan 4;2024:5880589. doi: 10.1155/2024/5880589. eCollection 2024. PMID- 38220187 OWN - NLM STAT- MEDLINE DCOM- 20240814 LR - 20260127 IS - 1349-7235 (Electronic) IS - 0918-2918 (Print) IS - 0918-2918 (Linking) VI - 63 IP - 16 DP - 2024 Aug 15 TI - Hot Water Eliminates the Bitter Taste of Oral Semaglutide: A Report of Four Cases. PG - 2297-2300 LID - 10.2169/internalmedicine.2608-23 [doi] AB - Semaglutide is a well-designed drug with a special coating that allows for oral administration to patients with type 2 diabetes mellitus. However, patients taking oral semaglutide complain of its bitter taste. We therefore considered suggesting that patients take oral semaglutide with hot water. When the hot water temperature was increased to above 46.0 degrees C but below 52.0 degrees C, no bitter taste was perceived, with the daily mean interstitial glucose level remaining at the target range. Taking oral semaglutide with hot water helps reduce its bitter taste. FAU - Okada, Shuichi AU - Okada S AD - Diabetes Center, Hidaka Hospital, Japan. FAU - Okada, Junichi AU - Okada J AD - Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, USA. FAU - Okada, Kazuya AU - Okada K AD - Department of Orthopedic Surgery, Tone Chuo Hospital, Japan. FAU - Yamada, Eijiro AU - Yamada E AD - Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Japan. FAU - Saito, Tsugumichi AU - Saito T AD - Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Japan. FAU - Kikkawa, Koji AU - Kikkawa K AD - Diabetes Center, Hidaka Hospital, Japan. FAU - Ando, Tetsurou AU - Ando T AD - Diabetes Center, Hidaka Hospital, Japan. FAU - Ohshima, Kihachi AU - Ohshima K AD - Diabetes Center, Hidaka Hospital, Japan. LA - eng PT - Case Reports PT - Journal Article DEP - 20240113 PL - Japan TA - Intern Med JT - Internal medicine (Tokyo, Japan) JID - 9204241 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 059QF0KO0R (Water) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage MH - *Hot Temperature/adverse effects MH - Hypoglycemic Agents/administration & dosage MH - Taste/drug effects MH - Water MH - Semaglutide PMC - PMC11414362 OTO - NOTNLM OT - bitterness OT - hot water OT - oral semaglutide OT - type 2 diabetes mellitus COIS- The authors state that they have no Conflict of Interest (COI). EDAT- 2024/01/15 00:42 MHDA- 2024/08/15 00:42 PMCR- 2024/08/15 CRDT- 2024/01/14 20:23 PHST- 2024/08/15 00:42 [medline] PHST- 2024/01/15 00:42 [pubmed] PHST- 2024/01/14 20:23 [entrez] PHST- 2024/08/15 00:00 [pmc-release] AID - 10.2169/internalmedicine.2608-23 [doi] PST - ppublish SO - Intern Med. 2024 Aug 15;63(16):2297-2300. doi: 10.2169/internalmedicine.2608-23. Epub 2024 Jan 13. PMID- 38219335 OWN - NLM STAT- MEDLINE DCOM- 20240219 LR - 20260127 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 38 IP - 2 DP - 2024 Feb TI - The effects of semaglutide, empagliflozin and their combination on the kidney sodium signal from magnetic resonance imaging: A prespecified, secondary analysis from a randomized, clinical trial. PG - 108673 LID - S1056-8727(23)00271-4 [pii] LID - 10.1016/j.jdiacomp.2023.108673 [doi] AB - AIMS: To evaluate the effect of treatment with semaglutide and empagliflozin on the cortico-medullary sodium gradient (MCR; medulla/cortex ratio), urine sodium/creatinine ratio (UNACR), and estimated plasma volume (ePV) and to compare the MCR between persons with and without type 2 diabetes. METHODS: Using the (23)Na magnetic resonance imaging ((23)Na-MRI) technique, we investigated the effects of 32 weeks of treatment with semaglutide, empagliflozin or their combination on MCR in 65 participants with type 2 diabetes and high risk of cardiovascular disease. The participants were recruited from a randomized, controlled interventional trial and further characterized by UNACR and ePV. In addition, in a cross-sectional design, we compared MCR by (23)Na-MRI in 12 persons with type 2 diabetes and 17 matched controls. Data from the interventional trial were analyzed using a single, multivariate linear mixed model strategy for repeated measurements. Data from the cross-sectional study were analyzed by fitting a linear regression model adjusted for age and sex. RESULTS: Compared to placebo, semaglutide, but not empagliflozin, significantly decreased the MCR (-9 %, 95%CI (-18, -0.06)%, p = 0.035 and -0.05 %, 95%CI(-0.15, 0.05)%, p = 0.319, respectively). The UNACR decreased in the semaglutide group(-35 %, 95 % CI(-52, -14) %, p = 0.003) but not in the empagliflozin group (7 %, 95 % CI(-21, 44)%, p = 0.657), whereas the ePV decreased in the combination group. The MCR was not different between persons with and without type 2 diabetes. CONCLUSION: (23)Na magnetic resonance imaging can identify drug induced changes in the MCR in persons with type 2 diabetes, and 32 weeks of semaglutide decreases the MCR in such persons. There is no difference in the MCR between persons with and without type 2 diabetes. TRIAL NUMBER AND REGISTRY: EUDRACT 2019-000781-38, clinicaltrialsregister.eu. CI - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Gullaksen, Soren AU - Gullaksen S AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark; Department of Internal Medicine & Endocrinology, Aarhus University Hospital, 8200 Aarhus N, Denmark; Department of Medicine, Regional Hospital Horsens, 8700 Horsens, Denmark. Electronic address: soegul@clin.au.dk. FAU - Vernstrom, Liv AU - Vernstrom L AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark; Department of Internal Medicine & Endocrinology, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Sorensen, Steffen S AU - Sorensen SS AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark; Department of Internal Medicine & Endocrinology, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Ringgaard, Steffen AU - Ringgaard S AD - The MR Research Center, Aarhus University, 8200 Aarhus N, Denmark. FAU - Laustsen, Christoffer AU - Laustsen C AD - The MR Research Center, Aarhus University, 8200 Aarhus N, Denmark. FAU - Birn, Henrik AU - Birn H AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark; Department of Renal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark. FAU - Funck, Kristian L AU - Funck KL AD - Department of Internal Medicine & Endocrinology, Aarhus University Hospital, 8200 Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Poulsen, Per L AU - Poulsen PL AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Laugesen, Esben AU - Laugesen E AD - Diagnostic Centre, Silkeborg Regional Hospital, 8600 Silkeborg, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20240105 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Hypoglycemic Agents) RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Cross-Sectional Studies MH - Kidney MH - Magnetic Resonance Imaging MH - Magnetic Resonance Spectroscopy MH - Hypoglycemic Agents/therapeutic use MH - *Benzhydryl Compounds MH - *Glucagon-Like Peptides MH - *Glucosides MH - Semaglutide OTO - NOTNLM OT - Diabetic kidney disease OT - Glucagon-like peptide 1 receptor agonist OT - Magnetic resonance imaging OT - Sodium-glucose transporter 2 inhibitors OT - Type 2 diabetes mellitus COIS- Declaration of competing interest The authors declare no conflicts of interests. EDAT- 2024/01/15 00:42 MHDA- 2024/02/19 06:42 CRDT- 2024/01/14 18:05 PHST- 2023/11/08 00:00 [received] PHST- 2023/12/17 00:00 [revised] PHST- 2023/12/24 00:00 [accepted] PHST- 2024/02/19 06:42 [medline] PHST- 2024/01/15 00:42 [pubmed] PHST- 2024/01/14 18:05 [entrez] AID - S1056-8727(23)00271-4 [pii] AID - 10.1016/j.jdiacomp.2023.108673 [doi] PST - ppublish SO - J Diabetes Complications. 2024 Feb;38(2):108673. doi: 10.1016/j.jdiacomp.2023.108673. Epub 2024 Jan 5. PMID- 38215986 OWN - NLM STAT- MEDLINE DCOM- 20240304 LR - 20260127 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 366 DP - 2024 Feb TI - Nanoparticles targeting the intestinal Fc receptor enhance intestinal cellular trafficking of semaglutide. PG - 621-636 LID - S0168-3659(24)00019-1 [pii] LID - 10.1016/j.jconrel.2024.01.015 [doi] AB - Semaglutide is the first oral glucagon-like peptide-1 (GLP-1) analog commercially available for the treatment of type 2 diabetes. In this work, semaglutide was incorporated into poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles (NPs) to improve its delivery across the intestinal barrier. The nanocarriers were surface-decorated with either a peptide or an affibody that target the human neonatal Fc receptor (hFcRn), located on the luminal cell surface of the enterocytes. Both ligands were successfully conjugated with the PLGA-PEG via maleimide-thiol chemistry and thereafter, the functionalized polymers were used to produce semaglutide-loaded NPs. Monodisperse NPs with an average size of 170 nm, neutral surface charge and 3% of semaglutide loading were obtained. Both FcRn-targeted NPs exhibited improved interaction and association with Caco-2 cells (cells that endogenously express the hFcRn), compared to non-targeted NPs. Additionally, the uptake of FcRn-targeted NPs was also observed to occur in human intestinal organoids (HIOs) expressing hFcRn through microinjection into the lumen of HIOs, resulting in potential increase of semaglutide permeability for both ligand-functionalized nanocarriers. Herein, our study demonstrates valuable data and insights that the FcRn-targeted NPs has the capacity to promote intestinal absorption of therapeutic peptides. CI - Copyright (c) 2024 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Pinto, Soraia AU - Pinto S AD - Instituto de Investigacao e Inovacao em Saude (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto de Ciencias Biomedicas Abel Salazar (ICBAS), Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal. FAU - Hosseini, Mahya AU - Hosseini M AD - Department of Biomedical Sciences of Cell and Systems, Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9713, AV, Groningen, the Netherlands. FAU - Buckley, Stephen T AU - Buckley ST AD - Global Research Technologies, Novo Nordisk, Novo Nordisk Park 1, 2760 Malov, Denmark. FAU - Yin, Wen AU - Yin W AD - Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Roslagstullsbacken 21, 114 17 Stockholm, Sweden. FAU - Garousi, Javad AU - Garousi J AD - Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Roslagstullsbacken 21, 114 17 Stockholm, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden. FAU - Graslund, Torbjorn AU - Graslund T AD - Department of Protein Science, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Roslagstullsbacken 21, 114 17 Stockholm, Sweden. FAU - van Ijzendoorn, Sven AU - van Ijzendoorn S AD - Department of Biomedical Sciences of Cell and Systems, Section Molecular Cell Biology, University Medical Center Groningen, University of Groningen, 9713, AV, Groningen, the Netherlands. FAU - Santos, Helder A AU - Santos HA AD - Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5E, Helsinki FI-00014, Finland; W.J. Kolff Institute for Biomedical Engineering and Materials Science, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands; Department of Biomedical Engineering, University Medical Center Groningen, University of Groningen, 9713 AV Groningen, the Netherlands. Electronic address: h.a.santos@umcg.nl. FAU - Sarmento, Bruno AU - Sarmento B AD - Instituto de Investigacao e Inovacao em Saude (i3S), Universidade do Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal; Instituto Universitario de Ciencias da Saude (IUCS-CESPU), Rua Central de Gandra 1317, 4585-116 Gandra, Portugal. Electronic address: bruno.sarmento@i3s.up.pt. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240117 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (Peptides) RN - 0 (Receptors, Fc) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Lactates) RN - 3WJQ0SDW1A (Polyethylene Glycols) RN - 53AXN4NNHX (Semaglutide) RN - 0 (poly(lactic acid-ethylene glycol)) SB - IM MH - Infant, Newborn MH - Humans MH - Caco-2 Cells MH - *Diabetes Mellitus, Type 2 MH - Peptides MH - *Nanoparticles MH - Receptors, Fc MH - *Glucagon-Like Peptides MH - *Lactates MH - *Polyethylene Glycols MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 analog OT - Human intestinal organoids OT - Neonatal Fc receptor-targeted ligands OT - Oral peptide delivery OT - Polymeric nanoparticles OT - Type 2 diabetes COIS- Declaration of competing interest Authors declare no competing of interests. EDAT- 2024/01/13 00:42 MHDA- 2024/03/04 06:49 CRDT- 2024/01/12 19:31 PHST- 2023/11/09 00:00 [received] PHST- 2023/12/29 00:00 [revised] PHST- 2024/01/09 00:00 [accepted] PHST- 2024/03/04 06:49 [medline] PHST- 2024/01/13 00:42 [pubmed] PHST- 2024/01/12 19:31 [entrez] AID - S0168-3659(24)00019-1 [pii] AID - 10.1016/j.jconrel.2024.01.015 [doi] PST - ppublish SO - J Control Release. 2024 Feb;366:621-636. doi: 10.1016/j.jconrel.2024.01.015. Epub 2024 Jan 17. PMID- 38206146 OWN - NLM STAT- MEDLINE DCOM- 20240112 LR - 20260127 IS - 1545-9616 (Print) IS - 1545-9616 (Linking) VI - 23 IP - 1 DP - 2024 Jan 1 TI - Natural Weight Loss or "Ozempic Face": Demystifying A Social Media Phenomenon. PG - 1367-1368 LID - 10.36849/JDD.7613 [doi] AB - New patients turning to semaglutide (Ozempic® and Wegovy®), a glucagon-like-peptide 1 (GLP-1) agonist, for weight loss, have captivated social media platforms.  Wegovy® carries a United States (US) Food and Drug Administration (FDA) approval for chronic weight management in patients who have a body mass index (BMI) 27 kg/m2 or greater and at least one weight-related condition (eg, hypertension, type 2 diabetes, cholesterol) or in patients with a 30 kg/m2 or greater BMI. Although other semaglutide formulations are not FDA approved for weight loss, the term "Ozempic face" has consumed the media with the medication's rising popularity. This term is a new purported side effect, used to describe the rapid facial weight loss leaving a distorted facial appearance. This challenges the healthcare team to discern whether a new adverse effect is a novel or a natural consequence of rapid weight loss. Dermatologists are well positioned to counsel patients receiving or discontinuing GLP-1 agonists and recommend appropriate countermeasures, as appropriate.  J Drugs Dermatol. 2024;23(1):1367-1368.      doi:10.36849/JDD.7613. FAU - Carboni, Alexa AU - Carboni A FAU - Woessner, Sabrina AU - Woessner S FAU - Martini, Olnita AU - Martini O FAU - Marroquin, Nathaniel A AU - Marroquin NA FAU - Waller, Jacquelyn AU - Waller J LA - eng PT - Journal Article PL - United States TA - J Drugs Dermatol JT - Journal of drugs in dermatology : JDD JID - 101160020 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - United States MH - Humans MH - *Diabetes Mellitus, Type 2 MH - *Social Media MH - Glucagon-Like Peptide 1 MH - Weight Loss MH - *Glucagon-Like Peptides MH - Semaglutide EDAT- 2024/01/11 12:42 MHDA- 2024/01/12 06:43 CRDT- 2024/01/11 09:56 PHST- 2024/01/12 06:43 [medline] PHST- 2024/01/11 12:42 [pubmed] PHST- 2024/01/11 09:56 [entrez] AID - S1545961624P1367X [pii] AID - 10.36849/JDD.7613 [doi] PST - ppublish SO - J Drugs Dermatol. 2024 Jan 1;23(1):1367-1368. doi: 10.36849/JDD.7613. PMID- 38189936 OWN - NLM STAT- MEDLINE DCOM- 20240206 LR - 20261010 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 67 IP - 3 DP - 2024 Mar TI - Glucagon-like peptide-1 receptor agonists reverse nerve morphological abnormalities in diabetic peripheral neuropathy. PG - 561-566 LID - 10.1007/s00125-023-06072-6 [doi] AB - AIMS/HYPOTHESIS: Diabetic peripheral neuropathy (DPN) is a highly prevalent cause of physical disability. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are used to treat type 2 diabetes and animal studies have shown that glucagon-like peptide-1 (GLP-1) receptors are present in the central and peripheral nervous systems. This study investigated whether GLP-1 RAs can improve nerve structure. METHODS: Nerve structure was assessed using peripheral nerve ultrasonography and measurement of tibial nerve cross-sectional area, in conjunction with validated neuropathy symptom scores and nerve conduction studies. A total of 22 consecutively recruited participants with type 2 diabetes were assessed before and 1 month after commencing GLP-1 RA therapy (semaglutide or dulaglutide). RESULTS: There was a pathological increase in nerve size before treatment in 81.8% of the cohort (n=22). At 1 month of follow-up, there was an improvement in nerve size in 86% of participants (p<0.05), with 32% returning to normal nerve morphology. A 3 month follow-up study (n=14) demonstrated further improvement in nerve size in 93% of participants, accompanied by reduced severity of neuropathy (p<0.05) and improved sural sensory nerve conduction amplitude (p<0.05). CONCLUSIONS/INTERPRETATION: This study demonstrates the efficacy of GLP-1 RAs in improving neuropathy outcomes, evidenced by improvements in mainly structural and morphological measures and supported by electrophysiological and clinical endpoints. Future studies, incorporating quantitative sensory testing and measurement of intraepidermal nerve fibre density, are needed to investigate the benefits for small fibre function and structure. CI - (c) 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Dhanapalaratnam, Roshan AU - Dhanapalaratnam R AD - School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia. AD - Department of Neurology, Prince of Wales Hospital, Sydney, NSW, Australia. FAU - Issar, Tushar AU - Issar T AD - School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia. FAU - Lee, Alexandra T K AU - Lee ATK AD - Department of Endocrinology, Prince of Wales Hospital, Sydney, NSW, Australia. FAU - Poynten, Ann M AU - Poynten AM AD - Department of Endocrinology, Prince of Wales Hospital, Sydney, NSW, Australia. FAU - Milner, Kerry-Lee AU - Milner KL AD - Department of Endocrinology, Prince of Wales Hospital, Sydney, NSW, Australia. FAU - Kwai, Natalie C G AU - Kwai NCG AD - School of Medical, Indigenous and Health Sciences, University of Wollongong, Wollongong, NSW, Australia. FAU - Krishnan, Arun V AU - Krishnan AV AD - School of Clinical Medicine, UNSW Sydney, Sydney, NSW, Australia. arun.krishnan@unsw.edu.au. AD - Department of Neurology, Prince of Wales Hospital, Sydney, NSW, Australia. arun.krishnan@unsw.edu.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240108 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) SB - IM MH - Animals MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Diabetic Neuropathies/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Follow-Up Studies MH - Glucagon-Like Peptide 1 MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - Diabetes OT - Diabetic peripheral neuropathy OT - Dulaglutide OT - Glucagon-like peptide-1 receptor agonist OT - Nerve ultrasonography OT - Peripheral nerve OT - Peripheral neuropathy OT - Semaglutide OT - Type 2 diabetes OT - Ultrasound EDAT- 2024/01/08 12:43 MHDA- 2024/02/06 06:42 CRDT- 2024/01/08 11:14 PHST- 2023/09/01 00:00 [received] PHST- 2023/11/10 00:00 [accepted] PHST- 2024/02/06 06:42 [medline] PHST- 2024/01/08 12:43 [pubmed] PHST- 2024/01/08 11:14 [entrez] AID - 10.1007/s00125-023-06072-6 [pii] AID - 10.1007/s00125-023-06072-6 [doi] PST - ppublish SO - Diabetologia. 2024 Mar;67(3):561-566. doi: 10.1007/s00125-023-06072-6. Epub 2024 Jan 8. PMID- 38186863 OWN - NLM STAT- MEDLINE DCOM- 20240109 LR - 20240109 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 29 IP - 48 DP - 2023 Dec 28 TI - Potential therapeutic targets for nonalcoholic fatty liver disease: Glucagon-like peptide 1. PG - 6235-6238 LID - 10.3748/wjg.v29.i48.6235 [doi] AB - Nonalcoholic fatty liver disease (NAFLD) is the most rapidly growing contributor to liver mortality and morbidity. Hepatocellular injury in nonalcoholic steatohepatitis (NASH) is caused by an increase in metabolic substrates (glucose, fructose, and fatty acids), leading fatty acids to participate in pathways that cause cellular injury and a poor response to injury. The pathogenesis of this disease is largely associated with obesity, type 2 diabetes, and increasing age. To date, there are no Food and Drug Administration-approved treatments for NAFLD/NASH or its associated fibrosis. Since one of the pathogenic drivers of NASH is insulin re-sistance, therapies approved for the treatment of type 2 diabetes are being evaluated in patients with NASH. Currently, the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is a safe, well-studied therapeutic for NAFLD/ NASH patients. Existing research demonstrates that semaglutide can increase the resolution of NASH but not improve fibrosis. However, improving the fibrosis of NAFLD is the only way to improve the long-term prognosis of NAFLD. Given the complex pathophysiology of NASH, combining therapies with complementary mechanisms may be beneficial. Researchers have conducted trials of semaglutide in combination with antifibrotic drugs. However, the results have not fully met expectations, and it cannot be ruled out that the reason is the short trial time. We should continue to pay increasing attention to GLP-1RAs. CI - (c)The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved. FAU - Yin, Yue-Hua AU - Yin YH AD - Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. FAU - Sang, Li-Xuan AU - Sang LX AD - Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China. FAU - Chang, Bing AU - Chang B AD - Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. cb000216@163.com. LA - eng PT - Journal Article PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Fatty Acids) SB - IM MH - Humans MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Glucagon-Like Peptide 1 MH - *Diabetes Mellitus, Type 2/drug therapy MH - Fatty Acids MH - Fibrosis PMC - PMC10768396 OTO - NOTNLM OT - Antidiabetic drugs OT - Glucagon-like peptide 1 OT - Nonalcoholic fatty liver disease OT - Nonalcoholic steatohepatitis OT - Semaglutide COIS- Conflict-of-interest statement: The authors declare that they have no conflict of interest. EDAT- 2024/01/08 06:42 MHDA- 2024/01/09 06:42 PMCR- 2023/12/28 CRDT- 2024/01/08 04:31 PHST- 2023/10/07 00:00 [received] PHST- 2023/11/08 00:00 [revised] PHST- 2023/12/06 00:00 [accepted] PHST- 2024/01/09 06:42 [medline] PHST- 2024/01/08 06:42 [pubmed] PHST- 2024/01/08 04:31 [entrez] PHST- 2023/12/28 00:00 [pmc-release] AID - 10.3748/wjg.v29.i48.6235 [doi] PST - ppublish SO - World J Gastroenterol. 2023 Dec 28;29(48):6235-6238. doi: 10.3748/wjg.v29.i48.6235. PMID- 38184193 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20260526 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 173 DP - 2024 Mar TI - Recent advances in peptide-based therapies for obesity and type 2 diabetes. PG - 171149 LID - S0196-9781(24)00002-0 [pii] LID - 10.1016/j.peptides.2024.171149 [doi] AB - Options for the treatment of type 2 diabetes mellitus (T2DM) and obesity have recently been expanded by the results of several large clinical trials with incretin-based peptide therapies. Most of these studies have been conducted with the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, which is available as a once weekly subcutaneous injection and once daily tablet, and the once weekly injected dual agonist tirzepatide, which interacts with receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). In individuals with T2DM these therapies have achieved reductions of glycated haemoglobin (HbA1c) by > 2% and lowered body weight by > 10%. In some studies, these agents tested in non-diabetic, obese individuals at much higher doses have lowered body weight by > 15%. Emerging evidence suggests these agents can also offer cardio-protective and potentially reno-protective effects. Other incretin-based peptide therapies in early clinical development, notably a triple GLP-1/GIP/glucagon receptor agonist (retatrutide) and a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), have shown strong efficacy. Although incretin therapies can incur adverse gastrointestinal effects these are for most patients mild-to-moderate and transient but result in cessation of treatment in some cases. Thus, the efficacy of new incretin-based peptide therapies is enhancing the opportunity to control body weight and blood glucose and improve the treatment of T2DM and obesity. CI - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Bailey, Clifford J AU - Bailey CJ AD - Life and Health Sciences, Aston University, Birmingham B4 7ET, UK. FAU - Flatt, Peter R AU - Flatt PR AD - Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK. FAU - Conlon, J Michael AU - Conlon JM AD - Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, UK. Electronic address: jmconlon1@gmail.com. LA - eng PT - Journal Article DEP - 20240105 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Incretins) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Incretins/therapeutic use MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Obesity MH - Glucagon-Like Peptide 1/therapeutic use MH - Body Weight MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cagrilintide OT - Incretin OT - Multi-agonist OT - Retatrutide OT - Semaglutide OT - Tirzepatide COIS- Declaration of Competing Interest CJB has served on steering committees for clinical trials and advisory boards for several pharmaceutical companies. PRF and JMC are named on patents held by Ulster University for peptide therapeutics. EDAT- 2024/01/07 06:44 MHDA- 2024/02/13 06:45 CRDT- 2024/01/06 19:16 PHST- 2023/12/04 00:00 [received] PHST- 2023/12/31 00:00 [revised] PHST- 2024/01/02 00:00 [accepted] PHST- 2024/02/13 06:45 [medline] PHST- 2024/01/07 06:44 [pubmed] PHST- 2024/01/06 19:16 [entrez] AID - S0196-9781(24)00002-0 [pii] AID - 10.1016/j.peptides.2024.171149 [doi] PST - ppublish SO - Peptides. 2024 Mar;173:171149. doi: 10.1016/j.peptides.2024.171149. Epub 2024 Jan 5. PMID- 38182782 OWN - NLM STAT- MEDLINE DCOM- 20240124 LR - 20260127 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 30 IP - 1 DP - 2024 Jan TI - Association of semaglutide with risk of suicidal ideation in a real-world cohort. PG - 168-176 LID - 10.1038/s41591-023-02672-2 [doi] AB - Concerns over reports of suicidal ideation associated with semaglutide treatment, a glucagon-like peptide 1 receptor (GLP1R) agonist medication for type 2 diabetes (T2DM) and obesity, has led to investigations by European regulatory agencies. In this retrospective cohort study of electronic health records from the TriNetX Analytics Network, we aimed to assess the associations of semaglutide with suicidal ideation compared to non-GLP1R agonist anti-obesity or anti-diabetes medications. The hazard ratios (HRs) and 95% confidence intervals (CIs) of incident and recurrent suicidal ideation were calculated for the 6-month follow-up by comparing propensity score-matched patient groups. The study population included 240,618 patients with overweight or obesity who were prescribed semaglutide or non-GLP1R agonist anti-obesity medications, with the findings replicated in 1,589,855 patients with T2DM. In patients with overweight or obesity (mean age 50.1 years, 72.6% female), semaglutide compared with non-GLP1R agonist anti-obesity medications was associated with lower risk for incident (HR = 0.27, 95% CI = 0.200.32-0.600.36) and recurrent (HR = 0.44, 95% CI = 0.32-0.60) suicidal ideation, consistent across sex, age and ethnicity stratification. Similar findings were replicated in patients with T2DM (mean age 57.5 years, 49.2% female). Our findings do not support higher risks of suicidal ideation with semaglutide compared with non-GLP1R agonist anti-obesity or anti-diabetes medications. CI - (c) 2024. The Author(s), under exclusive licence to Springer Nature America, Inc. FAU - Wang, William AU - Wang W AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Volkow, Nora D AU - Volkow ND AUID- ORCID: 0000-0001-6668-0908 AD - National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA. nvolkow@nida.nih.gov. FAU - Berger, Nathan A AU - Berger NA AUID- ORCID: 0000-0001-7086-9885 AD - Center for Science, Health, and Society, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Davis, Pamela B AU - Davis PB AUID- ORCID: 0000-0002-7113-5338 AD - Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, OH, USA. FAU - Kaelber, David C AU - Kaelber DC AUID- ORCID: 0000-0001-7855-9515 AD - Center for Clinical Informatics Research and Education, The MetroHealth System, Cleveland, OH, USA. FAU - Xu, Rong AU - Xu R AUID- ORCID: 0000-0003-3127-4795 AD - Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, OH, USA. rxx@case.edu. LA - eng GR - R01 AG057557/AG/NIA NIH HHS/United States GR - R01 AA029831/AA/NIAAA NIH HHS/United States GR - DP2 HD084068/HD/NICHD NIH HHS/United States GR - R56 AG062272/AG/NIA NIH HHS/United States GR - RF1 AG076649/AG/NIA NIH HHS/United States GR - R25 CA221718/CA/NCI NIH HHS/United States GR - P30 CA043703/CA/NCI NIH HHS/United States GR - R01 AG061388/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20240105 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Middle Aged MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology/complications MH - Suicidal Ideation MH - Retrospective Studies MH - Overweight MH - Obesity/complications/drug therapy/epidemiology MH - *Anti-Obesity Agents/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptides MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC11034947 MID - NIHMS1984698 COIS- Competing interests The authors declare no competing interests. EDAT- 2024/01/06 10:42 MHDA- 2024/01/24 06:43 PMCR- 2024/04/22 CRDT- 2024/01/05 23:33 PHST- 2023/07/31 00:00 [received] PHST- 2023/10/30 00:00 [accepted] PHST- 2024/01/24 06:43 [medline] PHST- 2024/01/06 10:42 [pubmed] PHST- 2024/01/05 23:33 [entrez] PHST- 2024/04/22 00:00 [pmc-release] AID - 10.1038/s41591-023-02672-2 [pii] AID - 10.1038/s41591-023-02672-2 [doi] PST - ppublish SO - Nat Med. 2024 Jan;30(1):168-176. doi: 10.1038/s41591-023-02672-2. Epub 2024 Jan 5. PMID- 38181103 OWN - NLM STAT- MEDLINE DCOM- 20240130 LR - 20260127 IS - 2329-9185 (Electronic) IS - 2329-9185 (Linking) VI - 12 IP - 1 DP - 2024 Jan 1 TI - Glucagon-like Peptide-1 Agonists: What the Orthopaedic Surgeon Needs to Know. LID - 10.2106/JBJS.RVW.23.00167 [doi] AB - >> Orthopaedic surgeons are increasingly likely to encounter patients with obesity and/or type 2 diabetes taking glucagon-like peptide-1 (GLP-1) agonists for weight loss.>> GLP-1 agonists are an effective treatment for weight loss with semaglutide and tirzepatide being the most effective agents. Randomized controlled trials using these agents have reported weight loss up to 21 kg (46 lb).>> The use of GLP-1 agonists preoperatively can improve glycemic control, which can potentially reduce the risk of postoperative complications. However, multiple cases of intraoperative aspiration/regurgitation have been reported, potentially related to the effect of GLP-1 agonists on gastric emptying.>> While efficacious, GLP-1 agonists may not produce sufficient weight loss to achieve body mass index cutoffs for total joint arthroplasty depending on individual patient factors, including starting bodyweight. Multifactorial approaches to weight loss with focus on lifestyle modification in addition to GLP-1 agonists should be considered in such patients.>> Although GLP-1 agonists are efficacious agents for weight loss, they may not be accessible or affordable for all patients. Each patient's unique circumstances should be considered when creating an ideal weight loss plan during optimization efforts. CI - Copyright (c) 2024 by The Journal of Bone and Joint Surgery, Incorporated. FAU - Chan, Peter Y W AU - Chan PYW AUID- ORCID: 0000-0002-3498-6301 AD - Department of Orthopaedics, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Mika, Aleksander P AU - Mika AP AUID- ORCID: 0000-0002-5260-4506 FAU - Martin, J Ryan AU - Martin JR AUID- ORCID: 0000-0002-4125-2154 FAU - Wilson, Jacob M AU - Wilson JM AUID- ORCID: 0000-0002-5044-7084 LA - eng PT - Journal Article DEP - 20240105 PL - United States TA - JBJS Rev JT - JBJS reviews JID - 101674872 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Arthroplasty MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Orthopedic Surgeons MH - Weight Loss MH - *Glucagon-Like Peptide-1 Receptor Agonists/therapeutic use MH - Semaglutide COIS- Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B39). EDAT- 2024/01/05 18:41 MHDA- 2024/01/08 06:42 CRDT- 2024/01/05 14:13 PHST- 2024/01/08 06:42 [medline] PHST- 2024/01/05 18:41 [pubmed] PHST- 2024/01/05 14:13 [entrez] AID - 01874474-202401000-00003 [pii] AID - 10.2106/JBJS.RVW.23.00167 [doi] PST - epublish SO - JBJS Rev. 2024 Jan 5;12(1). doi: 10.2106/JBJS.RVW.23.00167. eCollection 2024 Jan 1. PMID- 38177805 OWN - NLM STAT- MEDLINE DCOM- 20240207 LR - 20260127 IS - 2522-5812 (Electronic) IS - 2522-5812 (Linking) VI - 6 IP - 1 DP - 2024 Jan TI - Randomized open-label trial of semaglutide and dapagliflozin in patients with type 2 diabetes of different pathophysiology. PG - 50-60 LID - 10.1038/s42255-023-00943-3 [doi] AB - The limited understanding of the heterogeneity in the treatment response to antidiabetic drugs contributes to metabolic deterioration and cardiovascular complications(1,2), stressing the need for more personalized treatment(1). Although recent attempts have been made to classify diabetes into subgroups, the utility of such stratification in predicting treatment response is unknown(3). We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD). Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium-glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label). The primary endpoint was the change in glycated haemoglobin (HbA1c). Semaglutide induced a larger reduction in HbA1c levels than dapagliflozin (mean difference, 8.2 mmol mol(-1); 95% confidence interval, -10.0 to -6.3 mmol mol(-1)), with a pronounced effect in those with SIDD. No difference in adverse events was observed between participants with SIDD and those with SIRD. Analysis of secondary endpoints showed greater reductions in fasting and postprandial glucose concentrations in response to semaglutide in participants with SIDD than in those with SIRD and a more pronounced effect on postprandial glucose by dapagliflozin in participants with SIDD than in those with SIRD. However, no significant interaction was found between drug assignment and the SIDD or SIRD subgroup. In contrast, continuous measures of body mass index, blood pressure, insulin secretion and insulin resistance were useful in identifying those likely to have the largest improvements in glycaemic control and cardiovascular risk factors by adding semaglutide or dapagliflozin. Thus, systematic evaluation of continuous pathophysiological variables can guide the prediction of the treatment response to these drugs and provide more information than stratified subgroups ( NCT04451837 ). CI - (c) 2023. The Author(s). FAU - Dwibedi, Chinmay AU - Dwibedi C AUID- ORCID: 0000-0001-6416-4440 AD - Department of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. AD - Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. FAU - Ekstrom, Ola AU - Ekstrom O AD - Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, Malmo, Sweden. FAU - Brandt, Jasmine AU - Brandt J AD - Department of Clinical Chemistry and Pharmacology, Skane University Hospital, Lund, Sweden. AD - Clinical Studies Sweden, Forum South, Skane University Hospital, Lund, Sweden. FAU - Adiels, Martin AU - Adiels M AD - Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. FAU - Franzen, Stefan AU - Franzen S AD - Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. AD - AstraZeneca, Gothenburg, Sweden. FAU - Abrahamsson, Birgitta AU - Abrahamsson B AUID- ORCID: 0000-0003-4284-2188 AD - Department of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. FAU - Rosengren, Anders H AU - Rosengren AH AUID- ORCID: 0000-0002-9333-5736 AD - Department of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. anders.rosengren@gu.se. LA - eng SI - ClinicalTrials.gov/NCT04451837 PT - Journal Article PT - Randomized Controlled Trial DEP - 20240104 PL - Germany TA - Nat Metab JT - Nature metabolism JID - 101736592 RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucosides) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) RN - 1ULL0QJ8UC (dapagliflozin) SB - IM MH - Female MH - Humans MH - Male MH - *Benzhydryl Compounds MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides MH - Glucose MH - *Glucosides MH - Glycated Hemoglobin MH - Insulin/pharmacology MH - *Insulin Resistance MH - Treatment Outcome MH - Semaglutide PMC - PMC10822775 COIS- S.F. is an employee at AstraZeneca and reports owning stock in AstraZeneca. Study drugs were provided by AstraZeneca AB, Sweden (dapagliflozin), and Novo Nordisk A/S, Denmark (semaglutide), and Libre Pro glucose sensors were provided by Abbott Diabetes Care, USA, as part of investigator-sponsored study agreements. These companies had no role in the study execution, which was performed by academic investigators. All other authors declare no competing interest. EDAT- 2024/01/05 00:42 MHDA- 2024/01/30 12:43 PMCR- 2024/01/04 CRDT- 2024/01/04 23:35 PHST- 2023/05/09 00:00 [received] PHST- 2023/11/08 00:00 [accepted] PHST- 2024/01/30 12:43 [medline] PHST- 2024/01/05 00:42 [pubmed] PHST- 2024/01/04 23:35 [entrez] PHST- 2024/01/04 00:00 [pmc-release] AID - 10.1038/s42255-023-00943-3 [pii] AID - 943 [pii] AID - 10.1038/s42255-023-00943-3 [doi] PST - ppublish SO - Nat Metab. 2024 Jan;6(1):50-60. doi: 10.1038/s42255-023-00943-3. Epub 2024 Jan 4. PMID- 38172989 OWN - NLM STAT- MEDLINE DCOM- 20240105 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 23 IP - 1 DP - 2024 Jan 3 TI - Semaglutide modulates prothrombotic and atherosclerotic mechanisms, associated with epicardial fat, neutrophils and endothelial cells network. PG - 1 LID - 10.1186/s12933-023-02096-9 [doi] LID - 1 AB - BACKGROUND: Obesity has increased in recent years with consequences on diabetes and other comorbidities. Thus, 1 out of 3 diabetic patients suffers cardiovascular disease (CVD). The network among glucose, immune system, endothelium and epicardial fat has an important role on pro-inflammatory and thrombotic mechanisms of atherogenesis. Since semaglutide, long-acting glucagon like peptide 1- receptor agonist (GLP-1-RA), a glucose-lowering drug, reduces body weight, we aimed to study its effects on human epicardial fat (EAT), aortic endothelial cells and neutrophils as atherogenesis involved-cardiovascular cells. METHODS: EAT and subcutaneous fat (SAT) were collected from patients undergoing cardiac surgery. Differential glucose consumption and protein cargo of fat-released exosomes, after semaglutide or/and insulin treatment were analyzed by enzymatic and TripleTOF, respectively. Human neutrophils phenotype and their adhesion to aortic endothelial cells (HAEC) or angiogenesis were analyzed by flow cytometry and functional fluorescence analysis. Immune cells and plasma protein markers were determined by flow cytometry and Luminex-multiplex on patients before and after 6 months treatment with semaglutide. RESULTS: GLP-1 receptor was expressed on fat and neutrophils. Differential exosomes-protein cargo was identified on EAT explants after semaglutide treatment. This drug increased secretion of gelsolin, antithrombotic protein, by EAT, modulated CD11b on neutrophils, its migration and endothelial adhesion, induced by adiposity protein, FABP4, or a chemoattractant. Monocytes and neutrophils phenotype and plasma adiposity, stretch, mesothelial, fibrotic, and inflammatory markers on patients underwent semaglutide treatment for 6 months showed a 20% reduction with statistical significance on FABP4 levels and an 80% increase of neutrophils-CD88. CONCLUSION: Semaglutide increases endocrine activity of epicardial fat with antithrombotic properties. Moreover, this drug modulates the pro-inflammatory and atherogenic profile induced by the adiposity marker, FABP4, which is also reduced in patients after semaglutide treatment. CI - (c) 2023. The Author(s). FAU - Garcia-Vega, David AU - Garcia-Vega D AD - Cardiology department, Complejo Hospitalario Universitario de Santiago, Travesia de la Choupana SN, 15706, Santiago de Compostela, Spain. AD - CIBERCV, ISCIII, Madrid, Spain. AD - University of Santiago de Compostela (USC), Santiago de Compostela, Spain. FAU - Sanchez-Lopez, David AU - Sanchez-Lopez D AD - Translational Cardiology, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. AD - University of Santiago de Compostela (USC), Santiago de Compostela, Spain. FAU - Rodriguez-Carnero, Gemma AU - Rodriguez-Carnero G AD - Endocrinology and Nutrition Division, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain. AD - Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. FAU - Villar-Taibo, Rocio AU - Villar-Taibo R AD - Endocrinology and Nutrition Division, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain. AD - Neoplasia and Differentiation of Endocrine Cells Group, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. FAU - Vinuela, Juan E AU - Vinuela JE AD - Translational Cardiology, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. AD - Immunology Laboratory, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain. FAU - Lestegas-Soto, Adan AU - Lestegas-Soto A AD - Translational Cardiology, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. FAU - Seoane-Blanco, Ana AU - Seoane-Blanco A AD - Cardiology department, Complejo Hospitalario Universitario de Santiago, Travesia de la Choupana SN, 15706, Santiago de Compostela, Spain. AD - CIBERCV, ISCIII, Madrid, Spain. FAU - Moure-Gonzalez, Maria AU - Moure-Gonzalez M AD - Cardiology department, Complejo Hospitalario Universitario de Santiago, Travesia de la Choupana SN, 15706, Santiago de Compostela, Spain. AD - CIBERCV, ISCIII, Madrid, Spain. FAU - Bravo, Susana B AU - Bravo SB AD - Proteomics Unit, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain. FAU - Fernandez, Angel L AU - Fernandez AL AD - Department of Cardiac Surgery, Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, Spain. FAU - Gonzalez-Juanatey, Jose R AU - Gonzalez-Juanatey JR AD - Cardiology department, Complejo Hospitalario Universitario de Santiago, Travesia de la Choupana SN, 15706, Santiago de Compostela, Spain. AD - CIBERCV, ISCIII, Madrid, Spain. AD - University of Santiago de Compostela (USC), Santiago de Compostela, Spain. FAU - Eiras, Sonia AU - Eiras S AD - Cardiology department, Complejo Hospitalario Universitario de Santiago, Travesia de la Choupana SN, 15706, Santiago de Compostela, Spain. sonia.eiras.penas@sergas.es. AD - CIBERCV, ISCIII, Madrid, Spain. sonia.eiras.penas@sergas.es. AD - Translational Cardiology, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. sonia.eiras.penas@sergas.es. LA - eng GR - IN607B-2022-04/Xunta de Galicia/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20240103 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Fibrinolytic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Endothelial Cells/metabolism MH - Epicardial Adipose Tissue MH - Neutrophils MH - Fibrinolytic Agents/therapeutic use MH - *Atherosclerosis/metabolism MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - Obesity/metabolism MH - Glucose/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Semaglutide PMC - PMC10765851 OTO - NOTNLM OT - Atherosclerosis OT - Epicardial fat OT - Obesity OT - Semaglutide COIS- All other authors report no competing interests related to this study. EDAT- 2024/01/04 11:43 MHDA- 2024/01/05 06:42 PMCR- 2024/01/03 CRDT- 2024/01/04 00:01 PHST- 2023/08/10 00:00 [received] PHST- 2023/12/13 00:00 [accepted] PHST- 2024/01/05 06:42 [medline] PHST- 2024/01/04 11:43 [pubmed] PHST- 2024/01/04 00:01 [entrez] PHST- 2024/01/03 00:00 [pmc-release] AID - 10.1186/s12933-023-02096-9 [pii] AID - 2096 [pii] AID - 10.1186/s12933-023-02096-9 [doi] PST - epublish SO - Cardiovasc Diabetol. 2024 Jan 3;23(1):1. doi: 10.1186/s12933-023-02096-9. PMID- 38161982 OWN - NLM STAT- MEDLINE DCOM- 20240103 LR - 20241019 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - G protein-coupled receptors and obesity. PG - 1301017 LID - 10.3389/fendo.2023.1301017 [doi] LID - 1301017 AB - G protein-coupled receptors (GPCRs) have emerged as important drug targets for various chronic diseases, including obesity and diabetes. Obesity is a complex chronic disease that requires long term management predisposing to type 2 diabetes, heart disease, and some cancers. The therapeutic landscape for GPCR as targets of anti-obesity medications has undergone significant changes with the approval of semaglutide, the first peptide glucagon like peptide 1 receptor agonist (GLP-1RA) achieving double digit weight loss (>/=10%) and cardiovascular benefits. The enhanced weight loss, with the expected beneficial effect on obesity-related complications and reduction of major adverse cardiovascular events (MACE), has propelled the commercial opportunity for the obesity market leading to new players entering the space. Significant progress has been made on approaches targeting GPCRs such as single peptides that simultaneously activate GIP and/or GCGR in addition to GLP1, oral tablet formulation of GLP-1, small molecules nonpeptidic oral GLP1R and fixed-dose combination as well as add-on therapy for patients already treated with a GLP-1 agonist. CI - Copyright (c) 2023 Pocai. FAU - Pocai, Alessandro AU - Pocai A AD - Cardiovascular and Metabolic Disease, Johnson & Johnson Innovative Medicine Research & Development, Spring House, PA, United States. LA - eng PT - Journal Article PT - Review DEP - 20231214 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Peptides) RN - 0 (Receptors, G-Protein-Coupled) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/complications/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - Peptides MH - Weight Loss MH - Receptors, G-Protein-Coupled PMC - PMC10757641 OTO - NOTNLM OT - GIP OT - GLP-1 OT - amylin OT - glucagon OT - obesity OT - semaglutide OT - tirzepatide COIS- The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/01/02 11:43 MHDA- 2024/01/03 09:42 PMCR- 2023/01/01 CRDT- 2024/01/01 04:12 PHST- 2023/09/24 00:00 [received] PHST- 2023/11/29 00:00 [accepted] PHST- 2024/01/03 09:42 [medline] PHST- 2024/01/02 11:43 [pubmed] PHST- 2024/01/01 04:12 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1301017 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Dec 14;14:1301017. doi: 10.3389/fendo.2023.1301017. eCollection 2023. PMID- 38161305 OWN - NLM STAT- MEDLINE DCOM- 20240103 LR - 20260923 IS - 1535-7228 (Electronic) IS - 0002-953X (Linking) VI - 181 IP - 1 DP - 2024 Jan 1 TI - Psychotropic Drug-Related Weight Gain and Its Treatment. PG - 26-38 LID - 10.1176/appi.ajp.20230922 [doi] AB - Psychotropic drug-related weight gain (PDWG) is a common occurrence and is highly associated with non-initiation, discontinuation, and dissatisfaction with psychiatric drugs. Moreover, PDWG intersects with the elevated risk for obesity and associated morbidity that has been amply reported in the psychiatric population. Evidence indicates that differential liability for PDWG exists for antipsychotics, antidepressants, and anticonvulsants. During the past two decades, agents within these classes have become available with significantly lower or no liability for PDWG and as such should be prioritized. Although lithium is associated with weight gain, the overall extent of weight gain is significantly lower than previously estimated. The benefit of lifestyle and behavioral modification for obesity and/or PDWG in psychiatric populations is established, with effectiveness similar to that in the general population. Metformin is the most studied pharmacological treatment in the prevention and treatment of PDWG, and promising data are emerging for glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, exenatide, semaglutide). Most pharmacologic antidotes for PDWG are supported with low-confidence data (e.g., topiramate, histamine-2 receptor antagonists). Future vistas for pharmacologic treatment for PDWG include large, adequately controlled studies with GLP-1 receptor agonists and possibly GLP-1/glucose-dependent insulinotropic polypeptide co-agonists (e.g., tirzepatide) as well as specific dietary modifications. FAU - McIntyre, Roger S AU - McIntyre RS AD - Department of Psychiatry (McIntyre, Rosenblat, Mansur) and Department of Pharmacology and Toxicology (McIntyre, Rosenblat, Mansur), University of Toronto, Toronto; Brain and Cognition Discovery Foundation, Toronto (McIntyre, Kwan, Teopiz); Faculty of Medicine, University of Ottawa, Ottawa (Kwan). FAU - Kwan, Angela T H AU - Kwan ATH AD - Department of Psychiatry (McIntyre, Rosenblat, Mansur) and Department of Pharmacology and Toxicology (McIntyre, Rosenblat, Mansur), University of Toronto, Toronto; Brain and Cognition Discovery Foundation, Toronto (McIntyre, Kwan, Teopiz); Faculty of Medicine, University of Ottawa, Ottawa (Kwan). FAU - Rosenblat, Joshua D AU - Rosenblat JD AD - Department of Psychiatry (McIntyre, Rosenblat, Mansur) and Department of Pharmacology and Toxicology (McIntyre, Rosenblat, Mansur), University of Toronto, Toronto; Brain and Cognition Discovery Foundation, Toronto (McIntyre, Kwan, Teopiz); Faculty of Medicine, University of Ottawa, Ottawa (Kwan). FAU - Teopiz, Kayla M AU - Teopiz KM AD - Department of Psychiatry (McIntyre, Rosenblat, Mansur) and Department of Pharmacology and Toxicology (McIntyre, Rosenblat, Mansur), University of Toronto, Toronto; Brain and Cognition Discovery Foundation, Toronto (McIntyre, Kwan, Teopiz); Faculty of Medicine, University of Ottawa, Ottawa (Kwan). FAU - Mansur, Rodrigo B AU - Mansur RB AD - Department of Psychiatry (McIntyre, Rosenblat, Mansur) and Department of Pharmacology and Toxicology (McIntyre, Rosenblat, Mansur), University of Toronto, Toronto; Brain and Cognition Discovery Foundation, Toronto (McIntyre, Kwan, Teopiz); Faculty of Medicine, University of Ottawa, Ottawa (Kwan). LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Am J Psychiatry JT - The American journal of psychiatry JID - 0370512 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Psychotropic Drugs) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Liraglutide/therapeutic use MH - Weight Gain MH - Obesity/chemically induced/drug therapy MH - Psychotropic Drugs/adverse effects MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Adverse Effects of Medication OT - Anticonvulsants OT - Antidepressants OT - Antipsychotics OT - Glucagon-Like Peptide-1 Agonists OT - Psychotropic Drug-Related Weight Gain COIS- Dr. McIntyre has received research grant support from Canadian Institutes of Health Research/Global Alliance for Chronic Diseases/National Natural Science Foundation of China; he has received speaker or consultation fees from AbbVie, Alkermes, Atai Life Sciences, Axsome, Bausch Health, Biogen, Boehringer Ingelheim, Eisai, Intra-Cellular, Janssen, Kris, Lundbeck, Mitsubishi Tanabe, Neumora Therapeutics, Neurawell, Neurocrine, NewBridge Pharmaceuticals, Novo Nordisk, Otsuka, Pfizer, Purdue, Sage, Sanofi, Sunovion, Takeda, and Viatris; and he is CEO of Braxia Scientific Corp. Dr. Rosenblat has received research grant support from the American Psychiatric Association, American Society of Psychopharmacology, Brain and Cognition Discovery Foundation, Canadian Cancer Society, Canadian Institute of Health Research, Canadian Psychiatric Association, Joseph M. West Family Memorial Fund, Labatt Brain Health Network, Physician Services Inc. Foundation, University Health Network Center for Mental Health, and University of Toronto; he has received speaker, consultation, or research fees from Allergan, Boehringer Ingelheim, COMPASS, iGan, Janssen, Lundbeck, and Sunovion; and he was previously the chief medical and scientific officer of Braxia Scientific Corp. Ms. Teopiz has received fees from Braxia Scientific Corp. The other authors report no financial relationships with commercial interests. EDAT- 2024/01/02 11:44 MHDA- 2024/01/03 09:43 CRDT- 2024/01/01 03:07 PHST- 2024/01/03 09:43 [medline] PHST- 2024/01/02 11:44 [pubmed] PHST- 2024/01/01 03:07 [entrez] AID - 10.1176/appi.ajp.20230922 [doi] PST - ppublish SO - Am J Psychiatry. 2024 Jan 1;181(1):26-38. doi: 10.1176/appi.ajp.20230922. PMID- 38159613 OWN - NLM STAT- MEDLINE DCOM- 20240313 LR - 20260515 IS - 1872-6216 (Electronic) IS - 0047-6374 (Linking) VI - 218 DP - 2024 Apr TI - A feasibility study of the combination of intranasal insulin with oral semaglutide for cognition in older adults with metabolic syndrome at high dementia risk- Study rationale and design. PG - 111898 LID - S0047-6374(23)00124-0 [pii] LID - 10.1016/j.mad.2023.111898 [doi] AB - INTRODUCTION: We present the rationale and design of a double-blind placebo-controlled feasibility trial combining intranasal insulin (INI) with semaglutide, a GLP-1 receptor agonist, to improve cognition in older adults with metabolic syndrome (MetS) and mild cognitive impairment (MCI). Since both INI and dulaglutide have beneficial effects on the cerebrovascular disease (CVD), we anticipate that improved CVD will underlie the hypothesized cognitive benefits. METHODS: This 12-months trial will include 80 older adults aged > 60 with MetS and MCI, randomized to 4 groups: INI/oral semaglutide, intranasal placebo/oral semaglutide, INI/oral placebo, and intranasal placebo/oral placebo. Feasibility of combining INI with semaglutide will be tested by examining the ease of use of INI (20IU, twice/day) with semaglutide (14 once daily), adherence, and safety profile are the efficacy of combination therapy on global cognition and neurobiological markers: cerebral blood flow, cerebral glucose utilization, white matter hyperintensities, Alzheimer's related blood biomarkers and expression of insulin signaling proteins measured in brain-derived exosomes. Efficacy will be assessed for the intent-to-treat sample. DISCUSSION: This feasibility study is anticipated to provide the basis for a multi-center large-scale randomized clinical trial (RCT) of the cognitive benefits of the combination of INI with semaglutide in individuals enriched for CVD and at high dementia risk. CI - Copyright (c) 2024. Published by Elsevier B.V. FAU - Davidy, Tal AU - Davidy T AD - The Joseph Sagol Neuroscience, Center Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; Department of Neurology, Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel. Electronic address: Tal.davidy@mail.huji.ac.il. FAU - Yore, Iscka AU - Yore I AD - The Joseph Sagol Neuroscience, Center Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel. FAU - Cukierman-Yaffe, Tali AU - Cukierman-Yaffe T AD - Gertner Institute for Epidemiology and Health Policy Research, Endocrinology Institute Sheba Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Medicine and Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada. FAU - Ravona-Springer, Ramit AU - Ravona-Springer R AD - The Joseph Sagol Neuroscience, Center Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; Memory Clinic, Sheba Medical Center, Ramat Gan, Israel. FAU - Livny, Abigail AU - Livny A AD - The Joseph Sagol Neuroscience, Center Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. FAU - Lesman-Segev, Orit H AU - Lesman-Segev OH AD - The Joseph Sagol Neuroscience, Center Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel; Department of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. FAU - Azuri, Yossi AU - Azuri Y AD - Maccabi Healthcare Services, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. FAU - Carmichael, Owen AU - Carmichael O AD - Pennington Biomedical Research Center, Baton Rouge, LA, USA. FAU - Kapogiannis, Dimitrios AU - Kapogiannis D AD - Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging (NIA/NIH), Baltimore, MD, USA. FAU - Zetterberg, Henrik AU - Zetterberg H AD - Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Molndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, Sweden. FAU - Lin, HungMo AU - Lin H AD - Department of Anesthesiology and Yale Center for Analytical Sciences, USA. FAU - Sano, Mary AU - Sano M AD - James J. Peters VA Medical Research Center, New York, NY, USA. FAU - Beeri, Michal Schnaider AU - Beeri MS AD - The Krieger Klein Alzheimer's Research Center, Brain Health Institute, Rutgers University, NJ, USA. LA - eng PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231229 PL - Ireland TA - Mech Ageing Dev JT - Mechanisms of ageing and development JID - 0347227 RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Aged MH - Insulin MH - Feasibility Studies MH - *Metabolic Syndrome/drug therapy MH - Cognition MH - *Dementia MH - *Cardiovascular Diseases MH - Hypoglycemic Agents/pharmacology MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - *Glucagon-Like Peptides MH - Randomized Controlled Trials as Topic MH - Semaglutide OTO - NOTNLM OT - Cerebral blood flow OT - Cognition OT - Dulaglutide OT - Intranasal insulin OT - Metabolic syndrome OT - Mild cognitive impairment EDAT- 2024/01/02 11:46 MHDA- 2024/03/13 06:47 CRDT- 2023/12/30 19:13 PHST- 2023/12/17 00:00 [received] PHST- 2023/12/25 00:00 [accepted] PHST- 2024/03/13 06:47 [medline] PHST- 2024/01/02 11:46 [pubmed] PHST- 2023/12/30 19:13 [entrez] AID - S0047-6374(23)00124-0 [pii] AID - 10.1016/j.mad.2023.111898 [doi] PST - ppublish SO - Mech Ageing Dev. 2024 Apr;218:111898. doi: 10.1016/j.mad.2023.111898. Epub 2023 Dec 29. PMID- 38157134 OWN - NLM STAT- MEDLINE DCOM- 20240423 LR - 20261010 IS - 1720-8386 (Electronic) IS - 0391-4097 (Linking) VI - 47 IP - 5 DP - 2024 May TI - Comment on: Semaglutide and cardiovascular outcomes in obesity without diabetes. PG - 1047-1049 LID - 10.1007/s40618-023-02290-2 [doi] FAU - Basolo, A AU - Basolo A AUID- ORCID: 0000-0001-6888-7080 AD - Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, 56124, Pisa, Italy. alessio.basolo@unipi.it. FAU - Fierabracci, P AU - Fierabracci P AD - Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, 56124, Pisa, Italy. FAU - Salvetti, G AU - Salvetti G AD - Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, 56124, Pisa, Italy. FAU - Santini, F AU - Santini F AD - Obesity and Lipodystrophy Center, Endocrinology Unit, University Hospital of Pisa, 56124, Pisa, Italy. LA - eng PT - Letter DEP - 20231229 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Obesity/complications/drug therapy MH - *Cardiovascular Diseases/etiology/prevention & control MH - Hypoglycemic Agents/therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - Semaglutide OTO - NOTNLM OT - Cardiovascular outcomes OT - Obesity OT - Semaglutide EDAT- 2024/01/02 11:43 MHDA- 2024/04/23 15:49 CRDT- 2023/12/29 11:16 PHST- 2023/12/04 00:00 [received] PHST- 2023/12/19 00:00 [accepted] PHST- 2024/04/23 15:49 [medline] PHST- 2024/01/02 11:43 [pubmed] PHST- 2023/12/29 11:16 [entrez] AID - 10.1007/s40618-023-02290-2 [pii] AID - 10.1007/s40618-023-02290-2 [doi] PST - ppublish SO - J Endocrinol Invest. 2024 May;47(5):1047-1049. doi: 10.1007/s40618-023-02290-2. Epub 2023 Dec 29. PMID- 38151966 OWN - NLM STAT- MEDLINE DCOM- 20240305 LR - 20260918 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 4 DP - 2024 Apr TI - Real-world effectiveness and safety of oral semaglutide in people living with type 2 diabetes: A nationwide multicentre retrospective observational study (ENDO(2) S-RWD). PG - 1519-1523 LID - 10.1111/dom.15431 [doi] FAU - Moreno-Perez, Oscar AU - Moreno-Perez O AUID- ORCID: 0000-0002-8670-6404 AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Spain. AD - Department of Clinical Medicine, Miguel Hernandez University, Alicante, Spain. FAU - Reyes-Garcia, Rebeca AU - Reyes-Garcia R AUID- ORCID: 0000-0003-1729-4431 AD - Endocrinology Unit. University Hospital of Torrecardenas, Almeria, Spain. AD - CIBER de Fragilidad y Envejecimiento Saludable "CIBERFES", Instituto de Salud Carlos III, Madrid, Spain. FAU - Modrego-Pardo, Ines AU - Modrego-Pardo I AUID- ORCID: 0000-0003-3060-449X AD - Department of Endocrinology and Nutrition, Marina Baixa Hospital, Alicante, Spain. FAU - Doulatram-Gamgaram, Viyey Kishore AU - Doulatram-Gamgaram VK AUID- ORCID: 0000-0002-0178-0040 AD - Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Biomedical Research Institute of Malaga (IBIMA), Faculty of Medicine, University of Malaga, Malaga, Spain. FAU - Cases, Carlos Casado AU - Cases CC AUID- ORCID: 0009-0002-8648-5370 AD - Department of Endocrinology and Nutrition, University Hospital Fundacion Jimenez Diaz, Madrid, Spain. FAU - Guillen-Morote, Cristina AU - Guillen-Morote C AUID- ORCID: 0000-0002-6803-6988 AD - Department of Endocrinology and Nutrition, General University Hospital Dr. Balmis of Alicante. Institute of Health and Biomedical Research of Alicante (ISABIAL), Alicante, Spain. FAU - Mendoza, Nieves Arias AU - Mendoza NA AD - Department of Endocrinology and Nutrition, General University Hospital of Elda, Alicante, Spain. FAU - Tejera-Perez, Cristina AU - Tejera-Perez C AUID- ORCID: 0000-0002-2987-5922 AD - Department of Endocrinology and Nutrition, University Hospital Complex of Ferrol, A Coruna, Spain. FAU - Cardenas-Salas, Jersy AU - Cardenas-Salas J AUID- ORCID: 0000-0002-2485-484X AD - Department of Endocrinology and Nutrition, University Hospital Fundacion Jimenez Diaz, Madrid, Spain. FAU - Martinez-Fuster, Sandra AU - Martinez-Fuster S AD - Department of Endocrinology and Nutrition, General University Hospital of Elda, Alicante, Spain. FAU - Lardies-Sanchez, Beatriz AU - Lardies-Sanchez B AUID- ORCID: 0000-0001-7520-1489 AD - Department of Endocrinology and Nutrition, Obispo Polanco Hospital, Teruel, Spain. FAU - Marquez-Pardo, Rosa AU - Marquez-Pardo R AUID- ORCID: 0000-0002-4914-4131 AD - Department of Endocrinology and Nutrition, Hospital Juan Ramon Jimenez, Huelva, Spain. FAU - Pines, Pedro AU - Pines P AUID- ORCID: 0000-0003-4406-3647 AD - Albacete University Hospital Complex, Albacete, Spain. FAU - Fernandez-Garcia, Jose Carlos AU - Fernandez-Garcia JC AUID- ORCID: 0000-0003-2229-8488 AD - Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Biomedical Research Institute of Malaga (IBIMA), Faculty of Medicine, University of Malaga, Malaga, Spain. CN - SEEN Diabetes Area LA - eng PT - Letter PT - Multicenter Study PT - Observational Study DEP - 20231227 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Hypoglycemic Agents/adverse effects MH - Retrospective Studies MH - Semaglutide EDAT- 2023/12/28 06:42 MHDA- 2024/03/05 06:46 CRDT- 2023/12/28 02:33 PHST- 2023/12/11 00:00 [revised] PHST- 2023/10/13 00:00 [received] PHST- 2023/12/11 00:00 [accepted] PHST- 2024/03/05 06:46 [medline] PHST- 2023/12/28 06:42 [pubmed] PHST- 2023/12/28 02:33 [entrez] AID - 10.1111/dom.15431 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Apr;26(4):1519-1523. doi: 10.1111/dom.15431. Epub 2023 Dec 27. PMID- 38151964 OWN - NLM STAT- MEDLINE DCOM- 20240206 LR - 20260805 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 3 DP - 2024 Mar TI - Glucagon-like peptide-1 analogues in monogenic syndromic obesity: Real-world data from a large cohort of Alstrom syndrome patients. PG - 989-996 LID - 10.1111/dom.15398 [doi] AB - AIM: To examine the real-world efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in monogenic obesity in patients with Alstrom syndrome (ALMS). METHODS: We screened 72 UK adult patients with ALMS and offered treatment to 34 patients meeting one of the following criteria: body mass index of 25 kg/m(2) or higher, insulin resistance, suboptimal glycaemic control on antihyperglycaemic medications or non-alcoholic fatty liver disease. RESULTS: In total, 30 patients, with a mean age of 31 +/- 11 years and a male to-female ratio of 2:1, completed 6 months of treatment with GLP-1 RAs either in the form of semaglutide or exenatide. On average, treatment with GLP-1 RAs reduced body weight by 5.4 +/- 1.7 (95% confidence interval [CI] 3.6-7) kg and HbA1c by 12 +/- 3.3 (95% CI 8.7-15.3) mmol/mol, equating to 6% weight loss (P < .01) and 1.1% absolute reduction in HbA1c (P < .01). Significant improvements were also observed in serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and alanine aminotransferase. The improvement of metabolic variables in our cohort of monogenic syndromic obesity was comparable with data for polygenic obesity, irrespective of weight loss. CONCLUSIONS: Data from our centre highlight the non-inferiority of GLP-1 RAs in monogenic syndromic obesity to the available GLP-1 RA-use data in polygenic obesity, therefore, these agents can be considered as a treatment option in patients with ALMS, as well as other forms of monogenic obesity. CI - (c) 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ali, Sadaf AU - Ali S AUID- ORCID: 0000-0001-6768-5495 AD - University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. AD - Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. FAU - Baig, Shanat AU - Baig S AD - University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. AD - Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. FAU - Wanninayake, Subadra AU - Wanninayake S AD - University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. FAU - da Silva Xavier, Gabriela AU - da Silva Xavier G AD - Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. FAU - Dawson, Charlotte AU - Dawson C AD - University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. FAU - Paisey, Richard AU - Paisey R AD - Torbay and South Devon NHS Foundation Trust, Torquay, Torbay, UK. FAU - Geberhiwot, Tarekegn AU - Geberhiwot T AUID- ORCID: 0000-0002-3629-2338 AD - University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. AD - Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. LA - eng GR - RGT/1/010332749/Big Lottery Fund grant/ PT - Journal Article DEP - 20231227 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glycated Hemoglobin) RN - 839I73S42A (Liraglutide) RN - 0 (Peptides) RN - 0 (Blood Glucose) RN - 0 (Venoms) RN - 0 (Hypoglycemic Agents) RN - 97C5T2UQ7J (Cholesterol) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Humans MH - Male MH - Female MH - Young Adult MH - Glucagon-Like Peptide 1/agonists MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - *Alstrom Syndrome/complications/drug therapy/genetics MH - Liraglutide/therapeutic use MH - Peptides/therapeutic use MH - Blood Glucose/metabolism MH - Venoms/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Obesity/complications/drug therapy/genetics MH - Weight Loss MH - Cholesterol MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Alstrom OT - GLP-1 receptor agonists OT - insulin resistance OT - monogenic syndrome OT - obesity OT - type 2 diabetes EDAT- 2023/12/28 06:42 MHDA- 2024/02/06 06:42 CRDT- 2023/12/28 02:33 PHST- 2023/11/10 00:00 [revised] PHST- 2023/10/03 00:00 [received] PHST- 2023/11/20 00:00 [accepted] PHST- 2024/02/06 06:42 [medline] PHST- 2023/12/28 06:42 [pubmed] PHST- 2023/12/28 02:33 [entrez] AID - 10.1111/dom.15398 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Mar;26(3):989-996. doi: 10.1111/dom.15398. Epub 2023 Dec 27. PMID- 38148042 OWN - NLM STAT- MEDLINE DCOM- 20231228 LR - 20260127 IS - 1791-7549 (Electronic) IS - 0258-851X (Print) IS - 0258-851X (Linking) VI - 38 IP - 1 DP - 2024 Jan-Feb TI - Effects of Oral Semaglutide on Renal Function in Diabetic Kidney Disease: A Short-term Clinical Study. PG - 308-312 LID - 10.21873/invivo.13440 [doi] AB - BACKGROUND/AIM: In the SUSTAIN-6 trial, semaglutide reduced the risk of worsening nephropathy in patients with type 2 diabetes. The objective of this retrospective study was to elucidate the effect and safety of oral semaglutide (Rybelsus((R))) in patients with diabetic kidney disease (DKD). PATIENTS AND METHODS: Six patients with DKD received 3 mg/day semaglutide orally. The observation period was 9.0+/-5.0 months. Changes in estimated glomerular filtration rate (eGFR), urinary protein, fasting blood glucose, and hemoglobin A1c were studied from 6 months before the administration of oral semaglutide until 6 months after administration. RESULTS: The change in eGFR over the 6 months prior to semaglutide administration was -1.2+/-1.6 ml/min/1.73 m(2), showing a trend for a decrease; although not statistically significant, the change at 6 months after oral semaglutide initiation showed improved eGFR (1-50.7+/-1.8 ml/min/1.73 m(2)). Proteinuria was not reduced after treatment with oral semaglutide. No significant adverse effects (including retinopathy) were observed in any patient during the study. CONCLUSION: Despite the small sample size and short observation period, oral semaglutide was found to be a relatively well-tolerated drug for patients with DKD. CI - Copyright (c) 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. FAU - Mima, Akira AU - Mima A AD - Department of Nephrology, Osaka Medical and Pharmaceutical University, Osaka, Japan akira.mima@ompu.ac.jp. FAU - Kidooka, Sayumi AU - Kidooka S AD - Department of Nephrology, Osaka Medical and Pharmaceutical University, Osaka, Japan. FAU - Nakamoto, Takahiro AU - Nakamoto T AD - Department of Nephrology, Osaka Medical and Pharmaceutical University, Osaka, Japan. FAU - Kido, Suguru AU - Kido S AD - Department of Nephrology, Osaka Medical and Pharmaceutical University, Osaka, Japan. FAU - Gotoda, Hidemasa AU - Gotoda H AD - Department of Nephrology, Osaka Medical and Pharmaceutical University, Osaka, Japan. FAU - Lee, Rina AU - Lee R AD - Department of Nephrology, Osaka Medical and Pharmaceutical University, Osaka, Japan. FAU - Murakami, Ami AU - Murakami A AD - Department of Nephrology, Osaka Medical and Pharmaceutical University, Osaka, Japan. FAU - Lee, Shinji AU - Lee S AD - Department of Nephrology, Osaka Medical and Pharmaceutical University, Osaka, Japan. LA - eng PT - Journal Article PL - Greece TA - In Vivo JT - In vivo (Athens, Greece) JID - 8806809 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetic Nephropathies/drug therapy MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Retrospective Studies MH - Kidney/metabolism MH - Semaglutide PMC - PMC10756470 OTO - NOTNLM OT - CKD OT - DKD OT - ESRD OT - Oral semaglutide OT - chronic kidney disease OT - diabetic kidney disease OT - end-stage renal disease OT - estimated glomerular filtration rate OT - type 2 diabetes COIS- Akira Mima received a speaker honorarium from Otsuka, Kyowa Kirin, Mitsubishi Tanabe, Torii, Kowa, Bayer, Eli Lilly, Mochida, Sumitomo Pharma, Novo Nordisk and Boehringer Ingelheim. EDAT- 2023/12/27 00:41 MHDA- 2023/12/28 06:42 PMCR- 2024/01/03 CRDT- 2023/12/26 20:33 PHST- 2023/07/10 00:00 [received] PHST- 2023/09/06 00:00 [revised] PHST- 2023/09/12 00:00 [accepted] PHST- 2023/12/28 06:42 [medline] PHST- 2023/12/27 00:41 [pubmed] PHST- 2023/12/26 20:33 [entrez] PHST- 2024/01/03 00:00 [pmc-release] AID - 38/1/308 [pii] AID - 10.21873/invivo.13440 [doi] PST - ppublish SO - In Vivo. 2024 Jan-Feb;38(1):308-312. doi: 10.21873/invivo.13440. PMID- 38133594 OWN - NLM STAT- MEDLINE DCOM- 20231225 LR - 20250103 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 65 IP - 1692 DP - 2023 Dec 25 TI - Tirzepatide (Zepbound) for chronic weight management. PG - 205-207 LID - 10.58347/tml.2023.1692c [doi] LA - eng PT - Journal Article PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - OYN3CCI6QE (Tirzepatide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Gastric Inhibitory Polypeptide MH - *Diabetes Mellitus, Type 2 MH - Hypoglycemic Agents MH - Glucagon-Like Peptide-1 Receptor MH - Tirzepatide OTO - NOTNLM OT - Mounjaro OT - Saxenda OT - Wegovy OT - Zepbound OT - adverse effects OT - dosage OT - drug interactions OT - efficacy OT - lactation OT - liraglutide OT - pregnancy OT - safety OT - semaglutide OT - tirzepatide OT - weight loss EDAT- 2023/12/22 12:42 MHDA- 2023/12/25 06:41 CRDT- 2023/12/22 10:13 PHST- 2023/12/25 06:41 [medline] PHST- 2023/12/22 12:42 [pubmed] PHST- 2023/12/22 10:13 [entrez] AID - 10.58347/tml.2023.1692c [doi] PST - ppublish SO - Med Lett Drugs Ther. 2023 Dec 25;65(1692):205-207. doi: 10.58347/tml.2023.1692c. PMID- 38128857 OWN - NLM STAT- MEDLINE DCOM- 20240125 LR - 20260527 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 199 DP - 2024 Jan TI - Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide. PG - 107040 LID - S1043-6618(23)00396-1 [pii] LID - 10.1016/j.phrs.2023.107040 [doi] AB - Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor and semaglutide, a glucagon-like peptide 1 receptor agonist, have both demonstrated efficacy in glycemic control, reducing blood pressure, body weight, risk of renal and heart failure in type 2 diabetes mellitus. In this observational, real-world, study we aimed to investigate the efficacy of the combination therapy with those two agents over glycemic control. We thus obtained the data of 1335 patients with type 2 diabetes followed by 11 Diabetes centers in Lombardia, Italy. A group of 443 patients was treated with dapagliflozin alone, the other group of 892 patients was treated with the combination therapy of dapagliflozin plus oral semaglutide. We analyzed changes in glycated hemoglobin from baseline to 6 months of follow-up, as well as changes in fasting glycemia, body weight, body mass index, systolic and diastolic pressure, heart rate, creatinine, estimated glomerular filtration rate and albuminuria. Both groups of patients showed an improvement of glycometabolic control after 6 months of treatment; indeed, the treatment with dapagliflozin plus oral semaglutide showed a reduction of glycated hemoglobin of 1.2% as compared to the 0.5% reduction observed in the dapagliflozin alone group. Significant changes were observed in body mass index, fasting plasmatic glucose, blood pressure, total cholesterol, LDL and albumin to creatinine ratio, with a high rate (55%) of near-normalization of glycated hemoglobin. Our real world data confirmed the potential of the oral combination therapy dapagliflozin with semaglutide in inducing pharmacological remission of type 2 diabetes mellitus. CI - Copyright (c) 2023. Published by Elsevier Ltd. FAU - Lunati, Maria Elena AU - Lunati ME AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Cimino, Vincenzo AU - Cimino V AD - Department of Biomedical and Clinical Sciences L. Sacco Endocrinology and Diabetology, Milan, Italy. FAU - Bernasconi, Davide AU - Bernasconi D AD - University of Milan, Milan, Italy. FAU - Gandolfi, Alessandra AU - Gandolfi A AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Morpurgo, Paola Silvia AU - Morpurgo PS AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Tinari, Camilla AU - Tinari C AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Lazzaroni, Elisa AU - Lazzaroni E AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Baruffaldi, Laura AU - Baruffaldi L AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Muratori, Milena AU - Muratori M AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Montefusco, Laura AU - Montefusco L AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Pastore, Ida AU - Pastore I AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Rossi, Antonio AU - Rossi A AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Franzetti, Ivano Giuseppe AU - Franzetti IG AD - ASST Valle Olona, Varese, Italy. FAU - Muratori, Fabrizio AU - Muratori F AD - Division of Endocrinology and Diabetology, Sant'Anna Hospital, Como, Italy. FAU - Manfrini, Roberto AU - Manfrini R AD - Endocrinology and Metabolism, Department of Health Science, Universita di Milano, ASST Santi Paolo e Carlo, Milan, Italy. FAU - Disoteo, Olga Eugenia AU - Disoteo OE AD - Division of Diabetology, Niguarda Hospital, Milan, Italy. FAU - Terranova, Rosa AU - Terranova R AD - Division of Diabetology, Niguarda Hospital, Milan, Italy. FAU - Desenzani, Paolo AU - Desenzani P AD - ASST Spedali Civili Brescia, Milano, Italy. FAU - Girelli, Angela AU - Girelli A AD - ASST Spedali Civili Brescia, Milano, Italy. FAU - Ghelardi, Renata AU - Ghelardi R AD - ASST Melegnano-Martesana, Milan, Italy. FAU - D'Addio, Francesca AU - D'Addio F AD - International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita di Milano, Italy. FAU - Ben Nasr, Moufida AU - Ben Nasr M AD - International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita di Milano, Italy. FAU - Berra, Cesare AU - Berra C AD - IRCCS MultiMedica Sesto San Giovanni, Milano, Italy. FAU - Folli, Franco AU - Folli F AD - Endocrinology and Metabolism, Department of Health Science, Universita di Milano, ASST Santi Paolo e Carlo, Milan, Italy. FAU - Bucciarelli, Loredana AU - Bucciarelli L AD - IRCCS MultiMedica Sesto San Giovanni, Milano, Italy. FAU - Fiorina, Paolo AU - Fiorina P AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy; International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita di Milano, Italy; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: paolo.fiorina@childrens.harvard.edu. LA - eng PT - Journal Article PT - Observational Study DEP - 20231220 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Benzhydryl Compounds) RN - 0 (Blood Glucose) RN - AYI8EX34EU (Creatinine) RN - 62340-29-8 (Glucagon-Like Peptides) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucosides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) RN - 1ULL0QJ8UC (dapagliflozin) SB - IM MH - Humans MH - Benzhydryl Compounds/therapeutic use MH - Blood Glucose MH - Body Weight MH - Creatinine MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides MH - Glucose MH - *Glucosides MH - Glycated Hemoglobin MH - Hypoglycemic Agents/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - Combination therapy OT - Dual treatment OT - GLP-1RA OT - SGLT2-I OT - T2D COIS- Declaration of Competing Interest None. EDAT- 2023/12/22 00:42 MHDA- 2024/01/15 12:42 CRDT- 2023/12/21 19:29 PHST- 2023/11/09 00:00 [received] PHST- 2023/12/10 00:00 [revised] PHST- 2023/12/11 00:00 [accepted] PHST- 2024/01/15 12:42 [medline] PHST- 2023/12/22 00:42 [pubmed] PHST- 2023/12/21 19:29 [entrez] AID - S1043-6618(23)00396-1 [pii] AID - 10.1016/j.phrs.2023.107040 [doi] PST - ppublish SO - Pharmacol Res. 2024 Jan;199:107040. doi: 10.1016/j.phrs.2023.107040. Epub 2023 Dec 20. PMID- 38125558 OWN - NLM STAT- MEDLINE DCOM- 20240112 LR - 20260127 IS - 2046-1402 (Electronic) IS - 2046-1402 (Linking) VI - 12 DP - 2023 TI - The short-term cost-effectiveness of once-weekly semaglutide versus once-weekly dulaglutide for the treatment of type 2 diabetes mellitus in Colombian adults. PG - 914 LID - 10.12688/f1000research.128441.2 [doi] LID - 914 AB - BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a highly prevalent disease worldwide and in Colombia, representing one of the main causes of death and placing a considerable burden on healthcare systems. 13 classes of drugs are approved for the treatment of T2DM, with Glucagon-like Peptide-1 (GLP-1) receptor agonists being a first-line treatment option for patients with or at high risk of certain cardiovascular diseases and chronic kidney disease. The objective of this study is to conduct a short-term cost-effectiveness analysis of once-weekly semaglutide versus once-weekly dulaglutide in Colombian adults with T2DM, from a third-party payer perspective. METHODS: Numbers needed to treat were calculated for different single and composite endpoints of the SUSTAIN 7 trial, annual costs for once weekly semaglutide 1.0 mg and dulaglutide 1.5 mg were extracted from the public SISMED database. With these inputs a cost of control model was developed, to obtain the annual cost of bringing one T2DM patient to relevant clinical outcomes by using semaglutide or dulaglutide. RESULTS: Semaglutide was considered cost-effective compared to dulaglutide across all pre-specified endpoints, even in the different scenarios evaluated in the sensitivity analyses, and in a particularly pronounced manner for weight loss outcomes. Semaglutide at a dose of 1.0 mg once-weekly was cost-effective compared to dulaglutide 1.5 mg across all outcomes in the short-term, making it an appropriate first-line choice in the treatment of T2DM when deciding between these two GLP-1 receptor agonists. CONCLUSIONS: This is the first short-term cost-effectiveness study of semaglutide and dulaglutide in T2DM Colombian patients. Our modeled results suggest that once-weekly semaglutide represents a cost-effective option for treating individuals with T2DM in Colombia who are not achieving glycaemia control with metformin, and it would be expected to improve HbA1C, promote greater weight loss and reduce costs from a third-payer perspective compared with treatment with dulaglutide. CI - Copyright: (c) 2023 Liebisch-Rey H et al. FAU - Liebisch-Rey, Hans AU - Liebisch-Rey H AD - Evidence-Based Therapeutics Group, Department of Clinical Pharmacology, Faculty of Medicine, Universidad de La Sabana and Clinica Universidad de La Sabana, Chia, Cundinamarca, 140013, Colombia. FAU - Suarez-Chacon, Andrea-Marcela AU - Suarez-Chacon AM AD - Evidence-Based Therapeutics Group, Department of Clinical Pharmacology, Faculty of Medicine, Universidad de La Sabana and Clinica Universidad de La Sabana, Chia, Cundinamarca, 140013, Colombia. FAU - Fuentes, Yuli-V AU - Fuentes YV AD - Evidence-Based Therapeutics Group, Department of Clinical Pharmacology, Faculty of Medicine, Universidad de La Sabana and Clinica Universidad de La Sabana, Chia, Cundinamarca, 140013, Colombia. FAU - Blanco, Jhosep AU - Blanco J AD - Evidence-Based Therapeutics Group, Department of Clinical Pharmacology, Faculty of Medicine, Universidad de La Sabana and Clinica Universidad de La Sabana, Chia, Cundinamarca, 140013, Colombia. FAU - Kock, Joshua AU - Kock J AD - Department of Epidemiology, Faculty of Medicine, Universidad de La Sabana, Chia, Cundinamarca, 140013, Colombia. FAU - Lechtig-Wassermann, Sharon AU - Lechtig-Wassermann S AD - Evidence-Based Therapeutics Group, Department of Clinical Pharmacology, Faculty of Medicine, Universidad de La Sabana and Clinica Universidad de La Sabana, Chia, Cundinamarca, 140013, Colombia. FAU - Bustos, Rosa Helena AU - Bustos RH AD - Evidence-Based Therapeutics Group, Department of Clinical Pharmacology, Faculty of Medicine, Universidad de La Sabana and Clinica Universidad de La Sabana, Chia, Cundinamarca, 140013, Colombia. LA - eng PT - Journal Article DEP - 20231211 PL - England TA - F1000Res JT - F1000Research JID - 101594320 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Adult MH - Humans MH - Colombia MH - Cost-Effectiveness Analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Weight Loss MH - Clinical Trials as Topic MH - Semaglutide MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC10730985 OTO - NOTNLM OT - Cost-effectiveness OT - Dulaglutide OT - Pharmacoeconomic OT - Semaglutide COIS- No competing interests were disclosed. EDAT- 2023/12/21 06:42 MHDA- 2023/12/22 06:42 PMCR- 2023/12/11 CRDT- 2023/12/21 04:13 PHST- 2023/12/05 00:00 [accepted] PHST- 2023/12/22 06:42 [medline] PHST- 2023/12/21 06:42 [pubmed] PHST- 2023/12/21 04:13 [entrez] PHST- 2023/12/11 00:00 [pmc-release] AID - 10.12688/f1000research.128441.2 [doi] PST - epublish SO - F1000Res. 2023 Dec 11;12:914. doi: 10.12688/f1000research.128441.2. eCollection 2023. PMID- 38122931 OWN - NLM STAT- MEDLINE DCOM- 20240308 LR - 20250103 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 30 IP - 3 DP - 2024 Mar TI - A Review of Incretin Therapies Approved and in Late-Stage Development for Overweight and Obesity Management. PG - 292-303 LID - S1530-891X(23)00790-5 [pii] LID - 10.1016/j.eprac.2023.12.010 [doi] AB - OBJECTIVE: To review clinical trial data for incretin therapies that are approved or in late-stage development for overweight or obesity management, along with clinical implications of these therapies and future directions. METHODS: We searched for clinical trials involving incretin therapies studied specifically for overweight or obesity management in ClinicalTrials.gov and PubMed from registry inception through December 2023. RESULTS: Glucagon-like peptide-1 (GLP-1) receptor agonism, alone and in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonism or glucagon agonism, leads to significant weight reduction in people with overweight or obesity. Newer incretin therapies have demonstrated weight reduction between 15% to 25%, far outpacing non-incretin therapies for weight management and achieving levels of weight loss that may prevent weight-related complications. However, the discontinuation of incretin therapies is associated with weight regain. The main side effects of incretin therapies are transient, mild-to-moderate gastrointestinal side effects - nausea, diarrhea, constipation, and vomiting - that commonly occur in the first 4 to 8 weeks of treatment. There is a rich late-stage pipeline of incretin therapies for weight management, consisting of oral GLP-1 receptor agonists, dual GLP-1/GIP receptor agonists, dual GLP-1/glucagon receptor agonists, triple GLP-1/GIP/glucagon receptor agonists, and combination therapies with nonincretin drugs. CONCLUSION: Newer incretin therapies for weight management have the potential to improve the treatment for overweight and obesity, the treatment and prevention of weight-related complications, and the individualization of weight management. Ensuring that these therapies are accessible - and that treatment with them is consistent and sustainable - is necessary to translate findings from trials into the real world. CI - Copyright (c) 2024. Published by Elsevier Inc. FAU - Chetty, Ashwin Kanna AU - Chetty AK AD - Yale School of Medicine, New Haven, Connecticut; Close Concerns, San Francisco, California. FAU - Rafi, Ebne AU - Rafi E AD - Diabetes and Metabolic Care Center, University Hospitals, Cleveland, Ohio. FAU - Bellini, Natalie J AU - Bellini NJ AD - Diabetes and Metabolic Care Center, University Hospitals, Cleveland, Ohio. FAU - Buchholz, Natalie AU - Buchholz N AD - University of Southern California School of Pharmacy, Los Angeles, California. FAU - Isaacs, Diana AU - Isaacs D AD - Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: isaacsd@ccf.org. LA - eng PT - Journal Article PT - Review DEP - 20231218 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Receptors, Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Incretins/therapeutic use/pharmacology MH - Overweight/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - Gastric Inhibitory Polypeptide/pharmacology/therapeutic use MH - *Obesity Management MH - Receptors, Glucagon/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - glucagon-like peptide-1 (GLP-1) OT - glucose-dependent insulinotropic polypeptide (GIP) OT - incretin analog OT - semaglutide OT - tirzepatide OT - weight loss COIS- Disclosure A.K.C. is a contractor for Close Concerns, which publishes a paid information service to which numerous diabetes technology, therapy, and digital health companies subscribe. A full listing is available online (https://www.closeconcerns.com/disclosure.php). D.I. is a speaker for Eli Lilly and Novo Nordisk. The other authors have no conflicts of interest to disclose. EDAT- 2023/12/21 00:41 MHDA- 2024/03/08 06:42 CRDT- 2023/12/20 19:28 PHST- 2023/09/12 00:00 [received] PHST- 2023/12/10 00:00 [revised] PHST- 2023/12/11 00:00 [accepted] PHST- 2024/03/08 06:42 [medline] PHST- 2023/12/21 00:41 [pubmed] PHST- 2023/12/20 19:28 [entrez] AID - S1530-891X(23)00790-5 [pii] AID - 10.1016/j.eprac.2023.12.010 [doi] PST - ppublish SO - Endocr Pract. 2024 Mar;30(3):292-303. doi: 10.1016/j.eprac.2023.12.010. Epub 2023 Dec 18. PMID- 38117235 OWN - NLM STAT- MEDLINE DCOM- 20240112 LR - 20250103 IS - 1520-4804 (Electronic) IS - 0022-2623 (Linking) VI - 67 IP - 1 DP - 2024 Jan 11 TI - Discovery of a Novel Glucagon-like Peptide-1 (GLP-1) Analogue from Bullfrog and Investigation of Its Potential for Designing GLP-1-Based Multiagonists. PG - 180-198 LID - 10.1021/acs.jmedchem.3c01049 [doi] AB - In this study, we aimed to discover novel GLP-1 analogues from natural sources. We investigated GLP-1 analogues from fish and amphibians, and bullfrog GLP-1 (bGLP-1) showed the highest potency. Starting with bGLP-1, we explored the structure-activity relationship and performed optimization and long-acting modifications, resulting in a potent analogue called 2f. Notably, 2f exhibited superior effects on food intake, glycemic control, and body weight compared to semaglutide. Furthermore, we explored the usefulness of bGLP-1 in designing GLP-1-based multiagonists. Using the bGLP-1 sequence, we designed novel dual GLP-1/glucagon receptor agonists and triple GLP-1/GIP/glucagon receptor agonists. The selected dual GLP-1/glucagon receptor agonist 3o and triple GLP-1/GIP/glucagon receptor agonist 4b exhibited significant therapeutic effects on lipid regulation, glycemic control, and body weight. Overall, our study highlights the potential of discovering potent GLP-1 receptor agonists from natural sources. Additionally, utilizing natural GLP-1 analogues for designing multiagonists presents a practical approach for developing antiobesity and antidiabetic agents. FAU - Jiang, Neng AU - Jiang N AD - Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, PR China. FAU - Su, Di AU - Su D AD - Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, PR China. FAU - Chen, De AU - Chen D AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Huang, Shutong AU - Huang S AD - Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, PR China. AD - Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi 530021, PR China. FAU - Tang, Chunli AU - Tang C AD - Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, PR China. FAU - Jing, Lin AU - Jing L AD - Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, PR China. FAU - Yang, Caiyan AU - Yang C AD - School of Pharmacy, Youjiang Medical University for Nationalities, 98 Chengxiang Road, Baise, Guangxi 533000, PR China. FAU - Zhou, Zhongbo AU - Zhou Z AD - School of Pharmacy, Youjiang Medical University for Nationalities, 98 Chengxiang Road, Baise, Guangxi 533000, PR China. FAU - Yan, Zhiming AU - Yan Z AD - Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, PR China. AD - Pharmaceutical College, Guangxi Medical University, Nanning, Guangxi 530021, PR China. FAU - Han, Jing AU - Han J AUID- ORCID: 0000-0001-5605-1868 AD - Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, PR China. AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231220 PL - United States TA - J Med Chem JT - Journal of medicinal chemistry JID - 9716531 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Glucagon) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - *Glucagon-Like Peptide 1/agonists MH - Rana catesbeiana MH - Receptors, Glucagon MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Body Weight MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2023/12/20 12:42 MHDA- 2024/01/12 06:42 CRDT- 2023/12/20 10:24 PHST- 2024/01/12 06:42 [medline] PHST- 2023/12/20 12:42 [pubmed] PHST- 2023/12/20 10:24 [entrez] AID - 10.1021/acs.jmedchem.3c01049 [doi] PST - ppublish SO - J Med Chem. 2024 Jan 11;67(1):180-198. doi: 10.1021/acs.jmedchem.3c01049. Epub 2023 Dec 20. PMID- 38116693 OWN - NLM STAT- MEDLINE DCOM- 20240206 LR - 20260806 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 3 DP - 2024 Mar TI - Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta-analysis. PG - 1090-1104 LID - 10.1111/dom.15410 [doi] AB - AIM: The present systematic review aimed to summarize the available evidence from published randomized controlled trials (RCTs) regarding the effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Medline (via PubMed), Cochrane Library and Scopus were searched until 20 October 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with a three-level mixed-effects meta-analysis. RESULTS: In total, 9533 participants from eight RCTs were analysed. All RCTs had a low risk of bias, according to the Cochrane Collaboration tool (RoB2). Tirzepatide was associated with a significantly greater reduction in urine albumin-to-creatinine ratio compared with controls [mean difference (MD) -26.9%; 95% confidence interval (CI) (-34.76, -19.04); p < .001; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin-to-creatinine ratio >/=30 mg/g [MD -41.42%; 95% CI (-54.38, -28.45); p < .001; LoE moderate]. Based on subgroup analysis, the comparative effect of tirzepatide was significant against placebo and the insulin regimen, whereas no difference was observed compared with semaglutide. The beneficial effect of tirzepatide on albuminuria levels remained significant across all investigated doses (5, 10 and 15 mg), showing a dose-response relationship. A neutral effect was observed on the estimated glomerular filtration rate [MD 0.39 ml/min/1.73m(2) ; 95% CI (-0.64, 1.42); p = .46; LoE moderate]. CONCLUSION: Our findings suggest that tirzepatide probably leads to a significant reduction in albuminuria across all administered doses, while its use is associated with a neutral effect on creatinine clearance as a measure of renal function. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Karakasis, Paschalis AU - Karakasis P AUID- ORCID: 0000-0002-3561-5713 AD - Second Department of Cardiology, Aristotle University of Thessaloniki, General Hospital "Hippokration", Thessaloniki, Greece. FAU - Patoulias, Dimitrios AU - Patoulias D AUID- ORCID: 0000-0002-6899-684X AD - Outpatient Department of Cardiometabolic Medicine, Aristotle University of Thessaloniki, General Hospital "Hippokration", Thessaloniki, Greece. FAU - Fragakis, Nikolaos AU - Fragakis N AD - Second Department of Cardiology, Aristotle University of Thessaloniki, General Hospital "Hippokration", Thessaloniki, Greece. FAU - Klisic, Aleksandra AU - Klisic A AD - Primary Health Care Center, Faculty of Medicine, University of Montenegro, Podgorica, Montenegro. FAU - Rizzo, Manfredi AU - Rizzo M AUID- ORCID: 0000-0002-9549-8504 AD - Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, School of Medicine, University of Palermo, Palermo, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20231220 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - OYN3CCI6QE (Tirzepatide) RN - AYI8EX34EU (Creatinine) RN - 0 (Albumins) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) SB - IM MH - Humans MH - *Albuminuria/urine MH - Creatinine/urine MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Kidney MH - Albumins MH - *Glucagon-Like Peptide-2 Receptor MH - *Gastric Inhibitory Polypeptide MH - Tirzepatide OTO - NOTNLM OT - albuminuria OT - glomerular filtration rate OT - renal function OT - tirzepatide OT - type 2 diabetes mellitus EDAT- 2023/12/20 06:42 MHDA- 2024/02/06 06:43 CRDT- 2023/12/20 05:29 PHST- 2023/11/20 00:00 [revised] PHST- 2023/10/23 00:00 [received] PHST- 2023/11/29 00:00 [accepted] PHST- 2024/02/06 06:43 [medline] PHST- 2023/12/20 06:42 [pubmed] PHST- 2023/12/20 05:29 [entrez] AID - 10.1111/dom.15410 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Mar;26(3):1090-1104. doi: 10.1111/dom.15410. Epub 2023 Dec 20. PMID- 38103177 OWN - NLM STAT- MEDLINE DCOM- 20240223 LR - 20260127 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 45 IP - 8 DP - 2024 Feb 21 TI - Reducing cardiovascular outcomes with semaglutide: a metabolic route for a SELECT few. PG - 570-571 LID - 10.1093/eurheartj/ehad823 [doi] FAU - Liuzzo, Giovanna AU - Liuzzo G AUID- ORCID: 0000-0002-5714-0907 AD - Department of Cardiovascular and Pulmonary Sciences, Catholic University School of Medicine, Largo F.Vito 1, 00168 Rome, Italy. AD - Department of Cardiovascular Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy. FAU - Patrono, Carlo AU - Patrono C AUID- ORCID: 0000-0002-6447-2424 AD - Department of Cardiovascular and Pulmonary Sciences, Catholic University School of Medicine, Largo F.Vito 1, 00168 Rome, Italy. AD - Department of Pharmacology, Catholic University School of Medicine, Largo F.Vito 1, 00168 Rome, Italy. LA - eng PT - Journal Article PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Glucagon-Like Peptides/therapeutic use MH - *Cardiovascular System MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide EDAT- 2023/12/16 12:42 MHDA- 2024/02/23 06:43 CRDT- 2023/12/16 11:42 PHST- 2024/02/23 06:43 [medline] PHST- 2023/12/16 12:42 [pubmed] PHST- 2023/12/16 11:42 [entrez] AID - 7476077 [pii] AID - 10.1093/eurheartj/ehad823 [doi] PST - ppublish SO - Eur Heart J. 2024 Feb 21;45(8):570-571. doi: 10.1093/eurheartj/ehad823. PMID- 38097902 OWN - NLM STAT- MEDLINE DCOM- 20240301 LR - 20260420 IS - 1559-0100 (Electronic) IS - 1355-008X (Print) IS - 1355-008X (Linking) VI - 83 IP - 3 DP - 2024 Mar TI - The effect of semaglutide on blood pressure in patients with type-2 diabetes: a systematic review and meta-analysis. PG - 571-584 LID - 10.1007/s12020-023-03636-9 [doi] AB - OBJECTIVE: To evaluate the blood pressure (BP) lowering ability of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), in individuals with type-2 diabetes (T2D). METHODS: Randomized controlled trials (RCTs) comparing subcutaneous or oral semaglutide with placebo or other antihyperglycemic agents (AHAs) in T2D patients were identified by searching PubMed, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library. These screened studies included the outcomes of interest: systolic and/or diastolic BP. Weighted mean differences (WMDs) and 95 % confidence intervals (CIs) were used to present the meta-analysis results. Pooled and sensitivity analyses were performed, and the risk of bias was evaluated. RESULTS: Twenty-nine RCTs with a total of 26985 participants were recruited in the final analysis. The WMD in change from baseline in systolic BP (SBP) of semaglutide versus placebo or other AHAs was -2.31 mmHg (95% CI: -3.11 to -1.51), while that for diastolic BP (DBP) was 0.09 mmHg (95% CI: -0.16 to 0.33). It also reduced glycated hemoglobin A1c (HbA1c) by 0.75% (95% CI: -0.92 to -0.58) and body weight loss by 2.80 kg (95% CI: -3.51 to -2.08). The reduction in SBP was similar for subcutaneous and oral administration of semaglutide, with -2.36 (95% CI: -3.38 to -1.35) and -2.50 (95% CI: -3.48 to -1.53), respectively. CONCLUSIONS: In T2D, SBP decreased significantly in the semaglutide group compared with placebo or other active controls. According to the efficacy results from this meta-analysis, subcutaneous and oral semaglutide have similar SBP-reducing effects. Therefore, the treatment of T2D patients with subcutaneous semaglutide or oral preparations is beneficial for reducing SBP. CI - (c) 2023. The Author(s). FAU - Wu, Wei AU - Wu W AD - Department of Geriatrics, Chun'an First People's Hospital (Zhejiang Provincial People's Hospital Chun'an Branch), Hangzhou, 311700, Zhejiang, China. FAU - Tong, Huo-Mu AU - Tong HM AD - Department of Endocrinology, Chun'an First People's Hospital (Zhejiang Provincial People's Hospital Chun'an Branch), Hangzhou, 311700, Zhejiang, China. FAU - Li, Yun-Sheng AU - Li YS AD - Department of Geriatrics, Chun'an First People's Hospital (Zhejiang Provincial People's Hospital Chun'an Branch), Hangzhou, 311700, Zhejiang, China. FAU - Cui, Jia AU - Cui J AD - Department of Endocrinology, Chun'an First People's Hospital (Zhejiang Provincial People's Hospital Chun'an Branch), Hangzhou, 311700, Zhejiang, China. cuijiadl@outlook.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20231215 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Blood Pressure MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC10902041 OTO - NOTNLM OT - Blood pressure OT - Meta-analysis OT - Semaglutide OT - Type-2 diabetes COIS- The authors declare no competing interests. EDAT- 2023/12/15 06:42 MHDA- 2024/03/01 06:44 PMCR- 2023/12/15 CRDT- 2023/12/15 00:08 PHST- 2023/08/07 00:00 [received] PHST- 2023/11/29 00:00 [accepted] PHST- 2024/03/01 06:44 [medline] PHST- 2023/12/15 06:42 [pubmed] PHST- 2023/12/15 00:08 [entrez] PHST- 2023/12/15 00:00 [pmc-release] AID - 10.1007/s12020-023-03636-9 [pii] AID - 3636 [pii] AID - 10.1007/s12020-023-03636-9 [doi] PST - ppublish SO - Endocrine. 2024 Mar;83(3):571-584. doi: 10.1007/s12020-023-03636-9. Epub 2023 Dec 15. PMID- 38095657 OWN - NLM STAT- MEDLINE DCOM- 20240206 LR - 20260401 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 67 IP - 3 DP - 2024 Mar TI - Dose-response effects on HbA(1c) and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. PG - 470-482 LID - 10.1007/s00125-023-06053-9 [doi] AB - AIMS/HYPOTHESIS: The aim of this study was to assess the dose-response effects of the subcutaneous glucagon receptor/glucagon-like peptide-1 receptor dual agonist survodutide (BI 456906) on HbA(1c) levels and bodyweight reduction. METHODS: This Phase II, multicentre, randomised, double-blind, parallel-group, placebo-controlled study, conducted in clinical research centres, assessed survodutide in participants aged 18-75 years with type 2 diabetes, an HbA(1c) level of 53-86 mmol/mol (7.0-10.0%) and a BMI of 25-50 kg/m(2) on a background of metformin therapy. Participants were randomised via interactive response technology to receive survodutide (up to 0.3, 0.9, 1.8 or 2.7 mg once weekly [qw; dose group (DG) 1-4, respectively] or 1.2 or 1.8 mg twice weekly [DG 5 and 6, respectively]), placebo or semaglutide (up to 1.0 mg qw). Participants and all those involved in the trial conduct/analysis were blinded; the semaglutide arm was open-label. The primary endpoint was absolute change from baseline in HbA(1c) after 16 weeks' treatment. The key secondary endpoint was relative change from baseline in bodyweight after 16 weeks' treatment. RESULTS: A total of 413 participants were randomised (DG1, n=50; DG2, n=50; DG3, n=52; DG4, n=50; DG5, n=51; DG6, n=50; semaglutide, n=50; placebo, n=60). The full analysis set comprised 411 treated participants (DG6, n=49; placebo, n=59). Adjusted mean (95% CI) HbA(1c) decreased from baseline (mean +/- SD 64.7+/-9.2 mmol/mol [8.07+/-0.84%] after 16 weeks' treatment: DG1 (n=41), -9.92 mmol/mol (-12.27, -7.56; -0.91% [-1.12, -0.69]); DG2 (n=46), -15.95 mmol/mol (-18.27, -13.63; -1.46% [-1.67, -1.25]); DG3 (n=36), -18.72 mmol/mol (-21.15, -16.29; -1.71% [-1.94, -1.49]); DG4 (n=33), -17.01 mmol/mol (-19.59, -14.43; -1.56% [-1.79, -1.32]); DG5 (n=44), -17.84 mmol/mol (-20.18, -15.51; -1.63% [-1.85, -1.42]); DG6 (n=36), -18.38 mmol/mol (-20.90, -15.87; -1.68% [-1.91, -1.45]). The mean reduction in HbA(1c) was similar with low-dose survodutide (DG2: -15.95 mmol/mol [-1.46%]; n=46) and semaglutide (-16.07 mmol/mol [-1.47%]; n=45). Mean (95% CI) bodyweight decreased dose-dependently up to -8.7% (-10.1, -7.3; DG6, n=37); survodutide >/=1.8 mg qw produced greater bodyweight reductions than semaglutide (-5.3% [-6.6, -4.1]; n=45). Adverse events (AEs) were reported for 77.8% of survodutide-treated participants (mainly gastrointestinal), 52.5% receiving placebo and 52.0% receiving semaglutide. CONCLUSIONS/INTERPRETATION: Survodutide reduced HbA(1c) levels and bodyweight after 16 weeks' treatment in participants with type 2 diabetes. Dose-related gastrointestinal AEs could be mitigated with slower dose escalations. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153929 and EudraCT 2019-002390-60. FUNDING: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany. CI - (c) 2023. The Author(s). FAU - Bluher, Matthias AU - Bluher M AUID- ORCID: 0000-0003-0208-2065 AD - Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum Munchen, University of Leipzig and University Hospital Leipzig, Leipzig, Germany. matthias.blueher@medizin.uni-leipzig.de. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Velocity Clinical Research, Medical City, Dallas, TX, USA. FAU - Hoefler, Josef AU - Hoefler J AD - Staburo GmbH, Munich, Germany, on behalf of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany. FAU - Manuel, Raymond AU - Manuel R AD - Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA. FAU - Hennige, Anita M AU - Hennige AM AUID- ORCID: 0000-0002-5149-4966 AD - Boehringer Ingelheim International GmbH, Biberach an der Riss, Germany. anita.hennige@boehringer-ingelheim.com. LA - eng SI - ClinicalTrials.gov/NCT04153929 SI - EudraCT/EudraCT 2019-002390-60 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20231214 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Hypoglycemic Agents) RN - 9007-92-5 (Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Peptides) RN - 53AXN4NNHX (Semaglutide) RN - 0 (BI 456906) SB - IM EIN - Diabetologia. 2024 Apr;67(4):758. doi: 10.1007/s00125-024-06095-7. PMID: 38349400 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/chemically induced MH - Hypoglycemic Agents/adverse effects MH - Glucagon MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Treatment Outcome MH - Glucagon-Like Peptide 1 MH - Double-Blind Method MH - *Glucagon-Like Peptides MH - *Peptides MH - Semaglutide PMC - PMC10844353 OTO - NOTNLM OT - Bodyweight loss OT - Dual incretin agonist OT - Glucagon OT - Glucagon-like peptide-1 OT - Obesity OT - Pharmacotherapy OT - Semaglutide OT - Survodutide OT - Type 2 diabetes EDAT- 2023/12/14 12:41 MHDA- 2024/02/06 06:42 PMCR- 2023/12/14 CRDT- 2023/12/14 11:04 PHST- 2023/05/18 00:00 [received] PHST- 2023/08/17 00:00 [accepted] PHST- 2024/02/06 06:42 [medline] PHST- 2023/12/14 12:41 [pubmed] PHST- 2023/12/14 11:04 [entrez] PHST- 2023/12/14 00:00 [pmc-release] AID - 10.1007/s00125-023-06053-9 [pii] AID - 6053 [pii] AID - 10.1007/s00125-023-06053-9 [doi] PST - ppublish SO - Diabetologia. 2024 Mar;67(3):470-482. doi: 10.1007/s00125-023-06053-9. Epub 2023 Dec 14. PMID- 38093651 OWN - NLM STAT- MEDLINE DCOM- 20240126 LR - 20260613 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 7 IP - 1 DP - 2024 Jan TI - Glucagon-like peptide agonists: A prospective review. PG - e462 LID - 10.1002/edm2.462 [doi] LID - e462 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as promising therapeutic options for addressing Type-2 diabetes, obesity, and related conditions. Among these, semaglutide, tirzepatide, liraglutide etc., all notable GLP-1RA, have gained attention owing to their favourable pharmacological properties and clinical efficacy. AIMS: This comprehensive review aims to provide a detailed analysis of both the currently available GLP-1RAs in the market and those undergoing clinical trials. The focus is on examining their mechanism of action, pharmacokinetics, efficacy in glycemic control and weight management, safety profile, and potential applications. MATERIALS & METHODS: The review employs a systematic approach to gather information on GLP-1RAs. Relevant literature from the currently literature and ongoing clinical trials is thoroughly examined. Detailed scrutiny is applied to understand the mechanism of action, pharmacokinetic properties, and clinical outcomes of these agents. RESULTS: The review presents a comprehensive overview of the GLP-1RAs, highlighting their distinct mechanisms of action, pharmacokinetic profiles, and clinical effectiveness in glycemic control and weight management. Safety profiles are also discussed, providing a holistic understanding of these therapeutic agents. DISCUSSION: The findings are discussed in the context of advancements in the field of GLP-1RAs. Potential applications beyond diabetes and obesity are explored, shedding light on the broader implications of these agents in managing related conditions. CONCLUSION: In conclusion, this review underscores the significance of GLP-1RAs, with a specific focus on semaglutide, in the management of type 2 diabetes, obesity, and beyond. By synthesizing information on their mechanisms, pharmacokinetics, efficacy, and safety, this review provides valuable insights into the potential benefits these agents offer, contributing to the ongoing discourse in the field. CI - (c) 2023 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Mariam, Zamara AU - Mariam Z AD - Pharmaceutical Scientist, Inc., Chicago, Illinois, USA. FAU - Niazi, Sarfaraz K AU - Niazi SK AUID- ORCID: 0000-0002-0513-0336 AD - College of Pharmacy, University of Illinois, Chicago, Illinois, USA. LA - eng PT - Journal Article PT - Review DEP - 20231214 PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Prospective Studies MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10782143 OTO - NOTNLM OT - GLP-1 OT - GLP-2 OT - cancer OT - diabetes OT - glucagon OT - hormones OT - neurological disorders COIS- The authors declare no conflict of interest. Pharmaceutical Scientist, Inc. is a professional consulting company in pharmaceutical sciences. EDAT- 2023/12/14 06:42 MHDA- 2024/01/26 06:44 PMCR- 2023/12/14 CRDT- 2023/12/14 03:16 PHST- 2023/11/03 00:00 [revised] PHST- 2023/08/01 00:00 [received] PHST- 2023/11/19 00:00 [accepted] PHST- 2024/01/26 06:44 [medline] PHST- 2023/12/14 06:42 [pubmed] PHST- 2023/12/14 03:16 [entrez] PHST- 2023/12/14 00:00 [pmc-release] AID - EDM2462 [pii] AID - 10.1002/edm2.462 [doi] PST - ppublish SO - Endocrinol Diabetes Metab. 2024 Jan;7(1):e462. doi: 10.1002/edm2.462. Epub 2023 Dec 14. PMID- 38091192 OWN - NLM STAT- MEDLINE DCOM- 20240111 LR - 20261010 IS - 1708-0428 (Electronic) IS - 0960-8923 (Linking) VI - 34 IP - 1 DP - 2024 Jan TI - Effect of Swallow Balloon Therapy with the Combination of Semaglutide Oral Formulation: a Randomised Double-Blind Single-Centre Study. PG - 198-205 LID - 10.1007/s11695-023-06975-8 [doi] AB - BACKGROUND: Obesity is a significant public health issue; new therapies and pharmaceutical approaches to weight management are needed. OBJECTIVE: This study assesses weight reduction efficacy in the novel swallow balloon procedure and semaglutide, both promising non-surgical and pharmaceutical options, addressing obesity's critical public health challenge. METHODS: This was a computer-generated, blocked randomisation, double-blind, single-centre study. Fifty-seven participants were assigned to swallow balloon therapy group I (with semaglutide), and 58 were assigned to swallow balloon therapy group II (without semaglutide). All treatment doses were orally administered once daily (3 mg for the 1(st) month, 7 mg for the 2(nd) month, and 14 mg for the 3(rd) and 4(th) months after the placement of the swallow balloon). All the data were statistically analysed. RESULTS: The groups were highly well-matched. The %TWL in group I was 7.9%, 12.5%, 15.2%, and 17.6% and in group II was 6.1%, 10.5%, 12.8%, and 13.7% at 1, 2, 3, and 4 months, respectively. The most common adverse events (AEs) were nausea and vomiting, observed within the week. The resolution of T2DM, HTN, and OSA was 64.7% vs 55.5%, 64.3% vs 58.8%, and 72.0 vs 57.8% in groups I vs II, respectively. QoL significantly improved 4 months postoperatively in both groups. No major late complications occurred in either of the groups. CONCLUSION: The study supports the efficacy of swallow balloon therapy combined with semaglutide oral formulation in promoting weight loss and improving comorbid conditions. The findings highlight the potential of this combined approach in managing obesity and its associated health issues. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Mathur, Winni AU - Mathur W AD - Mohak Bariatrics and Robotics Center, Sri Aurobindo University, Indore-Ujjain Highway, Indore, Madhya Pradesh, 453555, India. FAU - Kosta, Susmit AU - Kosta S AD - Mohak Bariatrics and Robotics Center, Sri Aurobindo University, Indore-Ujjain Highway, Indore, Madhya Pradesh, 453555, India. FAU - Reddy, Manoj AU - Reddy M AD - Mohak Bariatrics and Robotics Center, Sri Aurobindo University, Indore-Ujjain Highway, Indore, Madhya Pradesh, 453555, India. FAU - Neto, Manoel Galvao AU - Neto MG AD - Mohak Bariatrics and Robotics Center, Sri Aurobindo University, Indore-Ujjain Highway, Indore, Madhya Pradesh, 453555, India. FAU - Bhandari, Mohit AU - Bhandari M AUID- ORCID: 0000-0001-9608-4808 AD - Mohak Bariatrics and Robotics Center, Sri Aurobindo University, Indore-Ujjain Highway, Indore, Madhya Pradesh, 453555, India. drmohitbhandari@gmail.com. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20231213 PL - United States TA - Obes Surg JT - Obesity surgery JID - 9106714 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Obes Surg. 2024 Oct;34(10):3914-3915. doi: 10.1007/s11695-024-07463-3. PMID: 39167150 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity, Morbid/drug therapy/surgery MH - Quality of Life MH - Treatment Outcome MH - Weight Loss MH - Semaglutide OTO - NOTNLM OT - Non-surgical approach OT - Obesity OT - Semaglutide OT - Swallow balloon OT - Weight loss EDAT- 2023/12/13 18:42 MHDA- 2024/01/11 07:43 CRDT- 2023/12/13 13:33 PHST- 2023/10/10 00:00 [received] PHST- 2023/11/26 00:00 [accepted] PHST- 2023/11/15 00:00 [revised] PHST- 2024/01/11 07:43 [medline] PHST- 2023/12/13 18:42 [pubmed] PHST- 2023/12/13 13:33 [entrez] AID - 10.1007/s11695-023-06975-8 [pii] AID - 10.1007/s11695-023-06975-8 [doi] PST - ppublish SO - Obes Surg. 2024 Jan;34(1):198-205. doi: 10.1007/s11695-023-06975-8. Epub 2023 Dec 13. PMID- 38087976 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20250103 IS - 1744-764X (Electronic) IS - 1474-0338 (Linking) VI - 23 IP - 1 DP - 2024 Jan TI - The association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: reports to the Food and Drug Administration Adverse Event Reporting System (FAERS). PG - 47-55 LID - 10.1080/14740338.2023.2295397 [doi] AB - INTRODUCTION: Recently, the European Medicines Agency (EMA) received reports of suicidal thoughts and self-injury associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) liraglutide and semaglutide. RESEARCH DESIGN AND METHODS: Herein, we sought to evaluate suicidality associated with all GLP-1 RAs relative to other glucose-lowering agents currently approved by the United States Food and Drug Administration (FDA). Reports of suicidal ideation, "depression/suicidal", suicidal behavior, suicidal attempts, and completed suicide associated with GLP-1 RA exposure reported to the FDA between 2005 and October 2023 were obtained from the FDA Adverse Event Reporting System (FAERS). We present data using the reporting odds ratio (ROR). The ROR was considered significant when the lower limit of the 95% confidence interval (CI) was greater than 1.0. RESULTS: Disproportionate reporting of suicidal ideation and "depression/suicidal" was observed with semaglutide and liraglutide. Disproportionate reporting of suicidal behavior, suicide attempts, and completed suicide was not observed for any of the FDA-approved GLP-1 RAs. CONCLUSIONS: Using the Bradford Hill criteria, however, and taking into consideration confounders, no causal link between GLP-1 RAs and suicidality exists. FAU - McIntyre, Roger S AU - McIntyre RS AUID- ORCID: 0000-0003-4733-2523 AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. AD - Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. FAU - Mansur, Rodrigo B AU - Mansur RB AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. AD - Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada. FAU - Rosenblat, Joshua D AU - Rosenblat JD AD - Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. AD - Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada. FAU - Kwan, Angela T H AU - Kwan ATH AUID- ORCID: 0000-0003-4013-1112 AD - Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada. AD - Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. LA - eng PT - Journal Article DEP - 20231219 PL - England TA - Expert Opin Drug Saf JT - Expert opinion on drug safety JID - 101163027 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - United States MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Liraglutide/adverse effects MH - *Diabetes Mellitus, Type 2 MH - Suicidal Ideation MH - Glucagon-Like Peptide-1 Receptor Agonists MH - United States Food and Drug Administration MH - *Suicide MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptides OTO - NOTNLM OT - Dulaglutide OT - Exenatide OT - Glucagon-like peptide 1 (GLP-1) OT - liraglutide OT - lixisenatide OT - semaglutide OT - suicide OT - tirzepatide EDAT- 2023/12/13 06:42 MHDA- 2024/02/12 15:44 CRDT- 2023/12/13 03:33 PHST- 2024/02/12 15:44 [medline] PHST- 2023/12/13 06:42 [pubmed] PHST- 2023/12/13 03:33 [entrez] AID - 10.1080/14740338.2023.2295397 [doi] PST - ppublish SO - Expert Opin Drug Saf. 2024 Jan;23(1):47-55. doi: 10.1080/14740338.2023.2295397. Epub 2023 Dec 19. PMID- 38082468 OWN - NLM STAT- MEDLINE DCOM- 20240206 LR - 20260806 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 3 DP - 2024 Mar TI - Once-weekly semaglutide reduces the risk of cardiovascular events in people with type 2 diabetes and polyvascular disease: A post hoc analysis. PG - 1129-1132 LID - 10.1111/dom.15396 [doi] FAU - Kobo, Ofer AU - Kobo O AUID- ORCID: 0000-0001-7418-498X AD - Hillel Yaffe Medical Centre, Hadera, Israel. FAU - Cavender, Matthew A AU - Cavender MA AUID- ORCID: 0000-0002-4466-4760 AD - University of North Carolina, Chapel Hill, North Carolina, USA. FAU - Jensen, Thomas Jon AU - Jensen TJ AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kuhlman, Anja Birk AU - Kuhlman AB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Verma, Subodh AU - Verma S AD - St. Michael's Hospital of Unity Health, Toronto, Canada. LA - eng GR - Novo Nordisk A/S/ PT - Letter DEP - 20231211 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Hypoglycemic Agents/adverse effects MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Semaglutide EDAT- 2023/12/12 06:42 MHDA- 2024/02/06 06:42 CRDT- 2023/12/12 00:14 PHST- 2023/10/27 00:00 [revised] PHST- 2023/08/03 00:00 [received] PHST- 2023/11/17 00:00 [accepted] PHST- 2024/02/06 06:42 [medline] PHST- 2023/12/12 06:42 [pubmed] PHST- 2023/12/12 00:14 [entrez] AID - 10.1111/dom.15396 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Mar;26(3):1129-1132. doi: 10.1111/dom.15396. Epub 2023 Dec 11. PMID- 38073422 OWN - NLM STAT- MEDLINE DCOM- 20240206 LR - 20260918 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 3 DP - 2024 Mar TI - Glycaemic control efficacy of switching from dipeptidyl peptidase-4 inhibitors to oral semaglutide in subjects with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 2 study). PG - 961-970 LID - 10.1111/dom.15393 [doi] AB - AIM: To assess whether oral semaglutide provides better glycaemic control, compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) continuation, in people with type 2 diabetes. MATERIALS AND METHODS: In this multicentre, open-label, prospective, randomized, parallel-group comparison study, participants receiving DPP-4is were either switched to oral semaglutide (3-14 mg/day) or continued on DPP-4is. The primary endpoint was the change in glycated haemoglobin (HbA1c) over 24 weeks. Secondary endpoints included changes in metabolic parameters and biomarkers, along with the occurrence of adverse events. Factors associated with HbA1c improvement were also explored. RESULTS: In total, 174 eligible participants were enrolled; 17 dropped out of the study. Consequently, 82 participants in the DPP-4i group and 75 participants in the semaglutide group completed the study and were included in the analysis. Improvement in HbA1c at week 24 was significantly greater when switching to semaglutide compared with DPP-4i continuation [-0.65 (95% confidence interval: -0.79, -0.51) vs. +0.05 (95% confidence interval: -0.07, 0.16) (p < .001)]. Body weight, lipid profiles and liver enzymes were significantly improved in the semaglutide group than in the DPP-4i continuation group. Multiple linear regression analysis revealed that baseline HbA1c and homeostasis model assessment 2-R were independently associated with HbA1c improvement after switching to semaglutide. Seven participants in the semaglutide group discontinued medication because of gastrointestinal symptoms. CONCLUSIONS: Although the potential for gastrointestinal symptoms should be carefully considered, switching from DPP-4is to oral semaglutide may be beneficial for glycaemic control and metabolic abnormalities in people with higher HbA1c and insulin resistance. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Furusawa, Sho AU - Furusawa S AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Nomoto, Hiroshi AU - Nomoto H AUID- ORCID: 0000-0003-0713-221X AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Yokoyama, Hiroki AU - Yokoyama H AD - Jiyugaoka Medical Clinic, Obihiro, Japan. FAU - Suzuki, Yuka AU - Suzuki Y AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Tsuzuki, Atsushi AU - Tsuzuki A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Takahashi, Kiyohiko AU - Takahashi K AD - Division of Diabetes and Endocrinology, Department of Medicine, Hakodate Central General Hospital, Hakodate, Japan. FAU - Miya, Aika AU - Miya A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Kameda, Hiraku AU - Kameda H AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Cho, Kyu Yong AU - Cho KY AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Takeuchi, Jun AU - Takeuchi J AD - Sapporo Diabetes and Thyroid Clinic, Sapporo, Japan. FAU - Nagai, So AU - Nagai S AD - Division of Diabetes and Endocrinology, Department of Medicine, Sapporo Medical Center, NTT East Corporation, Sapporo, Japan. FAU - Taneda, Shinji AU - Taneda S AD - Diabetes Center, Manda Memorial Hospital, Sapporo, Japan. FAU - Kurihara, Yoshio AU - Kurihara Y AD - Kurihara Clinic, Sapporo, Japan. FAU - Nakamura, Akinobu AU - Nakamura A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Atsumi, Tatsuya AU - Atsumi T AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. CN - SWITCH-SEMA 2 study group LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20231211 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects MH - Glycated Hemoglobin MH - Glycemic Control MH - Prospective Studies MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptides/adverse effects MH - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/therapeutic use MH - Semaglutide OTO - NOTNLM OT - DPP-IV inhibitor OT - GLP-1 analogue OT - clinical trial OT - glycaemic control OT - randomized trial OT - type 2 diabetes EDAT- 2023/12/11 06:45 MHDA- 2024/02/06 06:42 CRDT- 2023/12/11 03:43 PHST- 2023/11/10 00:00 [revised] PHST- 2023/10/13 00:00 [received] PHST- 2023/11/20 00:00 [accepted] PHST- 2024/02/06 06:42 [medline] PHST- 2023/12/11 06:45 [pubmed] PHST- 2023/12/11 03:43 [entrez] AID - 10.1111/dom.15393 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Mar;26(3):961-970. doi: 10.1111/dom.15393. Epub 2023 Dec 11. PMID- 38065435 OWN - NLM STAT- MEDLINE DCOM- 20240129 LR - 20260715 IS - 2212-8778 (Electronic) IS - 2212-8778 (Linking) VI - 79 DP - 2024 Jan TI - Evaluation of long acting GLP1R/GCGR agonist in a DIO and biopsy-confirmed mouse model of NASH suggest a beneficial role of GLP-1/glucagon agonism in NASH patients. PG - 101850 LID - S2212-8778(23)00184-9 [pii] LID - 10.1016/j.molmet.2023.101850 [doi] LID - 101850 AB - OBJECTIVE: The metabolic benefits of GLP-1 receptor (GLP-1R) agonists on glycemic and weight control are well established as therapy for type 2 diabetes and obesity. Glucagon's ability to increase energy expenditure is well described, and the combination of these mechanisms-of-actions has the potential to further lower hepatic steatosis in metabolic disorders and could therefore be attractive for the treatment for non-alcoholic steatohepatitis (NASH). Here, we have investigated the effects of a dual GLP-1/glucagon receptor agonist NN1177 on hepatic steatosis, fibrosis, and inflammation in a preclinical mouse model of NASH. Having observed strong effects on body weight loss in a pilot study with NN1177, we hypothesized that direct engagement of the hepatic glucagon receptor (GCGR) would result in a superior effect on steatosis and other liver related parameters as compared to the GLP-1R agonist semaglutide at equal body weight. METHODS: Male C57Bl/6 mice were fed a diet high in trans-fat, fructose, and cholesterol (Diet-Induced Obese (DIO)-NASH) for 36 weeks. Following randomization based on the degree of fibrosis at baseline, mice were treated once daily with subcutaneous administration of a vehicle or three different doses of NN1177 or semaglutide for 8 weeks. Hepatic steatosis, inflammation and fibrosis were assessed by immunohistochemistry and morphometric analyses. Plasma levels of lipids and liver enzymes were determined, and hepatic gene expression was analyzed by RNA sequencing. RESULTS: NN1177 dose-dependently reduced body weight up to 22% compared to vehicle treatment. Plasma levels of ALT, a measure of liver injury, were reduced in all treatment groups with body weight loss. The dual agonist reduced hepatic steatosis to a greater extent than semaglutide at equal body weight loss, as demonstrated by three independent methods. Both the co-agonist and semaglutide significantly decreased histological markers of inflammation such as CD11b and Galectin-3, in addition to markers of hepatic stellate activation (alphaSMA) and fibrosis (Collagen I). Interestingly, the maximal beneficial effects on above mentioned clinically relevant endpoints of NN1177 treatment on hepatic health appear to be achieved with the middle dose tested. Administering the highest dose resulted in a further reduction of liver fat and accompanied by a massive induction in genes involved in oxidative phosphorylation and resulted in exaggerated body weight loss and a downregulation of a module of co-expressed genes involved in steroid hormone biology, bile secretion, and retinol and linoleic acid metabolism that are also downregulated due to NASH itself. CONCLUSIONS: These results indicate that, in a setting of overnutrition, the liver health benefits of activating the fasting-related metabolic pathways controlled by the glucagon receptor displays a bell-shaped curve. This observation is of interest to the scientific community, due to the high number of ongoing clinical trials attempting to leverage the positive effects of glucagon biology to improve metabolic health. CI - Copyright (c) 2023 The Authors. Published by Elsevier GmbH.. All rights reserved. FAU - Monfeuga, Thomas AU - Monfeuga T AD - AI & Digital Research, Research & Early Development, Novo Nordisk Research Centre Oxford, UK. FAU - Norlin, Jenny AU - Norlin J AD - Novo Nordisk A/S, Novo Park, DK-2750 Maaloev, Denmark. FAU - Bugge, Anne AU - Bugge A AD - Novo Nordisk A/S, Novo Park, DK-2750 Maaloev, Denmark. FAU - Gaalsgaard, Elisabeth D AU - Gaalsgaard ED AD - Novo Nordisk A/S, Novo Park, DK-2750 Maaloev, Denmark. FAU - Prada-Medina, Cesar A AU - Prada-Medina CA AD - AI & Digital Research, Research & Early Development, Novo Nordisk Research Centre Oxford, UK. FAU - Latta, Markus AU - Latta M AD - Novo Nordisk A/S, Novo Park, DK-2750 Maaloev, Denmark. FAU - Veidal, Sanne S AU - Veidal SS AD - Gubra A/S, Horsholm Kongevej 11, B, DK-2970 Horsholm, Denmark. FAU - Petersen, Pia S AU - Petersen PS AD - Gubra A/S, Horsholm Kongevej 11, B, DK-2970 Horsholm, Denmark. FAU - Feigh, Michael AU - Feigh M AD - Gubra A/S, Horsholm Kongevej 11, B, DK-2970 Horsholm, Denmark. FAU - Holst, Dorte AU - Holst D AD - Novo Nordisk A/S, Novo Park, DK-2750 Maaloev, Denmark. Electronic address: doho@novonordisk.com. LA - eng SI - GEO/GSE162694 SI - GEO/SRP295965 SI - GEO/GSE130970 SI - GEO/SRP19735 SI - GEO/GSE220519 PT - Journal Article DEP - 20231207 PL - Germany TA - Mol Metab JT - Molecular metabolism JID - 101605730 RN - 9007-92-5 (Glucagon) RN - 0 (Receptors, Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - Male MH - Animals MH - Mice MH - *Non-alcoholic Fatty Liver Disease/metabolism MH - Glucagon MH - Receptors, Glucagon/genetics MH - *Diabetes Mellitus, Type 2/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Pilot Projects MH - Obesity/metabolism MH - Body Weight MH - Diet MH - Liver Cirrhosis/metabolism MH - Weight Loss MH - Glucagon-Like Peptide 1/agonists MH - Inflammation MH - Biopsy PMC - PMC10772820 OTO - NOTNLM OT - Fibrogenesis OT - GLP1R/GCGR agonist OT - Hepatic steatosis OT - Transcriptome profiling COIS- Declaration of competing interest Thomas Monfeuga, Jenny Norlin, Anne Bugge, Elisabeth D. Gaalsgaard, Cesar A. Prada-Medina, Markus Latta, Sanne S. Veidal and Dorte Holst are employees of Novo Nordisk A/S and shareholders in Novo Nordisk A/S. Pia S. Petersen is currently employee at Ascendis Pharma A/S and Michael Feigh is employee at Gubra A/S. EDAT- 2023/12/09 05:42 MHDA- 2024/01/29 06:44 PMCR- 2023/12/07 CRDT- 2023/12/08 19:29 PHST- 2023/10/04 00:00 [received] PHST- 2023/11/28 00:00 [revised] PHST- 2023/12/02 00:00 [accepted] PHST- 2024/01/29 06:44 [medline] PHST- 2023/12/09 05:42 [pubmed] PHST- 2023/12/08 19:29 [entrez] PHST- 2023/12/07 00:00 [pmc-release] AID - S2212-8778(23)00184-9 [pii] AID - 101850 [pii] AID - 10.1016/j.molmet.2023.101850 [doi] PST - ppublish SO - Mol Metab. 2024 Jan;79:101850. doi: 10.1016/j.molmet.2023.101850. Epub 2023 Dec 7. PMID- 38061595 OWN - NLM STAT- MEDLINE DCOM- 20240125 LR - 20260527 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 199 DP - 2024 Jan TI - Evaluation and comparison of efficacy and safety of tirzepatide and semaglutide in patients with type 2 diabetes mellitus: A Bayesian network meta-analysis. PG - 107031 LID - S1043-6618(23)00387-0 [pii] LID - 10.1016/j.phrs.2023.107031 [doi] AB - BACKGROUND: As new antidiabetic drugs, tirzepatide (Tir) and semaglutide (Sem) are progressively applied in clinical practice. However, their efficacy and safety profiles have not been comprehensively assessed. Therefore, a Bayesian network meta-analysis was used to evaluate and compare the efficacy and safety of Tir and Sem in treating type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov were systematically searched from inception to April 3rd, 2023. Randomized clinical trials (RCTs) comparing the efficacy and safety of Tir and Sem with placebo or the other antidiabetic drugs in treating T2DM were included. The efficacy outcomes included changes in glycated hemoglobin (HbA1c), body weight (BW), body mass index (BMI), and the proportion of participants with HbA1c< 7 %. The safety outcome was the proportion of participants experiencing gastrointestinal adverse events (GIAEs). RESULTS: A total of 38 studies involving 34,166 participants were included. Compared to 1 mg of subcutaneous Sem (Sem SC), 5 mg, 10 mg and 15 mg of Tir demonstrated superior efficacy in reducing HbA1c (mean difference (MD), [95 % CI], -0.22 [-0.40, -0.03] %, -0.42 [-0.60, -0.24] % and -0.53 [-0.71, -0.35] %, respectively) and BW (MD [95 % CI], -1.48 [-2.53, -0.43] kg, -4.00 [-5.05, -2.95] kg and -5.71 [-6.73, -4.68] kg, respectively). Conversely, 7 mg and 14 mg of oral Sem (Sem PO) displayed inferior efficacy in reducing HbA1c (MD [95 % CI], 0.47 [0.26, 0.68] % and 0.35 [0.16, 0.54] %, respectively) and BW (MD [95 % CI], 2.36 [1.24, 3.48] kg and 1.11 [0.10, 2.13] kg). However, 20 mg and 40 mg of Sem PO were non-inferior in reducing HbA1c (MD [95 % CI], 0.13 [-0.29, 0.55] % and 0.01 [-0.38, 0.40] %, respectively) and BW (MD [95 % CI], -0.41 [-2.71, 1.90] kg and -1.32 [-3.58, 0.92] kg). In terms of safety, compared to 1 mg of Sem SC, 5 mg, 10 mg and 15 mg of Tir did not significantly increase the incidence of GIAEs (odd ratio (OR) [95 % CI], 0.70 [0.42, 1.10], 0.87 [0.52, 1.36] and 0.99 [0.60, 1.54], respectively), while 7 mg of Sem PO showed a lower incidence of GIAEs (OR [95 % CI], 0.48 [0.25, 0.83]). Compared to insulin, 0.5 mg of Sem SC, 1 mg of Sem SC, 5 mg of Tir, 10 mg of Tir and 15 mg of Tir displayed better efficacy in lowering HbA1c (MD [95 % CI], -0.40 [-0.63, -0.18] %, -0.69 [-0.90, -0.48] %, -0.91 [-1.10, -0.72] %, -1.11 [-1.30, -0.92] % and -1.22 [-1.41, -1.03] %, respectively) and BW (MD [95 % CI], -5.34[-6.60, -4.09] kg, -6.70 [-7.90,-5.51] kg, -8.18 [-9.27, -7.10] kg, -10.70 [-11.79, -9.61] kg and -12.41 [-13.49,-11.33] kg, respectively). According to the surface under the cumulative ranking curve (SUCRA) value, among all the included interventions, 15 mg of Tir exhibited the most potent effect in reducing HbA1c (99.81 %) and BW (99.98 %), followed by 10 mg of Tir (96.83 % and 95.72 %), 5 mg of Tir (92.88 % and 86.04 %), 1 mg of Sem SC (85.85 % and 74.97 %), 40 mg of Sem PO (83.66 % and 84.31 %), 20 mg of Sem PO (76.98 % and 77.12 %), 300 mg of Can (49.93 % and 60.89 %), insulin (36.38 % and 0.22 %) and 100 mg of Sit (12.28 % and 18.51 %) respectively. Meanwhile, 5 mg, 10 mg, and 15 mg of Tir (48.32 %, 30.96 %, and 21.07 %, respectively), 0.5 mg and 1 mg of Sem SC (33.54 % and 24.77 %, respectively) significantly increased the incidence of GIAEs. CONCLUSION: Both Tir and Sem demonstrated favorable antidiabetic effects and were particularly suitable for T2DM patients who were obese or overweight. Despite a high incidence of GIAEs, their safety profile was deemed acceptable. Tir was the best option among all the included interventions. CI - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Ding, Yanan AU - Ding Y AD - School of Pharmacy, Fudan University, Shanghai 201203, PR China. FAU - Shi, Yufei AU - Shi Y AD - School of Pharmacy, Fudan University, Shanghai 201203, PR China. FAU - Guan, Ruifang AU - Guan R AD - School of Pharmacy, Fudan University, Shanghai 201203, PR China. FAU - Yan, Shiwei AU - Yan S AD - School of Pharmacy, Fudan University, Shanghai 201203, PR China. FAU - Liu, Haiyang AU - Liu H AD - School of Pharmacy, Fudan University, Shanghai 201203, PR China. FAU - Wang, Zihan AU - Wang Z AD - School of Pharmacy, Fudan University, Shanghai 201203, PR China. FAU - Li, Jiyifan AU - Li J AD - School of Pharmacy, Fudan University, Shanghai 201203, PR China. FAU - Wang, Tiandian AU - Wang T AD - School of Pharmacy, Fudan University, Shanghai 201203, PR China. FAU - Cai, Weimin AU - Cai W AD - School of Pharmacy, Fudan University, Shanghai 201203, PR China. FAU - Ma, Guo AU - Ma G AD - School of Pharmacy, Fudan University, Shanghai 201203, PR China. Electronic address: mg0328@fudan.edu.cn. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20231205 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Body Weight MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Gastric Inhibitory Polypeptide/adverse effects MH - *Glucagon-Like Peptide-2 Receptor MH - *Glucagon-Like Peptides/adverse effects MH - Glycated Hemoglobin MH - Hypoglycemic Agents/adverse effects MH - Insulin/therapeutic use MH - Tirzepatide MH - Semaglutide OTO - NOTNLM OT - Bayesian network meta-analysis OT - Semaglutide OT - Tirzepatide OT - Type 2 diabetes mellitus COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/12/08 00:42 MHDA- 2024/01/15 12:43 CRDT- 2023/12/07 19:27 PHST- 2023/09/15 00:00 [received] PHST- 2023/12/03 00:00 [revised] PHST- 2023/12/04 00:00 [accepted] PHST- 2024/01/15 12:43 [medline] PHST- 2023/12/08 00:42 [pubmed] PHST- 2023/12/07 19:27 [entrez] AID - S1043-6618(23)00387-0 [pii] AID - 10.1016/j.phrs.2023.107031 [doi] PST - ppublish SO - Pharmacol Res. 2024 Jan;199:107031. doi: 10.1016/j.phrs.2023.107031. Epub 2023 Dec 5. PMID- 38056618 OWN - NLM STAT- MEDLINE DCOM- 20231220 LR - 20250103 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 962 DP - 2024 Jan 5 TI - OXM-104, a potential candidate for the treatment of obesity, NASH and type 2 diabetes. PG - 176215 LID - S0014-2999(23)00729-X [pii] LID - 10.1016/j.ejphar.2023.176215 [doi] AB - OBJECTIVE: Dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonists are therapeutic agents with an interesting liver-specific mode of action suitable for metabolic complications. In this study, dual GLP-1 and glucagon receptor agonist OXM-104 is compared head-to-head with the once-daily dual GLP-1 and glucagon receptor agonist cotadutide and GLP-1 receptor agonist semaglutide to explore the metabolic efficacy of OXM-104. METHODS: The in vitro potencies of OXM-104, cotadutide and semaglutide were assessed using reporter assays. In addition, in vivo efficacy was investigated using mouse models of diet-induced obesity (DIO mice), diabetes (db/db mice) and diet-induced NASH mice (MS-NASH). RESULTS: OXM-104 was found to only activate the GLP-1 and glucagon with no cross-reactivity at the (GIP) receptor. Cotadutide was also found to activate the GLP-1 and glucagon receptors, whereas semaglutide only showed activity at the GLP-1 receptor. OXM-104, cotadutide, and semaglutide elicited marked reductions in body weight and improved glucose control. In contrast, hepatoprotective effects, i.e., reductions in steatosis and fibrosis, as well as liver fibrotic biomarkers, were more prominent with OXM-104 and cotadutide than those seen with semaglutide, demonstrated by an improved NAFLD activity score (NAS) by OXM-104 and cotadutide, underlining the importance of the glucagon receptor. CONCLUSION: These results show that dual GLP-1 and glucagon receptor agonism is superior to GLP-1 alone. OXM-104 was found to be a promising therapeutic candidate for the treatment of metabolic complications such as obesity, type 2 diabetes and NASH. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Melander, Simone Anna AU - Melander SA AD - Nordic Bioscience, 2730 Herlev, Denmark. Electronic address: sme@nordicbio.com. FAU - Kayed, Ashref AU - Kayed A AD - Nordic Bioscience, 2730 Herlev, Denmark. FAU - Andreassen, Kim Vietz AU - Andreassen KV AD - Nordic Bioscience, 2730 Herlev, Denmark. FAU - Karsdal, Morten Asser AU - Karsdal MA AD - Nordic Bioscience, 2730 Herlev, Denmark; KeyBioscience AG, Stans, Switzerland. FAU - Henriksen, Kim AU - Henriksen K AD - Nordic Bioscience, 2730 Herlev, Denmark; KeyBioscience AG, Stans, Switzerland. LA - eng PT - Journal Article DEP - 20231205 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Receptors, Glucagon) RN - 0 (Oxyntomodulin) RN - 9007-92-5 (Glucagon) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Mice MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - Receptors, Glucagon/metabolism MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Oxyntomodulin/pharmacology/therapeutic use MH - Glucagon/pharmacology MH - Obesity/drug therapy/metabolism MH - Glucagon-Like Peptide 1/pharmacology MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Diabetes OT - Dual GLP-1 and glucagon receptor agonist OT - NASH OT - Obesity OT - Oxyntomodulin COIS- Declaration of competing interest Morten A. Karsdal and Kim Henriksen own stock in Nordic Bioscience A/S. All authors are employed by Nordic Bioscience A/S. EDAT- 2023/12/07 00:42 MHDA- 2023/12/20 06:42 CRDT- 2023/12/06 19:24 PHST- 2023/07/05 00:00 [received] PHST- 2023/11/08 00:00 [revised] PHST- 2023/11/16 00:00 [accepted] PHST- 2023/12/20 06:42 [medline] PHST- 2023/12/07 00:42 [pubmed] PHST- 2023/12/06 19:24 [entrez] AID - S0014-2999(23)00729-X [pii] AID - 10.1016/j.ejphar.2023.176215 [doi] PST - ppublish SO - Eur J Pharmacol. 2024 Jan 5;962:176215. doi: 10.1016/j.ejphar.2023.176215. Epub 2023 Dec 5. PMID- 38055301 OWN - NLM STAT- MEDLINE DCOM- 20240109 LR - 20260127 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 331 IP - 1 DP - 2024 Jan 2 TI - At ObesityWeek, More Data and Questions About Semaglutide, Tirzepatide, and Retatrutide. PG - 9-11 LID - 10.1001/jama.2023.23141 [doi] FAU - Ruder, Kate AU - Ruder K LA - eng PT - Journal Article PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide Receptors) RN - 0 (Receptors, Gastrointestinal Hormone) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (retatrutide) RN - 0 (Fatty Acids) RN - 0 (Peptides) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Gastric Inhibitory Polypeptide/agonists/therapeutic use MH - Glucagon-Like Peptides/agonists/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - *Obesity/complications/drug therapy MH - *Anti-Obesity Agents/therapeutic use MH - Glucagon-Like Peptide Receptors/agonists/therapeutic use MH - Receptors, Gastrointestinal Hormone/agonists/therapeutic use MH - Tirzepatide MH - Semaglutide MH - Fatty Acids MH - Peptides OAB - This Medical News article discusses weight-loss medications highlighted at ObesityWeek 2023. OABL- eng EDAT- 2023/12/06 12:42 MHDA- 2024/01/03 09:43 CRDT- 2023/12/06 11:43 PHST- 2024/01/03 09:43 [medline] PHST- 2023/12/06 12:42 [pubmed] PHST- 2023/12/06 11:43 [entrez] AID - 2812829 [pii] AID - 10.1001/jama.2023.23141 [doi] PST - ppublish SO - JAMA. 2024 Jan 2;331(1):9-11. doi: 10.1001/jama.2023.23141. PMID- 38048543 OWN - NLM STAT- MEDLINE DCOM- 20240122 LR - 20260822 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 47 IP - 2 DP - 2024 Feb 1 TI - Occurrence of Gastrointestinal Adverse Events Upon GLP-1 Receptor Agonist Initiation With Concomitant Metformin Use: A Post Hoc Analysis of LEADER, STEP 2, SUSTAIN-6, and PIONEER 6. PG - 280-284 LID - 10.2337/dc23-1791 [doi] AB - OBJECTIVE: To assess the impact of concomitant metformin use on gastrointestinal adverse events during the initiation and titration of a glucagon-like peptide 1 receptor agonist (GLP-1RA). RESEARCH DESIGN AND METHODS: Using data from four clinical trials of liraglutide and semaglutide (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER], Semaglutide Treatment Effect in People with Obesity [STEP 2], Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6], and Peptide Innovation for Early Diabetes Treatment [PIONEER] 6), we compared the incidence of gastrointestinal adverse events during GLP-1RA initiation and titration in participants with and without concomitant metformin use. RESULTS: Of 16,996 participants, 12,928 (76%) were treated with metformin. Concomitant metformin use did not increase the percentage of participants who developed gastrointestinal adverse events or their severity during the observation window. Among participants experiencing gastrointestinal adverse events, metformin use did not increase study product discontinuation. Within treatment arms (GLP-1RA and placebo), a numerically higher percentage of metformin nonusers experienced gastrointestinal adverse events and discontinued the study product compared with metformin users. CONCLUSIONS: Concomitant metformin use does not increase occurrence of gastrointestinal symptoms during GLP-1RA initiation or impact GLP-1RA discontinuation. CI - (c) 2024 by the American Diabetes Association. FAU - Klein, Klara R AU - Klein KR AUID- ORCID: 0000-0002-5894-9054 AD - Division of Endocrinology and Metabolism, University of North Carolina School of Medicine, Chapel Hill, NC. FAU - Clemmensen, Kim K B AU - Clemmensen KKB AD - Novo Nordisk A/S, Soborg, Denmark. AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Fong, Edwin AU - Fong E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Olsen, Soren AU - Olsen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Abrahamsen, Trine AU - Abrahamsen T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - University of Texas Southwestern Medical Center, Dallas, TX. LA - eng SI - figshare/10.2337/figshare.24584865 GR - P30 DK127984/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 9100L32L2N (Metformin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Humans MH - *Metformin/adverse effects MH - *Diabetes Mellitus, Type 2/complications MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Liraglutide/adverse effects MH - Glucagon-Like Peptides/adverse effects PMC - PMC10834386 COIS- Duality of Interest. K.R.K. has received personal compensation from Novo Nordisk for consultation. I.L. received research funding (paid to institution) from Novo Nordisk, Sanofi, Merck, Pfizer, Mylan, and Boehringer Ingelheim, and received advisory/consulting fees and/or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, TargetPharma, Merck, Pfizer, Novartis, GI Dynamics, Mylan, Mannkind, Valeritas, Carmot, Zealand Pharma, Shionogi, Mediflix, and Bayer. E.F. is a former employee of Novo Nordisk. K.K.B.C., S.O., and T.J.A. are employees of Novo Nordisk. No other potential conflicts of interest relevant to this article were reported. EDAT- 2023/12/04 19:41 MHDA- 2024/01/22 06:43 PMCR- 2023/12/04 CRDT- 2023/12/04 16:33 PHST- 2023/09/22 00:00 [received] PHST- 2023/11/15 00:00 [accepted] PHST- 2024/01/22 06:43 [medline] PHST- 2023/12/04 19:41 [pubmed] PHST- 2023/12/04 16:33 [entrez] PHST- 2023/12/04 00:00 [pmc-release] AID - 153929 [pii] AID - 231791 [pii] AID - 10.2337/dc23-1791 [doi] PST - ppublish SO - Diabetes Care. 2024 Feb 1;47(2):280-284. doi: 10.2337/dc23-1791. PMID- 38038217 OWN - NLM STAT- MEDLINE DCOM- 20240118 LR - 20260127 IS - 1531-4995 (Electronic) IS - 0023-852X (Linking) VI - 134 IP - 2 DP - 2024 Feb TI - Semaglutide in Patients Undergoing Anesthesia for Otolaryngologic Procedures. PG - 543-544 LID - 10.1002/lary.31214 [doi] FAU - Casazza, Julia A AU - Casazza JA AUID- ORCID: 0000-0002-8358-2354 AD - Medical School, UT Southwestern Medical Center, Dallas, Texas, U.S.A. FAU - Kacker, Ashutosh AU - Kacker A AD - Department of Otolaryngology-Head and Neck Surgery, Weill Cornell Medical Center, New York, New York, U.S.A. LA - eng PT - Journal Article DEP - 20231201 PL - United States TA - Laryngoscope JT - The Laryngoscope JID - 8607378 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Anesthesia MH - *Anesthesiology MH - *Otolaryngology MH - Ear MH - *Diabetes Mellitus, Type 2 MH - *Glucagon-Like Peptides MH - Semaglutide EDAT- 2023/12/01 12:43 MHDA- 2024/01/18 06:42 CRDT- 2023/12/01 06:53 PHST- 2023/10/25 00:00 [revised] PHST- 2023/09/07 00:00 [received] PHST- 2023/11/22 00:00 [accepted] PHST- 2024/01/18 06:42 [medline] PHST- 2023/12/01 12:43 [pubmed] PHST- 2023/12/01 06:53 [entrez] AID - 10.1002/lary.31214 [doi] PST - ppublish SO - Laryngoscope. 2024 Feb;134(2):543-544. doi: 10.1002/lary.31214. Epub 2023 Dec 1. PMID- 38036669 OWN - NLM STAT- MEDLINE DCOM- 20240122 LR - 20261010 IS - 1759-5010 (Electronic) IS - 1759-5002 (Linking) VI - 21 IP - 2 DP - 2024 Feb TI - SELECT shows cardiovascular risk reduction with weight-loss drug semaglutide in people without diabetes. PG - 69 LID - 10.1038/s41569-023-00970-3 [doi] FAU - Fernandez-Ruiz, Irene AU - Fernandez-Ruiz I AD - Nature Reviews Cardiology, . nrcardio@nature.com. LA - eng PT - Comment PT - Journal Article PL - England TA - Nat Rev Cardiol JT - Nature reviews. Cardiology JID - 101500075 RN - 0 (Anti-Obesity Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. PMID: 37952131 MH - Humans MH - *Anti-Obesity Agents MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Risk Factors MH - Heart Disease Risk Factors MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptides MH - Semaglutide EDAT- 2023/12/01 00:43 MHDA- 2024/01/22 06:42 CRDT- 2023/11/30 23:40 PHST- 2024/01/22 06:42 [medline] PHST- 2023/12/01 00:43 [pubmed] PHST- 2023/11/30 23:40 [entrez] AID - 10.1038/s41569-023-00970-3 [pii] AID - 10.1038/s41569-023-00970-3 [doi] PST - ppublish SO - Nat Rev Cardiol. 2024 Feb;21(2):69. doi: 10.1038/s41569-023-00970-3. PMID- 38029929 OWN - NLM STAT- MEDLINE DCOM- 20240202 LR - 20250626 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 30 IP - 2 DP - 2024 Feb TI - Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists on Body Weight and Cardiometabolic Parameters in Individuals With Obesity and Without Diabetes: A Systematic Review and Meta-Analysis. PG - 160-171 LID - S1530-891X(23)00758-9 [pii] LID - 10.1016/j.eprac.2023.11.007 [doi] AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially for type 2 diabetes mellitus, show promise in promoting weight loss and improving heart health in obese individuals without diabetes. Our goal was to examine existing research for conclusive evidence on various types of GLP-1 RAs for weight loss and cardiometabolic benefits in obesity without diabetes. METHODS: We conducted an electronic search on PubMed, Scopus, and Cochrane Central using keywords, such as "GLP-1 RA," "obesity," and "weight loss." We considered all available global GLP-1 RAs for inclusion. Our analysis focused on weight loss, blood pressure (BP) changes (systolic and diastolic BPs), and lipid profile effects (high-density lipoprotein, low-density lipoprotein, total cholesterol, and triacylglycerol). We used a random-effects meta-analysis with the standardized mean difference (SMD), mean difference (MD), odds ratio, and relative risk to present the results. RESULTS: Our search yielded a total of 7535 articles. We included 15 trials in our study. GLP-1 RAs led to significant weight loss (MD, -8.77 kg; P <.01) in obese individuals. GLP-1 RAs also improved the systolic BP (MD, -4.13 mm Hg; P <.01), diastolic BP (MD, -1.39 mm Hg; P <.01), and lipid profiles, including improved levels of triacylglycerol (SMD, -0.99 mg/dL; P <.01), total cholesterol (SMD, -0.73 mg/dL; P <.01), very low-density lipoprotein (SMD, -1.11 mg/dL; P <.01), and low-density lipoprotein (SMD, -0.27 mg/dL; P <.01), and significantly increased high-density lipoprotein levels (SMD, 0.11 mg/dL; P <.01). However, GLP-1 RAs were associated with an increased risk of gastrointestinal adverse events. CONCLUSION: GLP-1 RAs were found to be beneficial for not only weight loss but also reduction in risk factors for cardiovascular disease such as BP and lipid profile. Consistent beneficial results were observed across the various subtypes of GLP-1 RAs. CI - Copyright (c) 2023 AACE. Published by Elsevier Inc. All rights reserved. FAU - Ansari, Huzaifa Ul Haq AU - Ansari HUH AD - Department of Internal Medicine, Dow University of Health Sciences, Pakistan. Electronic address: huzaifi1947123@gmail.com. FAU - Qazi, Shurjeel Uddin AU - Qazi SU AD - Department of Internal Medicine, Dow University of Health Sciences, Pakistan. FAU - Sajid, Faiza AU - Sajid F AD - Department of Medicine, Liaquat National Hospital and Medical College, Pakistan. FAU - Altaf, Zahabia AU - Altaf Z AD - Department of Internal Medicine, Dow University of Health Sciences, Pakistan. FAU - Ghazanfar, Shamas AU - Ghazanfar S AD - Department of Internal Medicine, Dow University of Health Sciences, Pakistan. FAU - Naveed, Naveen AU - Naveed N AD - Department of Medicine, Jinnah Sindh Medical University, Pakistan. FAU - Ashfaq, Amna Shakil AU - Ashfaq AS AD - Department of Internal Medicine, Dow University of Health Sciences, Pakistan. FAU - Siddiqui, Abdul Hannan AU - Siddiqui AH AD - Department of Internal Medicine, Dow University of Health Sciences, Pakistan. FAU - Iqbal, Hamza AU - Iqbal H AD - Department of Internal Medicine, Dow University of Health Sciences, Pakistan. FAU - Qazi, Sana AU - Qazi S AD - Department of Internal Medicine, Dow University of Health Sciences, Pakistan. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20231127 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Lipids) RN - 0 (Triglycerides) RN - 0 (Lipoproteins, HDL) RN - 0 (Lipoproteins, LDL) RN - 97C5T2UQ7J (Cholesterol) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide 1/adverse effects MH - Obesity/drug therapy/complications MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Weight Loss MH - Lipids MH - Triglycerides MH - Lipoproteins, HDL MH - Lipoproteins, LDL MH - Cholesterol OTO - NOTNLM OT - GIPRA OT - GLP-1 RAs OT - liraglutide OT - nondiabetic OT - obesity OT - semaglutide OT - tirzepatide COIS- Disclosure The authors have no conflicts of interest to disclose. EDAT- 2023/11/30 00:42 MHDA- 2024/02/02 06:43 CRDT- 2023/11/29 19:27 PHST- 2023/08/25 00:00 [received] PHST- 2023/11/02 00:00 [revised] PHST- 2023/11/19 00:00 [accepted] PHST- 2024/02/02 06:43 [medline] PHST- 2023/11/30 00:42 [pubmed] PHST- 2023/11/29 19:27 [entrez] AID - S1530-891X(23)00758-9 [pii] AID - 10.1016/j.eprac.2023.11.007 [doi] PST - ppublish SO - Endocr Pract. 2024 Feb;30(2):160-171. doi: 10.1016/j.eprac.2023.11.007. Epub 2023 Nov 27. PMID- 38019594 OWN - NLM STAT- MEDLINE DCOM- 20231201 LR - 20260127 IS - 1555-2101 (Electronic) IS - 0160-6689 (Linking) VI - 85 IP - 1 DP - 2023 Nov 27 TI - Significant Decrease in Alcohol Use Disorder Symptoms Secondary to Semaglutide Therapy for Weight Loss: A Case Series. LID - 23m15068 [pii] LID - 10.4088/JCP.23m15068 [doi] AB - Objective: Despite being a major cause of preventable death worldwide, alcohol use disorder (AUD) currently has only 3 FDA-approved pharmacotherapies. The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide has shown promise in preclinical studies for reducing alcohol consumption, but there are currently no randomized clinical trials that associate a decline in AUD symptoms with semaglutide use. This case series presents 6 patients with positive AUD screenings who were treated with semaglutide for weight loss. All subsequently exhibited significant improvement in AUD symptoms. Methods: Retrospective chart review was utilized to identify patients treated with semaglutide for weight loss who also had positive screenings for AUD on the Alcohol Use Disorder Identification Test (AUDIT; score > 8 considered positive) prior to initiation of semaglutide therapy. Six patients were identified who met these criteria. A paired t test was utilized to compare initial AUDIT scores with AUDIT scores after initiation of semaglutide therapy. Results: All 6 identified patients (100%) had significant reduction in AUD symptomatology based on AUDIT score improvement following treatment with semaglutide (mean decrease of 9.5 points, P < .001). Conclusions: This case series is consistent with preclinical data and suggests that GLP-1RAs have strong potential in the treatment of AUD. Additional randomized, placebo-controlled clinical studies are needed to fully assess the efficacy of semaglutide in treating AUD. CI - (c) Copyright 2023 Physicians Postgraduate Press, Inc. FAU - Richards, Jesse R AU - Richards JR AD - Department of Internal Medicine, University of Oklahoma School of Community Medicine, Tulsa. AD - Corresponding Author: Jesse R. Richards, DO, Schusterman Center, Office 3J33, 4502 E 41st St, Tulsa, OK 74135 (Jesse-R-Richards@ouhsc.edu). FAU - Dorand, Madisen Fae AU - Dorand MF AD - Department of Internal Medicine, University of Oklahoma School of Community Medicine, Tulsa. FAU - Royal, Kyleigh AU - Royal K AD - College of Medicine, University of Oklahoma School of Community Medicine, Tulsa. FAU - Mnajjed, Lana AU - Mnajjed L AD - College of Medicine, University of Oklahoma School of Community Medicine, Tulsa. FAU - Paszkowiak, Maria AU - Paszkowiak M AD - College of Medicine, University of Oklahoma School of Community Medicine, Tulsa. FAU - Simmons, W Kyle AU - Simmons WK AD - Department of Pharmacology & Physiology, Oklahoma State University, Center for Health Sciences, Tulsa. AD - Oklahoma State University Biomedical Imaging Center, OSU-Center for Health Sciences, Tulsa. LA - eng PT - Case Reports PT - Journal Article PT - Review DEP - 20231127 PL - United States TA - J Clin Psychiatry JT - The Journal of clinical psychiatry JID - 7801243 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/chemically induced MH - *Alcoholism/drug therapy MH - Retrospective Studies MH - Weight Loss MH - Alcohol Drinking MH - Semaglutide EDAT- 2023/11/29 18:42 MHDA- 2023/12/01 06:44 CRDT- 2023/11/29 12:03 PHST- 2023/12/01 06:44 [medline] PHST- 2023/11/29 18:42 [pubmed] PHST- 2023/11/29 12:03 [entrez] AID - 23m15068 [pii] AID - 10.4088/JCP.23m15068 [doi] PST - epublish SO - J Clin Psychiatry. 2023 Nov 27;85(1):23m15068. doi: 10.4088/JCP.23m15068. PMID- 38019508 OWN - NLM STAT- MEDLINE DCOM- 20231229 LR - 20260127 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 330 IP - 23 DP - 2023 Dec 19 TI - Semaglutide Improved Cardiovascular Health in People Without Diabetes. PG - 2241-2242 LID - 10.1001/jama.2023.23508 [doi] FAU - Harris, Emily AU - Harris E LA - eng PT - Journal Article PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Cardiovascular Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Cardiovascular Diseases/etiology/prevention & control MH - *Cardiovascular System/drug effects MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists/pharmacology/therapeutic use MH - Cardiovascular Agents/pharmacology/therapeutic use MH - Semaglutide EDAT- 2023/11/29 12:42 MHDA- 2023/12/20 06:43 CRDT- 2023/11/29 11:34 PHST- 2023/12/20 06:43 [medline] PHST- 2023/11/29 12:42 [pubmed] PHST- 2023/11/29 11:34 [entrez] AID - 2812511 [pii] AID - 10.1001/jama.2023.23508 [doi] PST - ppublish SO - JAMA. 2023 Dec 19;330(23):2241-2242. doi: 10.1001/jama.2023.23508. PMID- 38017205 OWN - NLM STAT- MEDLINE DCOM- 20231130 LR - 20260127 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 13 IP - 1 DP - 2023 Nov 28 TI - Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity. PG - 20998 LID - 10.1038/s41598-023-48267-2 [doi] LID - 20998 AB - Alcohol Use Disorder (AUD) contributes significantly to global mortality. GLP-1 (Glucagon-like peptide-1) and GLP-1/GIP (Glucose-dependent Insulinotropic Polypeptide) agonists, FDA-approved for managing type 2 diabetes and obesity, where the former has shown to effectively reduce the consumption of alcohol in animal models but no reports exist on the latter. In this report, we conducted two studies. In the first study, we conducted an analysis of abundant social media texts. Specifically, a machine-learning based attribution mapping of ~ 68,250 posts related to GLP-1 or GLP-1/GIP agonists on the Reddit platform. Secondly, we recruited participants (n = 153; current alcohol drinkers; BMI >/= 30) who self-reported either taking Semaglutide (GLP-1 agonist), Tirzepatide (the GLP-1/GIP combination) for >/= 30 days or, as a control group; no medication to manage diabetes or weight loss for a within and between subject remote study. In the social media study, we report 8 major themes including effects of medications (30%); diabetes (21%); and Weight loss and obesity (19%). Among the alcohol-related posts (n = 1580), 71% were identified as craving reduction, decreased desire to drink, and other negative effects. In the remote study, we observe a significantly lower self-reported intake of alcohol, drinks per drinking episode, binge drinking odds, Alcohol Use Disorders Identification Test (AUDIT) scores, and stimulating, and sedative effects in the Semaglutide or Tirzepatide group when compared to prior to starting medication timepoint (within-subjects) and the control group (between-subjects). In summary, we provide initial real-world evidence of reduced alcohol consumption in people with obesity taking Semaglutide or Tirzepatide medications, suggesting potential efficacy for treatment in AUD comorbid with obesity. CI - (c) 2023. The Author(s). FAU - Quddos, Fatima AU - Quddos F AD - Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA. AD - Graduate Program in Translational Biology, Medicine, and Health, Blacksburg, VA, USA. FAU - Hubshman, Zachary AU - Hubshman Z AD - Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA. AD - Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. FAU - Tegge, Allison AU - Tegge A AD - Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA. FAU - Sane, Daniel AU - Sane D AD - Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA. AD - Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. FAU - Marti, Erin AU - Marti E AD - Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA. FAU - Kablinger, Anita S AU - Kablinger AS AD - Virginia Tech Carilion School of Medicine, Roanoke, VA, USA. FAU - Gatchalian, Kirstin M AU - Gatchalian KM AD - Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA. FAU - Kelly, Amber L AU - Kelly AL AD - Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA. AD - Graduate Program in Translational Biology, Medicine, and Health, Blacksburg, VA, USA. FAU - DiFeliceantonio, Alexandra G AU - DiFeliceantonio AG AD - Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA. FAU - Bickel, Warren K AU - Bickel WK AD - Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA, USA. wkbickel@vtc.vt.edu. LA - eng PT - Journal Article DEP - 20231128 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 3K9958V90M (Ethanol) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - Humans MH - *Alcoholism/complications/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Alcohol Drinking/drug therapy MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptide 1 MH - Obesity/complications/drug therapy MH - Ethanol MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor MH - Hypoglycemic Agents MH - Tirzepatide MH - Semaglutide PMC - PMC10684505 COIS- Although the following activities/relationships do not create a conflict of interest pertaining to this manuscript, in the interest of full disclosure, Dr. Bickel would like to report the following: W. K. Bickel is a principal of HealthSim, LLC; BEAM Diagnostics, Inc.; and Red 5 Group, LLC. In addition, he serves on the scientific advisory board for Ria Health; and serves as a consultant for Lumanity. All other authors declare no potential conflict of interest. EDAT- 2023/11/29 00:42 MHDA- 2023/11/30 06:44 PMCR- 2023/11/28 CRDT- 2023/11/28 23:46 PHST- 2023/09/18 00:00 [received] PHST- 2023/11/24 00:00 [accepted] PHST- 2023/11/30 06:44 [medline] PHST- 2023/11/29 00:42 [pubmed] PHST- 2023/11/28 23:46 [entrez] PHST- 2023/11/28 00:00 [pmc-release] AID - 10.1038/s41598-023-48267-2 [pii] AID - 48267 [pii] AID - 10.1038/s41598-023-48267-2 [doi] PST - epublish SO - Sci Rep. 2023 Nov 28;13(1):20998. doi: 10.1038/s41598-023-48267-2. PMID- 38015216 OWN - NLM STAT- MEDLINE DCOM- 20231202 LR - 20240816 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 330 IP - 20 DP - 2023 Nov 28 TI - Obesity Management in Adults: A Review. PG - 2000-2015 LID - 10.1001/jama.2023.19897 [doi] AB - IMPORTANCE: Obesity affects approximately 42% of US adults and is associated with increased rates of type 2 diabetes, hypertension, cardiovascular disease, sleep disorders, osteoarthritis, and premature death. OBSERVATIONS: A body mass index (BMI) of 25 or greater is commonly used to define overweight, and a BMI of 30 or greater to define obesity, with lower thresholds for Asian populations (BMI >/=25-27.5), although use of BMI alone is not recommended to determine individual risk. Individuals with obesity have higher rates of incident cardiovascular disease. In men with a BMI of 30 to 39, cardiovascular event rates are 20.21 per 1000 person-years compared with 13.72 per 1000 person-years in men with a normal BMI. In women with a BMI of 30 to 39.9, cardiovascular event rates are 9.97 per 1000 person-years compared with 6.37 per 1000 person-years in women with a normal BMI. Among people with obesity, 5% to 10% weight loss improves systolic blood pressure by about 3 mm Hg for those with hypertension, and may decrease hemoglobin A1c by 0.6% to 1% for those with type 2 diabetes. Evidence-based obesity treatment includes interventions addressing 5 major categories: behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures. Comprehensive obesity care plans combine appropriate interventions for individual patients. Multicomponent behavioral interventions, ideally consisting of at least 14 sessions in 6 months to promote lifestyle changes, including components such as weight self-monitoring, dietary and physical activity counseling, and problem solving, often produce 5% to 10% weight loss, although weight regain occurs in 25% or more of participants at 2-year follow-up. Effective nutritional approaches focus on reducing total caloric intake and dietary strategies based on patient preferences. Physical activity without calorie reduction typically causes less weight loss (2-3 kg) but is important for weight-loss maintenance. Commonly prescribed medications such as antidepressants (eg, mirtazapine, amitriptyline) and antihyperglycemics such as glyburide or insulin cause weight gain, and clinicians should review and consider alternatives. Antiobesity medications are recommended for nonpregnant patients with obesity or overweight and weight-related comorbidities in conjunction with lifestyle modifications. Six medications are currently approved by the US Food and Drug Administration for long-term use: glucagon-like peptide receptor 1 (GLP-1) agonists (semaglutide and liraglutide only), tirzepatide (a glucose-dependent insulinotropic polypeptide/GLP-1 agonist), phentermine-topiramate, naltrexone-bupropion, and orlistat. Of these, tirzepatide has the greatest effect, with mean weight loss of 21% at 72 weeks. Endoscopic procedures (ie, intragastric balloon and endoscopic sleeve gastroplasty) can attain 10% to 13% weight loss at 6 months. Weight loss from metabolic and bariatric surgeries (ie, laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass) ranges from 25% to 30% at 12 months. Maintaining long-term weight loss is difficult, and clinical guidelines support the use of long-term antiobesity medications when weight maintenance is inadequate with lifestyle interventions alone. CONCLUSION AND RELEVANCE: Obesity affects approximately 42% of adults in the US. Behavioral interventions can attain approximately 5% to 10% weight loss, GLP-1 agonists and glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists can attain approximately 8% to 21% weight loss, and bariatric surgery can attain approximately 25% to 30% weight loss. Comprehensive, evidence-based obesity treatment combines behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures as appropriate for individual patients. FAU - Elmaleh-Sachs, Arielle AU - Elmaleh-Sachs A AD - Department of Medicine, Division of General Internal Medicine and Clinical Innovation, New York University Grossman School of Medicine, New York, New York. AD - Department of Population Health, New York University Grossman School of Medicine, New York, New York. AD - Family Health Centers at NYU Langone, New York, New York. FAU - Schwartz, Jessica L AU - Schwartz JL AD - Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland. FAU - Bramante, Carolyn T AU - Bramante CT AD - Division of General Internal Medicine, University of Minnesota Medical School, Minneapolis. FAU - Nicklas, Jacinda M AU - Nicklas JM AD - Division of General Internal Medicine, University of Colorado School of Medicine, Aurora. FAU - Gudzune, Kimberly A AU - Gudzune KA AD - Division of General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland. FAU - Jay, Melanie AU - Jay M AD - Department of Medicine, Division of General Internal Medicine and Clinical Innovation, New York University Grossman School of Medicine, New York, New York. AD - Department of Population Health, New York University Grossman School of Medicine, New York, New York. AD - New York Harbor Veteran Affairs, New York, New York. LA - eng GR - K23 DK124654/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Review PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - IY9XDZ35W2 (Glucose) RN - 0 (Peptides) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - *Anti-Obesity Agents/therapeutic use MH - Cardiovascular Diseases/epidemiology MH - Diabetes Mellitus, Type 2/epidemiology MH - Gastric Balloon MH - Glucagon-Like Peptide 1 MH - Glucose MH - Hypertension/epidemiology MH - *Obesity/diagnosis/epidemiology/therapy MH - *Obesity Management/methods MH - Overweight/diagnosis/epidemiology/therapy MH - Peptides MH - United States/epidemiology MH - Weight Loss MH - Body Mass Index PMC - PMC11325826 MID - NIHMS2013936 EDAT- 2023/11/28 12:43 MHDA- 2023/11/29 06:42 PMCR- 2024/08/15 CRDT- 2023/11/28 11:04 PHST- 2023/11/29 06:42 [medline] PHST- 2023/11/28 12:43 [pubmed] PHST- 2023/11/28 11:04 [entrez] PHST- 2024/08/15 00:00 [pmc-release] AID - 2812316 [pii] AID - 10.1001/jama.2023.19897 [doi] PST - ppublish SO - JAMA. 2023 Nov 28;330(20):2000-2015. doi: 10.1001/jama.2023.19897. PMID- 37999750 OWN - NLM STAT- MEDLINE DCOM- 20240123 LR - 20250103 IS - 1432-0827 (Electronic) IS - 0171-967X (Linking) VI - 114 IP - 2 DP - 2024 Feb TI - Narrative Review of Effects of Glucagon-Like Peptide-1 Receptor Agonists on Bone Health in People Living with Obesity. PG - 86-97 LID - 10.1007/s00223-023-01150-8 [doi] AB - Glucagon-like peptide-1 Receptor agonists (GLP-1Ras) such as liraglutide and semaglutide have been recently approved as medications for chronic weight management in people living with obesity (PwO); GLP-1 may enhance bone metabolism and improve bone quality. However, the effects of GLP-1Ras on skeletal health remain to be determined and that's the purpose of this narrative review. Nevertheless, bone consequences of intentional weight loss interventions in PwO are well known: (i) significant weight loss induced by caloric restriction and bariatric surgery results in accelerated bone turnover and bone loss, and (ii) unlike caloric restriction interventions, PwO experience a substantial deterioration in bone microarchitecture and strength associated with an increased risk of fracture after bariatric surgery especially malabsorptive procedures. Liraglutide seems to have a positive effect on bone material properties despite significant weight loss in several rodent models. However, most of positive effects on bone mineral density and microarchitecture were observed at concentration much higher than approved for obesity care in humans. No data have been reported in preclinical models with semaglutide. The current evidence of the effects of GLP-1Ra on bone health in PwO is limited. Indeed, studies on the use of GLP-1Ra mostly included patients with diabetes who were administered a dose used in this condition, did not have adequate bone parameters as primary endpoints, and had short follow-up periods. Further studies are needed to investigate the bone impact of GLP-1Ra, dual- and triple-receptor agonists for GLP-1, glucose-dependent insulin releasing polypeptide (GIP), and glucagon in PwO. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Herrou, Julia AU - Herrou J AD - Service de Rhumatologie, Inserm U 1153, AP-HP Centre, Hopital Cochin, Universite de Paris, Paris, France. FAU - Mabilleau, Guillaume AU - Mabilleau G AD - ONIRIS, Inserm, RMeS, UMR 1229, SFR ICAT, Univ Angers, Nantes Universite, Angers, France. FAU - Lecerf, Jean-Michel AU - Lecerf JM AD - Department of Nutrition and Physical Activity, Institut Pasteur de Lille, Lille, France. FAU - Thomas, Thierry AU - Thomas T AD - Department of Rheumatology, Hopital Nord, Centre Hospitalier Universitaire (CHU) Saint-Etienne, Inserm U1059, Lyon University, Saint-Etienne, France. FAU - Biver, Emmanuel AU - Biver E AD - Service of Bone Diseases, Faculty of Medicine, Geneva University Hospitals, Geneva, Switzerland. FAU - Paccou, Julien AU - Paccou J AUID- ORCID: 0000-0001-6599-8623 AD - Department of Rheumatology, CHU Lille, MABlab ULR 4490, Univ. Lille, 59000, Lille, France. julien.paccou@chru-lille.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20231124 PL - United States TA - Calcif Tissue Int JT - Calcified tissue international JID - 7905481 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Liraglutide/pharmacology/therapeutic use MH - Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Bone Density MH - Glucagon-Like Peptide 1/adverse effects MH - Obesity/complications/drug therapy MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor/therapeutic use OTO - NOTNLM OT - Bone mineral density OT - Fractures OT - Glucagon-like peptide receptor agonists OT - Obesity OT - Osteoporosis OT - Weight loss EDAT- 2023/11/24 12:42 MHDA- 2024/01/23 06:42 CRDT- 2023/11/24 11:04 PHST- 2023/08/18 00:00 [received] PHST- 2023/10/14 00:00 [accepted] PHST- 2024/01/23 06:42 [medline] PHST- 2023/11/24 12:42 [pubmed] PHST- 2023/11/24 11:04 [entrez] AID - 10.1007/s00223-023-01150-8 [pii] AID - 10.1007/s00223-023-01150-8 [doi] PST - ppublish SO - Calcif Tissue Int. 2024 Feb;114(2):86-97. doi: 10.1007/s00223-023-01150-8. Epub 2023 Nov 24. PMID- 37995806 OWN - NLM STAT- MEDLINE DCOM- 20240126 LR - 20260527 IS - 1532-8600 (Electronic) IS - 0026-0495 (Linking) VI - 151 DP - 2024 Feb TI - Advances in obesity pharmacotherapy; learning from metabolic surgery and beyond. PG - 155741 LID - S0026-0495(23)00345-1 [pii] LID - 10.1016/j.metabol.2023.155741 [doi] AB - Currently, metabolic surgery (MS) constitutes the most effective means for durable weight loss of clinically meaningful magnitude, type 2 diabetes remission and resolution of non-alcoholic steatohepatitis, as well as other obesity-related comorbidities. Accumulating evidence on the mechanisms through which MS exerts its actions has highlighted the altered secretion of hormonally active peptides of intestinal origin with biological actions crucial to energy metabolism as key drivers of MS clinical effects. The initial success of glucagon-like peptide-1 (GLP-1) receptor agonists regarding weight loss and metabolic amelioration have been followed by the development of unimolecular dual and triple polyagonists, additionally exploiting the effects of glucagon and/or glucose-dependent insulinotropic polypeptide (GIP) which achieves a magnitude of weight loss approximating that of common MS operations. Through the implementation of such therapies, the feasibility of a "medical bypass", namely the replication of the clinical effects of MS through non-surgical interventions may be foreseeable in the near future. Apart from weight loss, this approach ought to be put to the test also regarding other clinical outcomes, such as liver steatosis and steatohepatitis, cardiovascular disease, and overall prognosis, on which MS has a robustly demonstrated impact. Besides, a medical bypass as an alternative, salvage, or combination strategy to MS may promote precision medicine in obesity therapeutics. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Tsilingiris, Dimitrios AU - Tsilingiris D AD - First Department of Internal Medicine, University Hospital of Alexandroupolis, Alexandroupolis, Greece. FAU - Kokkinos, Alexander AU - Kokkinos A AD - 1st Department of Propaedeutic Internal Medicine, Athens University Medical School, Laiko Hospital, Athens, Greece. Electronic address: rjd@otenet.gr. LA - eng PT - Journal Article DEP - 20231122 PL - United States TA - Metabolism JT - Metabolism: clinical and experimental JID - 0375267 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Glucagon-Like Peptide 1/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/surgery/metabolism MH - Obesity/complications/drug therapy/surgery MH - Gastric Inhibitory Polypeptide/therapeutic use MH - *Bariatric Surgery MH - *Fatty Liver/drug therapy MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Bariatric surgery OT - Cotadutide OT - Glucagon-like peptide 1 OT - Gut hormones OT - Medical bypass OT - Metabolic surgery OT - Polyagonists OT - Retatrutide OT - Semaglutide OT - Tirzepatide COIS- Declaration of competing interest AK reports research grants by Novo Nordisk, consulting fees by Sanofi, Novo Nordisk, Boehringer Ingelheim, Astra Zeneca, and Pharmaserve-Lilly, lecture honoraria by Novo Nordisk, Sanofi, Astra Zeneca, Elpen Pharma, Pharmaserve Lilly, Boehringer-Ingelheim, MSD, Galenica, and Epsilon Health, support for congress attendance by Novo Nordisk, Pharmaserve Lilly, Astra Zeneca, and Boehringer Ingelheim. He also reports membership in the Steering Committee of the Metabolic Surgery Study Group, membership in the Lancet Commission on Clinical Obesity, and vice-presidency of the Hellenic Medical Association for Obesity. DT has received support for congress attendance by Novo Nordisk. None of the above are related to the work presented herein. EDAT- 2023/11/24 00:42 MHDA- 2024/01/26 06:43 CRDT- 2023/11/23 19:27 PHST- 2023/07/30 00:00 [received] PHST- 2023/11/05 00:00 [revised] PHST- 2023/11/16 00:00 [accepted] PHST- 2024/01/26 06:43 [medline] PHST- 2023/11/24 00:42 [pubmed] PHST- 2023/11/23 19:27 [entrez] AID - S0026-0495(23)00345-1 [pii] AID - 10.1016/j.metabol.2023.155741 [doi] PST - ppublish SO - Metabolism. 2024 Feb;151:155741. doi: 10.1016/j.metabol.2023.155741. Epub 2023 Nov 22. PMID- 37989717 OWN - NLM STAT- MEDLINE DCOM- 20240205 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 32 IP - 2 DP - 2024 Feb TI - Efficacy and safety of semaglutide 2.4 mg according to antidepressant use at baseline: A post hoc subgroup analysis. PG - 273-280 LID - 10.1002/oby.23946 [doi] AB - OBJECTIVE: To explore the efficacy and safety of semaglutide 2.4 mg in people with overweight/obesity who were also being treated with antidepressants (ADs). METHODS: Across the Semaglutide Treatment Effect for People with obesity (STEP) 1-3 and 5 trials, adults with overweight/obesity and type 2 diabetes (STEP 2 only) were enrolled. People with severe major depressive disorder within 2 years prior to screening or with a patient health questionnaire-9 score >/=15 at screening were excluded. Participants were categorized into subgroups according to baseline AD status (on/off ADs) in this post hoc exploratory analysis of the STEP trials. RESULTS: Of 3683 participants randomized, 539 were on ADs at baseline. Mean body weight change from baseline to week 68 was greater for semaglutide versus placebo, regardless of baseline AD use. In STEP 1, for participants on ADs at baseline, mean change from baseline was -15.7% with semaglutide versus -0.2% with placebo and -14.7% versus -2.8% for those not on ADs at baseline. Similar patterns were seen in STEP 2, 3, and 5. The prevalence of adverse events (AEs) was generally similar between semaglutide and placebo in participants on ADs at baseline. CONCLUSIONS: In adults with overweight/obesity, semaglutide provided clinically meaningful weight loss regardless of baseline AD use, with an AE profile consistent with previous studies. CI - (c) 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Kushner, Robert F AU - Kushner RF AUID- ORCID: 0000-0002-1380-3705 AD - Department of Medicine and Medical Education, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. FAU - Fink-Jensen, Anders AU - Fink-Jensen A AD - Psychiatric Centre Copenhagen and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Frenkel, Ofir AU - Frenkel O AD - Novo Nordisk A/S, Soborg, Denmark. FAU - McGowan, Barbara AU - McGowan B AUID- ORCID: 0000-0003-2015-726X AD - Cleveland Clinic London Hospital, Portland Place Outpatient Centre, London, UK. FAU - Goldman, Bryan AU - Goldman B AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Overvad, Maria AU - Overvad M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wadden, Thomas AU - Wadden T AUID- ORCID: 0000-0002-0438-4609 AD - Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231121 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Antidepressive Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects MH - *Obesity/drug therapy MH - Overweight/complications/drug therapy MH - Treatment Outcome MH - Antidepressive Agents/therapeutic use MH - Randomized Controlled Trials as Topic MH - Semaglutide EDAT- 2023/11/22 00:42 MHDA- 2024/01/26 06:43 CRDT- 2023/11/21 22:43 PHST- 2023/09/15 00:00 [revised] PHST- 2023/07/12 00:00 [received] PHST- 2023/09/28 00:00 [accepted] PHST- 2024/01/26 06:43 [medline] PHST- 2023/11/22 00:42 [pubmed] PHST- 2023/11/21 22:43 [entrez] AID - 10.1002/oby.23946 [doi] PST - ppublish SO - Obesity (Silver Spring). 2024 Feb;32(2):273-280. doi: 10.1002/oby.23946. Epub 2023 Nov 21. PMID- 37987649 OWN - NLM STAT- MEDLINE DCOM- 20231122 LR - 20260127 IS - 1473-2300 (Electronic) IS - 0300-0605 (Print) IS - 0300-0605 (Linking) VI - 51 IP - 11 DP - 2023 Nov TI - Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. PG - 3000605231211402 LID - 10.1177/03000605231211402 [doi] LID - 03000605231211402 AB - OBJECTIVE: To explore the effects of oral semaglutide on glycaemic parameters, body weight, and satisfaction in the first recipient patients with type 2 diabetes mellitus in Slovenia, in a real-world clinical practice setting. METHODS: The first consecutive adult patients with type 2 diabetes who were eligible for oral semaglutide treatment were included in this prospective, open-label interventional study. Patients received increasing doses of oral semaglutide and were evaluated at inclusion, at 1 month, then 3-5 months after starting treatment. Fasting blood glucose, glycosylated haemoglobin (HbA1c), body weight, patient satisfaction with oral semaglutide treatment (using the validated Treatment Satisfaction Questionnaire for Medication), and adverse effects, were analysed. Statistical analyses were performed using one-way analysis of variance, and, when significant interactions were found, Bonferroni post-hoc test. A P-value <0.05 was considered statistically significant. RESULTS: Twenty patients (11 male: 9 female; mean age, 59.9 +/- 1.5 years; mean diabetes duration, 8.5 +/- 1.4 years) were included. Oral semaglutide (7 and 14 mg) significantly decreased HbA1c (from 9.4 +/- 0.3% to 8.2 +/- 0.2% and 7.8 +/- 0.2%, respectively) and fasting plasma glucose (from 11.2 +/- 0.5 mmol/L to 9.2 +/- 0.7 mmol/L and 8.9 +/- 0.4 mmol/L, respectively). Oral semaglutide (14 mg) significantly decreased body weight (from 100.9 +/- 2.7 kg to 92.7 +/- 2.4 kg). Patients reported that treatment was easy to use and expressed high global satisfaction. Mild and transient, mostly gastrointestinal, adverse effects were reported in 10 patients. CONCLUSIONS: Oral semaglutide, the first oral glucagon-like peptide 1 receptor agonist, was effective and safe, and associated with high patient satisfaction, in its first recipients in Slovenia. The results are important for daily clinical practice involving patients with type 2 diabetes, however, due to the small study population, lack of placebo control, and short exposure to oral semaglutide, the effectiveness of oral semaglutide in clinical practice requires further investigation. FAU - Janic, Miodrag AU - Janic M AUID- ORCID: 0000-0001-7073-8922 AD - Clinical Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. FAU - Jovanovic, Marija AU - Jovanovic M AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. FAU - Janez, Andrej AU - Janez A AD - Clinical Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. FAU - Lunder, Mojca AU - Lunder M AD - Clinical Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. LA - eng PT - Journal Article PL - England TA - J Int Med Res JT - The Journal of international medical research JID - 0346411 RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - Female MH - Male MH - Middle Aged MH - Patient Satisfaction MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - Prospective Studies MH - Body Weight MH - *Drug-Related Side Effects and Adverse Reactions MH - Semaglutide PMC - PMC10664446 OTO - NOTNLM OT - Oral semaglutide OT - adverse effects OT - body weight OT - glycaemic control OT - patient satisfaction OT - type 2 diabetes COIS- Declaration of conflicting interestsThe authors declare that there is no conflict of interest. EDAT- 2023/11/21 12:43 MHDA- 2023/11/22 06:42 PMCR- 2023/11/21 CRDT- 2023/11/21 09:53 PHST- 2023/11/22 06:42 [medline] PHST- 2023/11/21 12:43 [pubmed] PHST- 2023/11/21 09:53 [entrez] PHST- 2023/11/21 00:00 [pmc-release] AID - 10.1177_03000605231211402 [pii] AID - 10.1177/03000605231211402 [doi] PST - ppublish SO - J Int Med Res. 2023 Nov;51(11):3000605231211402. doi: 10.1177/03000605231211402. PMID- 37983121 OWN - NLM STAT- MEDLINE DCOM- 20231122 LR - 20250103 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 65 IP - 1690 DP - 2023 Nov 27 TI - In brief: GI effects of GLP-1 receptor agonists. PG - 191-192 LID - 10.58347/tml.2023.1690e [doi] LA - eng PT - Journal Article PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Liraglutide MH - Glucagon-Like Peptides/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Bydureon BCise OT - Byetta OT - Mounjaro OT - Ozempic OT - Rybelsus OT - Saxenda OT - Trulicity OT - Victoza OT - Wegovy OT - Zepbound OT - adverse effects OT - drug interactions OT - dulaglutide OT - exenatide OT - liraglutide OT - safety OT - semaglutide OT - tirzepatide OT - type 2 diabetes EDAT- 2023/11/20 18:44 MHDA- 2023/11/22 06:43 CRDT- 2023/11/20 12:23 PHST- 2023/11/22 06:43 [medline] PHST- 2023/11/20 18:44 [pubmed] PHST- 2023/11/20 12:23 [entrez] AID - 10.58347/tml.2023.1690e [doi] PST - ppublish SO - Med Lett Drugs Ther. 2023 Nov 27;65(1690):191-192. doi: 10.58347/tml.2023.1690e. PMID- 37976053 OWN - NLM STAT- MEDLINE DCOM- 20240229 LR - 20261001 IS - 1473-5571 (Electronic) IS - 0269-9370 (Print) IS - 0269-9370 (Linking) VI - 38 IP - 4 DP - 2024 Mar 15 TI - Weight loss associated with semaglutide treatment among people with HIV. PG - 531-535 LID - 10.1097/QAD.0000000000003791 [doi] AB - OBJECTIVE: There is limited real-world evidence about the effectiveness of semaglutide for weight loss among people with HIV (PWH). We aimed to investigate weight change in a US cohort of PWH who initiated semaglutide treatment. DESIGN: Observational study using the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. METHODS: We identified adult PWH who initiated semaglutide between 2018 and 2022 and with at least two weight measurements. The primary outcome was within-person bodyweight change in kilograms at 1 year. The secondary outcome was within-person Hemoglobin A1c percentage (HbA1c) change. Both outcomes were estimated using multivariable linear mixed model. RESULTS: In total, 222 new users of semaglutide met inclusion criteria. Mean follow-up was 1.1 years. Approximately 75% of new semaglutide users were men, and at baseline, mean age was 53 years [standard deviation (SD): 10], average weight was 108 kg (SD: 23), mean BMI was 35.5 kg/m 2 , mean HbA1c was 7.7% and 77% had clinically recognized diabetes. At baseline, 97% were on ART and 89% were virally suppressed (viral load < 50 copies/ml). In the adjusted mixed model analysis, treatment with semaglutide was associated with an average weight loss of 6.47 kg at 1 year (95% CI -7.67 to -5.18) and with a reduction in HbA1c of 1.07% at 1 year (95% CI -1.64 to -0.50) among the 157 PWH with a postindex HbA1c value. CONCLUSION: Semaglutide was associated with significant weight loss and HbA1c reduction among PWH, comparable to results of previous studies from the general population. CI - Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved. FAU - Haidar, Lara AU - Haidar L AD - College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Crane, Heidi M AU - Crane HM AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Nance, Robin M AU - Nance RM AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Webel, Allison AU - Webel A AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Ruderman, Stephanie A AU - Ruderman SA AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Whitney, Bridget M AU - Whitney BM AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Willig, Amanda L AU - Willig AL AD - Department of Medicine, University of Alabama at Birmingham, Birmingham, AL. FAU - Napravnik, Sonia AU - Napravnik S AD - Department of Epidemiology, University of North Carolina, Chapel Hill, NC. FAU - Mixson, L Sarah AU - Mixson LS AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Leong, Christine AU - Leong C AD - College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Lavu, Alekhya AU - Lavu A AD - College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Aboulatta, Laila AU - Aboulatta L AD - College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Dai, Mindy AU - Dai M AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Hahn, Andrew AU - Hahn A AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Saag, Michael S AU - Saag MS AD - Department of Medicine, University of Alabama at Birmingham, Birmingham, AL. FAU - Bamford, Laura AU - Bamford L AD - Department of Medicine, University of California San Diego, San Diego, CA. FAU - Cachay, Edward AU - Cachay E AD - Department of Medicine, University of California San Diego, San Diego, CA. FAU - Kitahata, Mari M AU - Kitahata MM AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Mayer, Kenneth H AU - Mayer KH AD - Department of Medicine, Harvard Medical School, Fenway Institute, Boston, MA. FAU - Jacobson, Jeffrey AU - Jacobson J AD - Department of Medicine, Case Western Reserve University, Cleveland, Ohio. FAU - Moore, Richard D AU - Moore RD AD - Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. FAU - Delaney, Joseph A C AU - Delaney JAC AD - College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada. AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Drumright, Lydia N AU - Drumright LN AD - Department of Medicine, University of Washington, Seattle, WA. FAU - Eltonsy, Sherif AU - Eltonsy S AD - College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada. LA - eng GR - R56 AG057262/AG/NIA NIH HHS/United States GR - P30 AI094189/AI/NIAID NIH HHS/United States GR - R01 DA058938/DA/NIDA NIH HHS/United States GR - U01 DA036935/DA/NIDA NIH HHS/United States GR - R24 AI067039/AI/NIAID NIH HHS/United States GR - P30 AI117943/AI/NIAID NIH HHS/United States GR - K01 HL137557/HL/NHLBI NIH HHS/United States GR - R01 HL126538/HL/NHLBI NIH HHS/United States GR - P30 AI027757/AI/NIAID NIH HHS/United States PT - Journal Article PT - Observational Study DEP - 20231116 PL - England TA - AIDS JT - AIDS (London, England) JID - 8710219 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - AIDS. 2024 Mar 15;38(4):603-605. doi: 10.1097/QAD.0000000000003816. PMID: 38416553 MH - Male MH - Adult MH - Humans MH - Middle Aged MH - Female MH - Hypoglycemic Agents MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glycated Hemoglobin MH - *HIV Infections/complications/drug therapy MH - Weight Loss MH - *Glucagon-Like Peptides MH - Semaglutide PMC - PMC10922142 MID - NIHMS1945256 COIS- Conflict of interest disclosure: Amanda Willig is doing consulting work with Weight Watchers International specifically related to semaglutide and tirzepatide. No work occurred during the analysis of writing of the manuscript but will have occurred by the time of publication. None of the other authors have any coflict of interest to disclose. EDAT- 2023/11/17 15:30 MHDA- 2024/02/29 06:44 PMCR- 2025/03/15 CRDT- 2023/11/17 11:33 PHST- 2024/02/29 06:44 [medline] PHST- 2023/11/17 15:30 [pubmed] PHST- 2023/11/17 11:33 [entrez] PHST- 2025/03/15 00:00 [pmc-release] AID - 00002030-202403150-00011 [pii] AID - 10.1097/QAD.0000000000003791 [doi] PST - ppublish SO - AIDS. 2024 Mar 15;38(4):531-535. doi: 10.1097/QAD.0000000000003791. Epub 2023 Nov 16. PMID- 37972857 OWN - NLM STAT- MEDLINE DCOM- 20240109 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 206 DP - 2023 Dec TI - Once-weekly semaglutide use in glucagon-like peptide-1 receptor agonist naive patients with type 2 diabetes in North Macedonia: Real-world data from the MIRAGE study. PG - 111018 LID - S0168-8227(23)00781-7 [pii] LID - 10.1016/j.diabres.2023.111018 [doi] AB - AIMS: The MIRAGE study aimed to evaluate the real-world use of once weekly (OW) subcutaneous semaglutide in glucagon-like peptide-1 receptor agonist naive type 2 diabetes patients in routine clinical practice in North Macedonia. METHODS: MIRAGE was a multicentre, single-arm, retrospective and 30-weeks study, conducted in North Macedonia. Primary [change in glycated haemoglobin (HbA1c)] and secondary endpoints [change in body weight, fasting plasma glucose (FPG), lipid parameters, blood pressure, waist circumference, glycaemic and weight-loss target achievement] were evaluated between baseline and end of study (EOS). RESULTS: Baseline characteristics of 314 patients enrolled in the study were, mean age: 55.5 years, HbA1c: 9.0 %, diabetes duration: 7.8 years, body weight: 105.2 kg and waist circumference: 114 cm. Patients at EOS experienced statistically significant estimated mean change in HbA1c: -2.2 % points, body weight: -9.0 kg, and FPG: -4.1 mmol/L (all p < 0.0001). At EOS, 62.1 % patients achieved HbA1c < 7 %, and 79.3 % had >/= 1 % HbA1c reduction. A weight reduction of >/= 3 % and >/= 5 % was noted in 88.3 % and 73.3 % patients, respectively. No new safety concern has emerged. CONCLUSIONS: Findings from MIRAGE study demonstrated glycaemic and weight-loss benefits of semaglutide, with improvements in other cardiometabolic parameters. The study supports real-world OW subcutaneous semaglutide use in North Macedonia. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Milenkovikj, Tatjana AU - Milenkovikj T AD - University Clinic of Endocrinology, Diabetes and Metabolic Disorders, Skopje, North Macedonia; Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 1000 Skopje, Republic of North Macedonia. Electronic address: milenkovic.tatjana@yahoo.com. FAU - Chekorova Mitreva, Biljana AU - Chekorova Mitreva B AD - Novo Nordisk Farma Dooel, Skopje, North Macedonia. FAU - Jovanovska Mishevska, Sasha AU - Jovanovska Mishevska S AD - University Clinic of Endocrinology, Diabetes and Metabolic Disorders, Skopje, North Macedonia; Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 1000 Skopje, Republic of North Macedonia. FAU - Bitoska-Mileva, Iskra AU - Bitoska-Mileva I AD - University Clinic of Endocrinology, Diabetes and Metabolic Disorders, Skopje, North Macedonia; Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 1000 Skopje, Republic of North Macedonia. FAU - Ahmeti, Irfan AU - Ahmeti I AD - University Clinic of Endocrinology, Diabetes and Metabolic Disorders, Skopje, North Macedonia; Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 1000 Skopje, Republic of North Macedonia. CN - MIRAGE study group LA - eng PT - Journal Article DEP - 20231114 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Middle Aged MH - Body Weight MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glycated Hemoglobin MH - Hypoglycemic Agents/therapeutic use MH - Republic of North Macedonia MH - Retrospective Studies MH - Weight Loss MH - *Glucagon-Like Peptides/therapeutic use MH - Semaglutide OTO - NOTNLM OT - Fasting plasma glucose OT - Glucagon-like petide-1 receptor agonist OT - Glycated haemoglobin OT - Semaglutide OT - Subcutaneous OT - Type 2 diabetes COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Author TM has been invited speaker and/or attended advisory boards and received honorarium or consultant fees from Alkaloid, Belupo Boehringer Ingelheim, Berlin-Chemie, Krka, Merck, Novo Nordisk, Sanofi and TEVA (Pliva). Author BCM is an employee in Novo Nordisk Farma DOOEL, Skopje, North Macedonia and owns stocks in the company Novo Nordisk A/S. Author SJM has been invited speaker and/or attended advisory boards, and received honorarium or consultant fees from Alkaloid, Boehringer Ingelheim, Berlin-Chemie, Bayer, Krka, Lek Skopje (Sandoz), Merck, Novo Nordisk, Sanofi and Roche Diabetes. Author IBM has been invited speaker and/or attended advisory boards, and received honorarium or consultant fees from Boehringer, Belupo, Krka, Merck, and Novo Nordisk. Author IA has been invited speaker and/or attended advisory boards, and received honorarium or consultant fees from Belupo, Boehringer Ingelheim, Merck, MSD, Novo Nordisk, Sanofi, Roche Diagnostics and TEVA (Pliva).]. EDAT- 2023/11/17 15:25 MHDA- 2023/12/17 09:44 CRDT- 2023/11/16 19:28 PHST- 2023/10/04 00:00 [received] PHST- 2023/11/04 00:00 [revised] PHST- 2023/11/13 00:00 [accepted] PHST- 2023/12/17 09:44 [medline] PHST- 2023/11/17 15:25 [pubmed] PHST- 2023/11/16 19:28 [entrez] AID - S0168-8227(23)00781-7 [pii] AID - 10.1016/j.diabres.2023.111018 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2023 Dec;206:111018. doi: 10.1016/j.diabres.2023.111018. Epub 2023 Nov 14. PMID- 37955013 OWN - NLM STAT- MEDLINE DCOM- 20231114 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - Influence of chronic kidney disease and its severity on the efficacy of semaglutide in type 2 diabetes patients: a multicenter real-world study. PG - 1240279 LID - 10.3389/fendo.2023.1240279 [doi] LID - 1240279 AB - OBJECTIVES: Semaglutide is a glucagon-like peptide 1 receptor agonist that improves glycemic control and achieves weight loss in type 2 diabetes (T2D) patients. Subcutaneous (s.c.) semaglutide at 1 mg once weekly (OW) is safe in T2D patients with chronic kidney disease (CKD). Whether or not CKD and its severity influence treatment response remains undetermined. METHOD: This is an observational, ambispective, multicenter, nationwide, real-world study designed to compare safety/efficacy of OW s.c. 1 mg semaglutide in T2D patients with or without CKD. The influence of CKD severity was also addressed. Patients were followed up for 12 months. Primary end-points were glycosylated hemoglobin (HbA1c), weight, and renal outcomes. Secondary end-points included insulin resistance, atherogenic and hepatic steatosis indexes, and changes in antihyperglycemic medications. RESULTS: A total of 296 and 190 T2D patients without or with CKD, respectively, were recruited. Baseline CKD risk was moderate, high, or very high in 82, 53, and 45 patients, respectively. Treatment reduced HbA1c by 0.90%-1.20%. Relevant differences were seen neither between non-CKD and CKD patients nor among CKD subgroups. Notable weight losses were achieved in both non-CKD and CKD patients. The median reduction was higher in the former at 6 months (5.90 kg vs. 4.50 kg, P = 0.008) and at end of study (6.90 kg vs. 5.00 kg, P = 0.087). A trend toward slightly lower weight losses as CKD severity increased was observed. CKD markers improved across all CKD subgroups. Relevant differences were not observed for other variables, either between non-CKD and CKD patients, or among CKD subgroups. Safety concerns were not reported. CONCLUSION: The safety/efficacy of OW s.c. semaglutide to improve glycemic control and weight in T2D patients with CKD is not notably lower than that in T2D patients without renal failure. CKD severity barely influences treatment response. OW s.c. semaglutide can be useful to manage T2D patients with CKD in daily clinical practice. CI - Copyright (c) 2023 Garcia de Lucas, Caballero, Fernandez-Garcia, Dominguez-Rodriguez, Moreno-Moreno, Jimenez-Millan, Botana-Lopez, Aviles, Merino-Torres, Soto, Tejera and Morales. FAU - Garcia de Lucas, Maria Dolores AU - Garcia de Lucas MD AD - Internal Medicine Department, Hospital Costa del Sol, Marbella, Malaga, Spain. FAU - Caballero, Irene AU - Caballero I AD - Endocrinology and Nutrition Department, Virgen Macarena University Hospital, Sevilla, Spain. FAU - Fernandez-Garcia, Jose Carlos AU - Fernandez-Garcia JC AD - Endocrinology and Nutrition Department, Regional University Hospital, Malaga, Spain. FAU - Dominguez-Rodriguez, Manuel AU - Dominguez-Rodriguez M AD - Endocrinology and Nutrition Department, Virgen Macarena University Hospital, Sevilla, Spain. FAU - Moreno-Moreno, Paloma AU - Moreno-Moreno P AD - Endocrinology and Nutrition Department, Reina Sofia University Hospital, Cordoba, Spain. FAU - Jimenez-Millan, Anabel AU - Jimenez-Millan A AD - Endocrinology and Nutrition Department, University Hospital, Puerto Real, Cadiz, Spain. FAU - Botana-Lopez, Manuel AU - Botana-Lopez M AD - Endocrinology and Nutrition Department, Lucus Augusti University Hospital, Lugo, Spain. FAU - Aviles, Beatriz AU - Aviles B AD - Nephrology Department, Regional University Hospital, Malaga, Spain. FAU - Merino-Torres, Juan Francisco AU - Merino-Torres JF AD - Endocrinology and Nutrition Department, La Fe University Hospital, Valencia, Spain. FAU - Soto, Alfonso AU - Soto A AD - Endocrinology and Nutrition Department, A Coruna University Hospital Complex, A Coruna, Spain. FAU - Tejera, Cristina AU - Tejera C AD - Endocrinology and Nutrition Department, Hospital Basico da Defensa, Ferrol, A Coruna, Spain. FAU - Morales, Cristobal AU - Morales C AD - Endocrinology and Nutrition Department, Virgen Macarena University Hospital, Sevilla, Spain. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20231024 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glycated Hemoglobin MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Weight Loss MH - Semaglutide PMC - PMC10634592 OTO - NOTNLM OT - GLP-1 receptor agonists OT - chronic kidney disease OT - estimated glomerular filtration rate OT - glycosylated hemoglobin OT - semaglutide OT - type 2 diabetes OT - urinary albumin-to-creatinine ratio OT - weight loss COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/11/13 06:43 MHDA- 2023/11/14 06:43 PMCR- 2023/01/01 CRDT- 2023/11/13 04:44 PHST- 2023/06/14 00:00 [received] PHST- 2023/08/03 00:00 [accepted] PHST- 2023/11/14 06:43 [medline] PHST- 2023/11/13 06:43 [pubmed] PHST- 2023/11/13 04:44 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1240279 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Oct 24;14:1240279. doi: 10.3389/fendo.2023.1240279. eCollection 2023. PMID- 37952131 OWN - NLM STAT- MEDLINE DCOM- 20231220 LR - 20260618 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 389 IP - 24 DP - 2023 Dec 14 TI - Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. PG - 2221-2232 LID - 10.1056/NEJMoa2307563 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes. Whether semaglutide can reduce cardiovascular risk associated with overweight and obesity in the absence of diabetes is unknown. METHODS: In a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, we enrolled patients 45 years of age or older who had preexisting cardiovascular disease and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 27 or greater but no history of diabetes. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis. Safety was also assessed. RESULTS: A total of 17,604 patients were enrolled; 8803 were assigned to receive semaglutide and 8801 to receive placebo. The mean (+/-SD) duration of exposure to semaglutide or placebo was 34.2+/-13.7 months, and the mean duration of follow-up was 39.8+/-9.4 months. A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001). Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group (P<0.001). CONCLUSIONS: In patients with preexisting cardiovascular disease and overweight or obesity but without diabetes, weekly subcutaneous semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke at a mean follow-up of 39.8 months. (Funded by Novo Nordisk; SELECT ClinicalTrials.gov number, NCT03574597.). CI - Copyright (c) 2023 Massachusetts Medical Society. FAU - Lincoff, A Michael AU - Lincoff AM AUID- ORCID: 0000-0001-8175-2121 AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Brown-Frandsen, Kirstine AU - Brown-Frandsen K AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Colhoun, Helen M AU - Colhoun HM AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Deanfield, John AU - Deanfield J AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Emerson, Scott S AU - Emerson SS AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Esbjerg, Sille AU - Esbjerg S AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Hardt-Lindberg, Soren AU - Hardt-Lindberg S AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Hovingh, G Kees AU - Hovingh GK AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Kahn, Steven E AU - Kahn SE AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Kushner, Robert F AU - Kushner RF AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Oral, Tugce K AU - Oral TK AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Michelsen, Marie M AU - Michelsen MM AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Plutzky, Jorge AU - Plutzky J AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Tornoe, Christoffer W AU - Tornoe CW AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). FAU - Ryan, Donna H AU - Ryan DH AD - From the Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland (A.M.L.); Novo Nordisk, Soborg, Denmark (K.B.-F., S.E., S.H.-L., G.K.H., T.K.O., M.M.M., C.W.T.); the Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (H.M.C.), and the National Institute for Cardiovascular Outcomes Research, University College London, London (J.D.) - both in the United Kingdom; the Department of Biostatistics, University of Washington (S.S.E.), and the Department of Medicine, VA Puget Sound Health Care System and University of Washington (S.E.K.) - both in Seattle; the Department of Vascular Medicine, Academic Medical Center, Amsterdam (G.K.H.); the Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.); the Department of Internal Medicine (Endocrinology Division) and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas (I.L.); the Department of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (J.P.); and Pennington Biomedical Research Center, Baton Rouge, LA (D.H.R.). CN - SELECT Trial Investigators LA - eng SI - ClinicalTrials.gov/NCT03574597 PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20231111 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Cardiovascular Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Nat Rev Cardiol. 2024 Feb;21(2):69. doi: 10.1038/s41569-023-00970-3. PMID: 38036669 CIN - N Engl J Med. 2024 Feb 22;390(8):766. doi: 10.1056/NEJMc2400414. PMID: 38381682 CIN - N Engl J Med. 2024 Feb 22;390(8):766-767. doi: 10.1056/NEJMc2400414. PMID: 38381683 CIN - N Engl J Med. 2024 Feb 22;390(8):767. doi: 10.1056/NEJMc2400414. PMID: 38381684 CIN - N Engl J Med. 2024 Feb 22;390(8):767. doi: 10.1056/NEJMc2400414. PMID: 38381685 CIN - N Engl J Med. 2024 Feb 22;390(8):767-768. doi: 10.1056/NEJMc2400414. PMID: 38381686 CIN - N Engl J Med. 2024 Feb 22;390(8):768-769. doi: 10.1056/NEJMc2400414. PMID: 38381687 CIN - Ann Intern Med. 2024 Mar;177(3):JC31. doi: 10.7326/J24-0008. PMID: 38437690 CIN - MMW Fortschr Med. 2024 Apr;166(6):22-23. doi: 10.1007/s15006-024-3771-0. PMID: 38581499 CIN - Diabetes Obes Metab. 2024 Aug;26(8):3003-3005. doi: 10.1111/dom.15631. PMID: 38706104 MH - Humans MH - *Cardiovascular Diseases/epidemiology/etiology/mortality/prevention & control MH - Diabetes Mellitus, Type 2 MH - Double-Blind Method MH - Glucagon-Like Peptides MH - Hypoglycemic Agents MH - Myocardial Infarction MH - *Obesity/complications MH - Overweight/complications MH - Stroke MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage/adverse effects/therapeutic use MH - *Cardiovascular Agents/administration & dosage/adverse effects/therapeutic use MH - Semaglutide FIR - Porto, A IR - Porto A FIR - Villarino, A IR - Villarino A FIR - Chacon, C IR - Chacon C FIR - Zaidman, C J IR - Zaidman CJ FIR - Farias, E IR - Farias E FIR - Duronto, E IR - Duronto E FIR - Farias, J M IR - Farias JM FIR - Casas, M IR - Casas M FIR - Oviedo, A IR - Oviedo A FIR - Sanabria, H D IR - Sanabria HD FIR - Perez Terns, P IR - Perez Terns P FIR - Amerena, J IR - Amerena J FIR - Leung, M IR - Leung M FIR - Colquhoun, D M IR - Colquhoun DM FIR - Purnell, P IR - Purnell P FIR - William, M IR - William M FIR - Abhayaratna, W P IR - Abhayaratna WP FIR - Morbey, C IR - Morbey C FIR - Nicholls, S IR - Nicholls S FIR - Cross, D IR - Cross D FIR - Arstall, M IR - Arstall M FIR - Kostner, K IR - Kostner K FIR - Shirazi, M IR - Shirazi M FIR - Ekinci, E I IR - Ekinci EI FIR - Toplak, H IR - Toplak H FIR - Hanusch, U IR - Hanusch U FIR - Aigner, E IR - Aigner E FIR - Ludvik, B IR - Ludvik B FIR - Kautzky-Willer, A IR - Kautzky-Willer A FIR - Prager, R IR - Prager R FIR - Kaser, S IR - Kaser S FIR - Vanduynhoven, P IR - Vanduynhoven P FIR - Verwerft, J IR - Verwerft J FIR - Vrolix, M IR - Vrolix M FIR - De Pauw, M IR - De Pauw M FIR - Vercammen, C IR - Vercammen C FIR - Van De Borne, P IR - Van De Borne P FIR - Prakova-Teneva, Z R IR - Prakova-Teneva ZR FIR - Runev, N IR - Runev N FIR - Petrov, I IR - Petrov I FIR - Milanova, M IR - Milanova M FIR - Postadzhiyan, A IR - Postadzhiyan A FIR - Gelev, V IR - Gelev V FIR - Vasileva, S P IR - Vasileva SP FIR - Georgiev, B IR - Georgiev B FIR - Katova, T IR - Katova T FIR - Tokmakova, M IR - Tokmakova M FIR - Goudev, A IR - Goudev A FIR - Vassilev, D IR - Vassilev D FIR - Minkova, D A IR - Minkova DA FIR - Tisheva-Gospodinova, S IR - Tisheva-Gospodinova S FIR - Yotov, Y IR - Yotov Y FIR - Rossi, P IR - Rossi P FIR - Nicolau, J C IR - Nicolau JC FIR - Maia, L N IR - Maia LN FIR - Saraiva, J F IR - Saraiva JF FIR - Kormann, A P IR - Kormann AP FIR - Arantes, F B IR - Arantes FB FIR - Kaiser, S E IR - Kaiser SE FIR - Leite, S O IR - Leite SO FIR - Cercato, C IR - Cercato C FIR - Fonseca, A G IR - Fonseca AG FIR - Kurtz Lisboa, H R IR - Kurtz Lisboa HR FIR - Turatti, L A IR - Turatti LA FIR - Franco, D R IR - Franco DR FIR - Farsky, P S IR - Farsky PS FIR - Poirier, P IR - Poirier P FIR - Pandey, A S IR - Pandey AS FIR - St-Maurice, F IR - St-Maurice F FIR - Bourgeois, R IR - Bourgeois R FIR - Robitaille, Y IR - Robitaille Y FIR - Constance, C IR - Constance C FIR - Filteau, P IR - Filteau P FIR - Verma, S IR - Verma S FIR - Vijayaraghavan, R IR - Vijayaraghavan R FIR - Weisnagel, J IR - Weisnagel J FIR - Hartleib, M IR - Hartleib M FIR - Pedersen, S IR - Pedersen S FIR - Tellier, G IR - Tellier G FIR - Peters, K IR - Peters K FIR - Cha, J Y IR - Cha JY FIR - Langlois, M F IR - Langlois MF FIR - Garg, N IR - Garg N FIR - Datta, S IR - Datta S FIR - Salter, T IR - Salter T FIR - Spaic, T IR - Spaic T FIR - Lau, D IR - Lau D FIR - Tsoukas, G M IR - Tsoukas GM FIR - Stewart, J IR - Stewart J FIR - Vale, N IR - Vale N FIR - Rabasa-Lhoret, R IR - Rabasa-Lhoret R FIR - Vallieres, G IR - Vallieres G FIR - Allison, R IR - Allison R FIR - Martinez Cano, C A IR - Martinez Cano CA FIR - Accini Mendoza, J L IR - Accini Mendoza JL FIR - Botero Lopez, R IR - Botero Lopez R FIR - Urina Triana, M A IR - Urina Triana MA FIR - Rodriguez Plazas, J A IR - Rodriguez Plazas JA FIR - Cadena Bonfanti, A J IR - Cadena Bonfanti AJ FIR - Malecha, J IR - Malecha J FIR - Klimsa, Z IR - Klimsa Z FIR - Linhart, A IR - Linhart A FIR - Koleckar, P IR - Koleckar P FIR - Cermak, O IR - Cermak O FIR - Kuchar, L IR - Kuchar L FIR - Stasek, J IR - Stasek J FIR - Malicherova, E IR - Malicherova E FIR - Vesela, A IR - Vesela A FIR - Haluzik, M IR - Haluzik M FIR - Jungmair, W IR - Jungmair W FIR - Stahl, H D IR - Stahl HD FIR - Appel, K F IR - Appel KF FIR - Al-Zoebi, A IR - Al-Zoebi A FIR - Eggebrecht, H IR - Eggebrecht H FIR - Wagner, J IR - Wagner J FIR - Zeller, H IR - Zeller H FIR - Kreutzmann, K IR - Kreutzmann K FIR - Meyhofer, S IR - Meyhofer S FIR - Von Engelhardt, C IR - Von Engelhardt C FIR - Sauter, J IR - Sauter J FIR - Jacob, S IR - Jacob S FIR - Sturm, K IR - Sturm K FIR - Kahrmann, G IR - Kahrmann G FIR - Von Munchhausen, C IR - Von Munchhausen C FIR - Chevts, J IR - Chevts J FIR - Hagenow, A IR - Hagenow A FIR - Froer, M IR - Froer M FIR - Segner, A IR - Segner A FIR - Lehrke, M IR - Lehrke M FIR - Schaum, T IR - Schaum T FIR - Heymer, P IR - Heymer P FIR - Wendisch, U IR - Wendisch U FIR - Kempe, H P IR - Kempe HP FIR - Denger, R J IR - Denger RJ FIR - Steindorf, J IR - Steindorf J FIR - Bottcher, M IR - Bottcher M FIR - Mreng, M IR - Mreng M FIR - Gislason, G IR - Gislason G FIR - Egstrup, K IR - Egstrup K FIR - Hove, J D IR - Hove JD FIR - Jensen, S E IR - Jensen SE FIR - Nibouche, D E IR - Nibouche DE FIR - Chettibi, M IR - Chettibi M FIR - Hammoudi, N IR - Hammoudi N FIR - Tinahones, F IR - Tinahones F FIR - Morales Portillo, C IR - Morales Portillo C FIR - De La Cuesta, C IR - De La Cuesta C FIR - Soto Gonzalez, A IR - Soto Gonzalez A FIR - Rivas Fernandez, M IR - Rivas Fernandez M FIR - Castro, A IR - Castro A FIR - Gonzalez Albarran, O IR - Gonzalez Albarran O FIR - Mezquita Raya, P IR - Mezquita Raya P FIR - De Pablo, D IR - De Pablo D FIR - Merino Torres, J F IR - Merino Torres JF FIR - Masmiquel Comas, L IR - Masmiquel Comas L FIR - Lakka, T IR - Lakka T FIR - Ahtiainen, P IR - Ahtiainen P FIR - Pietila, M IR - Pietila M FIR - Ilveskoski, E IR - Ilveskoski E FIR - Ukkola, O IR - Ukkola O FIR - Niskanen, L IR - Niskanen L FIR - Keski-Opas, T IR - Keski-Opas T FIR - Cariou, B IR - Cariou B FIR - Demicheli, T IR - Demicheli T FIR - Petit, C IR - Petit C FIR - Kerneis, M IR - Kerneis M FIR - Schiele, F IR - Schiele F FIR - Thuan, J F IR - Thuan JF FIR - Gatta-Cherifi, B IR - Gatta-Cherifi B FIR - Verges, B IR - Verges B FIR - Hulot, J S IR - Hulot JS FIR - Stephan, D IR - Stephan D FIR - Serusclat, P IR - Serusclat P FIR - Steg, G IR - Steg G FIR - Barone Rochette, G IR - Barone Rochette G FIR - Keeling, P IR - Keeling P FIR - Sathyapalan, T IR - Sathyapalan T FIR - Randeva, H IR - Randeva H FIR - Wong, Y K IR - Wong YK FIR - Miras, A IR - Miras A FIR - Clifford, P IR - Clifford P FIR - Tatovic, D IR - Tatovic D FIR - Andrews, R IR - Andrews R FIR - Strzelecka, A IR - Strzelecka A FIR - Asamoah, N IR - Asamoah N FIR - Barber, M IR - Barber M FIR - Broadley, A IR - Broadley A FIR - Lee, K IR - Lee K FIR - Paul, N IR - Paul N FIR - Vaidya, B IR - Vaidya B FIR - Wyatt, N IR - Wyatt N FIR - Price, H IR - Price H FIR - Vincent, R IR - Vincent R FIR - Wakeling, J IR - Wakeling J FIR - Clark, R IR - Clark R FIR - Creely, S IR - Creely S FIR - English, P IR - English P FIR - Sharma, S IR - Sharma S FIR - Capehorn, M IR - Capehorn M FIR - Lang, C IR - Lang C FIR - Beerachee, Y IR - Beerachee Y FIR - Sharma, R IR - Sharma R FIR - Wilding, J IR - Wilding J FIR - Wilson, P IR - Wilson P FIR - Lynch, M IR - Lynch M FIR - Mcgowan, B IR - Mcgowan B FIR - Myint, M IR - Myint M FIR - Dang, C IR - Dang C FIR - Khoo, J IR - Khoo J FIR - Senior, R IR - Senior R FIR - Swanson, N IR - Swanson N FIR - Bellary, S IR - Bellary S FIR - Nair, S IR - Nair S FIR - Stoker, J IR - Stoker J FIR - Dobson, S IR - Dobson S FIR - Jackson-Voyzey, E IR - Jackson-Voyzey E FIR - Tait, G IR - Tait G FIR - Kartalis, A IR - Kartalis A FIR - Tsougos, E IR - Tsougos E FIR - Patsilinakos, S IR - Patsilinakos S FIR - Tziomalos, K IR - Tziomalos K FIR - Lambadiari, V IR - Lambadiari V FIR - Kokkinos, A IR - Kokkinos A FIR - Argyrakopoulou, G IR - Argyrakopoulou G FIR - Lanaras, L IR - Lanaras L FIR - Liberopoulos, E IR - Liberopoulos E FIR - Siasos, G IR - Siasos G FIR - Stamatelopoulos, K IR - Stamatelopoulos K FIR - Ntaios, G IR - Ntaios G FIR - Pagkalos, E IR - Pagkalos E FIR - Ruzic, A IR - Ruzic A FIR - Kruljac, I IR - Kruljac I FIR - Milicic, D IR - Milicic D FIR - Canecki Varzic, S IR - Canecki Varzic S FIR - Budincevic, H IR - Budincevic H FIR - Fuckar, K IR - Fuckar K FIR - Delic-Brkljacic, D IR - Delic-Brkljacic D FIR - Pall, D IR - Pall D FIR - Lupkovics, G IR - Lupkovics G FIR - Piros, A IR - Piros A FIR - Konyves, L IR - Konyves L FIR - Takacs, R IR - Takacs R FIR - Baranyai, M IR - Baranyai M FIR - Desai, P IR - Desai P FIR - Abhyankar, A IR - Abhyankar A FIR - Parvathareddy, K M IR - Parvathareddy KM FIR - Agarwal, D K IR - Agarwal DK FIR - Jitendra Pal Singh, S IR - Jitendra Pal Singh S FIR - Sethi, R IR - Sethi R FIR - Wander, G S IR - Wander GS FIR - Prafulla, K G IR - Prafulla KG FIR - Desai, D IR - Desai D FIR - Kaul, U IR - Kaul U FIR - Vijan, V IR - Vijan V FIR - Thomas, N IR - Thomas N FIR - Christopher, J IR - Christopher J FIR - Hiremath, S IR - Hiremath S FIR - Bhagwat, A IR - Bhagwat A FIR - Bansal, S IR - Bansal S FIR - Mahajan, A IR - Mahajan A FIR - Mittal, S IR - Mittal S FIR - Ajay, N IR - Ajay N FIR - Abhaichand, R K IR - Abhaichand RK FIR - Fulwani, M IR - Fulwani M FIR - Garg, S IR - Garg S FIR - Gandotra, D IR - Gandotra D FIR - Shah, M K IR - Shah MK FIR - Kahali, D IR - Kahali D FIR - Varghese, K IR - Varghese K FIR - Pothineni, R B IR - Pothineni RB FIR - Arneja, J IR - Arneja J FIR - Ambuj, R IR - Ambuj R FIR - Kannan, J IR - Kannan J FIR - Maher, V IR - Maher V FIR - Byrne, M IR - Byrne M FIR - Sreenan, S IR - Sreenan S FIR - Molony, D IR - Molony D FIR - Le Roux, C IR - Le Roux C FIR - Mcdonald, K IR - Mcdonald K FIR - Durst, R IR - Durst R FIR - Shechter, M IR - Shechter M FIR - Arbel, Y IR - Arbel Y FIR - Shehadeh, N IR - Shehadeh N FIR - Zornitzki, T IR - Zornitzki T FIR - Sofer, Y IR - Sofer Y FIR - Liberty, I IR - Liberty I FIR - Vishlitzky, V IR - Vishlitzky V FIR - Mosenzon, O IR - Mosenzon O FIR - Bashkin, A IR - Bashkin A FIR - Segal Lieberman, G IR - Segal Lieberman G FIR - Dicker, D IR - Dicker D FIR - Santini, F IR - Santini F FIR - Leonetti, F IR - Leonetti F FIR - Buscemi, S IR - Buscemi S FIR - Mingrone, G IR - Mingrone G FIR - Pagotto, U IR - Pagotto U FIR - Malavazos, A IR - Malavazos A FIR - Tuccinardi, D IR - Tuccinardi D FIR - Cogni, G IR - Cogni G FIR - Bo, S IR - Bo S FIR - Mannucci, E IR - Mannucci E FIR - Sbraccia, P IR - Sbraccia P FIR - Frittitta, L IR - Frittitta L FIR - Zatelli, M C IR - Zatelli MC FIR - Bucci, M IR - Bucci M FIR - Berra, C IR - Berra C FIR - Vettor, R IR - Vettor R FIR - Dotta, F IR - Dotta F FIR - Cortinovis, F IR - Cortinovis F FIR - Colao, A M IR - Colao AM FIR - Mirani, M IR - Mirani M FIR - Muratori, F IR - Muratori F FIR - Manita, M IR - Manita M FIR - Doi, M IR - Doi M FIR - Oh, F IR - Oh F FIR - Sato, A IR - Sato A FIR - Takeuchi, Y IR - Takeuchi Y FIR - Sueyoshi, A IR - Sueyoshi A FIR - Hata, Y IR - Hata Y FIR - Miyamoto, N IR - Miyamoto N FIR - Fujii, K IR - Fujii K FIR - Mitomo, S IR - Mitomo S FIR - Hanaoka, K IR - Hanaoka K FIR - Okada, Y IR - Okada Y FIR - Ezaki, H IR - Ezaki H FIR - Maeda, I IR - Maeda I FIR - Kawanishi, M IR - Kawanishi M FIR - Kitamura, R IR - Kitamura R FIR - Miyake, T IR - Miyake T FIR - Kiyosue, A IR - Kiyosue A FIR - Fukushima, Y IR - Fukushima Y FIR - Isawa, T IR - Isawa T FIR - Watanabe, A IR - Watanabe A FIR - Ueda, O IR - Ueda O FIR - Kunishige, H IR - Kunishige H FIR - Ono, Y IR - Ono Y FIR - Kadokami, T IR - Kadokami T FIR - Iwasawa, T IR - Iwasawa T FIR - Onaka, H IR - Onaka H FIR - Sugiura, T IR - Sugiura T FIR - Kinoshita, N IR - Kinoshita N FIR - Ando, T IR - Ando T FIR - Oguri, M IR - Oguri M FIR - Matsumoto, T IR - Matsumoto T FIR - Kato, T IR - Kato T FIR - Koga, T IR - Koga T FIR - Fujita, R IR - Fujita R FIR - Yamaguchi, H IR - Yamaguchi H FIR - Teragawa, H IR - Teragawa H FIR - Morisaki, K IR - Morisaki K FIR - Yamasaki, M IR - Yamasaki M FIR - Okayama, H IR - Okayama H FIR - Nagano, T IR - Nagano T FIR - Abe, M IR - Abe M FIR - Tanaka, H IR - Tanaka H FIR - Natsuaki, M IR - Natsuaki M FIR - Sakamoto, T IR - Sakamoto T FIR - Ohsugi, M IR - Ohsugi M FIR - Maeda, H IR - Maeda H FIR - Kodera, S IR - Kodera S FIR - Kinoshita, M IR - Kinoshita M FIR - Klavina, I IR - Klavina I FIR - Lace, A IR - Lace A FIR - Latkovskis, G IR - Latkovskis G FIR - Rezgale, I IR - Rezgale I FIR - Rancane, G IR - Rancane G FIR - Veze, I IR - Veze I FIR - Teterovska, D IR - Teterovska D FIR - Sime, I IR - Sime I FIR - Garcia Hernandez, P A IR - Garcia Hernandez PA FIR - Garcfa Reza, R IR - Garcfa Reza R FIR - Arias Mendoza, M A IR - Arias Mendoza MA FIR - Arenas Leon, J L IR - Arenas Leon JL FIR - Bazzoni Ruiz, A E IR - Bazzoni Ruiz AE FIR - Morales Villegas, E C IR - Morales Villegas EC FIR - Lazcano Soto, J R IR - Lazcano Soto JR FIR - Jimenez-Ramos, S A IR - Jimenez-Ramos SA FIR - De Los Rios Ibarra, M O IR - De Los Rios Ibarra MO FIR - Ong, T K IR - Ong TK FIR - Abidin, I B Z IR - Abidin IBZ FIR - Kasim, S S IR - Kasim SS FIR - Ali, N IR - Ali N FIR - Wan Mohamed, W M I IR - Wan Mohamed WMI FIR - Lee, L Y IR - Lee LY FIR - Krishinan, S IR - Krishinan S FIR - Ruhani, A I IR - Ruhani AI FIR - Hussein, Z IR - Hussein Z FIR - Rosman, A IR - Rosman A FIR - Bang, L H IR - Bang LH FIR - Van Der Zwaan, C IR - Van Der Zwaan C FIR - Vossenberg, T IR - Vossenberg T FIR - Martens, F M A C IR - Martens FMAC FIR - Groenemeijer, B IR - Groenemeijer B FIR - Nierop, P IR - Nierop P FIR - Dorman, R IR - Dorman R FIR - Van Beek, A P IR - Van Beek AP FIR - Swart, H IR - Swart H FIR - Schaap, J IR - Schaap J FIR - Romer, T J IR - Romer TJ FIR - Hoivik, H O IR - Hoivik HO FIR - Tonstad, S IR - Tonstad S FIR - Hjelmesaeth, J IR - Hjelmesaeth J FIR - Gullestad, L IR - Gullestad L FIR - Nygard, O K IR - Nygard OK FIR - H Galmen, R G IR - H Galmen RG FIR - Rice, E IR - Rice E FIR - Halvorsen, S IR - Halvorsen S FIR - Gretland Valderhaug, T IR - Gretland Valderhaug T FIR - Czochra, W IR - Czochra W FIR - Wozniak, I IR - Wozniak I FIR - Bogdanski, P IR - Bogdanski P FIR - Franek, E IR - Franek E FIR - Ostrowska, L IR - Ostrowska L FIR - Kania, G IR - Kania G FIR - Karczmarczyk, A IR - Karczmarczyk A FIR - Gajos, G IR - Gajos G FIR - Stogowska-Nikiciuk, B IR - Stogowska-Nikiciuk B FIR - Chrustowski, W IR - Chrustowski W FIR - Skoczylas, G IR - Skoczylas G FIR - Jurowiecki, J IR - Jurowiecki J FIR - Kujawiak, M IR - Kujawiak M FIR - Leksycka, A IR - Leksycka A FIR - Szyprowska, E IR - Szyprowska E FIR - Beckowski, M IR - Beckowski M FIR - Kalmucki, P IR - Kalmucki P FIR - Lukaszewicz, M IR - Lukaszewicz M FIR - Pulka, G IR - Pulka G FIR - Jozefowska, M IR - Jozefowska M FIR - Monteiro, P IR - Monteiro P FIR - Franca, S IR - Franca S FIR - Fonseca, L IR - Fonseca L FIR - Martins, C IR - Martins C FIR - Pinto, F IR - Pinto F FIR - Ferreira, D IR - Ferreira D FIR - Enculescu, D IR - Enculescu D FIR - Marin, L IR - Marin L FIR - Constantin, C IR - Constantin C FIR - Enache, G IR - Enache G FIR - Morosanu, M IR - Morosanu M FIR - Reurean Pintilei, D V IR - Reurean Pintilei DV FIR - Mistodie, C V IR - Mistodie CV FIR - Constantinescu, S IR - Constantinescu S FIR - Nicolescu, G IR - Nicolescu G FIR - Onaca, A IR - Onaca A FIR - Nafornita, V IR - Nafornita V FIR - Pop, L IR - Pop L FIR - Cif, A IR - Cif A FIR - Popa, B IR - Popa B FIR - Cosma, D IR - Cosma D FIR - Kurtinecz, M IR - Kurtinecz M FIR - Toarba, C IR - Toarba C FIR - Lupu, S IR - Lupu S FIR - Caceaune, E IR - Caceaune E FIR - M'fndrescu, N M IR - M'fndrescu NM FIR - Hancu, N IR - Hancu N FIR - Vladu, I M IR - Vladu IM FIR - Avram, R IR - Avram R FIR - Badiu, C V IR - Badiu CV FIR - Vlad, A IR - Vlad A FIR - Ermakova, P IR - Ermakova P FIR - Barbarash, O IR - Barbarash O FIR - Ruyatkin, D IR - Ruyatkin D FIR - Ezhov, M IR - Ezhov M FIR - Ryabov, V V IR - Ryabov VV FIR - Zrazhevskiy, K IR - Zrazhevskiy K FIR - Semashko, N A IR - Semashko NA FIR - Sergeeva-Kondrachenko, M Y IR - Sergeeva-Kondrachenko MY FIR - Gurieva, I IR - Gurieva I FIR - Kobalava, Z IR - Kobalava Z FIR - Zykov, M IR - Zykov M FIR - Khaisheva, L IR - Khaisheva L FIR - Gordeev, I G IR - Gordeev IG FIR - Zhdanova, E A IR - Zhdanova EA FIR - Sardinov, R IR - Sardinov R FIR - Zalevskaya, A IR - Zalevskaya A FIR - Boshchenko, A A IR - Boshchenko AA FIR - Shutemova, E IR - Shutemova E FIR - Samoilova, Y IR - Samoilova Y FIR - Lysenko, T A IR - Lysenko TA FIR - Sorokin, M IR - Sorokin M FIR - Suplotova, L A IR - Suplotova LA FIR - Bolshakova, O O IR - Bolshakova OO FIR - Dvoryashina, I V IR - Dvoryashina IV FIR - Smolenskaya, O IR - Smolenskaya O FIR - Veselovskaya, N G IR - Veselovskaya NG FIR - Belousova, L IR - Belousova L FIR - Antonova, E IR - Antonova E FIR - Peskov, A B IR - Peskov AB FIR - Shaydyuk, O IR - Shaydyuk O FIR - Markova, T IR - Markova T FIR - Obrezan, A IR - Obrezan A FIR - Sveklina, T IR - Sveklina T FIR - Shalaev, S IR - Shalaev S FIR - Gilinskaya, O IR - Gilinskaya O FIR - Khlevchuk, T IR - Khlevchuk T FIR - Galyavich, A IR - Galyavich A FIR - Mareev, V IR - Mareev V FIR - Guseva, G N IR - Guseva GN FIR - Zagrebelnaya, O IR - Zagrebelnaya O FIR - Vorobyeva, O IR - Vorobyeva O FIR - Krivosheeva, I IR - Krivosheeva I FIR - Reafan, Llc IR - Reafan L FIR - Alpenidze, D IR - Alpenidze D FIR - Platonov, G IR - Platonov G FIR - Vinogradova, O IR - Vinogradova O FIR - Pergaeva, Y IR - Pergaeva Y FIR - Kazakova, E E IR - Kazakova EE FIR - Ipatko, I IR - Ipatko I FIR - Ershova, O IR - Ershova O FIR - Kharakhulakh, M IR - Kharakhulakh M FIR - Lalic, N IR - Lalic N FIR - Stankovic, G IR - Stankovic G FIR - Ristic, A IR - Ristic A FIR - Djenic, N IR - Djenic N FIR - Stokic, E IR - Stokic E FIR - Lalic, K IR - Lalic K FIR - Asanin, M IR - Asanin M FIR - Vukicevic, M IR - Vukicevic M FIR - Eliasson, B IR - Eliasson B FIR - Ryden, L IR - Ryden L FIR - Eliasson, K IR - Eliasson K FIR - Lindholm, C J IR - Lindholm CJ FIR - Holmer, H IR - Holmer H FIR - Mooe, T IR - Mooe T FIR - Piyayotai, D IR - Piyayotai D FIR - Udommongkol, C IR - Udommongkol C FIR - Vathesatogkit, P IR - Vathesatogkit P FIR - Suwanagool, A IR - Suwanagool A FIR - Kiatchoosakun, S IR - Kiatchoosakun S FIR - Suwanwalaikorn, S IR - Suwanwalaikorn S FIR - Sansanayudh, N IR - Sansanayudh N FIR - Buranapin, S IR - Buranapin S FIR - Wongcharoen, W IR - Wongcharoen W FIR - Bakiner, O S IR - Bakiner OS FIR - Celik, A IR - Celik A FIR - Sari, R IR - Sari R FIR - Altuntas, Y IR - Altuntas Y FIR - Kayikcioglu, M IR - Kayikcioglu M FIR - Gogas, D IR - Gogas D FIR - Ozpelit, E IR - Ozpelit E FIR - Tuna, M M IR - Tuna MM FIR - Araz, M IR - Araz M FIR - Oguzhan, A IR - Oguzhan A FIR - Gul, I IR - Gul I FIR - Ozdogan, O IR - Ozdogan O FIR - Unubol, M IR - Unubol M FIR - Sonmez, Y A IR - Sonmez YA FIR - Sancak, S IR - Sancak S FIR - Adas, M IR - Adas M FIR - Kanadasi, M IR - Kanadasi M FIR - Dagdelen, S IR - Dagdelen S FIR - Yazici, D IR - Yazici D FIR - Soyluk Selcukbiricik, O IR - Soyluk Selcukbiricik O FIR - Liu, M E IR - Liu ME FIR - Wu, C C IR - Wu CC FIR - Yeh, H I IR - Yeh HI FIR - Hsieh, I C IR - Hsieh IC FIR - Lee, T L IR - Lee TL FIR - Rudenko, L IR - Rudenko L FIR - Myshanych, G IR - Myshanych G FIR - Parkhomenko, O IR - Parkhomenko O FIR - Ilashchuk, T IR - Ilashchuk T FIR - Vyshnyvetskyy, I IR - Vyshnyvetskyy I FIR - Leonidova, V IR - Leonidova V FIR - Horoshko, O IR - Horoshko O FIR - Buriakovska, O IR - Buriakovska O FIR - Velychko, V IR - Velychko V FIR - Kushnir, M IR - Kushnir M FIR - Stanislavchuk, M IR - Stanislavchuk M FIR - Kyyak, Y IR - Kyyak Y FIR - Todoriuk, L IR - Todoriuk L FIR - Levchenko, O IR - Levchenko O FIR - Lysak, Z IR - Lysak Z FIR - Mostovoy, Y IR - Mostovoy Y FIR - Serota, H IR - Serota H FIR - Doran, J A IR - Doran JA FIR - Concha, M IR - Concha M FIR - Lupovitch, S IR - Lupovitch S FIR - Fordan, S IR - Fordan S FIR - Samal, A K IR - Samal AK FIR - Desouza, C V IR - Desouza CV FIR - Rasouli, N IR - Rasouli N FIR - Smith, S K IR - Smith SK FIR - Shneker, A IR - Shneker A FIR - Harris, B IR - Harris B FIR - Kandath, D IR - Kandath D FIR - Al-Karadsheh, A IR - Al-Karadsheh A FIR - Clark, W IR - Clark W FIR - Carr, J IR - Carr J FIR - Anderson, R J IR - Anderson RJ FIR - Tran, H IR - Tran H FIR - Jardula, M F IR - Jardula MF FIR - Marso, S P IR - Marso SP FIR - O'donnell, P IR - O'donnell P FIR - Snyder, B IR - Snyder B FIR - Wynne, A IR - Wynne A FIR - Koren, M J IR - Koren MJ FIR - Harris, K IR - Harris K FIR - Buse, J B IR - Buse JB FIR - Lingvay, I IR - Lingvay I FIR - Murray, R IR - Murray R FIR - Swenson, B P IR - Swenson BP FIR - Bitar, F IR - Bitar F FIR - Singh, N IR - Singh N FIR - Wallace, J IR - Wallace J FIR - Cannon, K IR - Cannon K FIR - Murthy, A IR - Murthy A FIR - Bakdash, W IR - Bakdash W FIR - Iteld, B IR - Iteld B FIR - Logemann, T IR - Logemann T FIR - Busch, R IR - Busch R FIR - Correia, M IR - Correia M FIR - Usdan, L IR - Usdan L FIR - Bernstein, M IR - Bernstein M FIR - Jabbar, D IR - Jabbar D FIR - Mcgrew, F IR - Mcgrew F FIR - Sultan, S IR - Sultan S FIR - Allison, D C IR - Allison DC FIR - Garvey, W T IR - Garvey WT FIR - Zacher, J IR - Zacher J FIR - Sivalingam, K IR - Sivalingam K FIR - Robbins, D IR - Robbins D FIR - Aroda, V R IR - Aroda VR FIR - Brautigam, D IR - Brautigam D FIR - Jackson, R A IR - Jackson RA FIR - Riley, T H IR - Riley TH FIR - Sangrigoli, R IR - Sangrigoli R FIR - Baum, S IR - Baum S FIR - Mills, R E IR - Mills RE FIR - Reyes, C R IR - Reyes CR FIR - Morawski, E J IR - Morawski EJ FIR - Abou Assi, H IR - Abou Assi H FIR - Berk, M IR - Berk M FIR - Tripathy, D IR - Tripathy D FIR - Billings, L IR - Billings L FIR - Lewis, M IR - Lewis M FIR - Hewitt, E IR - Hewitt E FIR - Zarich, S IR - Zarich S FIR - Ariani, M IR - Ariani M FIR - Siddiqui, I A IR - Siddiqui IA FIR - Mcpherson, D D IR - Mcpherson DD FIR - Herzog, W IR - Herzog W FIR - Levins, P IR - Levins P FIR - Soufer, J IR - Soufer J FIR - Carrillo-Jimenez, R IR - Carrillo-Jimenez R FIR - Pereira, I IR - Pereira I FIR - Daboul, N Y IR - Daboul NY FIR - Buljubasic, N IR - Buljubasic N FIR - Geller, S A IR - Geller SA FIR - Rosen, G IR - Rosen G FIR - Wenocur, H S IR - Wenocur HS FIR - Audish, H IR - Audish H FIR - Dela Llana, A IR - Dela Llana A FIR - Biggs, W C IR - Biggs WC FIR - Calinescu, C V IR - Calinescu CV FIR - Agha, M IR - Agha M FIR - Brodie, S K IR - Brodie SK FIR - Bays, H E IR - Bays HE FIR - Budoff, M J IR - Budoff MJ FIR - Kastelic, R IR - Kastelic R FIR - Ledesma, G N IR - Ledesma GN FIR - Mclean, B K IR - Mclean BK FIR - Powell, T IR - Powell T FIR - Sathananthan, A IR - Sathananthan A FIR - Sigal, F IR - Sigal F FIR - Wilson, J P IR - Wilson JP FIR - Lash, J IR - Lash J FIR - Sidey, J IR - Sidey J FIR - Buynak, R IR - Buynak R FIR - Pereira, E S IR - Pereira ES FIR - Barnum, O IR - Barnum O FIR - Burguera, B IR - Burguera B FIR - Joyce, J M IR - Joyce JM FIR - Nayak, B M IR - Nayak BM FIR - Lenzmeier, T IR - Lenzmeier T FIR - Siraj, E IR - Siraj E FIR - Warren, M L IR - Warren ML FIR - Weintraub, H IR - Weintraub H FIR - Dukes, C E IR - Dukes CE FIR - Houser, P M IR - Houser PM FIR - Kereiakes, D J IR - Kereiakes DJ FIR - Lofton, H IR - Lofton H FIR - Raikhel, M A IR - Raikhel MA FIR - Weber, B IR - Weber B FIR - Opsahl, P J IR - Opsahl PJ FIR - Block, B IR - Block B FIR - Beshay, I IR - Beshay I FIR - Khadra, S IR - Khadra S FIR - Brockmyre, A P IR - Brockmyre AP FIR - Gandy, W H IR - Gandy WH FIR - Risser, J A IR - Risser JA FIR - Jaffrani, N A IR - Jaffrani NA FIR - Sotolongo, C IR - Sotolongo C FIR - Heimer, B IR - Heimer B FIR - Iranmanesh, A IR - Iranmanesh A FIR - Arif, A A IR - Arif AA FIR - Lovell, C F IR - Lovell CF FIR - Philis-Tsimikas, A IR - Philis-Tsimikas A FIR - Garza, J C IR - Garza JC FIR - Potu, R P IR - Potu RP FIR - Shah, N IR - Shah N FIR - Spriggs, D IR - Spriggs D FIR - Agaiby, J M IR - Agaiby JM FIR - Liu, J IR - Liu J FIR - Purighalla, R S IR - Purighalla RS FIR - Oaks, J B IR - Oaks JB FIR - Saggar, S IR - Saggar S FIR - Patel, M B IR - Patel MB FIR - Qureshi, M IR - Qureshi M FIR - Solano, R IR - Solano R FIR - Scott, J IR - Scott J FIR - Cornett, G M IR - Cornett GM FIR - Lepor, N IR - Lepor N FIR - Nakhle, S N IR - Nakhle SN FIR - Miller, G IR - Miller G FIR - Pop-Busui, R IR - Pop-Busui R FIR - Trusau, A IR - Trusau A FIR - Shea, H C IR - Shea HC FIR - Call, R S IR - Call RS FIR - Hartman, A N IR - Hartman AN FIR - Condit, J IR - Condit J FIR - Pullman, J IR - Pullman J FIR - Rodbard, H W IR - Rodbard HW FIR - Martinez, C IR - Martinez C FIR - Geohas, J G IR - Geohas JG FIR - Issa, M IR - Issa M FIR - Sofley, C W IR - Sofley CW FIR - Chaicha-Brom, T IR - Chaicha-Brom T FIR - Ward, K IR - Ward K FIR - Lorraine, R IR - Lorraine R FIR - Ghazi, A IR - Ghazi A FIR - Klein, E J IR - Klein EJ FIR - Klonoff, D IR - Klonoff D FIR - Ong, S IR - Ong S FIR - Vo, A IR - Vo A FIR - Aronne, L J IR - Aronne LJ FIR - Gambill, M L IR - Gambill ML FIR - Bhan, A IR - Bhan A FIR - Sargeant, W IR - Sargeant W FIR - Still, C IR - Still C FIR - Morin, R P IR - Morin RP FIR - Delibasic, M IR - Delibasic M FIR - Breton, C F IR - Breton CF FIR - Perez-Vargas, E A IR - Perez-Vargas EA FIR - Oneil, P IR - Oneil P FIR - Bosworth, H IR - Bosworth H FIR - Gilbert, M P IR - Gilbert MP FIR - Ruffin, O IR - Ruffin O FIR - Folkens, E M IR - Folkens EM FIR - Meyers, P IR - Meyers P FIR - Wierum, C IR - Wierum C FIR - Jastreboff, A IR - Jastreboff A FIR - Davuluri, A K IR - Davuluri AK FIR - Ahmed, A IR - Ahmed A FIR - Gorton, S C IR - Gorton SC FIR - Finneran, M P IR - Finneran MP FIR - Herman, L IR - Herman L FIR - Jerkins, T IR - Jerkins T FIR - Munir, I IR - Munir I FIR - Tamirisa, A IR - Tamirisa A FIR - Curtis, B IR - Curtis B FIR - Kubicki, T IR - Kubicki T FIR - Johnson, W IR - Johnson W FIR - Yuan, Q IR - Yuan Q FIR - Krishnasamy, S S IR - Krishnasamy SS FIR - Welker, J IR - Welker J FIR - Chandra, S IR - Chandra S FIR - Buffman, B IR - Buffman B FIR - Perkelvald, A IR - Perkelvald A FIR - Pratley, R E IR - Pratley RE FIR - Shlesinger, Y IR - Shlesinger Y FIR - Poremba, J IR - Poremba J FIR - Levy, L J IR - Levy LJ FIR - D'agostino, R IR - D'agostino R FIR - Friedman, K IR - Friedman K FIR - Ebrahim, I O IR - Ebrahim IO FIR - Badat, A IR - Badat A FIR - Burgess, L IR - Burgess L FIR - Fourie, N IR - Fourie N FIR - Urbach, D IR - Urbach D FIR - Fulat, M IR - Fulat M FIR - Van Nieuwenhuizen, E IR - Van Nieuwenhuizen E FIR - Tsabedze, N IR - Tsabedze N FIR - Coetzee, K IR - Coetzee K FIR - Klug, E IR - Klug E FIR - Makotoko, E M IR - Makotoko EM FIR - Moosa, N IR - Moosa N FIR - De Jong, D M IR - De Jong DM FIR - Van, E IR - Van E FIR - Zyl, L Van IR - Zyl LV FIR - Corbett, C IR - Corbett C FIR - Kapp, C IR - Kapp C FIR - Wadvalla, S IR - Wadvalla S FIR - Dawood, S Y IR - Dawood SY FIR - Punt, Z E IR - Punt ZE FIR - Lombard, L IR - Lombard L FIR - Lombaard, J J IR - Lombaard JJ FIR - Bandezi, V N IR - Bandezi VN FIR - Peter, J IR - Peter J FIR - Jugnundan, P IR - Jugnundan P FIR - Lincoff, A Michael IR - Lincoff AM FIR - Ryan, Donna H IR - Ryan DH FIR - Colhoun, Helen M IR - Colhoun HM FIR - Deanfield, John IR - Deanfield J FIR - Emerson, Scott S IR - Emerson SS FIR - Kahn, Steven E IR - Kahn SE FIR - Kushner, Robert F IR - Kushner RF FIR - Lingvay, Ildiko IR - Lingvay I FIR - Plutzky, Jorge IR - Plutzky J FIR - Brown-Frandsen, Kirstine IR - Brown-Frandsen K FIR - Hovingh, G Kees IR - Hovingh GK FIR - Hardt-Lindberg, Soren IR - Hardt-Lindberg S FIR - Tornoe, Christoffer W IR - Tornoe CW EDAT- 2023/11/12 12:44 MHDA- 2023/12/17 09:45 CRDT- 2023/11/12 07:33 PHST- 2023/12/17 09:45 [medline] PHST- 2023/11/12 12:44 [pubmed] PHST- 2023/11/12 07:33 [entrez] AID - 10.1056/NEJMoa2307563 [doi] PST - ppublish SO - N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. Epub 2023 Nov 11. PMID- 37951155 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20260127 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 688 DP - 2023 Dec 25 TI - Effect of combined administration of Acyl-CoA: Cholesterol acyltransferase 1 inhibitor and glucagon-like peptide 1 receptor agonist on a rodent model of diet-induced obesity. PG - 149164 LID - S0006-291X(23)01258-5 [pii] LID - 10.1016/j.bbrc.2023.149164 [doi] AB - A glucagon-like peptide 1 receptor agonist (GLP-1 RA) semaglutide was approved for the treatment of obesity by the Food and Drug Administration. However, it can cause gastrointestinal events at high doses, limiting its broader use. Combining drugs with multiple mechanisms of action could enhance the weight-reducing effects while minimizing side effects. To this end, we investigated the combined effects of semaglutide and avasimibe, an acyl-CoA:cholesterol acyltransferase 1 (ACAT1) inhibitor, on weight reduction in diet-induced obesity mice. Two cohorts of mice were used: In cohort 1, mice were fed a high-fat (HF) diet for 12 weeks and then randomly assigned to the vehicle, avasimibe [10 mg/kg body weight (BW)], semaglutide (0.4 mg/kg BW), or combination groups. The drugs were administered via subcutaneous (sc) injections on a daily basis. In cohort 2, mice were fed an HF diet for 8 weeks and randomly assigned to the same four groups, but avasimibe was administered at a dose of 20 mg/kg BW, and the drugs were administered every 3 days. In cohort 1, semaglutide initially reduced food intake initially, but this effect was diminished with prolonged administration. Avasimibe, on the other hand, did not affect food intake but prevented weight gain to a lesser extent than semaglutide. Importantly, the combination treatment resulted in the greatest percentage of body weight reduction, along with lower plasma glucose and leptin levels compared to the semaglutide single-treatment group. Cohort 2 confirmed that the superior weight loss in the combination group compared to the other three groups was largely due to a significant reduction in fat mass. Histological analysis of inguinal adipose tissue showed smaller adipocyte size across all treatment groups compared to the vehicle group, with no significant differences among the treatment groups. Collectively, these findings suggest combining semaglutide and avasimibe could be an effective approach to weight management. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Kim, Sora Q AU - Kim SQ AD - Department of Nutrition Science, Purdue University, West Lafayette, IN, 47907, USA. FAU - Kim, Jeonghoon AU - Kim J AD - EFIL BioScience Inc., Bando Ivyvalley, Cheonggyesan-ro, Soojeong-gu, Seongnam-si, Gyeonggi-do, 13105, Republic of Korea. FAU - Choi, Mulim AU - Choi M AD - EFIL BioScience Inc., Bando Ivyvalley, Cheonggyesan-ro, Soojeong-gu, Seongnam-si, Gyeonggi-do, 13105, Republic of Korea. FAU - Kim, Young AU - Kim Y AD - Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA, 90095, USA. FAU - Kim, Shin AU - Kim S AD - Department of Chemistry, New York University, New York, NY, 10003, USA. FAU - Kim, Kee-Hong AU - Kim KH AD - Department of Food Science, Purdue University, West Lafayette, IN, 47907, USA. Electronic address: keehong@purdue.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231107 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - EC 2.3.1.26 (Sterol O-Acyltransferase) RN - EC 2.3.- (Acyltransferases) RN - 0 (Acyl Coenzyme A) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 28LQ20T5RC (avasimibe) RN - 0 (Acetamides) RN - 0 (Sulfonamides) SB - IM MH - Humans MH - Mice MH - Animals MH - *Sterol O-Acyltransferase MH - Rodentia MH - Acyltransferases MH - Acyl Coenzyme A MH - Obesity/drug therapy/etiology MH - Diet MH - Weight Loss MH - Glucagon-Like Peptide 1 MH - Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Acetamides MH - Sulfonamides OTO - NOTNLM OT - Avasimibe OT - Diet-induced obesity OT - Glucagon-like peptide 1 receptor agonist OT - Semaglutide OT - Weight loss COIS- Declaration of competing interest KHK is a founder and shareholder of EFIL BioScience Inc. MC and JK are EFIL BioScience Inc. employees. All other authors declare no conflict of interest. EDAT- 2023/11/12 00:42 MHDA- 2023/11/27 12:43 CRDT- 2023/11/11 18:14 PHST- 2023/10/20 00:00 [received] PHST- 2023/10/26 00:00 [accepted] PHST- 2023/11/27 12:43 [medline] PHST- 2023/11/12 00:42 [pubmed] PHST- 2023/11/11 18:14 [entrez] AID - S0006-291X(23)01258-5 [pii] AID - 10.1016/j.bbrc.2023.149164 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2023 Dec 25;688:149164. doi: 10.1016/j.bbrc.2023.149164. Epub 2023 Nov 7. PMID- 37947489 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20231127 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 32 IP - 11 DP - 2023 Jul-Dec TI - Retatrutide showing promise in obesity (and type 2 diabetes). PG - 997-1001 LID - 10.1080/13543784.2023.2283020 [doi] AB - INTRODUCTION: Obesity is a major risk factor for cardiovascular disease, diabetes, osteoarthritis, and some cancers. Retatrutide stimulates Glucagon-like peptide 1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP) receptors, and glucagon receptors, and is being developed for the treatment of obesity and type 2 diabetes. AREAS COVERED: A phase 2 clinical trial of retatrutide (LY3437943) in the treatment of obesity. The primary end point was percentage change in weight from baseline to 24 weeks, which ranged from -7.2% to -~18% as the dose of retatrutide increased from 1 mg to 12 mg. The most frequent adverse events were gastrointestinal (nausea, diarrhea, vomiting). EXPERT OPINION: The results for retatrutide in phase 2 for obesity (and diabetes) are mostly encouraging. Consistent with being a GLP-1 receptor agonist, heart rate was increased by up to 6.7 beats/min by retatrutide, which may be detrimental and offset some of the benefits of weight loss. Presumably, retatrutide is being developed as a challenger to the recently developed weight loss medicines; semaglutide and/or tirzepatide. Thus, comparator studies are needed between retatrutide and these drugs, but none are ongoing and, in my opinion, this lack is a major omission in the development of retatrutide. FAU - Doggrell, Sheila A AU - Doggrell SA AD - School of Pharmacy and Medical Sciences, Gold Coast Campus, Griffith University, Queensland, Australia. LA - eng PT - Journal Article PT - Review DEP - 20231124 PL - England TA - Expert Opin Investig Drugs JT - Expert opinion on investigational drugs JID - 9434197 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/complications/drug therapy MH - Risk Factors MH - Glucagon-Like Peptide 1 MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor MH - Hypoglycemic Agents/adverse effects OTO - NOTNLM OT - Clinical trial OT - diabetes OT - obesity OT - phase 2 OT - retatrutide OT - semaglutide OT - tirzepatide EDAT- 2023/11/10 12:45 MHDA- 2023/11/27 12:41 CRDT- 2023/11/10 09:43 PHST- 2023/11/27 12:41 [medline] PHST- 2023/11/10 12:45 [pubmed] PHST- 2023/11/10 09:43 [entrez] AID - 10.1080/13543784.2023.2283020 [doi] PST - ppublish SO - Expert Opin Investig Drugs. 2023 Jul-Dec;32(11):997-1001. doi: 10.1080/13543784.2023.2283020. Epub 2023 Nov 24. PMID- 37944862 OWN - NLM STAT- MEDLINE DCOM- 20240318 LR - 20260528 IS - 1544-3450 (Electronic) IS - 1086-5802 (Linking) VI - 64 IP - 2 DP - 2024 Mar-Apr TI - Impact of a pharmacist-led weight management service in a cardiology clinic. PG - 557-563 LID - S1544-3191(23)00372-2 [pii] LID - 10.1016/j.japh.2023.11.011 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for weight management require frequent dose titration, patient education, and insurance coverage navigation, which pharmacists are well equipped to manage. Data are lacking regarding the benefit of a pharmacist-managed service using GLP-1 RAs for weight loss in a high-risk cardiac population. OBJECTIVE: This study aimed to evaluate the impact of a pharmacist-led weight loss service within a cardiology clinic using GLP-1 RAs and lifestyle counseling in patients with overweight and obesity. PRACTICE DESCRIPTION: An outpatient cardiology clinic employs clinical pharmacists who use collaborative practice agreements to provide cardiovascular risk reduction services that did not include weight management at baseline. PRACTICE INNOVATION: This is the first description of a pharmacist-led weight management clinic using solely GLP-1 RAs in a cardiology practice. Patients were referred to the clinical pharmacist, who initiated and titrated GLP-1 RA and provided lifestyle counseling. EVALUATION METHODS: This was a single-center, prospective, pre-post analysis of adults with a body mass index of at least 30 kg/m(2) or 27 kg/m(2) with a weight-related comorbidity, with a preceding failed dietary effort and insurance coverage for semaglutide (Wegovy, Novo Nordisk) or liraglutide (Saxenda, Novo Nordisk) and managed by a pharmacist. The primary outcome was patients achieving >/= 5% weight loss at 6 months, assessed via descriptive statistics. RESULTS: Between March 2022 and March 2023, 204 patients were referred by their cardiologist, and 59 patients started treatment with semaglutide (Wegovy, Novo Nordisk) or liraglutide (Saxenda, Novo Nordisk). A total of 31 patients completed 6 months of treatment at time of study completion, and all achieved >/= 5% weight loss at 6 months, with a mean weight loss of 12.6%. Glycated hemoglobin improved by 0.6%, low-density lipoprotein by 18 mg/dL, triglycerides by 29 mg/dL, systolic blood pressure by 9 mm Hg, and diastolic blood pressure by 2 mm Hg. CONCLUSION: Pharmacist-led management of GLP-1 RA in patients with obesity or overweight led to clinically meaningful weight loss and improvements in weight-related comorbidities. CI - Copyright (c) 2023 American Pharmacists Association(R). Published by Elsevier Inc. All rights reserved. FAU - Yates, Madison AU - Yates M FAU - Supple, Megan AU - Supple M FAU - Maccia, Melissa AU - Maccia M LA - eng PT - Journal Article DEP - 20231108 PL - United States TA - J Am Pharm Assoc (2003) JT - Journal of the American Pharmacists Association : JAPhA JID - 101176252 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Adult MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Pharmacists MH - Liraglutide/adverse effects MH - Overweight/chemically induced/drug therapy MH - Prospective Studies MH - Treatment Outcome MH - Obesity/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - *Cardiology MH - Weight Loss MH - *Diabetes Mellitus, Type 2/drug therapy COIS- Disclosure The authors declare no relevant conflicts of interest or financial relationships. EDAT- 2023/11/10 00:44 MHDA- 2024/03/18 06:42 CRDT- 2023/11/09 19:19 PHST- 2023/05/23 00:00 [received] PHST- 2023/10/13 00:00 [revised] PHST- 2023/11/04 00:00 [accepted] PHST- 2024/03/18 06:42 [medline] PHST- 2023/11/10 00:44 [pubmed] PHST- 2023/11/09 19:19 [entrez] AID - S1544-3191(23)00372-2 [pii] AID - 10.1016/j.japh.2023.11.011 [doi] PST - ppublish SO - J Am Pharm Assoc (2003). 2024 Mar-Apr;64(2):557-563. doi: 10.1016/j.japh.2023.11.011. Epub 2023 Nov 8. PMID- 37935463 OWN - NLM STAT- MEDLINE DCOM- 20240109 LR - 20260721 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 2 DP - 2024 Feb TI - Greater time spent with HbA1c less than 7.0% with oral semaglutide versus oral comparators: An exploratory analysis of the PIONEER studies. PG - 532-539 LID - 10.1111/dom.15339 [doi] AB - AIM: To assess how long participants with type 2 diabetes spent with HbA1c less than 7.0% and how likely they were to maintain this target with oral semaglutide 7 mg versus sitagliptin 100 mg or oral semaglutide 14 mg versus empagliflozin 25 mg, sitagliptin 100 mg or subcutaneous liraglutide 1.8 mg. MATERIALS AND METHODS: Analyses used on-treatment data without rescue medication for all randomized participants (semaglutide [approved maintenance doses], n = 1880; comparators [not including placebo], n = 1412). Duration of time with HbA1c less than 7.0% was calculated using an HbA1c time curve. A binary endpoint of achieving HbA1c less than 7.0% at weeks 26 (week 24 for PIONEER 7) and 52 of each trial (and week 78 for PIONEER 3) was analysed. RESULTS: Mean duration of time with HbA1c less than 7.0% was greater with oral semaglutide 7 mg versus sitagliptin in PIONEER 3 (27 vs. 22 weeks) and with oral semaglutide 14 mg versus empagliflozin and sitagliptin (27-34 vs. 19 vs. 22 weeks, respectively), and similar versus subcutaneous liraglutide. A greater proportion of participants achieved and maintained HbA1c less than 7.0% for more than 75% of the trial with oral semaglutide 14 mg versus oral comparators. The odds of achieving HbA1c less than 7.0% at weeks 24/26 and 52/78 were significantly greater with oral semaglutide 14 mg versus oral comparators or subcutaneous liraglutide, and with oral semaglutide 7 mg versus sitagliptin. CONCLUSIONS: Oral semaglutide 7 and 14 mg resulted in greater time spent with HbA1c less than 7.0%, and a greater likelihood of achieving and maintaining HbA1c less than 7.0% versus oral comparators. CI - (c) 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Velocity Clinical Research at Medical City, Dallas, Texas, USA. FAU - Cariou, Bertrand AU - Cariou B AUID- ORCID: 0000-0002-1580-8040 AD - Nantes Universite, CHU Nantes, CNRS, Inserm, l'institut du thorax, Nantes, France. FAU - Eliasson, Johanna AU - Eliasson J AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Frappin, Guillaume AU - Frappin G AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kaltoft, Margit S AU - Kaltoft MS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Montanya, Eduard AU - Montanya E AUID- ORCID: 0000-0003-2518-9076 AD - Hospital Universitari Bellvitge, IDIBELL, CIBERDEM, and University of Barcelona, Barcelona, Spain. FAU - Knop, Filip K AU - Knop FK AUID- ORCID: 0000-0002-2495-5034 AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article DEP - 20231107 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin MH - Liraglutide/adverse effects MH - Glucagon-Like Peptides/adverse effects MH - Sitagliptin Phosphate/adverse effects MH - Semaglutide MH - Benzhydryl Compounds MH - Glucosides OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - glycaemic control OT - incretin therapy OT - semaglutide OT - type 2 diabetes EDAT- 2023/11/08 00:41 MHDA- 2024/01/09 06:42 CRDT- 2023/11/07 20:43 PHST- 2023/09/29 00:00 [revised] PHST- 2023/07/20 00:00 [received] PHST- 2023/10/08 00:00 [accepted] PHST- 2024/01/09 06:42 [medline] PHST- 2023/11/08 00:41 [pubmed] PHST- 2023/11/07 20:43 [entrez] AID - 10.1111/dom.15339 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Feb;26(2):532-539. doi: 10.1111/dom.15339. Epub 2023 Nov 7. PMID- 37933169 OWN - NLM STAT- MEDLINE DCOM- 20231109 LR - 20260127 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 26 IP - 1 DP - 2023 Jan-Dec TI - Budget impact of introducing oral semaglutide to the public healthcare benefit package in Saudi Arabia. PG - 1455-1468 LID - 10.1080/13696998.2023.2277056 [doi] AB - BACKGROUND: The Kingdom of Saudi Arabia (KSA) has embarked on a Health Sector Transformation Program as part of the Kingdom's Vision 2030 initiatives with the facilitation of access to healthcare services for the millions in KSA with diabetes an essential part of the Program. Decision-making tools, such as budget impact models, are required to consider the addition of new medications like oral semaglutide that have multifaceted health benefits and address barriers related to therapeutic inertia to reduce diabetes-related complications. OBJECTIVE: To determine the financial impact of the introduction of oral semaglutide as a treatment option for people with type 2 diabetes mellitus (T2DM) in KSA. METHODS: From the public payer's perspective, the budget impact model estimates the costs before and after the introduction of oral semaglutide over a 5-year time horizon. The budget impact of introducing oral semaglutide (primary comparator) compared with three different classes of diabetes medicines: glucagon-like peptide-1 receptor agonists (GLP-1), sodium-glucose transport protein 2 inhibitors (SGLT 2i) and dipeptidyl peptidase 4 inhibitors (DDP-4i) have been calculated based on the projected market shares. The model includes the cost of care through the incorporation of health outcomes that have an impact on the national payer's budget in Saudi Riyals (SAR). RESULTS: The budget impact over the five-year time horizon indicates a medication cost increase (17,424,788 SAR), and cost offsets which include a difference in diabetes management costs (-3,625,287 SAR), CV complications costs (-810,733 SAR) and weight loss savings of 453,936 SAR. The cumulative total cost difference is 12,427,858 SAR (0.66%). CONCLUSION: The introduction of oral semaglutide 14 mg as a second-line treatment option after metformin is indicated as budget-neutral to slightly budget-inflating for the public pharmaceutical formulary of KSA. The price difference is offset by positive health outcomes and costs. This conclusion was confirmed through a probabilistic sensitivity analysis. FAU - Alluhidan, Mohammed AU - Alluhidan M AUID- ORCID: 0000-0003-3824-2059 AD - Health Economics Unit, Saudi Health Council, Riyadh, Saudi Arabia. FAU - Alabdulkarim, Hana AU - Alabdulkarim H AUID- ORCID: 0000-0002-5502-8743 AD - Drug Policy and Economic Centre, Ministry of National Guards Health Affairs, Riyadh, Saudi Arabia. AD - Doctoral School of Applied Informatics and Applied Mathematics, Obuda University, Budapest, Hungary. FAU - Alrumaih, Ali AU - Alrumaih A AD - Pharmaceutical Care Department, Medical Services Directorate, Ministry of Defence, Riyadh, Saudi Arabia. FAU - Al-Turaiki, Abdulrahman AU - Al-Turaiki A AUID- ORCID: 0000-0002-8006-8544 AD - Pharmaceutical Care Department, Ministry of National Guard-Health Affairs, King Abdul Aziz Medical City, Riyadh, Saudi Arabia. FAU - Alshahrani, Abdullah AU - Alshahrani A AD - Ministry of Defence Hospital, Khamis Mushait, Saudi Arabia. FAU - Al-Qahtani, Saad AU - Al-Qahtani S AD - Security Forces Hospital, Riyadh, Saudi Arabia. FAU - Alhossan, Abdulaziz AU - Alhossan A AUID- ORCID: 0000-0001-5849-6756 AD - College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Al-Jedai, Ahmed AU - Al-Jedai A AUID- ORCID: 0000-0002-4730-9086 AD - College of Pharmacy, Alfaisal University, Riyadh, Saudi Arabia. AD - Therapeutic Affairs, Ministry of Health, Riyadh, Saudi Arabia. LA - eng PT - Journal Article DEP - 20231108 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Drug Costs MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Saudi Arabia MH - Semaglutide OTO - NOTNLM OT - I OT - I1 OT - I13 OT - I18 OT - Kingdom of Saudi Arabia OT - Type 2 diabetes OT - budget impact OT - oral semaglutide OT - weight loss EDAT- 2023/11/07 06:45 MHDA- 2023/11/09 06:42 CRDT- 2023/11/07 03:40 PHST- 2023/11/09 06:42 [medline] PHST- 2023/11/07 06:45 [pubmed] PHST- 2023/11/07 03:40 [entrez] AID - 10.1080/13696998.2023.2277056 [doi] PST - ppublish SO - J Med Econ. 2023 Jan-Dec;26(1):1455-1468. doi: 10.1080/13696998.2023.2277056. Epub 2023 Nov 8. PMID- 37917871 OWN - NLM STAT- MEDLINE DCOM- 20240319 LR - 20250729 IS - 1476-5381 (Electronic) IS - 0007-1188 (Print) IS - 0007-1188 (Linking) VI - 181 IP - 8 DP - 2024 Apr TI - Newer pharmacological interventions directed at gut hormones for obesity. PG - 1153-1164 LID - 10.1111/bph.16278 [doi] AB - The objective is to review the newer pharmacological interventions for obesity, specifically single, dual and triple incretin receptor agonists that are either available or in the pipeline for treatment of obesity. The three incretin receptor targets are glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and glucagon. There are several approved single or dual incretin agonists which can be administered subcutaneously daily (e.g., liraglutide) or weekly (e.g., semaglutide, dulaglutide, and exenatide QW), and other experimental dual or triple incretin agonists. Analogues of amylin, peptide YY and oxyntomodulin, as well as the combination of a GLP1R agonist and GIPR antagonist also are in development. Oral semaglutide (administered daily) is approved for type 2 diabetes mellitus and is on track for regulatory review for obesity. The review includes specifically perspectives on the effects of these mechanisms and pharmacological agents on gastric emptying, which contribute to satiation and weight loss, in addition to the established evidence on effects on central mechanisms controlling appetite. In the future, it is anticipated that small molecule GLP-1 receptor agonists (e.g., oral danuglipron) will be developed for treating obesity. These pharmacological agents are having significant impact on glycaemic control and obesity and on their co-morbidities. CI - (c) 2023 British Pharmacological Society. FAU - Camilleri, Michael AU - Camilleri M AD - Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA. FAU - Acosta, Andres AU - Acosta A AD - Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), Mayo Clinic, Rochester, Minnesota, USA. LA - eng GR - K23 DK114460/DK/NIDDK NIH HHS/United States GR - R01 DK139028/DK/NIDDK NIH HHS/United States GR - K23-DK114460/NH/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review DEP - 20231130 PL - England TA - Br J Pharmacol JT - British journal of pharmacology JID - 7502536 RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - Glucagon-Like Peptide 1/pharmacology MH - Gastric Inhibitory Polypeptide/pharmacology MH - Hypoglycemic Agents/pharmacology MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10947960 MID - NIHMS1942873 OTO - NOTNLM OT - GIP OT - GLP-1 OT - agonists OT - gluagon OT - incretins OT - receptors COIS- Michael Camilleri is a stockholder in Phenomix Sciences and serves as a consultant to Kallyope (with consulting fee paid to his employer, Mayo Clinic). Andres Acosta is a stockholder in Gila Therapeutics, and Phenomix Sciences; he served on as a consultant for Rhythm Pharmaceuticals, General Mills, Nestle, Boehringer Ingelheim, Currax, Amgen, Bausch Health, RareDiseases. EDAT- 2023/11/02 18:43 MHDA- 2024/03/19 06:44 PMCR- 2025/04/01 CRDT- 2023/11/02 15:42 PHST- 2023/10/10 00:00 [revised] PHST- 2023/06/27 00:00 [received] PHST- 2023/10/12 00:00 [accepted] PHST- 2024/03/19 06:44 [medline] PHST- 2023/11/02 18:43 [pubmed] PHST- 2023/11/02 15:42 [entrez] PHST- 2025/04/01 00:00 [pmc-release] AID - 10.1111/bph.16278 [doi] PST - ppublish SO - Br J Pharmacol. 2024 Apr;181(8):1153-1164. doi: 10.1111/bph.16278. Epub 2023 Nov 30. PMID- 37917019 OWN - NLM STAT- MEDLINE DCOM- 20240123 LR - 20250104 IS - 1938-4114 (Electronic) IS - 1937-1888 (Print) IS - 1937-1888 (Linking) VI - 85 IP - 1 DP - 2024 Jan TI - Social Media as Pharmacovigilance: The Potential for Patient Reports to Inform Clinical Research on Glucagon-Like Peptide 1 (GLP-1) Receptor Agonists for Substance Use Disorders. PG - 5-11 LID - 10.15288/jsad.23-00318 [doi] AB - The surge in popularity of semaglutide (Ozempic, Wegovy, Rybelsus) and other glucagon-like-peptide 1 (GLP-1) receptor agonists has been accompanied by widespread reports of unintended reductions in alcohol use (and other addictive behaviors) during treatment. With clinical trials of GLP-1 receptor agonists for substance use only recently under way, anecdotal reports (including via social media) are now a primary reason for interest in potential effects of GLP-1 receptor agonists on alcohol use in patient populations. The nature and volume of these reports raises the prospect that social media data can potentially be leveraged to inform the study of novel addiction treatments and the prioritization of behavioral or neurobiological targets for mechanistic research. This approach, which aligns with recent efforts to apply social media data to pharmacovigilance, may be particularly relevant for drug repurposing efforts. This possibility is illustrated by a thematic analysis of anonymous online reports concerning changes in alcohol use or alcohol-related effects during treatment with GLP-1 receptor agonists. These reports not only support the rationale for clinical trials but also point to potential neurobehavioral mechanisms (e.g., satiety, craving/preoccupation, aversion, altered subjective response) that might inform hypotheses for human laboratory and neuroscience studies. Refined methods for capturing patient reports of incidental medication effects on addictive behaviors at large scale could potentially lead to novel, pharmacovigilance-based approaches to identify candidate therapies for drug repurposing efforts. FAU - Bremmer, Michael P AU - Bremmer MP AD - Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. AD - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. FAU - Hendershot, Christian S AU - Hendershot CS AD - Department of Psychology & Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. AD - Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. AD - Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. LA - eng GR - R21 AA026931/AA/NIAAA NIH HHS/United States GR - R21 DA047663/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20231030 PL - United States TA - J Stud Alcohol Drugs JT - Journal of studies on alcohol and drugs JID - 101295847 RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Pharmacovigilance MH - *Social Media MH - Glucagon-Like Peptide 1/therapeutic use MH - *Substance-Related Disorders/drug therapy PMC - PMC10846600 EDAT- 2023/11/02 12:45 MHDA- 2024/01/23 06:43 PMCR- 2025/01/01 CRDT- 2023/11/02 11:04 PHST- 2024/01/23 06:43 [medline] PHST- 2023/11/02 12:45 [pubmed] PHST- 2023/11/02 11:04 [entrez] PHST- 2025/01/01 00:00 [pmc-release] AID - 5 [pii] AID - 10.15288/jsad.23-00318 [doi] PST - ppublish SO - J Stud Alcohol Drugs. 2024 Jan;85(1):5-11. doi: 10.15288/jsad.23-00318. Epub 2023 Oct 30. PMID- 37908750 OWN - NLM STAT- MEDLINE DCOM- 20231102 LR - 20250103 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis. PG - 1214334 LID - 10.3389/fendo.2023.1214334 [doi] LID - 1214334 AB - PURPOSE: A systematic review and meta-analysis was conducted to synthesize the available data from clinical trials and assess the safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes (T2D) and obesity. METHODS: A systematic search was conducted in three electronic databases, namely Embase, PubMed, and the Cochrane Library, up until March 1, 2023, to identify randomized controlled trials (RCTs) comparing tirzepatide to either placebo or active hypoglycemic drugs in individuals with T2D and obesity. Heterogeneity was assessed using the I2 value and Cochran's Q test, and a fixed effects model was employed to estimate the safety profile of tirzepatide. The safety outcomes of interest, including pancreatitis, the composite of gallbladder or biliary diseases, cholecystitis, and cholelithiasis and biliary diseases, were evaluated. (The composite of gallbladder or biliary diseases incorporated cholelithiasis, cholecystitis, other gallbladder disorders, and biliary diseases.). RESULTS: A total of nine trials with 9871 participants (6828 in the tirzepatide group and 3043 in the control group) that met the pre-specified criteria were included. When compared to all control groups consisting of basal insulin (glargine or degludec), selective GLP1-RA (dulaglutide or semaglutide once weekly), and placebo, an increased risk of pancreatitis was not found to be significantly associated with tirzepatide (RR 1.46, [95% CI] 0.59 to 3.61; I2 = 0.0%, p = 0.436). For gallbladder or biliary disease, the composite of gallbladder or biliary disease was significantly associated with tirzepatide compared with placebo or basal insulin (RR 1.97, [95% CI] 1.14 to 3.42; I2 = 0.0%, p = 0.558), but not with the risk of cholelithiasis, cholecystitis or biliary diseases. CONCLUSION: Based on the currently available data, tirzepatide appears to be safe regarding the risk of pancreatitis. However, the increased risk of the composite outcome of gallbladder or biliary diseases observed in RCTs warrants further attention from physicians in clinical practice. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023412400. CI - Copyright (c) 2023 Zeng, Xu, Mu, Shi, Fan and Li. FAU - Zeng, Qingyue AU - Zeng Q AD - Department of General Practice Medicine Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Xu, Jiao AU - Xu J AD - Department of General Practice Medicine Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Mu, Xingyu AU - Mu X AD - Department of General Practice Medicine Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Shi, Yi AU - Shi Y AD - Department of General Practice Medicine Center, West China Hospital, Sichuan University, Chengdu, China. FAU - Fan, Hong AU - Fan H AD - Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China. FAU - Li, Shuangqing AU - Li S AD - Department of General Practice Medicine Center, West China Hospital, Sichuan University, Chengdu, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20231016 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - OYN3CCI6QE (Tirzepatide) RN - 2ZM8CX04RZ (Insulin Glargine) SB - IM EIN - Front Endocrinol (Lausanne). 2024 Mar 14;15:1342543. doi: 10.3389/fendo.2024.1342543. PMID: 38549766 MH - Humans MH - *Cholecystitis MH - *Diabetes Mellitus, Type 2/drug therapy MH - Insulin Glargine MH - Obesity/complications/drug therapy MH - *Pancreatitis/chemically induced/epidemiology MH - *Cholelithiasis MH - Tirzepatide PMC - PMC10613702 OTO - NOTNLM OT - dual agonists OT - glucagon-like peptide-1 receptor agonists OT - incretin based therapy OT - obesity OT - tirzepatide OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/11/01 06:43 MHDA- 2023/11/02 12:45 PMCR- 2023/01/01 CRDT- 2023/11/01 04:00 PHST- 2023/04/29 00:00 [received] PHST- 2023/09/25 00:00 [accepted] PHST- 2023/11/02 12:45 [medline] PHST- 2023/11/01 06:43 [pubmed] PHST- 2023/11/01 04:00 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1214334 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Oct 16;14:1214334. doi: 10.3389/fendo.2023.1214334. eCollection 2023. PMID- 37902577 OWN - NLM STAT- MEDLINE DCOM- 20231220 LR - 20260127 IS - 1365-2796 (Electronic) IS - 0954-6820 (Linking) VI - 295 IP - 1 DP - 2024 Jan TI - Switching from subcutaneous to oral semaglutide in type 2 diabetes: A prospective study. PG - 113-115 LID - 10.1111/joim.13737 [doi] FAU - Martinez-Montoro, Jose Ignacio AU - Martinez-Montoro JI AUID- ORCID: 0000-0001-9761-6888 AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain. AD - Instituto de Investigacion Biomedica de Malaga (IBIMA)-Plataforma Bionand, Malaga, Spain. AD - Faculty of Medicine, University of Malaga, Malaga, Spain. AD - Centro de Investigacion Biomedica en Red de la Fisiopatologia de la Obesidad y la Nutricion (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain. FAU - Picon-Cesar, Maria Jose AU - Picon-Cesar MJ AUID- ORCID: 0000-0001-7057-7962 AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain. AD - Instituto de Investigacion Biomedica de Malaga (IBIMA)-Plataforma Bionand, Malaga, Spain. AD - Centro de Investigacion Biomedica en Red de la Fisiopatologia de la Obesidad y la Nutricion (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain. FAU - Generoso-Pinar, Marta AU - Generoso-Pinar M AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain. FAU - Fernandez-Valero, Andrea AU - Fernandez-Valero A AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain. FAU - Lopez-Montalban, Angel AU - Lopez-Montalban A AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain. FAU - Simon-Frapolli, Victor Jose AU - Simon-Frapolli VJ AUID- ORCID: 0000-0002-3896-7992 AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain. FAU - Hernandez-Bayo, Juan AU - Hernandez-Bayo J AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain. FAU - Pinzon-Martin, Jose Luis AU - Pinzon-Martin JL AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain. AD - Faculty of Medicine, University of Malaga, Malaga, Spain. FAU - Tinahones, Francisco J AU - Tinahones FJ AUID- ORCID: 0000-0001-6871-4403 AD - Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Malaga, Spain. AD - Instituto de Investigacion Biomedica de Malaga (IBIMA)-Plataforma Bionand, Malaga, Spain. AD - Faculty of Medicine, University of Malaga, Malaga, Spain. AD - Centro de Investigacion Biomedica en Red de la Fisiopatologia de la Obesidad y la Nutricion (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain. LA - eng PT - Letter PT - Research Support, Non-U.S. Gov't DEP - 20231030 PL - England TA - J Intern Med JT - Journal of internal medicine JID - 8904841 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Prospective Studies MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Semaglutide EDAT- 2023/10/30 12:42 MHDA- 2023/12/20 06:42 CRDT- 2023/10/30 10:23 PHST- 2023/12/20 06:42 [medline] PHST- 2023/10/30 12:42 [pubmed] PHST- 2023/10/30 10:23 [entrez] AID - 10.1111/joim.13737 [doi] PST - ppublish SO - J Intern Med. 2024 Jan;295(1):113-115. doi: 10.1111/joim.13737. Epub 2023 Oct 30. PMID- 37902090 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20250103 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 32 IP - 11 DP - 2023 Jul-Dec TI - Retatrutide: a triple incretin receptor agonist for obesity management. PG - 1003-1008 LID - 10.1080/13543784.2023.2276754 [doi] AB - INTRODUCTION: Obesity treatment is evolving rapidly with the emergence of agents targeting incretin receptors. Retatrutide, a triple agonist of these receptors, shows promise in obesity management. AREAS COVERED: Retatrutide, in phase-2 trials, exhibited significant reductions in glycated hemoglobin (HbA1c) and dose-dependent weight loss in individuals with type 2 diabetes mellitus (T2DM). In non-T2DM individuals, it produced substantial weight loss and improved glucose levels, albeit with gastrointestinal side effects. The role of glucagon receptor agonism in the management of heart failure and its potential impact on eating patterns have also been covered in this article. EXPERT OPINION: Although the reductions in HbA1c and dose-dependent weight loss among individuals with T2DM were significantly more for higher doses of retatrutide, it needs to be observed that the active comparator was dulaglutide, which is not approved for the treatment of obesity, at a dose of 1.5 mg, which is much lower than the highest approved dose of 4.5 mg. Dose-dependent increase in heart rate and incidents of mild to moderate cardiac arrythmias raise cardiovascular safety concerns and signify that carrying out long-term cardiovascular outcome trials (CVOTs) will be critical. In addition, retatrutide's potential in heart failure management is intriguing given the series of positive findings of semaglutide on cardiovascular outcomes. FAU - Ray, Avik AU - Ray A AUID- ORCID: 0000-0002-0047-7453 AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. LA - eng PT - Journal Article DEP - 20231124 PL - England TA - Expert Opin Investig Drugs JT - Expert opinion on investigational drugs JID - 9434197 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Incretins/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Glycated Hemoglobin MH - *Obesity Management MH - Glucagon-Like Peptides/adverse effects MH - Weight Loss MH - Obesity/drug therapy MH - *Heart Failure/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Retatrutide OT - diabetes mellitus OT - glucagon OT - heart failure OT - obesity EDAT- 2023/10/30 12:43 MHDA- 2023/11/27 12:42 CRDT- 2023/10/30 06:38 PHST- 2023/11/27 12:42 [medline] PHST- 2023/10/30 12:43 [pubmed] PHST- 2023/10/30 06:38 [entrez] AID - 10.1080/13543784.2023.2276754 [doi] PST - ppublish SO - Expert Opin Investig Drugs. 2023 Jul-Dec;32(11):1003-1008. doi: 10.1080/13543784.2023.2276754. Epub 2023 Nov 24. PMID- 37888820 OWN - NLM STAT- MEDLINE DCOM- 20240506 LR - 20240521 IS - 1875-6417 (Electronic) IS - 1573-3998 (Linking) VI - 20 IP - 4 DP - 2024 TI - Novel Approaches for the Management of Type 2 Diabetes Mellitus: An Update. PG - e051023221768 LID - 10.2174/0115733998261903230921102620 [doi] AB - Diabetes mellitus is an irreversible, chronic metabolic disorder indicated by hyperglycemia. It is now considered a worldwide pandemic. T2DM, a spectrum of diseases initially caused by tissue insulin resistance and slowly developing to a state characterized by absolute loss of secretory action of the beta cells of the pancreas, is thought to be caused by reduced insulin secretion, resistance to tissue activities of insulin, or a combination of both. Insulin secretagogues, biguanides, insulin sensitizers, alpha-glucosidase inhibitors, incretin mimetics, amylin antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors are the main medications used to treat T2DM. Several of these medication's traditional dosage forms have some disadvantages, including frequent dosing, a brief half-life, and limited absorption. Hence, attempts have been made to develop new drug delivery systems for oral antidiabetics to ameliorate the difficulties associated with conventional dosage forms. In comparison to traditional treatments, this review examines the utilization of various innovative therapies (such as microparticles, nanoparticles, liposomes, niosomes, phytosomes, and transdermal drug delivery systems) to improve the distribution of various oral hypoglycemic medications. In this review, we have also discussed some new promising candidates that have been approved recently by the US Food and Drug Administration for the treatment of T2DM, like semaglutide, tirzepatide, and ertugliflozin. They are used as a single therapy and also as combination therapy with drugs like metformin and sitagliptin. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Kumar, Abhishek AU - Kumar A AD - Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, UP 201306, India. FAU - Mazumder, Rupa AU - Mazumder R AD - Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, UP 201306, India. FAU - Rani, Anjna AU - Rani A AUID- ORCID: 0000-0002-7575-7580 AD - Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, UP 201306, India. FAU - Pandey, Pratibha AU - Pandey P AD - Department of Biotechnology, Noida Institute of Engineering and Technology, Greater Noida, UP 201306, India. FAU - Khurana, Navneet AU - Khurana N AD - School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Diabetes Rev JT - Current diabetes reviews JID - 101253260 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Drug Delivery Systems OTO - NOTNLM OT - Type 2 diabetes mellitus OT - antidiabetic OT - current medication OT - insulin resistance OT - microparticles. OT - novel drug delivery system EDAT- 2023/10/27 12:43 MHDA- 2024/05/06 12:43 CRDT- 2023/10/27 07:34 PHST- 2023/05/22 00:00 [received] PHST- 2023/08/06 00:00 [revised] PHST- 2023/08/10 00:00 [accepted] PHST- 2024/05/06 12:43 [medline] PHST- 2023/10/27 12:43 [pubmed] PHST- 2023/10/27 07:34 [entrez] AID - CDR-EPUB-134847 [pii] AID - 10.2174/0115733998261903230921102620 [doi] PST - ppublish SO - Curr Diabetes Rev. 2024;20(4):e051023221768. doi: 10.2174/0115733998261903230921102620. PMID- 37879878 OWN - NLM STAT- MEDLINE DCOM- 20231201 LR - 20260127 IS - 1755-5248 (Electronic) IS - 0012-6543 (Linking) VI - 61 IP - 12 DP - 2023 Nov 29 TI - Semaglutide: a new drug for the treatment of obesity. PG - 182-188 LID - 10.1136/dtb.2023.000007 [doi] AB - Semaglutide (▼Ozempic solution for injection, ▼Rybelsus tablets-Novo Nordisk) was initially granted market authorisation for the treatment of type 2 diabetes as an adjunct to diet and exercise. In 2021 and 2022, regulatory agencies in the USA and Europe licensed semaglutide (▼Wegovy solution for injection-Novo Nordisk) for the treatment of individuals who are obese, or overweight and who have at least one weight-related comorbidity. Manufacturer-sponsored randomised controlled trials have shown a loss of almost 12% of body weight over a 68-week period, however, once the medication is stopped people regain most of their pretreatment weight. Gastrointestinal adverse events occur commonly with semaglutide, and pancreatitis, diabetic retinopathy and severe allergic reactions have also been reported. Extensive hype in social and general media has resulted in increased demand for semaglutide leading to supply problems across the various licensed products including those used for treatment of diabetes. In the UK, the National Institute for Health and Care Excellence has recommended semaglutide as an option for weight management for a maximum treatment duration of 2 years. Further studies are underway to assess the effect of semaglutide on longer-term health benefits. CI - (c) Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Lexchin, Joel AU - Lexchin J AUID- ORCID: 0000-0001-5120-8029 AD - School of Health Policy and Management, York University - Keele Campus, Toronto, Ontario, Canada jlexchin@yorku.ca. AD - Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Mintzes, Barbara AU - Mintzes B AUID- ORCID: 0000-0002-8671-915X AD - School of Pharmacy and Charles Perkins Centre, The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia. AD - The University of British Columbia School of Population and Public Health, Vancouver, British Columbia, Canada. LA - eng PT - Journal Article PT - Review DEP - 20231129 PL - England TA - Drug Ther Bull JT - Drug and therapeutics bulletin JID - 0112037 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptides/adverse effects MH - Obesity/drug therapy MH - Semaglutide OTO - NOTNLM OT - Drug-Related Side Effects and Adverse Reactions OT - Obesity COIS- Competing interests: None declared. Refer to the online supplementary files to view the ICMJE form(s). EDAT- 2023/10/26 00:42 MHDA- 2023/12/01 06:44 CRDT- 2023/10/25 21:22 PHST- 2023/12/01 06:44 [medline] PHST- 2023/10/26 00:42 [pubmed] PHST- 2023/10/25 21:22 [entrez] AID - dtb.2023.000007 [pii] AID - 10.1136/dtb.2023.000007 [doi] PST - epublish SO - Drug Ther Bull. 2023 Nov 29;61(12):182-188. doi: 10.1136/dtb.2023.000007. PMID- 37867175 OWN - NLM STAT- MEDLINE DCOM- 20240122 LR - 20260603 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 26 IP - 2 DP - 2024 Feb TI - 5-Year simulation of diabetes-related complications in people treated with tirzepatide or semaglutide versus insulin glargine. PG - 463-472 LID - 10.1111/dom.15332 [doi] AB - AIM: This study compared the 5-year incidence rate of macrovascular and microvascular complications for tirzepatide, semaglutide and insulin glargine in individuals with type 2 diabetes, using the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes simulation model. RESEARCH DESIGN AND METHODS: This study was a 5-year SURPASS-2 trial extrapolation, with an insulin glargine arm added as an additional comparator. The 1-year treatment effects of tirzepatide (5, 10 or 15 mg), semaglutide (1 mg) and insulin glargine on glycated haemoglobin, systolic blood pressure, low-density lipoprotein and body weights were obtained from the SUSTAIN-4 and SURPASS-2 trials. We used the BRAVO model to predict 5-year complications for each study arm under two scenarios: the 1-year treatment effects persisted (optimistic) or diminished to none in 5 years (conservative). RESULTS: When compared with insulin glargine, we projected a 5-year risk reduction in cardiovascular adverse events [rate ratio (RR) 0.64, 95% confidence interval (CI) 0.61-0.67] and microvascular composite (RR 0.67, 95% CI 0.64-0.70) with 15 mg tirzepatide, and 5-year risk reduction in cardiovascular adverse events (RR 0.75, 95% CI 0.72-0.79) and microvascular composite (RR 0.79, 95% CI 0.76-0.82) with semaglutide (1 mg) under an optimistic scenario. Lower doses of tirzepatide also had similar, albeit smaller benefits. Treatment effects for tirzepatide and semaglutide were smaller but still significantly higher than insulin glargine under a conservative scenario. The 5-year risk reduction in diabetes-related complication events and mortality for the 15 mg tirzepatide compared with insulin glargine ranged from 49% to 10% under an optimistic scenario, which was reduced by 17%-33% when a conservative scenario was assumed. CONCLUSION: With the use of the BRAVO diabetes model, tirzepatide and semaglutide exhibited potential to reduce the risk of macrovascular and microvascular complications among individuals with type 2 diabetes, compared with insulin glargine in a 5-year window. Based on the current modelling assumptions, tirzepatide (15 mg) may potentially outperform semaglutide (1 mg). While the BRAVO model offered insights, the long-term cardiovascular benefit of tirzepatide should be further validated in a prospective clinical trial. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Niu, Shu AU - Niu S AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Alkhuzam, Khalid A AU - Alkhuzam KA AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Guan, Dawei AU - Guan D AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Jiao, Tianze AU - Jiao T AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Shi, Lizheng AU - Shi L AUID- ORCID: 0000-0002-7827-6766 AD - Department of Health Policy and Management, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA. FAU - Fonseca, Vivian AU - Fonseca V AUID- ORCID: 0000-0002-3381-7151 AD - Section of Endocrinology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA. FAU - Laiteerapong, Neda AU - Laiteerapong N AD - Biological Sciences Division, Department of Medicine, University of Chicago, Chicago, Illinois, USA. FAU - Ali, Mohammed K AU - Ali MK AD - Hubert Department of Global Health, Emory University, Atlanta, Georgia, USA. AD - Department of Family and Preventive Medicine, Emory University, Atlanta, Georgia, USA. FAU - Schatz, Desmond A AU - Schatz DA AD - Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida, USA. FAU - Guo, Jingchuan AU - Guo J AUID- ORCID: 0000-0001-9799-2592 AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, College of Pharmacy, University of Florida, Gainesville, Florida, USA. FAU - Shao, Hui AU - Shao H AUID- ORCID: 0000-0002-4088-546X AD - Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA. AD - Center for Drug Evaluation and Safety, College of Pharmacy, University of Florida, Gainesville, Florida, USA. AD - Hubert Department of Global Health, Emory University, Atlanta, Georgia, USA. AD - Department of Family and Preventive Medicine, Emory University, Atlanta, Georgia, USA. LA - eng GR - R01 DK133465/DK/NIDDK NIH HHS/United States PT - Clinical Trial PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20231022 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 2ZM8CX04RZ (Insulin Glargine) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) RN - J718M71A7A (tetrachloroisophthalonitrile) RN - 0 (Nitriles) SB - IM MH - Humans MH - *Diabetes Complications/drug therapy MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Insulin Glargine/adverse effects MH - Prospective Studies MH - Tirzepatide MH - Semaglutide MH - Nitriles PMC - PMC11115367 MID - NIHMS1938551 OTO - NOTNLM OT - cardiovascular disease OT - diabetes complications OT - semaglutide OT - tirzepatide OT - trial extrapolation OT - type 2 diabetes COIS- Conflicts of Interests No potential conflicts of interest relevant to this article were reported. EDAT- 2023/10/23 00:41 MHDA- 2024/01/09 06:42 PMCR- 2025/02/01 CRDT- 2023/10/22 23:03 PHST- 2023/09/25 00:00 [revised] PHST- 2023/04/06 00:00 [received] PHST- 2023/10/02 00:00 [accepted] PHST- 2024/01/09 06:42 [medline] PHST- 2023/10/23 00:41 [pubmed] PHST- 2023/10/22 23:03 [entrez] PHST- 2025/02/01 00:00 [pmc-release] AID - 10.1111/dom.15332 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Feb;26(2):463-472. doi: 10.1111/dom.15332. Epub 2023 Oct 22. PMID- 37864548 OWN - NLM STAT- MEDLINE DCOM- 20240131 LR - 20250103 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 16 IP - 11 DP - 2023 Jul-Dec TI - The role of glucagon-like peptide-1 receptor agonists in nonalcoholic fatty liver disease. PG - 1063-1072 LID - 10.1080/17512433.2023.2274536 [doi] AB - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease, associated with obesity, type 2 diabetes mellitus and dyslipidemia, which can lead to liver cirrhosis and hepatocellular carcinoma in some patients. Apart from lifestyle modifications, which are the cornerstone for its management, several drugs are under evaluation, including glucagon-like peptide-1 receptor agonists (GLP-R1RAs). In this review, we summarized major clinical data concerning the effects of GLP-1RAs on NAFLD, trying to highlight existing knowledge and to elucidate areas of uncertainty, thus providing clues to potential clinical implications and research. AREAS COVERED: Selected clinical studies on GLP-R1As in NAFLD are presented in this narrative review. EXPERT OPINION: There is evidence that treatment with GLP-R1As in NAFLD has beneficial effects on NAFLD, i.e. improvement in liver function tests and histological improvement in hepatic steatosis and inflammation, but not fibrosis. Further research is required toward the early use of GLP-R1Alphas, i.e. in NAFLD patients without fibrosis to evaluate whether they may prevent the progression to fibrosis, or in patients with advanced disease in combination with other medications, which may have additive or even synergistic effects on NAFLD. FAU - Tsiampali, Chara AU - Tsiampali C AD - First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Papaioannidou, Paraskevi AU - Papaioannidou P AD - First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Goulas, Antonis AU - Goulas A AD - First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Polyzos, Stergios A AU - Polyzos SA AUID- ORCID: 0000-0001-9232-4042 AD - First Laboratory of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20231122 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Liver Cirrhosis/complications MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Exenatide OT - glucagon-like peptide-1 receptor agonists OT - hepatic steatosis OT - liraglutide OT - nonalcoholic fatty liver disease OT - nonalcoholic steatohepatitis OT - semaglutide OT - treatment EDAT- 2023/10/21 19:43 MHDA- 2023/11/23 06:42 CRDT- 2023/10/21 08:32 PHST- 2023/11/23 06:42 [medline] PHST- 2023/10/21 19:43 [pubmed] PHST- 2023/10/21 08:32 [entrez] AID - 10.1080/17512433.2023.2274536 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2023 Jul-Dec;16(11):1063-1072. doi: 10.1080/17512433.2023.2274536. Epub 2023 Nov 22. PMID- 37853960 OWN - NLM STAT- MEDLINE DCOM- 20240122 LR - 20260603 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 2 DP - 2024 Feb TI - Gastrointestinal adverse events and weight reduction in people with type 2 diabetes treated with tirzepatide in the SURPASS clinical trials. PG - 473-481 LID - 10.1111/dom.15333 [doi] AB - AIMS: To evaluate gastrointestinal adverse events (AEs) and the impact of nausea, vomiting or diarrhoea (N/V/D) and any gastrointestinal (GI) AEs overall on weight change with tirzepatide across the SURPASS-1 to -5 clinical trials. MATERIALS AND METHODS: Participants with type 2 diabetes were randomized to receive once-weekly tirzepatide (5, 10 or 15 mg) or comparator (placebo, semaglutide 1 mg once weekly, or titrated daily basal insulins) as monotherapy or added on to background antihyperglycaemic medication(s). This post hoc analysis subdivided participants within each trial into subgroups that self-reported (yes/no) any N/V/D or GI AEs. Change from baseline in body weight at the primary timepoint was assessed within each trial and subgroup. Mediation analyses were conducted to evaluate the contribution of direct and indirect (mediated by N/V/D or GI AEs) effects of tirzepatide on weight change versus comparators. RESULTS: Across the SURPASS-1 to -5 trials (N = 6263), nausea (12%-24%), diarrhoea (12%-22%), and vomiting (2%-13%) were the most common GI AEs reported with tirzepatide; these were transient and of mild-to-moderate severity. Mean weight reduction at the primary timepoint with tirzepatide was consistent between participants who reported N/V/D (-6.2 to -14.9 kg) and those who did not report N/V/D (-6.2 to -13.3 kg). Mean weight reduction was significantly (P < 0.01) greater with tirzepatide compared with placebo, semaglutide 1 mg, and basal insulins within the N/V/D and GI AEs subgroups. Mediation analyses suggested minimal contribution (<6%) of N/V/D and GI AEs to the overall difference in weight change between tirzepatide and comparators. CONCLUSIONS: Superior weight reduction with tirzepatide versus comparators appears to be independent of reported N/V/D or GI AEs. CI - (c) 2023 Eli Lilly and Company and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Patel, Hiren AU - Patel H AUID- ORCID: 0000-0003-2463-4916 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Khunti, Kamlesh AU - Khunti K AUID- ORCID: 0000-0003-2343-7099 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Rodbard, Helena W AU - Rodbard HW AUID- ORCID: 0000-0002-6187-8445 AD - Endocrine and Metabolic Consultants, Rockville, Maryland, USA. FAU - Bajaj, Harpreet S AU - Bajaj HS AUID- ORCID: 0000-0002-1461-1465 AD - LMC Diabetes and Endocrinology, Brampton, Ontario, Canada. FAU - Bray, Ross AU - Bray R AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Kindracki, Zbigniew AU - Kindracki Z AD - Eli Lilly and Company, Warsaw, Poland. FAU - Rodriguez, Angel AU - Rodriguez A AUID- ORCID: 0000-0001-8721-9539 AD - Lilly Spain, Madrid, Spain. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20231018 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulins) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/chemically induced MH - Diarrhea/chemically induced MH - Gastric Inhibitory Polypeptide/adverse effects MH - Glycated Hemoglobin MH - Hypoglycemic Agents/adverse effects MH - *Insulins MH - Nausea/chemically induced MH - Vomiting/chemically induced MH - Weight Loss MH - Tirzepatide OTO - NOTNLM OT - GIP and GLP-1 receptor agonist OT - diarrhoea OT - gastrointestinal adverse events OT - incretin therapy OT - nausea OT - tirzepatide OT - type 2 diabetes OT - vomiting OT - weight loss EDAT- 2023/10/19 06:44 MHDA- 2024/01/09 06:42 CRDT- 2023/10/19 04:04 PHST- 2023/09/22 00:00 [revised] PHST- 2023/06/30 00:00 [received] PHST- 2023/09/30 00:00 [accepted] PHST- 2024/01/09 06:42 [medline] PHST- 2023/10/19 06:44 [pubmed] PHST- 2023/10/19 04:04 [entrez] AID - 10.1111/dom.15333 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Feb;26(2):473-481. doi: 10.1111/dom.15333. Epub 2023 Oct 18. PMID- 37846993 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20260127 IS - 3135-8225 (Electronic) IS - 1565-1088 (Linking) VI - 25 IP - 10 DP - 2023 Oct TI - Subcutaneous Semaglutide Use for Weight Management: Practice and Attitudes of Physicians in Israel. PG - 664-668 AB - BACKGROUND: In 2019, 1 mg subcutaneous semaglutide was registered for the treatment of diabetes in Israel. Recognition of its effect on weight has led to its use as a treatment for obesity. OBJECTIVES: To explore physicians' pre-therapy considerations, therapy practices, and attitudes regarding subcutaneous semaglutide for weight loss. METHODS: A 22-item questionnaire was disseminated to physicians who prescribed semaglutide 1-mg for weight loss using an authorized off-label path. RESULTS: In total, 127 physicians completed the questionnaire. As for pretreatment requirements, in the absence of diabetes, 30% requested a minimal body mass index of 30 kg/m2. Additional requirements were documented lifestyle-change effort (67%) and prior weight loss medication use (13%). Half of the physicians regarded calorie restriction, and 23% considered physical activity as necessary for weight loss while on therapy. As for dose, most physicians (78%) started with a 0.25-mg weekly injection, 57% doubled the dose monthly, and all others recommended doubling when side effects subsided. Regarding weight loss goal, 43% of the physicians set a personal goal with each patient while 26% limited the goal to 10% of initial weight. Fewer than 50% of physicians discussed treatment duration with their patients, and 52% of patients discontinued therapy in the first 3 months. The main reasons for discontinuation were price, lack of effect, and fear of long-term side effects. CONCLUSIONS: The diverse approaches regarding off-label use of semaglutide for weight reduction highlight the necessity to guide physicians and standardize treatment regimen. FAU - Dicker, Dror AU - Dicker D AD - Department of Medicine D and Obesity Clinic, Rabin Medical Center (HaSharon Campus), Petah Tikva, Israel, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Tamir, Orly AU - Tamir O AD - Segal Israeli Center for Diabetes Research and Policy, Sheba Medical Center, Tel Hashomer, Israel. FAU - Lieberman-Segal, Gabriella AU - Lieberman-Segal G AD - Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Israel, Israel Center for Weight Management, Sheba Medical Center, Tel Hashomer, Israel, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Eldor, Roy AU - Eldor R AD - Department of Endocrinology, Metabolism, and Hypertension, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Accos-Carmel, Moran AU - Accos-Carmel M AD - Segal Israeli Center for Diabetes Research and Policy, Sheba Medical Center, Tel Hashomer, Israel. FAU - Kolobov, Tatyana AU - Kolobov T AD - Segal Israeli Center for Diabetes Research and Policy, Sheba Medical Center, Tel Hashomer, Israel. FAU - Karasik, Avraham AU - Karasik A AD - Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Israel, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. LA - eng PT - Journal Article PL - Israel TA - Isr Med Assoc J JT - The Israel Medical Association journal : IMAJ JID - 100930740 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Israel MH - Weight Loss MH - Semaglutide EDAT- 2023/10/17 12:42 MHDA- 2023/10/23 01:18 CRDT- 2023/10/17 09:03 PHST- 2023/10/23 01:18 [medline] PHST- 2023/10/17 12:42 [pubmed] PHST- 2023/10/17 09:03 [entrez] PST - ppublish SO - Isr Med Assoc J. 2023 Oct;25(10):664-668. PMID- 37828829 OWN - NLM STAT- MEDLINE DCOM- 20231222 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 1 DP - 2024 Jan TI - Effect of tirzepatide on glycaemic control and weight loss compared with other glucagon-like peptide-1 receptor agonists in Japanese patients with type 2 diabetes mellitus. PG - 262-274 LID - 10.1111/dom.15312 [doi] AB - AIM: To compare the therapeutic effects of glucose-dependent insulinotropic polypeptide (GIP)/ glucagon-like peptide-1 receptor agonists (GLP-1RAs) or GLP-1RAs in Japanese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: We systematically searched PubMed, MEDLINE, EMBASE, and the Cochrane Library up to July 2023. Randomized controlled trials (RCTs) that compared GLP-1RAs or GIP/GLP-1RAs in Japanese patients with T2D were selected. A network meta-analysis was conducted to indirectly compare the treatments, focusing on efficacy in reducing glycated haemoglobin (HbA1c) levels and body weight (BW). RESULTS: A total of 18 RCTs were included in this analysis. Tirzepatide 15 mg showed the most significant reduction in HbA1c levels and BW compared with subcutaneous semaglutide 1.0 mg and oral semaglutide 14 mg (HbA1c: mean difference [95% confidence interval] -0.52 [-0.96; -0.08] and - 1.23 [-1.64; -0.81]; BW: -5.07 [-8.28; -1.86] and -6.84 [-8.97; -4.71], respectively). Subcutaneous semaglutide showed a superior reduction in HbA1c compared with oral semaglutide. Both subcutaneous and oral semaglutide were more effective than conventional GLP-1RAs, such as dulaglutide, liraglutide and lixisenatide. CONCLUSIONS: Among Japanese patients with T2D, tirzepatide showed the greatest effectiveness in reducing HbA1c levels and inducing weight loss. The study provides evidence to guide GLP-1RA treatment strategies in Japanese patients with T2D. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Tsukamoto, Shunichiro AU - Tsukamoto S AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Tanaka, Shohei AU - Tanaka S AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Yamada, Takayuki AU - Yamada T AUID- ORCID: 0000-0001-5930-0022 AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. AD - Department of Medicine, University of Washington Medical Center, Seattle, Washington, USA. FAU - Uneda, Kazushi AU - Uneda K AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. AD - Department of Kampo Medicine, Aizu Medical Center, Fukushima Medical University, Aizuwakamatsu, Japan. FAU - Azushima, Kengo AU - Azushima K AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Kinguchi, Sho AU - Kinguchi S AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Wakui, Hiromichi AU - Wakui H AUID- ORCID: 0000-0001-8023-922X AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. FAU - Tamura, Kouichi AU - Tamura K AD - Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan. LA - eng GR - Yokohama Foundation for Advancement of Medical Science/ GR - Uehara Memorial Foundation/ GR - Japan Society for the Promotion of Science/ PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20231012 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Humans MH - Body Weight MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin MH - Glycemic Control MH - *Hypoglycemic Agents/adverse effects MH - Japan MH - Weight Loss MH - East Asian People MH - Tirzepatide OTO - NOTNLM OT - Japanese OT - glucagon-like peptide-1 receptor agonist OT - glucose-dependent insulinotropic peptide OT - tirzepatide OT - type 2 diabetes EDAT- 2023/10/13 06:45 MHDA- 2023/12/17 09:45 CRDT- 2023/10/13 03:02 PHST- 2023/09/10 00:00 [revised] PHST- 2023/08/04 00:00 [received] PHST- 2023/09/19 00:00 [accepted] PHST- 2023/12/17 09:45 [medline] PHST- 2023/10/13 06:45 [pubmed] PHST- 2023/10/13 03:02 [entrez] AID - 10.1111/dom.15312 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Jan;26(1):262-274. doi: 10.1111/dom.15312. Epub 2023 Oct 12. PMID- 37822270 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 1 DP - 2024 Jan TI - Proportion of participants with type 2 diabetes achieving a metabolic composite endpoint with once-weekly semaglutide treatment versus comparators: Post hoc pooled analysis from SUSTAIN 1-5, 7-10 and SUSTAIN China. PG - 233-241 LID - 10.1111/dom.15309 [doi] AB - AIM: To compare the proportion of participants with type 2 diabetes (T2D) treated with once-weekly (OW) subcutaneous (SC) semaglutide versus comparators who achieved a composite metabolic endpoint. MATERIALS AND METHODS: SUSTAIN 1-5, 7-10 and SUSTAIN China trial data were pooled. Participants with T2D (aged >/=18 years) and glycated haemoglobin >/=7.0% (>/=53 mmol/mol) who had been randomized to OW SC semaglutide (0.5 or 1.0 mg) or comparator in addition to background medication. Using patient-level data pooled by treatment, proportions of participants achieving the metabolic composite endpoint, defined as glycated haemoglobin <7% (<53 mmol/mol), blood pressure <140/90 mmHg and non-high-density lipoprotein cholesterol <130 mg/dl (<3.37 mmol/L), were evaluated following baseline adjustments. Endpoints were analysed per trial using a binomial logistic regression model with treatment, region/country and stratification factor as fixed effects and baseline value as covariate. Pooled analysis used logistic regression with treatment and trial as fixed effects and baseline value as covariate. RESULTS: This post hoc analysis included data from 7633 participants across 10 trials. The proportion of participants who achieved the metabolic composite endpoint was significantly higher with OW SC semaglutide 0.5 and 1.0 mg versus comparators (23.7% and 32.0% vs. 11.5%, respectively; p < .0001). Likewise, when the OW SC semaglutide doses were pooled, significantly higher proportions of patients receiving semaglutide achieved the composite metabolic endpoint versus comparators (29.1% vs. 11.4%, respectively; p < .0001). CONCLUSIONS: Treatment with OW SC semaglutide versus comparators was associated with increased proportions of participants with T2D meeting the composite metabolic endpoint. CI - (c) 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0003-1305-1598 AD - Peking University People's Hospital, Beijing, China. FAU - Ahmann, A J AU - Ahmann AJ AD - Oregon Health and Science University, Portland, Oregon, USA. FAU - Ahren, B AU - Ahren B AUID- ORCID: 0000-0002-9804-5340 AD - Lund University, Lund, Sweden. FAU - Capehorn, M S AU - Capehorn MS AD - Clifton Medical Centre, Rotherham, UK. FAU - Hu, P AU - Hu P AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Lingvay, I AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - University of Texas Southwestern Medical Center, Dallas, Texas, USA. FAU - Liu, W AU - Liu W AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Rodbard, H W AU - Rodbard HW AUID- ORCID: 0000-0002-6187-8445 AD - Endocrine and Metabolic Consultants, Rockville, Maryland, USA. FAU - Shen, Z AU - Shen Z AD - Novo Nordisk (Shanghai) Pharma Trading Co., Ltd, Beijing, China. FAU - Sorli, C AU - Sorli C AD - Acerus Pharma, Toronto, Ontario, Canada. LA - eng GR - Novo Nordisk Shanghai Ltd./ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20231012 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Adolescent MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin MH - Glucagon-Like Peptides/adverse effects MH - China/epidemiology MH - Semaglutide OTO - NOTNLM OT - GLP-1 analogue OT - cardiovascular disease OT - clinical trial OT - diabetes complications OT - semaglutide OT - type 2 diabetes EDAT- 2023/10/12 06:43 MHDA- 2023/12/17 09:46 CRDT- 2023/10/12 03:52 PHST- 2023/09/05 00:00 [revised] PHST- 2023/07/12 00:00 [received] PHST- 2023/09/15 00:00 [accepted] PHST- 2023/12/17 09:46 [medline] PHST- 2023/10/12 06:43 [pubmed] PHST- 2023/10/12 03:52 [entrez] AID - 10.1111/dom.15309 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Jan;26(1):233-241. doi: 10.1111/dom.15309. Epub 2023 Oct 12. PMID- 37813741 OWN - NLM STAT- MEDLINE DCOM- 20231103 LR - 20250103 IS - 2013-2514 (Electronic) IS - 2013-2514 (Linking) VI - 43 IP - 4 DP - 2023 Jul-Aug TI - Glucagon-like peptide 1(GLP-1) receptor agonists in the management of the patient with type 2diabetes mellitus and chronic kidney disease: an approach for the nephrologist. PG - 399-412 LID - S2013-2514(23)00147-5 [pii] LID - 10.1016/j.nefroe.2023.09.003 [doi] AB - Diabetic kidney disease, a common complication in patients with type 2 diabetes mellitus, is associated with a markedly increased morbidity and mortality, especially of cardiovascular origin, and faster progression to end-stage renal disease. To date, reducing cardiovascular and renal risk in this population was based on strict control of cardiovascular risk factors and the renin-angiotensin system blockade. More recently, sodium-glucose cotransporter type 2 inhibitors have demonstrated to offer cardiovascular and renal protection, but the residual risk remains high and their antihyperglycemic efficacy is limited in moderate-severe CKD. Therefore, drugs with a potent antihyperglycemic effect, independent of the glomerular filtration rate, with a low risk of hypoglycemia, that reduce weight in overweight/obese patients and that provide cardiovascular and renal protection, such as GLP-1 receptor agonists, are needed. However, these drugs require subcutaneous administration, which may limit their early use. The recent availability of oral semaglutide may facilitate the early introduction of this family with proven cardiovascular and renal benefits and excellent safety profile. In this review the family is analyzed as well as their cardiovascular and renal effects. CI - Copyright (c) 2022 Sociedad Espanola de Nefrologia. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Cases, Aleix AU - Cases A AD - Departament de Medicina, Facultat de Medicina, Campus Clinic, Universitat de Barcelona, Barcelona, Spain. Electronic address: acases@ub.edu. LA - eng PT - Journal Article PT - Review DEP - 20231008 PL - Spain TA - Nefrologia (Engl Ed) JT - Nefrologia JID - 101778581 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide 1 MH - Nephrologists MH - Hypoglycemic Agents MH - *Renal Insufficiency, Chronic/complications/drug therapy/chemically induced MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Agonistas del receptor del peptidosimilar al glucagon tipo 1 GLP-1 OT - Cardioproteccion OT - Cardioprotection OT - Diabetes mellitus tipo 2 OT - Diabetic kidney disease OT - Enfermedad renal diabetica OT - Glucagon-like peptide 1 GLP-1 receptor agonists OT - Nefroproteccion OT - Nephroprotection OT - Oral semaglutide OT - Semaglutida oral OT - Type 2 diabetes mellitus EDAT- 2023/10/10 00:42 MHDA- 2023/11/03 06:44 CRDT- 2023/10/09 22:21 PHST- 2022/02/28 00:00 [received] PHST- 2022/07/14 00:00 [revised] PHST- 2022/07/23 00:00 [accepted] PHST- 2023/11/03 06:44 [medline] PHST- 2023/10/10 00:42 [pubmed] PHST- 2023/10/09 22:21 [entrez] AID - S2013-2514(23)00147-5 [pii] AID - 10.1016/j.nefroe.2023.09.003 [doi] PST - ppublish SO - Nefrologia (Engl Ed). 2023 Jul-Aug;43(4):399-412. doi: 10.1016/j.nefroe.2023.09.003. Epub 2023 Oct 8. PMID- 37796527 OWN - NLM STAT- MEDLINE DCOM- 20231120 LR - 20250103 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 330 IP - 18 DP - 2023 Nov 14 TI - Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. PG - 1795-1797 LID - 10.1001/jama.2023.19574 [doi] FAU - Sodhi, Mohit AU - Sodhi M AD - Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. FAU - Rezaeianzadeh, Ramin AU - Rezaeianzadeh R AD - Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada. FAU - Kezouh, Abbas AU - Kezouh A AD - StatExpert Ltd, Laval, Quebec, Canada. FAU - Etminan, Mahyar AU - Etminan M AD - Department of Ophthalmology and Visual Sciences and Medicine, University of British Columbia, Vancouver, Canada. LA - eng PT - Journal Article PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - JAMA. 2024 Mar 12;331(10):884-885. doi: 10.1001/jama.2024.0046. PMID: 38470390 MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Liraglutide/adverse effects/therapeutic use MH - *Weight Loss/drug effects MH - *Anti-Obesity Agents/adverse effects/pharmacology/therapeutic use MH - *Overweight/drug therapy MH - *Gastrointestinal Diseases/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10557026 OAB - This database study examines the association between glucagon-like peptide 1 agonists (eg, semaglutide, liraglutide) used for weight loss and reports of gastrointestinal adverse events. OABL- eng COIS- Conflict of Interest Disclosures: None reported. EDAT- 2023/10/05 12:42 MHDA- 2023/11/15 06:42 PMCR- 2024/04/05 CRDT- 2023/10/05 11:34 PHST- 2023/11/15 06:42 [medline] PHST- 2023/10/05 12:42 [pubmed] PHST- 2023/10/05 11:34 [entrez] PHST- 2024/04/05 00:00 [pmc-release] AID - 2810542 [pii] AID - jld230072 [pii] AID - 10.1001/jama.2023.19574 [doi] PST - ppublish SO - JAMA. 2023 Nov 14;330(18):1795-1797. doi: 10.1001/jama.2023.19574. PMID- 37793464 OWN - NLM STAT- MEDLINE DCOM- 20231113 LR - 20260127 IS - 1879-260X (Electronic) IS - 0925-4439 (Print) IS - 0925-4439 (Linking) VI - 1870 IP - 1 DP - 2024 Jan TI - Head-to-head comparison of BAM15, semaglutide, rosiglitazone, NEN, and calorie restriction on metabolic physiology in female db/db mice. PG - 166908 LID - S0925-4439(23)00274-0 [pii] LID - 10.1016/j.bbadis.2023.166908 [doi] AB - Metabolic disorders such as type 2 diabetes, fatty liver disease, hyperlipidemia, and obesity commonly co-occur but clinical treatment options do not effectively target all disorders. Calorie restriction, semaglutide, rosiglitazone, and mitochondrial uncouplers have all demonstrated efficacy against one or more obesity-related metabolic disorders, but it currently remains unclear which therapeutic strategy best targets the combination of hyperglycaemia, liver fat, hypertriglyceridemia, and adiposity. Herein we performed a head-to-head comparison of 5 treatment interventions in the female db/db mouse model of severe metabolic disease. Treatments included approximately 60 % calorie restriction (CR), semaglutide, rosiglitazone, BAM15, and niclosamide ethanolamine (NEN). Results showed that BAM15 and CR improved body weight and liver steatosis to levels superior to semaglutide, NEN, and rosiglitazone, while BAM15, semaglutide, and rosiglitazone improved glucose tolerance better than CR and NEN. BAM15, CR, semaglutide, and rosiglitazone all had efficacy against hypertriglyceridaemia. These data provide a comprehensive head-to-head comparison of several key treatment strategies for metabolic disease and highlight the efficacy of mitochondrial uncoupling to correct multiple facets of the metabolic disease milieu in female db/db mice. CI - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Chen, Sing-Young AU - Chen SY AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. FAU - Beretta, Martina AU - Beretta M AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. FAU - Olzomer, Ellen M AU - Olzomer EM AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. FAU - Alexopoulos, Stephanie J AU - Alexopoulos SJ AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. FAU - Shah, Divya P AU - Shah DP AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. FAU - Byrne, Frances L AU - Byrne FL AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. FAU - Salamoun, Joseph M AU - Salamoun JM AD - Department of Chemistry and Virginia Tech Centre for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, USA. FAU - Garcia, Christopher J AU - Garcia CJ AD - Department of Chemistry and Virginia Tech Centre for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, USA. FAU - Smith, Greg C AU - Smith GC AD - School of Medical Science, University of New South Wales, Sydney, NSW 2052, Australia. FAU - Larance, Mark AU - Larance M AD - Charles Perkins Centre, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia. FAU - Philp, Andrew AU - Philp A AD - Charles Perkins Centre, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, Australia; Centre for Healthy Ageing, Centenary Institute, Camperdown, NSW 2050, Australia; School of Sport, Exercise and Rehabilitation Sciences, Faculty of Health, University of Technology Sydney, Sydney, NSW 2007, Australia. FAU - Turner, Nigel AU - Turner N AD - Cellular Bioenergetics Laboratory, Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia. FAU - Santos, Webster L AU - Santos WL AD - Department of Chemistry and Virginia Tech Centre for Drug Discovery, Virginia Tech, Blacksburg, VA 24061, USA. FAU - Cantley, James AU - Cantley J AD - School of Medicine, University of Dundee, Dundee DD1 4HN, UK. FAU - Hoehn, Kyle L AU - Hoehn KL AD - School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: k.hoehn@unsw.edu.au. LA - eng GR - R01 DK128612/DK/NIDDK NIH HHS/United States GR - R25 GM072767/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20231002 PL - Netherlands TA - Biochim Biophys Acta Mol Basis Dis JT - Biochimica et biophysica acta. Molecular basis of disease JID - 101731730 RN - 8KK8CQ2K8G (Niclosamide) RN - 05V02F2KDG (Rosiglitazone) RN - 5KV86114PT (Ethanolamine) RN - 0 (Ethanolamines) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Mice MH - Animals MH - Female MH - Niclosamide/therapeutic use MH - Rosiglitazone/pharmacology/therapeutic use MH - Ethanolamine/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Caloric Restriction MH - Ethanolamines/therapeutic use MH - *Non-alcoholic Fatty Liver Disease/metabolism MH - Obesity/drug therapy/metabolism MH - Semaglutide PMC - PMC10908303 MID - NIHMS1969904 OTO - NOTNLM OT - Calorie restriction OT - Diabetes OT - GLP-1 OT - Mitochondrial uncoupling OT - Obesity COIS- Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kyle Hoehn reports financial support was provided by National Institutes of Health and National Health and Medical Research Council. Kyle Hoehn reports a relationship with Uncoupler Therapeutics, Inc. that includes: board membership and equity or stocks. Kyle Hoehn reports a relationship with Life Biosciences, Inc. that includes: equity or stocks. Kyle Hoehn has a patent via University of Virginia. Webster Santos reports financial support was provided by National Institutes of Health. Webster Santos reports a relationship with Uncoupler Therapeutics, Inc. that includes: board membership and equity or stocks. Webster Santos reports a relationship with Life Biosciences, Inc. that includes: equity or stocks. EDAT- 2023/10/05 01:00 MHDA- 2023/11/13 06:42 PMCR- 2024/09/01 CRDT- 2023/10/04 19:11 PHST- 2023/07/31 00:00 [received] PHST- 2023/09/14 00:00 [revised] PHST- 2023/09/28 00:00 [accepted] PHST- 2023/11/13 06:42 [medline] PHST- 2023/10/05 01:00 [pubmed] PHST- 2023/10/04 19:11 [entrez] PHST- 2024/09/01 00:00 [pmc-release] AID - S0925-4439(23)00274-0 [pii] AID - 10.1016/j.bbadis.2023.166908 [doi] PST - ppublish SO - Biochim Biophys Acta Mol Basis Dis. 2024 Jan;1870(1):166908. doi: 10.1016/j.bbadis.2023.166908. Epub 2023 Oct 2. PMID- 37792556 OWN - NLM STAT- MEDLINE DCOM- 20231102 LR - 20250729 IS - 1531-7080 (Electronic) IS - 0268-4705 (Linking) VI - 38 IP - 6 DP - 2023 Nov 1 TI - Glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor co-agonists for cardioprotection, type 2 diabetes and obesity: a review of mechanisms and clinical data. PG - 539-545 LID - 10.1097/HCO.0000000000001084 [doi] AB - PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for the management of type 2 diabetes (T2D) and obesity, and some are recommended for cardiorenal risk reduction in T2D. To enhance the benefits with GLP-RA mono-agonist therapy, GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonists are in development to capitalize on the synergism of GLP-1 and GIP agonism. We review the mechanisms of action and clinical data for GLP-1/GIP receptor co-agonists in T2D and obesity and their potential role in cardiovascular protection. RECENT FINDINGS: Tirzepatide, a first-in-class unimolecular GLP-1/GIP receptor co-agonist, is approved for T2D and is awaiting approval for obesity management. Phase 3 trials in T2D cohorts revealed significant reductions in glycemia and body weight and superiority compared with GLP-1R mono-agonism with semaglutide. Tirzepatide has demonstrated significant body weight reductions in individuals with obesity but not diabetes. It enhances lipid metabolism, reduces blood pressure, and lowers liver fat content. Pooled phase 2/3 data showed cardiovascular safety in T2D while a post hoc analysis suggested tirzepatide slows the decline of kidney function in T2D. SUMMARY: GLP-1/GIP receptor co-agonists are a novel addition to the diabetes and obesity armamentarium. The cardiorenal-metabolic benefits position them as promising multiprong tools for metabolically complex individuals with chronic vascular complications. CI - Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved. FAU - Goldenberg, Ronald M AU - Goldenberg RM AD - LMC Diabetes & Endocrinology, Concord. FAU - Teoh, Hwee AU - Teoh H AD - Division of Cardiac Surgery. AD - Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute of St Michael's Hospital-Unity Health Toronto. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery. AD - Department of Surgery. AD - Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. LA - eng PT - Journal Article PT - Review DEP - 20230821 PL - United States TA - Curr Opin Cardiol JT - Current opinion in cardiology JID - 8608087 RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/metabolism MH - Glucagon-Like Peptide 1/metabolism/pharmacology/therapeutic use MH - *Receptors, Gastrointestinal Hormone/agonists/therapeutic use MH - Obesity/complications/drug therapy EDAT- 2023/10/04 18:42 MHDA- 2023/11/02 12:45 CRDT- 2023/10/04 12:43 PHST- 2023/11/02 12:45 [medline] PHST- 2023/10/04 18:42 [pubmed] PHST- 2023/10/04 12:43 [entrez] AID - 00001573-202311000-00015 [pii] AID - 10.1097/HCO.0000000000001084 [doi] PST - ppublish SO - Curr Opin Cardiol. 2023 Nov 1;38(6):539-545. doi: 10.1097/HCO.0000000000001084. Epub 2023 Aug 21. PMID- 37780624 OWN - NLM STAT- MEDLINE DCOM- 20231007 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study. PG - 1240263 LID - 10.3389/fendo.2023.1240263 [doi] LID - 1240263 AB - BACKGROUND: Oral semaglutide is the first glucagon-like peptide-1 receptor agonist (GLP-1RA) designed for oral administration; it offers a promising opportunity to facilitate an early approach to Type 2 Diabetes (T2D). The study aimed to evaluate, in a real-life setting, the effects of oral semaglutide on the body composition of patients with T2D after 26 weeks of therapy. METHODS: Thirty-two patients with T2D were evaluated at baseline (T0) and after three (T3) and six (T6) months of therapy with oral semaglutide. At each time point, body composition was assessed using a phase sensitive bioimpedance analyzer. Clinical, anthropometric and laboratory parameters, and the main biometric surrogates of liver steatosis and fibrosis, were also analyzed and compared. RESULTS: A significant and early reduction in anthropometric and glucometabolic parameters, alanine aminotransferase, Fatty Liver Index, and Fat Mass was observed. Visceral Adipose Tissue (VAT) decreased, while Fat Free Mass and Skeletal Muscle Mass (SMM) were preserved during therapy, resulting in a beneficial increase in the SMM/VAT ratio. Finally, an overall improvement in body fluid distribution was observed. CONCLUSION: Our real-world data confirm the clinical efficacy of oral semaglutide and highlight its ability to improve the nutritional status of patients with T2D. CI - Copyright (c) 2023 Volpe, Lisco, Fanelli, Racaniello, Colaianni, Lavarra, Triggiani, Crudele, Triggiani, Sabba, De Pergola and Piazzolla. FAU - Volpe, Sara AU - Volpe S AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. FAU - Lisco, Giuseppe AU - Lisco G AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. FAU - Fanelli, Margherita AU - Fanelli M AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. FAU - Racaniello, Davide AU - Racaniello D AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. FAU - Colaianni, Valentina AU - Colaianni V AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. FAU - Lavarra, Valentina AU - Lavarra V AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. FAU - Triggiani, Domenico AU - Triggiani D AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. FAU - Crudele, Lucilla AU - Crudele L AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. FAU - Triggiani, Vincenzo AU - Triggiani V AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. FAU - Sabba, Carlo AU - Sabba C AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. FAU - De Pergola, Giovanni AU - De Pergola G AD - Unit of Geriatrics and Internal Medicine, National Institute of Gastroenterology-IRCCS "Saverio de Bellis", Bari, Italy. FAU - Piazzolla, Giuseppina AU - Piazzolla G AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "A. Moro", Bari, Italy. LA - eng PT - Journal Article DEP - 20230913 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Gastrointestinal Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Body Composition/drug effects MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - *Glucagon-Like Peptide-1 Receptor/administration & dosage MH - Hypoglycemic Agents/therapeutic use MH - Prospective Studies MH - *Gastrointestinal Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC10534984 OTO - NOTNLM OT - GLP-1RA OT - body composition OT - fat free mass OT - fat mass OT - oral semaglutide OT - skeletal muscle mass OT - type 2 diabetes OT - visceral adipose tissue COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/10/02 06:42 MHDA- 2023/10/03 06:47 PMCR- 2023/01/01 CRDT- 2023/10/02 04:31 PHST- 2023/06/14 00:00 [received] PHST- 2023/08/28 00:00 [accepted] PHST- 2023/10/03 06:47 [medline] PHST- 2023/10/02 06:42 [pubmed] PHST- 2023/10/02 04:31 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1240263 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Sep 13;14:1240263. doi: 10.3389/fendo.2023.1240263. eCollection 2023. PMID- 37775297 OWN - NLM STAT- MEDLINE DCOM- 20231005 LR - 20260127 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 13 IP - 9 DP - 2023 Sep 29 TI - Early use of oral semaglutide in the UK: A cost-effectiveness analysis versus continuing metformin and SGLT-2 inhibitor therapy. PG - e070473 LID - 10.1136/bmjopen-2022-070473 [doi] LID - e070473 AB - OBJECTIVES: Many people with type 2 diabetes experience clinical inertia, remaining in poor glycaemic control on oral glucose-lowering medications rather than intensifying treatment with a glucagon-like peptide-1 receptor agonist, despite an efficacious, orally administered option, oral semaglutide, being available. The present study evaluated the long-term cost-effectiveness of initiating oral semaglutide versus continuing metformin plus sodium-glucose cotransporter-2 (SGLT-2) inhibitor therapy in the UK. DESIGN: Outcomes were projected over patients' lifetimes using the IQVIA Core Diabetes Model (V.9.0). Clinical data were taken from the oral semaglutide and placebo arms of the patient subgroup receiving metformin plus an SGLT-2 inhibitor in PIONEER 4. Costs, expressed in 2021 Pounds sterling (GBP), were accounted from a healthcare payer perspective. INTERVENTIONS: Modelled patients received oral semaglutide immediately (in the first year of the analysis) or after a 2-year delay, after which all physiological parameters were brought to values observed in the immediate therapy arm. During the simulation, patients intensified with the addition of basal insulin and, subsequently, by switching to basal-bolus insulin. RESULTS: Immediate oral semaglutide therapy was associated with improvements in life expectancy of 0.17 (95% CIs 0.16 to 0.19) years, and quality-adjusted life expectancy of 0.15 (0.14 to 0.16) quality-adjusted life years (QALYs), versus a 2-year delay. Benefits were due to a reduced incidence of diabetes-related complications. Direct costs were estimated to be GBP 1423 (1349 to 1496) higher with immediate oral semaglutide therapy versus a 2-year delay, with higher treatment costs partially offset by cost savings from avoidance of diabetes-related complications. Immediate oral semaglutide therapy was therefore associated with an incremental cost-effectiveness ratio of GBP 9404 (8380 to 10 538) per QALY gained versus a 2-year delay. CONCLUSIONS: Immediate oral semaglutide is likely to represent a cost-effective treatment in people with type 2 diabetes with inadequate glycaemic control on metformin plus an SGLT-2 inhibitor in the UK. TRIAL REGISTRATION NUMBER: NCT02863419. CI - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Ren, Hongye AU - Ren H AD - External Affairs, Diabetes & CV, Novo Nordisk Denmark A/S, Copenhagen, Denmark. FAU - Berry, Sasha AU - Berry S AD - Market Access, Novo Nordisk Ltd, Gatwick, UK. FAU - Malkin, Samuel Joseph Paul AU - Malkin SJP AUID- ORCID: 0000-0003-1306-7784 AD - Ossian Health Economics and Communications GmbH, Basel, Switzerland malkin@ossianconsulting.com. FAU - Hunt, Barnaby AU - Hunt B AD - Ossian Health Economics and Communications GmbH, Basel, Switzerland. FAU - Bain, Stephen AU - Bain S AD - Swansea University Medical School, Swansea, UK. LA - eng SI - ClinicalTrials.gov/NCT02863419 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230929 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - IY9XDZ35W2 (Glucose) RN - 0 (Insulins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/epidemiology MH - *Metformin/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Hypoglycemic Agents MH - Cost-Effectiveness Analysis MH - Cost-Benefit Analysis MH - *Diabetes Complications/epidemiology MH - Quality-Adjusted Life Years MH - Glucose/therapeutic use MH - United Kingdom/epidemiology MH - *Insulins/therapeutic use MH - Semaglutide PMC - PMC10546165 OTO - NOTNLM OT - DIABETES & ENDOCRINOLOGY OT - HEALTH ECONOMICS OT - ORAL MEDICINE COIS- Competing interests: HR is an employee of Novo Nordisk Denmark A/S. SBe is an employee of Novo Nordisk Ltd. SJPM and BH are employees of Ossian Health Economics and Communications, which received consulting fees from Novo Nordisk Denmark A/S to support preparation of the analysis. SBa has received honoraria, teaching and research sponsorship/grants from the following: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novo Nordisk, Pfizer, Sanofi and Takeda. SBa owns a share of Glycosmedia. EDAT- 2023/09/30 09:42 MHDA- 2023/10/05 06:44 PMCR- 2023/09/29 CRDT- 2023/09/29 21:23 PHST- 2023/10/05 06:44 [medline] PHST- 2023/09/30 09:42 [pubmed] PHST- 2023/09/29 21:23 [entrez] PHST- 2023/09/29 00:00 [pmc-release] AID - bmjopen-2022-070473 [pii] AID - 10.1136/bmjopen-2022-070473 [doi] PST - epublish SO - BMJ Open. 2023 Sep 29;13(9):e070473. doi: 10.1136/bmjopen-2022-070473. PMID- 37744474 OWN - NLM STAT- MEDLINE DCOM- 20231007 LR - 20260127 IS - 2296-2565 (Electronic) IS - 2296-2565 (Linking) VI - 11 DP - 2023 TI - Effectiveness and cost-effectiveness of six GLP-1RAs for treatment of Chinese type 2 diabetes mellitus patients that inadequately controlled on metformin: a micro-simulation model. PG - 1201818 LID - 10.3389/fpubh.2023.1201818 [doi] LID - 1201818 AB - OBJECTIVE: To systematically estimate and compare the effectiveness and cost-effectiveness of the glucagon-like peptide-1 receptor agonists (GLP-1RAs) approved in China and to quantify the relationship between the burden of diabetic comorbidities and glycosylated hemoglobin (HbA1c) or body mass index (BMI). METHODS: To estimate the costs (US dollars, USD) and quality-adjusted life years (QALY) for six GLP-1RAs (exenatide, loxenatide, lixisenatide, dulaglutide, semaglutide, and liraglutide) combined with metformin in the treatment of patients with type 2 diabetes mellitus (T2DM) which is inadequately controlled on metformin from the Chinese healthcare system perspective, a discrete event microsimulation cost-effectiveness model based on the Chinese Hong Kong Integrated Modeling and Evaluation (CHIME) simulation model was developed. A cohort of 30,000 Chinese patients was established, and one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) with 50,000 iterations were conducted considering parameter uncertainty. Scenario analysis was conducted considering the impacts of research time limits. A network meta-analysis was conducted to compare the effects of six GLP-1RAs on HbA1c, BMI, systolic blood pressure, and diastolic blood pressure. The incremental net monetary benefit (INMB) between therapies was used to evaluate the cost-effectiveness. China's per capita GDP in 2021 was used as the willingness-to-pay threshold. A generalized linear model was used to quantify the relationship between the burden of diabetic comorbidities and HbA1c or BMI. RESULTS: During a lifetime, the cost for a patient ranged from USD 42,092 with loxenatide to USD 47,026 with liraglutide, while the QALY gained ranged from 12.50 with dulaglutide to 12.65 with loxenatide. Compared to exenatide, the INMB of each drug from highest to lowest were: loxenatide (USD 1,124), dulaglutide (USD -1,418), lixisenatide (USD -1,713), semaglutide (USD -4,298), and liraglutide (USD -4,672). Loxenatide was better than the other GLP-1RAs in the base-case analysis. Sensitivity and scenario analysis results were consistent with the base-case analysis. Overall, the price of GLP-1RAs most affected the results. Medications with effective control of HbA1c or BMI were associated with a significantly smaller disease burden (p < 0.05). CONCLUSION: Loxenatide combined with metformin was identified as the most economical choice, while the long-term health benefits of patients taking the six GLP-1RAs are approximate. CI - Copyright (c) 2023 Yuan and Wu. FAU - Yuan, Shuai AU - Yuan S AD - Department of Pharmacoeconomics, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. FAU - Wu, Yingyu AU - Wu Y AD - Department of Pharmacoeconomics, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis DEP - 20230906 PL - Switzerland TA - Front Public Health JT - Frontiers in public health JID - 101616579 RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 74O62BB01U (lixisenatide) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - Chinese people SB - IM MH - Humans MH - Body Mass Index MH - Comorbidity MH - Cost of Illness MH - Cost-Benefit Analysis MH - Cost-Effectiveness Analysis MH - *Diabetes Mellitus, Type 2/blood/diagnosis/drug therapy/economics MH - East Asian People MH - Exenatide MH - *Glucagon-Like Peptide 1/analogs & derivatives MH - *Glycated Hemoglobin/analysis MH - *Hypoglycemic Agents/economics/therapeutic use MH - Liraglutide MH - *Metformin MH - Quality-Adjusted Life Years MH - Treatment Outcome MH - Drug Therapy, Combination MH - Computer Simulation MH - Glycemic Control/methods MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins MH - Peptides MH - Glucagon-Like Peptide-2 Receptor PMC - PMC10513082 OTO - NOTNLM OT - cost-effectiveness OT - discrete event micro-simulation model OT - effectiveness OT - glucagon-like peptide-1 receptor agonists OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/09/25 06:42 MHDA- 2023/09/26 13:42 PMCR- 2023/09/06 CRDT- 2023/09/25 04:45 PHST- 2023/06/20 00:00 [received] PHST- 2023/08/21 00:00 [accepted] PHST- 2023/09/26 13:42 [medline] PHST- 2023/09/25 06:42 [pubmed] PHST- 2023/09/25 04:45 [entrez] PHST- 2023/09/06 00:00 [pmc-release] AID - 10.3389/fpubh.2023.1201818 [doi] PST - epublish SO - Front Public Health. 2023 Sep 6;11:1201818. doi: 10.3389/fpubh.2023.1201818. eCollection 2023. PMID- 37740832 OWN - NLM STAT- MEDLINE DCOM- 20231124 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 40 IP - 11 DP - 2023 Nov TI - Real-World Hemoglobin A1c Changes, Prescribing Provider Types, and Medication Dose Among Patients with Type 2 Diabetes Mellitus Initiating Treatment with Oral Semaglutide. PG - 5102-5114 LID - 10.1007/s12325-023-02677-w [doi] AB - INTRODUCTION: Given the lack of real-world data on oral semaglutide use outside clinical trials, the purpose of this study was to describe dose, prescriber specialty, and change in hemoglobin A1c (HbA1c) after 6 months of oral semaglutide treatment for patients with type 2 diabetes mellitus (T2DM). METHODS: This was a retrospective study among adult patients with T2DM with >/= 1 claim for oral semaglutide between November 1, 2019;1-June 30, 2020. Patients had continuous health plan enrollment >/= 12 months prior to (pre-index) and >/= 6 months following (post-index) the date of the first oral semaglutide claim (index). Dose at initiation and specialty of the prescribing provider were captured. Change in HbA1c between the last post- and pre-index HbA1c measurement was calculated. Patients were stratified by pre-index HbA1c >/= 9% (poorly controlled) and HbA1c < 9%. RESULTS: A total of 744 HbA1c < 9% and 268 poorly controlled patients were included in the study. Most patients had an initial oral semaglutide dose of 7 mg (49.3%) or 3 mg (42.9%), prescribed most frequently by a primary care provider (27.8%). Mean HbA1c reduction was 0.8% (p < 0.001). Patients with poorly controlled T2DM had greater HbA1c reductions than patients with HbA1c < 9% (2.0% versus 0.4%, p < 0.001). Patients persistent with oral semaglutide (>/= 90 days continuous treatment) had a mean HbA1c reduction of 0.9% (p < 0.001); persistent patients with poorly controlled T2DM had a mean reduction of 2.5%. CONCLUSIONS: Patients with T2DM in this study experienced significant reductions in HbA1c within 6 months following initiation of oral semaglutide. Patients with a higher starting HbA1c experienced greater HbA1c reductions. The initial dose of oral semaglutide was higher than prescribing instructions indicated for more than half of the study patients. CI - (c) 2023. The Author(s). FAU - Frazer, Monica AU - Frazer M AD - QualityMetric, Johnston, RI, USA. AD - Optum, 11000 Optum Circle, Eden Prairie, MN, 55344, USA. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk, Inc., Plainsboro, NJ, USA. FAU - Gronroos, Noelle N AU - Gronroos NN AD - Optum, 11000 Optum Circle, Eden Prairie, MN, 55344, USA. Noelle.gronroos@optum.com. FAU - Sargent, Andrew AU - Sargent A AD - Optum, 11000 Optum Circle, Eden Prairie, MN, 55344, USA. FAU - Leszko, Michael AU - Leszko M AD - Optum, 11000 Optum Circle, Eden Prairie, MN, 55344, USA. FAU - Buysman, Erin AU - Buysman E AD - Optum, 11000 Optum Circle, Eden Prairie, MN, 55344, USA. FAU - Alvarez, Sara AU - Alvarez S AD - Novo Nordisk, Inc., Plainsboro, NJ, USA. FAU - Dunn, Tyler J AU - Dunn TJ AD - Novo Nordisk, Inc., Plainsboro, NJ, USA. FAU - Noone, Josh AU - Noone J AD - Novo Nordisk, Inc., Plainsboro, NJ, USA. FAU - Guevarra, Mico AU - Guevarra M AD - Novo Nordisk, Inc., Plainsboro, NJ, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230923 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) MH - Adult MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - Hypoglycemic Agents/adverse effects MH - Retrospective Studies MH - Glucagon-Like Peptides MH - Semaglutide PMC - PMC10567941 OTO - NOTNLM OT - Dose OT - HbA1c OT - Oral semaglutide OT - Prescriber type OT - Type 2 diabetes mellitus COIS- Caroline Swift, Sarah Alvarez, Tyler J. Dunn, Josh Noone, and Mico Guevarra are employees of Novo Nordisk. Monica Frazer was an employee of Optum at the time the study was conducted and is currently employed at QualityMetric. Andrew Sargent, Michael Leszko, Noelle N. Gronroos, and Erin Buysman are employees of Optum. EDAT- 2023/09/23 20:42 MHDA- 2023/11/24 06:42 PMCR- 2023/09/23 CRDT- 2023/09/23 11:08 PHST- 2023/08/07 00:00 [received] PHST- 2023/08/31 00:00 [accepted] PHST- 2023/11/24 06:42 [medline] PHST- 2023/09/23 20:42 [pubmed] PHST- 2023/09/23 11:08 [entrez] PHST- 2023/09/23 00:00 [pmc-release] AID - 10.1007/s12325-023-02677-w [pii] AID - 2677 [pii] AID - 10.1007/s12325-023-02677-w [doi] PST - ppublish SO - Adv Ther. 2023 Nov;40(11):5102-5114. doi: 10.1007/s12325-023-02677-w. Epub 2023 Sep 23. PMID- 37735340 OWN - NLM STAT- MEDLINE DCOM- 20240220 LR - 20261010 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 83 IP - 2 DP - 2024 Feb TI - Weight loss response in patients with obesity treated with injectable semaglutide in a real-world setting. PG - 392-398 LID - 10.1007/s12020-023-03534-0 [doi] AB - BACKGROUND: Obesity is defined as excess adipose tissue causing a deterioration in health, but diagnosing the causes and deciding on treatment can be challenging. Several randomized controlled clinical trials (RCT) have demonstrated the effectiveness of semaglutide as a treatment for obesity. This study investigated the clinical response to semaglutide as a weight loss treatment in a real-world setting. METHODS: This observational study investigated the response to injectable semaglutide in the first 3 months during the dose titration phase up to 1 mg. Weight loss after 6 months was also evaluated. The data were collected from the electronic medical records (EMR) from outpatient clinics between July 2021 to March 2023. All participants were older than 18 years, with no history of bariatric surgery within 1 year, and had a least one prescription of injectable semaglutide. The primary outcome was weight change at 3 months. Weight loss in those patients who attended at 6 months was a secondary outcome. RESULTS: A total of 350 patients were included in the study. The vast majority (80.3%) were female. 287 patients (82%) completed 3 months on injectable semaglutide and lost 6.6 +/- 3.8% bodyweight. 224 patients (64%) completed 6 months on semaglutide and lost 12 +/- 6.1% bodyweight. 188 (65.5%) of patients who completed 3-month follow-up lost >/=5% weight, 39 (13.5%) patients lost >/=10% weight, and 7 (2.4%) patients lost >/=15% weight. While for those patients who completed the 2nd visit (n = 224), 201 (89.7%) lost >/=5% weight, 135 (60.3%) lost >/=10% weight, and 54 (24.1%) lost >/= 15% body weight. CONCLUSION: Injectable semaglutide in a real-world setting resulted in similar weight loss and had a similar side effect profile as was observed in randomized controlled trials. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Alabduljabbar, Khaled AU - Alabduljabbar K AD - Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04V1W8, Dublin, Ireland. AD - Department of Family Medicine and Polyclinics, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia. FAU - Alsaqaaby, Moath AU - Alsaqaaby M AD - Obesity, Endocrine and Metabolism Centre, King Fahad Medical City, Riyadh, 11211, Saudi Arabia. FAU - Neff, Karl J AU - Neff KJ AD - Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04V1W8, Dublin, Ireland. FAU - Crotty, Michael AU - Crotty M AD - My Best Weight Clinic, Blackrock, A94A0D0, Dublin, Ireland. FAU - le Roux, Carel W AU - le Roux CW AD - Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04V1W8, Dublin, Ireland. carel.leroux@ucd.ie. LA - eng PT - Journal Article PT - Observational Study DEP - 20230921 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - Obesity/drug therapy MH - Treatment Outcome MH - Weight Loss MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - Obesity OT - Real-world OT - Semaglutide OT - Weight management EDAT- 2023/09/22 06:42 MHDA- 2024/02/08 06:43 CRDT- 2023/09/22 00:23 PHST- 2023/07/11 00:00 [received] PHST- 2023/09/10 00:00 [accepted] PHST- 2024/02/08 06:43 [medline] PHST- 2023/09/22 06:42 [pubmed] PHST- 2023/09/22 00:23 [entrez] AID - 10.1007/s12020-023-03534-0 [pii] AID - 10.1007/s12020-023-03534-0 [doi] PST - ppublish SO - Endocrine. 2024 Feb;83(2):392-398. doi: 10.1007/s12020-023-03534-0. Epub 2023 Sep 21. PMID- 37728959 OWN - NLM STAT- MEDLINE DCOM- 20231012 LR - 20260127 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 330 IP - 14 DP - 2023 Oct 10 TI - Semaglutide Associated With Less Insulin Need in Early Type 1 Diabetes. PG - 1318 LID - 10.1001/jama.2023.17818 [doi] FAU - Harris, Emily AU - Harris E LA - eng PT - Journal Article PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Insulin, Regular, Human) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 1/complications/drug therapy MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/administration & dosage/therapeutic use MH - *Insulin/administration & dosage/therapeutic use MH - Insulin, Regular, Human MH - Semaglutide EDAT- 2023/09/20 18:42 MHDA- 2023/10/11 06:45 CRDT- 2023/09/20 12:15 PHST- 2023/10/11 06:45 [medline] PHST- 2023/09/20 18:42 [pubmed] PHST- 2023/09/20 12:15 [entrez] AID - 2809894 [pii] AID - 10.1001/jama.2023.17818 [doi] PST - ppublish SO - JAMA. 2023 Oct 10;330(14):1318. doi: 10.1001/jama.2023.17818. PMID- 37728754 OWN - NLM STAT- MEDLINE DCOM- 20240304 LR - 20261010 IS - 1435-702X (Electronic) IS - 0721-832X (Linking) VI - 262 IP - 3 DP - 2024 Mar TI - Effects of newer-generation anti-diabetics on diabetic retinopathy: a critical review. PG - 717-752 LID - 10.1007/s00417-023-06236-5 [doi] AB - Diabetic retinopathy (DR) is the leading etiology of blindness in the working population of the USA. Its long-term management relies on effective glycemic control. Seven anti-diabetic classes have been introduced for patients with type 2 diabetes (T2D) in the past two decades, with different glucose-lowering and cardiovascular benefits. Yet, their effects specifically on DR have not been studied in detail. A systematic review of the literature was conducted to investigate this topic, focusing on the available clinical data for T2D. Published studies were evaluated based on their level of statistical evidence, as long as they incorporated at least one endpoint or adverse event pertaining to retinal health. Fifty nine articles met our inclusion criteria and were grouped per anti-diabetic class as follows: alpha-glucosidase inhibitors (1), peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists (8), amylin analogs (1), glucagon-like peptide-1 (GLP-1) receptor agonists (28), dipeptidyl peptidase 4 (DPP-4) inhibitors (9), and sodium glucose co-transporter-2 (SGLT-2) inhibitors (9), plus one retrospective study and two meta-analyses evaluating more than one of the aforementioned anti-diabetic categories. We also reviewed publicly-announced results of trials for the recently-introduced class of twincretins. The available data indicates that most drugs in the newer anti-diabetic classes are neutral to DR progression; however, there are subclasses differences in specific drugs and T2D populations. In particular, there is evidence suggesting there may be worse diabetic macular edema with PPAR-gamma agonists, potential slight DR worsening with semaglutide (GLP-1 receptor agonist), and potential slight increase in the incidence of retinal vein occlusion in elderly and patients with advanced kidney disease receiving SGLT-2 inhibitors. All these warrant further investigation. Longer follow-up and systematic assessment of at least one DR-related endpoint are highly recommended for all future trials in the T2D field, to ultimately address this topic. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Ntentakis, Dimitrios P AU - Ntentakis DP AD - Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA. FAU - Correa, Victor San Martin Carvalho AU - Correa VSMC AD - Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA. FAU - Ntentaki, Anastasia Maria AU - Ntentaki AM AD - Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA. FAU - Delavogia, Eleni AU - Delavogia E AD - Department of Pediatrics, Harvard Medical School, Boston, MA, USA. FAU - Narimatsu, Toshio AU - Narimatsu T AD - Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA. FAU - Efstathiou, Nikolaos E AU - Efstathiou NE AD - Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA. FAU - Vavvas, Demetrios G AU - Vavvas DG AUID- ORCID: 0000-0002-8622-6478 AD - Ines and Fredrick Yeatts Retina Research Laboratory, Angiogenesis Laboratory, Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Main Campus, 243 Charles Street, Harvard Medical School, Boston, MA, 02114, USA. Demetrios_Vavvas@MEEI.HARVARD.EDU. LA - eng PT - Journal Article PT - Systematic Review DEP - 20230920 PL - Germany TA - Graefes Arch Clin Exp Ophthalmol JT - Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie JID - 8205248 RN - 0 (Hypoglycemic Agents) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Aged MH - Humans MH - *Diabetic Retinopathy/complications/diagnosis/drug therapy MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Retrospective Studies MH - *Macular Edema MH - Hypoglycemic Agents/therapeutic use MH - Glucose OTO - NOTNLM OT - Diabetic retinopathy OT - Diabetic retinopathy complications OT - Newer-generation anti-diabetics OT - Type 2 diabetes EDAT- 2023/09/20 12:51 MHDA- 2024/03/04 06:48 CRDT- 2023/09/20 11:26 PHST- 2023/06/20 00:00 [received] PHST- 2023/09/07 00:00 [accepted] PHST- 2023/08/30 00:00 [revised] PHST- 2024/03/04 06:48 [medline] PHST- 2023/09/20 12:51 [pubmed] PHST- 2023/09/20 11:26 [entrez] AID - 10.1007/s00417-023-06236-5 [pii] AID - 10.1007/s00417-023-06236-5 [doi] PST - ppublish SO - Graefes Arch Clin Exp Ophthalmol. 2024 Mar;262(3):717-752. doi: 10.1007/s00417-023-06236-5. Epub 2023 Sep 20. PMID- 37722966 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20260323 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 26 IP - 1 DP - 2024 Jan TI - Albuminuria-lowering effect of adding semaglutide on top of empagliflozin in individuals with type 2 diabetes: A randomized and placebo-controlled study. PG - 54-64 LID - 10.1111/dom.15287 [doi] AB - AIM: To investigate whether combined treatment with empagliflozin (a sodium-glucose cotransporter-2 inhibitor) and semaglutide (a glucagon-like peptide-1 receptor agonist) can reduce urinary albumin-creatinine ratio (UACR) compared to treatment with empagliflozin alone in individuals with type 2 diabetes (T2D) and albuminuria. METHODS: We conducted a randomized, placebo-controlled, double-blind, parallel study including 60 individuals with T2D and albuminuria. All participants initiated open-label empagliflozin 25 mg once daily, on top of renin-angiotensin system inhibition, in a run-in period of 26 weeks. Subsequently, participants were randomized to semaglutide or placebo 1 mg once weekly for 26 weeks. The primary endpoint was change in UACR. Secondary endpoints were change in: (i) measured glomerular filtration rate (GFR); (ii) 24-hour systolic blood pressure; (iii) glycated haemoglobin (HbA1c) level; (iv) body weight; and (v) plasma renin and aldosterone levels. RESULTS: Addition of semaglutide to empagliflozin provided no additional change in UACR from randomization to end-of-treatment. The mean (95% confidence interval) difference in UACR was -22 (-44; 10)% (P = 0.15) between treatment groups. Neither GFR, 24-hour blood pressure, body weight, nor plasma renin activity was changed with semaglutide. HbA1c (-8 [-13; -3] mmol/mol; P = 0.003) and plasma aldosterone (-30 [-50; -3] pmol/L; P = 0.035) were reduced with semaglutide compared to placebo. CONCLUSIONS: Semaglutide added to empagliflozin did not change UACR, measured GFR, 24-hour systolic blood pressure, body weight or plasma renin levels in individuals with T2D and albuminuria. Semaglutide improved glycaemic control and plasma aldosterone levels compared to placebo. CI - (c) 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Sivalingam, Suvanjaa AU - Sivalingam S AUID- ORCID: 0000-0001-7520-2326 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Wasehuus, Victor Soendergaard AU - Wasehuus VS AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Rotbain Curovic, Viktor AU - Rotbain Curovic V AUID- ORCID: 0000-0002-4270-6701 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Blond, Martin Baek AU - Blond MB AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Hansen, Tine W AU - Hansen TW AUID- ORCID: 0000-0003-2274-0352 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Persson, Frederik AU - Persson F AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. LA - eng GR - Novo Nordisk/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230918 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glycated Hemoglobin) RN - EC 3.4.23.15 (Renin) RN - 4964P6T9RB (Aldosterone) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glycated Hemoglobin MH - Albuminuria/etiology/complications MH - Renin/therapeutic use MH - Aldosterone/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptides/therapeutic use MH - Body Weight MH - Double-Blind Method MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide MH - Benzhydryl Compounds MH - Glucosides OTO - NOTNLM OT - GLP-1 analogue OT - SGLT2 inhibitor OT - diabetic nephropathy OT - randomized trial EDAT- 2023/09/19 00:43 MHDA- 2023/12/17 09:45 CRDT- 2023/09/18 21:54 PHST- 2023/08/22 00:00 [revised] PHST- 2023/07/05 00:00 [received] PHST- 2023/08/29 00:00 [accepted] PHST- 2023/12/17 09:45 [medline] PHST- 2023/09/19 00:43 [pubmed] PHST- 2023/09/18 21:54 [entrez] AID - 10.1111/dom.15287 [doi] PST - ppublish SO - Diabetes Obes Metab. 2024 Jan;26(1):54-64. doi: 10.1111/dom.15287. Epub 2023 Sep 18. PMID- 37709961 OWN - NLM STAT- MEDLINE DCOM- 20240110 LR - 20251203 IS - 2522-5812 (Electronic) IS - 2522-5812 (Linking) VI - 5 IP - 10 DP - 2023 Oct TI - Human GLP1R variants affecting GLP1R cell surface expression are associated with impaired glucose control and increased adiposity. PG - 1673-1684 LID - 10.1038/s42255-023-00889-6 [doi] AB - The glucagon-like peptide 1 receptor (GLP1R) is a major drug target with several agonists being prescribed in individuals with type 2 diabetes and obesity(1,2). The impact of genetic variability of GLP1R on receptor function and its association with metabolic traits are unclear with conflicting reports. Here, we show an unexpected diversity of phenotypes ranging from defective cell surface expression to complete or pathway-specific gain of function (GoF) and loss of function (LoF), after performing a functional profiling of 60 GLP1R variants across four signalling pathways. The defective insulin secretion of GLP1R LoF variants is rescued by allosteric GLP1R ligands or high concentrations of exendin-4/semaglutide in INS-1 823/3 cells. Genetic association studies in 200,000 participants from the UK Biobank show that impaired GLP1R cell surface expression contributes to poor glucose control and increased adiposity with increased glycated haemoglobin A1c and body mass index. This study defines impaired GLP1R cell surface expression as a risk factor for traits associated with type 2 diabetes and obesity and provides potential treatment options for GLP1R LoF variant carriers. CI - (c) 2023. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Gao, Wenwen AU - Gao W AUID- ORCID: 0009-0007-6209-0493 AD - Universite Paris Cite, Institut Cochin, INSERM, CNRS, Paris, France. AD - State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China. FAU - Liu, Lei AU - Liu L AUID- ORCID: 0000-0002-9824-9570 AD - Universite Paris Cite, Institut Cochin, INSERM, CNRS, Paris, France. AD - Cellular Signaling Laboratory, International Research Center for Sensory Biology and Technology of MOST, Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. FAU - Huh, Eunna AU - Huh E AD - Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX, USA. FAU - Gbahou, Florence AU - Gbahou F AD - Universite Paris Cite, Institut Cochin, INSERM, CNRS, Paris, France. FAU - Cecon, Erika AU - Cecon E AD - Universite Paris Cite, Institut Cochin, INSERM, CNRS, Paris, France. FAU - Oshima, Masaya AU - Oshima M AD - Universite Paris Cite, Institut Cochin, INSERM, CNRS, Paris, France. FAU - Houze, Ludivine AU - Houze L AD - Universite Paris Cite, Institut Cochin, INSERM, CNRS, Paris, France. FAU - Katsonis, Panagiotis AU - Katsonis P AD - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. FAU - Hegron, Alan AU - Hegron A AUID- ORCID: 0000-0002-7588-9209 AD - Universite Paris Cite, Institut Cochin, INSERM, CNRS, Paris, France. AD - Institute for Research in Immunology and Cancer, University of Montreal, Montreal, Quebec, Canada. AD - Department of Biochemistry and Molecular Medicine, University of Montreal, Montreal, Quebec, Canada. FAU - Fan, Zhiran AU - Fan Z AD - Cellular Signaling Laboratory, International Research Center for Sensory Biology and Technology of MOST, Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. FAU - Hou, Guofei AU - Hou G AD - Cellular Signaling Laboratory, International Research Center for Sensory Biology and Technology of MOST, Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. FAU - Charpentier, Guillaume AU - Charpentier G AD - CERITD (Centre d'Etude et de Recherche pour l'Intensification du Traitement du Diabete), Evry, France. FAU - Boissel, Mathilde AU - Boissel M AUID- ORCID: 0000-0001-5719-8749 AD - University of Lille, Inserm UMR1283, CNRS UMR8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille University Hospital, Lille, France. FAU - Derhourhi, Mehdi AU - Derhourhi M AUID- ORCID: 0000-0001-5020-5379 AD - University of Lille, Inserm UMR1283, CNRS UMR8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille University Hospital, Lille, France. FAU - Marre, Michel AU - Marre M AD - Institut Necker-Enfants Malades, INSERM, Universite Paris Cite, Paris, France. AD - Clinique Ambroise Pare, Neuilly-sur-Seine, France. FAU - Balkau, Beverley AU - Balkau B AUID- ORCID: 0000-0003-2021-413X AD - Inserm U1018, Center for Research in Epidemiology and Population Health, Villejuif, France. AD - University Paris-Saclay, University Paris-Sud, Villejuif, France. FAU - Froguel, Philippe AU - Froguel P AUID- ORCID: 0000-0003-2972-0784 AD - University of Lille, Inserm UMR1283, CNRS UMR8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille University Hospital, Lille, France. AD - Department of Metabolism, Imperial College London, London, UK. FAU - Scharfmann, Raphael AU - Scharfmann R AUID- ORCID: 0000-0001-7619-337X AD - Universite Paris Cite, Institut Cochin, INSERM, CNRS, Paris, France. FAU - Lichtarge, Olivier AU - Lichtarge O AD - Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, TX, USA. AD - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. FAU - Dam, Julie AU - Dam J AUID- ORCID: 0000-0001-6871-2678 AD - Universite Paris Cite, Institut Cochin, INSERM, CNRS, Paris, France. FAU - Bonnefond, Amelie AU - Bonnefond A AD - University of Lille, Inserm UMR1283, CNRS UMR8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille University Hospital, Lille, France. AD - Department of Metabolism, Imperial College London, London, UK. FAU - Liu, Jianfeng AU - Liu J AUID- ORCID: 0000-0002-0284-8377 AD - Cellular Signaling Laboratory, International Research Center for Sensory Biology and Technology of MOST, Key Laboratory of Molecular Biophysics of Ministry of Education, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China. jfliu@mail.hust.edu.cn. FAU - Jockers, Ralf AU - Jockers R AUID- ORCID: 0000-0002-4354-1750 AD - Universite Paris Cite, Institut Cochin, INSERM, CNRS, Paris, France. ralf.jockers@inserm.fr. LA - eng GR - R01 GM066099/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20230914 PL - Germany TA - Nat Metab JT - Nature metabolism JID - 101736592 RN - 0 (Blood Glucose) RN - 0 (Insulin) SB - IM MH - Humans MH - *Blood Glucose MH - Insulin/metabolism MH - *Diabetes Mellitus, Type 2/genetics MH - Adiposity/genetics MH - Obesity/genetics PMC - PMC11610247 MID - NIHMS2026843 COIS- DECLARATION OF INTERESTS The authors declare no competing interes EDAT- 2023/09/15 00:42 MHDA- 2024/01/10 06:42 PMCR- 2024/12/02 CRDT- 2023/09/14 23:30 PHST- 2022/09/28 00:00 [received] PHST- 2023/08/09 00:00 [accepted] PHST- 2024/01/10 06:42 [medline] PHST- 2023/09/15 00:42 [pubmed] PHST- 2023/09/14 23:30 [entrez] PHST- 2024/12/02 00:00 [pmc-release] AID - 10.1038/s42255-023-00889-6 [pii] AID - 10.1038/s42255-023-00889-6 [doi] PST - ppublish SO - Nat Metab. 2023 Oct;5(10):1673-1684. doi: 10.1038/s42255-023-00889-6. Epub 2023 Sep 14. PMID- 37701904 OWN - NLM STAT- MEDLINE DCOM- 20230915 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - Comparison of the efficacy and safety of 10 glucagon-like peptide-1 receptor agonists as add-on to metformin in patients with type 2 diabetes: a systematic review. PG - 1244432 LID - 10.3389/fendo.2023.1244432 [doi] LID - 1244432 AB - PURPOSE: This study aimed to perform a network meta-analysis to objectively evaluate the efficacy and safety of 10 Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in combination with metformin that is approved for use worldwide in patients with type 2 diabetes and to provide evidence-based support and reference for the selection of clinical treatment. METHODS: Three databases (PubMed, Embase, and Cochrane Library) were searched from their respective inception until September 30, 2022. Only randomized controlled trials comparing the efficacy and safety of GLP-1RAs for treating type 2 diabetes (T2D) were included. The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide. RESULTS: 34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA). According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200mug, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively. There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg. PEX168-200mug, tirzepatide 15mg, and oral semaglutide 14mg had Surface Under the Cumulative Ranking (SUCRA) values greater than placebo, and only tirzepatide 15mg and oral semaglutide 14mg were significantly different from placebo in the rate of serious adverse events. All GLP-1RA did not lead to increased incidence of hypoglycemia. Albiglutide 30mg and semaglutide 1.0mg significantly differed from placebo in Adverse Event (AE) withdrawal. Finally, the sensitivity analysis and publication bias analysis results indicate that the study results are reliable. CONCLUSION: This study's results showed that GLP-1RAs were effective in lowering HbA1c and reducing body weight without increased incidence of hypoglycemic reactions. In addition, this study may provide reference and evidence-based medical evidence for clinicians to select GLP-1RAs in patients with T2D and high body mass index (BMI). Based on the NMA results, tirzepatide 15mg and semaglutide 1.0mg may be preferred. CI - Copyright (c) 2023 Xie, Hu, Gu, Li and Chen. FAU - Xie, Zeyu AU - Xie Z AD - Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China. FAU - Hu, Jia AU - Hu J AD - Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China. FAU - Gu, Hangye AU - Gu H AD - Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China. FAU - Li, Mengting AU - Li M AD - Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China. FAU - Chen, Jisheng AU - Chen J AD - Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20230828 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 0 (polyethylene glycol loxenatide) RN - 0 (Peptides) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Humans MH - Body Weight MH - *Diabetes Mellitus, Type 2/drug therapy MH - Exenatide MH - Glucagon-Like Peptide-1 Receptor MH - Glycated Hemoglobin MH - *Metformin/therapeutic use MH - Peptides MH - Polyethylene Glycols PMC - PMC10493284 OTO - NOTNLM OT - efficacy OT - glucagon-like peptide-1 receptor agonists OT - randomized controlled trials OT - safety OT - systematic review OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/09/13 06:42 MHDA- 2023/09/14 06:42 PMCR- 2023/01/01 CRDT- 2023/09/13 04:15 PHST- 2023/06/22 00:00 [received] PHST- 2023/08/07 00:00 [accepted] PHST- 2023/09/14 06:42 [medline] PHST- 2023/09/13 06:42 [pubmed] PHST- 2023/09/13 04:15 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1244432 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Aug 28;14:1244432. doi: 10.3389/fendo.2023.1244432. eCollection 2023. PMID- 37696925 OWN - NLM STAT- MEDLINE DCOM- 20231027 LR - 20240927 IS - 1476-5497 (Electronic) IS - 0307-0565 (Print) IS - 0307-0565 (Linking) VI - 47 IP - 11 DP - 2023 Nov TI - Laparoscopic adjustable gastric banding with liraglutide in adults with obesity and type 2 diabetes (GLIDE): a pilot randomised placebo controlled trial. PG - 1132-1142 LID - 10.1038/s41366-023-01368-4 [doi] AB - INTRODUCTION: Obesity drives type 2 diabetes (T2DM) development. Laparoscopic adjustable gastric banding (LAGB) has lower weight reduction than other bariatric procedures. Liraglutide, a GLP-1 receptor agonist, improves weight and glycaemic control in patients with T2DM. This study aimed to determine the efficacy and safety of liraglutide 1.8 mg in participants undergoing LAGB. METHODS: GLIDE, a pilot randomised, double-blind, placebo-controlled trial, evaluated LAGB with either liraglutide 1.8 mg or placebo in participants with T2DM and obesity. Participants were randomised (1:1) to 6-months therapy post-LAGB, with further 6 months off-treatment follow-up. The primary outcome was change in HbA1c from randomisation to the end of treatment, secondary outcomes included body weight change. A sample size of 58 (29 per group) had 80% power to detect a 0.6% difference in HbA1c between groups. RESULTS: Twenty-seven participants were randomised to liraglutide (n = 13) or placebo (n = 14). Multivariate analysis showed no difference between placebo and liraglutide arms in HbA1c at 6 months (HbA1c:0.2 mmol/mol, -11.3, 11.6, p = 0.98) however, at 12 months HbA1c was significantly higher in the liraglutide arm (HbA1c:10.9 mmol/mol, 1.1, 20.6, p = 0.032). There was no difference between arms in weight at 6 months (BW:2.0 kg, -4.2, 8.1, p = 0.50), however, at 12 months weight was significantly higher in the liraglutide arm (BW:8.2 kg, 1.6, 14.9, p = 0.02). There were no significant differences in adverse events between groups. CONCLUSIONS: Our pilot data suggest no additional improvement in glycaemic control or BW with LAGB and liraglutide therapy. However, this trial was significantly underpowered to detect a significant change in the primary or secondary outcomes. Further trials are needed to investigate whether GLP-1 agonists, and particularly with more effective weekly agents (i.e. semaglutide or tirzepatide), are of benefit following metabolic surgery. CLINICAL TRIAL REGISTRATION: EudraCT number 2015-005402-11. CI - (c) 2023. The Author(s). FAU - Coelho, Claudia AU - Coelho C AD - Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK. FAU - Dobbie, Laurence J AU - Dobbie LJ AD - Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK. FAU - Crane, James AU - Crane J AD - Department of Endocrinology, King's College Hospital NHS Foundation Trust, London, UK. FAU - Douiri, Abdel AU - Douiri A AD - School of Life Course and Population Sciences, Faculty of Life Sciences & Medicine, King College London, London, UK. FAU - Learoyd, Annastazia E AU - Learoyd AE AUID- ORCID: 0000-0001-6964-9041 AD - School of Life Course and Population Sciences, Faculty of Life Sciences & Medicine, King College London, London, UK. FAU - Okolo, Olanike AU - Okolo O AD - Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK. FAU - Panagiotopoulos, Spyros AU - Panagiotopoulos S AD - Department of Minimal Access Surgery, King's College Hospital NHS Foundation Trust, London, UK. FAU - Pournaras, Dimitri J AU - Pournaras DJ AD - Department of Upper GI and Bariatric/Metabolic Surgery, North Bristol NHS Trust, Southmead Hospital, Bristol, UK. FAU - Ramar, Sasindran AU - Ramar S AD - Department of Minimal Access Surgery, King's College Hospital NHS Foundation Trust, London, UK. FAU - Rubino, Francesco AU - Rubino F AD - Department of Diabetes, School of Life Course Sciences, King's College London, London, UK. FAU - Singhal, Rishi AU - Singhal R AD - Upper GI Unit at Heart of England, NHS Foundation Trust, Birmingham, UK. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland, UK. FAU - Taheri, Shahrad AU - Taheri S AD - Department of Medicine, Weill Cornell Medicine Qatar, Doha, Qatar. FAU - McGowan, Barbara AU - McGowan B AUID- ORCID: 0000-0003-2015-726X AD - Department of Diabetes and Endocrinology, Guy's and St Thomas' NHS Foundation Trust, London, UK. Barbara.McGowan@gstt.nhs.uk. LA - eng SI - EudraCT/2015-005402-11 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230911 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) SB - IM MH - Humans MH - Adult MH - Liraglutide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/surgery MH - Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin MH - *Gastroplasty MH - Pilot Projects MH - Obesity/drug therapy/surgery MH - *Laparoscopy MH - Double-Blind Method MH - Treatment Outcome PMC - PMC10599987 COIS- AEL does not declare any conflicts of interest. CLR declares grants to his institution from the Irish Research Council, Health Research Board, Science Foundation Ireland and Anabio; consulting fees from NovoNordisk, Eli Lily, Johnson & Johnson, Boehringer Ingelheim, GI dynamics and Herbalife; Honoraria for presentations and support for attending meetings from NovoNordisk, Herbalife and Johnson & Johnson; unpaid leadership roles for the Irish Society for Nutrition and Metabolism and stocks in Keyron. BM is a shareholder in Reset Health and also performs Advisory and educational work for Novonordisk and Advisory work for Lilly. DP declares honoraria and consulting fees from Johnson & Johnson, honoraria from Medtronic and NovoNordisk and unpaid leadership roles at the Royal College of Surgeons, England. All other authors do not declare any conflicts of interest. EDAT- 2023/09/12 00:42 MHDA- 2023/10/27 06:43 PMCR- 2023/09/11 CRDT- 2023/09/11 23:29 PHST- 2023/06/07 00:00 [received] PHST- 2023/08/16 00:00 [accepted] PHST- 2023/08/05 00:00 [revised] PHST- 2023/10/27 06:43 [medline] PHST- 2023/09/12 00:42 [pubmed] PHST- 2023/09/11 23:29 [entrez] PHST- 2023/09/11 00:00 [pmc-release] AID - 10.1038/s41366-023-01368-4 [pii] AID - 1368 [pii] AID - 10.1038/s41366-023-01368-4 [doi] PST - ppublish SO - Int J Obes (Lond). 2023 Nov;47(11):1132-1142. doi: 10.1038/s41366-023-01368-4. Epub 2023 Sep 11. PMID- 37688299 OWN - NLM STAT- MEDLINE DCOM- 20231025 LR - 20260127 IS - 1879-3479 (Electronic) IS - 0020-7292 (Linking) VI - 163 IP - 2 DP - 2023 Nov TI - Semaglutide and pregnancy. PG - 699-700 LID - 10.1002/ijgo.15092 [doi] FAU - Skov, Kenneth AU - Skov K AUID- ORCID: 0000-0003-3612-5828 AD - Clinical Pharmacology Unit, Zealand University Hospital Roskilde, Roskilde, Denmark. AD - Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark. FAU - Mandic, Ida Nikoline AU - Mandic IN AD - Pediatric Unit, Slagelse Hospital, Slagelse, Denmark. FAU - Nyborg, Kathinka Marie AU - Nyborg KM AD - Department of Obstetrics and Gynecology, Fetal Medicine Unit, Slagelse Hospital, Slagelse, Denmark. LA - eng PT - Journal Article DEP - 20230908 PL - United States TA - Int J Gynaecol Obstet JT - International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics JID - 0210174 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Female MH - Humans MH - Pregnancy MH - *Diabetes Mellitus, Type 2 MH - *Glucagon-Like Peptides/adverse effects MH - Hypoglycemic Agents/adverse effects MH - Overweight MH - *Pregnancy Outcome MH - Semaglutide OTO - NOTNLM OT - PCOS OT - case report OT - malformations OT - overweight OT - pregnancy OT - risk pregnancy OT - semaglutide OT - untoward fetal outcome EDAT- 2023/09/09 11:42 MHDA- 2023/10/23 12:42 CRDT- 2023/09/09 02:21 PHST- 2023/07/13 00:00 [received] PHST- 2023/08/17 00:00 [accepted] PHST- 2023/10/23 12:42 [medline] PHST- 2023/09/09 11:42 [pubmed] PHST- 2023/09/09 02:21 [entrez] AID - 10.1002/ijgo.15092 [doi] PST - ppublish SO - Int J Gynaecol Obstet. 2023 Nov;163(2):699-700. doi: 10.1002/ijgo.15092. Epub 2023 Sep 8. PMID- 37653675 OWN - NLM STAT- MEDLINE DCOM- 20231102 LR - 20231102 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 24 IP - 16 DP - 2023 Sep-Dec TI - Promising translatable pharmacological interventions for body weight management in individuals with severe mental illness - a narrative review. PG - 1823-1832 LID - 10.1080/14656566.2023.2254698 [doi] AB - INTRODUCTION: Psychotropic medications, especially antipsychotics, have been consistently shown to cause weight gain in individuals with severe mental illness (SMI), a population inherently challenged by poor physical health. Consequently, compared to the general population, this contributes to an increased cardiometabolic burden, including the risk of type 2 diabetes, dyslipidemia, and hypertension. Furthermore, comorbid obesity leads to treatment nonadherence, decreased quality of life, and increased risk of relapse, posing a challenge in the management of mental health. To address this, emerging agents investigated in the general population with potential to mitigate weight gain were explored to assess translatability to the SMI population. AREAS COVERED: A literature search was conducted including agents approved for the management of obesity in the general population, along with upcoming agents under investigation in phase III trials with weight loss properties. EXPERT OPINION: Metformin and topiramate along with lifestyle interventions are commonly prescribed for weight gain in individuals with SMI; however, their weight loss potential is modest at best. This review identified tirzepatide and cagrilintide-semaglutide among others as promising agents for adjunctive pharmacological management of weight gain. FAU - De, Riddhita AU - De R AUID- ORCID: 0000-0002-8953-4716 AD - Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, Canada. FAU - Prasad, Femin AU - Prasad F AUID- ORCID: 0000-0002-5445-2489 AD - Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, Canada. FAU - Stogios, Nicolette AU - Stogios N AUID- ORCID: 0000-0001-9136-4923 AD - Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, Canada. FAU - Burin, Luisa AU - Burin L AUID- ORCID: 0000-0001-7083-6020 AD - Center of Clinical Research and Center of Experimental Research, Hospital de Clinicas de Porto Alegre (HCPA), Porto Alegre, Brazil. AD - Post-Graduation Program in Psychiatry and Behavioral Sciences, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. AD - I-QOL Innovations and Interventions for Quality-of-Life research group, Porto Alegre, Brazil. FAU - Ebdrup, Bjorn H AU - Ebdrup BH AUID- ORCID: 0000-0002-2590-5055 AD - Center for Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Knop, Filip K AU - Knop FK AUID- ORCID: 0000-0002-2495-5034 AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Hahn, Margaret K AU - Hahn MK AUID- ORCID: 0000-0001-8884-9946 AD - Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, Canada. AD - Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. AD - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada. FAU - Agarwal, Sri Mahavir AU - Agarwal SM AUID- ORCID: 0000-0002-2705-5146 AD - Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada. AD - Institute of Medical Science, University of Toronto, Toronto, ON, Canada. AD - Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. AD - Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada. LA - eng PT - Journal Article PT - Review DEP - 20230911 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 0 (Antipsychotic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Quality of Life MH - *Mental Disorders/drug therapy/psychology MH - Obesity/drug therapy/epidemiology MH - Weight Gain MH - *Antipsychotic Agents/therapeutic use MH - Weight Loss OTO - NOTNLM OT - Weight gain OT - diabetes mellitus OT - obesity OT - schizophrenia OT - severe mental illness EDAT- 2023/09/01 06:43 MHDA- 2023/09/01 06:44 CRDT- 2023/09/01 00:43 PHST- 2023/09/01 06:44 [medline] PHST- 2023/09/01 06:43 [pubmed] PHST- 2023/09/01 00:43 [entrez] AID - 10.1080/14656566.2023.2254698 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2023 Sep-Dec;24(16):1823-1832. doi: 10.1080/14656566.2023.2254698. Epub 2023 Sep 11. PMID- 37648659 OWN - NLM STAT- MEDLINE DCOM- 20231201 LR - 20240103 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 30 IP - 17 DP - 2023 Nov 30 TI - Down the rabbit hole: reviewing the evidence for primary prevention of cardiovascular disease in people with obesity. PG - 1895-1905 LID - 10.1093/eurjpc/zwad280 [doi] AB - Obesity is a prevalent chronic disorder and a well-known risk factor for cardiovascular disease. However, the evidence of treating obesity for primary prevention of major cardiovascular events is still scarce and controversial. In this review, we provided a comprehensive description of the current evidence in treating obesity regarding cardiovascular protection. Bariatric surgery appears to be the most robust method to reduce events in people without established cardiovascular disease. High compliance to lifestyle interventions can further reduce cardiovascular risk. Concerning pharmacological therapies, a post hoc analysis from SUSTAIN-6 and a meta-analysis from STEP trials suggest that semaglutide, a GLP-1 receptor agonist, could reduce cardiovascular events in people without established cardiovascular disease. The first study addressed specifically a high-risk population with diabetes and, the second, low- or intermediary-risk individuals without diabetes. Tirzepatide, a novel dual GIP/GLP-1 agonist, although not yet tested in specific cardiovascular outcomes trials, could be an alternative since it induces loss in weight similar to the achieved by bariatric surgery. Therefore, extrapolated data in distinct baseline cardiovascular risk populations suggest that these two drugs could be used in primary prevention with the aim of preventing cardiovascular events, but the grade of this evidence is still low. Specifically designed studies are needed to address this specific topic. CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Stumpf, Matheo A M AU - Stumpf MAM AUID- ORCID: 0000-0002-6465-0972 AD - Obesity Unit, Division of Endocrinology and Metabolism, University of Sao Paulo Medical School Hospital, Street Dr. Ovidio Pires de Campos, 05403-010, Sao Paulo, Brazil. FAU - Cercato, Cintia AU - Cercato C AUID- ORCID: 0000-0002-6181-4951 AD - Obesity Unit, Division of Endocrinology and Metabolism, University of Sao Paulo Medical School Hospital, Street Dr. Ovidio Pires de Campos, 05403-010, Sao Paulo, Brazil. FAU - de Melo, Maria E AU - de Melo ME AUID- ORCID: 0000-0002-1216-7532 AD - Obesity Unit, Division of Endocrinology and Metabolism, University of Sao Paulo Medical School Hospital, Street Dr. Ovidio Pires de Campos, 05403-010, Sao Paulo, Brazil. FAU - Santos, Raul D AU - Santos RD AUID- ORCID: 0000-0002-9860-6582 AD - Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital, Sao Paulo, Brazil. AD - Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo, Brazil. FAU - Mancini, Marcio C AU - Mancini MC AUID- ORCID: 0000-0003-1278-0406 AD - Obesity Unit, Division of Endocrinology and Metabolism, University of Sao Paulo Medical School Hospital, Street Dr. Ovidio Pires de Campos, 05403-010, Sao Paulo, Brazil. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - Obesity/complications/epidemiology MH - Glucagon-Like Peptide 1 MH - *Diabetes Mellitus MH - Primary Prevention MH - *Diabetes Mellitus, Type 2 MH - Hypoglycemic Agents OTO - NOTNLM OT - Bariatric surgery OT - Cardiovascular disease OT - GLP-1 receptor agonist OT - Obesity OT - Tirzepatide COIS- Conflict of interest: C.C. has served as advisory board for Novo Nordisk and reports having received research grants from Eli-Lilly, Novo Nordisk, Merck, Boehringer Ingelheim, Eurofarma, Fractyl, and EMS. R.D.S. has received honoraria related to consulting, speaker activities, or research from Amgen, Amryt, Astra Zeneca, Biolab, Eli-Lilly, Kowa, Esperion, Pfizer, Novartis, Novo Nordisk, PTC, GETZ Pharma, and Sanofi/Regeneron. M.C.M. has received consulting fees, honoraria, and support for meetings or travel from Merck, Lilly, Novo Nordisk, Takeda, EMS, Eurofarma, and Ache. EDAT- 2023/08/31 00:41 MHDA- 2023/12/01 06:44 CRDT- 2023/08/30 22:23 PHST- 2023/05/14 00:00 [received] PHST- 2023/08/22 00:00 [revised] PHST- 2023/08/25 00:00 [accepted] PHST- 2023/12/01 06:44 [medline] PHST- 2023/08/31 00:41 [pubmed] PHST- 2023/08/30 22:23 [entrez] AID - 7256202 [pii] AID - 10.1093/eurjpc/zwad280 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2023 Nov 30;30(17):1895-1905. doi: 10.1093/eurjpc/zwad280. PMID- 37646192 OWN - NLM STAT- MEDLINE DCOM- 20231113 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 12 DP - 2023 Dec TI - Comparison of clinical efficacy and safety of weekly glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in Japanese patients with type 2 diabetes: Randomized, parallel-group, multicentre, open-label trial (COMING study). PG - 3632-3647 LID - 10.1111/dom.15258 [doi] AB - AIM: To compare the clinical usefulness of once-weekly glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide at the doses approved for use in Japanese patients with type 2 diabetes. METHODS: In total, 120 patients with glycated haemoglobin (HbA1c) >/=7% were randomly assigned to dulaglutide (n = 59) or semaglutide group (n = 61), and 107 participants (dulaglutide/semaglutide = 53/54) completed the 24-week trial. The primary endpoint was the difference of HbA1c level between the two groups at 24 weeks. RESULTS: HbA1c level at 24 weeks was significantly lower in the semaglutide group (7.9 +/- 0.5%-6.7 +/- 0.5%) compared with the dulaglutide group (8.1 +/- 0.6%-7.4 +/- 0.8%) (p < .0001). Reduction in body mass index and visceral fat area were also more significant in the semaglutide group (p < .05, respectively). The achievement rate of HbA1c <7% was higher in the semaglutide group (p < .0001). The parameters such as low-density lipoprotein cholesterol, alanine aminotransferase and gamma-glutamyl transpeptidase were decreased in the semaglutide group. Surprisingly, only semaglutide group significantly improved the apolipoprotein B/A1 ratio, which is considered a useful myocardial infarction risk index. Using computed tomography, the liver to spleen ratio was significantly elevated only in the semaglutide group. In contrast, gastrointestinal symptoms were observed in 13.2% of dulaglutide and 46.3% of semaglutide group (p < .01). The Diabetes Treatment-Related Quality of Life scores related to pain and gastrointestinal symptoms were also superior in the dulaglutide group. CONCLUSIONS: This prospective trial showed that semaglutide has more pronounced glucose- and body mass index-lowering effects and reduces liver fat percentage and visceral fat area and that dulaglutide has less gastrointestinal symptoms and superior Diabetes Treatment-Related Quality of Life scores related to pain and gastrointestinal symptoms. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Kimura, Tomohiko AU - Kimura T AUID- ORCID: 0000-0003-3986-9494 AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. AD - Department of Internal Medicine, Osugki Hospital, Takahashi, Japan. FAU - Katakura, Yukino AU - Katakura Y AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Shimoda, Masashi AU - Shimoda M AUID- ORCID: 0000-0002-4223-9613 AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Kawasaki, Fumiko AU - Kawasaki F AD - Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan. FAU - Yamabe, Mizuho AU - Yamabe M AD - Department of Internal Medicine, Murakami Memorial Hospital, Onomichi, Japan. FAU - Tatsumi, Fuminori AU - Tatsumi F AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Matsuki, Michihiro AU - Matsuki M AD - Department of Internal Medicine, Kurashiki Sweet Hospital, Kurashiki, Japan. FAU - Iwamoto, Yuichiro AU - Iwamoto Y AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Anno, Takatoshi AU - Anno T AD - Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan. FAU - Fushimi, Yoshiro AU - Fushimi Y AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Kamei, Shinji AU - Kamei S AD - Department of Diabetic Medicine, Kurashiki Central Hospital, Kurashiki, Japan. FAU - Kimura, Yukiko AU - Kimura Y AD - Department of Internal Medicine, Osugki Hospital, Takahashi, Japan. AD - Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan. FAU - Nakanishi, Shuhei AU - Nakanishi S AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Mune, Tomoatsu AU - Mune T AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Kaku, Kohei AU - Kaku K AUID- ORCID: 0000-0003-1574-0565 AD - Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan. FAU - Kaneto, Hideaki AU - Kaneto H AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. CN - COMING study Group LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230830 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/chemically induced MH - East Asian People MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Glycated Hemoglobin MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Pain/chemically induced MH - Prospective Studies MH - Quality of Life MH - Recombinant Fusion Proteins/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - BMI OT - HbA1c OT - L/S ratio OT - dulaglutide OT - once-weekly GLP-1 receptor agonist OT - semaglutide EDAT- 2023/08/30 06:48 MHDA- 2023/11/13 06:42 CRDT- 2023/08/30 05:29 PHST- 2023/08/04 00:00 [revised] PHST- 2023/06/30 00:00 [received] PHST- 2023/08/13 00:00 [accepted] PHST- 2023/11/13 06:42 [medline] PHST- 2023/08/30 06:48 [pubmed] PHST- 2023/08/30 05:29 [entrez] AID - 10.1111/dom.15258 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Dec;25(12):3632-3647. doi: 10.1111/dom.15258. Epub 2023 Aug 30. PMID- 37640171 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20260127 IS - 1535-6280 (Electronic) IS - 0146-2806 (Linking) VI - 49 IP - 1 Pt A DP - 2024 Jan TI - Obesity, Cardiovascular Disease, and the Promising Role of Semaglutide: Insights from the SELECT Trial. PG - 102060 LID - S0146-2806(23)00477-2 [pii] LID - 10.1016/j.cpcardiol.2023.102060 [doi] AB - Cardiovascular disease (CVD) is a leading global cause of death, with preventable risk factors like obesity contributing most to it. Obesity's association with CVD originate from factors like inflammation, insulin resistance, and altered lipid profiles. Obesity also raises the risk of atrial fibrillation (AF) and sudden cardiac death. Semaglutide, a GLP-1 receptor agonist, initially used for weight loss and diabetes, emerged as a breakthrough in CVD prevention. The SELECT trial assessed semaglutide's impact on major adverse cardiovascular events (MACE). In this double-blind, placebo-controlled trial, 17,604 adults with CVD and obesity were given a weekly 2.4 mg dose of semaglutide or placebo. The trial observed a significant 20% reduction in MACE risk for those receiving semaglutide, demonstrating its potential in obesity-associated CVD prevention. This shift marks a transformative approach to obesity management and CVD prevention. However, further research is needed to fully comprehend semaglutide's cardiovascular benefits and potential risks. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Irfan, Hamza AU - Irfan H AD - Department of Cardiology, Shaikh Khalifa Bin Zayed Al Nahyan Medical and Dental College Lahore, Lahore, Punjab, Pakistan. Electronic address: Hamy.khr.hi@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20230826 PL - Netherlands TA - Curr Probl Cardiol JT - Current problems in cardiology JID - 7701802 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Cardiovascular Diseases/etiology/prevention & control MH - Obesity/complications/epidemiology MH - Randomized Controlled Trials as Topic MH - Semaglutide COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/08/29 00:41 MHDA- 2023/12/17 09:46 CRDT- 2023/08/28 19:22 PHST- 2023/08/16 00:00 [received] PHST- 2023/08/23 00:00 [accepted] PHST- 2023/12/17 09:46 [medline] PHST- 2023/08/29 00:41 [pubmed] PHST- 2023/08/28 19:22 [entrez] AID - S0146-2806(23)00477-2 [pii] AID - 10.1016/j.cpcardiol.2023.102060 [doi] PST - ppublish SO - Curr Probl Cardiol. 2024 Jan;49(1 Pt A):102060. doi: 10.1016/j.cpcardiol.2023.102060. Epub 2023 Aug 26. PMID- 37639288 OWN - NLM STAT- MEDLINE DCOM- 20240122 LR - 20260415 IS - 1527-6473 (Electronic) IS - 1527-6465 (Linking) VI - 30 IP - 2 DP - 2024 Feb 1 TI - Semaglutide is effective in achieving weight loss in liver transplant recipients. PG - 223-225 LID - 10.1097/LVT.0000000000000247 [doi] FAU - Chow, Kenneth W AU - Chow KW AUID- ORCID: 0000-0003-2482-7734 AD - Department of Medicine, Harbor-UCLA Medical Center, Torrance, California, USA. FAU - Ibrahim, Brittney AU - Ibrahim B AUID- ORCID: 0009-0002-4345-5729 AD - Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA. AD - Department of Surgery, University of California at Los Angeles, Los Angeles, California, USA. FAU - Rahal, Kabir AU - Rahal K AD - Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA. FAU - Hsu, Ryan H AU - Hsu RH AUID- ORCID: 0000-0001-8221-224 AD - Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, California, USA. FAU - Tan, Teresa AU - Tan T AUID- ORCID: 0000-0002-8174-986 AD - Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA. FAU - Meneses, Katherine AU - Meneses K AUID- ORCID: 0000-0003-0680-562 AD - Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA. FAU - Saab, Sammy AU - Saab S AUID- ORCID: 0000-0003-3346-9297 AD - Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA. AD - Department of Surgery, University of California at Los Angeles, Los Angeles, California, USA. LA - eng PT - Journal Article DEP - 20230829 PL - United States TA - Liver Transpl JT - Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society JID - 100909185 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Liver Transpl. 2024 Aug 1;30(8):E36-E37. doi: 10.1097/LVT.0000000000000364. PMID: 38497771 MH - Humans MH - *Liver Transplantation/adverse effects MH - Weight Loss MH - Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2 MH - Hypoglycemic Agents MH - Semaglutide EDAT- 2023/08/28 12:42 MHDA- 2024/01/22 06:42 CRDT- 2023/08/28 11:43 PHST- 2023/06/12 00:00 [received] PHST- 2023/08/21 00:00 [accepted] PHST- 2024/01/22 06:42 [medline] PHST- 2023/08/28 12:42 [pubmed] PHST- 2023/08/28 11:43 [entrez] AID - 01445473-202402000-00016 [pii] AID - 10.1097/LVT.0000000000000247 [doi] PST - ppublish SO - Liver Transpl. 2024 Feb 1;30(2):223-225. doi: 10.1097/LVT.0000000000000247. Epub 2023 Aug 29. PMID- 37620807 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 22 IP - 1 DP - 2023 Aug 24 TI - Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis. PG - 220 LID - 10.1186/s12933-023-01949-7 [doi] LID - 220 AB - BACKGROUND: Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk. METHODS: Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] < 45 and >/= 45-<60 versus >/= 60 mL/min/1.73 m(2)) or damage (urine albumin:creatinine ratio [UACR] >/= 30- 300 versus < 30 mg/g). Relative risk of first MACE by baseline kidney parameters was evaluated using a Cox proportional hazards model. The same model, adjusted with inverse probability weighting, and a quadratic spline regression were applied to evaluate the effect of semaglutide on risk and event rate of first MACE across subgroups. The semaglutide effects on glycated haemoglobin (HbA(1c)), body weight (BW) and serious adverse events (SAEs) across subgroups were also evaluated. RESULTS: Independently of treatment, participants with reduced kidney function (eGFR >/= 45-<60 and < 45 mL/min/1.73 m(2): hazard ratio [95% confidence interval]; 1.36 [1.04;1.76] and 1.52 [1.15;1.99]) and increased albuminuria (UACR >/= 30- 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [p(INT)] > 0.05). Semaglutide reduced HbA(1c) regardless of baseline eGFR and UACR (p(INT)>0.05); reductions in BW were affected by baseline eGFR (p(INT)<0.001) but not UACR (p(INT)>0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup. CONCLUSIONS: MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage. TRIAL REGISTRATIONS: NCT01720446; NCT02692716. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center, Copenhagen, Denmark. peter.rossing@regionh.dk. FAU - Bain, Stephen C AU - Bain SC AD - Swansea University Medical School, Swansea, UK. FAU - Bosch-Traberg, Heidrun AU - Bosch-Traberg H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sokareva, Ekaterina AU - Sokareva E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Heerspink, Hiddo J L AU - Heerspink HJL AD - University of Groningen, Groningen, the Netherlands. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mellbin, Linda G AU - Mellbin LG AD - Karolinska Institutet, Solna, Sweden. LA - eng SI - ClinicalTrials.gov/NCT01720446 SI - ClinicalTrials.gov/NCT02692716 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230824 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Cardiovascular Diseases/diagnosis/prevention & control MH - *Diabetes Mellitus, Type 2/complications/diagnosis/drug therapy MH - *Cardiovascular System MH - Kidney MH - *Renal Insufficiency MH - Semaglutide PMC - PMC10463803 OTO - NOTNLM OT - Cardiovascular disease OT - Estimated glomerular filtration rate OT - Glucagon-like peptide-1 receptor agonist OT - Kidney disease OT - Major cardiovascular events OT - NCT01720446 OT - NCT02692716 OT - Semaglutide OT - Type 2 diabetes OT - Urine albumin:creatinine ratio COIS- PR received grants from AstraZeneca, Bayer, Novo Nordisk A/S, as well as consulting fees from AstraZeneca, Astellas, Bayer, Boehringer Ingelheim, Gilead, Merck, Mundipharma, Novo Nordisk A/S and Sanofi. SCB received grants, teaching sponsorship and honoraria from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novo Nordisk A/S, Pfizer, Sanofi and Takeda. HBT, ES and SR are employees of Novo Nordisk A/S, Denmark; HBT and SR also own stocks or stock options in Novo Nordisk A/S. HJLH received grants from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen and Novo Nordisk A/S; consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Behring, Dimerix, Eli Lilly, Fresenius, Gilead, Janssen, Novo Nordisk A/S, Novartis and Travere Therapeutics; honoraria from AstraZeneca and Novo Nordisk A/S; travel and/or other support for attending meetings from AstraZeneca and Eli Lilly. LGM received grants, honoraria and consulting fees for advisory boards from Novo Nordisk A/S. EDAT- 2023/08/25 00:42 MHDA- 2023/08/28 06:43 PMCR- 2023/08/24 CRDT- 2023/08/24 23:47 PHST- 2023/05/15 00:00 [received] PHST- 2023/08/02 00:00 [accepted] PHST- 2023/08/28 06:43 [medline] PHST- 2023/08/25 00:42 [pubmed] PHST- 2023/08/24 23:47 [entrez] PHST- 2023/08/24 00:00 [pmc-release] AID - 10.1186/s12933-023-01949-7 [pii] AID - 1949 [pii] AID - 10.1186/s12933-023-01949-7 [doi] PST - epublish SO - Cardiovasc Diabetol. 2023 Aug 24;22(1):220. doi: 10.1186/s12933-023-01949-7. PMID- 37610193 OWN - NLM STAT- MEDLINE DCOM- 20230824 LR - 20230824 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 19 IP - 838 DP - 2023 Aug 23 TI - [Effects of antidiabetic medications on metabolic-associated fatty liver disease]. PG - 1498-1502 LID - 10.53738/REVMED.2023.19.838.1498 [doi] AB - Metabolic-Associated Fatty Liver Disease (MAFLD) is a prevalent metabolic complication among patients with obesity and type 2 diabetes, associated with bad prognosis. Classical antidiabetics have little effects on this complication, except pioglitazone that exerts a positive impact but with uncertain safety. Gliptins are almost neutral, whereas glucagon-like peptide-1 receptor agonists showed benefits, the most potent ones being those associated with a greater weight loss such as liraglutide or semaglutide. Gliflozins also reduce hepatic fat content and liver enzymes used as biomarkers of steatosis. However, histological data remain scarce, especially those focusing on inflammation and fibrosis, and direct comparative data between available therapies are still lacking. FAU - Scheen, Andre J AU - Scheen AJ AUID- ORCID: 0000-0001-9743-4371 AD - Professeur honoraire, Service de diabetologie, nutrition et maladies metaboliques, Departement de medecine, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. AD - Unite de pharmacologie clinique, Departement de medecine, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. LA - fre PT - English Abstract PT - Journal Article TT - Effets des medicaments antidiabetiques sur la steatopathie metabolique (MAFLD). PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Hypoglycemic Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - *Dipeptidyl-Peptidase IV Inhibitors MH - Liraglutide/therapeutic use COIS- L'auteur n'a declare aucun conflit d'interets en relation avec cet article. EDAT- 2023/08/23 12:42 MHDA- 2023/08/24 06:42 CRDT- 2023/08/23 08:53 PHST- 2023/08/24 06:42 [medline] PHST- 2023/08/23 12:42 [pubmed] PHST- 2023/08/23 08:53 [entrez] AID - RMS0838-004 [pii] AID - 10.53738/REVMED.2023.19.838.1498 [doi] PST - ppublish SO - Rev Med Suisse. 2023 Aug 23;19(838):1498-1502. doi: 10.53738/REVMED.2023.19.838.1498. PMID- 37605636 OWN - NLM STAT- MEDLINE DCOM- 20230823 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 31 IP - 9 DP - 2023 Sep TI - Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity. PG - 2249-2259 LID - 10.1002/oby.23842 [doi] AB - OBJECTIVE: In the Semaglutide Treatment Effect in People with obesity (STEP) trials, once-weekly subcutaneous semaglutide 2.4 mg plus lifestyle intervention reduced body weight and improved cardiometabolic parameters in adults with obesity (or overweight with weight-related comorbidities). Effects on the risk of developing type 2 diabetes (T2D) require investigation. METHODS: STEP 1 (68 weeks) and 5 (104 weeks) randomized participants to semaglutide 2.4 mg or placebo. STEP 4 included a 20-week semaglutide run-in followed by randomization to 48 weeks of continued semaglutide or withdrawal (placebo). Ten-year T2D risk scores were calculated post hoc using Cardiometabolic Disease Staging. RESULTS: In STEP 1 (N = 1583), relative risk score reductions were greater with semaglutide versus placebo (semaglutide: -61.1%; placebo: -12.9%; p < 0.0001). These reductions were maintained to week 104 in STEP 5 (N = 295; semaglutide: -60.0%; placebo: 3.5%; p < 0.0001). Risk scores during the STEP 4 run-in period (N = 776) were reduced from 20.6% to 11.1% and further to 7.7% at week 68 with continued semaglutide, increasing to 15.4% with withdrawal (relative risk score change: semaglutide: -32.1%; placebo: +40.6%; p < 0.0001). Risk score reductions mirrored weight loss. CONCLUSIONS: Cardiometabolic Disease Staging risk assessment suggests that once-weekly semaglutide 2.4 mg may substantially lower 10-year T2D risk in people with overweight or obesity. CI - (c) 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Wilkinson, Lua AU - Wilkinson L AUID- ORCID: 0000-0001-6665-9463 AD - Medical Affairs, Novo Nordisk Inc., Plainsboro, New Jersey, USA. FAU - Holst-Hansen, Thomas AU - Holst-Hansen T AD - Medical Affairs, Novo Nordisk A/S, Soborg, Denmark. FAU - Laursen, Peter N AU - Laursen PN AD - Medical Affairs, Novo Nordisk A/S, Soborg, Denmark. FAU - Rinnov, Anders R AU - Rinnov AR AD - Medical Affairs, Novo Nordisk A/S, Soborg, Denmark. FAU - Batterham, Rachel L AU - Batterham RL AUID- ORCID: 0000-0002-5477-8585 AD - University College London Centre for Obesity Research, Division of Medicine, University College London, London, UK. AD - National Institute of Health Research, University College London Hospital Biomedical Research Centre, London, UK. AD - Centre for Weight Management and Metabolic Surgery, University College London Hospital, London, UK. FAU - Garvey, W Timothy AU - Garvey WT AUID- ORCID: 0000-0003-0822-0860 AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA. LA - eng SI - ClinicalTrials.gov/NCT03548987 SI - ClinicalTrials.gov/NCT03693430 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - *Cardiovascular Diseases MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/complications/drug therapy MH - Overweight/complications/drug therapy MH - Semaglutide EDAT- 2023/08/22 06:42 MHDA- 2023/08/23 06:42 CRDT- 2023/08/22 03:36 PHST- 2023/05/25 00:00 [revised] PHST- 2023/03/30 00:00 [received] PHST- 2023/05/31 00:00 [accepted] PHST- 2023/08/23 06:42 [medline] PHST- 2023/08/22 06:42 [pubmed] PHST- 2023/08/22 03:36 [entrez] AID - 10.1002/oby.23842 [doi] PST - ppublish SO - Obesity (Silver Spring). 2023 Sep;31(9):2249-2259. doi: 10.1002/oby.23842. PMID- 37602701 OWN - NLM STAT- MEDLINE DCOM- 20240119 LR - 20260611 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 109 IP - 2 DP - 2024 Jan 18 TI - Tirzepatide in Hispanic/Latino Patients With Type 2 Diabetes: A Subgroup Analysis of the SURPASS Program. PG - 557-568 LID - 10.1210/clinem/dgad495 [doi] AB - CONTEXT: Efficacy and safety of tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, have been studied in patients with type 2 diabetes in the global phase 3 SURPASS program. OBJECTIVE: This work aimed to assess the efficacy and safety of tirzepatide in Hispanic/Latino and non-Hispanic/Latino patients in SURPASS-1 to -4 clinical trials. METHODS: A total of 5679 patients were included, 2895 of self-reported Hispanic/Latino ethnicity, in this exploratory analysis of SURPASS-1 to -4 trial data. Interventions included tirzepatide 5, 10, or 15 mg, placebo, or active comparator (semaglutide 1 mg, insulin degludec, and insulin glargine). Change in glycated hemoglobin A1c (HbA1c) and body weight from baseline to week 40 (SURPASS-1 and -2) and to week 52 (SURPASS-3 and -4), and other efficacy and safety outcomes were evaluated within Hispanic/Latino and non-Hispanic/Latino subgroups. RESULTS: Among Hispanic/Latino and non-Hispanic/Latino patients treated with tirzepatide, respectively, HbA1c decreased significantly from baseline, ranging from 1.9% to 2.7% and 1.7% to 2.5%, and body weight decreased significantly from baseline, ranging from 5.3 kg to 12.4 and 6.5 kg to 17.1 kg (both P < .05) vs comparators across all trials. Subgroup trends were consistent with the overall trial populations. Treatment-emergent adverse events were reported in similar proportions across the subgroups and were primarily gastrointestinal disorders. The incidence of hypoglycemia was low. CONCLUSION: Tirzepatide significatively reduced HbA1c and body weight in Hispanic/Latino and non-Hispanic/Latino patients. Tirzepatide was generally well tolerated in both subgroups. Efficacy and safety trends were comparable between subgroups and within the overall trial populations. CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Frias, Juan Pablo AU - Frias JP AD - Velocity Clinical Research, Los Angeles, CA 90057, USA. FAU - Galindo, Rodolfo J AU - Galindo RJ AD - Division of Endocrinology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. FAU - Wang, Hui AU - Wang H AD - TechData Service, King of Prussia, PA 19406, USA. FAU - Malik, Raleigh E AU - Malik RE AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Chivukula, K Karthik AU - Chivukula KK AD - Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. FAU - Maldonado, Juan M AU - Maldonado JM AUID- ORCID: 0000-0002-1370-327X AD - Lilly Research Laboratories, Eli Lilly and Company, San Juan 00918, Puerto Rico. LA - eng GR - Eli Lilly and Company/ GR - P30 DK111024/DK/NIDDK NIH HHS/United States GR - K23 DK123384/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Body Weight MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptide-2 Receptor MH - Glycated Hemoglobin MH - Hispanic or Latino MH - *Hypoglycemic Agents/therapeutic use MH - *Incretins/therapeutic use MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10795909 OTO - NOTNLM OT - GIP and GLP-1 receptor agonist OT - Hispanic/Latino OT - glycemic control OT - incretin therapy OT - tirzepatide OT - type 2 diabetes EDAT- 2023/08/21 12:42 MHDA- 2024/01/19 06:42 PMCR- 2023/08/21 CRDT- 2023/08/21 08:23 PHST- 2023/06/28 00:00 [received] PHST- 2024/01/19 06:42 [medline] PHST- 2023/08/21 12:42 [pubmed] PHST- 2023/08/21 08:23 [entrez] PHST- 2023/08/21 00:00 [pmc-release] AID - 7246603 [pii] AID - dgad495 [pii] AID - 10.1210/clinem/dgad495 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2024 Jan 18;109(2):557-568. doi: 10.1210/clinem/dgad495. PMID- 37591343 OWN - NLM STAT- MEDLINE DCOM- 20260310 LR - 20260310 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 203 DP - 2023 Sep TI - The role of weight control in the management of type 2 diabetes mellitus: Perspectives on semaglutide. PG - 110881 LID - S0168-8227(23)00644-7 [pii] LID - 10.1016/j.diabres.2023.110881 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used to address multiple aspects of type 2 diabetes mellitus (T2DM) management, including glycaemic control, weight loss, and cardiovascular risk reduction. Semaglutide, a well-established GLP-1 RA approved for T2DM treatment and weight management, demonstrates marked efficacy in achieving these clinically important goals. The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus report emphasizes the importance of a holistic approach to T2DM treatment, with weight control as a key component for improving patient outcomes. Notably, semaglutide is mentioned in the consensus report as having 'very high' efficacy for both glucose lowering and weight loss in T2DM treatment. Nevertheless, as has been observed with other weight-lowering drugs, weight loss observed with semaglutide appears less profound in individuals with T2DM than in those with obesity without T2DM, a phenomenon requiring further investigation. The semaglutide safety and tolerability profiles are well established, and it is approved in some countries to reduce cardiovascular risk in certain populations with T2DM. Thus, semaglutide offers a well-established therapeutic option that aligns well with guideline recommendations for T2DM management, emphasizing the high importance of weight control and amelioration of other cardiometabolic risk factors. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Kurtzhals, Peter AU - Kurtzhals P AD - Novo Nordisk A/S, Vandtaarnsvej 110-114 DK-2860, Soborg, Denmark. Electronic address: pkur@novonordisk.com. FAU - Flindt Kreiner, Frederik AU - Flindt Kreiner F AD - Novo Nordisk A/S, Vandtaarnsvej 110-114 DK-2860, Soborg, Denmark. Electronic address: frfk@novonordisk.com. FAU - Singh Bindra, Rubdeep AU - Singh Bindra R AD - Novo Nordisk A/S, Vandtaarnsvej 110-114 DK-2860, Soborg, Denmark. Electronic address: rsib@novonordisk.com. LA - eng PT - Journal Article PT - Review DEP - 20230815 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptides/therapeutic use MH - *Hypoglycemic Agents/therapeutic use MH - Weight Loss/drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - *Obesity/drug therapy/complications OTO - NOTNLM OT - Cardiovascular risk OT - GLP-1 RA OT - Kidney protection OT - Semaglutide OT - Type 2 diabetes mellitus OT - Weight control COIS- Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Kurtzhals reports a relationship with Novo Nordisk AS that includes: employment and equity or stocks. Frederik Flindt Kreiner reports a relationship with Novo Nordisk AS that includes: employment and equity or stocks. Rubdeep Singh Bindra reports a relationship with Novo Nordisk AS that includes: employment and equity or stocks. EDAT- 2023/08/18 00:42 MHDA- 2026/03/11 01:11 CRDT- 2023/08/17 19:18 PHST- 2023/06/30 00:00 [received] PHST- 2023/08/01 00:00 [revised] PHST- 2023/08/13 00:00 [accepted] PHST- 2026/03/11 01:11 [medline] PHST- 2023/08/18 00:42 [pubmed] PHST- 2023/08/17 19:18 [entrez] AID - S0168-8227(23)00644-7 [pii] AID - 10.1016/j.diabres.2023.110881 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2023 Sep;203:110881. doi: 10.1016/j.diabres.2023.110881. Epub 2023 Aug 15. PMID- 37580307 OWN - NLM STAT- MEDLINE DCOM- 20231011 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 11 DP - 2023 Nov TI - Development of a novel Fc fusion protein dual glucagon-like peptide-1 and gastric inhibitory polypeptide receptor agonists. PG - 3356-3365 LID - 10.1111/dom.15235 [doi] AB - AIM: To develop and investigate an imbalanced dual gastric inhibitory polypeptide receptor (GIPR)/glucagon-like peptide-1 receptor (GLP-1 R) agonist with Fc fusion protein structure. METHODS: We designed and constructed an Fc fusion protein that is a dual agonist (HEC-CG115) with an empirically optimized potency ratio for GLP-1R and GIPR. The long-term effects of HEC-CG115 on body weight and glycaemic control were evaluated in diet-induced obese mice and diabetic db/db mice. Repeat dose toxicity assays were performed to investigate the safety profile of HEC-CG115 in Sprague-Dawley rats. RESULTS: HEC-CG115 displayed high potency for GIPR and relatively low potency for GLP-1R, and we labelled it 'imbalanced'. In animal models, HEC-CG115 (3 nmol/kg) led to more weight loss than semaglutide at a higher dose (10 nmol/kg) in diet-induced obese model mice. HEC-CG115 (one dose every 3 days) reduced fasting blood glucose and glycated haemoglobin levels similar to those after semaglutide (once daily) at the same dose. In a 4-week subcutaneous toxicity study conducted to assess the biosafety of HEC-CG115, the no observed adverse effect level was determined to be 3 mg/kg. CONCLUSION: HEC-CG115 is a novel Fc fusion protein with imbalanced dual agonism that shows superior weight loss, glycaemic control and metabolic improvement in animal models, and has an optimal safety profile according to a repeat-dose toxicity study. Therefore, the use of HEC-CG115 appears to be safe and effective for the treatment of obesity and type 2 diabetes. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Jiang, Peng AU - Jiang P AD - Dongguan HEC Biopharmaceutical R&D Co., Ltd., Dongguan, China. FAU - Sun, Ningyuan AU - Sun N AD - Sunshine Lake Pharma Co., Ltd., Dongguan, China. FAU - Yang, Wen AU - Yang W AD - Sunshine Lake Pharma Co., Ltd., Dongguan, China. FAU - Xiao, Lin AU - Xiao L AD - Dongguan HEC Biopharmaceutical R&D Co., Ltd., Dongguan, China. FAU - Zhou, Linjun AU - Zhou L AD - Dongguan HEC Biopharmaceutical R&D Co., Ltd., Dongguan, China. FAU - Gu, Baohua AU - Gu B AD - Sunshine Lake Pharma Co., Ltd., Dongguan, China. FAU - Li, Yong AU - Li Y AD - Sunshine Lake Pharma Co., Ltd., Dongguan, China. FAU - Li, Lijia AU - Li L AD - Dongguan HEC Biopharmaceutical R&D Co., Ltd., Dongguan, China. FAU - Li, Jing AU - Li J AD - Sunshine Lake Pharma Co., Ltd., Dongguan, China. FAU - Li, Xiaoping AU - Li X AD - Dongguan HEC Biopharmaceutical R&D Co., Ltd., Dongguan, China. FAU - Li, Wenjia AU - Li W AD - Dongguan HEC Biopharmaceutical R&D Co., Ltd., Dongguan, China. FAU - Guo, Linfeng AU - Guo L AUID- ORCID: 0009-0005-4487-1224 AD - Dongguan HEC Biopharmaceutical R&D Co., Ltd., Dongguan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230814 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Receptors, G-Protein-Coupled) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - 0 (Receptors, Gastrointestinal Hormone) SB - IM MH - Animals MH - Mice MH - Rats MH - *Diabetes Mellitus, Type 2 MH - Gastric Inhibitory Polypeptide/metabolism MH - *Glucagon-Like Peptide 1/therapeutic use MH - Rats, Sprague-Dawley MH - Receptors, G-Protein-Coupled MH - Weight Loss MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Receptors, Gastrointestinal Hormone OTO - NOTNLM OT - GIP OT - GLP-1 OT - glycaemic control OT - obesity therapy OT - weight control EDAT- 2023/08/15 00:42 MHDA- 2023/10/04 06:44 CRDT- 2023/08/14 22:52 PHST- 2023/07/08 00:00 [revised] PHST- 2023/03/30 00:00 [received] PHST- 2023/07/21 00:00 [accepted] PHST- 2023/10/04 06:44 [medline] PHST- 2023/08/15 00:42 [pubmed] PHST- 2023/08/14 22:52 [entrez] AID - 10.1111/dom.15235 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Nov;25(11):3356-3365. doi: 10.1111/dom.15235. Epub 2023 Aug 14. PMID- 37559355 OWN - NLM STAT- MEDLINE DCOM- 20240122 LR - 20240513 IS - 1099-1557 (Electronic) IS - 1053-8569 (Linking) VI - 33 IP - 1 DP - 2024 Jan TI - A case for screening real-world data for collateral drug benefits: Glucagon-like peptide 1 receptor agonists and bile acid diarrhea. PG - e5673 LID - 10.1002/pds.5673 [doi] AB - PURPOSE: Collateral drug benefits are hitherto unknown beneficial effects that might lead to repurposing of already marketed drugs. A randomized controlled trial has found liraglutide to be non-inferior to colesevelam in reducing bile acid diarrhea. We hypothesized that this collateral drug benefit of liraglutide could have been detected using observational data. METHODS: We performed a sequence symmetry analysis (SSA). In the SSA, we indexed individuals on the date of the first prescription of GLP1-RA and restricted the analysis to all individuals who had a first prescription of bile acid sequestrants between 365 days prior to until 365 days after the index date. Sequence ratios (SR), that is, the ratio between counts of persons initiating GLP1-RA first versus last, were calculated, and 95% confidence intervals were obtained. We adjusted for prescribing trends using null-effect SR adjustment. RESULTS: We included 158 individuals, with a median age of 58 years. The trend-adjusted SR was 0.96 (95% confidence interval 0.70-1.31). When stratifying on the type of GLP1-RA (liraglutide or semaglutide), we found results compatible with the previous trial (SR(liraglutide) 0.75, 0.51-1.10 and SR(semagltuide) 1.23, 0.80-1.89). Since BAS also can be used as a cholesterol lowering drug, we repeated the main analysis while excluded statin users, resulting in a stronger association (SR 0.56, 0.33-0.96). CONCLUSION: Using the SSA methodology, we obtained estimates of a collateral drug benefit that were compatible with trial results. These results support the use of epidemiological analyses of observational data as instrument for detecting collateral drug benefits. CI - (c) 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. FAU - Rahbek, Martin Torp AU - Rahbek MT AUID- ORCID: 0000-0001-7506-3426 AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark, Odense, Denmark. FAU - Lund, Lars Christian AU - Lund LC AUID- ORCID: 0000-0001-8651-6072 AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark, Odense, Denmark. FAU - Hallas, Jesper AU - Hallas J AUID- ORCID: 0000-0002-8097-8708 AD - Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark, Odense, Denmark. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20230809 PL - England TA - Pharmacoepidemiol Drug Saf JT - Pharmacoepidemiology and drug safety JID - 9208369 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Bile Acids and Salts) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Middle Aged MH - *Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2 MH - Liraglutide/adverse effects MH - Bile Acids and Salts MH - Glucagon-Like Peptide-1 Receptor MH - Diarrhea/drug therapy/epidemiology OTO - NOTNLM OT - bile acid associated diarrhea OT - collateral drug benefit OT - glucagon-like peptide 1 receptor agonists OT - sequence symmetry analysis EDAT- 2023/08/10 06:43 MHDA- 2024/01/22 06:42 CRDT- 2023/08/10 01:23 PHST- 2023/07/02 00:00 [revised] PHST- 2023/02/27 00:00 [received] PHST- 2023/07/17 00:00 [accepted] PHST- 2024/01/22 06:42 [medline] PHST- 2023/08/10 06:43 [pubmed] PHST- 2023/08/10 01:23 [entrez] AID - 10.1002/pds.5673 [doi] PST - ppublish SO - Pharmacoepidemiol Drug Saf. 2024 Jan;33(1):e5673. doi: 10.1002/pds.5673. Epub 2023 Aug 9. PMID- 37541662 OWN - NLM STAT- MEDLINE DCOM- 20231102 LR - 20260127 IS - 1098-8793 (Electronic) IS - 0736-6825 (Linking) VI - 39 IP - 6 DP - 2023 Dec TI - Implications of Ozempic and Other Semaglutide Medications for Facial Plastic Surgeons. PG - 719-721 LID - 10.1055/a-2148-6321 [doi] AB - Obesity is a growing global health concern, leading to various health issues, including diabetes. Semaglutide-based medications, such as Ozempic, Wegovy, and Rybelsus, have emerged as potential treatments. These medications, belonging to the glucagon-like peptide-1 (GLP-1) receptor agonist class, mimic the action of GLP-1, regulating appetite and promoting weight loss. Clinical trials have shown their effectiveness in reducing body weight and improving metabolic parameters. Ozempic, though Food and Drug Administration-approved for diabetes, is also used off-label for weight loss alone. Rapid weight and fat loss with Ozempic can lead to the characteristic "Ozempic face," where facial volume and fat are depleted, resulting in wrinkles and sagging skin. Providers prescribing Ozempic seldom counsel patients about the potential impact on the face. As a result, the plastic surgery community faces a challenge in managing facial changes associated with rapid weight loss. Dermal fillers, skin tightening techniques, and surgical interventions are useful for both restoration of facial volume and to manage excess skin. Discontinuation of Ozempic should be considered prior to general anesthesia due to gastrointestinal side effects including delayed gastric emptying. As the popularity of Ozempic grows, facial plastic surgeons must be aware of both the impact on facial appearance and perioperative considerations. CI - Thieme. All rights reserved. FAU - Humphrey, Clinton D AU - Humphrey CD AD - Department of Otolaryngology-Head and Neck Surgery, University of Kansas School of Medicine, Kansas City, Kansas. FAU - Lawrence, Anna C AU - Lawrence AC AUID- ORCID: 0000-0001-9942-445X AD - Department of Otolaryngology-Head and Neck Surgery, University of Kansas School of Medicine, Kansas City, Kansas. LA - eng PT - Journal Article DEP - 20230804 PL - United States TA - Facial Plast Surg JT - Facial plastic surgery : FPS JID - 8405303 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) CIN - Facial Plast Surg. 2023 Dec;39(6):e2-e3. doi: 10.1055/s-0044-1785450. PMID: 38604245 EIN - Facial Plast Surg. 2023 Dec;39(6):e1. doi: 10.1055/s-0044-1779676. PMID: 38604246 MH - United States MH - Humans MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - *Diabetes Mellitus, Type 2/chemically induced/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - Weight Loss MH - *Surgeons MH - Semaglutide COIS- None declared. EDAT- 2023/08/05 05:42 MHDA- 2023/11/02 12:42 CRDT- 2023/08/04 19:24 PHST- 2023/11/02 12:42 [medline] PHST- 2023/08/05 05:42 [pubmed] PHST- 2023/08/04 19:24 [entrez] AID - 10.1055/a-2148-6321 [doi] PST - ppublish SO - Facial Plast Surg. 2023 Dec;39(6):719-721. doi: 10.1055/a-2148-6321. Epub 2023 Aug 4. PMID- 37536423 OWN - NLM STAT- MEDLINE DCOM- 20230925 LR - 20231011 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 169 DP - 2023 Nov TI - Engineering a potent and long-acting GLP-1/Y(2) receptor dual agonist as a multi-agonist therapy for diabetes and obesity. PG - 171073 LID - S0196-9781(23)00136-5 [pii] LID - 10.1016/j.peptides.2023.171073 [doi] AB - Novel dual agonists for the glucagon-like peptide-1 (GLP-1) and Y(2) receptor hold the potential for enhanced efficacy over GLP-1 receptor (GLP-1R) agonists in treating obesity and diabetes. In this study, we aimed to improve the stability and increase the drug development success rate of our previously identified GLP-1/Y(2) receptor dual agonist, 6q. To achieve this, we first optimized the structure of the linker within 6q. Additionally, we explored various fatty acid albumin binders to further enhance the stability of 6q. These binders were mainly selected from approved or clinically developed GLP-1R agonists or GLP-1-based multi-agonists. Through this process, we were able to identify a lead peptide, xGLP/PYY-6, that exhibited comparable in vitro potency toward the GLP-1 and Y(2) receptors as 6q but with significantly improved stability compared to 6q. In Kunming and DIO mice, xGLP/PYY-6 showed a comparable hypoglycemic effect to semaglutide, and a significantly better effect on inhibiting food intake than semaglutide. In a chronic study in DIO mice, xGLP/PYY-6 exhibited significant metabolic benefits, as reflected by regulation of lipid levels, improved glucose tolerance, weight loss, decreased hepatocellular vacuolation, and the reversal of steatosis effects caused by xGLP/PYY-6. These results indicate the potential of developing xGLP/PYY-6 as an antiobesity, lipid regulation, antisteatotic, and antidiabetic agent. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Xu, Jing AU - Xu J AD - Department of Pharmacy, Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People's Hospital of Lianyungang, Lianyungang 222000, PR China. FAU - Wang, Shuang AU - Wang S AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Wu, Han AU - Wu H AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Chen, De AU - Chen D AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Han, Jing AU - Han J AD - Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning 530021, China; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning 530021, China.; School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. Electronic address: hj1986424@jsnu.edu.cn. FAU - Lin, Qisi AU - Lin Q AD - School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China. Electronic address: qslin074@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230801 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Lipids) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Mice MH - Animals MH - Glucagon-Like Peptide 1/metabolism MH - *Diabetes Mellitus/drug therapy MH - Obesity/metabolism MH - Hypoglycemic Agents/pharmacology/therapeutic use/chemistry MH - Lipids MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - Diabetes OT - Dual agonist OT - Glucagon-like peptide-1 OT - Obesity OT - Y(2) receptor COIS- Declaration of Competing Interest Authors have no conflict of interest concerning this study and have nothing to declare. EDAT- 2023/08/04 01:07 MHDA- 2023/09/25 06:42 CRDT- 2023/08/03 19:12 PHST- 2023/06/21 00:00 [received] PHST- 2023/07/25 00:00 [revised] PHST- 2023/07/28 00:00 [accepted] PHST- 2023/09/25 06:42 [medline] PHST- 2023/08/04 01:07 [pubmed] PHST- 2023/08/03 19:12 [entrez] AID - S0196-9781(23)00136-5 [pii] AID - 10.1016/j.peptides.2023.171073 [doi] PST - ppublish SO - Peptides. 2023 Nov;169:171073. doi: 10.1016/j.peptides.2023.171073. Epub 2023 Aug 1. PMID- 37536118 OWN - NLM STAT- MEDLINE DCOM- 20230905 LR - 20230918 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 37 IP - 9 DP - 2023 Sep TI - A beneficial role of GLP-1 receptor agonist therapy in ABCC8-MODY (MODY 12). PG - 108566 LID - S1056-8727(23)00164-2 [pii] LID - 10.1016/j.jdiacomp.2023.108566 [doi] AB - Maturity-onset diabetes of the young (MODY) is an inherited form of diabetes resulting from a mutation in a single gene. ABCC8-MODY is caused by mutations in the ABCC8 gene, which encodes sulfonylurea receptor 1 (SUR1), a regulatory component of the ATP-sensitive potassium (K(ATP)) channel found in beta cells. In ABCC8-MODY, mutations in the ABCC8 gene interfere with insulin secretion in response to glucose. Recent evidence suggests that therapy with GLP-1 receptor agonists (GLP-1 RAs) may be beneficial in ABCC8-MODY. This report presents a successful treatment of a 49-year-old woman diagnosed with ABCC8-MODY using the GLP-1 RA semaglutide. The patient, who had been previously receiving insulin therapy, experienced significant improvements in glycemic control and weight loss after transitioning to semaglutide. GLP-1 RAs potentially enhance insulin secretion in ABCC8-MODY by activating multiple signaling pathways involved in insulin secretion. The report highlights the potential of GLP-1 RA therapy as an alternative to sulfonylureas and insulin for individuals with ABCC8-MODY. GLP-1 RAs have previously demonstrated benefits in other forms of MODY. Understanding the molecular mechanisms through which GLP-1 RAs promote insulin secretion, including their effects on KATP channels and activation of PKA and Epac signaling, offers valuable insights into their therapeutic effects. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Nakhleh, Afif AU - Nakhleh A AD - Diabetes and Endocrinology Clinic, Maccabi Healthcare Services, Haifa, Israel; Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa, Israel; The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel. Electronic address: anakhleh@gmail.com. FAU - Goldenberg-Furmanov, Mirela AU - Goldenberg-Furmanov M AD - The Genetic Institute of Maccabi Health Services, Rehovot, Israel. FAU - Goldstein, Rayna AU - Goldstein R AD - The Genetic Institute of Maccabi Health Services, Rehovot, Israel. FAU - Shohat, Mordechai AU - Shohat M AD - The Genetic Institute of Maccabi Health Services, Rehovot, Israel. FAU - Shehadeh, Naim AU - Shehadeh N AD - Diabetes and Endocrinology Clinic, Maccabi Healthcare Services, Haifa, Israel; Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa, Israel; The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel. LA - eng PT - Case Reports PT - Journal Article DEP - 20230728 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Potassium Channels, Inwardly Rectifying) RN - 0 (Insulin) RN - 0 (Transcription Factors) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - 0 (ABCC8 protein, human) RN - 0 (Sulfonylurea Receptors) RN - Mason-Type Diabetes SB - IM MH - Female MH - Humans MH - Middle Aged MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Potassium Channels, Inwardly Rectifying/genetics MH - *Diabetes Mellitus, Type 2/drug therapy/genetics MH - Insulin/therapeutic use/metabolism MH - Transcription Factors/metabolism MH - Adenosine Triphosphate/therapeutic use MH - Sulfonylurea Receptors/genetics OTO - NOTNLM OT - ABCC8-MODY OT - GLP-1 receptor agonist OT - K(ATP) channel COIS- Declaration of competing interest The authors declare that there are no conflicts of interest. EDAT- 2023/08/04 01:07 MHDA- 2023/09/05 06:42 CRDT- 2023/08/03 18:06 PHST- 2023/06/22 00:00 [received] PHST- 2023/07/15 00:00 [revised] PHST- 2023/07/24 00:00 [accepted] PHST- 2023/09/05 06:42 [medline] PHST- 2023/08/04 01:07 [pubmed] PHST- 2023/08/03 18:06 [entrez] AID - S1056-8727(23)00164-2 [pii] AID - 10.1016/j.jdiacomp.2023.108566 [doi] PST - ppublish SO - J Diabetes Complications. 2023 Sep;37(9):108566. doi: 10.1016/j.jdiacomp.2023.108566. Epub 2023 Jul 28. PMID- 37531876 OWN - NLM STAT- MEDLINE DCOM- 20260311 LR - 20260312 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 17 IP - 9 DP - 2023 Sep TI - Semaglutide and cancer: A systematic review and meta-analysis. PG - 102834 LID - S1871-4021(23)00130-3 [pii] LID - 10.1016/j.dsx.2023.102834 [doi] AB - BACKGROUND: French national health care insurance system database has suggested 1-3 years use of glucagon like peptide-1 receptor agonists (GLP1RA) (exenatide, liraglutide and dulaglutide) may be linked with increased occurrence of thyroid cancer. Similar data on semaglutide is not-available. Hence, we undertook this systematic review to look at the safety of semaglutide focussing on different cancers. METHODS: Databases were searched for randomized controlled trials (RCTs) and real-world studies involving patients receiving semaglutide in the intervention-arm. Primary outcome was to evaluate the occurrence of pancreatic and thyroid cancers. Secondary outcomes were to the evaluate occurrence of any other malignancies or severe adverse-events. RESULTS: Data from 37 RCTs and 19 real-world studies having 16,839 patients in placebo-control group, 16,550 patients in active-control group and 13,330 patients in real-world studies were analysed. Compared to placebo, occurrence of pancreatic cancer [OR 0.25 (95%CI: 0.03-2.24); P = 0.21], thyroid cancer [OR 2.04 (95%CI: 0.33-12.61); P = 0.44; I(2) = 0%] and all neoplasms (benign, malignant and otherwise unspecified) [OR 0.95 (95%CI:0.62-1.45); P = 0.82; I(2) = 0%] was similar in the semaglutide group. Compared to active controls, occurrence of pancreatic cancer [OR 0.40 (95%CI:0.09-1.87); P = 0.26; I(2) = 0%], thyroid cancer [OR 1.19 (95%CI:0.15-9.66); P = 0.87; I(2) = 0%] and all neoplasms (benign, malignant and otherwise unspecified) [OR 0.91 (95% CI: 0.44-1.89); P = 0.79; I(2) = 0%] were similar in the semaglutide group. Real-world data analysis revealed single case each of pancreatic cancer and B-cell lymphoma. CONCLUSION: Semaglutide use in RCTs and real-world studies was not associated with an increased risk of any types of cancer, and this conclusion is supported by a high grade of evidence. CI - Copyright (c) 2023 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Nagendra, Lakshmi AU - Nagendra L AD - Department of Endocrinology, JSS Academy of Higher Education and Research, Mysore, India. Electronic address: drlakshminagendra@gmail.com. FAU - Bg, Harish AU - Bg H AD - Department of Anaesthesiology, JSS Academy of Higher Education and Research, Mysore, India. Electronic address: bgharish07@gmail.com. FAU - Sharma, Meha AU - Sharma M AD - Department of Rheumatology, Center for Endocrinology Diabetes Arthritis & Rheumatism (CEDAR) Superspeciality Healthcare, Dwarka, New Delhi, India. Electronic address: docmsharma@gmail.com. FAU - Dutta, Deep AU - Dutta D AD - Department of Endocrinology, Center for Endocrinology Diabetes Arthritis & Rheumatism (CEDAR) Superspeciality Healthcare, Dwarka, New Delhi, India. Electronic address: deepdutta2000@yahoo.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20230726 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives/therapeutic use MH - *Pancreatic Neoplasms/chemically induced/epidemiology MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Thyroid Neoplasms/chemically induced/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Neoplasms/chemically induced/epidemiology MH - Randomized Controlled Trials as Topic MH - Prognosis OTO - NOTNLM OT - Cancer OT - Pancreatic cancer OT - Semaglutide OT - Systematic review OT - Thyroid cancer COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/08/03 01:06 MHDA- 2026/03/11 06:56 CRDT- 2023/08/02 18:09 PHST- 2023/06/26 00:00 [received] PHST- 2023/07/24 00:00 [revised] PHST- 2023/07/25 00:00 [accepted] PHST- 2026/03/11 06:56 [medline] PHST- 2023/08/03 01:06 [pubmed] PHST- 2023/08/02 18:09 [entrez] AID - S1871-4021(23)00130-3 [pii] AID - 10.1016/j.dsx.2023.102834 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2023 Sep;17(9):102834. doi: 10.1016/j.dsx.2023.102834. Epub 2023 Jul 26. PMID- 37529870 OWN - NLM STAT- MEDLINE DCOM- 20231011 LR - 20250103 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 11 DP - 2023 Nov TI - Effects of once-weekly glucagon-like peptide-1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin-angiotensin system. PG - 3223-3234 LID - 10.1111/dom.15219 [doi] AB - AIM: To investigate the potential mechanism of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the treatment of type 2 diabetes mellitus (T2DM) complicated with coronary artery disease (CAD). METHODS: We searched both Chinese and English databases for randomized controlled trials related to once-weekly GLP-1 RA for T2DM complicated with CAD to verify the safety and efficacy of GLP-1 RA. The underlying mechanism was analysed by network pharmacology. RESULTS: In total, 13 studies with 35 563 participants were included in the analysis. The pooled analysis found that dulaglutide, exenatide and semaglutide outperformed placebo in cardiovascular outcomes in patients with T2DM, with a significant reduction in the incidence of non-fatal stroke (p < .00). Levels of cardiovascular risk factors were significantly reduced in the once-weekly GLP-1 RA group compared with the conventional treatment group (glycated haemoglobin: p < .00; fasting blood glucose: p < .00; weight: p < .00; systolic blood pressure: p < .00; total cholesterol: p < .00; low-density lipoprotein cholesterol: p < .00). Network pharmacology results were enriched to the renin-angiotensin system, and matrix metalloproteinase 2 and renin (REN) may be the key targets. In addition, four key targets of dulaglutide, five key targets of exenatide and two key targets of semaglutide were enriched. CONCLUSIONS: Our study suggests that once-weekly GLP-1 RA may have a potential protective effect on cardiovascular events in patients with T2DM combined with CAD, possibly through the renin-angiotensin system. However, further research is needed to confirm these findings and determine cause and effect. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Kan, Mengfan AU - Kan M AD - Teaching and Research Section of Internal Medicine, College of Medicine, Shandong University of Traditional Chinese Medicine; Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital; The Third Affiliated Hospital of Shandong First Medical University, Jinan, China. FAU - Fu, Hui AU - Fu H AD - Medical Integration and Practice Center, Shandong University, Jinan, China. FAU - Xu, Yunsheng AU - Xu Y AD - The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Yue, Zhaodi AU - Yue Z AD - College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Du, Bingyu AU - Du B AD - College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Chen, Qiang AU - Chen Q AD - College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Wang, Xueyin AU - Wang X AD - Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Shandong First Medical University; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital; Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China. FAU - Yu, Shaohong AU - Yu S AD - Teaching and Research Section of Internal Medicine, College of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. AD - Department of Rehabilitation Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Zhang, Zhongwen AU - Zhang Z AUID- ORCID: 0000-0001-8490-5074 AD - Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Shandong First Medical University; Department of Endocrinology and Metabolism, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital; Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Jinan, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20230802 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 97C5T2UQ7J (Cholesterol) RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Cholesterol MH - *Coronary Artery Disease/complications/drug therapy MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Exenatide/therapeutic use MH - Glucagon-Like Peptide 1/therapeutic use MH - Glucagon-Like Peptides MH - Hypoglycemic Agents/adverse effects MH - Matrix Metalloproteinase 2 MH - Renin-Angiotensin System MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - coronary artery disease OT - meta-analysis OT - network pharmacology OT - once-weekly GLP-1 receptor agonists OT - renin-angiotensin system OT - type 2 diabetes mellitus EDAT- 2023/08/02 06:42 MHDA- 2023/10/04 06:44 CRDT- 2023/08/02 04:14 PHST- 2023/06/08 00:00 [revised] PHST- 2023/01/27 00:00 [received] PHST- 2023/07/04 00:00 [accepted] PHST- 2023/10/04 06:44 [medline] PHST- 2023/08/02 06:42 [pubmed] PHST- 2023/08/02 04:14 [entrez] AID - 10.1111/dom.15219 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Nov;25(11):3223-3234. doi: 10.1111/dom.15219. Epub 2023 Aug 2. PMID- 37522468 OWN - NLM STAT- MEDLINE DCOM- 20240315 LR - 20260706 IS - 1542-6270 (Electronic) IS - 1060-0280 (Linking) VI - 58 IP - 4 DP - 2024 Apr TI - Incretin Analogs for Weight Management in Adults Without Diabetes. PG - 398-406 LID - 10.1177/10600280231190089 [doi] AB - OBJECTIVE: This is a narrative review of incretin analogs and their effect on weight management in adult without diabetes. DATA SOURCES: Randomized controlled trials were identified by English language. PubMed/MEDLINE, Scopus, and Embase databases were searched from inception through June 2023 to identify all pertinent trials reporting outcomes on efficacy and safety search using the terms: tirzepatide, semaglutide, liraglutide, and obesity. STUDY SELECTION AND DATA EXTRACTION: Selected studies were included if the study population was composed of adults without diabetes being treated by glucagon-like peptide 1 (GLP-1) receptor agonists or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists for weight management, and weight loss was assessed as a primary outcome. DATA SYNTHESIS: Fifteen studies involving 3 pharmacotherapies (liraglutide, semaglutide, and tirzepatide) were identified. Efficacy data supporting the use of these agents for weight management were promising when compared to placebo and/or other behavioral therapies. Percent weight loss ranged from 5.7% to 11.8%, 14.9% to 17.4%, and 15% to 20.9% for liraglutide, semaglutide, and tirzepatide, respectively. Safety data were relatively similar across all trials and identified gastrointestinal adverse effects as most common. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Glucagon-like peptide 1 agonists are preferred for overweight or obese patients by the American Gastroenterological Association. Future guidelines may address tirzepatides' place in therapy as new evidence comes forth. Providers should consider patient-specific factors such as cost, adverse effects, drug interactions, and comorbidities when prescribing these agents and provide education regarding the need for concurrent diet and exercise modifications. CONCLUSIONS: All incretin analogs in this review are superior to placebo when used for weight management in adults without diabetes. FAU - Lobkovich, Alison AU - Lobkovich A AD - Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University and Henry Ford Health, Detroit, MI, USA. FAU - Kale-Pradhan, Pramodini AU - Kale-Pradhan P AUID- ORCID: 0000-0002-8729-7710 AD - Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University and Ascension St. John Hospital, Detroit, MI, USA. FAU - Lipari, Melissa AU - Lipari M AUID- ORCID: 0000-0003-2658-8247 AD - Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University and Ascension St. John Hospital, Detroit, MI, USA. LA - eng PT - Journal Article PT - Review DEP - 20230731 PL - United States TA - Ann Pharmacother JT - The Annals of pharmacotherapy JID - 9203131 RN - 0 (Incretins) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Humans MH - *Incretins/adverse effects MH - Liraglutide/adverse effects MH - Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Obesity/drug therapy/epidemiology MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - glucagon-like peptide 1 receptor agonist OT - glucose-dependent insulinotropic polypeptide receptor agonist OT - incretin analog OT - obesity OT - weight loss COIS- Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2023/07/31 13:08 MHDA- 2024/03/15 06:43 CRDT- 2023/07/31 07:33 PHST- 2024/03/15 06:43 [medline] PHST- 2023/07/31 13:08 [pubmed] PHST- 2023/07/31 07:33 [entrez] AID - 10.1177/10600280231190089 [doi] PST - ppublish SO - Ann Pharmacother. 2024 Apr;58(4):398-406. doi: 10.1177/10600280231190089. Epub 2023 Jul 31. PMID- 37498865 OWN - NLM STAT- MEDLINE DCOM- 20230731 LR - 20260127 IS - 1365-2060 (Electronic) IS - 0785-3890 (Print) IS - 0785-3890 (Linking) VI - 55 IP - 2 DP - 2023 TI - Comparative efficacy and safety profile of once-weekly Semaglutide versus once-daily Sitagliptin as an add-on to metformin in patients with type 2 diabetes: a systematic review and meta-analysis. PG - 2239830 LID - 10.1080/07853890.2023.2239830 [doi] LID - 2239830 AB - BACKGROUND: The emergence of genetically-modified human proteins and glucagon-like peptide-1 (GLP-1) receptor agonists have presented a promising strategy for effectively managing diabetes. Due to the scarcity of clinical trials focusing on the safety and efficacy of semaglutide as an adjunctive treatment for patients with type 2 diabetes who had inadequate glycemic control with metformin, we conducted a systematic review and meta-analysis. This was necessary to fill the gap and provide a comprehensive assessment of semaglutide compared to sitagliptin, a commonly prescribed DPP-4 inhibitor, in this patient population. METHODS: A comprehensive and systematic search was carried out on reputable databases including PubMed, the Cochrane Library, and Elsevier's ScienceDirect to identify relevant studies that compared the efficacy of once-weekly Semaglutide with once-daily Sitagliptin in individuals diagnosed with type 2 diabetes mellitus. The analysis of the gathered data was performed utilizing the random-effects model, which considers both within-study and between-study variations. RESULTS: The meta-analysis incorporated three randomized controlled trials (RCTs), encompassing 2401 participants, with a balanced distribution across the treatment groups. The primary focus of the study revolved around evaluating changes in HbA1C, blood pressure, pulse rate, body weight, waist circumference, and BMI. The findings revealed that once-weekly Semaglutide showed substantially improved HbA1C (WMD: -0.98; 95% CI: -1.28, -0.69, p-value: < 0.0001; I2: 100%), systolic (WMD: -3.73; 95% CI: -5.42, -2.04, p-value: <0.0001; I2: 100%) and diastolic blood pressures (WMD: -0.66; 95% CI: -1.02, -0.29, p-value: 0.0005; I2: 100%), and body weight (WMD: -3.17; 95% CI: -3.84, -2.49, p-value: <0.00001; I2: 100%) compared to once-daily Sitagliptin. However, there was an observed increase in pulse rate (WMD: 3.33; 95% CI: 1.61, 5.06, p-value: <0.00001; I2: 100%) associated with Semaglutide treatment. Regarding secondary outcomes, there was an elevated risk of total adverse events and premature treatment discontinuation with Semaglutide. The risk of serious, severe, moderate, and mild adverse events did not significantly differ between the two treatments. CONCLUSIONS: In conclusion, the administration of once-weekly Semaglutide exhibited a substantial reduction in HbA1c, average systolic blood pressure (SBP), mean diastolic blood pressure (DBP), body weight, waist circumference, body mass index (BMI), and a rise in pulse rate, as opposed to the once-daily administration of Sitagliptin. FAU - Patel, Tirath AU - Patel T AD - Medicine, American University of Antigua, Antigua and Barbuda. FAU - Nageeta, Fnu AU - Nageeta F AD - Medicine, Ghulam Muhammad Mahar Medical College, Sukkur, Pakistan. FAU - Sohail, Rohab AU - Sohail R AD - Medicine, Quaid-e-Azam Medical College Bahawalpur, Pakistan, Pakistan. FAU - Butt, Tooba Shaukat AU - Butt TS AD - Medicine, United Medical and Dental College, Karachi, Pakistan. FAU - Ganesan, Shyamala AU - Ganesan S AD - Medicine, American University of Antigua, Antigua and Barbuda. FAU - Madhurita, Fnu AU - Madhurita F AD - Medicine, Chanda Medical College, Larkana, Pakistan. FAU - Ahmed, Muhammad AU - Ahmed M AD - Medicine, American University of the Carribean, United States of America. FAU - Zafar, Mahrukh AU - Zafar M AD - Medicine, University of Medicine and health sciences, St. Kitts, Carribean, United States of America. FAU - Zafar, Wirda AU - Zafar W AD - Medicine, University of Medicine and health sciences, St. Kitts, Carribean, United States of America. FAU - Zaman, Mohammad Uzair AU - Zaman MU AD - Medicine, Bacha Khan Medical College, Mardan, Pakistan. FAU - Varrassi, Giustino AU - Varrassi G AD - Anesthesiology, Paolo Procacci Foundation, Rome, Italy. FAU - Khatri, Mahima AU - Khatri M AUID- ORCID: 0000-0003-0217-8331 AD - Medicine, Dow University of Health Sciences, Karachi, Pakistan. FAU - Kumar, Satesh AU - Kumar S AUID- ORCID: 0000-0001-7975-6297 AD - Medicine, Shaheed Mohtarma Benazir Bhutto Medical College, Karachi, Pakistan. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - England TA - Ann Med JT - Annals of medicine JID - 8906388 RN - 9100L32L2N (Metformin) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Metformin/adverse effects MH - Sitagliptin Phosphate/adverse effects MH - Glycated Hemoglobin MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Body Weight MH - Semaglutide PMC - PMC10375936 OTO - NOTNLM OT - Semaglutide OT - meta-analysis OT - once daily OT - once-weekly OT - sitagliptin OT - type 2 diabetes mellitus COIS- No potential conflict of interest was reported by the author(s). EDAT- 2023/07/27 19:10 MHDA- 2023/07/31 11:41 PMCR- 2023/07/27 CRDT- 2023/07/27 13:43 PHST- 2023/07/31 11:41 [medline] PHST- 2023/07/27 19:10 [pubmed] PHST- 2023/07/27 13:43 [entrez] PHST- 2023/07/27 00:00 [pmc-release] AID - 2239830 [pii] AID - 10.1080/07853890.2023.2239830 [doi] PST - ppublish SO - Ann Med. 2023;55(2):2239830. doi: 10.1080/07853890.2023.2239830. PMID- 37484944 OWN - NLM STAT- MEDLINE DCOM- 20230727 LR - 20250623 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - GLP-1RAs caused gastrointestinal adverse reactions of drug withdrawal: a system review and network meta-analysis. PG - 1149328 LID - 10.3389/fendo.2023.1149328 [doi] LID - 1149328 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce postprandial blood glucose, inhibit appetite, and delay gastrointestinal emptying. However, it is controversial that some patients are intolerant to GLP-1RAs. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched for randomized controlled trials (RCTs) using GLP-1RAs with documented withdrawal due to gastrointestinal adverse reactions (GI AEs) from their inception to September 28, 2022. After extracting the information incorporated into the studies, a random-effects network meta-analysis was performed within a frequentist framework. RESULTS: 64 RCTs were finally enrolled, which included six major categories of the GLP-1RA. The sample size of the GLP-1RAs treatment group was 16,783 cases. The risk of intolerable gastrointestinal adverse reactions of Liraglutide and Semaglutide was higher than that of Dulaglutide. Meanwhile, the higher the dose of the same GLP-1RA preparation, the more likely to cause these adverse reactions. These intolerable GI AEs were not significantly related to drug homology or formulations and may be related to the degree of suppression of the appetite center. CONCLUSION: Dulaglutide caused the lowest intolerable GI AEs, while Liraglutide and Semaglutide were the highest. For Semaglutide, the higher the dose, the more likely it is to drive GI AEs. Meanwhile, the risk of these GI AEs is independent of the different formulations of the drug. All these findings can effectively guide individualized treatment. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022359346, identifier CRD42022359346. CI - Copyright (c) 2023 Zhang, Zhang, Tan, Chen, Zhou, Liu and Yu. FAU - Zhang, Ziqi AU - Zhang Z AD - The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. FAU - Zhang, Qiling AU - Zhang Q AD - The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. FAU - Tan, Ying AU - Tan Y AD - The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. FAU - Chen, Yu AU - Chen Y AD - The First Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China. FAU - Zhou, Xiqiao AU - Zhou X AD - Department of Endocrinology, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China. FAU - Liu, Su AU - Liu S AD - Department of Endocrinology, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China. FAU - Yu, Jiangyi AU - Yu J AD - Department of Endocrinology, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20230706 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM EIN - Front Endocrinol (Lausanne). 2023 Oct 09;14:1270115. doi: 10.3389/fendo.2023.1270115. PMID: 37900146 MH - Humans MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10359616 OTO - NOTNLM OT - Dulaglutide OT - Glucagon-like peptide-1 receptor agonist OT - Liraglutide OT - Semaglutide OT - gastrointestinal adverse effects OT - intolerance OT - network meta-analysis COIS- The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/07/24 06:42 MHDA- 2023/07/26 06:43 PMCR- 2023/01/01 CRDT- 2023/07/24 04:51 PHST- 2023/01/21 00:00 [received] PHST- 2023/06/14 00:00 [accepted] PHST- 2023/07/26 06:43 [medline] PHST- 2023/07/24 06:42 [pubmed] PHST- 2023/07/24 04:51 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1149328 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Jul 6;14:1149328. doi: 10.3389/fendo.2023.1149328. eCollection 2023. PMID- 37466909 OWN - NLM STAT- MEDLINE DCOM- 20230811 LR - 20260127 IS - 1496-8975 (Electronic) IS - 0832-610X (Linking) VI - 70 IP - 8 DP - 2023 Aug TI - Influence of semaglutide use on the presence of residual gastric solids on gastric ultrasound: a prospective observational study in volunteers without obesity recently started on semaglutide. PG - 1300-1306 LID - 10.1007/s12630-023-02549-5 [doi] AB - PURPOSE: Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) have become increasingly popular as both diabetic and weight loss therapies. One effect of this class of medication is delayed gastric emptying, which may impact the risk of aspiration during anesthesia delivery. METHODS: In this prospective study, we used gastric ultrasound to evaluate the presence of solid gastric contents in both supine and lateral positions after an eight-hour fast in those taking GLP-1RA compared with controls. Participants underwent a second ultrasound evaluation two hours later after drinking 12 fluid ounces of water (approximately 350 mL). RESULTS: Twenty adults voluntarily enrolled, giving a total of ten participants in each group. In the supine position, 70% of semaglutide participants and 10% of control participants had solids present on gastric ultrasound (risk ratio [RR], 3.50; 95% confidence interval [CI], 1.26 to 9.65; P = 0.02.) In the lateral position, 90% of semaglutide participants and 20% of control participants had solids identified on gastric ultrasound (RR, 7.36; 95% CI, 1.13 to 47.7; P = 0.005). Two hours after drinking clear liquids, the two groups did not differ in the lateral position, but in the supine position, 90% of control group participants were rated as empty compared with only 30% of semaglutide group participants (P = 0.02). CONCLUSIONS: This study provides preliminary evidence that GLP-1RAs may affect gastric emptying and residual gastric contents following an overnight fast and two hours after clear liquids, which may have implications for aspiration risk during anesthetic care. CI - (c) 2023. Canadian Anesthesiologists' Society. FAU - Sherwin, Marc AU - Sherwin M AD - Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L., Levy Place, Box 1010, New York, NY, 10029, USA. FAU - Hamburger, Joshua AU - Hamburger J AD - Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L., Levy Place, Box 1010, New York, NY, 10029, USA. FAU - Katz, Daniel AU - Katz D AD - Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L., Levy Place, Box 1010, New York, NY, 10029, USA. FAU - DeMaria, Samuel Jr AU - DeMaria S Jr AUID- ORCID: 0000-0003-2808-5539 AD - Department of Anesthesiology, Perioperative and Pain Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L., Levy Place, Box 1010, New York, NY, 10029, USA. samuel.demaria@mssm.edu. LA - eng PT - Journal Article PT - Observational Study TT - Influence de l'utilisation du semaglutide sur la presence de solides gastriques residuels a l'echographie gastrique : une etude observationnelle prospective aupres de volontaires sans obesite ayant recemment commence a prendre du semaglutide. DEP - 20230719 PL - United States TA - Can J Anaesth JT - Canadian journal of anaesthesia = Journal canadien d'anesthesie JID - 8701709 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - *Hypoglycemic Agents MH - *Diabetes Mellitus, Type 2/drug therapy MH - Prospective Studies MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Obesity MH - Volunteers MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - aspiration OT - gastric ultrasound OT - receptor agonists EDAT- 2023/07/19 13:06 MHDA- 2023/08/11 06:43 CRDT- 2023/07/19 11:14 PHST- 2023/05/01 00:00 [received] PHST- 2023/06/22 00:00 [accepted] PHST- 2023/05/30 00:00 [revised] PHST- 2023/08/11 06:43 [medline] PHST- 2023/07/19 13:06 [pubmed] PHST- 2023/07/19 11:14 [entrez] AID - 10.1007/s12630-023-02549-5 [pii] AID - 10.1007/s12630-023-02549-5 [doi] PST - ppublish SO - Can J Anaesth. 2023 Aug;70(8):1300-1306. doi: 10.1007/s12630-023-02549-5. Epub 2023 Jul 19. PMID- 37455226 OWN - NLM STAT- MEDLINE DCOM- 20230904 LR - 20250626 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 45 IP - 8 DP - 2023 Aug TI - Effect of the Dual Glucose-Dependent Insulinotropic Peptide/Gulcagon-like Peptide 1 Receptor Agonist Tirzepatide on Lipid Profile and Waist Circumference: A Systematic Review and Meta-analysis. PG - 787-796 LID - S0149-2918(23)00200-X [pii] LID - 10.1016/j.clinthera.2023.06.008 [doi] AB - PURPOSE: Tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide 1 receptor agonist, has been approved by the US Food and Drug Administration for the treatment of type 2 diabetes. The purpose of this meta-analysis is to evaluate the impact of tirzepatide on lipid profile and waist circumference (WC), both of which are risk factors of cardiovascular diseases. METHODS: The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were systematically searched for articles published from database inception to July 31, 2022. This meta-analysis included 7 randomized controlled trials with a minimum duration of 12 weeks that compared tirzepatide with placebo or other antidiabetic medications. The random-effects model was used to estimate mean differences in lipid profile and WC from baseline. The Cochrane risk-of-bias tool for randomized trials, version 2 was used to assess the outcome's risk of bias. We evaluated the evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. FINDINGS: A total of 8 articles from 7 trials with 7151 participants were included. All 3 eligible maintenance doses of tirzepatide (5, 10, and 15 mg once a week) were effective in increasing total cholesterol (TC) (P < 0.05), HDL-C (P < 0.05), VLDL-C (P < 0.01), triglyceride (TG) (P < 0.01), and WC (P < 0.01) changes from baseline compared with control agents including placebo, semaglutide, dulaglutide, and degludec. Although the evidence for VLDL-C and TGs by GRADE were high or moderate, the evidences for TC, HDL-C, and WC were low or moderate. Only 5mg once-weekly tirzepatide (P < 0.05), not 10 or 15 mg, could induce significant alteration in LDL-C before sensitivity analysis. The evidence by GRADE was moderate. IMPLICATIONS: Tirzepatide had superiority over placebo or other antidiabetic agents in controlling lipid and WC levels. However, the levels of evidence by GRADE varied greatly across different outcome indicators. Limitations of the study include evaluating secondary outcomes of original trials for the meta-analyses, not assessing the effect of baseline lipid-lowering therapy on lipid levels, and not exploring the bias induced by glycemic improvement and weight loss. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Yu, Dan AU - Yu D AD - Department of Endocrinology, Zhejiang Hospital, Hangzhou, China. FAU - Shen, Shanshan AU - Shen S AD - Department of Geriatrics, Zhejiang Hospital, Hangzhou, China. FAU - Zhang, Jinghong AU - Zhang J AD - Department of Endocrinology, Zhejiang Hospital, Hangzhou, China. FAU - Wang, Qijun AU - Wang Q AD - Department of Endocrinology, Zhejiang Hospital, Hangzhou, China. Electronic address: wqjevoly@163.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20230714 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - OYN3CCI6QE (Tirzepatide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Lipids) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Gastric Inhibitory Polypeptide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Waist Circumference MH - Peptides/adverse effects MH - Hypoglycemic Agents/adverse effects MH - Lipids MH - Glucagon-Like Peptide-1 Receptor MH - Tirzepatide OTO - NOTNLM OT - Cardiovascular diseases OT - Dual GIP/GLP-1 receptor agonist OT - Lipid profile OT - Meta-analysis OT - Tirzepatide OT - Waist circumference COIS- Declaration of Competing Interest None. EDAT- 2023/07/17 00:42 MHDA- 2023/09/04 06:43 CRDT- 2023/07/16 21:59 PHST- 2022/11/24 00:00 [received] PHST- 2023/05/28 00:00 [revised] PHST- 2023/06/07 00:00 [accepted] PHST- 2023/09/04 06:43 [medline] PHST- 2023/07/17 00:42 [pubmed] PHST- 2023/07/16 21:59 [entrez] AID - S0149-2918(23)00200-X [pii] AID - 10.1016/j.clinthera.2023.06.008 [doi] PST - ppublish SO - Clin Ther. 2023 Aug;45(8):787-796. doi: 10.1016/j.clinthera.2023.06.008. Epub 2023 Jul 14. PMID- 37449993 OWN - NLM STAT- MEDLINE DCOM- 20230817 LR - 20250103 IS - 1432-1041 (Electronic) IS - 0031-6970 (Print) IS - 0031-6970 (Linking) VI - 79 IP - 9 DP - 2023 Sep TI - Trends in use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in Australia in the era of increased evidence of their cardiovascular benefits (2014-2022). PG - 1239-1248 LID - 10.1007/s00228-023-03539-8 [doi] AB - PURPOSE: To investigate trends in SGLT2i and GLP-1RA use in Australia in the era of increased evidence of their cardiovascular benefits. METHODS: We used national dispensing claims for a 10% random sample of Australians to estimate the number of prevalent and new users (no dispensing in the prior year) of SGLT2i or GLP-1RA per month from January 2014 to July 2022. We assessed prescriber specialty and prior use of other antidiabetic and cardiovascular medicines as a proxy for evidence of type 2 diabetes (T2D) and cardiovascular conditions, respectively. RESULTS: We found a large increase in the number of prevalent users (216-fold for SGLT2i; 11-fold for GLP-1RA); in July 2022 approximately 250,000 Australians were dispensed SGLT2i and 120,000 GLP-1RA. Most new users of SGLT2i or GLP-1RA had evidence of both T2D and cardiovascular conditions, although from 2022 onwards, approximately one in five new users of SGLT2i did not have T2D. The proportion of new users initiating SGLT2i by cardiologists increased after 2021, reaching 10.0% of initiations in July 2022. Among new users with evidence of cardiovascular conditions, empagliflozin was the most commonly prescribed SGLT2i, while dulaglutide or semaglutide was the most common GLP-1RA. CONCLUSION: SGLT2i and GLP-1RA use is increasing in Australia, particularly in populations with higher cardiovascular risk. The increased use of SGLT2i among people without evidence of T2D suggests that best-evidence medicines are adopted in Australia across specialties, aligning with new evidence and expanding indications. CI - (c) 2023. The Author(s). FAU - Lin, Jialing AU - Lin J AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. jialing.lin@unsw.edu.au. FAU - Pearson, Sallie-Anne AU - Pearson SA AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. FAU - Greenfield, Jerry R AU - Greenfield JR AD - Department of Diabetes and Endocrinology, St Vincent's Hospital, Darlinghurst, Australia. AD - St Vincent's Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. AD - Clinical Diabetes, Appetite and Metabolism, Garvan Institute of Medical Research, Darlinghurst, Australia. FAU - Park, Kyeong Hye AU - Park KH AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. AD - Endocrinology and Metabolism, National Health Insurance Ilsan Hospital, Goyang-shi, Gyeonggi-do, South Korea. FAU - Havard, Alys AU - Havard A AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. AD - National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia. FAU - Brieger, David AU - Brieger D AD - Department of Cardiology, Concord Repatriation General Hospital, Sydney, Australia. AD - Faculty of Medicine and Health, University of Sydney, Sydney, Australia. FAU - Day, Richard O AU - Day RO AD - St Vincent's Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. AD - Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Sydney, Australia. FAU - Falster, Michael O AU - Falster MO AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. FAU - de Oliveira Costa, Juliana AU - de Oliveira Costa J AD - Medicines Intelligence Research Program, School of Population Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia. LA - eng GR - 105609/WT_/Wellcome Trust/United Kingdom GR - 105609/WT_/Wellcome Trust/United Kingdom PT - Journal Article DEP - 20230714 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Symporters) RN - IY9XDZ35W2 (Glucose) RN - 9NEZ333N27 (Sodium) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Australia MH - Hypoglycemic Agents/therapeutic use MH - *Cardiovascular Diseases/drug therapy/epidemiology MH - *Symporters MH - Glucose MH - Sodium MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10427543 OTO - NOTNLM OT - Cardiovascular disease OT - Glucagon-like peptide-1 receptor agonists OT - Pharmacoepidemiology OT - Sodium-glucose co-transporter 2 inhibitors OT - Trends OT - Type 2 diabetes COIS- SAP is a member of the Drug Utilisation Sub Committee of the Pharmaceutical Benefits Advisory Committee. The views expressed in this paper do not represent those of the Committee. EDAT- 2023/07/14 13:08 MHDA- 2023/08/17 06:42 PMCR- 2023/07/14 CRDT- 2023/07/14 11:04 PHST- 2023/06/07 00:00 [received] PHST- 2023/07/07 00:00 [accepted] PHST- 2023/08/17 06:42 [medline] PHST- 2023/07/14 13:08 [pubmed] PHST- 2023/07/14 11:04 [entrez] PHST- 2023/07/14 00:00 [pmc-release] AID - 10.1007/s00228-023-03539-8 [pii] AID - 3539 [pii] AID - 10.1007/s00228-023-03539-8 [doi] PST - ppublish SO - Eur J Clin Pharmacol. 2023 Sep;79(9):1239-1248. doi: 10.1007/s00228-023-03539-8. Epub 2023 Jul 14. PMID- 37449929 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20260127 IS - 1536-3686 (Electronic) IS - 1075-2765 (Linking) VI - 30 IP - 4 DP - 2023 Jul-Aug 01 TI - Evaluating the Efficacy and Pharmacoeconomics of Semaglutide and Tirzepatide in the Setting of Obesity. PG - e347-e352 LID - 10.1097/MJT.0000000000001643 [doi] AB - BACKGROUND: Obesity is a major and growing public health concern. The associated cost for obesity and its related comorbidities is approximately 30% of US health care expenditures annually. As additional pharmacotherapeutic options join the market to combat obesity, it is important to understand the financial impact it may have on overall health care costs. This article explores the efficacy and pharmacoeconomics of incretin mimetics, semaglutide and tirzepatide, in the setting of obesity. AREA OF UNCERTAINTY: The cost of incretin mimetics (semaglutide and tirzepatide) and its overall impact on obesity management within the health care arena is being explored. The cost comparison of these medications is to be determined; however, it may represent an added cost to the total US health care expenditures. DATA SOURCES: A PubMed and Google Scholar search was conducted using various search terms (eg, semaglutide, tirzepatide, pharmacoeconomics, and obesity). THERAPEUTIC ADVANCES: Based on the data reviewed, both semaglutide and tirzepatide are effective medication options for obesity management. Obesity-related management expenditures exceed $173 billion for the US health care system annually. The cost needed to treat for 1% of weight loss with semaglutide and tirzepatide was reported as $1845 and $985, respectively. More than 40% of adults (60 years or older) experience obesity. If 1%, 5%, or 10% of this population is treated with semaglutide, the annual Medicare costs will translate to excess of $2.6 billion, $13.3 billion, and $26.8 billion, respectively. Tirzepatide is not yet approved in the United States for obesity and its financial impact remains to be seen. CONCLUSIONS: Obesity is associated with burdensome health complications and costs. Semaglutide and tirzepatide are effective drug options for the management of obesity. The cost of these medications will no doubt present a challenge to the total health care expenditures, although the cost-benefit ratio may ultimately be favorable. CI - Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved. FAU - Nguyen, Timothy AU - Nguyen T AD - Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY. FAU - Wong, Elaine AU - Wong E FAU - Cope, Rebecca AU - Cope R LA - eng PT - Journal Article PL - United States TA - Am J Ther JT - American journal of therapeutics JID - 9441347 RN - 0 (Incretins) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - Aged MH - United States MH - *Economics, Pharmaceutical MH - Incretins/therapeutic use MH - Medicare MH - Obesity/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - Semaglutide COIS- The authors have no conflicts of interest to declare. EDAT- 2023/07/14 13:08 MHDA- 2023/07/17 06:42 CRDT- 2023/07/14 10:06 PHST- 2023/07/17 06:42 [medline] PHST- 2023/07/14 13:08 [pubmed] PHST- 2023/07/14 10:06 [entrez] AID - 00045391-202308000-00005 [pii] AID - 10.1097/MJT.0000000000001643 [doi] PST - ppublish SO - Am J Ther. 2023 Jul-Aug 01;30(4):e347-e352. doi: 10.1097/MJT.0000000000001643. PMID- 37448270 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20260127 IS - 2308-1430 (Electronic) IS - 0375-9660 (Print) IS - 0375-9660 (Linking) VI - 69 IP - 2 DP - 2023 May 11 TI - [Efficacy of treatment with glucagon-like peptide receptor agonists-1 in Asian patients with type 2 diabetes mellitus]. PG - 38-46 LID - 10.14341/probl13245 [doi] AB - BACKGROUND: The projected 68% increase in patients with type 2 diabetes mellitus (T2D) in the upcoming decades and the specific pathophysiological course of the disease are critical factors for the development of optimal disease management tactics in the Asian population. It is now known that beta-cell dysfunction is dominant in the pathogenesis of T2D in Asians. In a number of Asian countries, incretin therapy is the leading therapy. AIM: To review literature on glucagon-like peptide-1 (GLP-1) secretion and clinical trial results of GLP-1 receptor agonist class (GLP-1RA) drugs as well as to evaluate their effectiveness in Asian population with T2D. MATERIALS AND METHODS: A review of studies on pathophysiological aspects of GLP-1 secretion and evaluation of the efficacy of therapy with GLP-1RA preparations registered and used in clinical practice in Asian regions. RESULTS: Several studies in Asian countries have shown that intact GLP-1 levels were significantly lower in both T2D patients and healthy Japanese volunteers; as well as in patients with impaired glucose tolerance. It is suggested that either impaired secretion of GLP-1 in the gut, accelerated processing by dipeptidyl peptidase-4, or a combination of both are responsible for the decrease in GLP-1. The greater efficacy of GLP-1RA treatment in achieving glycemic control in Asian T2D patients was presented by Kim Y.G. et al. in a meta-analysis of 15 randomised controlled trials, the reduction in HbA1c on GLP-1RA treatment averaged -1.16% in Asian-dominated studies and -0.83% in non-Asian-dominated studies. In the PIONEER 9 clinical programme, similar results were obtained, with oral semaglutide having a more pronounced effect on glycaemic control in Japanese patients. Thus, the mean change in HbA 1c was -1.1%, 7 mg -1.5%, and 14 mg -1.7% at the 3 mg dose; whereas in the PIONEER 1 study in the global population, the mean change in HbA1c was -0.6%, -0.9% and -1.1% for 3, 7, 14 mg semaglutide, respectively. The PIONEER 10 study concluded that oral semaglutide was well tolerated by Japanese patients with T2D. Oral semaglutide reduced HbA1c (14 mg dose) and body weight (7 and 14 mg doses) more significantly compared to dulaglutide at 0.75 mg dose. Results of a pooled analysis of long-acting GLP-1RA showed a more significant reduction in cardiovascular event risk in the Asian subpopulation. CONCLUSION: The presented review describes benefits in glycemic control as well as in the reduction of relative cardiovascular event risks with GLP-1RA treatment in the Asian population, which requires further in-depth research and implies optimal management tactics in patients with T2DM. FAU - Khamnueva, L Yu AU - Khamnueva LY AD - Irkutsk State Medical University. FAU - Andreeva, L S AU - Andreeva LS AD - Irkutsk State Medical University. LA - rus PT - English Abstract PT - Journal Article PT - Review DEP - 20230511 PL - Russia (Federation) TA - Probl Endokrinol (Mosk) JT - Problemy endokrinologii JID - 0140673 RN - 0 (Glucagon-Like Peptide Receptors) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Asian MH - Cardiovascular Diseases MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide Receptors/agonists MH - Glycated Hemoglobin MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide PMC - PMC10204790 EDAT- 2023/07/14 13:06 MHDA- 2023/07/17 06:42 PMCR- 2023/05/11 CRDT- 2023/07/14 02:54 PHST- 2023/02/01 00:00 [received] PHST- 2023/02/19 00:00 [accepted] PHST- 2023/02/17 00:00 [revised] PHST- 2023/07/17 06:42 [medline] PHST- 2023/07/14 13:06 [pubmed] PHST- 2023/07/14 02:54 [entrez] PHST- 2023/05/11 00:00 [pmc-release] AID - 10.14341/probl13245 [doi] PST - epublish SO - Probl Endokrinol (Mosk). 2023 May 11;69(2):38-46. doi: 10.14341/probl13245. PMID- 37448249 OWN - NLM STAT- MEDLINE DCOM- 20230721 LR - 20251229 IS - 2308-1430 (Electronic) IS - 0375-9660 (Print) IS - 0375-9660 (Linking) VI - 69 IP - 3 DP - 2023 Jun 30 TI - [Semaglutide - effectiveness in weight loss and side effects when used according to studies by SUSTAIN, PIONEER, STEP]. PG - 68-82 LID - 10.14341/probl13197 [doi] AB - Overweight and obesity are a worldwide common problem and are diagnosed with a body mass index (BMI) value in the range of 25.0-29.9 kg/m2 and >/=30.0 kg/m2, respectively. Obese patients are at high risk of developing concomitant diseases, such as hypertension, type 2 diabetes mellitus (DM2), hyperlipidemia, stroke and even some types of cancer. In the Russian Federation in 2016, the proportion of overweight people was 62.0%, with obesity - 26.2%. The authors performed an electronic search in the PubMed information database. Two search elements were used: <> and <>. The search included studies published from the date of foundation of the database to August 2022. The search was limited only to the results of clinical trials. The authors obtained 26 results, but only the studies of SUSTAIN, PIONEER (Peptide Innovation for Early Diabetes Treatment) and STEP were considered, since they were original, randomized, controlled clinical trials conducted before the approval of semaglutide for the treatment of DM2 and obesity. FAU - Shabutdinova, O R AU - Shabutdinova OR AD - Bashkir state medical university. FAU - Dautov, A R AU - Dautov AR AD - Bashkir state medical university. FAU - Samkov, A A AU - Samkov AA AD - Bashkir state medical university. FAU - Kononenko, A V AU - Kononenko AV AD - Bashkir state medical university. FAU - Sargaliev, A F AU - Sargaliev AF AD - Bashkir state medical university. FAU - Davletshin, A R AU - Davletshin AR AD - Bashkir state medical university. FAU - Andresova, P A AU - Andresova PA AD - Bashkir state medical university. FAU - Zarbeeva, K R AU - Zarbeeva KR AD - Bashkir state medical university. FAU - Torshkhoeva, D A AU - Torshkhoeva DA AD - Dagestan state medical university. FAU - Rakhmonkulov, U A AU - Rakhmonkulov UA AD - Bashkir state medical university. FAU - Afanasyev, A A AU - Afanasyev AA AD - Samara state medical university. LA - rus PT - English Abstract PT - Journal Article PT - Review DEP - 20230630 PL - Russia (Federation) TA - Probl Endokrinol (Mosk) JT - Problemy endokrinologii JID - 0140673 SB - IM MH - Humans MH - Body Mass Index MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - *Drug-Related Side Effects and Adverse Reactions MH - Obesity/complications/drug therapy MH - Overweight MH - Weight Loss PMC - PMC10350618 EDAT- 2023/07/14 13:08 MHDA- 2023/07/17 06:42 PMCR- 2023/06/30 CRDT- 2023/07/14 02:53 PHST- 2022/11/17 00:00 [received] PHST- 2023/01/17 00:00 [accepted] PHST- 2023/01/16 00:00 [revised] PHST- 2023/07/17 06:42 [medline] PHST- 2023/07/14 13:08 [pubmed] PHST- 2023/07/14 02:53 [entrez] PHST- 2023/06/30 00:00 [pmc-release] AID - 10.14341/probl13197 [doi] PST - epublish SO - Probl Endokrinol (Mosk). 2023 Jun 30;69(3):68-82. doi: 10.14341/probl13197. PMID- 37445623 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20230718 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 13 DP - 2023 Jun 21 TI - Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials. LID - 10.3390/ijms241310449 [doi] LID - 10449 AB - Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation diseases, depression, and others, which have a negative impact on health and increase morbidity and mortality. GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. This review summarizes numerous studies conducted on the main drugs in the GLP-1 agonists class, outlining the maximum achievable weight loss. Our aim is to emphasize the active role and main outcomes of GLP-1 agonists in promoting weight loss, as well as in improving hyperglycemia, insulin sensitivity, blood pressure, cardio-metabolic, and renal protection. We highlight the pleiotropic effects of these medications, along with their indications, contraindications, and precautions for both diabetic and non-diabetic patients, based on long-term follow-up studies. FAU - Popoviciu, Mihaela-Simona AU - Popoviciu MS AD - Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410073 Oradea, Romania. FAU - Paduraru, Lorena AU - Paduraru L AD - Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410073 Oradea, Romania. FAU - Yahya, Galal AU - Yahya G AUID- ORCID: 0000-0002-9466-7863 AD - Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Al Sharqia 44519, Egypt. AD - Department of Molecular Genetics, Faculty of Biology, Technical University of Kaiserslautern, Paul-Ehrlich Str. 24, 67663 Kaiserslautern, Germany. FAU - Metwally, Kamel AU - Metwally K AD - Department of Medicinal Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia. AD - Department of Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt. FAU - Cavalu, Simona AU - Cavalu S AUID- ORCID: 0000-0001-7810-8925 AD - Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410073 Oradea, Romania. LA - eng PT - Journal Article PT - Review DEP - 20230621 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications MH - Hypoglycemic Agents/therapeutic use MH - Exenatide MH - Glucagon-Like Peptide 1/therapeutic use MH - Peptides/pharmacology MH - Glucagon-Like Peptide-1 Receptor MH - Obesity/drug therapy/complications MH - Weight Loss MH - Liraglutide/therapeutic use MH - Randomized Controlled Trials as Topic PMC - PMC10341852 OTO - NOTNLM OT - GLP-1 agonists OT - Lixisenatide OT - exenatide OT - liraglutide OT - obesity OT - semaglutide OT - tirzepatide OT - type 2 diabetes OT - weight loss COIS- The authors declare no conflict of interest. EDAT- 2023/07/14 13:05 MHDA- 2023/07/17 06:41 PMCR- 2023/06/21 CRDT- 2023/07/14 01:12 PHST- 2023/05/01 00:00 [received] PHST- 2023/06/13 00:00 [revised] PHST- 2023/06/20 00:00 [accepted] PHST- 2023/07/17 06:41 [medline] PHST- 2023/07/14 13:05 [pubmed] PHST- 2023/07/14 01:12 [entrez] PHST- 2023/06/21 00:00 [pmc-release] AID - ijms241310449 [pii] AID - ijms-24-10449 [pii] AID - 10.3390/ijms241310449 [doi] PST - epublish SO - Int J Mol Sci. 2023 Jun 21;24(13):10449. doi: 10.3390/ijms241310449. PMID- 37442659 OWN - NLM STAT- MEDLINE DCOM- 20230904 LR - 20260127 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 45 IP - 8 DP - 2023 Aug TI - Fathoming the Role of Semaglutide in Obesity Therapeutics. PG - 804-805 LID - S0149-2918(23)00228-X [pii] LID - 10.1016/j.clinthera.2023.06.021 [doi] FAU - George, Melvin AU - George M AD - Clinical Pharmacology, SRM Medical College Hospital and Research Centre, Kattankulathur, Tamil Nadu, India. Electronic address: melvingeorge2003@gmail.com. FAU - Balachandran, Karthik AU - Balachandran K AD - Endocrinology, Sri Ramachandra Medical College and Research Institute, Chennai, Tamil Nadu, India. FAU - Jinson, Juanna AU - Jinson J AD - Clinical Pharmacology, SRM Medical College Hospital and Research Centre, Kattankulathur, Tamil Nadu, India. LA - eng PT - Letter DEP - 20230711 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Semaglutide COIS- Declaration of Competing Interest The authors have no conflicts of interest to declare. We have not received grants or other funding from Novo Nordisk or any other agency directly or indirectly related to the drug discussed in this article. None of the authors hold any shares with the above mentioned pharmaceutical company. EDAT- 2023/07/14 13:06 MHDA- 2023/09/04 06:42 CRDT- 2023/07/13 21:57 PHST- 2023/04/13 00:00 [received] PHST- 2023/06/07 00:00 [revised] PHST- 2023/06/23 00:00 [accepted] PHST- 2023/09/04 06:42 [medline] PHST- 2023/07/14 13:06 [pubmed] PHST- 2023/07/13 21:57 [entrez] AID - S0149-2918(23)00228-X [pii] AID - 10.1016/j.clinthera.2023.06.021 [doi] PST - ppublish SO - Clin Ther. 2023 Aug;45(8):804-805. doi: 10.1016/j.clinthera.2023.06.021. Epub 2023 Jul 11. PMID- 37440751 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20260127 IS - 1532-0650 (Electronic) IS - 0002-838X (Linking) VI - 108 IP - 1 DP - 2023 Jul TI - Semaglutide Once Weekly Helps Adolescents Lose Weight, but 4% Developed Acute Cholelithiasis. PG - Online FAU - Ebell, Mark H AU - Ebell MH AD - University of Georgia, Athens, Ga. LA - eng PT - Journal Article PL - United States TA - Am Fam Physician JT - American family physician JID - 1272646 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Adolescent MH - *Hypoglycemic Agents MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides/therapeutic use MH - Weight Loss MH - Body Weight MH - Semaglutide EDAT- 2023/07/13 19:14 MHDA- 2023/07/17 06:42 CRDT- 2023/07/13 15:13 PHST- 2023/07/17 06:42 [medline] PHST- 2023/07/13 19:14 [pubmed] PHST- 2023/07/13 15:13 [entrez] AID - e2f1bfd6-1313-4e51-8470-753c0cebe225 [pii] PST - ppublish SO - Am Fam Physician. 2023 Jul;108(1):Online. PMID- 37430117 OWN - NLM STAT- MEDLINE DCOM- 20230904 LR - 20250103 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 66 IP - 10 DP - 2023 Oct TI - Incretin hormones and type 2 diabetes. PG - 1780-1795 LID - 10.1007/s00125-023-05956-x [doi] AB - Incretin hormones (glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide-1 [GLP-1]) play a role in the pathophysiology of type 2 diabetes. Along with their derivatives they have shown therapeutic success in type 2 diabetes, with the potential for further improvements in glycaemic, cardiorenal and body weight-related outcomes. In type 2 diabetes, the incretin effect (greater insulin secretory response after oral glucose than with 'isoglycaemic' i.v. glucose, i.e. with an identical glycaemic stimulus) is markedly reduced or absent. This appears to be because of a reduced ability of GIP to stimulate insulin secretion, related either to an overall impairment of beta cell function or to specific defects in the GIP signalling pathway. It is likely that a reduced incretin effect impacts on postprandial glycaemic excursions and, thus, may play a role in the deterioration of glycaemic control. In contrast, the insulinotropic potency of GLP-1 appears to be much less impaired, such that exogenous GLP-1 can stimulate insulin secretion, suppress glucagon secretion and reduce plasma glucose concentrations in the fasting and postprandial states. This has led to the development of incretin-based glucose-lowering medications (selective GLP-1 receptor agonists or, more recently, co-agonists, e.g. that stimulate GIP and GLP-1 receptors). Tirzepatide (a GIP/GLP-1 receptor co-agonist), for example, reduces HbA(1c) and body weight in individuals with type 2 diabetes more effectively than selective GLP-1 receptor agonists (e.g. semaglutide). The mechanisms by which GIP receptor agonism may contribute to better glycaemic control and weight loss after long-term exposure to tirzepatide are a matter of active research and may change the pessimistic view that developed after the disappointing lack of insulinotropic activity in people with type 2 diabetes when exposed to GIP in short-term experiments. Future medications that stimulate incretin hormone and other receptors simultaneously may have the potential to further increase the ability to control plasma glucose concentrations and induce weight loss. CI - (c) 2023. The Author(s). FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes, Endocrinology, Metabolism Section, Medical Department I, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany. michael.nauck@rub.de. AD - Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. michael.nauck@rub.de. FAU - Muller, Timo D AU - Muller TD AD - Institute for Diabetes and Obesity, Helmholtz Munchen, Neuherberg, Germany. AD - German Center for Diabetes Research (DZD), Munchen Neuherberg, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20230711 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Incretins) RN - 0 (Blood Glucose) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - IY9XDZ35W2 (Glucose) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Blood Glucose/metabolism MH - Gastric Inhibitory Polypeptide/metabolism MH - Glucagon-Like Peptide 1/metabolism MH - Glucose/metabolism MH - Body Weight MH - Weight Loss MH - Insulin/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10474001 OTO - NOTNLM OT - Body weight regulation OT - Gastric emptying OT - Gastric inhibitory polypeptide OT - Glucagon secretion OT - Glucagon-like peptide-1 OT - Glucose-dependent insulinotropic polypeptide OT - Incretin OT - Insulin secretion OT - Review OT - Type 2 diabetes EDAT- 2023/07/11 01:07 MHDA- 2023/09/04 06:43 PMCR- 2023/07/11 CRDT- 2023/07/10 23:31 PHST- 2023/02/10 00:00 [received] PHST- 2023/05/04 00:00 [accepted] PHST- 2023/09/04 06:43 [medline] PHST- 2023/07/11 01:07 [pubmed] PHST- 2023/07/10 23:31 [entrez] PHST- 2023/07/11 00:00 [pmc-release] AID - 10.1007/s00125-023-05956-x [pii] AID - 5956 [pii] AID - 10.1007/s00125-023-05956-x [doi] PST - ppublish SO - Diabetologia. 2023 Oct;66(10):1780-1795. doi: 10.1007/s00125-023-05956-x. Epub 2023 Jul 11. PMID- 37424165 OWN - NLM STAT- MEDLINE DCOM- 20231004 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 11 DP - 2023 Nov TI - A model-based approach to predict individual weight loss with semaglutide in people with overweight or obesity. PG - 3171-3180 LID - 10.1111/dom.15211 [doi] AB - AIMS: To determine the relationship between exposure and weight-loss trajectories for the glucagon-like peptide-1 analogue semaglutide for weight management. MATERIALS AND METHODS: Data from one 52-week, phase 2, dose-ranging trial (once-daily subcutaneous semaglutide 0.05-0.4 mg) and two 68-week phase 3 trials (once-weekly subcutaneous semaglutide 2.4 mg) for weight management in people with overweight or obesity with or without type 2 diabetes were used to develop a population pharmacokinetic (PK) model describing semaglutide exposure. An exposure-response model describing weight change was then developed using baseline demographics, glycated haemoglobin and PK data during treatment. The ability of the exposure-response model to predict 1-year weight loss based on weight data collected at baseline and after up to 28 weeks of treatment, was assessed using three independent phase 3 trials. RESULTS: Based on population PK, exposure levels over time consistently explained the weight-loss trajectories across trials and dosing regimens. The exposure-response model had high precision and limited bias for predicting body weight loss at 1 year in independent datasets, with increased precision when data from later time points were included in the prediction. CONCLUSION: An exposure-response model has been established that quantitatively describes the relationship between systemic semaglutide exposure and weight loss and predicts weight-loss trajectories for people with overweight or obesity who are receiving semaglutide doses up to 2.4 mg once weekly. CI - (c) 2023 Novo Nordisk A/S. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Strathe, Anders AU - Strathe A AUID- ORCID: 0000-0002-1598-2591 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Horn, Deborah B AU - Horn DB AUID- ORCID: 0000-0003-3493-9609 AD - University of Texas McGovern Medical School, Houston, Texas, USA. FAU - Larsen, Malte Selch AU - Larsen MS AUID- ORCID: 0000-0002-8146-1399 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rubino, Domenica AU - Rubino D AUID- ORCID: 0000-0002-3072-2819 AD - Washington Center for Weight Management, Arlington, Virginia, USA. FAU - Sorrig, Rasmus AU - Sorrig R AUID- ORCID: 0000-0002-0059-1555 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Tran, Marie Thi Dao AU - Tran MTD AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - York University, McMaster University and Wharton Weight Management Clinic, Toronto, Ontario, Canada. FAU - Overgaard, Rune Viig AU - Overgaard RV AUID- ORCID: 0000-0001-7095-4270 AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230709 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Overweight/complications/drug therapy MH - Weight Loss MH - Glucagon-Like Peptides/adverse effects MH - Obesity/complications/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - Semaglutide OTO - NOTNLM OT - GLP-1 analogue OT - clinical trial OT - dose-response relationship OT - pharmacodynamics OT - pharmacokinetics OT - semaglutide EDAT- 2023/07/10 06:42 MHDA- 2023/10/04 06:43 CRDT- 2023/07/10 02:01 PHST- 2023/06/15 00:00 [revised] PHST- 2023/03/30 00:00 [received] PHST- 2023/06/22 00:00 [accepted] PHST- 2023/10/04 06:43 [medline] PHST- 2023/07/10 06:42 [pubmed] PHST- 2023/07/10 02:01 [entrez] AID - 10.1111/dom.15211 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Nov;25(11):3171-3180. doi: 10.1111/dom.15211. Epub 2023 Jul 9. PMID- 37417602 OWN - NLM STAT- MEDLINE DCOM- 20230712 LR - 20260127 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 102 IP - 27 DP - 2023 Jul 7 TI - Comparative efficacy and safety of glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes: A network meta-analysis. PG - e34122 LID - 10.1097/MD.0000000000034122 [doi] LID - e34122 AB - INTRODUCTION: This study aimed to evaluate the clinical efficacy and safety of 4 weekly formulations of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on glycemic control, including glycemic control, by using a network meta-analysis (NMA). METHODS: PubMed, EMBASE, and Cochrane Library Central Register of Controlled Trials were searched from inception until June 10, 2022. Randomized clinical trials (RCTs) enrolling participants with diabetes mellitus type 2 and a follow-up of at least 12 weeks were included, for which 4 eligible GLP-1RAs Exenatide, Dulaglutide, Semaglutide, Loxenatide were compared with either each other or placebo. The primary outcome is the change of hemoglobin A1c level. Secondary outcomes including additional glycemic control indicators and adverse events (AE). Frequentist random-effect NMA were conducted for effect comparison. This meta-analysis was registered on PROSPERO, CRD42022342241. RESULTS: The NMA synthesized evidence from 12 studies covering 6213 patients and 10 GLP-1RA regimens. A pairwise comparison of glycosylated hemoglobin type A1C (HbA1c) lowering effects showed that once-weekly GLP-1 receptor agonists were significantly better than placebo, and their glucose-lowering intensity was Semaglutide 2.0mg, Semaglutide 1.0mg, Dulaglutide 4.5mg, and Semaglutide 0.5mg, Dulaglutide 3.0mg, PEX168 200ug, Dulaglutide 1.5mg, PEX168 100ug and Dulaglutide 0.75mg. The GLP-1RA regimen has a comparable safety profile for hypoglycemia. And with the exception of PEX168, all other long-acting GLP-1RA drugs had lower rates of diarrhea, nausea and vomiting than placebo. CONCLUSION: Regimens of GLP-1RAs had differential glycemic control. The efficacy and safety of Semaglutide 2.0mg in comprehensively lowering blood sugar showed the best performance. CI - Copyright (c) 2023 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Chen, Han AU - Chen H AUID- ORCID: 0000-0002-1525-392 AD - Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, People's Republic of China. FAU - Li, Xin-Zhu AU - Li XZ AD - Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China. FAU - Chen, Jia-Qing AU - Chen JQ AD - Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China. FAU - Ren, Tian-Shu AU - Ren TS AD - Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, People's Republic of China. AD - Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China. FAU - Zhang, Ying-Shi AU - Zhang YS AD - Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China. FAU - Wang, Yi-Nuo AU - Wang YN AD - Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China. FAU - Zhao, Qing-Chun AU - Zhao QC AUID- ORCID: 0000-0001-9256-9971 AD - Department of Pharmacy, General Hospital of Northern Theater Command, Shenyang, People's Republic of China. AD - Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China. LA - eng PT - Journal Article PT - Network Meta-Analysis PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (polyethylene glycol loxenatide) RN - 0 (Peptides) RN - 3WJQ0SDW1A (Polyethylene Glycols) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Peptides MH - Polyethylene Glycols PMC - PMC10328610 COIS- The authors have no funding and conflicts of interest to disclose. EDAT- 2023/07/07 13:05 MHDA- 2023/07/10 06:42 PMCR- 2023/07/07 CRDT- 2023/07/07 08:03 PHST- 2023/07/10 06:42 [medline] PHST- 2023/07/07 13:05 [pubmed] PHST- 2023/07/07 08:03 [entrez] PHST- 2023/07/07 00:00 [pmc-release] AID - 00005792-202307070-00013 [pii] AID - 10.1097/MD.0000000000034122 [doi] PST - ppublish SO - Medicine (Baltimore). 2023 Jul 7;102(27):e34122. doi: 10.1097/MD.0000000000034122. PMID- 37415503 OWN - NLM STAT- MEDLINE DCOM- 20230822 LR - 20260127 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 39 IP - 8 DP - 2023 Aug TI - Semaglutide versus tirzepatide for people with type 2 diabetes: cost of glycemic control in Austria, the Netherlands, Lithuania, and the United Arab Emirates. PG - 1055-1060 LID - 10.1080/03007995.2023.2231275 [doi] AB - OBJECTIVES: The glucagon-like peptide-1 agonist semaglutide and the dual glucose-dependent insulinotropic polypeptide tirzepatide have proven to significantly reduce glucose levels in people with type 2 diabetes. However, the costs needed to achieve a sustained decrease in HbA1c level and disease control with semaglutide and tirzepatide, respectively, are unclear. Therefore, this study aimed to compare the cost of treatment with semaglutide with the cost of treatment with tirzepatide for type 2 diabetes in Austria, the Netherlands, Lithuania, and the United Arab Emirates in order to determine their respective value for money. METHODS: The primary outcome of this analysis was the cost in euros needed to achieve disease control in one person with type 2 diabetes based on the composite endpoint of HbA1c <7%, >/=5% weight loss, and no hypoglycemic events. In addition, analyses regarding the cost needed to reach relevant HbA1c endpoints were performed. Clinical data were obtained from the SURPASS 2 trial, registered at clinicaltrials.gov (NCT03987919), and drug cost was based on wholesale acquisition cost or pharmacy purchase prices from public domains obtained in Q1 of 2023. RESULTS: The cost needed to achieve disease control in one person with type 2 diabetes (HbA1c <7%, >/=5% weight loss, and no hypoglycemic events) was up to three times lower using semaglutide compared with all three doses of tirzepatide in most markets. In the HbA1c analyses, semaglutide was also found to be the least expensive treatment option. CONCLUSION: Semaglutide provides better value for money than tirzepatide for HbA1c-lowering endpoints. FAU - Reitzel, Signe Baattrup AU - Reitzel SB AUID- ORCID: 0000-0002-2839-4510 AD - Department of Economics, EY Denmark, Frederiksberg, Denmark. FAU - Bogelund, Mette AU - Bogelund M AUID- ORCID: 0000-0003-0866-9414 AD - Department of Economics, EY Denmark, Frederiksberg, Denmark. FAU - Basse, Amaury AU - Basse A AUID- ORCID: 0009-0006-2412-8799 AD - Middle East & Africa, Novo Nordisk Region South East Europe, Zurich, Switzerland. FAU - Barszczewska, Olga AU - Barszczewska O AUID- ORCID: 0000-0002-5953-7414 AD - Middle East & Africa, Novo Nordisk Region South East Europe, Zurich, Switzerland. FAU - Ren, Hongye AU - Ren H AUID- ORCID: 0000-0003-0080-4765 AD - Middle East & Africa, Novo Nordisk Region North West Europe, Copenhagen S, Denmark. LA - eng SI - ClinicalTrials.gov/NCT03987919 PT - Journal Article DEP - 20230710 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - IY9XDZ35W2 (Glucose) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - Glycemic Control MH - Austria MH - Lithuania MH - Netherlands MH - United Arab Emirates MH - Hypoglycemic Agents/therapeutic use MH - Weight Loss MH - Glucagon-Like Peptide 1 MH - Glucose MH - Tirzepatide MH - Semaglutide OTO - NOTNLM OT - Diabetes mellitus OT - cost of control OT - glycemic control OT - treatment cost OT - type 2 EDAT- 2023/07/07 06:42 MHDA- 2023/08/22 06:42 CRDT- 2023/07/07 03:15 PHST- 2023/08/22 06:42 [medline] PHST- 2023/07/07 06:42 [pubmed] PHST- 2023/07/07 03:15 [entrez] AID - 10.1080/03007995.2023.2231275 [doi] PST - ppublish SO - Curr Med Res Opin. 2023 Aug;39(8):1055-1060. doi: 10.1080/03007995.2023.2231275. Epub 2023 Jul 10. PMID- 37402640 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20260127 IS - 1527-330X (Electronic) IS - 1090-820X (Linking) VI - 44 IP - 1 DP - 2023 Dec 14 TI - Public Interest in the Off-Label Use of Glucagon-like Peptide 1 Agonists (Ozempic) for Cosmetic Weight Loss: A Google Trends Analysis. PG - 60-67 LID - 10.1093/asj/sjad211 [doi] AB - Glucagon-like peptide 1 (GLP-1) agonists are a drug class used for the treatment of diabetes that have recently gained FDA approval for medical management of obesity. The off-label use of Ozempic (Novo Nordisk, Bagsvaerd, Denmark), the brand name of the GLP-1 agonist semaglutide, for cosmetic weight loss has been popularized by social media and celebrity influence. The aim of this study was to analyze with Google Trends (Alphabet Inc., Mountain View, CA) the recent search popularity of Ozempic and related GLP-1 agonists. The term "Ozempic" was analyzed with Google Trends. Search popularity was assessed in terms of relative search volume (RSV) over a 5-year period. Changes in RSV were further compared with other GLP-1 agonists, "Wegovy" (Novo NordisK) and "Mounjaro" (Eli Lilly and Company, Indianapolis, IN). Between March 2018 and February 2023, overall RSV in "Ozempic" grew exponentially in the United States. Simple linear regression analysis showed significantly increased RSV over time with an R2 of 0.915 and a regression coefficient of 0.957 (P < .001). When comparing "Ozempic," "Wegovy," and "Mounjaro" since June 2021 (FDA approval of Wegovy), Ozempic remained at the greatest RSV. One-way analysis of variance found statistically significant differences between the 3 search terms at all time points between December 2021 and February 2023 (P < .001). This study demonstrates a significant and growing public interest in Ozempic and related GLP-1 agonists. As the use of GLP-1 agonists for weight loss becomes more prevalent, plastic surgeons, particularly in the aesthetic setting, must be prepared for the downstream implications. Increased awareness, understanding, and further scientific studies led by plastic surgeons will help deliver the safest possible patient outcomes. CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Han, Sabrina H AU - Han SH FAU - Safeek, Rachel AU - Safeek R FAU - Ockerman, Kyle AU - Ockerman K FAU - Trieu, Nhan AU - Trieu N FAU - Mars, Patricia AU - Mars P FAU - Klenke, Audrey AU - Klenke A FAU - Furnas, Heather AU - Furnas H FAU - Sorice-Virk, Sarah AU - Sorice-Virk S LA - eng PT - Journal Article PL - England TA - Aesthet Surg J JT - Aesthetic surgery journal JID - 9707469 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Aesthet Surg J. 2023 Dec 14;44(1):80-83. doi: 10.1093/asj/sjad263. PMID: 37610239 MH - Humans MH - United States MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Off-Label Use MH - Search Engine MH - Weight Loss MH - Glucagon-Like Peptide 1/therapeutic use MH - Semaglutide EDAT- 2023/07/05 01:06 MHDA- 2023/12/17 09:45 CRDT- 2023/07/04 22:33 PHST- 2023/12/17 09:45 [medline] PHST- 2023/07/05 01:06 [pubmed] PHST- 2023/07/04 22:33 [entrez] AID - 7218900 [pii] AID - 10.1093/asj/sjad211 [doi] PST - ppublish SO - Aesthet Surg J. 2023 Dec 14;44(1):60-67. doi: 10.1093/asj/sjad211. PMID- 37385279 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 402 IP - 10403 DP - 2023 Aug 26 TI - Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial. PG - 693-704 LID - S0140-6736(23)01127-3 [pii] LID - 10.1016/S0140-6736(23)01127-3 [doi] AB - BACKGROUND: Once-daily oral semaglutide is an effective type 2 diabetes treatment. We aimed to investigate a new formulation of oral semaglutide at higher investigational doses versus the approved 14 mg dose in adults with inadequately controlled type 2 diabetes. METHODS: This global, multicentre, randomised, double-blind, phase 3b trial, carried out at 177 sites in 14 countries, enrolled adults with type 2 diabetes, glycated haemoglobin (HbA(1c)) 8.0-10.5% (64-91 mmol/mol), a BMI of 25.0 kg/m(2) or greater, receiving stable daily doses of one to three oral glucose-lowering drugs. Participants were randomly assigned (1:1:1), by means of an interactive web response system, to once-daily oral semaglutide 14 mg, 25 mg, or 50 mg for 68 weeks. Investigators, site personnel, trial participants, and trial sponsor staff were masked to dose assignment throughout the trial. The primary endpoint was change in HbA(1c) from baseline to week 52, evaluated with a treatment policy estimand in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of trial drug. This trial is registered with ClinicalTrials.gov, NCT04707469, and the European Clinical Trials register, EudraCT 2020-000299-39, and is complete. FINDINGS: Between Jan 15 and Sept 29, 2021, of 2294 people screened, 1606 (n=936 [58.3%] male; n=670 [41.7%] female; mean [SD] age 58.2 [10.8] years) received oral semaglutide 14 mg (n=536), 25 mg (n=535), or 50 mg (n=535). At baseline, mean (SD) HbA(1c) was 9.0% (0.8; 74.4 mmol/L [SD 8.3]) and mean bodyweight was 96.4 kg (21.6). Mean changes (SE) in HbA(1c) at week 52 were -1.5 percentage points (SE 0.05) with oral semaglutide 14 mg, -1.8 percentage points (0.06) with 25 mg (estimated treatment difference [ETD] -0.27, 95% CI -0.42 to -0.12; p=0.0006), and -2.0 percentage points (0.06) with 50 mg (ETD -0.53, -0.68 to -0.38; p<0.0001). Adverse events were reported by 404 (76%) participants in the oral semaglutide 14 mg group, 422 (79%) in the 25 mg group, and 428 (80%) in the 50 mg group. Gastrointestinal disorders, which were mostly mild to moderate, occurred more frequently with oral semaglutide 25 mg and 50 mg than with 14 mg. Ten deaths occurred during the trial; none were judged to be treatment related. INTERPRETATION: Oral semaglutide 25 mg and 50 mg were superior to 14 mg in reducing HbA(1c) and bodyweight in adults with inadequately controlled type 2 diabetes. No new safety concerns were identified. FUNDING: Novo Nordisk. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Aroda, Vanita R AU - Aroda VR AD - Department of Medicine, Division of Endocrinology, Diabetes & Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: varoda@bwh.harvard.edu. FAU - Aberle, Jens AU - Aberle J AD - Department of Endocrinology and Diabetes, University Medical Center Hamburg Eppendorf, Hamburg, Germany. FAU - Bardtrum, Lars AU - Bardtrum L AD - Novo Nordisk, Soborg, Denmark. FAU - Christiansen, Erik AU - Christiansen E AD - Novo Nordisk, Soborg, Denmark. FAU - Knop, Filip K AU - Knop FK AD - Center for Clinical Metabolic Research, Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark; Department of Clinical Medicine and Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Gabery, Sanaz AU - Gabery S AD - Novo Nordisk, Soborg, Denmark. FAU - Pedersen, Sue D AU - Pedersen SD AD - C-ENDO Diabetes & Endocrinology Clinic Calgary, Calgary, AB, Canada. FAU - Buse, John B AU - Buse JB AD - Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. LA - eng SI - ClinicalTrials.gov/NCT04707469 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20230626 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet. 2023 Aug 26;402(10403):668-669. doi: 10.1016/S0140-6736(23)01233-3. PMID: 37385277 MH - Humans MH - Male MH - Adult MH - Female MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides MH - Treatment Outcome MH - Double-Blind Method MH - Body Weight MH - Semaglutide COIS- Declaration of interests VRA reports receiving consultancy fees from Applied Therapeutics, Fractyl, Novo Nordisk, Pfizer, and Sanofi, and research grant support (to their institution) from Applied Therapeutics, Eli Lilly, Fractyl, Novo Nordisk, and Sanofi. LB, EC, and SG are employees and shareholders in Novo Nordisk. JA reports consulting fees or speaking honoraria from Astra Zeneca, Boehringer Ingelheim, Lilly, and Novo Nordisk. FKK reports participating in scientific advisory panels or speakers' bureaus for, consulting fees, or receiving research support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, Lupin, MedImmune, MSD-Merck, Mundipharma, Norgine, Novo Nordisk, Pharmacosmos, Sanofi, ShouTi, Zealand Pharma, and Zucara; is a minority shareholder in Antag Therapeutics, and co-owner of the weight loss clinic Medicinsk Vaegttabsbehandling ApS. SDP reports consulting fees or speaking honoraria from Abbott, AstraZeneca, Bausch, Bayer, Boehringer Ingelheim, Dexcom, HLS, Janssen, Lilly, Merck, Novo Nordisk, Pfizer, and Sanofi; and research studies for AstraZeneca, Boehringer Ingelheim, Lilly, Medpace, and Novo Nordisk. JBB contracted consulting fees and travel support for contracted activities that are paid to the University of North Carolina by Novo Nordisk and vTv Therapeutics; has received grant support from Dexcom, NovaTarg, Novo Nordisk, Sanofi, Tolerion, and vTv Therapeutics; has received personal compensation for consultation from Alkahest, Altimmune, Anji, AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, CeQur, Cirius Therapeutics, Corcept Therapeutics, Dasman Diabetes Institute (Kuwait), Eli Lilly, Fortress Biotech, GentiBio, Glycadia, Glyscend, Janssen, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, Sanofi, Stability Health, Terns, and Valo; has received payment for expert testimony from Medtronic; and in lieu of payment for consultation he has received stock or options in Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego, and Stability Health. EDAT- 2023/06/30 01:06 MHDA- 2023/08/28 06:43 CRDT- 2023/06/29 18:52 PHST- 2023/05/15 00:00 [received] PHST- 2023/05/26 00:00 [revised] PHST- 2023/05/30 00:00 [accepted] PHST- 2023/08/28 06:43 [medline] PHST- 2023/06/30 01:06 [pubmed] PHST- 2023/06/29 18:52 [entrez] AID - S0140-6736(23)01127-3 [pii] AID - 10.1016/S0140-6736(23)01127-3 [doi] PST - ppublish SO - Lancet. 2023 Aug 26;402(10403):693-704. doi: 10.1016/S0140-6736(23)01127-3. Epub 2023 Jun 26. PMID- 37385277 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 402 IP - 10403 DP - 2023 Aug 26 TI - The pursuit of optimal semaglutide dosing in type 2 diabetes continues. PG - 668-669 LID - S0140-6736(23)01233-3 [pii] LID - 10.1016/S0140-6736(23)01233-3 [doi] FAU - Sherrill, Christina H AU - Sherrill CH AD - Department of Clinical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC, USA. Electronic address: csherril@highpoint.edu. FAU - Hwang, Andrew Y AU - Hwang AY AD - Department of Pharmacy Practice, School of Pharmacy, MCPHS University, Boston, MA, USA. LA - eng PT - Comment PT - Journal Article DEP - 20230626 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - Lancet. 2023 Aug 26;402(10403):693-704. doi: 10.1016/S0140-6736(23)01127-3. PMID: 37385279 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide COIS- CHS holds grants from the National Association of Chain Drug Stores Foundation and American Association of Colleges of Pharmacy. CHS has received honoraria from Pharmacy Times Continuing Education (PTCE) through grants that PTCE received from Abbott, but her work for PTCE was not reviewed or influenced by Abbott. AYH declares no competing interests. EDAT- 2023/06/30 01:06 MHDA- 2023/08/28 06:42 CRDT- 2023/06/29 18:52 PHST- 2023/06/05 00:00 [received] PHST- 2023/06/13 00:00 [accepted] PHST- 2023/08/28 06:42 [medline] PHST- 2023/06/30 01:06 [pubmed] PHST- 2023/06/29 18:52 [entrez] AID - S0140-6736(23)01233-3 [pii] AID - 10.1016/S0140-6736(23)01233-3 [doi] PST - ppublish SO - Lancet. 2023 Aug 26;402(10403):668-669. doi: 10.1016/S0140-6736(23)01233-3. Epub 2023 Jun 26. PMID- 37369232 OWN - NLM STAT- MEDLINE DCOM- 20230807 LR - 20240629 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 402 IP - 10400 DP - 2023 Aug 5 TI - Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study. PG - 472-483 LID - S0140-6736(23)01302-8 [pii] LID - 10.1016/S0140-6736(23)01302-8 [doi] AB - BACKGROUND: Orforglipron, an oral, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist, is in development for type 2 diabetes and obesity. We assessed the efficacy and safety of orforglipron versus placebo or dulaglutide in participants with type 2 diabetes. METHODS: In this 26-week, phase 2, double-blind, randomised, multicentre study, participants were recruited from 45 centres (private clinics, hospitals, and research centers) in the USA, Hungary, Poland, and Slovakia. Adult participants aged 18 years or older with type 2 diabetes treated with diet and exercise, with or without metformin, and with a glycated haemoglobin (HbA(1c)) of 7.0-10.5%, and stable BMI of 23 kg/m(2) or more, were randomly assigned (5:5:5:5:5:3:3:3:3) via an interactive web-response system to placebo, dulaglutide 1.5 mg once per week, or orforglipron 3 mg, 12 mg, 24 mg, 36 mg (group 1), 36 mg (group 2), 45 mg (group 1), or 45 mg (group 2) once per day with no food or water restrictions. Two different dose escalation regimens were evaluated for each of the 36 mg and 45 mg cohorts. Participants were masked to the study drug, dulaglutide, and placebo. The primary efficacy outcome The primary efficacy outcome was mean change in HbA(1c) from baseline with orforglipron versus placebo at week 26. Efficacy was analysed in all randomly assigned participants who received at least one dose of study drug and excluded data after the permanent discontinuation of study drug or initiation of rescue medication. Safety was analysed in all participants who received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov (NCT05048719) and is completed. FINDINGS: Between Sept 15, 2021, and Sept 30, 2022, 569 participants were screened and 383 were enrolled and randomly assigned to a group. 352 (92%) completed the study and 303 (79%) completed 26 weeks of treatment. At baseline, the mean age was 58.9 years, HbA(1c) was 8.1%, BMI was 35.2 kg/m(2), 226 (59%) were men, and 157 (41%) were women. At week 26, mean change in HbA(1c) with orforglipron was up to -2.10% (-1.67% placebo adjusted), versus -0.43% with placebo and -1.10% with dulaglutide. HbA(1c) reduction was statistically superior with orforglipron versus placebo (estimated treatment difference -0.8% to -1.7%). Change in mean bodyweight at week 26 was up to -10.1 kg (95% CI -11.5 to -8.7; 7.9 kg placebo adjusted [-9.9 to -5.9]) with orforglipron versus -2.2 kg (-3.6 to -0.7) for placebo and -3.9 kg (-5.3 to -2.4) for dulaglutide. The incidence of treatment-emergent adverse events ranged from 61.8% to 88.9% in orforglipron-treated participants, compared with 61.8% with placebo and 56.0% with dulaglutide. The majority were gastrointestinal events (44.1% to 70.4% with orforglipron, 18.2% with placebo, and 34.0% with dulaglutide) of mild to moderate severity. Three participants receiving orforglipron and one participant receiving dulaglutide had clinically significant (<54 mg/dL [<3 mmol/L]) hypoglycaemia and no participants had severe hypoglycaemia. One death occurred in the placebo group and was not related to study treatment. INTERPRETATION: In this phase 2 trial the novel, oral, non-peptide GLP-1 receptor agonist orforglipron at doses of 12 mg or greater showed significant reductions in HbA(1c) and bodyweight compared with placebo or dulaglutide. The adverse event profile was similar to other GLP-1 receptor agonists in similar stage of development. Orforglipron might provide an alternative to injectable GLP-1 receptor agonists and oral semaglutide, with the prospect of less burdensome administration to achieve treatment goals in people with type 2 diabetes. FUNDING: Eli Lilly and Company. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Frias, Juan P AU - Frias JP AD - Velocity Clinical Research, Los Angeles, CA, USA. FAU - Hsia, Stanley AU - Hsia S AD - Velocity Clinical Research, Huntington Park, CA, USA. FAU - Eyde, Sarah AU - Eyde S AD - Tigermed-BDM, Somerset, NJ, USA. FAU - Liu, Rong AU - Liu R AD - Eli Lilly, Indianapolis, IN, USA. FAU - Ma, Xiaosu AU - Ma X AD - Eli Lilly, Indianapolis, IN, USA. FAU - Konig, Manige AU - Konig M AD - Eli Lilly, Indianapolis, IN, USA. Electronic address: konig_manige@lilly.com. FAU - Kazda, Christof AU - Kazda C AD - Eli Lilly, Indianapolis, IN, USA. FAU - Mather, Kieren J AU - Mather KJ AD - Eli Lilly, Indianapolis, IN, USA. FAU - Haupt, Axel AU - Haupt A AD - Velocity Clinical Research, Los Angeles, CA, USA. FAU - Pratt, Edward AU - Pratt E AD - Velocity Clinical Research, Los Angeles, CA, USA. FAU - Robins, Deborah AU - Robins D AD - Eli Lilly, Indianapolis, IN, USA. LA - eng SI - ClinicalTrials.gov/NCT05048719 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230624 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM CIN - Lancet. 2023 Aug 5;402(10400):429-431. doi: 10.1016/S0140-6736(23)01201-1. PMID: 37369233 EIN - Lancet. 2023 Sep 2;402(10404):774. doi: 10.1016/S0140-6736(23)01811-1. PMID: 37659778 EIN - Lancet. 2024 Jun 29;403(10446):2786. doi: 10.1016/S0140-6736(24)01314-X. PMID: 38944526 MH - Male MH - Adult MH - Humans MH - Female MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptides MH - *Hypoglycemia/chemically induced MH - Body Weight MH - Double-Blind Method COIS- Declaration of interests JPF reports research funding from Akero, AstraZeneca, Boehringer Ingelheim, 89bio, Eli Lilly, Intercept, Ionis, Janssen, Madrigal, Metacrine, Merck, NorthSea Therapeutics, Novartis, Novo Nordisk, Oramed, Pfizer, Poxel, and Sanofi; consulting fees from Akero, Altimmune, Boehringer Ingelheim, Carmot Therapeutics, Echosens, 89bio, Eli Lilly, Merck, Novo Nordisk, Pfizer, and Sanofi; speaker bureau from Eli Lilly; support for attending meetings or travel from Eli Lilly, Novo Nordisk, Pfizer, and Sanofi; participant advisory boards and consulting for Altimmune, Becton Dickinson, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gilead, Intercept, Merck, Novo Nordisk, Pfizer, and Sanofi; and is on the board of directors for T1D Exchange. SH reports research funding from Eli Lilly. SE reports funding from Eli Lilly for statistical services provided by employer Tigermed and travel support from Eli Lilly. RL, XM, MK, CK, KJM, AH, and EP are employees and shareholders of Eli Lilly. DR is a shareholder and retired employee of Eli Lilly. EDAT- 2023/06/28 01:06 MHDA- 2023/08/07 06:42 CRDT- 2023/06/27 18:52 PHST- 2023/08/07 06:42 [medline] PHST- 2023/06/28 01:06 [pubmed] PHST- 2023/06/27 18:52 [entrez] AID - S0140-6736(23)01302-8 [pii] AID - 10.1016/S0140-6736(23)01302-8 [doi] PST - ppublish SO - Lancet. 2023 Aug 5;402(10400):472-483. doi: 10.1016/S0140-6736(23)01302-8. Epub 2023 Jun 24. PMID- 37364710 OWN - NLM STAT- MEDLINE DCOM- 20230807 LR - 20250211 IS - 2212-8778 (Electronic) IS - 2212-8778 (Linking) VI - 75 DP - 2023 Sep TI - Discovery of ecnoglutide - A novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog. PG - 101762 LID - S2212-8778(23)00096-0 [pii] LID - 10.1016/j.molmet.2023.101762 [doi] LID - 101762 AB - OBJECTIVE: Glucagon-like peptide (GLP)-1 is an incretin hormone that acts after food intake to stimulate insulin production, enhance satiety, and promote weight loss. Here we describe the discovery and characterization of ecnoglutide (XW003), a novel GLP-1 analog. METHODS: We engineered a series of GLP-1 peptide analogs with an alanine to valine substitution (Ala8Val) and a gammaGlu-2xAEEA linked C18 diacid fatty acid at various positions. Ecnoglutide was selected and characterized in GLP-1 receptor signaling assays in vitro, as well as in db/db mice and a diet induced obese (DIO) rat model. A Phase 1, double-blind, randomized, placebo-controlled, single (SAD) and multiple ascending dose (MAD) study was conducted to evaluate the safety, tolerability, and pharmacokinetics of subcutaneous ecnoglutide injection in healthy participants. SAD doses ranged from 0.03 to 1.0 mg; MAD doses ranged from 0.2 to 0.6 mg once weekly for 6 weeks (ClinicalTrials.gov Identifier: NCT04389775). RESULTS: In vitro, ecnoglutide potently induced cAMP (EC(50) = 0.018 nM) but not GLP-1 receptor internalization (EC(50) > 10 muM), suggesting a desirable signaling bias. In rodent models, ecnoglutide significantly reduced blood glucose, promoted insulin induction, and led to more pronounced body weight reduction compared to semaglutide. In a Phase 1 trial, ecnoglutide was generally safe and well tolerated as a once-weekly injection for up to 6 weeks. Adverse events included decreased appetite, nausea, and headache. The half-life at steady state ranged from 124 to 138 h, supporting once-weekly dosing. CONCLUSIONS: Ecnoglutide showed a favorable potency, pharmacokinetic, and tolerability profile, as well as a simplified manufacturing process. These results support the continued development of ecnoglutide for the treatment of type 2 diabetes and obesity. CI - Copyright (c) 2023 The Authors. Published by Elsevier GmbH.. All rights reserved. FAU - Guo, Wanjun AU - Guo W AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Xu, Zheng AU - Xu Z AD - Kawin Technology, No. 6 Rongjing East Street, BDA Beijing 100176, China. FAU - Zou, Haixia AU - Zou H AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Li, Feng AU - Li F AD - Kawin Technology, No. 6 Rongjing East Street, BDA Beijing 100176, China. FAU - Li, Yao AU - Li Y AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Feng, Jing AU - Feng J AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Zhu, Zhiyi AU - Zhu Z AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Zheng, Qing AU - Zheng Q AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Zhu, Rui AU - Zhu R AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Wang, Bin AU - Wang B AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Li, Yan AU - Li Y AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Hao, Sujuan AU - Hao S AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Qin, Hong AU - Qin H AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. FAU - Jones, Catherine L AU - Jones CL AD - Sciwind Biosciences, 3001 Bishop Drive, Suite 300, San Ramon, CA 94583, USA. FAU - Adegbite, Eric AU - Adegbite E AD - Sciwind Biosciences, 3001 Bishop Drive, Suite 300, San Ramon, CA 94583, USA. FAU - Telusca, Libnir AU - Telusca L AD - Sciwind Biosciences, 3001 Bishop Drive, Suite 300, San Ramon, CA 94583, USA. FAU - Fenaux, Martijn AU - Fenaux M AD - Sciwind Biosciences, 3001 Bishop Drive, Suite 300, San Ramon, CA 94583, USA. FAU - Zhong, Weidong AU - Zhong W AD - Sciwind Biosciences, 3001 Bishop Drive, Suite 300, San Ramon, CA 94583, USA. FAU - Junaidi, Mohammed K AU - Junaidi MK AD - Sciwind Biosciences, 3001 Bishop Drive, Suite 300, San Ramon, CA 94583, USA. FAU - Xu, Susan AU - Xu S AD - Sciwind Biosciences, 3001 Bishop Drive, Suite 300, San Ramon, CA 94583, USA. FAU - Pan, Hai AU - Pan H AD - Sciwind Biosciences, No. 600 Jinsha Road, Qiantang New District, Hangzhou, Zhejiang 310000, China. Electronic address: hai.pan@sciwindbio.com. LA - eng SI - ClinicalTrials.gov/NCT04389775 PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial DEP - 20230624 PL - Germany TA - Mol Metab JT - Molecular metabolism JID - 101605730 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) SB - IM MH - Animals MH - Mice MH - Rats MH - Body Weight MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1 MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Insulin/therapeutic use MH - Obesity/drug therapy/chemically induced MH - Weight Loss MH - Humans PMC - PMC10339203 OTO - NOTNLM OT - Ecnoglutide OT - Glucagon-like peptide-1 OT - Obesity OT - Peptide analog OT - Phase 1 OT - Type 2 diabetes OT - XW003 COIS- Declaration of competing interest WG, HZ, YL, JF, ZZ, QZ, RZ, BW, YL, SH, HQ, CLJ, EA, LT, MF, WZ, MKJ, SX, and HP are, or were at the time the work was conducted, employees of Sciwind Biosciences. EDAT- 2023/06/27 01:06 MHDA- 2023/08/07 06:42 PMCR- 2023/06/24 CRDT- 2023/06/26 19:21 PHST- 2023/04/17 00:00 [received] PHST- 2023/06/21 00:00 [revised] PHST- 2023/06/22 00:00 [accepted] PHST- 2023/08/07 06:42 [medline] PHST- 2023/06/27 01:06 [pubmed] PHST- 2023/06/26 19:21 [entrez] PHST- 2023/06/24 00:00 [pmc-release] AID - S2212-8778(23)00096-0 [pii] AID - 101762 [pii] AID - 10.1016/j.molmet.2023.101762 [doi] PST - ppublish SO - Mol Metab. 2023 Sep;75:101762. doi: 10.1016/j.molmet.2023.101762. Epub 2023 Jun 24. PMID- 37364590 OWN - NLM STAT- MEDLINE DCOM- 20230828 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 402 IP - 10403 DP - 2023 Aug 26 TI - Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. PG - 720-730 LID - S0140-6736(23)01163-7 [pii] LID - 10.1016/S0140-6736(23)01163-7 [doi] AB - BACKGROUND: Combining the GLP-1 receptor agonist semaglutide with the long-acting amylin analogue cagrilintide has weight-loss benefits; the impact on glycated haemoglobin (HbA(1c)) is unknown. This trial assessed the efficacy and safety of co-administered semaglutide with cagrilintide (CagriSema) in participants with type 2 diabetes. METHODS: This 32-week, multicentre, double-blind, phase 2 trial was conducted across 17 sites in the USA. Adults with type 2 diabetes and a BMI of 27 kg/m(2) or higher on metformin with or without an SGLT2 inhibitor were randomly assigned (1:1:1) to once-weekly subcutaneous CagriSema, semaglutide, or cagrilintide (all escalated to 2.4 mg). Randomisation was done centrally using an interactive web response system and was stratified according to use of SGLT2 inhibitor treatment (yes vs no). The trial participants, investigators, and trial sponsor staff were masked to treatment assignment throughout the trial. The primary endpoint was change from baseline in HbA(1c); secondary endpoints were bodyweight, fasting plasma glucose, continuous glucose monitoring (CGM) parameters, and safety. Efficacy analyses were performed in all participants who had undergone randomisation, and safety analyses in all participants who had undergone randomisation and received at least one dose of the trial medication. This trial is registered on ClinicalTrials.gov (NCT04982575) and is complete. FINDINGS: Between Aug 2 and Oct 18, 2021, 92 participants were randomly assigned to CagriSema (n=31), semaglutide (n=31), or cagrilintide (n=30). 59 (64%) participants were male; the mean age of participants was 58 years (SD 9). The mean change in HbA(1c) from baseline to week 32 (CagriSema: -2.2 percentage points [SE 0.15]; semaglutide: -1.8 percentage points [0.16]; cagrilintide: -0.9 percentage points [0.15]) was greater with CagriSema versus cagrilintide (estimated treatment difference -1.3 percentage points [95% CI -1.7 to -0.8]; p<0.0001), but not versus semaglutide (-0.4 percentage points [-0.8 to 0.0]; p=0.075). The mean change in bodyweight from baseline to week 32 (CagriSema: -15.6% [SE 1.26]; semaglutide: -5.1% [1.26]; cagrilintide: -8.1% [1.23]) was greater with CagriSema versus both semaglutide (p<0.0001) and cagrilintide (p<0.0001). The mean change in fasting plasma glucose from baseline to week 32 (CagriSema: -3.3 mmol/L [SE 0.3]; semaglutide: -2.5 mmol/L [0.4]; cagrilintide: -1.7 mmol/L [0.3]) was greater with CagriSema versus cagrilintide (p=0.0010) but not versus semaglutide (p=0.10). Time in range (3.9-10.0 mmol/L) was 45.9%, 32.6%, and 56.9% at baseline and 88.9%, 76.2%, and 71.7% at week 32 with CagriSema, semaglutide, and cagrilintide, respectively. Adverse events were reported by 21 (68%) participants in the CagriSema group, 22 (71%) in the semaglutide group, and 24 (80%) in the cagrilintide group. Mild or moderate gastrointestinal adverse events were most common; no level 2 or 3 hypoglycaemia was reported. No fatal adverse events were reported. INTERPRETATION: In people with type 2 diabetes, treatment with CagriSema resulted in clinically relevant improvements in glycaemic control (including CGM parameters). The mean change in HbA(1c) with CagriSema was greater versus cagrilintide, but not versus semaglutide. Treatment with CagriSema resulted in significantly greater weight loss versus semaglutide and cagrilintide and was well tolerated. These data support further investigation of CagriSema in this population in longer and larger phase 3 studies. FUNDING: Novo Nordisk. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Frias, Juan P AU - Frias JP AD - Velocity Clinical Research, Los Angeles, CA, USA. Electronic address: jfrias@velocityclinical.com. FAU - Deenadayalan, Srikanth AU - Deenadayalan S AD - Novo Nordisk, Soborg, Denmark. FAU - Erichsen, Lars AU - Erichsen L AD - Novo Nordisk, Soborg, Denmark. FAU - Knop, Filip K AU - Knop FK AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AD - Division of Endocrinology, Department of Internal Medicine and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Macura, Stanislava AU - Macura S AD - Novo Nordisk, Soborg, Denmark. FAU - Mathieu, Chantal AU - Mathieu C AD - Clinical and Experimental Endocrinology, UZ Gasthuisberg, KU Leuven, Leuven, Belgium. FAU - Pedersen, Sue D AU - Pedersen SD AD - C-ENDO Diabetes and Endocrinology Clinic, Calgary, AB, Canada. FAU - Davies, Melanie AU - Davies M AD - Diabetes Research Centre, University of Leicester, Leicester, UK; Leicester NIHR Biomedical Research Centre, Leicester General Hospital, Leicester, UK. LA - eng SI - ClinicalTrials.gov/NCT04982575 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230623 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Islet Amyloid Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) RN - AO43BIF1U8 (cagrilintide) SB - IM CIN - Lancet. 2023 Aug 26;402(10403):671-673. doi: 10.1016/S0140-6736(23)01291-6. PMID: 37364591 MH - Adult MH - Male MH - Humans MH - Middle Aged MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy MH - Islet Amyloid Polypeptide/therapeutic use MH - Hypoglycemic Agents/adverse effects MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Blood Glucose MH - Blood Glucose Self-Monitoring MH - Treatment Outcome MH - Glucagon-Like Peptides MH - Double-Blind Method MH - Semaglutide COIS- Declaration of interests JPF has received research funding (paid to institution) from 89bio, Akero, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Intercept, IONIS, Janssen, Madrigal, Merck, Metacrine, NorthSea Therapeutics, Novartis, Novo Nordisk, Oramed, Pfizer, Poxel, and Sanofi; is involved with advisory boards and consulting for 89bio, Akero, Altimmune, Becton Dickenson, Boehringer Ingelheim, Carmot Therapeutics, Echosens, Eli Lilly, Gilead, Intercept, Merck, Novo Nordisk, Pfizer, and Sanofi; and has received payment or honoraria for speaker bureaus for Eli Lilly. They are seated on the board of directors in T1D Exchange (non-compensated position). SD, LE, and SM are employed at Novo Nordisk and are stockholders of Novo Nordisk shares. FKK has received research grants (paid to institution) from AstraZeneca, Gubra, Novo Nordisk, Sanofi, and Zealand Pharma; and received personal honoraria for consulting, participating in advisory boards, and/or speaking for 89bio, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi, Structure Therapeutics, Zealand Pharma, and Zucara. They are a co-founder and minority shareholder in Antag Therapeutics and co-owner of the medical weight-loss clinic Medicinsk Vaegttabsbehandling ApS. IL has received research funding (paid to institution) from Boehringer Ingelheim, Merck, Mylan, Novo Nordisk, Pfizer, and Sanofi. They received advisory/consulting fees and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GI Dynamics, Intarcia, Intercept, Johnson and Johnson, Mannkind, Merck, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, Shionogi, Structure Therapeutics, TARGETPharma, Valeritas, and Zealand Pharma. CM has received research funding (paid to institution) from the European Commission, FWO, Helmsley Charitable Trust, JDRF, and Novo Nordisk Foundation. They have received honoraria (paid to institution) for consulting, participating in advisory boards, and/or giving lectures/presentations from ActoBio Therapeutics, AstraZeneca, Avotres, Boehringer Ingelheim, Eli Lilly and Company, Imcyse, Insulet, Mannkind, Medtronic, Novartis, Novo Nordisk, Pfizer, Roche, Sandoz, Sanofi, Vertex, and Zealand Pharma; and are Chair of the Board of Hippo and Friends iVZW, Vice President of EUDF, President of EASD, and Chair of the Board of INNODIA iVZW. SDP acted as consultant, advisory board member, and/or speaker for Abbott, AstraZeneca, Bausch, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, HLS, Janssen, Merck, Novo Nordisk, Pfizer, and Sanofi. They are/have been an investigator in clinical trials funded by AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Prometic, and Sanofi. MD has acted as consultant, advisory board member, and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Sanofi; an advisory board member for Lexicon, Medtronic, Pfizer, and ShouTi Pharma; and as a speaker for Amgen, AstraZeneca, Napp Pharmaceuticals, and Novartis. MD has received grants in support of investigator and investigator-initiated trials from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk, and Sanofi-Aventis. EDAT- 2023/06/27 01:06 MHDA- 2023/08/28 06:42 CRDT- 2023/06/26 18:52 PHST- 2023/05/19 00:00 [received] PHST- 2023/06/01 00:00 [revised] PHST- 2023/06/02 00:00 [accepted] PHST- 2023/08/28 06:42 [medline] PHST- 2023/06/27 01:06 [pubmed] PHST- 2023/06/26 18:52 [entrez] AID - S0140-6736(23)01163-7 [pii] AID - 10.1016/S0140-6736(23)01163-7 [doi] PST - ppublish SO - Lancet. 2023 Aug 26;402(10403):720-730. doi: 10.1016/S0140-6736(23)01163-7. Epub 2023 Jun 23. PMID- 37364260 OWN - NLM STAT- MEDLINE DCOM- 20230911 LR - 20260127 IS - 1758-8111 (Electronic) IS - 1758-8103 (Linking) VI - 13 IP - 5 DP - 2023 Oct TI - Sustained weight loss with semaglutide once weekly in patients without type 2 diabetes and post-bariatric treatment failure. PG - e12593 LID - 10.1111/cob.12593 [doi] AB - About 20%-25% of patients experience weight regain (WR) or insufficient weight loss (IWL) following bariatric surgery (BS). Therefore, we aimed to retrospectively assess the effectiveness of adjunct treatment with semaglutide in patients without type 2 diabetes (T2D) with post-bariatric treatment failure over a 12 months period. Post-bariatric patients without T2D with WR or IWL (n = 29) were included in the analysis. The primary endpoint was weight loss 12 months after initiation of adjunct treatment. Secondary endpoints included change in body mass index, HbA1c, lipid profile, high sensitive C-reactive protein and liver enzymes. Total weight loss during semaglutide treatment added up to 14.7% +/- 8.9% (mean +/- SD, p < .001) after 12 months. Categorical weight loss was >5% in 89.7% of patients, >10% in 62.1% of patients, >15% in 34.5% of patients, >20% in 24.1% of patients and > 25% in 17.2% of patients. Adjunct treatment with semaglutide resulted in sustained weight loss regardless of sex, WR or IWL and type of surgery. Among patients with prediabetes (n = 6), 12 months treatment led to normoglycemia in all patients (p < .05). Treatment options to manage post-bariatric treatment failure are scarce. Our results imply a clear benefit of adjunct treatment with semaglutide in post-bariatric patients over a 12 months follow-up period. CI - (c) 2023 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation. FAU - Lautenbach, Anne AU - Lautenbach A AUID- ORCID: 0000-0002-7763-1527 AD - III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Kantowski, Tobias AU - Kantowski T AD - III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Wagner, Jonas AU - Wagner J AD - Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Mann, Oliver AU - Mann O AD - Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Stoll, Fabian AU - Stoll F AD - III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Aberle, Jens AU - Aberle J AD - III Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. LA - eng PT - Journal Article DEP - 20230626 PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Weight Loss MH - *Bariatrics MH - Treatment Failure MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - bariatric surgery OT - semaglutide OT - treatment failure OT - weight regain EDAT- 2023/06/26 19:07 MHDA- 2023/09/11 06:43 CRDT- 2023/06/26 17:03 PHST- 2023/03/10 00:00 [revised] PHST- 2023/01/14 00:00 [received] PHST- 2023/04/06 00:00 [accepted] PHST- 2023/09/11 06:43 [medline] PHST- 2023/06/26 19:07 [pubmed] PHST- 2023/06/26 17:03 [entrez] AID - 10.1111/cob.12593 [doi] PST - ppublish SO - Clin Obes. 2023 Oct;13(5):e12593. doi: 10.1111/cob.12593. Epub 2023 Jun 26. PMID- 37355043 OWN - NLM STAT- MEDLINE DCOM- 20230918 LR - 20260518 IS - 1600-0641 (Electronic) IS - 0168-8278 (Linking) VI - 79 IP - 4 DP - 2023 Oct TI - A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. PG - 888-897 LID - S0168-8278(23)00342-2 [pii] LID - 10.1016/j.jhep.2023.05.013 [doi] AB - BACKGROUND & AIMS: This study assessed the effects of the glucagon-like peptide-1 (GLP-1)/glucagon receptor co-agonist efinopegdutide relative to the selective GLP-1 receptor agonist semaglutide on liver fat content (LFC) in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: This was a phase IIa, randomized, active-comparator-controlled, parallel-group, open-label study. A magnetic resonance imaging-estimated proton density fat fraction assessment was performed to determine LFC at screening and Week 24. Participants with an LFC of >/=10% at screening were randomized 1:1 to efinopegdutide 10 mg or semaglutide 1 mg, both administered subcutaneously once weekly for 24 weeks. Participants were stratified according to the concurrent diagnosis of type 2 diabetes mellitus (T2DM). Both drugs were titrated to the target dose over an 8-week time period. The primary efficacy endpoint was relative reduction from baseline in LFC (%) after 24 weeks of treatment. RESULTS: Among 145 randomized participants (efinopegdutide n = 72, semaglutide n = 73), 33.1% had T2DM. At baseline, mean BMI was 34.3 kg/m(2) and mean LFC was 20.3%. The least squares (LS) mean relative reduction from baseline in LFC at Week 24 was significantly (p <0.001) greater with efinopegdutide (72.7% [90% CI 66.8-78.7]) than with semaglutide (42.3% [90% CI 36.5-48.1]). Both treatment groups had an LS mean percent reduction from baseline in body weight at Week 24 (efinopegdutide 8.5% vs. semaglutide 7.1%; p = 0.085). Slightly higher incidences of adverse events and drug-related adverse events were observed in the efinopegdutide group compared with the semaglutide group, primarily related to an imbalance in gastrointestinal adverse events. CONCLUSIONS: In patients with NAFLD, treatment with efinopegdutide 10 mg weekly led to a significantly greater reduction in LFC than semaglutide 1 mg weekly. CLINICAL TRIAL NUMBER: EudraCT: 2020-005136-30; NCT: 04944992. IMPACT AND IMPLICATIONS: Currently, there are no approved therapies for non-alcoholic steatohepatitis (NASH). The weight loss associated with glucagon-like peptide-1 (GLP-1) receptor agonists has been shown to decrease hepatic inflammation in patients with NASH. In addition to reducing liver fat content (LFC) indirectly through weight loss, glucagon receptor agonism may also reduce LFC by acting on the liver directly to stimulate fatty acid oxidation and reduce lipogenesis. This study demonstrated that treatment of patients with non-alcoholic fatty liver disease with the GLP-1/glucagon receptor co-agonist efinopegdutide (10 mg weekly) led to a significantly greater reduction in LFC compared to treatment with the GLP-1 receptor agonist semaglutide (1 mg weekly), suggesting that efinopegdutide may be an effective treatment for NASH. CI - Copyright (c) 2023 Manuel Romero-Gomez, Eric Lawitz, R. Ravi Shankar, Eirum Chaudhri, Jie Liu, Raymond L.H. Lam, Keith D. Kaufman, Samuel S. Engel, MK-6024 P001 Study Group. Published by Elsevier B.V. All rights reserved. FAU - Romero-Gomez, Manuel AU - Romero-Gomez M AD - Digestive Diseases Unit and CIBERehd, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), University of Seville, Seville, Spain. FAU - Lawitz, Eric AU - Lawitz E AD - Texas Liver Institute, University of Texas Health San Antonio, San Antonio, Texas, USA. FAU - Shankar, R Ravi AU - Shankar RR AD - Merck & Co., Inc., Rahway, NJ, USA. FAU - Chaudhri, Eirum AU - Chaudhri E AD - Merck & Co., Inc., Rahway, NJ, USA. FAU - Liu, Jie AU - Liu J AD - Merck & Co., Inc., Rahway, NJ, USA. FAU - Lam, Raymond L H AU - Lam RLH AD - Merck & Co., Inc., Rahway, NJ, USA. FAU - Kaufman, Keith D AU - Kaufman KD AD - Merck & Co., Inc., Rahway, NJ, USA. FAU - Engel, Samuel S AU - Engel SS AD - Merck & Co., Inc., Rahway, NJ, USA. Electronic address: samuel_engel@merck.com. CN - MK-6024 P001 Study Group LA - eng SI - EudraCT/2020-005136-30 SI - ClinicalTrials.gov/NCT04944992 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230622 PL - Netherlands TA - J Hepatol JT - Journal of hepatology JID - 8503886 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Diabetes Mellitus, Type 2/drug therapy/complications MH - *Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Hypoglycemic Agents/adverse effects MH - *Non-alcoholic Fatty Liver Disease/complications/drug therapy MH - Weight Loss MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - efinopegdutide OT - liver fat content OT - nonalcoholic fatty liver disease OT - semaglutide FIR - Bruzone, Santiago Oscar IR - Bruzone SO FIR - Coronel, Maria Jimena IR - Coronel MJ FIR - Gruz, Fernando M IR - Gruz FM FIR - MacKinnon, Ignacio IR - MacKinnon I FIR - George, Jacob IR - George J FIR - Muller, Kate IR - Muller K FIR - Lee, Samuel S IR - Lee SS FIR - Caussy, Cyrielle IR - Caussy C FIR - Petit, Jean Michel IR - Petit JM FIR - Ari, Ziv Ben IR - Ari ZB FIR - Braun, Marius IR - Braun M FIR - Katchman, Helena IR - Katchman H FIR - Lurie, Yoav IR - Lurie Y FIR - Veitsman, Ella IR - Veitsman E FIR - Zuckerman, Eli IR - Zuckerman E FIR - Aghemo, Alessio IR - Aghemo A FIR - Basili, Stenfania IR - Basili S FIR - Fracanzani, Anna Ludovica IR - Fracanzani AL FIR - Pietrangelo, Antonello IR - Pietrangelo A FIR - Sacerdoti, David IR - Sacerdoti D FIR - Rubio Arce, Jose Francisco IR - Rubio Arce JF FIR - de Guevara Cetina, Alma Laura Ladron IR - de Guevara Cetina ALL FIR - Chavez-Tapia, Norberto Carlos IR - Chavez-Tapia NC FIR - Reyes, Eira Cerda IR - Reyes EC FIR - Pinzon Te, Lourdes Lol-Be IR - Pinzon Te LL FIR - Baker, John R IR - Baker JR FIR - Ngu, Jeffrey IR - Ngu J FIR - Orr, David IR - Orr D FIR - Janczewska, Ewa IR - Janczewska E FIR - Matusik, Pawel IR - Matusik P FIR - Stanislaw Sadurski, Maciej Murawski IR - Stanislaw Sadurski MM FIR - Akinina, Anna Valerievna IR - Akinina AV FIR - Alpenidze, Diana Nodarievna IR - Alpenidze DN FIR - Bogomolov, Pavel IR - Bogomolov P FIR - Ermakova, Polina Yurievna IR - Ermakova PY FIR - Golovach, Albina V IR - Golovach AV FIR - Kim, Sang Gyune IR - Kim SG FIR - Lee, Jin-Woo IR - Lee JW FIR - Paik, Yong Han IR - Paik YH FIR - Park, Jun Yong IR - Park JY FIR - Yeon, Jong Eun IR - Yeon JE FIR - Blasco, Victor Vargas IR - Blasco VV FIR - Madueno, Francisco Jose Tinahones IR - Madueno FJT FIR - Panero, Jose Luis Calleja IR - Panero JLC FIR - Perez, Esther Molina IR - Perez EM FIR - Romero-Gomez, Manuel IR - Romero-Gomez M FIR - Cheng, Pin-Nan IR - Cheng PN FIR - Jeng, Wen-Juei IR - Jeng WJ FIR - Liu, Chun-Jen IR - Liu CJ FIR - Akyuz, Filiz IR - Akyuz F FIR - Balaban, Hatice Yasemin IR - Balaban HY FIR - Basaranoglu, Metin IR - Basaranoglu M FIR - Demir, Tevfik IR - Demir T FIR - Idilman, Ramazan IR - Idilman R FIR - Karakan, Tarkan IR - Karakan T FIR - Gyrina, Olga IR - Gyrina O FIR - Kolesnikova, Olena Vadimivna IR - Kolesnikova OV FIR - Pyvovar, Sergiy M IR - Pyvovar SM FIR - Oliinyk, Oleksandr IR - Oliinyk O FIR - Skrypnyk, Igor IR - Skrypnyk I FIR - Bassan, Isaac IR - Bassan I FIR - Bowman, William Kelly IR - Bowman WK FIR - Denham, Douglas Scott IR - Denham DS FIR - Ghalib, Reem IR - Ghalib R FIR - Lawitz, Eric J IR - Lawitz EJ FIR - Lucas, Kathryn Jean IR - Lucas KJ FIR - Mohseni, Rizwana H IR - Mohseni RH FIR - Sanchez, William Eduardo IR - Sanchez WE FIR - Vierling, John Moore IR - Vierling JM EDAT- 2023/06/25 01:08 MHDA- 2023/09/18 12:43 CRDT- 2023/06/24 19:15 PHST- 2023/04/07 00:00 [received] PHST- 2023/05/19 00:00 [revised] PHST- 2023/05/22 00:00 [accepted] PHST- 2023/09/18 12:43 [medline] PHST- 2023/06/25 01:08 [pubmed] PHST- 2023/06/24 19:15 [entrez] AID - S0168-8278(23)00342-2 [pii] AID - 10.1016/j.jhep.2023.05.013 [doi] PST - ppublish SO - J Hepatol. 2023 Oct;79(4):888-897. doi: 10.1016/j.jhep.2023.05.013. Epub 2023 Jun 22. PMID- 37344384 OWN - NLM STAT- MEDLINE DCOM- 20230803 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 9 DP - 2023 Sep TI - Tirzepatide 10 and 15 mg compared with semaglutide 2.4 mg for the treatment of obesity: An indirect treatment comparison. PG - 2626-2633 LID - 10.1111/dom.15148 [doi] AB - AIM: To compare the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison. MATERIALS AND METHODS: Using SURMOUNT-1 and STEP 1 trial data, mean percentage change in body weight from baseline and odds ratio (OR) of achieving 5% or greater weight loss were compared between tirzepatide 10 and 15 mg at week 72 and semaglutide 2.4 mg at week 68 using matching-adjusted indirect comparison of the efficacy estimand. Sensitivity analyses were completed using different methods, including the Bucher method, also using different estimands and/or time points. RESULTS: Greater reductions in percentage change in body weight were observed with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg (tirzepatide 10 mg mean difference: -4.67% [95% CI -5.91%, -3.43%]; tirzepatide 15 mg mean difference: -5.92% [95% CI -7.16%, -4.68%]; both P < .001). Similarly, more participants achieved 5% or greater weight loss with tirzepatide 10 mg (OR 2.61 [95% CI 1.48, 4.57]; P < .001) and 15 mg (OR 2.75 [95% CI 1.57, 4.81]; P < .001) compared with semaglutide 2.4 mg. All sensitivity analyses were consistent, except for an OR of achieving 5% or greater weight loss with tirzepatide 10 mg using the Bucher method to analyse the treatment regimen estimand (P = .074). CONCLUSIONS: Currently there are no direct comparisons of tirzepatide and semaglutide for weight management. Using the matching-adjusted indirect treatment comparison method to compare the efficacy of tirzepatide and semaglutide for chronic weight management, this analysis showed greater weight loss with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg. CI - (c) 2023 Eli Lilly & Company and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland. FAU - Hankosky, Emily R AU - Hankosky ER AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Wang, Duzhe AU - Wang D AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Malik, Raleigh AU - Malik R AUID- ORCID: 0000-0002-2797-3545 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Yu, Maria AU - Yu M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Hickey, Ana AU - Hickey A AUID- ORCID: 0000-0002-0179-6114 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Kan, Hong AU - Kan H AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Bunck, Mathijs C AU - Bunck MC AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Stefanski, Adam AU - Stefanski A AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Garcia-Perez, Luis-Emilio AU - Garcia-Perez LE AUID- ORCID: 0000-0003-3840-787X AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - McMaster University, York University and Wharton Weight Management Clinic, Toronto, Ontario, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230621 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Hypoglycemic Agents MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides/adverse effects MH - Obesity/drug therapy MH - Body Weight MH - Weight Loss MH - Tirzepatide MH - Semaglutide OTO - NOTNLM OT - incretin-based therapies OT - obesity OT - semaglutide OT - tirzepatide OT - weight loss EDAT- 2023/06/22 01:07 MHDA- 2023/08/03 06:43 CRDT- 2023/06/21 22:52 PHST- 2023/05/02 00:00 [revised] PHST- 2023/01/27 00:00 [received] PHST- 2023/05/12 00:00 [accepted] PHST- 2023/08/03 06:43 [medline] PHST- 2023/06/22 01:07 [pubmed] PHST- 2023/06/21 22:52 [entrez] AID - 10.1111/dom.15148 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Sep;25(9):2626-2633. doi: 10.1111/dom.15148. Epub 2023 Jun 21. PMID- 37342259 OWN - NLM STAT- MEDLINE DCOM- 20230626 LR - 20250623 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 14 DP - 2023 TI - Comparing the effectiveness of long-term use of daily and weekly glucagon-like peptide-1 receptor agonists treatments in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus: a network meta-analysis. PG - 1170881 LID - 10.3389/fendo.2023.1170881 [doi] LID - 1170881 AB - OBJECTIVE: In the present network meta-analysis (NMA), we aimed to compare the effectiveness of daily and weekly treatment with glucagon-like peptide-1 receptor agonists for patients with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). METHOD: We used Stata 17.0 for the NMA. Eligible Randomized controlled trials (RCTs) were searched in PubMed, Cochrane, and Embase databases until December 2022. Two researchers independently screened the available studies. The Cochrane Risk of Bias tool was used to assess the risk of bias in the included studies. We used GRADEprofiler (version3.6) to analyze the evidence certainty. Primary outcomes such as liver fat content (LFC), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels, as well as secondary outcomes such as gamma-glutamyltransferase (gammaGGT) and body weight, were evaluated. Then, each intervention was ranked by the surface under the cumulative ranking curve (SUCRA). As a supplement, we drew forest plots of subgroup using RevMan (version 5.4). RESULTS: Fourteen RCTs involving 1666 participants were included in the present study. The NMA results showed that exenatide (bid) was the best treatment for improving LFC compared with other agents, liraglutide, dulaglutide, semaglutide (qw) and placebo), and the SUCRA values were 66.8%. Among five interventions (except exenatide (bid) and semaglutide (qw)) evaluated for AST outcome, and six interventions (except exenatide (bid)) evaluated for ALT outcome, semaglutide (qd) was the most effective drug (SUCRA (AST) = 100%, SUCRA (ALT) = 95.6%). The result of LFC in daily group was MD = -3.66, 95% CI [-5.56, -1.76] and in weekly GLP-1RAs group, it was MD = -3.51, 95% CI [-4, -3.02]. As to AST and ALT, the results in daily group versus weekly group were AST: MD = -7.45, 95% CI [-14.57, -0.32] versus MD= -0.58, 95% CI [-3.18, 2.01] and ALT: MD = -11.12, 95% CI [-24.18, 1.95] versus MD = -5.62, 95% CI [-15.25, 4]. The quality of evidence was assessed as moderate or low. CONCLUSION: The daily GLP-1RAs may be more effective in primary outcomes. And the daily semaglutide may be the most effective treatment for NAFLD and T2DM among the six interventions. CI - Copyright (c) 2023 Yuan, Gao, Yang, Duan, Ren and Song. FAU - Yuan, Xia AU - Yuan X AD - Department of Internal Medicine, Graduate School of Hebei Medical University, Shijiazhuang, Hebei, China. AD - Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, China. FAU - Gao, Zhe AU - Gao Z AD - Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, China. FAU - Yang, Caixuan AU - Yang C AD - Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, China. AD - Department of Internal Medicine, Graduate School of Hebei North University, Zhangjiakou, Hebei, China. FAU - Duan, Kaixin AU - Duan K AD - Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, China. AD - Department of Internal Medicine, Graduate School of Hebei North University, Zhangjiakou, Hebei, China. FAU - Ren, Luping AU - Ren L AD - Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, China. FAU - Song, Guangyao AU - Song G AD - Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, China. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20230605 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - Exenatide/therapeutic use MH - Hypoglycemic Agents MH - *Non-alcoholic Fatty Liver Disease/drug therapy/chemically induced MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10277636 OTO - NOTNLM OT - alanine aminotransferase OT - aspartate aminotransferase OT - glucagon-like peptide-1 receptor agonists OT - liver fat content OT - nonalcoholic fatty liver disease OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/06/21 13:04 MHDA- 2023/06/23 06:42 PMCR- 2023/01/01 CRDT- 2023/06/21 11:57 PHST- 2023/02/21 00:00 [received] PHST- 2023/05/22 00:00 [accepted] PHST- 2023/06/23 06:42 [medline] PHST- 2023/06/21 13:04 [pubmed] PHST- 2023/06/21 11:57 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2023.1170881 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Jun 5;14:1170881. doi: 10.3389/fendo.2023.1170881. eCollection 2023. PMID- 37340561 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20241018 IS - 1468-1293 (Electronic) IS - 1464-2662 (Linking) VI - 24 IP - 10 DP - 2023 Oct TI - GLP-1 agonists for people living with HIV and obesity, is there a potential? PG - 1029-1034 LID - 10.1111/hiv.13521 [doi] AB - BACKGROUND AND OBJECTIVES: Obesity trends and metabolic dysregulation are rising in people living with HIV using antiretrovirals (ARVs). Underlying causes and preventive strategies are being investigated. Two glucagon like-peptide 1 (GLP-1) agonists, liraglutide and semaglutide, were formerly approved as glucose-lowering drugs and have been recently approved for long-term weight loss in people with obesity. Due to the lack of therapeutic guidelines or clinical trials in people with HIV, we discuss the potential benefits, safety aspects and pharmacological considerations of prescribing liraglutide and semaglutide in people with HIV. RESULTS: Clinical experience is limited to two clinical cases of diabetic people with HIV using liraglutide after which a successful weight loss and glycaemic control were observed. None of the adverse events associated with liraglutide and semaglutide usage indicate an additional risk for people with HIV. Extra caution showed be warranted when initiating GLP-1 agonist therapy in people with HIV taking protease inhibitors who have pre-existing risk factors for heart rate variability to reduce the incidence of RP interval prolongation. GLP-1 agonists are metabolized by endopeptidases, and thus do not generate major drug-drug interactions with most drugs, including ARVs. GLP-s agonists are known to inhibit gastric acid secretion, which warrants caution and close monitoring when combined with atazanavir and oral rilpivirine, two ARVs that require low gastric pH for an optimal absorption. CONCLUSION: Theoretical considerations and a few available clinical observations support semaglutide and liraglutide prescription in people with HIV, with, thus far, no indications of concern regarding efficacy, safety or pharmacological interactions with ARVs. CI - (c) 2023 British HIV Association. FAU - Zino, L AU - Zino L AUID- ORCID: 0000-0001-5577-5557 AD - Radboud University Medical Center, Department of Pharmacy and Radboudumc Research Institute for Medical Innovation (RIMI), Nijmegen, The Netherlands. FAU - Tack, C J AU - Tack CJ AD - Radboud University Medical Center, Department of Internal Medicine and Radboudumc Research Institute for Medical Innovation (RIMI), Nijmegen, The Netherlands. FAU - Richel, O AU - Richel O AD - Radboud University Medical Center, Department of Internal Medicine and Radboudumc Research Institute for Medical Innovation (RIMI), Nijmegen, The Netherlands. FAU - Burger, D M AU - Burger DM AUID- ORCID: 0000-0001-7279-2818 AD - Radboud University Medical Center, Department of Pharmacy and Radboudumc Research Institute for Medical Innovation (RIMI), Nijmegen, The Netherlands. LA - eng PT - Journal Article DEP - 20230620 PL - England TA - HIV Med JT - HIV medicine JID - 100897392 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM CIN - HIV Med. 2024 Jul;25(7):893-894. doi: 10.1111/hiv.13631. PMID: 38433467 MH - Humans MH - Liraglutide/adverse effects MH - Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2 MH - *HIV Infections/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - Obesity/complications/drug therapy MH - Weight Loss OTO - NOTNLM OT - GLP-1 agonist OT - HIV OT - liraglutide OT - obesity OT - semaglutide EDAT- 2023/06/21 06:42 MHDA- 2023/10/23 00:41 CRDT- 2023/06/21 00:22 PHST- 2023/03/14 00:00 [received] PHST- 2023/06/09 00:00 [accepted] PHST- 2023/10/23 00:41 [medline] PHST- 2023/06/21 06:42 [pubmed] PHST- 2023/06/21 00:22 [entrez] AID - 10.1111/hiv.13521 [doi] PST - ppublish SO - HIV Med. 2023 Oct;24(10):1029-1034. doi: 10.1111/hiv.13521. Epub 2023 Jun 20. PMID- 37337740 OWN - NLM STAT- MEDLINE DCOM- 20251006 LR - 20260127 IS - 2724-6116 (Electronic) IS - 2724-6116 (Linking) VI - 50 IP - 3 DP - 2025 Sep TI - Results of semaglutide in patients older than 70 years, a real-world study of efficacy and safety. PG - 296-301 LID - 10.23736/S2724-6507.23.03985-4 [doi] AB - BACKGROUND: The aim of this study is to investigate the use of once-weekly semaglutide in a real population of patients with type 2 diabetes mellitus (T2DM) over 70 years in two Spanish hospitals. METHODS: An observational, retrospective, and multicenter clinical study was designed. It included 60 patients with T2DM, with a mean age of 76.5 years, 63.3% women, and a mean of 15.5 years of evolution of T2DM, all managed in the outpatient clinical setting. The primary endpoint was the change in HbA1c from baseline to the end of the study. The secondary endpoints included changes in body weight and the proportion of patients achieving HbA1c <7.0% and body weight loss >5%. RESULTS: After 12 months of follow-up, the reductions in HbA1c were -0.61+/-0.9% (P<0.0001) in the total cohort. Body weight reductions were -8.2+/-5.3 kg (P<0.0001). Overall, 67% reached the objective of an HbA1c level of <7%, and 73% achieved a weight loss of >/=5%. CONCLUSIONS: In routine clinical practice in Spain, the use of semaglutide once a week was associated with statistically significant and clinically relevant improvements in HbA1c and body weight in adults aged over 70 years with T2DM, without notable adverse effects, which supports real-world use. FAU - Garcia DE Lucas, Maria D AU - Garcia DE Lucas MD AD - Department of Internal Medicine, Costa del Sol Hospital, Marbella, Spain. FAU - Perez-Belmonte, Luis AU - Perez-Belmonte L AD - Department of Internal Medicine, Regional University Hospital and Biomedical Research Institute, Malaga, Spain. FAU - Aviles-Bueno, Beatriz AU - Aviles-Bueno B AD - Department of Nephrology, Costa del Sol Hospital, Marbella, Spain. FAU - Jimenez-Millan, Anabel AU - Jimenez-Millan A AD - Department of Endocrinology, University Hospital of Puerto Real, Puerto Real, Spain. FAU - Rivas Ruiz, Francisco AU - Rivas Ruiz F AD - Research Unit, Costa del Sol Hospital, Marbella, Spain. FAU - Miramontes-Gonzalez, Jose P AU - Miramontes-Gonzalez JP AD - Department of Internal Medicine, Rio Hortega University Hospital, Valladolid University, Valladolid, Spain - jpmiramontes@hotmail.com. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20230620 PL - Italy TA - Minerva Endocrinol (Torino) JT - Minerva endocrinology JID - 101777342 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Aged MH - *Glucagon-Like Peptides/therapeutic use/adverse effects/administration & dosage MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy/blood MH - Male MH - Retrospective Studies MH - *Hypoglycemic Agents/therapeutic use/adverse effects/administration & dosage MH - Aged, 80 and over MH - Treatment Outcome MH - Weight Loss/drug effects MH - Spain MH - Glycated Hemoglobin/analysis MH - Follow-Up Studies MH - Body Weight/drug effects MH - Glucagon-Like Peptide 1 MH - Semaglutide EDAT- 2023/06/20 06:42 MHDA- 2025/10/06 12:31 CRDT- 2023/06/20 03:37 PHST- 2025/10/06 12:31 [medline] PHST- 2023/06/20 06:42 [pubmed] PHST- 2023/06/20 03:37 [entrez] AID - S2724-6507.23.03985-4 [pii] AID - 10.23736/S2724-6507.23.03985-4 [doi] PST - ppublish SO - Minerva Endocrinol (Torino). 2025 Sep;50(3):296-301. doi: 10.23736/S2724-6507.23.03985-4. Epub 2023 Jun 20. PMID- 37330144 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20250103 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 207 DP - 2024 Jan TI - Perspectives in weight control in diabetes - Survodutide. PG - 110779 LID - S0168-8227(23)00542-9 [pii] LID - 10.1016/j.diabres.2023.110779 [doi] AB - Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved treatments for Type 2 diabetes mellitus, with liraglutide and semaglutide also approved for the treatment of obesity. The natural gut hormone oxyntomodulin is a weak dual agonist of the glucagon receptor (GCGR) and GLP-1R. Development of poly-agonists mimicking oxyntomodulin, such as the novel dual GCGR/GLP-1R agonist survodutide, represents an important step towards a more effective treatment for people with Type 2 diabetes mellitus and obesity. Survodutide is a 29-amino acid peptide derived from glucagon, with the incorporation of potent GLP-1 activities. It contains a C18 diacid which mediates binding to albumin, thereby prolonging the half-life to enable once-weekly subcutaneous dosing. The utilisation of GCGR agonism aims to enhance body weight-lowering effects by increasing energy expenditure in addition to the anorectic action of GLP-1R agonists. Glucose-lowering efficacy of survodutide has been demonstrated in a Phase II trial in patients with Type 2 diabetes mellitus and obesity and was associated with clinically meaningful body weight loss. These data highlight the potential of dual GCGR/GLP-1R agonism for reducing glycated haemoglobin and body weight in patients with Type 2 diabetes mellitus, and for greater therapeutic efficacy compared with GLP-1R agonism alone. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Klein, Thomas AU - Klein T AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany. FAU - Augustin, Robert AU - Augustin R AD - Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany. FAU - Hennige, Anita M AU - Hennige AM AD - Boehringer Ingelheim International GmbH, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany. Electronic address: anita.hennige@boehringer-ingelheim.com. LA - eng PT - Journal Article DEP - 20230615 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Oxyntomodulin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9007-92-5 (Glucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications MH - Oxyntomodulin/therapeutic use MH - Obesity/complications MH - Glucagon-Like Peptide 1/therapeutic use MH - Glucagon MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Diabetes Mellitus, Type 2 OT - Glucagon-Like Peptide 1 OT - Incretins OT - Obesity management OT - Receptors, Glucagon COIS- Declaration of Competing Interest The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and did not receive payment related to the development of this manuscript. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy, as well as intellectual property considerations. Thomas Klein, Robert Augustin and Anita M. Hennige are employees of Boehringer Ingelheim. EDAT- 2023/06/18 01:07 MHDA- 2024/02/12 05:00 CRDT- 2023/06/17 19:17 PHST- 2023/04/14 00:00 [received] PHST- 2023/06/09 00:00 [revised] PHST- 2023/06/11 00:00 [accepted] PHST- 2024/02/12 05:00 [medline] PHST- 2023/06/18 01:07 [pubmed] PHST- 2023/06/17 19:17 [entrez] AID - S0168-8227(23)00542-9 [pii] AID - 10.1016/j.diabres.2023.110779 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2024 Jan;207:110779. doi: 10.1016/j.diabres.2023.110779. Epub 2023 Jun 15. PMID- 37329973 OWN - NLM STAT- MEDLINE DCOM- 20230724 LR - 20260127 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 954 DP - 2023 Sep 5 TI - Treatment sequencing using the dual amylin and calcitonin receptor agonist KBP-336 and semaglutide results in durable weight loss. PG - 175837 LID - S0014-2999(23)00348-5 [pii] LID - 10.1016/j.ejphar.2023.175837 [doi] AB - OBJECTIVE: Long-acting dual amylin and calcitonin receptor agonists (DACRAs) hold great promise as potential treatments for obesity and its associated comorbidities. These agents have demonstrated beneficial effects on body weight, glucose control, and insulin action mirroring the effects observed with glucagon-like peptide-1 (GLP-1) agonist treatment. Strategies aimed at enhancing and prolonging treatment efficacy include treatment sequencing and combination therapy. Here, we sought to investigate the impact of switching between or combining treatment with the DACRA KBP-336 and the GLP-1 analog semaglutide in fed rats with obesity induced by a high-fat diet (HFD). METHODS: Two studies were performed in which HFD-induced obese Sprague Dawley rats were switched between treatment with KBP-336 (4.5 nmol/kg, Q3D) and semaglutide (50 nmol/kg, Q3D) or a combination of the two. Treatment efficacy on weight loss and food intake was evaluated, and glucose tolerance was assessed by oral glucose tolerance tests. RESULTS: KBP-336 and semaglutide monotherapy resulted in a similar reduction in body weight and food intake. Treatment sequencing resulted in continuous weight loss and all monotherapies resulted in similar weight loss independent of the treatment regimen (P < 0.001 compared to vehicle). The combination of KBP-336 and semaglutide significantly improved the weight loss compared to either monotherapy alone (P < 0.001), which was evident in the adiposity at the study end. All treatments improved glucose tolerance, with the KBP-effect on insulin sensitivity as the dominant response. CONCLUSIONS: These findings highlight KBP-336 as a promising anti-obesity therapy both alone, in treatment sequencing, and in combination with semaglutide or other incretin-based therapies. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Thorso Larsen, Anna AU - Thorso Larsen A AD - Nordic Bioscience, 2730 Herlev, Denmark. Electronic address: atl@nordicbio.com. FAU - Karsdal, Morten A AU - Karsdal MA AD - Nordic Bioscience, 2730 Herlev, Denmark; KeyBioscience AG, Stans, Switzerland. FAU - Henriksen, Kim AU - Henriksen K AD - Nordic Bioscience, 2730 Herlev, Denmark; KeyBioscience AG, Stans, Switzerland. LA - eng PT - Journal Article DEP - 20230616 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Amylin Receptor Agonists) RN - 0 (Receptors, Calcitonin) RN - 0 (Islet Amyloid Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Bone Density Conservation Agents) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Rats MH - Animals MH - *Amylin Receptor Agonists/pharmacology MH - Receptors, Calcitonin/agonists MH - Islet Amyloid Polypeptide MH - Rats, Sprague-Dawley MH - Weight Loss MH - Body Weight MH - Obesity/drug therapy MH - Glucagon-Like Peptide 1 MH - *Bone Density Conservation Agents MH - Glucose MH - Glucagon-Like Peptide-1 Receptor MH - Hypoglycemic Agents MH - *Diabetes Mellitus, Type 2 MH - Semaglutide OTO - NOTNLM OT - DACRA OT - GLP-1 OT - Obesity OT - Weight loss COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper EDAT- 2023/06/18 01:08 MHDA- 2023/07/24 06:42 CRDT- 2023/06/17 19:13 PHST- 2023/03/28 00:00 [received] PHST- 2023/06/06 00:00 [revised] PHST- 2023/06/06 00:00 [accepted] PHST- 2023/07/24 06:42 [medline] PHST- 2023/06/18 01:08 [pubmed] PHST- 2023/06/17 19:13 [entrez] AID - S0014-2999(23)00348-5 [pii] AID - 10.1016/j.ejphar.2023.175837 [doi] PST - ppublish SO - Eur J Pharmacol. 2023 Sep 5;954:175837. doi: 10.1016/j.ejphar.2023.175837. Epub 2023 Jun 16. PMID- 37328931 OWN - NLM STAT- MEDLINE DCOM- 20230731 LR - 20260127 IS - 1365-2036 (Electronic) IS - 0269-2813 (Linking) VI - 58 IP - 4 DP - 2023 Aug TI - Improved health-related quality of life with semaglutide in people with non-alcoholic steatohepatitis: A randomised trial. PG - 395-403 LID - 10.1111/apt.17598 [doi] AB - BACKGROUND: Non-alcoholic steatohepatitis (NASH) can adversely affect health-related quality of life (HRQoL). AIMS: This double-blind, placebo-controlled, phase 2 trial aimed to report the effects of the glucagon-like peptide-1 receptor agonist, semaglutide, on HRQoL in patients with NASH as a secondary endpoint. METHODS: Adults with biopsy-proven NASH and stage 1-3 fibrosis were randomised (3:3:3:1:1:1) to once-daily subcutaneous semaglutide 0.1, 0.2 or 0.4 mg, or placebo, for 72 weeks. Patients were invited to complete the Short Form-36 version 2.0 questionnaire at weeks 0, 28, 52 and 72. RESULTS: Between January 2017 and September 2018, 320 patients were enrolled. At 72 weeks, semaglutide was associated with significant improvements in physical component summary (PCS) score (estimated treatment difference [ETD] 4.26; 95% confidence interval [CI]: 1.96-6.55; p = 0.0003); bodily pain (ETD 5.07; 95% CI: 2.15-7.99; p = 0.0007); physical functioning (ETD 3.51; 95% CI: 1.16-5.86; p = 0.0034); role limitations due to physical health problems (ETD 2.80; 95% CI: 0.28-5.33; p = 0.0294); social functioning (ETD 3.16; 95% CI: 0.53-5.78; p = 0.0183) and vitality (ETD 4.47; 95% CI: 1.63-7.32; p = 0.0021). There was no significant difference in the mental component summary score (ETD 1.02; 95% CI: -1.59 to 3.62; p = 0.4441). After 72 weeks, improvements in PCS scores were significantly greater in patients (pooled semaglutide and placebo) with NASH resolution than without (p = 0.014). CONCLUSIONS: Treatment with semaglutide is associated with improvements in the physical components of HRQoL in patients with biopsy-proven NASH and fibrosis compared with placebo. CLINICALTRIALS: gov: NCT02970942. CI - (c) 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. FAU - Romero-Gomez, Manuel AU - Romero-Gomez M AUID- ORCID: 0000-0001-8494-8947 AD - UCM Digestive Diseases and CIBEREHD, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville (CSIC/HUVR/US), University of Seville, Seville, Spain. FAU - Armstrong, Matthew J AU - Armstrong MJ AUID- ORCID: 0000-0002-3425-1161 AD - Department of Hepatology and Liver Transplantation, Queen Elizabeth University Hospital Birmingham, Birmingham, UK. FAU - Funuyet-Salas, Jesus AU - Funuyet-Salas J AUID- ORCID: 0000-0002-4133-140X AD - Department of Personality, Assessment and Psychological Treatment, Faculty of Psychology, University of Seville, Seville, Spain. FAU - Mangla, Kamal Kant AU - Mangla KK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ladelund, Steen AU - Ladelund S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sejling, Anne-Sophie AU - Sejling AS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Shrestha, Ichhya AU - Shrestha I AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sanyal, Arun J AU - Sanyal AJ AUID- ORCID: 0000-0001-8682-5748 AD - Virginia Commonwealth University, School of Medicine, Richmond, Virginia, USA. LA - eng SI - ClinicalTrials.gov/NCT02970942 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230616 PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Aliment Pharmacol Ther. 2023 Aug;58(4):484-485. doi: 10.1111/apt.17641. PMID: 37499101 CIN - Aliment Pharmacol Ther. 2023 Aug;58(4):482-483. doi: 10.1111/apt.17621. PMID: 37499103 MH - Adult MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Quality of Life MH - Treatment Outcome MH - Double-Blind Method MH - Semaglutide EDAT- 2023/06/17 09:41 MHDA- 2023/07/31 06:42 CRDT- 2023/06/17 00:23 PHST- 2023/02/15 00:00 [revised] PHST- 2023/01/27 00:00 [received] PHST- 2023/05/19 00:00 [accepted] PHST- 2023/07/31 06:42 [medline] PHST- 2023/06/17 09:41 [pubmed] PHST- 2023/06/17 00:23 [entrez] AID - 10.1111/apt.17598 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2023 Aug;58(4):395-403. doi: 10.1111/apt.17598. Epub 2023 Jun 16. PMID- 37302962 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20250103 IS - 1471-6771 (Electronic) IS - 0007-0912 (Linking) VI - 131 IP - 2 DP - 2023 Aug TI - Clinically significant emesis in a patient taking a long-acting GLP-1 receptor agonist for weight loss. PG - e37-e39 LID - S0007-0912(23)00239-8 [pii] LID - 10.1016/j.bja.2023.05.005 [doi] FAU - Weber, Marissa AU - Weber M AD - Department of Anesthesiology, Weill Cornell Medical College, New York, NY, USA. Electronic address: MarissaWeberMD@gmail.com. FAU - Siddarthan, Ingharan AU - Siddarthan I AD - Department of Anesthesiology, Weill Cornell Medical College, New York, NY, USA. FAU - Mack, Patricia Fogarty AU - Mack PF AD - Department of Anesthesiology, Weill Cornell Medical College, New York, NY, USA. LA - eng PT - Letter DEP - 20230609 PL - England TA - Br J Anaesth JT - British journal of anaesthesia JID - 0372541 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Hypoglycemic Agents MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Weight Loss MH - Vomiting/chemically induced MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1RA OT - aspiration OT - delayed gastric emptying OT - glucagon-like peptide-1 OT - semaglutide OT - tirzepatide EDAT- 2023/06/12 00:42 MHDA- 2023/10/23 00:43 CRDT- 2023/06/11 21:57 PHST- 2023/03/30 00:00 [received] PHST- 2023/04/28 00:00 [revised] PHST- 2023/05/02 00:00 [accepted] PHST- 2023/10/23 00:43 [medline] PHST- 2023/06/12 00:42 [pubmed] PHST- 2023/06/11 21:57 [entrez] AID - S0007-0912(23)00239-8 [pii] AID - 10.1016/j.bja.2023.05.005 [doi] PST - ppublish SO - Br J Anaesth. 2023 Aug;131(2):e37-e39. doi: 10.1016/j.bja.2023.05.005. Epub 2023 Jun 9. PMID- 37301509 OWN - NLM STAT- MEDLINE DCOM- 20231102 LR - 20250103 IS - 1544-3450 (Electronic) IS - 1086-5802 (Linking) VI - 63 IP - 5 DP - 2023 Sep-Oct TI - Glucagon-like peptide-1 receptor agonists use for type 2 diabetes mellitus in end-stage renal disease. PG - 1612-1616 LID - S1544-3191(23)00170-X [pii] LID - 10.1016/j.japh.2023.06.003 [doi] AB - BACKGROUND: Management of type 2 diabetes mellitus (T2DM) in patients with end-stage renal disease (ESRD) remains a challenge given limited data. Although current guidelines recommend use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for the treatment of T2DM in patients with concomitant chronic kidney disease, supporting safety and efficacy evidence is lacking for patients with ESRD or hemodialysis. OBJECTIVE: This retrospective study was conducted to evaluate the efficacy and safety of GLP-1 RAs for the treatment of T2DM in patients with ESRD. DESIGN, SETTING, AND PARTICIPANTS: This is a single-centered, multifacility retrospective cohort analysis. Patients were included if they had a diagnosis of T2DM and ESRD and were prescribed a GLP-1 RA. Patients were excluded if the GLP-1 RA was prescribed solely for weight loss. OUTCOME MEASURES: The primary outcome was change in A1C. Secondary outcomes included (1) incidence of acute kidney injury (AKI), (2) change in weight, (3) change in estimated glomerular filtration rate, (4) ability to discontinue basal or bolus insulin, and (5) incidence of emergent hypoglycemia. RESULTS: There were 46 unique patients and 64 individual GLP-1 RA prescriptions included. The mean reduction in A1C was 0.8%. There were 10 incidences of AKI, although none occurred in the semaglutide cohort. Emergent hypoglycemia occurred in 3 patients who were all prescribed concomitant insulin. CONCLUSION: Results from this retrospective review provide additional real-world data on use of GLP-1 RAs in this unique population. Prospective studies to control for confounding factors are warranted given that GLP-1RAs are a safer alternative to insulin in this high-risk population. CI - Published by Elsevier Inc. FAU - Thomas, Ashley M AU - Thomas AM FAU - Lamb, Kristen AU - Lamb K FAU - Howard, Olivia AU - Howard O LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230608 PL - United States TA - J Am Pharm Assoc (2003) JT - Journal of the American Pharmacists Association : JAPhA JID - 101176252 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Acute Kidney Injury/chemically induced MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide 1 MH - Glycated Hemoglobin MH - *Hypoglycemia/chemically induced MH - Hypoglycemic Agents/adverse effects MH - Insulin MH - *Kidney Failure, Chronic/complications/chemically induced MH - Prospective Studies MH - Retrospective Studies MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2023/06/11 01:06 MHDA- 2023/06/11 01:07 CRDT- 2023/06/10 19:30 PHST- 2023/04/04 00:00 [received] PHST- 2023/05/30 00:00 [revised] PHST- 2023/06/04 00:00 [accepted] PHST- 2023/06/11 01:07 [medline] PHST- 2023/06/11 01:06 [pubmed] PHST- 2023/06/10 19:30 [entrez] AID - S1544-3191(23)00170-X [pii] AID - 10.1016/j.japh.2023.06.003 [doi] PST - ppublish SO - J Am Pharm Assoc (2003). 2023 Sep-Oct;63(5):1612-1616. doi: 10.1016/j.japh.2023.06.003. Epub 2023 Jun 8. PMID- 37301063 OWN - NLM STAT- MEDLINE DCOM- 20230804 LR - 20260127 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 37 IP - 8 DP - 2023 Aug TI - Effect of semaglutide versus other glucagon-like peptide-1 receptor agonists on cardio-metabolic risk factors in patients with type 2 diabetes: A systematic review and meta-analysis of head-to-head, phase 3, randomized controlled trials. PG - 108529 LID - S1056-8727(23)00127-7 [pii] LID - 10.1016/j.jdiacomp.2023.108529 [doi] AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a cornerstone treatment for type 2 diabetes mellitus (T2DM). The aim of the present meta-analysis was to assess whether semaglutide exerts greater effects on glycemia and other cardio-metabolic risk factors compared to other GLP-1RAs. METHODS: PubMed and Cochrane Library databases, along with grey literature sources, were searched form inception to 8th February 2023, in order to retrieve head-to-head, phase 3 randomized controlled trials (RCTs) assessing the effect of semaglutide versus other GLP-1RAs on glycemia and other cardio-metabolic risk factors in T2DM. RESULTS: We finally pooled data from 5 RCTs in a total of 3760 randomized participants. Semaglutide compared to other GLP-1RAs provided a significantly greater reduction in HbA1c levels by 0.44 %, in fasting plasma glucose by 0.48 mmol/L, in body weight by 2.53 kg and in body mass index by 0.91 kg/m(2). Subjects receiving semaglutide experienced significantly greater odds for achieving target and optimal HbA1c, along with significantly greater odds for weight loss >5 % and 10 %. However, subjects randomized to semaglutide also experienced significantly greater odds for gastrointestinal adverse events and treatment discontinuation. CONCLUSION: Semaglutide is more effective than rest GLP-1RAs, in terms of improvement in glycemia and other cardio-metabolic risk factors, among individuals with T2DM. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Patoulias, Dimitrios AU - Patoulias D AD - Outpatient Department of Cardiometabolic Medicine, Second Department of Cardiology, Aristotle University of Thessaloniki, General Hospital "Hippokration", Thessaloniki, Greece. Electronic address: patoulias@auth.gr. FAU - Popovic, Djordje S AU - Popovic DS AD - Clinic for Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Vojvodina, Medical Faculty, University of Novi Sad, Novi Sad, Serbia. FAU - Stoian, Anca Pantea AU - Stoian AP AD - Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania. FAU - Janez, Andrej AU - Janez A AD - Department of Endocrinology, Diabetes and Metabolic Diseases, Medical Center, University of Ljubljana Medical Faculty, Ljubljana, Slovenia. FAU - Sahebkar, Amirhossein AU - Sahebkar A AD - Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran. FAU - Rizzo, Manfredi AU - Rizzo M AD - School of Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), University of Palermo, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20230607 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Hypoglycemic Agents/adverse effects MH - Glycated Hemoglobin MH - Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Glycemia OT - Risk factor OT - Semaglutide OT - Type 2 diabetes COIS- Declaration of competing interest This manuscript was written independently, and the authors did not receive financial or professional help for its preparation. The authors have given lectures, received honoraria and research support, and participated in conferences, advisory boards, and clinical trials sponsored by many pharmaceutical companies. Yet, the industry had no role in this article. EDAT- 2023/06/11 01:06 MHDA- 2023/08/04 06:43 CRDT- 2023/06/10 18:07 PHST- 2023/04/04 00:00 [received] PHST- 2023/05/26 00:00 [revised] PHST- 2023/06/04 00:00 [accepted] PHST- 2023/08/04 06:43 [medline] PHST- 2023/06/11 01:06 [pubmed] PHST- 2023/06/10 18:07 [entrez] AID - S1056-8727(23)00127-7 [pii] AID - 10.1016/j.jdiacomp.2023.108529 [doi] PST - ppublish SO - J Diabetes Complications. 2023 Aug;37(8):108529. doi: 10.1016/j.jdiacomp.2023.108529. Epub 2023 Jun 7. PMID- 37298276 OWN - NLM STAT- MEDLINE DCOM- 20230613 LR - 20250103 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 11 DP - 2023 May 26 TI - Therapeutic Mechanisms and Clinical Effects of Glucagon-like Peptide 1 Receptor Agonists in Nonalcoholic Fatty Liver Disease. LID - 10.3390/ijms24119324 [doi] LID - 9324 AB - Nonalcoholic fatty liver disease (NAFLD) can lead to liver fibrosis and cirrhosis. Recently, glucagon-like peptide 1 receptor agonists (GLP-1RAs), a class of drugs used to treat type 2 diabetes and obesity, have shown therapeutic effects against NAFLD. In addition to reducing blood glucose levels and body weight, GLP-1RAs are effective in improving the clinical, biochemical, and histological markers of hepatic steatosis, inflammation, and fibrosis in patients with NAFLD. Additionally, GLP-1RAs have a good safety profile with minor side effects, such as nausea and vomiting. Overall, GLP-1RAs show promise as a potential treatment for NAFLD, and further studies are required to determine their long-term safety and efficacy. FAU - Lee, Han Ah AU - Lee HA AUID- ORCID: 0000-0002-0430-1607 AD - Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea. FAU - Kim, Hwi Young AU - Kim HY AUID- ORCID: 0000-0003-0723-1285 AD - Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea. LA - eng GR - . 2022R1I1A1A01065244, 2018R1A5A2025286/National Research Foundation of Korea/ GR - research program/Korea Medical Institute/ PT - Journal Article PT - Review DEP - 20230526 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptide 1/therapeutic use MH - Hypoglycemic Agents/adverse effects/pharmacology/therapeutic use MH - Liver Cirrhosis/drug therapy MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10253495 OTO - NOTNLM OT - diabetes OT - liraglutide OT - nonalcoholic steatohepatitis OT - semaglutide OT - tirzepatide COIS- The authors declare no conflict of interest. EDAT- 2023/06/10 15:14 MHDA- 2023/06/12 06:43 PMCR- 2023/05/26 CRDT- 2023/06/10 01:11 PHST- 2023/04/19 00:00 [received] PHST- 2023/05/19 00:00 [revised] PHST- 2023/05/25 00:00 [accepted] PHST- 2023/06/12 06:43 [medline] PHST- 2023/06/10 15:14 [pubmed] PHST- 2023/06/10 01:11 [entrez] PHST- 2023/05/26 00:00 [pmc-release] AID - ijms24119324 [pii] AID - ijms-24-09324 [pii] AID - 10.3390/ijms24119324 [doi] PST - epublish SO - Int J Mol Sci. 2023 May 26;24(11):9324. doi: 10.3390/ijms24119324. PMID- 37294245 OWN - NLM STAT- MEDLINE DCOM- 20230811 LR - 20260127 IS - 2213-1787 (Electronic) IS - 2213-1779 (Linking) VI - 11 IP - 8 Pt 1 DP - 2023 Aug TI - Design and Baseline Characteristics of STEP-HFpEF Program Evaluating Semaglutide in Patients With Obesity HFpEF Phenotype. PG - 1000-1010 LID - S2213-1779(23)00245-7 [pii] LID - 10.1016/j.jchf.2023.05.010 [doi] AB - BACKGROUND: The majority of patients with heart failure with preserved ejection fraction (HFpEF) have the obesity phenotype, but no therapies specifically targeting obesity in HFpEF exist. OBJECTIVES: The aim of this study was to describe the design and baseline characteristics of 2 trials of semaglutide, a glucagon-like peptide-1 receptor agonist, in patients with the obesity HFpEF phenotype: STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF; NCT04788511) and STEP-HFpEF DM (Semaglutide Treatment Effect in People with obesity and HFpEF and type 2 diabetes; NCT04916470). METHODS: Both STEP-HFpEF and STEP-HFpEF DM are international multicenter, double-blind, placebo-controlled trials that randomized adults with HFpEF and a body mass index >/=30 kg/m(2) to once-weekly semaglutide at a dose of 2.4 mg or placebo. Participants were eligible if they had a left ventricular ejection fraction (LVEF) >/=45%; NYHA functional class II to IV; a Kansas City Cardiomyopathy Questionnaire (KCCQ)-Clinical Summary Score (CSS) <90 points; and >/=1 of the following: elevated filling pressures, elevated natriuretic peptides plus structural echocardiographic abnormalities, recent heart failure hospitalization plus ongoing diuretic use, and/or structural abnormalities. The dual primary endpoints are the 52-week change in the KCCQ-CSS and body weight. RESULTS: In STEP-HFpEF and STEP-HFpEF DM (N = 529 and N = 617, respectively), nearly half were women, and most had severe obesity (median body mass index of 37 kg/m(2)) with typical features of HFpEF (median LVEF of 57%, frequent comorbidities, and elevated natriuretic peptides). Most participants received diuretic agents and renin-angiotensin blockers at baseline, and approximately one-third were on mineralocorticoid receptor antagonists. Sodium-glucose cotransporter-2 inhibitor use was rare in STEP-HFpEF but not in STEP HFpEF DM (32%). Patients in both trials had marked symptomatic and functional impairments (KCCQ-CSS approximately 59 points, 6-minute walking distance approximately 300 m). CONCLUSIONS: In total, STEP-HFpEF program randomized 1,146 participants with the obesity phenotype of HFpEF and will determine whether semaglutide improves symptoms, physical limitations, and exercise function in addition to weight loss in this vulnerable group. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. Electronic address: mkosiborod@saint-lukes.org. FAU - Abildstrom, Steen Z AU - Abildstrom SZ AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Borlaug, Barry A AU - Borlaug BA AD - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA. FAU - Butler, Javed AU - Butler J AD - Baylor Scott and White Research Institute, Dallas, Texas, USA; Department of Medicine, University of Mississippi, Jackson, Mississippi, USA. Electronic address: https://twitter.com/JavedButler1. FAU - Christensen, Louise AU - Christensen L AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Davies, Melanie AU - Davies M AD - Diabetes Research Centre, University of Leicester, Leicester, United Kingdom; National Institute for Health Care and Research, Leicester Biomedical Research Centre, Leicester, United Kingdom. FAU - Hovingh, Kees G AU - Hovingh KG AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kitzman, Dalane W AU - Kitzman DW AD - Department of Internal Medicine, Sections of Cardiovascular Medicine and Geriatrics and Gerontology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. FAU - Lindegaard, Marie L AU - Lindegaard ML AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Moller, Daniel Vega AU - Moller DV AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Shah, Sanjiv J AU - Shah SJ AD - Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Electronic address: https://twitter.com/HFpEF. FAU - Treppendahl, Marianne Bach AU - Treppendahl MB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada. FAU - Petrie, Mark C AU - Petrie MC AD - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom. Electronic address: https://twitter.com/markcpetrie20. LA - eng SI - ClinicalTrials.gov/NCT04916470 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230521 PL - United States TA - JACC Heart Fail JT - JACC. Heart failure JID - 101598241 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Diuretics) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Male MH - *Heart Failure/drug therapy MH - Stroke Volume/physiology MH - Ventricular Function, Left MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Obesity/complications MH - Diuretics/therapeutic use MH - Phenotype MH - Double-Blind Method MH - Multicenter Studies as Topic MH - Randomized Controlled Trials as Topic MH - Semaglutide OTO - NOTNLM OT - 6-minute walking distance OT - HFpEF OT - Kansas City Cardiomyopathy Questionnaire OT - health status OT - obesity OT - semaglutide OT - weight loss COIS- Funding Support and Author Disclosures The STEP-HFpEF and STEP-HFpEF DM trials were funded by Novo Nordisk. Dr Kosiborod served as a consultant or on an advisory board for 35Pharma, Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; has received research grants from AstraZeneca and Boehringer Ingelheim; holds stocks in Artera Health and Saghmos Therapeutics; has received honorarium from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and has received other research support from AstraZeneca. Dr Abildstrom is employed by Novo Nordisk; and has shares in Novo Nordisk. Dr Borlaug has received research support from the National Institutes of Health and the United States Department of Defense; has received research grant funding from AstraZeneca, Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, Rivus, and Tenax Therapeutics; has served as a consultant for Actelion, Amgen, Aria, Axon Therapies, BD, Boehringer Ingelheim, Cytokinetics, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM, NXT, and VADovations; and is named inventor (U.S. patent number 10,307,179) for the tools and approach for a minimally invasive pericardial modification procedure to treat heart failure. Dr Butler is a consultant to Abbott, American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Roche, Sequana, SQ Innovation, 3live, and Vifor. Dr Christensen is employed by Novo Nordisk; and has shares in Novo Nordisk. Dr Davies has acted as a consultant, advisory board member, and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk, and Sanofi; is an advisory board member and speaker for AstraZeneca; is an advisory board member for Pfizer, Medtronic, and ShouTi Pharma Inc; is a speaker for Novartis, Sanofi, and Amgen; and has received grants in support of investigator and investigator-initiated trials from AstraZeneca, Sanofi-Aventis, Eli Lilly, Boehringer Ingelheim, Janssen, and Novo Nordisk. Dr Hovingh is employed by Novo Nordisk and The Amsterdam University Medical Center; and has shares in Novo Nordisk. Dr Kitzman has served as a paid consultant for Novo Nordisk; and his institution has received grant awards from Novo Nordisk. Dr Lindegaard is employed by Novo Nordisk; and has shares in Novo Nordisk. Dr Moller is employed by Novo Nordisk; and has shares in Novo Nordisk. Dr Shah has been supported by research grants from the National Institutes of Health (U54 HL160273, R01 HL107577, R01 HL127028, R01 HL140731, and R01 HL149423); and reports receiving consulting fees from Abbott, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer-Ingelheim, Boston Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Lilly, Merck, Metabolic Flux, MyoKardia, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya, and United Therapeutics. Dr Treppendahl is employed by Novo Nordisk; and has shares in Novo Nordisk. Dr Verma has received speaking honoraria and/or consulting fees from Abbott, AstraZeneca, Bayer, Boehringer-Ingelheim, Novo Nordisk, Novartis, Merck, PhaseBio, HLS Therapeutics, Amarin, Eli Lilly, Janssen, Pfizer, TIMI, and Canadian Medical and Surgical Knowledge Translation Research Group. Dr Petrie has received research grants or consultancy fees from SQ Innovations, AstraZeneca, Roche, Boehringer Ingelheim, Pharmacosmos, Eli Lilly, Napp Pharmaceuticals, Novartis, and Novo Nordisk; has served on committees for AbbVie, Akero, Alnylam, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Resverlogix, Teikoku, New Amsterdam, and Novo Nordisk; and is director of Global Clinical Trial Partners. EDAT- 2023/06/09 13:42 MHDA- 2023/08/11 06:43 CRDT- 2023/06/09 10:33 PHST- 2023/04/16 00:00 [received] PHST- 2023/05/10 00:00 [revised] PHST- 2023/05/15 00:00 [accepted] PHST- 2023/08/11 06:43 [medline] PHST- 2023/06/09 13:42 [pubmed] PHST- 2023/06/09 10:33 [entrez] AID - S2213-1779(23)00245-7 [pii] AID - 10.1016/j.jchf.2023.05.010 [doi] PST - ppublish SO - JACC Heart Fail. 2023 Aug;11(8 Pt 1):1000-1010. doi: 10.1016/j.jchf.2023.05.010. Epub 2023 May 21. PMID- 37286889 OWN - NLM STAT- MEDLINE DCOM- 20230711 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 40 IP - 8 DP - 2023 Aug TI - Dosing Patterns of Dulaglutide and Semaglutide in Patients with Type 2 Diabetes in the United Kingdom and Germany: A Retrospective Cohort Study. PG - 3446-3464 LID - 10.1007/s12325-023-02540-y [doi] AB - INTRODUCTION: As new glucagon-like peptide 1 receptor agonist (GLP-1 RA) formulations are available, the aim of this study was to understand dulaglutide and subcutaneous (s.c.) semaglutide dosing patterns in people with type 2 diabetes mellitus (T2DM) in the UK and Germany as well as oral semaglutide in the UK. METHODS: Adults with evidence of T2DM and a prescription of dulaglutide or semaglutide between August 2020 and December 2021 were identified using the IQVIA Longitudinal Prescription Data (LRx). Patients were divided into cohort 1 (incident users) and cohort 2 (prevalent users) based on previous exposure to GLP-1 RAs and were followed up to 12 months post-index. RESULTS: During the patient selection window in Germany and the UK, 368,320 and 123,548 patients respectively received at least one prescription of a study GLP-1 RA. Among dulaglutide users in Germany at 12 months post-index, the 1.5-mg dosage formulation was the most common for both cohort 1 (65.6%) and 2 (71.2%). Among s.c. semaglutide users at 12 months post-index, 39.2% and 58.4% of cohort 1 received 0.5 mg and 1.0 mg, respectively. In the UK, at 12 months post-index, the most common dulaglutide dosage formulation was 1.5 mg (71.7% cohort 1 and 80.9% cohort 2). Among s.c. semaglutide users at 12 months post-index, 0.5- and 1.0-mg formulations were the most common for both cohort 1 (38.9% and 56.0%, respectively) and cohort 2 (29.5% and 67.1%, respectively). Prescribing of the more recently introduced 3.0- and 4.5-mg formulations for dulaglutide and oral semaglutide was also reported in the study. CONCLUSION: Dosing patterns of GLP-1 RAs, although similar between the UK and Germany, were heterogeneous over time. Given that the higher dulaglutide doses and oral semaglutide were recently introduced to the market, additional real-world evidence studies which include clinical outcomes is required. CI - (c) 2023. The Author(s). FAU - Barrett, Annabel AU - Barrett A AD - Eli Lilly and Company, 8 Arlington Square West, Downshire Way, Bracknell, RG12 1PU, UK. barrett_annabel@lilly.com. FAU - Debackere, Nele AU - Debackere N AD - Eli Lilly and Company, Brussels, Belgium. FAU - Ribeiro, Anderson AU - Ribeiro A AD - Eli Lilly and Company, Sao Paulo, Brazil. FAU - Keapoletswe, Karabo AU - Keapoletswe K AD - IQVIA, London, UK. FAU - Zingel, Rebecca AU - Zingel R AD - IQVIA, Frankfurt, Germany. FAU - Coles, Briana AU - Coles B AD - IQVIA, London, UK. LA - eng PT - Journal Article DEP - 20230607 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) MH - Adult MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Glucagon-Like Peptides/therapeutic use/analogs & derivatives MH - Glucagon-Like Peptide 1 MH - United Kingdom MH - Semaglutide MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC10246869 OTO - NOTNLM OT - Dose distribution OT - Dulaglutide OT - GLP-1 RA OT - Germany OT - Observational study OT - Oral semaglutide OT - Pharmacy OT - Subcutaneous semaglutide OT - Type 2 diabetes OT - United Kingdom COIS- Annabel Barrett, Nele Debackere, and Anderson Ribeiro are employees and shareholders of Eli Lilly and Company. Karabo Keapoletswe and Rebecca Zingel are employees of IQVIA, which was contracted by Eli Lilly and Company to conduct the study. Briana Coles is an employee of IQVIA, which was contracted by Eli Lilly and Company to conduct the study. She declares a grant from Novo Nordisk, an unpaid participation to a Data Safety Monitoring Committee for the North Bristol NHS Trust, and she is unpaid member of the Board of Directors of "Black Girls Do STEM". EDAT- 2023/06/08 01:08 MHDA- 2023/07/11 06:42 PMCR- 2023/06/07 CRDT- 2023/06/07 23:34 PHST- 2023/02/09 00:00 [received] PHST- 2023/04/28 00:00 [accepted] PHST- 2023/07/11 06:42 [medline] PHST- 2023/06/08 01:08 [pubmed] PHST- 2023/06/07 23:34 [entrez] PHST- 2023/06/07 00:00 [pmc-release] AID - 10.1007/s12325-023-02540-y [pii] AID - 2540 [pii] AID - 10.1007/s12325-023-02540-y [doi] PST - ppublish SO - Adv Ther. 2023 Aug;40(8):3446-3464. doi: 10.1007/s12325-023-02540-y. Epub 2023 Jun 7. PMID- 37280458 OWN - NLM STAT- MEDLINE DCOM- 20230811 LR - 20260127 IS - 1496-8975 (Electronic) IS - 0832-610X (Linking) VI - 70 IP - 8 DP - 2023 Aug TI - Regurgitation under anesthesia in a fasted patient prescribed semaglutide for weight loss: a case report. PG - 1397-1400 LID - 10.1007/s12630-023-02521-3 [doi] AB - PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide are a class of medications prescribed to treat type 2 diabetes mellitus, and more recently, as an adjunct for weight loss because of its effects of delaying gastric emptying and suppressing appetite. Semaglutide is a long-acting agent with a half-life of approximately one week, and there are currently no guidelines that address the perioperative management of such agents. CLINICAL FEATURES: We describe an unexpected case of regurgitation of a large volume of gastric contents upon induction of general anesthesia in a nondiabetic, nonobese patient despite a long preoperative fasting period (20 hr for solids and eight hours for clear fluids). This patient had no traditional risk factors for regurgitation or aspiration but was taking the GLP-1 RA semaglutide for weight loss and had last taken the medication two days before their scheduled procedure. CONCLUSIONS: Patients taking long-acting GLP-1 RAs such as semaglutide may be at risk of pulmonary aspiration under anesthesia. We propose strategies to mitigate this risk including holding the medication four weeks prior to a scheduled procedure when feasible and considering full stomach precautions. CI - (c) 2023. Canadian Anesthesiologists' Society. FAU - Gulak, Michael A AU - Gulak MA AUID- ORCID: 0000-0002-3427-8356 AD - Department of Anesthesiology and Pain Medicine, University of Toronto, 12th Floor, 123 Edward Street, Toronto, ON, M5G 1E2, Canada. mike.gulak@mail.utoronto.ca. FAU - Murphy, Patricia AU - Murphy P AD - Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, 200 Elizabeth Street, Toronto, ON, M5G 2C4, Canada. LA - eng PT - Case Reports PT - Journal Article TT - Regurgitation sous anesthesie chez une personne a jeun a qui du semaglutide a ete prescrit pour une perte de poids : une presentation de cas. DEP - 20230606 PL - United States TA - Can J Anaesth JT - Canadian journal of anaesthesia = Journal canadien d'anesthesie JID - 8701709 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Glucagon-Like Peptide 1/therapeutic use MH - Weight Loss MH - Fasting MH - Anesthesia, General MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - general anesthesia OT - glucagon-like peptide-1 receptor agonists OT - pulmonary aspiration OT - semaglutide EDAT- 2023/06/07 01:07 MHDA- 2023/08/11 06:43 CRDT- 2023/06/06 23:31 PHST- 2023/03/03 00:00 [received] PHST- 2023/03/15 00:00 [accepted] PHST- 2023/03/10 00:00 [revised] PHST- 2023/08/11 06:43 [medline] PHST- 2023/06/07 01:07 [pubmed] PHST- 2023/06/06 23:31 [entrez] AID - 10.1007/s12630-023-02521-3 [pii] AID - 10.1007/s12630-023-02521-3 [doi] PST - ppublish SO - Can J Anaesth. 2023 Aug;70(8):1397-1400. doi: 10.1007/s12630-023-02521-3. Epub 2023 Jun 6. PMID- 37276988 OWN - NLM STAT- MEDLINE DCOM- 20230807 LR - 20260127 IS - 1879-260X (Electronic) IS - 0925-4439 (Linking) VI - 1869 IP - 7 DP - 2023 Oct TI - Glucagon-like peptide-1 receptor agonist, semaglutide attenuates chronic liver disease-induced skeletal muscle atrophy in diabetic mice. PG - 166770 LID - S0925-4439(23)00136-9 [pii] LID - 10.1016/j.bbadis.2023.166770 [doi] AB - A glucagon-like peptide-1 receptor agonist (GLP-1RA) has recently been established as a pharmacological option for the treatment of type 2 diabetes. Recent studies have demonstrated the molecular role of GLP-1R in skeletal muscle homeostasis; however, the therapeutic efficacy of semaglutide, a GLP-1RA, on skeletal muscle atrophy in chronic liver disease (CLD) under diabetic conditions remains unclear. In the present study, semaglutide effectively inhibited psoas muscle atrophy and suppressed declines in grip strength in a diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-fed diabetic KK-A(y) mouse model. Moreover, semaglutide inhibited ubiquitin-proteosome-mediated skeletal muscle proteolysis and promoted myogenesis in palmitic acid (PA)-stimulated C2C12 murine myocytes. Mechanistically, this effect of semaglutide on skeletal muscle atrophy was mediated by multiple functional pathways. First, semaglutide protected against hepatic injury in mice accompanied by increased production of insulin-like growth factor 1 and reduced accumulation of reactive oxygen species (ROS). These effects were associated with decreased proinflammatory cytokines and ROS accumulation, leading to the suppression of ubiquitin-proteosome muscle degradation. Moreover, semaglutide inhibited the amino acid starvation-related stress signaling that was activated under chronic liver injury, resulting in the recovery of the mammalian target of rapamycin activity in the skeletal muscle of DDC-diet fed KK-A(y) mice. Second, semaglutide improved skeletal muscle atrophy by directly stimulating GLP-1R in myocytes. Semaglutide induced cAMP-mediated activation of PKA and AKT, enhanced mitochondrial biogenesis, and reduced ROS accumulation, thereby resulting in inhibition of NF-kappaB/myostatin-mediated ubiquitin-proteosome degradation and the augmentation of heat-shock factor-1-mediated myogenesis. Collectively, semaglutide may have potential as a new therapeutic strategy for CLD-related skeletal muscle wasting. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Iwai, Satoshi AU - Iwai S AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Kaji, Kosuke AU - Kaji K AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. Electronic address: kajik@naramed-u.ac.jp. FAU - Nishimura, Norihisa AU - Nishimura N AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Kubo, Takahiro AU - Kubo T AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Tomooka, Fumimasa AU - Tomooka F AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Shibamoto, Akihiko AU - Shibamoto A AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Suzuki, Junya AU - Suzuki J AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Tsuji, Yuki AU - Tsuji Y AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Fujinaga, Yukihisa AU - Fujinaga Y AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Kitagawa, Koh AU - Kitagawa K AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Namisaki, Tadashi AU - Namisaki T AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Akahane, Takemi AU - Akahane T AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. FAU - Yoshiji, Hitoshi AU - Yoshiji H AD - Department of Gastroenterology, Nara Medical University, Kashihara, Nara 634-8521, Japan. LA - eng PT - Journal Article DEP - 20230603 PL - Netherlands TA - Biochim Biophys Acta Mol Basis Dis JT - Biochimica et biophysica acta. Molecular basis of disease JID - 101731730 RN - 0 (Reactive Oxygen Species) RN - 0 (Ubiquitins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Mice MH - Animals MH - *Diabetes Mellitus, Type 2/complications/drug therapy/metabolism MH - *Diabetes Mellitus, Experimental/metabolism MH - Reactive Oxygen Species/metabolism MH - Muscular Atrophy/drug therapy/etiology/metabolism MH - Muscle, Skeletal/metabolism MH - *Liver Diseases/pathology MH - Ubiquitins/metabolism MH - Mammals MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Liver cirrhosis OT - Sarcopenia OT - Semaglutide OT - Type 2 diabetes COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/06/06 01:11 MHDA- 2023/08/07 06:42 CRDT- 2023/06/05 19:22 PHST- 2023/02/24 00:00 [received] PHST- 2023/05/15 00:00 [revised] PHST- 2023/05/28 00:00 [accepted] PHST- 2023/08/07 06:42 [medline] PHST- 2023/06/06 01:11 [pubmed] PHST- 2023/06/05 19:22 [entrez] AID - S0925-4439(23)00136-9 [pii] AID - 10.1016/j.bbadis.2023.166770 [doi] PST - ppublish SO - Biochim Biophys Acta Mol Basis Dis. 2023 Oct;1869(7):166770. doi: 10.1016/j.bbadis.2023.166770. Epub 2023 Jun 3. PMID- 37265222 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20260611 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 108 IP - 11 DP - 2023 Oct 18 TI - Effects of Aerobic Training and Semaglutide Treatment on Pancreatic beta-Cell Secretory Function in Patients With Type 2 Diabetes. PG - 2798-2811 LID - 10.1210/clinem/dgad326 [doi] AB - CONTEXT: Prior to this study, it is known that type 2 diabetes is linked to obesity and a sedentary lifestyle, leading to inadequate beta-cell function and insulin resistance. Limited research has explored the metabolic effects of combining exercise training with antidiabetic medications, particularly focusing on insulin secretion in patients with type 2 diabetes and moderately preserved beta-cell function. OBJECTIVE: The effect of the interaction of semaglutide and physical training on pancreatic beta-cell secretory function is unknown in patients with type 2 diabetes. METHODS: Thirty-one patients with type 2 diabetes underwent 12 weeks of aerobic training alone or concurrent to treatment with semaglutide. Patients randomly allocated to concurrent semaglutide and training were treated with semaglutide for 20 weeks before the training and evaluated at inclusion and again before and after the training intervention. Patients randomized to training were evaluated before and after training. The primary outcome was a change in insulin secretory capacity with training, evaluated by a 2-stepped hyperglycemic (20 and 30 mM) clamp. RESULTS: Training increased the incremental area under the curve for insulin from 21 to 27 nM x 2 hours (ratio 1.28, 95% CI 1.02-1.60) during clamp step 1 and from 40 to 64 nM x 2 hours (ratio 1.61, 95% CI 1.25-2.07) during step 2. Semaglutide treatment increased insulin secretion from 16 to 111 nM x 2 hours (ratio 7.10, 95% CI 3.68-13.71), and from 35 to 447 nM x 2 hours (ratio 12.74, 95% CI 5.65-28.71), correspondingly. Semaglutide and training increased insulin secretion from 130 to 171 nM x 2 hours (ratio 1.31, 95% CI 1.06-1.63), and from 525 to 697 nM x 2 hours (ratio 1.33, 95% CI 1.02-1.72), correspondingly. The median increase in total insulin secretion with the combination was 134 nM x 2 hours greater (95% CI 108-232) than with training. CONCLUSION: The combination of aerobic training and semaglutide treatment synergistically improved beta-cell secretory function. (ClinicalTrials.gov number, ID NCT04383197). CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Ingersen, Arthur AU - Ingersen A AUID- ORCID: 0000-0001-6112-3563 AD - Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. AD - Department of Geriatrics, Bispebjerg-Frederiksberg University Hospital, DK-2400 Copenhagen, Denmark. FAU - Schmucker, Malte AU - Schmucker M AD - Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. AD - Department of Geriatrics, Bispebjerg-Frederiksberg University Hospital, DK-2400 Copenhagen, Denmark. FAU - Alexandersen, Christina AU - Alexandersen C AD - Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. FAU - Graungaard, Benjamin AU - Graungaard B AD - Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. FAU - Thorngreen, Tobias AU - Thorngreen T AD - Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. FAU - Borch, Jacob AU - Borch J AD - Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. FAU - Holst, Jens Juul AU - Holst JJ AUID- ORCID: 0000-0001-6853-3805 AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. FAU - Helge, Jorn Wulff AU - Helge JW AUID- ORCID: 0000-0001-9724-5423 AD - Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. FAU - Dela, Flemming AU - Dela F AUID- ORCID: 0000-0001-9970-9535 AD - Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. AD - Department of Geriatrics, Bispebjerg-Frederiksberg University Hospital, DK-2400 Copenhagen, Denmark. LA - eng SI - ClinicalTrials.gov/NCT04383197 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - J Clin Endocrinol Metab. 2024 Jan 18;109(2):e860-e861. doi: 10.1210/clinem/dgad426. PMID: 37493062 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Insulin/therapeutic use MH - Semaglutide OTO - NOTNLM OT - exercise OT - glucagon-like peptide 1 OT - insulin secretion EDAT- 2023/06/02 13:15 MHDA- 2023/10/23 00:44 CRDT- 2023/06/02 08:12 PHST- 2023/02/28 00:00 [received] PHST- 2023/10/23 00:44 [medline] PHST- 2023/06/02 13:15 [pubmed] PHST- 2023/06/02 08:12 [entrez] AID - 7188955 [pii] AID - 10.1210/clinem/dgad326 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2023 Oct 18;108(11):2798-2811. doi: 10.1210/clinem/dgad326. PMID- 37264484 OWN - NLM STAT- MEDLINE DCOM- 20230803 LR - 20240902 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 25 IP - 9 DP - 2023 Sep TI - Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness. PG - 2586-2594 LID - 10.1111/dom.15143 [doi] AB - AIM: Glucagon-like peptide-1 receptor agonists provide multiple benefits to patients with type 2 diabetes, including improved glycaemic control, weight loss and decreased risk of major adverse cardiovascular events. Because drug responses vary among individuals, we initiated investigations to identify genetic variants associated with the magnitude of drug responses. METHODS: Exenatide (5 mug, subcutaneously) or saline (0.2 ml, subcutaneously) was administered to 62 healthy volunteers. Frequently sampled intravenous glucose tolerance tests were conducted to assess the impact of exenatide on insulin secretion and insulin action. This pilot study was a crossover design in which participants received exenatide and saline in random order. RESULTS: Exenatide increased first phase insulin secretion 1.9-fold (p = 1.9 x 10(-9) ) and accelerated the rate of glucose disappearance 2.4-fold (p = 2 x 10(-10) ). Minimal model analysis showed that exenatide increased glucose effectiveness (S(g) ) by 32% (p = .0008) but did not significantly affect insulin sensitivity (S(i) ). The exenatide-induced increase in insulin secretion made the largest contribution to interindividual variation in exenatide-induced acceleration of glucose disappearance while interindividual variation in the drug effect on S(g) contributed to a lesser extent (beta = 0.58 or 0.27, respectively). CONCLUSIONS: This pilot study provides validation for the value of a frequently sampled intravenous glucose tolerance test (including minimal model analysis) to provide primary data for our ongoing pharmacogenomic study of pharmacodynamic effects of semaglutide (NCT05071898). Three endpoints provide quantitative assessments of the effects of glucagon-like peptide-1 receptor agonists on glucose metabolism: first phase insulin secretion, glucose disappearance rates and glucose effectiveness. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Taylor, Simeon I AU - Taylor SI AUID- ORCID: 0000-0001-7500-7854 AD - Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Montasser, May E AU - Montasser ME AD - Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Yuen, Ashley H AU - Yuen AH AD - Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Fan, Hubert AU - Fan H AD - Diabetes, Endocrinology, and Obesity Branch, National institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. FAU - Yazdi, Zhinoosossadat Shahidzadeh AU - Yazdi ZS AD - Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Whitlatch, Hilary B AU - Whitlatch HB AD - Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Mitchell, Braxton D AU - Mitchell BD AD - Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Shuldiner, Alan R AU - Shuldiner AR AD - Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Muniyappa, Ranganath AU - Muniyappa R AD - Diabetes, Endocrinology, and Obesity Branch, National institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. FAU - Streeten, Elizabeth A AU - Streeten EA AD - Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Beitelshees, Amber L AU - Beitelshees AL AD - Department of Medicine, Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. LA - eng SI - ClinicalTrials.gov/NCT05071898 SI - ClinicalTrials.gov/NCT05762744 GR - P30 DK072488/DK/NIDDK NIH HHS/United States GR - R01 DK130238/DK/NIDDK NIH HHS/United States GR - T32 DK098107/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230601 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 9P1872D4OL (Exenatide) RN - IY9XDZ35W2 (Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Insulin) RN - 0 (Peptides) RN - 0 (Venoms) RN - 0 (Blood Glucose) SB - IM UOF - medRxiv. 2023 May 03:2023.03.15.23287166. doi: 10.1101/2023.03.15.23287166. PMID: 36993363 MH - Humans MH - Exenatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucose/therapeutic use MH - Insulin Secretion MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Pilot Projects MH - Glucagon-Like Peptide 1/therapeutic use MH - Insulin/therapeutic use MH - Peptides/pharmacology/therapeutic use MH - Venoms/adverse effects MH - Blood Glucose PMC - PMC10524849 MID - NIHMS1902218 OTO - NOTNLM OT - GLP-1 OT - clinical trial OT - exenatide OT - incretin therapy OT - insulin secretion OT - pharmacodynamics COIS- SIT serves as a consultant for Ionis Pharmaceuticals and receives an inventor's share of royalties from NIDDK for metreleptin as a treatment for generalized lipodystrophy. ARS is an employee of Regeneron Genetics Center. BDM and MEM receive grant support from Regeneron Genetics Center. BDM, MEM, EAS, and HBW have received partial salary support from funds provided by RGC. ALB, ZSY, RM, and HF declare no competing interests. EDAT- 2023/06/02 01:07 MHDA- 2023/08/03 06:43 PMCR- 2024/09/01 CRDT- 2023/06/01 23:47 PHST- 2023/05/02 00:00 [revised] PHST- 2023/03/23 00:00 [received] PHST- 2023/05/10 00:00 [accepted] PHST- 2023/08/03 06:43 [medline] PHST- 2023/06/02 01:07 [pubmed] PHST- 2023/06/01 23:47 [entrez] PHST- 2024/09/01 00:00 [pmc-release] AID - 10.1111/dom.15143 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Sep;25(9):2586-2594. doi: 10.1111/dom.15143. Epub 2023 Jun 1. PMID- 37256645 OWN - NLM STAT- MEDLINE DCOM- 20230623 LR - 20260127 IS - 1538-3598 (Electronic) IS - 0098-7484 (Linking) VI - 329 IP - 23 DP - 2023 Jun 20 TI - Oral Semaglutide Led to Similar Weight Loss as Injection, Company Says. PG - 2011 LID - 10.1001/jama.2023.9601 [doi] FAU - Harris, Emily AU - Harris E LA - eng PT - Journal Article PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/pharmacology MH - *Hypoglycemic Agents/adverse effects/pharmacology MH - *Weight Loss/drug effects MH - Semaglutide EDAT- 2023/05/31 13:11 MHDA- 2023/06/22 06:42 CRDT- 2023/05/31 11:43 PHST- 2023/06/22 06:42 [medline] PHST- 2023/05/31 13:11 [pubmed] PHST- 2023/05/31 11:43 [entrez] AID - 2805746 [pii] AID - 10.1001/jama.2023.9601 [doi] PST - ppublish SO - JAMA. 2023 Jun 20;329(23):2011. doi: 10.1001/jama.2023.9601. PMID- 37253796 OWN - NLM STAT- MEDLINE DCOM- 20230724 LR - 20261010 IS - 1476-5497 (Electronic) IS - 0307-0565 (Linking) VI - 47 IP - 8 DP - 2023 Aug TI - Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. PG - 677-685 LID - 10.1038/s41366-023-01321-5 [doi] AB - BACKGROUND: Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant weight loss effects. This systematic review and meta-analysis aims to assess the efficacy and safety of tirzepatide for weight loss in patients with overweight or obesity. METHODS: Medline, Embase and Cochrane CENTRAL were searched for randomized controlled trials (RCTs) on tirzepatide's weight loss efficacy for these patients. A single arm meta-analysis of proportions estimated primary outcomes, >/=5%, >/=10%, and >/=15% weight loss, and adverse events (AEs); while meta-analysis of means estimated secondary outcomes. Comparative meta-analysis was conducted between tirzepatide and control arms where mean differences and odds ratios were estimated for continuous and dichotomous outcomes respectively. RESULTS: RCTs included in this study revealed that among 5800 patients, 78.22% (95% CI: 72.15% to 83.73%), 55.60% (95% CI: 46.54% to 64.47%), 32.28% (95% CI: 23.17% to 42.12%) achieved >/=5%, >/=10%, and >/=15% weight loss, respectively. Tirzepatide 5 mg demonstrated weight loss superiority relative to placebo (MD: -12.47 kg, 95% CI: -13.94 kg to -11.00 kg) and semaglutide (n = 1409, MD: -1.90 kg, 95% CI: -2.97 kg to -0.83 kg) with dose-dependent increase for 10 mg and 15 mg doses. The comparison between tirzepatide and semaglutide was examined in the SURPASS-2 trial that was included in this systematic review. For AEs, there was increase odds of experiencing gastrointestinal AEs with tirzepatide compared to placebo, but no significant difference with semaglutide. CONCLUSION: Tirzepatide has significant potential as a weight loss drug in patients with overweight and obesity, with little increase in AEs compared to other weight loss drugs. With its ability to concurrently target multiple aspects of metabolic syndrome, it should be considered as the next helm of weight loss therapies. CI - (c) 2023. The Author(s), under exclusive licence to Springer Nature Limited. FAU - Tan, Bryan AU - Tan B AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Pan, Xin-Hui AU - Pan XH AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Chew, Han Shi Jocelyn AU - Chew HSJ AD - Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Goh, Rachel Sze Jen AU - Goh RSJ AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Lin, Chaoxing AU - Lin C AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Anand, Vickram Vijay AU - Anand VV AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. FAU - Lee, Ethan Cheng Zhe AU - Lee ECZ AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. FAU - Chan, Kai En AU - Chan KE AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Kong, Gwyneth AU - Kong G AD - Ministry of Health Holdings, Ministry of Health, Singapore, Singapore. FAU - Ong, Christen En Ya AU - Ong CEY AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Chung, Hui Charlotte AU - Chung HC AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Young, Dan Yock AU - Young DY AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. FAU - Chan, Mark Y AU - Chan MY AUID- ORCID: 0000-0003-0389-7450 AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. AD - Department of Cardiology, National University Heart Centre, Singapore, Singapore. FAU - Khoo, Chin Meng AU - Khoo CM AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. AD - Department of Endocrinology, National University Hospital, Singapore, Singapore. FAU - Mehta, Anurag AU - Mehta A AD - VCU Health Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA. FAU - Muthiah, Mark Dhinesh AU - Muthiah MD AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. AD - Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore. AD - National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore. FAU - Noureddin, Mazen AU - Noureddin M AD - Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Centre, Cedars-Sinai Medical Centre, Los Angeles, CA, USA. FAU - Ng, Cheng Han AU - Ng CH AD - Ministry of Health Holdings, Ministry of Health, Singapore, Singapore. chenhanng@gmail.com. FAU - Chew, Nicholas W S AU - Chew NWS AUID- ORCID: 0000-0002-0640-0430 AD - Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. AD - Department of Cardiology, National University Heart Centre, Singapore, Singapore. FAU - Chin, Yip Han AU - Chin YH AUID- ORCID: 0000-0002-8417-5996 AD - Ministry of Health Holdings, Ministry of Health, Singapore, Singapore. yiphan97@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20230531 PL - England TA - Int J Obes (Lond) JT - International journal of obesity (2005) JID - 101256108 RN - OYN3CCI6QE (Tirzepatide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - Overweight/drug therapy MH - Obesity/drug therapy MH - Gastric Inhibitory Polypeptide MH - *Anti-Obesity Agents/adverse effects MH - Weight Loss MH - *Diabetes Mellitus, Type 2 MH - Hypoglycemic Agents MH - Glucagon-Like Peptide-1 Receptor MH - Tirzepatide EDAT- 2023/05/31 01:09 MHDA- 2023/07/24 06:42 CRDT- 2023/05/30 23:20 PHST- 2022/12/30 00:00 [received] PHST- 2023/04/26 00:00 [accepted] PHST- 2023/04/23 00:00 [revised] PHST- 2023/07/24 06:42 [medline] PHST- 2023/05/31 01:09 [pubmed] PHST- 2023/05/30 23:20 [entrez] AID - 10.1038/s41366-023-01321-5 [pii] AID - 10.1038/s41366-023-01321-5 [doi] PST - ppublish SO - Int J Obes (Lond). 2023 Aug;47(8):677-685. doi: 10.1038/s41366-023-01321-5. Epub 2023 May 31. PMID- 37252413 OWN - NLM STAT- MEDLINE DCOM- 20230601 LR - 20260127 IS - 2308-118X (Electronic) IS - 0857-1074 (Print) IS - 0857-1074 (Linking) VI - 38 IP - 1 DP - 2023 TI - Real-World Use of Once-Weekly Semaglutide in Thai Patients With Type 2 Diabetes Mellitus in a Private Hospital Setting. PG - 21-28 LID - 10.15605/jafes.038.01.11 [doi] AB - OBJECTIVE: To evaluate the real-world use of once-weekly semaglutide among Thai patients with type 2 diabetes (T2DM) in a private hospital setting. METHODOLOGY: A retrospective review of Thai patients with T2DM who have initiated semaglutide for at least 1 month between June 2020 and March 2022 at Theptarin Hospital, Bangkok, Thailand. RESULTS: A total of 58 patients (50% female, mean age 55.6 +/- 15.9 years, with duration of diabetes 12.6 +/- 10.3 years, BMI 31.5 +/- 4.4 kg/m(2), baseline HbA(1c) 7.9 +/- 1.9%, with prior GLP-1 RA use 24.1%, and concomitant SGLT2i intake (41.4%) were included. During a median follow-up of 6 months, the mean serum HbA(1c) level reduction was 1.3 +/- 1.7% with weight loss of 4.7 +/- 4.1 kg. The proportion of patients who achieved optimal and sustainable glycemic control (HbA(1c) < 7.0%) increased from 43.1% to 55.8% at the last follow-up. The proportion of patients reaching both HbA(1c) targets of <7.0% and 5% weight loss was 27.8%. No cases of pancreatitis, cancer, or progressive retinopathy were observed. CONCLUSIONS: In this single center undertaking, it was shown that in among persons with T2DM and obesity in Thailand, semaglutide was associated with short-term glycemic control and weight loss comparable with what has been observed in randomized clinical trials and other RWE. CI - (c) 2023 Journal of the ASEAN Federation of Endocrine Societies. FAU - Thewjitcharoen, Yotsapon AU - Thewjitcharoen Y AD - Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand. FAU - Yenseung, Nalin AU - Yenseung N AD - Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand. FAU - Butadej, Siriwan AU - Butadej S AD - Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand. FAU - Nakasatien, Soontaree AU - Nakasatien S AD - Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand. FAU - Chotwanvirat, Phawinpon AU - Chotwanvirat P AD - Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand. FAU - Chatchomchuan, Waralee AU - Chatchomchuan W AD - Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand. FAU - Wanothayaroj, Ekgaluck AU - Wanothayaroj E AD - Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand. FAU - Krittiyawong, Sirinate AU - Krittiyawong S AD - Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand. FAU - Himathongkam, Thep AU - Himathongkam T AD - Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230302 PL - Philippines TA - J ASEAN Fed Endocr Soc JT - Journal of the ASEAN Federation of Endocrine Societies JID - 8608483 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - Hospitals, Private MH - *Hypoglycemic Agents/therapeutic use MH - Southeast Asian People MH - Thailand/epidemiology MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC10213164 OTO - NOTNLM OT - Thai OT - once-weekly OT - real-world OT - semaglutide COIS- The authors declared no conflict of interest. EDAT- 2023/05/30 13:07 MHDA- 2023/06/01 06:42 PMCR- 2023/01/01 CRDT- 2023/05/30 11:54 PHST- 2022/10/13 00:00 [received] PHST- 2022/11/30 00:00 [accepted] PHST- 2023/06/01 06:42 [medline] PHST- 2023/05/30 13:07 [pubmed] PHST- 2023/05/30 11:54 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - JAFES-38-1-21 [pii] AID - 10.15605/jafes.038.01.11 [doi] PST - ppublish SO - J ASEAN Fed Endocr Soc. 2023;38(1):21-28. doi: 10.15605/jafes.038.01.11. Epub 2023 Mar 2. PMID- 37233137 OWN - NLM STAT- MEDLINE DCOM- 20230529 LR - 20260127 IS - 1538-7488 (Electronic) IS - 0002-936X (Linking) VI - 123 IP - 6 DP - 2023 Jun 1 TI - New Indication for Weight Loss Drug Semaglutide. PG - 19 LID - 10.1097/01.NAJ.0000938724.36679.23 [doi] AB - The weight loss drug semaglutide (Wegovy) is now approved for pediatric patients ages 12 and older whose body mass index categorizes them as obese. CI - Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved. FAU - Aschenbrenner, Diane S AU - Aschenbrenner DS AD - Diane S. Aschenbrenner is a former member of the faculty at Notre Dame of Maryland University and the Johns Hopkins University School of Nursing. She coordinates Drug Watch : diane.aschenbrenner@gmail.com . LA - eng PT - Journal Article PL - United States TA - Am J Nurs JT - The American journal of nursing JID - 0372646 RN - 0 (Hypoglycemic Agents) RN - 0 (Anti-Obesity Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Child MH - Hypoglycemic Agents/adverse effects MH - *Anti-Obesity Agents/adverse effects MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides/therapeutic use MH - Semaglutide EDAT- 2023/05/26 13:09 MHDA- 2023/05/29 06:42 CRDT- 2023/05/26 09:53 PHST- 2023/05/29 06:42 [medline] PHST- 2023/05/26 13:09 [pubmed] PHST- 2023/05/26 09:53 [entrez] AID - 00000446-202306000-00017 [pii] AID - 10.1097/01.NAJ.0000938724.36679.23 [doi] PST - ppublish SO - Am J Nurs. 2023 Jun 1;123(6):19. doi: 10.1097/01.NAJ.0000938724.36679.23. PMID- 37231200 OWN - NLM STAT- MEDLINE DCOM- 20230808 LR - 20250626 IS - 1573-2606 (Electronic) IS - 1389-9155 (Print) IS - 1389-9155 (Linking) VI - 24 IP - 4 DP - 2023 Aug TI - Effects of GLP-1 receptor agonists on neurological complications of diabetes. PG - 655-672 LID - 10.1007/s11154-023-09807-3 [doi] AB - Emerging evidence suggests that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) could be an interesting treatment strategy to reduce neurological complications such as stroke, cognitive impairment, and peripheral neuropathy. We performed a systematic review to examine the evidence concerning the effects of GLP-1 RAs on neurological complications of diabetes. The databases used were Pubmed, Scopus and Cochrane. We selected clinical trials which analysed the effect of GLP-1 RAs on stroke, cognitive impairment, and peripheral neuropathy. We found a total of 19 studies: 8 studies include stroke or major cardiovascular events, 7 involve cognitive impairment and 4 include peripheral neuropathy. Semaglutide subcutaneous and dulaglutide reduced stroke cases. Liraglutide, albiglutide, oral semaglutide and efpeglenatide, were not shown to reduce the number of strokes but did reduce major cardiovascular events. Exenatide, dulaglutide and liraglutide improved general cognition but no significant effect on diabetic peripheral neuropathy has been reported with GLP-1 RAs. GLP-1 RAs are promising drugs that seem to be useful in the reduction of some neurological complications of diabetes. However, more studies are needed. CI - (c) 2023. The Author(s). FAU - Garcia-Casares, Natalia AU - Garcia-Casares N AD - Facultad de Medicina, Departamento de Medicina, Universidad de Malaga, Malaga, Spain. Nagcasares@uma.es. AD - Instituto de Investigacion Biomedica de Malaga (I.B.I.M.A), Malaga, Spain. Nagcasares@uma.es. AD - Centro de Investigaciones Medico-Sanitarias (C.I.M.ES), Malaga, Spain. Nagcasares@uma.es. AD - Departamento de Medicina, Facultad de Medicina, Universidad de Malaga, Centro de Investigaciones Medico Sanitarias (C.I.M.E.S), Universidad de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Campus Universitario de Teatinos s/n., Malaga, 29010, Espana. Nagcasares@uma.es. FAU - Gonzalez-Gonzalez, Guillermo AU - Gonzalez-Gonzalez G AD - Facultad de Medicina, Departamento de Medicina, Universidad de Malaga, Malaga, Spain. FAU - de la Cruz-Cosme, Carlos AU - de la Cruz-Cosme C AD - Instituto de Investigacion Biomedica de Malaga (I.B.I.M.A), Malaga, Spain. AD - Hospital Universitario Virgen de la Victoria de Malaga, Malaga, Spain. FAU - Garzon-Maldonado, Francisco J AU - Garzon-Maldonado FJ AD - Instituto de Investigacion Biomedica de Malaga (I.B.I.M.A), Malaga, Spain. AD - Hospital Universitario Virgen de la Victoria de Malaga, Malaga, Spain. FAU - de Rojas-Leal, Carmen AU - de Rojas-Leal C AD - Facultad de Medicina, Departamento de Medicina, Universidad de Malaga, Malaga, Spain. FAU - Ariza, Maria J AU - Ariza MJ AD - Facultad de Medicina, Departamento de Medicina, Universidad de Malaga, Malaga, Spain. AD - Instituto de Investigacion Biomedica de Malaga (I.B.I.M.A), Malaga, Spain. AD - Centro de Investigaciones Medico-Sanitarias (C.I.M.ES), Malaga, Spain. FAU - Narvaez, Manuel AU - Narvaez M AD - Facultad de Medicina, Departamento de Medicina, Universidad de Malaga, Malaga, Spain. AD - Instituto de Investigacion Biomedica de Malaga (I.B.I.M.A), Malaga, Spain. FAU - Barbancho, Miguel Angel AU - Barbancho MA AD - Facultad de Medicina, Departamento de Medicina, Universidad de Malaga, Malaga, Spain. AD - Instituto de Investigacion Biomedica de Malaga (I.B.I.M.A), Malaga, Spain. AD - Centro de Investigaciones Medico-Sanitarias (C.I.M.ES), Malaga, Spain. FAU - Garcia-Arnes, Juan Antonio AU - Garcia-Arnes JA AD - Facultad de Medicina, Departamento de Medicina, Universidad de Malaga, Malaga, Spain. FAU - Tinahones, Francisco J AU - Tinahones FJ AD - Facultad de Medicina, Departamento de Medicina, Universidad de Malaga, Malaga, Spain. fjtinahones@hotmail.com. AD - Instituto de Investigacion Biomedica de Malaga (I.B.I.M.A), Malaga, Spain. fjtinahones@hotmail.com. AD - Hospital Universitario Virgen de la Victoria de Malaga, Malaga, Spain. fjtinahones@hotmail.com. AD - Departamento de Medicina, Facultad de Medicina, Universidad de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Campus Universitario de Teatinos s/n., Malaga, 29010, Espana. fjtinahones@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20230526 PL - Germany TA - Rev Endocr Metab Disord JT - Reviews in endocrine & metabolic disorders JID - 100940588 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Liraglutide/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Glucagon-Like Peptide 1 MH - *Cardiovascular Diseases MH - *Stroke MH - *Diabetes Complications/drug therapy PMC - PMC10404567 OTO - NOTNLM OT - Alzheimer's disease OT - Cardiovascular disease OT - Cognitive impairment OT - Peripheral neuropathy OT - Stroke COIS- The authors have no competing interests to declare that are relevant to the content of this article. EDAT- 2023/05/26 01:05 MHDA- 2023/08/08 06:42 PMCR- 2023/05/26 CRDT- 2023/05/25 23:29 PHST- 2023/04/21 00:00 [accepted] PHST- 2023/08/08 06:42 [medline] PHST- 2023/05/26 01:05 [pubmed] PHST- 2023/05/25 23:29 [entrez] PHST- 2023/05/26 00:00 [pmc-release] AID - 10.1007/s11154-023-09807-3 [pii] AID - 9807 [pii] AID - 10.1007/s11154-023-09807-3 [doi] PST - ppublish SO - Rev Endocr Metab Disord. 2023 Aug;24(4):655-672. doi: 10.1007/s11154-023-09807-3. Epub 2023 May 26. PMID- 37230813 OWN - NLM STAT- MEDLINE DCOM- 20230801 LR - 20250103 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 17 IP - 4 DP - 2023 Aug TI - Differences in weight loss and safety between the glucagon-like peptide-1 receptor agonists: A non-randomized multicenter study from the titration phase. PG - 366-372 LID - S1751-9918(23)00095-5 [pii] LID - 10.1016/j.pcd.2023.05.004 [doi] AB - INTRODUCTION: Obesity increases the risk of type 2 diabetes mellitus and cardiovascular disease (CVD). Weight loss (>/=5 %) reduces the risk of CVD. Glucagon-like peptide-1 receptor agonists (GLP1 RA) have shown clinically weight loss. OBJECTIVES: 1) To assess differences in the efficacy of weight loss and HbA1c; 2) to evaluate the safety and adherence during the titration phase. METHODS: It is a multicenter, prospective, and observational study on GLP1 RA naive patients. The primary end point was the weight loss (>/=5 %). Changes in weight, BMI and HbA1c were also calculated as co-primary endpoints. Secondary endpoints were safety, adherence, and tolerance. RESULTS: Among 94 subjects, 42.4 % received dulaglutide, 29,3 % subcutaneous semaglutide, 22,8 % oral semaglutide. 45 % female and the mean age was 62. Baseline characteristics were body weight 99.3 kg, BMI 36.7 kg/m(2) and Hba1c 8.2 %. Oral semaglutide achieved the highest reduction: 61.1 % of patients achieving >/= 5 %, subcutaneous semaglutide 45.8 % and dulaglutide 40.6 %. GLP1 RA significantly reduced body weight (-4.95 kg, p < 0.001) and BMI (-1.86 kg/m(2), p < 0.001), without significant differences between groups. Gastrointestinal disorders were the most frequently reported events (74.5 %). 62 % of patients on dulaglutide, 25 % on oral semaglutide and 22 % on subcutaneous semaglutide. CONCLUSIONS: Oral semaglutide achieved the highest proportion of patients that lost >/= 5 %. GLP1 RA significantly reduced BMI and HbA1c. Most of the reported adverse events were gastrointestinal disorders and they were reported in a major frequency in the dulaglutide group. Oral semaglutide would be a reasonable switch in case of future shortages. CI - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Seijas-Amigo, Jose AU - Seijas-Amigo J AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Fundacion Instituto de Investigacion Sanitaria de Santiago de Compostela (FIDIS), Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Universidade de Santiago de Compostela. Electronic address: jose.seijas.amigo@sergas.es. FAU - Salgado-Barreira, Angel AU - Salgado-Barreira A AD - Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain; Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER en Epidemiologia y Salud PublicaCIBERESP), Carlos III Health Institute, Madrid, Spain. FAU - Castelo-Dominguez, Rosana AU - Castelo-Dominguez R AD - Centro de Salud, Ribeira, A Coruna, Spain. FAU - Perez-Alvarez, Maria Teresa AU - Perez-Alvarez MT AD - Centro de Salud de Culleredo, A Coruna, Spain. FAU - Ponce-Pinon, Belen AU - Ponce-Pinon B AD - Centro de Salud de Fene, A Coruna, Spain. FAU - Fernandez-Silva, Marlen AU - Fernandez-Silva M AD - Centro de Salud O Ventorillo, A Coruna, Spain. FAU - Rodriguez-Barreiro, Marta AU - Rodriguez-Barreiro M AD - Centro de Salud. Virxe Peregrina, Pontevedra, Spain. FAU - Pereira-Pia, Mercedes AU - Pereira-Pia M AD - Centro de Salud de San Roque, Lugo, Spain. FAU - Iglesias-Moreno, Jose Manuel AU - Iglesias-Moreno JM AD - Centro de Salud de Val Minor, Nigran, Pontevedra, Spain. FAU - Gago-Garcia, Mar AU - Gago-Garcia M AD - Centro de Salud de Ribadeo, Lugo, Spain. FAU - Montans-Garcia, Raquel AU - Montans-Garcia R AD - Centro de Salud de Cee, A Coruna, Spain. FAU - Fernandez-Perez, Agustina AU - Fernandez-Perez A AD - Centro de Salud Vilalba, Lugo, Spain. FAU - FragaGayoso, Dolores AU - FragaGayoso D AD - Centro de Salud de Sarria, Lugo, Spain. FAU - Fernandez-Montenegro, Montse AU - Fernandez-Montenegro M AD - Centro de Salud de O Carballino, Ourense, Spain. FAU - Riveiro-Barciela, Beatriz AU - Riveiro-Barciela B AD - Centro de Salud O Temple, A Coruna, Spain. FAU - Rilla-Villar, Natalia AU - Rilla-Villar N AD - Centro de Salud de Arriondas, Asturias, Spain. FAU - Cordero, Alberto AU - Cordero A AD - Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain; Cardiology Department. Hospital Universitario de San Juan, Alicante, Spain; Unidad de Investigacion en Cardiologia. Fundacion para el Fomento de la Investigacion Sanitaria y Biomedica de la Comunitat Valenciana (FISABIO), Spain. FAU - RodriguezManero, Moises AU - RodriguezManero M AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. FAU - Gonzalez-Juanatey, Jose R AU - Gonzalez-Juanatey JR AD - Cardiology Department. Complejo Hospitalario Universidad de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20230523 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Female MH - Middle Aged MH - Male MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Glycated Hemoglobin MH - Prospective Studies MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Adherence OT - Glucagon-like peptide 1 OT - Glycemic control OT - Obesity OT - Safety OT - Type 2 diabetes OT - Weight change COIS- Declaration of Competing Interest Authors declare that there are no conflicts of interest related to the results of this study. Jose Seijas Amigo reports consulting fees from Astra Zeneca. All authors accept the rules of the announcement. EDAT- 2023/05/26 01:05 MHDA- 2023/08/01 06:44 CRDT- 2023/05/25 21:58 PHST- 2023/02/13 00:00 [received] PHST- 2023/04/18 00:00 [revised] PHST- 2023/05/11 00:00 [accepted] PHST- 2023/08/01 06:44 [medline] PHST- 2023/05/26 01:05 [pubmed] PHST- 2023/05/25 21:58 [entrez] AID - S1751-9918(23)00095-5 [pii] AID - 10.1016/j.pcd.2023.05.004 [doi] PST - ppublish SO - Prim Care Diabetes. 2023 Aug;17(4):366-372. doi: 10.1016/j.pcd.2023.05.004. Epub 2023 May 23. PMID- 37225492 OWN - NLM STAT- MEDLINE DCOM- 20240105 LR - 20260127 IS - 1349-7235 (Electronic) IS - 0918-2918 (Print) IS - 0918-2918 (Linking) VI - 63 IP - 1 DP - 2024 Jan 1 TI - Daily Glucose Profiles after Switching from Injectable to Oral Semaglutide in Patients with Type 2 Diabetes Mellitus. PG - 43-50 LID - 10.2169/internalmedicine.1441-22 [doi] AB - Objective This prospective observational study explored the changes in the daily glycemic profile after switching from injectable to oral semaglutide in patients with type 2 diabetes mellitus. Methods Patients with type 2 diabetes mellitus who were treated with once-weekly 0.5 mg injectable semaglutide and wished to switch to once-daily oral semaglutide participated in this study. Oral semaglutide was initiated at 3 mg and increased to 7 mg a month later, according to the package insert. Before and two months after the switch, participants wore a sensor for continuous glucose monitoring for up to 14 days. We also evaluated the questionnaire-based treatment satisfaction and the preference between the two formulations. Patients Twenty-three patients participated. Results Mean glucose levels significantly increased by 9 mg/dL on average, from 132+/-20 to 141+/-27 mg/dL (p=0.047), which was equivalent to a change of 0.2% in the estimated hemoglobin A1c (6.5+/-0.5% to 6.7+/-0.7%). The inter-individual variability assessed with standard deviation also significantly increased (p=0.004). The change in treatment satisfaction varied considerably among patients, with no specific trend in the overall population. After trying oral semaglutide, 48% of patients responded that they preferred the oral formulation, while 35% preferred the injectable formulation, and 17% had no preference. Conclusion The mean glucose levels increased by 9 mg/dL on average after switching from once-weekly 0.5 mg injectable semaglutide to once-daily 7 mg oral semaglutide, with an increased inter-individual variability. The change in treatment satisfaction considerably varied among patients. FAU - Takahara, Mitsuyoshi AU - Takahara M AD - Department of Diabetes Care Medicine, Osaka University Graduate School of Medicine, Japan. FAU - Shiraiwa, Toshihiko AU - Shiraiwa T AD - Shiraiwa Medical Clinic, Japan. FAU - Katakami, Naoto AU - Katakami N AD - Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Japan. FAU - Maeno, Yoshifumi AU - Maeno Y AD - Shiraiwa Medical Clinic, Japan. FAU - Yamamoto, Kaoru AU - Yamamoto K AD - Shiraiwa Medical Clinic, Japan. FAU - Shiraiwa, Yuka AU - Shiraiwa Y AD - Shiraiwa Medical Clinic, Japan. FAU - Yoshida, Yoko AU - Yoshida Y AD - Shiraiwa Medical Clinic, Japan. FAU - Kozawa, Junji AU - Kozawa J AD - Department of Diabetes Care Medicine, Osaka University Graduate School of Medicine, Japan. FAU - Shimomura, Iichiro AU - Shimomura I AD - Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Japan. LA - eng PT - Journal Article PT - Observational Study DEP - 20230524 PL - Japan TA - Intern Med JT - Internal medicine (Tokyo, Japan) JID - 9204241 RN - 0 (Hypoglycemic Agents) RN - IY9XDZ35W2 (Glucose) RN - 0 (Blood Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucose MH - Blood Glucose Self-Monitoring MH - Blood Glucose MH - Semaglutide PMC - PMC10824647 OTO - NOTNLM OT - continuous glucose monitoring OT - semaglutide OT - treatment satisfaction COIS- Author's disclosure of potential Conflicts of Interest (COI). Mitsuyoshi Takahara: Endowed chair, MSD. Junji Kozawa: Endowed chair, MSD. Iichiro Shimomura: Honoraria, Novo Nordisk Pharma; Scholarship grants, Novo Nordisk Pharma. EDAT- 2023/05/25 01:07 MHDA- 2024/01/05 06:42 PMCR- 2024/01/01 CRDT- 2023/05/24 21:53 PHST- 2024/01/05 06:42 [medline] PHST- 2023/05/25 01:07 [pubmed] PHST- 2023/05/24 21:53 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - 10.2169/internalmedicine.1441-22 [doi] PST - ppublish SO - Intern Med. 2024 Jan 1;63(1):43-50. doi: 10.2169/internalmedicine.1441-22. Epub 2023 May 24. PMID- 37203328 OWN - NLM STAT- MEDLINE DCOM- 20230522 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 31 IP - 6 DP - 2023 Jun TI - Liraglutide versus semaglutide for weight reduction-a cost needed to treat analysis. PG - 1510-1513 LID - 10.1002/oby.23752 [doi] AB - OBJECTIVE: Higher doses of the glucagon-like peptide-1 agonists liraglutide and, more recently, semaglutide have demonstrated a significant reduction in body weight. However, their comparative value for money for this indication is unclear. METHODS: The cost needed to treat to achieve a 1% reduction in body weight using semaglutide or liraglutide was calculated. The body weight reductions were extracted from the published STEP 1 trial and the SCALE trial results, respectively. A scenario analysis was performed to mitigate the primary differences between the two studies' populations. Drug costs were based on US GoodRx prices as of October 2022. RESULTS: Liraglutide in STEP 1 resulted in a weight loss of 5.4% (95% CI: 5%-5.8%). Semaglutide in SCALE resulted in a weight loss of 12.4% (95% CI: 11.5%-13.4%). The total cost of therapy with liraglutide during the trial was estimated at $17,585 compared with $22,878 with semaglutide. Accordingly, the cost needed to treat per 1% of body weight reduction with liraglutide is estimated at $3256 (95% CI: $3032-$3517) compared with $1845 (95% CI: $1707-$1989) with semaglutide. CONCLUSIONS: Semaglutide provides significantly better value for money than liraglutide for weight reduction. CI - (c) 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Azuri, Joseph AU - Azuri J AUID- ORCID: 0000-0003-1049-9848 AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Maccabi Healthcare Services, Tel Aviv, Israel. FAU - Hammerman, Ariel AU - Hammerman A AUID- ORCID: 0000-0002-4396-5246 AD - Clalit Health Services, Tel Aviv, Israel. FAU - Aboalhasan, Enis AU - Aboalhasan E AUID- ORCID: 0000-0001-7763-566X AD - Maximizing Health Outcomes Research Lab, Sapir College, Israel. FAU - Sluckis, Ben AU - Sluckis B AD - Meuhedet Health Services, Jerusalem, Israel. FAU - Arbel, Ronen AU - Arbel R AD - Clalit Health Services, Tel Aviv, Israel. AD - Maximizing Health Outcomes Research Lab, Sapir College, Israel. LA - eng PT - Journal Article PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Liraglutide/pharmacology/therapeutic use MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - Weight Loss MH - Body Weight MH - Semaglutide EDAT- 2023/05/19 06:42 MHDA- 2023/05/22 06:42 CRDT- 2023/05/19 03:52 PHST- 2022/12/16 00:00 [revised] PHST- 2022/11/02 00:00 [received] PHST- 2022/12/31 00:00 [accepted] PHST- 2023/05/22 06:42 [medline] PHST- 2023/05/19 06:42 [pubmed] PHST- 2023/05/19 03:52 [entrez] AID - 10.1002/oby.23752 [doi] PST - ppublish SO - Obesity (Silver Spring). 2023 Jun;31(6):1510-1513. doi: 10.1002/oby.23752. PMID- 37199890 OWN - NLM STAT- MEDLINE DCOM- 20230810 LR - 20231011 IS - 1434-9949 (Electronic) IS - 0770-3198 (Print) IS - 0770-3198 (Linking) VI - 42 IP - 9 DP - 2023 Sep TI - Eosinophil-related diseases during treatment with glucagon-like peptide one receptor (GLP-1 RA): a case report and review of the literature. PG - 2501-2506 LID - 10.1007/s10067-023-06612-w [doi] AB - Glucagon-like peptide one-receptor agonists (GLP-1 RA) are drugs that differ in their pharmacological composition and homology to human GLP-1 and are used most frequently for the treatment of type 2 diabetes and weight loss. There are isolated reports of eosinophilic adverse reactions associated with GLP-1 RA. We present the case of a 42-year-old female patient who, after starting weekly subcutaneous semaglutide, developed eosinophilic fasciitis with favorable clinical evolution after the discontinuation of semaglutide and the initiation of immunosuppression. A review of the eosinophilic adverse events that have been previously reported with GLP-1 RA is provided. CI - (c) 2023. The Author(s). FAU - Posso-Osorio, Ivan AU - Posso-Osorio I AD - Universidad Icesi, Facultad de Ciencias de la Salud, Cali, 760031, Colombia. AD - Unit of Rheumatology, Fundacion Valle del Lili, Unidad de Reumatologia, Cali, 760031, Colombia. AD - Universidad Icesi, CIRAT: Centro de Investigacion en Reumatologia, Autoinmunidad y Medicina Traslacional, Cali, 760031, Colombia. FAU - Vargas-Potes, Carlos Julio AU - Vargas-Potes CJ AD - Universidad Icesi, Facultad de Ciencias de la Salud, Cali, 760031, Colombia. FAU - Mejia, Mauricio AU - Mejia M AD - Fundacion Valle del Lili, Unidad de Radiologia, Cali, 760031, Colombia. FAU - Canas, Carlos A AU - Canas CA AUID- ORCID: 0000-0002-6879-3700 AD - Universidad Icesi, Facultad de Ciencias de la Salud, Cali, 760031, Colombia. cacanas@icesi.edu.co. AD - Unit of Rheumatology, Fundacion Valle del Lili, Unidad de Reumatologia, Cali, 760031, Colombia. cacanas@icesi.edu.co. AD - Universidad Icesi, CIRAT: Centro de Investigacion en Reumatologia, Autoinmunidad y Medicina Traslacional, Cali, 760031, Colombia. cacanas@icesi.edu.co. LA - eng PT - Case Reports PT - Journal Article PT - Review DEP - 20230518 PL - Germany TA - Clin Rheumatol JT - Clinical rheumatology JID - 8211469 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide Receptors) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Female MH - Humans MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide Receptors MH - Eosinophils MH - Glucagon-Like Peptide 1/therapeutic use PMC - PMC10412476 OTO - NOTNLM OT - Adverse event OT - Eosinophilic fasciitis OT - Semaglutide OT - Side effect COIS- The authors declare no competing interests. EDAT- 2023/05/18 13:09 MHDA- 2023/08/10 06:43 PMCR- 2023/05/18 CRDT- 2023/05/18 11:13 PHST- 2023/03/30 00:00 [received] PHST- 2023/04/21 00:00 [accepted] PHST- 2023/04/14 00:00 [revised] PHST- 2023/08/10 06:43 [medline] PHST- 2023/05/18 13:09 [pubmed] PHST- 2023/05/18 11:13 [entrez] PHST- 2023/05/18 00:00 [pmc-release] AID - 10.1007/s10067-023-06612-w [pii] AID - 6612 [pii] AID - 10.1007/s10067-023-06612-w [doi] PST - ppublish SO - Clin Rheumatol. 2023 Sep;42(9):2501-2506. doi: 10.1007/s10067-023-06612-w. Epub 2023 May 18. PMID- 37196421 OWN - NLM STAT- MEDLINE DCOM- 20230724 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 31 IP - 8 DP - 2023 Aug TI - Reducing BMI below the obesity threshold in adolescents treated with once-weekly subcutaneous semaglutide 2.4 mg. PG - 2139-2149 LID - 10.1002/oby.23808 [doi] AB - OBJECTIVE: The aim of this study was to examine how improvement in BMI with the glucagon-like peptide-1 receptor agonist semaglutide translated to changes in BMI category in a post hoc analysis of the double-blind, phase 3a randomized controlled Semaglutide Treatment Effect in People with obesity (STEP) TEENS trial. METHODS: Adolescents with obesity received once-weekly subcutaneous semaglutide 2.4 mg or placebo plus lifestyle intervention, which comprised counseling in healthy nutrition and a goal of 60 minutes of moderate- to high-intensity physical activity per day. Achievement of an improvement in BMI category and attainment of normal-weight or overweight BMI by week 68 were analyzed using logistic regression models. RESULTS: In the overall population, 44.9% of participants receiving semaglutide achieved weight reduction resulting in reclassification to a normal-weight or overweight BMI category versus 12.1% receiving placebo at week 68 (odds ratio: 22.7; 95% CI: 7.6-67.9). The proportion of semaglutide-treated participants in obesity class III decreased from 37.3% to 13.6% but increased with placebo. The odds ratio for achieving an improvement of at least one BMI category was significantly greater with semaglutide versus placebo (23.5; 95% CI: 9.9-55.5); an improvement of at least one BMI category was seen in 73.7% of participants receiving semaglutide compared with 19.0% of participants receiving placebo. CONCLUSIONS: Semaglutide was highly effective in reducing BMI category. While on treatment, most trial participants' BMI improved by at least one category, and >40% reached a category below the obesity threshold. CI - (c) 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Kelly, Aaron S AU - Kelly AS AUID- ORCID: 0000-0001-8530-107X AD - Department of Pediatrics and Center for Pediatric Obesity Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA. FAU - Arslanian, Silva AU - Arslanian S AD - Division of Pediatric Endocrinology, Diabetes and Metabolism, Center for Pediatric Research in Obesity and Metabolism, University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA. FAU - Hesse, Dan AU - Hesse D AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Iversen, Aske Thorn AU - Iversen AT AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Korner, Antje AU - Korner A AD - Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum Munchen at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany. AD - Center for Pediatric Research (CPL), Leipzig University, Medical Faculty, Hospital for Children and Adolescents, Leipzig, Germany. FAU - Schmidt, Signe AU - Schmidt S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sorrig, Rasmus AU - Sorrig R AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Weghuber, Daniel AU - Weghuber D AD - Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria. FAU - Jastreboff, Ania M AU - Jastreboff AM AUID- ORCID: 0000-0003-1446-0991 AD - Department of Medicine (Endocrinology and Metabolism) and Department of Pediatrics (Pediatric Endocrinology), Yale University School of Medicine, New Haven, Connecticut, USA. LA - eng SI - ClinicalTrials.gov/NCT04102189 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230709 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Adolescent MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Body Mass Index MH - Overweight/drug therapy MH - Treatment Outcome MH - Obesity/drug therapy MH - Double-Blind Method MH - Semaglutide EDAT- 2023/05/18 01:07 MHDA- 2023/07/24 06:42 CRDT- 2023/05/17 18:03 PHST- 2023/04/28 00:00 [revised] PHST- 2023/03/30 00:00 [received] PHST- 2023/04/28 00:00 [accepted] PHST- 2023/07/24 06:42 [medline] PHST- 2023/05/18 01:07 [pubmed] PHST- 2023/05/17 18:03 [entrez] AID - 10.1002/oby.23808 [doi] PST - ppublish SO - Obesity (Silver Spring). 2023 Aug;31(8):2139-2149. doi: 10.1002/oby.23808. Epub 2023 Jul 9. PMID- 37189293 OWN - NLM STAT- MEDLINE DCOM- 20230822 LR - 20260127 IS - 1445-5994 (Electronic) IS - 1444-0903 (Linking) VI - 53 IP - 8 DP - 2023 Aug TI - Weight loss with subcutaneous semaglutide versus other glucagon-like peptide 1 receptor agonists in type 2 diabetes: a systematic review. PG - 1311-1320 LID - 10.1111/imj.16126 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduce elevated blood glucose levels and induce weight loss. Multiple GLP-1 RAs and one combined GLP-1/glucose-dependent insulinotropic polypeptide agonist are currently available. This review was conducted with the aim of summarising direct comparisons between subcutaneous semaglutide and other GLP-1 RAs in individuals with type 2 diabetes (T2D), particularly with respect to efficacy for inducing weight loss and improving other markers of metabolic health. This systematic review of PubMed and Embase from inception to early 2022 was registered on PROSPERO and was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. Of the 740 records identified in the search, five studies fulfilled the inclusion criteria. Comparators included liraglutide, exenatide, dulaglutide and tirzepatide. In the identified studies, multiple dosing regimens were utilised for semaglutide. Randomised trials support the superior efficacy of semaglutide over other GLP-1 RAs with respect to weight loss in T2D, but tirzepatide is more effective than semaglutide. CI - (c) 2023 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians. FAU - Stretton, Brandon AU - Stretton B AUID- ORCID: 0000-0002-7939-3489 AD - Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. FAU - Kovoor, Joshua AU - Kovoor J AUID- ORCID: 0000-0002-3880-3840 AD - Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. FAU - Bacchi, Stephen AU - Bacchi S AD - Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. FAU - Chang, Shantel AU - Chang S AD - School of Medicine, Griffith University, Brisbane, Queensland, Australia. FAU - Ngoi, Benjamin AU - Ngoi B AD - Central Adelaide Local Health Network, Adelaide, South Australia, Australia. FAU - Murray, Tess AU - Murray T AD - Central Adelaide Local Health Network, Adelaide, South Australia, Australia. FAU - Bristow, Thomas C AU - Bristow TC AD - Central Adelaide Local Health Network, Adelaide, South Australia, Australia. FAU - Heng, Jonathan AU - Heng J AD - Central Adelaide Local Health Network, Adelaide, South Australia, Australia. FAU - Gupta, Aashray AU - Gupta A AD - Gold Coast University Hospital, Brisbane, Queensland, Australia. FAU - Ovenden, Christopher AU - Ovenden C AD - Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. FAU - Maddern, Guy AU - Maddern G AD - Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. FAU - Thompson, Campbell H AU - Thompson CH AUID- ORCID: 0000-0002-5164-3327 AD - Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. FAU - Heilbronn, Leonie AU - Heilbronn L AD - Metabolic Health Unit, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia. FAU - Boyd, Mark AU - Boyd M AD - Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. AD - Northern Adelaide Local Health Network, Adelaide, South Australia, Australia. FAU - Rayner, Christopher AU - Rayner C AD - Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. FAU - Talley, Nicholas J AU - Talley NJ AD - Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia. AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA. FAU - Horowtiz, Michael AU - Horowtiz M AD - Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. AD - National Health and Medical Research Council, Centre of Research Excellence in Translating Nutritional Science to Good Health, The University. of Adelaide, Adelaide, South Australia, Australia. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20230621 PL - Australia TA - Intern Med J JT - Internal medicine journal JID - 101092952 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide 1 MH - Weight Loss MH - Observational Studies as Topic MH - Semaglutide OTO - NOTNLM OT - obesity OT - type 2 diabetes OT - weight loss EDAT- 2023/05/16 06:42 MHDA- 2023/08/22 06:42 CRDT- 2023/05/16 00:44 PHST- 2023/03/31 00:00 [received] PHST- 2023/05/11 00:00 [accepted] PHST- 2023/08/22 06:42 [medline] PHST- 2023/05/16 06:42 [pubmed] PHST- 2023/05/16 00:44 [entrez] AID - 10.1111/imj.16126 [doi] PST - ppublish SO - Intern Med J. 2023 Aug;53(8):1311-1320. doi: 10.1111/imj.16126. Epub 2023 Jun 21. PMID- 37137527 OWN - NLM STAT- MEDLINE DCOM- 20230505 LR - 20260127 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 11 IP - 3 DP - 2023 May TI - Study design and baseline profile for adults with type 2 diabetes in the once-weekly subcutaneous SEmaglutide randomized PRAgmatic (SEPRA) trial. LID - 10.1136/bmjdrc-2022-003206 [doi] LID - e003206 AB - INTRODUCTION: Once-weekly subcutaneous semaglutide, a glucagon-like peptide-1 analog, is approved in the USA as an adjunct to diet and exercise for adults with inadequately controlled type 2 diabetes (T2D) to improve glycemic control and reduce the risk of major adverse cardiovascular events in people with T2D and established cardiovascular disease. The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) phase III clinical trial program demonstrated the efficacy and safety of once-weekly subcutaneous semaglutide; however, determining its effectiveness in a real-world setting could support decision-making by clinicians, payers and policy makers in routine clinical practice. RESEARCH DESIGN AND METHODS: SEmaglutide PRAgmatic (SEPRA) is an ongoing open-label, randomized, pragmatic clinical trial designed to compare the effects of once-weekly subcutaneous semaglutide versus standard of care in US health-insured adults with T2D and physician-determined inadequate glycemic control. The primary end point is the proportion of participants achieving glycated hemoglobin (HbA1c) <7.0% at year 1; other key outcomes include glycemic control, weight loss, healthcare utilization, and patient-reported outcomes. Individual-level data will be collected from routine clinical practice and health insurance claims. The last patient last visit is expected by June 2023. RESULTS: Between July 2018 and March 2021, 1278 participants were enrolled from 138 study sites across the USA. At baseline, 54% were male with mean+/-SD age 57.4+/-11.1 years and body mass index 35.7+/-8.0 kg/m(2). Mean diabetes duration was 7.4+/-6.0 years and mean HbA1c was 8.5+/-1.6%. At baseline, concomitant antidiabetes medications included metformin, sulfonylureas, sodium-glucose co-transporter-2 inhibitors, and dipeptidyl peptidase-4 inhibitors. The majority of participants had hypertension and dyslipidemia. The trial design was self-assessed using the PRagmatic Explanatory Continuum Indicator Summary-2 tool by the study steering group and was scored 4-5 in all domains suggesting a highly pragmatic study. CONCLUSIONS: SEPRA, a highly pragmatic ongoing study, will provide data on the effects of once-weekly subcutaneous semaglutide in a real-world setting when used during routine management of T2D. TRIAL REGISTRATION NUMBER: NCT03596450. CI - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. FAU - Nordahl Christensen, Helene AU - Nordahl Christensen H AD - Clinical Development & Outcomes Research, Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Harty, Brian J AU - Harty BJ AD - Clinical Research - Biostatistics, HealthCore, Inc, Watertown, Massachusetts, USA. FAU - Mitchell, Julie AU - Mitchell J AD - Commercial Clinical Operations, Anthem Inc, Milwaukee, Wisconsin, USA. FAU - Soule, Benjamin P AU - Soule BP AD - Clinical Development & Outcomes Research, Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Zacherle, Emily AU - Zacherle E AD - Clinical Development & Outcomes Research, Novo Nordisk Inc, Plainsboro, New Jersey, USA. FAU - Cziraky, Mark AU - Cziraky M AD - Scientific Affairs, HealthCore Inc, Wilmington, Delaware, USA. FAU - Willey, Vincent J AU - Willey VJ AUID- ORCID: 0000-0002-6473-6469 AD - Scientific Affairs, HealthCore Inc, Wilmington, Delaware, USA vwilley@healthcore.com. LA - eng SI - ClinicalTrials.gov/NCT03596450 GR - P30 DK124723/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Male MH - Humans MH - Adult MH - Middle Aged MH - Aged MH - Female MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Glycated Hemoglobin MH - *Metformin/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Semaglutide PMC - PMC10163526 OTO - NOTNLM OT - diabetes mellitus, type 2 OT - glucagon-like peptide 1 COIS- Competing interests: BPS received support for the present manuscript from Novo Nordisk as a full-time employee. Holds stock or stock options for Novo Nordisk as an employee and Bristol Myers Squibb as a former employee. JBB received support for the present manuscript from Novo Nordisk, funded the study, writing support, and fees to my institution. Received grants from NIH, Dexcom, NovaTarg, Novo Nordisk, Sanofi, Tolerion, and vTv Therapeutics for clinical trials. Consulting fees (personal) from Alkahest, Altimmune, Anji, AstraZeneca, Bayer, Biomea Fusion, Boehringer-Ingelheim, CeQur, Cirius Therapeutics, Dasman Diabetes Center (Kuwait), Eli Lilly, Fortress Biotech, GentiBio, Glycadia, Glyscend, Janssen, MannKind, Mediflix, Medscape, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, ReachMD, Sanofi, Stability Health, Valo, Zealand Pharma. Consulting fees (funds to institution) from Novo Nordisk. Support for attending meetings and/or travel from AstraZeneca, Boehringer-Ingelheim, Dasman Diabetes Institute, Eli Lilly, Novo Nordisk, Zealand in the context of consulting. Participation on a data safety monitoring board or advisory board from Alkahest, Altimmune, Anji, AstraZeneca, Bayer, Biomea Fusion, Boehringer Ingelheim, CeQur, Cirius Therapeutics, Eli Lilly, GentiBio, Glycadia, Glyscend, Janssen, MannKind, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, Sanofi, Stability Health, Valo, Zealand Pharma. Leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid from Association for Clinical and Translational Science. Holds stock or stock options for Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego, and Stability Health. Is a member of the Editorial Board of BMJ Open Diabetes Research & Care. MJC received support for the present manuscript from HealthCore. Employer HealthCore received funding from Novo Nordisk to perform the study services. Holds stock or stock options for Elevance Health as a stockholder in ELV, which is the parent company of HealthCore. EWZ received medical writing support from Spirit Medical Communications. Support for attending meetings and/or travel from Novo Nordisk as an employee. Other financial or non-financial interests from Novo Nordisk as an employee. BJH received support for the present manuscript from Novo Nordisk, as sponsor of the SEPRA trial, contracted with employer, HealthCore, to serve as the data coordinating center for the trial, performing all data collection and analysis, and supporting manuscript writing activities. HNC received support for the present manuscript from Novo Nordisk as an employee. Holds stock or stock options for Novo Nordisk. VW received support for the present manuscript from HealthCore. Employer HealthCore received funding from Novo Nordisk to perform the study services. Holds stock or stock options for Elevance Health as a stockholder in ELV, which is the parent company of HealthCore. EDAT- 2023/05/04 00:42 MHDA- 2023/05/05 06:42 PMCR- 2023/05/03 CRDT- 2023/05/03 20:43 PHST- 2022/11/02 00:00 [received] PHST- 2023/04/10 00:00 [accepted] PHST- 2023/05/05 06:42 [medline] PHST- 2023/05/04 00:42 [pubmed] PHST- 2023/05/03 20:43 [entrez] PHST- 2023/05/03 00:00 [pmc-release] AID - 11/3/e003206 [pii] AID - bmjdrc-2022-003206 [pii] AID - 10.1136/bmjdrc-2022-003206 [doi] PST - ppublish SO - BMJ Open Diabetes Res Care. 2023 May;11(3):e003206. doi: 10.1136/bmjdrc-2022-003206. PMID- 37134170 OWN - NLM STAT- MEDLINE DCOM- 20230509 LR - 20260127 IS - 2375-2548 (Electronic) IS - 2375-2548 (Linking) VI - 9 IP - 18 DP - 2023 May 3 TI - Divergent acute versus prolonged pharmacological GLP-1R responses in adult beta cell-specific beta-arrestin 2 knockout mice. PG - eadf7737 LID - 10.1126/sciadv.adf7737 [doi] LID - eadf7737 AB - The glucagon-like peptide-1 receptor (GLP-1R) is a major type 2 diabetes therapeutic target. Stimulated GLP-1Rs are rapidly desensitized by beta-arrestins, scaffolding proteins that not only terminate G protein interactions but also act as independent signaling mediators. Here, we have assessed in vivo glycemic responses to the pharmacological GLP-1R agonist exendin-4 in adult beta cell-specific beta-arrestin 2 knockout (KO) mice. KOs displayed a sex-dimorphic phenotype consisting of weaker acute responses that improved 6 hours after agonist injection. Similar effects were observed for semaglutide and tirzepatide but not with biased agonist exendin-phe1. Acute cyclic adenosine 5'-monophosphate increases were impaired, but desensitization reduced in KO islets. The former defect was attributed to enhanced beta-arrestin 1 and phosphodiesterase 4 activities, while reduced desensitization co-occurred with impaired GLP-1R recycling and lysosomal targeting, increased trans-Golgi network signaling, and reduced GLP-1R ubiquitination. This study has unveiled fundamental aspects of GLP-1R response regulation with direct application to the rational design of GLP-1R-targeting therapeutics. FAU - Bitsi, Stavroula AU - Bitsi S AUID- ORCID: 0000-0001-5536-7123 AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - El Eid, Liliane AU - El Eid L AUID- ORCID: 0000-0002-6511-6210 AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Manchanda, Yusman AU - Manchanda Y AUID- ORCID: 0000-0002-2874-5608 AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Oqua, Affiong I AU - Oqua AI AUID- ORCID: 0000-0002-0584-120X AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Mohamed, Nimco AU - Mohamed N AD - Department of Bioengineering, Imperial College London, London, UK. FAU - Hansen, Ben AU - Hansen B AD - Department of Bioengineering, Imperial College London, London, UK. FAU - Suba, Kinga AU - Suba K AD - Department of Bioengineering, Imperial College London, London, UK. FAU - Rutter, Guy A AU - Rutter GA AUID- ORCID: 0000-0001-6360-0343 AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. AD - CHUM Research Centre, Faculty of Medicine, University of Montreal, Quebec H2X 0A9, Canada. AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 637553, Singapore. FAU - Salem, Victoria AU - Salem V AUID- ORCID: 0000-0001-6463-7471 AD - Department of Bioengineering, Imperial College London, London, UK. FAU - Jones, Ben AU - Jones B AUID- ORCID: 0000-0003-0461-2584 AD - Section of Endocrinology and Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. FAU - Tomas, Alejandra AU - Tomas A AUID- ORCID: 0000-0002-2290-8453 AD - Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK. LA - eng GR - MR/R010676/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article DEP - 20230503 PL - United States TA - Sci Adv JT - Science advances JID - 101653440 RN - 0 (beta-Arrestin 2) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (Glp1r protein, mouse) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Animals MH - Mice MH - beta-Arrestin 2/genetics/metabolism MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptide 1/metabolism MH - Mice, Knockout MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor PMC - PMC10156113 EDAT- 2023/05/03 18:41 MHDA- 2023/05/05 06:42 PMCR- 2023/05/03 CRDT- 2023/05/03 14:03 PHST- 2023/05/05 06:42 [medline] PHST- 2023/05/03 18:41 [pubmed] PHST- 2023/05/03 14:03 [entrez] PHST- 2023/05/03 00:00 [pmc-release] AID - adf7737 [pii] AID - 10.1126/sciadv.adf7737 [doi] PST - ppublish SO - Sci Adv. 2023 May 3;9(18):eadf7737. doi: 10.1126/sciadv.adf7737. Epub 2023 May 3. PMID- 37100640 OWN - NLM STAT- MEDLINE DCOM- 20230517 LR - 20250103 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 33 IP - 6 DP - 2023 Jun TI - Glucagon-like peptide 1 receptor agonists in end-staged kidney disease and kidney transplantation: A narrative review. PG - 1111-1120 LID - S0939-4753(23)00143-6 [pii] LID - 10.1016/j.numecd.2023.03.023 [doi] AB - AIMS: Glucagon-like peptide 1 receptor agonists (GLP-1RA) improve glycemic control and promote weight loss in type 2 diabetes (DM2) and obesity. We identified studies describing the metabolic benefits of GLP-1RA in end-staged kidney disease (ESKD) and kidney transplantation. DATA SYNTHESIS: We searched for randomized controlled trials (RCTs) and observational studies that investigated the metabolic benefits of GLP-1RA in ESKD and kidney transplantation. We summarized the effect of GLP-1RA on measures of obesity and glycemic control, examined adverse events, and explored adherence with therapy. In small RCTs of patients with DM2 on dialysis, liraglutide for up to 12 weeks lowered HbA1c by 0.8%, reduced time in hyperglycemia by approximately 2%, lowered blood glucose by 2 mmol/L and reduced weight by 1-2 kg, compared with placebo. In prospective studies inclusive of ESKD, 12 months of semaglutide reduced HbA1c by 0.8%, and contributed to weight losses of 8 kg. In retrospective cohort studies in DM2 and kidney transplantation, 12 months of GLP-1RA lowered HbA1c by 2%, and fasting glucose by approximately 3 mmol/L compared with non-use, and in some reports, weight losses of up to 4 kg were described. Gastrointestinal (GI) side effects were most commonly reported, with hypoglycemia described with GLP-1RA in hemodialysis, particularly in those using insulin. CONCLUSIONS: GLP-1RA are growing in popularity in those with DM2 and obesity. In small RCTs and observational cohort studies modest glycemic and weight benefits have been described in ESKD and transplantation, but GI side effects may limit adherence. Larger and longer term studies of GLP-1RA remain important. CI - Copyright (c) 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. FAU - Clemens, Kristin K AU - Clemens KK AD - Department of Medicine, Division of Endocrinology and Metabolism, Western University, 268 Grosvenor Street, N6A 4V2, London, Ontario, Canada; Department of Epidemiology and Biostatistics, Western University, 1465 Richmond Street, N6G 2M1, London, Ontario, Canada; Centre for Diabetes, Endocrinology and Metabolism, St. Joseph's Health Care London, 268 Grosvenor Street, N6A 4V2, London, Ontario, Canada; ICES Western, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada; Lawson Health Research Institute, 750 Base Line Road East, Suite 300, N6C 2R5, London, Ontario, Canada; Department of Medicine, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada. Electronic address: kristin.clemens@sjhc.london.on.ca. FAU - Ernst, Jaclyn AU - Ernst J AD - Department of Medicine, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada. FAU - Khan, Tayyab AU - Khan T AD - Department of Medicine, Division of Endocrinology and Metabolism, Western University, 268 Grosvenor Street, N6A 4V2, London, Ontario, Canada; Centre for Diabetes, Endocrinology and Metabolism, St. Joseph's Health Care London, 268 Grosvenor Street, N6A 4V2, London, Ontario, Canada. FAU - Reichert, Sonja AU - Reichert S AD - Department of Family Medicine, Western University, 1465 Richmond Street, N6G 2M1, London, Ontario, Canada. FAU - Khan, Qasim AU - Khan Q AD - Department of Medicine, Division of Gastroenterology, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada. FAU - LaPier, Heather AU - LaPier H AD - Centre for Diabetes, Endocrinology and Metabolism, St. Joseph's Health Care London, 268 Grosvenor Street, N6A 4V2, London, Ontario, Canada. FAU - Chiu, Michael AU - Chiu M AD - Department of Medicine, Division of Nephrology, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada. FAU - Stranges, Saverio AU - Stranges S AD - Department of Epidemiology and Biostatistics, Western University, 1465 Richmond Street, N6G 2M1, London, Ontario, Canada; Department of Medicine, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada; Department of Family Medicine, Western University, 1465 Richmond Street, N6G 2M1, London, Ontario, Canada. FAU - Sahi, Gurleen AU - Sahi G AD - Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, N6A 5C1, London, Ontario, Canada. FAU - Castrillon-Ramirez, Fabio AU - Castrillon-Ramirez F AD - Schulich School of Medicine and Dentistry, Western University, 1151 Richmond Street, N6A 5C1, London, Ontario, Canada. FAU - Moist, Louise AU - Moist L AD - Department of Epidemiology and Biostatistics, Western University, 1465 Richmond Street, N6G 2M1, London, Ontario, Canada; Lawson Health Research Institute, 750 Base Line Road East, Suite 300, N6C 2R5, London, Ontario, Canada; Department of Medicine, Division of Nephrology, Western University, 800 Commissioners Road East, N6A 5W9, London, Ontario, Canada. CN - OK TRANSPLANT Investigators LA - eng GR - CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20230405 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Glycated Hemoglobin MH - *Kidney Transplantation/adverse effects MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Liraglutide/adverse effects MH - *Kidney Failure, Chronic/diagnosis/surgery MH - Weight Loss MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Blood glucose OT - Diabetes mellitus OT - End stage kidney disease OT - Glucagon like peptide 1 receptor OT - Hemoglobin A1c OT - Kidney transplantation COIS- Declaration of competing interest KKC has received honoraria for delivering certified medical education from the CPD Network, and the Canadian Medical and Surgical Knowledge Translation Group. TK has received honoraria for speaking engagements from Novo Nordisk Canada, Eli-Lily Canada. EDAT- 2023/04/27 00:42 MHDA- 2023/05/17 06:42 CRDT- 2023/04/26 21:59 PHST- 2022/12/21 00:00 [received] PHST- 2023/03/22 00:00 [revised] PHST- 2023/03/27 00:00 [accepted] PHST- 2023/05/17 06:42 [medline] PHST- 2023/04/27 00:42 [pubmed] PHST- 2023/04/26 21:59 [entrez] AID - S0939-4753(23)00143-6 [pii] AID - 10.1016/j.numecd.2023.03.023 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2023 Jun;33(6):1111-1120. doi: 10.1016/j.numecd.2023.03.023. Epub 2023 Apr 5. PMID- 37098289 OWN - NLM STAT- MEDLINE DCOM- 20230508 LR - 20250103 IS - 1464-3391 (Electronic) IS - 0968-0896 (Linking) VI - 85 DP - 2023 May 1 TI - Design, synthesis, and biological evaluation of a potential long-acting glucagon-like peptide-1 (GLP-1) analog. PG - 117291 LID - S0968-0896(23)00139-6 [pii] LID - 10.1016/j.bmc.2023.117291 [doi] AB - By binding to its receptor, glucagon-like peptide-1 (GLP-1) plays various physiological roles, including activating glucose-dependent insulin secretion, inhibiting gastric emptying, and reducing appetite. This suite of activities makes GLP-1 and its analogs an attractive choice for treating type 2 diabetes mellitus in the context of overweight or obesity. This study used different types and lengths of fatty acids to design dual fatty acid side chains for GLP-1 receptor agonists including decanoic, dodecanoic, tetradecanoic, hexadecanoic, dodecanedioic, tetradecanedioic, hexadecanedioic, and octadecanedioic acids. Sixteen GLP-1 receptor agonists (conjugates 13-28) with dual fatty acid side chains were obtained by liquid-phase synthesis. After structural confirmation using high-resolution mass spectrometry, peptide mapping, and circular dichroism, the biological activities of the conjugates were screened. First, the conjugates were screened for albumin binding and activity in GLP-1R-CRE-bla CHO-K1 cells. Albumin binding results suggested a synergistic effect between the two fatty acids in the conjugates. Next, conjugates 18, 19, and 21 selected after primary screening were assessed for receptor affinity, activity in INS-1 cells, plasma stability across different species, and efficacy and pharmacokinetics in normal and db/db mice. One candidate (conjugate 19) was found to have albumin binding of >99 %, good receptor affinity, activities of INS-1 cells, and plasma stability. We found that cellular activities in GLP-1R-CRE-bla CHO-K1 cells and pharmacodynamics and pharmacokinetics in normal and db/db mice for conjugate 19 were superior to those of semaglutide. CI - Copyright (c) 2023 Elsevier Ltd. All rights reserved. FAU - Zhang, Jinhua AU - Zhang J AD - Shanghai Institute of Pharmaceutical Industry, Shanghai, China; Shanghai Duomirui Biotechnology Ltd., Shanghai, China. FAU - Xu, Hongjiang AU - Xu H AD - Shanghai Institute of Pharmaceutical Industry, Shanghai, China; Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd., Nanjing, China. FAU - Lu, Jianguang AU - Lu J AD - Shanghai Duomirui Biotechnology Ltd., Shanghai, China. FAU - Dong, Yuanzhen AU - Dong Y AD - Shanghai Institute of Pharmaceutical Industry, Shanghai, China; Shanghai Duomirui Biotechnology Ltd., Shanghai, China. Electronic address: 13818994696@163.com. FAU - Feng, Jun AU - Feng J AD - Shanghai Institute of Pharmaceutical Industry, Shanghai, China; Shanghai Duomirui Biotechnology Ltd., Shanghai, China. Electronic address: Fengjdmr@163.com. LA - eng PT - Journal Article DEP - 20230420 PL - England TA - Bioorg Med Chem JT - Bioorganic & medicinal chemistry JID - 9413298 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Albumins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Mice MH - Cricetinae MH - Animals MH - *Glucagon-Like Peptide 1/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/pharmacology/therapeutic use/chemistry MH - Cricetulus MH - Albumins MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Dual fatty acid side chains OT - Glucagon-like peptide-1 OT - Pharmacokinetics OT - Synergistic effect OT - Type 2 diabetes mellitus COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/04/25 18:42 MHDA- 2023/05/08 06:41 CRDT- 2023/04/25 18:00 PHST- 2023/02/25 00:00 [received] PHST- 2023/04/01 00:00 [revised] PHST- 2023/04/13 00:00 [accepted] PHST- 2023/05/08 06:41 [medline] PHST- 2023/04/25 18:42 [pubmed] PHST- 2023/04/25 18:00 [entrez] AID - S0968-0896(23)00139-6 [pii] AID - 10.1016/j.bmc.2023.117291 [doi] PST - ppublish SO - Bioorg Med Chem. 2023 May 1;85:117291. doi: 10.1016/j.bmc.2023.117291. Epub 2023 Apr 20. PMID- 37086147 OWN - NLM STAT- MEDLINE DCOM- 20230614 LR - 20250103 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 32 IP - 5 DP - 2023 May TI - Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity? PG - 355-359 LID - 10.1080/13543784.2023.2206560 [doi] AB - INTRODUCTION: Despite there being a wide range of medicines available for the treatment of type 2 diabetes, the high rate of mortality suggests treatment needs to be improved. Only a few medicines have shown long-term effectiveness in obesity, and new medicines are urgently needed. AREAS COVERED: A multiple-ascending dose phase 1b clinical trial of a new drug retatrutide (LY3437943), which in addition to stimulating Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP) receptors, stimulates glucagon receptors, in subjects with type 2 diabetes. Retatrutide was relatively safe and pharmacokinetics support once-weekly dosing. EXPERT OPINION: The role of stimulating glucagon receptors in the treatment of type 2 diabetes and/or obesity is poorly defined and needs to be clarified. Although retatrutide may be superior to the GLP-1 receptor agonist dulaglutide in reducing plasma glucose and body weight, this is not a meaningful comparison, as another GLP-1 receptor agonist (semaglutide) is more potent than dulaglutide at this and may have similar efficacy to retatrutide. Retatrutide also needs to be compared to another Eli Lilly and Company drug, the combined GLP-1 and GIP receptor agonist, tirzepatide. The safety of retatrutide needs to be determined in larger and longer trials. FAU - Doggrell, Sheila A AU - Doggrell SA AD - School of Pharmacy and Medical Sciences, Gold Coast Campus, Griffith University, Gold Coast, Queensland, Australia. LA - eng PT - Journal Article DEP - 20230424 PL - England TA - Expert Opin Investig Drugs JT - Expert opinion on investigational drugs JID - 9434197 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9007-92-5 (Glucagon) RN - 0 (Receptors, Glucagon) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1 MH - Glucagon MH - *Diabetes Mellitus, Type 2/drug therapy MH - Receptors, Glucagon MH - Hypoglycemic Agents/therapeutic use MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Diabetes OT - GLP-1 receptors OT - dulaglutide OT - obesity OT - retatrutide OT - semaglutide OT - tirzepatide EDAT- 2023/04/22 19:42 MHDA- 2023/06/14 06:42 CRDT- 2023/04/22 06:53 PHST- 2023/06/14 06:42 [medline] PHST- 2023/04/22 19:42 [pubmed] PHST- 2023/04/22 06:53 [entrez] AID - 10.1080/13543784.2023.2206560 [doi] PST - ppublish SO - Expert Opin Investig Drugs. 2023 May;32(5):355-359. doi: 10.1080/13543784.2023.2206560. Epub 2023 Apr 24. PMID- 37062189 OWN - NLM STAT- MEDLINE DCOM- 20230428 LR - 20260127 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 37 IP - 5 DP - 2023 May TI - Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes: A prespecified secondary analysis of a randomised clinical trial. PG - 108472 LID - S1056-8727(23)00070-3 [pii] LID - 10.1016/j.jdiacomp.2023.108472 [doi] AB - AIMS: Semaglutide and empagliflozin have shown cardiovascular protection. In SUSTAIN-6, semaglutide was associated with an increased risk of diabetic retinopathy. We investigated whether changes in retinal oxygenation, retinal vascular autoregulation, and central retinal thickness are altered by semaglutide, empagliflozin or the combination. METHODS: This study was a prespecified, secondary outcome from a randomised, 32 weeks partly placebo-controlled, partly open-label, clinical trial on the effects of semaglutide and empagliflozin on arterial stiffness and kidney oxygenation. A total of 120 participants with type 2 diabetes, established or high risk of cardiovascular disease and age >/=50 years were randomised into four parallel groups (semaglutide, empagliflozin, the combination or tablet placebo, n = 30 for each group). We primarily hypothesized that semaglutide would increase venular oxygenation. RESULTS: We found no changes in retinal arteriolar, venular or venular-arteriolar oxygenation nor in retinal vessel diameter regardless of treatment group. Semaglutide increased central retinal thickness compared to placebo with ~1 % (3.8 mum 95 % CI [0.9;6.7], p = 0.009) with no changes in the empagliflozin or combination group. CONCLUSION: Neither semaglutide, empagliflozin nor the combination alters markers of retinal function. The effect of semaglutide on central retinal thickness was small, but the clinical significance is uncertain. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Gullaksen, Soren AU - Gullaksen S AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark. Electronic address: soer.gull@auh.rm.dk. FAU - Vernstrom, Liv AU - Vernstrom L AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Sorensen, Steffen Skovgaard AU - Sorensen SS AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Funck, Kristian Lokke AU - Funck KL AD - Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Petersen, Line AU - Petersen L AD - Department of Ophthalmology, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Bek, Toke AU - Bek T AD - Department of Ophthalmology, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Poulsen, Per Logstrup AU - Poulsen PL AD - Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark. FAU - Laugesen, Esben AU - Laugesen E AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark; Steno Diabetes Center, Aarhus University Hospital, 8200 Aarhus N, Denmark; Diagnostic Centre, Silkeborg Regional Hospital, 8600 Silkeborg, Denmark. LA - eng SI - EudraCT/2019-000781-38 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230405 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) SB - IM CIN - J Diabetes Complications. 2023 Aug;37(8):108553. doi: 10.1016/j.jdiacomp.2023.108553. PMID: 37385011 MH - Humans MH - Middle Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - Hypoglycemic Agents/therapeutic use MH - Retina MH - Treatment Outcome MH - Semaglutide MH - Benzhydryl Compounds MH - Glucosides OTO - NOTNLM OT - Diabetic retinopathy OT - Glucagon-like peptide 1 receptor agonist OT - Oximetry OT - Sodium-glucose transporter 2 inhibitors EDAT- 2023/04/17 06:00 MHDA- 2023/04/28 06:42 CRDT- 2023/04/16 18:06 PHST- 2023/02/21 00:00 [received] PHST- 2023/03/20 00:00 [revised] PHST- 2023/04/04 00:00 [accepted] PHST- 2023/04/28 06:42 [medline] PHST- 2023/04/17 06:00 [pubmed] PHST- 2023/04/16 18:06 [entrez] AID - S1056-8727(23)00070-3 [pii] AID - 10.1016/j.jdiacomp.2023.108472 [doi] PST - ppublish SO - J Diabetes Complications. 2023 May;37(5):108472. doi: 10.1016/j.jdiacomp.2023.108472. Epub 2023 Apr 5. PMID- 37055715 OWN - NLM STAT- MEDLINE DCOM- 20230704 LR - 20250103 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 8 DP - 2023 Aug TI - New insights into the treatment of obesity. PG - 2058-2072 LID - 10.1111/dom.15077 [doi] AB - Obesity is a chronic, progressive and relapsing disease with a rising global prevalence associated with increased morbidity and mortality and reduced quality of life. Treatment of obesity requires a comprehensive medical approach that includes behavioural interventions, pharmacotherapy and bariatric surgery. The degree of weight loss with all approaches is highly heterogeneous, and long-term weight maintenance remains challenging. For years, antiobesity medications have been limited in number, often delivering meagre efficacy and raising numerous safety concerns. Therefore, there is a need for the development of highly efficacious and safe new agents. Recent insights into the complex pathophysiology of obesity have increased our understanding of intervenable targets for pharmacotherapies to treat obesity and improve weight-related cardiometabolic complications, namely, type 2 diabetes, hyperlipidaemia and hypertension. As a result, novel potent therapies have emerged, such as semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA) recently approved for the treatment of obesity. Semaglutide 2.4 mg once weekly significantly reduces body weight by approximately 15%, with simultaneous improvement in cardiometabolic risk factors and physical functioning in people with obesity. Tirzepatide, the first dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA, has recently demonstrated that body weight reduction exceeding 20% in people with obesity and coupled with improved cardiometabolic measures is feasible. Thus, these novel agents promise to narrow the gap between the weight-loss effects of behaviour interventions, previous pharmacotherapies, and bariatric surgery. In this narrative review, we highlight established and emerging therapeutic treatments for long-term obesity management and position them in a framework according to their weight loss effects. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Bluher, Matthias AU - Bluher M AUID- ORCID: 0000-0003-0208-2065 AD - Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany. AD - Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum Munchen, the University of Leipzig and University Hospital Leipzig, Leipzig, Germany. FAU - Aras, Mohini AU - Aras M AD - Comprehensive Weight Control Center, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York, New York, USA. FAU - Aronne, Louis J AU - Aronne LJ AUID- ORCID: 0000-0002-9890-9401 AD - Comprehensive Weight Control Center, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine, New York, New York, USA. FAU - Batterham, Rachel L AU - Batterham RL AUID- ORCID: 0000-0002-5477-8585 AD - University College London Centre for Obesity Research, Division of Medicine, University College London, London, UK. AD - National Institute for Health and Care Research, UCLH Biomedical Research Centre, London, UK. FAU - Giorgino, Francesco AU - Giorgino F AUID- ORCID: 0000-0001-7372-2678 AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China. FAU - Pietilainen, Kirsi H AU - Pietilainen KH AUID- ORCID: 0000-0002-8522-1288 AD - Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. AD - HealthyWeightHub, Endocrinology, Abdominal Center, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland. FAU - Schnell, Oliver AU - Schnell O AUID- ORCID: 0000-0003-4968-2367 AD - Forschergruppe Diabetes e. V, Munich, Germany. AD - Sciarc GmbH, Baierbrunn, Germany. FAU - Tonchevska, Elena AU - Tonchevska E AUID- ORCID: 0000-0001-6529-7544 AD - Sciarc GmbH, Baierbrunn, Germany. FAU - Wilding, John P H AU - Wilding JPH AUID- ORCID: 0000-0003-2839-8404 AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20230505 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/chemically induced MH - Quality of Life MH - Obesity/complications/therapy/chemically induced MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Weight Loss MH - *Cardiovascular Diseases/chemically induced MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GIP OT - GLP-1 analogue OT - antiobesity drug OT - drug development OT - incretin therapy OT - obesity therapy EDAT- 2023/04/14 06:00 MHDA- 2023/07/04 06:42 CRDT- 2023/04/13 23:33 PHST- 2023/03/24 00:00 [revised] PHST- 2023/02/06 00:00 [received] PHST- 2023/04/02 00:00 [accepted] PHST- 2023/07/04 06:42 [medline] PHST- 2023/04/14 06:00 [pubmed] PHST- 2023/04/13 23:33 [entrez] AID - 10.1111/dom.15077 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Aug;25(8):2058-2072. doi: 10.1111/dom.15077. Epub 2023 May 5. PMID- 37055712 OWN - NLM STAT- MEDLINE DCOM- 20230712 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 8 DP - 2023 Aug TI - The improved health utility of once-weekly subcutaneous semaglutide 2.4 mg compared with placebo in the STEP 1-4 obesity trials. PG - 2142-2150 LID - 10.1111/dom.15090 [doi] AB - AIM: To assess health utility values in the Semaglutide Treatment Effect in People with obesity (STEP) 1-4 trials. MATERIALS AND METHODS: The STEP 1-4 phase 3a, 68-week, double-blind randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with a body mass index (BMI) of 30 kg/m(2) or higher or a BMI of 27 kg/m(2) or higher and at least one comorbidity (STEP 1, 3 and 4), or a BMI of 27 kg/m(2) or higher and type 2 diabetes (STEP 2). Patients received lifestyle intervention plus intensive behavioural therapy in STEP 3. Health-related quality of life was assessed using the Short Form 36-item Health Survey version 2 (SF-36v2) at baseline and week 68. Scores were converted into Short Form Six-Dimension version 2 (SF-6Dv2) utility scores or mapped onto the European Quality of Life Five-Dimension Three-Level (EQ-5D-3L) utility index using UK health utility weights. RESULTS: At week 68, semaglutide 2.4 mg was associated with minor health utility score improvements from baseline (all trials), while scores for placebo typically decreased. SF-6Dv2 treatment differences by week 68 for semaglutide 2.4 mg versus placebo were significant in STEP 1 and 4 (P /=50 years with type 2 diabetes and evidence of ASCVD (coronary artery disease [CAD], cerebrovascular disease, symptomatic peripheral arterial disease [PAD]) and/or CKD (estimated glomerular filtration rate <60 mL/min/1.73 m(2) ). The primary outcome is time from randomization to first occurrence of a major adverse CV event (MACE; a composite of CV death, nonfatal myocardial infarction or nonfatal stroke). This event-driven trial will continue until 1225 first adjudication-confirmed MACEs have occurred. Enrolment has been completed. RESULTS: Overall, 9650 participants were enrolled between June 17, 2019 and March 24, 2021 (men 71.1%, White ethnicity 68.9%, mean age 66.1 years, diabetes duration 15.4 years, body mass index 31.1 kg/m(2) , glycated haemoglobin 63.5 mmol/mol [8.0%]). The most frequently used antihyperglycaemic medications at baseline were metformin (75.7%), insulin and insulin analogues (50.5%), sulphonylureas (29.1%), sodium-glucose cotransporter-2 inhibitors (26.7%) and dipeptidyl peptidase-4 inhibitors (23.0%). At randomization, 70.7% of participants had CAD, 42.3% had CKD, 21.1% had cerebrovascular disease and 15.7% had symptomatic PAD (categories not mutually exclusive). Prevalent heart failure was reported in 23.0% of participants. CONCLUSION: SOUL will provide evidence regarding the CV effects of oral semaglutide in individuals with type 2 diabetes and established ASCVD and/or CKD. CI - (c) 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - McGuire, Darren K AU - McGuire DK AD - University of Texas Southwestern Medical Center, and Parkland Health and Hospital System, Dallas, Texas, USA. FAU - Busui, Rodica P AU - Busui RP AD - Department of Internal Medicine, Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan, USA. FAU - Deanfield, John AU - Deanfield J AD - Institute of Cardiovascular Sciences, University College London, London, UK. FAU - Inzucchi, Silvio E AU - Inzucchi SE AUID- ORCID: 0000-0003-1254-6636 AD - Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut, USA. FAU - Mann, Johannes F E AU - Mann JFE AUID- ORCID: 0000-0002-3154-5332 AD - KfH Kidney Center, Munich, Germany. AD - Friedrich Alexander University of Erlangen, Erlangen, Germany. FAU - Marx, Nikolaus AU - Marx N AD - Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Aachen, Germany. FAU - Mulvagh, Sharon L AU - Mulvagh SL AD - Department of Medicine, Division of Cardiology, Dalhousie University, Halifax, Nova Scotia, Canada. FAU - Poulter, Neil AU - Poulter N AD - Imperial Clinical Trials Unit, Imperial College London, London, UK. FAU - Engelmann, Mads D M AU - Engelmann MDM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ripa, Maria Sejersten AU - Ripa MS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Gislum, Mette AU - Gislum M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Brown-Frandsen, Kirstine AU - Brown-Frandsen K AUID- ORCID: 0000-0002-1752-2054 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. LA - eng PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230411 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Insulins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Male MH - Humans MH - Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - *Cardiovascular Diseases/complications/epidemiology/prevention & control MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptides/adverse effects MH - *Renal Insufficiency, Chronic/complications/drug therapy/chemically induced MH - *Atherosclerosis/complications/drug therapy/epidemiology MH - *Coronary Artery Disease MH - *Insulins MH - Randomized Controlled Trials as Topic MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - cardiovascular disease OT - randomized trial OT - semaglutide OT - type 2 diabetes EDAT- 2023/03/23 06:00 MHDA- 2023/06/05 06:42 CRDT- 2023/03/22 02:03 PHST- 2023/03/10 00:00 [revised] PHST- 2023/01/13 00:00 [received] PHST- 2023/03/16 00:00 [accepted] PHST- 2023/06/05 06:42 [medline] PHST- 2023/03/23 06:00 [pubmed] PHST- 2023/03/22 02:03 [entrez] AID - 10.1111/dom.15058 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Jul;25(7):1932-1941. doi: 10.1111/dom.15058. Epub 2023 Apr 11. PMID- 36934740 OWN - NLM STAT- MEDLINE DCOM- 20230515 LR - 20260127 IS - 2468-1253 (Electronic) VI - 8 IP - 6 DP - 2023 Jun TI - Semaglutide 2.4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. PG - 511-522 LID - S2468-1253(23)00068-7 [pii] LID - 10.1016/S2468-1253(23)00068-7 [doi] AB - BACKGROUND: Patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis are at high risk of liver-related and all-cause morbidity and mortality. We investigated the efficacy and safety of the glucagon-like peptide-1 analogue semaglutide in patients with NASH and compensated cirrhosis. METHODS: This double-blind, placebo-controlled phase 2 trial enrolled patients from 38 centres in Europe and the USA. Adults with biopsy-confirmed NASH-related cirrhosis and body-mass index (BMI) of 27 kg/m(2) or more were randomly assigned (2:1) to receive either once-weekly subcutaneous semaglutide 2.4 mg or visually matching placebo. Patients were randomly allocated via an interactive web response system, stratified by presence or absence of type 2 diabetes. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH after 48 weeks, assessed by biopsy in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. The trial is closed and completed, and registered with ClinicalTrials.gov, number NCT03987451. FINDINGS: 71 patients were enrolled between June 18, 2019, and April 22, 2021; 49 (69%) patients were female and 22 (31%) were male. Patients had a mean age of 59.5 years (SD 8.0) and mean BMI of 34.9 kg/m(2) (SD 5.9); 53 (75%) patients had diabetes. 47 patients were randomly assigned to the semaglutide group and 24 to the placebo group. After 48 weeks, there was no statistically significant difference between the two groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH (five [11%] of 47 patients in the semaglutide group vs seven [29%] of 24 in the placebo group; odds ratio 0.28 [95% CI 0.06-1.24; p=0.087). There was also no significant difference between groups in the proportion of patients who achieved NASH resolution (p=0.29). Similar proportions of patients in each group reported adverse events (42 [89%] patients in the semaglutide group vs 19 [79%] in the placebo group) and serious adverse events (six [13%] vs two [8%]). The most common adverse events were nausea (21 [45%] vs four [17%]), diarrhoea (nine [19%] vs two [8%]), and vomiting (eight [17%] vs none). Hepatic and renal function remained stable. There were no decompensating events or deaths. INTERPRETATION: In patients with NASH and compensated cirrhosis, semaglutide did not significantly improve fibrosis or achievement of NASH resolution versus placebo. No new safety concerns were raised. FUNDING: Novo Nordisk A/S. CI - Copyright (c) 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved. FAU - Loomba, Rohit AU - Loomba R AD - NAFLD Research Center, Division of Gastroenterology and Epidemiology, University of California at San Diego, La Jolla, CA, USA. Electronic address: roloomba@ucsd.edu. FAU - Abdelmalek, Manal F AU - Abdelmalek MF AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Armstrong, Matthew J AU - Armstrong MJ AD - National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. FAU - Jara, Maximilian AU - Jara M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kjaer, Mette Skalshoi AU - Kjaer MS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Krarup, Niels AU - Krarup N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lawitz, Eric AU - Lawitz E AD - Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, USA. FAU - Ratziu, Vlad AU - Ratziu V AD - Institute for Cardiometabolism and Nutrition, Sorbonne Universite, Hopital Pitie-Salpetriere, Paris, France. FAU - Sanyal, Arun J AU - Sanyal AJ AD - Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. FAU - Schattenberg, Jorn M AU - Schattenberg JM AD - Metabolic Liver Research Program, I Department of Medicine, University Medical Centre, Mainz, Germany. FAU - Newsome, Philip N AU - Newsome PN AD - National Institute for Health Research, Birmingham Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. CN - NN9931-4492 investigators LA - eng SI - ClinicalTrials.gov/NCT03987451 GR - U01 DK130190/DK/NIDDK NIH HHS/United States GR - UL1 TR001442/TR/NCATS NIH HHS/United States GR - DH_/Department of Health/United Kingdom GR - P30 DK120515/DK/NIDDK NIH HHS/United States GR - U01 AA029019/AA/NIAAA NIH HHS/United States GR - R01 DK124318/DK/NIDDK NIH HHS/United States GR - U01 DK061734/DK/NIDDK NIH HHS/United States GR - P01 HL147835/HL/NHLBI NIH HHS/United States GR - R01 DK121378/DK/NIDDK NIH HHS/United States GR - R01 DK106419/DK/NIDDK NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20230316 PL - Netherlands TA - Lancet Gastroenterol Hepatol JT - The lancet. Gastroenterology & hepatology JID - 101690683 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet Gastroenterol Hepatol. 2023 Jun;8(6):494-495. doi: 10.1016/S2468-1253(23)00069-9. PMID: 36934739 CIN - Lancet Gastroenterol Hepatol. 2023 Aug;8(8):694. doi: 10.1016/S2468-1253(23)00109-7. PMID: 37453428 MH - Adult MH - Humans MH - Male MH - Female MH - Middle Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Non-alcoholic Fatty Liver Disease/complications/drug therapy MH - Glucagon-Like Peptide 1 MH - Liver Cirrhosis/complications/drug therapy MH - Semaglutide PMC - PMC10792518 MID - NIHMS1950507 COIS- Declaration of interests RL, MFA, MJA, EL, VR, AJS, JMS, and PNN were investigators in the trial and received grants from the study sponsor paid to their institutions to conduct the study. RL is co-founder of LipoNexus Inc, and a consultant to Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen, Madrigal, Metacrine, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89bio, Terns Pharmaceuticals, and Viking Therapeutics. In addition, his institutions have received research grants from Arrowhead Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Gilead, Hanmi, Intercept, Inventiva, Ionis, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Novo Nordisk, Pfizer, Sonic Incytes, and Terns Pharmaceuticals. MFA has received research/grant support from Allergan, Boeringher Ingelheim, BMS, Celgene, Durect, Enanta, Enyo, Galmed, Genentech, Gilead, Hanmi, Intercept, Inventiva, Madrigal, Novo Nordisk, Poxel, TARGET Pharma, and Viking; has acted as a consultant for Hanmi, NGM, BMS, 89bio, Madrigal, Intercept, Merck, Inventiva, Novo Nordisk, Sonic Incytes, and Theratechnologies; has served as a speaker for Clinical Care Options, Medscape, Fishawack LLC, and Terra Firma; has received royalties from UptoDate; and holds stock in Pfizer. MJA has received consultation fees, speaker fees, and research grants from Novo Nordisk and speaker fees and consultation fees from Norgine. JS has acted as a consultant for Apollo Endoscopy, Bristol Myers Squibb, Boehringer Ingelheim, Echosens, Genfit, Gilead Sciences, Intercept Pharmaceuticals, Madrigal, Merck, Nordic Bioscience, Novartis, Pfizer, Roche, Sanofi, and Siemens Healthcare GmbH; received research funding from Boehringer Ingelheim, Gilead Sciences, and Siemens Healthcare GmbH; and received speaker honorarium from Falk Foundation and Madrigal. MJ, MSK, and NK are employees of Novo Nordisk A/S; MSK and MJ are shareholders in Novo Nordisk A/S. EL has received research/grant support from 89bio, AbbVie, Akero Therapeutics, Allergan, Alnylam Pharmaceuticals, Amgen, Ascelia Pharma, Assemblybio, AstraZeneca, Axcella Health, Biocryst Pharmaceuticals, Bird Rock Bio, Boehringer Ingelheim, Bristol Myers Squibb, Conatus Pharmaceuticals, Cymabay Therapeutics, CytoDyn, DSM, Durect Corporation, Eli Lilly and Company, Enanta Pharmaceuticals, Enyo Pharma, Exalenz Bioscience, Galectin Therapeutics, Galmed Pharmaceuticals, Genfit, Genentech, Gilead Sciences, GlaxoSmithKline, Hanmi Pharmaceuticals, Hightide Biopharma, Intercept Pharmaceuticals, Inventiva, Janssen Pharmaceuticals, Laboratory for Advanced Medicine, Loxo Oncology, Madrigal Pharmaceuticals, Merck & Co, Metacrine, NGM Biopharmaceuticals, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Poxel, Roche, Sagimet Biosciences, Synlogic Therapeutics, Terns Pharmaceuticals, Viking Therapeutics, and Zydus Pharmaceuticals; has acted as a consultant for Akero, Boehringer Ingelheim, BMS, Intercept, Novo Nordisk, Metacrine, Sagimet, and Terns; and has received speaker honorarium from Gilead Sciences, AbbVie, and Intercept. AJS is President of Sanyal Biotechnology and has stock options in Exhalenz, Genfit, Hemoshear, Durect, Indalo, Northsea, Tiziana, and Rivus. He has served as a consultant to Genfit, Gilead, Malinckrodt, Pfizer, Salix, Boehringer Ingelheim, Novartis, Bristol Myers Squibb, Merck, Hemoshear, Lilly, Novo Nordisk, Terns, Albireo, Janssen, Poxel, 89bio, Siemens, AstraZeneca, NGM Bio, Amgen, Regeneron, Genentech, Alnylam, Roche, Madrigal, Inventiva, Covance, Prosciento, Histoindex, and PathAI. His institution has received grant support from Gilead, Malinckrodt, Boehringer Ingelheim, Novartis, Bristol Myers Squibb, Merck, Lilly, Novo Nordisk, Fractyl, Madrigal, and Inventiva. He has received royalties from Elsevier and UptoDate. PNN has received grants from Novo Nordisk and Boehringer Ingelheim; and has acted as a consultant on behalf of the University of Birmingham for Novo Nordisk, Boehringer Ingelheim, Gilead, Intercept Pharmaceuticals, Pfizer, and Poxel Pharmaceuticals. VR has acted as a consultant for Boehringer Ingelheim, Novo Nordisk, Poxel, Enyo, Madrigal, Terns, Intercept, NGM Bio, and Pfizer; and received research grants from Gilead Sciences and Intercept Pharmaceuticals. EDAT- 2023/03/20 06:00 MHDA- 2023/05/15 06:42 PMCR- 2024/01/17 CRDT- 2023/03/19 19:54 PHST- 2023/01/26 00:00 [received] PHST- 2023/02/17 00:00 [revised] PHST- 2023/02/23 00:00 [accepted] PHST- 2023/05/15 06:42 [medline] PHST- 2023/03/20 06:00 [pubmed] PHST- 2023/03/19 19:54 [entrez] PHST- 2024/01/17 00:00 [pmc-release] AID - S2468-1253(23)00068-7 [pii] AID - 10.1016/S2468-1253(23)00068-7 [doi] PST - ppublish SO - Lancet Gastroenterol Hepatol. 2023 Jun;8(6):511-522. doi: 10.1016/S2468-1253(23)00068-7. Epub 2023 Mar 16. PMID- 36932797 OWN - NLM STAT- MEDLINE DCOM- 20230321 LR - 20260127 IS - 0030-9982 (Print) IS - 0030-9982 (Linking) VI - 73 IP - 3 DP - 2023 Mar TI - Semaglutide: new dawn for diabetics. PG - 721 LID - 10.47391/JPMA.7558 [doi] FAU - Memon, Areeba AU - Memon A AD - Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan. FAU - Tehrim, Moniba AU - Tehrim M AD - Karachi Medical and Dental College, Karachi, Pakistan. FAU - Kumari, Beena AU - Kumari B AD - Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan. LA - eng PT - Letter PL - Pakistan TA - J Pak Med Assoc JT - JPMA. The Journal of the Pakistan Medical Association JID - 7501162 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide EDAT- 2023/03/19 06:00 MHDA- 2023/03/22 06:00 CRDT- 2023/03/18 04:13 PHST- 2023/03/18 04:13 [entrez] PHST- 2023/03/19 06:00 [pubmed] PHST- 2023/03/22 06:00 [medline] AID - 11903 [pii] AID - 10.47391/JPMA.7558 [doi] PST - ppublish SO - J Pak Med Assoc. 2023 Mar;73(3):721. doi: 10.47391/JPMA.7558. PMID- 36932262 OWN - NLM STAT- MEDLINE DCOM- 20230412 LR - 20260127 IS - 1179-1926 (Electronic) IS - 0312-5963 (Print) IS - 0312-5963 (Linking) VI - 62 IP - 4 DP - 2023 Apr TI - Effect of Various Dosing Schedules on the Pharmacokinetics of Oral Semaglutide: A Randomised Trial in Healthy Subjects. PG - 635-644 LID - 10.1007/s40262-023-01223-9 [doi] AB - BACKGROUND: Prescribing information instructs taking oral semaglutide (a glucagon-like peptide-1 analogue) in the fasting state, followed by a post-dose fasting period of >/= 30 min. This trial compared the recommended dosing schedule with alternative schedules. METHODS: This was a randomised, single-centre, multiple-dose, open-label, five-armed, parallel-group trial in healthy subjects who received once-daily oral semaglutide (3 mg for 5 days followed by 7 mg for 5 days). Subjects (n = 156) were randomised to five dosing schedules: 2-, 4-, or 6-h pre-dose fast followed by a 30-min post-dose fast (treatment arms: 2 h-30 min, 4-30 min, 6 h-30 min); 2-h pre-dose fast followed by an overnight post-dose fast (treatment arm: 2 h-night); or overnight pre-dose fast followed by a 30-min post-dose fast (reference arm: night-30 min). Semaglutide plasma concentration was measured regularly until 24 h after the 10th dose. Endpoints included area under the semaglutide plasma concentration-time curve during a 24-h interval after the 10th dose (AUC(0-24h)) (primary endpoint) and maximum observed semaglutide plasma concentration after the 10th dose (C(max)) (secondary endpoint). RESULTS: Compared with an overnight pre-dose fast (reference arm: night-30 min), shorter pre-dose fasting times in the 2 h-night, 2 h-30 min, 4 h-30 min, and 6 h-30 min treatment arms resulted in significantly lower semaglutide AUC(0-24h) and C(max) after the 10th dose (estimated treatment ratio ranges: 0.12-0.43 and 0.11-0.44, respectively; p < 0.0001 for all comparisons). Semaglutide AUC(0-24h) and C(max) after the 10th dose were similar for the 2 h-30 min and 2 h-night treatment arms. CONCLUSION: This trial supports dosing oral semaglutide in accordance with prescribing information, which requires dosing in the fasting state. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04513704); registered August 14, 2020. CI - (c) 2023. The Author(s). FAU - van Hout, Marloes AU - van Hout M AUID- ORCID: 0000-0002-5753-9563 AD - Novo Nordisk A/S, Soborg, Denmark. mvhz@novonordisk.com. FAU - Forte, Pablo AU - Forte P AUID- ORCID: 0000-0001-9355-7067 AD - PAREXEL, Early Phase Clinical Unit, London, UK. FAU - Jensen, Thomas B AU - Jensen TB AUID- ORCID: 0000-0002-8920-9374 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Boschini, Cristina AU - Boschini C AUID- ORCID: 0000-0001-6905-7038 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Baekdal, Tine A AU - Baekdal TA AUID- ORCID: 0000-0002-1348-0352 AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT04513704 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230317 PL - Switzerland TA - Clin Pharmacokinet JT - Clinical pharmacokinetics JID - 7606849 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Clin Pharmacokinet. 2023 Jul;62(7):1045-1047. doi: 10.1007/s40262-023-01276-w. PMID: 37378793 MH - Humans MH - *Hypoglycemic Agents/pharmacokinetics MH - Healthy Volunteers MH - Glucagon-Like Peptides MH - Glucagon-Like Peptide 1 MH - Area Under Curve MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide PMC - PMC10023024 OAB - Oral semaglutide is a human glucagon-like peptide-1 analogue that has been approved for the treatment of type 2 diabetes. It has been established that taking oral semaglutide with food or large volumes of water decreases absorption of the drug in the body. Current prescribing information instructs taking oral semaglutide on an empty stomach (known as the fasting state), with 120 mL/4 oz of water, then waiting for at least 30 min before consuming any food, water, or taking other oral medications. This study investigates whether different dosing schedules for oral semaglutide could potentially offer more flexibility to patients in the timing of their oral semaglutide dosing. The trial, conducted in healthy volunteers, compares the dosing schedule described in the prescribing information with different fasting times before (pre-dose) and after (post-dose) taking oral semaglutide during the day or evening, to see if there were any effects on the concentration of drug in the body. Compared to the recommended overnight fasting period, shorter pre-dose fasting periods of 2-6 h with a 30-min post-dose fast considerably reduced semaglutide exposure in the body. Similarly, semaglutide exposure was also reduced with a 2-h pre-dose fast combined with post-dose overnight fasting. These findings further support the current prescribing information, which states that patients should take their oral semaglutide dose after an overnight fast. OABL- eng COIS- MvH, TBJ, CB, and TAB are employees, and MvH, TBJ, and TAB are shareholders, of Novo Nordisk A/S, the sponsors of this trial. PF is an employee of PAREXEL International. EDAT- 2023/03/19 06:00 MHDA- 2023/04/12 06:42 PMCR- 2023/03/17 CRDT- 2023/03/18 00:26 PHST- 2023/02/08 00:00 [accepted] PHST- 2023/04/12 06:42 [medline] PHST- 2023/03/19 06:00 [pubmed] PHST- 2023/03/18 00:26 [entrez] PHST- 2023/03/17 00:00 [pmc-release] AID - 10.1007/s40262-023-01223-9 [pii] AID - 1223 [pii] AID - 10.1007/s40262-023-01223-9 [doi] PST - ppublish SO - Clin Pharmacokinet. 2023 Apr;62(4):635-644. doi: 10.1007/s40262-023-01223-9. Epub 2023 Mar 17. PMID- 36931642 OWN - NLM STAT- MEDLINE DCOM- 20230321 LR - 20260127 IS - 1756-1833 (Electronic) IS - 0959-8138 (Linking) VI - 380 DP - 2023 Mar 17 TI - Semaglutide: should the media slim down its enthusiasm? PG - 624 LID - 10.1136/bmj.p624 [doi] FAU - McCartney, Margaret AU - McCartney M AD - Glasgow. LA - eng PT - Journal Article DEP - 20230317 PL - England TA - BMJ JT - BMJ (Clinical research ed.) JID - 8900488 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Semaglutide EDAT- 2023/03/18 06:00 MHDA- 2023/03/22 06:00 CRDT- 2023/03/17 20:43 PHST- 2023/03/17 20:43 [entrez] PHST- 2023/03/18 06:00 [pubmed] PHST- 2023/03/22 06:00 [medline] AID - 10.1136/bmj.p624 [doi] PST - epublish SO - BMJ. 2023 Mar 17;380:624. doi: 10.1136/bmj.p624. PMID- 36927378 OWN - NLM STAT- MEDLINE DCOM- 20230417 LR - 20230417 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 24 IP - 5 DP - 2023 Apr TI - GLP-1/GIP analogs: potential impact in the landscape of obesity pharmacotherapy. PG - 587-597 LID - 10.1080/14656566.2023.2192865 [doi] AB - INTRODUCTION: Obesity is recognized as a major healthcare challenge. Following years of slow progress in discovery of safe, effective therapies for weight management, recent approval of the glucagon-like peptide 1 receptor (GLP-1R) mimetics, liraglutide and semaglutide, for obesity has generated considerable excitement. It is anticipated these agents will pave the way for application of tirzepatide, a highly effective glucose-dependent insulinotropic polypeptide receptor (GIPR), GLP-1R co-agonist, recently approved for management of type 2 diabetes mellitus. AREAS COVERED: Following promising weight loss in obese individuals in Phase III clinical trials, liraglutide and semaglutide were approved for weight management without diabetes. Tirzepatide has attained Fast Track designation for obesity management by the US Food and Drug Association. This narrative review summarizes experimental, preclinical, and clinical data for these agents and related GLP-1R/GIPR co-agonists, prioritizing clinical research published within the last 10 years where possible. EXPERT OPINION: GLP-1R mimetics are often discontinued within 24 months meaning long-term application of these agents in obesity is questioned. Combined GIPR/GLP-1R agonism appears to induce fewer side effects, indicating GLP-1R/GIPR co-agonists may be more suitable for enduring obesity management. After years of debate, this GIPR-biased GLP-1R/GIPR co-agonist highlights the therapeutic promise of including GIPR modulation for diabetes and obesity therapy. FAU - Lafferty, Ryan A AU - Lafferty RA AD - Diabetes Research Centre, Department of Life and Health Sciences, Ulster University, Coleraine, Northern Ireland. FAU - Flatt, Peter R AU - Flatt PR AD - Diabetes Research Centre, Department of Life and Health Sciences, Ulster University, Coleraine, Northern Ireland. FAU - Irwin, Nigel AU - Irwin N AD - Diabetes Research Centre, Department of Life and Health Sciences, Ulster University, Coleraine, Northern Ireland. LA - eng PT - Journal Article PT - Review DEP - 20230328 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 839I73S42A (Liraglutide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1 MH - Liraglutide/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Obesity/drug therapy MH - Gastric Inhibitory Polypeptide/pharmacology/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/therapeutic use OTO - NOTNLM OT - GIP OT - GLP-1 OT - Obesity OT - peptide OT - therapy OT - unimolecular EDAT- 2023/03/18 06:00 MHDA- 2023/04/17 06:41 CRDT- 2023/03/17 08:18 PHST- 2023/04/17 06:41 [medline] PHST- 2023/03/18 06:00 [pubmed] PHST- 2023/03/17 08:18 [entrez] AID - 10.1080/14656566.2023.2192865 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2023 Apr;24(5):587-597. doi: 10.1080/14656566.2023.2192865. Epub 2023 Mar 28. PMID- 36924152 OWN - NLM STAT- MEDLINE DCOM- 20230320 LR - 20250103 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 78 IP - 3 DP - 2023 Mar TI - [Anti-obesity drugs : from previous disappointments to new hopes]. PG - 147-152 AB - Both physicians and patients dream of an efficacious and safe pharmacological approach to treat obesity. Unfortunately, most anti-obesity drugs prescribed since the fifties were associated with an unfavourable risk profile that led to numerous withdrawals. Medications issued from pharmaco-chemistry that mainly target brain amines to reduce appetite have been abandoned because of potential cardiovascular and neuropsychiatric toxicities. More recently, biological medications emerged, especially GLP-1 (Glucagon-Like Peptide-1) receptor agonists, well-known to manage type 2 diabetes and now recommended at higher doses for the treatment of obesity (liraglutide, semaglutide). A dual agonist that targets both GLP-1 and GIP (Glucose-dependent Insulinotropic Polypeptide) receptors (tirzepatide) appears to be even more potent as glucose-lowering agent and is currently tested as an anti-obesity agent. Many other pharmacological approaches are currently investigated but they should not mask the importance of life-style measurements. FAU - Scheen, Andre AU - Scheen A AD - Service de Diabetologie, Nutrition et Maladies metaboliques, Departement de Medecine, CHU Liege, Belgique. FAU - De Flines, Jenny AU - De Flines J AD - Service de Diabetologie, Nutrition et Maladies metaboliques, Departement de Medecine, CHU Liege, Belgique. FAU - Paquot, Nicolas AU - Paquot N AD - Service de Diabetologie, Nutrition et Maladies metaboliques, Departement de Medecine, CHU Liege, Belgique. LA - fre PT - English Abstract PT - Journal Article TT - Medicaments anti-obesite : des deceptions aux espoirs. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - IY9XDZ35W2 (Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Anti-Obesity Agents/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/pharmacology/therapeutic use MH - Obesity/drug therapy MH - Glucose/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Anorectic drugs OT - Gastrointestinal peptides OT - Glucagon-like peptide-1 OT - Obesity OT - Pharmacotherapy OT - Safety EDAT- 2023/03/17 06:00 MHDA- 2023/03/21 06:00 CRDT- 2023/03/16 04:23 PHST- 2023/03/16 04:23 [entrez] PHST- 2023/03/17 06:00 [pubmed] PHST- 2023/03/21 06:00 [medline] PST - ppublish SO - Rev Med Liege. 2023 Mar;78(3):147-152. PMID- 36919944 OWN - NLM STAT- MEDLINE DCOM- 20230524 LR - 20250103 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 14 IP - 6 DP - 2023 Jun TI - Association of glucagon-like peptide-1 receptor agonist treatment with gastric residue in an esophagogastroduodenoscopy. PG - 767-773 LID - 10.1111/jdi.14005 [doi] AB - AIMS/INTRODUCTION: Previous studies have reported that the glucagon-like peptide-1 receptor agonist (GLP-1RA) delays gastric emptying, and gastric emptying was assessed by the (13) C breath test or paracetamol absorption technique. However, neither of them is clinically familiar in real-world clinical practice. The purpose of the present study was to investigate the association between GLP-1RA treatment and gastric residue in an esophagogastroduodenoscopy. MATERIALS AND METHODS: This study was a matched pair case-control study. The study population consisted of 1,128 individuals with diabetes who had esophagogastroduodenoscopy at our clinic between July 2020 and June 2022. To account for differences in characteristics, such as age, sex, insulin treatment and glycated hemoglobin, we carried out a one-to-one nearest neighbor propensity score matching analysis between diabetes patients with and without GLP-1RA treatment. After matching, we compared the presence of gastric residue in an esophagogastroduodenoscopy by the McNemar test between patients with and without GLP-1RA treatment. RESULTS: After the propensity score matching, we selected 205 pairs. In the propensity score-matched comparison, the proportion of gastric residue was statistically significantly higher in the GLP-1RA treatment group (0.49% vs 5.4%, P = 0.004). The details of GLP-1RA prescribed for the 11 patients with gastric residue were liraglutide once daily 1.8 mg (n = 2), dulaglutide once weekly 0.75 mg (n = 5), semaglutide once weekly 0.5 mg (n = 2) and semaglutide once weekly 1.0 mg (n = 2). CONCLUSION: GLP-1RA treatment is associated with gastric residue in an esophagogastroduodenoscopy in patients with diabetes. CI - (c) 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Kobori, Toshiko AU - Kobori T AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. FAU - Onishi, Yukiko AU - Onishi Y AUID- ORCID: 0000-0003-1180-5982 AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. FAU - Yoshida, Yoko AU - Yoshida Y AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. FAU - Tahara, Tazu AU - Tahara T AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. FAU - Kikuchi, Takako AU - Kikuchi T AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. FAU - Kubota, Tetsuya AU - Kubota T AUID- ORCID: 0000-0003-0341-3137 AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. FAU - Iwamoto, Masahiko AU - Iwamoto M AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. FAU - Sawada, Tomonobu AU - Sawada T AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. FAU - Kobayashi, Reo AU - Kobayashi R AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. FAU - Fujiwara, Hiroaki AU - Fujiwara H AD - Division of Gastroenterology, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. FAU - Kasuga, Masato AU - Kasuga M AD - Division of Diabetes and Metabolism, The Institute of Medical Science, Asahi Life Foundation, Chuo-ku, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20230315 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Case-Control Studies MH - Liraglutide/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10204182 OTO - NOTNLM OT - Esophagogastroduodenoscopy OT - Gastric residue OT - Glucagon-like peptide-1 receptor agonist treatment EDAT- 2023/03/16 06:00 MHDA- 2023/05/24 06:42 PMCR- 2023/03/15 CRDT- 2023/03/15 08:05 PHST- 2023/02/07 00:00 [revised] PHST- 2022/11/25 00:00 [received] PHST- 2023/02/20 00:00 [accepted] PHST- 2023/05/24 06:42 [medline] PHST- 2023/03/16 06:00 [pubmed] PHST- 2023/03/15 08:05 [entrez] PHST- 2023/03/15 00:00 [pmc-release] AID - JDI14005 [pii] AID - 10.1111/jdi.14005 [doi] PST - ppublish SO - J Diabetes Investig. 2023 Jun;14(6):767-773. doi: 10.1111/jdi.14005. Epub 2023 Mar 15. PMID- 36905345 OWN - NLM STAT- MEDLINE DCOM- 20230718 LR - 20260127 IS - 1758-8111 (Electronic) IS - 1758-8103 (Linking) VI - 13 IP - 4 DP - 2023 Aug TI - Effect of once-weekly subcutaneous semaglutide 2.4 mg on weight- and health-related quality of life in an East Asian population: Patient-reported outcomes from the STEP 6 trial. PG - e12589 LID - 10.1111/cob.12589 [doi] AB - We assessed the effect of semaglutide 2.4 and 1.7 mg versus placebo on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL) in the STEP 6 trial. Adults from East Asia (body mass index [BMI] >/=27.0 kg/m(2) with >/=2 weight-related comorbidities, or >/=35.0 kg/m(2) with >/=1 weight-related comorbidity) were randomized 4:1:2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo, or semaglutide 1.7 mg or placebo, plus lifestyle intervention for 68 weeks. WRQOL and HRQOL were assessed from baseline to Week 68 using the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) and the 36-Item-Short-Form-Survey-version-2.0 acute (SF-36v2), with changes in scores by categories of baseline BMI (/=30 and >/=35 kg/m(2) ) also assessed. In total, 401 participants (mean body weight 87.5 kg, aged 51 years, BMI 31.9 kg/m(2) , waist circumference 103.2 cm) were included. From baseline to Week 68, the IWQOL-Lite-CT Psychosocial and Total scores were significantly improved with semaglutide 2.4 and 1.7 mg versus placebo. For Physical score, effects were only in favour of semaglutide 2.4 mg versus placebo. In the SF-36v2, Physical Functioning was significantly improved with semaglutide 2.4 mg versus placebo, but no beneficial effects favouring either semaglutide treatment arms versus placebo were seen in the other SF-36v2 domains. Benefits favouring semaglutide 2.4 mg versus placebo were also observed in subgroups with higher BMIs for IWQOL-Lite-CT and SF-36v2 Physical Functioning scores. Treatment with semaglutide 2.4 mg improved aspects of WRQOL and HRQOL in people from East Asia with overweight/obesity. CI - (c) 2023 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation. FAU - Kolotkin, Ronette L AU - Kolotkin RL AUID- ORCID: 0000-0002-1300-2131 AD - Quality of Life Consulting, Durham, North Carolina, USA. AD - Family Medicine and Community Health, Duke University School of Medicine, Durham, North Carolina, USA. AD - Centre of Health Research, Helse Forde Hospital Trust, Forde, Norway. AD - Morbid Obesity Centre, Vestfold Hospital Trust, Tonsberg, Norway. FAU - Jeppesen, Ole Kleist AU - Jeppesen OK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Baker-Knight, James AU - Baker-Knight J AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lee, Sang Yeoup AU - Lee SY AD - Family Medicine Clinic and Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan-si, Gyeongsangnam-do, South Korea. AD - Department of Medical Education, Pusan National University School of Medicine, Yangsan-si, Gyeongsangnam-do, South Korea. FAU - Tokita, Asako AU - Tokita A AD - Novo Nordisk Pharma Ltd, Chiyoda-ku, Tokyo, Japan. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Toranomon Hospital, Minato City, Japan. LA - eng GR - Novo Nordisk A/S/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20230311 PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - *Quality of Life MH - East Asian People MH - Obesity/psychology MH - Patient Reported Outcome Measures MH - *Diabetes Mellitus, Type 2 MH - Semaglutide OTO - NOTNLM OT - East Asian OT - IWQOL-Lite-CT OT - SF-36v2 OT - obesity OT - patient-reported outcomes OT - semaglutide EDAT- 2023/03/12 06:00 MHDA- 2023/07/18 13:08 CRDT- 2023/03/11 08:12 PHST- 2023/01/26 00:00 [revised] PHST- 2022/10/31 00:00 [received] PHST- 2023/02/04 00:00 [accepted] PHST- 2023/07/18 13:08 [medline] PHST- 2023/03/12 06:00 [pubmed] PHST- 2023/03/11 08:12 [entrez] AID - 10.1111/cob.12589 [doi] PST - ppublish SO - Clin Obes. 2023 Aug;13(4):e12589. doi: 10.1111/cob.12589. Epub 2023 Mar 11. PMID- 36904097 OWN - NLM STAT- MEDLINE DCOM- 20230314 LR - 20230314 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 15 IP - 5 DP - 2023 Feb 22 TI - Legume-Derived Bioactive Peptides in Type 2 Diabetes: Opportunities and Challenges. LID - 10.3390/nu15051096 [doi] LID - 1096 AB - Diabetes mellitus is a complex disorder characterized by insufficient insulin production or insulin resistance, which results in a lifelong dependence on glucose-lowering drugs for almost all patients. During the fight with diabetes, researchers are always thinking about what characteristics the ideal hypoglycemic drugs should have. From the point of view of the drugs, they should maintain effective control of blood sugar, have a very low risk of hypoglycemia, not increase or decrease body weight, improve beta-cell function, and delay disease progression. Recently, the advent of oral peptide drugs, such as semaglutide, brings exciting hope to patients with chronic diabetes. Legumes, as an excellent source of protein, peptides, and phytochemicals, have played significant roles in human health throughout human history. Some legume-derived peptides with encouraging anti-diabetic potential have been gradually reported over the last two decades. Their hypoglycemic mechanisms have also been clarified at some classic diabetes treatment targets, such as the insulin receptor signaling pathway or other related pathways involved in the progress of diabetes, and key enzymes including alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase-IV (DPP-4). This review summarizes the anti-diabetic activities and mechanisms of peptides from legumes and discusses the prospects of these peptide-based drugs in type 2 diabetes (T2D) management. FAU - Hu, Kanghong AU - Hu K AUID- ORCID: 0000-0002-5913-2767 AD - Sino-German Biomedical Center, Hubei Provincial Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China. FAU - Huang, Huizhong AU - Huang H AD - Sino-German Biomedical Center, Hubei Provincial Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China. FAU - Li, Hanluo AU - Li H AD - Sino-German Biomedical Center, Hubei Provincial Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China. FAU - Wei, Yanhong AU - Wei Y AD - Sino-German Biomedical Center, Hubei Provincial Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China. FAU - Yao, Chenguang AU - Yao C AD - Sino-German Biomedical Center, Hubei Provincial Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan 430068, China. LA - eng GR - No.202209EF09/Open Project Funding of the Key Laboratory of Fermentation Engineering/ GR - No.2021CFB289/Hubei Province Natural Science Foundation/ PT - Journal Article PT - Review DEP - 20230222 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Peptides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2 MH - *Fabaceae MH - *Dipeptidyl-Peptidase IV Inhibitors/chemistry MH - Hypoglycemic Agents/therapeutic use MH - Peptides/chemistry PMC - PMC10005352 OTO - NOTNLM OT - bioactive peptide OT - hypoglycemic peptide OT - legume OT - type 2 diabetes (T2D) COIS- The authors declare no conflict of interest. EDAT- 2023/03/12 06:00 MHDA- 2023/03/15 06:00 PMCR- 2023/02/22 CRDT- 2023/03/11 01:29 PHST- 2023/02/07 00:00 [received] PHST- 2023/02/17 00:00 [revised] PHST- 2023/02/20 00:00 [accepted] PHST- 2023/03/11 01:29 [entrez] PHST- 2023/03/12 06:00 [pubmed] PHST- 2023/03/15 06:00 [medline] PHST- 2023/02/22 00:00 [pmc-release] AID - nu15051096 [pii] AID - nutrients-15-01096 [pii] AID - 10.3390/nu15051096 [doi] PST - epublish SO - Nutrients. 2023 Feb 22;15(5):1096. doi: 10.3390/nu15051096. PMID- 36899150 OWN - NLM STAT- MEDLINE DCOM- 20230419 LR - 20260127 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 60 IP - 5 DP - 2023 May TI - Response to "Effects of semaglutide on cardiovascular risk factors and eating behaviors in type 2 diabetes". PG - 715-716 LID - 10.1007/s00592-023-02061-8 [doi] FAU - Cheema, Muhammad Rafay Shahzad AU - Cheema MRS AUID- ORCID: 0000-0002-4798-804X AD - Allama Iqbal Medical College, Allama Shabbir Ahmad Usmani Road, Lahore, 54550, Punjab, Pakistan. rafayshahzadcheema@gmail.com. FAU - Kumar, Satesh AU - Kumar S AD - Shaheed Mohtarma Benazir Bhutto Medical College, Liyari, Karachi, Pakistan. LA - eng PT - Comment PT - Letter DEP - 20230311 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - Acta Diabetol. 2022 Oct;59(10):1287-1294. doi: 10.1007/s00592-022-01936-6. PMID: 35842847 EIN - Acta Diabetol. 2023 May;60(5):717. doi: 10.1007/s00592-023-02078-z. PMID: 36951996 MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - *Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - Risk Factors MH - Glucagon-Like Peptides/therapeutic use MH - Hypoglycemic Agents/adverse effects MH - Feeding Behavior/drug effects MH - Heart Disease Risk Factors MH - Semaglutide EDAT- 2023/03/11 06:00 MHDA- 2023/04/19 06:41 CRDT- 2023/03/10 23:23 PHST- 2023/01/23 00:00 [received] PHST- 2023/02/20 00:00 [accepted] PHST- 2023/04/19 06:41 [medline] PHST- 2023/03/11 06:00 [pubmed] PHST- 2023/03/10 23:23 [entrez] AID - 10.1007/s00592-023-02061-8 [pii] AID - 10.1007/s00592-023-02061-8 [doi] PST - ppublish SO - Acta Diabetol. 2023 May;60(5):715-716. doi: 10.1007/s00592-023-02061-8. Epub 2023 Mar 11. PMID- 36883831 OWN - NLM STAT- MEDLINE DCOM- 20231207 LR - 20250619 IS - 1538-4683 (Electronic) IS - 1061-5377 (Linking) VI - 32 IP - 1 DP - 2024 Jan-Feb 01 TI - Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. PG - 83-90 LID - 10.1097/CRD.0000000000000513 [doi] AB - Despite the worldwide epidemic of obesity, there remain few approved pharmacological treatment options to bridge the gap between lifestyle therapy and bariatric surgery. Cagrilintide is an amylin-analog, now being developed in combination with the GLP-1 agonist semaglutide to achieve sustained weight loss in persons with overweight and obesity. Amylin, released with insulin from beta cells in the pancreas, induces its satiating effect via both the homoeostatic and hedonic regions of the brain. Semaglutide, a GLP-1 receptor agonist, reduces appetite via GLP-1 receptors in the hypothalamus and increases the production of insulin, and reduces glucagon secretion, delaying gastric emptying. These separate, but related mechanisms of action of an amylin-analog and a GLP-1 receptor agonist appear to have an additive effect on appetite reduction. Given the heterogeneity and complex pathogenesis of obesity, combination therapy with multiple pathophysiological targets is a logical approach to increasing weight loss response with pharmacotherapy. Cagrilintide alone, as well as cagrilintide in combination with semaglutide have shown promising weight loss in clinical trials that supports the further development of this therapy for sustained weight management. CI - Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved. FAU - D'Ascanio, Antonella M AU - D'Ascanio AM AD - From the New York Medical College (Medical Student). FAU - Mullally, Jamie A AU - Mullally JA AD - Department of Medicine, Division of Endocrinology, New York Medical College/Westchester Medical Center, Valhalla, NY. FAU - Frishman, William H AU - Frishman WH AD - Department of Medicine, New York Medical College, Valhalla, NY. LA - eng PT - Journal Article DEP - 20231020 PL - United States TA - Cardiol Rev JT - Cardiology in review JID - 9304686 RN - AO43BIF1U8 (cagrilintide) RN - 0 (Islet Amyloid Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Insulin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Islet Amyloid Polypeptide/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Glucagon-Like Peptide 1/pharmacology/therapeutic use MH - Obesity/drug therapy MH - Insulin/therapeutic use MH - Weight Loss MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists COIS- Disclosure: The authors declare no conflict of interest. EDAT- 2023/03/09 06:00 MHDA- 2023/12/07 12:43 CRDT- 2023/03/08 09:04 PHST- 2023/12/07 12:43 [medline] PHST- 2023/03/09 06:00 [pubmed] PHST- 2023/03/08 09:04 [entrez] AID - 00045415-202401000-00013 [pii] AID - 10.1097/CRD.0000000000000513 [doi] PST - ppublish SO - Cardiol Rev. 2024 Jan-Feb 01;32(1):83-90. doi: 10.1097/CRD.0000000000000513. Epub 2023 Oct 20. PMID- 36876594 OWN - NLM STAT- MEDLINE DCOM- 20231014 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 31 IP - 4 DP - 2023 Apr TI - Impact of BMI and comorbidities on efficacy of once-weekly semaglutide: Post hoc analyses of the STEP 1 randomized trial. PG - 990-999 LID - 10.1002/oby.23732 [doi] AB - OBJECTIVE: This study assessed the effects of semaglutide on body weight, cardiometabolic risk factors, and glycemic status in individuals categorized by baseline BMI with or without additional obesity-related comorbidities, including prediabetes and high risk of cardiovascular disease (CVD). METHODS: This was a post hoc exploratory subgroup analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) 1 trial (NCT03548935), in which participants without diabetes and BMI >/=30 kg/m(2) , or BMI >/=27 kg/m(2) with >/=1 weight-related comorbidity, were randomized to once-weekly subcutaneous semaglutide 2.4 mg or placebo for 68 weeks. For this analysis, individuals were categorized into subgroups based on baseline BMI <35 versus >/=35 kg/m(2) (with no additional criteria, with >/=1 comorbidity, with prediabetes, and with prediabetes and high risk of CVD). RESULTS: Mean changes in body weight from baseline to week 68 with semaglutide were -16.2% and -14.0% in the subgroups with baseline BMI <35 and >/=35 kg/m(2) , respectively (both p < 0.0001 vs. placebo). Similar changes were observed in individuals with comorbidities, with prediabetes, and with prediabetes plus high CVD risk. The beneficial effects of semaglutide on cardiometabolic risk factors were consistent across all subgroups. CONCLUSIONS: This subgroup analysis confirms that semaglutide is effective in individuals with baseline BMI <35 and >/=35 kg/m(2) , including in those with comorbidities. CI - (c) 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - McGowan, Barbara M AU - McGowan BM AUID- ORCID: 0000-0003-2015-726X AD - Department of Diabetes and Endocrinology, Guy's and St. Thomas' NHS Foundation Trust, London, UK. FAU - Houshmand-Oeregaard, Azadeh AU - Houshmand-Oeregaard A AUID- ORCID: 0000-0002-1595-5892 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Laursen, Peter Norkjaer AU - Laursen PN AUID- ORCID: 0000-0002-3905-292X AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Zeuthen, Niels AU - Zeuthen N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Baker-Knight, James AU - Baker-Knight J AUID- ORCID: 0000-0002-7936-9593 AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT03548935 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230306 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/administration & dosage/therapeutic use MH - Comorbidity MH - *Cardiovascular Diseases/epidemiology MH - *Obesity/epidemiology MH - Body Mass Index MH - *Body Weight/drug effects MH - *Diabetes Mellitus, Type 2/epidemiology MH - Semaglutide EDAT- 2023/03/07 06:00 MHDA- 2023/03/23 06:00 CRDT- 2023/03/06 05:43 PHST- 2022/12/16 00:00 [revised] PHST- 2022/10/21 00:00 [received] PHST- 2023/01/12 00:00 [accepted] PHST- 2023/03/07 06:00 [pubmed] PHST- 2023/03/23 06:00 [medline] PHST- 2023/03/06 05:43 [entrez] AID - 10.1002/oby.23732 [doi] PST - ppublish SO - Obesity (Silver Spring). 2023 Apr;31(4):990-999. doi: 10.1002/oby.23732. Epub 2023 Mar 6. PMID- 36872170 OWN - NLM STAT- MEDLINE DCOM- 20230425 LR - 20250103 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 45 IP - 3 DP - 2023 Mar TI - Use and Interchange of Incretin Mimetics in the Treatment of Metabolic Diseases: A Narrative Review. PG - 248-261 LID - S0149-2918(23)00062-0 [pii] LID - 10.1016/j.clinthera.2023.02.003 [doi] AB - PURPOSE: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and now tirzepatide, a dual GLP-1 RA/glucose-dependent insulinotropic polypeptide agonist, have numerous advantages in the treatment of type 2 diabetes and obesity, yet only 11% of patients with type 2 diabetes are prescribed a GLP-1 RA. This narrative review addresses the complexity and cost issues surrounding incretin mimetics to support clinicians. METHODS: This narrative review summarizes key trials on the differing effects of incretin mimetics on glycosylated hemoglobin and weight, provides a table with rationale for how to interchange among agents, and summarizes the key factors that guide drug selection beyond guidance from the American Diabetes Association. To support proposed dose interchanges, we preferentially selected high-quality, prospective randomized controlled trials with direct comparisons of agents and doses when available. FINDINGS: Tirzepatide produces the greatest reductions in glycosylated hemoglobin and weight, but its impact on cardiovascular events is still under investigation. Subcutaneous semaglutide and liraglutide are approved for weight loss specifically and are effective in the secondary prevention of cardiovascular disease. Although producing less weight loss, only dulaglutide has effectiveness in the primary and secondary prevention of cardiovascular disease. Semaglutide is the only orally available incretin mimetic; however, the oral formulation produces less weight loss versus its subcutaneous alternative and did not have cardioprotection in its outcomes trial. Although effective in controlling type 2 diabetes, exenatide extended release has the least impact on glycosylated hemoglobin and weight among commonly used agents, while not having cardioprotection. However, exenatide extended release may be preferred on some restrictive insurance formularies. IMPLICATIONS: Although trials have not explicitly studied how to interchange among agents, interchanges can be guided by comparisons between agents' impact on glycosylated hemoglobin and weight. Efficient changes among agents can help clinicians optimize patient-centered care, particularly in the face of changing patient needs and preferences, insurance formularies, and drug shortages. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Teague, Madison AU - Teague M AD - USF Health Taneja College of Pharmacy, University of South Florida, Tampa, Florida. FAU - Martinez, Amanda AU - Martinez A AD - Department of Pharmacy, Ambulatory Care, Tampa General Hospital, Tampa, Florida. FAU - Walker, Erica AU - Walker E AD - Department of Pharmacy, Ambulatory Care, Tampa General Hospital, Tampa, Florida. FAU - El-Rifai, Mohammad AU - El-Rifai M AD - Department of Internal Medicine, Endocrinology, Tampa General Hospital, Tampa, Florida. FAU - Carris, Nicholas W AU - Carris NW AD - USF Health Taneja College of Pharmacy, University of South Florida, Tampa, Florida. Electronic address: carris@usf.edu. LA - eng PT - Journal Article PT - Review DEP - 20230303 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Incretins) RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Incretins/adverse effects MH - Exenatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents MH - Glycated Hemoglobin MH - *Cardiovascular Diseases/drug therapy MH - Prospective Studies MH - Glucagon-Like Peptide 1 MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - antihyperglycemics OT - diabetes OT - dosing OT - interchange OT - obesity COIS- Declaration of interest None declared. EDAT- 2023/03/06 06:00 MHDA- 2023/04/25 10:20 CRDT- 2023/03/05 22:06 PHST- 2022/11/18 00:00 [received] PHST- 2023/02/02 00:00 [revised] PHST- 2023/02/08 00:00 [accepted] PHST- 2023/04/25 10:20 [medline] PHST- 2023/03/06 06:00 [pubmed] PHST- 2023/03/05 22:06 [entrez] AID - S0149-2918(23)00062-0 [pii] AID - 10.1016/j.clinthera.2023.02.003 [doi] PST - ppublish SO - Clin Ther. 2023 Mar;45(3):248-261. doi: 10.1016/j.clinthera.2023.02.003. Epub 2023 Mar 3. PMID- 36871874 OWN - NLM STAT- MEDLINE DCOM- 20230410 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 198 DP - 2023 Apr TI - Efficacy and safety of oral semaglutide in type 2 diabetes mellitus: A systematic review and meta-analysis. PG - 110605 LID - S0168-8227(23)00080-3 [pii] LID - 10.1016/j.diabres.2023.110605 [doi] AB - OBJECTIVES: To investigate the efficacy and safety of oral semaglutide 7 and 14 mg, the only orally delivered glucagon-like peptide-1 (GLP-1) receptor agonist tablet approved for type 2 diabetes mellitus (T2DM) patients. METHODS: Search several databases for randomized controlled trials (RCTs) of oral semaglutide in patients with T2DM from inception through May 31, 2021. The primary outcomes included change from baseline in hemoglobin A1c (HbA1c) and body weight. Risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated to evaluate the outcomes. RESULTS: This meta-analysis included 11 RCTs with a total of 9821 patients. Compared with placebo, semaglutide 7 and 14 mg reduced HbA1c by 1.06% (95% CI, 0.81-1.30) and 1.10% (95% CI, 0.88-1.31), respectively. While in comparison with other antidiabetic agents, semaglutide 7 and 14 mg reduced HbA1c by 0.26% (95% CI, 0.15-0.38) and 0.38% (95%CI, 0.31-0.45). Both doses of semaglutide could significantly reduce body weight. Semaglutide 14 mg did increase the incidence of medication discontinuation and gastrointestinal events (nausea, vomiting and diarrhea). CONCLUSION: Once-daily semaglutide 7 and 14 mg can significantly lowered HbA1c and body weight in patients with T2DM, and this effect increases with dose. Significantly, more gastrointestinal events occurred with semaglutide 14 mg. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Li, Aihua AU - Li A AD - Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China. FAU - Su, Xiaorong AU - Su X AD - Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China. FAU - Hu, Shanshan AU - Hu S AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address: h1435086126@163.com. FAU - Wang, Yong AU - Wang Y AD - Department of Pharmacy, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China; Laboratory of Research of New Chinese Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong, China. Electronic address: yongwh2005@163.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20230305 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Glycated Hemoglobin MH - Treatment Outcome MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Body Weight MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Meta-analysis OT - Oral semaglutide OT - Systematic review OT - Type 2 diabetes mellitus COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/03/06 06:00 MHDA- 2023/04/10 06:42 CRDT- 2023/03/05 19:33 PHST- 2022/02/22 00:00 [received] PHST- 2022/09/24 00:00 [revised] PHST- 2023/02/28 00:00 [accepted] PHST- 2023/04/10 06:42 [medline] PHST- 2023/03/06 06:00 [pubmed] PHST- 2023/03/05 19:33 [entrez] AID - S0168-8227(23)00080-3 [pii] AID - 10.1016/j.diabres.2023.110605 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2023 Apr;198:110605. doi: 10.1016/j.diabres.2023.110605. Epub 2023 Mar 5. PMID- 36871272 OWN - NLM STAT- MEDLINE DCOM- 20230524 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 14 IP - 6 DP - 2023 Jun TI - Effects of switching from liraglutide to semaglutide or dulaglutide in patients with type 2 diabetes: A randomized controlled trial. PG - 774-781 LID - 10.1111/jdi.14000 [doi] AB - INTRODUCTION: Few studies have examined the effects of glucagon-like peptide-1 receptor agonist switching, particularly in Japanese patients. Therefore, we aimed to investigate the effects of switching from liraglutide to semaglutide or dulaglutide on blood glucose, body weight, and the occurrence of adverse effects in clinical practice. MATERIALS AND METHODS: This was an open-label, prospective, randomized, parallel-group controlled trial. Patients with type 2 diabetes treated with liraglutide (0.6 or 0.9 mg) at Yokosuka Kyosai Hospital in Japan were recruited from September 2020 to March 2022 and, after obtaining informed consent, randomly assigned to the semaglutide or dulaglutide group (1:1). Changes in the glycated hemoglobin level from baseline to weeks 8, 16, and 26 were evaluated post-treatment. RESULTS: Initially, 32 participants were enrolled, of whom 30 completed the study. Glycemic control was significantly better in the semaglutide group than in the dulaglutide group (-0.42 +/- 0.49% vs -0.00 +/- 0.34%, P = 0.0120). Body weight significantly decreased in the semaglutide group (-2.6 +/- 3.6 kg, P = 0.0153), whereas no change was observed in the dulaglutide group (-0.1 +/- 2.7 kg, P = 0.8432). We found a significant difference in body weight between the groups (P = 0.0469). The proportion of participants who reported adverse events was 75.0% and 18.8% in the semaglutide and dulaglutide groups, respectively. One patient in the semaglutide group had difficulty continuing treatment due to severe vomiting and weight loss. CONCLUSIONS: Switching from once-daily liraglutide to once-weekly semaglutide 0.5 mg significantly improved glycemic control and body weight compared with switching to once-weekly dulaglutide 0.75 mg. CI - (c) 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Iijima, Takahiro AU - Iijima T AUID- ORCID: 0000-0001-6030-7600 AD - Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Japan. AD - Department of Endocrinology, Diabetes and Metabolism, Yokosuka Kyosai Hospital, Yokosuka, Japan. FAU - Shibuya, Makoto AU - Shibuya M AD - Department of Endocrinology, Diabetes and Metabolism, Yokosuka Kyosai Hospital, Yokosuka, Japan. FAU - Ito, Yuzuru AU - Ito Y AD - Yuzuru Clinic, Saitama, Japan. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine, Yokohama, Japan. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20230305 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) SB - IM EIN - J Diabetes Investig. 2023 Dec;14(12):1423-1424. doi: 10.1111/jdi.14080. PMID: 37767853 MH - Humans MH - *Diabetes Mellitus, Type 2 MH - Liraglutide/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - Prospective Studies MH - Glycated Hemoglobin MH - Recombinant Fusion Proteins/adverse effects MH - Body Weight MH - Semaglutide MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments PMC - PMC10204181 OTO - NOTNLM OT - Diabetes mellitus OT - Dulaglutide OT - Semaglutide EDAT- 2023/03/06 06:00 MHDA- 2023/05/24 06:42 PMCR- 2023/03/05 CRDT- 2023/03/05 14:29 PHST- 2023/02/02 00:00 [revised] PHST- 2022/11/29 00:00 [received] PHST- 2023/02/15 00:00 [accepted] PHST- 2023/05/24 06:42 [medline] PHST- 2023/03/06 06:00 [pubmed] PHST- 2023/03/05 14:29 [entrez] PHST- 2023/03/05 00:00 [pmc-release] AID - JDI14000 [pii] AID - 10.1111/jdi.14000 [doi] PST - ppublish SO - J Diabetes Investig. 2023 Jun;14(6):774-781. doi: 10.1111/jdi.14000. Epub 2023 Mar 5. PMID- 36870274 OWN - NLM STAT- MEDLINE DCOM- 20230501 LR - 20230502 IS - 1873-4529 (Electronic) IS - 0952-8180 (Linking) VI - 87 DP - 2023 Aug TI - Relationship between perioperative semaglutide use and residual gastric content: A retrospective analysis of patients undergoing elective upper endoscopy. PG - 111091 LID - S0952-8180(23)00041-7 [pii] LID - 10.1016/j.jclinane.2023.111091 [doi] AB - STUDY OBJECTIVE: Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist used for management of type 2 diabetes and/or obesity. To test the hypothesis that perioperative semaglutide use is associated with delayed gastric emptying and increased residual gastric content (RGC) despite adequate preoperative fasting, we compared the RGC of patients who had and had not taken semaglutide prior to elective esophagogastroduodenoscopy. The primary outcome was the presence of increased RGC. DESIGN: Single-center retrospective electronic chart review. SETTING: Tertiary hospital. PATIENTS: Patients undergoing esophagogastroduodenoscopy under deep sedation/general anesthesia between July/2021-March/2022. INTERVENTIONS: Patients were divided into two (SG = semaglutide, NSG = non-semaglutide) groups, according to whether they had received semaglutide within 30 days prior to the esophagogastroduodenoscopy. MEASUREMENTS: Increased RGC was defined as any amount of solid content, or > 0.8 mL/Kg (measured from the aspiration/suction canister) of fluid content. MAIN RESULTS: Of the 886 esophagogastroduodenoscopies performed, 404 (33 in the SG and 371 in the NSG) were included in the final analysis. Increased RGC was observed in 27 (6.7%) patients, being 8 (24.2%) in the SG and 19 (5.1%) in the NSG (p < 0.001). Semaglutide use [5.15 (95%CI 1.92-12.92)] and the presence of preoperative digestive symptoms (nausea/vomiting, dyspepsia, abdominal distension) [3.56 (95%CI 2.2-5.78)] were associated with increased RGC in the propensity weighted analysis. Conversely, a protective [0.25 (95%CI 0.16-0.39)] effect against increased RGC was observed in patients undergoing esophagogastroduodenoscopy combined with colonoscopy. In the SG, the mean time of preoperative semaglutide interruption in patients with and without increased RGC was 10.5 +/- 5.5 and 10.2 +/- 5.6 days, respectively (p = 0.54). There was no relationship between semaglutide use and the amount/volume of RGC found on esophagogastroduodenoscopy (p = 0.99). Only one case (in the SG) of pulmonary aspiration was reported. CONCLUSIONS: Semaglutide was associated with increased RGC in patients undergoing elective esophagogastroduodenoscopy. Digestive symptoms prior to esophagogastroduodenoscopy were also predictive of increased RGC. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Silveira, Saullo Queiroz AU - Silveira SQ AD - Department of Anesthesiology, Vila Nova Star Hospital / Rede D'Or - CMA Anesthesia group, Sao Paulo, SP, Brazil. FAU - da Silva, Leopoldo Muniz AU - da Silva LM AD - Department of Anesthesiology, Sao Luiz Hospital - ITAIM / Rede D'Or - CMA Anesthesia group, Sao Paulo, SP, Brazil. FAU - de Campos Vieira Abib, Arthur AU - de Campos Vieira Abib A AD - Department of Anesthesiology, Vila Nova Star Hospital / Rede D'Or - CMA Anesthesia group, Sao Paulo, SP, Brazil. FAU - de Moura, Diogo Turiani Hourneaux AU - de Moura DTH AD - Department of Endoscopy, Vila Nova Star Hospital / Rede D'Or - CMA Anesthesia group, Sao Paulo, SP, Brazil. FAU - de Moura, Eduardo Guimaraes Hourneaux AU - de Moura EGH AD - Department of Endoscopy, Vila Nova Star Hospital / Rede D'Or - CMA Anesthesia group, Sao Paulo, SP, Brazil. FAU - Santos, Leonardo Barbosa AU - Santos LB AD - Department of Anesthesiology, Sao Luiz Hospital - Jabaquara, Sao Paulo, SP, Brazil. FAU - Ho, Anthony M-H AU - Ho AM AD - Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, ON, Canada. FAU - Nersessian, Rafael Souza Fava AU - Nersessian RSF AD - Department of Anesthesiology, Sao Luiz Hospital - ITAIM / Rede D'Or - CMA Anesthesia group, Sao Paulo, SP, Brazil. FAU - Lima, Filipe Lugon Moulin AU - Lima FLM AD - Department of Anesthesiology, Vila Nova Star Hospital / Rede D'Or - CMA Anesthesia group, Sao Paulo, SP, Brazil. FAU - Silva, Marcela Viana AU - Silva MV AD - Department of Endoscopy, Vila Nova Star Hospital / Rede D'Or - CMA Anesthesia group, Sao Paulo, SP, Brazil. FAU - Mizubuti, Glenio B AU - Mizubuti GB AD - Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, ON, Canada. Electronic address: Gleniomizubuti@hotmail.com. LA - eng PT - Journal Article DEP - 20230302 PL - United States TA - J Clin Anesth JT - Journal of clinical anesthesia JID - 8812166 RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications MH - Retrospective Studies MH - Endoscopy, Gastrointestinal/adverse effects MH - Colonoscopy MH - Anesthesia, General MH - Hypoglycemic Agents/adverse effects OTO - NOTNLM OT - Anesthesia OT - Esophagogastroduodenoscopy OT - Pulmonary aspiration OT - Residual gastric content OT - Semaglutide OT - Upper endoscopy COIS- Declaration of Competing Interest None. EDAT- 2023/03/05 06:00 MHDA- 2023/05/01 06:42 CRDT- 2023/03/04 18:17 PHST- 2022/10/04 00:00 [received] PHST- 2023/02/12 00:00 [revised] PHST- 2023/02/22 00:00 [accepted] PHST- 2023/05/01 06:42 [medline] PHST- 2023/03/05 06:00 [pubmed] PHST- 2023/03/04 18:17 [entrez] AID - S0952-8180(23)00041-7 [pii] AID - 10.1016/j.jclinane.2023.111091 [doi] PST - ppublish SO - J Clin Anesth. 2023 Aug;87:111091. doi: 10.1016/j.jclinane.2023.111091. Epub 2023 Mar 2. PMID- 36869853 OWN - NLM STAT- MEDLINE DCOM- 20230605 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 7 DP - 2023 Jul TI - Once-weekly semaglutide use in patients with type 2 diabetes: Results from the SURE France multicentre, prospective, observational study. PG - 1855-1864 LID - 10.1111/dom.15045 [doi] AB - AIMS: Real-world data are required to support glucagon-like peptide-1 receptor agonist use in type 2 diabetes (T2D). SURE France assessed once-weekly semaglutide in adults with T2D in real-world clinical practice. MATERIALS AND METHODS: This multicentre, prospective, open-label, single-arm study included adults with T2D and >/=1 documented glycated haemoglobin (HbA1c) value T (p. Arg424*). Current treatment targets diabetes (Metformin, Gliclazide and the GLP-1 analog semaglutide) and epilepsy (Carbamazepine and Clonazepam). This case report presents a rare association between type 2 diabetes mellitus and Tuberous Sclerosis Complex. We suggest that the diabetes medication Metformin may have positive effects on both the progression of the tumor associated with TSC and the seizures specific to TSC and we assume that the association of TSC and T2DM in the presented cases is accidental, as there are no similar cases reported in the literature. FAU - Jurca, Claudia Maria AU - Jurca CM AD - Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410081 Oradea, Romania. AD - Regional Center of Medical Genetics Bihor, County Emergency Clinical Hospital Oradea (Part of ERN-ITHACA), 410469 Oradea, Romania. FAU - Kozma, Kinga AU - Kozma K AUID- ORCID: 0000-0002-6276-0094 AD - Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410081 Oradea, Romania. AD - Regional Center of Medical Genetics Bihor, County Emergency Clinical Hospital Oradea (Part of ERN-ITHACA), 410469 Oradea, Romania. FAU - Petchesi, Codruta Diana AU - Petchesi CD AUID- ORCID: 0000-0002-8442-6791 AD - Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410081 Oradea, Romania. AD - Regional Center of Medical Genetics Bihor, County Emergency Clinical Hospital Oradea (Part of ERN-ITHACA), 410469 Oradea, Romania. FAU - Zaha, Dana Carmen AU - Zaha DC AUID- ORCID: 0000-0003-4021-4989 AD - Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410081 Oradea, Romania. FAU - Magyar, Ioan AU - Magyar I AD - Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410081 Oradea, Romania. FAU - Munteanu, Mihai AU - Munteanu M AUID- ORCID: 0000-0002-4538-7574 AD - Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410081 Oradea, Romania. FAU - Faur, Lucian AU - Faur L AD - Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410081 Oradea, Romania. FAU - Jurca, Aurora AU - Jurca A AD - Faculty of Medicine and Pharmacy, University of Oradea, 410081 Oradea, Romania. FAU - Bembea, Dan AU - Bembea D AD - Faculty of Medicine, University of Medicine and Pharmacy "Iuliu Hatieganu", 400012 Cluj Napoca, Romania. FAU - Severin, Emilia AU - Severin E AD - Department of Genetics, University of Medicine and Pharmacy "Carol Davila", 020021 Bucharest, Romania. FAU - Jurca, Alexandru Daniel AU - Jurca AD AD - Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410081 Oradea, Romania. LA - eng PT - Case Reports PT - Journal Article PT - Review DEP - 20230208 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 RN - 0 (Tumor Suppressor Proteins) RN - 0 (Tuberous Sclerosis Complex 2 Protein) RN - 0 (Tuberous Sclerosis Complex 1 Protein) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - 9100L32L2N (Metformin) RN - EC 2.7.1.1 (MTOR protein, human) SB - IM MH - Female MH - Humans MH - Adult MH - Infant MH - Adolescent MH - Tumor Suppressor Proteins/genetics MH - *Tuberous Sclerosis/genetics MH - Tuberous Sclerosis Complex 2 Protein MH - Tuberous Sclerosis Complex 1 Protein MH - *Diabetes Mellitus, Type 2/complications MH - Phosphatidylinositol 3-Kinases MH - Proto-Oncogene Proteins c-akt MH - *Epilepsy/complications MH - Seizures MH - TOR Serine-Threonine Kinases MH - Signal Transduction MH - *Metformin PMC - PMC9957184 OTO - NOTNLM OT - Metformin OT - TSC1 OT - TSC2 OT - epilepsy OT - hamartomas OT - tuberous sclerosis OT - type 2 diabetes mellitus COIS- The authors declare no conflict of interest. EDAT- 2023/02/26 06:00 MHDA- 2023/03/03 06:00 PMCR- 2023/02/08 CRDT- 2023/02/25 02:15 PHST- 2022/12/29 00:00 [received] PHST- 2023/01/23 00:00 [revised] PHST- 2023/02/05 00:00 [accepted] PHST- 2023/02/25 02:15 [entrez] PHST- 2023/02/26 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/02/08 00:00 [pmc-release] AID - genes14020433 [pii] AID - genes-14-00433 [pii] AID - 10.3390/genes14020433 [doi] PST - epublish SO - Genes (Basel). 2023 Feb 8;14(2):433. doi: 10.3390/genes14020433. PMID- 36809678 OWN - NLM STAT- MEDLINE DCOM- 20230504 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 6 DP - 2023 Jun TI - Real-world impact of once-weekly subcutaneous semaglutide after 2 years of follow-up: Results from a nationwide observational study in people with type 2 diabetes. PG - 1740-1749 LID - 10.1111/dom.15031 [doi] AB - AIM: To investigate the impact of treatment with once-weekly subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), for up to 2 years in people with type 2 diabetes (T2D) managed in routine clinical practice. MATERIALS AND METHODS: The study was based on data from national registries. People who redeemed at least one prescription of semaglutide and had 2 years of follow-up were included. Data were collected at baseline and after 180, 360, 540 and 720 days of treatment (all timepoints +/- 90 days). RESULTS: In total, 9284 people redeemed at least one semaglutide prescription (intention-to-treat) and 4132 people redeemed semaglutide continuously (on-treatment). For the on-treatment cohort, the median (interquartile range) age was 62.0 (16.0) years, diabetes duration was 10.8 (8.7) years, and glycated haemoglobin (HbA1c) level was 62.0 (18.0) mmol/mol at baseline. A subset of the on-treatment cohort, comprising 2676 people, had HbA1c measurements at baseline and at least once during 720 days. The mean (95% confidence interval) changes in HbA1c after 720 days were -12.6 (-13.6; -11.6) mmol/mol (P < 0.001) for GLP-1RA-naive people, and -5.6 (-6.2; -5.0) mmol/mol (P < 0.001) for GLP-1RA-experienced people. Similarly, 55% of GLP-1RA-naive people and 43% of GLP-1RA-experienced people reached a HbA1c target of /=24 weeks duration in adults with T2DM (PROSPERO: CRD42022331547). Adjudicated cerebrovascular events in GLP-1RA treatment vs control arms were pooled together to calculate risk ratios (RR) using fixed-effects model. Subgroup analysis was performed based on individual drugs, treatment duration, and baseline patient characteristics. Quality of evidence was assessed using GRADE framework. RESULTS: We identified 28 RCTs involving 74 148 patients (57% male; median [range], age 58 [52-67] years, BMI 32 [25.4-37.2] kg/m2, T2DM duration 9 [3.5-15.4] years, treatment duration 52 [24-259] weeks). GLP-1RA use in T2DM was associated with significantly decreased risk of adverse cerebrovascular outcomes vs placebo/active comparator (RR, 0.83; 95% CI, 0.76-0.91; I2 = 0%). Pooling data from cardiovascular outcome trials (n = 8), GLP-1RA treatment vs placebo was associated with reduced risk of nonfatal stroke (RR, 0.85; 95% CI, 0.76-0.94; I2 = 0%) but not fatal stroke (RR, 0.80; 95% CI, 0.61-1.05; I2 = 0%). GLP-1RA use was associated with reduced risk of ischemic stroke (RCTs = 12; RR, 0.73; 95% CI, 0.60-0.89; I2 = 0%), composite of ischemic stroke/TIA (RCTs = 16; RR, 0.76; 95% CI, 0.65-0.90; I2 = 0%), but not hemorrhagic stroke (RCTs = 3; RR, 0.92; 95% CI, 0.51-1.64; I2 = 0%). Treatment benefits differed according to baseline eGFR and diabetes duration (P interaction < .1). Benefits were statistically significant for dulaglutide, subcutaneous/oral semaglutide (P < .05). Sensitivity analysis, excluding shorter-acting lixisenatide, eliminated the heterogeneity between individual GLP-1RA effects. CONCLUSION: GLP-1RAs, particularly longer-acting formulations, reduced ischemic cerebrovascular events in T2DM. Observed benefits were significantly higher in patients with shorter T2DM duration and higher eGFR. CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Banerjee, Mainak AU - Banerjee M AUID- ORCID: 0000-0002-6656-8569 AD - Department of Endocrinology, Institute of Post Graduate Medical Education and Research, Kolkata 700020, India. FAU - Pal, Rimesh AU - Pal R AD - Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. FAU - Mukhopadhyay, Satinath AU - Mukhopadhyay S AD - Department of Endocrinology, Institute of Post Graduate Medical Education and Research, Kolkata 700020, India. FAU - Nair, Kirthana AU - Nair K AD - Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - J Clin Endocrinol Metab. 2023 Oct 18;108(11):e1454-e1455. doi: 10.1210/clinem/dgad191. PMID: 37009694 MH - Male MH - Adult MH - Humans MH - Middle Aged MH - Female MH - Hypoglycemic Agents/adverse effects MH - *Ischemic Attack, Transient/chemically induced/drug therapy MH - Randomized Controlled Trials as Topic MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - *Ischemic Stroke/chemically induced/drug therapy MH - *Stroke/epidemiology/etiology/prevention & control MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 receptor agonists OT - T2DM OT - cardiovascular outcome OT - ischemic stroke OT - mortality OT - transient ischemic attacks EDAT- 2023/02/18 06:00 MHDA- 2023/06/19 13:08 CRDT- 2023/02/17 12:33 PHST- 2022/12/27 00:00 [received] PHST- 2023/06/19 13:08 [medline] PHST- 2023/02/18 06:00 [pubmed] PHST- 2023/02/17 12:33 [entrez] AID - 7044761 [pii] AID - 10.1210/clinem/dgad076 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2023 Jun 16;108(7):1806-1812. doi: 10.1210/clinem/dgad076. PMID- 36796719 OWN - NLM STAT- MEDLINE DCOM- 20230321 LR - 20260127 IS - 1879-0631 (Electronic) IS - 0024-3205 (Linking) VI - 319 DP - 2023 Apr 15 TI - Treatment with semaglutide, a GLP-1 receptor agonist, improves extracellular matrix remodeling in the pancreatic islet of diet-induced obese mice. PG - 121502 LID - S0024-3205(23)00136-4 [pii] LID - 10.1016/j.lfs.2023.121502 [doi] AB - AIMS: The extracellular matrix (ECM) is fundamental for the normal endocrine functions of pancreatic islet cells and plays key roles in the pathophysiology of type 2 diabetes. Here we investigated the turnover of islet ECM components, including islet amyloid polypeptide (IAPP), in an obese mouse model treated with semaglutide, a glucagon-like peptide type 1 receptor agonist. MAIN METHODS: Male one-month-old C57BL/6 mice were fed a control diet (C) or a high-fat diet (HF) for 16 weeks, then treated with semaglutide (subcutaneous 40 mug/kg every three days) for an additional four weeks (HFS). The islets were immunostained and gene expressions were assessed. KEY FINDINGS: Comparisons refer to HFS vs HF. Thus, IAPP immunolabeling and beta-cell-enriched beta-amyloid precursor protein cleaving enzyme (Bace2, -40 %) and heparanase immunolabeling and gene (Hpse, -40 %) were mitigated by semaglutide. In contrast, perlecan (Hspg2, +900 %) and vascular endothelial growth factor A (Vegfa, +420 %) were enhanced by semaglutide. Also, semaglutide lessened syndecan 4 (Sdc4, -65 %) and hyaluronan synthases (Has1, -45 %; Has2, -65 %) as well as chondroitin sulfate immunolabeling, and collagen type 1 (Col1a1, -60 %) and type 6 (Col6a3, -15 %), lysyl oxidase (Lox, -30 %) and metalloproteinases (Mmp2, -45 %; Mmp9, -60 %). SIGNIFICANCE: Semaglutide improved the turnover of islet heparan sulfate proteoglycans, hyaluronan, chondroitin sulfate proteoglycans, and collagens in the islet ECM. Such changes should contribute to restoring a healthy islet functional milieu and should reduce the formation of cell-damaging amyloid deposits. Our findings also provide additional evidence for the involvement of islet proteoglycans in the pathophysiology of type 2 diabetes. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Cardoso, Luiz E M AU - Cardoso LEM AD - Laboratory of Morphometry, Metabolism, and Cardiovascular disease, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: luizemcardoso@gmail.com. FAU - Marinho, Thatiany Souza AU - Marinho TS AD - Laboratory of Morphometry, Metabolism, and Cardiovascular disease, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Martins, Fabiane Ferreira AU - Martins FF AD - Laboratory of Morphometry, Metabolism, and Cardiovascular disease, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Aguila, Marcia Barbosa AU - Aguila MB AD - Laboratory of Morphometry, Metabolism, and Cardiovascular disease, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: mbaguila@uerj.br. FAU - Mandarim-de-Lacerda, Carlos A AU - Mandarim-de-Lacerda CA AD - Laboratory of Morphometry, Metabolism, and Cardiovascular disease, Biomedical Center, Institute of Biology, The University of the State of Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: mandarim@uerj.br. LA - eng PT - Journal Article DEP - 20230214 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Islet Amyloid Polypeptide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Mice MH - Animals MH - Male MH - Mice, Obese MH - Vascular Endothelial Growth Factor A/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Mice, Inbred C57BL MH - *Islets of Langerhans/metabolism MH - Glucagon-Like Peptides/pharmacology MH - Extracellular Matrix/metabolism MH - Islet Amyloid Polypeptide/genetics/metabolism/pharmacology MH - Diet MH - Semaglutide OTO - NOTNLM OT - Beta-cell OT - Heparanase OT - Islet amyloid polypeptide OT - Perlecan OT - Syndecan COIS- Declaration of competing interest The authors declare no competing interests. EDAT- 2023/02/17 06:00 MHDA- 2023/03/22 06:00 CRDT- 2023/02/16 19:28 PHST- 2022/12/24 00:00 [received] PHST- 2023/02/02 00:00 [revised] PHST- 2023/02/10 00:00 [accepted] PHST- 2023/02/17 06:00 [pubmed] PHST- 2023/03/22 06:00 [medline] PHST- 2023/02/16 19:28 [entrez] AID - S0024-3205(23)00136-4 [pii] AID - 10.1016/j.lfs.2023.121502 [doi] PST - ppublish SO - Life Sci. 2023 Apr 15;319:121502. doi: 10.1016/j.lfs.2023.121502. Epub 2023 Feb 14. PMID- 36789682 OWN - NLM STAT- MEDLINE DCOM- 20230504 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 6 DP - 2023 Jun TI - Once-weekly semaglutide use in patients with type 2 diabetes: Real-world data from the SURE Italy observational study. PG - 1658-1667 LID - 10.1111/dom.15020 [doi] AB - AIMS: SURE Italy, a multicentre, prospective, open-label, observational, real-world study, investigated once-weekly semaglutide in patients with type 2 diabetes (T2D) in routine clinical practice. MATERIALS AND METHODS: Adults with T2D and >/=1 documented glycated haemoglobin (HbA1c) level within 12 weeks of semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~30 weeks). Other endpoints included changes in body weight, waist circumference and patient-reported outcomes, and the proportion of patients achieving HbA1c <7.0% or <6.5%, weight loss >/=5% and a post-hoc composite endpoint (HbA1c reduction of >/=1%-point and weight loss >/=5%). These endpoints were reported for patients on semaglutide at EOS [effectiveness analysis set (EAS)]. Safety data were reported in the full analysis set. RESULTS: Of 579 patients who initiated semaglutide (full analysis set), 491 completed the study on treatment (EAS). Mean baseline HbA1c was 8.0%, and 20.7% (120 of 579) of patients had HbA1c <7.0%. Mean semaglutide dose at EOS was 0.66 +/- 0.28 mg. In the EAS, mean HbA1c and body weight decreased by 1.1%-point (95% confidence interval 1.20, 1.05; P < .0001) and 4.2 kg (95% confidence interval 4.63, 3.67; P < .0001), respectively. At EOS, 61.7% and 40.8% of patients achieved HbA1c <7.0% and <6.5%, respectively, 40.5% achieved weight loss >/=5% and 25.3% achieved the post-hoc composite endpoint. Patient-reported outcomes improved from baseline to EOS. No new safety concerns were identified. CONCLUSIONS: In routine clinical practice in Italy, patients with T2D treated with once-weekly semaglutide for 30 weeks achieved clinically significant improvements in HbA1c, body weight and other outcomes. CI - (c) 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Napoli, Raffaele AU - Napoli R AUID- ORCID: 0000-0002-3366-2321 AD - Department of Translational Medical Sciences Federico, II University School of Medicine, Naples, Italy. FAU - Berra, Cesare AU - Berra C AD - IRCCS Multimedica, Milan, Italy. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Di Loreto, Chiara AU - Di Loreto C AD - Diabetic Clinic, USL Umbria1, Perugia Territorial Health Structure, Perugia, Italy. FAU - Donatiello, Emily AU - Donatiello E AD - Novo Nordisk spa, Rome, Italy. FAU - Berentzen, Tina Landsvig AU - Berentzen TL AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Pitocco, Dario AU - Pitocco D AD - Diabetes Care Unit Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. FAU - Giorgino, Francesco AU - Giorgino F AUID- ORCID: 0000-0001-7372-2678 AD - Department of Precision and Regenerative Medicine and Ionian Area, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20230312 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - Hypoglycemic Agents/adverse effects MH - Glycated Hemoglobin MH - Prospective Studies MH - Glucagon-Like Peptides/adverse effects MH - Body Weight MH - Weight Loss MH - Semaglutide OTO - NOTNLM OT - GLP-1 analogue OT - glycaemic control OT - observational study OT - real-world evidence OT - semaglutide OT - type 2 diabetes EDAT- 2023/02/16 06:00 MHDA- 2023/05/04 12:41 CRDT- 2023/02/15 04:12 PHST- 2023/02/02 00:00 [revised] PHST- 2022/12/01 00:00 [received] PHST- 2023/02/12 00:00 [accepted] PHST- 2023/05/04 12:41 [medline] PHST- 2023/02/16 06:00 [pubmed] PHST- 2023/02/15 04:12 [entrez] AID - 10.1111/dom.15020 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Jun;25(6):1658-1667. doi: 10.1111/dom.15020. Epub 2023 Mar 12. PMID- 36765019 OWN - NLM STAT- MEDLINE DCOM- 20230411 LR - 20260327 IS - 1708-0428 (Electronic) IS - 0960-8923 (Print) IS - 0960-8923 (Linking) VI - 33 IP - 4 DP - 2023 Apr TI - Efficacy of the Glucagon-Like Peptide-1 Receptor Agonists Liraglutide and Semaglutide for the Treatment of Weight Regain After Bariatric surgery: a Retrospective Observational Study. PG - 1017-1025 LID - 10.1007/s11695-023-06484-8 [doi] AB - PURPOSE: Weight regain after bariatric surgery occurs in up to a third of patients and reduces treatment-associated health benefits. The efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RA) for treatment of type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains to be defined. MATERIALS AND METHODS: This was a single centre retrospective observational study conducted at a Swiss bariatric reference centre. Patients with 6 months of treatment with GLP1-RA, up until November 2021, due to weight regain after bariatric surgery were identified. Data on body weight and relevant clinical parameters were collected before and after 6 months of treatment with GLP1-RA. Data are presented as median (interquartile range). RESULTS: Fifty patients (82% female) were included. Before GLP1-RA treatment (liraglutide, n=29; semaglutide, n=21), weight and BMI were 90.5 kg (83.4, 107.9) and 34.0 kg/m(2) (31.7, 38.7), respectively, with a post-bariatric weight regain of 15.1% (10.6, 22.8) of total body weight and 4.6 kg/m(2) (3.3, 6.2). After 6 months of GLP1-RA treatment, a reduction in weight and BMI of 8.8% (5.2, 11.4) of total body weight and 2.9 kg/m(2) (1.8, 4.0) was observed (P value <0.0001), corresponding to 67.4% (40.4, 92.2) of the weight regain. No serious adverse events were reported. CONCLUSION: For patients experiencing weight regain after bariatric surgery, two-thirds of the weight regain can be safely lost with GLP1-RA, providing clinicians with a therapeutic option for this clinical challenge, and highlights the need for a large-scale randomized clinical trial. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Jensen, Anders Boisen AU - Jensen AB AUID- ORCID: 0000-0003-4752-041X AD - Division of Endocrinology and Diabetes, Department of Internal Medicine, Cantonal Hospital of St. Gallen, Rorschacher Strasse 95, 9007, St. Gallen, Switzerland. anders.jensen@spitalbuelach.ch. FAU - Renstrom, Frida AU - Renstrom F AUID- ORCID: 0000-0001-6053-298X AD - Division of Endocrinology and Diabetes, Department of Internal Medicine, Cantonal Hospital of St. Gallen, Rorschacher Strasse 95, 9007, St. Gallen, Switzerland. FAU - Aczel, Stefan AU - Aczel S AD - Division of Endocrinology and Diabetes, Department of Internal Medicine, Cantonal Hospital of St. Gallen, Rorschacher Strasse 95, 9007, St. Gallen, Switzerland. FAU - Folie, Patrick AU - Folie P AD - Division of Surgery, Cantonal Hospital of St. Gallen, Rorschacher Strasse 95, 9007, St. Gallen, Switzerland. FAU - Biraima-Steinemann, Magdalena AU - Biraima-Steinemann M AD - Division of Surgery, Cantonal Hospital of St. Gallen, Rorschacher Strasse 95, 9007, St. Gallen, Switzerland. FAU - Beuschlein, Felix AU - Beuschlein F AD - Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Ramistrasse 100, 8091, Zurich, Switzerland. AD - Medizinische Klinik und Poliklinik IV, Klinikum der Universitat Munchen, Ziemssenstrasse 1, 80336, Munich, Germany. FAU - Bilz, Stefan AU - Bilz S AD - Division of Endocrinology and Diabetes, Department of Internal Medicine, Cantonal Hospital of St. Gallen, Rorschacher Strasse 95, 9007, St. Gallen, Switzerland. LA - eng PT - Journal Article PT - Observational Study DEP - 20230211 PL - United States TA - Obes Surg JT - Obesity surgery JID - 9106714 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) SB - IM MH - Female MH - Humans MH - Male MH - *Bariatric Surgery MH - *Diabetes Mellitus, Type 2/drug therapy/surgery MH - Glucagon-Like Peptide-1 Receptor MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/pharmacology/therapeutic use MH - *Obesity, Morbid/surgery MH - Weight Gain MH - Semaglutide PMC - PMC9918402 OTO - NOTNLM OT - Bariatric surgery OT - GLP-1 receptor agonist OT - Liraglutide OT - Obesity OT - Semaglutide OT - Weight regain COIS- Anders Boisen Jensen is a previous employee of Novo Nordisk (2008-2010) and has received speaker honoraria and financial support for attending congresses from Novo Nordisk. Frida Renstrom has no conflict of interest to declare. Stefan Aczel has received speaker honoraria and financial support for attending congresses from Novo Nordisk. Patrick Folie and Magdalena Biraima-Steinemann have received speaker honoraria from Novo Nordisk. Felix Beuschlein has received financial support for attending symposia and for educational programmes by Novo Nordisk. EDAT- 2023/02/11 06:00 MHDA- 2023/04/10 10:16 PMCR- 2023/02/11 CRDT- 2023/02/10 23:17 PHST- 2022/07/11 00:00 [received] PHST- 2023/01/27 00:00 [accepted] PHST- 2023/01/22 00:00 [revised] PHST- 2023/04/10 10:16 [medline] PHST- 2023/02/11 06:00 [pubmed] PHST- 2023/02/10 23:17 [entrez] PHST- 2023/02/11 00:00 [pmc-release] AID - 10.1007/s11695-023-06484-8 [pii] AID - 6484 [pii] AID - 10.1007/s11695-023-06484-8 [doi] PST - ppublish SO - Obes Surg. 2023 Apr;33(4):1017-1025. doi: 10.1007/s11695-023-06484-8. Epub 2023 Feb 11. PMID- 36757837 OWN - NLM STAT- MEDLINE DCOM- 20230213 LR - 20260127 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 65 IP - 1670 DP - 2023 Feb 20 TI - In brief: Semaglutide (Wegovy) for weight loss in children. PG - 31-32 LID - 10.58347/tml.2023.1670d [doi] LA - eng PT - Journal Article PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Anti-Obesity Agents) RN - C045TQL4WP (Phentermine) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Child MH - Obesity MH - Weight Loss MH - Glucagon-Like Peptides/adverse effects MH - *Anti-Obesity Agents MH - Phentermine MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Semaglutide OTO - NOTNLM OT - Bydureon OT - Qsymia OT - Saxenda OT - Wegovy OT - Xenical OT - adverse effects OT - dosage OT - drug interactions OT - efficacy OT - liraglutide OT - metformin OT - orlistat OT - phentermine OT - safety OT - semaglutide OT - topiramate OT - weight loss EDAT- 2023/02/10 06:00 MHDA- 2023/02/14 06:00 CRDT- 2023/02/09 12:22 PHST- 2023/02/09 12:22 [entrez] PHST- 2023/02/10 06:00 [pubmed] PHST- 2023/02/14 06:00 [medline] AID - 10.58347/tml.2023.1670d [doi] PST - ppublish SO - Med Lett Drugs Ther. 2023 Feb 20;65(1670):31-32. doi: 10.58347/tml.2023.1670d. PMID- 36749220 OWN - NLM STAT- MEDLINE DCOM- 20230320 LR - 20230320 IS - 1520-4804 (Electronic) IS - 0022-2623 (Linking) VI - 66 IP - 4 DP - 2023 Feb 23 TI - Discovery of Novel PTP1B Inhibitors with Once-Weekly Therapeutic Potential for Type 2 Diabetes: Design, Synthesis, and In Vitro and In Vivo Investigations of BimBH3 Peptide Analogues. PG - 3030-3044 LID - 10.1021/acs.jmedchem.2c02003 [doi] AB - Poor medication adherence in patients with type 2 diabetes mellitus has become one of the main causes of suboptimal glycemic control. Once-weekly drugs can markedly improve the convenience, adherence, and quality of life of T2DM patients; thus, they are clinically needed and preferred. PTP1B plays a negative role in both insulin and leptin signaling pathways, which makes it an important target for diabetes. Herein, we design and synthesize 35 analogues of core BimBH3 peptide via lipidation/acylation strategy based on our previous work and evaluate their PTP1B inhibitory activity, obtaining the primary structure-activity relationship. Five compounds with good PPT1B inhibitory activity, target selectivity, and significantly improved stability were selected for molecular docking study and searching candidate molecules with long-acting antidiabetic potential. The in vivo anti-T2DM evaluation validated the once-weekly therapeutic potential of analogues 19, 26, 27, 31, and 33, which were comparable with semaglutide and therefore presented as promising drug candidates. FAU - Zhang, Chuanliang AU - Zhang C AUID- ORCID: 0000-0002-9719-0554 AD - College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. AD - School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. FAU - Yang, Xianmin AU - Yang X AD - College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. FAU - Meng, Xinjia AU - Meng X AD - College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. FAU - Wu, Lijuan AU - Wu L AD - School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. AD - Marine Biomedical Research Institute, Ocean University of China, Qingdao 266071, China. FAU - Liu, Xiaochun AU - Liu X AD - School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. AD - Marine Biomedical Research Institute, Ocean University of China, Qingdao 266071, China. FAU - Gao, Jiangming AU - Gao J AD - Marine Biomedical Research Institute, Ocean University of China, Qingdao 266071, China. FAU - Liu, Shan AU - Liu S AD - Marine Biomedical Research Institute, Ocean University of China, Qingdao 266071, China. FAU - Wu, Juan AU - Wu J AD - Marine Biomedical Research Institute, Ocean University of China, Qingdao 266071, China. FAU - Huang, Dingmin AU - Huang D AD - College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. FAU - Wang, Zhenwei AU - Wang Z AD - College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. FAU - Su, Xianbin AU - Su X AD - College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230207 PL - United States TA - J Med Chem JT - Journal of medicinal chemistry JID - 9716531 RN - 0 (Enzyme Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - EC 3.1.3.48 (PTPN1 protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Enzyme Inhibitors/chemistry/pharmacology MH - *Hypoglycemic Agents/chemistry/pharmacology MH - Insulin/metabolism MH - Molecular Docking Simulation MH - *Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors MH - *Drug Design EDAT- 2023/02/08 06:00 MHDA- 2023/02/25 06:00 CRDT- 2023/02/07 10:06 PHST- 2023/02/08 06:00 [pubmed] PHST- 2023/02/25 06:00 [medline] PHST- 2023/02/07 10:06 [entrez] AID - 10.1021/acs.jmedchem.2c02003 [doi] PST - ppublish SO - J Med Chem. 2023 Feb 23;66(4):3030-3044. doi: 10.1021/acs.jmedchem.2c02003. Epub 2023 Feb 7. PMID- 36746803 OWN - NLM STAT- MEDLINE DCOM- 20230327 LR - 20261010 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 66 IP - 5 DP - 2023 May TI - Separate and combined effects of semaglutide and empagliflozin on kidney oxygenation and perfusion in people with type 2 diabetes: a randomised trial. PG - 813-825 LID - 10.1007/s00125-023-05876-w [doi] AB - AIMS/HYPOTHESIS: Glucagon-like peptide-1 receptor agonists (GLP-1ras) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown kidney-protective effects. Improved kidney oxygenation and haemodynamic changes are suggested mechanisms; however, human data are scarce. We therefore investigated whether semaglutide (GLP-1ra), empagliflozin (SGLT2i) or their combination improve kidney oxygenation and perfusion. METHODS: The trial was undertaken at Aarhus University Hospital, Denmark. A total of 120 people with type 2 diabetes (HbA(1c) >/=48 mmol/mol [6.5%]) and at high risk of CVD (age >/=50 years) were randomised into four parallel groups (n=30 in each group) for 32 weeks: 1.0 mg semaglutide (open label); 10 mg empagliflozin (blinded to participants, caregivers, examiners and outcome assessors); their combination (1.0 mg semaglutide open label plus 10 mg empagliflozin blinded to participants, caregivers, examiners and outcome assessors); and placebo tablet (blinded to participants, caregivers, examiners and outcome assessors). Sequentially numbered, sealed envelopes containing computer-generated randomisation codes, provided by Glostrup Pharmacy, Glostrup, Denmark, determined the intervention. The two co-primary outcomes were change in kidney oxygenation and change in arterial stiffness. This paper reports on kidney oxygenation, for which 80 individuals as prespecified, 20 in each group, underwent MRI. We primarily hypothesised that kidney oxygenation would be improved in the active treatment groups compared with placebo after 32 weeks. Secondary outcomes included changes in kidney perfusion, erythropoietin, haematocrit, urine albumin/creatinine ratio (UACR) and GFR (measured using technetium-99m) compared with baseline and between treatment groups at week 32. RESULTS: Our model estimated a common baseline R2* value across all four groups in the cortex and the medulla. At baseline, the value was 24.5 (95% CI 23.9, 24.9) Hz in the medulla. After 32 weeks, the R2* values in the medulla were estimated to be 25.4 (95% CI 24.7, 26.2) Hz in the empagliflozin group and 24.5 (95% CI 23.9, 25.1) Hz in the placebo group (p=0.016) (higher R2* corresponds to a lower oxygenation). Semaglutide decreased perfusion in both the cortex and the medulla. Empagliflozin increased erythropoietin and haematocrit. All three active treatments decreased GFR but not UACR. Ten serious adverse events were reported, among them two occurrences of semaglutide-associated obstipation. CONCLUSIONS/INTERPRETATION: Our hypothesis, that semaglutide, empagliflozin or their combination improve kidney oxygenation, was rejected. On the contrary, empagliflozin induced a reduction in medullary kidney oxygenation. Semaglutide substantially reduced kidney perfusion without affecting oxygenation. TRIAL REGISTRATION: Clinicaltrialsregister.eu EudraCT 2019-000781-38 FUNDING: Novo Nordisk Foundation, Central Denmark Region Research Fund and Danish Medical Associations Research Foundation. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Gullaksen, Soren AU - Gullaksen S AUID- ORCID: 0000-0001-8275-1278 AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. soegul@clin.au.dk. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. soegul@clin.au.dk. AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. soegul@clin.au.dk. FAU - Vernstrom, Liv AU - Vernstrom L AUID- ORCID: 0000-0003-2875-435X AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. FAU - Sorensen, Steffen S AU - Sorensen SS AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. FAU - Ringgaard, Steffen AU - Ringgaard S AUID- ORCID: 0000-0001-5353-7379 AD - Department of Clinical Medicine, The MR Research Centre, Aarhus University, Aarhus, Denmark. FAU - Laustsen, Christoffer AU - Laustsen C AUID- ORCID: 0000-0002-0317-2911 AD - Department of Clinical Medicine, The MR Research Centre, Aarhus University, Aarhus, Denmark. FAU - Funck, Kristian L AU - Funck KL AUID- ORCID: 0000-0003-0213-5550 AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. FAU - Poulsen, Per L AU - Poulsen PL AUID- ORCID: 0000-0001-6468-2715 AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. FAU - Laugesen, Esben AU - Laugesen E AUID- ORCID: 0000-0003-1782-1596 AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. AD - Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230206 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Hypoglycemic Agents) RN - 11096-26-7 (Erythropoietin) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) SB - IM EIN - Diabetologia. 2024 Jul;67(7):1451. doi: 10.1007/s00125-024-06167-8. PMID: 38739291 MH - Humans MH - Middle Aged MH - *Diabetes Mellitus, Type 2/complications MH - Hypoglycemic Agents/adverse effects MH - Kidney MH - Perfusion MH - *Erythropoietin/therapeutic use MH - Treatment Outcome MH - Double-Blind Method MH - Semaglutide MH - Benzhydryl Compounds MH - Glucosides OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Kidney OT - MRI OT - Sodium-glucose cotransporter 2 inhibitor OT - Type 2 diabetes EDAT- 2023/02/07 06:00 MHDA- 2023/03/28 06:00 CRDT- 2023/02/06 23:13 PHST- 2022/09/26 00:00 [received] PHST- 2022/11/30 00:00 [accepted] PHST- 2023/02/07 06:00 [pubmed] PHST- 2023/03/28 06:00 [medline] PHST- 2023/02/06 23:13 [entrez] AID - 10.1007/s00125-023-05876-w [pii] AID - 10.1007/s00125-023-05876-w [doi] PST - ppublish SO - Diabetologia. 2023 May;66(5):813-825. doi: 10.1007/s00125-023-05876-w. Epub 2023 Feb 6. PMID- 36743930 OWN - NLM STAT- MEDLINE DCOM- 20230207 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 13 DP - 2022 TI - Real world effectiveness of subcutaneous semaglutide in type 2 diabetes: A retrospective, cohort study (Sema-MiDiab01). PG - 1099451 LID - 10.3389/fendo.2022.1099451 [doi] LID - 1099451 AB - INTRODUCTION: Aim of the present study was to evaluate the real-world impact of once-weekly (OW) subcutaneous semaglutide on different end-points indicative of metabolic control, cardiovascular risk factors, and beta-cell function in type 2 diabetes (T2D). METHODS: This was a retrospective, observational study conducted in 5 diabetes clinics in Italy. Changes in HbA1c, fasting blood glucose (FBG), body weight, blood pressure, lipid profile, renal function, and beta-cell function (HOMA-B) during 12 months were evaluated. RESULTS: Overall, 594 patients (97% GLP-1RA naive) were identified (mean age 63.9 +/- 9.5 years, 58.7% men, diabetes duration 11.4 +/- 8.0 years). After 6 months of treatment with OW semaglutide, HbA1c levels were reduced by 0.90%, FBG by 26 mg/dl, and body weight by 3.43 kg. Systolic blood pressure, total and LDL-cholesterol significantly improved. Benefits were sustained at 12 months. Renal safety was documented. HOMA-B increased from 40.2% to 57.8% after 6 months (p<0.0001). DISCUSSION: The study highlighted benefits of semaglutide on metabolic control, multiple CV risk factors, and renal safety in the real-world. Semaglutide seems to be an advisable option for preservation of beta-cell function and early evidence suggests it might have a role in modifying insulin resistance (HOMA-IR), the pathogenetic basis of prediabetes and T2D. CI - Copyright (c) 2023 Berra, Rossi, Mirani, Ceccarelli Ceccarelli, Romano, Sassi, Peretti, Favacchio, Pastore, Folini, Graziano, Lunati, Solerte and Fiorina. FAU - Berra, Cesare C AU - Berra CC AD - Department of Endocrine and Metabolic Diseases, I.R.C.C.S. MultiMedica - Sesto San Giovanni, Milan, Italy. FAU - Rossi, Maria Chiara AU - Rossi MC AD - CORESEARCH - Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy. FAU - Mirani, Marco AU - Mirani M AD - Department of Internal Medicine, I.R.C.C.S Humanitas Research Hospital - Rozzano, Milan, Italy. FAU - Ceccarelli Ceccarelli, Daniela AU - Ceccarelli Ceccarelli D AD - Department of Internal Medicine, UOC Geriatrics and Diabetology, University of Pavia, Pavia, Italy. FAU - Romano, Cristina AU - Romano C AD - Diabetology, Azienda Ospedaliera ASST Sette Laghi - Osp. di Circolo, Varese, Italy. FAU - Sassi, Lorenza AU - Sassi L AD - Diabetology, Azienda Ospedaliera ASST Sette Laghi - Osp. di Circolo, Varese, Italy. FAU - Peretti, Elena AU - Peretti E AD - Diabetology, Azienda Ospedaliera ASST Sette Laghi - Osp. di Circolo, Varese, Italy. FAU - Favacchio, Giuseppe AU - Favacchio G AD - Department of Internal Medicine, I.R.C.C.S Humanitas Research Hospital - Rozzano, Milan, Italy. FAU - Pastore, Ida AU - Pastore I AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Folini, Laura AU - Folini L AD - Department of Endocrine and Metabolic Diseases, I.R.C.C.S. MultiMedica - Sesto San Giovanni, Milan, Italy. FAU - Graziano, Giusi AU - Graziano G AD - CORESEARCH - Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy. FAU - Lunati, Maria Elena AU - Lunati ME AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Solerte, Sebastiano Bruno AU - Solerte SB AD - Department of Internal Medicine, UOC Geriatrics and Diabetology, University of Pavia, Pavia, Italy. FAU - Fiorina, Paolo AU - Fiorina P AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. AD - International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita di Milano, Milan, Italy. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20230118 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Male MH - Humans MH - Middle Aged MH - Aged MH - Female MH - *Diabetes Mellitus, Type 2 MH - Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin MH - Retrospective Studies MH - Cohort Studies MH - Body Weight MH - Semaglutide PMC - PMC9889982 OTO - NOTNLM OT - HbA1c OT - beta-cell function OT - cardiovascular risk factors OT - effectiveness OT - insulin resistance OT - semaglutide OT - type 2 diabetes COIS- MR has received funding for research from NovoNordisk, Sanofi, Alfasigma, Artsana, AstraZeneca, Johnson&Johnson, Medtronic, Shionogi, SOBI, Meteda and Theras. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/02/07 06:00 MHDA- 2023/02/08 06:00 PMCR- 2022/01/01 CRDT- 2023/02/06 04:02 PHST- 2022/11/15 00:00 [received] PHST- 2022/12/23 00:00 [accepted] PHST- 2023/02/06 04:02 [entrez] PHST- 2023/02/07 06:00 [pubmed] PHST- 2023/02/08 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2022.1099451 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2023 Jan 18;13:1099451. doi: 10.3389/fendo.2022.1099451. eCollection 2022. PMID- 36738891 OWN - NLM STAT- MEDLINE DCOM- 20230324 LR - 20260127 IS - 1523-1755 (Electronic) IS - 0085-2538 (Linking) VI - 103 IP - 4 DP - 2023 Apr TI - Post hoc analysis of SUSTAIN 6 and PIONEER 6 trials suggests that people with type 2 diabetes at high cardiovascular risk treated with semaglutide experience more stable kidney function compared with placebo. PG - 772-781 LID - S0085-2538(23)00056-X [pii] LID - 10.1016/j.kint.2022.12.028 [doi] AB - Glucagon-like peptide-1 receptor agonists reduce albuminuria and may stabilize the estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (T2D). In this post hoc analysis of the SUSTAIN 6/PIONEER 6 trials encompassing 6480 participants at high cardiovascular risk (semaglutide, 3239 participants; placebo, 3241 participants), we investigated the effects of semaglutide versus placebo on eGFR decline. Pooled data by treatment were evaluated for annual eGFR change (total annual eGFR slope in ml/min per 1.73 m(2)) from baseline to end of treatment and time to persistent eGFR reductions of 30%, 40%, 50% and 57% or more, including subgroup analyses by baseline eGFR (30 to under 60 or 60 and over ml/min per 1.73 m(2)). In the overall population, the estimated treatment difference (ETD; semaglutide versus placebo) in annual eGFR slope was significant at 0.59 ml/min per 1.73 m(2) (95% confidence interval 0.29; 0.89). The ETD was numerically largest in the 30 to under 60 ml/min per 1.73 m(2) eGFR subgroup, 1.06 ml/min per 1.73 m(2) (0.45; 1.67), but no significant interaction was observed for treatment effect by subgroup. Hazard ratios (semaglutide versus placebo) for time to persistent eGFR decline were under 1.0 for all eGFR thresholds in the overall population; and were numerically lower in the baseline eGFR 30 to under 60 ml/min per 1.73 m(2) subgroup versus the overall population, although no significant interaction was observed for treatment effect by subgroup. Thus, pooled analyses of clinical trial data in patients with T2D suggest that semaglutide may reduce the rate of eGFR decline. CI - Copyright (c) 2023 International Society of Nephrology. Published by Elsevier Inc. All rights reserved. FAU - Tuttle, Katherine R AU - Tuttle KR AD - Providence Health Care, University of Washington, Spokane, Washington, USA. Electronic address: Katherine.Tuttle@providence.org. FAU - Bosch-Traberg, Heidrun AU - Bosch-Traberg H AD - Novo Nordisk A/S, Medical & Science, Soborg, Denmark. FAU - Cherney, David Z I AU - Cherney DZI AD - Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada. FAU - Hadjadj, Samy AU - Hadjadj S AD - Departement d'Endocrinologie, Diabetologie et Nutrition, Nantes Universite, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France. FAU - Lawson, Jack AU - Lawson J AD - Novo Nordisk A/S, Global Medical Affairs, Soborg, Denmark. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Biostatistics, Soborg, Denmark. FAU - Bain, Stephen C AU - Bain SC AD - Diabetes Research Unit, Swansea University, Swansea, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230202 PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Kidney Int. 2023 Sep;104(3):618-619. doi: 10.1016/j.kint.2023.06.009. PMID: 37599022 MH - Humans MH - *Diabetes Mellitus, Type 2/complications/diagnosis/drug therapy MH - *Cardiovascular Diseases/etiology/prevention & control MH - Risk Factors MH - Kidney MH - Hypoglycemic Agents/adverse effects MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - cardiovascular outcomes trial OT - kidney function OT - renal function OT - semaglutide EDAT- 2023/02/05 06:00 MHDA- 2023/03/25 06:00 CRDT- 2023/02/04 19:25 PHST- 2022/02/23 00:00 [received] PHST- 2022/11/24 00:00 [revised] PHST- 2022/12/22 00:00 [accepted] PHST- 2023/02/05 06:00 [pubmed] PHST- 2023/03/25 06:00 [medline] PHST- 2023/02/04 19:25 [entrez] AID - S0085-2538(23)00056-X [pii] AID - 10.1016/j.kint.2022.12.028 [doi] PST - ppublish SO - Kidney Int. 2023 Apr;103(4):772-781. doi: 10.1016/j.kint.2022.12.028. Epub 2023 Feb 2. PMID- 36722623 OWN - NLM STAT- MEDLINE DCOM- 20230504 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 6 DP - 2023 Jun TI - Improvement of glycaemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study). PG - 1503-1511 LID - 10.1111/dom.14998 [doi] AB - AIM: To investigate the effects of switching from liraglutide or dulaglutide to once-weekly semaglutide on glycaemic control and treatment satisfaction in patients with type 2 diabetes. MATERIALS AND METHODS: In this multicentre, open-labelled, prospective, randomized, parallel-group comparison study, patients treated with liraglutide 0.9-1.8 mg/day (plan A) or dulaglutide 0.75 mg/week (plan B) were either switched to semaglutide or continued current therapy. The primary endpoint was the mean change in glycated haemoglobin over 24 weeks. The secondary endpoints included the changes of Diabetes Treatment Satisfaction Questionnaire scores, body weight and metabolic indices. RESULTS: In total, 110 patients were enrolled, and 10 were excluded; therefore, 37 patients in plan A and 63 patients in plan B completed the study. Glycated haemoglobin levels were significantly reduced in the semaglutide group in both plans [plan A, 7.8% +/- 1.0% to 7.8% +/- 0.7% (liraglutide) vs. 7.9% +/- 0.7% to 7.3% +/- 0.7% (semaglutide), p < .01; plan B, 7.8% +/- 1.0% to 7.9% +/- 1.2% (dulaglutide) vs. 7.8% +/- 0.8% to 7.1% +/- 0.6% (semaglutide), p < .01]. Semaglutide also improved Diabetes Treatment Satisfaction Questionnaire scores in both groups (plan A, +0.1 vs. +8.3, p < .01; plan B, -1.2 vs. +3.5, p < .01). Switching from dulaglutide yielded greater reductions in body weight and improved metabolic parameters. CONCLUSIONS: Once-weekly semaglutide administration improved glycaemic control and treatment satisfaction after switching from liraglutide or dulaglutide. These results highlighted a useful treatment option for patients with metabolic abnormalities despite glucagon-like receptor-1 receptor agonist treatment. CI - (c) 2023 John Wiley & Sons Ltd. FAU - Takahashi, Yuka AU - Takahashi Y AUID- ORCID: 0000-0002-0639-3170 AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Nomoto, Hiroshi AU - Nomoto H AUID- ORCID: 0000-0003-0713-221X AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Yokoyama, Hiroki AU - Yokoyama H AD - Jiyugaoka Medical Clinic, Obihiro, Japan. FAU - Takano, Yoshinari AU - Takano Y AD - Department of Diabetes and Endocrinology, Tonan Hospital, Sapporo, Japan. FAU - Nagai, So AU - Nagai S AD - Division of Diabetes and Endocrinology, Department of Medicine, Sapporo Medical Center, NTT East Corporation, Sapporo, Japan. FAU - Tsuzuki, Atsushi AU - Tsuzuki A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Cho, Kyu Yong AU - Cho KY AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. AD - Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan. FAU - Miya, Aika AU - Miya A AUID- ORCID: 0000-0002-3313-6946 AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Kameda, Hiraku AU - Kameda H AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Takeuchi, Jun AU - Takeuchi J AD - Sapporo Diabetes and Thyroid Clinic, Sapporo, Japan. FAU - Taneda, Shinji AU - Taneda S AD - Diabetes Center, Manda Memorial Hospital, Sapporo, Japan. FAU - Kurihara, Yoshio AU - Kurihara Y AD - Kurihara Clinic, Sapporo, Japan. FAU - Atsumi, Tatsuya AU - Atsumi T AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Nakamura, Akinobu AU - Nakamura A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. FAU - Miyoshi, Hideaki AU - Miyoshi H AUID- ORCID: 0000-0002-5909-3243 AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. AD - Aoki Clinic, Sapporo, Japan. CN - SWITCH-SEMA 1 study group LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230228 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/chemically induced MH - Liraglutide/adverse effects MH - Hypoglycemic Agents/adverse effects MH - Glycated Hemoglobin MH - Prospective Studies MH - Glycemic Control MH - Patient Satisfaction MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Immunoglobulin Fc Fragments/adverse effects MH - Recombinant Fusion Proteins/adverse effects MH - Body Weight MH - Personal Satisfaction MH - Semaglutide OTO - NOTNLM OT - GLP-1 analogue OT - clinical trial OT - dulaglutide OT - liraglutide OT - semaglutide OT - type 2 diabetes EDAT- 2023/02/02 06:00 MHDA- 2023/05/04 12:42 CRDT- 2023/02/01 07:23 PHST- 2023/01/14 00:00 [revised] PHST- 2022/11/25 00:00 [received] PHST- 2023/01/26 00:00 [accepted] PHST- 2023/05/04 12:42 [medline] PHST- 2023/02/02 06:00 [pubmed] PHST- 2023/02/01 07:23 [entrez] AID - 10.1111/dom.14998 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Jun;25(6):1503-1511. doi: 10.1111/dom.14998. Epub 2023 Feb 28. PMID- 36720576 OWN - NLM STAT- MEDLINE DCOM- 20230202 LR - 20260127 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 13 IP - 1 DP - 2023 Jan 31 TI - Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry). PG - e068652 LID - 10.1136/bmjopen-2022-068652 [doi] LID - e068652 AB - INTRODUCTION: Clozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. Non-pharmacological/behavioural interventions have had limited effects counteracting these adverse effects. Semaglutide, a glucagon-like peptide 1 receptor agonist, is approved for the treatment of type 2 diabetes and obesity. We will investigate the long-term effects of add-on treatment with semaglutide once a week versus placebo once a week on the metabolic status in pre-diabetic (glycated haemoglobin A1c (HbA1c) 35-47 mmol/mol (5.4%-6.4%) and diabetic (HbA1c 48-57 mmol/mol (6.5%-7.4%)) patients diagnosed with a schizophrenia spectrum disorder who initiated clozapine or olanzapine treatment within the last 60 months. METHODS AND ANALYSIS: This is a 26-week, double-blinded, randomised, placebo-controlled trial. Altogether, 104 patients diagnosed with a schizophrenia spectrum disorder, aged 18-65 years, with pre-diabetes or diabetes will be randomised to injections of 1.0 mg semaglutide once a week or placebo for 26 weeks. The primary endpoint is change from baseline in HbA1c. Secondary endpoints include changes in body weight, hip and waist circumference and plasma levels of insulin, glucagon, glucose, and C-peptide, insulin sensitivity, beta cell function, hepatic function, fibrosis-4 score, lipid profile, incretin hormones, bone markers, body composition, bone density, proteomic analyses and oxidative stress markers. Together with alcohol, tobacco and drug use, potential effects on the reward value of a sweet-fat stimulus, psychopathology, level of activity and quality of life will also be assessed. ETHICS AND DISSEMINATION: This study is approved by the Danish Medicines Agency and the regional scientific ethics committee of the Capital Region of Denmark (committee C, #H-20019008) and will be carried out in accordance with International Council for Harmonisation Good Clinical Practice guidelines and the Helsinki Declaration. The results will be disseminated through peer-review publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04892199. CI - (c) Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Sass, Marie Reeberg AU - Sass MR AUID- ORCID: 0000-0002-0934-8463 AD - Mental Health Centre Copenhagen, Copenhagen University Hospital, Capital Region of Denmark Mental Health Services, Copenhagen, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Danielsen, Andreas Aalkjaer AU - Danielsen AA AD - Psychiatry, Psychosis Research Unit, Aarhus University Hospital Skejby, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Kohler-Forsberg, Ole AU - Kohler-Forsberg O AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. AD - Psychiatry, Psychosis Research Unit, Aarhus Universitetshospital Skejby, Aarhus, Denmark. FAU - Storgaard, Heidi AU - Storgaard H AD - Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Knop, Filip K AU - Knop FK AUID- ORCID: 0000-0002-2495-5034 AD - Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. AD - Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Nielsen, Mette Odegaard AU - Nielsen MO AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Mental Health Centre Glostrup, Copenhagen University Hospital, Capital Region of Denmark Mental Health Services, Glostrup, Denmark. FAU - Sjodin, Anders Mikael AU - Sjodin AM AD - Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark. FAU - Mors, Ole AU - Mors O AD - Psychiatry, Psychosis Research Unit, Aarhus University Hospital Skejby, Aarhus, Denmark. AD - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. FAU - Correll, Christoph U AU - Correll CU AD - Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine at Hofstra University, Hempstead, New York, USA. AD - Department of Child and Adolescent Psychiatry, Charite Universitatsmedizin Berlin, Berlin, Germany. FAU - Ekstrom, Claus AU - Ekstrom C AD - Department of Biostatistics, University of Copenhagen Department of Public Health, Copenhagen, Denmark. FAU - Vinberg, Maj AU - Vinberg M AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Psychiatric Center North Zeeland, Copenhagen University Hospital, Capital Region of Denmark Mental Health Services, Hillerod, Denmark. FAU - Nielsen, Jimmi AU - Nielsen J AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Mental Health Centre Glostrup, Copenhagen University Hospital, Capital Region of Denmark Mental Health Services, Glostrup, Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AD - Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. AD - Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Fink-Jensen, Anders AU - Fink-Jensen A AD - Mental Health Centre Copenhagen, Copenhagen University Hospital, Capital Region of Denmark Mental Health Services, Copenhagen, Denmark Anders.Fink-Jensen@regionh.dk. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng SI - ClinicalTrials.gov/NCT04892199 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230131 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - J60AR2IKIC (Clozapine) RN - N7U69T4SZR (Olanzapine) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Schizophrenia/drug therapy MH - *Clozapine MH - Olanzapine/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - *Prediabetic State MH - *Diabetes Mellitus, Type 2 MH - Glycated Hemoglobin MH - Proteomics MH - Quality of Life MH - Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC9890830 OTO - NOTNLM OT - Adult psychiatry OT - DIABETES & ENDOCRINOLOGY OT - MENTAL HEALTH OT - PSYCHIATRY OT - Schizophrenia & psychotic disorders COIS- Competing interests: AFJ received an unrestricted research grant from Novo Nordisk A/S for the present clinical study. TV served on scientific advisory panels and/or speaker's bureaus for Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Gilead, GSK, Merck Sharp & Dohme, Mundipharma, Novo Nordisk, Sanofi and Sun Pharma. TV served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Gilead, GSK, Merck Sharp & Dohme, Mundipharma, Novo Nordisk, Sanofi and Sun Pharma. HS served on scientific advisory panels for Boehringer Ingelheim and Novo Nordisk. CUC has been a consultant and/or advisor to or has received honoraria from AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic. OKF reports speaker fees for Lundbeck Pharma A/S and consultant work for WCG Clinical. FKK served on scientific advisory panels and/or been part of speaker's bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Sanofi and Zealand Pharma. MV received consultancy fees from Lundbeck and Janssen-Cilag. AAD received a speaker honorarium from Otsuka Pharmaceutical. MRS has nothing to disclose. Novo Nordisk A/S commented on the study design but will not influence trial conduction, data analysis, interpretation or publication. All data are owned by the authors, who all have full data access. EDAT- 2023/02/01 06:00 MHDA- 2023/02/03 06:00 PMCR- 2023/01/31 CRDT- 2023/01/31 21:03 PHST- 2023/01/31 21:03 [entrez] PHST- 2023/02/01 06:00 [pubmed] PHST- 2023/02/03 06:00 [medline] PHST- 2023/01/31 00:00 [pmc-release] AID - bmjopen-2022-068652 [pii] AID - 10.1136/bmjopen-2022-068652 [doi] PST - epublish SO - BMJ Open. 2023 Jan 31;13(1):e068652. doi: 10.1136/bmjopen-2022-068652. PMID- 36710450 OWN - NLM STAT- MEDLINE DCOM- 20230213 LR - 20250103 IS - 1744-8417 (Electronic) IS - 1744-6651 (Linking) VI - 18 IP - 1 DP - 2023 Jan TI - Obesity and diabetes: the final frontier. PG - 81-94 LID - 10.1080/17446651.2023.2168643 [doi] AB - INTRODUCTION: Obesity is a key target in the treatment and prevention of diabetes and independently to reduce the burden of cardiovascular disease. We reviewed the options now available and anticipated to deal with obesity. AREAS COVERED: We considered the epidemiology, genetics, and causation of obesity and the relationship to diabetes, and the dietary, pharmaceutical, and surgical management of the condition. The literature search covered both popular media via Google Search and the academic literature as indexed on PubMed with search terms including obesity, childhood obesity, adipocytes, insulin resistance, mechanisms of satiety, bariatric surgery, GLP-1 receptor agonists, and SGLT2 inhibitors. EXPERT OPINION: Although bariatric surgery has been the primary approach to treating obese individuals, the emergence of agents impacting the brain satiety centers now promises effective, non-invasive treatment of obesity for individuals with and without diabetes. The GLP-1 receptor agonists have assumed the primary role in treating obesity with significant weight loss. Long-term results with semaglutide and tirzepatide are now approaching the success seen with bariatric surgery. Future agents combining the benefits of satiety control and thermogenesis to dissipate caloric excess are under investigation. FAU - Rendell, Marc S AU - Rendell MS AD - The Association of Diabetes Investigators, Newport Coast, CA, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20230129 PL - England TA - Expert Rev Endocrinol Metab JT - Expert review of endocrinology & metabolism JID - 101278293 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Bariatric Surgery MH - *Diabetes Mellitus, Type 2/epidemiology MH - Hypoglycemic Agents/pharmacology MH - *Obesity/epidemiology MH - Cardiovascular Diseases/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Obesity OT - liraglutide OT - prediabetes OT - semaglutide OT - tirzapatide OT - type 2 diabetes EDAT- 2023/01/31 06:00 MHDA- 2023/02/11 06:00 CRDT- 2023/01/30 01:02 PHST- 2023/01/31 06:00 [pubmed] PHST- 2023/02/11 06:00 [medline] PHST- 2023/01/30 01:02 [entrez] AID - 10.1080/17446651.2023.2168643 [doi] PST - ppublish SO - Expert Rev Endocrinol Metab. 2023 Jan;18(1):81-94. doi: 10.1080/17446651.2023.2168643. Epub 2023 Jan 29. PMID- 36706368 OWN - NLM STAT- MEDLINE DCOM- 20230215 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 16 IP - 2 DP - 2023 Feb TI - Real-world clinical effectiveness of once-weekly semaglutide in patients with type 2 diabetes: a systematic literature review. PG - 161-176 LID - 10.1080/17512433.2023.2174099 [doi] AB - INTRODUCTION: The efficacy of once-weekly (O.W.) semaglutide for the treatment of type 2 diabetes mellitus (T2DM) has been demonstrated in clinical trials. The aim of this systematic literature review was to summarize real-world evidence for O.W. semaglutide. METHODS: A comprehensive search of PubMed, Web of Science, Embase, and Scilit databases was performed from January 2017 to June 2022 to identify eligible real-world studies examining O.W. semaglutide in T2DM. RESULTS: Thirty-one records (18 full-text and 13 abstracts) were identified. The general characteristics of studies and included patients were summarized. Changes in glycated hemoglobin (HbA1c) and body weight were analyzed across studies and according to patient characteristics: baseline HbA1c/weight level, GLP-1 RA-naive/ GLP-1RA-experienced. The effectiveness of O.W. semaglutide compared with dulaglutide, and the dose of O.W. semaglutide in the real world were also summarized. CONCLUSIONS: This systematic literature review provided complementary evidence to findings from the clinical trials and provided a more comprehensive picture of the use of O.W. semaglutide in routine clinical practice. Results of the review suggested that O.W. semaglutide therapy was associated with improving glycemic control and weight loss in both T2DM patients naive to GLP-1RA and those previously treated with other GLP-1RA in routine clinical practice. PROSPERO REGISTRATION: CRD42022306164. FAU - Ruan, Zhen AU - Ruan Z AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. FAU - Jiang, Yixuan AU - Jiang Y AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. FAU - Shi, Honghao AU - Shi H AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. FAU - Jia, Ruxu AU - Jia R AD - Global Business School for Health, University College London, London, UK. FAU - Ung, Carolina Oi Lam AU - Ung COL AUID- ORCID: 0000-0003-1915-5099 AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. AD - Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao SAR, China. FAU - Hu, Hao AU - Hu H AD - State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. AD - Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao SAR, China. LA - eng PT - Journal Article PT - Systematic Review DEP - 20230202 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents MH - Glycated Hemoglobin MH - Drug Administration Schedule MH - Glucagon-Like Peptides MH - Body Weight MH - Glucagon-Like Peptide 1/therapeutic use MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - Effectiveness OT - GLP-1RA OT - HbA1c OT - O.W. semaglutide OT - Real-world evidence OT - review OT - type 2 diabetes OT - weight EDAT- 2023/01/28 06:00 MHDA- 2023/02/16 06:00 CRDT- 2023/01/27 16:23 PHST- 2023/01/28 06:00 [pubmed] PHST- 2023/02/16 06:00 [medline] PHST- 2023/01/27 16:23 [entrez] AID - 10.1080/17512433.2023.2174099 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2023 Feb;16(2):161-176. doi: 10.1080/17512433.2023.2174099. Epub 2023 Feb 2. PMID- 36700417 OWN - NLM STAT- MEDLINE DCOM- 20230404 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 5 DP - 2023 May TI - Safety and tolerability of semaglutide across the SUSTAIN and PIONEER phase IIIa clinical trial programmes. PG - 1385-1397 LID - 10.1111/dom.14990 [doi] AB - AIM: Glucagon-like peptide-1 receptor agonists improve glycaemic control: some are now available as oral and subcutaneous formulations, and some have indications for reducing cardiovascular risk. The expanded scope for these therapies warrants comprehensive safety evaluations. We report the safety/tolerability of subcutaneous and oral semaglutide from the SUSTAIN and PIONEER clinical trial programmes, respectively. MATERIALS AND METHODS: Adverse events (AEs) from 16 randomized placebo- or active-controlled phase IIIa trials in patients with type 2 diabetes (n = 11 159) including once-weekly subcutaneous semaglutide (n = 3150; SUSTAIN trials) or once-daily oral semaglutide (n = 4116; PIONEER trials) were analysed. Data pools were analysed for each programme, with separate analyses of cardiovascular outcomes trials (CVOTs; n = 6480). RESULTS: In the phase IIIa pools, gastrointestinal disorders were reported in 41.9%/39.1% of patients with subcutaneous/oral semaglutide, respectively (most prevalent during initiation/escalation) versus 22.0%/24.8% with comparators. Rates of kidney disorders, acute pancreatitis, malignant neoplasms, hypoglycaemia, diabetic retinopathy, heart failure and other cardiovascular events were similar for semaglutide versus comparators. Cholelithiasis incidence was higher with subcutaneous and oral semaglutide versus placebo. Diabetic retinopathy incidence was higher with subcutaneous semaglutide versus placebo in SUSTAIN 6. Small pulse rate increases occurred with both formulations; there was no increased rate of arrhythmias. Fatal AE incidence was similar between semaglutide and comparators. Versus placebo, CVOTs showed a reduced risk of major adverse cardiovascular events with subcutaneous semaglutide and non-inferiority criteria were met with oral semaglutide. CONCLUSIONS: The most common AEs with semaglutide were gastrointestinal disorders, which decreased with continued therapy. These comprehensive safety/tolerability data may better inform patient selection and guidance in care. CI - (c) 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Erhan, Umut AU - Erhan U AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jelnes, Peter AU - Jelnes P AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Meier, Juris J AU - Meier JJ AUID- ORCID: 0000-0002-5835-8019 AD - Department of Internal Medicine, Gastroenterology, Hepatology and Diabetology, Augusta Clinic, Bochum, Germany. FAU - Abildlund, Morten Tind AU - Abildlund MT AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Pratley, Richard AU - Pratley R AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. FAU - Vilsboll, Tina AU - Vilsboll T AUID- ORCID: 0000-0002-0456-6787 AD - Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark. FAU - Husain, Mansoor AU - Husain M AUID- ORCID: 0000-0002-3740-6739 AD - Ted Rogers Centre for Heart Research, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. LA - eng GR - Novo Nordisk A/S, Soborg, Denmark/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230221 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/epidemiology MH - Hypoglycemic Agents/adverse effects MH - Acute Disease MH - *Diabetic Retinopathy/chemically induced MH - *Pancreatitis/chemically induced MH - Glucagon-Like Peptides/adverse effects MH - *Gastrointestinal Diseases/chemically induced/epidemiology/drug therapy MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - antidiabetic drug OT - phase III study OT - randomized trial OT - type 2 diabetes EDAT- 2023/01/27 06:00 MHDA- 2023/04/04 06:42 CRDT- 2023/01/26 04:52 PHST- 2023/01/20 00:00 [revised] PHST- 2022/09/30 00:00 [received] PHST- 2023/01/24 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2023/01/27 06:00 [pubmed] PHST- 2023/01/26 04:52 [entrez] AID - 10.1111/dom.14990 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 May;25(5):1385-1397. doi: 10.1111/dom.14990. Epub 2023 Feb 21. PMID- 36695099 OWN - NLM STAT- MEDLINE DCOM- 20231102 LR - 20260127 IS - 1744-764X (Electronic) IS - 1474-0338 (Linking) VI - 22 IP - 6 DP - 2023 Jan-Jun TI - Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. PG - 455-461 LID - 10.1080/14740338.2023.2172159 [doi] AB - BACKGROUND: Semaglutide is a Glucagon-like peptide-1 receptor agonist used in the second-line treatment of poorly controlled type 2 diabetes and can be used in monotherapy or associated with other oral antidiabetics or even insulin, increasing the effectiveness of the treatment. This work aims to analyze the profile of adverse drug reactions reported for semaglutide in Eudravigilance. RESEARCH DESIGN AND METHODS: Data on Individual Cases Safety Reports were obtained from the database of the centralized European spontaneous reporting system Eudravigilance by accessing www.adrreports.eu. (1 December 2021). RESULTS: It is possible to observe a high prevalence of gastrointestinal disorders (N = 3502, 53.2%). The most severe reported cases were primarily gastrointestinal disorders, metabolic, and nutritional disorders, eye disorders, renal and urinary disorders and cardiac disorders, with an evident higher prevalence of adverse gastrointestinal events both in oral and injectable dosage form (N = 133, 50.0% vs N = 588, 47.2%, respectively). Through a comparative analysis, semaglutide had a greater number of reported gastrointestinal adverse events compared to sitagliptin and empaglifozin (p < 0.00001). CONCLUSIONS: Semaglutide has a good safety profile, however the definition of subgroups within the type 2 diabetes population who are particularly prone to develop serious adverse event when treated with GLP-1 RAs is crucial. FAU - Cabral Lopes, Antonio AU - Cabral Lopes A AD - Pharmaceutical Services of Unity Local of Health of Guarda (ULS da Guarda), Guarda, Portugal. AD - Health Sciences Faculty, University of Beira Interior (FCS-UBI), Covilha, Portugal. FAU - Roque, Fatima AU - Roque F AUID- ORCID: 0000-0003-0169-3788 AD - Research Unit for Inland Development, Polytechnic Institute of Guarda (UDI-IPG), Guarda, Portugal. AD - Health Sciences Research Centre, University of Beira Interior (CICS-UBI), Covilha, Portugal. FAU - Lourenco, Olga AU - Lourenco O AUID- ORCID: 0000-0002-8401-5976 AD - Health Sciences Faculty, University of Beira Interior (FCS-UBI), Covilha, Portugal. AD - Health Sciences Research Centre, University of Beira Interior (CICS-UBI), Covilha, Portugal. FAU - Herdeiro, Maria Teresa AU - Herdeiro MT AD - Institute of Biomedicine, Department of Medical Sciences (iBiMED-UA), University of Aveiro, Portugal. FAU - Morgado, Manuel AU - Morgado M AUID- ORCID: 0000-0003-2112-2835 AD - Health Sciences Faculty, University of Beira Interior (FCS-UBI), Covilha, Portugal. AD - Research Unit for Inland Development, Polytechnic Institute of Guarda (UDI-IPG), Guarda, Portugal. AD - Health Sciences Research Centre, University of Beira Interior (CICS-UBI), Covilha, Portugal. AD - Pharmaceutical Services of University Hospital Center of Cova da Beira, Covilha, Portugal. LA - eng PT - Journal Article DEP - 20230202 PL - England TA - Expert Opin Drug Saf JT - Expert opinion on drug safety JID - 101163027 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Hypoglycemic Agents MH - Glucagon-Like Peptides/adverse effects MH - *Gastrointestinal Diseases/chemically induced/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Eudravigilance Database OT - Glucagon-like peptide-1 OT - Semaglutide OT - adverse drug reactions OT - type 2 diabetes EDAT- 2023/01/26 06:00 MHDA- 2023/01/26 06:01 CRDT- 2023/01/25 04:03 PHST- 2023/01/26 06:01 [medline] PHST- 2023/01/26 06:00 [pubmed] PHST- 2023/01/25 04:03 [entrez] AID - 10.1080/14740338.2023.2172159 [doi] PST - ppublish SO - Expert Opin Drug Saf. 2023 Jan-Jun;22(6):455-461. doi: 10.1080/14740338.2023.2172159. Epub 2023 Feb 2. PMID- 36692268 OWN - NLM STAT- MEDLINE DCOM- 20230407 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 5 DP - 2023 May TI - Therapeutic inertia related to the injectable glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes in UK primary care. PG - 1331-1340 LID - 10.1111/dom.14985 [doi] AB - AIMS: To determine the extent of therapeutic inertia related to the weekly injectable glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes (T2D) in the United Kingdom. MATERIALS AND METHODS: Adults with T2D who received their first primary care prescription of dulaglutide or semaglutide between January and July 2019 were identified from the UK Clinical Practice Research Datalink GOLD primary care database. Doses prescribed, glycated haemoglobin (HbA1c), body mass index (BMI) and concomitant T2D medications were assessed at first prescription and at 3, 6 and 9 months. RESULTS: Of the patients prescribed dulaglutide (N = 748; mean [SD] age 59.0 [11.2] years) and semaglutide (N = 437; mean [SD] age 58.4 [10.6] years), 93.0% and 89.0%, respectively, had an HbA1c level >/=7.5% (>/=58.46 mmol/mol), and 56.4% and 54.9%, respectively, had an HbA1c level >/=9.0% (>/=74.86 mmol/mol), at first prescription. At 6 to 9 months, 75.0% of those on dulaglutide 0.75 mg and 57.6% of those on semaglutide 0.25 mg or 0.5 mg had an HbA1c level >/=7.5% (>/=58.46 mmol/mol). At 9 months, 21.9% of the dulaglutide cohort were on the suboptimal dose of 0.75 mg, and 46.1% of the semaglutide cohort were on the suboptimal doses of 0.25 mg or 0.5 mg. CONCLUSIONS: Multiple examples of therapeutic inertia were identified, including first prescription at HbA1c levels considerably above target and failure to escalate to optimal doses even with evidence of suboptimal metabolic control. A substantial proportion of patients therefore did not achieve optimal HbA1c targets. CI - (c) 2023 Eli Lilly and Company and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - von Arx, Lill-Brith AU - von Arx LB AUID- ORCID: 0000-0002-7170-6268 AD - Eli Lilly and Company, Herlev, Denmark. FAU - Rachman, Jonathan AU - Rachman J AD - Eli Lilly and Company, Basingstoke, UK. FAU - Webb, Joanne AU - Webb J AD - Eli Lilly and Company, Basingstoke, UK. FAU - Casey, Caroline AU - Casey C AD - Adelphi Real World, Bollington, UK. FAU - Patel, Amisha AU - Patel A AD - Adelphi Real World, Bollington, UK. FAU - Diomatari, Christina AU - Diomatari C AD - Adelphi Real World, Bollington, UK. FAU - Wood, Robert AU - Wood R AD - Adelphi Real World, Bollington, UK. FAU - Idris, Iskandar AU - Idris I AD - University of Nottingham, Nottingham, UK. LA - eng GR - Eli Lilly and Company/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230210 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Adult MH - Humans MH - Middle Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - Hypoglycemic Agents/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Primary Health Care MH - Recombinant Fusion Proteins/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptides/analogs & derivatives OTO - NOTNLM OT - GLP-1RA OT - dulaglutide OT - observational study OT - primary care OT - subcutaneous semaglutide OT - therapeutic inertia OT - type 2 diabetes EDAT- 2023/01/25 06:00 MHDA- 2023/04/04 06:42 CRDT- 2023/01/24 08:53 PHST- 2023/01/18 00:00 [revised] PHST- 2022/10/27 00:00 [received] PHST- 2023/01/22 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2023/01/25 06:00 [pubmed] PHST- 2023/01/24 08:53 [entrez] AID - 10.1111/dom.14985 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 May;25(5):1331-1340. doi: 10.1111/dom.14985. Epub 2023 Feb 10. PMID- 36691310 OWN - NLM STAT- MEDLINE DCOM- 20230125 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 134 IP - sup1 DP - 2022 Jan TI - Introducing an important therapy for obesity to primary care: once-weekly subcutaneous semaglutide 2.4 mg. PG - 1-4 LID - 10.1080/00325481.2022.2149005 [doi] FAU - Kyrillos, Janine V AU - Kyrillos JV AUID- ORCID: 0000-0002-1604-971X AD - Jefferson Comprehensive Weight Management, Thomas Jefferson University, Philadelphia, PA, USA. FAU - O'Neil, Patrick M AU - O'Neil PM AUID- ORCID: 0000-0002-0388-4046 AD - Weight Management Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - York University, McMaster University and Wharton Weight Management Clinic, Toronto, ON, Canada. LA - eng PT - Editorial PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Obesity/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Primary Health Care MH - *Diabetes Mellitus, Type 2/drug therapy MH - Injections, Subcutaneous MH - Semaglutide OTO - NOTNLM OT - Semaglutide 2.4 mg OT - best-practices OT - cardiometabolic OT - obesity OT - primary care OT - quality of life OT - weight management EDAT- 2023/01/25 06:00 MHDA- 2023/01/26 06:00 CRDT- 2023/01/24 00:23 PHST- 2023/01/24 00:23 [entrez] PHST- 2023/01/25 06:00 [pubmed] PHST- 2023/01/26 06:00 [medline] AID - 10.1080/00325481.2022.2149005 [doi] PST - ppublish SO - Postgrad Med. 2022 Jan;134(sup1):1-4. doi: 10.1080/00325481.2022.2149005. PMID- 36691309 OWN - NLM STAT- MEDLINE DCOM- 20230125 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 134 IP - sup1 DP - 2022 Jan TI - Efficacy and safety of semaglutide for weight management: evidence from the STEP program. PG - 5-17 LID - 10.1080/00325481.2022.2147326 [doi] AB - Obesity is a global health challenge. It is a multifactorial, complex, and progressive disease associated with various health complications and increased mortality. Lifestyle modifications are central to weight management but may be insufficient to maintain clinically meaningful weight loss. Pharmacotherapies are recommended as an adjunct to lifestyle interventions to induce and sustain clinically meaningful weight loss and reduce the risk of comorbidities in appropriate patients. Glucagon-like peptide-1 is an incretin metabolic hormone responsible for a range of physiological effects, including glucose and appetite regulation. Several glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been approved for the treatment of type 2 diabetes since 2005 including exenatide (short- and extended-release), lixisenatide, liraglutide, dulaglutide, albiglutide, and semaglutide. Of these, semaglutide (subcutaneous) and liraglutide are currently US Food and Drug Administration (FDA)-approved for chronic weight management in patients with or without diabetes. The phase 3 Semaglutide Treatment Effect in People with obesity (STEP) program was designed to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with overweight or obesity. Following the submission of the results of the STEP 1-4 trials, the FDA approved once-weekly subcutaneous semaglutide 2.4 mg for chronic weight management in people with overweight or obesity in April 2021. Data from the program demonstrated that semaglutide (2.4 mg once weekly) achieved significant and sustained weight loss, together with improvements in cardiometabolic risk factors compared with placebo, and was generally well tolerated, with a safety profile consistent with other GLP-1RAs. The most common adverse events reported in STEP 1-5 were gastrointestinal events, which were transient, mild-to-moderate in severity, and typically resolved without permanent treatment discontinuation. This article reviews the data from STEP 1-5 and highlights clinically relevant findings for primary care providers. FAU - Amaro, Anastassia AU - Amaro A AUID- ORCID: 0000-0002-3132-5778 AD - Penn Metabolic Medicine, Division of Endocrinology, University of Pennsylvania, Philadelphia, PA, USA. FAU - Sugimoto, Danny AU - Sugimoto D AUID- ORCID: 0000-0002-7801-1231 AD - Cedar Crosse Research Center, Chicago, IL, USA. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - York University, McMaster University and Wharton Weight Management Clinic, Toronto, Ontario, Canada. LA - eng PT - Journal Article PT - Review PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - Overweight MH - Glycated Hemoglobin MH - Glucagon-Like Peptides MH - Incretins/therapeutic use MH - Weight Loss MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Obesity OT - glucagon-like peptide-1 receptor agonist OT - primary care OT - semaglutide EDAT- 2023/01/25 06:00 MHDA- 2023/01/26 06:00 CRDT- 2023/01/24 00:23 PHST- 2023/01/24 00:23 [entrez] PHST- 2023/01/25 06:00 [pubmed] PHST- 2023/01/26 06:00 [medline] AID - 10.1080/00325481.2022.2147326 [doi] PST - ppublish SO - Postgrad Med. 2022 Jan;134(sup1):5-17. doi: 10.1080/00325481.2022.2147326. PMID- 36691308 OWN - NLM STAT- MEDLINE DCOM- 20230130 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 134 IP - sup1 DP - 2022 Jan TI - Cardiometabolic risk factors efficacy of semaglutide in the STEP program. PG - 18-27 LID - 10.1080/00325481.2022.2147325 [doi] AB - People with overweight or obesity often suffer from associated cardiometabolic diseases and comorbidities. Current therapies for obesity include lifestyle intervention, bariatric surgery, and pharmacotherapy. The magnitude of weight loss achieved with these therapies can determine the level of improvement in various comorbidities. Once-weekly subcutaneous semaglutide 2.4 mg is a glucagon-like peptide-1 receptor agonist recently approved by the US Food and Drug Administration for the treatment of obesity. This article reviews data from the global phase 3 Semaglutide Treatment Effect in People with obesity (STEP) program, comparing the efficacy of once-weekly subcutaneous semaglutide 2.4 mg versus placebo for weight loss and improvements in cardiometabolic parameters across the STEP 1 to 5 trials. In STEP 1 to 3 and STEP 5, semaglutide led to greater reductions from baseline versus placebo in body weight, waist circumference, body mass index, systolic blood pressure (SBP), and diastolic blood pressure, as well as positive changes in glycated hemoglobin (HbA(1c)), C-reactive protein, and lipid levels. In STEP 4, all participants had a 20-week run-in period on semaglutide before either continuing on semaglutide or switching to placebo at week 20 in a 2:1 ratio for 48 weeks. At week 68, continued semaglutide led to further reductions from week 20 in HbA(1c), improvements in lipid profile, and stabilization of SBP. Overall, across the STEP trials, treatment with semaglutide 2.4 mg versus placebo improved cardiometabolic risk factors associated with obesity, illustrating an effective treatment option for people with overweight (and associated comorbidities) or obesity. FAU - Amaro, Anastassia AU - Amaro A AUID- ORCID: 0000-0002-3132-5778 AD - Penn Metabolic Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Skolnik, Neil S AU - Skolnik NS AD - Abington Family Medicine, Abington Jefferson Health, Jenkintown, PA, USA. FAU - Sugimoto, Danny AU - Sugimoto D AUID- ORCID: 0000-0002-7801-1231 AD - Cedar Crosse Research Center, Chicago, IL, USA. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Lipids) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Cardiometabolic Risk Factors MH - *Cardiovascular Diseases/drug therapy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Hypoglycemic Agents/therapeutic use MH - Lipids MH - Obesity/drug therapy MH - Overweight MH - Weight Loss MH - Semaglutide OTO - NOTNLM OT - Semaglutide 2.4 mg OT - anti-obesity medication OT - cardiometabolic parameters OT - obesity OT - overweight OT - weight loss EDAT- 2023/01/25 06:00 MHDA- 2023/01/26 06:00 CRDT- 2023/01/24 00:23 PHST- 2023/01/24 00:23 [entrez] PHST- 2023/01/25 06:00 [pubmed] PHST- 2023/01/26 06:00 [medline] AID - 10.1080/00325481.2022.2147325 [doi] PST - ppublish SO - Postgrad Med. 2022 Jan;134(sup1):18-27. doi: 10.1080/00325481.2022.2147325. PMID- 36691307 OWN - NLM STAT- MEDLINE DCOM- 20230125 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 134 IP - sup1 DP - 2022 Jan TI - Exploring the wider benefits of semaglutide treatment in obesity: insight from the STEP program. PG - 28-36 LID - 10.1080/00325481.2022.2150006 [doi] AB - Obesity negatively impacts patients' health-related quality of life (QOL) and is associated with a range of complications such as type 2 diabetes (T2D), cardiovascular disease, and sleep apnea, alongside decreased physical function, mobility, and control of eating. The Semaglutide Treatment Effect in People with obesity (STEP) trials compared once-weekly subcutaneous semaglutide 2.4 mg with placebo in adults with overweight or obesity, with or without T2D. This article reviews the effects of semaglutide 2.4 mg on QOL, control of eating, and body composition. Weight-related QOL was assessed using the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT), and health-related QOL was assessed with the 36-item Short Form Health Survey version 2 (SF-36v2(R)). Control of eating was evaluated using the Control of Eating questionnaire in a subgroup of participants in one trial. Body composition was evaluated via dual-energy x-ray absorptiometry in another trial, in a subgroup of participants with a body mass index of /=50‒300‒<5000 mg/g or eGFR >/=25‒<50 ml/min/1.73 m2 and UACR >100‒<5000 mg/g were randomised 1:1 to OW semaglutide 1.0 mg or matched placebo, with renin-angiotensin-aldosterone system blockade (unless not tolerated/contraindicated). The composite primary endpoint is time to first kidney failure (persistent eGFR <15 ml/min/1.73 m2 or initiation of chronic kidney replacement therapy), persistent >/=50% reduction in eGFR or death from kidney or CV causes. RESULTS: Enrolled participants (N = 3534) had a baseline mean age of 66.6 years [standard deviation (SD) 9.0], haemoglobin A1c of 7.8% (SD 1.3), diabetes duration of 17.4 years (SD 9.3), eGFR of 47.0 ml/min/1.73 m2 (SD 15.2) and median UACR of 568 mg/g (range 2‒11 852). According to Kidney Disease: Improving Global Outcomes guidelines categorisation, 68.2% were at very high risk for CKD progression. CONCLUSION: FLOW will evaluate the effect of semaglutide on kidney outcomes in participants with CKD and T2D, and is expected to be completed in late 2024. CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the ERA. FAU - Rossing, Peter AU - Rossing P AUID- ORCID: 0000-0002-1531-4294 AD - Complication Research, Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Baeres, Florian M M AU - Baeres FMM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bakris, George AU - Bakris G AD - Department of Medicine, AHA Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, IL, USA. FAU - Bosch-Traberg, Heidrun AU - Bosch-Traberg H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Gislum, Mette AU - Gislum M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Gough, Stephen C L AU - Gough SCL AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lawson, Jack AU - Lawson J AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Department of Medicine, Stanford Center for Clinical Research, Stanford School of Medicine, Palo Alto, CA, USA. FAU - Mann, Johannes F E AU - Mann JFE AD - Outpatients Clinic, KfH Kidney Center, Munchen, Germany. FAU - Mersebach, Henriette AU - Mersebach H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Perkovic, Vlado AU - Perkovic V AD - Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. FAU - Tuttle, Katherine AU - Tuttle K AD - Division of Nephrology, University of Washington/Providence Health Care, Spokane, WA, USA. FAU - Pratley, Richard AU - Pratley R AD - Translational Research Institute, AdventHealth, Orlando, FL, USA. LA - eng SI - ClinicalTrials.gov/NCT03819153 PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Nephrol Dial Transplant JT - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JID - 8706402 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Nephrol Dial Transplant. 2024 Mar 27;39(4):724. doi: 10.1093/ndt/gfad252. PMID: 38033315 MH - Humans MH - Aged MH - *Diabetes Mellitus, Type 2/complications/drug therapy/urine MH - Kidney MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - Glucagon-Like Peptides/therapeutic use/pharmacology MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Clinical Trials, Phase III as Topic MH - Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC10469096 OTO - NOTNLM OT - albuminuria OT - cardiovascular disease OT - diabetic kidney disease OT - glomerular filtration rate OT - glucagon-like peptide-1 receptor agonist COIS- P.R. has received grants from Bayer, AstraZeneca and Novo Nordisk; received honoraria to the Steno Diabetes Centre Copenhagen from AstraZeneca, Astellas, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi and Bayer; and consulting fees from AstraZeneca, Astellas, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi and Bayer. M.G., F.M.M.B., H.B.-T., H.M., J.L., S.G. and T.I. are employees of Novo Nordisk A/S. F.M.M.B., H.B.-T., H.M., S.G. and T.I. also hold stock in Novo Nordisk A/S. G.B. reports consulting fees from Bayer, KBP Biosciences, Ionis, Alnylam, AstraZeneca, Quantum Genomics, Novo Nordisk and Dia Medica Therapeutics. K.W.M. has received consulting fees from Amgen, Applied Therapeutics, AstraZeneca, Bayer, CSL Behring, Elsevier Fibrogen, Inova, Johnson & Johnson, Lexicon Myokardia, Novartis, Novo Nordisk, Otsuka Phasebio, Portola Sanofi and Theravance. J.M. reports grants from Novo Nordisk, the European Union and McMaster University Hamilton, Canada; consulting fees from Novo Nordisk, AstraZeneca, Bayer and Boehringer Ingelheim; honoraria from Novo Nordisk, AstraZeneca, Bayer, Fresenius and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi and Boehringer Ingelheim as well as a leadership role in the KDIGO group. V.P. has received honoraria for steering committee, data monitoring committee or advisory board roles or for scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, Dimerix, GlaxoSmithKline, Janssen, Medimmune, Mitsubishi Tanabe, Mundipharma, Novo Nordisk, Novartis, Otsuka, Travere, Tricida and Vifor Pharma; is a Board Director for George Clinical, St. Vincents Health Australia and several independent medical research institutes. K.T. reports grants/contracts from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)/National Institutes of Health (NIH), National Heart, Lung, and Blood Institute/NIH, National Center for Advancing Translational Sciences/NIH, Centers for Disease Control and Travere; consulting fees from Eli Lilly, Boehringer Ingelheim, Gilead, Goldfinch Bio, Bayer, Novo Nordisk and AstraZeneca; honoraria from Eli Lilly, AstraZeneca, Gilead, Goldfinch Bio and Bayer; support for travel and meetings from Eli Lilly and Novo Nordisk; has participated on a data safety monitoring board/advisory board for NIDDK/NIH and George Clinical Institute; was Chair of the Diabetic Kidney Disease Collaborative Task Force, American Society of Nephrology and was on the Board of Directors for Kidney Health Initiative, US Food and Drug Administration and the American Society of Nephrology. EDAT- 2023/01/19 06:00 MHDA- 2023/09/01 06:43 PMCR- 2023/01/18 CRDT- 2023/01/18 09:33 PHST- 2022/09/29 00:00 [received] PHST- 2023/09/01 06:43 [medline] PHST- 2023/01/19 06:00 [pubmed] PHST- 2023/01/18 09:33 [entrez] PHST- 2023/01/18 00:00 [pmc-release] AID - 6991221 [pii] AID - gfad009 [pii] AID - 10.1093/ndt/gfad009 [doi] PST - ppublish SO - Nephrol Dial Transplant. 2023 Aug 31;38(9):2041-2051. doi: 10.1093/ndt/gfad009. PMID- 36639119 OWN - NLM STAT- MEDLINE DCOM- 20230407 LR - 20250103 IS - 2213-3941 (Electronic) IS - 0003-4266 (Linking) VI - 84 IP - 2 DP - 2023 Apr TI - Dual GIP/GLP-1 receptor agonists: New advances for treating type-2 diabetes. PG - 316-321 LID - S0003-4266(23)00004-5 [pii] LID - 10.1016/j.ando.2022.12.423 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists currently occupy a privileged place in the management of type-2 diabetes (T2D). Dual glucose-dependent insulinotropic polypeptides (GIP/GLP-1) have been recently developed. Tirzepatide is the most advanced unimolecular dual GIP/GLP-1 receptor agonist to be used as once weekly subcutaneous injection in T2D and recently received approval by the European Medicines Agency. Because of the complementarity of action of the two incretins, tirzepatide showed better dose-dependent (5, 10 and 15mg) efficacy (greater reduction in HbA1c and body weight) than placebo, basal insulin or two GLP-1 analogues (dulaglutide and semaglutide) in the SURPASS program. Its cardiovascular protective effect is currently being assessed versus dulaglutide in the SURPASS-CVOT study. Finally, studies for the treatment of obesity (SURMOUNT program) and metabolic-associated fatty liver disease (MAFLD) are also ongoing. Gastrointestinal tolerance of tirzepatide appears comparable to that of GLP-1 analogues, except for higher incidence of diarrhea. Other original molecules have been built, including triple GIP/GLP-1/glucagon receptor agonists. The risk/benefit ratio will decide whether dual (or triple) receptor agonists should replace pure GLP-1 receptor agonists for the management of T2D in the near future, with a significant role in the pharmacotherapy of obesity. CI - Copyright (c) 2023 Elsevier Masson SAS. All rights reserved. FAU - Scheen, Andre J AU - Scheen AJ AD - Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU de Liege, Liege, Belgium; Division of Clinical Pharmacology, Centre for Interdisciplinary Research on Medicines (CIRM), University of Liege, Liege, Belgium. Electronic address: andre.scheen@chuliege.be. LA - eng PT - Journal Article PT - Review DEP - 20230110 PL - France TA - Ann Endocrinol (Paris) JT - Annales d'endocrinologie JID - 0116744 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1/agonists MH - Hypoglycemic Agents/therapeutic use MH - Incretins/therapeutic use MH - Obesity MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Dual agonist OT - GIP OT - Glucagon-like peptide-1 OT - Obesity OT - Tirzepatide OT - Type-2 diabetes EDAT- 2023/01/14 06:00 MHDA- 2023/04/04 06:42 CRDT- 2023/01/13 19:28 PHST- 2022/10/06 00:00 [received] PHST- 2022/12/02 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2023/01/14 06:00 [pubmed] PHST- 2023/01/13 19:28 [entrez] AID - S0003-4266(23)00004-5 [pii] AID - 10.1016/j.ando.2022.12.423 [doi] PST - ppublish SO - Ann Endocrinol (Paris). 2023 Apr;84(2):316-321. doi: 10.1016/j.ando.2022.12.423. Epub 2023 Jan 10. PMID- 36634066 OWN - NLM STAT- MEDLINE DCOM- 20230116 LR - 20250103 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 78 IP - 1 DP - 2023 Jan TI - [A new era for glucagon-like peptide-1 receptor agonists]. PG - 40-45 AB - Glucagon-like peptide-1 (GLP-1) receptor agonists have a privileged place in the management of type 2 diabetes (T2D). They not only improve glucose control without inducing hypoglycaemia and trigger weight loss, but also protect against atherosclerotic cardiovascular disease. Increasing the dose of three of them (liraglutide, semaglutide, dulaglutide) allows better glycaemic results and of potential interest a greater weight reduction. Liraglutide at a daily dose of 3.0 mg and semaglutide at a weekly dose of 2.4 mg received the indication for the therapy of obesity. A recent innovation consists in the development of dual unimolecular agonists that target GLP-1 and GIP (<>) receptors (tirzepatide) or GLP-1 and glucagon receptors (cotadutide). Tirzepatide, in the SURPASS programme, showed impressive reductions in glycated haemoglobin level and body weight, greater than those observed with dulaglutide or semaglutide. Tirzepatide received the indication of the treatment of T2D and is currently tested in obesity (SURMOUNT programme). Interestingly, triagonists GIP/GLP-1/glucagon are currently developed for the management of T2D and obesity, with also perspectives for treating metabolic-associated fatty liver disease. FAU - Neuville, M F AU - Neuville MF AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. FAU - Paquot, N AU - Paquot N AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. FAU - Scheen, A J AU - Scheen AJ AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. LA - fre PT - English Abstract PT - Journal Article TT - Une nouvelle ere pour les agonistes des recepteurs du glucagon-like peptide-1. PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Liraglutide/pharmacology/therapeutic use MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - Glucagon-Like Peptide 1/therapeutic use MH - Weight Loss MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP OT - Glucagon OT - Obesity OT - Tirzepatide OT - Type 2 diabetes OT - 1 OT - GIP EDAT- 2023/01/13 06:00 MHDA- 2023/01/17 06:00 CRDT- 2023/01/12 13:34 PHST- 2023/01/12 13:34 [entrez] PHST- 2023/01/13 06:00 [pubmed] PHST- 2023/01/17 06:00 [medline] PST - ppublish SO - Rev Med Liege. 2023 Jan;78(1):40-45. PMID- 36630047 OWN - NLM STAT- MEDLINE DCOM- 20230308 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 40 IP - 3 DP - 2023 Mar TI - Once-Weekly Subcutaneous Semaglutide 2.4 mg Injection is Cost-Effective for Weight Management in the United Kingdom. PG - 1282-1291 LID - 10.1007/s12325-022-02423-8 [doi] AB - OBJECTIVES: The objective of the current preliminary study was to present the cost-effectiveness analyses submitted to the National Institute for Health and Care Excellence (NICE) (TA10765) that deemed semaglutide 2.4 mg subcutaneous (s.c.) injection a cost-effective option for weight management in the United Kingdom (UK) alongside diet and exercise (D&E). METHODS: The study was conducted from the National Health Service (NHS) and Personal Social Services perspective and based on the NICE reference case. The clinical safety and efficacy of semaglutide 2.4 mg s.c. injection were obtained from the Semaglutide Treatment Effect in People with Obesity (STEP) 1 trial. The previously published and validated Core Obesity Model was used to project lifetime occurrence of obesity complications, their costs and quality of life consequences over 40 years. The base case cohort had a mean starting age of 48 years and BMI of 38.7 kg/m(2). The confidential NHS price for semaglutide 2.4 mg s.c. injection was provided by Novo Nordisk. The incremental cost-effectiveness ratios (ICERs) were expressed as cost/quality-adjusted life-year (QALY). Uncertainty was assessed through sensitivity analyses, including a scenario analysis using clinical data from the STEP 2 trial and a previously published and validated Core Diabetes Model to investigate a cohort with type 2 diabetes at baseline. RESULTS: Semaglutide 2.4 mg s.c. injection showed higher total costs and health benefits compared with D&E, with an ICER of pound14,827/QALY gained. The probabilistic sensitivity analysis showed that semaglutide 2.4 mg s.c. injection was cost-effective in 90% of cases at a willingness-to-pay threshold of pound20,000/QALY. The ICER from the scenario analysis for the diabetic population was pound16,613/QALY gained, using the Core Diabetes Model. CONCLUSION: Semaglutide 2.4 mg s.c. injection is a cost-effective therapy compared to D&E alone for patients with obesity and weight-related comorbidities in the UK. Sensitivity and scenario analyses confirm the robustness of the analyses. CI - (c) 2023. The Author(s). FAU - Sandhu, Hera AU - Sandhu H AD - IQVIA, London, UK. FAU - Xu, Weiwei AU - Xu W AD - IQVIA, Amsterdam, The Netherlands. FAU - Olivieri, Anamaria-Vera AU - Olivieri AV AD - IQVIA, Basel, Switzerland. FAU - Lubker, Christopher AU - Lubker C AUID- ORCID: 0000-0003-3220-801X AD - Novo Nordisk A/S, Soborg, Denmark. CJLU@novonordisk.com. FAU - Smith, Inger AU - Smith I AD - White Box Health Economics Ltd, Worthing, UK. FAU - Antavalis, Vasileios AU - Antavalis V AD - Novo Nordisk, Gatwick, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230111 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 53AXN4NNHX (Semaglutide) MH - Humans MH - Middle Aged MH - *Diabetes Mellitus, Type 2/epidemiology MH - Cost-Benefit Analysis MH - Quality of Life MH - State Medicine MH - United Kingdom MH - Quality-Adjusted Life Years MH - Obesity/complications/drug therapy MH - Semaglutide PMC - PMC9988790 OTO - NOTNLM OT - Core obesity model OT - Cost-effectiveness analysis OT - Obesity OT - Semaglutide 2.4 mg OT - United Kingdom EDAT- 2023/01/12 06:00 MHDA- 2023/03/09 06:00 PMCR- 2023/01/11 CRDT- 2023/01/11 11:20 PHST- 2022/11/18 00:00 [received] PHST- 2022/12/22 00:00 [accepted] PHST- 2023/01/12 06:00 [pubmed] PHST- 2023/03/09 06:00 [medline] PHST- 2023/01/11 11:20 [entrez] PHST- 2023/01/11 00:00 [pmc-release] AID - 10.1007/s12325-022-02423-8 [pii] AID - 2423 [pii] AID - 10.1007/s12325-022-02423-8 [doi] PST - ppublish SO - Adv Ther. 2023 Mar;40(3):1282-1291. doi: 10.1007/s12325-022-02423-8. Epub 2023 Jan 11. PMID- 36608818 OWN - NLM STAT- MEDLINE DCOM- 20230214 LR - 20250103 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 161 DP - 2023 Mar TI - An update on peptide-based therapies for type 2 diabetes and obesity. PG - 170939 LID - S0196-9781(23)00001-3 [pii] LID - 10.1016/j.peptides.2023.170939 [doi] AB - Long-acting analogues of the naturally occurring incretin, glucagon-like peptide-1 (GLP-1) and those modified to interact also with receptors for glucose-dependent insulinotropic polypeptide (GIP) have shown high glucose-lowering and weight-lowering efficacy when administered by once-weekly subcutaneous injection. These analogues herald an exciting new era in peptide-based therapy for type 2 diabetes (T2D) and obesity. Of note is the GLP-1R agonist semaglutide, available in oral and injectable formulations and in clinical trials combined with the long-acting amylin analogue, cagrilintide. Particularly high efficacy in both glucose- and weight lowering capacities has also been observed with the GLP-1R/GIP-R unimolecular dual agonist, tirzepatide. In addition, a number of long-acting unimolecular GLP-1R/GCGR dual agonist peptides and GLP-1R/GCGR/GIPR triagonist peptides have entered clinical trials. Other pharmacological approaches to chronic weight management include the human monoclonal antibody, bimagrumab which blocks activin type II receptors and is associated with growth of skeletal muscle, an antibody blocking activation of GIPR to which are conjugated GLP-1R peptide agonists (AMG-133), and the melanocortin-4 receptor agonist, setmelanotide for use in certain inherited obesity conditions. The high global demand for the GLP-1R agonists liraglutide and semaglutide as anti-obesity agents has led to shortage so that their use in T2D therapy is currently being prioritized. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Bailey, Clifford J AU - Bailey CJ AD - Life and Health Sciences, Aston University, Birmingham B4 7ET, UK. FAU - Flatt, Peter R AU - Flatt PR AD - Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, UK. FAU - Conlon, J Michael AU - Conlon JM AD - Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, UK. Electronic address: jmconlon1@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20230103 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Incretins) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/complications MH - Obesity/drug therapy/complications MH - Glucagon-Like Peptide 1/therapeutic use MH - Incretins/therapeutic use MH - Gastric Inhibitory Polypeptide/pharmacology MH - Glucose MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cagrilintide OT - GIP OT - GLP-1 OT - Glucagon OT - Obesity OT - Semaglutide OT - Tirzepatide OT - Type 2 diabetes COIS- Declaration of competing interest CJB has served on steering committees for clinical trials and advisory boards for several pharmaceutical companies. PRF and JMC are named on patents held by Ulster University for peptide therapeutics and have served as advisor to several pharmaceutical companies. EDAT- 2023/01/08 06:00 MHDA- 2023/02/15 06:00 CRDT- 2023/01/07 16:04 PHST- 2022/12/02 00:00 [received] PHST- 2023/01/01 00:00 [revised] PHST- 2023/01/02 00:00 [accepted] PHST- 2023/01/08 06:00 [pubmed] PHST- 2023/02/15 06:00 [medline] PHST- 2023/01/07 16:04 [entrez] AID - S0196-9781(23)00001-3 [pii] AID - 10.1016/j.peptides.2023.170939 [doi] PST - ppublish SO - Peptides. 2023 Mar;161:170939. doi: 10.1016/j.peptides.2023.170939. Epub 2023 Jan 3. PMID- 36601368 OWN - NLM STAT- MEDLINE DCOM- 20230106 LR - 20260127 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 16 DP - 2022 TI - Clinical Insight on Semaglutide for Chronic Weight Management in Adults: Patient Selection and Special Considerations. PG - 4449-4461 LID - 10.2147/DDDT.S365416 [doi] AB - Losses of 5-10% or more of initial body weight are associated with improvements in obesity-related comorbidities. However, attaining and sustaining this level of weight loss is challenging. The novel anti-obesity medication semaglutide 2.4 mg injected subcutaneously once weekly as an adjunct to a reduced-calorie diet and physical activity helps patients achieve average losses of 9.6-17.4% of initial body weight at week 68, as well as improvements in cardiometabolic and psychosocial indices. Despite these average benefits, prescribers should carefully assess the suitability of patients for this medication. In this paper, we discuss considerations for the selection of individuals who are candidates for semaglutide and special considerations related to the use of this medication. These include its efficacy and safety, as well as its contraindications, potential adverse effects, management of comorbidities and drug interactions, insurance coverage and cost, and patient preferences. CI - (c) 2022 Chao et al. FAU - Chao, Ariana M AU - Chao AM AD - Department of Biobehavioral Health Sciences, University of Pennsylvania School of Nursing, Philadelphia, PA, USA. AD - Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. FAU - Tronieri, Jena Shaw AU - Tronieri JS AD - Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. FAU - Amaro, Anastassia AU - Amaro A AD - Division of Endocrinology, Diabetes and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. FAU - Wadden, Thomas A AU - Wadden TA AD - Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. LA - eng GR - K23 DK116935/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Review DEP - 20221229 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Adult MH - *Hypoglycemic Agents/adverse effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - Patient Selection MH - Body Weight MH - Semaglutide PMC - PMC9807016 OTO - NOTNLM OT - GLP-1 OT - obesity OT - pharmacotherapy OT - semaglutide OT - weight loss COIS- Dr. Chao reports grants from WW International Co and Eli Lilly and Co, outside the submitted work. Dr. Tronieri reports a grant from Novo Nordisk, outside the submitted work. Dr. Wadden reports serving on advisory boards for Novo Nordisk and WW International Co and receiving grants from Epitomee Medical and Novo Nordisk. Dr. Amaro reports receiving grants from Fractyl Laboratories and Altimmune and serving on advisory boards for Novo Nordisk and Fractyl Laboratories. The authors report no other conflicts of interest in this work. No funding was received to assist with the preparation of this manuscript. EDAT- 2023/01/06 06:00 MHDA- 2023/01/07 06:00 PMCR- 2022/12/29 CRDT- 2023/01/05 02:30 PHST- 2022/10/17 00:00 [received] PHST- 2022/12/15 00:00 [accepted] PHST- 2023/01/05 02:30 [entrez] PHST- 2023/01/06 06:00 [pubmed] PHST- 2023/01/07 06:00 [medline] PHST- 2022/12/29 00:00 [pmc-release] AID - 365416 [pii] AID - 10.2147/DDDT.S365416 [doi] PST - epublish SO - Drug Des Devel Ther. 2022 Dec 29;16:4449-4461. doi: 10.2147/DDDT.S365416. eCollection 2022. PMID- 36599459 OWN - NLM STAT- MEDLINE DCOM- 20230417 LR - 20260127 IS - 1439-3646 (Electronic) IS - 0947-7349 (Print) IS - 0947-7349 (Linking) VI - 131 IP - 4 DP - 2023 Apr TI - Real-World Use of Once-Weekly Semaglutide in Type 2 Diabetes: Results from SemaglUtide Real-world Evidence (SURE) Germany. PG - 205-215 LID - 10.1055/a-2007-2061 [doi] AB - CONTEXT: Efficacy and safety of once-weekly semaglutide in type 2 diabetes were established in the phase 3 SUSTAIN trials, which included patients across the continuum of type 2 diabetes care. It is useful to complement these findings with real-world evidence. OBJECTIVE: SURE Germany evaluated once-weekly semaglutide in a real-world type 2 diabetes patient population. DESIGN/SETTING: The prospective observational study was conducted at 93 clinical practices in adults with+>/= 1 documented glycated haemoglobin value 1 year (rr = 1.559,1.068,2.276, p = 0.022) and with decreases in A1c > 1.0% (rr = 1.59; 1.092,2.316, p = 0.016). For the class of GLP1-RA, the rate difference (rd) for worsening retinopathy was = 0.001 (and number needed to harm [NNH] = 1000) compared with rd for MACE = -0.013 (number needed to treat [NNT] = 77). The computation for semaglutide was NNH = 77 and NNT = 43. CONCLUSIONS: This meta-analysis may assist in decisions balancing the relative risk (of existing retinopathy) versus benefits (to existing CVD). There should be close collaboration with ophthalmology to grade the baseline degree of retinopathy when initiating and following patients. CI - Copyright (c) 2023 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved. FAU - Albert, Stewart G AU - Albert SG AD - Department of Internal Medicine, Division of Endocrinology Saint Louis University School of Medicine, USA. Electronic address: stewart.albert@health.slu.edu. FAU - Wood, Emily M AU - Wood EM AD - Department of Internal Medicine, Division of Endocrinology Saint Louis University School of Medicine, USA. FAU - Ahir, Vaishaliben AU - Ahir V AD - Department of Internal Medicine, Division of Endocrinology Saint Louis University School of Medicine, USA. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20221228 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (GLP1R protein, human) SB - IM MH - Humans MH - *Cardiovascular Diseases/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Diabetic Retinopathy MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptide-1 Receptor MH - Glycated Hemoglobin MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - Diabetic retinopathy OT - GLP1-RA OT - Glucagon like peptide1-receptor agonists OT - Meta-analysis OT - Meta-regression EDAT- 2023/01/04 06:00 MHDA- 2023/03/03 06:00 CRDT- 2023/01/03 17:59 PHST- 2022/09/08 00:00 [received] PHST- 2022/11/17 00:00 [revised] PHST- 2022/12/16 00:00 [accepted] PHST- 2023/01/04 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/01/03 17:59 [entrez] AID - S1871-4021(22)00313-7 [pii] AID - 10.1016/j.dsx.2022.102696 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2023 Jan;17(1):102696. doi: 10.1016/j.dsx.2022.102696. Epub 2022 Dec 28. PMID- 36579723 OWN - NLM STAT- MEDLINE DCOM- 20230208 LR - 20250418 IS - 1467-789X (Electronic) IS - 1467-7881 (Linking) VI - 24 IP - 3 DP - 2023 Mar TI - Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials. PG - e13543 LID - 10.1111/obr.13543 [doi] AB - Tirzepatide is a new glucagon-like peptide-1 receptor agonist (GLP-1RA) that has shown promising results for weight loss. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of GLP-1RAs for obesity management. Embase and MEDLINE were searched looking for randomized clinical trials (RCTs) that evaluated the efficacy of GLP-1RAs for weight loss in patients without diabetes. The main efficacy outcomes evaluated were the mean change in actual and percentage weight loss and the proportion of patients with weight loss of >/=5%-20%. Main safety outcomes evaluated include nausea, vomiting, diarrhea, constipation, loss of appetite, pancreatitis, gallbladder-related disorders, and withdrawal due to adverse events. Seven RCTs with more than 12,300 patients were analyzed, including patients with body mass index (BMI) >/= 30 kg/m(2) , or BMI >/= 27 kg/m(2) with comorbidities. Weekly tirzepatide 10 and 15 mg resulted in more weight loss than weekly semaglutide 2.4 mg, daily semaglutide 0.4 mg, or liraglutide 3 mg. Tirzepatide and weekly semaglutide demonstrated comparable results but with significantly higher odds of achieving >/=5%-20% weight loss compared with liraglutide. GLP-1RAs triggered more gastrointestinal adverse events than placebo, with no in-between difference. Although all GLP-1RAs lead to significant weight reduction, tirzepatide was associated with better efficacy outcomes while having a comparable safety profile. CI - (c) 2022 World Obesity Federation. FAU - Alkhezi, Omar S AU - Alkhezi OS AUID- ORCID: 0000-0001-7714-2945 AD - Department of Pharmacy Services, Brigham and Women's Hospital, Boston, Massachusetts, USA. AD - Department of Pharmacy Practice, Unaizah College of Pharmacy, Qassim University, Qassim, Saudi Arabia. FAU - Alahmed, Abdullah A AU - Alahmed AA AUID- ORCID: 0000-0002-4739-5535 AD - Department of Pharmacy Services, Brigham and Women's Hospital, Boston, Massachusetts, USA. AD - Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia. FAU - Alfayez, Osamah M AU - Alfayez OM AUID- ORCID: 0000-0003-4362-6508 AD - Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia. FAU - Alzuman, Osama A AU - Alzuman OA AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. FAU - Almutairi, Abdulaali R AU - Almutairi AR AUID- ORCID: 0000-0002-3141-0606 AD - Drug Sector, Saudi Food and Drug Authority, Riyadh, Saudi Arabia. FAU - Almohammed, Omar A AU - Almohammed OA AUID- ORCID: 0000-0002-3792-4106 AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. AD - Pharmacoeconomics Research Unit, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20221229 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Humans MH - *Liraglutide/therapeutic use MH - Hypoglycemic Agents/therapeutic use/adverse effects MH - Randomized Controlled Trials as Topic MH - Obesity/complications/drug therapy/chemically induced MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonist OT - liraglutide OT - meta-analysis OT - obesity OT - semaglutide OT - tirzepatide OT - weight loss EDAT- 2022/12/30 06:00 MHDA- 2023/02/09 06:00 CRDT- 2022/12/29 06:22 PHST- 2022/10/09 00:00 [revised] PHST- 2022/07/11 00:00 [received] PHST- 2022/12/06 00:00 [accepted] PHST- 2022/12/30 06:00 [pubmed] PHST- 2023/02/09 06:00 [medline] PHST- 2022/12/29 06:22 [entrez] AID - 10.1111/obr.13543 [doi] PST - ppublish SO - Obes Rev. 2023 Mar;24(3):e13543. doi: 10.1111/obr.13543. Epub 2022 Dec 29. PMID- 36578889 OWN - NLM STAT- MEDLINE DCOM- 20221230 LR - 20260127 IS - 2308-118X (Electronic) IS - 0857-1074 (Print) IS - 0857-1074 (Linking) VI - 37 IP - 2 DP - 2022 TI - Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis. PG - 65-72 LID - 10.15605/jafes.037.02.14 [doi] AB - BACKGROUND: The weight loss benefit of semaglutide in patients with diabetes is well-documented, but its clinical utility in treating obesity among patients without diabetes is less described. We therefore assessed the efficacy and safety of subcutaneous semaglutide as treatment for obesity in patients without diabetes. METHODOLOGY: A comprehensive search of PubMed/MEDLINE, Cochrane and Google scholar was performed to identify trials on the efficacy and safety of subcutaneous semaglutide on patients with obesity without diabetes. Primary outcome was expressed as percent mean weight difference. Secondary outcomes including risk for gastrointestinal adverse events, discontinuation of treatment and serious adverse events were expressed as risk ratios. These were calculated using the random effects model. RESULTS: The study included 4 randomized controlled trials having a total of 3,613 individuals with obesity without diabetes. The mean difference for weight reduction was -11.85%, favoring semaglutide [95% confidence interval (CI) (-12.81,-10.90), p<0.00001]. Secondary outcomes showed that the risk of developing gastrointestinal adverse events was 1.59 times more likely with semaglutide (RR 1.59, 95%CI [1.34, 1.88], p<0.00001). Risk for discontinuation due to adverse events was twice as likely in the semaglutide group (RR 2.19, 95%CI [1.36,3.55], p=0.001) and the risk for serious adverse events was 1.6 times more likely for semaglutide (RR1.60, 95%CI [1.24, 2.07], p=0.0003). Serious events were mostly of gastrointestinal and hepatobiliary disorders such as acute pancreatitis and cholelithiasis. CONCLUSION: Among individuals with obesity without type 2 diabetes, subcutaneous semaglutide is effective for weight loss with an 11.85% reduction from baseline compared to placebo. This supports the use of semaglutide for weight management in obesity. However, risk of gastrointestinal adverse events, discontinuation of treatment and serious adverse events were higher in the semaglutide group versus placebo. CI - (c) 2022 Journal of the ASEAN Federation of Endocrine Societies. FAU - Tan, Hanna Clementine AU - Tan HC AD - Department of Medicine, St. Luke's Medical Center, Quezon City, Philippines. FAU - Dampil, Oliver Allan AU - Dampil OA AD - Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, St. Luke's Medical Center, Quezon City, Philippines. FAU - Marquez, Maricar Mae AU - Marquez MM AD - Department of Medicine, St. Luke's Medical Center, Quezon City, Philippines. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20220823 PL - Philippines TA - J ASEAN Fed Endocr Soc JT - Journal of the ASEAN Federation of Endocrine Societies JID - 8608483 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications MH - Hypoglycemic Agents MH - Acute Disease MH - Treatment Outcome MH - Double-Blind Method MH - *Pancreatitis/chemically induced MH - Weight Loss MH - Obesity/complications MH - Randomized Controlled Trials as Topic MH - Semaglutide PMC - PMC9758543 OTO - NOTNLM OT - Glucagon-like Peptide -1 OT - obesity OT - semaglutide OT - weight loss COIS- OAD reports receiving consulting fees from Eli Lilly and Novo Nordisk for service outside the submitted work, as well as honoraria for speaking engagements from Astra Zeneca, Novo Nordisk, and Eli Lilly outside the submitted work. HCT and MMM declare no conflict of interest in association with this study. EDAT- 2022/12/30 06:00 MHDA- 2022/12/31 06:00 PMCR- 2022/01/01 CRDT- 2022/12/29 02:38 PHST- 2022/03/02 00:00 [received] PHST- 2022/06/02 00:00 [accepted] PHST- 2022/12/29 02:38 [entrez] PHST- 2022/12/30 06:00 [pubmed] PHST- 2022/12/31 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - JAFES-37-2-65 [pii] AID - 10.15605/jafes.037.02.14 [doi] PST - ppublish SO - J ASEAN Fed Endocr Soc. 2022;37(2):65-72. doi: 10.15605/jafes.037.02.14. Epub 2022 Aug 23. PMID- 36568085 OWN - NLM STAT- MEDLINE DCOM- 20230110 LR - 20250103 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 13 DP - 2022 TI - Association between different GLP-1 receptor agonists and gastrointestinal adverse reactions: A real-world disproportionality study based on FDA adverse event reporting system database. PG - 1043789 LID - 10.3389/fendo.2022.1043789 [doi] LID - 1043789 AB - OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have significantly improved clinical effects on glycemic control. However, real-world data concerning the difference in gastrointestinal adverse events (AEs) among different GLP-1 RAs are still lacking. Our study aimed to characterize and compare gastrointestinal AEs among different marketed GLP-1 RAs (exenatide, liraglutide, dulaglutide, lixisenatide, and semaglutide) based on real-world data. METHODS: Disproportionality analysis was used to evaluate the association between GLP-1 RAs and gastrointestinal adverse events. Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database between January 2018 and September 2022. Clinical characteristics, the time-to-onset, and the severe proportion of GLP-1 RAs-associated gastrointestinal AEs were further analyzed. RESULTS: A total of 21,281 reports of gastrointestinal toxicity were analyzed out of 81,752 adverse event reports, and the median age of the included patients was 62 (interquartile range [IQR] 54-70) years old. Overall GLP-1 RAs were associated with increased risk of gastrointestinal system disorders (ROR, 1.46; 95% CI, 1.44-1.49), which were further attributed to liraglutide (ROR, 2.39; 95% CI, 2.28-2.51), dulaglutide (ROR, 1.39; 95% CI, 1.36-1.42), and semaglutide (ROR, 3.00; 95% CI, 2.89-3.11). Adverse events uncovered in the labels included gastroesophageal reflux disease, gastritis, bezoar, breath odor, intra-abdominal hematoma, etc. Furthermore, it was observed that semaglutide had the greatest risk of nausea (ROR, 7.41; 95% CI, 7.10-7.74), diarrhea (ROR, 3.55; 95% CI, 3.35-3.77), vomiting (ROR, 6.67; 95% CI, 6.32-7.05), and constipation (ROR, 6.17; 95% CI, 5.72-6.66); liraglutide had the greatest risk of abdominal pain upper (ROR, 4.63; 95% CI, 4.12-5.21) and pancreatitis (ROR, 32.67; 95% CI, 29.44-36.25). Most gastrointestinal AEs tended to occur within one month. Liraglutide had the highest severe rate of gastrointestinal AEs (23.31%), while dulaglutide had the lowest, with a severe rate of 12.29%. CONCLUSION: GLP-1 RA were significantly associated with gastrointestinal AEs, and the association was further attributed to liraglutide, dulaglutide, and semaglutide. In addition, semaglutide had the greatest risk of nausea, diarrhea, vomiting, constipation, and pancreatitis, while liraglutide had the greatest risk of upper abdominal pain. Our study provided valuable evidence for selecting appropriate GLP-1 RAs to avoid the occurrence of GLP-1 RA-induced gastrointestinal AEs. CI - Copyright (c) 2022 Liu, Chen, Wang, Chen and Chen. FAU - Liu, Lulu AU - Liu L AD - Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China. AD - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China. FAU - Chen, Jia AU - Chen J AD - Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China. AD - Department of Pharmacy, Sichuan Provincial People's Hospital Jinniu Hospital, Chengdu, China. FAU - Wang, Lei AU - Wang L AD - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China. FAU - Chen, Chen AU - Chen C AD - West China School of Pharmacy, Sichuan University, Chengdu, China. FAU - Chen, Li AU - Chen L AD - Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China. AD - Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221207 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - Humans MH - Middle Aged MH - Abdominal Pain MH - Constipation/chemically induced MH - *Diabetes Mellitus, Type 2/chemically induced MH - Diarrhea/chemically induced MH - *Gastrointestinal Diseases/chemically induced/epidemiology MH - Glucagon-Like Peptide 1 MH - *Hypoglycemic Agents/adverse effects MH - Liraglutide/adverse effects MH - Nausea/chemically induced MH - Pancreatitis/chemically induced MH - Vomiting/chemically induced MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - United States/epidemiology MH - United States Food and Drug Administration/statistics & numerical data MH - Databases, Factual/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC9770009 OTO - NOTNLM OT - GLP-1 receptor agonists OT - adverse drug reactions OT - data mining OT - gastrointestinal toxicities OT - pharmacovigilance COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/12/27 06:00 MHDA- 2022/12/28 06:00 PMCR- 2022/01/01 CRDT- 2022/12/26 03:44 PHST- 2022/09/14 00:00 [received] PHST- 2022/11/21 00:00 [accepted] PHST- 2022/12/26 03:44 [entrez] PHST- 2022/12/27 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2022.1043789 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2022 Dec 7;13:1043789. doi: 10.3389/fendo.2022.1043789. eCollection 2022. PMID- 36567502 OWN - NLM STAT- MEDLINE DCOM- 20230511 LR - 20250512 IS - 2047-4881 (Electronic) IS - 2047-4873 (Linking) VI - 30 IP - 7 DP - 2023 May 9 TI - Nationwide cardiovascular risk categorization: applying the European Society of Cardiology guidelines to the Swedish National Diabetes Register. PG - 546-551 LID - 10.1093/eurjpc/zwac308 [doi] AB - AIMS: The 2021 European Society of Cardiology (ESC) guidelines recommend that patients with type 2 diabetes (T2D) with a very high cardiovascular disease (CVD) risk receive cardiovascular (CV)-protective glucose-lowering medication (glucagon-like peptide-1 receptor agonists or sodium-glucose co-transporter-2 inhibitors). This analysis compared previous prescribing practices with the ESC recommendations. METHODS AND RESULTS: Patients in the Swedish National Diabetes Register (NDR) with T2D, aged 18-90 years, not receiving CV-protective glucose-lowering medication in 2017 were identified, and the ESC criteria for very high CVD risk were applied. The composite outcome of major adverse CV events (MACEs; defined as CV death, non-fatal stroke or non-fatal myocardial infarction) during 2017 was calculated, and the number of MACE avoided with semaglutide, an example of a CV-protective glucose-lowering medication, was estimated for patients with a certain CV risk score. Of the 320 028 patients in the NDR with T2D who were not receiving CV-protective glucose-lowering medication, 129 512 patients had a very high CVD risk. Patients with a very high CVD risk had a high incidence of MACE (75.4 events/1000 person-years), which was higher in those with atherosclerotic CVD (ASCVD) with and without elevated glycated haemoglobin (>9%; 136.5 and 90.8 events/1000 person-years, respectively). If patients with a very high CVD risk, according to the ESC, and ASCVD received semaglutide, 803 MACE may have been avoided in 2017. CONCLUSIONS: This analysis highlights differences between previous prescribing practices in Sweden and the 2021 ESC guidelines and offers strategies to prioritize CV-protective glucose-lowering medication for patients who would benefit most. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Eliasson, Bjorn AU - Eliasson B AUID- ORCID: 0000-0003-2569-4160 AD - Department of Medicine, Sahlgrenska University Hospital, Bla Straket 5, 413 45 Gothenburg, Sweden. FAU - Ekelund, Jan AU - Ekelund J AD - National Diabetes Register, Centre of Registers, Gothenburg, Sweden. FAU - Holmberg, Cecilia Nagorny AU - Holmberg CN AD - Novo Nordisk Scandinavia AB, Malmo, Sweden. FAU - Wolden, Michael Lyng AU - Wolden ML AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Matthiessen, Kasper Sommer AU - Matthiessen KS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - James, Stefan AU - James S AD - Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Prev Cardiol JT - European journal of preventive cardiology JID - 101564430 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/diagnosis/drug therapy MH - *Cardiovascular Diseases/diagnosis/epidemiology/prevention & control MH - Sweden/epidemiology MH - Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - *Cardiology MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Heart Disease Risk Factors MH - Glucose/therapeutic use OAB - Type 2 diabetes, or T2D, causes blood sugar levels to get too high. Nearly one-third of people with T2D also have diseases of the heart and blood vessels, such as heart attacks and strokes. These are known as cardiovascular diseases or events. Some T2D medications can also lower the risk of cardiovascular disease. Using data from national healthcare registries, we looked at how many people with T2D in Sweden had a very high cardiovascular disease risk. Healthcare systems often have limited budgets and may not treat all people with a very high cardiovascular disease risk. So, we looked at ways to identify which patients with T2D would benefit most from treatment. We also estimated how many cardiovascular events may be prevented by giving these patients cardiovascular risk-lowering T2D medication, using a medication called semaglutide as an example.The registry included 348 857 people with T2D, and 91.7% (320 028) were not given cardiovascular risk-lowering T2D medications. Of the people not given medications, 40.5% (129 512) had a very high cardiovascular disease risk. On average, we found that people with a very high cardiovascular disease risk and previous cardiovascular events ended up having more cardiovascular events than those without previous events. People who also regularly had high average blood sugar levels, measured using a marker in the blood called glycated haemoglobin, or HbA1c, had even more cardiovascular events.Giving semaglutide to people with a very high cardiovascular disease risk who have already had a cardiovascular event may prevent around 803 cardiovascular events each year. OABL- eng OTO - NOTNLM OT - Cardiovascular disease OT - Cardiovascular disease risk OT - Epidemiology OT - European Society of Cardiology guidelines OT - Type 2 diabetes COIS- Conflict of interest: B.E. has received personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Mundipharma, Navamedic, Novo Nordisk, and RLS Global, and grants and personal fees from Sanofi. C.N.H. is an employee of Novo Nordisk Scandinavia AB. M.L.W. and K.S.M. are employees of Novo Nordisk A/S. S.J. reports no personal conflicts of interest. Their institution has received research from Amgen, AstraZeneca, Bayer, Janssen, Novartis, and Novo Nordisk. EDAT- 2022/12/27 06:00 MHDA- 2023/05/11 06:42 CRDT- 2022/12/26 01:02 PHST- 2022/09/27 00:00 [received] PHST- 2022/12/15 00:00 [revised] PHST- 2022/12/19 00:00 [accepted] PHST- 2023/05/11 06:42 [medline] PHST- 2022/12/27 06:00 [pubmed] PHST- 2022/12/26 01:02 [entrez] AID - 6960735 [pii] AID - 10.1093/eurjpc/zwac308 [doi] PST - ppublish SO - Eur J Prev Cardiol. 2023 May 9;30(7):546-551. doi: 10.1093/eurjpc/zwac308. PMID- 36562481 OWN - NLM STAT- MEDLINE DCOM- 20230307 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 4 DP - 2023 Apr TI - Body weight loss with oral semaglutide is mediated predominantly by effects other than gastrointestinal adverse events in patients with type 2 diabetes: A post hoc analysis. PG - 1130-1135 LID - 10.1111/dom.14957 [doi] FAU - Meier, Juris J AU - Meier JJ AUID- ORCID: 0000-0002-5835-8019 AD - Department of Internal Medicine, Gastroenterology and Diabetology, Augusta Clinic, Bochum, Germany. FAU - Bardtrum, Lars AU - Bardtrum L AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Cheng, Alice Y Y AU - Cheng AYY AD - Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada. FAU - Malling, Brian AU - Malling B AUID- ORCID: 0000-0002-8570-4327 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Montanya, Eduard AU - Montanya E AUID- ORCID: 0000-0003-2518-9076 AD - Hospital Universitari Bellvitge-IDIBELL CIBERDEM, and University of Barcelona, Barcelona, Spain. FAU - Wagner, Lily AU - Wagner L AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230117 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/chemically induced MH - Glucagon-Like Peptides/adverse effects MH - Hypoglycemic Agents/adverse effects MH - Weight Loss MH - Body Weight MH - Semaglutide OTO - NOTNLM OT - GLP-1 analogue OT - incretin therapy OT - phase 3 study OT - type 2 diabetes EDAT- 2022/12/24 06:00 MHDA- 2023/03/08 06:00 CRDT- 2022/12/23 07:02 PHST- 2022/12/12 00:00 [revised] PHST- 2022/09/14 00:00 [received] PHST- 2022/12/19 00:00 [accepted] PHST- 2022/12/24 06:00 [pubmed] PHST- 2023/03/08 06:00 [medline] PHST- 2022/12/23 07:02 [entrez] AID - 10.1111/dom.14957 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Apr;25(4):1130-1135. doi: 10.1111/dom.14957. Epub 2023 Jan 17. PMID- 36549643 OWN - NLM STAT- MEDLINE DCOM- 20230307 LR - 20260127 IS - 2254-8874 (Electronic) IS - 2254-8874 (Linking) VI - 223 IP - 3 DP - 2023 Mar TI - Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity. PG - 134-143 LID - S2254-8874(22)00104-7 [pii] LID - 10.1016/j.rceng.2022.12.001 [doi] AB - AIM: This work aims to assess the effect of weekly subcutaneous semaglutide on biomarkers of metabolic-associated fatty liver disease (MAFLD), namely the hepatic steatosis index (HSI) and the fibrosis-4 (FIB-4) index, at 24 weeks in outpatients attended to in internal medicine departments. METHODS: This study analyzed patients in an ongoing, multicenter, prospective, pre-post, uncontrolled cohort registry that enrolls unique, consecutive patients with type 2 diabetes treated with weekly subcutaneous semaglutide. Steatosis/fibrosis were determined by HSI (<30 ruled out, >36 steatosis) and FIB-4 (<1.3 ruled out, >2.67 fibrosis), respectively. RESULTS: The sample included 213 patients (46.9% women) with a median age of 64 (19) years. The median baseline body mass index and weight were 36.1 (8.4) kg/m(2) and 98 (26.9) kg, respectively. A total of 99.9% had HSI values indicating steatosis, with a mean HSI of 47.9 (8.2). Additionally, 10.8% had fibrosis (FIB-4 > 2.67) and 42.72% had values in intermediate ranges (FIB-4 1.3-2.67). At 24 weeks, there was a significant reduction in HSI (-2.36 (95%CI 1.83-2.9) p < 0.00001) and FIB-4 (-0.075 (95%CI 0.015-0.14) p < 0.016), mainly related to declines in body weight, triglyceride levels, insulin resistance (estimated by the triglyceride-glucose index), and liver enzymes. CONCLUSION: These results show that weekly subcutaneous semaglutide had a beneficial effect on liver steatosis that went beyond glucose control. Its effects were mainly related to weight loss, a decline in biomarkers, and improvements in insulin sensitivity. For many patients, early detection is essential for improving MAFLD outcomes and may allow for selecting the most efficient treatment options. CI - Copyright (c) 2022. Published by Elsevier Espana, S.L.U. FAU - Carretero-Gomez, Juana AU - Carretero-Gomez J AD - Servicio de Medicina Interna, Hospital Universitario de Badajoz, Badajoz, Spain. Electronic address: juanicarretero@gmail.com. FAU - Carrasco-Sanchez, Francisco Javier AU - Carrasco-Sanchez FJ AD - Servicio de Medicina Interna, Hospital Universitario Juan Ramon Jimenez, Huelva, Spain. FAU - Fernandez-Rodriguez, Jose Maria AU - Fernandez-Rodriguez JM AD - Servicio de Medicina Interna, Hospital Universitario Ramon y Cajal, Madrid, Spain. FAU - Casado-Escribano, Pedro AU - Casado-Escribano P AD - Servicio de Medicina Interna, Hospital Universitario La Princesa, Madrid, Spain. FAU - Miramontes-Gonzalez, Jose Pablo AU - Miramontes-Gonzalez JP AD - Servicio de Medicina Interna, Hospital Universitario Rio Hortega, Valladolid, IBSAL - Instituto de Investigaciones Biomedicas de Salamanca, Salamanca, Spain. FAU - Segui-Ripoll, Jose Miguel AU - Segui-Ripoll JM AD - Servicio de Medicina Interna, Hospital Universitario San Juan de Alicante, Alicante, Spain. FAU - Ena, Javier AU - Ena J AD - Servicio de Medicina Interna, Hospital Universitario Marina Baixa Hospital, La Villajoyosa (Alicante), Spain. FAU - Arevalo-Lorido, Jose Carlos AU - Arevalo-Lorido JC AD - Servicio de Medicina Interna, Hospital Universitario de Badajoz, Badajoz, Spain. CN - Diabetes, Obesity, and Nutrition Working Group of the Spanish Society of Internal Medicine (SEMI) LA - eng PT - Journal Article PT - Multicenter Study DEP - 20221219 PL - Spain TA - Rev Clin Esp (Barc) JT - Revista clinica espanola JID - 101632437 RN - 0 (Biomarkers) RN - 0 (Triglycerides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Female MH - Middle Aged MH - Male MH - *Diabetes Mellitus, Type 2/complications MH - Prospective Studies MH - *Non-alcoholic Fatty Liver Disease/complications MH - Obesity/complications MH - Biomarkers MH - *Insulin Resistance MH - Triglycerides MH - Fibrosis MH - Semaglutide OTO - NOTNLM OT - Biomarcadores OT - Biomarkers OT - Diabetes mellitus tipo 2 OT - Diabetes mellitus type 2 OT - Fibrosis OT - Higado graso no alcoholico OT - Non-alcoholic fatty liver disease OT - Perdida de peso OT - Semaglutida OT - Semaglutide OT - Weight loss EDAT- 2022/12/23 06:00 MHDA- 2023/03/08 06:00 CRDT- 2022/12/22 19:17 PHST- 2022/09/12 00:00 [received] PHST- 2022/11/17 00:00 [accepted] PHST- 2022/12/23 06:00 [pubmed] PHST- 2023/03/08 06:00 [medline] PHST- 2022/12/22 19:17 [entrez] AID - S2254-8874(22)00104-7 [pii] AID - 10.1016/j.rceng.2022.12.001 [doi] PST - ppublish SO - Rev Clin Esp (Barc). 2023 Mar;223(3):134-143. doi: 10.1016/j.rceng.2022.12.001. Epub 2022 Dec 19. PMID- 36542260 OWN - NLM STAT- MEDLINE DCOM- 20230308 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 40 IP - 3 DP - 2023 Mar TI - Once-Weekly Semaglutide Use in Type 2 Diabetes: Real-World Data from the SURE Netherlands Observational Study. PG - 920-933 LID - 10.1007/s12325-022-02385-x [doi] AB - INTRODUCTION: SURE Netherlands (NCT03929679) evaluated the use of once-weekly (OW) semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), in routine clinical care for individuals with type 2 diabetes (T2D). METHODS: Adults (age >/= 18 years) with T2D were enrolled into the single-arm study. The primary endpoint was change from baseline to end of study (EOS; approx. 30 weeks) in glycated haemoglobin (HbA(1c)). Secondary endpoints were change from baseline to EOS in body weight (BW) and waist circumference (WC). Proportions of participants achieving predefined HbA(1c) targets and weight-loss responses at EOS, safety, health-related quality of life (HRQoL) and treatment satisfaction were assessed. RESULTS: In total, 211 participants (mean age 60.5 years; diabetes duration 13.3 years) initiated semaglutide; most were receiving metformin (82.9%) and/or basal insulin (59.2%) at baseline, and 6.2% switched from another GLP-1RA. Mean baseline HbA(1c), BW and WC were 8.6%, 105.2 kg and 118.8 cm. In the 186 (88.2%) participants receiving semaglutide at EOS, mean reduction in HbA(1c) with semaglutide was - 1.2%-points (95% [confidence interval] CI - 1.3; - 1.0; p < 0.0001), with 124 (70.5%), 95 (54.0%) and 65 (36.9%) participants achieving HbA(1c) targets of < 8.0%, < 7.5% and < 7.0%, respectively. Mean reduction in BW was - 7.8 kg [95% CI - 8.7; - 6.8; p < 0.0001], corresponding to relative reduction of - 7.5% [95% CI - 8.4; - 6.6; p < 0.0001]. Improvements in WC (- 8.8 cm [95% CI - 10.4; - 7.2; p < 0.0001]), HRQoL and treatment satisfaction were observed, including across most Short-Form 36 Health Survey domains. One serious adverse drug reaction (cholecystitis) was reported. Eight participants (all receiving concomitant insulin) experienced severe or documented hypoglycaemia. CONCLUSION: Individuals with T2D treated with OW semaglutide experienced significant and clinically relevant improvements in glycaemic control and BW from baseline. These results from a diverse real-world population in the Netherlands support the use of OW semaglutide in treating adults with T2D in routine clinical practice. CI - (c) 2022. The Author(s). FAU - Wolffenbuttel, Bruce H R AU - Wolffenbuttel BHR AD - Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. bwo@umcg.nl. FAU - Brugts, Michel P AU - Brugts MP AD - Ikazia Hospital, Rotterdam, The Netherlands. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Clark, Alice AU - Clark A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kok, Maarten AU - Kok M AD - Novo Nordisk, Alphen aan den Rijn, The Netherlands. FAU - Lieverse, Aloysius G AU - Lieverse AG AD - Maxima Medisch Centrum, Ds Theodor Fliednerstraat, Eindhoven, The Netherlands. FAU - van Soest, Jaap AU - van Soest J AD - Huisartsenmaatschap Medisch Centrum Nijverdal, Nijverdal, The Netherlands. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20221221 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) MH - Adult MH - Humans MH - Middle Aged MH - Adolescent MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Netherlands MH - Quality of Life MH - Glucagon-Like Peptides/adverse effects MH - Body Weight MH - Insulin/therapeutic use MH - Semaglutide PMC - PMC9768392 OTO - NOTNLM OT - Body weight OT - Glucagon-like peptide 1 receptor agonist OT - Glycated haemoglobin OT - Health-related quality of life OT - Observational study OT - Real-world evidence OT - SURE OT - Semaglutide OT - Type 2 diabetes EDAT- 2022/12/22 06:00 MHDA- 2023/03/09 06:00 PMCR- 2022/12/21 CRDT- 2022/12/21 11:19 PHST- 2022/09/28 00:00 [received] PHST- 2022/11/18 00:00 [accepted] PHST- 2022/12/22 06:00 [pubmed] PHST- 2023/03/09 06:00 [medline] PHST- 2022/12/21 11:19 [entrez] PHST- 2022/12/21 00:00 [pmc-release] AID - 10.1007/s12325-022-02385-x [pii] AID - 2385 [pii] AID - 10.1007/s12325-022-02385-x [doi] PST - ppublish SO - Adv Ther. 2023 Mar;40(3):920-933. doi: 10.1007/s12325-022-02385-x. Epub 2022 Dec 21. PMID- 36525677 OWN - NLM STAT- MEDLINE DCOM- 20221221 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 28 IP - 15 Suppl DP - 2022 Dec TI - Semaglutide 2.4-mg injection as a novel approach for chronic weight management. PG - S297-S306 LID - 10.37765/ajmc.2022.89293 [doi] AB - Anti-obesity medications used with lifestyle intervention produce greater and more sustained weight loss than does lifestyle intervention alone. However, until 2021, FDA-approved medications for the long-term treatment of obesity in the general adult population had not demonstrated the sustained loss of 15% body weight needed to meet or exceed all guideline-recommended targets for weight-related complications. To meet this need, investigators launched the Semaglutide Treatment Effect in People with obesity (STEP) program of phase 3 clinical trials to assess the safety and efficacy of a weekly 2.4-mg subcutaneous injection of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA). Following the results of STEPs 1 to 4, the FDA approved semaglutide therapy in patients with obesity. This article examines the design, efficacy, and safety of semaglutide therapy as revealed by the results of STEPs 1 to 4. These trials included adults with obesity who reported at least 1 unsuccessful attempt to reduce body weight by means of diet. STEP 2 studied effects on patients who also had type 2 diabetes (T2D); STEPs 1, 3, and 4 excluded patients with this condition. STEP 3 examined the effect of this pharmacotherapy plus intensive behavioral therapy and a 2-step, intensively restricted dietary plan. STEP 4 assessed the effects of continuing semaglutide 2.4 mg vs switching to placebo after an initial treatment period. In the trials comparing the effects of semaglutide 2.4‑mg treatment with those of placebo across 68 weeks and in patients with no T2D (ie, STEPs 1 and 3), patients treated with semaglutide achieved a mean -14.9% to -16.0% weight change. This far exceeds the 4.0% to 10.9% weight loss seen with other approved antiobesity medications. In STEPs 2 and 4, the estimated treatment differences between the semaglutide 2.4-mg and placebo arms were -6.2% and -14.8%, respectively. Safety and tolerability of this treatment in STEPs 1 to 4 was consistent with those of other GLP-1RA-based therapies. Ultimately, the results of the first 4 STEP trials demonstrated that semaglutide 2.4 mg is a safe, well-tolerated, and highly effective treatment to promote weight loss, avoid weight regain, and mitigate the effects of the prevalent, chronic disease of obesity. In November 2022, based upon the results of STEPs 1 to 3 and other trials, the American Gastroenterological Association recommended that semaglutide 2.4 mg "be prioritized over other approved [anti-obesity medications] for the long-term treatment of obesity for most patients." FAU - Kyrillos, Janine AU - Kyrillos J AD - Jefferson Health and Sidney Kimmel Medical College at Thomas Jefferson University, 225 East City Ave, Bala Cynwyd, PA 19004. Email: janine.kyrillos@jefferson.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Anti-Obesity Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) MH - Adult MH - Humans MH - *Anti-Obesity Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Hypoglycemic Agents MH - Weight Loss MH - Clinical Trials, Phase III as Topic MH - Semaglutide EDAT- 2022/12/17 06:00 MHDA- 2022/12/21 06:00 CRDT- 2022/12/16 17:56 PHST- 2022/12/16 17:56 [entrez] PHST- 2022/12/17 06:00 [pubmed] PHST- 2022/12/21 06:00 [medline] AID - 89293 [pii] AID - 10.37765/ajmc.2022.89293 [doi] PST - ppublish SO - Am J Manag Care. 2022 Dec;28(15 Suppl):S297-S306. doi: 10.37765/ajmc.2022.89293. PMID- 36520578 OWN - NLM STAT- MEDLINE DCOM- 20221219 LR - 20260127 IS - 2171-8695 (Electronic) IS - 1130-6343 (Linking) VI - 46 IP - 6 DP - 2022 Aug 30 TI - Semaglutide versus GLP-1 agonists. Effectiveness, safety, and quality of life in patients with diabetes mellitus 2. The SEVERAL study. PG - 372-379 AB - OBJECTIVE: The cardiovascular disease is the first cause of deaths in patients with diabetes mellitus 2. The objective is to evaluate and compare the weight loss in patients with diabetes treated with the different GLP-1 receptor agonists for the first time. Secondary endpoints are glycosylated hemoglobin reduction, changes in quality of life and physical activity and the safety of these drugs. METHOD: It is a postauthorization, multicenter, non-randomized and prospective study. 360 Patients that will start treatment for the first time with GLP-1 receptor agonists will be recruited in 10 centers in the National Health System for a period of 6 months and 44 weeks of follow-up. The primary endpoint will be weight loss achieved with the different GLP-1 receptor agonists and the secondary endpoint will be glycosylated hemoglobin reduction, changes in the quality of life through the EuroQol‑5D and changes physical activity through the SF-12 questionnaire, and also the safety of these drugs. The estimate recruitment period will be 6 months, from 1 December 2021 to 1 May 2022. The follow up will finish in December 2022. DISCUSSION: The SEVERAL study will try to provide information about weight loss efficacy, changes in quality of life, physical activity and safety of the GLP-1 receptor agonists in patients with diabetes that start treatment with these drugs in the real life. This study try to compare different GLP-1 receptor gonists in terms of effectiveness and safety for a better posterior election when these drugs are used in patients with diabetes mellitus 2 and obesity. CI - Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved. FAU - Seijas-Amigo, Jose AU - Seijas-Amigo J AD - Cardiology Department. Complexo Hospitalario Universitario de Santiago de Compostela, A Coruna. Spain. Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV). Fundacion IDIS de Santiago de Compostela, A Coruna. Spain. jose.seijas.amigo@gmail.com. FAU - Salgado-Barreira, Angel AU - Salgado-Barreira A AD - Unidad de Epidemiologia e Investigacion Clinica, Universidad de Santiago de Compostela, A Coruna. Spain. Pharmacy Department, Centro de Salud de Ribeira, A Coruna. Spain.. jose.seijas.amigo@sergas.es. FAU - Castelo-Dominguez, Rosana AU - Castelo-Dominguez R AD - Pharmacy Department, Centro de Salud de Ribeira, A Coruna. Spain.. jose.seijas.amigo@sergas.es. FAU - Pereira-Pia, Mercedes AU - Pereira-Pia M AD - Pharmacy Department, Centro de Salud de San Roque, Lugo. Spain.. jose.seijas.amigo@sergas.es. FAU - Rodriguez-Manero, Moises AU - Rodriguez-Manero M AD - Cardiology Department. Complexo Hospitalario Universitario de Santiago de Compostela, A Coruna. Spain. Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV).. jose.seijas.amigo@sergas.es. FAU - Gonzalez-Juanatey, Jose Ramon AU - Gonzalez-Juanatey JR AD - Cardiology Department. Complexo Hospitalario Universitario de Santiago de Compostela, A Coruna. Spain. Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV).. jose.seijas.amigo@sergas.es. LA - eng PT - Journal Article PT - Multicenter Study TT - Semaglutida versus agonistas GLP-1. Efectividad, seguridad y calidad de vida en pacientes con diabetes mellitus 2. Estudio SEVERAL. DEP - 20220830 PL - Spain TA - Farm Hosp JT - Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria JID - 9440679 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Hypoglycemic Agents/adverse effects MH - Glycated Hemoglobin MH - Quality of Life MH - Prospective Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2022/12/16 06:00 MHDA- 2022/12/20 06:00 CRDT- 2022/12/15 12:13 PHST- 2022/12/15 12:13 [entrez] PHST- 2022/12/16 06:00 [pubmed] PHST- 2022/12/20 06:00 [medline] PST - epublish SO - Farm Hosp. 2022 Aug 30;46(6):372-379. PMID- 36514843 OWN - NLM STAT- MEDLINE DCOM- 20230307 LR - 20250103 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 4 DP - 2023 Apr TI - Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: A post hoc analysis of the SURPASS-1 to -5 studies. PG - 965-974 LID - 10.1111/dom.14943 [doi] AB - AIM: To assess composite endpoints combining glycaemic control (HbA1c < 7.0%, /= 5%, >/= 10% or >/= 15%) and without hypoglycaemia with tirzepatide in type 2 diabetes (T2D). MATERIALS AND METHODS: Data from the phase 3 SURPASS programme were evaluated post hoc by trial. Participants with T2D were randomized to tirzepatide (5, 10 and 15 mg), placebo (SURPASS-1,5), semaglutide 1 mg (SURPASS-2) or titrated basal insulin (SURPASS-3,4). The proportions of participants achieving the composite endpoints were compared between tirzepatide and the respective comparator groups at week 40/52. RESULTS: The proportions of participants achieving an HbA1c value of less than 7.0% with 5% or more weight loss and without hypoglycaemia ranged from 43% to 82% with tirzepatide across the SURPASS-1 to -5 trials versus 4%-5% with placebo, 51% with semaglutide 1 mg and 5% with basal insulin (P < .001 vs. all comparators). The proportions of participants achieving an HbA1c value of less than 7.0% with 10% or more, or 15% or more weight loss and without hypoglycaemia were significantly higher with all tirzepatide doses versus comparators across trials (P < .001 or P < .05). Similar results were observed for all other combinations of endpoints with an HbA1c value of 6.5% or less, or less than 5.7%, with more tirzepatide-treated participants achieving these endpoints versus those in the comparator groups, including semaglutide. CONCLUSIONS: Across the SURPASS-1 to -5 clinical trials, more tirzepatide-treated participants with T2D achieved clinically meaningful composite endpoints, which included reaching glycaemic targets with various degrees of weight loss and without hypoglycaemia, than those in the comparator groups. CI - (c) 2022 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology and Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas. FAU - Cheng, Alice Yy AU - Cheng AY AD - Division of Endocrinology and Metabolism, Department of Medicine, Trillium Health Partners and Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada. FAU - Levine, Joshua A AU - Levine JA AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana. FAU - Gomez-Valderas, Elisa AU - Gomez-Valderas E AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana. FAU - Allen, Sheryl E AU - Allen SE AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana. FAU - Ranta, Kari AU - Ranta K AD - Eli Lilly and Company, Helsinki, Finland. FAU - Torcello-Gomez, Amelia AU - Torcello-Gomez A AUID- ORCID: 0000-0003-3276-1296 AD - Eli Lilly and Company, Cork, Ireland. FAU - Thieu, Vivian T AU - Thieu VT AUID- ORCID: 0000-0001-9803-4134 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20221227 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glycated Hemoglobin) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Insulins) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin MH - Weight Loss MH - *Hypoglycemia/drug therapy MH - Gastric Inhibitory Polypeptide/therapeutic use MH - *Insulins MH - Glucose/therapeutic use MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GIP and GLP-1 receptor agonist OT - composite endpoint OT - glycaemic control OT - hypoglycaemia OT - incretin therapy OT - tirzepatide OT - type 2 diabetes OT - weight loss EDAT- 2022/12/15 06:00 MHDA- 2023/03/08 06:00 CRDT- 2022/12/14 02:42 PHST- 2022/11/30 00:00 [revised] PHST- 2022/10/03 00:00 [received] PHST- 2022/12/08 00:00 [accepted] PHST- 2022/12/15 06:00 [pubmed] PHST- 2023/03/08 06:00 [medline] PHST- 2022/12/14 02:42 [entrez] AID - 10.1111/dom.14943 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Apr;25(4):965-974. doi: 10.1111/dom.14943. Epub 2022 Dec 27. PMID- 36514266 OWN - NLM STAT- MEDLINE DCOM- 20230307 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 25 IP - 4 DP - 2023 Apr TI - Effects of once-weekly subcutaneous semaglutide on coronary artery disease outcomes in patients with type 2 diabetes with or at high risk for cardiovascular disease: Insights from the SUSTAIN-6 trial. PG - 1117-1120 LID - 10.1111/dom.14941 [doi] FAU - Kolkailah, Ahmed A AU - Kolkailah AA AUID- ORCID: 0000-0002-3327-1718 AD - Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. AD - Parkland Health and Hospital System, Dallas, Texas, USA. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. FAU - Dobrecky-Mery, Idit AU - Dobrecky-Mery I AD - Department of Cardiology, Bnai Zion Medical Center, Haifa, Israel. FAU - Aharonovich, Alona AU - Aharonovich A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - David, Jens-Peter AU - David JP AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Holse, Cecilie AU - Holse C AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - McGuire, Darren K AU - McGuire DK AUID- ORCID: 0000-0002-6412-7989 AD - Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA. AD - Parkland Health and Hospital System, Dallas, Texas, USA. LA - eng GR - T32 HL125247/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20221223 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/chemically induced MH - *Cardiovascular Diseases/chemically induced MH - *Coronary Artery Disease MH - Glucagon-Like Peptides/adverse effects MH - Hypoglycemic Agents/adverse effects MH - Semaglutide PMC - PMC9991975 MID - NIHMS1858458 EDAT- 2022/12/15 06:00 MHDA- 2023/03/08 06:00 PMCR- 2024/04/01 CRDT- 2022/12/14 01:23 PHST- 2022/11/24 00:00 [revised] PHST- 2022/10/14 00:00 [received] PHST- 2022/12/07 00:00 [accepted] PHST- 2022/12/15 06:00 [pubmed] PHST- 2023/03/08 06:00 [medline] PHST- 2022/12/14 01:23 [entrez] PHST- 2024/04/01 00:00 [pmc-release] AID - 10.1111/dom.14941 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Apr;25(4):1117-1120. doi: 10.1111/dom.14941. Epub 2022 Dec 23. PMID- 36507900 OWN - NLM STAT- MEDLINE DCOM- 20230307 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 4 DP - 2023 Apr TI - Tirzepatide versus semaglutide for weight loss in patients with type 2 diabetes mellitus: A value for money analysis. PG - 961-964 LID - 10.1111/dom.14940 [doi] AB - AIMS: Higher doses of the glucagon-like peptide-1 agonist semaglutide and, more recently, tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 agonist showed a significant reduction in body weight in patients with type 2 diabetes mellitus. However, their comparative value for money for this indication is unclear. Therefore, we aimed to establish which provides better value for money. MATERIALS AND METHODS: We calculated the cost needed to treat to achieve a 1% reduction in body weight using high-dose tirzepatide (15 mg) versus semaglutide (2.4 mg). The body weight reductions were extracted from published results of SURMOUNT-1 and STEP 1 trials, respectively. In addition, we performed a scenario analysis to mitigate the primary differences between the two study populations. Drug costs were based on US GoodRx prices as of October 2022. RESULTS: Using tirzepatide resulted in a weight loss of 17.8% (95% CI: 16.3%-19.3%) compared with 12.4% (95% CI: 11.5%-13.4%) for semaglutide. The total cost of 72 weeks of tirzepatide was estimated at $17 527 compared with $22 878 for 68 weeks of semaglutide. Accordingly, the cost needed to treat per 1% of body weight reduction with tirzepatide is estimated at $985 (95% CI: $908-$1075) compared with $1845 (95% CI: $1707-$1989) with semaglutide. Scenario analysis confirmed these findings. CONCLUSIONS: Tirzepatide provides better value for money than semaglutide for weight reduction. CI - (c) 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Azuri, Joseph AU - Azuri J AUID- ORCID: 0000-0003-1049-9848 AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. AD - Maccabi Healthcare Services, Tel Aviv, Israel. FAU - Hammerman, Ariel AU - Hammerman A AUID- ORCID: 0000-0002-4396-5246 AD - Clalit Health Services, Tel Aviv, Israel. FAU - Aboalhasan, Enis AU - Aboalhasan E AUID- ORCID: 0000-0001-7763-566X AD - Sapir College, Ashkelon, Israel. FAU - Sluckis, Ben AU - Sluckis B AD - Meuhedet Health Services, Jerusalem, Israel. FAU - Arbel, Ronen AU - Arbel R AUID- ORCID: 0000-0002-6058-8665 AD - Clalit Health Services, Tel Aviv, Israel. AD - Sapir College, Ashkelon, Israel. LA - eng PT - Journal Article DEP - 20221227 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin MH - Weight Loss MH - Glucagon-Like Peptides/therapeutic use MH - Body Weight MH - Glucagon-Like Peptide 1/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Tirzepatide MH - Semaglutide OTO - NOTNLM OT - cost-effectiveness OT - obesity therapy OT - type 2 diabetes OT - weight control EDAT- 2022/12/13 06:00 MHDA- 2023/03/08 06:00 CRDT- 2022/12/12 11:56 PHST- 2022/12/01 00:00 [revised] PHST- 2022/10/17 00:00 [received] PHST- 2022/12/09 00:00 [accepted] PHST- 2022/12/13 06:00 [pubmed] PHST- 2023/03/08 06:00 [medline] PHST- 2022/12/12 11:56 [entrez] AID - 10.1111/dom.14940 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Apr;25(4):961-964. doi: 10.1111/dom.14940. Epub 2022 Dec 27. PMID- 36502289 OWN - NLM STAT- MEDLINE DCOM- 20221223 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 31 IP - 1 DP - 2023 Jan TI - Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics. PG - 111-122 LID - 10.1002/oby.23621 [doi] AB - OBJECTIVE: This paper describes the baseline characteristics of the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) study, one of the largest cardiovascular (CV) outcome studies in the field of obesity, which evaluates the effect of semaglutide versus placebo on major CV events. METHODS: SELECT enrolled individuals with overweight or obesity without diabetes, with prior myocardial infarction, stroke, and/or peripheral artery disease. This study reports participants' baseline characteristics in the full study population and subgroups defined by baseline glycated hemoglobin (HbA(1c) ; <5.7%, >/=5.7 to <6.0%, >/=6.0 to <6.5%), baseline waist to height ratio tertile, and qualifying prior CV event or condition. RESULTS: The study enrolled 17,605 participants (72.5% male) with an average (SD) age of 61.6 (8.9) years and BMI of 33.34 (5.04) kg/m(2) . The most common prior CV event was myocardial infarction (76.3% of participants), followed by stroke (23.3%) and peripheral artery disease (8.6%). Furthermore, 24.3% had a heart failure diagnosis. Two-thirds of participants (66%) had HbA(1c) in the prediabetes range (5.7%-6.4%). Across groups of increasing HbA(1c) , prevalence of all CV risk factors increased. CONCLUSIONS: The enrolled population in SELECT includes participants across a broad range of relevant risk categories. This will allow the study to garner information about the CV benefits of semaglutide across these relevant clinical subgroups. CI - (c) 2022 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology and Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas, USA. FAU - Brown-Frandsen, Kirstine AU - Brown-Frandsen K AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Colhoun, Helen M AU - Colhoun HM AD - Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. FAU - Deanfield, John AU - Deanfield J AD - Farr Institute of Health Informatics Research at London, London, UK and National Institute for Cardiovascular Outcomes Research, University College London, London, UK. FAU - Emerson, Scott S AU - Emerson SS AD - Department of Biostatistics, University of Washington, Seattle, Washington, USA. FAU - Esbjerg, Sille AU - Esbjerg S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hardt-Lindberg, Soren AU - Hardt-Lindberg S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hovingh, G Kees AU - Hovingh GK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kahn, Steven E AU - Kahn SE AD - Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington, USA. FAU - Kushner, Robert F AU - Kushner RF AUID- ORCID: 0000-0002-1380-3705 AD - Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. FAU - Lincoff, A Michael AU - Lincoff AM AD - Cleveland Clinic Coordinating Center for Clinical Research (C5Research) and Department of Cardiovascular Medicine, Cleveland, Ohio, USA. FAU - Marso, Steven P AU - Marso SP AD - HCA Midwest Health Heart and Vascular Institute, Kansas City, Missouri, USA. FAU - Fries, Tea Monk AU - Fries TM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Plutzky, Jorge AU - Plutzky J AD - Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Ryan, Donna H AU - Ryan DH AD - Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA. CN - SELECT Study Group LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221210 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Cardiovascular Diseases/epidemiology/prevention & control/chemically induced MH - *Diabetes Mellitus, Type 2/drug therapy/diagnosis MH - Hypoglycemic Agents/therapeutic use MH - *Myocardial Infarction/epidemiology/prevention & control MH - Obesity/complications/drug therapy/chemically induced MH - Overweight/complications/drug therapy/chemically induced MH - *Peripheral Arterial Disease/chemically induced MH - *Stroke MH - Semaglutide PMC - PMC10107832 COIS- Ildiko Lingvay received research funding (paid to institution) from Boehringer Ingelheim, Merck, Mylan, Novo Nordisk A/S, Pfizer, and Sanofi and advisory/consulting fees and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company, GI Dynamics, Intarcia, Intercept, Janssen, Mannkind, Merck, Mylan, Novartis, Novo Nordisk A/S, Pfizer, Sanofi, Shionogi, TARGETPharma, Valeritas, and Zealand Pharma. A. Michael Lincoff received research funding from AbbVie, AstraZeneca, CSL Behring, Eli Lilly and Company, Esperion, and Novartis and consulting fees from Akebia, Becton-Dickson, Eli Lilly and Company, Endologix, Fibrogen, GlaxoSmithKline, Novo Nordisk A/S, and Provention Bio. Donna H. Ryan received consulting fees from Altimmune, Amgen, Boehringer Ingelheim, Calibrate, Epitomee, Gila, Ifa Celtic, Janssen, Eli Lilly and Company, Novo Nordisk A/S, Real Appeal (UnitedHealthcare), Roman Scientific Intake, Wondr Health, Xeno Bioscience, Ysopia, and Zealand; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Novo Nordisk A/S; payment for expert testimony from Simmons and Simmons; participated in a data safety monitoring board and/or advisory board for IQVIA and Rhythm Pharmaceuticals; and holds stock options in Calibrate, Epitomee, Roman, and Scientific Intake. Helen M. Colhoun received research support from AstraZeneca LP, Eli Lilly and Company, Novo Nordisk A/S, Pfizer, and Public Health Scotland; honoraria from Eli Lilly and Company, Novartis Pharmaceuticals, and Regeneron; served as board member/advisory panel member for Eli Lilly and Company, Novartis Pharmaceuticals, Novo Nordisk A/S, Regeneron, and Sanofi Aventis; and holds stocks/shares in Bayer AG and Roche Pharmaceuticals. John Deanfield received consulting fees from GENinCode UK Ltd; received CME honoraria and/or consulting fees from Aegerion, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk A/S, Pfizer, Sanofi, and Takeda; and holds the following unpaid positions: Chief Medical Advisor for Our Future Health, senior advisor for Cardiovascular Disease Prevention for Public Health England, and Chair of the NHS Healthcheck Expert Scientific and Clinical Advisory Panel (ESCAP) and Review of the National Health Check Programme for Public Health England. Jorge Plutzky received consulting fees from Alnylam, Altimmune, Amgen, Esperion (clinical trial steering committee), Merck, MJ Health Lifesciences, and Novo Nordisk A/S (clinical trial steering committee) and received grant support from Boehringer Ingelheim and Novartis. Robert F. Kushner is a member of a medical advisory board for Novo Nordisk A/S. G. Kees Hobingh, Kirstine Brown-Frandsen, Sille Esbjerg, Soren Hardt-Lindberg, and Tea Monk Fries are employees of Novo Nordisk A/S and own stocks in the company. G. Kees Hovingh is also employed part-time by Amsterdam UMC. Steven E. Kahn received advisory/consulting fees from Bayer, Boehringer Ingelheim, Casma Therapeutics, Eli Lilly and Company, Intarcia, Merck, Novo Nordisk A/S, Pfizer, and Third Rock Ventures. Steven P. Marso received consulting and/or honoraria from Boston Scientific, Change Healthcare, Novo Nordisk A/S, and Population Health Partners. Scott S. Emerson received consulting fees from Novo Nordisk A/S. EDAT- 2022/12/12 06:00 MHDA- 2022/12/23 06:00 PMCR- 2023/04/17 CRDT- 2022/12/11 02:42 PHST- 2022/09/13 00:00 [revised] PHST- 2022/07/26 00:00 [received] PHST- 2022/09/28 00:00 [accepted] PHST- 2022/12/12 06:00 [pubmed] PHST- 2022/12/23 06:00 [medline] PHST- 2022/12/11 02:42 [entrez] PHST- 2023/04/17 00:00 [pmc-release] AID - OBY23621 [pii] AID - 10.1002/oby.23621 [doi] PST - ppublish SO - Obesity (Silver Spring). 2023 Jan;31(1):111-122. doi: 10.1002/oby.23621. Epub 2022 Dec 10. PMID- 36470445 OWN - NLM STAT- MEDLINE DCOM- 20221219 LR - 20250103 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 938 DP - 2023 Jan 5 TI - Alternative role of glucagon-like Peptide-1 receptor agonists in neurodegenerative diseases. PG - 175439 LID - S0014-2999(22)00700-2 [pii] LID - 10.1016/j.ejphar.2022.175439 [doi] AB - Aging is a crucial risk factor for common neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Limited options are available for the treatment of age-related, multiple pathogenic mechanism-contributed diseases that usually advance to irreversible conditions with severe neurological deficits and result in a heavy socioeconomic burden on patients, families, and society. A therapy that decelerates disease progression and reduces the socioeconomic burden stemming from these diseases is required. Glucagon-like peptide-1 receptor (GLP-1R) is an important class of medication for type 2 diabetes mellitus (T2DM). Through pancreatic effects, GLP-1R agonists can stimulate insulin secretion, increase beta-cell proliferation, reduce beta-cell apoptosis, and inhibit glucagon secretion in patients with T2DM. Currently, seven clinically approved GLP-1R agonists are used for T2DM: exenatide, liraglutide, lixisenatide, extended-release exenatide, albiglutide, dulaglutide, and semaglutide. Besides the pancreas, GLP-1Rs are also expressed in organs, such as the gastrointestinal tract, heart, lung, kidney, and brain, indicating their potential use in diseases other than T2DM. Emerging evidence reveals that GLP-1R agonists possess pleiotropic effects that enrich neurogenesis, diminish apoptosis, preclude neurons from oxidative stress, and reduce neuroinflammation in various neurological conditions. These favorable effects may also be employed in neurodegenerative diseases. Herein, we reviewed the recent progress, both in preclinical studies and clinical trials, regarding these clinically used GLP-1R agonists in aging-related neurodegenerative diseases, mainly AD and PD. We stress the pleiotropic characteristics of GLP-1R agonists as repurposing drugs to target multiple pathological mechanisms and for use in the future for these devastating neurodegenerative conditions. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Chen, Shang-Der AU - Chen SD AD - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, 83301, Taiwan; Institute for Translation Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, 83301, Taiwan. Electronic address: chensd@adm.cgmh.org.tw. FAU - Chuang, Yao-Chung AU - Chuang YC AD - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, 83301, Taiwan; Institute for Translation Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, 83301, Taiwan; College of Medicine, Chang Gung University, Taoyuan City, 33302, Taiwan; Department of Neurology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, 80708, Taiwan. Electronic address: ycchuang@cgmh.org.tw. FAU - Lin, Tsu-Kung AU - Lin TK AD - Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, 83301, Taiwan; College of Medicine, Chang Gung University, Taoyuan City, 33302, Taiwan; Center for Mitochondrial Research and Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, 83301, Taiwan. Electronic address: tklin@adm.cgmh.org.tw. FAU - Yang, Jenq-Lin AU - Yang JL AD - Institute for Translation Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, 83301, Taiwan. Electronic address: jyang@cgmh.org.tw. LA - eng PT - Journal Article PT - Review DEP - 20221202 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 9P1872D4OL (Exenatide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Exenatide/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/chemically induced MH - Hypoglycemic Agents/pharmacology MH - *Neurodegenerative Diseases/drug therapy/chemically induced MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Alzheimer's disease OT - GLP-1 receptor agonist OT - Neurodegenerative diseases OT - Parkinson's disease COIS- Declaration of competing interest None. EDAT- 2022/12/06 06:00 MHDA- 2022/12/20 06:00 CRDT- 2022/12/05 19:33 PHST- 2022/07/18 00:00 [received] PHST- 2022/11/02 00:00 [revised] PHST- 2022/11/29 00:00 [accepted] PHST- 2022/12/06 06:00 [pubmed] PHST- 2022/12/20 06:00 [medline] PHST- 2022/12/05 19:33 [entrez] AID - S0014-2999(22)00700-2 [pii] AID - 10.1016/j.ejphar.2022.175439 [doi] PST - ppublish SO - Eur J Pharmacol. 2023 Jan 5;938:175439. doi: 10.1016/j.ejphar.2022.175439. Epub 2022 Dec 2. PMID- 36469361 OWN - NLM STAT- MEDLINE DCOM- 20221207 LR - 20260127 IS - 1538-4683 (Electronic) IS - 1061-5377 (Linking) VI - 31 IP - 1 DP - 2023 Jan-Feb 01 TI - Semaglutide for Weight Loss: Was It Worth the Weight?: Erratum. PG - 57 LID - 10.1097/CRD.0000000000000504 [doi] LA - eng PT - Journal Article DEP - 20221202 PL - United States TA - Cardiol Rev JT - Cardiology in review JID - 9304686 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Glucagon-Like Peptides/therapeutic use MH - Weight Loss MH - *Diabetes Mellitus, Type 2/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Glycated Hemoglobin/analysis MH - Semaglutide EDAT- 2022/12/06 06:00 MHDA- 2022/12/15 06:00 CRDT- 2022/12/05 11:43 PHST- 2022/12/05 11:43 [entrez] PHST- 2022/12/06 06:00 [pubmed] PHST- 2022/12/15 06:00 [medline] AID - 00045415-202301000-00011 [pii] AID - 10.1097/CRD.0000000000000504 [doi] PST - ppublish SO - Cardiol Rev. 2023 Jan-Feb 01;31(1):57. doi: 10.1097/CRD.0000000000000504. Epub 2022 Dec 2. PMID- 36469293 OWN - NLM STAT- MEDLINE DCOM- 20230418 LR - 20261010 IS - 1720-8386 (Electronic) IS - 0391-4097 (Linking) VI - 46 IP - 5 DP - 2023 May TI - Parameters influencing renal response to SGLT2 inhibitors and GLP1 receptor agonists in type 2 diabetes patients with preserved renal function: a comparative, prospective study. PG - 991-999 LID - 10.1007/s40618-022-01969-2 [doi] AB - PURPOSE: SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1-RA) protect the kidney in type 2 diabetes (T2DM) subjects. The role of patient's phenotype years before starting the treatment in determining the kidney response to these drugs has never been evaluated. SUBJECTS AND METHODS: Clinical and biochemical parameters were collected in 92 T2DM patients with preserved kidney function from year -4 (T-4) to year +3 (T+3) from the introduction of semaglutide or empagliflozin (T0). Glomerular filtration rate (eGFR) slopes were evaluated to identify eGFR changes (DeltaGFR) and predictors of treatment response. Urinary markers of kidney impairment were measured at T0, including KIM-1, TNFR1 and L-FABP. RESULTS: Characteristics of patients on semaglutide (n = 46) or empagliflozin (n = 37) were similar at T-4 and T0. DeltaGFR from T0 to T+3 was -5.5 [-10.0; -0.7] vs -2.6 [-102.4] ml/min/1.73 m(2) for GLP1-RA and SGLT2i, respectively (p = ns). Compared with patients with a slower eGFR decline, those with DeltaGFR > 5 ml/min/1.73 m(2) from T0 to T+3 (49%) or DeltaGFR > 10 ml/min/1.73 m(2) from T-4 to T+3 (25%) had similar characteristics and urinary markers at T-4 and T0. The latter group showed greater eGFR decline from T-3 to T0, which tended to be delayed more by SGLT2i than GLP1-RA (p = 0.09). CONCLUSION: In our cohort, subjects with T2DM and preserved renal function show similar eGFR response to treatment with GLP1-RA or SGLT2i. Baseline urinary biomarkers or prior phenotyping do not predict treatment response. An early eGFR decline identifies patients prone to lose more eGFR over time, who may benefit more from SGLT2i treatment. CI - (c) 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE). FAU - Biancalana, E AU - Biancalana E AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Petralli, G AU - Petralli G AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Raggi, F AU - Raggi F AD - Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, 56126, Pisa, Italy. FAU - Distaso, M R AU - Distaso MR AD - Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, 56126, Pisa, Italy. FAU - Piazza, G AU - Piazza G AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Rossi, C AU - Rossi C AD - Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, 56126, Pisa, Italy. FAU - Trico, D AU - Trico D AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Solini, A AU - Solini A AUID- ORCID: 0000-0002-7855-8253 AD - Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Via Roma 67, 56126, Pisa, Italy. anna.solini@unipi.it. LA - eng PT - Journal Article DEP - 20221205 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - HDC1R2M35U (empagliflozin) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use/pharmacology MH - Prospective Studies MH - Kidney MH - Benzhydryl Compounds MH - Glucosides OTO - NOTNLM OT - Empagliflozin OT - Phenotype OT - Semaglutide OT - eGFR slope EDAT- 2022/12/06 06:00 MHDA- 2023/04/18 06:42 CRDT- 2022/12/05 11:23 PHST- 2022/09/08 00:00 [received] PHST- 2022/11/15 00:00 [accepted] PHST- 2023/04/18 06:42 [medline] PHST- 2022/12/06 06:00 [pubmed] PHST- 2022/12/05 11:23 [entrez] AID - 10.1007/s40618-022-01969-2 [pii] AID - 10.1007/s40618-022-01969-2 [doi] PST - ppublish SO - J Endocrinol Invest. 2023 May;46(5):991-999. doi: 10.1007/s40618-022-01969-2. Epub 2022 Dec 5. PMID- 36462999 OWN - NLM STAT- MEDLINE DCOM- 20221227 LR - 20230227 IS - 1873-3735 (Electronic) IS - 0165-6147 (Linking) VI - 44 IP - 1 DP - 2023 Jan TI - Obesity pharmacotherapy: incretin action in the central nervous system. PG - 50-63 LID - S0165-6147(22)00251-6 [pii] LID - 10.1016/j.tips.2022.11.001 [doi] AB - The prevalence of obesity is rising, creating an urgent need for efficacious therapies. Recent clinical trials show that tirzepatide, a dual agonist of receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), yields more weight loss than selective GLP-1 receptor (GLP-1R) agonists. Incretin receptors in the central nervous system (CNS) may contribute to these effects. Yet exactly how each receptor regulates body weight from within the CNS is not clearly understood. It remains especially unclear how GIP receptor (GIPR) signalling contributes to the effects of tirzepatide because both stimulation and inhibition of CNS GIPRs yield weight loss in preclinical models. We summarise current knowledge on CNS incretin receptor pharmacology to provide insight into the potential mechanisms of action of dual GIPR/GLP-1R agonists, with tirzepatide as the exemplar. In addition, we discuss recent developments in incretin-based dual- and tri-agonism for inducing weight loss in obese individuals. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Boer, Geke Aline AU - Boer GA AD - Centre for Neuroendocrinology, Department of Physiology, University of Otago, Otago, New Zealand. FAU - Hay, Debbie L AU - Hay DL AD - Department of Pharmacology and Toxicology, University of Otago, Otago, New Zealand; Maurice Wilkins Centre, Auckland, New Zealand. FAU - Tups, Alexander AU - Tups A AD - Centre for Neuroendocrinology, Department of Physiology, University of Otago, Otago, New Zealand; Maurice Wilkins Centre, Auckland, New Zealand. Electronic address: alexander.tups@otago.ac.nz. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20221130 PL - England TA - Trends Pharmacol Sci JT - Trends in pharmacological sciences JID - 7906158 RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Incretins/therapeutic use MH - Glucagon-Like Peptide 1/pharmacology/therapeutic use MH - Obesity/drug therapy MH - Weight Loss MH - *Diabetes Mellitus, Type 2/drug therapy OTO - NOTNLM OT - GIP OT - GLP-1 OT - incretin OT - liraglutide OT - neuroendocrinology OT - obesity OT - semaglutide OT - tirzepatide COIS- Declaration of interests The authors declare no conflicts of interest. EDAT- 2022/12/04 06:00 MHDA- 2022/12/28 06:00 CRDT- 2022/12/03 22:04 PHST- 2022/09/20 00:00 [received] PHST- 2022/11/02 00:00 [revised] PHST- 2022/11/08 00:00 [accepted] PHST- 2022/12/04 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] PHST- 2022/12/03 22:04 [entrez] AID - S0165-6147(22)00251-6 [pii] AID - 10.1016/j.tips.2022.11.001 [doi] PST - ppublish SO - Trends Pharmacol Sci. 2023 Jan;44(1):50-63. doi: 10.1016/j.tips.2022.11.001. Epub 2022 Nov 30. PMID- 36448672 OWN - NLM STAT- MEDLINE DCOM- 20240219 LR - 20250103 IS - 1755-3245 (Electronic) IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 119 IP - 18 DP - 2024 Feb 17 TI - New therapies for obesity. PG - 2825-2842 LID - 10.1093/cvr/cvac176 [doi] AB - Obesity is a chronic disease associated with serious complications and increased mortality. Weight loss (WL) through lifestyle changes results in modest WL long-term possibly due to compensatory biological adaptations (increased appetite and reduced energy expenditure) promoting weight gain. Bariatric surgery was until recently the only intervention that consistently resulted in >/= 15% WL and maintenance. Our better understanding of the endocrine regulation of appetite has led to the development of new medications over the last decade for the treatment of obesity with main target the reduction of appetite. The efficacy of semaglutide 2.4 mg/week-the latest glucagon-like peptide-1 (GLP-1) receptor analogue-on WL for people with obesity suggests that we are entering a new era in obesity pharmacotherapy where >/=15% WL is feasible. Moreover, the WL achieved with the dual agonist tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide) for people with type 2 diabetes and most recently also obesity, indicate that combining the GLP-1 with other gut hormones may lead to additional WL compared with GLP-1 receptor analogues alone and in the future, multi-agonist molecules may offer the potential to bridge further the efficacy gap between bariatric surgery and the currently available pharmacotherapies. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. FAU - Papamargaritis, Dimitris AU - Papamargaritis D AUID- ORCID: 0000-0001-5044-1515 AD - Diabetes Research Centre, Leicester General Hospital, University of Leicester College of Medicine Biological Sciences and Psychology, Leicester LE5 4PW, UK. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin 4, Ireland. AD - Diabetes Research Centre, Ulster University, Coleraine BT52 1SA, UK. FAU - Holst, Jens J AU - Holst JJ AUID- ORCID: 0000-0001-6853-3805 AD - Department of Biomedical Sciences and the NNF Center for Basic Metabolic Research, University of Copenhagen Panum Institute, Copenhagen 2200, Denmark. FAU - Davies, Melanie J AU - Davies MJ AUID- ORCID: 0000-0002-9987-9371 AD - Diabetes Research Centre, Leicester General Hospital, University of Leicester College of Medicine Biological Sciences and Psychology, Leicester LE5 4PW, UK. LA - eng GR - Leicester NIHR Biomedical Research Centre/ GR - National Institute of Clinical Research Clinical Lectureship/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Obesity/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - Appetite MH - Weight Loss MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10874276 OTO - NOTNLM OT - Bariatric surgery OT - Liraglutide OT - Obesity OT - Pharmacotherapy OT - Semaglutide OT - Tirzepatide COIS- Conflict of interest: D.P. has acted as speaker for Novo Nordisk and has received grants from Novo Nordisk, Novo Nordisk UK Research Foundation, Academy of Medical Sciences/Diabetes UK, and Health Education East Midlands. C.W.l.R. reports grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He serves on the advisory boards of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Sanofi Aventis, AstraZeneca, Janssen, Bristol-Myers Squibb, Glia, and Boehringer Ingelheim. C.W.l.R. is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He is the chief medical officer and director of the Medical Device Division of Keyron since January 2011. Both of these are unremunerated positions. C.W.l.R. was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. The product has only been tested in rodents and none of Keyron's products are currently licensed. They do not have any contracts with other companies to put their products into clinical practice. No patients have been included in any of Keyron's studies and they are not listed on the stock market. C.W.l.R. was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. J.J.H. is a member of advisory boards for Novo Nordisk and has acted as a speaker for Novo Nordisk and Lilly. M.J.D. has acted as consultant, advisory board member and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk and Sanofi, an advisory board member and speaker for AstraZeneca, an advisory board member for Janssen, Lexicon, Pfizer, and ShouTi Pharma Inc., a speaker for Napp Pharmaceuticals, Novartis, and Takeda Pharmaceuticals International Inc. and has received grants in support of investigator and investigator initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Astrazeneca, and Janssen. EDAT- 2022/12/01 06:00 MHDA- 2024/02/19 06:43 PMCR- 2022/11/30 CRDT- 2022/11/30 07:53 PHST- 2022/06/01 00:00 [received] PHST- 2022/09/16 00:00 [revised] PHST- 2022/10/19 00:00 [accepted] PHST- 2024/02/19 06:43 [medline] PHST- 2022/12/01 06:00 [pubmed] PHST- 2022/11/30 07:53 [entrez] PHST- 2022/11/30 00:00 [pmc-release] AID - 6854907 [pii] AID - cvac176 [pii] AID - 10.1093/cvr/cvac176 [doi] PST - ppublish SO - Cardiovasc Res. 2024 Feb 17;119(18):2825-2842. doi: 10.1093/cvr/cvac176. PMID- 36414113 OWN - NLM STAT- MEDLINE DCOM- 20221219 LR - 20260127 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 938 DP - 2023 Jan 5 TI - Improved metabolic efficacy of a dual amylin and calcitonin receptor agonist when combined with semaglutide or empagliflozin. PG - 175397 LID - S0014-2999(22)00658-6 [pii] LID - 10.1016/j.ejphar.2022.175397 [doi] AB - Pharmacotherapies for obesity and type 2 diabetes (T2D) are thought to bridge the gap between lifestyle modification and the weight loss obtained with bariatric surgery. Although the effect of monotherapies, namely amylin and glucagon-like peptide-1 receptor (GLP-1R) agonists, has shown great potential, combination therapy is now becoming a strategy to optimize efficacy for weight management while minimizing adverse effects. This study investigated a dual amylin and calcitonin receptor agonist (DACRA); KBP-066A in combination with the GLP-1R agonist semaglutide or the sodium-glucose co transporter-2 inhibitor (SGLT2i) empagliflozin for anti-obesity and anti-diabetic treatment. The effect of KBP-066A, semaglutide, and empagliflozin alone and in combination was studied with respect to their impact on body weight, food intake, and glucose metabolism in high-fat diet (HFD) and Zucker diabetic fatty (fa/fa) (ZDF) rats. Treatment with KBP-066A and semaglutide lowered body weight by 13% and 9.7%. In contrast, a combination of both KBP-066A + semaglutide reduced body weight by 21% in HFD rats demonstrating superiority compared to monotherapies alone. A combination of KBP-066A with semaglutide or empagliflozin significantly lowered fasting blood glucose, and HbA1C (%) levels in ZDF rats. The complementary action by KBP-066A to GLP-1R agonist and SGLT2i on BW, food intake and glucose control endorsed the potential of DACRAs as an add-on therapy to therapeutic options for T2D and obesity. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Melander, Simone A AU - Melander SA AD - Nordic Bioscience, 2730, Herlev, Denmark. Electronic address: Sme@nordicbio.com. FAU - Katri, Anna AU - Katri A AD - Nordic Bioscience, 2730, Herlev, Denmark. FAU - Karsdal, Morten A AU - Karsdal MA AD - Nordic Bioscience, 2730, Herlev, Denmark; KeyBioscience AG, Stans, Switzerland. FAU - Henriksen, Kim AU - Henriksen K AD - Nordic Bioscience, 2730, Herlev, Denmark; KeyBioscience AG, Stans, Switzerland. LA - eng PT - Journal Article DEP - 20221119 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Amylin Receptor Agonists) RN - 0 (Receptors, Calcitonin) RN - 0 (Islet Amyloid Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) SB - IM MH - Rats MH - Animals MH - *Amylin Receptor Agonists/pharmacology/therapeutic use MH - Receptors, Calcitonin/agonists/therapeutic use MH - Islet Amyloid Polypeptide MH - *Diabetes Mellitus, Type 2/drug therapy MH - Rats, Zucker MH - Body Weight MH - Obesity/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Semaglutide MH - Benzhydryl Compounds MH - Glucosides OTO - NOTNLM OT - DACRA OT - GLP-1R OT - Obesity OT - Preclinical OT - SGLT2i OT - Type 2 diabetes COIS- Declaration of competing interest MAK and KH own stock in Nordic Bioscience A/S. All authors are employed by Nordic Bioscience A/S. EDAT- 2022/11/23 06:00 MHDA- 2022/12/20 06:00 CRDT- 2022/11/22 19:24 PHST- 2022/08/19 00:00 [received] PHST- 2022/11/15 00:00 [revised] PHST- 2022/11/15 00:00 [accepted] PHST- 2022/11/23 06:00 [pubmed] PHST- 2022/12/20 06:00 [medline] PHST- 2022/11/22 19:24 [entrez] AID - S0014-2999(22)00658-6 [pii] AID - 10.1016/j.ejphar.2022.175397 [doi] PST - ppublish SO - Eur J Pharmacol. 2023 Jan 5;938:175397. doi: 10.1016/j.ejphar.2022.175397. Epub 2022 Nov 19. PMID- 36384763 OWN - NLM STAT- MEDLINE DCOM- 20221121 LR - 20221129 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 64 IP - 1663 DP - 2022 Nov 14 TI - Drugs for type 2 diabetes. PG - 177-184 LA - eng PT - Journal Article PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - 0 (Hypoglycemic Agents) RN - 0 (Antipsychotic Agents) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Hypoglycemic Agents/adverse effects MH - *Antipsychotic Agents OTO - NOTNLM OT - Actoplus OT - Actos OT - Adlyxin OT - Amaryl OT - Bydureon OT - Byetta OT - Duetact OT - Farxiga OT - Glucotrol OT - Glumetza OT - Glynase OT - Glyxambi OT - Invokamet OT - Invokana OT - Janumet OT - Januvia OT - Jardiance OT - Jentadueto OT - Kazano OT - Kombiglyze OT - Mounjaro OT - Nesina OT - Onglyza OT - Oseni OT - Ozempic OT - Qtern OT - Riomet OT - Rybelsus OT - Saxenda OT - Segluromet OT - Soliqua OT - Steglatro OT - Steglujan OT - Synjardy OT - Tradjenta OT - Trulicity OT - Victoza OT - Wegovy OT - Xigduo OT - Xultophy OT - acarbose OT - adverse effects OT - alogliptin OT - canagliflozin OT - dapagliflozin OT - degludec OT - dosage OT - drug interactions OT - dulaglutide OT - efficacy OT - empagliflozin OT - ertugliflozin OT - exenatide OT - glargine OT - glimepiride OT - glipizide OT - glyburide OT - insulin OT - lactation OT - linagliptin OT - liraglutide OT - lixisenatide OT - metformin OT - miglitol OT - nateglinide OT - pioglitazone OT - pregnancy OT - repaglinide OT - rosiglitazone OT - safety OT - saxagliptin OT - semaglutide OT - sitagliptin OT - tirzepatide OT - type 2 diabetes EDAT- 2022/11/18 06:00 MHDA- 2022/11/22 06:00 CRDT- 2022/11/17 09:58 PHST- 2022/11/17 09:58 [entrez] PHST- 2022/11/18 06:00 [pubmed] PHST- 2022/11/22 06:00 [medline] PST - ppublish SO - Med Lett Drugs Ther. 2022 Nov 14;64(1663):177-184. PMID- 36375235 OWN - NLM STAT- MEDLINE DCOM- 20221212 LR - 20250103 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 36 IP - 12 DP - 2022 Dec TI - Tirzepatide: A novel, first-in-class, dual GIP/GLP-1 receptor agonist. PG - 108332 LID - S1056-8727(22)00244-6 [pii] LID - 10.1016/j.jdiacomp.2022.108332 [doi] AB - The objective of this article is to review the efficacy and safety of tirzepatide and discuss its potential role in the treatment of type 2 diabetes. Tirzepatide is a novel once-weekly dual GIP and GLP-1 receptor agonist which has been studied in the SURPASS clinical trials in doses of 5 mg, 10 mg, and 15 mg. Tirzepatide phase III clinical trials, SURPASS-1 through SURPASS-5, demonstrate that this medication is safe and effective in treating type 2 diabetes both with and without a variety of background medications versus placebo, semaglutide, insulin degludec, and insulin glargine in different patient populations. Most adverse events were gastrointestinal in nature, with a relatively low withdrawal rate in the active treatment arms. It seems likely that tirzepatide will be recommended as a preferred option in the American Diabetes Association treatment algorithm for high glucose lowering effects in patients with a compelling need for low hypoglycemia risk and weight loss. However, the positioning of tirzepatide in the treatment algorithm will ultimately be dependent on the results of the cardiovascular outcomes trial (CVOT) or other outcome-based trials. Tirzepatide is effective for treating type 2 diabetes by lowering glycated hemoglobin and contributing to significant weight loss. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Tall Bull, Shasta AU - Tall Bull S AD - University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, United States of America. Electronic address: shasta.tallbull@cuanschutz.edu. FAU - Nuffer, Wesley AU - Nuffer W AD - Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, United States of America. FAU - Trujillo, Jennifer M AU - Trujillo JM AD - Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, United States of America. LA - eng PT - Journal Article PT - Review DEP - 20221005 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - Gastric Inhibitory Polypeptide/adverse effects MH - Glycated Hemoglobin MH - Hypoglycemic Agents/adverse effects MH - Weight Loss MH - Clinical Trials, Phase III as Topic MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Antihyperglycemics OT - Diabetes OT - Drug information OT - Medication safety OT - Tirzepatide OT - Type 2 COIS- Declaration of competing interest The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Jennifer Trujillo serves as an advisory board member for Sanofi, Inc. Dr. Tall Bull and Dr. Nuffer have no conflicts to disclose. EDAT- 2022/11/15 06:00 MHDA- 2022/12/07 06:00 CRDT- 2022/11/14 18:15 PHST- 2022/08/12 00:00 [received] PHST- 2022/09/26 00:00 [revised] PHST- 2022/09/29 00:00 [accepted] PHST- 2022/11/15 06:00 [pubmed] PHST- 2022/12/07 06:00 [medline] PHST- 2022/11/14 18:15 [entrez] AID - S1056-8727(22)00244-6 [pii] AID - 10.1016/j.jdiacomp.2022.108332 [doi] PST - ppublish SO - J Diabetes Complications. 2022 Dec;36(12):108332. doi: 10.1016/j.jdiacomp.2022.108332. Epub 2022 Oct 5. PMID- 36367094 OWN - NLM STAT- MEDLINE DCOM- 20230626 LR - 20250103 IS - 1542-6270 (Electronic) IS - 1060-0280 (Linking) VI - 57 IP - 7 DP - 2023 Jul TI - Tirzepatide, the Newest Medication for Type 2 Diabetes: A Review of the Literature and Implications for Clinical Practice. PG - 822-836 LID - 10.1177/10600280221134127 [doi] AB - OBJECTIVE: The objective of this article was to review pharmacology, efficacy, safety, and place in therapy of tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. DATA SOURCES: PubMed/MEDLINE and ClinicalTrials.gov were searched through September 7, 2022, using the keyword "tirzepatide." STUDY SELECTION AND DATA EXTRACTION: Clinical trials with available results were included. DATA SYNTHESIS: Seven published phase 3, multicenter, randomized, parallel-group trials investigated efficacy and safety of tirzepatide versus placebo, semaglutide, insulin degludec, and insulin glargine for type 2 diabetes mellitus (T2DM) treatment. Studies included adults with uncontrolled T2DM and body mass index above 23 or 25 kg/m(2). Hemoglobin A1c reduction from baseline was greater with tirzepatide across all studies with absolute reductions up to 3.02% and relative reductions ranging 0.44% (vs semaglutide) to 2.11% (vs placebo). Weight loss was significant. Incidence of gastrointestinal adverse effects (AE) was similar to semaglutide, and major cardiovascular events was similar to insulin glargine. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Studies demonstrated greater A1c lowering and weight reduction versus placebo and active comparators with AE similar to semaglutide, suggesting tirzepatide will be a valuable addition to the growing list of antidiabetic medications. Although tirzepatide's effects on major cardiovascular events was not increased when compared with insulin glargine, further evidence is needed to assess long-term implications on cardiovascular outcomes compared with agents with proven cardiovascular benefits. CONCLUSIONS: Tirzepatide has the potential to significantly impact the clinical management of T2DM, and results of ongoing clinical trials will help to fully determine its place in therapy. FAU - Bradley, Courtney L AU - Bradley CL AD - Department of Clinical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC, USA. FAU - McMillin, Sara M AU - McMillin SM AD - Department of Basic Pharmaceutical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC, USA. FAU - Hwang, Andrew Y AU - Hwang AY AUID- ORCID: 0000-0002-9766-7711 AD - Department of Clinical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC, USA. FAU - Sherrill, Christina H AU - Sherrill CH AUID- ORCID: 0000-0003-1054-0644 AD - Department of Clinical Sciences, Fred Wilson School of Pharmacy, High Point University, High Point, NC, USA. LA - eng PT - Journal Article PT - Review DEP - 20221111 PL - United States TA - Ann Pharmacother JT - The Annals of pharmacotherapy JID - 9203131 RN - 2ZM8CX04RZ (Insulin Glargine) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Insulin Glargine/therapeutic use MH - Glycated Hemoglobin MH - Hypoglycemic Agents/adverse effects MH - Gastric Inhibitory Polypeptide/therapeutic use MH - Weight Loss MH - Multicenter Studies as Topic MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - diabetes OT - glucagon-like peptide-1 OT - glucose-dependent insulinotropic polypeptide OT - obesity OT - tirzepatide OT - twincretin OT - type 2 diabetes OT - weight loss EDAT- 2022/11/12 06:00 MHDA- 2023/06/26 06:41 CRDT- 2022/11/11 05:02 PHST- 2023/06/26 06:41 [medline] PHST- 2022/11/12 06:00 [pubmed] PHST- 2022/11/11 05:02 [entrez] AID - 10.1177/10600280221134127 [doi] PST - ppublish SO - Ann Pharmacother. 2023 Jul;57(7):822-836. doi: 10.1177/10600280221134127. Epub 2022 Nov 11. PMID- 36364937 OWN - NLM STAT- MEDLINE DCOM- 20221114 LR - 20260127 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 14 IP - 21 DP - 2022 Nov 4 TI - Once-Weekly Subcutaneous Semaglutide Improves Fatty Liver Disease in Patients with Type 2 Diabetes: A 52-Week Prospective Real-Life Study. LID - 10.3390/nu14214673 [doi] LID - 4673 AB - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is commonly observed in patients with type 2 diabetes (T2D). Semaglutide, a glucagon-like peptide 1 receptor agonist, may have a therapeutic role by targeting common mechanisms involved in the pathophysiology of T2D and NAFLD. The study aimed to assess the effectiveness of Semaglutide on NAFLD in patients with T2D. METHODS: Forty-eight patients were treated with subcutaneous Semaglutide in add-on to metformin for 52 weeks. After the baseline visit (T0), follow-up was scheduled quarterly (T3, and T6) and then at 12 months of therapy (T12). During each visit, body composition was analyzed by phase-sensitive bio-impedance, and NAFLD was diagnosed and staged by Ultrasound (US) imaging. Surrogate biomarkers of NAFLD were also calculated and followed over time. RESULTS: A significant decrease in anthropometric and glucometabolic parameters, insulin resistance, liver enzymes, and laboratory indices of hepatic steatosis was observed during treatment. Similarly, fat mass and visceral adipose tissue (VAT) decreased over time more than skeletal muscle and free-fat mass. US-assessed VAT thickness and the 12-point steatosis score also declined at T3 up to T12. Liver steatosis improved in most patients (70%), showing a reduction by at least one class in the semiquantitative US staging. CONCLUSION: Besides glucose control and body composition improvements, Semaglutide was effective in ameliorating the clinical appearance and severity of NAFLD in T2D patients. FAU - Volpe, Sara AU - Volpe S AUID- ORCID: 0000-0002-6831-0457 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Lisco, Giuseppe AU - Lisco G AUID- ORCID: 0000-0001-6521-8578 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Fanelli, Margherita AU - Fanelli M AUID- ORCID: 0000-0002-0128-9745 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Racaniello, Davide AU - Racaniello D AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Colaianni, Valentina AU - Colaianni V AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Triggiani, Domenico AU - Triggiani D AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Donghia, Rossella AU - Donghia R AUID- ORCID: 0000-0002-9140-673X AD - National Institute of Gastroenterology, "Saverio de Bellis", Research Hospital, Castellana Grotte, Via Turi 27, 70013 Bari, Italy. FAU - Crudele, Lucilla AU - Crudele L AUID- ORCID: 0000-0002-0541-6211 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Rinaldi, Roberta AU - Rinaldi R AUID- ORCID: 0000-0002-3817-8643 AD - National Institute of Gastroenterology, "Saverio de Bellis", Research Hospital, Castellana Grotte, Via Turi 27, 70013 Bari, Italy. FAU - Sabba, Carlo AU - Sabba C AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Triggiani, Vincenzo AU - Triggiani V AUID- ORCID: 0000-0001-6308-0528 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - De Pergola, Giovanni AU - De Pergola G AD - National Institute of Gastroenterology, "Saverio de Bellis", Research Hospital, Castellana Grotte, Via Turi 27, 70013 Bari, Italy. FAU - Piazzolla, Giuseppina AU - Piazzolla G AUID- ORCID: 0000-0003-3221-6562 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. LA - eng PT - Journal Article DEP - 20221104 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy/chemically induced MH - *Non-alcoholic Fatty Liver Disease/complications/drug therapy/chemically induced MH - Prospective Studies MH - Glucagon-Like Peptides/adverse effects MH - Semaglutide PMC - PMC9657108 OTO - NOTNLM OT - liver steatosis OT - metabolic associated fatty liver disease (MAFLD) OT - nonalcoholic fatty liver disease (NAFLD) OT - obesity OT - prospective study OT - real-life study OT - semaglutide OT - type 2 diabetes COIS- The authors declare no relevant conflict of interest. EDAT- 2022/11/12 06:00 MHDA- 2022/11/15 06:00 PMCR- 2022/11/04 CRDT- 2022/11/11 01:46 PHST- 2022/10/07 00:00 [received] PHST- 2022/10/29 00:00 [revised] PHST- 2022/11/01 00:00 [accepted] PHST- 2022/11/11 01:46 [entrez] PHST- 2022/11/12 06:00 [pubmed] PHST- 2022/11/15 06:00 [medline] PHST- 2022/11/04 00:00 [pmc-release] AID - nu14214673 [pii] AID - nutrients-14-04673 [pii] AID - 10.3390/nu14214673 [doi] PST - epublish SO - Nutrients. 2022 Nov 4;14(21):4673. doi: 10.3390/nu14214673. PMID- 36339230 OWN - NLM STAT- MEDLINE DCOM- 20221108 LR - 20260127 IS - 2296-2565 (Electronic) IS - 2296-2565 (Linking) VI - 10 DP - 2022 TI - Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system. PG - 996179 LID - 10.3389/fpubh.2022.996179 [doi] LID - 996179 AB - BACKGROUND: Semaglutide was approved for treatment of type 2 diabetes mellitus (T2DM) and chronic weight management in obesity or overweight adults. However, real-world data regarding its long-term gastrointestinal safety and tolerability in large sample population are incomplete. We evaluated semaglutide-associated gastrointestinal safety signals by data mining of the FDA pharmacovigilance database. METHODS: Reporting odds ratio (ROR) was employed to quantify the signals of semaglutide-related gastrointestinal adverse events (AEs) from 2018 to 2022. Serious and non-serious cases were compared by Mann-Whitney U test or Chi-squared (chi(2)) test, and signals were prioritized using a rating scale. RESULTS: We identified 5,442 cases of semaglutide-associated gastrointestinal AEs, with 45 signals detected, ranging from a ROR(025) of 1.01 (hypoaesthesia oral) to 42.03 (eructation), among which 17 AEs were identified as new and unexpected signals. Patient age (p < 0.001) and body weight (p = 0.006) rather than sex (p = 0.251) might be associated with an increased risk of gastrointestinal AEs severity. Notably, the association between semaglutide and gastrointestinal disorders remained when stratified by age, body weight, sex and reporter type. One strong, 22 moderate and 22 weak clinical priority signals were defined. The median time-to-onset (TTO) for strong clinical priority signal was 23 days, while for moderate and weak, they were 6 and 7 days, respectively. All of the disproportionality signals had early failure type features, suggesting that the risk of gastrointestinal AEs occurrence gradually decreased over time. CONCLUSION: Our study provided a deeper and broader understanding of semaglutide's gastrointestinal safety profiles, which would help healthcare professionals to mitigate the risk of gastrointestinal AEs in clinical practice. CI - Copyright (c) 2022 Shu, He, Wu, Liu, Ding and Zhang. FAU - Shu, Yamin AU - Shu Y AD - Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - He, Xucheng AU - He X AD - Department of Pharmacy, Pengzhou Second People's Hospital, Pengzhou, China. FAU - Wu, Pan AU - Wu P AD - Department of Pharmacy, Chengfei Hospital, Chengdu, China. FAU - Liu, Yanxin AU - Liu Y AD - Department of Pharmacy, Pengzhou People's Hospital, Pengzhou, China. FAU - Ding, Yufeng AU - Ding Y AD - Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Qilin AU - Zhang Q AD - Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221020 PL - Switzerland TA - Front Public Health JT - Frontiers in public health JID - 101616579 RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Humans MH - Pharmacovigilance MH - Adverse Drug Reaction Reporting Systems MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Drug-Related Side Effects and Adverse Reactions/epidemiology MH - Body Weight MH - Semaglutide PMC - PMC9631444 OTO - NOTNLM OT - FAERS OT - data mining OT - gastrointestinal adverse events OT - pharmacovigilance OT - semaglutide COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/11/08 06:00 MHDA- 2022/11/09 06:00 PMCR- 2022/10/20 CRDT- 2022/11/07 04:41 PHST- 2022/07/17 00:00 [received] PHST- 2022/09/30 00:00 [accepted] PHST- 2022/11/07 04:41 [entrez] PHST- 2022/11/08 06:00 [pubmed] PHST- 2022/11/09 06:00 [medline] PHST- 2022/10/20 00:00 [pmc-release] AID - 10.3389/fpubh.2022.996179 [doi] PST - epublish SO - Front Public Health. 2022 Oct 20;10:996179. doi: 10.3389/fpubh.2022.996179. eCollection 2022. PMID- 36254579 OWN - NLM STAT- MEDLINE DCOM- 20221215 LR - 20240916 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 25 IP - 1 DP - 2023 Jan TI - Semaglutide for the treatment of overweight and obesity: A review. PG - 18-35 LID - 10.1111/dom.14863 [doi] AB - Obesity is a chronic, relapsing disease associated with multiple complications and a substantial morbidity, mortality and health care burden. Pharmacological treatments for obesity provide a valuable adjunct to lifestyle intervention, which often achieves only limited weight loss that is difficult to maintain. The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme is evaluating once-weekly subcutaneous semaglutide 2.4 mg (a glucagon-like peptide-1 analogue) in people with overweight or obesity. Across STEP 1, 3, 4 and 8, semaglutide 2.4 mg was associated with mean weight losses of 14.9%-17.4% in individuals with overweight or obesity without type 2 diabetes from baseline to week 68; 69%-79% of participants achieved >/=10% weight loss with semaglutide 2.4 mg (vs. 12%-27% with placebo) and 51%-64% achieved >/=15% weight loss (vs. 5%-13% with placebo). In STEP 5, mean weight loss was -15.2% with semaglutide 2.4 mg versus -2.6% with placebo from baseline to week 104. In STEP 2 (individuals with overweight or obesity, and type 2 diabetes), mean weight loss was -9.6% with semaglutide 2.4 mg versus -3.4% with placebo from baseline to week 68. Improvements in cardiometabolic risk factors, including high blood pressure, atherogenic lipids and benefits on physical function and quality of life were seen with semaglutide 2.4 mg. The safety profile of semaglutide 2.4 mg was consistent across trials, primarily gastrointestinal adverse events. The magnitude of weight loss reported in the STEP trials offers the potential for clinically relevant improvement for individuals with obesity-related diseases. CI - (c) 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Bergmann, Natasha Chidekel AU - Bergmann NC AUID- ORCID: 0000-0002-6797-8041 AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Davies, Melanie J AU - Davies MJ AUID- ORCID: 0000-0002-9987-9371 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - NIHR Leicester Biomedical Research Centre, Leicester, UK. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology and Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA. FAU - Knop, Filip K AU - Knop FK AUID- ORCID: 0000-0002-2495-5034 AD - Steno Diabetes Center Copenhagen, Herlev, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Review DEP - 20221018 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Quality of Life MH - Weight Loss MH - Obesity/complications/drug therapy PMC - PMC10092086 OTO - NOTNLM OT - GLP-1 analogue OT - anti-obesity drug OT - obesity therapy OT - weight management COIS- NCB declared no conflict of interest. MJD is a consultant, advisory board member and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi-Aventis; advisory board member and speaker for AstraZeneca; advisory board member for Gilead Sciences Ltd, Janssen, Lexicon, Pfizer and Servier; speaker for Mitsubishi Tanabe Pharma Corporation, Napp Pharmaceuticals and Takeda Pharmaceuticals International Inc.; received grants to support investigator and investigator-initiated trials from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Novo Nordisk and Sanofi-Aventis. MJD is co-funded by the NIHR Leicester Biomedical Research Centre. IL obtained research funding, advisory/consulting fees, and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, GI Dynamics, Intarcia, Intercept, Janssen, Eli Lilly, Mannkind, Merck, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, TARGETPharma, Valeritas and Zealand Pharma. FKK served on scientific advisory panels and/or been part of speaker bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gubra, Lupin, MedImmune, MSD/Merck, Mundipharma, Norgine, Novo Nordisk, Pharmacosmos, Sanofi, ShouTi, Zealand Pharma and Zucara; minority shareholder in Antag Therapeutics. EDAT- 2022/10/19 06:00 MHDA- 2022/12/15 06:00 PMCR- 2023/04/12 CRDT- 2022/10/18 03:43 PHST- 2022/09/01 00:00 [revised] PHST- 2022/05/31 00:00 [received] PHST- 2022/09/04 00:00 [accepted] PHST- 2022/10/19 06:00 [pubmed] PHST- 2022/12/15 06:00 [medline] PHST- 2022/10/18 03:43 [entrez] PHST- 2023/04/12 00:00 [pmc-release] AID - DOM14863 [pii] AID - 10.1111/dom.14863 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Jan;25(1):18-35. doi: 10.1111/dom.14863. Epub 2022 Oct 18. PMID- 36251282 OWN - NLM STAT- MEDLINE DCOM- 20230104 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 25 IP - 2 DP - 2023 Feb TI - Once-weekly semaglutide versus insulin aspart for the treatment of type 2 diabetes in the UK: A long-term cost-effectiveness analysis based on SUSTAIN 11. PG - 491-500 LID - 10.1111/dom.14892 [doi] AB - AIM: To evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus insulin aspart in the UK. MATERIALS AND METHODS: Long-term outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (vers 9.0). SUSTAIN 11 was used to inform baseline cohort characteristics and treatment effects. Patients were modelled to receive once-weekly semaglutide plus basal insulin for 3 years before intensifying to basal-bolus insulin, compared with basal-bolus insulin for lifetimes in the aspart arm. Costs were accounted from a healthcare payer perspective in the UK, expressed in 2021 pounds sterling (GBP). RESULTS: Once-weekly semaglutide 1 mg was associated with improvements in quality-adjusted life expectancy of 0.18 quality-adjusted life years (QALYs) versus insulin aspart, due to a reduced incidence and delayed time to onset of diabetes-related complications. Direct costs were estimated to be GBP 800 higher with semaglutide, with higher treatment costs partially offset by cost savings from avoidance of diabetes-related complications. Once-weekly semaglutide 1 mg was therefore associated with an incremental cost-effectiveness ratio of GBP 4457 per QALY gained versus insulin aspart. CONCLUSIONS: Based on a willingness-to-pay threshold of GBP 20 000 per QALY gained, once-weekly semaglutide 1 mg was projected to be highly cost-effective versus insulin aspart for the treatment of type 2 diabetes in the UK. CI - (c) 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Evans, Marc AU - Evans M AUID- ORCID: 0000-0003-0671-0778 AD - Diabetes Resource Centre, University Hospital Llandough, Cardiff, UK. FAU - Chubb, Barrie AU - Chubb B AUID- ORCID: 0000-0001-7271-051X AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Malkin, Samuel J P AU - Malkin SJP AUID- ORCID: 0000-0003-1306-7784 AD - Ossian Health Economics and Communications, Basel, Switzerland. FAU - Berry, Sasha AU - Berry S AD - Novo Nordisk Ltd, Gatwick, UK. FAU - Lawson, Jack AU - Lawson J AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hunt, Barnaby AU - Hunt B AUID- ORCID: 0000-0001-5420-279X AD - Ossian Health Economics and Communications, Basel, Switzerland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221102 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - D933668QVX (Insulin Aspart) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/epidemiology MH - Insulin Aspart/adverse effects MH - Hypoglycemic Agents MH - Cost-Effectiveness Analysis MH - Cost-Benefit Analysis MH - *Diabetes Complications/epidemiology MH - Quality-Adjusted Life Years MH - United Kingdom/epidemiology MH - Semaglutide PMC - PMC10092031 OTO - NOTNLM OT - UK OT - cost OT - cost-effectiveness OT - insulin aspart OT - semaglutide COIS- ME has received consulting fees or honoraria from Novo Nordisk, NAPP, MSD, AstraZeneca, Sunovion and Novartis; and lecture/speaker bureau fees from Novo Nordisk, NAPP, Mundipharma, AstraZeneca, MSD, Sunovion and Novartis. SB is an employee of Novo Nordisk Ltd. BC and JL are employees of Novo Nordisk A/S. BC holds stock in Novo Nordisk A/S. SJPM and BH are employees of Ossian Health Economics and Communications, which received consulting fees from Novo Nordisk A/S to support preparation of the analysis. EDAT- 2022/10/18 06:00 MHDA- 2023/01/05 06:00 PMCR- 2023/04/12 CRDT- 2022/10/17 11:28 PHST- 2022/09/29 00:00 [revised] PHST- 2022/07/27 00:00 [received] PHST- 2022/10/09 00:00 [accepted] PHST- 2022/10/18 06:00 [pubmed] PHST- 2023/01/05 06:00 [medline] PHST- 2022/10/17 11:28 [entrez] PHST- 2023/04/12 00:00 [pmc-release] AID - DOM14892 [pii] AID - 10.1111/dom.14892 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Feb;25(2):491-500. doi: 10.1111/dom.14892. Epub 2022 Nov 2. PMID- 36250469 OWN - NLM STAT- MEDLINE DCOM- 20221130 LR - 20230222 IS - 1473-6543 (Electronic) IS - 1062-4821 (Linking) VI - 32 IP - 1 DP - 2023 Jan 1 TI - The changing trajectory of diabetic kidney disease. PG - 98-102 LID - 10.1097/MNH.0000000000000844 [doi] AB - PURPOSE OF REVIEW: Progression of diabetic kidney disease has slowed over the past 40 years by as much as 70-75%, thanks to a diversity of drug classes that have less effect on glucose and more on reducing cardiorenal risk. RECENT FINDINGS: With the advent of sodium-glucose co-transporter 2 (SGLT2) inhibitors and the novel nonsteroidal mineralocorticoid antagonist, finerenone, we now have three 'pillars of therapy' considering the renin-angiotensin system (RAS) inhibitors as already established treatment to slow diabetic kidney disease. Both renal and cardiovascular outcomes trials have provided solid evidence of the benefit by these agents to slow kidney disease progression and reduce heart failure hospitalizations. Using these agents together reduces the risk of hyperkalemia by finerenone and further reduces albuminuria in animal models. Trials are underway to also see if the glucagon-like peptide 1 receptor agonist, semaglutide, will also protect against diabetic kidney disease progression as seen in post hoc analyses of positive cardiovascular outcome trials. If positive, this would be the fourth pillar to support cardiorenal protection without fear of hypoglycemia. SUMMARY: Nephrologists now have three different agents neither of which has a major effect on blood pressure but both add to further reduce progression of diabetic nephropathy and hospitalization from heart failure. CI - Copyright (c) 2022 Wolters Kluwer Health, Inc. All rights reserved. FAU - Mistry, Nupur AU - Mistry N AD - Department of Medicine, Am Heart Assoc Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, Illinois, USA. FAU - Bakris, George L AU - Bakris GL LA - eng PT - Journal Article PT - Review DEP - 20221013 PL - England TA - Curr Opin Nephrol Hypertens JT - Current opinion in nephrology and hypertension JID - 9303753 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Mineralocorticoid Receptor Antagonists) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Humans MH - *Diabetic Nephropathies MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Mineralocorticoid Receptor Antagonists/therapeutic use MH - *Heart Failure/drug therapy MH - Glucose/therapeutic use EDAT- 2022/10/18 06:00 MHDA- 2022/12/01 06:00 CRDT- 2022/10/17 06:03 PHST- 2022/10/18 06:00 [pubmed] PHST- 2022/12/01 06:00 [medline] PHST- 2022/10/17 06:03 [entrez] AID - 00041552-202301000-00015 [pii] AID - 10.1097/MNH.0000000000000844 [doi] PST - ppublish SO - Curr Opin Nephrol Hypertens. 2023 Jan 1;32(1):98-102. doi: 10.1097/MNH.0000000000000844. Epub 2022 Oct 13. PMID- 36243180 OWN - NLM STAT- MEDLINE DCOM- 20221216 LR - 20230216 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 370 DP - 2023 Jan 1 TI - How important it is to know the preferences of the diabetic patient. PG - 425-426 LID - S0167-5273(22)01528-5 [pii] LID - 10.1016/j.ijcard.2022.10.017 [doi] FAU - Tamargo, Juan AU - Tamargo J AD - Department of Pharmacology and Toxicology, School of Medicine, Universidad Complutense, Instituto De Investigacion Sanitaria Gregorio Maranon, Madrid, Spain. Electronic address: jtamargo@med.ucm.es. LA - eng PT - Editorial DEP - 20221013 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 62340-29-8 (Glucagon-Like Peptides) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Hypoglycemic Agents) SB - IM CIN - Int J Cardiol. 2023 Feb 15;373:79. doi: 10.1016/j.ijcard.2022.11.061. PMID: 36462701 MH - Humans MH - *Glucagon-Like Peptides MH - Sitagliptin Phosphate MH - *Diabetes Mellitus, Type 2/diagnosis MH - Hypoglycemic Agents OTO - NOTNLM OT - Empagliflozin OT - Glucose-lowering drugs OT - Patient preferences OT - Semaglutide OT - Sitagliptin OT - Type 2 diabetes mellitus COIS- Declaration of Competing Interest The author states no conflict of interest. EDAT- 2022/10/16 06:00 MHDA- 2022/12/15 06:00 CRDT- 2022/10/15 19:34 PHST- 2022/10/05 00:00 [received] PHST- 2022/10/07 00:00 [accepted] PHST- 2022/10/16 06:00 [pubmed] PHST- 2022/12/15 06:00 [medline] PHST- 2022/10/15 19:34 [entrez] AID - S0167-5273(22)01528-5 [pii] AID - 10.1016/j.ijcard.2022.10.017 [doi] PST - ppublish SO - Int J Cardiol. 2023 Jan 1;370:425-426. doi: 10.1016/j.ijcard.2022.10.017. Epub 2022 Oct 13. PMID- 36238196 OWN - NLM STAT- MEDLINE DCOM- 20221017 LR - 20260127 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 16 DP - 2022 TI - Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120/ABHD6. PG - 3557-3572 LID - 10.2147/DDDT.S384884 [doi] AB - OBJECTIVE: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has been extensively studied, the role of its underlying pathogenesis remains unclear, and there is currently no approved therapeutic strategy for NAFLD. The purpose of this study was to observe the beneficial effects of Semaglutide on NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. METHODS: Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by liver function, blood lipids, liver lipids, H&E staining, oil red staining and Sirius staining. The expression of alpha/beta hydrolase domain-6 (ABHD6) was measured by qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. RESULTS: Our data revealed that Semaglutide administration significantly improved liver function and hepatic steatosis in T2DM combined with NAFLD mice. Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 1-6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression was significantly decreased in the liver of T2DM+NAFLD mice and in HG+FFA-stimulated Hepa 1-6 hepatocytes, while miR-5120 expression was increased. We also found that miR-5120 could regulate the expression of ABHD6 in hepatocytes, while Semaglutide could modulate the expression of ABHD6 through miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and Hepa 1-6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through GLP-1R. CONCLUSION: Our data revealed the underlying mechanism by which Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD. CI - (c) 2022 Li et al. FAU - Li, Ran AU - Li R AUID- ORCID: 0000-0003-2304-6282 AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. FAU - Ye, Zhengqin AU - Ye Z AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. FAU - She, Dunmin AU - She D AD - Clinical Medical College, Yangzhou University, Yangzhou, People's Republic of China. AD - Department of Endocrinology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, People's Republic of China. FAU - Fang, Ping AU - Fang P AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. FAU - Zong, Guannan AU - Zong G AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. FAU - Hu, Kerong AU - Hu K AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. FAU - Kong, Dehong AU - Kong D AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. FAU - Xu, Wei AU - Xu W AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. FAU - Li, Ling AU - Li L AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. FAU - Zhou, Yun AU - Zhou Y AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. FAU - Zhang, Keqin AU - Zhang K AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. FAU - Xue, Ying AU - Xue Y AUID- ORCID: 0000-0002-6812-5665 AD - Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China. LA - eng PT - Journal Article DEP - 20221012 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (MicroRNAs) RN - EC 3.1.1.23 (Monoacylglycerol Lipases) RN - 53AXN4NNHX (Semaglutide) RN - EC 3.1.1.23 (ABHD6 protein, mouse) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2/metabolism MH - Glucagon-Like Peptides MH - Liver/metabolism MH - Mice MH - Mice, Inbred C57BL MH - *MicroRNAs/genetics/metabolism MH - Monoacylglycerol Lipases/metabolism MH - *Non-alcoholic Fatty Liver Disease/metabolism MH - Semaglutide PMC - PMC9553160 OTO - NOTNLM OT - Semaglutide OT - microRNA-5120 OT - non-alcoholic fatty liver disease OT - type 2 diabetes mellitus OT - alpha/beta hydrolase domain-6 COIS- The authors declare that they have no conflict of interest. EDAT- 2022/10/15 06:00 MHDA- 2022/10/18 06:00 PMCR- 2022/10/12 CRDT- 2022/10/14 03:01 PHST- 2022/08/03 00:00 [received] PHST- 2022/10/06 00:00 [accepted] PHST- 2022/10/14 03:01 [entrez] PHST- 2022/10/15 06:00 [pubmed] PHST- 2022/10/18 06:00 [medline] PHST- 2022/10/12 00:00 [pmc-release] AID - 384884 [pii] AID - 10.2147/DDDT.S384884 [doi] PST - epublish SO - Drug Des Devel Ther. 2022 Oct 12;16:3557-3572. doi: 10.2147/DDDT.S384884. eCollection 2022. PMID- 36222597 OWN - NLM STAT- MEDLINE DCOM- 20221206 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 13 IP - 12 DP - 2022 Dec TI - Efficacy and safety of once-weekly semaglutide in Japanese individuals with type 2 diabetes in the SUSTAIN 1, 2, 5 and 9 trials: Post-hoc analysis. PG - 1971-1980 LID - 10.1111/jdi.13905 [doi] AB - AIMS/INTRODUCTION: The etiology and treatment of type 2 diabetes might differ between specific populations. This post-hoc exploratory analysis assessed the efficacy and safety of once-weekly subcutaneous semaglutide vs comparators in Japanese individuals with type 2 diabetes in comparison with the total population from four phase III studies in the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN) program. MATERIALS AND METHODS: This analysis was carried out with data from the SUSTAIN 1, 2, 5 and 9 trials. Post-hoc analyses were carried out to assess outcomes in all participants and in Japanese participants in each study. The primary end-point was the change from baseline to end of study in glycated hemoglobin (%). The confirmatory secondary end-point was change from baseline to end of study in bodyweight (kg). RESULTS: Change from baseline to end of study in glycated hemoglobin with once-weekly semaglutide ranged from -1.32 to -1.85% points in the overall populations, and -1.69 to -2.49% points in Japanese participants. With once-weekly semaglutide, relative bodyweight was reduced from baseline to end of study by 4.0-7.3% in the overall populations, and 2.7-10.4% in Japanese participants. In the Japanese subpopulation, no new safety concerns were identified with once-weekly semaglutide, and there were no adverse events leading to death or severe hypoglycemic episodes. CONCLUSIONS: In this post-hoc analysis, participants with type 2 diabetes initiating once-weekly semaglutide experienced improvements in glycated hemoglobin and bodyweight in both the overall and Japanese population, and no new safety concerns were identified among Japanese participants, supporting the efficacy of once-weekly semaglutide in this population. CI - (c) 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Araki, Eiichi AU - Araki E AUID- ORCID: 0000-0002-4064-7525 AD - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. FAU - Harashima, Shinichi AU - Harashima S AD - Goshominami Harashima Clinic, Human Health Science Graduate School of Medicine, Kyoto University, Kyoto, Japan. FAU - Nishida, Tomoyuki AU - Nishida T AD - Novo Nordisk Pharma Ltd., Tokyo, Japan. FAU - Nakamura, Jiro AU - Nakamura J AD - Aichi Medical University, Nagakute, Japan. LA - eng PT - Journal Article DEP - 20221012 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/chemically induced MH - Glycated Hemoglobin/analysis MH - Japan MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptides/adverse effects MH - Body Weight MH - Treatment Outcome MH - Semaglutide PMC - PMC9720207 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor OT - Glycated hemoglobin OT - Treatment EDAT- 2022/10/13 06:00 MHDA- 2022/12/07 06:00 PMCR- 2022/12/01 CRDT- 2022/10/12 09:33 PHST- 2022/08/23 00:00 [revised] PHST- 2022/06/24 00:00 [received] PHST- 2022/08/29 00:00 [accepted] PHST- 2022/10/13 06:00 [pubmed] PHST- 2022/12/07 06:00 [medline] PHST- 2022/10/12 09:33 [entrez] PHST- 2022/12/01 00:00 [pmc-release] AID - JDI13905 [pii] AID - 10.1111/jdi.13905 [doi] PST - ppublish SO - J Diabetes Investig. 2022 Dec;13(12):1971-1980. doi: 10.1111/jdi.13905. Epub 2022 Oct 12. PMID- 36216945 OWN - NLM STAT- MEDLINE DCOM- 20221014 LR - 20260127 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 28 IP - 10 DP - 2022 Oct TI - Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. PG - 2083-2091 LID - 10.1038/s41591-022-02026-4 [doi] AB - The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment of adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes. The co-primary endpoints were the percentage change in body weight and achievement of weight loss of >/=5% at week 104. Efficacy was assessed among all randomized participants regardless of treatment discontinuation or rescue intervention. From 5 October 2018 to 1 February 2019, 304 participants were randomly assigned to semaglutide 2.4 mg (n = 152) or placebo (n = 152), 92.8% of whom completed the trial (attended the end-of-trial safety visit). Most participants were female (236 (77.6%)) and white (283 (93.1%)), with a mean (s.d.) age of 47.3 (11.0) years, body mass index of 38.5 (6.9) kg m(-2) and weight of 106.0 (22.0) kg. The mean change in body weight from baseline to week 104 was -15.2% in the semaglutide group (n = 152) versus -2.6% with placebo (n = 152), for an estimated treatment difference of -12.6 %-points (95% confidence interval, -15.3 to -9.8; P < 0.0001). More participants in the semaglutide group than in the placebo group achieved weight loss >/=5% from baseline at week 104 (77.1% versus 34.4%; P < 0.0001). Gastrointestinal adverse events, mostly mild-to-moderate, were reported more often with semaglutide than with placebo (82.2% versus 53.9%). In summary, in adults with overweight (with at least one weight-related comorbidity) or obesity, semaglutide treatment led to substantial, sustained weight loss over 104 weeks versus placebo. NCT03693430. CI - (c) 2022. The Author(s). FAU - Garvey, W Timothy AU - Garvey WT AUID- ORCID: 0000-0003-0822-0860 AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA. garveyt@uab.edu. FAU - Batterham, Rachel L AU - Batterham RL AUID- ORCID: 0000-0002-5477-8585 AD - University College London Centre for Obesity Research, Division of Medicine, University College London, London, UK. AD - National Institute of Health Research, UCLH Biomedical Research Centre, London, UK. AD - Centre for Weight Management and Metabolic Surgery, University College London Hospital, London, UK. FAU - Bhatta, Meena AU - Bhatta M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Buscemi, Silvio AU - Buscemi S AUID- ORCID: 0000-0003-0730-7649 AD - Unit of Clinical Nutrition, Policlinico University Hospital, Palermo, Italy. AD - Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy. FAU - Christensen, Louise N AU - Christensen LN AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Frias, Juan P AU - Frias JP AD - National Research Institute, Los Angeles, CA, USA. FAU - Jodar, Esteban AU - Jodar E AUID- ORCID: 0000-0002-1234-8560 AD - Department of Endocrinology and Nutrition, Hospital Universitario QuironSalud Madrid, Universidad Europea de Madrid, Madrid, Spain. FAU - Kandler, Kristian AU - Kandler K AUID- ORCID: 0000-0003-0686-0549 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rigas, Georgia AU - Rigas G AD - Department of Bariatric Metabolic Surgery, St George Private Hospital, Kogarah, Sydney, Australia. FAU - Wadden, Thomas A AU - Wadden TA AD - Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Wharton, Sean AU - Wharton S AD - York University, McMaster University and Wharton Weight Management Clinic, Toronto, ON, Canada. CN - STEP 5 Study Group LA - eng SI - ClinicalTrials.gov/NCT03693430 GR - P30 DK056336/DK/NIDDK NIH HHS/United States GR - P30 DK079626/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20221010 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Nat Med. 2022 Oct;28(10):2005-2006. doi: 10.1038/s41591-022-02032-6. PMID: 36216946 MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Male MH - Middle Aged MH - Obesity/complications/drug therapy MH - *Overweight/complications/drug therapy MH - Treatment Outcome MH - Weight Loss MH - Semaglutide PMC - PMC9556320 COIS- W.T.G. reports a grant from Novo Nordisk; serving as site principal investigator for the current clinical trial, which was sponsored by his university during the conduct of the study; and receiving grants to serve as site principal investigator for other university-sponsored clinical trials funded by Eli Lilly & Company, Lexicon, Epitomee and Pfizer outside the submitted work. He also served as a compensated consultant on advisory committees for Alnylam, Amgen, Boehringer Ingelheim, Fractyl and Novo Nordisk, and a volunteer uncompensated consultant on advisory committees for Boehringer Ingelheim, Jazz Pharmaceuticals, Novo Nordisk and Pfizer. R.L.B. reports research grant support, on behalf of their institution, from Novo Nordisk and advisory/consultancy fees from Boehringer Ingelheim, Eli Lilly & Company, Gila Therapeutics Inc, GLW-01, International Medical Press, Novo Nordisk, Pfizer and ViiV. M.B. is an employee of Novo Nordisk A/S. S.B. served as site principal investigator for the clinical trial (he received no financial compensation, nor was there a financial relationship) and reports advisory/consulting fees and/or other support from Boehringer Ingelheim, Eli Lilly & Company, Guidotti Laboratories, Menarini Diagnostics, Novo Nordisk and Therascience Lignaform. L.N.C. is an employee of Novo Nordisk A/S. J.P.F. reports research support grants from Akero, AstraZeneca, Boehringer Ingelheim, BMS, 89bio, Eli Lilly & Company, Intercept, IONIS, Janssen, Madrigal, Metacrine, Merck, NorthSea Therapeutics, Novartis, Novo Nordisk, Oramed, Pfizer, Poxel and Sanofi; and advisory/consultancy fees from Akero, Altimmune, Axcella Health, Becton Dickenson, Boehringer Ingelheim, Carmot Therapeutics, Echosens, 89bio, Eli Lilly & Company, Gilead, Intercept, Metacrine, Merck, Novo Nordisk, Pfizer and Sanofi. E.J. reports grants from Amgen, AstraZeneca, Boehringer Ingelheim, FAES, Janssen, Eli Lilly & Company, MSD, Novo Nordisk, Pfizer, Sanofi, Shire and UCB; personal fees from Amgen, AstraZeneca, FAES, Helios-Fresenius, Italfarmaco, Eli Lilly & Company, MSD, Mundipharma, Novo Nordisk, UCB and Viatris. K.K. is an employee of Novo Nordisk A/S. G.R. reports personal (advisory/consultancy and lecture) fees and nonfinancial support from iNova Pharmaceuticals, Nestle HealthScience and Novo Nordisk; personal (lecture) fees from Johnson & Johnson, Medtronic (formerly Covidien), Merck Sharpe & Dohme, ReShape Lifesciences (formerly Apollo-Endosurgery and Allergan Australia) and W.L. Gore Device Technologies. T.A.W. serves on advisory boards for Novo Nordisk and WW (formerly Weight Watchers), and has received grant support, on behalf of the University of Pennsylvania, from Novo Nordisk and from Epitomee Medical Ltd (the latter outside of the submitted work). S.W. reports research funding, advisory/consulting fees and/or other support from AstraZeneca, Bausch Health Inc., Boehringer Ingelheim, CIHR, Janssen, Eli Lilly & Company and Novo Nordisk. EDAT- 2022/10/11 06:00 MHDA- 2022/10/15 06:00 PMCR- 2022/10/10 CRDT- 2022/10/10 23:27 PHST- 2022/03/30 00:00 [received] PHST- 2022/08/24 00:00 [accepted] PHST- 2022/10/11 06:00 [pubmed] PHST- 2022/10/15 06:00 [medline] PHST- 2022/10/10 23:27 [entrez] PHST- 2022/10/10 00:00 [pmc-release] AID - 10.1038/s41591-022-02026-4 [pii] AID - 2026 [pii] AID - 10.1038/s41591-022-02026-4 [doi] PST - ppublish SO - Nat Med. 2022 Oct;28(10):2083-2091. doi: 10.1038/s41591-022-02026-4. Epub 2022 Oct 10. PMID- 36208922 OWN - NLM STAT- MEDLINE DCOM- 20221011 LR - 20260127 IS - 0042-773X (Print) IS - 0042-773X (Linking) VI - 68 IP - 2 DP - 2022 Summer TI - [Oral semaglutide - Rybelsus(R), the first GLP-1 receptor agonist for oral use in clinical practice]. PG - 89-95 AB - Glucagon like peptide-1 receptor agonists (GLP-1 RA) are potent antidiabetic drugs associated with significant weight loss and minimal risk of hypoglycemia. Semaglutide is a GLP-1 RA with a proven cardiovascular benefit. It is currently also available in oral form, which is especially suitable for the treatment of the initial phase of type 2 diabetes. However, it is also effective at later initiation of therapy, in different diabetic populations. The PIONEER 6 trial demonstrated cardiovascular safety of oral semaglutide, its administration was accompanied by a significant reduction in cardiovascular and overall mortality. FAU - Karasek, David AU - Karasek D LA - cze PT - Journal Article TT - Oralni semaglutid - Rybelsus(R), prvni agonista GLP-1 receptoru pro peroralni použiti v klinicke praxi. PL - Czech Republic TA - Vnitr Lek JT - Vnitrni lekarstvi JID - 0413602 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptides MH - Glycated Hemoglobin MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - cardiovascular benefit OT - glycated hemoglobin OT - oral semaglutide OT - type 2 diabetes OT - type 2 diabetes EDAT- 2022/10/09 06:00 MHDA- 2022/10/12 06:00 CRDT- 2022/10/08 21:38 PHST- 2022/10/08 21:38 [entrez] PHST- 2022/10/09 06:00 [pubmed] PHST- 2022/10/12 06:00 [medline] AID - 131836 [pii] PST - ppublish SO - Vnitr Lek. 2022 Summer;68(2):89-95. PMID- 36201244 OWN - NLM STAT- MEDLINE DCOM- 20221010 LR - 20260127 IS - 1538-4683 (Electronic) IS - 1061-5377 (Linking) VI - 30 IP - 6 DP - 2022 Nov-Dec 01 TI - Semaglutide for Weight Loss: Was It Worth the Weight? PG - 324-329 LID - 10.1097/CRD.0000000000000430 [doi] AB - Obesity is a major public health issue with an increasing prevalence worldwide. Excess body fat is associated with various comorbidities, as well as increased overall mortality risk. The benefits of weight loss are evident by the reductions in morbidity and mortality. The foundation for most weight loss programs involves strict lifestyle modification, including dietary change and exercise. Unfortunately, many individuals struggle with weight loss and chronic weight management due to difficulty adhering to long-term lifestyle modification and the metabolic adaptations that promote weight regain. The use of adjunctive pharmacotherapy has been employed to help patients not only achieve greater weight loss than lifestyle modification alone but also to assist with long-term weight management. Historically, antiobesity drugs have produced only modest weight loss and required at least once daily administration. Glucagon-like peptide-1 (GLP-1), a hormone with significant effects on glycemic control and weight regulation, has been explored for use as adjunctive pharmacotherapy for weight loss. Semaglutide, a GLP-1 receptor agonist, was recently approved by the Food and Drug Administration for chronic weight management in adults with obesity or who are overweight. The approval came after the publication of the Semaglutide Treatment Effect in People with Obesity clinical trials. In these 68-week trials, semaglutide 2.4 mg was associated with significantly greater weight loss compared to placebo. Semaglutide differs from other GLP-1 receptor agonists by having a longer half-life and producing greater weight loss. This article provides an overview of the discovery and mechanism of action of semaglutide 2.4 mg, and the clinical trials that led to its approval. CI - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved. FAU - Novograd, Joel AU - Novograd J AD - From the New York Medical College (student) Valhalla, NY. FAU - Mullally, Jaime AU - Mullally J AD - Department of Medicine, Division of Endocrinology, New York Medical College/Westchester Medical Center, Valhalla, NY. FAU - Frishman, William H AU - Frishman WH AD - Department of Medicine, New York Medical College Valhalla, NY. LA - eng PT - Journal Article DEP - 20220121 PL - United States TA - Cardiol Rev JT - Cardiology in review JID - 9304686 RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - *Anti-Obesity Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Obesity/complications/drug therapy/epidemiology MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide COIS- Disclosure: The authors have no conflicts of interest to report. EDAT- 2022/10/07 06:00 MHDA- 2022/10/12 06:00 CRDT- 2022/10/06 11:53 PHST- 2022/10/06 11:53 [entrez] PHST- 2022/10/07 06:00 [pubmed] PHST- 2022/10/12 06:00 [medline] AID - 00045415-202211000-00009 [pii] AID - 10.1097/CRD.0000000000000430 [doi] PST - ppublish SO - Cardiol Rev. 2022 Nov-Dec 01;30(6):324-329. doi: 10.1097/CRD.0000000000000430. Epub 2022 Jan 21. PMID- 36200477 OWN - NLM STAT- MEDLINE DCOM- 20230104 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 25 IP - 2 DP - 2023 Feb TI - Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses. PG - 468-478 LID - 10.1111/dom.14890 [doi] AB - AIMS: Evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on cardiometabolic risk factors in people with overweight/obesity without diabetes in the STEP 1 and 4 trials. MATERIALS AND METHODS: STEP 1 and 4 were phase III, 68-week, placebo-controlled trials of once-weekly semaglutide 2.4 mg combined with lifestyle intervention; STEP 4 had a 20-week semaglutide run-in and 48-week randomized withdrawal period. Participants had a body mass index >/=30 kg/m(2) or >/=27 kg/m(2) with one or more weight-related comorbidity, without diabetes. Pre-specified endpoints were changes in waist circumference, systolic/diastolic blood pressure (SBP/DBP), lipids, fasting plasma glucose (FPG), fasting serum insulin and antihypertensive/lipid-lowering medication use. Post-hoc assessments included non-high-density lipoprotein (HDL) cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR; STEP 1 only), atherosclerotic cardiovascular disease (ASCVD) risk (American College of Cardiology/American Heart Association algorithm; STEP 1 only) and cardiometabolic risk factors by weight loss achieved (<5%, 5% to <10%, 10% to <15%, or >/=15%) (STEP 1 only). RESULTS: Of the 1961 participants in STEP 1 and 803 in STEP 4, most had one or more complication/comorbidity at baseline, with dyslipidaemia and hypertension most prevalent. In STEP 1, reductions in waist circumference, SBP, DBP, FPG, fasting serum insulin, lipids and HOMA-IR were greater with semaglutide versus placebo (p .05). In STEP 4, improvements in waist circumference, SBP, FPG, fasting serum insulin and lipids during the semaglutide run-in (week 0-20) were maintained over week 20-68 with continued semaglutide, but deteriorated following the switch to placebo (p < .001 [week 20-68]). Net reductions in antihypertensive/lipid-lowering medication use occurred with semaglutide versus placebo (both trials). CONCLUSIONS: Semaglutide may improve cardiometabolic risk factors and reduce antihypertensive/lipid-lowering medication use versus placebo in adults with overweight/obesity without diabetes. These potential benefits were not maintained after treatment discontinuation. GOV NUMBERS: STEP 1 NCT03548935, STEP 4 NCT03548987. CI - (c) 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kosiborod, Mikhail N AU - Kosiborod MN AUID- ORCID: 0000-0002-3750-9789 AD - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute and University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. FAU - Bhatta, Meena AU - Bhatta M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Davies, Melanie AU - Davies M AUID- ORCID: 0000-0002-9987-9371 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - NIHR Leicester Biomedical Research Centre, Leicester, UK. FAU - Deanfield, John E AU - Deanfield JE AD - Institute of Cardiovascular Science, University College London, London, UK. FAU - Garvey, W Timothy AU - Garvey WT AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA. FAU - Khalid, Usman AU - Khalid U AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kushner, Robert AU - Kushner R AD - Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. FAU - Rubino, Domenica M AU - Rubino DM AD - Washington Center for Weight Management and Research, Arlington, Virginia, USA. FAU - Zeuthen, Niels AU - Zeuthen N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Verma, Subodh AU - Verma S AD - Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada. LA - eng SI - ClinicalTrials.gov/NCT03548935 SI - ClinicalTrials.gov/NCT03548987 GR - P30 DK056336/DK/NIDDK NIH HHS/United States GR - P30 DK079626/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221028 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Antihypertensive Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Lipids) RN - 0 (Insulins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - Adult MH - Overweight/complications/drug therapy/chemically induced MH - Cardiometabolic Risk Factors MH - Antihypertensive Agents/therapeutic use MH - Obesity/complications/drug therapy/chemically induced MH - Glucagon-Like Peptides MH - Weight Loss MH - Lipids MH - *Insulins MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide PMC - PMC10092593 OTO - NOTNLM OT - GLP-1 analogue OT - cardiovascular disease OT - obesity therapy OT - randomized trial OT - weight control COIS- MB is an employee of Novo Nordisk A/S. MD has received research funding from AstraZeneca, Boehringer Ingelheim, Janssen, Novo Nordisk and Sanofi-Aventis, paid to her institution; has acted as a consultant, advisory board member, and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi-Aventis; an advisory board member and speaker for AstraZeneca; an advisory board member for Gilead Sciences Ltd and Lexicon; and a speaker for Napp Pharmaceuticals and Takeda Pharmaceuticals International Inc. She is co-funded by the NIHR Leicester Biomedical Research Centre. JED has received honoraria, speaker, or other fees from Aegerion Pharmaceuticals, Amgen, Bayer, Boehringer Ingelheim, Merck, Novartis, Novo Nordisk, Pfizer, Sanofi-Aventis and Takeda Pharmaceuticals International Inc.; has acted as a consultant for GENinCode. He has unpaid leadership or fiduciary roles in Our Future Health and Public Health England. WTG has served as a volunteer on advisory boards, without receipt of financial compensation, for Boehringer Ingelheim, Eli Lilly, JAZZ Pharmaceuticals, Novo Nordisk and Pfizer, and served on advisory boards for Alnylam Pharmaceuticals and Fractyl Health, where he received financial compensation for this service. He has participated as site principal investigator for multicentred clinical trials sponsored by his university and funded by Eli Lilly, Epitomee, Novo Nordisk, and Pfizer. UK was an employee of Novo Nordisk A/S during the conduct of the trials. MNK has received research grants from AstraZeneca and Boehringer Ingelheim; has served as a consultant/advisory board member for Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Esperion Therapeutics, Janssen, Lexicon, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Sanofi and Vifor Pharma; has received honoraria from AstraZeneca, Boehringer Ingelheim and Novo Nordisk. RK has received grants and speaker fees from, and served as an advisory board member for, Novo Nordisk; and has received honoraria from CME Outfitters, Medscape, Pri-Med, Rockpointe and Vindico Medical Education. DMR has received research grants, consultancy fees, travel fees and honoraria from, acted as an advisory board member, speaker, and principal investigator for Novo Nordisk; has received research grants from, and is a principal investigator and advisor for Boehringer Ingelheim; has received research funds from Epitomee Medical; and has received honoraria from the Endocrine Society, Medscape and the PeerView Institute. SV has received research grants and/or contracts, honoraria, and consulting fees from, and acted as an advisory board member for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Novo Nordisk; has received research grants and/or contracts and honoraria from, and acted as an advisory board member for Amarin, Bayer, HLS Therapeutics, Janssen and Novartis; has received research grants and/or contracts from, and acted as an advisory board member for Amgen; has received research grants and/or contracts and honoraria from PhaseBio, Pfizer and Sanofi; has received research grants and/or contracts from Bristol-Myers Squibb and Otsuka; has received honoraria from the Canadian Medical & Surgical Knowledge Translation Research Group, EOCI Pharmacomm Ltd, Sun Pharmaceuticals and Toronto Knowledge Translation Working Group. He is also the President of the Canadian Medical and Surgical Knowledge Translation Research Group and holds the Tier 1 Canada Research Chair in Cardiovascular Surgery. NZ is an employee and shareholder of Novo Nordisk A/S. EDAT- 2022/10/07 06:00 MHDA- 2023/01/05 06:00 PMCR- 2023/04/12 CRDT- 2022/10/06 05:13 PHST- 2022/09/23 00:00 [revised] PHST- 2022/05/18 00:00 [received] PHST- 2022/10/03 00:00 [accepted] PHST- 2022/10/07 06:00 [pubmed] PHST- 2023/01/05 06:00 [medline] PHST- 2022/10/06 05:13 [entrez] PHST- 2023/04/12 00:00 [pmc-release] AID - DOM14890 [pii] AID - 10.1111/dom.14890 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Feb;25(2):468-478. doi: 10.1111/dom.14890. Epub 2022 Oct 28. PMID- 36200219 OWN - NLM STAT- MEDLINE DCOM- 20230619 LR - 20250103 IS - 2212-3873 (Electronic) IS - 1871-5303 (Print) IS - 1871-5303 (Linking) VI - 23 IP - 8 DP - 2023 TI - Tirzepatide: A New Generation Therapeutic for Diabetes Type 2. PG - 1046-1050 LID - 10.2174/1871530322666221004151212 [doi] AB - Tirzepatide (mounjaro((R))) is a derivative of the human glucose-dependent insulinotropic polypeptide (GIP) hormone with a position-20 being modified with 1,20- eicosanedioic acid via a chemical linker. It acts as a glucagon-like peptide-1 (GLP-1) receptor and GIP receptor agonist. It has recently been approved by FDA as an adjunct therapy to exercise and diet to improve glycemic control in patients with type II diabetes mellitus (T2DM). It represents a new transforming paradigm in the management of T2DM. This mini-review will shed light on its different pharmacokinetic and pharmacodynamic aspects. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Al-Horani, Rami A AU - Al-Horani RA AD - Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans LA 70125, United States of America. FAU - Chedid, Milad AU - Chedid M AD - Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans LA 70125, United States of America. LA - eng GR - SC3 GM131986/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Review PL - United Arab Emirates TA - Endocr Metab Immune Disord Drug Targets JT - Endocrine, metabolic & immune disorders drug targets JID - 101269157 RN - OYN3CCI6QE (Tirzepatide) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide/therapeutic use/pharmacology MH - Hypoglycemic Agents/therapeutic use/pharmacology MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10473544 MID - NIHMS1925816 OTO - NOTNLM OT - Dulaglutide OT - GIP OT - GLP-1 OT - Semaglutide OT - T2DM OT - Tirzepatide COIS- CONFLICT OF INTEREST The authors declare no conflict of interest with the work being reported here. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding institutions. EDAT- 2022/10/07 06:00 MHDA- 2023/06/19 13:08 PMCR- 2024/01/01 CRDT- 2022/10/06 02:54 PHST- 2022/05/29 00:00 [received] PHST- 2022/08/27 00:00 [revised] PHST- 2022/09/19 00:00 [accepted] PHST- 2023/06/19 13:08 [medline] PHST- 2022/10/07 06:00 [pubmed] PHST- 2022/10/06 02:54 [entrez] PHST- 2024/01/01 00:00 [pmc-release] AID - EMIDDT-EPUB-126744 [pii] AID - 10.2174/1871530322666221004151212 [doi] PST - ppublish SO - Endocr Metab Immune Disord Drug Targets. 2023;23(8):1046-1050. doi: 10.2174/1871530322666221004151212. PMID- 36198436 OWN - NLM STAT- MEDLINE DCOM- 20230120 LR - 20250103 IS - 1708-8267 (Electronic) IS - 1081-5589 (Linking) VI - 71 IP - 1 DP - 2023 Jan TI - Frequency of GLP-1 receptor agonists use in diabetic patients diagnosed with delayed gastric emptying and their demographic profile. PG - 11-16 LID - 10.1136/jim-2022-002480 [doi] AB - Advances in the management of diabetes mellitus have come a long way in the 21st century. One of the most important developments in diabetes management has been the discovery of glucagon-like peptide-1 (GLP-1) receptor agonists. The most common side effects of GLP-1 receptor (GLP-1R) agonists are nausea and vomiting which have been attributed to delayed gastric emptying. While the effects of GLP-1R agonists on gastric emptying have prompted further research in this field, there are limited studies evaluating their effects on patients with pre-existing gastroparesis. Additionally, the frequency of GLP-1R agonist use among patients with gastroparesis has not been assessed in the past and this study aims to identify that percentage along with evaluating for possible iatrogenic gastroparesis. A retrospective review of all the gastric emptying studies performed at one academic medical center between January 2019 and January 2021 was performed. We found that although patients on GLP-1R agonists were more likely to have delayed gastric emptying, we could not establish a statistical significance. This could be due to the small sample size in the study. However, GLP-1R agonists use was associated with delayed gastric emptying in patients with diabetes for <10 years. Moreover, a significant proportion (24%) of patients with diabetes with delayed gastric emptying were on a GLP-1R agonist. Recently, semaglutide (GLP-1R agonist) gained Food and Drug Administration approval as a weight loss medication in both patients with and without diabetes. This should prompt further research to evaluate the safety profile of these medications in patients with and without pre-existing gastroparesis. FAU - Kalas, M Ammar AU - Kalas MA AUID- ORCID: 0000-0002-6230-9172 AD - Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA. FAU - Dang, The Q AU - Dang TQ AD - Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA. FAU - Galura, Gian AU - Galura G AD - Gastroenterology, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA. FAU - Alvarado, Luis AU - Alvarado L AD - Division of Biostatistics and Epidemiology, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA. FAU - Dwivedi, Alok Kumar AU - Dwivedi AK AUID- ORCID: 0000-0003-4574-1761 AD - Division of Biostatistics and Epidemiology, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA. FAU - Deoker, Abhizith AU - Deoker A AD - Internal Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA. FAU - McCallum, Richard AU - McCallum R AD - Gastroenterology, Texas Tech University Health Sciences Center El Paso, El Paso, Texas, USA. LA - eng PT - Journal Article PL - England TA - J Investig Med JT - Journal of investigative medicine : the official publication of the American Federation for Clinical Research JID - 9501229 RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Gastroparesis/complications/drug therapy MH - *Diabetes Mellitus/drug therapy MH - Retrospective Studies MH - Demography MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - abdominal pain OT - diabetes complications OT - digestive system OT - gastrointestinal contents EDAT- 2022/10/06 06:00 MHDA- 2023/01/21 06:00 CRDT- 2022/10/05 20:52 PHST- 2022/10/06 06:00 [pubmed] PHST- 2023/01/21 06:00 [medline] PHST- 2022/10/05 20:52 [entrez] AID - jim-2022-002480 [pii] AID - 10.1136/jim-2022-002480 [doi] PST - ppublish SO - J Investig Med. 2023 Jan;71(1):11-16. doi: 10.1136/jim-2022-002480. PMID- 36193880 OWN - NLM STAT- MEDLINE DCOM- 20230104 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 25 IP - 2 DP - 2023 Feb TI - Cost-utility analysis of semaglutide for type 2 diabetes after its addition to the National Medical Insurance System in China. PG - 387-397 LID - 10.1111/dom.14881 [doi] AB - INTRODUCTION: The main research purpose is to compare the long-term cost-effectiveness of semaglutide (SEMA) with that of dulaglutide (DULA) for patients with inadequately controlled type 2 diabetes throughout their lifetime. If necessary, the second aim is to investigate a further price cut for SEMA to provide sound advice for government drug price adjustments. METHODS: Cost-utility analysis was performed by the United Kingdom Prospective Diabetes Study Outcomes Model 2 (UKPDS OM2) from the perspective of health care providers in China. Baseline characteristics and clinical efficacy of SEMA and DULA were sourced from the high-dose comparison in the SUSTAIN-7 trial. A binary search was used to identify the scope for further reduction in the price of SEMA. The impact of individual parameters was assessed with sensitivity analyses. RESULTS: Main analysis (SEMA vs. DULA) revealed a mean difference in quality-adjusted life years (QALYs) of 0.04 QALYs and costs of $1132.29. The incremental cost-utility ratio was $26 957.44/QALY, showing that SEMA was a better option compared with DULA. In sensitivity analyses, the discount rate made the greatest contribution to the incremental cost-utility ratio. In the binary search, there was still scope to reduce the SEMA cost further by approximately 6.83% to be cost-effective, taking DULA as a reference. CONCLUSION: After its addition to the National Medical Insurance System in China, SEMA is expected to be a cost-effective choice compared with DULA for patients with type 2 diabetes with inadequately controlled from the cost-utility analysis. However, there is still scope to reduce the annual cost of SEMA further. CI - (c) 2022 John Wiley & Sons Ltd. FAU - Hu, Shanshan AU - Hu S AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Gu, Shengying AU - Gu S AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Qi, Chendong AU - Qi C AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Shuowen AU - Wang S AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Qian, Fengdan AU - Qian F AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Shi, Chenyang AU - Shi C AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Fan, Guorong AU - Fan G AUID- ORCID: 0000-0001-5141-5896 AD - Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221023 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Cost-Benefit Analysis MH - Hypoglycemic Agents/therapeutic use MH - Prospective Studies MH - Quality-Adjusted Life Years MH - *Insurance MH - Semaglutide OTO - NOTNLM OT - cost-utility analysis OT - decision-making OT - diabetes management OT - dulaglutide OT - semaglutide EDAT- 2022/10/05 06:00 MHDA- 2023/01/05 06:00 CRDT- 2022/10/04 07:32 PHST- 2022/09/22 00:00 [revised] PHST- 2022/06/23 00:00 [received] PHST- 2022/09/28 00:00 [accepted] PHST- 2022/10/05 06:00 [pubmed] PHST- 2023/01/05 06:00 [medline] PHST- 2022/10/04 07:32 [entrez] AID - 10.1111/dom.14881 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Feb;25(2):387-397. doi: 10.1111/dom.14881. Epub 2022 Oct 23. PMID- 36187123 OWN - NLM STAT- MEDLINE DCOM- 20221004 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 13 DP - 2022 TI - Real-world use of once-weekly semaglutide in patients with type 2 diabetes at an outpatient clinic in Spain. PG - 995646 LID - 10.3389/fendo.2022.995646 [doi] LID - 995646 AB - OBJECTIVES: To investigate the use of once-weekly semaglutide in a real population of people with type 2 diabetes mellitus (T2DM) in three Spanish hospitals. METHOD: An observational, retrospective and multicenter clinical study was designed that included 166 participants with T2DM, distinguishing between a group naive to GLP-1RA (n=72) and another switching from another GLP-1RA (n=94), all managed in the outpatient clinical setting. The primary endpoint was the change in HbA1c from baseline to the end of the study. The secondary endpoints included changes in body weight and the proportion of people with T2DM, achieving HbA1c <7.0% and body weight loss >5%. RESULTS: After 24 months of follow-up, the reductions in HbA1c were -0.91 +/- 0.7% (p<0.001) in the total cohort, -1.13 +/- 1.38% (p<0.019) for GLP-1RA-naive participants, and -0.74 +/- 0.9% (p<0.023) for GLP-1RA-experienced participants. Body weight reductions were -12.42 +/- 9.1% in GLP-1RA-naive participants vs. -7.65 +/- 9.7% in GLP-1RA-experienced participants (p<0.001). In the total cohort, 77.1% reached the objective of an HbA1c level <7%, and 12.7% reached between 7.1% and 7.5%. Additionally, 66.9% achieved a weight reduction >/=5%. Of all cohort, 90% received 1 mg of semaglutide once a week. The reported adverse events were consistent with the known safety profile of semaglutide. CONCLUSIONS: In routine clinical practice in Spain, the use of semaglutide once a week was associated with statistically significant and clinically relevant improvements in HbA1c and body weight in a wide range of adults with T2DM, without notable adverse effects, which supports real-world use. CI - Copyright (c) 2022 Garcia de Lucas, Miramontes-Gonzalez, Aviles-Bueno, Jimenez-Millan, Rivas-Ruiz and Perez-Belmonte. FAU - Garcia de Lucas, Maria Dolores AU - Garcia de Lucas MD AD - Department of Internal Medicine, Hospital Costa del Sol, Marbella, Spain. FAU - Miramontes-Gonzalez, Jose Pablo AU - Miramontes-Gonzalez JP AD - Department of Internal Medicine, University Hospital Rio Hortega, Valladolid, Spain. FAU - Aviles-Bueno, Beatriz AU - Aviles-Bueno B AD - Nephrology Department, Hospital Costa del Sol, Marbella, Spain. FAU - Jimenez-Millan, Ana Isabel AU - Jimenez-Millan AI AD - Endocrinology Department, Hospital P, Puerto Real Hospital, Cadiz, Spain. FAU - Rivas-Ruiz, Francisco AU - Rivas-Ruiz F AD - Research Unit, Hospital Costa del Sol, Marbella, Spain. FAU - Perez-Belmonte, Luis M AU - Perez-Belmonte LM AD - Internal Medicine Department, Regional University Hospital of Malaga, Biomedical Research Institute of Malaga (IBIMA), University of Malaga (UMA), Malaga, Spain. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study DEP - 20220916 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Ambulatory Care Facilities MH - Body Weight MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Retrospective Studies MH - Spain/epidemiology MH - Semaglutide PMC - PMC9523693 OTO - NOTNLM OT - HbA1c OT - T2DM OT - body weight OT - once-weekly semaglutide OT - real-world use COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/10/04 06:00 MHDA- 2022/10/05 06:00 PMCR- 2022/01/01 CRDT- 2022/10/03 04:46 PHST- 2022/07/16 00:00 [received] PHST- 2022/08/29 00:00 [accepted] PHST- 2022/10/03 04:46 [entrez] PHST- 2022/10/04 06:00 [pubmed] PHST- 2022/10/05 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2022.995646 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2022 Sep 16;13:995646. doi: 10.3389/fendo.2022.995646. eCollection 2022. PMID- 36136053 OWN - NLM STAT- MEDLINE DCOM- 20230209 LR - 20230209 IS - 1099-1387 (Electronic) IS - 1075-2617 (Linking) VI - 29 IP - 3 DP - 2023 Mar TI - Hectogram-scale synthesis of [Aib(8) , Arg(34) ]-GLP-1 (7-37) by liquid-phase fragment condensation. PG - e3452 LID - 10.1002/psc.3452 [doi] AB - Based on small-scale synthesis (0.3 g), a 100-g scale-up synthesis of crude [Aib(8) , Arg(34) ]-glucagon-like peptide-1 (GLP-1) (7-37) was completed. The crude [Aib(8) , Arg(34) ]-GLP-1 (7-37) was purified using a dynamic axial compression column 200 (DAC-200). Approximately 61 g of [Aib(8) , Arg(34) ]-GLP-1 (7-37) with a purity of >99% was obtained through one-step reverse-phase chromatography. The purification yield was approximately 92%. The yield from the total reaction was approximately 60%. In summary, we developed an economical and environmentally friendly route to the synthesis and purification of crude [Aib(8) , Arg(34) ]-GLP-1 (7-37), laying a foundation for subsequent industrial production. CI - (c) 2022 European Peptide Society and John Wiley & Sons Ltd. FAU - Zhang, Jinhua AU - Zhang J AD - China State Institute of Pharmaceutical Industry, Shanghai, China. AD - Shanghai Duomirui Biotechnology Ltd., Shanghai, China. FAU - Zhao, Mengjia AU - Zhao M AD - China State Institute of Pharmaceutical Industry, Shanghai, China. FAU - He, Yufeng AU - He Y AD - China State Institute of Pharmaceutical Industry, Shanghai, China. AD - Shanghai Duomirui Biotechnology Ltd., Shanghai, China. FAU - Dong, Yuanzhen AU - Dong Y AUID- ORCID: 0000-0001-9568-1547 AD - China State Institute of Pharmaceutical Industry, Shanghai, China. AD - Shanghai Duomirui Biotechnology Ltd., Shanghai, China. LA - eng PT - Journal Article DEP - 20220930 PL - England TA - J Pept Sci JT - Journal of peptide science : an official publication of the European Peptide Society JID - 9506309 RN - PI470C66NT (glucagon-like peptide 1 (7-37)) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Peptide Fragments) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Humans MH - *Glucagon-Like Peptide 1 MH - Peptide Fragments MH - Glucagon-Like Peptide-1 Receptor MH - *Diabetes Mellitus, Type 2 MH - Hypoglycemic Agents OTO - NOTNLM OT - DAC-200 OT - [Aib8, Arg34]-GLP-1 (7-37) OT - scale-up synthesis OT - semaglutide OT - type 2 diabetes EDAT- 2022/09/23 06:00 MHDA- 2023/02/10 06:00 CRDT- 2022/09/22 10:43 PHST- 2022/09/16 00:00 [revised] PHST- 2022/09/03 00:00 [received] PHST- 2022/09/19 00:00 [accepted] PHST- 2022/09/23 06:00 [pubmed] PHST- 2023/02/10 06:00 [medline] PHST- 2022/09/22 10:43 [entrez] AID - 10.1002/psc.3452 [doi] PST - ppublish SO - J Pept Sci. 2023 Mar;29(3):e3452. doi: 10.1002/psc.3452. Epub 2022 Sep 30. PMID- 36121652 OWN - NLM STAT- MEDLINE DCOM- 20220922 LR - 20260127 IS - 2574-3805 (Electronic) IS - 2574-3805 (Linking) VI - 5 IP - 9 DP - 2022 Sep 1 TI - Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity. PG - e2231982 LID - 10.1001/jamanetworkopen.2022.31982 [doi] LID - e2231982 AB - IMPORTANCE: No retrospective cohort study has assessed the effectiveness of semaglutide at doses used in randomized clinical trials to treat obesity (ie, 1.7 and 2.4 mg). OBJECTIVE: To study weight loss outcomes associated with semaglutide treatment at doses used in randomized clinical trials for patients with overweight or obesity. DESIGN, SETTING, AND PARTICIPANTS: This cohort study, conducted at a referral center for weight management, retrospectively collected data on the use of semaglutide for adults with overweight or obesity between January 1, 2021, and March 15, 2022, with a follow-up of up to 6 months. A total of 408 patients with a body mass index (BMI) of 27 or more were prescribed weekly semaglutide subcutaneous injections for 3 months or more. Patients with a history of bariatric procedures, taking other antiobesity medications, and with an active malignant neoplasm were excluded. EXPOSURES: Weekly 1.7-mg or 2.4-mg semaglutide subcutaneous injections for 3 to 6 months. MAIN OUTCOMES AND MEASURES: The primary end point was the percentage of weight loss. Secondary end points were the proportion of patients achieving weight loss of 5% or more, 10% or more, 15% or more, and 20% or more after 3 and 6 months and the percentage of weight loss for patients with or without type 2 diabetes after 3 and 6 months. RESULTS: The study included 175 patients (132 women [75.4%]; mean [SD] age, 49.3 [12.5] years; mean [SD] BMI, 41.3 [9.1]) in the analysis at 3 months and 102 patients at 6 months. The mean (SD) weight loss after 3 months was 6.7 (4.4) kg, equivalent to a mean (SD) weight loss of 5.9% (3.7%) (P < .001), and the mean (SD) weight loss after 6 months was 12.3 (6.6) kg, equivalent to a mean (SD) weight loss of 10.9% (5.8%) (P < .001 from baseline). Of the 102 patients who were followed up at 6 months, 89 (87.3%) achieved weight loss of 5% or more, 56 (54.9%) achieved weight loss of 10% or more, 24 (23.5%) achieved weight loss of 15% or more, and 8 (7.8%) achieved weight loss of 20% or more. Patients with type 2 diabetes had a lower mean (SD) percentage weight loss at 3 and 6 months compared with those without type 2 diabetes: 3.9% (3.1%) vs 6.3% (3.7%) at 3 months (P = .001) and 7.2% (6.3%) vs 11.8% (5.3%) at 6 months (P = .005). CONCLUSIONS AND RELEVANCE: The results of this cohort study suggest that weekly 1.7-mg and 2.4-mg doses of semaglutide were associated with weight loss similar to that seen in randomized clinical trials. Studies with longer periods of follow-up are needed to evaluate prolonged weight loss outcomes. FAU - Ghusn, Wissam AU - Ghusn W AD - Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - De la Rosa, Alan AU - De la Rosa A AD - Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Sacoto, Daniel AU - Sacoto D AD - Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Cifuentes, Lizeth AU - Cifuentes L AD - Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Campos, Alejandro AU - Campos A AD - Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Feris, Fauzi AU - Feris F AD - Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. FAU - Hurtado, Maria Daniela AU - Hurtado MD AD - Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. AD - Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Jacksonville, Florida. FAU - Acosta, Andres AU - Acosta A AD - Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural DEP - 20220901 PL - United States TA - JAMA Netw Open JT - JAMA network open JID - 101729235 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Middle Aged MH - Obesity/drug therapy MH - *Overweight/chemically induced MH - Retrospective Studies MH - Weight Loss MH - Semaglutide PMC - PMC9486455 COIS- Conflict of Interest Disclosures: Dr Acosta reported receiving grants from the National Institute of Diabetes and Digestive and Kidney Diseases during the conduct of the study; holding stock in Gila Therapeutics and Phenomix Sciences; and serving as a consultant for Rhythm Pharmaceuticals, General Mills, and Amgen Pharmaceuticals outside the submitted work. No other disclosures were reported. EDAT- 2022/09/20 06:00 MHDA- 2022/09/23 06:00 PMCR- 2022/09/19 CRDT- 2022/09/19 11:33 PHST- 2022/09/19 11:33 [entrez] PHST- 2022/09/20 06:00 [pubmed] PHST- 2022/09/23 06:00 [medline] PHST- 2022/09/19 00:00 [pmc-release] AID - 2796491 [pii] AID - zoi220917 [pii] AID - 10.1001/jamanetworkopen.2022.31982 [doi] PST - epublish SO - JAMA Netw Open. 2022 Sep 1;5(9):e2231982. doi: 10.1001/jamanetworkopen.2022.31982. PMID- 36120448 OWN - NLM STAT- MEDLINE DCOM- 20220920 LR - 20240904 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 13 DP - 2022 TI - Which is the optimal antiobesity agent for patients with nonalcoholic fatty liver disease? PG - 984041 LID - 10.3389/fendo.2022.984041 [doi] LID - 984041 AB - Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and affects a considerable proportion of the general population worldwide. Obesity is a major risk factor for development and progression of NAFLD and weight loss is an effective intervention for the management of NAFLD. However, few patients achieve substantial and sustained weight loss with lifestyle measures. Therefore, antiobesity agents are frequently considered in patients with NAFLD but there are limited data on their safety and efficacy. In the present review, we discuss the role of antiobesity agents in the management of NAFLD. All approved antiobesity agents appear to reduce transaminase levels and to improve steatosis in patients with NAFLD. However, their effects on fibrosis are less well studied and whether they affect liver-related outcomes, including progression to cirrhosis and hepatocellular cancer, is unknown. The glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, appear to represent a first-line option in obese patients with NAFLD and type 2 diabetes mellitus (T2DM) since they induce considerable weight loss and have been extensively studied in patients with T2DM. However, more studies are needed to evaluated their effects on liver-related and cardiovascular outcomes in patients with NAFLD, particularly in those without T2DM. CI - Copyright (c) 2022 Tsankof, Neokosmidis, Koureta, Veneti, Cholongitas and Tziomalos. FAU - Tsankof, Alexandra AU - Tsankof A AD - First Propedeutic Department of Internal Medicine, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece. FAU - Neokosmidis, Georgios AU - Neokosmidis G AD - First Propedeutic Department of Internal Medicine, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece. FAU - Koureta, Evgenia AU - Koureta E AD - Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. FAU - Veneti, Stavroula AU - Veneti S AD - First Propedeutic Department of Internal Medicine, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece. FAU - Cholongitas, Evangelos AU - Cholongitas E AD - Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. FAU - Tziomalos, Konstantinos AU - Tziomalos K AD - First Propedeutic Department of Internal Medicine, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20220902 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Platelet Aggregation Inhibitors) RN - 839I73S42A (Liraglutide) RN - EC 2.6.1.- (Transaminases) SB - IM MH - *Anti-Obesity Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/epidemiology MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Liraglutide MH - *Non-alcoholic Fatty Liver Disease/complications/drug therapy/epidemiology MH - Obesity/complications/drug therapy MH - Platelet Aggregation Inhibitors MH - Transaminases MH - Weight Loss PMC - PMC9478023 OTO - NOTNLM OT - liraglutide OT - lorcaserin OT - naltrexone/bupropion OT - nonalcoholic fatty liver disease OT - obesity OT - orlistat OT - phentermine/topiramate OT - semaglutide COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/09/20 06:00 MHDA- 2022/09/21 06:00 PMCR- 2022/01/01 CRDT- 2022/09/19 04:41 PHST- 2022/07/01 00:00 [received] PHST- 2022/08/12 00:00 [accepted] PHST- 2022/09/19 04:41 [entrez] PHST- 2022/09/20 06:00 [pubmed] PHST- 2022/09/21 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2022.984041 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2022 Sep 2;13:984041. doi: 10.3389/fendo.2022.984041. eCollection 2022. PMID- 36114904 OWN - NLM STAT- MEDLINE DCOM- 20230626 LR - 20260127 IS - 1618-7601 (Electronic) IS - 1618-7598 (Print) IS - 1618-7598 (Linking) VI - 24 IP - 6 DP - 2023 Aug TI - The long-term cost-effectiveness of once-weekly semaglutide 1 mg vs. dulaglutide 3 mg and 4.5 mg in the UK. PG - 895-907 LID - 10.1007/s10198-022-01514-1 [doi] AB - AIMS: Once-weekly semaglutide and dulaglutide represent two highly efficacious treatment options for type 2 diabetes. A recent indirect treatment comparison (ITC) has associated semaglutide 1 mg with similar and greater improvements in glycated haemoglobin (HbA1c) and body weight, respectively, vs. dulaglutide 3 mg and 4.5 mg. The present study aimed to evaluate the long-term cost-effectiveness of semaglutide 1 mg vs. dulaglutide 3 mg and 4.5 mg in the UK. MATERIALS AND METHODS: The IQVIA CORE Diabetes Model (v9.0) was used to project outcomes over patients' lifetimes. Baseline cohort characteristics were sourced from SUSTAIN 7, with changes in HbA1c and body mass index applied as per the ITC. Modelled patients received semaglutide or dulaglutide for 3 years, after which treatment was intensified to basal insulin. Costs (expressed in 2020 pounds sterling [GBP]) were accounted from a healthcare payer perspective. RESULTS: Semaglutide 1 mg was associated with improvements in quality-adjusted life expectancy of 0.05 and 0.04 quality-adjusted life years (QALYs) vs. dulaglutide 3 mg and 4.5 mg, respectively, due to a reduced incidence of diabetes-related complications with semaglutide. Direct costs were estimated to be GBP 76 lower and GBP 8 higher in the comparisons with dulaglutide 3 mg and 4.5 mg, respectively. Overall outcomes were similar, but favoured semaglutide, and based on modelled mean outcomes it was considered dominant vs. dulaglutide 3 mg and associated with an incremental cost-effectiveness ratio of GBP 228 per QALY gained vs. dulaglutide 4.5 mg. CONCLUSIONS: Semaglutide 1 mg represents a cost-effective treatment vs. dulaglutide 3 mg and 4.5 mg for type 2 diabetes from a healthcare payer perspective in the UK. CI - (c) 2022. The Author(s). FAU - Viljoen, Adie AU - Viljoen A AD - Borthwick Diabetes Research Centre, Lister Hospital (East and North Hertfordshire NHS Trust), Stevenage, UK. FAU - Chubb, Barrie AU - Chubb B AUID- ORCID: 0000-0001-7271-051X AD - Novo Nordisk Ltd, Gatwick, UK. FAU - Malkin, Samuel J P AU - Malkin SJP AD - Ossian Health Economics and Communications GmbH, Baumleingasse 20, 4051, Basel, Switzerland. malkin@ossianconsulting.com. FAU - Berry, Sasha AU - Berry S AD - Novo Nordisk Ltd, Gatwick, UK. FAU - Hunt, Barnaby AU - Hunt B AD - Ossian Health Economics and Communications GmbH, Baumleingasse 20, 4051, Basel, Switzerland. FAU - Bain, Stephen C AU - Bain SC AD - Swansea University Medical School, Swansea, UK. LA - eng PT - Journal Article DEP - 20220917 PL - Germany TA - Eur J Health Econ JT - The European journal of health economics : HEPAC : health economics in prevention and care JID - 101134867 RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2 MH - Hypoglycemic Agents/therapeutic use MH - Cost-Benefit Analysis MH - Glycated Hemoglobin MH - United Kingdom/epidemiology MH - Semaglutide MH - Glucagon-Like Peptides/analogs & derivatives MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins PMC - PMC10290607 OTO - NOTNLM OT - Cost OT - Cost-effectiveness OT - Dulaglutide OT - Semaglutide OT - UK EDAT- 2022/09/18 06:00 MHDA- 2023/06/26 06:42 PMCR- 2022/09/17 CRDT- 2022/09/17 11:15 PHST- 2022/04/29 00:00 [received] PHST- 2022/08/09 00:00 [accepted] PHST- 2023/06/26 06:42 [medline] PHST- 2022/09/18 06:00 [pubmed] PHST- 2022/09/17 11:15 [entrez] PHST- 2022/09/17 00:00 [pmc-release] AID - 10.1007/s10198-022-01514-1 [pii] AID - 1514 [pii] AID - 10.1007/s10198-022-01514-1 [doi] PST - ppublish SO - Eur J Health Econ. 2023 Aug;24(6):895-907. doi: 10.1007/s10198-022-01514-1. Epub 2022 Sep 17. PMID- 36096275 OWN - NLM STAT- MEDLINE DCOM- 20221219 LR - 20260127 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 371 DP - 2023 Jan 15 TI - Patient preferences for newer oral therapies in type 2 diabetes. PG - 526-532 LID - S0167-5273(22)01319-5 [pii] LID - 10.1016/j.ijcard.2022.09.009 [doi] AB - BACKGROUND: We aimed to evaluate patient preferences towards three oral antihyperglycaemic therapies using conjoint analysis to determine which attributes may influence use. METHODS: We used an online survey, completed by 553 US respondents with type 2 diabetes mellitus (T2DM; mean age 64 +/- 9 years; 55% had cardiovascular [CV] risk; 27% had CV disease), to present hypothetical, blinded, pairwise, drug profile comparison choices, between different benefit/risk attributes and effect ranges. Attributes were derived from phase 3 trials for empagliflozin 25 mg (SGLT2 inhibitor), oral semaglutide 14 mg (GLP-1 receptor agonist) and sitagliptin 100 mg (DPP-4 inhibitor). Predicted therapy preference outcomes and relative importance of each attribute were calculated (presented as a percentage). RESULTS: Preference score was highest for the profile matching empagliflozin (56%), versus sitagliptin (38%; z-test, P < 0.001) and oral semaglutide (6%, z-test, P < 0.001). Results were overall consistent in subgroup analyses. Genital infection risk was the most important attribute (relative score: 19% [z-test, P = 0.077]). Other important attributes were fasting requirements (15%), weight reduction (15%), risk of vomiting (14%), CV benefit (12%), and risk of nausea (11%). HbA1c reduction (8%) and ability to take medication with other drugs (6%) were considered less important. While blinded to drug name/dose, respondents chose a drug profile similar to empagliflozin (41%) versus sitagliptin (31%), oral semaglutide (11%), or 'none of the options' (17%). CONCLUSION: While the drug profile comparable to empagliflozin was preferred, CV benefit was not the top patient priority. A shared physician-patient decision model and increased patient education are needed to ensure optimal use of guideline-directed T2DM therapies. CI - Copyright (c) 2022 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Savarese, Gianluigi AU - Savarese G AD - Division of Cardiology, Department of Medicine, Karolinska Institute; Heart and Vascular Theme, Karolinska University Hospital, Stockholm, Sweden. Electronic address: gianluigi.savarese@ki.se. FAU - Sharma, Abhinav AU - Sharma A AD - Division of Cardiology, McGill University, Montreal, QC, Canada. Electronic address: abhinav.sharma@mcgill.ca. FAU - Pang, Christianne AU - Pang C AD - dQ&A - The Diabetes Research Company, San Francisco, CA, USA. FAU - Wood, Richard AU - Wood R AD - dQ&A - The Diabetes Research Company, San Francisco, CA, USA. FAU - Soleymanlou, Nima AU - Soleymanlou N AD - Boehringer Ingelheim Pharmaceutical Inc., Ridgefield, CT, USA. LA - eng PT - Journal Article DEP - 20220910 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Hypoglycemic Agents) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - HDC1R2M35U (empagliflozin) RN - 0 (Benzhydryl Compounds) RN - 0 (Glucosides) SB - IM MH - Aged MH - Humans MH - Middle Aged MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Patient Preference MH - Sitagliptin Phosphate/therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Clinical Trials, Phase III as Topic MH - Adult MH - Benzhydryl Compounds MH - Glucosides OTO - NOTNLM OT - DPP-4 inhibitor OT - Empagliflozin OT - GLP-1 OT - SGLT2i OT - Sitagliptin OT - Type 2 diabetes EDAT- 2022/09/13 06:00 MHDA- 2022/12/15 06:00 CRDT- 2022/09/12 19:24 PHST- 2022/08/18 00:00 [received] PHST- 2022/09/05 00:00 [accepted] PHST- 2022/09/13 06:00 [pubmed] PHST- 2022/12/15 06:00 [medline] PHST- 2022/09/12 19:24 [entrez] AID - S0167-5273(22)01319-5 [pii] AID - 10.1016/j.ijcard.2022.09.009 [doi] PST - ppublish SO - Int J Cardiol. 2023 Jan 15;371:526-532. doi: 10.1016/j.ijcard.2022.09.009. Epub 2022 Sep 10. PMID- 36056351 OWN - NLM STAT- MEDLINE DCOM- 20220908 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 21 IP - 1 DP - 2022 Sep 2 TI - Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials. PG - 172 LID - 10.1186/s12933-022-01585-7 [doi] LID - 172 AB - BACKGROUND: Exploratory analysis to determine the effect of semaglutide versus comparators on high-sensitivity C-reactive protein (hsCRP) in subjects with type 2 diabetes. METHODS: Trials of once-weekly subcutaneous (SUSTAIN 3) and once-daily oral (PIONEER 1, 2, 5) semaglutide with hsCRP data were analyzed. Subjects with type 2 diabetes (N = 2482) received semaglutide (n = 1328) or comparators (placebo, n = 339; exenatide extended-release, n = 405; empagliflozin, n = 410). hsCRP ratio to baseline at end-of-treatment was analyzed overall, by clinical cutoff (< 1.0, >/= 1.0 to 3.0 mg/L), by tertile, and by estimated glomerular filtration rate in PIONEER 5 (a trial which was conducted in a population with type 2 diabetes and chronic kidney disease [CKD]). Mediation analyses assessed the effect of change in glycated hemoglobin (HbA(1c)) and/or change in body weight (BW) on hsCRP reductions. RESULTS: Geometric mean baseline hsCRP was similar across trials (range 2.7-3.0 mg/L). Semaglutide reduced hsCRP levels by clinical cutoffs and tertiles from baseline to end-of-treatment in all trials versus comparators (estimated treatment ratios [ETRs] versus comparators: 0.70-0.76; p < 0.01) except versus placebo in PIONEER 5 (ETR [95% CI]: 0.83 [0.67-1.03]; p > 0.05). The effect of semaglutide on hsCRP was partially mediated (20.6-61.8%) by change in HbA(1c) and BW. CONCLUSIONS: Semaglutide reduced hsCRP ratios-to-baseline versus comparators in subjects with type 2 diabetes (not significant with CKD). This effect was partially mediated via reductions in HbA(1c) and BW and potentially by a direct effect of semaglutide. Semaglutide appears to have an anti-inflammatory effect, which is being further investigated in ongoing trials. TRIAL REGISTRATIONS: ClinicalTrials.gov identifiers: NCT01885208 (first registered June 2013), NCT02906930 (first registered September 2016), NCT02863328 (first registered August 2016), NCT02827708 (first registered July 2016). CI - (c) 2022. The Author(s). FAU - Mosenzon, Ofri AU - Mosenzon O AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, PO Box 12000, Jerusalem, Israel. ofrim@hadassah.org.il. FAU - Capehorn, Matthew S AU - Capehorn MS AD - Clifton Medical Centre, Rotherham Institute for Obesity, Rotherham, UK. FAU - De Remigis, Alessandra AU - De Remigis A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Weimers, Petra AU - Weimers P AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rosenstock, Julio AU - Rosenstock J AD - Velocity Clinical Research at Medical City, Dallas, TX, USA. LA - eng SI - ClinicalTrials.gov/NCT02906930 SI - ClinicalTrials.gov/NCT02863328 SI - ClinicalTrials.gov/NCT02827708 SI - ClinicalTrials.gov/NCT01885208 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220902 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 9007-41-4 (C-Reactive Protein) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Body Weight MH - *C-Reactive Protein/analysis/drug effects MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/pharmacology MH - Glycated Hemoglobin/analysis MH - Humans MH - Randomized Controlled Trials as Topic MH - Renal Insufficiency, Chronic/drug therapy MH - Treatment Outcome MH - Semaglutide PMC - PMC9440529 OTO - NOTNLM OT - Body weight OT - Chronic kidney disease OT - GLP-1RAs OT - HbA1c OT - High-sensitivity C-reactive protein OT - Inflammation OT - PIONEER OT - SUSTAIN OT - Semaglutide OT - Type 2 diabetes COIS- OM reports personal fees for advisory board consultancy and speaker's bureau from AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novo Nordisk, and Sanofi; and research grant support from AstraZeneca and Novo Nordisk. MC reports being a partner at Clifton Medical Centre, a director at RIO Weight Management, Ltd, and a consultant for LighterLife and McDonald's; he also reports research funding from Abbott, Boehringer Ingelheim/Lilly Alliance, Janssen, MSD, and Novo Nordisk; advisory board consultancy, consultancy and honoraria from Abbott, Boehringer Ingelheim/Lilly Alliance, and Novo Nordisk; and meeting support from Boehringer Ingelheim/Lilly Alliance and Novo Nordisk. ADR, SR, and PW are full-time employees of Novo Nordisk; SR also owns shares in Novo Nordisk. JR reports research funding from Applied Therapeutics Inc., Boehringer Ingelheim, Eli Lilly, Genentech, GlaxoSmithKline, Hanmi, Intarcia, Janssen, Lexicon, Merck, Metacrine, Novo Nordisk, Novartis, Oramed, Pfizer, and Sanofi; and advisory board consultancy, consultancy, and honoraria from Applied Therapeutics Inc., Boehringer Ingelheim, Eli Lilly, Hanmi, Intarcia, Janssen, Novo Nordisk, Oramed, Sanofi, and Zealand. EDAT- 2022/09/03 06:00 MHDA- 2022/09/09 06:00 PMCR- 2022/09/02 CRDT- 2022/09/02 23:43 PHST- 2022/04/26 00:00 [received] PHST- 2022/07/27 00:00 [accepted] PHST- 2022/09/02 23:43 [entrez] PHST- 2022/09/03 06:00 [pubmed] PHST- 2022/09/09 06:00 [medline] PHST- 2022/09/02 00:00 [pmc-release] AID - 10.1186/s12933-022-01585-7 [pii] AID - 1585 [pii] AID - 10.1186/s12933-022-01585-7 [doi] PST - epublish SO - Cardiovasc Diabetol. 2022 Sep 2;21(1):172. doi: 10.1186/s12933-022-01585-7. PMID- 36050763 OWN - NLM STAT- MEDLINE DCOM- 20220908 LR - 20250103 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 21 IP - 1 DP - 2022 Sep 1 TI - Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. PG - 169 LID - 10.1186/s12933-022-01604-7 [doi] LID - 169 AB - Tirzepatide is the first dual GIP/GLP-1 receptor co-agonist approved for the treatment of type 2 diabetes in the USA, Europe, and the UAE. Tirzepatide is an acylated peptide engineered to activate the GIP and GLP-1 receptors, key mediators of insulin secretion that are also expressed in regions of the brain that regulate food intake. Five clinical trials in type 2-diabetic subjects (SURPASS 1-5) have shown that tirzepatide at 5-15 mg per week reduces both HbA(1c) (1.24 to 2.58%) and body weight (5.4-11.7 kg) by amounts unprecedented for a single agent. A sizable proportion of patients (23.0 to 62.4%) reached an HbA(1c) of < 5.7% (which is the upper limit of the normal range indicating normoglycaemia), and 20.7 to 68.4% lost more than 10% of their baseline body weight. Tirzepatide was significantly more effective in reducing HbA(1c) and body weight than the selective GLP-1 RA semaglutide (1.0 mg per week), and titrated basal insulin. Adverse events related to tirzepatide were similar to what has been reported for selective GLP-1RA, mainly nausea, vomiting, diarrhoea, and constipation, that were more common at higher doses. Cardiovascular events have been adjudicated across the whole study program, and MACE-4 (nonfatal myocardial infarction, non-fatal stroke, cardiovascular death and hospital admission for angina) events tended to be reduced over up to a 2 year-period, albeit with low numbers of events. For none of the cardiovascular events analysed (MACE-4, or its components) was a hazard ratio > 1.0 vs. pooled comparators found in a meta-analysis covering the whole clinical trial program, and the upper bounds of the confidence intervals for MACE were < 1.3, fulfilling conventional definitions of cardiovascular safety. Tirzepatide was found to improve insulin sensitivity and insulin secretory responses to a greater extent than semaglutide, and this was associated with lower prandial insulin and glucagon concentrations. Both drugs caused similar reductions in appetite, although tirzepatide caused greater weight loss. While the clinical effects of tirzepatide have been very encouraging, important questions remain as to the mechanism of action. While GIP reduces food intake and body weight in rodents, these effects have not been demonstrated in humans. Moreover, it remains to be shown that GIPR agonism can improve insulin secretion in type 2 diabetic patients who have been noted in previous studies to be unresponsive to GIP. Certainly, the apparent advantage of tirzepatide, a dual incretin agonist, over GLP-1RA will spark renewed interest in the therapeutic potential of GIP in type 2 diabetes, obesity and related co-morbidities. CI - (c) 2022. The Author(s). FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes, Endocrinology and Metabolism Section, Medical Department I, Katholisches Klinikum Bochum gGmbH, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstr. 56, 44791, Bochum, Germany. michael.nauck@rub.de. FAU - D'Alessio, David A AU - D'Alessio DA AD - Division of Endocrinology and Metabolism, Department of Medicine, Duke University Medical Center, Durham, NC, 27701, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20220901 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Body Weight MH - Cardiovascular Diseases/epidemiology MH - Clinical Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Gastric Inhibitory Polypeptide/adverse effects MH - Glucagon-Like Peptide 1/therapeutic use MH - Glycemic Control MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Insulin/therapeutic use MH - Meta-Analysis as Topic MH - Weight Loss MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC9438179 OTO - NOTNLM OT - Body weight OT - GIP/GLP-1 receptor co-agonists OT - GLP-1 receptor agonists OT - Glycemic control OT - HbA1c OT - Type 2 diabetes COIS- MAN has been member on advisory boards or has consulted with Boehringer Ingelheim, Eli Lilly & Co., Menarini/Berlin Chemie, Merck, Sharp & Dohme, NovoNordisk, Regor, and ShouTi Inc./Gasherbrum. He has received grant support from Merck, Sharp & Dohme. He is member of a data monitoring and safety board for Inventiva. He has also served on the speakers' bureau of Eli Lilly & Co., Medscape, Medical Learning Institute, Menarini/Berlin Chemie, Merck, Sharp & Dohme, NovoNordisk, and Sun Pharmaceuticals. D.A.D. consults for Eli Lilly & Co. and Sun Pharmaceuticals. EDAT- 2022/09/02 06:00 MHDA- 2022/09/09 06:00 PMCR- 2022/09/01 CRDT- 2022/09/01 23:48 PHST- 2022/07/11 00:00 [received] PHST- 2022/08/19 00:00 [accepted] PHST- 2022/09/01 23:48 [entrez] PHST- 2022/09/02 06:00 [pubmed] PHST- 2022/09/09 06:00 [medline] PHST- 2022/09/01 00:00 [pmc-release] AID - 10.1186/s12933-022-01604-7 [pii] AID - 1604 [pii] AID - 10.1186/s12933-022-01604-7 [doi] PST - epublish SO - Cardiovasc Diabetol. 2022 Sep 1;21(1):169. doi: 10.1186/s12933-022-01604-7. PMID- 36044100 OWN - NLM STAT- MEDLINE DCOM- 20221007 LR - 20261010 IS - 1534-6242 (Electronic) IS - 1523-3804 (Linking) VI - 24 IP - 11 DP - 2022 Nov TI - GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far? PG - 867-884 LID - 10.1007/s11883-022-01062-2 [doi] AB - PURPOSE OF REVIEW: To discuss evidence supporting the use of glucagon-like peptide 1 receptor agonists (GLP-1RA) to treat obesity and their role as a cardioprotective drug. Obesity is not just a hypertrophy of the adipose tissue because it may become dysfunctional and inflamed resulting in increased insulin resistance. Being overweight is associated with increased incidence of cardiovascular events and weight loss achieved through lifestyle changes lowers risk factors, but has no clear effect on cardiovascular outcomes. In contrast, treating obesity with GLP-1RA decreases cardiovascular risk and the possible mechanisms of cardioprotection achieved by this class of drugs are discussed. GLP-1RA were initially developed to treat type 2 diabetes patients, in whom the effects upon glycemia and, moreover, weight loss, especially with long-acting GLP-1RA, were evident. However, cardiovascular safety trials in type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight, showed that GLP-1 receptor agonists were indeed capable of decreasing cardiovascular risk. RECENT FINDINGS: Type 2 diabetes treatment with GLP-1RA liraglutide and semaglutide paved way to a ground-breaking therapy specific for obesity, as shown with the SCALE 3 mg/day liraglutide program and the STEP 2.4 mg/week semaglutide program. A novel molecule with superior performance is tirzepatide, a GLP-1 and GIP (Gastric Inhibitory Peptide) receptor agonist and recent results from the SURPASS and SURMOUNT programs are briefly described. Liraglutide was approved without a CVOT (Cardiovascular Outcome Trial) because authorities accepted the results from the LEADER study, designed for superiority. The SELECT study with semaglutide will report results only in 2023 and tirzepatide is being tested in patients with diabetes in the SURPASS-CVOT. Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Pedrosa, Mauricio Reis AU - Pedrosa MR AUID- ORCID: 0000-0001-7966-2602 AD - CPCLIN - Centro de Pesquisas Clinicas, Av. Angelica, 2162 - Consolacao, Sao Paulo, SP, 01228-200, Brazil. mauricio.pedrosa@dasa.com.br. FAU - Franco, Denise Reis AU - Franco DR AUID- ORCID: 0000-0003-4961-0638 AD - CPCLIN - Centro de Pesquisas Clinicas, Av. Angelica, 2162 - Consolacao, Sao Paulo, SP, 01228-200, Brazil. FAU - Gieremek, Hannah Waisberg AU - Gieremek HW AUID- ORCID: 0000-0002-5167-8212 AD - CPCLIN - Centro de Pesquisas Clinicas, Av. Angelica, 2162 - Consolacao, Sao Paulo, SP, 01228-200, Brazil. FAU - Vidal, Camila Maia AU - Vidal CM AUID- ORCID: 0000-0003-4251-4184 AD - CPCLIN - Centro de Pesquisas Clinicas, Av. Angelica, 2162 - Consolacao, Sao Paulo, SP, 01228-200, Brazil. FAU - Bronzeri, Fernanda AU - Bronzeri F AUID- ORCID: 0000-0002-3660-3247 AD - CPCLIN - Centro de Pesquisas Clinicas, Av. Angelica, 2162 - Consolacao, Sao Paulo, SP, 01228-200, Brazil. FAU - de Cassia Rocha, Alexia AU - de Cassia Rocha A AUID- ORCID: 0000-0002-9616-8427 AD - CPCLIN - Centro de Pesquisas Clinicas, Av. Angelica, 2162 - Consolacao, Sao Paulo, SP, 01228-200, Brazil. FAU - de Carvalho Cara, Luis Gabriel AU - de Carvalho Cara LG AUID- ORCID: 0000-0001-6678-0415 AD - CPCLIN - Centro de Pesquisas Clinicas, Av. Angelica, 2162 - Consolacao, Sao Paulo, SP, 01228-200, Brazil. FAU - Fogo, Sofia Lenzi AU - Fogo SL AUID- ORCID: 0000-0002-6390-5056 AD - CPCLIN - Centro de Pesquisas Clinicas, Av. Angelica, 2162 - Consolacao, Sao Paulo, SP, 01228-200, Brazil. FAU - Eliaschewitz, Freddy Goldberg AU - Eliaschewitz FG AUID- ORCID: 0000-0002-9283-1842 AD - CPCLIN - Centro de Pesquisas Clinicas, Av. Angelica, 2162 - Consolacao, Sao Paulo, SP, 01228-200, Brazil. LA - eng PT - Journal Article PT - Review DEP - 20220831 PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Cardiovascular Diseases/chemically induced/prevention & control MH - Clinical Trials as Topic MH - *Diabetes Mellitus, Type 2/chemically induced/complications/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - Obesity/complications/drug therapy MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Fat OT - GLP-1 OT - Glucagon-like peptide 1 OT - Liraglutide OT - Obesity OT - Semaglutide OT - Tirzepatide EDAT- 2022/09/01 06:00 MHDA- 2022/10/12 06:00 CRDT- 2022/08/31 11:20 PHST- 2022/08/01 00:00 [accepted] PHST- 2022/09/01 06:00 [pubmed] PHST- 2022/10/12 06:00 [medline] PHST- 2022/08/31 11:20 [entrez] AID - 10.1007/s11883-022-01062-2 [pii] AID - 10.1007/s11883-022-01062-2 [doi] PST - ppublish SO - Curr Atheroscler Rep. 2022 Nov;24(11):867-884. doi: 10.1007/s11883-022-01062-2. Epub 2022 Aug 31. PMID- 36004653 OWN - NLM STAT- MEDLINE DCOM- 20220826 LR - 20250103 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 18 IP - 792 DP - 2022 Aug 24 TI - [Focus on tirzepatide, a dual unimolecular GIP-GLP-1 receptor agonist in type 2 diabetes]. PG - 1539-1544 LID - 10.53738/REVMED.2022.18.792.1539 [doi] AB - Tirzepatide is a unimolecular dual agonist of both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, which is developed as once-weekly injection for the treatment of type 2 diabetes. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, basal insulin and two GLP-1 analogues (dulaglutide and semaglutide) in the SURPASS program. Its cardiovascular protection (versus dulaglutide) is currently tested in SURPASS-CVOT. Finally, studies for the treatment of obesity and metabolic associated fatty liver disease are also ongoing. Gastrointestinal tolerance of tirzepatide appears comparable to that of GLP-1 analogues, except more diarrhoea. FAU - Scheen, Andre J AU - Scheen AJ AD - Service de diabetologie, nutrition et maladies metaboliques, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. AD - Unite de pharmacologie clinique, Centre interdisciplinaire de recherche sur le medicament (CIRM), Liege Universite, 4000 Liege, Belgique. FAU - Radermecker, Regis P AU - Radermecker RP AD - Service de diabetologie, nutrition et maladies metaboliques, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. AD - Unite de pharmacologie clinique, Centre interdisciplinaire de recherche sur le medicament (CIRM), Liege Universite, 4000 Liege, Belgique. FAU - Paquot, Nicolas AU - Paquot N AD - Service de diabetologie, nutrition et maladies metaboliques, Centre hospitalier universitaire de Liege, 4000 Liege, Belgique. LA - fre PT - Journal Article PT - Randomized Controlled Trial TT - Focus sur le tirzepatide, un double agoniste unimoleculaire GIP-GLP-1 dans le diabete de type 2. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptide 1 MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists COIS- Le Pr Andre J. Scheen declare avoir recu des honoraires comme orateur et/ou membre d'un conseil scientifique de la part des firmes AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck Sharp & Dohme, Novartis, NovoNordisk et Sanofi. Il a ete investigateur clinicien dans les etudes LEADER, HARMONY Cardiovascular et PIONEER-6 avec des analogues du GLP-1 et est actuellement co-investigateur dans l'essai SURPASS-CVOT. Le Pr Regis P. Radermecker est investigateur principal pour le CHU de Liege dans l'essai SURPASS-CVOT. L'auteur de cet article n'a pas de conflit d'interets en rapport avec la presente publication. Les honoraires recus de l'industrie pharmaceutique par Radermecker sont disponibles sur le site betransparent.be. Le Pr Nicolas Paquot est co-investigateur principal pour le CHU de Liege dans l'essai SURPASS-CVOT. Il declare avoir recu des honoraires comme orateur et/ou membre d'un conseil scientifique de la part des firmes AstraZeneca, Boehringer Ingelheim, Lilly, MSD Belgium, NovoNordisk, Fresenius et Sanofi. EDAT- 2022/08/26 06:00 MHDA- 2022/08/27 06:00 CRDT- 2022/08/25 05:12 PHST- 2022/08/25 05:12 [entrez] PHST- 2022/08/26 06:00 [pubmed] PHST- 2022/08/27 06:00 [medline] AID - RMS0792-003 [pii] AID - 10.53738/REVMED.2022.18.792.1539 [doi] PST - ppublish SO - Rev Med Suisse. 2022 Aug 24;18(792):1539-1544. doi: 10.53738/REVMED.2022.18.792.1539. PMID- 35985949 OWN - NLM STAT- MEDLINE DCOM- 20221128 LR - 20260127 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 106 DP - 2022 Dec TI - Gastrointestinal adverse events of semaglutide in patients with overweight or obesity. PG - 138-139 LID - S0953-6205(22)00293-X [pii] LID - 10.1016/j.ejim.2022.08.015 [doi] FAU - Tariq, Muhammad Ali AU - Tariq MA AD - Dow University Hospital, Dow International Medical College, Karachi, Pakistan. Electronic address: m.alitariqpk@gmail.com. FAU - Amin, Hamza AU - Amin H AD - Ruth KM Pfau Civil Hospital, Dow University of Health Sciences, Karachi, Pakistan. FAU - Shurjeel, Qazi AU - Shurjeel Q AD - Ruth KM Pfau Civil Hospital, Dow University of Health Sciences, Karachi, Pakistan. FAU - Gang, Ahmed AU - Gang A AD - Jinnah Postgraduate Medical Center, Karachi, Pakistan. FAU - Mohiuddin, Ashar AU - Mohiuddin A AD - Dow University Hospital, Dow International Medical College, Karachi, Pakistan. LA - eng PT - Letter DEP - 20220816 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Overweight/complications MH - Glucagon-Like Peptides/adverse effects MH - Hypoglycemic Agents/adverse effects MH - Obesity MH - *Diabetes Mellitus, Type 2/drug therapy MH - Semaglutide COIS- Declaration of Competing Interest The authors declare that they have no conflict of interest. EDAT- 2022/08/20 06:00 MHDA- 2022/11/29 06:00 CRDT- 2022/08/19 22:07 PHST- 2022/07/26 00:00 [received] PHST- 2022/08/11 00:00 [accepted] PHST- 2022/08/20 06:00 [pubmed] PHST- 2022/11/29 06:00 [medline] PHST- 2022/08/19 22:07 [entrez] AID - S0953-6205(22)00293-X [pii] AID - 10.1016/j.ejim.2022.08.015 [doi] PST - ppublish SO - Eur J Intern Med. 2022 Dec;106:138-139. doi: 10.1016/j.ejim.2022.08.015. Epub 2022 Aug 16. PMID- 35970890 OWN - NLM STAT- MEDLINE DCOM- 20220817 LR - 20251031 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 12 IP - 1 DP - 2022 Aug 15 TI - A GLP1 receptor agonist diabetes drug ameliorates neurodegeneration in a mouse model of infantile neurometabolic disease. PG - 13825 LID - 10.1038/s41598-022-17338-1 [doi] LID - 13825 AB - Infantile neuroaxonal dystrophy (INAD) is a rare paediatric neurodegenerative condition caused by mutations in the PLA2G6 gene, which is also the causative gene for PARK14-linked young adult-onset dystonia parkinsonism. INAD patients usually die within their first decade of life, and there are currently no effective treatments available. GLP1 receptor (GLP-1R) agonists are licensed for treating type 2 diabetes mellitus but have also demonstrated neuroprotective properties in a clinical trial for Parkinson's disease. Therefore, we evaluated the therapeutic efficacy of a new recently licensed GLP-1R agonist diabetes drug in a mouse model of INAD. Systemically administered high-dose semaglutide delivered weekly to juvenile INAD mice improved locomotor function and extended the lifespan. An investigation into the mechanisms underlying these therapeutic effects revealed that semaglutide significantly increased levels of key neuroprotective molecules while decreasing those involved in pro-neurodegenerative pathways. The expression of mediators in both the apoptotic and necroptotic pathways were also significantly reduced in semaglutide treated mice. A reduction of neuronal loss and neuroinflammation was observed. Finally, there was no obvious inflammatory response in wild-type mice associated with the repeated high doses of semaglutide used in this study. CI - (c) 2022. The Author(s). FAU - Poupon-Bejuit, L AU - Poupon-Bejuit L AD - UCL School of Pharmacy, University College London, London, UK. FAU - Hughes, M P AU - Hughes MP AD - UCL School of Pharmacy, University College London, London, UK. FAU - Liu, W AU - Liu W AD - UCL School of Pharmacy, University College London, London, UK. FAU - Geard, A AU - Geard A AD - UCL School of Pharmacy, University College London, London, UK. FAU - Faour-Slika, N AU - Faour-Slika N AD - UCL School of Pharmacy, University College London, London, UK. FAU - Whaler, S AU - Whaler S AD - UCL School of Pharmacy, University College London, London, UK. FAU - Massaro, G AU - Massaro G AD - UCL School of Pharmacy, University College London, London, UK. giulia.massaro.13@ucl.ac.uk. FAU - Rahim, A A AU - Rahim AA AD - UCL School of Pharmacy, University College London, London, UK. a.rahim@ucl.ac.uk. LA - eng GR - MR/N026101/1/MRC_/Medical Research Council/United Kingdom GR - MR/T044853/1/MRC_/Medical Research Council/United Kingdom GR - 562646/WT_/Wellcome Trust/United Kingdom GR - MR/S036784/1/MRC_/Medical Research Council/United Kingdom GR - MR/R025134/1/MRC_/Medical Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom GR - 204841/Z/16/Z/WT_/Wellcome Trust/United Kingdom GR - MR/R015325/1/MRC_/Medical Research Council/United Kingdom GR - 562868/DH_/Department of Health/United Kingdom GR - MR/S009434/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220815 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - EC 3.1.1.4 (Group VI Phospholipases A2) RN - EC 3.1.1.4 (Pla2g6 protein, mouse) RN - Dystonia-Parkinsonism, Adult-Onset SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2 MH - Disease Models, Animal MH - Dystonic Disorders MH - Group VI Phospholipases A2/deficiency MH - Mice MH - *Neuroaxonal Dystrophies/genetics MH - *Parkinsonian Disorders/genetics PMC - PMC9378686 COIS- The authors declare no competing interests. EDAT- 2022/08/16 06:00 MHDA- 2022/08/18 06:00 PMCR- 2022/08/15 CRDT- 2022/08/15 23:19 PHST- 2021/10/28 00:00 [received] PHST- 2022/07/25 00:00 [accepted] PHST- 2022/08/15 23:19 [entrez] PHST- 2022/08/16 06:00 [pubmed] PHST- 2022/08/18 06:00 [medline] PHST- 2022/08/15 00:00 [pmc-release] AID - 10.1038/s41598-022-17338-1 [pii] AID - 17338 [pii] AID - 10.1038/s41598-022-17338-1 [doi] PST - epublish SO - Sci Rep. 2022 Aug 15;12(1):13825. doi: 10.1038/s41598-022-17338-1. PMID- 35929488 OWN - NLM STAT- MEDLINE DCOM- 20221215 LR - 20240916 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 25 IP - 1 DP - 2023 Jan TI - Tirzepatide for the treatment of adults with type 2 diabetes: An endocrine perspective. PG - 3-17 LID - 10.1111/dom.14831 [doi] AB - Tirzepatide is a novel glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 (GLP-1) receptor agonist approved in the United States as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes and under investigation for use in chronic weight management, major adverse cardiovascular events and the management of other conditions, including heart failure with preserved ejection fraction and obesity and non-cirrhotic non-alcoholic steatohepatitis. The Phase 3 SURPASS 1-5 clinical trial programme was designed to assess efficacy and safety of once-weekly subcutaneously injected tirzepatide (5, 10 and 15 mg), as monotherapy or combination therapy, across a broad spectrum of people with type 2 diabetes. Use of tirzepatide in clinical studies was associated with marked reductions of glycated haemoglobin (-1.87 to -2.59%, -20 to -28 mmol/mol) and body weight (-6.2 to -12.9 kg), as well as reductions in parameters commonly associated with heightened cardiometabolic risk such as blood pressure, visceral adiposity and circulating triglycerides. In SUPRASS-2, these reductions were greater than with the GLP-1 receptor agonist semaglutide 1 mg. Tirzepatide was well tolerated, with a low risk of hypoglycaemia when used without insulin or insulin secretagogues and showed a generally similar safety profile to the GLP-1 receptor agonist class. Accordingly, evidence from these clinical trials suggests that tirzepatide offers a new opportunity for the effective lowering of glycated haemoglobin and body weight in adults with type 2 diabetes. CI - (c) 2022 Eli Lilly and Company and The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - De Block, Christophe AU - De Block C AUID- ORCID: 0000-0002-0679-3203 AD - Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Edegem, Belgium. AD - Faculty of Medicine and Health Sciences, Laboratory of Experimental Medicine and Paediatrics (LEMP), University of Antwerp, Wilrijk, Belgium. FAU - Bailey, Clifford AU - Bailey C AUID- ORCID: 0000-0002-6998-6811 AD - Health and Life Sciences, Aston University, Birmingham, UK. FAU - Wysham, Carol AU - Wysham C AUID- ORCID: 0000-0002-3056-0047 AD - Section of Endocrinology and Metabolism, MultiCare Rockwood Clinic, Spokane, WA, USA. FAU - Hemmingway, Andrea AU - Hemmingway A AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Allen, Sheryl Elaine AU - Allen SE AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Peleshok, Jennifer AU - Peleshok J AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng PT - Journal Article PT - Review DEP - 20220831 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glycated Hemoglobin) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glycated Hemoglobin MH - Glucagon-Like Peptide-1 Receptor MH - Body Weight PMC - PMC10087310 COIS- CDB reports consulting fees from Eli Lilly and Company, Novo Nordisk, AstraZeneca, Boehringer-Ingelheim and Abbott Diagnostics; and payment/honoraria from Eli Lilly and Company and Novo Nordisk. CB reports consulting fees from Abbott, BI, Eli Lilly and Company, and Merck; and payment/honoraria from BI, Intas, Merck and Novo. CW reports research funding from Eli Lilly and Company, Abbott, Corcept, Regeneron, Mylan and Novo Nordisk; participation on a Data Safety Monitoring Board for the NIH Artificial Pancreas Project; and is president of the Endocrine Society. AH, SEA and JP are employees and shareholders of Eli Lilly and Company. EDAT- 2022/08/06 06:00 MHDA- 2022/12/15 06:00 PMCR- 2023/04/11 CRDT- 2022/08/05 05:43 PHST- 2022/07/26 00:00 [revised] PHST- 2022/05/19 00:00 [received] PHST- 2022/08/02 00:00 [accepted] PHST- 2022/08/06 06:00 [pubmed] PHST- 2022/12/15 06:00 [medline] PHST- 2022/08/05 05:43 [entrez] PHST- 2023/04/11 00:00 [pmc-release] AID - DOM14831 [pii] AID - 10.1111/dom.14831 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Jan;25(1):3-17. doi: 10.1111/dom.14831. Epub 2022 Aug 31. PMID- 35925683 OWN - NLM STAT- MEDLINE DCOM- 20230504 LR - 20250103 IS - 1755-3245 (Electronic) IS - 0008-6363 (Linking) VI - 119 IP - 4 DP - 2023 May 2 TI - Cardiovascular effects of incretins: focus on glucagon-like peptide-1 receptor agonists. PG - 886-904 LID - 10.1093/cvr/cvac112 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been used to treat patients with type 2 diabetes since 2005 and have become popular because of the efficacy and durability in relation to glycaemic control in combination with weight loss in most patients. Today in 2022, seven GLP-1 RAs, including oral semaglutide are available for treatment of type 2 diabetes. Since the efficacy in relation to reduction of HbA1c and body weight as well as tolerability and dosing frequency vary between agents, the GLP-1 RAs cannot be considered equal. The short acting lixisenatide showed no cardiovascular benefits, while once daily liraglutide and the weekly agonists, subcutaneous semaglutide, dulaglutide, and efpeglenatide, all lowered the incidence of cardiovascular events. Liraglutide, oral semaglutide and exenatide once weekly also reduced mortality. GLP-1 RAs reduce the progression of diabetic kidney disease. In the 2019 consensus report from European Association for the Study of Diabetes/American Diabetes Association, GLP-1 RAs with demonstrated cardio-renal benefits (liraglutide, semaglutide and dulaglutide) are recommended after metformin to patients with established cardiovascular diseases or multiple cardiovascular risk factors. European Society of Cardiology suggests starting with a sodium-glucose cotransprter-2 inhibitor or a GLP-1 RA in drug naive patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (CVD) or high CV Risk. However, the results from cardiovascular outcome trials (CVOT) are very heterogeneous suggesting that some GLP-1RAs are more suitable to prevent CVD than others. The CVOTs provide a basis upon which individual treatment decisions for patients with T2D and CVD can be made. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com. FAU - Madsbad, Sten AU - Madsbad S AD - Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Copenhagen 2630, Denmark. FAU - Holst, Jens J AU - Holst JJ AUID- ORCID: 0000-0001-6853-3805 AD - Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. AD - Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. LA - eng PT - Journal Article PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (Incretins) RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - Incretins/adverse effects MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Liraglutide/pharmacology MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide 1 MH - *Cardiovascular Diseases/diagnosis/drug therapy/prevention & control MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Body weight OT - CVOT OT - Cardiovascular outcome trials OT - Cardiovascular risk factors OT - Glycaemic control OT - Kidney disease COIS- Conflict of interest: S.M.: Advisory boards: AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novo Nordisk; Sanofi. Lecture fees: AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novartis; Novo Nordisk; Sanofi. Research Grant Recipient: Novo Nordisk and Boehringer-Ingelheim. J.J.H.: Advisory boards: Novo Nordisk. Lecture fees: Novo Nordisk. EDAT- 2022/08/05 06:00 MHDA- 2023/05/04 12:42 CRDT- 2022/08/04 12:03 PHST- 2022/01/03 00:00 [received] PHST- 2022/03/29 00:00 [revised] PHST- 2022/04/04 00:00 [accepted] PHST- 2023/05/04 12:42 [medline] PHST- 2022/08/05 06:00 [pubmed] PHST- 2022/08/04 12:03 [entrez] AID - 6655794 [pii] AID - 10.1093/cvr/cvac112 [doi] PST - ppublish SO - Cardiovasc Res. 2023 May 2;119(4):886-904. doi: 10.1093/cvr/cvac112. PMID- 35909534 OWN - NLM STAT- MEDLINE DCOM- 20220802 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 13 DP - 2022 TI - Effectiveness and Tolerability of Once-Weekly GLP-1 Receptor Agonists in Clinical Practice: A Focus on Switching Between Once-Weekly Molecules in Type 2 Diabetes. PG - 892702 LID - 10.3389/fendo.2022.892702 [doi] LID - 892702 AB - AIMS: This study aims to evaluate the effectiveness and tolerability of once-weekly glucagon-like peptide receptor agonists (OW GLP-1RAs) and to assess the clinical benefits of switching from one GLP-1RA to another (switchers) in a routine clinical setting. MATERIALS AND METHODS: This is a retrospective, real-world cohort study, based on electronic medical records utilized in one Italian diabetes clinic. Estimated mean changes in HbA1c and body weight after 6 and 12 months from the first prescription of a long-acting GLP1-RA were evaluated using longitudinal linear mixed models for repeated measures. The effectiveness of the three long-acting GLP1-RAs was compared separately in the GLP1-RA naive and switchers cohorts, after propensity score adjustment. RESULTS: Initiating a long-acting GLP1-RA was associated with statistically significant improvements in HbA1c (-1%) and body weight (-2.6 kg) after 6 months, and benefits were maintained after 12 months. In GLP1-RA naive cohort, semaglutide showed the largest effect on HbA1c (-1.55%; 95%CI, -1.77;-1.34) and body weight (-3.76 kg; 95%CI, -5.05;-2.47) at 6 months, maintained at 12 months (-1.55%; 95%CI, -1.82;-1.28 and -6.29 kg; 95%CI, -7.94;-4.63). In the switchers' cohort, statistically significant reductions at 6 months in HbA1c and body weight were documented with semaglutide and dulaglutide only, with semaglutide associated with the most marked reduction (-0.84%; 95%CI, -1.03;-0.65 and -3.43 kg; 95%, -4.67;-2.19). Dropout rates were 9.2%, 28.5%, and 41.7% in semaglutide, dulaglutide, and exenatide groups, respectively. CONCLUSIONS: The effectiveness and tolerability of the OW GLP-1RAs in the real world were documented. Semaglutide was associated with the highest response without impact on safety. Clinical improvements were obtained even in switchers, especially in those switching to semaglutide. CI - Copyright (c) 2022 Di Dalmazi, Coluzzi, Baldassarre, Ghit, Graziano, Rossi, Ciappini, Milo, Carrieri, Nicolucci, Consoli and Formoso. FAU - Di Dalmazi, Giulia AU - Di Dalmazi G AD - Department of Medicine and Aging Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Endocrinology and Metabolic Disease Clinic of Pescara, Pescara, Italy. FAU - Coluzzi, Sara AU - Coluzzi S AD - Endocrinology and Metabolic Disease Clinic of Pescara, Pescara, Italy. FAU - Baldassarre, Maria Pompea Antonia AU - Baldassarre MPA AD - Department of Medicine and Aging Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. FAU - Ghit, Amr AU - Ghit A AD - Department of Medicine and Aging Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. FAU - Graziano, Giusi AU - Graziano G AD - CORESEARCH-Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy. FAU - Rossi, Maria Chiara AU - Rossi MC AD - CORESEARCH-Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy. FAU - Ciappini, Beatrice AU - Ciappini B AD - Department of Medicine and Aging Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. FAU - Milo, Marica AU - Milo M AD - Department of Medicine and Aging Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. FAU - Carrieri, Federica AU - Carrieri F AD - Department of Medicine and Aging Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. FAU - Nicolucci, Antonio AU - Nicolucci A AD - CORESEARCH-Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy. FAU - Consoli, Agostino AU - Consoli A AD - Department of Medicine and Aging Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Endocrinology and Metabolic Disease Clinic of Pescara, Pescara, Italy. FAU - Formoso, Gloria AU - Formoso G AD - Department of Medicine and Aging Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. AD - Endocrinology and Metabolic Disease Clinic of Pescara, Pescara, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220715 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Body Weight MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Drug Administration Schedule MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Retrospective Studies MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC9335857 OTO - NOTNLM OT - GLP-1 receptor agonists OT - dulaglutide OT - effectiveness OT - once-weekly exenatide OT - once-weekly semaglutide OT - real-world evidence OT - type 2 diabetes mellitus COIS- GG, MR, and AN are employed by CORESEARCH SRL. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/08/02 06:00 MHDA- 2022/08/03 06:00 PMCR- 2022/01/01 CRDT- 2022/08/01 03:16 PHST- 2022/03/09 00:00 [received] PHST- 2022/05/24 00:00 [accepted] PHST- 2022/08/01 03:16 [entrez] PHST- 2022/08/02 06:00 [pubmed] PHST- 2022/08/03 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2022.892702 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2022 Jul 15;13:892702. doi: 10.3389/fendo.2022.892702. eCollection 2022. PMID- 35905827 OWN - NLM STAT- MEDLINE DCOM- 20220829 LR - 20250103 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 365 DP - 2022 Oct 15 TI - Translating results from the cardiovascular outcomes trials with glucagon-like peptide-1 receptor agonists into clinical practice: Recommendations from a Eastern and Southern Europe diabetes expert group. PG - 8-18 LID - S0167-5273(22)01085-3 [pii] LID - 10.1016/j.ijcard.2022.07.017 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists mimic the action of the endogenous GLP-1 incretin hormone, improving glycaemic control in type 2 diabetes mellitus (T2DM) by increasing insulin secretion and decreasing glucagon secretion in a glucose-dependent manner. However, as cardiovascular (CV) morbidity and mortality is common in patients with T2DM, several trials with the use of GLP-1 receptor agonists (RAs) have been performed focusing on endpoints related to cardiovascular disease rather than metabolic control of T2DM. Following the positive cardiovascular effects of liraglutide, dulaglutide and semaglutide observed in these trials, major changes in T2DM management guidelines have occurred. This document from a Eastern and Southern European Diabetes Expert Group discusses the results of GLP-1 RA CV outcomes trials, their impact on recent clinical guidelines for the management of T2DM, and some selected combination regimens utilising GLP-1 RAs. We also propose an algorithm for guiding GLP-1 RA-based treatment according to patients' characteristics, which can be easily applied in every day clinical practice. CI - Copyright (c) 2022. Published by Elsevier B.V. FAU - Janez, Andrej AU - Janez A AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Slovenia. Electronic address: andrej.janez@kclj.si. FAU - Muzurovic, Emir AU - Muzurovic E AD - Faculty of Medicine, University of Montenegro, Department of Internal Medicine, Endocrinology Section, Clinical Centre of Montenegro, Podgorica, Montenegro. FAU - Stoian, Anca Pantea AU - Stoian AP AD - Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. FAU - Haluzik, Martin AU - Haluzik M AD - Diabetes Centre and Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine and Institute of Endocrinology, Prague, Czech Republic. FAU - Guja, Cristian AU - Guja C AD - Department of Diabetes, Nutrition and Metabolic Diseases, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania. FAU - Czupryniak, Leszek AU - Czupryniak L AD - Department of Diabetology and Internal Medicine, Medical University of Warsaw, Poland. FAU - Duvnjak, Lea AU - Duvnjak L AD - School of Medicine University of Zagreb, Vuk Vrhovac University Clinic, Zagreb, Croatia. FAU - Lalic, Nebojsa AU - Lalic N AD - Faculty of Medicine University of Belgrade, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia. FAU - Tankova, Tsvetalina AU - Tankova T AD - Department of Endocrinology, Medical University, Sofia, Bulgaria. FAU - Bogdanski, Pawel AU - Bogdanski P AD - Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, University of Medical Sciences, Poznan, Poland. FAU - Papanas, Nikolaos AU - Papanas N AD - Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece. FAU - Nunes, Jose Silva AU - Nunes JS AD - Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitario Lisboa Central, Lisbon, Portugal. FAU - Kempler, Peter AU - Kempler P AD - First Department of Medicine, Semmelweis University, Budapest, Hungary. FAU - Fras, Zlatko AU - Fras Z AD - Preventive Cardiology Unit, Division of Medicine, University Medical Centre Ljubljana and Chair of Internal Medicine, Medical Faculty, University of Ljubljana, Slovenia. FAU - Rizzo, Manfredi AU - Rizzo M AD - Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (Promise), School of Medicine, University of Palermo, Italy. LA - eng PT - Journal Article DEP - 20220726 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Int J Cardiol. 2022 Nov 15;367:63-64. doi: 10.1016/j.ijcard.2022.08.041. PMID: 36028093 MH - *Cardiovascular Diseases/drug therapy/epidemiology MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy/epidemiology MH - Glucagon-Like Peptide 1/metabolism MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Liraglutide/pharmacology/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Algorithm OT - Cardiovascular outcomes trials OT - GLP-1 receptor agonists OT - Treatment OT - Type 2 diabetes mellitus EDAT- 2022/07/30 06:00 MHDA- 2022/08/30 06:00 CRDT- 2022/07/29 19:14 PHST- 2022/05/29 00:00 [received] PHST- 2022/07/05 00:00 [revised] PHST- 2022/07/12 00:00 [accepted] PHST- 2022/07/30 06:00 [pubmed] PHST- 2022/08/30 06:00 [medline] PHST- 2022/07/29 19:14 [entrez] AID - S0167-5273(22)01085-3 [pii] AID - 10.1016/j.ijcard.2022.07.017 [doi] PST - ppublish SO - Int J Cardiol. 2022 Oct 15;365:8-18. doi: 10.1016/j.ijcard.2022.07.017. Epub 2022 Jul 26. PMID- 35879524 OWN - NLM STAT- MEDLINE DCOM- 20221006 LR - 20260127 IS - 1708-0428 (Electronic) IS - 0960-8923 (Print) IS - 0960-8923 (Linking) VI - 32 IP - 10 DP - 2022 Oct TI - The Potential of Semaglutide Once-Weekly in Patients Without Type 2 Diabetes with Weight Regain or Insufficient Weight Loss After Bariatric Surgery-a Retrospective Analysis. PG - 3280-3288 LID - 10.1007/s11695-022-06211-9 [doi] AB - PURPOSE: About 20-25% of patients experience weight regain (WR) or insufficient weight loss (IWL) after bariatric metabolic surgery (BS). Therefore, we aimed to retrospectively assess the effectiveness of adjunct treatment with the GLP-1 receptor agonist semaglutide in non-diabetic patients with WR or IWL after BS. MATERIALS AND METHODS: Post-bariatric patients without type 2 diabetes (T2D) with WR or IWL (n = 44) were included in the analysis. The primary endpoint was weight loss 3 and 6 months after initiation of adjunct treatment. Secondary endpoints included change in BMI, HbA1c, lipid profile, hs-CRP, and liver enzymes. RESULTS: Patients started semaglutide 64.7 +/- 47.6 months (mean +/- SD) after BS. At initiation of semaglutide, WR after post-bariatric weight nadir was 12.3 +/- 14.4% (mean +/- SD). Total weight loss during semaglutide treatment was - 6.0 +/- 4.3% (mean +/- SD, p < 0.001) after 3 months (3.2 months, IQR 3.0-3.5, n = 38) and - 10.3 +/- 5.5% (mean +/- SD, p < 0.001) after 6 months (5.8 months, IQR 5.8-6.4, n = 20). At 3 months, categorical weight loss was > 5% in 61% of patients, > 10% in 16% of patients, and > 15% in 2% of patients. Triglycerides (OR = 0.99; p < 0.05), ALT (OR = 0.87; p = 0.05), and AST (OR = 0.89; p < 0.05) at baseline were negatively associated with weight loss of at least 5% at 3 months' follow-up (p < 0.05). CONCLUSION: Treatment options to manage post-bariatric excess weight (regain) are scarce. Our results imply a clear benefit of adjunct treatment with semaglutide in post-bariatric patients. However, these results need to be confirmed in a prospective randomized controlled trial to close the gap between lifestyle intervention and revision surgery in patients with IWL or WR after BS. CI - (c) 2022. The Author(s). FAU - Lautenbach, Anne AU - Lautenbach A AUID- ORCID: 0000-0002-7763-1527 AD - III Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. a.lautenbach@uke.de. FAU - Wernecke, Marie AU - Wernecke M AD - III Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. FAU - Huber, Tobias B AU - Huber TB AD - III Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. FAU - Stoll, Fabian AU - Stoll F AD - III Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. FAU - Wagner, Jonas AU - Wagner J AD - Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany. FAU - Meyhofer, Sebastian M AU - Meyhofer SM AD - Institute for Endocrinology & Diabetes, University of Lubeck, 23562, Lubeck, Germany. AD - German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany. FAU - Meyhofer, Svenja AU - Meyhofer S AD - Institute for Endocrinology & Diabetes, University of Lubeck, 23562, Lubeck, Germany. AD - German Center for Diabetes Research (DZD), 85764, Neuherberg, Germany. AD - First Department of Medicine Endocrinology and Diabetes, University Clinic Schleswig-Holstein - Campus Lubeck, 23538, Lubeck, Germany. FAU - Aberle, Jens AU - Aberle J AD - III Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. LA - eng PT - Journal Article DEP - 20220725 PL - United States TA - Obes Surg JT - Obesity surgery JID - 9106714 RN - 9007-41-4 (C-Reactive Protein) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Lipids) RN - 0 (Triglycerides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Bariatric Surgery MH - C-Reactive Protein MH - *Diabetes Mellitus, Type 2/drug therapy/surgery MH - Glucagon-Like Peptide-1 Receptor MH - *Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Lipids MH - *Obesity, Morbid/surgery MH - Prospective Studies MH - Retrospective Studies MH - Triglycerides MH - Weight Gain MH - Weight Loss MH - Semaglutide PMC - PMC9532334 OTO - NOTNLM OT - Bariatric surgery OT - GLP-1 receptor agonist OT - Semaglutide OT - Weight regain COIS- Anne Lautenbach, Tobias B. Huber, Sebastian M. Meyhofer, Jens Aberle: The authors have received honoraria for speaking at symposia, financial support for attending symposia, financial support for educational programs, and consultation from Novo Nordisk. Marie Wernecke, Fabian Stoll, Jonas Wagner, Svenja Meyhofer: The authors declare that they have no conflict of interest. EDAT- 2022/07/26 06:00 MHDA- 2022/10/07 06:00 PMCR- 2022/07/25 CRDT- 2022/07/25 23:35 PHST- 2022/04/24 00:00 [received] PHST- 2022/07/14 00:00 [accepted] PHST- 2022/07/10 00:00 [revised] PHST- 2022/07/26 06:00 [pubmed] PHST- 2022/10/07 06:00 [medline] PHST- 2022/07/25 23:35 [entrez] PHST- 2022/07/25 00:00 [pmc-release] AID - 10.1007/s11695-022-06211-9 [pii] AID - 6211 [pii] AID - 10.1007/s11695-022-06211-9 [doi] PST - ppublish SO - Obes Surg. 2022 Oct;32(10):3280-3288. doi: 10.1007/s11695-022-06211-9. Epub 2022 Jul 25. PMID- 35872608 OWN - NLM STAT- MEDLINE DCOM- 20220825 LR - 20250103 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 30 IP - 9 DP - 2022 Sep TI - Glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon receptor poly-agonists: a new era in obesity pharmacotherapy. PG - 1718-1721 LID - 10.1002/oby.23521 [doi] AB - Achieving successful long-term weight loss with lifestyle modification in people with obesity is difficult and underscores the need for effective pharmacotherapy. Since 1947, a total of 18 medications have been approved by the US Food and Drug Administration for treating obesity; however, only 5 remain available for long-term use in the US. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist approved in 2021, demonstrated much greater weight loss than previous medications, which stimulated the development of poly-agonists that combine GLP-1 receptor agonism with glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptor agonism. The potential of this approach was recently demonstrated by the extraordinary weight loss achieved by tirzepatide, a GLP-1/GIP receptor dual agonist. The therapeutic efficacy of poly-agonists is likely to change the treatment paradigm for obesity. However, the use of medications for obesity, as for other chronic diseases, will likely require lifelong treatment, which makes it important to analyze the long-term efficacy, safety, and economic implications of chronic pharmacotherapy. CI - (c) 2022 The Obesity Society. FAU - Malik, Is-Haq O AU - Malik IO AD - Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA. AD - Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Petersen, Max C AU - Petersen MC AUID- ORCID: 0000-0001-8646-2377 AD - Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA. AD - Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri, USA. FAU - Klein, Samuel AU - Klein S AUID- ORCID: 0000-0001-7127-1156 AD - Center for Human Nutrition, Washington University School of Medicine, St. Louis, Missouri, USA. LA - eng GR - P30 DK056341/DK/NIDDK NIH HHS/United States GR - P30 DK020579/DK/NIDDK NIH HHS/United States GR - UL1 TR002345/TR/NCATS NIH HHS/United States GR - UL1 TR000448/TR/NCATS NIH HHS/United States GR - T32 DK007120/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20220724 PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Receptors, Gastrointestinal Hormone) RN - 0 (Receptors, Glucagon) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) RN - IY9XDZ35W2 (Glucose) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Gastric Inhibitory Polypeptide/therapeutic use MH - Glucose MH - Humans MH - *Obesity/drug therapy MH - Receptors, Gastrointestinal Hormone MH - *Receptors, Glucagon/agonists MH - Weight Loss MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC9420816 MID - NIHMS1818195 EDAT- 2022/07/26 06:00 MHDA- 2022/08/26 06:00 PMCR- 2023/09/01 CRDT- 2022/07/25 02:52 PHST- 2022/06/19 00:00 [revised] PHST- 2022/06/16 00:00 [received] PHST- 2022/06/20 00:00 [accepted] PHST- 2022/07/26 06:00 [pubmed] PHST- 2022/08/26 06:00 [medline] PHST- 2022/07/25 02:52 [entrez] PHST- 2023/09/01 00:00 [pmc-release] AID - 10.1002/oby.23521 [doi] PST - ppublish SO - Obesity (Silver Spring). 2022 Sep;30(9):1718-1721. doi: 10.1002/oby.23521. Epub 2022 Jul 24. PMID- 35842847 OWN - NLM STAT- MEDLINE DCOM- 20220826 LR - 20260127 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 59 IP - 10 DP - 2022 Oct TI - Effects of semaglutide on cardiovascular risk factors and eating behaviors in type 2 diabetes. PG - 1287-1294 LID - 10.1007/s00592-022-01936-6 [doi] AB - AIMS: Aim of the present study was to evaluate the impact of once-weekly semaglutide on different end-points indicative of metabolic control, cardiovascular risk, dietary behavior, and treatment satisfaction in T2DM. METHODS: This was a retrospective observational study conducted in a diabetes clinic. Changes in HbA1c, fasting blood glucose (FBG), weight, blood pressure, lipid profile, and number of antihypertensive drugs at 32 weeks (T1) after the first prescription of semaglutide (T0) were analyzed. Furthermore, at T1 patients were asked to fill-in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the Control of Eating Questionnaire (COEQ). RESULTS: Overall, 104 patients were identified (mean age 63.6 +/- 10.4 years, 58.7% men, diabetes duration 12.7 +/- 8.7 years). After 32 weeks of treatment with semaglutide, HbA1c levels were reduced by 1.38%, FBG by - 56.53 mg/dl, weight by 6.03 kg. Systolic and diastolic blood pressure, total, HDL-, LDL-, and non -HDL cholesterol, and triglycerides significantly improved. The number of glucose-lowering and antihypertensive drugs also decreased. At T1, DTSQ score was 32.23 +/- 1.44, whereas COEQ indicated low levels of hunger and good control of eating. CONCLUSIONS: The study documented benefits of semaglutide on metabolic control and multiple CV risk factors, simplification of therapeutic schemes and high satisfaction with diabetes treatment, and eating behaviors indicative of healthy diet and reduced food intake. CI - (c) 2022. The Author(s). FAU - Di Folco, Ugo AU - Di Folco U AUID- ORCID: 0000-0003-0531-7691 AD - Diabetes Unit, "S. Camillo-Forlanini" Hospital, Rome, Italy. difolcougo@gmail.com. FAU - Vallecorsa, Noemi AU - Vallecorsa N AD - Diabetes Unit, "S. Camillo-Forlanini" Hospital, Rome, Italy. FAU - Nardone, Maria Rosaria AU - Nardone MR AD - Diabetes Unit, "S. Camillo-Forlanini" Hospital, Rome, Italy. FAU - Pantano, Angelo Lauria AU - Pantano AL AD - Diabetes Unit, "S. Camillo-Forlanini" Hospital, Rome, Italy. FAU - Tubili, Claudio AU - Tubili C AD - Diabetes Unit, "S. Camillo-Forlanini" Hospital, Rome, Italy. LA - eng PT - Journal Article PT - Observational Study DEP - 20220717 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Antihypertensive Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Acta Diabetol. 2023 May;60(5):715-716. doi: 10.1007/s00592-023-02061-8. PMID: 36899150 MH - Aged MH - Antihypertensive Agents/therapeutic use MH - *Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Feeding Behavior MH - Female MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/metabolism MH - Heart Disease Risk Factors MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Male MH - Middle Aged MH - Risk Factors MH - Semaglutide PMC - PMC9288662 OTO - NOTNLM OT - Eating behaviors HbA1c OT - Effectiveness OT - Hyperglycemia OT - Non-HDL cholesterol OT - Semaglutide OT - Treatment satisfaction OT - Type 2 diabetes OT - Weight COIS- The author(s) declared no potential conflict of interest with respect to the research, authorship, and/or publication of this article. EDAT- 2022/07/18 06:00 MHDA- 2022/08/27 06:00 PMCR- 2022/07/17 CRDT- 2022/07/17 14:08 PHST- 2022/05/27 00:00 [received] PHST- 2022/06/29 00:00 [accepted] PHST- 2022/07/18 06:00 [pubmed] PHST- 2022/08/27 06:00 [medline] PHST- 2022/07/17 14:08 [entrez] PHST- 2022/07/17 00:00 [pmc-release] AID - 10.1007/s00592-022-01936-6 [pii] AID - 1936 [pii] AID - 10.1007/s00592-022-01936-6 [doi] PST - ppublish SO - Acta Diabetol. 2022 Oct;59(10):1287-1294. doi: 10.1007/s00592-022-01936-6. Epub 2022 Jul 17. PMID- 35838946 OWN - NLM STAT- MEDLINE DCOM- 20220929 LR - 20260127 IS - 1573-2606 (Electronic) IS - 1389-9155 (Print) IS - 1389-9155 (Linking) VI - 23 IP - 5 DP - 2022 Oct TI - A new era for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes. PG - 979-994 LID - 10.1007/s11154-022-09735-8 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) were first introduced for the treatment of type 2 diabetes (T2D) in 2005. Despite the high efficacy and other benefits of GLP-1RAs, their uptake was initially limited by the fact that they could only be administered by injection. Semaglutide is a human GLP-1 analog that has been shown to significantly improve glycemic control and reduce body weight, in addition to improving cardiovascular outcomes, in patients with T2D. First approved as a once-weekly subcutaneous injection, semaglutide was considered an ideal peptide candidate for oral delivery with a permeation enhancer on account of its low molecular weight, long half-life, and high potency. An oral formulation of semaglutide was therefore developed by co-formulating semaglutide with sodium N-(8-[2-hydroxybenzoyl]amino)caprylate, a well-characterized transcellular permeation enhancer, to produce the first orally administered GLP-1RA. Pharmacokinetic analysis showed that stable steady-state concentrations could be achieved with once-daily dosing owing to the long half-life of oral semaglutide. Upper gastrointestinal disease and renal and hepatic impairment did not affect the pharmacokinetic profile. In the phase III PIONEER clinical trial program, oral semaglutide was shown to reduce glycated hemoglobin and body weight compared with placebo and active comparators in patients with T2D, with no new safety signals reported. Cardiovascular efficacy and safety are currently being assessed in a dedicated outcomes trial. The development of an oral GLP-1RA represents a significant milestone in the management of T2D, providing an additional efficacious treatment option for patients. CI - (c) 2022. The Author(s). FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. varoda@bwh.harvard.edu. FAU - Blonde, Lawrence AU - Blonde L AUID- ORCID: 0000-0003-0492-6698 AD - Endocrinology Department, Ochsner Health, New Orleans, LA, USA. FAU - Pratley, Richard E AU - Pratley RE AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, FL, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20220715 PL - Germany TA - Rev Endocr Metab Disord JT - Reviews in endocrine & metabolic disorders JID - 100940588 RN - 0 (Caprylates) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Peptides) RN - 9NEZ333N27 (Sodium) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Body Weight MH - Caprylates/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Glucagon-Like Peptides/adverse effects MH - Glycated Hemoglobin MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Peptides/therapeutic use MH - Sodium/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC9515042 OTO - NOTNLM OT - GLP-1RA OT - Glucagon-like peptide-1 receptor agonists OT - Oral OT - Peptides OT - SNAC OT - Semaglutide OT - Sodium N-(8-[2-hydroxybenzoyl]amino)caprylate OT - Type 2 diabetes COIS- VRA has served as a consultant for Applied Therapeutics, Fractyl Health, Novo Nordisk, Pfizer, and Sanofi; VRA's spouse is employed by Janssen Pharmaceuticals, Inc. and receives employment benefits; VRA has received institutional contracts for research from Applied Therapeutics, Eli Lilly, Fractyl Health, Novo Nordisk, and Sanofi. LB has received consultancy fees from Corcept Therapeutics, Gilead, Janssen Pharmaceuticals, Inc., Lyndra Therapeutics, Merck, Novo Nordisk, Salix Pharmaceuticals, and Sanofi; and has received speaker fees from Sanofi. REP reports consulting fees from Bayer AG, Corcept Therapeutics, Dexcom, Hanmi Pharmaceutical Co., Merck, Novo Nordisk, Pfizer, Sanofi, Scohia Pharma Inc., and Sun Pharmaceutical Industries; and grants/research support from Hanmi Pharmaceutical Co., Janssen Pharmaceuticals, Inc., Metavention, Novo Nordisk, Poxel SA, and Sanofi. All funds are paid directly to Dr. Pratley's employer, AdventHealth, a nonprofit organization that supports education and research. EDAT- 2022/07/16 06:00 MHDA- 2022/09/30 06:00 PMCR- 2022/07/15 CRDT- 2022/07/15 12:05 PHST- 2022/04/19 00:00 [accepted] PHST- 2022/07/16 06:00 [pubmed] PHST- 2022/09/30 06:00 [medline] PHST- 2022/07/15 12:05 [entrez] PHST- 2022/07/15 00:00 [pmc-release] AID - 10.1007/s11154-022-09735-8 [pii] AID - 9735 [pii] AID - 10.1007/s11154-022-09735-8 [doi] PST - ppublish SO - Rev Endocr Metab Disord. 2022 Oct;23(5):979-994. doi: 10.1007/s11154-022-09735-8. Epub 2022 Jul 15. PMID- 35817678 OWN - NLM STAT- MEDLINE DCOM- 20220809 LR - 20250623 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 36 IP - 8 DP - 2022 Aug TI - Progression of retinopathy with glucagon-like peptide-1 receptor agonists with cardiovascular benefits in type 2 diabetes - A systematic review and meta-analysis. PG - 108255 LID - S1056-8727(22)00164-7 [pii] LID - 10.1016/j.jdiacomp.2022.108255 [doi] AB - AIMS: The effect of Glucagon-like peptide 1 receptor agonists (GLP1 RA) on diabetic retinopathy (DR) remains controversial. Previous reviews combined data from randomized clinical trials (RCTs) with or without cardiovascular (CV) benefits and did not address confounders, therefore may have generated misleading results. The study aimed to examine the effect of GLP1RA on DR in type 2 diabetes (T2DM) in RCTs with or without CV benefits and distinguish the effect by major confounders. METHODS: We conducted electronic searches of multiple databases and a manual search using references lists. We included 13 RCTs examining the effect of GLP1 RA on health outcomes/adverse events including DR or DR complications in T2DM. We performed a random-effects model meta-analysis. RESULTS: GLP1RA was associated with an elevated risk of rapidly worsening DR in four major RCTs with CV benefits in T2DM (OR 1.23, 95 % CI 1.05-1.44). The association between GLP1 RA and DR was significant in subgroups of RCTs with length over 52 weeks (1.2, 1.00-1.43), using placebo as a comparator (1.22, 1.05-1.42). In subgroups with patients who had T2DM >/=10 years (1.19, 0.99-1.42) or with subjects enrolled from multiple countries (1.2, 0.99-1.46), the association appeared to be evident but did not reach statistical significance. CONCLUSIONS: GLP1 RA including liraglutide, semaglutide, and dulaglutide are associated with an increased risk of rapidly worsening DR in RCTs with CV benefits. Further data from clinical studies with longer follow-up purposefully designed for DR risk assessment, particularly including patients of established DR are warranted. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Yoshida, Yilin AU - Yoshida Y AD - Section of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, United States of America. Electronic address: yyoshida1@tulane.edu. FAU - Joshi, Preeti AU - Joshi P AD - Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States of America. FAU - Barri, Saba AU - Barri S AD - Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, United States of America. FAU - Wang, Jia AU - Wang J AD - Section of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, United States of America. FAU - Corder, Amy L AU - Corder AL AD - Rudolph Matas Library of the Health Sciences, Tulane University, New Orleans, LA, United States of America. FAU - O'Connell, Samantha S AU - O'Connell SS AD - Tulane University Office of Academic Affairs and Provost, United States of America. FAU - Fonseca, Vivian A AU - Fonseca VA AD - Section of Endocrinology and Metabolism, Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, United States of America. Electronic address: vfonseca@tulane.edu. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20220705 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - J Diabetes Complications. 2022 Sep;36(9):108285. doi: 10.1016/j.jdiacomp.2022.108285. PMID: 35998555 MH - *Cardiovascular Diseases/complications/epidemiology MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Diabetic Retinopathy/complications/epidemiology MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Liraglutide/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP1-RA OT - Retinopathy OT - Type 2 diabetes OT - meta-analysis EDAT- 2022/07/12 06:00 MHDA- 2022/08/10 06:00 CRDT- 2022/07/11 22:06 PHST- 2022/05/18 00:00 [received] PHST- 2022/06/20 00:00 [revised] PHST- 2022/06/28 00:00 [accepted] PHST- 2022/07/12 06:00 [pubmed] PHST- 2022/08/10 06:00 [medline] PHST- 2022/07/11 22:06 [entrez] AID - S1056-8727(22)00164-7 [pii] AID - 10.1016/j.jdiacomp.2022.108255 [doi] PST - ppublish SO - J Diabetes Complications. 2022 Aug;36(8):108255. doi: 10.1016/j.jdiacomp.2022.108255. Epub 2022 Jul 5. PMID- 35813629 OWN - NLM STAT- MEDLINE DCOM- 20220712 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 13 DP - 2022 TI - Efficacy and Safety of Semaglutide for the Management of Obese Patients With Type 2 Diabetes and Chronic Heart Failure in Real-World Clinical Practice. PG - 851035 LID - 10.3389/fendo.2022.851035 [doi] LID - 851035 AB - BACKGROUND: The impact of glucagon-like peptide-1 receptor agonists on patients with heart failure has not been fully described. Our main objective was to evaluate the safety and clinical and glycemic efficacy of once-weekly semaglutide in obese patients with type 2 diabetes and heart failure. METHODS: In this observational, retrospective, real-world study, we enrolled outpatients with type 2 diabetes, obesity, and heart failure who started semaglutide and were followed-up on at 3, 6, and 12 months. RESULTS: A total of 136 patients were included. From baseline to 12 months, there was a significant improvement on the Kansas City Cardiomyopathy Questionnaire total symptom score (59.0 +/- 24.1 vs 79.9 +/- 28.4 points, p<0.01), a reduction in the proportion of patients with New York Heart Association functional class III (40.4% to 16.2%, p<0.01), and a reduction in N-terminal pro-brain natriuretic peptide levels (969.5 +/- 653.5 vs 577.4 +/- 322.1 pg/mL, p<0.01). Emergency department visits due to heart failure, hospitalizations due to heart failure, and all-cause hospitalizations also declined. Additionally, significant reductions in glycated hemoglobin (-1.4%) and body weight (-12.7 kilograms) were observed as well as a de-intensification of antidiabetic therapy. Moreover, semaglutide was safe and well-tolerated. CONCLUSION: In obese patients with type 2 diabetes and heart failure, the use of once-weekly semaglutide was safe and clinically efficacious, improving health and functional status. Nevertheless, more strong evidence on glucagon-like peptide-1 receptor agonists in heart failure is required. CI - Copyright (c) 2022 Perez-Belmonte, Sanz-Canovas, Garcia de Lucas, Ricci, Aviles-Bueno, Cobos-Palacios, Perez-Velasco, Lopez-Sampalo, Bernal-Lopez, Jansen-Chaparro, Miramontes-Gonzalez and Gomez-Huelgas. FAU - Perez-Belmonte, Luis M AU - Perez-Belmonte LM AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Spain. AD - Servicio de Medicina Interna, Hospital Hospital Helicopteros Sanitarios, Marbella, Spain. AD - Centro de Investigacion Biomedica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain. FAU - Sanz-Canovas, Jaime AU - Sanz-Canovas J AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Spain. FAU - Garcia de Lucas, Maria D AU - Garcia de Lucas MD AD - Servicio de Medicina Interna, Hospital Costa del Sol, Marbella, Spain. FAU - Ricci, Michele AU - Ricci M AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Spain. FAU - Aviles-Bueno, Beatriz AU - Aviles-Bueno B AD - Servicio de Nefrologia, Hospital Costal del Sol, Marbella, Spain. FAU - Cobos-Palacios, Lidia AU - Cobos-Palacios L AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Spain. FAU - Perez-Velasco, Miguel A AU - Perez-Velasco MA AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Spain. FAU - Lopez-Sampalo, Almudena AU - Lopez-Sampalo A AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Spain. FAU - Bernal-Lopez, M Rosa AU - Bernal-Lopez MR AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Spain. AD - Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. FAU - Jansen-Chaparro, Sergio AU - Jansen-Chaparro S AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Spain. FAU - Miramontes-Gonzalez, Jose P AU - Miramontes-Gonzalez JP AD - Servicio de Medicina Interna, Hospital Universitario Rio Hortega, Departamento de Medicina, Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain. AD - Instituto de investigaciones biomedicas de Salamanca (IBSAL), Salamanca, Spain. FAU - Gomez-Huelgas, Ricardo AU - Gomez-Huelgas R AD - Servicio de Medicina Interna, Hospital Regional Universitario de Malaga, Instituto de Investigacion Biomedica de Malaga (IBIMA), Universidad de Malaga (UMA), Malaga, Spain. AD - Centro de Investigacion Biomedica en Red Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. LA - eng PT - Journal Article PT - Observational Study DEP - 20220624 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - *Heart Failure/complications/drug therapy MH - Humans MH - Obesity/chemically induced/complications/drug therapy MH - Retrospective Studies MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC9263111 OTO - NOTNLM OT - health status OT - heart failure OT - obesity OT - semaglutide OT - type 2 diabetes COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/07/12 06:00 MHDA- 2022/07/14 06:00 PMCR- 2022/01/01 CRDT- 2022/07/11 04:05 PHST- 2022/01/08 00:00 [received] PHST- 2022/05/26 00:00 [accepted] PHST- 2022/07/11 04:05 [entrez] PHST- 2022/07/12 06:00 [pubmed] PHST- 2022/07/14 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2022.851035 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2022 Jun 24;13:851035. doi: 10.3389/fendo.2022.851035. eCollection 2022. PMID- 35803320 OWN - NLM STAT- MEDLINE DCOM- 20221004 LR - 20250103 IS - 1532-8600 (Electronic) IS - 0026-0495 (Linking) VI - 136 DP - 2022 Nov TI - Recent guidelines for Non-Alcoholic Fatty Liver disease (NAFLD)/ Fatty Liver Disease (FLD): Are they already outdated and in need of supplementation? PG - 155248 LID - S0026-0495(22)00126-3 [pii] LID - 10.1016/j.metabol.2022.155248 [doi] AB - Non-Alcoholic Fatty Liver Disease (NAFLD) is a highly prevalent disease and unmet clinical need that we have recently proposed to be renamed for simplicity and accuracy as Fatty Liver Disease (FLD), with specific subclassifications. It has been commonly associated with metabolic comorbidities, including obesity, type 2 diabetes (T2D), hypertension, and hyperlipidemia. Since no Federal and Drug Administration (FDA) approved treatments exist to date, recent guidelines recommend lifestyle interventions, bariatric surgery, and pharmacotherapy, i.e. glucagon-like peptide-1 receptor agonists (GLP-1RA), peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists, and SGLT-2 inhibitors for its treatment. A new and novel medication for the treatment of T2D, tirzepatide, a dual GIP/GLP-1RA, was approved by the FDA only one week after guidelines were published, and ongoing clinical trials demonstrate promising results not only for T2D but also for body weight and steatosis. Moreover, we realize that distinct subgroups exist under the umbrella of FLD and, thus, more precise therapeutic recommendations would be needed towards the goal of personalized medicine and therapeutics for these subgroups. As the metabolism field is moving forward very fast and as several molecules in development will most likely demonstrate benefits in NAFLD treatment in the foreseeable future, guidelines will need to be frequently updated. This rapid pace of change prompts us to propose that guidelines should exist as living online documents on the websites of professional societies, so that they continue being updated following and reflecting the rapid progress in this and other fields of medicine. CI - Copyright (c) 2022. Published by Elsevier Inc. FAU - Valenzuela-Vallejo, Laura AU - Valenzuela-Vallejo L AD - Department of Medicine, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States of America. FAU - Guatibonza-Garcia, Valentina AU - Guatibonza-Garcia V AD - Department of Medicine, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States of America. FAU - Mantzoros, Christos S AU - Mantzoros CS AD - Department of Medicine, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States of America; Department of Medicine, Boston VA Healthcare System, Boston, MA 02130, United States of America. Electronic address: cmantzor@bidmc.harvard.edu. LA - eng PT - Editorial DEP - 20220705 PL - United States TA - Metabolism JT - Metabolism: clinical and experimental JID - 0375267 RN - 0 (Peroxisome Proliferator-Activated Receptors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Dietary Supplements MH - Humans MH - *Non-alcoholic Fatty Liver Disease/complications/drug therapy MH - Peroxisome Proliferator-Activated Receptors MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Diabetes OT - GIP OT - GLP-1 OT - Liraglutide OT - NAFLD OT - NASH OT - Obesity OT - Semaglutide OT - Tirzepatide COIS- Declaration of competing interest CSM has been a shareholder of and reports grants through his institution and personal consulting fees from Coherus Inc., AltrixBio, grants through his institution from Merck, and grants through his institution personal consulting fees from Novo Nordisk, reports personal consulting fees and support with research reagents from Ansh Inc., reports personal consulting fees from Genfit, Lumos, Amgen, Corcept, Intercept, 89Bio, Astra Zeneca and Regeneron, reports support (educational activity meals at and through his institution) from Amarin, Novo Nordisk and travel support and fees from TMIOA, Elsevier, the California Walnut Commission, College Internationale Research Servier and the Cardio Metabolic Health Conference. None is related to the medication presented herein or its manufacturer. EDAT- 2022/07/09 06:00 MHDA- 2022/10/05 06:00 CRDT- 2022/07/08 19:23 PHST- 2022/06/16 00:00 [received] PHST- 2022/06/22 00:00 [revised] PHST- 2022/06/22 00:00 [accepted] PHST- 2022/07/09 06:00 [pubmed] PHST- 2022/10/05 06:00 [medline] PHST- 2022/07/08 19:23 [entrez] AID - S0026-0495(22)00126-3 [pii] AID - 10.1016/j.metabol.2022.155248 [doi] PST - ppublish SO - Metabolism. 2022 Nov;136:155248. doi: 10.1016/j.metabol.2022.155248. Epub 2022 Jul 5. PMID- 35802842 OWN - NLM STAT- MEDLINE DCOM- 20220712 LR - 20260127 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 64 IP - 1654 DP - 2022 Jul 11 TI - Tirzepatide (Mounjaro) for type 2 diabetes. PG - 105-107 LA - eng PT - Journal Article PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - 0 (Blood Glucose) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 2ZM8CX04RZ (Insulin Glargine) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptides MH - Glycated Hemoglobin MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Insulin Glargine MH - Tirzepatide OTO - NOTNLM OT - Lantus OT - Mounjaro OT - Ozempic OT - Saxenda OT - Tresiba OT - Trulicity OT - Victoza OT - Wegovy OT - adverse effects OT - degludec OT - dosage OT - drug interactions OT - dulaglutide OT - efficacy OT - glargine OT - insulin OT - lactation OT - liraglutide OT - pregnancy OT - safety OT - semaglutide OT - tirzepatide OT - type 2 diabetes EDAT- 2022/07/09 06:00 MHDA- 2022/07/14 06:00 CRDT- 2022/07/08 16:03 PHST- 2022/07/08 16:03 [entrez] PHST- 2022/07/09 06:00 [pubmed] PHST- 2022/07/14 06:00 [medline] PST - ppublish SO - Med Lett Drugs Ther. 2022 Jul 11;64(1654):105-107. PMID- 35799471 OWN - NLM STAT- MEDLINE DCOM- 20220711 LR - 20260127 IS - 2052-1707 (Electronic) IS - 2052-1707 (Linking) VI - 10 IP - 4 DP - 2022 Aug TI - Population pharmacokinetic of paracetamol and atorvastatin with co-administration of semaglutide. PG - e00962 LID - 10.1002/prp2.962 [doi] LID - e00962 AB - Semaglutide is a glucagon-like-peptide-1 (GLP-1) analogue marketed for once-weekly subcutaneous administration for type 2 diabetes mellitus. Like other long-acting GLP-1 analogues, semaglutide reduces gastric emptying and, potentially, alters the rate of absorption of orally co-administered drugs. The objective of the current analysis was to evaluate the effects on the gastric emptying rate caused by semaglutide on pharmacokinetic model parameters of paracetamol and atorvastatin in healthy subjects. Non-linear mixed effect modeling was used to estimate population pharmacokinetic model parameters of paracetamol and atorvastatin after single doses with or without semaglutide. The absorption rate (ka) of paracetamol decreased by 53% when co-administered with semaglutide. For atorvastatin, ka and transit compartment rate (ktr) decreased by 72% and 91%, respectively. Thus, gastric emptying, measured as T50, i.e., drug disappearance from the absorption compartments, showed an additional 5-min delay for paracetamol and a 67-min delay for atorvastatin when co-administered with semaglutide. Semaglutide affected pharmacokinetic model parameters of paracetamol and atorvastatin, and minor quantitative differences in gastric emptying between placebo vs. semaglutide administration were observed. However, these effects of semaglutide were considered not to be of clinical relevance. CI - (c) 2022 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics. FAU - Langeskov, Emilie K AU - Langeskov EK AUID- ORCID: 0000-0001-6181-7151 AD - Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. FAU - Kristensen, Kim AU - Kristensen K AUID- ORCID: 0000-0001-8988-8023 AD - Discovery & Development PKPD, Novo Nordisk A/S, Malov, Denmark. LA - eng PT - Journal Article PL - United States TA - Pharmacol Res Perspect JT - Pharmacology research & perspectives JID - 101626369 RN - 362O9ITL9D (Acetaminophen) RN - A0JWA85V8F (Atorvastatin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Acetaminophen/therapeutic use MH - Atorvastatin MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/pharmacokinetics MH - Semaglutide PMC - PMC9263537 OTO - NOTNLM OT - GLP-1 OT - acetaminophen OT - atorvastatin OT - drug interactions OT - gastric emptying OT - humans OT - models biological OT - pharmacokinetics EDAT- 2022/07/09 06:00 MHDA- 2022/07/12 06:00 PMCR- 2022/07/07 CRDT- 2022/07/08 02:21 PHST- 2021/09/24 00:00 [received] PHST- 2022/04/02 00:00 [accepted] PHST- 2022/07/08 02:21 [entrez] PHST- 2022/07/09 06:00 [pubmed] PHST- 2022/07/12 06:00 [medline] PHST- 2022/07/07 00:00 [pmc-release] AID - PRP2962 [pii] AID - 10.1002/prp2.962 [doi] PST - ppublish SO - Pharmacol Res Perspect. 2022 Aug;10(4):e00962. doi: 10.1002/prp2.962. PMID- 35797004 OWN - NLM STAT- MEDLINE DCOM- 20220826 LR - 20250728 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 39 IP - 9 DP - 2022 Sep TI - Preference for Type 2 Diabetes Therapies in the United States: A Discrete Choice Experiment. PG - 4114-4130 LID - 10.1007/s12325-022-02181-7 [doi] AB - INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a chronic condition associated with substantial clinical and economic burden. As multiple therapeutic options are available, patient preferences on treatment characteristics are key in T2DM therapeutic decision-making. This study aimed to determine the preferences of US patients with T2DM for therapies recommended for first pharmacologic intensification after metformin. METHODS: As part of a discrete choice experiment, an online survey was designed using literature review and qualitative interview findings. Eligibility was met by US patients with T2DM who were aged 18 years or older with an HbA(1c) >/= 6.5%. Anonymized therapy profiles were created from six antidiabetic therapies including oral and injectable semaglutide, dulaglutide, empagliflozin, sitagliptin, and thiazolidinediones. RESULTS: Eligible patients (n = 500) had a mean HbA(1c) of 7.4%, and a mean BMI of 32.0 kg/m(2), the majority of which (72.2%) were injectable-naive. The treatment characteristic with greatest importance was mode and frequency of administration (35.5%), followed by body weight change (29.2%), cardiovascular event risk (19.1%), hypoglycemic event risk (9.9%), and HbA(1c) change (6.5%). An oral semaglutide-like profile was preferred by 91.9-70.1% of respondents depending on the comparator agent, and preference was significant in each comparison (p < 0.05); an injectable semaglutide-like profile was preferred by 89.3-55.7% of respondents in each comparison depending on the comparator agent. CONCLUSION: Patients with T2DM in the USA are significantly more likely to prefer oral or injectable semaglutide-like profiles over those of key comparators from the glucagon-like peptide 1 receptor agonist, sodium-glucose cotransporter 2 inhibitor, dipeptidyl peptidase 4 inhibitor, and thiazolidinedione classes. CI - (c) 2022. The Author(s). FAU - Shubrook, Jay H AU - Shubrook JH AD - Primary Care Department, Touro University California College of Osteopathic Medicine, Vallejo, CA, USA. FAU - Radin, Michael AU - Radin M AD - Novo Nordisk Pharma Ltd., Plainsboro, NJ, USA. FAU - Ali, Sarah N AU - Ali SN AD - Novo Nordisk Pharma Ltd., Plainsboro, NJ, USA. FAU - Chubb, Barrie AU - Chubb B AD - Novo Nordisk Ltd., London, UK. FAU - DiPietrantonio, Kristina AU - DiPietrantonio K AD - Adelphi Values PROVE, Cheshire, UK. FAU - Collings, Hannah AU - Collings H AUID- ORCID: 0000-0002-5345-6007 AD - Adelphi Values PROVE, Cheshire, UK. hannah.collings@adelphivalues.com. FAU - Wyn, Robin AU - Wyn R AD - Adelphi Values PROVE, Cheshire, UK. FAU - Smith, Martina AU - Smith M AD - Adelphi Values PROVE, Cheshire, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220707 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 9100L32L2N (Metformin) RN - TS63EW8X6F (Sitagliptin Phosphate) MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents MH - *Metformin/therapeutic use MH - Sitagliptin Phosphate MH - United States PMC - PMC9402769 OTO - NOTNLM OT - Discrete choice experiment OT - Patient preference OT - Therapy OT - Type 2 diabetes (T2D) EDAT- 2022/07/08 06:00 MHDA- 2022/08/27 06:00 PMCR- 2022/07/07 CRDT- 2022/07/07 11:22 PHST- 2021/12/17 00:00 [received] PHST- 2022/05/05 00:00 [accepted] PHST- 2022/07/08 06:00 [pubmed] PHST- 2022/08/27 06:00 [medline] PHST- 2022/07/07 11:22 [entrez] PHST- 2022/07/07 00:00 [pmc-release] AID - 10.1007/s12325-022-02181-7 [pii] AID - 2181 [pii] AID - 10.1007/s12325-022-02181-7 [doi] PST - ppublish SO - Adv Ther. 2022 Sep;39(9):4114-4130. doi: 10.1007/s12325-022-02181-7. Epub 2022 Jul 7. PMID- 35791625 OWN - NLM STAT- MEDLINE DCOM- 20221004 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 11 DP - 2022 Nov TI - Ease-of-use and acceptability of the novel semaglutide 2.4 mg single-dose pen-injector in people with overweight or obesity in the STEP 8 phase III trial. PG - 2273-2276 LID - 10.1111/dom.14809 [doi] FAU - Snitker, Soren AU - Snitker S AUID- ORCID: 0000-0001-8313-6701 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Egebjerg, Christina AU - Egebjerg C AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Frederiksen, Marie AU - Frederiksen M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sparre, Thomas AU - Sparre T AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT04074161 PT - Clinical Trial, Phase III PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220807 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents MH - Obesity/complications/drug therapy MH - *Overweight/complications/drug therapy MH - Semaglutide PMC - PMC9805145 OTO - NOTNLM OT - GLP-1 analogue OT - antiobesity drug OT - clinical trial OT - obesity therapy OT - phase III study OT - weight control COIS- All authors are employees of Novo Nordisk, Soborg, Denmark, and TS owns stock in the company. EDAT- 2022/07/07 06:00 MHDA- 2022/10/05 06:00 PMCR- 2022/12/31 CRDT- 2022/07/06 03:12 PHST- 2022/06/24 00:00 [revised] PHST- 2022/03/23 00:00 [received] PHST- 2022/07/01 00:00 [accepted] PHST- 2022/07/07 06:00 [pubmed] PHST- 2022/10/05 06:00 [medline] PHST- 2022/07/06 03:12 [entrez] PHST- 2022/12/31 00:00 [pmc-release] AID - DOM14809 [pii] AID - 10.1111/dom.14809 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Nov;24(11):2273-2276. doi: 10.1111/dom.14809. Epub 2022 Aug 7. PMID- 35778801 OWN - NLM STAT- MEDLINE DCOM- 20230216 LR - 20260127 IS - 1542-6270 (Electronic) IS - 1060-0280 (Linking) VI - 57 IP - 3 DP - 2023 Mar TI - The Effects of Adding Semaglutide to High Daily Dose Insulin Regimens in Patients With Type 2 Diabetes. PG - 241-250 LID - 10.1177/10600280221107381 [doi] AB - BACKGROUND: Escalating doses of insulin required with progression of type 2 diabetes may lead to weight gain. Weight loss associated with semaglutide may be beneficial. However, data on the use of semaglutide in patients requiring high daily doses of insulin are currently lacking. OBJECTIVE: The purpose of this project was to evaluate the impact of semaglutide on total daily dose (TDD) of insulin when initiated in patients with type 2 diabetes mellitus (T2DM) on high daily doses of insulin. Secondary objectives assessed included changes in weight, body mass index (BMI), blood pressure, heart rate, and diabetes and blood pressure medications. METHODS: This IRB exempt retrospective medical record review included patients with T2DM prescribed semaglutide and at least 100 units TDD of insulin between January 1, 2019, and December 31, 2019. RESULTS: Of the 72 patients included, the TDD of insulin decreased from baseline to 6 months (183 +/- 98 units and 143 +/- 99 units, P < 0.001). Average A1c and body weight also decreased from baseline to 6 months (8.9% +/- 1.3% and 7.6% +/- 1.5%, P < 0.001 and 123.9 +/- 23.5 kg and 118.9 +/- 22.9 kg, P < 0.001, respectively). Limitations included a homogenous patient population and inability to control confounding factors. CONCLUSION AND RELEVANCE: Improvement in glycemic control occurred despite reductions in TDD of insulin. Improvements in A1c and body weight were clinically significant. This analysis adds to existing literature supporting the use of GLP-1 RAs in patients on high daily doses of insulin. FAU - Meyer, Jodi AU - Meyer J AUID- ORCID: 0000-0001-6619-2373 AD - Department of Pharmacy, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. FAU - Dreischmeier, Emma AU - Dreischmeier E AUID- ORCID: 0000-0002-2658-9744 AD - Department of Pharmacy, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. FAU - Lehmann, Molly AU - Lehmann M AD - Department of Pharmacy, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. FAU - Phelan, Jessica AU - Phelan J AD - Department of Endocrinology, William S. Middleton Memorial Veterans Hospital, Madison, WI, USA. LA - eng PT - Journal Article DEP - 20220701 PL - United States TA - Ann Pharmacother JT - The Annals of pharmacotherapy JID - 9203131 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin MH - Hypoglycemic Agents/therapeutic use MH - Insulin/therapeutic use MH - Retrospective Studies MH - Weight Loss MH - Semaglutide OTO - NOTNLM OT - GLP-1 RA OT - Semaglutide OT - glucagon-like peptide-1 receptor agonists OT - insulin OT - type 2 diabetes mellitus EDAT- 2022/07/03 06:00 MHDA- 2023/02/16 06:00 CRDT- 2022/07/02 01:02 PHST- 2022/07/03 06:00 [pubmed] PHST- 2023/02/16 06:00 [medline] PHST- 2022/07/02 01:02 [entrez] AID - 10.1177/10600280221107381 [doi] PST - ppublish SO - Ann Pharmacother. 2023 Mar;57(3):241-250. doi: 10.1177/10600280221107381. Epub 2022 Jul 1. PMID- 35745144 OWN - NLM STAT- MEDLINE DCOM- 20220627 LR - 20260127 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 14 IP - 12 DP - 2022 Jun 10 TI - Once-Weekly Semaglutide Induces an Early Improvement in Body Composition in Patients with Type 2 Diabetes: A 26-Week Prospective Real-Life Study. LID - 10.3390/nu14122414 [doi] LID - 2414 AB - BACKGROUND: Body weight (BW) loss is an essential therapeutic goal in type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists are effective in reducing BW, but their effect on body composition has not yet been fully explored. The study aim was to assess the impact of Semaglutide on body composition in patients with T2D. METHODS: Forty patients with T2D were treated with subcutaneous Semaglutide and evaluated at the baseline (T0) and after three (T3) and six (T6) months. Body composition was assessed by a phase-sensitive bioimpedance analyzer. Visceral adipose tissue (VAT) thickness was also measured with an ultrasonographic method (US-VAT). Anthropometric variables, muscular strength, and laboratory tests were analyzed and compared. RESULTS: A significant decrease in VAT, the fat mass index (FMI), and BW loss was observed at all observation times. US-VAT, the skeletal mass index (SMI), the fat-free mass index (FFMI), waist circumferences, and glycated hemoglobin had lessened after three months and remained stable at T6. No variations in muscle strength, the muscle quality index, and body water were found. DISCUSSION: In a real-life setting, Semaglutide provided significant weight loss mainly due to a reduction in the FMI and VAT, with non-clinically relevant changes in the SMI, the FFMI, and muscle strength. Most importantly, the results were obtained after three months of treatment and persisted thereafter. FAU - Volpe, Sara AU - Volpe S AUID- ORCID: 0000-0002-6831-0457 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Lisco, Giuseppe AU - Lisco G AUID- ORCID: 0000-0001-6521-8578 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Racaniello, Davide AU - Racaniello D AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Fanelli, Margherita AU - Fanelli M AUID- ORCID: 0000-0002-0128-9745 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Colaianni, Valentina AU - Colaianni V AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Vozza, Alfredo AU - Vozza A AUID- ORCID: 0000-0002-0843-8248 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Triggiani, Vincenzo AU - Triggiani V AUID- ORCID: 0000-0001-6308-0528 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Sabba, Carlo AU - Sabba C AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - Tortorella, Cosimo AU - Tortorella C AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. FAU - De Pergola, Giovanni AU - De Pergola G AD - Unit of Internal Medicine and Geriatrics, National Institute of Gastroenterology, "Saverio de Bellis" Research Hospital, Castellana Grotte, Via Turi 27, 70013 Bari, Italy. FAU - Piazzolla, Giuseppina AU - Piazzolla G AUID- ORCID: 0000-0003-3221-6562 AD - Interdisciplinary Department of Medicine, School of Medicine, University of Bari "Aldo Moro", Piazza Giulio Cesare 11, 70124 Bari, Italy. LA - eng PT - Journal Article DEP - 20220610 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Body Composition MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Prospective Studies MH - Semaglutide PMC - PMC9227575 OTO - NOTNLM OT - Semaglutide OT - body composition OT - glucagon-like peptide-1 receptor agonist OT - obesity OT - real-life study OT - type 2 diabetes COIS- The authors declare no conflict of interest. EDAT- 2022/06/25 06:00 MHDA- 2022/06/28 06:00 PMCR- 2022/06/10 CRDT- 2022/06/24 01:34 PHST- 2022/05/12 00:00 [received] PHST- 2022/06/06 00:00 [revised] PHST- 2022/06/08 00:00 [accepted] PHST- 2022/06/24 01:34 [entrez] PHST- 2022/06/25 06:00 [pubmed] PHST- 2022/06/28 06:00 [medline] PHST- 2022/06/10 00:00 [pmc-release] AID - nu14122414 [pii] AID - nutrients-14-02414 [pii] AID - 10.3390/nu14122414 [doi] PST - epublish SO - Nutrients. 2022 Jun 10;14(12):2414. doi: 10.3390/nu14122414. PMID- 35738455 OWN - NLM STAT- MEDLINE DCOM- 20220809 LR - 20250103 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 182 DP - 2022 Aug TI - The anti-inflammatory and immunological properties of GLP-1 Receptor Agonists. PG - 106320 LID - S1043-6618(22)00265-1 [pii] LID - 10.1016/j.phrs.2022.106320 [doi] AB - In the last few years, a great interest has emerged in investigating the pleiotropic effects of Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs). While GLP-1RAs ability to lower plasma glucose and to induce weight loss has allowed them to be approved for the treatment of diabetes and obesity, consistent evidences from in vitro studies and preclinical models suggested that GLP-1RAs have anti-inflammatory properties and that may modulate the immune-system. Notably, such anti-inflammatory effects target different pathways in different tissues, underling the broad spectrum of GLP-1RAs actions. This review examines some of the currently proposed molecular mechanisms of GLP-1RAs actions and explores their potential benefits in reducing inflammatory responses, which may well suggest a future therapeutic use of GLP-1RAs in new indications. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Bendotti, Giulia AU - Bendotti G AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Montefusco, Laura AU - Montefusco L AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Lunati, Maria Elena AU - Lunati ME AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Usuelli, Vera AU - Usuelli V AD - International Center for T1D, Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Pastore, Ida AU - Pastore I AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Lazzaroni, Elisa AU - Lazzaroni E AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Assi, Emma AU - Assi E AD - International Center for T1D, Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Seelam, Andy Joe AU - Seelam AJ AD - International Center for T1D, Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - El Essawy, Basset AU - El Essawy B AD - Transplantation Research Center, Nephrology Division, Children's Hospital and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Medicine, Al-Azhar University, Cairo, Egypt. FAU - Jang, Jun AU - Jang J AD - Institute of Organ Transplantation, Tongji Hospital and Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Loretelli, Cristian AU - Loretelli C AD - International Center for T1D, Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - D'Addio, Francesca AU - D'Addio F AD - International Center for T1D, Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy. FAU - Berra, Cesare AU - Berra C AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS Multimedica, Milan, Italy. FAU - Ben Nasr, Moufida AU - Ben Nasr M AD - International Center for T1D, Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Zuccotti, GianVincenzo AU - Zuccotti G AD - Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita di Milano and Department of Pediatrics, Buzzi Children's Hospital, Milan, Italy. FAU - Fiorina, Paolo AU - Fiorina P AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy; International Center for T1D, Pediatric Clinical Research Center "Romeo ed Enrica Invernizzi", Department of Biomedical and Clinical Science L. Sacco, University of Milan, Milan, Italy; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: paolo.fiorina@childrens.harvard.edu. LA - eng PT - Journal Article PT - Review DEP - 20220620 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Anti-Inflammatory Agents/pharmacology/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/pharmacology MH - Obesity/drug therapy MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Exenatide (PubChem CID: 45588096) OT - Glucagon-like peptide 1 OT - Immune system OT - Inflammation OT - Liraglutide (PubChem CID: 16134956) OT - Lymphocytes OT - Macrophages OT - Semaglutide (PubChem CID: 56843331) EDAT- 2022/06/24 06:00 MHDA- 2022/08/10 06:00 CRDT- 2022/06/23 19:24 PHST- 2022/05/30 00:00 [received] PHST- 2022/06/16 00:00 [revised] PHST- 2022/06/16 00:00 [accepted] PHST- 2022/06/24 06:00 [pubmed] PHST- 2022/08/10 06:00 [medline] PHST- 2022/06/23 19:24 [entrez] AID - S1043-6618(22)00265-1 [pii] AID - 10.1016/j.phrs.2022.106320 [doi] PST - ppublish SO - Pharmacol Res. 2022 Aug;182:106320. doi: 10.1016/j.phrs.2022.106320. Epub 2022 Jun 20. PMID- 35724304 OWN - NLM STAT- MEDLINE DCOM- 20220928 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 45 IP - 10 DP - 2022 Oct 1 TI - Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program. PG - 2396-2405 LID - 10.2337/dc21-1785 [doi] AB - OBJECTIVE: This analysis of 3,375 adults with overweight/obesity across the Semaglutide Treatment Effect in People with obesity (STEP) 1, 3, and 4 trials evaluated whether more participants with prediabetes had normoglycemia after 68 weeks' treatment with once-weekly semaglutide 2.4 mg plus lifestyle intervention versus placebo and assessed changes in glucose metabolism in participants with prediabetes. RESEARCH DESIGN AND METHODS: STEP 1, 3, and 4 were phase 3, 68-week, randomized, placebo-controlled, multinational trials; STEP 4 had a 20-week semaglutide run-in and 48-week randomized period. Analyses included changes (week 0-68; before the washout period) in glycemic status (prespecified: STEP 1 and 3; post hoc: STEP 4), and in HbA1c, fasting plasma glucose (FPG), and HOMA insulin resistance (HOMA-IR) among participants with prediabetes (post hoc). RESULTS: Significantly more participants with baseline (week 0) prediabetes (n = 1,536) had normoglycemia at week 68 with semaglutide versus placebo (STEP 1, 84.1% vs. 47.8%; STEP 3, 89.5% vs. 55.0%; STEP 4, 89.8% vs. 70.4%; all P < 0.0001). Fewer participants with baseline normoglycemia had prediabetes at week 68 with semaglutide versus placebo (STEP 1, 2.9% vs. 10.9%; STEP 3, 3.2% vs. 5.8%; STEP 4, 1.1% vs. 5.0%). Semaglutide resulted in greater improvements in HbA1c, FPG, and HOMA-IR than placebo among participants with baseline prediabetes (all P < 0.01). CONCLUSIONS: STEP 1, 3, and 4 collectively provide a robust assessment of the effects of semaglutide on glucose metabolism and prediabetes in a large cohort of adults with overweight/obesity while on treatment. Among participants with baseline prediabetes, 68 weeks' treatment with semaglutide versus placebo led to significant improvements in glucose metabolism and a higher likelihood of normoglycemia. CI - (c) 2022 by the American Diabetes Association. FAU - Perreault, Leigh AU - Perreault L AUID- ORCID: 0000-0002-1481-7535 AD - Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO. FAU - Davies, Melanie AU - Davies M AD - Diabetes Research Centre, University of Leicester; and NIHR Leicester Biomedical Research Centre, Leicester, U.K. FAU - Frias, Juan P AU - Frias JP AUID- ORCID: 0000-0001-9486-1255 AD - National Research Institute, Los Angeles, CA. FAU - Laursen, Peter Norkjaer AU - Laursen PN AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology and Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX. FAU - Machineni, Sriram AU - Machineni S AD - Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC. FAU - Varbo, Anette AU - Varbo A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wilding, John P H AU - Wilding JPH AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, U.K. FAU - Wallenstein, Signe Olrik Rytter AU - Wallenstein SOR AD - Novo Nordisk A/S, Soborg, Denmark. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - Diabetes Complications Research Centre, Conway Institute, University College, Dublin, Ireland. LA - eng SI - ClinicalTrials.gov/NCT03548935 SI - ClinicalTrials.gov/NCT03611582 SI - ClinicalTrials.gov/NCT03548987 SI - figshare/10.2337/figshare.19692427 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Diabetes Care. 2022 Oct 1;45(10):2204-2206. doi: 10.2337/dci22-0019. PMID: 36150060 MH - Adult MH - Blood Glucose/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Insulin Resistance MH - Obesity/drug therapy MH - Overweight/drug therapy MH - *Prediabetic State/drug therapy MH - Semaglutide PMC - PMC9862484 EDAT- 2022/06/21 06:00 MHDA- 2022/09/28 06:00 PMCR- 2022/06/20 CRDT- 2022/06/20 14:22 PHST- 2021/08/24 00:00 [received] PHST- 2022/04/17 00:00 [accepted] PHST- 2022/06/21 06:00 [pubmed] PHST- 2022/09/28 06:00 [medline] PHST- 2022/06/20 14:22 [entrez] PHST- 2022/06/20 00:00 [pmc-release] AID - 147113 [pii] AID - 211785 [pii] AID - 10.2337/dc21-1785 [doi] PST - ppublish SO - Diabetes Care. 2022 Oct 1;45(10):2396-2405. doi: 10.2337/dc21-1785. PMID- 35718129 OWN - NLM STAT- MEDLINE DCOM- 20220712 LR - 20260311 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 928 DP - 2022 Aug 5 TI - GZR18, a novel long-acting GLP-1 analog, demonstrated positive in vitro and in vivo pharmacokinetic and pharmacodynamic characteristics in animal models. PG - 175107 LID - S0014-2999(22)00368-5 [pii] LID - 10.1016/j.ejphar.2022.175107 [doi] AB - GZR18 is a novel analog of glucagon-like peptide-1 (GLP-1). This study evaluates the pharmacology, pharmacokinetics, and efficacy of GZR18, and its potential for the treatment of Type 2 diabetes mellitus (T2DM). In vitro pharmacology and activity of GZR18 were characterized by a binding assay of GZR18 using human serum albumin (HSA), an activation assay in human GLP-1 receptor-expressing cell lines, and its effect on glucose-stimulated insulin secretion (GSIS) in primary mice islets. Pharmacokinetic profiling was performed in Sprague Dawley rats and cynomolgus monkeys, and efficacy evaluated using GZR18 single or repeated doses in db/db mice. GZR18 showed similar binding affinity for HSA and GLP-1 receptor compared with semaglutide and liraglutide. GZR18 increased GSIS, which was confirmed by dynamic islet perifusion and fluorescence imaging using PKZnR-5 for real-time detection. In cynomolgus monkeys, the average GZR18 maximal concentration was 527 nmol L(-1), the terminal half-life (T(1/2)) was 61.3 h, and the time to maximum concentration was 14 h. Single-dose GZR18 lowered blood glucose levels and reduced body weight over 72 h in db/db mice. GZR18 successive administration (every three days for 33 days, i.e. 11 doses) lowered nonfasting and fasting blood glucose levels (p < 0.05 versus control) and glycated hemoglobin, following the 11th dose. Food and water consumption in db/db mice was lowered following repeated doses of GZR18 (p < 0.05 versus control), without a reduction in body weight. These results demonstrate the potential of GZR18 as a long-acting GLP-1 analog for the treatment of T2DM. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Zhang, Man AU - Zhang M AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Zhang, Yining AU - Zhang Y AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Peng, Xiaohong AU - Peng X AD - State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing, China. FAU - He, Anshun AU - He A AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Wang, Yue AU - Wang Y AD - Gan & Lee Pharmaceuticals USA Corp., Bridgewater, NJ, USA. FAU - Deng, Ying AU - Deng Y AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Cui, Cheng AU - Cui C AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Xue, Fangkai AU - Xue F AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Wei, Bing AU - Wei B AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Xing, Wancai AU - Xing W AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Qian, Yuzhen AU - Qian Y AD - Gan & Lee Pharmaceuticals, Beijing, China. FAU - Mazuranic, Michelle AU - Mazuranic M AD - Gan & Lee Pharmaceuticals USA Corp., Bridgewater, NJ, USA. FAU - Chen, Wei AU - Chen W AD - Gan & Lee Pharmaceuticals, Beijing, China. Electronic address: wei.chen@ganlee.com. LA - eng PT - Journal Article DEP - 20220616 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM EIN - Eur J Pharmacol. 2026 Mar 28;1019:178742. doi: 10.1016/j.ejphar.2026.178742. PMID: 41813513 MH - Animals MH - Blood Glucose/metabolism MH - Body Weight MH - *Diabetes Mellitus, Experimental/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1/pharmacology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Hypoglycemic Agents/chemistry/pharmacology/therapeutic use MH - Insulin/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred Strains MH - Models, Animal MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - GLP-1 analog OT - GLP-1 receptor agonist OT - GZR18 OT - Pharmacokinetics OT - Pharmacology OT - Type 2 diabetes EDAT- 2022/06/20 06:00 MHDA- 2022/07/14 06:00 CRDT- 2022/06/19 19:33 PHST- 2022/02/10 00:00 [received] PHST- 2022/06/06 00:00 [revised] PHST- 2022/06/13 00:00 [accepted] PHST- 2022/06/20 06:00 [pubmed] PHST- 2022/07/14 06:00 [medline] PHST- 2022/06/19 19:33 [entrez] AID - S0014-2999(22)00368-5 [pii] AID - 10.1016/j.ejphar.2022.175107 [doi] PST - ppublish SO - Eur J Pharmacol. 2022 Aug 5;928:175107. doi: 10.1016/j.ejphar.2022.175107. Epub 2022 Jun 16. PMID- 35713074 OWN - NLM STAT- MEDLINE DCOM- 20220620 LR - 20250103 IS - 0030-9982 (Print) IS - 0030-9982 (Linking) VI - 72 IP - 5 DP - 2022 May TI - Glucagon-Like Peptide 1 Receptor Agonists (GLP1RA) and Sodium-glucose co-transporter-2 inhibitors (SGLT2i): Making a pragmatic choice in diabetes management. PG - 989-990 LID - 10.47391/JPMA.22-64 [doi] AB - The availability of newer glucose-lowering drugs has created opportunities for comprehensive diabetes care. Two classes of drugs, GLP1RA (glucagon-like peptide 1 receptor agonists), and SGLT2i (sodium glucose cotransporter 2 inhibitors) have demonstrated their efficacy in glucose control as well as cardiovascular risk reduction. While both can be used together, there is an ongoing debate regarding their relative advantages and limitations. We present a clinical perspective to compare and control these two classes of drugs, and promote rational prescription in diabetes praxis. FAU - Kalra, Sanjay AU - Kalra S AD - Department of Endocrinology, Bharti Hospital, Karnal, India. FAU - Bhattacharya, Saptarshi AU - Bhattacharya S AD - Department of Endocrinology, Max Hospital, Patparganj, New Delhi, India. FAU - Kapoor, Nitin AU - Kapoor N AD - Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore (TN) -632004, India, and Non Communicable Disease Unit, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PL - Pakistan TA - J Pak Med Assoc JT - JPMA. The Journal of the Pakistan Medical Association JID - 7501162 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Symporters) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9NEZ333N27 (Sodium) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Cardiovascular Diseases MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Glucose MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Sodium MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Symporters MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Canagliflozin, CV risk reduction, dapagliflozin, dulaglutide, empagliflozin, GLP1RA, liraglutide, obesity, semaglutide, SGLT2i. EDAT- 2022/06/18 06:00 MHDA- 2022/06/22 06:00 CRDT- 2022/06/17 05:23 PHST- 2022/06/17 05:23 [entrez] PHST- 2022/06/18 06:00 [pubmed] PHST- 2022/06/22 06:00 [medline] AID - 11299 [pii] AID - 10.47391/JPMA.22-64 [doi] PST - ppublish SO - J Pak Med Assoc. 2022 May;72(5):989-990. doi: 10.47391/JPMA.22-64. PMID- 35709586 OWN - NLM STAT- MEDLINE DCOM- 20220628 LR - 20260127 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 16 IP - 6 DP - 2022 Jun TI - Impact of semaglutide on biochemical and radiologic measures of metabolic-dysfunction associated fatty liver disease across the spectrum of glycaemia: A meta-analysis. PG - 102539 LID - S1871-4021(22)00153-9 [pii] LID - 10.1016/j.dsx.2022.102539 [doi] AB - BACKGROUND AND AIMS: No meta-analysis has analysed efficacy and safety of semaglutide in metabolic-dysfunction associated fatty-liver disease (MAFLD). METHODS: Electronic databases were searched for RCTs involving people with MAFLD and/or type-2 diabetes (T2DM) receiving semaglutide. Primary outcome was to evaluate changes in alanine aminotransferase (ALT). Secondary outcomes were to evaluate alterations in other measures of NAFLD, glycaemia, lipids and adverse-events. RESULTS: Data from 4 RCTs (2115 patients) was analysed. A greater lowering with injectable semaglutide 0.4mg/0.5 mg once weekly was seen with regards to ALT [MD -3.89U/L (95%CI: -5.41 to -2.36); P < 0.01; I(2) = 0%; 2050 patients], liver stiffness (fibroscan(R)) [MD -3.19 kPa (95%CI: -3.26 to -3.12); P < 0.01; 162 patients], steatosis [MD -13.40 dB/m (95%CI: 20.56 to -6.24); P < 0.01; 162 patients], triglycerides [MD -21.43 mg/dl (95% CI: 41.63 to -1.23); P = 0.04; I(2) = 99%; 2050 patients], total cholesterol [MD -5.53 mg/dl (95% CI: -8.45 to -2.61); P < 0.01; I(2) = 0%; 1888 patients], LDL-cholesterol [MD -3.55 mg/dl (95% CI: -5.87 to -1.23); P < 0.01; I(2) = 0%; 1888 patients], percent-weight [MD -8.99% (95%CI: -14.64 to -3.34); P = 0.002; I(2) = 100%; 2115 patient] and HbA1c [MD -0.77% (95%CI: 1.10 to -0.45); P = 0.002; I(2) = 100%; 2115 patients]. Number of patients inadequate to comment on histopathologic measures of MAFLD. Occurrence of treatment-emergent adverse-events [RR 2.31 (95% CI: 0.76-7.06); P = 0.14; I(2) = 82%] and severe adverse events [RR 1.07 (95%CI: 0.69-1.65); P = 0.77; I(2) = 33%] were comparable. Adverse-events leading to trial discontinuation [RR 2.37 (95% CI: 1.33-4.22); P = 0.003; I(2) = 24%], diarrhea [RR 2.05 (95%CI: 1.17-3.60); P = 0.01; I(2) = 66%], nausea [RR 4.98 (95%CI: 3.23-7.67); P < 0.001; I(2) = 0%] and vomiting [RR 3.90 (95%CI: 1.75-8.68); P < 0.01; I(2) = 54%] were higher with semaglutide. CONCLUSION: This meta-analysis provides reassuring data on efficacy of low dose semaglutide injections in improving ALT and certain radiologic features in MAFLD. Current conclusions are limited by small number of patients evaluated. Urgent need remains for larger studies focussing on liver biopsy. CI - Copyright (c) 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved. FAU - Dutta, Deep AU - Dutta D AD - Department of Endocrinology, Center for Endocrinology Diabetes Arthritis & Rheumatism (CEDAR) Superspeciality Healthcare, Dwarka, New Delhi, India. Electronic address: deepdutta2000@yahoo.com. FAU - Kumar, Manoj AU - Kumar M AD - Department of Endocrinology, CEDAR Superspeciality Healthcare, Zirakpur, Punjab, India. Electronic address: manojkattu@gmail.com. FAU - Shivaprasad, K S AU - Shivaprasad KS AD - Department of Endocrinology, CEDAR Superspeciality Healthcare, Bengaluru, Karnataka, India. Electronic address: shivaprasadks@outlook.com. FAU - Kumar, Ashok AU - Kumar A AD - Department of Endocrinology, CEDAR Superspeciality Healthcare, Panipat, Haryana, India. Electronic address: ashoka08@gmail.com. FAU - Sharma, Meha AU - Sharma M AD - Department of Rheumatology, CEDAR Superspeciality Healthcare, Dwarka, New Delhi, India. Electronic address: docmsharma@gmail.com. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20220610 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 0 (Blood Glucose) RN - 0 (Cholesterol, LDL) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose MH - Cholesterol, LDL MH - *Diabetes Mellitus, Type 2/chemically induced/complications/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - *Liver Diseases MH - Semaglutide OTO - NOTNLM OT - Fatty liver disease OT - Meta-analysis OT - Semaglutide OT - Steatohepatitis COIS- Declaration of competing interest None. EDAT- 2022/06/17 06:00 MHDA- 2022/06/29 06:00 CRDT- 2022/06/16 18:17 PHST- 2022/05/06 00:00 [received] PHST- 2022/06/02 00:00 [revised] PHST- 2022/06/04 00:00 [accepted] PHST- 2022/06/17 06:00 [pubmed] PHST- 2022/06/29 06:00 [medline] PHST- 2022/06/16 18:17 [entrez] AID - S1871-4021(22)00153-9 [pii] AID - 10.1016/j.dsx.2022.102539 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2022 Jun;16(6):102539. doi: 10.1016/j.dsx.2022.102539. Epub 2022 Jun 10. PMID- 35701876 OWN - NLM STAT- MEDLINE DCOM- 20220919 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 134 IP - 7 DP - 2022 Sep TI - Oral versus subcutaneous semaglutide for prevention of major adverse cardiovascular events: cost per outcome analysis of SUSTAIN-6 and PIONEER-6. PG - 654-658 LID - 10.1080/00325481.2022.2090794 [doi] AB - BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP1a), reduces the risk of major adverse cardiovascular events (MACE) in patients with Type 2 diabetes mellitus (T2DM). An oral version of semaglutide is now available, and patients may prefer it over the subcutaneous form. Our objective was to compare the value for money of the two modalities by assessing the cost needed to treat (CNT) to prevent MACE. METHODS: The CNT to prevent MACE was figured by multiplying the one-year number needed to treat (NNT) with either oral or subcutaneous semaglutide by the annual cost of therapy. Efficacy estimates and the resulting NNT figures were extracted from the published results of the SUSTAIN-6 and the PIONEER-6 trials for the injectable and oral versions of semaglutide, respectively. Drug costs were estimated as 75% of the United States national average drug acquisition cost listing in June 2021. We performed a scenario analysis to mitigate the primary differences between the populations in the two trials. Sensitivity analysis was performed to evaluate the effect of price changes of the interventions. RESULTS: The CNT to prevent one MACE with subcutaneous semaglutide in SUSTAIN-6 was $966,693 ($594,888-$5,035,302) compared to $948,689 ($463,465-infinity) with oral semaglutide in PIONEER-6. The scenario analysis demonstrated a 17% lower CNT for oral semaglutide. The difference between CNTs was sensitive to price fluctuations of the two interventions. CONCLUSIONS: Oral and subcutaneous semaglutide prescribed to prevent MACE in patients with T2DM provide similar value for money. The choice between both therapies should be guided mainly by patient preferences. FAU - Hammerman, Ariel AU - Hammerman A AUID- ORCID: 0000-0002-4396-5246 AD - Community Medical Services, Clalit Health Services Headquarters, Tel Aviv, Israel. FAU - Moore, Candace Makeda AU - Moore CM AUID- ORCID: 0000-0003-1672-7565 AD - Research Software department, Netherlands eScience Center, Amsterdam, The Netherlands. FAU - Aboalhasan, Enis AU - Aboalhasan E AUID- ORCID: 0000-0001-7763-566X AD - Maximizing Health Outcomes Research Lab, Sapir College, Sderot, Israel. FAU - Azuri, Joseph AU - Azuri J AUID- ORCID: 0000-0003-1049-9848 AD - Maccabi Healthcare Services, Diabetes Clinic, Tel Aviv, Israel. AD - Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Arbel, Ronen AU - Arbel R AUID- ORCID: 0000-0002-6058-8665 AD - Community Medical Services, Clalit Health Services Headquarters, Tel Aviv, Israel. AD - Maximizing Health Outcomes Research Lab, Sapir College, Sderot, Israel. LA - eng PT - Journal Article DEP - 20220621 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Cardiovascular Diseases/drug therapy MH - *Diabetes Mellitus, Type 2/chemically induced/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - MACE OT - Oral semaglutide OT - outcomes OT - subcutaneous semaglutide EDAT- 2022/06/16 06:00 MHDA- 2022/09/20 06:00 CRDT- 2022/06/15 00:12 PHST- 2022/06/16 06:00 [pubmed] PHST- 2022/09/20 06:00 [medline] PHST- 2022/06/15 00:12 [entrez] AID - 10.1080/00325481.2022.2090794 [doi] PST - ppublish SO - Postgrad Med. 2022 Sep;134(7):654-658. doi: 10.1080/00325481.2022.2090794. Epub 2022 Jun 21. PMID- 35698011 OWN - NLM STAT- MEDLINE DCOM- 20220727 LR - 20261028 IS - 1573-904X (Electronic) IS - 0724-8741 (Linking) VI - 39 IP - 8 DP - 2022 Aug TI - Design and Development of a New Glucagon-Like Peptide-1 Receptor Agonist to Obtain High Oral Bioavailability. PG - 1891-1906 LID - 10.1007/s11095-022-03265-3 [doi] AB - PURPOSE: Semaglutide is the only oral GLP-1 RA in the market, but oral bioavailability is generally limited in range of 0.4-1%. In this study, a new GLP-1RA named SHR-2042 was developed to gain higher oral bioavailability than semaglutide. METHOD: Self-association of SHR-2042, semaglutide and liraglutide were assessed using SEC-MALS. The intestinal perfusion test in SD rats was used to select permeation enhancers (PEs) including SNAC, C10 and LCC. ITC, CD and DLS were used to explore the interaction between SHR-2042 and SNAC. Gastric administrated test in SD rats was used to screen SHR-2042 granules with different SHR-2042/SNAC ratios. The oral bioavailability of SHR-2042 was studied in rats and monkeys. RESULT: The designed GLP-1RA, SHR-2042, gives a better solubility and lipophilicity than semaglutide. While it forms a similar oligomer with that of semaglutide. During the selection of PEs, SNAC shows better exposure than the other competing PEs including C10 and LCC. SHR-2042 and SNAC bind quickly and exhibit hydrophobic interaction. SNAC could promote monomerization of SHR-2042 and form micelles to trap the monomerized SHR-2042. The oral bioavailability of SHR-2042 paired with SNAC is 0.041% (1:0, w/w), 0.083% (1:10, w/w), 0.32% (1:30, w/w) and 2.83% (1:60, w/w) in rats. And the oral bioavailability of SHR-2042 matched with SNAC is 3.39% (1:30, w/w) in monkeys, which is over 10 times higher than that of semaglutide. CONCLUSION: We believe that the design and development of oral SHR-2042 will provide a new way to design more and more GLP-1RAs with high oral bioavailability in the future. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Chen, Hao AU - Chen H AD - School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. AD - Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China. FAU - Lu, Yun AU - Lu Y AD - Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China. FAU - Shi, Shuai AU - Shi S AD - Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China. FAU - Zhang, Qiang AU - Zhang Q AD - Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China. FAU - Cao, Xiaoli AU - Cao X AD - Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China. FAU - Sun, Lei AU - Sun L AD - Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China. FAU - An, Dong AU - An D AD - Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China. FAU - Zhang, Xiaojie AU - Zhang X AD - Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China. FAU - Kong, Xianglin AU - Kong X AD - Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, 222000, People's Republic of China. FAU - Liu, Jianping AU - Liu J AUID- ORCID: 0000-0003-1825-7122 AD - School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. jianpingliu1293@163.com. LA - eng PT - Journal Article DEP - 20220613 PL - United States TA - Pharm Res JT - Pharmaceutical research JID - 8406521 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - Biological Availability MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptide 1 MH - Hypoglycemic Agents MH - Rats MH - Rats, Inbred SHR MH - Rats, Sprague-Dawley MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1RA OT - Monkeys OT - Oligomer OT - Oral bioavailability OT - Rats EDAT- 2022/06/14 06:00 MHDA- 2022/07/28 06:00 CRDT- 2022/06/13 23:35 PHST- 2022/01/08 00:00 [received] PHST- 2022/04/18 00:00 [accepted] PHST- 2022/06/14 06:00 [pubmed] PHST- 2022/07/28 06:00 [medline] PHST- 2022/06/13 23:35 [entrez] AID - 10.1007/s11095-022-03265-3 [pii] AID - 10.1007/s11095-022-03265-3 [doi] PST - ppublish SO - Pharm Res. 2022 Aug;39(8):1891-1906. doi: 10.1007/s11095-022-03265-3. Epub 2022 Jun 13. PMID- 35689162 OWN - NLM STAT- MEDLINE DCOM- 20220726 LR - 20250103 IS - 1865-8652 (Electronic) IS - 0741-238X (Linking) VI - 39 IP - 8 DP - 2022 Aug TI - A Retrospective Observational Study Examining the Generalizability of Glucagon-Like Peptide 1 Receptor Agonist Cardiovascular Outcome Trials to the Real-World Population with Type 2 Diabetes in Spain: The REPRESENT Study. PG - 3589-3601 LID - 10.1007/s12325-022-02196-0 [doi] AB - INTRODUCTION: The REPRESENT study aims to examine whether participants enrolled in glucagon-like peptide 1 receptor agonist cardiovascular outcome trials (CVOTs) LEADER (liraglutide), REWIND (dulaglutide), and SUSTAIN-6 (injectable semaglutide) are representative of the Spanish population with type 2 diabetes (T2D). METHODS: This retrospective observational study used the IQVIA Electronic Medical Records database in Spain to identify adults aged 18 years and older with T2D diagnosed before/between January 2013 and December 2015. Demographic and clinical characteristics were analyzed descriptively. The proportions of individuals in the Spanish cohort who met the key selection criteria of each CVOT were calculated from individuals with available database entries for estimated glomerular filtration rate and body mass index using proxies. RESULTS: A total of 24,268 adults with T2D were identified from the IQVIA database. The Spanish cohort was predominantly male (55.5%) and had a mean (+/- SD) age of 66.8 +/- 12.5 years and HbA1c of 7.2 +/- 1.5%, with 14.0% having established cardiovascular disease and 2.9% having prior myocardial infarction. The characteristics of the Spanish cohort were more similar to that of REWIND than LEADER or SUSTAIN-6. The proportions of subjects in the Spanish cohort who met the CVOTs key selection criteria were 10.1% for LEADER, 53.6% for REWIND, and 10.4% for SUSTAIN-6. CONCLUSIONS: Although none of the CVOTs was fully representative of the Spanish cohort, the REWIND population was found to be more representative of the real-world Spanish population with T2D than those of LEADER and SUSTAIN-6. These findings reinforce the applicability of the results of REWIND in clinical practice. CI - (c) 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature. FAU - Romera, Irene AU - Romera I AD - Eli Lilly and Company, Alcobendas, Madrid, Spain. romera_irene@lilly.com. FAU - Artime, Esther AU - Artime E AD - Eli Lilly and Company, Alcobendas, Madrid, Spain. FAU - Ihle, Katharina AU - Ihle K AD - Lilly Deutschland GmbH, Bad Homburg, Germany. FAU - Diaz-Cerezo, Silvia AU - Diaz-Cerezo S AD - Eli Lilly and Company, Alcobendas, Madrid, Spain. FAU - Rubio de-Santos, Miriam AU - Rubio de-Santos M AD - Eli Lilly and Company, Alcobendas, Madrid, Spain. FAU - de Prado, Anna AU - de Prado A AD - IQVIA, Madrid, Spain. FAU - Cebrian-Cuenca, Ana AU - Cebrian-Cuenca A AD - Cartagena Casco Antiguo Primary Health Center, 30201, Cartagena, Murcia, Spain. FAU - Conget, Ignacio AU - Conget I AD - Endocrinology and Nutrition Unit, Hospital Clinic de Barcelona, Barcelona, Spain. LA - eng PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20220611 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) MH - Aged MH - *Cardiovascular Diseases/epidemiology MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Female MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - Male MH - Middle Aged MH - Spain/epidemiology MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular outcome trials OT - Dulaglutide OT - Glucagon-like peptide 1 receptor agonists OT - Injectable semaglutide OT - Liraglutide OT - Observational study design OT - REWIND OT - Spain OT - Type 2 diabetes mellitus EDAT- 2022/06/11 06:00 MHDA- 2022/07/27 06:00 CRDT- 2022/06/10 23:34 PHST- 2022/02/22 00:00 [received] PHST- 2022/05/13 00:00 [accepted] PHST- 2022/06/11 06:00 [pubmed] PHST- 2022/07/27 06:00 [medline] PHST- 2022/06/10 23:34 [entrez] AID - 10.1007/s12325-022-02196-0 [pii] AID - 10.1007/s12325-022-02196-0 [doi] PST - ppublish SO - Adv Ther. 2022 Aug;39(8):3589-3601. doi: 10.1007/s12325-022-02196-0. Epub 2022 Jun 11. PMID- 35684020 OWN - NLM STAT- MEDLINE DCOM- 20220613 LR - 20260127 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 14 IP - 11 DP - 2022 May 26 TI - The Impact Once-Weekly Semaglutide 2.4 mg Will Have on Clinical Practice: A Focus on the STEP Trials. LID - 10.3390/nu14112217 [doi] LID - 2217 AB - Obesity is a complex and chronic disease that raises the risk of various complications. Substantial reduction in body weight improves these risk factors. Lifestyle changes, including physical activity, reduced caloric ingestion, and behavioral therapy, have been the principal pillars in the management of obesity. In recent years, pharmacologic interventions have improved remarkably. The Semaglutide Treatment Effect in People with Obesity (STEP) program is a collection of phase-III trials geared toward exploring the utility of once-weekly 2.4 mg semaglutide administered subcutaneously as a pharmacologic agent for patients with obesity. All the STEP studies included diet and exercise interventions but at different intensities. This review paper aims to explore the impact of the behavioral programs on the effect of semaglutide 2.4 mg on weight loss. The results of the STEP trials supported the efficacy of high-dose, once-weekly 2.4 mg semaglutide on body weight reduction among patients with obesity with/without diabetes mellitus. Semaglutide was associated with more gastrointestinal-related side effects compared to placebo but was generally safe and well tolerated. In all the STEP studies, despite the varying intestines of the behavioral programs, weight loss was very similar. For the first time, there may be a suggestion that these behavioral programs might not increase weight reduction beyond the effect of semaglutide. Nevertheless, the importance of nutritional support during substantial weight loss with pharmacotherapy needs to be re-evaluated. FAU - Alabduljabbar, Khaled AU - Alabduljabbar K AUID- ORCID: 0000-0002-6323-2525 AD - Department of Family Medicine and Polyclinics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia. AD - Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland. FAU - Al-Najim, Werd AU - Al-Najim W AD - Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland. FAU - le Roux, Carel W AU - le Roux CW AUID- ORCID: 0000-0001-5521-5445 AD - Diabetes Complications Research Centre, Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland. LA - eng PT - Journal Article PT - Review DEP - 20220526 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Body Weight MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Humans MH - *Hypoglycemic Agents/pharmacology MH - Obesity/drug therapy MH - Weight Loss MH - Semaglutide PMC - PMC9182751 OTO - NOTNLM OT - GLP-1 OT - STEP program OT - clinical trial OT - obesity OT - semaglutide OT - weight loss OT - weight management COIS- C.W.l.R. reports grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He serves on the advisory boards of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Sanofi Aventis, AstraZeneca, Janssen, Bristol-Myers Squibb, Glia, and Boehringer Ingelheim. C.W.l.R. is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He has been the chief medical officer and director of the Medical Device Division of Keyron since January 2011. Both of these are unremunerated positions. C.W.l.R. was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. He continues to provide scientific advice to Keyron for no remuneration. The other authors declare no conflict of interest. EDAT- 2022/06/11 06:00 MHDA- 2022/06/14 06:00 PMCR- 2022/05/26 CRDT- 2022/06/10 01:21 PHST- 2022/04/19 00:00 [received] PHST- 2022/05/18 00:00 [revised] PHST- 2022/05/24 00:00 [accepted] PHST- 2022/06/10 01:21 [entrez] PHST- 2022/06/11 06:00 [pubmed] PHST- 2022/06/14 06:00 [medline] PHST- 2022/05/26 00:00 [pmc-release] AID - nu14112217 [pii] AID - nutrients-14-02217 [pii] AID - 10.3390/nu14112217 [doi] PST - epublish SO - Nutrients. 2022 May 26;14(11):2217. doi: 10.3390/nu14112217. PMID- 35676825 OWN - NLM STAT- MEDLINE DCOM- 20221004 LR - 20250530 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 11 DP - 2022 Nov TI - In vivo and in vitro characterization of GL0034, a novel long-acting glucagon-like peptide-1 receptor agonist. PG - 2090-2101 LID - 10.1111/dom.14794 [doi] AB - AIMS: To describe the in vitro characteristics and antidiabetic in vivo efficacy of the novel glucagon-like peptide-1 receptor agonist (GLP-1RA) GL0034. MATERIALS AND METHODS: Glucagon-like peptide-1 receptor (GLP-1R) kinetic binding parameters, cyclic adenosine monophosphate (cAMP) signalling, endocytosis and recycling were measured using HEK293 and INS-1832/3 cells expressing human GLP-1R. Insulin secretion was measured in vitro using INS-1832/3 cells, mouse islets and human islets. Chronic administration studies to evaluate weight loss and glycaemic effects were performed in db/db and diet-induced obese mice. RESULTS: Compared to the leading GLP-1RA semaglutide, GL0034 showed increased binding affinity and potency-driven bias in favour of cAMP over GLP-1R endocytosis and beta-arrestin-2 recruitment. Insulin secretory responses were similar for both ligands. GL0034 (6 nmol/kg) led to at least as much weight loss and lowering of blood glucose as did semaglutide at a higher dose (14 nmol/kg). CONCLUSIONS: GL0034 is a G protein-biased agonist that shows powerful antidiabetic effects in mice, and may serve as a promising new GLP-1RA for obese patients with type 2 diabetes. CI - (c) 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Jones, Ben AU - Jones B AD - Section of Endocrinology and Investigative Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Burade, Vinod AU - Burade V AD - High Impact Innovations-Sustainable Health Solutions, Sun Pharmaceutical Industries Limited, Vadodara, India. FAU - Akalestou, Elina AU - Akalestou E AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Manchanda, Yusman AU - Manchanda Y AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Ramchunder, Zenouska AU - Ramchunder Z AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Carrat, Gaelle AU - Carrat G AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Nguyen-Tu, Marie-Sophie AU - Nguyen-Tu MS AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Marchetti, Piero AU - Marchetti P AD - Department of Clinical and Experimental Medicine, Islet Cell Laboratory, University of Pisa, Pisa, Italy. FAU - Piemonti, Lorenzo AU - Piemonti L AUID- ORCID: 0000-0002-2172-2198 AD - Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy. FAU - Leclerc, Isabelle AU - Leclerc I AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. AD - CRCHUM, University of Montreal, Montreal, Canada. FAU - Thennati, Rajamannar AU - Thennati R AD - High Impact Innovations-Sustainable Health Solutions, Sun Pharmaceutical Industries Limited, Vadodara, India. FAU - Vilsboll, Tina AU - Vilsboll T AD - Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. FAU - Thorens, Bernard AU - Thorens B AD - Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland. FAU - Tomas, Alejandra AU - Tomas A AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. FAU - Rutter, Guy A AU - Rutter GA AUID- ORCID: 0000-0001-6360-0343 AD - Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK. AD - CRCHUM, University of Montreal, Montreal, Canada. AD - Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. LA - eng GR - WT212625/Z/18/Z/WT_/Wellcome Trust/United Kingdom GR - MR/R010676/1/MRC_/Medical Research Council/United Kingdom GR - R022259/WT_/Wellcome Trust/United Kingdom GR - MR/K023667/1/MRC_/Medical Research Council/United Kingdom GR - WT212625/WT_/Wellcome Trust/United Kingdom GR - MR/R022259/1/MRC_/Medical Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220718 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulins) RN - 0 (Ligands) RN - 0 (beta-Arrestins) RN - 415SHH325A (Adenosine Monophosphate) RN - E0399OZS9N (Cyclic AMP) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adenosine Monophosphate MH - Animals MH - Blood Glucose MH - Cyclic AMP/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy MH - HEK293 Cells MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - *Insulins MH - Ligands MH - Mice MH - Weight Loss MH - beta-Arrestins/metabolism MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC9796023 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - antiobesity drug OT - beta-cell function OT - drug development OT - incretin therapy COIS- Vinod Burade and Thennati Rajamannar are employees of Sun Pharmaceuticals, from whom Guy A. Rutter and Alejandra Tomas have received grant funding. EDAT- 2022/06/10 06:00 MHDA- 2022/10/05 06:00 PMCR- 2022/12/28 CRDT- 2022/06/09 01:14 PHST- 2022/05/20 00:00 [revised] PHST- 2021/08/19 00:00 [received] PHST- 2022/06/01 00:00 [accepted] PHST- 2022/06/10 06:00 [pubmed] PHST- 2022/10/05 06:00 [medline] PHST- 2022/06/09 01:14 [entrez] PHST- 2022/12/28 00:00 [pmc-release] AID - DOM14794 [pii] AID - 10.1111/dom.14794 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Nov;24(11):2090-2101. doi: 10.1111/dom.14794. Epub 2022 Jul 18. PMID- 35653929 OWN - NLM STAT- MEDLINE DCOM- 20220628 LR - 20260127 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 16 IP - 6 DP - 2022 Jun TI - The role of oral semaglutide in managing type 2 diabetes in Indian clinical settings: Addressing the unmet needs. PG - 102508 LID - S1871-4021(22)00122-9 [pii] LID - 10.1016/j.dsx.2022.102508 [doi] AB - AIMS: Despite their established benefits, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remain underutilized for type 2 diabetes mellitus (T2DM) management, which indicates that subcutaneous injection is an unfavorable mode of delivery from the patient's perspective. This review summarizes existing challenges related to medication adherence and the use of antihyperglycemia injectables, revisits the established safety and efficacy of oral semaglutide, and explores its features and considerations for use among the Indian T2DM population. METHODS: We performed a literature search using MEDLINE and the National Institutes of Health Clinical Trials Registry from July 1, 2016, to July 1, 2021, to identify publications on oral semaglutide approval, T2DM treatment guidelines, and clinical evidence for oral drug formulation. RESULTS: Oral semaglutide is the first oral GLP-1 RA approved for T2DM patients based on phase 3, randomized PIONEER trials. The multitargeted action of this drug offers glycemic control, weight control, and cardiovascular, renal, and additional benefits, including patient convenience and enhanced medication adherence. In addition to achieving glycemic control, the cost of semaglutide is reported to be lower than other GLP-1 RA in the West, thus potentially mitigating the economic burden that appears to be high among the Indian population. CONCLUSIONS: Currently, there is no data available on oral semaglutide in Indian clinical settings. However, significant improvements in glycemic control, cardiac and renal benefits, as well as weight loss across clinical trials should encourage clinicians to prioritize oral semaglutide over other antidiabetic agents. CI - Copyright (c) 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved. FAU - Joshi, Shashank R AU - Joshi SR AD - Grant Medical College and Consulting Endocrinologist, Lilavati Hospital, Mumbai, India. Electronic address: shashank.sr@gmail.com. FAU - Rajput, Rajesh AU - Rajput R AD - Department of Endocrinology, PGIMS, Rohtak, Haryana, India. Electronic address: drrajeshrajput@outlook.com. FAU - Chowdhury, Subhankar AU - Chowdhury S AD - Dept. of Endocrinology, IPGME&R and SSKM Hospital, Kolkata, India. Electronic address: subhankar.chowdhury@gmail.com. FAU - Singh, Awadhesh K AU - Singh AK AD - G. D. Hospital & Diabetes Institute, Kolkata, West Bengal, India. Electronic address: drawadheshkumarsingh@gmail.com. FAU - Bantwal, Ganapathi AU - Bantwal G AD - St. John's Hospital Medical College, Bangalore, India. Electronic address: mallyaganapathi@rediffmail.com. FAU - Das, Ashok K AU - Das AK AD - Department of General Medicine, Pondicherry Institute of Medical Sciences, Puducherry, India. Electronic address: ashokdas82@gmail.com. FAU - Unnikrishnan, A G AU - Unnikrishnan AG AD - Chellaram Diabetes Institute, Pune, India. Electronic address: ceo@CDI.ORG.IN. FAU - Saboo, Banshi D AU - Saboo BD AD - Diabetes Care and Hormone Clinic, Ahmedabad, India. Electronic address: banshisaboo@hotmail.com. FAU - Kesavadev, Jothydev AU - Kesavadev J AD - Jothydev's Diabetes Research Centres, Kerala, India. Electronic address: jothydev@gmail.com. FAU - Ghosal, Samit AU - Ghosal S AD - Nightingale Hospital, Kolkata, India. Electronic address: ramdasghosal@gmail.com. FAU - Mohan, Viswanathan AU - Mohan V AD - Dr. Mohan's Diabetes Specialties Centre & Madras Diabetes Research Foundation, Chennai, India. Electronic address: drmohans@diabetes.ind.in. LA - eng PT - Journal Article PT - Review DEP - 20220523 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Antidiabetic drugs OT - Glucagon-like peptide-1 receptor agonists OT - Medication adherence OT - Oral semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest VM acted as consultant and speaker, received research or educational grants from Novo Nordisk, Johnson & Johnson, USV Private Limited, Abbott, Biocon, Astra Zeneca, Boehringer Ingelheim, Dr. Reddy's Laboratories, LifeScan, Lilly, MSD, Novartis, Roche Diabetes Care India Pvt. Ltd, Sanofi-Aventis, and other Indian pharmaceutical companies. AGU, AKS, GB, and JK received honoraria from Novo Nordisk. SJ, AD, BS, and SG received speaker honoraria from Novo Nordisk for conducting medical education lectures. No potential conflict of interest was reported by SC and RR. Novo Nordisk neither influenced the content of this publication nor was it involved in the study design, data collection, analysis, interpretation, or review. EDAT- 2022/06/03 06:00 MHDA- 2022/06/29 06:00 CRDT- 2022/06/02 18:23 PHST- 2021/12/20 00:00 [received] PHST- 2022/05/10 00:00 [revised] PHST- 2022/05/12 00:00 [accepted] PHST- 2022/06/03 06:00 [pubmed] PHST- 2022/06/29 06:00 [medline] PHST- 2022/06/02 18:23 [entrez] AID - S1871-4021(22)00122-9 [pii] AID - 10.1016/j.dsx.2022.102508 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2022 Jun;16(6):102508. doi: 10.1016/j.dsx.2022.102508. Epub 2022 May 23. PMID- 35650449 OWN - NLM STAT- MEDLINE DCOM- 20220616 LR - 20260127 IS - 1573-904X (Electronic) IS - 0724-8741 (Print) IS - 0724-8741 (Linking) VI - 39 IP - 6 DP - 2022 Jun TI - Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review. PG - 1233-1248 LID - 10.1007/s11095-022-03302-1 [doi] AB - INTRODUCTION: Semaglutide, a peptidic GLP-1 receptor agonist, has been clinically approved for treatment of type 2 diabetes mellitus and is available in subcutaneous and oral dosage form. Diabetes, insulin resistance, and obesity are responsible for the pathological manifestations of non-alcoholic steatohepatitis (NASH). Similarly, insulin resistance in brain is also responsible for neurodegeneration and impaired cognitive functions. BACKGROUND: Observations from phase-3 clinical trials like SUSTAIN and PIONEER indicated anti-obesity potential of semaglutide, which was established in STEP trials. Various pre-clinical and phase-2 studies have indicated the therapeutic potential of semaglutide in non-alcoholic steatohepatitis and neurodegenerative disorders like Parkinson's and Alzheimer's disease. DISCUSSION: Significant weight reduction ability of semaglutide has been demonstrated in various phase-3 clinical trials, for which recently semaglutide became the first long-acting GLP-1 receptor agonist to be approved by the United States Food and Drug Administration for management of obesity. Various pre-clinical and clinical studies have revealed the hepatoprotective effect of semaglutide in NASH and neuroprotective effect in Parkinson's and Alzheimer's disease. CONCLUSION: Many GLP-1 receptor agonists have shown hepatoprotective and neuroprotective activity in animal and human trials. As semaglutide is an already clinically approved drug, successful human trials would hasten its inclusion into therapeutic treatment of NASH and neurodegenerative diseases. Semaglutide improves insulin resistance, insulin signalling pathway, and reduce body weight which are responsible for prevention or progression of NASH and neurodegenerative diseases. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Mahapatra, Manoj K AU - Mahapatra MK AD - Department of Pharmaceutical Chemistry, Kanak Manjari Institute of Pharmaceutical Sciences, Chhend, Rourkela, 769015, Odisha, India. manojbit07@gmail.com. FAU - Karuppasamy, Muthukumar AU - Karuppasamy M AD - YaAn Pharmaceutical and Medical Communications, 1798, Balaji Nagar, Sithurajapuram, Sivakasi, 626189, Tamilnadu, India. FAU - Sahoo, Biswa M AU - Sahoo BM AD - Roland Institute of Pharmaceutical Sciences, Berhampur, 760010, Odisha, India. LA - eng PT - Journal Article PT - Review DEP - 20220601 PL - United States TA - Pharm Res JT - Pharmaceutical research JID - 8406521 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Alzheimer Disease/drug therapy MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Glucagon-Like Peptides MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - *Insulin Resistance MH - *Neurodegenerative Diseases/drug therapy MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Obesity/drug therapy MH - *Parkinson Disease/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC9159769 OTO - NOTNLM OT - GLP-1 receptor agonist OT - metabolic diseases OT - neurodegenerative diseases OT - obesity OT - semaglutide COIS- The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript. EDAT- 2022/06/02 06:00 MHDA- 2022/06/18 06:00 PMCR- 2022/06/01 CRDT- 2022/06/01 23:30 PHST- 2022/03/21 00:00 [received] PHST- 2022/05/23 00:00 [accepted] PHST- 2022/06/02 06:00 [pubmed] PHST- 2022/06/18 06:00 [medline] PHST- 2022/06/01 23:30 [entrez] PHST- 2022/06/01 00:00 [pmc-release] AID - 10.1007/s11095-022-03302-1 [pii] AID - 3302 [pii] AID - 10.1007/s11095-022-03302-1 [doi] PST - ppublish SO - Pharm Res. 2022 Jun;39(6):1233-1248. doi: 10.1007/s11095-022-03302-1. Epub 2022 Jun 1. PMID- 35624390 OWN - NLM STAT- MEDLINE DCOM- 20220714 LR - 20261028 IS - 1534-6242 (Electronic) IS - 1523-3804 (Linking) VI - 24 IP - 8 DP - 2022 Aug TI - Glucagon-Like Peptide 1 Receptor Agonists: A Medication for Obesity Management. PG - 643-654 LID - 10.1007/s11883-022-01041-7 [doi] AB - PURPOSE OF REVIEW: The burden of obesity worldwide is high and projected to rise. Obesity increases the risk of several cardiovascular diseases and cardiometabolic risk factors; hence, utilizing effective long-term therapies for obesity is of utmost importance. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as effective therapies that achieve substantial weight loss and improve cardiometabolic risk. The purpose of this review is to discuss the role of GLP-1RAs in obesity management. RECENT FINDINGS: Two subcutaneous GLP-1RAs, liraglutide and semaglutide, have been evaluated in several clinical trials for weight loss. Liraglutide achieves a mean weight loss of 4-7 kg, and more than 50% of treated individuals achieve 5% or more weight loss. Semaglutide has a greater impact on weight loss, with a mean weight loss of 9-16 kg, and more than 50% of treated individuals achieve 10-15% or more weight loss. These results led to regulatory approval of these agents for weight loss in individuals with obesity, regardless of diabetes status. In addition to weight loss, the benefits of GLP-1RAs extend to other risk factors, such as glycemic control and blood pressure. Gastrointestinal symptoms are the most frequently encountered adverse events with incidences between 5 and 30%. Finally, the cost remains one of the most critical challenges that limit GLP-1RAs use. GLP-1RAs have robust weight loss benefits and are expected to have a critical role in the management of obesity in the coming years. Upcoming studies will evaluate the durability of weight loss achieved with GLP-1RAs and the impact on cardiovascular outcomes. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Taha, Mohamad B AU - Taha MB AD - Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin St Suite 1801, Houston, TX77030, USA. AD - Center for Outcomes Research, Houston Methodist, Houston, TX, USA. FAU - Yahya, Tamer AU - Yahya T AD - Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin St Suite 1801, Houston, TX77030, USA. AD - Center for Outcomes Research, Houston Methodist, Houston, TX, USA. FAU - Satish, Priyanka AU - Satish P AD - Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin St Suite 1801, Houston, TX77030, USA. FAU - Laird, Rachel AU - Laird R AD - Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin St Suite 1801, Houston, TX77030, USA. FAU - Agatston, Arthur S AU - Agatston AS AD - Department of Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA. FAU - Cainzos-Achirica, Miguel AU - Cainzos-Achirica M AD - Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin St Suite 1801, Houston, TX77030, USA. AD - Center for Outcomes Research, Houston Methodist, Houston, TX, USA. FAU - Patel, Kershaw V AU - Patel KV AD - Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin St Suite 1801, Houston, TX77030, USA. FAU - Nasir, Khurram AU - Nasir K AD - Division of Cardiovascular Prevention and Wellness, Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin St Suite 1801, Houston, TX77030, USA. knasir@houstonmethodist.org. AD - Center for Outcomes Research, Houston Methodist, Houston, TX, USA. knasir@houstonmethodist.org. LA - eng PT - Journal Article PT - Review DEP - 20220528 PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - Obesity/complications/drug therapy MH - *Obesity Management MH - Weight Loss MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular risk factors OT - Glucagon-like peptide 1 receptor agonists OT - Liraglutide OT - Obesity OT - Semaglutide OT - Weight loss EDAT- 2022/05/28 06:00 MHDA- 2022/07/15 06:00 CRDT- 2022/05/27 23:28 PHST- 2022/04/11 00:00 [accepted] PHST- 2022/05/28 06:00 [pubmed] PHST- 2022/07/15 06:00 [medline] PHST- 2022/05/27 23:28 [entrez] AID - 10.1007/s11883-022-01041-7 [pii] AID - 10.1007/s11883-022-01041-7 [doi] PST - ppublish SO - Curr Atheroscler Rep. 2022 Aug;24(8):643-654. doi: 10.1007/s11883-022-01041-7. Epub 2022 May 28. PMID- 35623229 OWN - NLM STAT- MEDLINE DCOM- 20220628 LR - 20260127 IS - 1878-0334 (Electronic) IS - 1871-4021 (Linking) VI - 16 IP - 6 DP - 2022 Jun TI - Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes. PG - 102511 LID - S1871-4021(22)00125-4 [pii] LID - 10.1016/j.dsx.2022.102511 [doi] AB - BACKGROUND AND AIMS: To assess the safety and efficacy of semaglutide compared with placebo and other anti-hyperglycaemic agents in type 2 diabetes (T2DM). METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane library for relevant randomized controlled trials (RCTs). A network meta-analysis was conducted to compare different doses, durations, and interventions in T2DM. We presented results as mean difference (MD) or relative risk (RR) and 95% confidence interval (CI). RESULTS: Twenty-six included RCTs studied different doses of subcutaneous (SC) and oral semaglutide, tirzepatide, liraglutide, sitagliptin, canagliflozin, and empagliflozin compared with placebo. Tirzepatide showed the highest efficacy, however, it was comparable to semaglutide. SC semaglutide 1 mg once-weekly showed higher reduction in HbA(1c) (MD = -1.72, 95% CI [-2.32; -1.12]), and fasting blood glucose (MD = -1.93, 95% CI [-2.81; -1.04]) versus placebo at 30 weeks and other timepoints. Adverse events (ADs) were comparable to placebo with oral and SC semaglutide, oral sitagliptin, SC liraglutide, and oral empagliflozin at most timepoints. However, SC semaglutide 0.8 mg and tirzepatide 10 mg groups had the highest gastrointestinal adverse events. CONCLUSION: Tirzepatide, oral and SC semaglutide has a favourable efficacy in treating T2DM. The adverse events were comparable to placebo; however, gastrointestinal adverse events were highly recorded in tirzepatide, oral and SC semaglutide groups. CI - Copyright (c) 2022 Diabetes India. Published by Elsevier Ltd. All rights reserved. FAU - Zaazouee, Mohamed Sayed AU - Zaazouee MS AD - Faculty of Medicine, Al-Azhar University, Assiut, Egypt; International Medical Research Association (IMedRA), Egypt. FAU - Hamdallah, Aboalmagd AU - Hamdallah A AD - Faculty of Medicine Al-Azhar University, Damietta, Egypt; International Medical Research Association (IMedRA), Egypt. FAU - Helmy, Sara Kamel AU - Helmy SK AD - Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt; International Medical Research Association (IMedRA), Egypt. FAU - Hasabo, Elfatih A AU - Hasabo EA AD - Faculty of Medicine, University of Khartoum, Khartoum, Sudan; International Medical Research Association (IMedRA), Egypt. FAU - Sayed, Ahmed Kamal AU - Sayed AK AD - Faculty of Medicine, Minia University, Minia, Egypt; Minia Medical Research Society (MMRS), Minia University, Egypt. FAU - Gbreel, Mohamed Ibrahim AU - Gbreel MI AD - Faculty of Medicine, October 6 University, Giza, Egypt; International Medical Research Association (IMedRA), Egypt. FAU - Elmegeed, Aya Abd AU - Elmegeed AA AD - Faculty of Science, Menofia University, Shebin El-Kom, Menofia, Egypt; International Medical Research Association (IMedRA), Egypt. FAU - Aladwan, Hala AU - Aladwan H AD - Faculty of Pharmacy, The University of Jordan, Amman, Jordan; International Medical Research Association (IMedRA), Egypt. FAU - Elshanbary, Alaa Ahmed AU - Elshanbary AA AD - Faculty of Medicine, Alexandria University, Alexandria, Egypt; International Medical Research Association (IMedRA), Egypt. Electronic address: Alaa.mohamed1603@alexmed.edu.eg. FAU - Abdel-Aziz, Walid AU - Abdel-Aziz W AD - Faculty of Medicine, Al-Azhar University, Assiut, Egypt; International Medical Research Association (IMedRA), Egypt. FAU - Elshahawy, Israa Mohamed AU - Elshahawy IM AD - Faculty of Pharmacy Zagazig University, Zagazig, Egypt; International Medical Research Association (IMedRA), Egypt. FAU - Rabie, Shehab AU - Rabie S AD - Faculty of Science, Al-Azhar University, Cairo, Egypt; International Medical Research Association (IMedRA), Egypt. FAU - Elkady, Sherouk AU - Elkady S AD - Department of Medical Biochemistry, Faculty of Medicine, Assiut University, Egypt; International Medical Research Association (IMedRA), Egypt. FAU - Ali, Ahmed Said AU - Ali AS AD - Faculty of Medicine, Al-Azhar University, Cairo, Egypt. FAU - Ragab, Khaled Mohamed AU - Ragab KM AD - Faculty of Medicine, Minia University, Minia, Egypt; International Medical Research Association (IMedRA), Egypt. FAU - Nourelden, Anas Zakarya AU - Nourelden AZ AD - Faculty of Medicine, Al-Azhar University, Cairo, Egypt; International Medical Research Association (IMedRA), Egypt. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20220520 PL - Netherlands TA - Diabetes Metab Syndr JT - Diabetes & metabolic syndrome JID - 101462250 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - *Liraglutide/therapeutic use MH - Sitagliptin Phosphate/therapeutic use MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Hyperglycaemia OT - Network meta-analysis OT - Semaglutide OT - Type 2 diabetes mellitus COIS- Declaration of competing interest None. EDAT- 2022/05/28 06:00 MHDA- 2022/06/29 06:00 CRDT- 2022/05/27 18:22 PHST- 2021/08/05 00:00 [received] PHST- 2022/05/12 00:00 [revised] PHST- 2022/05/14 00:00 [accepted] PHST- 2022/05/28 06:00 [pubmed] PHST- 2022/06/29 06:00 [medline] PHST- 2022/05/27 18:22 [entrez] AID - S1871-4021(22)00125-4 [pii] AID - 10.1016/j.dsx.2022.102511 [doi] PST - ppublish SO - Diabetes Metab Syndr. 2022 Jun;16(6):102511. doi: 10.1016/j.dsx.2022.102511. Epub 2022 May 20. PMID- 35610766 OWN - NLM STAT- MEDLINE DCOM- 20220526 LR - 20260127 IS - 2639-9636 (Print) IS - 2639-9636 (Linking) VI - 37 IP - 6 DP - 2022 Jun 1 TI - Semaglutide Initiation in a Type 2 Diabetes Mellitus, Post-Liver Transplant Patient. PG - 221-226 LID - 10.4140/TCP.n.2022.221 [doi] AB - Objective To describe the process of initiation of semaglutide for complex management of type 2 diabetes mellitus (T2DM) in a patient after liver transplantation. Setting Family medicine clinic. Practice Description A family medicine clinic comprising six physicians with an ambulatory care pharmacist. The pharmacist has direct interaction with patients and providers within the clinic assisting in the management of chronic disease states under a collaborative practice agreement. Practice Innovation A 63-year-old White male with a history of liver transplantation in the context of T2DM, treated with basal-bolus insulin therapy, was referred by his family medicine provider to the ambulatory care pharmacist for diabetes management because of a hemoglobin A1c (HbA1c) level greater than 10%. Semaglutide was initiated and titrated to improve blood glucose control in combination with basal-bolus insulin adjustments taking disease states, cost, and health literacy into consideration. Results The addition of semaglutide, over an eight-month period, assisted with glycemic control to an HbA1c of less than 7%. Conclusion Semaglutide, in addition to basal-bolus insulin therapy, allowed for overall improved glycemic control; however, further studies are needed to evaluate efficacy because of the complexity of diabetes management in this patient population. Throughout the course of treatment of patients with T2DM and organ transplantation, dual monitoring of antidiabetic therapy and antirejection medications is essential to reduce the risk of organ rejection. FAU - Newell, Bradley J AU - Newell BJ AD - University of Kansas, Wichita, Kansas. FAU - Melton, Brittany L AU - Melton BL AD - University of Kansas, Wichita, Kansas. FAU - Burkhardt, Crystal D AU - Burkhardt CD AD - University of Kansas, Wichita, Kansas. FAU - Ruisinger, Janelle F AU - Ruisinger JF AD - University of Kansas, Wichita, Kansas. LA - eng PT - Case Reports PT - Journal Article PL - United States TA - Sr Care Pharm JT - The Senior care pharmacist JID - 101737969 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Insulins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin/analysis/therapeutic use MH - Humans MH - *Insulins/therapeutic use MH - *Liver Transplantation MH - Male MH - Middle Aged MH - Semaglutide EDAT- 2022/05/26 06:00 MHDA- 2022/05/27 06:00 CRDT- 2022/05/25 00:43 PHST- 2022/05/25 00:43 [entrez] PHST- 2022/05/26 06:00 [pubmed] PHST- 2022/05/27 06:00 [medline] AID - 10.4140/TCP.n.2022.221 [doi] PST - ppublish SO - Sr Care Pharm. 2022 Jun 1;37(6):221-226. doi: 10.4140/TCP.n.2022.221. PMID- 35594964 OWN - NLM STAT- MEDLINE DCOM- 20220608 LR - 20250103 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 153 DP - 2022 Jul TI - Discovery of once-weekly, peptide-based selective GLP-1 and cholecystokinin 2 receptors co-agonizts. PG - 170811 LID - S0196-9781(22)00077-8 [pii] LID - 10.1016/j.peptides.2022.170811 [doi] AB - A group of long-acting, peptide-based, and selective GLP-1R/CCK-2R dual agonizts were identified by rational design. Guided by sequence analysis, structural elements of the CCK-2R agonist moiety were engineered into the GLP-1R agonist Xenopus GLP-1, resulting in hybrid peptides with potent GLP-1R/CCK-2R dual activity. Further modifications with fatty acids resulted in novel metabolically stable peptides, among which 3d and 3 h showed potent GLP-1R and CCK-2R activation potencies and comparable stability to semaglutide. In food intake tests, 3d and 3 h also showed a potent reduction in food intake, superior to that of semaglutide. Moreover, the acute hypoglycemic and insulinotropic activities of 3d and 3 h were better than that of semaglutide and ZP3022. Importantly, the limited pica response following 3d and 3 h administration in SD rats preliminarily indicated that the food intake reduction effects of 3d and 3 h are independent of nausea/vomiting. In a 35-day study in db/db mice, every two days administration of 3d and 3 h increased islet areas and numbers, insulin contents, beta-cell area, beta-cell proliferation, as well as improved glucose tolerance, and decreased HbA1c, to a greater extent than ZP3022 and semaglutide. In a 21-day study in DIO mice, once-weekly administration of 3d and 3 h significantly induced body weight loss, improved glucose tolerance, and normalized lipid metabolism, to a greater extent than semaglutide. The current study showed the antidiabetic and antiobesity potentials of GLP-1R/CCK-2R dual agonizts that warrant further investigation. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Zhou, Feng AU - Zhou F AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Song, Peng AU - Song P AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Tang, Xueling AU - Tang X AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Yang, Qimeng AU - Yang Q AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Zhou, Siyuan AU - Zhou S AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Xu, Ronglian AU - Xu R AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Fang, Ting AU - Fang T AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China. FAU - Jia, Zhiruo AU - Jia Z AD - College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530001, PR China. Electronic address: jzr7929@163.com. FAU - Han, Jing AU - Han J AD - School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, PR China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi 530021, PR China. Electronic address: hj1986424@jsnu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220517 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Anti-Obesity Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Peptides) RN - 0 (Receptor, Cholecystokinin B) RN - 0 (ZP3022) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9011-97-6 (Cholecystokinin) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - Anti-Obesity Agents/pharmacology MH - Cholecystokinin/metabolism MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptide 1/metabolism MH - *Glucagon-Like Peptide-1 Receptor/drug effects/metabolism MH - Glucose MH - *Hypoglycemic Agents/pharmacology MH - Mice MH - *Peptides/chemistry/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - *Receptor, Cholecystokinin B/agonists/drug effects/metabolism MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Diabetes OT - Glucagon-like peptide-1 OT - Metabolic disorders EDAT- 2022/05/21 06:00 MHDA- 2022/06/09 06:00 CRDT- 2022/05/20 19:23 PHST- 2022/02/12 00:00 [received] PHST- 2022/04/23 00:00 [revised] PHST- 2022/05/12 00:00 [accepted] PHST- 2022/05/21 06:00 [pubmed] PHST- 2022/06/09 06:00 [medline] PHST- 2022/05/20 19:23 [entrez] AID - S0196-9781(22)00077-8 [pii] AID - 10.1016/j.peptides.2022.170811 [doi] PST - ppublish SO - Peptides. 2022 Jul;153:170811. doi: 10.1016/j.peptides.2022.170811. Epub 2022 May 17. PMID- 35589616 OWN - NLM STAT- MEDLINE DCOM- 20220803 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 9 DP - 2022 Sep TI - Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison. PG - 1861-1868 LID - 10.1111/dom.14775 [doi] AB - AIM: To conduct an adjusted indirect treatment comparison (aITC) of the efficacy of tirzepatide 5/10/15 mg versus semaglutide 2 mg in patients with type 2 diabetes. MATERIALS AND METHODS: The primary analysis was a Bucher aITC of the change from baseline at week 40 in HbA1c (%) and body weight (kg). Aggregate data from the SURPASS-2 study that met the HbA1c inclusion criterion of the SUSTAIN FORTE study and from SUSTAIN FORTE metformin-only treated patients were used for primary analysis. RESULTS: The SURPASS-2 refined population comprised 238/245/240 and 240 participants for tirzepatide 5/10/15 mg and semaglutide 1 mg, respectively. The SUSTAIN FORTE metformin-only population comprised 222 and 227 participants for semaglutide 1 and 2 mg, respectively. In this aITC, tirzepatide 10 and 15 mg significantly reduced HbA1c versus semaglutide 2 mg with an estimated treatment difference (ETD) of -0.36% (95% confidence interval [CI] -0.63, -0.09) and -0.4% (95% CI -0.67, -0.13), respectively. Tirzepatide 10 and 15 mg significantly reduced body weight versus semaglutide 2 mg with an ETD of -3.15 kg (95% CI -4.84, -1.46) and -5.15 kg (95% CI -6.85, -3.45), respectively. There were no significant differences between tirzepatide 5 mg and semaglutide 2 mg on change from baseline in HbA1c and body weight. CONCLUSIONS: In this aITC, HbA1c and weight reductions were significantly greater for tirzepatide 10 and 15 mg versus semaglutide 2 mg and were similar for tirzepatide 5 mg versus semaglutide 2 mg. These findings provide comparative effectiveness insights in the absence of a head-to-head clinical trial. CI - (c) 2022 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Vadher, Karan AU - Vadher K AUID- ORCID: 0000-0002-6287-5596 AD - Eli Lilly and Company, Bracknell, UK. FAU - Patel, Hiren AU - Patel H AUID- ORCID: 0000-0003-2463-4916 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana. FAU - Mody, Reema AU - Mody R AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana. FAU - Levine, Joshua A AU - Levine JA AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana. FAU - Hoog, Meredith AU - Hoog M AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana. FAU - Cheng, Alice Yy AU - Cheng AY AD - Division of Endocrinology and Metabolism, Department of Medicine, Trillium Health Partners and Unity Health Toronto, University of Toronto, Toronto, Ontario, Canada. FAU - Pantalone, Kevin M AU - Pantalone KM AUID- ORCID: 0000-0002-3897-4551 AD - Department of Endocrinology, Cleveland Clinic, Cleveland, Ohio. FAU - Sapin, Helene AU - Sapin H AD - Lilly France SAS, Neuilly-sur-Seine, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220613 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Body Weight MH - *Diabetes Mellitus, Type 2/chemically induced/drug therapy MH - Double-Blind Method MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptides/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Metformin/therapeutic use MH - Treatment Outcome MH - Tirzepatide MH - Semaglutide PMC - PMC9546430 OTO - NOTNLM OT - GIP/GLP-1 receptor agonist OT - adjusted indirect treatment comparison OT - incretin mimetic OT - incretins OT - matching-adjusted indirect comparison OT - semaglutide OT - tirzepatide OT - type 2 diabetes COIS- AYYC declares advisory board and/or speaking honoraria from Abbott, AstraZeneca, Bausch, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly and Company, HLS Therapeutics, Insulet, Janssen, Medtronic, Merck, Novo Nordisk, Pfizer, Sanofi and Takeda. KMP reports receiving research support from Bayer, Merck, Novo Nordisk and Twin Health; consulting honoraria from AstraZeneca, Bayer, Corcept Therapeutics, Diasome, Eli Lilly and Company, Merck, Novo Nordisk and Sanofi; and speaker honoraria from AstraZeneca, Corcept Therapeutics, Merck and Novo Nordisk. KV, HP, RM, JAL, MH and HS are employees and shareholders of Eli Lilly and Company. EDAT- 2022/05/20 06:00 MHDA- 2022/08/04 06:00 PMCR- 2022/10/07 CRDT- 2022/05/19 22:33 PHST- 2022/05/05 00:00 [revised] PHST- 2022/03/31 00:00 [received] PHST- 2022/05/17 00:00 [accepted] PHST- 2022/05/20 06:00 [pubmed] PHST- 2022/08/04 06:00 [medline] PHST- 2022/05/19 22:33 [entrez] PHST- 2022/10/07 00:00 [pmc-release] AID - DOM14775 [pii] AID - 10.1111/dom.14775 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Sep;24(9):1861-1868. doi: 10.1111/dom.14775. Epub 2022 Jun 13. PMID- 35584872 OWN - NLM STAT- MEDLINE DCOM- 20220520 LR - 20260127 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 12 IP - 5 DP - 2022 May 18 TI - Effects of switching from a dipeptidyl peptidase-4 inhibitor to oral semaglutide on glucose metabolism in patients with type 2 diabetes: protocol for a multicentre, prospective, randomised, open-label, parallel-group comparison study (the SWITCH-SEMA 2 study). PG - e056885 LID - 10.1136/bmjopen-2021-056885 [doi] LID - e056885 AB - INTRODUCTION: Incretin-based therapies exert antihyperglycaemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent fashion. The first-in-class oral glucagon-like peptide-1 receptor agonist semaglutide has potent effects on glycaemic and weight control, but little evidence has been published for the superiority of semaglutide for glycaemic control in patients after switching from a dipeptidyl peptidase-4 (DPP-4) inhibitor. Therefore, we aim to verify the efficacy of oral semaglutide in patients with T2D being treated with a DPP-4 inhibitor. METHODS AND ANALYSIS: This study is a multicentre, prospective, randomised, open-label, parallel-group trial. In total, 172 participants with T2D who have been treated with a DPP-4 inhibitor for more than 12 weeks and who have a glycated haemoglobin (HbA1c) level of 7.0%-9.9% will be randomised to continue using their existing DPP-4 inhibitor or switch to oral semaglutide for 24 weeks. Biochemical analyses and physical assessment will be performed, and adverse events will be recorded at baseline and at the end of the study. The primary endpoint will be the effect of oral semaglutide on the change in HbA1c. The secondary endpoints will be the mean changes in body weight, abdominal circumference, systolic and diastolic blood pressure (BP), pulse rate, the relationship between improvement of metabolic parameters including HbA1c and patient background characteristics, side effects and other laboratory parameters. ETHICS AND DISSEMINATION: This will be the first study to compare the effects of switching from a DPP-4 inhibitor to oral semaglutide on glycaemic control in patients with T2D. The results will be disseminated in peer-reviewed journals and at scientific conferences. Hokkaido University Certified Review Board (CRB no.1180001) has approved the protocol (no. 020-013). TRIAL REGISTRATION NUMBER: UMIN000045270 in the University Hospital Medical Information Network; jRCT1011210032 in the Japan Registry of Clinical Trials. CI - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Nomoto, Hiroshi AU - Nomoto H AUID- ORCID: 0000-0003-0713-221X AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. FAU - Furusawa, Sho AU - Furusawa S AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. FAU - Nakamura, Akinobu AU - Nakamura A AUID- ORCID: 0000-0002-8192-0006 AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. FAU - Takeuchi, Jun AU - Takeuchi J AD - Sapporo Diabetes and Thyroid Clinic, Sapporo, Japan. FAU - Nagai, So AU - Nagai S AD - Division of Diabetes and Endocrinology, Department of Medicine, Sapporo Medical Center NTT EC, Sapporo, Japan. FAU - Yokoyama, Hiroki AU - Yokoyama H AD - Jiyugaoka Medical Clinic, Obihiro, Japan. FAU - Sakuma, Ichiro AU - Sakuma I AD - Caress Sapporo Hokko Memorial Clinic, Sapporo, Japan. FAU - Taneda, Shinji AU - Taneda S AD - Diabetes Center, Manda Memorial Hospital, Sapporo, Japan. FAU - Kurihara, Yoshio AU - Kurihara Y AD - Kurihara Clinic, Sapporo, Japan. FAU - Aoki, Shin AU - Aoki S AD - Aoki Clinic, Sapporo, Japan. FAU - Miya, Aika AU - Miya A AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. FAU - Kameda, Hiraku AU - Kameda H AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. FAU - Cho, Kyu Yong AU - Cho KY AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. AD - Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Japan. FAU - Atsumi, Tatsuya AU - Atsumi T AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan. FAU - Miyoshi, Hideaki AU - Miyoshi H AUID- ORCID: 0000-0002-5909-3243 AD - Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan hmiyoshi@med.hokudai.ac.jp. AD - Division of Diabetes and Obesity, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. LA - eng SI - UMIN-CTR/UMIN000045270 PT - Clinical Trial Protocol PT - Journal Article DEP - 20220518 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Blood Glucose) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose/metabolism MH - *Diabetes Mellitus, Type 2/complications MH - *Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/therapeutic use MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Multicenter Studies as Topic MH - Prospective Studies MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Semaglutide PMC - PMC9119155 OTO - NOTNLM OT - dipeptidyl peptidase-4 inhibitor OT - glucagon-like peptide-1 receptor agonist OT - type 2 diabetes mellitus COIS- Competing interests: AN, TA and HM have received honoraria for lectures and received research funding from some organisations as described further. AN has obtained research support from Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim Co, Kissei Pharmaceutical Co, Ltd and Taisho Pharmaceutical Co, Ltd. AT has received research grants from Astellas Pharma Inc, Takeda Pharmaceutical Co, Ltd, Mitsubishi Tanabe Pharma Co, Chugai Pharmaceutical Co, Ltd, Daiichi Sankyo Co Ltd, Otsuka Pharmaceutical Co, Ltd, Pfizer Inc, Alexion Inc, Ono Pharmaceutical Co, Ltd and Teijin Pharma Ltd; speaking fees from Mitsubishi Tanabe Pharma Co, Chugai Pharmaceutical Co, Ltd, Astellas Pharma Inc, Takeda Pharmaceutical Co, Ltd, Pfizer Inc, AbbVie Inc, Eisai Co Ltd, Daiichi Sankyo Co, Ltd, Bristol-Myers Squibb Co, UCB Japan Co Ltd, Eli Lilly Japan K.K., Novartis Pharma K.K., Eli Lilly Japan K.K., Kyowa Kirin Co, Ltd and Taiho Pharmaceutical Co, Ltd; and fees for consultancies from AstraZeneca plc., Medical & Biological Laboratories Co, Ltd, Pfizer Inc, AbbVie Inc, Ono Pharmaceutical Co Ltd, Novartis Pharma K.K. and Nippon Boehringer Ingelheim Co, Ltd. HM has received honoraria for lectures from Astellas Pharma Inc, Sumitomo Dainippon Pharma Co, Ltd, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co, MSD K.K., Novo Nordisk Pharma Ltd, Kowa Pharmaceutical Co, Ltd, Nippon Boehringer Ingelheim Co, Ono Pharmaceutical Co, Ltd and Sanofi; and has received research funding from Astellas Pharma Inc, Daiichi Sankyo Co, Sumitomo Dainippon Pharma Co, Ltd, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma Co, Novo Nordisk Pharma, Kowa Pharmaceutical Co, Ltd, Abbott Japan Co, Nippon Boehringer Ingelheim Co, Ono Pharmaceutical Co, Ltd, LifeScan Japan Inc and Taisho Pharmaceutical Co, Ltd. HN, SF, JT, SN, HY, IS, ST, YK, SA, AM, HK and KYC have no conflicts of interest to declare. EDAT- 2022/05/19 06:00 MHDA- 2022/05/21 06:00 PMCR- 2022/05/17 CRDT- 2022/05/18 20:43 PHST- 2022/05/18 20:43 [entrez] PHST- 2022/05/19 06:00 [pubmed] PHST- 2022/05/21 06:00 [medline] PHST- 2022/05/17 00:00 [pmc-release] AID - bmjopen-2021-056885 [pii] AID - 10.1136/bmjopen-2021-056885 [doi] PST - epublish SO - BMJ Open. 2022 May 18;12(5):e056885. doi: 10.1136/bmjopen-2021-056885. PMID- 35582947 OWN - NLM STAT- MEDLINE DCOM- 20220824 LR - 20260127 IS - 1524-4628 (Electronic) IS - 0039-2499 (Print) IS - 0039-2499 (Linking) VI - 53 IP - 9 DP - 2022 Sep TI - Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6. PG - 2749-2757 LID - 10.1161/STROKEAHA.121.037775 [doi] AB - BACKGROUND: GLP-1 RA (glucagon-like peptide-1 receptor agonists), including semaglutide, may reduce stroke risk in people with type 2 diabetes. This post hoc analysis examined the subcutaneous and oral semaglutide effects, versus placebo, on stroke and its subtypes in people with type 2 diabetes at high cardiovascular risk. METHODS: SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (Peptide Innovation for Early Diabetes Treatment) were randomized cardiovascular outcome trials of subcutaneous and oral semaglutide in people with type 2 diabetes at high cardiovascular risk, respectively. Time to first stroke and stroke subtypes were analyzed using a Cox proportional hazards model stratified by trial with pooled treatment as a factor. The impact of prior stroke, prior myocardial infarction or stroke, age, sex, systolic blood pressure, estimated glomerular filtration rate, and prior atrial fibrillation on treatment effects was assessed using interaction P values. Risk of major adverse cardiovascular event was analyzed according to prior stroke. RESULTS: A total of 106/6480 participants had a stroke (1.0 event/100 patient-years of observation [PYO]). Semaglutide reduced incidence of any stroke versus placebo (0.8 versus 1.1 events/100 PYO; hazard ratio, 0.68 [95% CI, 0.46-1.00]; P=0.048), driven by significant reductions in risk of small-vessel occlusion (0.3 versus 0.7 events/100 PYO; hazard ratio, 0.51 [95% CI, 0.29-0.89]; P=0.017). Hazard ratios for risk of any stroke with semaglutide versus placebo were 0.60 (95% CI, 0.37-0.99; 0.5 versus 0.9 events/100 PYO) and 0.89 (95% CI, 0.47-1.69; 2.7 versus 3.0 events/100 PYO) in those without and with prior stroke, respectively. Except for prior atrial fibrillation (P(interaction)=0.025), no significant interactions were observed between treatment effects on risk of any stroke and subgroups investigated, or between treatment effects on risk of major adverse cardiovascular event and prior stroke (P(interaction) >0.05 for all). CONCLUSIONS: Semaglutide reduced incidence of any first stroke during the trials versus placebo in people with type 2 diabetes at high cardiovascular risk, primarily driven by small-vessel occlusion prevention. Semaglutide treatment, versus placebo, lowered the risk of stroke irrespective of prior stroke at baseline. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01720446 and NCT02692716. FAU - Strain, W David AU - Strain WD AUID- ORCID: 0000-0002-6826-418X AD - University of Exeter Medical School, St Luke's Campus, United Kingdom (W.D.S., M.A.J.). AD - Academic Department of Healthcare for Older People, Royal Devon and Exeter NHS Foundation Trust, United Kingdom (W.D.S., M.A.J.). FAU - Frenkel, Ofir AU - Frenkel O AD - Novo Nordisk A/S, Soborg, Denmark (O.F., S.R., M.S.R.). FAU - James, Martin A AU - James MA AUID- ORCID: 0000-0001-6065-6018 AD - University of Exeter Medical School, St Luke's Campus, United Kingdom (W.D.S., M.A.J.). AD - Academic Department of Healthcare for Older People, Royal Devon and Exeter NHS Foundation Trust, United Kingdom (W.D.S., M.A.J.). FAU - Leiter, Lawrence A AU - Leiter LA AUID- ORCID: 0000-0002-1040-6229 AD - Li Ka Shing Knowledge Institute, St Michael's Hospital (L.A.L.), University of Toronto, ON, Canada. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark (O.F., S.R., M.S.R.). FAU - Rothwell, Peter M AU - Rothwell PM AUID- ORCID: 0000-0001-9739-9211 AD - Wolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, United Kingdom (P.M.R.). FAU - Sejersten Ripa, Maria AU - Sejersten Ripa M AUID- ORCID: 0000-0002-5491-6327 AD - Novo Nordisk A/S, Soborg, Denmark (O.F., S.R., M.S.R.). FAU - Truelsen, Thomas C AU - Truelsen TC AUID- ORCID: 0000-0001-6648-7761 AD - Department of Neurology, University of Copenhagen, Rigshospitalet, Denmark (T.C.T.). FAU - Husain, Mansoor AU - Husain M AUID- ORCID: 0000-0002-3740-6739 AD - Ted Rogers Centre for Heart Research (M.H.), University of Toronto, ON, Canada. LA - eng SI - ClinicalTrials.gov/NCT01720446 SI - ClinicalTrials.gov/NCT02692716 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20220518 PL - United States TA - Stroke JT - Stroke JID - 0235266 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Atrial Fibrillation/drug therapy MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Humans MH - Hypoglycemic Agents MH - *Stroke/drug therapy/epidemiology/prevention & control MH - Semaglutide PMC - PMC9389936 OTO - NOTNLM OT - atrial fibrillation OT - blood pressure OT - myocardial infarction OT - peptides OT - prevalence EDAT- 2022/05/19 06:00 MHDA- 2022/08/25 06:00 PMCR- 2022/05/18 CRDT- 2022/05/18 05:03 PHST- 2022/05/19 06:00 [pubmed] PHST- 2022/08/25 06:00 [medline] PHST- 2022/05/18 05:03 [entrez] PHST- 2022/05/18 00:00 [pmc-release] AID - 10.1161/STROKEAHA.121.037775 [doi] PST - ppublish SO - Stroke. 2022 Sep;53(9):2749-2757. doi: 10.1161/STROKEAHA.121.037775. Epub 2022 May 18. PMID- 35553372 OWN - NLM STAT- MEDLINE DCOM- 20220630 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Linking) VI - 39 IP - 7 DP - 2022 Jul TI - The Cost-Effectiveness of Oral Semaglutide in Spain: A Long-Term Health Economic Analysis Based on the PIONEER Clinical Trials. PG - 3180-3198 LID - 10.1007/s12325-022-02156-8 [doi] AB - INTRODUCTION: Novel glucagon-like peptide-1 (GLP-1) receptor agonist oral semaglutide has demonstrated greater improvements in glycated hemoglobin (HbA1c) and body weight versus oral medications empagliflozin and sitagliptin, and injectable GLP-1 analog liraglutide, in the PIONEER clinical trial program. Based on these data, the present analysis aimed to evaluate the long-term cost-effectiveness of oral semaglutide versus empagliflozin, sitagliptin and liraglutide in Spain. METHODS: Outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 3.0% annually. Cohort characteristics and treatment effects were sourced from PIONEER 2 and 4 for the comparisons of oral semaglutide 14 mg versus empagliflozin 25 mg and liraglutide 1.8 mg, respectively, and PIONEER 3 for oral semaglutide 7 and 14 mg versus sitagliptin 100 mg. Costs were accounted from a healthcare payer perspective in 2020 euros (EUR). Patients were assumed to receive initial therapies until HbA1c exceeded 7.5% and then treatment-intensified to basal insulin. RESULTS: Oral semaglutide 14 mg was associated with improvements in quality-adjusted life expectancy of 0.13, 0.19 and 0.06 quality-adjusted life years (QALYs) versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg, respectively, with direct costs EUR 168 higher versus empagliflozin and EUR 236 and 1415 lower versus sitagliptin and liraglutide, respectively. Oral semaglutide 14 mg was associated with an incremental cost-effectiveness ratio (ICER) of EUR 1339 per QALY gained versus empagliflozin and was considered dominant (clinically superior and cost saving) versus sitagliptin and liraglutide. Additional analyses demonstrated that oral semaglutide 7 mg was associated with improvements of 0.11 QALYs and increased costs of EUR 226 versus sitagliptin and was therefore associated with an ICER of EUR 2011 per QALY gained. CONCLUSION: Oral semaglutide 14 mg was dominant versus sitagliptin and liraglutide, and cost-effective versus empagliflozin, for the treatment of type 2 diabetes in Spain. CI - (c) 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature. FAU - Franch-Nadal, Josep AU - Franch-Nadal J AD - Centro de Investigacion Biomedica en Red en Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Barcelona, Spain. AD - Primary Health Care Center Raval Sud, Gerencia d'Ambit d'Atencio Primaria Barcelona Ciutat, Institut Catala de La Salut, Barcelona, Spain. FAU - Malkin, Samuel J P AU - Malkin SJP AUID- ORCID: 0000-0003-1306-7784 AD - Ossian Health Economics and Communications GmbH, Baumleingasse 20, 4051, Basel, Switzerland. malkin@ossianconsulting.com. FAU - Hunt, Barnaby AU - Hunt B AD - Ossian Health Economics and Communications GmbH, Baumleingasse 20, 4051, Basel, Switzerland. FAU - Martin, Virginia AU - Martin V AD - Novo Nordisk Pharma SA, Madrid, Spain. FAU - Gallego Estebanez, Maria AU - Gallego Estebanez M AD - Novo Nordisk Pharma SA, Madrid, Spain. FAU - Vidal, Josep AU - Vidal J AD - Centro de Investigacion Biomedica en Red en Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Barcelona, Spain. AD - Endocrinology and Nutrition Department, Hospital Clinic, Barcelona, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220512 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) MH - Administration, Oral MH - Benzhydryl Compounds/therapeutic use MH - Clinical Trials as Topic MH - Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/economics/therapeutic use MH - Glucosides/therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - *Hypoglycemic Agents/economics/therapeutic use MH - Liraglutide/therapeutic use MH - Sitagliptin Phosphate/therapeutic use MH - Spain MH - Semaglutide OTO - NOTNLM OT - Cost-effectiveness OT - Costs and cost analysis OT - Diabetes mellitus OT - Empagliflozin OT - GLP-1 receptor agonist OT - Liraglutide OT - Oral semaglutide OT - Sitagliptin OT - Spain EDAT- 2022/05/14 06:00 MHDA- 2022/07/01 06:00 CRDT- 2022/05/13 15:01 PHST- 2022/02/25 00:00 [received] PHST- 2022/03/30 00:00 [accepted] PHST- 2022/05/14 06:00 [pubmed] PHST- 2022/07/01 06:00 [medline] PHST- 2022/05/13 15:01 [entrez] AID - 10.1007/s12325-022-02156-8 [pii] AID - 10.1007/s12325-022-02156-8 [doi] PST - ppublish SO - Adv Ther. 2022 Jul;39(7):3180-3198. doi: 10.1007/s12325-022-02156-8. Epub 2022 May 12. PMID- 35546664 OWN - NLM STAT- MEDLINE DCOM- 20220519 LR - 20250103 IS - 1472-6823 (Electronic) IS - 1472-6823 (Linking) VI - 22 IP - 1 DP - 2022 May 12 TI - Glucagon-like peptide-1 (GLP-1) receptor agonists and cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of double-blind, randomized, placebo-controlled clinical trials. PG - 125 LID - 10.1186/s12902-022-01036-0 [doi] LID - 125 AB - BACKGROUND: The cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are still controversial in the treatment of type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the risk of cardiovascular events of GLP-1 (albiglutide, exenatide, liraglutide, semaglutide, lixisenatide and dulaglutide) receptor agonists in T2DM patients. METHODS: PubMed and Embase were searched to find relevant randomized controlled trials (RCTs) from inception to June 2019 that evaluated the effect of GLP-1 receptor agonists on cardiovascular events in patients with T2DM. The T2DM patients of all the eligible trials received either GLP-1 therapy or placebo, and the cardiovascular outcomes included death from cardiovascular causes, fatal or non-fatal myocardial infarction and fatal or non-fatal stroke. RESULTS: We included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients. The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.90; 95% CI: 0.83-0.97; P = 0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77-0.94; P = 0.001) compared with the placebo controls. But GLP-1 receptor agonists did not significantly alter the fatal or non-fatal myocardial infarction compared with the placebo (RR: 0.91; 95% CI: 0.82 - 1.01; P = 0.06). CONCLUSION: We concluded that GLP-1 receptor agonist therapy could reduce the risk of death from cardiovascular causes and fatal or non-fatal stroke compared with the placebo in the treatment of T2DM patients in trials with cardiovascular outcomes. CI - (c) 2022. The Author(s). FAU - Qin, Jing AU - Qin J AD - Department of Emergency, The Second hospital of Lanzhou University, Lanzhou, China. FAU - Song, Li AU - Song L AD - Department of Emergency, The Second hospital of Lanzhou University, Lanzhou, China. songli81@yeah.net. AD - Department of Internal Medicine 1 and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany. songli81@yeah.net. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20220512 PL - England TA - BMC Endocr Disord JT - BMC endocrine disorders JID - 101088676 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/chemically induced/complications/drug therapy MH - Glucagon-Like Peptide 1 MH - Humans MH - Hypoglycemic Agents/adverse effects MH - *Myocardial Infarction/epidemiology/etiology/prevention & control MH - Randomized Controlled Trials as Topic MH - *Stroke MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC9097124 OTO - NOTNLM OT - Cardiovascular events OT - Glucagon-like peptide-1 OT - Type 2 diabetes mellitus COIS- All authors declare that there are no conflict of interests or special relationships with industry in this meta-analysis. EDAT- 2022/05/14 06:00 MHDA- 2022/05/20 06:00 PMCR- 2022/05/12 CRDT- 2022/05/13 02:01 PHST- 2019/09/19 00:00 [received] PHST- 2020/02/27 00:00 [accepted] PHST- 2022/05/13 02:01 [entrez] PHST- 2022/05/14 06:00 [pubmed] PHST- 2022/05/20 06:00 [medline] PHST- 2022/05/12 00:00 [pmc-release] AID - 10.1186/s12902-022-01036-0 [pii] AID - 1036 [pii] AID - 10.1186/s12902-022-01036-0 [doi] PST - epublish SO - BMC Endocr Disord. 2022 May 12;22(1):125. doi: 10.1186/s12902-022-01036-0. PMID- 35546450 OWN - NLM STAT- MEDLINE DCOM- 20220803 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 9 DP - 2022 Sep TI - Effect of once-weekly semaglutide versus thrice-daily insulin aspart, both as add-on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open-label, multinational, phase 3b trial. PG - 1788-1799 LID - 10.1111/dom.14765 [doi] AB - AIM: To compare the efficacy and safety of once-weekly (OW) semaglutide versus thrice-daily (TID) insulin aspart (IAsp) in participants with inadequately controlled type 2 diabetes (T2D) treated with insulin glargine (IGlar) and metformin. MATERIALS AND METHODS: SUSTAIN 11 (NCT03689374) was a randomized (1:1), parallel, open-label, multinational, phase 3b trial. After a 12-week run-in to optimize once-daily IGlar U100, 1748 adults with T2D (HbA1c >7.5% to /=9% by the study end was low (5.3% vs 18.9% at baseline). Weight loss occurred in 73.5% and 78.1% of cases and, compared to baseline, it was >/=5% in 21.2- 25.4% and >/=10% in 6.8-18.2% after 6 and 12 months, respectively. Significant predictors of HbA1c reduction after 6 months of OW semaglutide treatment were baseline HbA1c (p<0.0001), bodyweight reduction (p<0.0001) and disease duration (p<0.001), while baseline HbA1c was the only predictor of HbA1c response after 12 months (p<0.0001). Reported adverse events were consistent with the known safety profile of semaglutide. CONCLUSIONS: Real-world evaluation of weekly subcutaneous treatment with semaglutide in a cohort of Italian diabetic patients. CI - (c) 2022. The Author(s). FAU - Marzullo, P AU - Marzullo P AUID- ORCID: 0000-0003-3215-5747 AD - Department of Translational Medicine, Universita del Piemonte Orientale, Via Solaroli 17, 28100, Novara, Italy. paolo.marzullo@med.uniupo.it. AD - Laboratory of Metabolic Diseases, IRCCS, Istituto Auxologico Italiano, Piancavallo, Verbania, Italy. paolo.marzullo@med.uniupo.it. FAU - Daffara, T AU - Daffara T AD - Endocrinology and Diabetes Unit, AOU Ospedale Maggiore Della Carita, Novara, Italy. FAU - Mele, C AU - Mele C AD - Department of Translational Medicine, Universita del Piemonte Orientale, Via Solaroli 17, 28100, Novara, Italy. FAU - Zavattaro, M AU - Zavattaro M AD - Endocrinology and Diabetes Unit, AOU Ospedale Maggiore Della Carita, Novara, Italy. FAU - Ferrero, A AU - Ferrero A AD - Endocrinology and Diabetes Unit, AOU Ospedale Maggiore Della Carita, Novara, Italy. FAU - Caputo, M AU - Caputo M AD - Endocrinology and Diabetes Unit, AOU Ospedale Maggiore Della Carita, Novara, Italy. AD - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy. FAU - Prodam, F AU - Prodam F AD - Endocrinology and Diabetes Unit, AOU Ospedale Maggiore Della Carita, Novara, Italy. AD - Department of Health Sciences, Universita del Piemonte Orientale, Novara, Italy. FAU - Aimaretti, G AU - Aimaretti G AD - Department of Translational Medicine, Universita del Piemonte Orientale, Via Solaroli 17, 28100, Novara, Italy. AD - Endocrinology and Diabetes Unit, AOU Ospedale Maggiore Della Carita, Novara, Italy. LA - eng PT - Journal Article DEP - 20220416 PL - Italy TA - J Endocrinol Invest JT - Journal of endocrinological investigation JID - 7806594 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Retrospective Studies MH - Semaglutide PMC - PMC9270295 OTO - NOTNLM OT - GLP-1 receptor agonists OT - Obesity OT - Once-weekly semaglutide OT - Type 2 diabetes mellitus COIS- The authors declare that they have no conflict of interest. EDAT- 2022/04/17 06:00 MHDA- 2022/07/14 06:00 PMCR- 2022/04/16 CRDT- 2022/04/16 12:02 PHST- 2021/12/22 00:00 [received] PHST- 2022/03/29 00:00 [accepted] PHST- 2022/04/17 06:00 [pubmed] PHST- 2022/07/14 06:00 [medline] PHST- 2022/04/16 12:02 [entrez] PHST- 2022/04/16 00:00 [pmc-release] AID - 10.1007/s40618-022-01799-2 [pii] AID - 1799 [pii] AID - 10.1007/s40618-022-01799-2 [doi] PST - ppublish SO - J Endocrinol Invest. 2022 Aug;45(8):1587-1598. doi: 10.1007/s40618-022-01799-2. Epub 2022 Apr 16. PMID- 35414304 OWN - NLM STAT- MEDLINE DCOM- 20230922 LR - 20260127 IS - 1531-1937 (Electronic) IS - 0897-1900 (Linking) VI - 36 IP - 5 DP - 2023 Oct TI - Comparison of the Effectiveness of Liraglutide vs Semaglutide in a Veteran Population. PG - 1095-1101 LID - 10.1177/08971900221087127 [doi] AB - Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly prescribed medications for patients with type 2 diabetes mellitus (T2DM) based on cardiovascular benefits. Objective: This study aimed to evaluate efficacy and tolerability of once daily liraglutide vs once weekly semaglutide on T2DM in a Veteran population. Methods: This was a retrospective, single-center, cohort study that included T2DM patients with a prescription for liraglutide or semaglutide between September 1st, 2019, and September 30th, 2020. Patients between groups were matched based on age and insulin use at baseline. The primary endpoint was the difference in hemoglobin A1c (A1c) between the most recent A1c in the study period and baseline A1c obtained prior to GLP-1 RA initiation. Results: There were 154 patients included in the study. While mean reduction in A1c was numerically higher in the liraglutide group (-1.1% vs. -.8%), this was not statistically significant (P = .22). The proportion of patients achieving A1c < 7%, < 8%, < 9%, or their patient-specific A1c goal did not differ between groups. Although baseline total daily doses of insulin were higher in the semaglutide group, these patients had numerically greater reductions in total daily dose of insulin and weight from baseline; however, no statistical difference was observed. Adverse drug reactions were more common in the semaglutide group (n = 14 vs. 9), leading to higher discontinuation rates as well (n = 11 vs. 8). Conclusion: The results of this study indicate no difference between liraglutide and semaglutide in terms of A1c-lowering potential, but it provides insights into key considerations for the Veteran population. FAU - Rana, Krishna B AU - Rana KB AUID- ORCID: 0000-0001-8077-1726 AD - Department of Pharmacy, Durham VA Health Care System, Durham, NC, USA. RINGGOLD: 20054 FAU - Britnell, Sara R AU - Britnell SR AD - Department of Pharmacy, Durham VA Health Care System, Durham, NC, USA. RINGGOLD: 20054 FAU - Gilbertson, Megan E AU - Gilbertson ME AD - Department of Pharmacy, Durham VA Health Care System, Durham, NC, USA. RINGGOLD: 20054 FAU - Ibrahim, Sarai L AU - Ibrahim SL AD - Department of Pharmacy, Durham VA Health Care System, Durham, NC, USA. RINGGOLD: 20054 LA - eng PT - Journal Article DEP - 20220412 PL - United States TA - J Pharm Pract JT - Journal of pharmacy practice JID - 8900945 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 0 (Glycated Hemoglobin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Liraglutide/adverse effects MH - Hypoglycemic Agents/adverse effects MH - Cohort Studies MH - Retrospective Studies MH - Glycated Hemoglobin MH - *Veterans MH - Glucagon-Like Peptide 1/therapeutic use MH - Insulin/therapeutic use MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonists OT - type 2 diabetes mellitus EDAT- 2022/04/14 06:00 MHDA- 2023/09/22 06:42 CRDT- 2022/04/13 05:27 PHST- 2023/09/22 06:42 [medline] PHST- 2022/04/14 06:00 [pubmed] PHST- 2022/04/13 05:27 [entrez] AID - 10.1177/08971900221087127 [doi] PST - ppublish SO - J Pharm Pract. 2023 Oct;36(5):1095-1101. doi: 10.1177/08971900221087127. Epub 2022 Apr 12. PMID- 35408810 OWN - NLM STAT- MEDLINE DCOM- 20220413 LR - 20250103 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 7 DP - 2022 Mar 22 TI - Glucagon-like Peptide-1 Receptor Agonists in the Management of Type 2 Diabetes Mellitus and Obesity: The Impact of Pharmacological Properties and Genetic Factors. LID - 10.3390/ijms23073451 [doi] LID - 3451 AB - Glucagon-like peptide-1 (GLP-1) receptor agonists are a new class of antihyperglycemic drugs that enhance appropriate pancreatic beta-cell secretion, pancreatic alpha-cell (glucagon) suppression, decrease liver glucose production, increase satiety through their action on the central nervous system, slow gastric emptying time, and increase insulin action on peripheral tissue. They are effective in the management of type 2 diabetes mellitus and have a favorable effect on weight loss. Their cardiovascular and renal safety has been extensively investigated and confirmed in many clinical trials. Recently, evidence has shown that in addition to the existing approaches for the treatment of obesity, semaglutide in higher doses promotes weight loss and can be used as a drug to treat obesity. However, some T2DM and obese patients do not achieve a desired therapeutic effect of GLP-1 receptor agonists. This could be due to the multifactorial etiologies of T2DM and obesity, but genetic variability in the GLP-1 receptor or signaling pathways also needs to be considered in non-responders to GLP-1 receptor agonists. This review focuses on the pharmacological, clinical, and genetic factors that may influence the response to GLP-1 receptor agonists in the treatment of type 2 diabetes mellitus and obesity. FAU - Klen, Jasna AU - Klen J AD - Department of Abdominal Surgery, Division of Surgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia. FAU - Dolzan, Vita AU - Dolzan V AUID- ORCID: 0000-0001-6707-6649 AD - Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia. LA - eng GR - P1-0170, P3-0298/Slovenian Research Agency/ PT - Journal Article PT - Review DEP - 20220322 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Glucagon-Like Peptide 1/metabolism MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Incretins/therapeutic use MH - Obesity/drug therapy/metabolism MH - Weight Loss MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC8998939 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cardiovascular safety OT - genetic polymorphisms OT - incretins OT - obesity OT - type 2 diabetes mellitus COIS- The authors declare no conflict of interest. EDAT- 2022/04/13 06:00 MHDA- 2022/04/14 06:00 PMCR- 2022/03/22 CRDT- 2022/04/12 01:11 PHST- 2022/02/28 00:00 [received] PHST- 2022/03/19 00:00 [revised] PHST- 2022/03/21 00:00 [accepted] PHST- 2022/04/12 01:11 [entrez] PHST- 2022/04/13 06:00 [pubmed] PHST- 2022/04/14 06:00 [medline] PHST- 2022/03/22 00:00 [pmc-release] AID - ijms23073451 [pii] AID - ijms-23-03451 [pii] AID - 10.3390/ijms23073451 [doi] PST - epublish SO - Int J Mol Sci. 2022 Mar 22;23(7):3451. doi: 10.3390/ijms23073451. PMID- 35395332 OWN - NLM STAT- MEDLINE DCOM- 20230619 LR - 20230619 IS - 1535-6280 (Electronic) IS - 0146-2806 (Linking) VI - 48 IP - 8 DP - 2023 Aug TI - Knowledge Domain and Emerging Trends of Glucagon-Like Peptide 1 Receptor Agonists in Cardiovascular Research: A Bibliometric Analysis. PG - 101194 LID - S0146-2806(22)00091-3 [pii] LID - 10.1016/j.cpcardiol.2022.101194 [doi] AB - Patients with type 2 diabetes (T2DM) are more likely to have cardiovascular disease (CVD). Glucose-lowering drugs with cardiovascular benefits represented by Glucagon-like peptide 1 receptor agonists (GLP1RAs) were discovered and gained more and more attention. Data from 1985 to the 2021 were downloaded in the Web of Science Core Collection (WoSCC) database. CiteSpaceV was used for bibliometric analysis to find research hotspots and frontiers. The 2088 papers were published by 74 countries (regions), 876 institutions, and 2203 authors. The annual publications increased over time from 2005 to 2020. DIABETES OBESITY METABOLISM published the most papers. The USA and China were the top 2 productive nations. The leading institution was the University of Copenhagen, and the most productive researcher was John B Buse. The most cited paper is "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes" (by Marso SP, 2016). The research hotspots include the effects of GLP1RA on cardiovascular outcomes, efficacy, complicated metabolic abnormalities, protective mechanisms, and other novel anti-diabetic drugs for cardiovascular protection. Research frontiers include cardiovascular studies on semaglutide, as well as the most prominent research approach in the field-placebo-controlled trial. Numerous countries, institutions, and authors have focused on GLP1RA in cardiovascular research and a great deal of literature has been published. Five research hotspots and two frontiers illustrate the current status and emerging trends of GLP1RA in cardiovascular research. The cardiovascular effects and clinical efficacy of GLP1RA are a current hot topic that is rapidly evolving and of high research value. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Shou, Xintian AU - Shou X AD - Department of Cardiovascular, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. FAU - Wang, Yumeng AU - Wang Y AD - Graduate School, Beijing University of Chinese Medicine, Beijing, China. FAU - Duan, Chenglin AU - Duan C AD - Graduate School, Beijing University of Chinese Medicine, Beijing, China. FAU - Yuan, Guozhen AU - Yuan G AD - Department of Cardiovascular, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. FAU - Wei, Namin AU - Wei N AD - School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China. FAU - Yang, Yihan AU - Yang Y AD - Department of Cardiovascular, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. FAU - Hu, Yuanhui AU - Hu Y AD - Department of Cardiovascular, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: huiyuhui55@sohu.com. LA - eng PT - Journal Article PT - Review DEP - 20220405 PL - Netherlands TA - Curr Probl Cardiol JT - Current problems in cardiology JID - 7701802 RN - IY9XDZ35W2 (Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - *Cardiovascular Diseases/drug therapy/epidemiology MH - Bibliometrics MH - Glucose MH - Glucagon-Like Peptide 1 EDAT- 2022/04/09 06:00 MHDA- 2023/06/19 13:08 CRDT- 2022/04/08 20:09 PHST- 2022/03/26 00:00 [received] PHST- 2022/04/02 00:00 [accepted] PHST- 2023/06/19 13:08 [medline] PHST- 2022/04/09 06:00 [pubmed] PHST- 2022/04/08 20:09 [entrez] AID - S0146-2806(22)00091-3 [pii] AID - 10.1016/j.cpcardiol.2022.101194 [doi] PST - ppublish SO - Curr Probl Cardiol. 2023 Aug;48(8):101194. doi: 10.1016/j.cpcardiol.2022.101194. Epub 2022 Apr 5. PMID- 35383100 OWN - NLM STAT- MEDLINE DCOM- 20220407 LR - 20260127 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 10 IP - 2 DP - 2022 Apr TI - Real-world use of once-weekly semaglutide in patients with type 2 diabetes: pooled analysis of data from four SURE studies by baseline characteristic subgroups. LID - 10.1136/bmjdrc-2021-002619 [doi] LID - e002619 AB - INTRODUCTION: This post hoc pooled analysis of four real-world studies (SURE Canada, Denmark/Sweden, Switzerland and UK) aimed to characterize the use of once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: The Semaglutide Real-world Evidence (SURE) studies had a duration of ~30 weeks. Changes in glycated hemoglobin (HbA(1c)) and body weight (BW) were analyzed for the overall population and the following baseline subgroups: GLP-1RA-naive/GLP-1RA switchers; body mass index <25/>/=25-<30/>/=30-<35/>/=35 kg/m(2); age <65/>/=65 years; HbA(1c) <7%/>/=7-8-9%; T2D duration <5/>/=5-<10/>/=10 years. Data for patients achieving treatment targets were analyzed in the overall population and the baseline HbA(1c) >/=7% subgroup. RESULTS: Of 1212 patients, 960 were GLP-1RA-naive and 252 had switched to semaglutide from another GLP-1RA. In the overall population, HbA(1c) was reduced from baseline to end of study (EOS) by -1.1% point and BW by -4.7 kg; changes were significant for all subgroups. There were significantly larger reductions of HbA(1c) and BW in GLP-1RA-naive versus GLP-1RA switchers and larger reductions in HbA(1c) for patients with higher versus lower baseline HbA(1c). At EOS, 52.6% of patients in the overall population achieved HbA(1c) <7%. No new safety concerns were identified in any of the completed SURE studies. CONCLUSIONS: In this pooled analysis, patients with T2D initiating OW semaglutide showed significant improvements from baseline to EOS in HbA(1c) and BW across various baseline subgroups, including patients previously treated with a GLP-1RA other than semaglutide, supporting OW semaglutide use in clinical practice. TRAIL REGISTRATION NUMBERS: NCT03457012; NCT03631186; NCT03648281; NCT03876015. CI - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Yale, Jean-Francois AU - Yale JF AUID- ORCID: 0000-0002-7833-9050 AD - Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada jean-francois.yale@mcgill.ca. FAU - Bodholdt, Ulrik AU - Bodholdt U AD - Kastruplaegerne, Kastrup, Denmark. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk AS, Soborg, Denmark. FAU - Catrina, Sergiu AU - Catrina S AUID- ORCID: 0000-0002-6914-3902 AD - Karolinska Institutet, Stockholm, Sweden. AD - Center for Diabetes, Academic Specialist Center, Stockholm, Sweden. FAU - Clark, Alice AU - Clark A AD - Novo Nordisk AS, Soborg, Denmark. FAU - Ekberg, Neda Rajamand AU - Ekberg NR AD - Karolinska Institutet, Stockholm, Sweden. FAU - Erhan, Umut AU - Erhan U AD - Novo Nordisk AS, Soborg, Denmark. FAU - Holmes, Patrick AU - Holmes P AD - St. George's Medical Practice, Darlington, UK. FAU - Knudsen, Soren Tang AU - Knudsen ST AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. FAU - Liutkus, Joanne AU - Liutkus J AD - Joanne F. Liutkus Medicine Professional Corporation, Cambridge, Ontario, Canada. FAU - Sathyapalan, Thozhukat AU - Sathyapalan T AD - Academic Diabetes, Endocrinology and Metabolism, University of Hull, Hull, UK. FAU - Schultes, Bernd AU - Schultes B AUID- ORCID: 0000-0002-5301-1163 AD - Metabolic Center St. Gallen, friendlyDocs, St. Gallen, Switzerland. FAU - Rudofsky, Gottfried AU - Rudofsky G AUID- ORCID: 0000-0002-2576-7190 AD - Clinic for Endocrinology and Metabolic Diseases, Cantonal Hospital Olten, Olten, Switzerland. LA - eng SI - ClinicalTrials.gov/NCT03457012 SI - ClinicalTrials.gov/NCT03631186 SI - ClinicalTrials.gov/NCT03648281 SI - ClinicalTrials.gov/NCT03876015 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide PMC - PMC8984040 OTO - NOTNLM OT - glucagon-like peptide 1 OT - glycated hemoglobin A OT - incretins COIS- Competing interests: J-FY reports receiving grants from Novo Nordisk during the conduct of the study; grants and personal fees from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Merck, Janssen, AstraZeneca, and Sanofi, all outside the submitted work. UB reports personal fees for participation in a scientific advisory board from Novo Nordisk, outside the submitted work. A-MC, AC and UE are employees of Novo Nordisk, and A-MC and UE own stock in the company. SC reports consultancy payment for Novo Nordisk (paid to his employer). NRE reports payment for lecturing and reimbursement for participation in scientific advisory boards from Novo Nordisk (paid to her employer), outside the submitted work. PH reports personal fees from AstraZeneca, Eli Lilly, and Novo Nordisk, outside the submitted work. STK reports grants and personal fees for lectures and/or consultancy from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk, and personal fees for lectures and/or consultancy from MSD, Mundipharma and Sanofi, outside of the submitted work. JL reports compensation for clinical trial research, personal fees from continuing medical education events, outside the submitted work. TS reports grants from Abbott and Novo Nordisk outside the submitted work. BS reports fees for advisory board meetings and lectures from Novo Nordisk. GR reports research funding from Novo Nordisk. EDAT- 2022/04/07 06:00 MHDA- 2022/04/08 06:00 PMCR- 2022/04/04 CRDT- 2022/04/06 05:23 PHST- 2021/10/04 00:00 [received] PHST- 2022/02/28 00:00 [accepted] PHST- 2022/04/06 05:23 [entrez] PHST- 2022/04/07 06:00 [pubmed] PHST- 2022/04/08 06:00 [medline] PHST- 2022/04/04 00:00 [pmc-release] AID - 10/2/e002619 [pii] AID - bmjdrc-2021-002619 [pii] AID - 10.1136/bmjdrc-2021-002619 [doi] PST - ppublish SO - BMJ Open Diabetes Res Care. 2022 Apr;10(2):e002619. doi: 10.1136/bmjdrc-2021-002619. PMID- 35373893 OWN - NLM STAT- MEDLINE DCOM- 20220608 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 7 DP - 2022 Jul TI - Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. PG - 1338-1350 LID - 10.1111/dom.14710 [doi] AB - AIMS: To evaluate the efficacy and safety of oral semaglutide versus comparators by patient characteristic subgroups in patients with type 2 diabetes. MATERIALS AND METHODS: Change from baseline in glycated haemoglobin (HbA1c) and body weight, and achievement of HbA1c <7.0% with oral semaglutide 7 mg, oral semaglutide 14 mg, flexibly dosed oral semaglutide (flex) and comparators were assessed across baseline subgroups (age, race, ethnicity, diabetes duration, body mass index and HbA1c) from the PIONEER programme. Treatment differences were analysed using a mixed model for repeated measurements for continuous variables and a logistic regression model for the binary endpoint. Pooled safety data were analysed descriptively. RESULTS: Changes from baseline in HbA1c and body weight, and the odds of achieving HbA1c <7.0%, were greater with oral semaglutide 14 mg/flex (n = 1934) and higher or similar with oral semaglutide 7 mg (n = 823) versus comparators (n = 2077) across most subgroups. Changes in HbA1c with oral semaglutide 14 mg/flex were greater for patients with higher baseline HbA1c (HbA1c >9.0%: -1.7% to -2.6%; HbA1c <8.0%: -0.7% to -1.2%). In some trials, Asian patients experienced greater HbA1c reductions with oral semaglutide 14 mg/flex (-1.5% to -1.8%) than other racial groups (-0.6% to -1.6%). The overall incidence of adverse events (AEs) with oral semaglutide was similar to that with comparators and was consistent across subgroups. More gastrointestinal AEs were observed with oral semaglutide, versus comparators, across subgroups. CONCLUSIONS: Oral semaglutide demonstrated consistently greater HbA1c and body weight reductions across a range of patient characteristics, with greater HbA1c reductions seen at higher baseline HbA1c levels. CI - (c) 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Bauer, Robert AU - Bauer R AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Christiansen, Erik AU - Christiansen E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Haluzik, Martin AU - Haluzik M AUID- ORCID: 0000-0002-0201-6888 AD - Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. FAU - Kallenbach, Klaus AU - Kallenbach K AUID- ORCID: 0000-0002-4451-2644 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Montanya, Eduard AU - Montanya E AUID- ORCID: 0000-0003-2518-9076 AD - Hospital Universitari Bellvitge-IDIBELL, CIBERDEM and University of Barcelona, Barcelona, Spain. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Dallas Diabetes Research Center at Medical City, Dallas, Texas, USA. FAU - Meier, Juris J AU - Meier JJ AUID- ORCID: 0000-0002-5835-8019 AD - Department of Internal Medicine, Gastroenterology and Diabetology, Augusta Clinic, Bochum, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220509 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Body Weight MH - *Diabetes Mellitus, Type 2/chemically induced/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Semaglutide PMC - PMC9321749 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - glycaemic control OT - incretin therapy OT - type 2 diabetes OT - weight control COIS- V.R.A. reports receiving consultancy fees from Applied Therapeutics, Fractyl, Novo Nordisk A/S, Pfizer and Sanofi, and research grant support (to institution) from Applied Therapeutics/Medpace; Eli Lilly; Premier/Fractyl, Novo Nordisk and Sanofi/Medpace. V.R.A.'s spouse is employed by Janssen. E.M. reports scientific advisory board, consulting, lecturing and/or research grants from AstraZeneca, Menarini, Merck Sharp & Dohme, Novo Nordisk and Sanofi. M.H. has served as an advisory board member for AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Novo Nordisk and Sanofi; a speaker for AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Mundipharma, Novartis, Novo Nordisk and Sanofi; and received research support from Eli Lilly and Sanofi. J.R. has served on advisory panels for Applied Therapeutics, Boehringer Ingelheim, Eli Lilly, Intarcia, Novo Nordisk, Oramed, Sanofi and Zealand, and has received research support from Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Genentech, GlaxoSmithKline, Intarcia, Janssen, Lexicon, Merck and company, Novo Nordisk, Oramed, Pfizer and Sanofi. J.J.M. has received grants from Merck and company, Novo Nordisk and Sanofi, and lecture/other fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck and company, Novo Nordisk, Sanofi and Servier. R.B., E.C. and K.K. are employees of Novo Nordisk. R.B. and E.C are shareholders in Novo Nordisk. EDAT- 2022/04/05 06:00 MHDA- 2022/06/09 06:00 PMCR- 2022/07/26 CRDT- 2022/04/04 08:44 PHST- 2022/03/29 00:00 [revised] PHST- 2021/12/16 00:00 [received] PHST- 2022/03/30 00:00 [accepted] PHST- 2022/04/05 06:00 [pubmed] PHST- 2022/06/09 06:00 [medline] PHST- 2022/04/04 08:44 [entrez] PHST- 2022/07/26 00:00 [pmc-release] AID - DOM14710 [pii] AID - 10.1111/dom.14710 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Jul;24(7):1338-1350. doi: 10.1111/dom.14710. Epub 2022 May 9. PMID- 35344191 OWN - NLM STAT- MEDLINE DCOM- 20220621 LR - 20260127 IS - 1179-1896 (Electronic) IS - 1175-5652 (Print) IS - 1175-5652 (Linking) VI - 20 IP - 4 DP - 2022 Jul TI - Cost-Effectiveness of Once-Weekly Semaglutide 1 mg versus Canagliflozin 300 mg in Patients with Type 2 Diabetes Mellitus in a Canadian Setting. PG - 543-555 LID - 10.1007/s40258-022-00726-z [doi] AB - OBJECTIVE: Our objective was to evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus once-daily canagliflozin 300 mg in patients with type 2 diabetes mellitus (T2DM) uncontrolled with metformin from the healthcare payer and societal perspectives in Canada. METHODS: Head-to-head data from the SUSTAIN 8 randomised trial (NCT03136484) were extrapolated over 40 years using economic simulation modelling. The cost-effectiveness of once-weekly semaglutide 1 mg versus canagliflozin 300 mg for treating T2DM was estimated using the Swedish Institute for Health Economics-Diabetes Cohort Model (IHE-DCM) and the Economic and Health Outcomes Model of T2DM (ECHO-T2DM). Unit costs and disutility weights capturing treatments and key macro- and microvascular complications were sourced from the literature to best match the Canadian setting. A probabilistic base-case simulation and sensitivity analyses were conducted. RESULTS: Once-weekly semaglutide 1 mg was associated with reductions in macro- and microvascular complications, yielding incremental cost-effectiveness ratios (ICERs) of (Canadian dollars [CAD]) CAD16,392 and 18,098 per incremental quality-adjusted life-year (QALY) gained versus canagliflozin 300 mg for IHE-DCM and ECHO-T2DM, respectively, from a healthcare payer perspective. Accounting for productivity loss as well, ICERs were CAD14,127 and 13,188 per QALY gained for IHE-DCM and ECHO-T2DM, respectively, from a societal perspective. Sensitivity analyses confirmed that the base-case results were robust to changes in input parameters and assumptions used. CONCLUSIONS: At a willingness-to-pay threshold of CAD50,000 per QALY gained, once-weekly semaglutide 1 mg was cost-effective over 40 years versus once-daily canagliflozin 300 mg for the treatment of T2DM in patients failing to maintain glycemic control with metformin alone. CI - (c) 2022. The Author(s). FAU - Stafford, Sara AU - Stafford S AUID- ORCID: 0000-0002-1551-6208 AD - Fraser Health Division of Endocrinology, 902-13737 96th Avenue, Surrey, BC, V3V 0C6, Canada. sara.stafford@fraserhealth.ca. FAU - Bech, Peter G AU - Bech PG AD - Novo Nordisk Canada Inc., 2476 Argentia Rd, Mississauga, ON, L5N 6M1, Canada. FAU - Fridhammar, Adam AU - Fridhammar A AD - The Swedish Institute for Health Economics, Box 2127, 220 02, Lund, Sweden. FAU - Miresashvili, Nino AU - Miresashvili N AD - Novo Nordisk A/S, Vandtarnsvej 108, 2860, Soborg, Denmark. FAU - Nilsson, Andreas AU - Nilsson A AD - The Swedish Institute for Health Economics, Box 2127, 220 02, Lund, Sweden. FAU - Willis, Michael AU - Willis M AD - The Swedish Institute for Health Economics, Box 2127, 220 02, Lund, Sweden. FAU - Liu, Aiden AU - Liu A AD - Novo Nordisk Canada Inc., 2476 Argentia Rd, Mississauga, ON, L5N 6M1, Canada. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20220328 PL - New Zealand TA - Appl Health Econ Health Policy JT - Applied health economics and health policy JID - 101150314 RN - 0SAC974Z85 (Canagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Appl Health Econ Health Policy. 2022 Jul;20(4):623. doi: 10.1007/s40258-022-00734-z. PMID: 35441978 MH - Canada MH - Canagliflozin/therapeutic use MH - Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Metformin MH - Quality-Adjusted Life Years MH - Semaglutide PMC - PMC9206917 COIS- SS has received continuing medical education honoraria from Novo Nordisk, Boehringer Ingelheim, Lilly, Sanofi, Janssen, AstraZeneca, Medtronic, Tandem, Abbott, Dexcom, CCRN, CPD Network, and MD Briefcase; participated in advisory boards for Novo Nordisk, Boehringer Ingelheim, Lilly, Sanofi, Janssen, AstraZeneca, and Abbott; and received research support from Sanofi, AstraZeneca, and Novo Nordisk. AL is an employee of Novo Nordisk Canada Inc. PB is an employee and shareholder of Novo Nordisk Canada Inc. AF and AN are employees of, and MW is an employee, minority owner, and unpaid director of the Swedish Institute for Health Economics, which provides consulting services for governmental bodies, academic institutions, and commercial life science enterprises, including Novo Nordisk A/S. The Swedish Institute for Health Economics owns the ECHO-T2DM and IHE-DCM, used in this analysis. The Swedish Institute for Health Economics is owned principally by the non-profit Bengt Jonsson Foundation for Health Economic Research. NM is an employee of Novo Nordisk A/S. EDAT- 2022/03/29 06:00 MHDA- 2022/06/22 06:00 PMCR- 2022/03/28 CRDT- 2022/03/28 12:17 PHST- 2022/02/27 00:00 [accepted] PHST- 2022/03/29 06:00 [pubmed] PHST- 2022/06/22 06:00 [medline] PHST- 2022/03/28 12:17 [entrez] PHST- 2022/03/28 00:00 [pmc-release] AID - 10.1007/s40258-022-00726-z [pii] AID - 726 [pii] AID - 10.1007/s40258-022-00726-z [doi] PST - ppublish SO - Appl Health Econ Health Policy. 2022 Jul;20(4):543-555. doi: 10.1007/s40258-022-00726-z. Epub 2022 Mar 28. PMID- 35333446 OWN - NLM STAT- MEDLINE DCOM- 20220414 LR - 20220414 IS - 1930-739X (Electronic) IS - 1930-7381 (Linking) VI - 30 IP - 4 DP - 2022 Apr TI - Benefits of weight loss of 10% or more in patients with overweight or obesity: A review. PG - 802-840 LID - 10.1002/oby.23371 [doi] AB - OBJECTIVE: Modest weight loss (5%-10%) is clinically meaningful in patients with overweight or obesity. However, greater weight loss may be required to achieve improvements in or remission of certain weight-related complications. Therefore, this study reviewed the effect of large weight loss (>/=10%). Most studies reporting large weight loss and relevant outcomes used bariatric surgery or lifestyle modifications. RESULTS: Benefits of large weight loss were observed in patients with various overweight- or obesity-related complications, including improvements in comorbidities such as type 2 diabetes and hypertension. Improvements in glucose metabolism and cardiovascular risk factors were observed in patients who achieved large weight loss through lifestyle interventions or pharmacotherapy (phentermine/topiramate 15/92 mg once daily or subcutaneous semaglutide 2.4 mg once weekly). Other benefits associated with large weight loss included reduced cancer risk and improvements in knee osteoarthritis, sleep apnea, fertility-related end points, and health-related quality of life. While costly, bariatric surgery is currently the most cost-effective intervention, although most weight-management programs are deemed cost-effective. CONCLUSIONS: Overall, large weight loss has a major beneficial impact on overweight- and obesity-related complications. Large weight loss should be the main treatment target when modest weight loss has had insufficient effects on obesity-related complications and for patients with severe obesity. CI - (c) 2022 The Obesity Society. FAU - Tahrani, Abd A AU - Tahrani AA AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Morton, John AU - Morton J AUID- ORCID: 0000-0002-9542-1283 AD - Department of Surgery, Yale School of Medicine, New Haven, Connecticut, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 0 (Anti-Obesity Agents) RN - 0H73WJJ391 (Topiramate) RN - C045TQL4WP (Phentermine) SB - IM MH - *Anti-Obesity Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy/therapy MH - Humans MH - Obesity/drug therapy/therapy MH - Overweight/drug therapy/therapy MH - Phentermine/therapeutic use MH - Quality of Life MH - Topiramate/therapeutic use MH - Weight Loss EDAT- 2022/03/26 06:00 MHDA- 2022/04/15 06:00 CRDT- 2022/03/25 12:11 PHST- 2021/11/23 00:00 [revised] PHST- 2021/01/22 00:00 [received] PHST- 2021/12/10 00:00 [accepted] PHST- 2022/03/25 12:11 [entrez] PHST- 2022/03/26 06:00 [pubmed] PHST- 2022/04/15 06:00 [medline] AID - 10.1002/oby.23371 [doi] PST - ppublish SO - Obesity (Silver Spring). 2022 Apr;30(4):802-840. doi: 10.1002/oby.23371. PMID- 35332654 OWN - NLM STAT- MEDLINE DCOM- 20220608 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 7 DP - 2022 Jul TI - Cardiovascular efficacy of liraglutide and semaglutide in individuals with diabetes and peripheral artery disease. PG - 1288-1299 LID - 10.1111/dom.14700 [doi] AB - AIM: To evaluate the cardiovascular (CV) efficacy of liraglutide and semaglutide in patients with type 2 diabetes (T2D) and peripheral artery disease (PAD). MATERIALS AND METHODS: LEADER and SUSTAIN 6 trials investigated subcutaneous liraglutide (/=18 years old) without type 1/type 2 diabetes up to September 30, 2021, using Pubmed and Embase. Of 36 clinical trials assessed for eligibility, 12 trials were included, with a combined total of 11,459 participants. Compared with control groups, a more significant weight loss was seen in GLP-1 RA groups with an overall mean difference of -7.1 kg (95% CI -9.2 to -5.0) (I(2) = 99%). The overall analysis results showed that GLP-1 RA improved glycemic control without increasing the risk of hypoglycemic events. Better control of blood pressure and plasma levels of LDL, HDL, and triglycerides was seen with GLP-1 RA treatment. Subgroup analysis showed greater treatment effect of semaglutide than liraglutide. Vomiting, nausea, dyspepsia, diarrhea, constipation, and abdominal pain were GLP-1 RA-associated common adverse effects. CI - (c) 2022 World Obesity Federation. FAU - Iqbal, Junaid AU - Iqbal J AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Wu, Hui-Xuan AU - Wu HX AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Hu, Nan AU - Hu N AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Zhou, Ying-Hui AU - Zhou YH AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Li, Long AU - Li L AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Xiao, Fen AU - Xiao F AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Wang, Ting AU - Wang T AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Jiang, Hong-Li AU - Jiang HL AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Xu, Shi-Na AU - Xu SN AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Huang, Bi-Ling AU - Huang BL AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. FAU - Zhou, Hou-De AU - Zhou HD AUID- ORCID: 0000-0001-9131-4141 AD - Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20220222 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adolescent MH - Adult MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide 1 MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Obesity/chemically induced/complications/drug therapy MH - Weight Loss MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - diabetes mellitus OT - glucagon-like peptide OT - obesity OT - weight loss EDAT- 2022/02/24 06:00 MHDA- 2022/05/11 06:00 CRDT- 2022/02/23 05:37 PHST- 2022/01/05 00:00 [revised] PHST- 2021/11/15 00:00 [received] PHST- 2022/01/30 00:00 [accepted] PHST- 2022/02/24 06:00 [pubmed] PHST- 2022/05/11 06:00 [medline] PHST- 2022/02/23 05:37 [entrez] AID - 10.1111/obr.13435 [doi] PST - ppublish SO - Obes Rev. 2022 Jun;23(6):e13435. doi: 10.1111/obr.13435. Epub 2022 Feb 22. PMID- 35184645 OWN - NLM STAT- MEDLINE DCOM- 20220408 LR - 20250103 IS - 2165-5987 (Electronic) IS - 2165-5979 (Print) IS - 2165-5979 (Linking) VI - 13 IP - 3 DP - 2022 Mar TI - Novel glucagon-like peptide-1 analogue exhibits potency-driven G-protein biased agonism with promising effects on diabetes and diabetic dry eye syndrome. PG - 5467-5479 LID - 10.1080/21655979.2022.2031418 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are considered as effective treatments for type 2 diabetes. Here, we describe the in vitro characteristics and in vivo anti-diabetic efficacies of a novel GLP-1RA, termed SM102. The in vitro functions of SM102, including GLP-1R kinetic binding parameter, cAMP activation, endocytosis and recycling, were all evaluated using the INS-1 832/13 cells expressing human GLP-1R. Chronic efficacies study was performed to evaluate the effects of SM102 on the glycemic benefits, body weight loss and other diabetic complications in db/db mice. As a result, SM102 exhibited enhanced binding affinity and potency-driven bias in favor of cAMP over GLP-1R endocytosis and beta-Arrestin 2 recruitment, as well as comparable insulin secretory response compared with Semaglutide. In addition, chronic treatment of SM102 led to more promising therapeutical effects on hyperglycemia, weight control and insulin resistance as well as dry eye syndrome (DES) than Semaglutide. Furthermore, SM102 could ameliorate diabetic DES via improving antioxidant properties, inflammatory factors and inhibiting MAPKs pathway in diabetic mice. In conclusion, SM102 is a G protein-biased agonist serving as a promising new GLP-1RA for treating diabetes and diabetic complications. FAU - Hao, Yongna AU - Hao Y AD - Corneal Department, Handan City Eye Hospital, Handan, PR China. FAU - Wei, Min AU - Wei M AD - Corneal Department, Handan City Eye Hospital, Handan, PR China. FAU - Zhang, Ning AU - Zhang N AD - Corneal Department, Handan City Eye Hospital, Handan, PR China. FAU - Zhang, Xinying AU - Zhang X AUID- ORCID: 0000-0001-7092-9446 AD - Infection Control Office, Affiliated Hospital of Hebei University, Baoding, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Bioengineered JT - Bioengineered JID - 101581063 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - EC 3.6.1.- (GTP-Binding Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - *Diabetes Mellitus, Experimental MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Dry Eye Syndromes/drug therapy MH - GTP-Binding Proteins/metabolism MH - *Glucagon-Like Peptide 1/analogs & derivatives MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Mice MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC8975272 OTO - NOTNLM OT - G-protein OT - GLP-1 OT - dry eye syndrome OT - long-lasting diabetes OT - obesity COIS- No potential conflict of interest was reported by the author(s). EDAT- 2022/02/22 06:00 MHDA- 2022/04/09 06:00 PMCR- 2022/02/19 CRDT- 2022/02/21 05:35 PHST- 2022/02/21 05:35 [entrez] PHST- 2022/02/22 06:00 [pubmed] PHST- 2022/04/09 06:00 [medline] PHST- 2022/02/19 00:00 [pmc-release] AID - 2031418 [pii] AID - 10.1080/21655979.2022.2031418 [doi] PST - ppublish SO - Bioengineered. 2022 Mar;13(3):5467-5479. doi: 10.1080/21655979.2022.2031418. PMID- 35175229 OWN - NLM STAT- MEDLINE DCOM- 20220624 LR - 20260127 IS - 1531-7080 (Electronic) IS - 0268-4705 (Linking) VI - 37 IP - 4 DP - 2022 Jul 1 TI - Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. PG - 350-355 LID - 10.1097/HCO.0000000000000955 [doi] AB - PURPOSE OF REVIEW: Cardiovascular disease is the most common cause of morbidity and mortality worldwide, and the risk is heightened in the presence of obesity. We review semaglutide, a drug recently approved for chronic weight management in adults with obesity or who are overweight. RECENT FINDINGS: On 4 June 2021, the US Food and Drug Administration approved semaglutide injection at 2.4 mg once weekly for chronic weight management in adults with obesity or overweight with at least one weight-related condition such as high blood pressure, type 2 diabetes mellitus, or high cholesterol. This subcutaneous injection is the first approved drug for chronic weight management in adults with general obesity or overweight since 2014. The drug is indicated for weight management in patients with a BMI of 27 kg/m2 or greater who have at least one weight-related ailment or in patients with a BMI of 30 kg/m2 or greater. SUMMARY: Semaglutide offers adults with obesity or overweight a new treatment in conjunction with a weight management program consisting of reduced calorie diet and increased physical activity. CI - Copyright (c) 2022 Wolters Kluwer Health, Inc. All rights reserved. FAU - Mares, Adriana C AU - Mares AC AD - Department of Internal Medicine, Texas Tech University Health Sciences Center at El Paso, El Paso, Texas. FAU - Chatterjee, Saurav AU - Chatterjee S AD - Division of Cardiovascular Medicine, North Shore-Long Island Jewish Medical Centers, Northwell Health. AD - Zucker School of Medicine, New York, New York, USA. FAU - Mukherjee, Debabrata AU - Mukherjee D AD - Department of Internal Medicine, Texas Tech University Health Sciences Center at El Paso, El Paso, Texas. LA - eng SI - ClinicalTrials.gov/NCT03574597 PT - Journal Article PT - Review DEP - 20220216 PL - United States TA - Curr Opin Cardiol JT - Current opinion in cardiology JID - 8608087 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - *Cardiovascular Diseases/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Obesity/complications MH - Overweight/complications MH - Risk Reduction Behavior MH - Weight Loss MH - Semaglutide EDAT- 2022/02/18 06:00 MHDA- 2022/06/25 06:00 CRDT- 2022/02/17 12:24 PHST- 2022/02/18 06:00 [pubmed] PHST- 2022/06/25 06:00 [medline] PHST- 2022/02/17 12:24 [entrez] AID - 00001573-202207000-00008 [pii] AID - 10.1097/HCO.0000000000000955 [doi] PST - ppublish SO - Curr Opin Cardiol. 2022 Jul 1;37(4):350-355. doi: 10.1097/HCO.0000000000000955. Epub 2022 Feb 16. PMID- 35174649 OWN - NLM STAT- MEDLINE DCOM- 20220706 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 13 IP - 7 DP - 2022 Jul TI - Efficacy and safety of once-weekly semaglutide in Japanese individuals with type 2 diabetes by baseline age and body mass index. PG - 1161-1174 LID - 10.1111/jdi.13773 [doi] AB - AIMS/INTRODUCTION: Many East Asians with type 2 diabetes are elderly and have a low body mass index (BMI), especially in 'super-aged' populations, such as Japan. This post-hoc analysis assessed once-weekly semaglutide efficacy and safety in Japanese individuals with type 2 diabetes across baseline age and BMI subgroups. MATERIALS AND METHODS: Data were derived from the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) Japan monotherapy and SUSTAIN Japan oral antidiabetes drug (OAD) combination trials comparing once-weekly semaglutide with sitagliptin or OADs, respectively. Participants were grouped by baseline age (<65 and >/=65 years) and/or BMI (<25 and >/=25 kg/m(2) ). Reductions from baseline in glycosylated hemoglobin and bodyweight (efficacy), and adverse events (safety) were assessed. RESULTS: In this analysis, participants from the SUSTAIN Japan monotherapy trial (n = 308; n per subgroup; range, 8-73) and SUSTAIN Japan OAD combination trial (n = 601; n per subgroup; range, 20-168) were included. Reductions in glycosylated hemoglobin and bodyweight were numerically greater with semaglutide versus comparators across all age and BMI subgroups. Reductions from baseline in glycosylated hemoglobin ranged from -1.7 to -2.1 with semaglutide 0.5 mg, -1.8 to -2.4 with semaglutide 1.0 mg and -0.6 to -1.0 with comparators. Corresponding ranges for bodyweight (kg) were -1.0 to -2.5, -2.4 to -4.3 and 1.0 to -1.0 kg, respectively. The safety profile of semaglutide was broadly similar across BMI and age subgroups. CONCLUSIONS: In this post-hoc analysis with modest subgroup numbers, once-weekly semaglutide appeared consistently more efficacious versus comparators across age and BMI subgroups in Japanese patients, with a similar safety profile. CI - (c) 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Metabolism/Department of Rheumatology and Clinical Nutrition, Gifu University Graduate School of Medicine, Gifu, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan. FAU - Yamada, Yuichiro AU - Yamada Y AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan. AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. FAU - Kaku, Kohei AU - Kaku K AUID- ORCID: 0000-0003-1574-0565 AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School Hospital, Kurashiki, Japan. FAU - Nishida, Tomoyuki AU - Nishida T AD - Novo Nordisk Pharma Ltd, Tokyo, Japan. FAU - Sato, Toshihiro AU - Sato T AD - Novo Nordisk Pharma Ltd, Tokyo, Japan. FAU - Seino, Yutaka AU - Seino Y AUID- ORCID: 0000-0002-1099-7989 AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan. AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. LA - eng GR - Novo Nordisk/ PT - Clinical Trial PT - Journal Article DEP - 20220309 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Body Mass Index MH - Body Weight MH - *Diabetes Mellitus, Type 2/chemically induced/drug therapy MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Japan MH - Semaglutide PMC - PMC9248424 OTO - NOTNLM OT - Body mass index OT - Diabetes mellitus OT - Glucagon-like peptide-1 OT - type 2 EDAT- 2022/02/18 06:00 MHDA- 2022/07/07 06:00 PMCR- 2022/07/01 CRDT- 2022/02/17 05:42 PHST- 2022/02/01 00:00 [revised] PHST- 2021/11/19 00:00 [received] PHST- 2022/02/14 00:00 [accepted] PHST- 2022/02/18 06:00 [pubmed] PHST- 2022/07/07 06:00 [medline] PHST- 2022/02/17 05:42 [entrez] PHST- 2022/07/01 00:00 [pmc-release] AID - JDI13773 [pii] AID - 10.1111/jdi.13773 [doi] PST - ppublish SO - J Diabetes Investig. 2022 Jul;13(7):1161-1174. doi: 10.1111/jdi.13773. Epub 2022 Mar 9. PMID- 35172067 OWN - NLM STAT- MEDLINE DCOM- 20220223 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 386 IP - 7 DP - 2022 Feb 17 TI - Tirzepatide versus Semaglutide Once Weekly in Type 2 Diabetes. Reply. PG - e17 LID - 10.1056/NEJMc2114590#sa3 [pii] LID - 10.1056/NEJMc2114590 [doi] FAU - Frias, Juan P AU - Frias JP AD - National Research Institute, Los Angeles, CA juan.frias@nritrials.com. FAU - Fernandez Lando, Laura AU - Fernandez Lando L AD - Eli Lilly, Indianapolis, IN. FAU - Brown, Katelyn AU - Brown K AD - Eli Lilly, Indianapolis, IN. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2022 Feb 17;386(7):e17. doi: 10.1056/NEJMc2114590. PMID: 35172065 CON - N Engl J Med. 2022 Feb 17;386(7):e17. doi: 10.1056/NEJMc2114590. PMID: 35172066 MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptides/adverse effects MH - Humans MH - Tirzepatide MH - Semaglutide EDAT- 2022/02/17 06:00 MHDA- 2022/02/24 06:00 CRDT- 2022/02/16 17:13 PHST- 2022/02/16 17:13 [entrez] PHST- 2022/02/17 06:00 [pubmed] PHST- 2022/02/24 06:00 [medline] AID - 10.1056/NEJMc2114590#sa3 [pii] AID - 10.1056/NEJMc2114590 [doi] PST - ppublish SO - N Engl J Med. 2022 Feb 17;386(7):e17. doi: 10.1056/NEJMc2114590. PMID- 35172066 OWN - NLM STAT- MEDLINE DCOM- 20220223 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Print) IS - 0028-4793 (Linking) VI - 386 IP - 7 DP - 2022 Feb 17 TI - Tirzepatide versus Semaglutide Once Weekly in Type 2 Diabetes. PG - e17 LID - 10.1056/NEJMc2114590#sa2 [pii] LID - 10.1056/NEJMc2114590 [doi] FAU - Santulli, Gaetano AU - Santulli G AD - Albert Einstein College of Medicine, New York, NY gsantulli001@gmail.com. LA - eng GR - R01 DK123259/DK/NIDDK NIH HHS/United States GR - R01 HL146691/HL/NHLBI NIH HHS/United States PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. PMID: 34170647 CIN - N Engl J Med. 2022 Feb 17;386(7):e17. doi: 10.1056/NEJMc2114590. PMID: 35172067 MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptides/adverse effects MH - Humans MH - Tirzepatide MH - Semaglutide PMC - PMC8941980 MID - NIHMS1786782 COIS- No potential conflict of interest relevant to this letter was reported. EDAT- 2022/02/17 06:00 MHDA- 2022/02/24 06:00 PMCR- 2022/03/23 CRDT- 2022/02/16 17:13 PHST- 2022/02/16 17:13 [entrez] PHST- 2022/02/17 06:00 [pubmed] PHST- 2022/02/24 06:00 [medline] PHST- 2022/03/23 00:00 [pmc-release] AID - 10.1056/NEJMc2114590#sa2 [pii] AID - 10.1056/NEJMc2114590 [doi] PST - ppublish SO - N Engl J Med. 2022 Feb 17;386(7):e17. doi: 10.1056/NEJMc2114590. PMID- 35172065 OWN - NLM STAT- MEDLINE DCOM- 20220223 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 386 IP - 7 DP - 2022 Feb 17 TI - Tirzepatide versus Semaglutide Once Weekly in Type 2 Diabetes. PG - e17 LID - 10.1056/NEJMc2114590#sa1 [pii] LID - 10.1056/NEJMc2114590 [doi] FAU - Patoulias, Dimitrios AU - Patoulias D AD - Aristotle University of Thessaloniki, Thessaloniki, Greece dipatoulias@gmail.com. FAU - Papadopoulos, Christodoulos AU - Papadopoulos C AD - Aristotle University of Thessaloniki, Thessaloniki, Greece dipatoulias@gmail.com. FAU - Doumas, Michael AU - Doumas M AD - Aristotle University of Thessaloniki, Thessaloniki, Greece dipatoulias@gmail.com. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. PMID: 34170647 CIN - N Engl J Med. 2022 Feb 17;386(7):e17. doi: 10.1056/NEJMc2114590. PMID: 35172067 MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptides/adverse effects MH - Humans MH - Tirzepatide MH - Semaglutide EDAT- 2022/02/17 06:00 MHDA- 2022/02/24 06:00 CRDT- 2022/02/16 17:13 PHST- 2022/02/16 17:13 [entrez] PHST- 2022/02/17 06:00 [pubmed] PHST- 2022/02/24 06:00 [medline] AID - 10.1056/NEJMc2114590#sa1 [pii] AID - 10.1056/NEJMc2114590 [doi] PST - ppublish SO - N Engl J Med. 2022 Feb 17;386(7):e17. doi: 10.1056/NEJMc2114590. PMID- 35131037 OWN - NLM STAT- MEDLINE DCOM- 20220421 LR - 20260202 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 10 IP - 3 DP - 2022 Mar TI - Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an east Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial. PG - 193-206 LID - S2213-8587(22)00008-0 [pii] LID - 10.1016/S2213-8587(22)00008-0 [doi] AB - BACKGROUND: Semaglutide 2.4 mg once weekly has been investigated for weight management in global populations. Differences exist between Asian and non-Asian populations in terms of body composition and definitions of obesity. In the Semaglutide Treatment Effect in People with obesity (STEP) 6 trial, we assessed the effect of semaglutide versus placebo for weight management in adults from east Asia with obesity, with or without type 2 diabetes. METHODS: This randomised, double-blind, double-dummy, placebo-controlled, phase 3a superiority trial was done at 28 outpatient clinics in Japan and South Korea. Eligible participants were adults (aged >/=18 years in South Korea; >/=20 years in Japan) with a BMI of at least 27.0 kg/m(2) with two or more weight-related comorbidities or a BMI of 35.0 kg/m(2) or more with one or more weight-related comorbidity (one comorbidity had to be either hypertension, dyslipidaemia, or, in Japan only, type 2 diabetes) who had at least one self-reported unsuccessful dietary attempt to lose bodyweight. Participants were randomly assigned (4:1:2:1) to once-weekly subcutaneous semaglutide 2.4 mg or matching placebo, or semaglutide 1.7 mg or matching placebo, plus lifestyle recommendations for 68 weeks. Data for the placebo groups were pooled in statistical analyses. The primary endpoints were percentage change in bodyweight from baseline at week 68 and the proportion of participants who had achieved a reduction of at least 5% of baseline bodyweight at week 68. Change in abdominal visceral fat area was assessed as a supportive secondary endpoint using computed tomography scanning in a subset of participants. Efficacy outcomes were assessed in the full analysis set, which included all randomly assigned participants according to the intention-to-treat principle. Safety was assessed in all participants who received at least one dose of the study drug. This trial was registered with ClinicalTrials.gov, NCT03811574. FINDINGS: Between Jan 21, 2019 and June 4, 2019, 437 participants were screened, of whom 401 were randomly assigned to semaglutide 2.4 mg (n=199), semaglutide 1.7 mg (n=101), or placebo (n=101) and included in the intention-to-treat analysis. Estimated mean change in bodyweight from baseline to week 68 was -13.2% (SEM 0.5) in the semaglutide 2.4 mg group and -9.6% (0.8) in the semaglutide 1.7 mg group versus -2.1% (0.8) in the placebo group (estimated treatment difference [ETD] -11.1 percentage points [95% CI -12.9 to -9.2] for semaglutide 2.4 mg vs placebo; -7.5 percentage points [95% CI -9.6 to -5.4] for semaglutide 1.7 mg vs placebo; both p<0.0001). At week 68, a larger proportion of participants had achieved a 5% or higher reduction in baseline bodyweight in the semaglutide 2.4 mg group (160 [83%] of 193 participants) and semaglutide 1.7 mg group (71 [72%] of 98 participants) than in the placebo group (21 [21%] of 100 participants); odds ratio [OR] 21.7 [95% CI 11.3 to 41.9] for semaglutide 2.4 mg vs placebo; OR 11.1 [95% CI 5.5 to 22.2] for semaglutide 1.7 mg vs placebo; both p<0.0001). Abdominal visceral fat area was reduced by 40.0% (SEM 2.6) among participants in the semaglutide 2.4 mg group and 22.2% (3.7) among participants in the semaglutide 1.7 mg group versus 6.9% (3.8) in the placebo group (ETD -33.2% [95% CI -42.1 to -24.2] for semaglutide 2.4 mg vs placebo; -15.3% [95% CI -25.6 to -4.9] for semaglutide 1.7 mg vs placebo). 171 (86%) of 199 participants in the semaglutide 2.4 mg group, 82 (82%) of 100 participants in the semaglutide 1.7 mg group, and 80 (79%) of 101 participants in the placebo group reported adverse events. Gastrointestinal disorders, which were mostly mild to moderate, were reported in 118 (59%) of 199 participants in the semaglutide 2.4 mg group, 64 (64%) of 100 participants in the semaglutide 1.7 mg group, and 30 (30%) of 101 participants in the placebo group. Adverse events leading to trial product discontinuation occurred in five (3%) of 199 participants in the semaglutide 2.4 mg group, three (3%) of 100 participants in the semaglutide 1.7 mg group, and one (1%) of 101 participants in the placebo group. INTERPRETATION: Adults from east Asia with obesity, with or without type 2 diabetes, given semaglutide 2.4 mg once a week had superior and clinically meaningful reductions in bodyweight, and greater reductions in abdominal visceral fat area compared with placebo, representing a promising treatment option for weight management in this population. FUNDING: Novo Nordisk. TRANSLATIONS: For the Korean and Japanese translations of the abstract see Supplementary Materials section. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Toranomon Hospital, Tokyo, Japan. Electronic address: t-kadowaki@toranomon.kkr.or.jp. FAU - Isendahl, Joakim AU - Isendahl J AD - Novo Nordisk, Soborg, Denmark. FAU - Khalid, Usman AU - Khalid U AD - Novo Nordisk, Soborg, Denmark. FAU - Lee, Sang Yeoup AU - Lee SY AD - Family Medicine Clinic and Biomedical Research Institute, Pusan National University Yangsan Hospital, Yangsan, South Korea; Department of Medical Education, Pusan National University School of Medicine, Yangsan, South Korea. FAU - Nishida, Tomoyuki AU - Nishida T AD - Novo Nordisk Pharma, Tokyo, Japan. FAU - Ogawa, Wataru AU - Ogawa W AD - Department of Internal Medicine, Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Tobe, Kazuyuki AU - Tobe K AD - First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, Japan. FAU - Yamauchi, Toshimasa AU - Yamauchi T AD - Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. FAU - Lim, Soo AU - Lim S AD - Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea. Electronic address: limsoo@snu.ac.kr. CN - STEP 6 investigators LA - eng SI - ClinicalTrials.gov/NCT03811574 PT - Clinical Trial, Phase III PT - Equivalence Trial PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20220204 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet Diabetes Endocrinol. 2022 Mar;10(3):153-154. doi: 10.1016/S2213-8587(22)00038-9. PMID: 35131036 MH - Adolescent MH - Adult MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Double-Blind Method MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Obesity/complications/drug therapy/epidemiology MH - Overweight MH - Treatment Outcome MH - Semaglutide COIS- Declaration of interests TK is President of Toranomon Hospital; and reports lecture fees from Abbott Japan, Astellas Pharma, AstraZeneca, Teijin Healthcare, Eli Lilly Japan, Mitsubishi Tanabe Pharma Corporation, MSD, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Ono Pharmaceutical, Sanofi, Sumitomo Dainippon Pharma, Terumo Corporation, and Takeda Pharmaceutical Company; grants from AstraZeneca, Takeda Pharmaceutical Company, and Daiichi Sankyo; donations for research from Astellas Pharma, Daiichi Sankyo, Kissei Pharmaceutical, Mitsubishi Tanabe Pharma, Novo Nordisk Pharma, Ono Pharmaceutical, Sanofi, Taisho Pharma, Sumitomo Dainippon Pharma, and Takeda Pharmaceutical Company; and donations for research laboratories from Asahi Mutual Life Insurance Company, Kowa Company, Mitsubishi Tanabe Pharma, MSD, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Ono Pharmaceutical, and Takeda Pharmaceutical Company. JI and UK are employees of Novo Nordisk. TN is an employee and shareholder of Novo Nordisk Pharma. WO has received lecture fees from Dainippon-Sumitomo Pharma, Novartis, Nippon Boehringer Ingelheim, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, and Abbott Japan; research funding from Noster, Nippon Boehringer Ingelheim, Boehringer Ingelheim Pharma GmbH, Nippon Eli-Lilly, Novo Nordisk Pharma, Abbott Japan, Abbott Diabetes Care UK, Dainippon-Sumitomo Pharma; and subsidies or donations from Kowa Pharmaceutical, Novo Nordisk Pharma, Astellas, Dainippon-Sumitomo Pharma, Ono Pharmaceutical, Takeda Pharmaceutical, Abbott Japan, Novartis, Daiichi Sankyo, Nippon Eli-Lilly, Mitsubishi Tanabe Pharma, and Nippon Boehringer Ingelheim. KT has received lecture fees from MSD, Novo Nordisk Pharma, Kowa Pharmaceutical; grants from Daiichi Sankyo, Ono Pharmaceutical, Takeda Pharmaceutical, Nippon Boehringer Ingelheim, MSD, Mitsubishi Tanabe Pharma, Teijin Pharma, Eli Lilly Japan, Asahi Kasei Pharma, The Mitsubishi Foundation, and Suntory Global Innovation Center. IN and SU are employees of Astellas Pharma. TY reports lecture fees from Mitsubishi Tanabe, Covidien Japan, Takeda, Novo Nordisk, Astellas, AstraZeneca, Ono, Novartis, Boehringer Ingelheim, Kyowa Kirin, Kowa, MSD, Sanofi, Daiichi Sankyo, Taisho, Eli Lilly, Kissei, Sanwa Chemistry Laboratory, Shionogi, Sumitomo Dainippon, FUJIFILM Toyama Chemical, Covidien Japan (Medtronic Japan) Nippon Becton Dickinson, Dojindo Laboratories, Kyorin Pharmaceutical, Abbott Japan, and Teijin Healthcare; and donations for research and research laboratories from Mitsubishi Tanabe, Takeda, Novo Nordisk, Astellas, AstraZeneca, Ono, Novartis, Boehringer Ingelheim, Kyowa Kirin, Kowa, MSD, Sanofi, Daiichi Sankyo, Tosoh, Sanwa Chemistry Laboratory, Shionogi, Minophagen, NTT DoCoMo, Mitsubishi Corporation Life Sciences, Aero Switch Therapeutics, Nipro, Asahi Mutual Life Insurance, and Bayer AG. SL is an advisory board member for Novo Nordisk and AstraZeneca; has received honoraria from Novo Nordisk, Sanofi, Boehringer Ingelheim, AstraZeneca and MSD; and has received research funding from CKD and Eli Lilly. SYL declares no competing interests. EDAT- 2022/02/09 06:00 MHDA- 2022/04/22 06:00 CRDT- 2022/02/08 05:38 PHST- 2021/11/03 00:00 [received] PHST- 2021/12/23 00:00 [revised] PHST- 2021/12/23 00:00 [accepted] PHST- 2022/02/09 06:00 [pubmed] PHST- 2022/04/22 06:00 [medline] PHST- 2022/02/08 05:38 [entrez] AID - S2213-8587(22)00008-0 [pii] AID - 10.1016/S2213-8587(22)00008-0 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2022 Mar;10(3):193-206. doi: 10.1016/S2213-8587(22)00008-0. Epub 2022 Feb 4. PMID- 35128745 OWN - NLM STAT- MEDLINE DCOM- 20221115 LR - 20230411 IS - 1460-9568 (Electronic) IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 56 IP - 9 DP - 2022 Nov TI - Diabetes: Risk factor and translational therapeutic implications for Alzheimer's disease. PG - 5727-5757 LID - 10.1111/ejn.15619 [doi] AB - Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) commonly co-occur. T2DM increases the risk for AD by approximately twofold. Animal models provide one means of interrogating the relationship of T2DM to AD and investigating brain insulin resistance in the pathophysiology of AD. Animal models show that persistent hyperglycaemia results in chronic low-grade inflammation that may contribute to the development of neuroinflammation and accelerate the pathobiology of AD. Epidemiological studies suggest that patients with T2DM who received treatment with specific anti-diabetic agents have a decreased risk for the occurrence of AD and all-cause dementia. Agents such as metformin ameliorate T2DM and may have other important systemic effects that lower the risk of AD. Glucagon-like peptide 1 (GLP-1) agonists have been associated with a decreased risk for AD in patients with T2DM. Both insulin and non-insulin anti-diabetic treatments have been evaluated for the treatment of AD in clinical trials. In most cases, patients included in the trials have clinical features of AD but do not have T2DM. Many of the trials were conducted prior to the use of diagnostic biomarkers for AD. Trials have had a wide range of durations and population sizes. Many of the agents used to treat T2DM do not cross the blood brain barrier, and the effects are posited to occur via lowering of peripheral hyperglycaemia and reduction of peripheral and central inflammation. Clinical trials of anti-diabetic agents to treat AD are ongoing and will provide insight into the therapeutic utility of these agents. CI - (c) 2022 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd. FAU - Cummings, Jeffrey AU - Cummings J AUID- ORCID: 0000-0001-8944-4158 AD - Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas (UNLV), Las Vegas, Nevada, USA. FAU - Ortiz, Andrew AU - Ortiz A AUID- ORCID: 0000-0002-5432-046X AD - Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas (UNLV), Las Vegas, Nevada, USA. FAU - Castellino, Janelle AU - Castellino J AD - School of Medicine, University of Nevada Las Vegas, Las Vegas, Nevada, USA. FAU - Kinney, Jefferson AU - Kinney J AD - Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas (UNLV), Las Vegas, Nevada, USA. AD - Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas (UNLV), Las Vegas, Nevada, USA. LA - eng GR - P20 AG068053/AG/NIA NIH HHS/United States GR - R35 AG071476/AG/NIA NIH HHS/United States GR - U01 NS093334/NS/NINDS NIH HHS/United States GR - P30 AG072980/AG/NIA NIH HHS/United States GR - P20 GM109025/GM/NIGMS NIH HHS/United States GR - R01 AG053798/AG/NIA NIH HHS/United States GR - R56 AG062762/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220223 PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Hypoglycemic Agents) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Alzheimer Disease/drug therapy MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Risk Factors MH - *Hyperglycemia/chemically induced/complications/drug therapy MH - Inflammation/complications PMC - PMC9393901 MID - NIHMS1778165 OTO - NOTNLM OT - Alzheimer's disease OT - GLP-1 agonist OT - dapagliflozin OT - diabetes OT - empagliflozin OT - insulin OT - liraglutide OT - metformin OT - mouse model OT - pioglitazone OT - rosiglitazone OT - semaglutide COIS- JC has provided consultation to AB Science, Acadia, Alkahest, AlphaCognition, ALZPath, Annovis, AriBio, Artery, Avanir, Biogen, Cassava, Cerevel, Clinilabs, Cortexyme, Diadem, EIP Pharma, Eisai, GatehouseBio, GemVax, Genentech, Green Valley, Grifols, Janssen, Karuna, Lexeo, Lilly, Lundbeck, LSP, Merck, NervGen, Novo Nordisk, Oligomerix, Otsuka, PharmacotrophiX, PRODEO, Prothena, ReMYND, Renew, Resverlogix, Roche, Signant Health, Suven, Unlearn AI, Vaxxinity, VigilNeuro, Zai Laboratories pharmaceutical, assessment and investment companies. AO, JC and JK have no conflicts of interest. EDAT- 2022/02/08 06:00 MHDA- 2022/11/16 06:00 PMCR- 2022/12/25 CRDT- 2022/02/07 05:40 PHST- 2022/01/25 00:00 [revised] PHST- 2021/10/25 00:00 [received] PHST- 2022/01/27 00:00 [accepted] PHST- 2022/02/08 06:00 [pubmed] PHST- 2022/11/16 06:00 [medline] PHST- 2022/02/07 05:40 [entrez] PHST- 2022/12/25 00:00 [pmc-release] AID - EJN15619 [pii] AID - 10.1111/ejn.15619 [doi] PST - ppublish SO - Eur J Neurosci. 2022 Nov;56(9):5727-5757. doi: 10.1111/ejn.15619. Epub 2022 Feb 23. PMID- 35120085 OWN - NLM STAT- MEDLINE DCOM- 20220208 LR - 20230821 IS - 2327-6924 (Electronic) IS - 2327-6886 (Linking) VI - 34 IP - 2 DP - 2022 Feb 1 TI - GLP-1 receptor agonists and cardiovascular outcomes in patients with type 2 diabetes: Clinical evidence and best practice. PG - 418-440 LID - 10.1097/JXX.0000000000000661 [doi] AB - Cardiovascular disease (CVD) is a major cause of death and disability among people with type 2 diabetes (T2D), presenting a significant impact on longevity, patient quality of life, and health care costs. In the United States, attainment of recommended glycemic targets is low and T2D-related cardiovascular complications remain a significant burden. Many glucose-lowering treatment options are available, but glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors are recommended in recent guidelines as the preferred add-on therapy to metformin to improve glycemic control. This is particularly the case for patients with T2D and established atherosclerotic CVD, at high risk of atherosclerotic CVD, and/or with chronic kidney disease. Recommendations were based on GLP-1RA and SGLT-2 inhibitor cardiovascular outcomes trials (CVOTs), which consistently showed that these agents pose no additional cardiovascular risk compared with placebo. Three GLP-1RAs (liraglutide, dulaglutide, and subcutaneous semaglutide) demonstrated significantly lower major adverse cardiovascular events versus placebo and are now approved for this indication. However, to realize improvement in outcomes in the clinical setting, organized, systematic, and coordinated approaches to patient management are also needed. For example, nurse-led diabetes self-management education and support programs have been shown to be effective. This article explores T2D management with emphasis on cardiovascular risk and CVOTs performed to date and reviews the clinical experience with GLP-1RAs for managing hyperglycemia and their impact on cardiovascular risk. In addition, practical guidance is given for key health care providers involved in the care of patients with T2D with cardiovascular risk outside of diabetes clinics/endocrinology centers. CI - Copyright (c) 2022 American Association of Nurse Practitioners. FAU - Coke, Lola A AU - Coke LA AD - Kirkhof College of Nursing, Grand Valley State University, Allendale, Michigan. FAU - Deedwania, Prakash C AU - Deedwania PC AD - UCSF School of Medicine, San Francisco, California. FAU - Hinnen, Debbie AU - Hinnen D AD - University of Colorado Health, Diabetes Clinic, Colorado Springs, Colorado. FAU - Magwire, Melissa AU - Magwire M AD - Cardiometabolic Center Alliance, Kansas City, Missouri. FAU - Miller, Nancy H AU - Miller NH AD - The LifeCare Company, Menlo Park, California. LA - eng PT - Journal Article PL - United States TA - J Am Assoc Nurse Pract JT - Journal of the American Association of Nurse Practitioners JID - 101600770 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) MH - *Cardiovascular Diseases/drug therapy/etiology MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide MH - Quality of Life COIS- Competing interests: P. C. Deedwania has acted as a consultant for Janssen and has received research grants for their institution from Boehringer Ingelheim, Novartis, and Sanofi. D. Hinnen has attended advisory boards and served on speakers' bureaus for Eli Lilly and Co., Janssen Pharmaceuticals, Novo Nordisk, and Sanofi. M. Magwire has attended advisory boards and acted as a consultant for Boehringer Ingelheim/Lilly and Novo Nordisk. The remaining authors report no conflicts of interest. EDAT- 2022/02/05 06:00 MHDA- 2022/02/09 06:00 CRDT- 2022/02/04 17:11 PHST- 2020/11/09 00:00 [received] PHST- 2021/09/02 00:00 [accepted] PHST- 2022/02/04 17:11 [entrez] PHST- 2022/02/05 06:00 [pubmed] PHST- 2022/02/09 06:00 [medline] AID - 01741002-202202000-00032 [pii] AID - 10.1097/JXX.0000000000000661 [doi] PST - ppublish SO - J Am Assoc Nurse Pract. 2022 Feb 1;34(2):418-440. doi: 10.1097/JXX.0000000000000661. PMID- 35119622 OWN - NLM STAT- MEDLINE DCOM- 20220411 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Linking) VI - 39 IP - 4 DP - 2022 Apr TI - Evaluation of Patient-Reported Satisfaction and Clinical Efficacy of Once-Weekly Semaglutide in Patients with Type 2 Diabetes: An Ambispective Study. PG - 1582-1595 LID - 10.1007/s12325-022-02053-0 [doi] AB - INTRODUCTION: The method of therapy administration and injection device characteristics have been documented to influence perceptions and preference of treatment among patients with type 2 diabetes (T2D). We aimed to assess the metabolic effectiveness and patient-reported satisfaction of once-weekly semaglutide compared to liraglutide in suboptimally controlled patients with T2D. METHODS: We conducted this single-center cohort study at diabetes center clinics at a tertiary care hospital between February 2021 and August 2021. We included suboptimally controlled patients with T2D who had been treated with liraglutide for at least 3 months at baseline, then shifted to once-weekly semaglutide and followed up for the same period. Ambulatory glucose profile (AGP) metrics [i.e., mean glucose level, glycemic variability (GV), time above range (TAR), and time in range (TIR)] for baseline and follow-up were compared. To assess the satisfaction with shifting, we used the valid Arabic version of the Diabetes Treatment Satisfaction Questionnaire status (DTSQs) and change (DTSQc) while the injection device preference was assessed using the Diabetes Injection Device Preference Questionnaire (DID-PQ). RESULTS: We included 52 patients (25 male and 27 female), with a mean age of 48 (+/- 6) years and a mean diabetes mellitus duration of 7.27 (+/- 3.79) years. We observed a significantly decreased mean HbA1c level following semaglutide treatment (7.79% at study end vs. 8.07% at baseline, p < 0.001) and body weight (84.64 +/- 7.68 vs. 87.15 +/- 8.011, p < 0.001). Compared to the glucometrics data at baseline, we observed a significantly improved mean average glucose, GV, TAR, and TIR (p < 0.001). Data from the DTSQs and DTSQc questionnaires showed a high level of patient-reported satisfaction after shifting to semaglutide treatment. All patients preferred/strongly preferred once-weekly semaglutide over liraglutide in most DID-PQ questionnaire domains. CONCLUSIONS: Switching from once-daily liraglutide to once-weekly semaglutide led to improvements in both clinical measures of glycemic control and patient-reported satisfaction. CI - (c) 2022. The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature. FAU - Al Hayek, Ayman A AU - Al Hayek AA AUID- ORCID: 0000-0002-3483-3196 AD - Department of Endocrinology and Diabetes, Diabetes Treatment Center, Prince Sultan Military Medical City, P.O. Box 7897, Riyadh, 11159, Saudi Arabia. ayman.alhayek@yahoo.com. FAU - Al Dawish, Mohamed A AU - Al Dawish MA AD - Department of Endocrinology and Diabetes, Diabetes Treatment Center, Prince Sultan Military Medical City, P.O. Box 7897, Riyadh, 11159, Saudi Arabia. LA - eng PT - Journal Article DEP - 20220204 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) MH - Blood Glucose MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Liraglutide/therapeutic use MH - Male MH - Middle Aged MH - Patient Reported Outcome Measures MH - Patient Satisfaction MH - Personal Satisfaction MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide 1 receptor agonist OT - Liraglutide OT - Semaglutide OT - Treatment satisfaction OT - Type 2 diabetes mellitus EDAT- 2022/02/05 06:00 MHDA- 2022/04/12 06:00 CRDT- 2022/02/04 12:13 PHST- 2021/12/14 00:00 [received] PHST- 2022/01/17 00:00 [accepted] PHST- 2022/02/05 06:00 [pubmed] PHST- 2022/04/12 06:00 [medline] PHST- 2022/02/04 12:13 [entrez] AID - 10.1007/s12325-022-02053-0 [pii] AID - 10.1007/s12325-022-02053-0 [doi] PST - ppublish SO - Adv Ther. 2022 Apr;39(4):1582-1595. doi: 10.1007/s12325-022-02053-0. Epub 2022 Feb 4. PMID- 35112504 OWN - NLM STAT- MEDLINE DCOM- 20220602 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 13 IP - 6 DP - 2022 Jun TI - Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A subgroup analysis by baseline variables in the PIONEER 9 and PIONEER 10 trials. PG - 975-985 LID - 10.1111/jdi.13764 [doi] AB - AIMS/INTRODUCTION: To assess the impact of baseline characteristics on the efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes. MATERIALS AND METHODS: In the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) 9 and 10 trials, Japanese patients were randomized to once-daily oral semaglutide (3, 7, or 14 mg) or a comparator (placebo or once-daily subcutaneous liraglutide 0.9 mg in PIONEER 9; once-weekly subcutaneous dulaglutide 0.75 mg in PIONEER 10) for 52 weeks, with 5 weeks of follow up. An exploratory analysis grouped patients in each trial according to baseline glycated hemoglobin (HbA(1c) ; 8.0-9.0%), body mass index (<25, >/=25-<30, or >/=30 kg/m(2) ) and, for PIONEER 10 only, by background medication (sulfonylurea, glinide, thiazolidinedione, alpha-glucosidase inhibitor, sodium-glucose cotransporter 2 inhibitor). Efficacy (changes from baseline to week 26 in HbA(1c) and bodyweight) and safety were assessed. RESULTS: Seven hundred and one patients were included (PIONEER 9: N = 243; PIONEER 10: N = 458). In both trials, HbA(1c) reductions increased as baseline HbA(1c) increased; there were no other apparent patterns between the variables investigated and HbA(1c) or bodyweight changes. There was one statistically significant subgroup interaction between baseline HbA(1c) and estimated treatment differences in bodyweight change for oral semaglutide 14 mg versus placebo in PIONEER 9 (P = 0.0286). Baseline HbA(1c) , baseline body mass index and background medication did not appear to affect the proportions of patients reporting adverse events. CONCLUSIONS: Oral semaglutide is effective across a range of baseline subgroups of Japanese patients with type 2 diabetes, with no unexpected safety findings. CI - (c) 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes, Endocrinology and Metabolism and Department of Rheumatology and Clinical Immunology, Gifu University Graduate School of Medicine, Gifu, Japan. FAU - Deenadayalan, Srikanth AU - Deenadayalan S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Horio, Hiroshi AU - Horio H AD - Novo Nordisk Pharma Ltd., Tokyo, Japan. FAU - Kaneto, Hideaki AU - Kaneto H AUID- ORCID: 0000-0001-7898-1943 AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Jensen, Thomas Bo AU - Jensen TB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. FAU - Yamada, Yuichiro AU - Yamada Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. FAU - Inagaki, Nobuya AU - Inagaki N AUID- ORCID: 0000-0001-8261-2593 AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. LA - eng GR - Novo Nordisk A/S, Soborg, Denmark/ PT - Journal Article PT - Randomized Controlled Trial DEP - 20220303 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/chemically induced/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Japan MH - Treatment Outcome MH - Semaglutide PMC - PMC9153832 OTO - NOTNLM OT - Glucagon-like peptide-1 analog OT - Glycemic control OT - Type 2 diabetes EDAT- 2022/02/04 06:00 MHDA- 2022/06/03 06:00 PMCR- 2022/06/01 CRDT- 2022/02/03 05:41 PHST- 2022/01/27 00:00 [revised] PHST- 2021/09/29 00:00 [received] PHST- 2022/01/31 00:00 [accepted] PHST- 2022/02/04 06:00 [pubmed] PHST- 2022/06/03 06:00 [medline] PHST- 2022/02/03 05:41 [entrez] PHST- 2022/06/01 00:00 [pmc-release] AID - JDI13764 [pii] AID - 10.1111/jdi.13764 [doi] PST - ppublish SO - J Diabetes Investig. 2022 Jun;13(6):975-985. doi: 10.1111/jdi.13764. Epub 2022 Mar 3. PMID- 35099465 OWN - NLM STAT- MEDLINE DCOM- 20220202 LR - 20220202 IS - 0030-9982 (Print) IS - 0030-9982 (Linking) VI - 72 IP - 1 DP - 2022 Jan TI - Classification of Non-Insulin Glucose Lowering Drugs. PG - 181-182 LID - 10.47391/JPMA.22-003 [doi] AB - The ever-changing scenario of diabetes care, especially pharmacotherapy, calls for a framework to help classify non-insulin glucose drugs. Such a taxonomic structure should be of contemporary relevance as well as futuristic in vision; scholarly in intent but easy to understand; and based on pathophysiologic principles while being useful for the clinician. We propose a rubric which lists four classes of non-insulin glucose lowering drugs; insulin secretagogues, insulin sensitizers, calorie restriction mimetics, and calorie restrictors. This classification serves the need of students and teachers as well as pharmacologists and clinicians alike. FAU - Kalra, Sanjay AU - Kalra S AD - Department of Endocrinology, Bharti Hospital, Karnal, New Delhi, India. FAU - Arora, Saurabh AU - Arora S AD - Department of Endocrinology, Dayanand Medical College and Hospital, Ludhiana, India. FAU - Kapoor, Nitin AU - Kapoor N AD - Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore (TN) -632004, India, and Non Communicable Disease Unit, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia. LA - eng PT - Journal Article PL - Pakistan TA - J Pak Med Assoc JT - JPMA. The Journal of the Pakistan Medical Association JID - 7501162 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Pharmaceutical Preparations) RN - IY9XDZ35W2 (Glucose) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucose MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Insulin MH - *Pharmaceutical Preparations OTO - NOTNLM OT - Alpha glucosidase inhibitors, DPP4i, GLP1RA, liraglutide, pharmacotherapy sulfonylureas, semaglutide, SGLT2i. EDAT- 2022/02/01 06:00 MHDA- 2022/02/03 06:00 CRDT- 2022/01/31 12:15 PHST- 2022/01/31 12:15 [entrez] PHST- 2022/02/01 06:00 [pubmed] PHST- 2022/02/03 06:00 [medline] AID - 11073 [pii] AID - 10.47391/JPMA.22-003 [doi] PST - ppublish SO - J Pak Med Assoc. 2022 Jan;72(1):181-182. doi: 10.47391/JPMA.22-003. PMID- 35080714 OWN - NLM STAT- MEDLINE DCOM- 20220504 LR - 20261012 IS - 1534-6242 (Electronic) IS - 1523-3804 (Linking) VI - 24 IP - 1 DP - 2022 Jan TI - The Effect of GLP-1 Receptor Agonists on Postprandial Lipaemia. PG - 13-21 LID - 10.1007/s11883-022-00982-3 [doi] AB - PURPOSE OF REVIEW: To review the currently available data on the effect of Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on postprandial lipaemia. RECENT FINDINGS: Out of the available studies that examined the respective lipid parameter, exenatide reduced postprandial triacyglycerol (TAG) in 4/6, apolipoprotein B-48 in 3/3, non-esterified fatty acids in 2/2, and apolipoprotein C-III and very low-density lipoprotein cholesterol (VLDL-C) in 1/1 studies. Liraglutide reduced postprandial TAG in 2/2, apolipoprotein B-48 in 3/3 and apolipoprotein C-III, chylomicron-TAG and VLDL(1)-TAG in 1/1 studies. Lixisenatide reduced postprandial chylomicron-TAG and apolipoprotein B-48 in 1 study. Semaglutide reduced postprandial TAG, apolipoprotein B-48 and VLDL in 1 study. Dulaglutide reduced postprandial apolipoprotein B-48 in 1 study. GLP-1 RAs have consistent beneficial effects on postprandial lipaemia with most of the data coming from studies with exenatide and liraglutide. Reduction of postprandial lipaemia might be one of the mechanisms behind the pleiotropic effects of GLP-1 RAs. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Novodvorsky, Peter AU - Novodvorsky P AD - Diabetes Centre, Institute for Clinical and Experimental Medicine (IKEM), Videnska 1958, 140 21, Prague 4, Czech Republic. AD - Department of Oncology & Metabolism, University of Sheffield, Sheffield, UK. FAU - Haluzik, Martin AU - Haluzik M AD - Diabetes Centre, Institute for Clinical and Experimental Medicine (IKEM), Videnska 1958, 140 21, Prague 4, Czech Republic. halm@ikem.cz. AD - Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. halm@ikem.cz. LA - eng GR - IN 00023001/Ministerstvo Zdravotnictvi Ceske Republiky/ GR - RVO VFN64165/Vseobecni Fakultni Nemocnice Praha (CZ)/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20220124 PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 0 (Apolipoprotein B-48) RN - 0 (Apolipoprotein C-III) RN - 0 (Chylomicrons) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Apolipoprotein B-48 MH - Apolipoprotein C-III MH - Chylomicrons MH - *Diabetes Mellitus, Type 2 MH - Exenatide/therapeutic use MH - Glucagon-Like Peptide 1 MH - Humans MH - *Hyperlipidemias/drug therapy MH - Hypoglycemic Agents MH - Liraglutide/pharmacology/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Atherosclerosis OT - Glucagon-like peptide-1 receptor agonist (GLP-1 RA) OT - Postprandial lipaemia OT - Type 2 diabetes (T2DM) EDAT- 2022/01/27 06:00 MHDA- 2022/05/06 06:00 CRDT- 2022/01/26 12:12 PHST- 2021/11/03 00:00 [accepted] PHST- 2022/01/27 06:00 [pubmed] PHST- 2022/05/06 06:00 [medline] PHST- 2022/01/26 12:12 [entrez] AID - 10.1007/s11883-022-00982-3 [pii] AID - 10.1007/s11883-022-00982-3 [doi] PST - ppublish SO - Curr Atheroscler Rep. 2022 Jan;24(1):13-21. doi: 10.1007/s11883-022-00982-3. Epub 2022 Jan 24. PMID- 35065096 OWN - NLM STAT- MEDLINE DCOM- 20220413 LR - 20220531 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 151 DP - 2022 May TI - GLP-1 and GIP receptor signaling in beta cells - A review of receptor interactions and co-stimulation. PG - 170749 LID - S0196-9781(22)00015-8 [pii] LID - 10.1016/j.peptides.2022.170749 [doi] AB - Glucagon-like peptide 1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) are two class B1 G protein-coupled receptors, which are stimulated by the gastrointestinal hormones GLP-1 and GIP, respectively. In the pancreatic beta cells, activation of both receptors lead to increased cyclic adenosine monophosphate (cAMP) and glucose-dependent insulin secretion. Marketed GLP-1R agonists such as dulaglutide, liraglutide, exenatide and semaglutide constitute an expanding drug class with beneficial effects for persons suffering from type 2 diabetes and/or obesity. In recent years another drug class, the GLP-1R-GIPR co-agonists, has emerged. Especially the peptide-based, co-agonist tirzepatide is a promising candidate for a better treatment of type 2 diabetes by improving glycemic control and weight reduction. The mechanism of action for tirzepatide include biased signaling of the GLP-1R as well as potent GIPR signaling. Since the implications of co-targeting these closely related receptors concomitantly are challenging to study in vivo, the pharmacodynamic mechanisms and downstream signaling pathways of the GLP-1R-GIPR co-agonists in general, are not fully elucidated. In this review, we present the individual signaling pathways for GLP-1R and GIPR in the pancreatic beta cell with a focus on the shared signaling pathways of the two receptors and interpret the implications of GLP-1R-GIPR co-activation in the light of recent co-activating therapeutic compounds. CI - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Mayendraraj, Ashok AU - Mayendraraj A AD - Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Rosenkilde, Mette M AU - Rosenkilde MM AD - Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Gasbjerg, Laerke S AU - Gasbjerg LS AD - Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: lsg@sund.ku.dk. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20220119 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Receptors, Gastrointestinal Hormone) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Gastric Inhibitory Polypeptide/metabolism MH - Glucagon-Like Peptide 1/metabolism MH - *Glucagon-Like Peptide-1 Receptor/metabolism MH - Humans MH - *Insulin-Secreting Cells MH - *Receptors, Gastrointestinal Hormone/metabolism OTO - NOTNLM OT - Beta cell OT - Co-agonist OT - G protein-coupled receptors (GPCRs) OT - Glucagon-like peptide 1 OT - Glucose-dependent insulinotropic polypeptide OT - Incretin hormones OT - Insulin secretion OT - Type 2 diabetes EDAT- 2022/01/23 06:00 MHDA- 2022/04/14 06:00 CRDT- 2022/01/22 20:09 PHST- 2021/10/03 00:00 [received] PHST- 2022/01/14 00:00 [revised] PHST- 2022/01/17 00:00 [accepted] PHST- 2022/01/23 06:00 [pubmed] PHST- 2022/04/14 06:00 [medline] PHST- 2022/01/22 20:09 [entrez] AID - S0196-9781(22)00015-8 [pii] AID - 10.1016/j.peptides.2022.170749 [doi] PST - ppublish SO - Peptides. 2022 May;151:170749. doi: 10.1016/j.peptides.2022.170749. Epub 2022 Jan 19. PMID- 35064598 OWN - NLM STAT- MEDLINE DCOM- 20220804 LR - 20250728 IS - 1099-1387 (Electronic) IS - 1075-2617 (Linking) VI - 28 IP - 9 DP - 2022 Sep TI - Efficient synthesis of Aib(8) -Arg(34) -GLP-1 (7-37) by liquid-phase fragment condensation. PG - e3407 LID - 10.1002/psc.3407 [doi] AB - Glucagon-like peptide-1 (GLP-1) is a potential therapeutic agent for treating Type 2 diabetes, owing to its glucose-dependent capability to stimulate insulin secretion. Semaglutide is currently the best GLP-1 analogue; however, the Aib(8) -Arg(34) -GLP-1 (7-37) of semaglutide contains an unnatural amino acid at the eighth position (Aib: 2-aminoisobutyric acid), which hinders its fermentation process. Aib(8) -Arg(34) -GLP-1 (7-37) is mainly synthesised by solid-phase synthesis. However, solid-phase synthesis of Aib(8) -Arg(34) -GLP-1 (7-37) has many shortcomings: (i) The synthesis requires many organic solvents, (ii) the existence of deletion peptides impedes the subsequent purification process, (iii) the yield is low (approximately 16%), and (iv) it is not suitable for large-scale synthesis. However, the synthesis of Aib(8) -Arg(34) -GLP-1 (7-37) by liquid-phase fragment condensation of expressed and synthetic peptides (Arg(34) -GLP-1 (9-37) and Boc-His (Boc)-Aib) has many advantages: (i) The synthesis process only requires a few organic reagents, (ii) the yield is high (approximately 60%), (iii) the purification conditions are simple and Aib(8) -Arg(34) -GLP-1 (7-37) with a purity of over 98% is obtained through one-step reverse-phase purification, and (iv) the raw materials are inexpensive and large-scale synthesis is possible. In conclusion, here, we developed an efficient method for synthesising Aib(8) -Arg(34) -GLP-1 (7-37). CI - (c) 2022 European Peptide Society and John Wiley & Sons, Ltd. FAU - Zhang, Jinhua AU - Zhang J AD - China State Institute of Pharmaceutical Industry, Shanghai, China. AD - Department of Biological Medicines & Shanghai Engineering Research Centre of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai, China. FAU - Dong, Yuanzhen AU - Dong Y AD - China State Institute of Pharmaceutical Industry, Shanghai, China. AD - Shanghai Duomirui Biotechnology Ltd., Shanghai, China. FAU - He, Yufeng AU - He Y AD - China State Institute of Pharmaceutical Industry, Shanghai, China. AD - Shanghai Duomirui Biotechnology Ltd., Shanghai, China. FAU - Han, Jinzhu AU - Han J AD - China State Institute of Pharmaceutical Industry, Shanghai, China. AD - Department of Biological Medicines & Shanghai Engineering Research Centre of Immunotherapeutics, Fudan University School of Pharmacy, Shanghai, China. FAU - Hu, Haifeng AU - Hu H AD - China State Institute of Pharmaceutical Industry, Shanghai, China. FAU - Feng, Jun AU - Feng J AUID- ORCID: 0000-0002-3695-1209 AD - China State Institute of Pharmaceutical Industry, Shanghai, China. AD - Shanghai Duomirui Biotechnology Ltd., Shanghai, China. LA - eng PT - Journal Article DEP - 20220215 PL - England TA - J Pept Sci JT - Journal of peptide science : an official publication of the European Peptide Society JID - 9506309 RN - 0 (Peptide Fragments) RN - 0 (Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - PI470C66NT (glucagon-like peptide 1 (7-37)) SB - IM MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptide 1 MH - Humans MH - Peptide Fragments MH - Peptides/chemistry OTO - NOTNLM OT - GLP-1 OT - Type 2 diabetes OT - liquid-phase fragment condensation OT - solid-phase synthesis OT - yield EDAT- 2022/01/23 06:00 MHDA- 2022/08/05 06:00 CRDT- 2022/01/22 05:46 PHST- 2022/01/15 00:00 [revised] PHST- 2021/11/27 00:00 [received] PHST- 2022/01/18 00:00 [accepted] PHST- 2022/01/23 06:00 [pubmed] PHST- 2022/08/05 06:00 [medline] PHST- 2022/01/22 05:46 [entrez] AID - 10.1002/psc.3407 [doi] PST - ppublish SO - J Pept Sci. 2022 Sep;28(9):e3407. doi: 10.1002/psc.3407. Epub 2022 Feb 15. PMID- 35048301 OWN - NLM STAT- MEDLINE DCOM- 20221026 LR - 20231102 IS - 1525-1497 (Electronic) IS - 0884-8734 (Print) IS - 0884-8734 (Linking) VI - 37 IP - 14 DP - 2022 Nov TI - Incidence and Predictors of Primary Nonadherence to Sodium Glucose Co-transporter 2 Inhibitors and Glucagon-Like Peptide 1 Agonists in a Large Integrated Healthcare System. PG - 3562-3569 LID - 10.1007/s11606-021-07331-1 [doi] AB - BACKGROUND: Newer glucose-lowering drugs, including sodium glucose co-transporter 2 inhibitors (SGLT2i) and GLP-1 agonists, have a key role in the pharmacologic management of type 2 diabetes. No studies have measured primary nonadherence for these two drug classes, defined as when a medication is prescribed for a patient but ultimately not dispensed to them. OBJECTIVE: To describe the incidence and predictors of primary nonadherence to SGLT2i (canagliflozin, empagliflozin) or GLP-1 agonists (dulaglutide, liraglutide, semaglutide) using a dataset that links electronic prescribing with health insurance claims. DESIGN AND PARTICIPANTS: A retrospective cohort design using data of adult patients from a large health system who had at least one prescription order for a SGLT2i or GLP-1 agonist between 2012 and 2019. We used mixed-effects multivariable logistic regression to determine associations between sociodemographic, clinical, and provider variables and primary nonadherence. MAIN MEASURES: Primary medication nonadherence, defined as no dispensed claim within 30 days of an electronic prescription order for any drug within each medication class. KEY RESULTS: The cohort included 5146 patients newly prescribed a SGLT2i or GLP-1 agonist. The overall incidence of 30-day primary medication nonadherence was 31.8% (1637/5146). This incidence rate was 29.8% (n = 726) and 33.6% (n = 911) among those initiating a GLP-1 agonist and SGLT2i, respectively. Age >/= 65 (aOR 1.37 (95% CI 1.09 to 1.72)), Black race vs White (aOR 1.29 (95% CI 1.02 to 1.62)), diabetic nephropathy (aOR 1.31 (95% CI 1.02 to 1.68)), and hyperlipidemia (aOR 1.18 (95% CI 1.01 to 1.39)) were associated with a higher odds of primary nonadherence. Female sex (aOR 0.86 (95% CI 0.75 to 0.99)), peripheral artery disease (aOR 0.73 (95% CI 0.56 to 0.94)), and having the index prescription ordered by an endocrinologist vs a primary care provider (aOR 0.76 (95% CI 0.61 to 0.95)) were associated with lower odds of primary nonadherence. CONCLUSIONS: One third of patients prescribed SGLT2i or GLP-1 agonists in this sample did not fill their prescription within 30 days. Black race, male sex, older age, having greater baseline comorbidities, and having a primary care provider vs endocrinologist prescribe the index drug were associated with higher odds of primary nonadherence. Interventions targeting medication adherence for these newer drugs must consider primary nonadherence as a barrier to optimal clinical care. CI - (c) 2022. The Author(s) under exclusive licence to Society of General Internal Medicine. FAU - Luo, Jing AU - Luo J AUID- ORCID: 0000-0002-1190-553X AD - Division of General Internal Medicine, University of Pittsburgh School of Medicine, Pittsburg, PA, USA. luoj@pitt.edu. FAU - Feldman, Robert AU - Feldman R AD - Division of General Internal Medicine, University of Pittsburgh School of Medicine, Pittsburg, PA, USA. FAU - Rothenberger, Scott AU - Rothenberger S AD - Division of General Internal Medicine, University of Pittsburgh School of Medicine, Pittsburg, PA, USA. FAU - Korytkowski, Mary AU - Korytkowski M AD - Division of Endocrinology and Metabolism, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. FAU - Fischer, Michael A AU - Fischer MA AD - Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA, USA. FAU - Gellad, Walid F AU - Gellad WF AD - Division of General Internal Medicine, University of Pittsburgh School of Medicine, Pittsburg, PA, USA. AD - Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. LA - eng GR - K23 DK120956/DK/NIDDK NIH HHS/United States GR - KL2 TR001856/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220119 PL - United States TA - J Gen Intern Med JT - Journal of general internal medicine JID - 8605834 RN - 0SAC974Z85 (Canagliflozin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - IY9XDZ35W2 (Glucose) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 9NEZ333N27 (Sodium) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Symporters) SB - IM MH - Adult MH - Female MH - Humans MH - Male MH - Canagliflozin/therapeutic use MH - *Delivery of Health Care, Integrated MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucagon-Like Peptide 1/agonists/metabolism MH - Glucose/metabolism MH - Hypoglycemic Agents/therapeutic use MH - Incidence MH - Liraglutide/therapeutic use MH - Retrospective Studies MH - Sodium/metabolism MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Symporters/metabolism PMC - PMC9585108 COIS- The authors declare that they do not have a conflict of interest. EDAT- 2022/01/21 06:00 MHDA- 2022/10/25 06:00 PMCR- 2023/11/01 CRDT- 2022/01/20 06:20 PHST- 2021/07/12 00:00 [received] PHST- 2021/12/14 00:00 [accepted] PHST- 2022/01/21 06:00 [pubmed] PHST- 2022/10/25 06:00 [medline] PHST- 2022/01/20 06:20 [entrez] PHST- 2023/11/01 00:00 [pmc-release] AID - 10.1007/s11606-021-07331-1 [pii] AID - 7331 [pii] AID - 10.1007/s11606-021-07331-1 [doi] PST - ppublish SO - J Gen Intern Med. 2022 Nov;37(14):3562-3569. doi: 10.1007/s11606-021-07331-1. Epub 2022 Jan 19. PMID- 35042144 OWN - NLM STAT- MEDLINE DCOM- 20220127 LR - 20220127 IS - 1873-264X (Electronic) IS - 0731-7085 (Linking) VI - 210 DP - 2022 Feb 20 TI - Oligomerization, albumin binding and catabolism of therapeutic peptides in the subcutaneous compartment: An investigation on lipidated GLP-1 analogs. PG - 114566 LID - S0731-7085(21)00677-4 [pii] LID - 10.1016/j.jpba.2021.114566 [doi] AB - Lipidation, a common strategy to improve half-life of therapeutic peptides, affects their tendency to oligomerize, their interaction with plasmatic proteins, and their catabolism. In this work, we have leveraged the use of NMR and SPR spectroscopy to elucidate oligomerization propensity and albumin interaction of different analogs of the two marketed lipidated GLP-1 agonists liraglutide and semaglutide. As most lipidated therapeutic peptides are administered by subcutaneous injection, we have also assessed in vitro their catabolism in the SC tissue using the LC-HRMS-based SCiMetPep assay. We observed that oligomerization had a shielding effect against catabolism. At the same time, binding to albumin may provide only limited protection from proteolysis due to the higher unbound peptide fraction present in the subcutaneous compartment with respect to the plasma. Finally, identification of catabolites in rat plasma after SC dosing of semaglutide showed a good correlation with the in vitro data, with Tyr(19)-Leu(20) being the major cleavage site. Early characterization of the complex interplay between oligomerization, albumin binding, and catabolism at the injection site is essential for the synthesis of lipidated peptides with good pharmacokinetic profiles. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Gallo, Mariana AU - Gallo M AD - Structural Biology and Computational Chemistry, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. FAU - Vanni, Domitilla AU - Vanni D AD - Drug Metabolism and Pharmacokinetics, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy; Department of Chemical Science and Technology, University of Rome "Tor Vergata", 00133 Rome, Italy. FAU - Esposito, Simone AU - Esposito S AD - Drug Metabolism and Pharmacokinetics, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. FAU - Alaimo, Nadine AU - Alaimo N AD - Discovery Biology, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. FAU - Orvieto, Federica AU - Orvieto F AD - Peptides and Small Molecules R&D Department, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. FAU - Rulli, Federica AU - Rulli F AD - Peptides and Small Molecules R&D Department, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. FAU - Missineo, Antonino AU - Missineo A AD - Discovery Biology, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. FAU - Caretti, Fulvia AU - Caretti F AD - Drug Metabolism and Pharmacokinetics, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. FAU - Bonelli, Fabio AU - Bonelli F AD - Drug Metabolism and Pharmacokinetics, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. FAU - Veneziano, Maria AU - Veneziano M AD - Drug Metabolism and Pharmacokinetics, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. FAU - Orsatti, Laura AU - Orsatti L AD - Drug Metabolism and Pharmacokinetics, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. FAU - Monteagudo, Edith AU - Monteagudo E AD - Drug Metabolism and Pharmacokinetics, IRBM SpA, Via Pontina Km 30 600, 00 071 Pomezia, Rome, Italy. Electronic address: edith.monteagudo@chdifoundation.org. LA - eng PT - Journal Article DEP - 20220107 PL - England TA - J Pharm Biomed Anal JT - Journal of pharmaceutical and biomedical analysis JID - 8309336 RN - 0 (Albumins) RN - 0 (Hypoglycemic Agents) RN - 0 (Peptides) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Albumins MH - Animals MH - *Diabetes Mellitus, Type 2 MH - *Glucagon-Like Peptide 1 MH - Half-Life MH - Hypoglycemic Agents MH - Liraglutide MH - Peptides MH - Rats OTO - NOTNLM OT - Albumin binding OT - GLP-1 OT - Metabolism OT - Peptide OT - Peptide self-association OT - Subcutaneous COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/01/19 06:00 MHDA- 2022/01/28 06:00 CRDT- 2022/01/18 20:22 PHST- 2021/09/10 00:00 [received] PHST- 2021/12/22 00:00 [revised] PHST- 2021/12/28 00:00 [accepted] PHST- 2022/01/19 06:00 [pubmed] PHST- 2022/01/28 06:00 [medline] PHST- 2022/01/18 20:22 [entrez] AID - S0731-7085(21)00677-4 [pii] AID - 10.1016/j.jpba.2021.114566 [doi] PST - ppublish SO - J Pharm Biomed Anal. 2022 Feb 20;210:114566. doi: 10.1016/j.jpba.2021.114566. Epub 2022 Jan 7. PMID- 35030323 OWN - NLM STAT- MEDLINE DCOM- 20220420 LR - 20250623 IS - 2468-1253 (Electronic) VI - 7 IP - 4 DP - 2022 Apr TI - Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review. PG - 367-378 LID - S2468-1253(21)00261-2 [pii] LID - 10.1016/S2468-1253(21)00261-2 [doi] AB - There are no licensed treatments for non-alcoholic fatty liver disease (NAFLD), but three different classes of antihyperglycaemic drugs-peroxisome proliferator-activated receptor (PPAR) agonists, glucagon-like peptide-1 receptor (GLP-1R) agonists, and sodium-glucose cotransporter-2 (SGLT2) inhibitors-show promise in the treatment of the disease. We did a systematic review of randomised controlled trials examining the efficacy of PPAR agonists, GLP-1R agonists, or SGLT2 inhibitors for specifically treating NAFLD in adults with or without type 2 diabetes. A total of 25 active-controlled or placebo-controlled trials met our inclusion criteria: eight for PPAR agonists, ten for GLP-1R agonists, and seven for SGLT2 inhibitors. 2597 individuals (1376 [53%] men vs 1221 [47%] women; mean age 52 years (SD 6); mean BMI 32 kg/m(2) (SD 3); 1610 [62%] with type 2 diabetes) were included. Pioglitazone, lanifibranor, and GLP1-R agonists (mostly liraglutide and semaglutide) improved individual histological features of NASH (ie, steatosis, ballooning, lobular inflammation) or achieved resolution of NASH without worsening of fibrosis. SGLT2 inhibitors (mostly empagliflozin and dapagliflozin) reduced liver fat content, as assessed by magnetic resonance-based techniques. CI - Copyright (c) 2022 Elsevier Ltd. All rights reserved. FAU - Mantovani, Alessandro AU - Mantovani A AD - Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. FAU - Byrne, Christopher D AU - Byrne CD AD - Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK. FAU - Targher, Giovanni AU - Targher G AD - Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. Electronic address: giovanni.targher@univr.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20220112 PL - Netherlands TA - Lancet Gastroenterol Hepatol JT - The lancet. Gastroenterology & hepatology JID - 101690683 RN - 0 (Hypoglycemic Agents) RN - 0 (Peroxisome Proliferator-Activated Receptors) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 9NEZ333N27 (Sodium) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Female MH - Glucose MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Male MH - Middle Aged MH - *Non-alcoholic Fatty Liver Disease/drug therapy MH - Peroxisome Proliferator-Activated Receptors MH - Sodium MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists COIS- Declaration of interests CDB is supported in part by grants from the Southampton National Institute for Health Research Biomedical Research Centre, outside of the submitted work. GT is supported in part by grants from the University School of Medicine of Verona, Verona, Italy, outside of the submitted work. AM declares no competing interests. EDAT- 2022/01/15 06:00 MHDA- 2022/04/21 06:00 CRDT- 2022/01/14 20:07 PHST- 2021/05/19 00:00 [received] PHST- 2021/07/09 00:00 [revised] PHST- 2021/07/12 00:00 [accepted] PHST- 2022/01/15 06:00 [pubmed] PHST- 2022/04/21 06:00 [medline] PHST- 2022/01/14 20:07 [entrez] AID - S2468-1253(21)00261-2 [pii] AID - 10.1016/S2468-1253(21)00261-2 [doi] PST - ppublish SO - Lancet Gastroenterol Hepatol. 2022 Apr;7(4):367-378. doi: 10.1016/S2468-1253(21)00261-2. Epub 2022 Jan 12. PMID- 34999021 OWN - NLM STAT- MEDLINE DCOM- 20230404 LR - 20260127 IS - 1873-2615 (Electronic) IS - 1050-1738 (Linking) VI - 33 IP - 3 DP - 2023 Apr TI - Editorial commentary: Weight loss for cardiovascular disease prevention - is semaglutide the answer? PG - 167-169 LID - S1050-1738(22)00001-9 [pii] LID - 10.1016/j.tcm.2021.12.018 [doi] FAU - Lavie, Carl J AU - Lavie CJ AD - John Ochsner Heart and Vascular Institute, Ochsner Clinical School-the University of Queensland School of Medicine, 1514 Jefferson Highway, New Orleans, LA 70121-2483, USA. Electronic address: clavie@ochsner.org. FAU - Bhatt, Deepak L AU - Bhatt DL AD - Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, USA. FAU - Neeland, Ian J AU - Neeland IJ AD - UH Center for Cardiovascular Prevention and Center for Integrated, and Novel Approaches in Vascular-Metabolic Disease (CINEMA), Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland OH, USA. FAU - Heymsfield, Steven B AU - Heymsfield SB AD - Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA. LA - eng PT - Comment PT - Editorial DEP - 20220105 PL - United States TA - Trends Cardiovasc Med JT - Trends in cardiovascular medicine JID - 9108337 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - Trends Cardiovasc Med. 2023 Apr;33(3):159-166. doi: 10.1016/j.tcm.2021.12.008. PMID: 34942372 MH - Humans MH - *Cardiovascular Diseases/diagnosis/prevention & control MH - Glucagon-Like Peptides/adverse effects MH - Weight Loss MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Semaglutide EDAT- 2022/01/10 06:00 MHDA- 2023/04/04 06:42 CRDT- 2022/01/09 20:45 PHST- 2021/12/28 00:00 [received] PHST- 2021/12/29 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2022/01/10 06:00 [pubmed] PHST- 2022/01/09 20:45 [entrez] AID - S1050-1738(22)00001-9 [pii] AID - 10.1016/j.tcm.2021.12.018 [doi] PST - ppublish SO - Trends Cardiovasc Med. 2023 Apr;33(3):167-169. doi: 10.1016/j.tcm.2021.12.018. Epub 2022 Jan 5. PMID- 34993760 OWN - NLM STAT- MEDLINE DCOM- 20220602 LR - 20260127 IS - 1573-2606 (Electronic) IS - 1389-9155 (Print) IS - 1389-9155 (Linking) VI - 23 IP - 3 DP - 2022 Jun TI - Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. PG - 521-539 LID - 10.1007/s11154-021-09699-1 [doi] AB - Semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, is available as monotherapy in both subcutaneous as well as oral dosage form (first approved oral GLP-1 receptor agonist). It has been approved as a second line treatment option for better glycaemic control in type 2 diabetes and currently under scrutiny for anti-obesity purpose. Semaglutide has been proved to be safe in adults and elderly patients with renal or hepatic disorders demanding no dose modification. Cardiovascular (CV) outcome trials established that it can reduce various CV risk factors in patients with established CV disorders. Semaglutide is well tolerated with no risk of hypoglycaemia in monotherapy but suffers from gastrointestinal adverse effects. A large population affected with COVID-19 infection were diabetic; therefore use of semaglutide in diabetes as well as CV patients would be very much supportive in maintaining health care system during this pandemic situation. Hence, this peptidic drug can be truly considered as a quintessential of GLP-1 agonists for management of type 2 diabetes. CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Mahapatra, Manoj Kumar AU - Mahapatra MK AUID- ORCID: 0000-0001-8147-5283 AD - Kanak Manjari Institute of Pharmaceutical Sciences, Rourkela, 769015, Odisha, India. manojbit07@gmail.com. FAU - Karuppasamy, Muthukumar AU - Karuppasamy M AUID- ORCID: 0000-0003-0034-9950 AD - YaAn Pharmaceutical and Medical Communications, 6/691H1, Balaji Nagar, Sithurajapuram, Sivakasi, 626189, Tamilnadu, India. FAU - Sahoo, Biswa Mohan AU - Sahoo BM AUID- ORCID: 0000-0001-8822-0427 AD - Roland Institute of Pharmaceutical Sciences, Berhampur, 760010, Odisha, India. LA - eng PT - Journal Article PT - Review DEP - 20220107 PL - Germany TA - Rev Endocr Metab Disord JT - Reviews in endocrine & metabolic disorders JID - 100940588 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *COVID-19 Drug Treatment MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC8736331 OTO - NOTNLM OT - COVID-19 OT - GLP-1 agonist OT - PIONEER OT - SUSTAIN OT - Semaglutide OT - Type 2 diabetes COIS- Authors declare no conflicts of interest. EDAT- 2022/01/08 06:00 MHDA- 2022/06/03 06:00 PMCR- 2022/01/07 CRDT- 2022/01/07 06:43 PHST- 2021/11/27 00:00 [accepted] PHST- 2022/01/08 06:00 [pubmed] PHST- 2022/06/03 06:00 [medline] PHST- 2022/01/07 06:43 [entrez] PHST- 2022/01/07 00:00 [pmc-release] AID - 10.1007/s11154-021-09699-1 [pii] AID - 9699 [pii] AID - 10.1007/s11154-021-09699-1 [doi] PST - ppublish SO - Rev Endocr Metab Disord. 2022 Jun;23(3):521-539. doi: 10.1007/s11154-021-09699-1. Epub 2022 Jan 7. PMID- 34981419 OWN - NLM STAT- MEDLINE DCOM- 20220323 LR - 20261010 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 75 IP - 3 DP - 2022 Mar TI - Efficacy and safety of once-weekly semaglutide in adults with overweight or obesity: a meta-analysis. PG - 718-724 LID - 10.1007/s12020-021-02945-1 [doi] AB - PURPOSE: This meta-analysis aimed to assess the efficacy and safety of once-weekly semaglutide among adults with overweight or obesity. METHODS: We searched multiple electronic databases for randomized controlled trials that compared once-weekly semaglutide versus placebo in adults with overweight or obesity. The primary outcomes were the percentage change and absolute change in body weight. Secondary outcomes included achievement of categorical weight loss targets (at least 5, 10, 15, or 20%), cardiometabolic risk profiles, and health-related quality of life. RESULTS: This meta-analysis included a total of four trials with 3447 patients. Once-weekly semaglutide was superior to placebo in terms of the percentage change and absolute change in body weight. Compared with placebo, once-weekly semaglutide also led to significant increases in the proportions of achievement of categorical weight reduction targets. Moreover, once-weekly semaglutide induced superior reductions in waist circumference and body-mass index compared with placebo. Furthermore, the effect on improving other cardiometabolic risk factors and health-related quality of life was more pronounced for once-weekly semaglutide relative to placebo. CONCLUSION: Among adults with overweight or obesity, once-weekly semaglutide could result in clinically meaningful weight loss, which was a promising therapy for treating overweight or obesity. CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Zhong, Ping AU - Zhong P AD - Department of Acupuncture and Moxibustion, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Zeng, Hai AU - Zeng H AD - College of Traditional Chinese Medicine, Jinan University, Guangzhou, China. FAU - Huang, Miaochun AU - Huang M AD - Emergency Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. FAU - Fu, Wenbin AU - Fu W AD - Department of Acupuncture and Moxibustion, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China. fuwenbin@gzucm.edu.cn. FAU - Chen, Zhixia AU - Chen Z AD - Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. chenzx116@163.com. LA - eng GR - No. 2020KT1112/scientific research project of guangdong provincial administration of traditional chinese medicine/ PT - Journal Article PT - Meta-Analysis DEP - 20220104 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Obesity/therapy MH - *Overweight/drug therapy MH - Quality of Life MH - Semaglutide OTO - NOTNLM OT - Meta-analysis OT - Obesity OT - Once-weekly semaglutide OT - Overweight OT - Weight management EDAT- 2022/01/05 06:00 MHDA- 2022/03/24 06:00 CRDT- 2022/01/04 06:17 PHST- 2021/07/21 00:00 [received] PHST- 2021/11/10 00:00 [accepted] PHST- 2022/01/05 06:00 [pubmed] PHST- 2022/03/24 06:00 [medline] PHST- 2022/01/04 06:17 [entrez] AID - 10.1007/s12020-021-02945-1 [pii] AID - 10.1007/s12020-021-02945-1 [doi] PST - ppublish SO - Endocrine. 2022 Mar;75(3):718-724. doi: 10.1007/s12020-021-02945-1. Epub 2022 Jan 4. PMID- 34957654 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 24 IP - 4 DP - 2022 Apr TI - Effect of upper gastrointestinal disease on the pharmacokinetics of oral semaglutide in subjects with type 2 diabetes. PG - 684-692 LID - 10.1111/dom.14632 [doi] AB - AIM: To investigate whether upper gastrointestinal (GI) disease has any effect on the exposure of oral semaglutide, an important consideration given that its absorption occurs primarily in the stomach. MATERIALS AND METHODS: In an open-label, parallel-group trial (NCT02877355), subjects aged 18-80 years with type 2 diabetes with mild-to-moderate upper GI disease (N = 36; chronic gastritis [n = 5], gastroesophageal reflux disease [n = 8], and both [n = 23]) or without upper GI disease (N = 19) received oral semaglutide 3 mg once daily for 5 days, followed by 7 mg for 5 days. The primary and key supportive endpoints were the area under the semaglutide plasma concentration-time curve (AUC) from 0 to 24 hours after last trial product administration on day 10 (AUC(0-24h,day10) ) and the maximum semaglutide plasma concentration (C(max,day10) ), respectively. RESULTS: Semaglutide exposure was not statistically significantly different between subjects with and without upper GI disease. Estimated group ratios (subjects with/without upper GI disease) were 1.18 (95% confidence interval [CI], 0.80, 1.75) for AUC(0-24h,day10) and 1.16 (95% CI, 0.77, 1.76) for C(max) . Time to C(max) and semaglutide half-life were similar in subjects with and without upper GI disease. Oral semaglutide was well tolerated; all adverse events were mild-to-moderate, with no withdrawals because of adverse events. CONCLUSIONS: There was no significant difference in exposure to oral semaglutide in subjects with or without upper GI disease, hence no dose adjustment is required. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Meier, Juris J AU - Meier JJ AUID- ORCID: 0000-0002-5835-8019 AD - Diabetes Division, Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. FAU - Granhall, Charlotte AU - Granhall C AD - Translational Medicine, Novo Nordisk A/S, Soborg, Denmark. FAU - Hoevelmann, Ulrike AU - Hoevelmann U AUID- ORCID: 0000-0002-0940-8972 AD - Profil, Neuss, Germany. FAU - Navarria, Andrea AU - Navarria A AD - Translational Medicine, Novo Nordisk A/S, Soborg, Denmark. FAU - Plum-Moerschel, Leona AU - Plum-Moerschel L AD - Profil, Mainz, Germany. FAU - Ramesh, Chethana AU - Ramesh C AD - Novo Nordisk Service Centre India Private Ltd, Novo Nordisk, Bangalore, India. FAU - Tannapfel, Andrea AU - Tannapfel A AD - Diabetes Division, Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. FAU - Kapitza, Christoph AU - Kapitza C AUID- ORCID: 0000-0002-9700-2373 AD - Profil, Neuss, Germany. LA - eng PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220117 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - *Diabetes Mellitus, Type 2/chemically induced/complications/drug therapy MH - *Gastrointestinal Diseases/chemically induced/drug therapy MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Middle Aged MH - Young Adult MH - Semaglutide OTO - NOTNLM OT - GLP-1RA OT - pharmacokinetics OT - type 2 diabetes EDAT- 2021/12/28 06:00 MHDA- 2022/04/01 06:00 CRDT- 2021/12/27 06:52 PHST- 2021/12/06 00:00 [revised] PHST- 2021/09/09 00:00 [received] PHST- 2021/12/22 00:00 [accepted] PHST- 2021/12/28 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/12/27 06:52 [entrez] AID - 10.1111/dom.14632 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Apr;24(4):684-692. doi: 10.1111/dom.14632. Epub 2022 Jan 17. PMID- 34949728 OWN - NLM STAT- MEDLINE DCOM- 20220328 LR - 20260127 IS - 1708-8267 (Electronic) IS - 1081-5589 (Linking) VI - 70 IP - 1 DP - 2022 Jan TI - Semaglutide 2.4 mg: the latest GLP-1RA approved for obesity. PG - 3-4 LID - 10.1136/jim-2021-002227 [doi] FAU - Villela, Ricardo AU - Villela R AD - Deparment of Medicine, National Autonomous University of Honduras, Tegucigalpa, Francisco Morazan, Honduras. FAU - Correa, Ricardo AU - Correa R AUID- ORCID: 0000-0003-2761-2907 AD - Department of Medicine, The University of Arizona College of Medicine - Phoenix and Phoenix VAMC, Phoenix, Arizona, USA riccorrea20@gmail.com. LA - eng PT - Editorial PL - England TA - J Investig Med JT - Journal of investigative medicine : the official publication of the American Federation for Clinical Research JID - 9501229 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides/*therapeutic use MH - Humans MH - Hypoglycemic Agents MH - Obesity/*drug therapy MH - Semaglutide OTO - NOTNLM OT - body weight OT - body weights and measures OT - glucagon-like peptide 1 OT - obesity COIS- Competing interests: None declared. EDAT- 2021/12/25 06:00 MHDA- 2022/03/29 06:00 CRDT- 2021/12/24 05:36 PHST- 2021/11/22 00:00 [accepted] PHST- 2021/12/24 05:36 [entrez] PHST- 2021/12/25 06:00 [pubmed] PHST- 2022/03/29 06:00 [medline] AID - 70/1/3 [pii] AID - 10.1136/jim-2021-002227 [doi] PST - ppublish SO - J Investig Med. 2022 Jan;70(1):3-4. doi: 10.1136/jim-2021-002227. PMID- 34942372 OWN - NLM STAT- MEDLINE DCOM- 20230404 LR - 20260127 IS - 1873-2615 (Electronic) IS - 1050-1738 (Print) IS - 1050-1738 (Linking) VI - 33 IP - 3 DP - 2023 Apr TI - Semaglutide for the treatment of obesity. PG - 159-166 LID - S1050-1738(21)00158-4 [pii] LID - 10.1016/j.tcm.2021.12.008 [doi] AB - Semaglutide is a glucagon-like peptide-1 receptor agonist that was recently approved by the US Food and Drug Administration for chronic weight management. This paper reviews data on the mechanism of action, weight-loss and cardiometabolic efficacy, and safety of semaglutide 2.4 mg/week for obesity. Semaglutide has demonstrated the largest weight loss of any obesity medication to date with reductions of approximately 15% of initial weight at 68 weeks, accompanied by improvements in cardiovascular risks factors and physical functioning. The approval of this medication provides patients with greater options for weight management. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Chao, Ariana M AU - Chao AM AD - University of Pennsylvania School of Nursing, Department of Biobehavioral Health Sciences; Perelman School of Medicine at the University of Pennsylvania, Department of Psychiatry. Electronic address: arichao@upenn.edu. FAU - Tronieri, Jena S AU - Tronieri JS AD - Perelman School of Medicine at the University of Pennsylvania, Department of Psychiatry. FAU - Amaro, Anastassia AU - Amaro A AD - Perelman School of Medicine at the University of Pennsylvania, Division of Endocrinology, Diabetes and Metabolism and Penn Metabolic Medicine. FAU - Wadden, Thomas A AU - Wadden TA AD - Perelman School of Medicine at the University of Pennsylvania, Department of Psychiatry. LA - eng GR - K23 NR017209/NR/NINR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review DEP - 20211221 PL - United States TA - Trends Cardiovasc Med JT - Trends in cardiovascular medicine JID - 9108337 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Trends Cardiovasc Med. 2023 Apr;33(3):167-169. doi: 10.1016/j.tcm.2021.12.018. PMID: 34999021 MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Obesity/diagnosis/drug therapy MH - Weight Loss MH - Hypoglycemic Agents/adverse effects MH - Semaglutide PMC - PMC9209591 MID - NIHMS1768574 EDAT- 2021/12/24 06:00 MHDA- 2023/04/04 06:42 PMCR- 2024/04/01 CRDT- 2021/12/23 20:16 PHST- 2021/08/31 00:00 [received] PHST- 2021/11/30 00:00 [revised] PHST- 2021/12/15 00:00 [accepted] PHST- 2023/04/04 06:42 [medline] PHST- 2021/12/24 06:00 [pubmed] PHST- 2021/12/23 20:16 [entrez] PHST- 2024/04/01 00:00 [pmc-release] AID - S1050-1738(21)00158-4 [pii] AID - 10.1016/j.tcm.2021.12.008 [doi] PST - ppublish SO - Trends Cardiovasc Med. 2023 Apr;33(3):159-166. doi: 10.1016/j.tcm.2021.12.008. Epub 2021 Dec 21. PMID- 34922691 OWN - NLM STAT- MEDLINE DCOM- 20220201 LR - 20220201 IS - 1548-5609 (Electronic) IS - 1548-5595 (Linking) VI - 28 IP - 4 DP - 2021 Jul TI - Kidney Outcomes With Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes. PG - 347-360 LID - S1548-5595(21)00038-0 [pii] LID - 10.1053/j.ackd.2021.04.005 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective in reducing glycemia in patients with type 2 diabetes (T2D). These medications effectively reduce cardiovascular (CV) risk in patients with T2D and established CV disease or with multiple risk factors. In addition, treatment with GLP-1 RA may exert protective effects on the diabetic kidney. Herein, we summarize the findings regarding the kidney safety and efficacy of GLP-1 RAs in patients with T2D. We review data from GLP-1 RAs phase 3 kidney studies, CV outcome trials, as well as real-world evidence. The accumulating data show that treatment with GLP-1 RAs is safe, well-tolerated, and effective in patients with different levels of kidney dysfunction. Furthermore, CV outcome trials suggest that GLP-1 RAs reduce albuminuria and may attenuate the decline in kidney function over time. The ongoing FLOW trial studying the effects of semaglutide in patients with diabetic kidney disease is expected to shed light on the effects of GLP-1 RAs on kidney outcomes and clarify their role in the management of patients with T2D and kidney disease. CI - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Faculty of Medicine, Hebrew University of Jerusalem, Israel; Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. Electronic address: ofrim@hadassah.org.il. FAU - Schechter, Meir AU - Schechter M AD - Faculty of Medicine, Hebrew University of Jerusalem, Israel; Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. FAU - Leibowitz, Gil AU - Leibowitz G AD - Faculty of Medicine, Hebrew University of Jerusalem, Israel; Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Jerusalem, Israel. LA - eng PT - Journal Article PT - Review PL - United States TA - Adv Chronic Kidney Dis JT - Advances in chronic kidney disease JID - 101209214 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Kidney OTO - NOTNLM OT - Albuminuria OT - Diabetic kidney disease OT - GLP-1 RAs OT - Kidney outcome trials OT - Type 2 diabetes EDAT- 2021/12/20 06:00 MHDA- 2022/02/02 06:00 CRDT- 2021/12/19 20:36 PHST- 2021/03/24 00:00 [received] PHST- 2021/04/14 00:00 [revised] PHST- 2021/04/23 00:00 [accepted] PHST- 2021/12/19 20:36 [entrez] PHST- 2021/12/20 06:00 [pubmed] PHST- 2022/02/02 06:00 [medline] AID - S1548-5595(21)00038-0 [pii] AID - 10.1053/j.ackd.2021.04.005 [doi] PST - ppublish SO - Adv Chronic Kidney Dis. 2021 Jul;28(4):347-360. doi: 10.1053/j.ackd.2021.04.005. PMID- 34922383 OWN - NLM STAT- MEDLINE DCOM- 20220420 LR - 20260127 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 107 IP - 5 DP - 2022 Apr 19 TI - An Indirect Treatment Comparison of Semaglutide 2.0 mg vs Dulaglutide 3.0 mg and 4.5 mg Using Multilevel Network Meta-regression. PG - 1461-1469 LID - 10.1210/clinem/dgab905 [doi] AB - AIMS: Currently, no head-to-head data are available comparing semaglutide 2.0 mg with dulaglutide 3.0 mg or 4.5 mg. We conducted an indirect treatment comparison (ITC) of their effects on glycated hemoglobin (HbA1c) and body weight in patients with type 2 diabetes. MATERIALS AND METHODS: Multilevel network meta-regression was conducted, based on a connected evidence network of published results from the A Study of the Efficacy and Safety of Dulaglutide (LY2189265) in Participants With Type 2 Diabetes 11 trial and individual patient data from the A Research Study to Compare Two Doses of Semaglutide Taken Once Weekly in People With Type 2 Diabetes (SUSTAIN) and SUSTAIN 7 trials. RESULTS: Semaglutide 2.0 mg significantly reduced HbA1c vs dulaglutide 3.0 mg and 4.5 mg, with estimated treatment differences (ETDs) of -0.44% points (95% credible interval [CrI], -0.68 to -0.19) and -0.28% points (95% CrI, -0.52 to -0.03), respectively. Semaglutide 2.0 mg also significantly reduced body weight vs dulaglutide 3.0 mg and 4.5 mg with ETDs of -3.29 kg (95% CrI, -4.62 to -1.96) and -2.57 kg (95% CrI, -3.90 to -1.24), respectively. Odds of achieving HbA1c < 7.0% were significantly greater for semaglutide 2.0 vs dulaglutide 3.0 mg (odds ratio [OR]: 2.23 [95% CrI, 1.15-3.90]), whereas this did not reach significance for semaglutide 2.0 mg vs dulaglutide 4.5 mg (OR: 1.58 [95% CrI, 0.82-2.78]). Sensitivity analyses supported the main analysis findings. CONCLUSIONS: This ITC demonstrated significantly greater reductions from baseline in HbA1c and body weight with semaglutide 2.0 mg vs dulaglutide 3.0 mg and 4.5 mg. The findings of this study provide important comparative effectiveness information until randomized head-to-head studies become available. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology, Department of Clinical Sciences, UT Southwestern Medical Center, University of Texas, Dallas, TX 75390, USA. FAU - Bauer, Robert AU - Bauer R AD - Novo Nordisk A/S, 2860 Soborg, Denmark. FAU - Baker-Knight, James AU - Baker-Knight J AUID- ORCID: 0000-0002-7936-9593 AD - Novo Nordisk A/S, 2860 Soborg, Denmark. FAU - Lawson, Jack AU - Lawson J AD - Novo Nordisk A/S, 2860 Soborg, Denmark. FAU - Pratley, Richard AU - Pratley R AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, FL 32804, USA. LA - eng GR - Novo Nordisk/ PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Body Weight MH - Clinical Trials as Topic MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - *Immunoglobulin Fc Fragments/adverse effects MH - *Recombinant Fusion Proteins/adverse effects MH - Semaglutide PMC - PMC9016460 OTO - NOTNLM OT - HbA1c OT - body weight OT - diabetes OT - dulaglutide OT - multilevel network meta regression OT - semaglutide EDAT- 2021/12/19 06:00 MHDA- 2022/04/21 06:00 PMCR- 2021/12/18 CRDT- 2021/12/18 20:35 PHST- 2021/10/08 00:00 [received] PHST- 2021/12/19 06:00 [pubmed] PHST- 2022/04/21 06:00 [medline] PHST- 2021/12/18 20:35 [entrez] PHST- 2021/12/18 00:00 [pmc-release] AID - 6469945 [pii] AID - dgab905 [pii] AID - 10.1210/clinem/dgab905 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2022 Apr 19;107(5):1461-1469. doi: 10.1210/clinem/dgab905. PMID- 34911560 OWN - NLM STAT- MEDLINE DCOM- 20220221 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 20 IP - 1 DP - 2021 Dec 15 TI - Oral GLP-1 analogue: perspectives and impact on atherosclerosis in type 2 diabetic patients. PG - 235 LID - 10.1186/s12933-021-01417-0 [doi] LID - 235 AB - Cardiovascular events related to atherosclerosis are responsible for high morbidity and mortality among patients with type 2 diabetes. Improvement in care, especially in early stages, is crucial. Oral semaglutide, a glucagon-like peptide 1 analogue, controls blood glucose and results in significant body weight loss in patients with type 2 diabetes. Beyond these well-known effects, an interesting aspect of this drug is its antiatherogenic activity, which should be further explored in clinical practice. This paper reviews the evidence related to oral semaglutide decreasing cardiovascular risk in patients with type 2 diabetes, focusing on the drug's antiatherosclerotic properties. The glucagon-like peptide 1 analogue restores endothelial dysfunction, induces vasodilatation, and reduces plasma lipids. Oral semaglutide showed cardiovascular safety profile, with significant reduced risk of death from cardiovascular events. Based on current data, clinicians should consider oral semaglutide for type 2 diabetes management. CI - (c) 2021. The Author(s). FAU - Saraiva, Jose Francisco Kerr AU - Saraiva JFK AD - Faculdade de Medicina do Centro de Ciencias da Vida - Pontificia, Universidade Catolica de Campinas, Av John Boyd Dunlop, s/n - Jd. Ipaussurama, Campinas, SP, CEP: 13060-904, Brazil. FAU - Franco, Denise AU - Franco D AD - CPCLIN/DASA Centro de Pesquisas Clinicas, Av Angelica, 2162 - Consolacao, Sao Paulo, SP, CEP: 01228-200, Brazil. d9franco@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20211215 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Administration, Oral MH - Animals MH - Atherosclerosis/diagnosis/*drug therapy/mortality MH - Biomarkers/blood MH - Blood Glucose/*drug effects/metabolism MH - Cause of Death MH - Diabetes Mellitus, Type 2/diagnosis/*drug therapy/mortality MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - *Glycemic Control/adverse effects MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Incretins/*administration & dosage/adverse effects MH - Risk Assessment MH - Risk Factors MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor PMC - PMC8675489 OTO - NOTNLM OT - Atherosclerosis OT - Cardiovascular disease OT - Diabetes OT - Glucagon-like peptide 1 OT - Oral semaglutide OT - Stroke prevention COIS- Dr. Jose Francisco Kerr Saraiva is the national leader of the SOUL and SELECT trials. He is part of the Novo Nordisk Global Expert Panel. He receives fees to give lectures by Novo Nordisk, Lilly, Novartis, Boehringer Ingelheim, Merck, and Sharp & Dohme. Dr. Denise Franco is the principal investigator in cardiovascular risk studies of oral and injectable semaglutide. She is part of the Novo Nordisk, Medtronic, Sanofi, Abbott, and Biomm advisory boards. She receives fees to give lectures by Novo Nordisk, Lilly, Novartis, AstraZeneca, Medtronic, Biomm, Sanofi, Abbott, and Roche. EDAT- 2021/12/17 06:00 MHDA- 2022/02/22 06:00 PMCR- 2021/12/15 CRDT- 2021/12/16 05:34 PHST- 2021/08/13 00:00 [received] PHST- 2021/11/07 00:00 [accepted] PHST- 2021/12/16 05:34 [entrez] PHST- 2021/12/17 06:00 [pubmed] PHST- 2022/02/22 06:00 [medline] PHST- 2021/12/15 00:00 [pmc-release] AID - 10.1186/s12933-021-01417-0 [pii] AID - 1417 [pii] AID - 10.1186/s12933-021-01417-0 [doi] PST - epublish SO - Cardiovasc Diabetol. 2021 Dec 15;20(1):235. doi: 10.1186/s12933-021-01417-0. PMID- 34903039 OWN - NLM STAT- MEDLINE DCOM- 20220310 LR - 20260127 IS - 1524-4539 (Electronic) IS - 0009-7322 (Print) IS - 0009-7322 (Linking) VI - 145 IP - 8 DP - 2022 Feb 22 TI - Effect of the Glucagon-Like Peptide-1 Receptor Agonists Semaglutide and Liraglutide on Kidney Outcomes in Patients With Type 2 Diabetes: Pooled Analysis of SUSTAIN 6 and LEADER. PG - 575-585 LID - 10.1161/CIRCULATIONAHA.121.055459 [doi] AB - BACKGROUND: We assessed the effect of once-weekly semaglutide and once-daily liraglutide on kidney outcomes in type 2 diabetes. METHODS: Pooled (n=12 637) and by-trial data from SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes; n=3297) and LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results; n=9340) were assessed for albuminuria change, annual slope of estimated glomerular filtration rate (eGFR) change, and time to persistent eGFR reduction (30%, 40%, 50%, and 57%) from baseline. RESULTS: The median follow-up durations were 2.1 years for SUSTAIN 6 and 3.8 years for LEADER. In the pooled analysis, semaglutide/liraglutide lowered albuminuria from baseline to 2 years after randomization by 24% versus placebo (95% CI, 20%-27%; P<0.001). Significant reductions were also observed in by-trial data analyses (P<0.001 for all), the largest being with semaglutide 1.0 mg (33% [95% CI, 24%-40%]; P<0.001) at 2 years. With semaglutide 1.0 mg and liraglutide, eGFR slope decline was significantly slowed by 0.87 and 0.26 mL/min/1.73 m(2)/y (P<0.0001 and P<0.001), respectively, versus placebo. Effects appeared larger in patients with baseline eGFR <60 versus >/=60 mL/min/1.73 m(2) (P(interaction)=0.06 and 0.008 for semaglutide 1.0 mg and liraglutide, respectively). Semaglutide/liraglutide significantly lowered risk of persistent 40% and 50% eGFR reductions versus placebo (hazard ratio [HR], 0.86 [95% CI, 0.75-0.99]; P=0.039 and HR, 0.80 [95% CI, 0.66-0.97]; P=0.023, respectively). Similar, nonsignificant, directional results were observed for 30% and 57% eGFR reductions (HR, 0.92 [95% CI, 0.84-1.02]; P=0.10 and HR, 0.89 [95% CI, 0.69-1.13]; P=0.34). In patients with baseline eGFR 30 to <60 mL/min/1.73 m(2), the likelihood of persistent reduction for all thresholds was increased, ranging from HR 0.71 for 30% reduction (95% CI, 0.59-0.85; P=0.0003, P(interaction)=0.017) to 0.54 for 57% reduction (95% CI, 0.36-0.81; P=0.003, P(interaction)=0.035). CONCLUSIONS: In patients with type 2 diabetes, semaglutide/liraglutide offered kidney-protective effects, which appeared more pronounced in patients with preexisting chronic kidney disease. FAU - Shaman, Ahmed M AU - Shaman AM AD - Sydney School of Public Health, University of Sydney, Australia (A.M.S.). AD - The George Institute for Global Health, The University of New South Wales, Sydney, Australia (A.M.S., V.P.). AD - College of Pharmacy, King Saud University, Riyadh, Saudi Arabia (A.M.S.). FAU - Bain, Stephen C AU - Bain SC AD - Institute of Life Science, Swansea University Medical School, Singleton Hospital, Swansea, United Kingdom (S.C.B.). FAU - Bakris, George L AU - Bakris GL AUID- ORCID: 0000-0003-1183-1267 AD - University of Chicago Medicine, IL (G.L.B.). FAU - Buse, John B AU - Buse JB AUID- ORCID: 0000-0002-9723-3876 AD - University of North Carolina School of Medicine, Chapel Hill (J.B.B.). FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark (T.I., S.R., B.W.). FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Stanford Center for Clinical Research (SCCR), Department of Medicine, Stanford School of Medicine, CA (K.W.M.). FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Center, Munich, Germany (J.F.E.M.). AD - Friedrich Alexander University, Erlangen, Germany (J.F.E.M.). FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes Division, Katholisches Klinikum Bochum, St Josef Hospital (Ruhr-Universitat Bochum), Bochum, Germany (M.A.N.). FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark (T.I., S.R., B.W.). FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark (P.R.). AD - Department of Clinical Medicine, University of Copenhagen, Denmark (P.R.). FAU - Wolthers, Benjamin AU - Wolthers B AD - Novo Nordisk A/S, Soborg, Denmark (T.I., S.R., B.W.). FAU - Zinman, Bernard AU - Zinman B AD - Lunenfeld-Tanenbaum Research Institute, Mt Sinai Hospital, University of Toronto, Canada (B.Z.). FAU - Perkovic, Vlado AU - Perkovic V AUID- ORCID: 0000-0002-4257-7620 AD - The George Institute for Global Health, The University of New South Wales, Sydney, Australia (A.M.S., V.P.). LA - eng GR - P30 DK124723/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20211214 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Albuminuria/prevention & control/urine MH - *Diabetes Mellitus, Type 2/drug therapy/urine MH - Female MH - Follow-Up Studies MH - Glomerular Filtration Rate/drug effects MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Humans MH - Liraglutide/*administration & dosage/adverse effects MH - Male MH - Middle Aged MH - Semaglutide PMC - PMC8860212 OTO - NOTNLM OT - albuminuria OT - chronic kidney disease OT - eGFR OT - glucagon-like peptide-1 receptor agonists OT - liraglutide OT - semaglutide OT - type 2 diabetes EDAT- 2021/12/15 06:00 MHDA- 2022/03/11 06:00 PMCR- 2022/02/21 CRDT- 2021/12/14 05:56 PHST- 2021/12/15 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] PHST- 2021/12/14 05:56 [entrez] PHST- 2022/02/21 00:00 [pmc-release] AID - 10.1161/CIRCULATIONAHA.121.055459 [doi] PST - ppublish SO - Circulation. 2022 Feb 22;145(8):575-585. doi: 10.1161/CIRCULATIONAHA.121.055459. Epub 2021 Dec 14. PMID- 34894326 OWN - NLM STAT- MEDLINE DCOM- 20220114 LR - 20261012 IS - 1179-1918 (Electronic) IS - 1173-2563 (Linking) VI - 42 IP - 1 DP - 2022 Jan TI - Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials. PG - 17-28 LID - 10.1007/s40261-021-01110-w [doi] AB - BACKGROUND: Semaglutide is a recently approved glucagon-like peptide-1 receptor agonist used to treat patients with type 2 diabetes mellitus (T2DM). The SUSTAIN 6 trial found a significantly higher rate of retinopathy complications in the semaglutide-treated group compared with the placebo group. OBJECTIVE: This study aimed to evaluate the association between semaglutide and the risk of retinopathy in patients with T2DM. METHODS: Electronic databases were systematically searched up to April 2021 to identify randomized controlled trials that reported diabetic retinopathy (DR) events in semaglutide-treated and control groups. A meta-analysis was conducted using Review Manager 5.4 software to calculate the risk ratio (RR) and 95% confidence intervals (CIs). RESULTS: A total of 23 randomized trials involving 22,096 patients with T2DM were included. There were 730 incident DR cases-463 in the semaglutide group and 267 in the control group. Overall, semaglutide was not associated with increased DR risk compared with controls when all trials were combined (RR 1.14, 95% CI 0.98-1.33). Subgroup analysis showed that semaglutide was associated with an increased risk of DR compared with placebo (RR 1.24, 95% CI 1.03-1.50). Moreover, patient age >/= 60 years and diabetes duration >/= 10 years were also factors for increased risk of DR when using semaglutide (RR 1.27, 95% CI 1.02-1.59; RR 1.28, 95% CI 1.04-1.58, respectively). CONCLUSIONS: Semaglutide was not associated with an increased risk of DR; however, caution regarding DR risk is needed for older patients or those with long diabetes duration when taking semaglutide. CI - (c) 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG. FAU - Wang, Feiyu AU - Wang F AD - Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Chazhong Road No. 20, Fuzhou, 350005, China. FAU - Mao, Yinjun AU - Mao Y AD - Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Chazhong Road No. 20, Fuzhou, 350005, China. FAU - Wang, Hang AU - Wang H AD - Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Chazhong Road No. 20, Fuzhou, 350005, China. FAU - Liu, Yiwei AU - Liu Y AD - Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Chazhong Road No. 20, Fuzhou, 350005, China. FAU - Huang, Pinfang AU - Huang P AUID- ORCID: 0000-0002-2699-9663 AD - Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Chazhong Road No. 20, Fuzhou, 350005, China. abstract2016@163.com. LA - eng GR - 2018QH1071/the Startup Fund for Scientific Research, Fujian Medical University/ GR - JT180186/Fujian Youth Education Research Project/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20211211 PL - New Zealand TA - Clin Drug Investig JT - Clinical drug investigation JID - 9504817 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy/epidemiology MH - *Diabetic Retinopathy/chemically induced/diagnosis/drug therapy MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Middle Aged MH - Randomized Controlled Trials as Topic MH - Semaglutide EDAT- 2021/12/12 06:00 MHDA- 2022/01/15 06:00 CRDT- 2021/12/11 12:11 PHST- 2021/11/24 00:00 [accepted] PHST- 2021/12/12 06:00 [pubmed] PHST- 2022/01/15 06:00 [medline] PHST- 2021/12/11 12:11 [entrez] AID - 10.1007/s40261-021-01110-w [pii] AID - 10.1007/s40261-021-01110-w [doi] PST - ppublish SO - Clin Drug Investig. 2022 Jan;42(1):17-28. doi: 10.1007/s40261-021-01110-w. Epub 2021 Dec 11. PMID- 34889083 OWN - NLM STAT- MEDLINE DCOM- 20220506 LR - 20250103 IS - 2163-8306 (Electronic) IS - 2163-8306 (Linking) VI - 11 IP - 3 DP - 2022 Mar TI - A novel integrated QSP model of in vivo human glucose regulation to support the development of a glucagon/GLP-1 dual agonist. PG - 302-317 LID - 10.1002/psp4.12752 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) and dual GLP-1/glucagon receptor agonists improve glycaemic control and cause significant weight loss in patients with type 2 diabetes.(1) These effects are driven in part by augmenting glucose-stimulated insulin release (incretin effect), reducing caloric intake and delayed gastric emptying. We developed and externally validated a novel integrated quantitative systems pharmacology (QSP) model to gain quantitative insight into the relative contributions and mechanisms of drugs modulating glucose regulatory pathways. This model (4GI model) incorporates known feedback mechanisms among glucose, GLP-1, glucagon, glucose-dependent insulinotropic peptide (GIP), and insulin after glucose provocation (i.e., food intake) and drug intervention utilizing published nonpharmacological and pharmacological (liraglutide, a GLP-1RA) data. The resulting model accurately describes the aforementioned mechanisms and independently predicts the effects of the GLP-1RAs (dulaglutide and semaglutide) on system dynamics. Therefore, the validated 4GI model represents a quantitative decision-making tool to support the advancement of novel therapeutics and combination strategies modulating these pathways. CI - (c) 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. FAU - Bosch, Rolien AU - Bosch R AD - LAP&P Consultants, Leiden, The Netherlands. FAU - Petrone, Marcella AU - Petrone M AD - Clinical Pharmacology and Safety Sciences, AstraZeneca, Cambridge, UK. FAU - Arends, Rosalin AU - Arends R AD - AstraZeneca, Gaithersburg, Maryland, USA. FAU - Vicini, Paolo AU - Vicini P AD - Clinical Pharmacology and Safety Sciences, AstraZeneca, Cambridge, UK. FAU - Sijbrands, Eric J G AU - Sijbrands EJG AD - Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. FAU - Hoefman, Sven AU - Hoefman S AD - LAP&P Consultants, Leiden, The Netherlands. FAU - Snelder, Nelleke AU - Snelder N AD - LAP&P Consultants, Leiden, The Netherlands. LA - eng PT - Journal Article DEP - 20211224 PL - United States TA - CPT Pharmacometrics Syst Pharmacol JT - CPT: pharmacometrics & systems pharmacology JID - 101580011 RN - 0 (Blood Glucose) RN - 0 (Insulin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9007-92-5 (Glucagon) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon MH - *Glucagon-Like Peptide 1 MH - Glucose/metabolism MH - Humans MH - Insulin MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC8923724 COIS- R.B., S.H., and N.S. are consultants at LAP&P. M.P. and R.A. are AstraZeneca employees and shareholders. P.V. was an employee of MedImmune/AstraZeneca at the time of the conduct of this work, and is currently an employee of ConfoTherapeutics. Confo Therapeutics had no role in the conduct of this work or the writing of this manuscript. E.J.G.S. declared no competing interests for this work. EDAT- 2021/12/11 06:00 MHDA- 2022/05/07 06:00 PMCR- 2022/03/01 CRDT- 2021/12/10 07:20 PHST- 2021/10/12 00:00 [revised] PHST- 2020/11/18 00:00 [received] PHST- 2021/09/23 00:00 [accepted] PHST- 2021/12/11 06:00 [pubmed] PHST- 2022/05/07 06:00 [medline] PHST- 2021/12/10 07:20 [entrez] PHST- 2022/03/01 00:00 [pmc-release] AID - PSP412752 [pii] AID - 10.1002/psp4.12752 [doi] PST - ppublish SO - CPT Pharmacometrics Syst Pharmacol. 2022 Mar;11(3):302-317. doi: 10.1002/psp4.12752. Epub 2021 Dec 24. PMID- 34881835 OWN - NLM STAT- MEDLINE DCOM- 20211210 LR - 20260127 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 76 IP - 12 DP - 2021 Dec TI - [Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus(R))]. PG - 896-903 AB - Oral semaglutide (Rybelsus(R)) is a co-formulation of semaglutide, a glucagon-like peptide-1 (GLP-1 RA) receptor agonist, with an absorption enhancer, sodium N- (8- [2- hydroxybenzoyl] amino) caprylate (SNAC), which facilitates the absorption of semaglutide across the gastric epithelium in a concentration dependent manner. The safety and efficacy of oral semaglutide were assessed in the PIONEER clinical trial programme, which included 9543 patients with type 2 diabetes (T2DM). Across a range of different T2DM patients receiving different background medications, oral semaglutide provides more effective glycaemic control than common oral glucose-lowering therapies, associated with a clinically relevant reduction in body weight, including in patients with more advanced T2DM on insulin treatment. The tolerability profile for oral semaglutide was consistent with the other GLP-1 RAs. Cardiovascular (CV) safety of oral semaglutide was noninferior to placebo in CV high-risk patients. Available in three doses (3, 7 and 14 mg) to be gradually increased, Rybelsus(R) is currently reimbursed in Belgium after failure of antidiabetic treatment (including metformin; HbA1C superior to 7.5 % or 58 mmol/mol) in T2DM patients with a body mass index ? 30 kg/m(2). FAU - Paquot, N AU - Paquot N AD - Service de Diabetologie, Nutrition et Maladies metaboliques, CHU Liege, Belgique. LA - fre PT - Journal Article PT - Randomized Controlled Trial TT - Le medicament du mois. Le semaglutide oral, premier agoniste des recepteurs du GLP-1 administre par voie orale (Rybelsus(R)). PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Semaglutide OTO - NOTNLM OT - Cardiovascular safety OT - Obesity - Glucagon OT - Semaglutide OT - Type 2 diabetes OT - 1 OT - Oral administration OT - like peptide EDAT- 2021/12/10 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/12/09 08:42 PHST- 2021/12/09 08:42 [entrez] PHST- 2021/12/10 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PST - ppublish SO - Rev Med Liege. 2021 Dec;76(12):896-903. PMID- 34866313 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 24 IP - 4 DP - 2022 Apr TI - Once-weekly semaglutide for obesity or overweight: A systematic review and meta-analysis. PG - 722-726 LID - 10.1111/dom.14612 [doi] FAU - He, Ke AU - He K AUID- ORCID: 0000-0002-7471-8029 AD - Department of Pharmacy, The Fourth Hospital of Shijiazhuang/Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, China. FAU - Guo, Qing AU - Guo Q AD - Department of Obstetrics and Gynecology, The Fourth Hospital of Shijiazhuang/Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, China. FAU - Zhang, Haijuan AU - Zhang H AD - Department of Obstetrics and Gynecology, The Fourth Hospital of Shijiazhuang/Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, China. FAU - Xi, Wang AU - Xi W AD - Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Li, Jingxin AU - Li J AD - Department of Chinese Pharmacy, Hebei Maternity Hospital, Shijiazhuang, China. FAU - Jing, Zeng AU - Jing Z AD - Department of Pharmacy, The Fourth Hospital of Shijiazhuang/Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, China. LA - eng PT - Letter PT - Meta-Analysis PT - Systematic Review DEP - 20211220 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Obesity/drug therapy MH - *Overweight/complications/drug therapy MH - Semaglutide OTO - NOTNLM OT - meta-analysis OT - obesity OT - overweight OT - randomized controlled trials OT - semaglutide EDAT- 2021/12/07 06:00 MHDA- 2022/04/01 06:00 CRDT- 2021/12/06 06:15 PHST- 2021/11/12 00:00 [revised] PHST- 2021/09/07 00:00 [received] PHST- 2021/12/01 00:00 [accepted] PHST- 2021/12/07 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/12/06 06:15 [entrez] AID - 10.1111/dom.14612 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Apr;24(4):722-726. doi: 10.1111/dom.14612. Epub 2021 Dec 20. PMID- 34865050 OWN - NLM STAT- MEDLINE DCOM- 20220415 LR - 20240923 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 107 IP - 4 DP - 2022 Mar 24 TI - New Horizons. A New Paradigm for Treating to Target with Second-Generation Obesity Medications. PG - e1339-e1347 LID - 10.1210/clinem/dgab848 [doi] AB - In treating obesity as a chronic disease, the essential goal of weight loss therapy is not the quantity of weight loss as an end unto itself but rather the prevention and treatment of complications to enhance health and mitigate morbidity and mortality. This perspective on obesity care is consistent with the complications-centric American Association of Clinical Endocrinology (AACE) obesity guidelines and the diagnostic term of adiposity-based chronic disease (ABCD). Many complications require 10% to 20% weight loss to achieve therapeutic goals; however, existing obesity medications fail to produce >/=10% weight loss in the majority of patients. In June, 2021, semaglutide 2.4 mg/week was approved for chronic weight management. Phase 3 clinical trials demonstrated that this medication produced > 10% placebo-subtracted weight loss, more than half of patents lost >/=15%, and over one third lost >/=20% of baseline weight. This essentially doubles effectiveness over existing obesity medications, provides sufficient weight loss to ameliorate a broad range of complications, and qualifies as the first member of a second-generation class of obesity medications. The advent of second-generation medications fully enables a treat-to-target approach for management of ABCD as a chronic disease. Specifically, with this degree of efficacy, second-generation medications permit active management of body weight as a biomarker to targets associated with effective treatment and prevention of specific complications. ABCD can now be managed similar to other chronic diseases such as type 2 diabetes, hypertension, and atherosclerosis, which are treated to biomarker targets that can be modified based on the clinical status of individual patients [ie, hemoglobin A1c (HbA1c), blood pressure, and low-density lipoprotein cholesterol (LDL-c)] to prevent the respective complications of these diseases. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Garvey, W Timothy AU - Garvey WT AUID- ORCID: 0000-0003-0822-0860 AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA. LA - eng GR - P30 DK056336/DK/NIDDK NIH HHS/United States GR - P30 DK079626/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 SB - IM MH - Chronic Disease MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Endocrinology MH - Humans MH - Obesity/drug therapy MH - Weight Loss PMC - PMC8947217 OTO - NOTNLM OT - anti-obesity medications OT - chronic disease OT - obesity OT - obesity complications EDAT- 2021/12/06 06:00 MHDA- 2022/04/16 06:00 PMCR- 2021/12/05 CRDT- 2021/12/05 21:43 PHST- 2021/10/06 00:00 [received] PHST- 2021/12/06 06:00 [pubmed] PHST- 2022/04/16 06:00 [medline] PHST- 2021/12/05 21:43 [entrez] PHST- 2021/12/05 00:00 [pmc-release] AID - 6453059 [pii] AID - dgab848 [pii] AID - 10.1210/clinem/dgab848 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1339-e1347. doi: 10.1210/clinem/dgab848. PMID- 34861327 OWN - NLM STAT- MEDLINE DCOM- 20220323 LR - 20260127 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 147 DP - 2022 Jan TI - Dual-agonist incretin peptides from fish with potential for obesity-related Type 2 diabetes therapy - A review. PG - 170706 LID - S0196-9781(21)00214-X [pii] LID - 10.1016/j.peptides.2021.170706 [doi] AB - The long-acting glucagon-like peptide-1 receptor (GLP1R) agonist, semaglutide and the unimolecular glucose-dependent insulinotropic polypeptide receptor (GIPR)/GLP1R dual-agonist, tirzepatide have been successfully introduced as therapeutic options for patients with Type-2 diabetes (T2DM) and obesity. Proglucagon-derived peptides from phylogenetically ancient fish act as naturally occurring dual agonists at the GLP1R and the glucagon receptor (GCGR) with lamprey GLP-1 and paddlefish glucagon being the most potent and effective in stimulating insulin release from BRIN-BD11 clonal beta-cells. These peptides were also the most effective in lowering blood glucose and elevating plasma insulin concentrations when administered intraperitoneally to overnight-fasted mice together with a glucose load. Zebrafish GIP acts as a dual agonist at the GIPR and GLP1R receptors. Studies with the high fat-fed mouse, an animal model with obesity, impaired glucose-tolerance and insulin-resistance, have shown that twice-daily administration of the long-acting analogs [D-Ala(2)]palmitoyl-lamprey GLP-1 and [D-Ser(2)]palmitoyl-paddlefish glucagon over 21 days improves glucose tolerance and insulin sensitivity. This was associated with beta-cell proliferation, protection of beta-cells against apoptosis, decreased pancreatic glucagon content, improved lipid profile, reduced food intake and selective alteration in the expression of genes involved in beta-cell stimulus-secretion coupling. In insulin-deficient Glu(CreERT2);ROSA26-eYFP transgenic mice, the peptides promoted an increase in beta-cell mass with positive effects on transdifferentiation of glucagon-producing to insulin-producing cells. Naturally occurring fish dual agonist peptides, particularly lamprey GLP-1 and paddlefish glucagon, provide templates for development into therapeutic agents for obesity-related T2DM. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Conlon, J Michael AU - Conlon JM AD - Diabetes Research Group, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, UK. Electronic address: jmconlon1@gmail.com. FAU - O'Harte, Finbarr P M AU - O'Harte FPM AD - Diabetes Research Group, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, UK. FAU - Flatt, Peter R AU - Flatt PR AD - Diabetes Research Group, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, Northern Ireland, UK. LA - eng PT - Journal Article PT - Review DEP - 20211130 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Anti-Obesity Agents) RN - 0 (Fish Proteins) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - IY9XDZ35W2 (Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 55963-74-1 (Proglucagon) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Animals MH - Anti-Obesity Agents/pharmacology MH - Diabetes Mellitus, Type 2/*drug therapy/etiology MH - Eating/drug effects MH - Fish Proteins/*pharmacology MH - Glucagon-Like Peptide 1/agonists MH - Glucose/metabolism MH - Humans MH - Hypoglycemic Agents/pharmacology MH - Incretins/*agonists/pharmacology MH - Insulin Resistance MH - Obesity/complications/*drug therapy MH - Proglucagon/chemistry MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Dogfish glucagon OT - Dual agonist OT - Lamprey GLP-1 OT - Obesity OT - Paddlefish glucagon OT - Type 2 diabetes EDAT- 2021/12/04 06:00 MHDA- 2022/03/24 06:00 CRDT- 2021/12/03 20:13 PHST- 2021/10/20 00:00 [received] PHST- 2021/11/28 00:00 [revised] PHST- 2021/11/29 00:00 [accepted] PHST- 2021/12/04 06:00 [pubmed] PHST- 2022/03/24 06:00 [medline] PHST- 2021/12/03 20:13 [entrez] AID - S0196-9781(21)00214-X [pii] AID - 10.1016/j.peptides.2021.170706 [doi] PST - ppublish SO - Peptides. 2022 Jan;147:170706. doi: 10.1016/j.peptides.2021.170706. Epub 2021 Nov 30. PMID- 34852347 OWN - NLM STAT- MEDLINE DCOM- 20231207 LR - 20250103 IS - 1663-2826 (Electronic) IS - 1663-2818 (Linking) VI - 96 IP - 6 DP - 2023 TI - Glucagon-Like Peptide-1 Receptor Agonists in the Treatment of Obesity. PG - 599-608 LID - 10.1159/000521264 [doi] AB - BACKGROUND: Obesity treatment based on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) proved to limit morbidity and mortality in adult population. In children, optimizing lifestyle intervention (LSI) and reducing culpable environmental exposures represent the mainstay strategy for obesity prevention and management. However, there remains a subset of children and adolescents whose obesity is resistant to lifestyle approach. For these poor responders, the need for safe and effective weight-reducing agents is apparent. The purpose of this review is to provide an overview of the efficacy and safety of approved GLP-1 RA in the management of adult and pediatric obesity. SUMMARY: We presented the main outcomes of clinical trial programs called SCALE and STEP that supported a market authorization approval for liraglutide and semaglutide for the treatment of obesity in adult population. Then, we summarized the studies on the efficacy of GLP-1 RA in pediatric obesity that have been accumulating from 2 larger studies with liraglutide and few other smaller studies with exenatide and liraglutide. The results indicate that GLP-1 RA is safe, tolerable, and effective in reducing weight and also in improving cardiometabolic profile in children with obesity and poor response to LSI alone. At present, liraglutide is the first and so far the only GLP-1 RA that received FDA approval in 2020 for use in children aged 12-17 years with obesity. New trials including semaglutide for pediatric obesity are ongoing. KEY MESSAGES: There is a strong interest in current use and further development of obesity treatments based on glucagon-like peptide-1 (GLP-1) agonism. In adolescents with obesity, who are poor responders to lifestyle approach, the use of GLP-1 RA as an adjunct to LSI is effective and safe. Due to limited experience, a general recommendation is to prioritize long acting over short acting GLP-1 RA because they are approved for the treatment of obesity and have better tolerability, safety, and treatment response effect. In the future research, more high-grade evidence including novel iterations of GLP-1 agonism and long-term follow-ups are needed in pediatric population. CI - (c) 2021 S. Karger AG, Basel. FAU - Jensterle, Mojca AU - Jensterle M AD - Department of Endocrinology, Diabetes and Metabolic Disease, University Medical Centre Ljubljana, Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. FAU - Janez, Andrej AU - Janez A AD - Department of Endocrinology, Diabetes and Metabolic Disease, University Medical Centre Ljubljana, Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. LA - eng PT - Journal Article PT - Review DEP - 20211201 PL - Switzerland TA - Horm Res Paediatr JT - Hormone research in paediatrics JID - 101525157 RN - 839I73S42A (Liraglutide) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Child MH - Humans MH - Adolescent MH - Liraglutide/therapeutic use MH - Hypoglycemic Agents/therapeutic use MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Pediatric Obesity/drug therapy MH - Glucagon-Like Peptide 1/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Adolescents OT - Glucagon-like peptide-1 OT - Liraglutide OT - Obesity OT - Semaglutide EDAT- 2021/12/02 06:00 MHDA- 2023/12/07 12:42 CRDT- 2021/12/01 20:10 PHST- 2021/10/01 00:00 [received] PHST- 2021/11/28 00:00 [accepted] PHST- 2023/12/07 12:42 [medline] PHST- 2021/12/02 06:00 [pubmed] PHST- 2021/12/01 20:10 [entrez] AID - 000521264 [pii] AID - 10.1159/000521264 [doi] PST - ppublish SO - Horm Res Paediatr. 2023;96(6):599-608. doi: 10.1159/000521264. Epub 2021 Dec 1. PMID- 34841893 OWN - NLM STAT- MEDLINE DCOM- 20220321 LR - 20260127 IS - 2042-6313 (Electronic) IS - 2042-6305 (Linking) VI - 11 IP - 1 DP - 2022 Jan TI - The cost-effectiveness of oral semaglutide versus empagliflozin in Type 2 diabetes in Denmark. PG - 29-37 LID - 10.2217/cer-2021-0169 [doi] AB - Aim: To evaluate the cost-effectiveness of oral semaglutide+metformin versus empagliflozin+metformin in people with Type 2 diabetes uncontrolled on msetformin alone. Materials and methods: The IQVIA Core Diabetes Model was populated with efficacy data from a head-to-head study between oral semaglutide+metformin and empagliflozin+metformin. Danish costs and quality-of-life data were sourced from literature. Price per day was Danish Krone (DKK) 25.53 for oral semaglutide and DKK11.40 for empagliflozin. Discounting was fixed at 4%. Scenario and sensitivity analyses were performed. Results: Over a lifetime, Core Diabetes Model projected 8.78 and 8.75 quality-adjusted life-years and a total cost of DKK 447,633 and DKK 387,786, thereby generating an incremental cost-effectiveness ratio of DKK 1,930,548 for oral semaglutide+metformin versus empagliflozin+metformin. Scenario and sensitivity analyses showed the robustness of the outcomes. Duration of treatment with oral semaglutide is the key driver of the analyses. Conclusion: Oral semaglutide+metformin seems not cost effective versus empagliflozin+metformin in patients uncontrolled on metformin in Denmark. FAU - Ehlers, Lars H AU - Ehlers LH AUID- ORCID: 0000-0002-9521-9931 AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. FAU - Lamotte, Mark AU - Lamotte M AD - IQVIA Real World Evidence Solutions, Zaventem 1930, Belgium. FAU - Ramos, Mafalda C AU - Ramos MC AUID- ORCID: 0000-0002-8472-3841 AD - IQVIA Global HEOR, Porto Salvo 2740-266, Portugal. FAU - Sandgaard, Susanne AU - Sandgaard S AUID- ORCID: 0000-0002-9607-7103 AD - Boehringer Ingelheim Denmark A/S, Copenhagen, Denmark. FAU - Holmgaard, Pia AU - Holmgaard P AUID- ORCID: 0000-0003-2137-9673 AD - Boehringer Ingelheim Denmark A/S, Copenhagen, Denmark. FAU - Frary, Evan C AU - Frary EC AUID- ORCID: 0000-0001-5998-2086 AD - Boehringer Ingelheim Denmark A/S, Copenhagen, Denmark. FAU - Ejskjaer, Niels AU - Ejskjaer N AUID- ORCID: 0000-0003-3749-3403 AD - Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. AD - Steno Diabetes Centre North Denmark, Aalborg University Hospital, Aalborg, Denmark. AD - Department of Endocrinology, Aalborg University Hospital, Aalborg 9000, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211129 PL - England TA - J Comp Eff Res JT - Journal of comparative effectiveness research JID - 101577308 RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Benzhydryl Compounds MH - Cost-Benefit Analysis MH - Denmark MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Glucosides MH - Humans MH - Hypoglycemic Agents MH - Semaglutide OTO - NOTNLM OT - Denmark OT - GLP-1 receptor agonists OT - SGLT-2 inhibitors OT - costs and cost analysis OT - cost-effectiveness OT - diabetes mellitus OT - empagliflozin OT - oral semaglutide OT - treatment intensification EDAT- 2021/11/30 06:00 MHDA- 2022/03/22 06:00 CRDT- 2021/11/29 08:46 PHST- 2021/11/30 06:00 [pubmed] PHST- 2022/03/22 06:00 [medline] PHST- 2021/11/29 08:46 [entrez] AID - 10.2217/cer-2021-0169 [doi] PST - ppublish SO - J Comp Eff Res. 2022 Jan;11(1):29-37. doi: 10.2217/cer-2021-0169. Epub 2021 Nov 29. PMID- 34772713 OWN - NLM STAT- MEDLINE DCOM- 20211213 LR - 20260127 IS - 1715-5258 (Electronic) IS - 0008-350X (Print) IS - 0008-350X (Linking) VI - 67 IP - 11 DP - 2021 Nov TI - Semaglutide for weight loss. PG - 842 LID - 10.46747/cfp.6711842 [doi] FAU - Ojeniran, Mo AU - Ojeniran M AD - Student pharmacist in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta in Edmonton. FAU - Dube, Betty AU - Dube B AD - Student pharmacist in the Faculty of Pharmacy and Pharmaceutical Sciences at the University of Alberta in Edmonton. FAU - Paige, Allison AU - Paige A AD - Medical Lead of Kildonan Medical Centre at Seven Oaks General Hospital in Winnipeg and Lecturer at the University of Manitoba. FAU - Ton, Joey AU - Ton J AD - Clinical Evidence Expert for the CFPC. FAU - Lindblad, Adrienne J AU - Lindblad AJ AD - Clinical Evidence Expert for the CFPC. LA - eng PT - Journal Article PL - Canada TA - Can Fam Physician JT - Canadian family physician Medecin de famille canadien JID - 0120300 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Weight Loss MH - Semaglutide PMC - PMC8589135 EDAT- 2021/11/14 06:00 MHDA- 2021/12/15 06:00 PMCR- 2021/11/01 CRDT- 2021/11/13 05:43 PHST- 2021/11/13 05:43 [entrez] PHST- 2021/11/14 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/11/01 00:00 [pmc-release] AID - 67/11/842 [pii] AID - 10.46747/cfp.6711842 [doi] PST - ppublish SO - Can Fam Physician. 2021 Nov;67(11):842. doi: 10.46747/cfp.6711842. PMID- 34728099 OWN - NLM STAT- MEDLINE DCOM- 20220128 LR - 20260127 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 43 IP - 11 DP - 2021 Nov TI - Lifetime Cost-effectiveness of Oral Semaglutide Versus Dulaglutide and Liraglutide in Patients With Type 2 Diabetes Inadequately Controlled With Oral Antidiabetics. PG - 1812-1826.e7 LID - S0149-2918(21)00314-3 [pii] LID - 10.1016/j.clinthera.2021.08.015 [doi] AB - PURPOSE: To estimate the incremental cost-utility ratio of oral semaglutide (14 mg once daily) vs other glucagon-like peptide 1 receptor agonist treatments among adults with type 2 diabetes that was inadequately controlled with 1 to 2 oral antidiabetic drugs from a US payer perspective. METHODS: A state-transition model with a competing risk approach was developed for diabetic complications and risk of cardiovascular events based on the UK Prospective Diabetes Study Outcomes Model 1 equations. Baseline population characteristics reflect the PIONEER 4 trial (Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus) of oral semaglutide. Model comparators included subcutaneous semaglutide, dulaglutide, and liraglutide. Treatment effects (change in glycosylated hemoglobin, weight, and systolic blood pressure) were estimated by network meta-analysis. Drug, management, and event costs (in 2019 US dollars), survival after nonfatal events, and utilities were obtained from the literature. Costs and quality-adjusted life-year (QALY) outcomes were discounted at 3% annually over a lifetime horizon. Probabilistic and 1-way sensitivity analyses were performed. FINDINGS: Total estimated costs and QALYs were $144,065 and 12.98 for oral semaglutide, $145,721 and 12.96 for dulaglutide, $145,833 and 12.99 for SC semaglutide, and $149,428 and 12.97 for liraglutide, respectively. Oral semaglutide was less costly and more effective than dulaglutide and liraglutide but less costly than subcutaneous semaglutide with similar effectiveness. Oral semaglutide was favored versus subcutaneous semaglutide in 52.10% of model replications at a willingness-to-pay of $150,000 per QALY. IMPLICATIONS: Oral semaglutide is predicted to offer health benefits similar to subcutaneous semaglutide and ahead of dulaglutide and liraglutide. Oral semaglutide is a cost-effective glucagon-like peptide 1 receptor agonist treatment option. CI - Copyright (c) 2021. Published by Elsevier Inc. FAU - Risebrough, Nancy A AU - Risebrough NA AD - ICON plc, Toronto, Ontario, Canada. Electronic address: Nancy.Risebrough@iconplc.com. FAU - Baker, Timothy M AU - Baker TM AD - ICON plc, New York, New York. FAU - Zhang, Lirong AU - Zhang L AD - ICON plc, Oxfordshire, United Kingdom. FAU - Ali, Sarah N AU - Ali SN AD - Novo Nordisk Inc, Plainsboro Township, New Jersey. FAU - Radin, Michael AU - Radin M AD - Novo Nordisk Inc, Plainsboro Township, New Jersey. FAU - Dang-Tan, Tam AU - Dang-Tan T AD - Novo Nordisk Inc, Plainsboro Township, New Jersey. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20211031 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Adult MH - Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/analogs & derivatives MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Immunoglobulin Fc Fragments MH - *Liraglutide MH - Prospective Studies MH - Recombinant Fusion Proteins MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - cost utility OT - diabetes OT - model OT - semaglutide EDAT- 2021/11/04 06:00 MHDA- 2022/01/29 06:00 CRDT- 2021/11/03 05:48 PHST- 2021/03/11 00:00 [received] PHST- 2021/07/15 00:00 [revised] PHST- 2021/08/30 00:00 [accepted] PHST- 2021/11/04 06:00 [pubmed] PHST- 2022/01/29 06:00 [medline] PHST- 2021/11/03 05:48 [entrez] AID - S0149-2918(21)00314-3 [pii] AID - 10.1016/j.clinthera.2021.08.015 [doi] PST - ppublish SO - Clin Ther. 2021 Nov;43(11):1812-1826.e7. doi: 10.1016/j.clinthera.2021.08.015. Epub 2021 Oct 31. PMID- 34724396 OWN - NLM STAT- MEDLINE DCOM- 20211130 LR - 20260127 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 174 IP - 11 DP - 2021 Nov TI - In type 2 diabetes, tirzepatide reduced HbA(1c) vs. semaglutide. PG - JC127 LID - 10.7326/ACPJ202111160-127 [doi] AB - Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503-15. 34170647. FAU - Gandhi, Gunjan Y AU - Gandhi GY AD - University of Florida College of Medicine, Jacksonville, Florida, USA (G.Y.G.). LA - eng PT - Comment PT - Journal Article DEP - 20211102 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - OYN3CCI6QE (Tirzepatide) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. PMID: 34170647 MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Tirzepatide MH - Semaglutide EDAT- 2021/11/02 06:00 MHDA- 2021/12/01 06:00 CRDT- 2021/11/01 17:20 PHST- 2021/11/02 06:00 [pubmed] PHST- 2021/12/01 06:00 [medline] PHST- 2021/11/01 17:20 [entrez] AID - 10.7326/ACPJ202111160-127 [doi] PST - ppublish SO - Ann Intern Med. 2021 Nov;174(11):JC127. doi: 10.7326/ACPJ202111160-127. Epub 2021 Nov 2. PMID- 34721294 OWN - NLM STAT- MEDLINE DCOM- 20220215 LR - 20250623 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 12 DP - 2021 TI - Effects of Anti-Diabetic Drugs on Fracture Risk: A Systematic Review and Network Meta-Analysis. PG - 735824 LID - 10.3389/fendo.2021.735824 [doi] LID - 735824 AB - PURPOSE: Available data on the effects of anti-diabetic drugs on fracture risk are contradictory. Therefore, our study aimed to analyze all available data on the effects of anti-diabetic drugs on fracture risk in type 2 diabetes mellitus (T2DM) patients. METHODS: Embase, Medline, ClinicalTrials.gov, and Cochrane CENTRAL were searched for relevant trials. All data analyses were performed with STATA (12.0) and R language (3.6.0). Risk ratio (RR) with its 95% confidence interval (CI) was calculated by combining data for the fracture effects of anti-diabetic drugs, including sodium-glucose co-transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, meglitinides, alpha-glucosidase inhibitors, thiazolidinediones, biguanides, insulin, and sulfonylureas. RESULTS: One hundred seventeen eligible randomized controlled trials (RCTs) with 221,364 participants were included in this study. Compared with placebo, trelagliptin (RR 3.51; 1.58-13.70) increased the risk of fracture, whereas albiglutide (RR 0.29; 0.04-0.93) and voglibose (RR 0.03; 0-0.11) decreased the risk of fracture. Other medications were comparable in terms of their effects on fracture risk, and no statistical significance was observed. In terms of fractures, voglibose (0.01%) may be the safest option, and trelagliptin (13.64%) may be the worst. Sensitivity analysis results were consistent with those of the main analysis. No statistically significant differences were observed in the regression coefficients of age (1.03; 0.32-2.1), follow-up duration (0.79; 0.27-1.64), and sex distribution (0.63; 0.15-1.56). CONCLUSIONS: We found varied results on the association between the use of anti-diabetic drugs and fracture risk. Specifically, trelagliptin raised the risk of fracture, whereas voglibose and albiglutide showed benefit with statistical difference. Other drugs were comparable in terms of their effects on fracture risk. Some drugs (omarigliptin, sitagliptin, vildagliptin, saxagliptin, empagliflozin, ertugliflozin, rosiglitazone, pioglitazone, and nateglinide) may increase the risk of fracture, while others (such as dulaglutide, exenatide, liraglutide, semaglutide, lixisenatide, linagliptin, alogliptin, canagliflozin, dapagliflozin, glipizide, gliclazide, glibenclamide, glimepiride, metformin, and insulin) may show benefits. The risk of fracture was independent of age, sex distribution, and the duration of exposure to anti-diabetic drugs. When developing individualized treatment strategies, the clinical efficacy of anti-diabetic drugs must be weighed against their benefits and risks brought about by individual differences of patients. SYSTEMATIC REVIEW REGISTRATION: This Systematic Review was prospectively registered on the PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number CRD42020189464). CI - Copyright (c) 2021 Zhang, Zheng, Yuan, Chen and Xie. FAU - Zhang, Yu-Sheng AU - Zhang YS AD - Department of Pharmacy, The First People's Hospital of Foshan, Foshan, China. FAU - Zheng, Yan-Dan AU - Zheng YD AD - Department of Clinical Laboratory, The First People's Hospital of Foshan, Foshan, China. FAU - Yuan, Yan AU - Yuan Y AD - Department of Pharmacy, The First People's Hospital of Foshan, Foshan, China. FAU - Chen, Shi-Chun AU - Chen SC AD - Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, China. FAU - Xie, Bao-Cheng AU - Xie BC AD - Affiliated Dongguan Hospital, Southern Medical University, Dongguan, Guangdong, China. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20211014 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Hypoglycemic Agents) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Fractures, Bone/*etiology MH - Humans MH - Hypoglycemic Agents/*adverse effects/therapeutic use MH - Risk Factors PMC - PMC8553257 OTO - NOTNLM OT - anti-diabetic drug OT - fracture OT - meta-analysis OT - systematic review OT - type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/11/02 06:00 MHDA- 2022/02/16 06:00 PMCR- 2021/01/01 CRDT- 2021/11/01 09:11 PHST- 2021/07/08 00:00 [received] PHST- 2021/09/22 00:00 [accepted] PHST- 2021/11/01 09:11 [entrez] PHST- 2021/11/02 06:00 [pubmed] PHST- 2022/02/16 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2021.735824 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2021 Oct 14;12:735824. doi: 10.3389/fendo.2021.735824. eCollection 2021. PMID- 34715595 OWN - NLM STAT- MEDLINE DCOM- 20211213 LR - 20211214 IS - 1873-4367 (Electronic) IS - 0927-7765 (Linking) VI - 209 IP - Pt 1 DP - 2022 Jan TI - Amyloidogenicity of peptides targeting diabetes and obesity. PG - 112157 LID - S0927-7765(21)00601-9 [pii] LID - 10.1016/j.colsurfb.2021.112157 [doi] AB - Since the discovery of insulin, a century ago, the repertoire of therapeutic polypeptides targeting diabetes - and now also obesity - have increased substantially. The focus on quality has shifted from impure and unstable preparations of animal insulin to highly pure, homologous recombinant insulin, along with other peptide-based hormones and analogs such as amylin analogs (pramlintide, davalintide, cagrilintide), glucagon and glucagon-like peptide-1 receptor agonists (GLP-1, liraglutide, exenatide, semaglutide). Proper formulation, storage, manipulation and usage by professionals and patients are required in order to avoid agglomeration into high molecular weight products (HMWP), either amorphous or amyloid, which could result in potential loss of biological activity and short- or long-term immune reaction and silent inactivation. In this narrative review, we present perspective of the aggregation of therapeutic polypeptides used in diabetes and other metabolic diseases, covering the nature and mechanisms, analytical techniques, physical and chemical stability, strategies aimed to hamper the formation of HMWP, and perspectives on future biopharmaceutical developments. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Lima, Luis Mauricio T R AU - Lima LMTR AD - Pharmaceutical Biotechnology Laboratory (pbiotech), Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil; Laboratory of Macromolecules (LAMAC/DIMAV), National Institute for Metrology, Quality and Technology (INMETRO), INMETRO, Duque de Caxias, RJ 25250-020, Brazil. Electronic address: Mauricio@pharma.ufrj.br. FAU - Icart, Luis Pena AU - Icart LP AD - Pharmaceutical Biotechnology Laboratory (pbiotech), Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil. Electronic address: icartluis@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20211012 PL - Netherlands TA - Colloids Surf B Biointerfaces JT - Colloids and surfaces. B, Biointerfaces JID - 9315133 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Islet Amyloid Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - AO43BIF1U8 (cagrilintide) SB - IM MH - Animals MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptide 1 MH - *Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/pharmacology MH - Islet Amyloid Polypeptide MH - Obesity/drug therapy OTO - NOTNLM OT - GLP-1 OT - amylin OT - amyloid OT - diabetes OT - glucagon OT - insulin OT - obesity EDAT- 2021/10/30 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/10/29 20:30 PHST- 2021/06/01 00:00 [received] PHST- 2021/09/20 00:00 [revised] PHST- 2021/10/09 00:00 [accepted] PHST- 2021/10/30 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/10/29 20:30 [entrez] AID - S0927-7765(21)00601-9 [pii] AID - 10.1016/j.colsurfb.2021.112157 [doi] PST - ppublish SO - Colloids Surf B Biointerfaces. 2022 Jan;209(Pt 1):112157. doi: 10.1016/j.colsurfb.2021.112157. Epub 2021 Oct 12. PMID- 34706925 OWN - NLM STAT- MEDLINE DCOM- 20220328 LR - 20260127 IS - 1708-8267 (Electronic) IS - 1081-5589 (Print) IS - 1081-5589 (Linking) VI - 70 IP - 1 DP - 2022 Jan TI - Wegovy (semaglutide): a new weight loss drug for chronic weight management. PG - 5-13 LID - 10.1136/jim-2021-001952 [doi] AB - Obesity is a growing epidemic within the USA. Because weight gain is associated with an increased risk of developing life-threatening comorbidities, such as hypertension or type 2 diabetes, there is great interest in developing non-invasive pharmacotherapeutics to help combat obesity. Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of antidiabetic medications that have shown promise in encouraging glycemic control and promoting weight loss in patients with or without type 2 diabetes. This literature review summarizes and discusses the weight loss results from the SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes), PIONEER (Peptide Innovation for Early Diabetes Treatment), and STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial programs. The SUSTAIN and PIONEER clinical trials studied the use of 1.0 mg, once-weekly, subcutaneous and oral semaglutide (a new GLP-1 homolog), respectively, on participants with type 2 diabetes. The STEP trial examined the effects of 2.4 mg, once-weekly, subcutaneous semaglutide on patients with obesity. Trial data and other pertinent articles were obtained via database search through the US National Library of Medicine Clinical Trials and the National Center for Biotechnology Information. All three clinical trials demonstrated that semaglutide (injected or oral) has superior efficacy compared with placebo and other antidiabetic medications in weight reduction, which led to Food and Drug Administration approval of Wegovy (semaglutide) for weight loss. CI - (c) American Federation for Medical Research 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ. FAU - Singh, Gurdeep AU - Singh G AUID- ORCID: 0000-0001-6044-7419 AD - Internal Medicine, Our Lady of Lourdes Memorial Hospital, Binghamton, New York, USA drgsingh803@gmail.com. FAU - Krauthamer, Matthew AU - Krauthamer M AD - Emergency Medicine, Our Lady of Lourdes Memorial Hospital, Binghamton, New York, USA. FAU - Bjalme-Evans, Meghan AU - Bjalme-Evans M AD - Endocrinology, Our Lady of Lourdes Memorial Hospital, Binghamton, New York, USA. LA - eng PT - Journal Article PT - Review DEP - 20211027 PL - England TA - J Investig Med JT - Journal of investigative medicine : the official publication of the American Federation for Clinical Research JID - 9501229 RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - doi: 10.1136/jim-2021-002227 CIN - doi: 10.1136/jim-2021-002268 MH - Anti-Obesity Agents/*therapeutic use MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides/*therapeutic use MH - Glycated Hemoglobin MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Injections, Subcutaneous MH - Obesity/*drug therapy MH - Weight Loss/*drug effects MH - Semaglutide PMC - PMC8717485 OTO - NOTNLM OT - diabetes mellitus OT - glucagon-like peptide 1 OT - obesity COIS- Competing interests: None declared. EDAT- 2021/10/29 06:00 MHDA- 2022/03/29 06:00 PMCR- 2021/12/30 CRDT- 2021/10/28 05:49 PHST- 2021/10/06 00:00 [accepted] PHST- 2021/10/29 06:00 [pubmed] PHST- 2022/03/29 06:00 [medline] PHST- 2021/10/28 05:49 [entrez] PHST- 2021/12/30 00:00 [pmc-release] AID - jim-2021-001952 [pii] AID - 10.1136/jim-2021-001952 [doi] PST - ppublish SO - J Investig Med. 2022 Jan;70(1):5-13. doi: 10.1136/jim-2021-001952. Epub 2021 Oct 27. PMID- 34697882 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 2 DP - 2022 Feb TI - A model-based simulation of glycaemic control and body weight when switching from semaglutide to 3.0- and 4.5-mg doses of once-weekly dulaglutide. PG - 302-311 LID - 10.1111/dom.14582 [doi] AB - AIM: To evaluate HbA1c and body weight changes when semaglutide 0.5- or 1.0-mg once-weekly (QW) is switched to dulaglutide 3.0- or 4.5-mg QW via exposure-response modelling. METHODS: HbA1c and body weight time-course models were developed and validated with data from the SUSTAIN 1 to 10 trials for semaglutide and the AWARD-11 trial for dulaglutide. Simulations were conducted for HbA1c and body weight over 52 weeks. In the initial 26 weeks, semaglutide was initiated at 0.25-mg and titrated to 0.5- or 1.0-mg QW via 4-weekly stepwise titration, followed by 26 weeks of dulaglutide initiated at 0.75- or 1.5-mg QW and escalated to 3.0- or 4.5-mg QW via 4-weekly stepwise titration. RESULTS: At 26 weeks, model-predicted mean changes from baseline in HbA1c and weight for semaglutide 0.5 mg were up to -1.55% and -3.44 kg, respectively. After switching to dulaglutide 3.0 mg, further reductions were 0.19% and 1.40 kg, respectively, at 52 weeks. Predicted mean HbA1c and weight changes for semaglutide 1.0 mg at 26 weeks were -1.84% and -4.96 kg, respectively; after switching to dulaglutide 4.5 mg, HbA1c was maintained with additional weight reduction of up to 0.57 kg at 52 weeks. Glycaemic control was preserved when switching from semaglutide 1.0 mg to dulaglutide 3.0 mg. CONCLUSION: Switching from semaglutide 0.5 mg to dulaglutide 3.0 or 4.5 mg with dose escalation potentially yields additional HbA1c and weight reductions; switching from semaglutide 1.0 mg to dulaglutide 4.5 mg may enhance weight loss. CI - (c) 2021 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Tham, Lai San AU - Tham LS AUID- ORCID: 0000-0002-1249-8526 AD - Lilly Centre for Clinical Pharmacology, Singapore. FAU - Pantalone, Kevin M AU - Pantalone KM AUID- ORCID: 0000-0002-3897-4551 AD - Department of Endocrinology, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Dungan, Kathleen AU - Dungan K AUID- ORCID: 0000-0003-1289-1595 AD - Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, Ohio, USA. FAU - Munir, Kashif AU - Munir K AUID- ORCID: 0000-0002-1075-1284 AD - Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA. FAU - Tang, Cheng Cai AU - Tang CC AD - Lilly Centre for Clinical Pharmacology, Singapore. FAU - Konig, Manige AU - Konig M AUID- ORCID: 0000-0002-1584-8309 AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Kwan, Anita Y M AU - Kwan AYM AD - Eli Lilly and Company, Indianapolis, Indiana, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211108 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Glycated Hemoglobin/analysis MH - *Glycemic Control MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Immunoglobulin Fc Fragments/adverse effects MH - Recombinant Fusion Proteins/adverse effects MH - Weight Loss MH - Semaglutide PMC - PMC9298861 OTO - NOTNLM OT - dulaglutide OT - glycaemic control OT - incretin therapy OT - pharmacodynamics OT - pharmacokinetics OT - type 2 diabetes COIS- L.S.T., C.C.T., M.K., and A.Y.M.K. are employees and stockholders of Eli Lilly and Company. K.M.P. declares speaker honoraria from AstraZeneca, Corcept Therapeutics, Merck, and Novo Nordisk; consultant honoraria from AstraZeneca, Bayer, Corcept Therapeutics, Diasome, Novo Nordisk, and Merck; and research support from Bayer, Novo Nordisk, and Merck. K.D. declares research support from Novo Nordisk, Sanofi, Abbott, and Viacyte; consulting fees from Eli Lilly and Company, Jansen, Novo Nordisk, and Tolerion; and honoraria from UpToDate, Elsevier, Cardiometabolic Health Conference, and the Academy for Continued Healthcare Learning. K.M. declares no conflicts of interest. EDAT- 2021/10/27 06:00 MHDA- 2022/04/01 06:00 PMCR- 2022/07/20 CRDT- 2021/10/26 06:43 PHST- 2021/10/12 00:00 [revised] PHST- 2021/07/22 00:00 [received] PHST- 2021/10/20 00:00 [accepted] PHST- 2021/10/27 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/10/26 06:43 [entrez] PHST- 2022/07/20 00:00 [pmc-release] AID - DOM14582 [pii] AID - 10.1111/dom.14582 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Feb;24(2):302-311. doi: 10.1111/dom.14582. Epub 2021 Nov 8. PMID- 34676658 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20220722 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 2 DP - 2022 Feb TI - The importance of addressing multiple risk markers in type 2 diabetes: Results from the LEADER and SUSTAIN 6 trials. PG - 281-288 LID - 10.1111/dom.14578 [doi] AB - AIMS: To investigate to what extent multiple risk marker improvements confer lower risk of cardiovascular and kidney complications in a contemporary type 2 diabetes population. MATERIALS AND METHODS: Post-hoc analysis of the LEADER (n = 8638; median follow-up 3.8 years) and SUSTAIN 6 (n = 3040; median follow-up 2.1 years) cardiovascular outcome trials. Participants were those with baseline and year-1 assessment of at least one of the parameters of interest; we pooled the liraglutide-/semaglutide- and placebo-treated groups and categorized them by number of risk markers with clinically relevant improvements after 1 year of study participation. We investigated risk of major adverse cardiovascular events (MACE), expanded MACE, cardiovascular death and nephropathy. Predefined clinically relevant changes: body weight loss >/=5%; reductions in: glycated haemoglobin >/=1%, systolic blood pressure >/=5 mmHg and low-density lipoprotein cholesterol >/=0.5 mmol/L; estimated glomerular filtration rate change >/=0 ml/min/1.73 m(2) and urinary albumin-to-creatinine ratio change >/=30% of baseline value. Cox regression analysed risk of outcomes adjusted for baseline risk marker levels and treatment group and stratified by trial. RESULTS: Participants with two, three, or four or more improved risk markers versus participants with no risk marker improvement had reduced risk of expanded MACE [hazard ratio (95% confidence interval) 0.80 (0.67-0.96); 0.80 (0.66-0.97); 0.82 (0.66-1.02)], cardiovascular death [0.66 (0.45-0.96), 0.67 (0.45-0.99), 0.60 (0.38-0.94)] and nephropathy [0.71 (0.52-0.97), 0.48 (0.34-0.68), 0.43 (0.29-0.65)]. CONCLUSIONS: In persons with type 2 diabetes, improvements in >/=2 risk markers conferred cardiovascular risk reduction versus none or one improved risk marker. The nephropathy risk decreased with improvement in more risk markers. These findings stress the importance of multifactorial interventions targeting all risk markers. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Zobel, Emilie H AU - Zobel EH AUID- ORCID: 0000-0003-3318-7070 AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. FAU - von Scholten, Bernt Johan AU - von Scholten BJ AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hansen, Tine W AU - Hansen TW AUID- ORCID: 0000-0003-2274-0352 AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. FAU - Persson, Frederik AU - Persson F AUID- ORCID: 0000-0001-6242-6638 AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wolthers, Benjamin AU - Wolthers B AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. AD - University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211105 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) SB - IM MH - *Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/chemically induced/complications/drug therapy MH - Glomerular Filtration Rate MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Kidney Diseases/chemically induced MH - Liraglutide PMC - PMC9297860 OTO - NOTNLM OT - cardiovascular disease OT - diabetic nephropathy OT - type 2 diabetes COIS- EHZ is now a Novo Nordisk A/S full-time employee, but work related to this article was carried out when EHZ was employed full-time by Steno Diabetes Center Copenhagen. BW, BJvS and SR are Novo Nordisk A/S full-time employees and BW, BJvS, SR and TWH are Novo Nordisk shareholders. FP reports research grants from AstraZeneca and lecture fees from AstraZeneca, MSD, Janssen, Eli Lilly, Boehringer Ingelheim, Novo Nordisk A/S and Novartis, as well as being a consultant/advisory board member for AstraZeneca, Bayer, Amgen and MSD. PR has received honoraria from Steno Diabetes Center Copenhagen for advisory work, and for consultancy/education from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, MSD, Merck, Mundipharma, Novo Nordisk, Vifor and Sanofi. EDAT- 2021/10/23 06:00 MHDA- 2022/04/01 06:00 PMCR- 2022/07/20 CRDT- 2021/10/22 07:11 PHST- 2021/10/13 00:00 [revised] PHST- 2021/08/10 00:00 [received] PHST- 2021/10/15 00:00 [accepted] PHST- 2021/10/23 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/10/22 07:11 [entrez] PHST- 2022/07/20 00:00 [pmc-release] AID - DOM14578 [pii] AID - 10.1111/dom.14578 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Feb;24(2):281-288. doi: 10.1111/dom.14578. Epub 2021 Nov 5. PMID- 34668637 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20250103 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 2 DP - 2022 Feb TI - Cardiovascular risk profiles: A cross-sectional study evaluating the generalizability of the glucagon-like peptide-1 receptor agonist cardiovascular outcome trials REWIND, LEADER and SUSTAIN-6 to the real-world type 2 diabetes population in the United Kingdom. PG - 289-295 LID - 10.1111/dom.14580 [doi] AB - AIMS: To determine the proportion of UK patients with type 2 diabetes (T2D) who meet the cardiovascular (CV) or combined CV/core eligibility criteria used for the CV outcome trials (CVOTs) of UK-marketed glucagon-like peptide-1 receptor agonists (GLP-1RAs) showing CV benefit (dulaglutide in REWIND, liraglutide in LEADER and injectable semaglutide in SUSTAIN-6). MATERIALS AND METHODS: Adults with T2D on/before June 2018 were identified from the UK Clinical Practice Research Datalink GOLD primary care database and linked to Hospital Episode Statistics data (Protocol 19_262). Patient CV and clinical data were evaluated against the CVOT eligibility criteria. Data were analysed descriptively. RESULTS: The study cohort (N = 33 118 patients with T2D) had a mean (standard deviation) age of 66.0 (13.3) years and 56.6% were male. Almost two-thirds (64.5%) of the study cohort met the CV criteria for REWIND, versus 43.0% for both LEADER and SUSTAIN-6. The proportions of the study cohort who met the CVOT criteria of "established CV disease" and "CV risk factors only" for REWIND were 22.4% and 42.1%, respectively, versus 38.7% and 4.3%, respectively, for both LEADER and SUSTAIN-6. The proportions of patients satisfying both CV and core criteria were 44.4% for REWIND, 13.3% for LEADER and 13.5% for SUSTAIN-6. Study findings remained consistent when restricted to GLP-1RA users. CONCLUSIONS: REWIND captured a trial population more representative of the real-world T2D population in the United Kingdom than LEADER or SUSTAIN-6 with regard to both CV and combined CV/core eligibility criteria. CI - (c) 2021 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Webb, Joanne AU - Webb J AUID- ORCID: 0000-0001-5883-9077 AD - Eli Lilly and Company, Basingstoke, UK. FAU - Mount, Julie AU - Mount J AD - Eli Lilly and Company, Basingstoke, UK. FAU - von Arx, Lill-Brith AU - von Arx LB AD - Eli Lilly and Company, Herlev, Denmark. FAU - Rachman, Jonathan AU - Rachman J AD - Eli Lilly and Company, Basingstoke, UK. FAU - Spanopoulos, Dionysis AU - Spanopoulos D AD - Eli Lilly and Company, Basingstoke, UK. FAU - Wood, Robert AU - Wood R AD - Adelphi Real World, Bollington, UK. FAU - Tritton, Theo AU - Tritton T AD - Adelphi Real World, Bollington, UK. FAU - Massey, Olivia AU - Massey O AD - Adelphi Real World, Bollington, UK. FAU - Idris, Iskandar AU - Idris I AD - University of Nottingham, Nottingham, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211124 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Aged MH - *Cardiovascular Diseases/chemically induced/epidemiology/prevention & control MH - Clinical Trials as Topic MH - Cross-Sectional Studies MH - *Diabetes Mellitus, Type 2/chemically induced/drug therapy/epidemiology MH - Female MH - Glucagon-Like Peptides/therapeutic use MH - Heart Disease Risk Factors MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Male MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC9299650 OTO - NOTNLM OT - GLP-1RA OT - cardiovascular disease OT - cardiovascular outcome trials OT - real-world evidence OT - type 2 diabetes COIS- Joanne Webb, Julie Mount, Lill-Brith von Arx, Jonathan Rachman are employees of Eli Lilly and Company. Joanne Webb and Julie Mount are minor shareholders of Eli Lilly and Company. Dionysis Spanopoulos is a former employee of Eli Lilly and Company. Robert Wood, Theo Tritton and Olivia Massey are employees of Adelphi Real World, who were funded by Eli Lilly and Company to conduct this research. Iskandar Idris has received payment and/or honoraria from Eli Lilly and Company, Novo Nordisk, Astra Zeneca, MSD, Boehringer Ingelheim, and has participated on Data Safety Monitoring Boards or Advisory Boards for Eli Lilly and Company, Novo Nordisk and MSD. EDAT- 2021/10/21 06:00 MHDA- 2022/04/01 06:00 PMCR- 2022/07/20 CRDT- 2021/10/20 08:55 PHST- 2021/10/01 00:00 [revised] PHST- 2021/07/19 00:00 [received] PHST- 2021/10/15 00:00 [accepted] PHST- 2021/10/21 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/10/20 08:55 [entrez] PHST- 2022/07/20 00:00 [pmc-release] AID - DOM14580 [pii] AID - 10.1111/dom.14580 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Feb;24(2):289-295. doi: 10.1111/dom.14580. Epub 2021 Nov 24. PMID- 34626851 OWN - NLM STAT- MEDLINE DCOM- 20220404 LR - 20220405 IS - 2212-8778 (Electronic) IS - 2212-8778 (Linking) VI - 57 DP - 2022 Mar TI - GLP-1 physiology informs the pharmacotherapy of obesity. PG - 101351 LID - S2212-8778(21)00198-8 [pii] LID - 10.1016/j.molmet.2021.101351 [doi] LID - 101351 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP1RA) augment glucose-dependent insulin release and reduce glucagon secretion and gastric emptying, enabling their successful development for the treatment of type 2 diabetes (T2D). These agents also inhibit food intake and reduce body weight, fostering investigation of GLP1RA for the treatment of obesity. SCOPE OF REVIEW: Here I discuss the physiology of Glucagon-like peptide-1 (GLP-1) action in the control of food intake in animals and humans, highlighting the importance of gut vs. brain-derived GLP-1 for the control of feeding and body weight. The widespread distribution and function of multiple GLP-1 receptor (GLP1R) populations in the central and autonomic nervous system are outlined, and the importance of pathways controlling energy expenditure in preclinical studies vs. reduction of food intake in both animals and humans is highlighted. The relative contributions of vagal afferent pathways vs. GLP1R+ populations in the central nervous system for the physiological reduction of food intake and the anorectic response to GLP1RA are compared and reviewed. Key data enabling the development of two GLP1RA for obesity therapy (liraglutide 3 mg daily and semaglutide 2.4 mg once weekly) are discussed. Finally, emerging data potentially supporting the combination of GLP-1 with additional peptide epitopes in unimolecular multi-agonists, as well as in fixed-dose combination therapies, are highlighted. MAJOR CONCLUSIONS: The actions of GLP-1 to reduce food intake and body weight are highly conserved in obese animals and humans, in both adolescents and adults. The well-defined mechanisms of GLP-1 action through a single G protein-coupled receptor, together with the extensive safety database of GLP1RA in people with T2D, provide reassurance surrounding the long-term use of these agents in people with obesity and multiple co-morbidities. GLP1RA may also be effective in conditions associated with obesity, such as cardiovascular disease and non-alcoholic steatohepatitis (NASH). Progressive improvements in the efficacy of GLP1RA suggest that GLP-1-based therapies may soon rival bariatric surgery as viable options for the treatment of obesity and its complications. CI - Copyright (c) 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved. FAU - Drucker, Daniel J AU - Drucker DJ AD - Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, ON M5G 1X5, Canada. Electronic address: drucker@lunenfeld.ca. LA - eng GR - 154321/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20211006 PL - Germany TA - Mol Metab JT - Molecular metabolism JID - 101605730 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 839I73S42A (Liraglutide) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Adolescent MH - Animals MH - *Diabetes Mellitus, Type 2/metabolism MH - *Glucagon-Like Peptide 1/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Humans MH - Liraglutide/therapeutic use MH - Obesity/drug therapy/metabolism PMC - PMC8859548 OTO - NOTNLM OT - Brain OT - Diabetes OT - G protein-coupled receptor OT - Hunger OT - Obesity OT - Weight loss EDAT- 2021/10/10 06:00 MHDA- 2022/04/05 06:00 PMCR- 2021/10/06 CRDT- 2021/10/09 20:15 PHST- 2021/08/13 00:00 [received] PHST- 2021/09/28 00:00 [revised] PHST- 2021/10/02 00:00 [accepted] PHST- 2021/10/10 06:00 [pubmed] PHST- 2022/04/05 06:00 [medline] PHST- 2021/10/09 20:15 [entrez] PHST- 2021/10/06 00:00 [pmc-release] AID - S2212-8778(21)00198-8 [pii] AID - 101351 [pii] AID - 10.1016/j.molmet.2021.101351 [doi] PST - ppublish SO - Mol Metab. 2022 Mar;57:101351. doi: 10.1016/j.molmet.2021.101351. Epub 2021 Oct 6. PMID- 34622548 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 2 DP - 2022 Feb TI - Efficacy and safety of oral semaglutide by baseline age in Japanese patients with type 2 diabetes: A subgroup analysis of the PIONEER 9 and 10 Japan trials. PG - 321-326 LID - 10.1111/dom.14571 [doi] AB - A post-hoc exploratory analysis of the PIONEER 9 and 10 trials evaluated the effect of baseline age (<65 and >/=65 years) on the efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes. In PIONEER 9 and 10, patients were randomized to once-daily oral semaglutide (3, 7 or 14 mg) or a comparator (placebo or once-daily subcutaneous liraglutide 0.9 mg [PIONEER 9]; once-weekly subcutaneous dulaglutide 0.75 mg [PIONEER 10]) for 52 weeks, with 5 weeks' follow-up. In total, 701 patients were included (PIONEER 9: N = 243; PIONEER 10: N = 458). Glycaemic efficacy of oral semaglutide was similar in Japanese patients aged <65 years compared with those >/=65 years, and there did not appear to be a clear pattern between age subgroup and body weight changes. Across treatment arms, adverse events generally occurred in greater proportions of patients aged >/=65 versus <65 years. There was generally a higher rate of premature trial product discontinuation because of adverse events in the older age group. These results indicate that oral semaglutide is efficacious in Japanese patients irrespective of age. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Yamada, Yuichiro AU - Yamada Y AUID- ORCID: 0000-0003-1623-0815 AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. FAU - Yabe, Daisuke AU - Yabe D AUID- ORCID: 0000-0002-5334-7687 AD - Department of Diabetes and Endocrinology, Gifu University Graduate School of Medicine, Gifu, Japan. AD - Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Research Institute, Kobe, Japan. AD - Division of Molecular and Metabolic Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Hertz, Christin Loth AU - Hertz CL AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Horio, Hiroshi AU - Horio H AD - Novo Nordisk Pharma Ltd, Tokyo, Japan. FAU - Nakamura, Jiro AU - Nakamura J AD - Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan. FAU - Nielsen, Anne Moller AU - Nielsen AM AUID- ORCID: 0000-0003-0268-5763 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Seino, Yutaka AU - Seino Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. AD - Kansai Electric Power Research Institute, Kobe, Japan. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20211109 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Aged MH - *Diabetes Mellitus, Type 2/chemically induced/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Japan/epidemiology MH - Semaglutide PMC - PMC9299616 OTO - NOTNLM OT - antidiabetic drug OT - glucagon-like peptide-1 analogue OT - glycaemic control OT - incretin therapy OT - randomized trial OT - type 2 diabetes COIS- K.F. is an employee of Novo Nordisk Pharma Limited. C.L.H. and A.M.N. are employees and shareholders of Novo Nordisk A/S, the sponsor of this trial. H.H. is an employee and shareholder of Novo Nordisk Pharma Limited. Y.Y. has received consulting or speaker fees from Daiichi Sankyo, Mitsubishi Tanabe Pharma, MSD, Novo Nordisk Pharma Limited, Ono Pharmaceutical, Sanofi, Sumitomo Dainippon and Takeda Pharmaceutical Company; and research grants from Daiichi Sankyo, Mitsubishi Tanabe Pharma, Ono Pharmaceutical, Sanwa Kagaku Kenkyusho and Takeda Pharmaceutical Company. D.Y. has received consulting or speaker fees from Astellas, Eli Lilly Japan, MSD, Nippon Boehringer Ingelheim, Novo Nordisk Pharma Limited, Ono Pharmaceutical, Sumitomo Dainippon and Takeda Pharmaceutical Company; and clinically commissioned and joint research grants from Arklay, Novo Nordisk Pharma Limited, Ono Pharmaceutical, Taisho Pharmaceutical, Takeda Pharmaceutical Company and Terumo. J.N. has received lecture fees from Astellas Pharma, AstraZeneca, Boehringer Ingelheim Japan, Daiichi Sankyo, Eli Lilly Japan, Kowa Pharmaceutical, Mitsubishi Tanabe Pharma, MSD, Novartis Pharma, Novo Nordisk, Ono Pharmaceutical, Sanofi, Takeda Pharmaceutical Company and Terumo; research funding from Boehringer Ingelheim Japan, EPS Corporation and Kissei Pharmaceuticals; and donations from Astellas Pharma, Daiichi Sankyo, Eli Lilly Japan, Japan Tobacco, MSD, Novartis Pharma, Novo Nordisk Pharma Limited, Ono Pharmaceuticals, Sanofi, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceuticals and Takeda Pharmaceuticals. Y.S. has received consulting or speaker fees from Eli Lilly and Company, MSD, Nippon Boehringer Ingelheim, Novo Nordisk Pharma Limited, Taisho Pharmaceutical and Takeda Pharmaceutical Company; and clinically commissioned and joint research grants from Arklay, Eli Lilly and Company, MSD, Nippon Boehringer Ingelheim, Novo Nordisk, Ono Pharmaceutical, Sumitomo Dainippon Pharma, Taisho Toyama Pharmaceutical, Takeda Pharmaceutical Company and Terumo Corporation. EDAT- 2021/10/09 06:00 MHDA- 2022/04/01 06:00 PMCR- 2022/07/20 CRDT- 2021/10/08 07:35 PHST- 2021/09/29 00:00 [revised] PHST- 2021/06/30 00:00 [received] PHST- 2021/10/01 00:00 [accepted] PHST- 2021/10/09 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/10/08 07:35 [entrez] PHST- 2022/07/20 00:00 [pmc-release] AID - DOM14571 [pii] AID - 10.1111/dom.14571 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Feb;24(2):321-326. doi: 10.1111/dom.14571. Epub 2021 Nov 9. PMID- 34622228 OWN - NLM STAT- MEDLINE DCOM- 20220303 LR - 20260127 IS - 2666-3791 (Electronic) IS - 2666-3791 (Linking) VI - 2 IP - 9 DP - 2021 Sep 21 TI - Levels of circulating semaglutide determine reductions in HbA1c and body weight in people with type 2 diabetes. PG - 100387 LID - 10.1016/j.xcrm.2021.100387 [doi] LID - 100387 AB - Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used for the treatment of type 2 diabetes. Whether clinically important responses and adverse events (AEs) are dependent on the route of administration has not been determined. We demonstrate that nearly identical exposure-response pharmacodynamic relationships are determined by plasma semaglutide levels achieved through oral versus injectable administration for changes in HbA(1c), body weight, biomarkers of cardiovascular risk, and AEs such as nausea and vomiting. At typical exposure levels for oral semaglutide, the estimated response is 1.58% (oral) versus -1.62% (subcutaneous) for HbA(1c) and 3.77% (oral) versus 3.48% (subcutaneous) reduction in body weight relative to baseline after 6 months. Increased body weight is the most important variable associated with reduced semaglutide exposure for both formulations. Hence, interindividual variation in GLP-1R responsivity or route of administration are not major determinants of GLP-1RA effectiveness in the clinic. CI - (c) 2021 The Author(s). FAU - Overgaard, Rune V AU - Overgaard RV AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hertz, Christin L AU - Hertz CL AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ingwersen, Steen H AU - Ingwersen SH AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Navarria, Andrea AU - Navarria A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Drucker, Daniel J AU - Drucker DJ AD - Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, ON, Canada. LA - eng GR - 154321/CIHR/Canada PT - Clinical Trial, Phase III PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210903 PL - United States TA - Cell Rep Med JT - Cell reports. Medicine JID - 101766894 RN - 9007-41-4 (C-Reactive Protein) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Triglycerides) RN - 53AXN4NNHX (Semaglutide) MH - Administration, Oral MH - Blood Pressure MH - *Body Weight MH - C-Reactive Protein/metabolism MH - Diabetes Mellitus, Type 2/*blood/physiopathology MH - Female MH - Glucagon-Like Peptides/administration & dosage/*blood MH - Glycated Hemoglobin/*analysis MH - Humans MH - Injections MH - Injections, Subcutaneous MH - Male MH - Middle Aged MH - Triglycerides/blood MH - Semaglutide PMC - PMC8484505 OTO - NOTNLM OT - Alzheimer's disease OT - G protein coupled receptor OT - GLP-1 OT - diabetes OT - glucagon-like peptide OT - non-alcoholic hepatosteatosis OT - obesity OT - peptide OT - weight loss COIS- R.V.O., C.L.H., S.H.I., and A.N. are full-time employees of and own stock in Novo Nordisk A/S. D.J.D. has served as an advisor or consultant or speaker within the past 12 months to Eli Lilly, Forkhead Biotherapeutics, Intarcia Therapeutics, Kallyope, Merck Research Laboratories, and Novo Nordisk, and holds non-exercised options in Kallyope. EDAT- 2021/10/09 06:00 MHDA- 2021/10/09 06:01 PMCR- 2021/09/03 CRDT- 2021/10/08 07:17 PHST- 2021/04/20 00:00 [received] PHST- 2021/06/30 00:00 [revised] PHST- 2021/08/11 00:00 [accepted] PHST- 2021/10/08 07:17 [entrez] PHST- 2021/10/09 06:00 [pubmed] PHST- 2021/10/09 06:01 [medline] PHST- 2021/09/03 00:00 [pmc-release] AID - S2666-3791(21)00245-7 [pii] AID - 100387 [pii] AID - 10.1016/j.xcrm.2021.100387 [doi] PST - epublish SO - Cell Rep Med. 2021 Sep 3;2(9):100387. doi: 10.1016/j.xcrm.2021.100387. eCollection 2021 Sep 21. PMID- 34576096 OWN - NLM STAT- MEDLINE DCOM- 20211022 LR - 20260127 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 18 DP - 2021 Sep 14 TI - Oral Semaglutide, the First Ingestible Glucagon-Like Peptide-1 Receptor Agonist: Could It Be a Magic Bullet for Type 2 Diabetes? LID - 10.3390/ijms22189936 [doi] LID - 9936 AB - The gastrointestinal tract secretes gut hormones in response to food consumption, and some of these stimulate insulin secretion. Glucagon-like peptide-1 (GLP-1) is an incretin peptide hormone released from the lower digestive tract that stimulates insulin secretion, suppresses glucagon secretion, and decreases hunger. GLP-1 receptor agonist (GLP-1RA) mimics the action of endogenous GLP-1, consequently reversing hyperglycemia and causing weight reduction, demonstrating its efficacy as an antidiabetic and antiobesity agent. Previously restricted to injection only, the invention of the absorption enhancer sodium N-(8-[2-hydroxybenzoyl]amino) caprylate resulted in the development of oral semaglutide, the first ingestible GLP-1RA. Oral semaglutide demonstrated its efficacy in glycemic management and body weight loss with a low risk of hypoglycemia as a monotherapy and in combination with other hypoglycemic medications in its clinical trial programs named Peptide Innovation for Early Diabetes Treatment. Consistent with other injectable GLP-1RAs, gastrointestinal side effects were often reported. Additionally, cardiovascular safety was established by demonstrating that oral semaglutide was not inferior to a placebo in terms of cardiovascular outcomes. Thus, oral semaglutide represents a novel treatment option that is particularly well-suited for patients with type 2 diabetes and/or obesity. FAU - Kim, Hwi Seung AU - Kim HS AUID- ORCID: 0000-0001-5113-9895 AD - Asan Medical Center, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul 05505, Korea. AD - Asan Diabetes Center, Asan Medical Center, Seoul 05505, Korea. FAU - Jung, Chang Hee AU - Jung CH AUID- ORCID: 0000-0003-4043-2396 AD - Asan Medical Center, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul 05505, Korea. AD - Asan Diabetes Center, Asan Medical Center, Seoul 05505, Korea. LA - eng PT - Journal Article PT - Review DEP - 20210914 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Animals MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/*administration & dosage/chemistry/pharmacokinetics/*therapeutic use MH - Humans MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC8470357 OTO - NOTNLM OT - GLP-1 receptor OT - obesity OT - semaglutide OT - type 2 diabetes COIS- The authors declare no conflict of interest. EDAT- 2021/09/29 06:00 MHDA- 2023/02/25 06:00 PMCR- 2021/09/14 CRDT- 2021/09/28 01:18 PHST- 2021/08/30 00:00 [received] PHST- 2021/09/10 00:00 [revised] PHST- 2021/09/12 00:00 [accepted] PHST- 2021/09/28 01:18 [entrez] PHST- 2021/09/29 06:00 [pubmed] PHST- 2023/02/25 06:00 [medline] PHST- 2021/09/14 00:00 [pmc-release] AID - ijms22189936 [pii] AID - ijms-22-09936 [pii] AID - 10.3390/ijms22189936 [doi] PST - epublish SO - Int J Mol Sci. 2021 Sep 14;22(18):9936. doi: 10.3390/ijms22189936. PMID- 34570916 OWN - NLM STAT- MEDLINE DCOM- 20211028 LR - 20260127 IS - 1365-2036 (Electronic) IS - 0269-2813 (Print) IS - 0269-2813 (Linking) VI - 54 IP - 9 DP - 2021 Nov TI - Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging. PG - 1150-1161 LID - 10.1111/apt.16608 [doi] AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists may be a treatment option in patients with non-alcoholic fatty liver disease (NAFLD). AIMS: To investigate the effects of semaglutide on liver stiffness and liver fat in subjects with NAFLD using non-invasive magnetic resonance imaging (MRI) methods. METHODS: This randomised, double-blind, placebo-controlled trial enrolled subjects with liver stiffness 2.50-4.63 kPa by magnetic resonance elastography (MRE) and liver steatosis >/=10% by MRI proton density fat fraction (MRI-PDFF). The primary endpoint was change from baseline to week 48 in liver stiffness assessed by MRE. RESULTS: Sixty-seven subjects were randomised to once-daily subcutaneous semaglutide 0.4 mg (n = 34) or placebo (n = 33). Change from baseline in liver stiffness was not significantly different between semaglutide and placebo at week 48 (estimated treatment ratio 0.96 (95% CI 0.89, 1.03; P = 0.2798); significant differences in liver stiffness were not observed at weeks 24 or 72. Reductions in liver steatosis were significantly greater with semaglutide (estimated treatment ratios: 0.70 [0.59, 0.84], P = 0.0002; 0.47 [0.36, 0.60], P < 0.0001; and 0.50 [0.39, 0.66], P < 0.0001) and more subjects achieved a >/= 30% reduction in liver fat content with semaglutide at weeks 24, 48 and 72, (all P < 0.001). Decreases in liver enzymes, body weight and HbA(1c) were also observed with semaglutide. CONCLUSIONS: The change in liver stiffness in subjects with NAFLD was not significantly different between semaglutide and placebo. However, semaglutide significantly reduced liver steatosis compared with placebo which, together with improvements in liver enzymes and metabolic parameters, suggests a positive impact on disease activity and metabolic profile. ClinicalTrials.gov identifier: NCT03357380. CI - (c) 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. FAU - Flint, Anne AU - Flint A AUID- ORCID: 0000-0003-1604-8714 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Andersen, Grit AU - Andersen G AD - Profil, Neuss, Germany. FAU - Hockings, Paul AU - Hockings P AD - Antaros Medical, BioVenture Hub, Molndal, Sweden. AD - MedTech West, Chalmers University of Technology, Gothenburg, Sweden. FAU - Johansson, Lars AU - Johansson L AD - Antaros Medical, BioVenture Hub, Molndal, Sweden. FAU - Morsing, Anni AU - Morsing A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sundby Palle, Mads AU - Sundby Palle M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Vogl, Thomas AU - Vogl T AD - University Hospital, Frankfurt, Germany. FAU - Loomba, Rohit AU - Loomba R AUID- ORCID: 0000-0002-4845-9991 AD - University of California San Diego School of Medicine, San Diego, California, USA. FAU - Plum-Morschel, Leona AU - Plum-Morschel L AD - Profil, Mainz, Germany. LA - eng SI - ClinicalTrials.gov/NCT03357380 GR - UL1 TR001442/TR/NCATS NIH HHS/United States GR - P42 ES010337/ES/NIEHS NIH HHS/United States GR - P30 DK120515/DK/NIDDK NIH HHS/United States GR - U01 AA029019/AA/NIAAA NIH HHS/United States GR - R01 DK124318/DK/NIDDK NIH HHS/United States GR - U01 DK061734/DK/NIDDK NIH HHS/United States GR - P01 HL147835/HL/NHLBI NIH HHS/United States GR - R01 DK121378/DK/NIDDK NIH HHS/United States GR - R01 DK106419/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210927 PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Aliment Pharmacol Ther. 2021 Dec;54(11-12):1496-1497. doi: 10.1111/apt.16641. PMID: 34741326 CIN - Aliment Pharmacol Ther. 2021 Dec;54(11-12):1498. doi: 10.1111/apt.16669. PMID: 34741327 MH - *Diabetes Mellitus, Type 2 MH - Double-Blind Method MH - *Elasticity Imaging Techniques MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Magnetic Resonance Imaging MH - *Non-alcoholic Fatty Liver Disease/diagnostic imaging/drug therapy MH - Semaglutide PMC - PMC9292692 EDAT- 2021/09/28 06:00 MHDA- 2021/10/29 06:00 PMCR- 2022/07/18 CRDT- 2021/09/27 17:30 PHST- 2021/06/04 00:00 [revised] PHST- 2021/05/10 00:00 [received] PHST- 2021/09/03 00:00 [accepted] PHST- 2021/09/28 06:00 [pubmed] PHST- 2021/10/29 06:00 [medline] PHST- 2021/09/27 17:30 [entrez] PHST- 2022/07/18 00:00 [pmc-release] AID - APT16608 [pii] AID - 10.1111/apt.16608 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2021 Nov;54(9):1150-1161. doi: 10.1111/apt.16608. Epub 2021 Sep 27. PMID- 34543259 OWN - NLM STAT- MEDLINE DCOM- 20210927 LR - 20260127 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 63 IP - 1628 DP - 2021 Jul 12 TI - Semaglutide (Wegovy) for weight loss. PG - 106-108 LA - eng PT - Journal Article PT - Review PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Clinical Trials as Topic/methods MH - Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucagon-Like Peptide 1/*agonists/physiology MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Humans MH - Injections, Subcutaneous MH - Nausea/chemically induced MH - Weight Loss/*drug effects/physiology MH - Semaglutide OTO - NOTNLM OT - Qsymia OT - Saxenda OT - Wegovy OT - adverse effects OT - dosage OT - drug interactions OT - efficacy OT - lactation OT - liraglutide OT - phentermine OT - pregnancy OT - safety OT - semaglutide OT - topiramate OT - type 2 diabetes OT - weight loss EDAT- 2021/09/21 06:00 MHDA- 2021/09/28 06:00 CRDT- 2021/09/20 17:20 PHST- 2021/09/20 17:20 [entrez] PHST- 2021/09/21 06:00 [pubmed] PHST- 2021/09/28 06:00 [medline] PST - ppublish SO - Med Lett Drugs Ther. 2021 Jul 12;63(1628):106-108. PMID- 34526024 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 20 IP - 1 DP - 2021 Sep 15 TI - GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs. PG - 189 LID - 10.1186/s12933-021-01366-8 [doi] LID - 189 AB - BACKGROUND: A meta-analysis is presented of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) versus placebo on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM). METHODS: We did an electronic search up to June 30, 2021, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). We included data from 8 CVOTs and 60,080 patients (72.4% with established cardiovascular disease). RESULTS: GLP-1RA reduced major cardiovascular events (MACE) by 14% (HR = 0.86, 95% CI 0.79-0.94, P = 0.006) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (P = 0.127). GLP-1RA also reduced the risk of cardiovascular death by 13% (P = 0.016), nonfatal stroke by 16% (P = 0.007), hospitalization for heart failure by 10% (P = 0.023), all-cause mortality by 12% (P = 0.012), and the broad composite kidney outcome by 17% (P = 0.012), which was driven by a reduction in macroalbuminuria only (HR = 0.74, 0.67-0.82, P < 0.001). CONCLUSIONS: GLP-1RA have moderate benefits on MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria. CI - (c) 2021. The Author(s). FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. dario.giugliano@unicampania.it. AD - PHD Program of Translational Medicine, Department Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. dario.giugliano@unicampania.it. FAU - Scappaticcio, Lorenzo AU - Scappaticcio L AD - Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - PHD Program of Translational Medicine, Department Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Longo, Miriam AU - Longo M AD - Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - PHD Program of Translational Medicine, Department Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Caruso, Paola AU - Caruso P AD - Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - PHD Program of Translational Medicine, Department Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Maiorino, Maria Ida AU - Maiorino MI AUID- ORCID: 0000-0003-4659-7546 AD - Diabetes Unit, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Bellastella, Giuseppe AU - Bellastella G AD - Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Ceriello, Antonio AU - Ceriello A AD - IRCCS MultiMedica, Milan, Italy. FAU - Chiodini, Paolo AU - Chiodini P AD - Medical Statistics Unit, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AD - PHD Program of Translational Medicine, Department Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. AD - Diabetes Unit, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20210915 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Aged MH - Cardio-Renal Syndrome/diagnosis/mortality/*prevention & control MH - Cardiovascular Diseases/diagnosis/mortality/*prevention & control MH - Cause of Death MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/diagnosis/*drug therapy/mortality MH - Female MH - Hospitalization MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Incidence MH - Incretins/adverse effects/*therapeutic use MH - Kidney Diseases/diagnosis/mortality/*prevention & control MH - Male MH - Middle Aged MH - Risk Assessment MH - Risk Factors MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor PMC - PMC8442438 OTO - NOTNLM OT - Albiglutide OT - Cardiorenal outcomes OT - Cardiovascular outcome trials OT - Dulaglutide OT - Efpeglenatide OT - Exenatide OT - GLP-1RA OT - Liraglutide OT - Lixisenatide OT - Oral semaglutide OT - Semaglutide OT - Type 2 diabetes COIS- D. G. received a consultancy fee from Eli Lilly and has held lectures for Eli Lilly, Boehringer Ingelheim, Novo Nordisk, Novartis, Mundipharma, Sanofi. M. I. M. has held lectures for Astrazeneca, Sanofi, NovoNordisk, and MSD. K. E. received a consultancy fee from Eli Lilly and has held lectures for Eli Lilly, Sanofi, and Novo Nordisk. A.C. has been an advisory board member for Abbott, Astra Zeneca, Boehringer Ingelheim, DOC Generici, Eli Lilly, Janssen, Mundipharma, Novo Nordisk and OM Pharma; has given lectures for Astra Zeneca, Berlin Chemie, Boehringer Ingelheim, Eli Lilly, Mundipharma, Novo Nordisk and Roche Diagnostics; and has received research grants from Astra Zeneca, Eli Lilly, Mitsubishi and Novartis. No other potential conflicts of interest relevant to this article were reported. EDAT- 2021/09/17 06:00 MHDA- 2022/02/08 06:00 PMCR- 2021/09/15 CRDT- 2021/09/16 05:44 PHST- 2021/07/08 00:00 [received] PHST- 2021/08/19 00:00 [accepted] PHST- 2021/09/16 05:44 [entrez] PHST- 2021/09/17 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/09/15 00:00 [pmc-release] AID - 10.1186/s12933-021-01366-8 [pii] AID - 1366 [pii] AID - 10.1186/s12933-021-01366-8 [doi] PST - epublish SO - Cardiovasc Diabetol. 2021 Sep 15;20(1):189. doi: 10.1186/s12933-021-01366-8. PMID- 34514682 OWN - NLM STAT- MEDLINE DCOM- 20220331 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 24 IP - 1 DP - 2022 Jan TI - Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss. PG - 94-105 LID - 10.1111/dom.14551 [doi] AB - AIM: We evaluated gastrointestinal (GI) adverse events (AEs) with once-weekly semaglutide 2.4 mg in adults with overweight or obesity and their contribution to weight loss (WL). MATERIALS AND METHODS: AE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262). WL was analysed by presence/absence of GI AEs. Mediation analysis estimated WL effects mediated by and unrelated to GI AEs. GI tolerability with semaglutide 2.4 mg maintenance and cessation after dose escalation was evaluated using STEP 4 data among 803 participants tolerating 20 weeks of semaglutide run-in. RESULTS: GI AEs were more common with semaglutide 2.4 mg than placebo, with most frequently nausea (43.9% vs. 16.1% of participants), diarrhoea (29.7% vs. 15.9%), vomiting (24.5% vs. 6.3%) and constipation (24.2% vs. 11.1%). Most GI AEs with semaglutide were non-serious (99.5% of AEs), mild-to-moderate (98.1%), transient and occurred most frequently during/shortly after dose escalation. Few semaglutide-treated participants (4.3%) permanently discontinued treatment for GI AEs. In STEP 1-3, mean WL with semaglutide 2.4 mg was similar in participants without (9.6%-17.1%) versus with GI AEs (11.4%-17.7%). Consistent with this observation, mediation analysis found that GI AEs contributed little to semaglutide-induced WL: of the additional 7.6%-14.4% WL with semaglutide versus placebo, <1 percentage point was mediated by GI AEs. In STEP 4, semaglutide 2.4 mg maintenance was well tolerated. CONCLUSIONS: GI AEs were more common with semaglutide 2.4 mg than placebo, but typically mild-to-moderate and transient. Semaglutide-induced WL was largely independent of GI AEs. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - York University, McMaster University and Wharton Weight Management Clinic, Toronto, Ontario, Canada. FAU - Calanna, Salvatore AU - Calanna S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Davies, Melanie AU - Davies M AUID- ORCID: 0000-0002-9987-9371 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - NIHR Leicester Biomedical Research Centre, Leicester, UK. FAU - Dicker, Dror AU - Dicker D AD - Internal Medicine Department & Obesity Clinic, Hasharon Hospital-Rabin Medical Center, Petach-Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Goldman, Bryan AU - Goldman B AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA. FAU - Mosenzon, Ofri AU - Mosenzon O AUID- ORCID: 0000-0002-5702-7584 AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. FAU - Rubino, Domenica M AU - Rubino DM AD - Washington Center for Weight Management and Research, Arlington, Virginia, USA. FAU - Thomsen, Mette AU - Thomsen M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wadden, Thomas A AU - Wadden TA AD - Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Pedersen, Sue D AU - Pedersen SD AD - C-ENDO Diabetes & Endocrinology Clinic Calgary, Calgary, Alberta, Canada. LA - eng PT - Journal Article PT - Randomized Controlled Trial DEP - 20211004 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - Glucagon-Like Peptides/adverse effects MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Injections, Subcutaneous MH - Obesity/chemically induced/complications/drug therapy MH - *Overweight/drug therapy MH - Weight Loss MH - Semaglutide PMC - PMC9293236 OTO - NOTNLM OT - GLP-1 analogue OT - antiobesity drug OT - obesity therapy OT - phase III study OT - randomized trial OT - weight control COIS- SW reports research funding, advisory/consulting fees and/or other support from AstraZeneca, Bausch Health Inc., Boehringer Ingelheim, CIHR, Janssen, Lilly and Novo Nordisk. SC is an employee of and shareholder at Novo Nordisk A/S. MD is a consultant, advisory board member and speaker for AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck Sharp & Dohme, Novo Nordisk and Sanofi-Aventis; advisory board member for Gilead Sciences Ltd. and Servier; speaker for Mitsubishi Tanabe Pharma Corporation, NAPP and Takeda Pharmaceuticals International Inc.; received research funding from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Novo Nordisk and Sanofi-Aventis. MD is also co-funded by the NIHR Leicester Biomedical Research Centre. DD is a consultant, advisory board member and speaker for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk and Sanofi-Aventis; received research funding from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi-Aventis. BG is an employee of and shareholder at Novo Nordisk A/S. IL reports research funding, advisory/consulting fees and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GI Dynamics, Intarcia, Intercept, Janssen, Mannkind, Merck, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, TARGETPharma, Valeritas and Zealand Pharma. OM is an advisory board member for AstraZeneca, Boehringer Ingelheim, BOL Pharma, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk and Sanofi; received research grant support through Hadassah Hebrew University Hospital from AstraZeneca and Novo Nordisk; speaker's bureau for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck Sharp & Dohme, Novo Nordisk and Sanofi. DMR is a consultant, advisory board member, speaker and clinical investigator for Novo Nordisk; clinical investigator for AstraZeneca and Boehringer Ingelheim; received honoraria from Medscape; received research funding from Obesinov and SARL; holds stock/shares in Novo Nordisk. MT is an employee of and shareholder at Novo Nordisk A/S. TAW serves on advisory boards for Novo Nordisk and WW (formerly Weight Watchers) and has received grant support, on behalf of the University of Pennsylvania, from Novo Nordisk. SDP has received consulting fees and/or speaking honoraria from Abbott, AstraZeneca, Bausch, Bayer, Boehringer Ingelheim, Dexcom, Eli Lilly, HLS, Janssen, Merck, Novo Nordisk and Sanofi; was involved in research studies for Abbott, AstraZeneca, Bausch, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk and Sanofi. EDAT- 2021/09/14 06:00 MHDA- 2022/04/01 06:00 PMCR- 2022/07/18 CRDT- 2021/09/13 07:18 PHST- 2021/08/27 00:00 [revised] PHST- 2021/06/21 00:00 [received] PHST- 2021/09/07 00:00 [accepted] PHST- 2021/09/14 06:00 [pubmed] PHST- 2022/04/01 06:00 [medline] PHST- 2021/09/13 07:18 [entrez] PHST- 2022/07/18 00:00 [pmc-release] AID - DOM14551 [pii] AID - 10.1111/dom.14551 [doi] PST - ppublish SO - Diabetes Obes Metab. 2022 Jan;24(1):94-105. doi: 10.1111/dom.14551. Epub 2021 Oct 4. PMID- 34491708 OWN - NLM STAT- MEDLINE DCOM- 20210909 LR - 20210909 IS - 2159-3000 (Print) IS - 2159-3000 (Linking) VI - 508 DP - 2021 Sep TI - Drug Prescribing: New Drugs and Drug Classes in Family Medicine. PG - 18-24 AB - New drug approvals and safety information are constantly being released. Staying up-to-date can be a daunting task for family physicians. Several electronic resources provide valuable, concise information directly. It is important to be well informed about new drugs, and drug mechanisms, indications, and administration routes. Pertinent new drug mechanisms include calcitonin gene-related peptide receptor antagonists for migraine prevention, selective inhibitors of influenza cap-dependent endonuclease, and adenosine triphosphate-citrate lyase inhibitors for hypercholesterolemia. Dapagliflozin recently gained approval for heart failure with reduced ejection fraction with or without type 2 diabetes. Newly approved administration routes include oral semaglutide and intranasal esketamine and glucagon. Drug accessibility, cost, and advantages over existing drugs should be considered. Physicians also should search formularies and promptly respond to prior authorization requests. Physicians should be knowledgeable about drug safety updates, such as adverse events and drug recalls. When a drug has been recalled, it is imperative for prescribers to provide accurate patient advice and therapeutic alternatives. Clinical pharmacists are excellent resources for new drug information, formulary and cost savings management, and drug recall navigation. CI - Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium. FAU - Yuet, Wei Cheng AU - Yuet WC AD - University of North Texas Health Science Center at Fort Worth College of Pharmacy, 3500 Camp Bowie Blvd, Fort Worth, Texas, 76107. FAU - Lounsbery, Jody AU - Lounsbery J AD - University of Minnesota College of Pharmacy Twin Cities, 5-130 Weaver-Densford Hall 308 Harvard Street SE, Minneapolis, MN 55455. LA - eng PT - Journal Article PL - United States TA - FP Essent JT - FP essentials JID - 101578821 RN - 0 (Pharmaceutical Preparations) SB - IM MH - *Diabetes Mellitus, Type 2 MH - Drug Prescriptions MH - Family Practice MH - Humans MH - *Pharmaceutical Preparations EDAT- 2021/09/08 06:00 MHDA- 2021/09/10 06:00 CRDT- 2021/09/07 17:11 PHST- 2021/09/07 17:11 [entrez] PHST- 2021/09/08 06:00 [pubmed] PHST- 2021/09/10 06:00 [medline] PST - ppublish SO - FP Essent. 2021 Sep;508:18-24. PMID- 34490786 OWN - NLM STAT- MEDLINE DCOM- 20211027 LR - 20260127 IS - 2042-6313 (Electronic) IS - 2042-6305 (Print) IS - 2042-6305 (Linking) VI - 10 IP - 15 DP - 2021 Oct TI - Cost-effectiveness of empagliflozin versus weekly semaglutide as add-on therapy for Type 2 diabetes. PG - 1133-1141 LID - 10.2217/cer-2021-0016 [doi] AB - Aim: Perform a cost-effectiveness analysis of addition of subcutaneous semaglutide versus empagliflozin to usual treatment for patients with Type 2 diabetes and cardiovascular disease in US setting. Materials & methods: A Markov decision model estimated the impact of each strategy using cardiovascular complication rates based on EMPA-REG and SUSTAIN-6 trials. Modeled cohorts were followed for 3 years at 1-month intervals beginning at age 66. Results: Compared with empagliflozin, semaglutide resulted in cost of US$19,964 per quality-adjusted life-year gained. In one-way sensitivity analysis, only semaglutide cost >US$36.25/day (base case US$18.04) resulted in empagliflozin being preferred at a willingness-to-pay threshold of US$50,000/quality-adjusted life-year gained. Conclusion: For patients with Type 2 diabetes and cardiovascular disease, semaglutide is likely more cost-effective than empagliflozin added to usual treatment. FAU - Zupa, Margaret F AU - Zupa MF AUID- ORCID: 0000-0002-8244-9295 AD - Division of Endocrinology & Metabolism, University of Pittsburgh, PA 15213, USA. FAU - Codario, Ronald A AU - Codario RA AUID- ORCID: 0000-0002-2193-1539 AD - Division of Endocrinology & Metabolism, University of Pittsburgh, PA 15213, USA. AD - Division of Endocrinology, Veteran's Health Administration Pittsburgh Health System, PA 15240, USA. FAU - Smith, Kenneth J AU - Smith KJ AUID- ORCID: 0000-0001-8088-566X AD - University of Pittsburgh, Center for Research on Healthcare, PA 15213, USA. LA - eng GR - T32 DK007052/DK/NIDDK NIH HHS/United States GR - 5T32DK007052-45/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210907 PL - England TA - J Comp Eff Res JT - Journal of comparative effectiveness research JID - 101577308 RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Aged MH - Benzhydryl Compounds MH - Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Glucosides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide PMC - PMC8656343 OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT2 inhibitor OT - cost-effectiveness analysis OT - diabetes OT - pharmacoeconomics COIS- Financial & competing interests disclosure This work was supported by the NIDDK T32 Research Training in Diabetes and Endocrinology (grant number: 5T32DK007052-45) provided to the University of Pittsburgh which supports MF Zupa's salary. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. EDAT- 2021/09/08 06:00 MHDA- 2021/10/28 06:00 PMCR- 2022/08/01 CRDT- 2021/09/07 08:38 PHST- 2021/09/08 06:00 [pubmed] PHST- 2021/10/28 06:00 [medline] PHST- 2021/09/07 08:38 [entrez] PHST- 2022/08/01 00:00 [pmc-release] AID - 10.2217/cer-2021-0016 [doi] PST - ppublish SO - J Comp Eff Res. 2021 Oct;10(15):1133-1141. doi: 10.2217/cer-2021-0016. Epub 2021 Sep 7. PMID- 34472698 OWN - NLM STAT- MEDLINE DCOM- 20211209 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 12 DP - 2021 Dec TI - Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials. PG - 2785-2794 LID - 10.1111/dom.14536 [doi] AB - AIMS: To evaluate, through exploratory post hoc subgroup analyses, the efficacy and safety of oral semaglutide versus comparators in Japanese patients enrolled in the global PIONEER 1, 3, 4 and 8 clinical trials. MATERIALS AND METHODS: Patients were randomized to once-daily oral semaglutide 3, 7 or 14 mg or comparator (placebo, sitagliptin 100 mg or liraglutide 1.8 mg). Change from baseline in glycated haemoglobin (HbA1c) and body weight, and proportions of patients attaining HbA1c <7.0% (53 mmol/mol) and body weight loss >/=5%, were analysed at week 26 for all Japanese patients in each trial separately using the treatment policy estimand (regardless of treatment discontinuation or rescue medication use). Adverse events (AEs) were analysed descriptively. RESULTS: Reductions in HbA1c from baseline in Japanese patients were 1.0% to 1.2% (11.3 mmol/mol to 13.3 mmol/mol) and 1.4% to 1.7% (15.7 mmol/mol to 18.3 mmol/mol) for oral semaglutide 7 mg and 14 mg, respectively. HbA1c reductions were similar or greater than with comparators. Body weight reductions were 1.0% to 2.7% and 3.7% to 4.7% for oral semaglutide 7 mg and 14 mg, respectively, and were generally greater with oral semaglutide than comparators. As expected, the main class of AEs was gastrointestinal, and these AEs comprised most commonly mild-to-moderate constipation, nausea and diarrhoea. CONCLUSIONS: Oral semaglutide appears efficacious and well tolerated in Japanese patients across the type 2 diabetes spectrum. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Araki, Eiichi AU - Araki E AUID- ORCID: 0000-0002-4064-7525 AD - Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. FAU - Terauchi, Yasuo AU - Terauchi Y AUID- ORCID: 0000-0002-8872-3697 AD - Yokohama City University, Yokohama, Japan. FAU - Watada, Hirotaka AU - Watada H AUID- ORCID: 0000-0001-5961-1816 AD - Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Deenadayalan, Srikanth AU - Deenadayalan S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Christiansen, Erik AU - Christiansen E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Horio, Hiroshi AU - Horio H AD - Novo Nordisk Pharma Ltd, Tokyo, Japan. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Toranomon Hospital, Tokyo, Japan. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210927 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Japan/epidemiology MH - Treatment Outcome MH - Semaglutide PMC - PMC9293331 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Japanese OT - PIONEER OT - oral semaglutide OT - post hoc OT - subgroup analyses COIS- E.A. has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, Kowa Company, Merck Sharp and Dohme (MSD), Novo Nordisk Pharma, Ono Pharmaceutical, Sanofi and Sumitomo Dainippon Pharma, and scholarship grants from Astellas Pharma, Bayer, Daiichi Sankyo, Eli Lilly Japan, Kowa Company, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, Novartis Pharma, Novo Nordisk Pharma, Sanofi, Sumitomo Dainippon Pharma and Takeda Pharmaceutical. Y.T. reports receiving honoraria for serving on advisory boards for MSD, Boehringer Ingelheim, Tanabe-Mitsubishi, Daiichi Sankyo, Novo Nordisk, Eli Lilly, Sanofi, Astellas Pharma, AstraZeneca and Teijin, speaker's fees from MSD, Ono, Boehringer Ingelheim, Takeda, Tanabe-Mitsubishi, Daiichi Sankyo, Sanwa Kagaku Kenkyusho, Novo Nordisk, Eli Lilly, Sanofi, Dainippon-Sumitomo, Shionogi, Bayer Yakuhin, Astellas and AstraZeneca, and research support from MSD, Ono, Boehringer Ingelheim, Novartis, Takeda, Daiichi Sankyo, Sanwa Kagaku Kenkyusho, Novo Nordisk, Eli Lilly, Sanofi, Dainippon-Sumitomo, Shionogi, Astellas Pharma and AstraZeneca. H.W. reports receiving honoraria (eg, lecture fees) from Mitsubishi Tanabe Pharma, Sumitomo Dainippon Pharma, Sanwa Kagaku Kenkyusho, Takeda, Sanofi, Kowa, MSD, Boehringer Ingelheim, Novo Nordisk and Eli Lilly, research support from Takeda, Boehringer Ingelheim, Kissei Pharma, Novo Nordisk, Mitsubishi Tanabe Pharma, Lifescan Japan, Dainippon-Sumitomo, Kyowa-Kirin and MSD, and endowed courses supported by Boehringer Ingelheim, Kowa, MSD, Mitsubishi Tanabe Pharma, Ono Pharmaceutical, Sanwa Kagaku Kenkyusho, Soiken, Takeda and Dainippon Sumitomo Pharma. S.D., E.C., and H.H. are employees of Novo Nordisk. E.C. holds shares in Novo Nordisk. T.K. reports receiving honoraria (eg, lecture fees) from MSD Corporation, Daiichi Sankyo Co., Ltd, Takeda Pharmaceutical Co., Ltd, Mitsubishi Tanabe Pharma Corporation, Kowa Pharmaceutical Co., Ltd, Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd, AstraZeneca K.K., Sumitomo Dainippon Pharma Co., Ltd, Sanofi K.K., Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd, Sanwa Kagaku Kenkyusho Co., Ltd, Kyowa Hakko Kirin Co., Ltd, Taisho Pharmaceutical Co., Ltd and Novo Nordisk Pharma Ltd, research funding (endowed departments by commercial entities) from Asahi Mutual Life Insurance Company, Takeda Pharmaceutical Co., Ltd, TERUMO Corporation, MSD Corporation, Novo Nordisk Pharma Ltd and Nippon Boehringer Ingelheim Co., Ltd, and scholarship donation from MSD Corporation, Daiichi Sankyo Co., Ltd, Novo Nordisk Pharma Ltd, Sanofi K.K., Takeda Pharmaceutical Co., Ltd, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd, Sumitomo Dainippon Pharma Co., Ltd, Eli Lilly Japan K.K. and Kyowa Hakko Kirin Co., Ltd. EDAT- 2021/09/03 06:00 MHDA- 2021/12/15 06:00 PMCR- 2022/07/18 CRDT- 2021/09/02 08:59 PHST- 2021/08/23 00:00 [revised] PHST- 2021/06/10 00:00 [received] PHST- 2021/08/26 00:00 [accepted] PHST- 2021/09/03 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/09/02 08:59 [entrez] PHST- 2022/07/18 00:00 [pmc-release] AID - DOM14536 [pii] AID - 10.1111/dom.14536 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Dec;23(12):2785-2794. doi: 10.1111/dom.14536. Epub 2021 Sep 27. PMID- 34468297 OWN - NLM STAT- MEDLINE DCOM- 20220502 LR - 20260127 IS - 1873-5592 (Electronic) IS - 1389-4501 (Linking) VI - 23 IP - 3 DP - 2022 TI - Oral Semaglutide in the Management of Type 2 DM: Clinical Status and Comparative Analysis. PG - 311-327 LID - 10.2174/1389450122666210901125420 [doi] AB - BACKGROUND: In the incretin system, Glucagon-like peptide-1 (GLP-1) is a hormone that inhibits the release of glucagon and regulates glucose-dependent insulin secretion. In type 2 diabetes, correcting the impaired incretin system using GLP-1 agonist is a well-defined therapeutic strategy. OBJECTIVES: This review article aims to discuss the mechanism of action, key regulatory events, clinical trials for glycaemic control, and comparative analysis of semaglutide with the second-line antidiabetic drugs. DESCRIPTION: Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist with enhanced glycaemic control in diabetes patients. In 2019, USFDA approved the first oral GLP-1 receptor agonist, semaglutide, to be administered as a once-daily tablet. Further, recent studies highlight the ability of semaglutide to improve Glycemic control in obese patients with a reduction in body weight. Still, in clinical practice, in the type 2 DM treatment paradigm, the impact of oral semaglutide remains unidentified. This review article discusses the mechanism of action, pharmacodynamics, key regulatory events, and clinical trials regarding glycaemic control. CONCLUSION: The review highlights the comparative analysis of semaglutide with the existing second- line drugs for the management of type 2 diabetes mellitus by stressing its benefits and adverse events. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Bandyopadhyay, Ilora AU - Bandyopadhyay I AD - Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India. FAU - Dave, Sunny AU - Dave S AD - Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India. FAU - Rai, Amita AU - Rai A AD - Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India. FAU - Nampoothiri, Madhavan AU - Nampoothiri M AD - Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka,India. FAU - Chamallamudi, Mallikarjuna Rao AU - Chamallamudi MR AD - Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka,India. FAU - Kumar, Nitesh AU - Kumar N AD - Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Drug Targets JT - Current drug targets JID - 100960531 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Incretins MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - Oral Semaglutide OT - glycemic control OT - incretin system OT - mechanism of action OT - type 2 diabetes EDAT- 2021/09/02 06:00 MHDA- 2022/05/03 06:00 CRDT- 2021/09/01 12:21 PHST- 2021/02/13 00:00 [received] PHST- 2021/06/09 00:00 [revised] PHST- 2021/06/24 00:00 [accepted] PHST- 2021/09/02 06:00 [pubmed] PHST- 2022/05/03 06:00 [medline] PHST- 2021/09/01 12:21 [entrez] AID - CDT-EPUB-117611 [pii] AID - 10.2174/1389450122666210901125420 [doi] PST - ppublish SO - Curr Drug Targets. 2022;23(3):311-327. doi: 10.2174/1389450122666210901125420. PMID- 34431633 OWN - NLM STAT- MEDLINE DCOM- 20210826 LR - 20210826 IS - 1660-9379 (Print) IS - 1660-9379 (Linking) VI - 17 IP - 747 DP - 2021 Aug 25 TI - [Potentiation of weight reduction with GLP-1 receptor agonists]. PG - 1405-1410 AB - Glucagon-like peptide-1 receptor agonists are the antidiabetic agents that are associated with the greatest weight loss beyond a marked reduction in glycated haemoglobin. Weight loss results from a reduction in appetite through a predominant central effect combined with a peripheral effect. Liraglutide and semaglutide are developed for the treatment of obesity, independently of type 2 diabetes. Three approaches may be considered to potentiate weight loss: an increase of the drug dosage because of the demonstration of a dose-response, an add-on therapy with a sodium-glucose cotransporter type 2 inhibitor as this agent exerts a complementary action through urinary calorie loss (glucosuria) or a combination of the effects of two incretin hormones (GLP-1 and GIP), as the potent dual agonist tirzepatide currently in development. FAU - Scheen, Andre J AU - Scheen AJ AD - Service de diabetologie, nutrition et maladies metaboliques, CHU Liege, Liege Universite, 4000 Liege, Belgique. AD - Unite de pharmacologie clinique, CHU Liege, Liege Universite, 4000 Liege, Belgique. FAU - Paquot, Nicolas AU - Paquot N AD - Service de diabetologie, nutrition et maladies metaboliques, CHU Liege, Liege Universite, 4000 Liege, Belgique. LA - fre PT - Journal Article TT - Potentialiser la perte de poids avec les agonistes des recepteurs du GLP-1. PL - Switzerland TA - Rev Med Suisse JT - Revue medicale suisse JID - 101219148 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Pharmaceutical Preparations) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - *Pharmaceutical Preparations MH - Weight Loss COIS- A. Scheen declare avoir recu des honoraires comme orateur, membre d'un conseil scientifique ou investigateur clinicien de la part des firmes AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi et Servier. A. Scheen a ete investigateur clinicien dans les etudes SCALE, STEP-1, LEADER, HARMONY OUTCOMES, EMPA-REG OUTCOME, CANVAS-R et DECLARE-TIMI 58. N. Paquot declare avoir recu des honoraires comme orateur, membre d'un conseil scientifique ou investigateur clinicien de la part des firmes AstraZeneca, Boehringer Ingelheim et Eli Lilly. EDAT- 2021/08/26 06:00 MHDA- 2021/08/27 06:00 CRDT- 2021/08/25 08:55 PHST- 2021/08/25 08:55 [entrez] PHST- 2021/08/26 06:00 [pubmed] PHST- 2021/08/27 06:00 [medline] AID - RMS0747-005 [pii] PST - ppublish SO - Rev Med Suisse. 2021 Aug 25;17(747):1405-1410. PMID- 34416133 OWN - NLM STAT- MEDLINE DCOM- 20211208 LR - 20211214 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 133 IP - 8 DP - 2021 Nov TI - Primary care management of type 2 diabetes: a comparison of the efficacy and safety of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. PG - 843-853 LID - 10.1080/00325481.2021.1971461 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 inhibitors (DPP4is) exert their effects via the incretin system, which augments glucose-dependent insulin secretion in response to nutrient intake (the 'incretin effect'). Both classes are well-established pharmacologic options for the management of glycemic control in individuals with type 2 diabetes (T2D) after failure of first-line metformin; however, they have inherent differences in their mechanisms of action that are reflected in their clinical safety and efficacy profiles. GLP-1RAs have high glycemic efficacy and are associated with weight loss and, in some cases, cardioprotective effects, with a side-effect profile of predominantly transient gastrointestinal adverse events. Most GLP-1RAs are administered as subcutaneous injection, although an oral formulation of one GLP-1RA, semaglutide, has recently become available. DPP4is provide moderate glycemic control, are weight-neutral, and do not offer any cardiovascular benefits, but are generally well tolerated. DPP4is are all administered orally. This narrative review aims to provide guidance for a primary care audience on the similarities and differences between GLP-1RA and DPP4i therapies, with a focus on their mechanism of action, clinical safety, efficacy, and real-world effectiveness. The role of incretin-based therapies in the T2D treatment paradigm, including key considerations for guiding treatment decisions, will also be discussed. FAU - Campos, Carlos AU - Campos C AD - Department of Family Medicine, University of Texas Health Science Center, San Antonio, USA. FAU - Unger, Jeff AU - Unger J AUID- ORCID: 0000-0001-9462-6626 AD - Unger Primary Care Concierge Medical Group, Rancho Cucamonga, USA. LA - eng PT - Comparative Study PT - Journal Article DEP - 20210912 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Diabetes Mellitus, Type 2/*drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use MH - Female MH - Glucagon-Like Peptide-1 Receptor/*antagonists & inhibitors/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Middle Aged MH - *Practice Guidelines as Topic MH - Primary Health Care/*standards MH - Treatment Outcome OTO - NOTNLM OT - dipeptidyl peptidase-4 inhibitor OT - glucagon-like peptide-1 receptor agonist OT - glycemic control OT - incretin therapy OT - type 2 diabetes EDAT- 2021/08/21 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/08/20 20:10 PHST- 2021/08/21 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/08/20 20:10 [entrez] AID - 10.1080/00325481.2021.1971461 [doi] PST - ppublish SO - Postgrad Med. 2021 Nov;133(8):843-853. doi: 10.1080/00325481.2021.1971461. Epub 2021 Sep 12. PMID- 34406410 OWN - NLM STAT- MEDLINE DCOM- 20220218 LR - 20250103 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 107 IP - 1 DP - 2022 Jan 1 TI - The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD. PG - 29-38 LID - 10.1210/clinem/dgab578 [doi] AB - CONTEXT: The burden of cirrhosis from nonalcoholic fatty liver disease (NAFLD) is reaching epidemic proportions in the United States. This calls for greater awareness among endocrinologists, who often see but may miss the diagnosis in adults with obesity or type 2 diabetes mellitus (T2D) who are at the highest risk. At the same time, recent studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) are beneficial vs nonalcoholic steatohepatitis (NASH) in this population. This minireview aims to assist endocrinologists to recognize the condition and recent work on the role of GLP-1RAs in NAFLD/NASH. EVIDENCE ACQUISITION: Evidence from observational studies, randomized controlled trials, and meta-analyses. EVIDENCE SYNTHESIS: Endocrinologists should lead multidisciplinary teams to implement recent consensus statements on NAFLD that call for screening and treatment of clinically significant fibrosis to prevent cirrhosis, especially in the high-risk groups (ie, people with obesity, prediabetes, or T2D). With no US Food and Drug Administration (FDA)-approved agents, weight loss is central to successful management, with pharmacological treatment options limited today to vitamin E (in people without T2D) and diabetes medications that reverse steatohepatitis, such as pioglitazone or GLP-1RA. Recently, the benefit of GLP-1RAs in NAFLD, suggested from earlier trials, has been confirmed in adults with biopsy-proven NASH. In 2021, the FDA also approved semaglutide for obesity management. CONCLUSION: A paradigm change is developing between the endocrinologist's greater awareness about their critical role to curve the epidemic of NAFLD and new clinical care pathways that include a broader use of GLP-1RAs in the management of these complex patients. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Patel Chavez, Chandani AU - Patel Chavez C AUID- ORCID: 0000-0002-8323-7761 AD - Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL 32610, USA. FAU - Cusi, Kenneth AU - Cusi K AUID- ORCID: 0000-0002-8629-418X AD - Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL 32610, USA. AD - Malcom Randall Veteran Administration Medical Center at Gainesville, FL 32610, USA. FAU - Kadiyala, Sushma AU - Kadiyala S AUID- ORCID: 0000-0003-3412-4418 AD - Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL 32610, USA. AD - Malcom Randall Veteran Administration Medical Center at Gainesville, FL 32610, USA. LA - eng PT - Journal Article PT - Review PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cost of Illness MH - Diabetes Mellitus, Type 2/complications/*drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Humans MH - Hypoglycemic Agents/pharmacology/*therapeutic use MH - Liver Cirrhosis/epidemiology/*prevention & control MH - Meta-Analysis as Topic MH - Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/metabolism/pathology MH - Obesity/complications/*drug therapy/metabolism MH - Observational Studies as Topic MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - United States/epidemiology MH - Weight Loss MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC8684453 OTO - NOTNLM OT - GLP-1 receptor agonists OT - diabetes OT - liraglutide OT - metabolic syndrome OT - nonalcoholic fatty liver disease (NAFLD) OT - obesity OT - primary care OT - semaglutide EDAT- 2021/08/19 06:00 MHDA- 2022/02/19 06:00 PMCR- 2021/08/18 CRDT- 2021/08/18 12:28 PHST- 2021/06/23 00:00 [received] PHST- 2021/08/19 06:00 [pubmed] PHST- 2022/02/19 06:00 [medline] PHST- 2021/08/18 12:28 [entrez] PHST- 2021/08/18 00:00 [pmc-release] AID - 6354361 [pii] AID - dgab578 [pii] AID - 10.1210/clinem/dgab578 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2022 Jan 1;107(1):29-38. doi: 10.1210/clinem/dgab578. PMID- 34397684 OWN - NLM STAT- MEDLINE DCOM- 20210824 LR - 20250623 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 100 IP - 30 DP - 2021 Jul 30 TI - Comparative efficacy of 5 sodium glucose cotransporter 2 inhibitor and 7 glucagon-like peptide 1 receptor agonists interventions on cardiorenal outcomes in type 2 diabetes patients: A network meta-analysis based on cardiovascular or renal outcome trials. PG - e26431 LID - 10.1097/MD.0000000000026431 [doi] LID - e26431 AB - BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been demonstrated to be able to improve the cardiovascular and renal prognosis in patients with type 2 diabetes (T2D). However, the relative efficacy of various SGLT2 inhibitors and GLP-1 RAs on cardiorenal outcomes is unestablished. METHODS: We searched PubMed and Embase for relevant cardiovascular or renal outcome trials (CVOTs). Endpoints of interest were major adverse cardiovascular events (MACE), stroke, myocardial infarction (MI), cardiovascular death (CVD), all-cause death (ACD), kidney function progression (KFP), and hospitalization for heart failure (HHF). Bayesian network meta-analysis was conducted to produce pooled hazard ratio (HR) and 95% confidence interval (CI). We calculated the probability values of surface under the cumulative ranking curve to rank active and placebo interventions. RESULTS: Fourteen COVTs were included in analysis. Sotagliflozin (HR 0.76, 95% CI 0.61-0.94), subcutaneous semaglutide, and albiglutide lowered MACE versus lixisenatide among others. Sotagliflozin (HR 0.59, 95% CI 0.40-0.89), canagliflozin, and empagliflozin lowered HHF versus subcutaneous semaglutide among others. Dapagliflozin and empagliflozin lowered KFP versus exenatide among others. Empagliflozin and oral semaglutide lowered CVD versus dapagliflozin among others. Sotagliflozin (HR 0.65, 95% CI 0.47-0.91) and albiglutide lowered MI versus ertugliflozin among others. Sotagliflozin (HR 0.56, 95% CI 0.37-0.85) and subcutaneous semaglutide lowered stroke versus empagliflozin among others. Oral semaglutide and empagliflozin lowered ACD versus subcutaneous semaglutide among others. The maximum surface under the cumulative ranking curve values followed sotagliflozin, subcutaneous semaglutide, and albiglutide in lowering MACE; sotagliflozin, canagliflozin, and empagliflozin in lowering HHF; dapagliflozin and empagliflozin in lowering KFP; empagliflozin and oral semaglutide in lowering CVD; sotagliflozin and albiglutide in lowering MI; sotagliflozin and subcutaneous semaglutide in lowering stroke; and oral semaglutide and empagliflozin in lowering ACD. CONCLUSIONS: This updated network meta-analysis reproduced the findings in the first network meta-analysis, and moreover revealed that sotagliflozin was one of the most effective drugs as for lowering MI, stroke, MACE, and HHF, whereas ertugliflozin was not. These findings will provide the according evidence regarding the usage of specific SGLT2 inhibitors and GLP-1 RAs in T2D patients for prevention of specific cardiorenal endpoints. CI - Copyright (c) 2021 the Author(s). Published by Wolters Kluwer Health, Inc. FAU - Duan, Xue-Yan AU - Duan XY AD - Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen. FAU - Liu, Shu-Yan AU - Liu SY AUID- ORCID: 0000-0001-9345-0825 AD - Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. FAU - Yin, Dao-Gen AU - Yin DG AD - Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - Glucagon-Like Peptide-1 Receptor/*antagonists & inhibitors/therapeutic use MH - Heart/*drug effects/physiopathology MH - Humans MH - Kidney/*drug effects/physiopathology MH - Sodium-Glucose Transporter 2 Inhibitors/*adverse effects/therapeutic use MH - Treatment Outcome PMC - PMC8322563 COIS- The authors report no conflicts of interest. EDAT- 2021/08/17 06:00 MHDA- 2021/08/25 06:00 PMCR- 2021/07/30 CRDT- 2021/08/16 12:49 PHST- 2020/12/25 00:00 [received] PHST- 2021/06/03 00:00 [accepted] PHST- 2021/08/16 12:49 [entrez] PHST- 2021/08/17 06:00 [pubmed] PHST- 2021/08/25 06:00 [medline] PHST- 2021/07/30 00:00 [pmc-release] AID - 00005792-202107300-00005 [pii] AID - MD-D-20-12808 [pii] AID - 10.1097/MD.0000000000026431 [doi] PST - ppublish SO - Medicine (Baltimore). 2021 Jul 30;100(30):e26431. doi: 10.1097/MD.0000000000026431. PMID- 34385300 OWN - NLM STAT- MEDLINE DCOM- 20210923 LR - 20240426 IS - 1473-4893 (Electronic) IS - 1470-2118 (Print) IS - 1470-2118 (Linking) VI - 21 IP - 5 DP - 2021 Sep TI - Research in brief: Effective pharmacotherapy for the management of obesity. PG - e517-e518 LID - 10.7861/clinmed.2021-0253 [doi] FAU - Cacciottolo, Tessa M AU - Cacciottolo TM AD - Wellcome-MRC Institute of Metabolic Science, Cambridge, UK. FAU - Evans, Kate AU - Evans K AD - University Hospitals Plymouth NHS Trust, Plymouth, UK. LA - eng PT - Journal Article DEP - 20210811 PL - England TA - Clin Med (Lond) JT - Clinical medicine (London, England) JID - 101092853 RN - 0 (Hypoglycemic Agents) SB - IM MH - *Diabetes Mellitus, Type 2 MH - Humans MH - Hypoglycemic Agents MH - *Obesity/drug therapy PMC - PMC8439523 OTO - NOTNLM OT - GLP-1 agonist OT - melanocortin OT - obesity OT - semaglutide OT - setmelanotide EDAT- 2021/08/14 06:00 MHDA- 2021/09/24 06:00 PMCR- 2021/09/01 CRDT- 2021/08/13 06:13 PHST- 2021/08/14 06:00 [pubmed] PHST- 2021/09/24 06:00 [medline] PHST- 2021/08/13 06:13 [entrez] PHST- 2021/09/01 00:00 [pmc-release] AID - S1470-2118(24)03073-2 [pii] AID - clinmedicine [pii] AID - 10.7861/clinmed.2021-0253 [doi] PST - ppublish SO - Clin Med (Lond). 2021 Sep;21(5):e517-e518. doi: 10.7861/clinmed.2021-0253. Epub 2021 Aug 11. PMID- 34373613 OWN - NLM STAT- MEDLINE DCOM- 20220415 LR - 20260127 IS - 1476-5454 (Electronic) IS - 0950-222X (Print) IS - 0950-222X (Linking) VI - 36 IP - 1 DP - 2022 Jan TI - Semaglutide and the risk of diabetic retinopathy-current perspective. PG - 10-11 LID - 10.1038/s41433-021-01741-5 [doi] FAU - Sharma, Ashish AU - Sharma A AUID- ORCID: 0000-0002-8550-9791 AD - Lotus Eye Hospital and Institute, Avinashi Road, Coimbatore, TN, India. drashish79@hotmail.com. FAU - Parachuri, Nikulaa AU - Parachuri N AD - Lotus Eye Hospital and Institute, Avinashi Road, Coimbatore, TN, India. FAU - Kumar, Nilesh AU - Kumar N AUID- ORCID: 0000-0002-7439-2081 AD - Lotus Eye Hospital and Institute, Avinashi Road, Coimbatore, TN, India. AD - Madhavi Netralaya, Ara, Bihar, India. FAU - Saboo, Bharat AU - Saboo B AD - Prayas Diabetic Centre, Indore, India. FAU - Tripathi, Hridaya Nath AU - Tripathi HN AD - Sahara Hospital, Lucknow, UP, India. FAU - Kuppermann, Baruch D AU - Kuppermann BD AD - Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA, USA. FAU - Bandello, Francesco AU - Bandello F AUID- ORCID: 0000-0003-3238-9682 AD - University Vita-Salute, Scientific Institute San Raffaele, Milano, Italy. LA - eng PT - Journal Article DEP - 20210809 PL - England TA - Eye (Lond) JT - Eye (London, England) JID - 8703986 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2 MH - *Diabetic Retinopathy MH - Glucagon-Like Peptides/adverse effects MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Semaglutide PMC - PMC8727607 COIS- AS: CONSULTANT: for Novartis, Allergan, Bayer and Intas. BDK: CLINICAL RESEARCH: Alcon, Alimera, Allegro, Allergan, Apellis, Clearside, Genentech, GSK, Ionis, jCyte, Novartis, Regeneron, ThromboGenics; CONSULTANT: Alimera, Allegro, Allergan, Cell Care, Dose, Eyedaptic, Galimedix, Genentech, Glaukos, Interface Biologics, jCyte, Novartis, Ophthotech, Regeneron, Revana, Theravance Biopharma. BDK acknowledges an unrestricted grant from Research to Prevent Blindness to the Gavin Herbert Eye Institute at the University of California, Irvine. FB: CONSULTANT: Allergan, Bayer, Boehringer- Ingelheim, Fidia Sooft, Hofmann La Roche, Novartis, NTC Pharma, Sifi, Thrombogenics, Zeiss. NK: None. NP: None. BS: None. HNT: None. EDAT- 2021/08/11 06:00 MHDA- 2022/04/16 06:00 PMCR- 2023/01/01 CRDT- 2021/08/10 06:33 PHST- 2021/07/09 00:00 [received] PHST- 2021/07/30 00:00 [accepted] PHST- 2021/07/21 00:00 [revised] PHST- 2021/08/11 06:00 [pubmed] PHST- 2022/04/16 06:00 [medline] PHST- 2021/08/10 06:33 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.1038/s41433-021-01741-5 [pii] AID - 1741 [pii] AID - 10.1038/s41433-021-01741-5 [doi] PST - ppublish SO - Eye (Lond). 2022 Jan;36(1):10-11. doi: 10.1038/s41433-021-01741-5. Epub 2021 Aug 9. PMID- 34338402 OWN - NLM STAT- MEDLINE DCOM- 20211019 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 11 DP - 2021 Nov TI - Semaglutide single-dose pen-injector: Post hoc analysis of summative usability testing for weight management. PG - 2590-2594 LID - 10.1111/dom.14509 [doi] AB - Subcutaneous semaglutide, at a 2.4 mg once-weekly maintenance dose, is approved in the United States for weight management in individuals with a body mass index (BMI) of 30 kg/m(2) or higher, or with a BMI of 27 kg/m(2) or higher and at least one obesity-related co-morbidity. To investigate the usability of the semaglutide pen-injector in individuals who met these criteria, we report post hoc analysis of the summative (human factors validation) usability testing and safety analysis involving patients with type 2 diabetes (an obesity-related co-morbidity) with the same pen-injector, limited to the 26 out of 30 patients with a BMI of 27 kg/m(2) or higher (11 pen-injector-naive, 15 pen-injector-experienced) and 15 non-pharmacist healthcare professionals (HCPs). Participants performed two simulated injections into an injection pad. No potentially serious use errors occurred. Mean subjective ease-of-use rating on a seven-point scale, where 1 = difficult and 7 = easy, was 6.9 for the second injection in all three groups. These results suggest that the semaglutide pen-injector is easy to use and not associated with serious use errors when used by pen-injector-naive or pen-injector-experienced patients meeting the requirement for weight management with semaglutide treatment, and by non-pharmacist HCPs. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Klonoff, David C AU - Klonoff DC AUID- ORCID: 0000-0001-6394-6862 AD - Mills-Peninsula Medical Center, San Mateo, California, USA. FAU - Bassock, Stephanie AU - Bassock S AD - Emergo by UL, Chicago, Illinois, USA. FAU - Engels, Ella AU - Engels E AD - Emergo by UL, Concord, Massachusetts, USA. FAU - Frederiksen, Marie AU - Frederiksen M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Marber, Matthew AU - Marber M AD - Emergo by UL, Concord, Massachusetts, USA. FAU - Qvist, Marianne AU - Qvist M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sparre, Thomas AU - Sparre T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Snitker, Soren AU - Snitker S AUID- ORCID: 0000-0001-8313-6701 AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210831 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Injections, Subcutaneous MH - User-Centered Design MH - User-Computer Interface MH - Semaglutide PMC - PMC9292194 OTO - NOTNLM OT - GLP-1 analogue OT - antiobesity drug OT - type 2 diabetes COIS- DCK is a consultant for EoFlow, Fractyl, Lifecare, Novo Nordisk, Roche Diagnostics, Samsung, and Thirdwayv. SB is an employee of Emergo by UL, based in Chicago, Illinois. Over the time of this analysis and the development of this report, EE and MM were employees at Emergo by UL, Concord, Massachusetts. Emergo by UL performs various usability testing studies on behalf of Novo Nordisk and is paid by Novo Nordisk. MF, MQ, TS, and SS are employees of Novo Nordisk, Soborg, Denmark, and MQ and TS own stock in the company. EDAT- 2021/08/03 06:00 MHDA- 2021/10/21 06:00 PMCR- 2022/07/18 CRDT- 2021/08/02 09:01 PHST- 2021/07/16 00:00 [revised] PHST- 2021/05/22 00:00 [received] PHST- 2021/07/28 00:00 [accepted] PHST- 2021/08/03 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/08/02 09:01 [entrez] PHST- 2022/07/18 00:00 [pmc-release] AID - DOM14509 [pii] AID - 10.1111/dom.14509 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Nov;23(11):2590-2594. doi: 10.1111/dom.14509. Epub 2021 Aug 31. PMID- 34337999 OWN - NLM STAT- MEDLINE DCOM- 20220203 LR - 20260127 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 27 IP - 8 DP - 2021 Aug TI - A RESPONSE TO: "COST-EFFECTIVENESS OF ORAL SEMAGLUTIDE ADDED TO CURRENT ANTIHYPERGLYCEMIC TREATMENT FOR TYPE 2 DIABETES". PG - 1140-1141 LID - 10.18553/jmcp.2021.27.8.1140 [doi] FAU - Kohli-Lynch, Ciaran N AU - Kohli-Lynch CN AD - Northwestern University Center for Health Services & Outcomes Research Chicago, IL. FAU - Ruiz-Negron, Natalia AU - Ruiz-Negron N AD - University of Utah Department of Pharmacotherapy L. S. Skaggs Pharmacy Institute Salt Lake City, UT. FAU - Beal, Amy AU - Beal A AD - SelectHealth Murray, UT. FAU - Bellows, Brandon K AU - Bellows BK AD - Columbia University Department of Medicine New York, NY. LA - eng PT - Comment PT - Letter PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - J Manag Care Spec Pharm. 2021 Apr;27(4):455-468. PMID: 33769850 CIN - J Manag Care Spec Pharm. 2021 Aug;27(8):1141. doi: 10.18553/jmcp.2021.27.8.1141. PMID: 34337997 MH - Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide PMC - PMC10394429 EDAT- 2021/08/03 06:00 MHDA- 2022/02/04 06:00 PMCR- 2021/08/01 CRDT- 2021/08/02 08:43 PHST- 2021/08/02 08:43 [entrez] PHST- 2021/08/03 06:00 [pubmed] PHST- 2022/02/04 06:00 [medline] PHST- 2021/08/01 00:00 [pmc-release] AID - 10.18553/jmcp.2021.27.8.1140 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2021 Aug;27(8):1140-1141. doi: 10.18553/jmcp.2021.27.8.1140. PMID- 34305810 OWN - NLM STAT- MEDLINE DCOM- 20220107 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 12 DP - 2021 TI - Safety of Semaglutide. PG - 645563 LID - 10.3389/fendo.2021.645563 [doi] LID - 645563 AB - The glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is the most recently approved agent of this drug class, and the only GLP-1RA currently available as both subcutaneous and oral formulation. While GLP-1RAs effectively improve glycemic control and cause weight loss, potential safety concerns have arisen over the years. For semaglutide, such concerns have been addressed in the extensive phase 3 registration trials including cardiovascular outcome trials for both subcutaneous (SUSTAIN: Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) and oral (PIONEER: Peptide InnOvatioN for the Early diabEtes tReatment) semaglutide and are being studied in further trials and registries, including real world data studies. In the current review we discuss the occurrence of adverse events associated with semaglutide focusing on hypoglycemia, gastrointestinal side effects, pancreatic safety (pancreatitis and pancreatic cancer), thyroid cancer, gallbladder events, cardiovascular aspects, acute kidney injury, diabetic retinopathy (DRP) complications and injection-site and allergic reactions and where available, we highlight potential underlying mechanisms. Furthermore, we discuss whether effects are specific for semaglutide or a class effect. We conclude that semaglutide induces mostly mild-to-moderate and transient gastrointestinal disturbances and increases the risk of biliary disease (cholelithiasis). No unexpected safety issues have arisen to date, and the established safety profile for semaglutide is similar to that of other GLP-1RAs where definitive conclusions for pancreatic and thyroid cancer cannot be drawn at this point due to low incidence of these conditions. Due to its potent glucose-lowering effect, patients at risk for deterioration of existing DRP should be carefully monitored if treated with semaglutide, particularly if also treated with insulin. Given the beneficial metabolic and cardiovascular actions of semaglutide, and the low risk for severe adverse events, semaglutide has an overall favorable risk/benefit profile for patient with type 2 diabetes. CI - Copyright (c) 2021 Smits and Van Raalte. FAU - Smits, Mark M AU - Smits MM AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands. FAU - Van Raalte, Daniel H AU - Van Raalte DH AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20210707 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM EIN - Front Endocrinol (Lausanne). 2021 Nov 10;12:786732. doi: 10.3389/fendo.2021.786732. PMID: 34858353 MH - Acute Kidney Injury/chemically induced MH - Animals MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Cardiovascular System/drug effects MH - Cholelithiasis/*drug therapy MH - Clinical Trials as Topic MH - Clinical Trials, Phase III as Topic MH - Diabetes Mellitus, Type 2/*drug therapy MH - Diabetic Retinopathy/drug therapy MH - Gallbladder/drug effects MH - Gastrointestinal Tract/drug effects MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/*adverse effects/*therapeutic use MH - Humans MH - Hypoglycemic Agents/administration & dosage MH - Insulin/therapeutic use MH - Nausea/chemically induced MH - Pancreas/drug effects MH - Pancreatic Neoplasms/chemically induced MH - Pancreatitis/chemically induced MH - Patient Safety MH - Peptides/chemistry MH - Thyroid Neoplasms/chemically induced MH - Time Factors MH - Semaglutide PMC - PMC8294388 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonist (GLP-1RA) OT - oral OT - safety OT - semaglutide OT - subcutaneous OT - type 2 diabetes COIS- DVR has acted as a consultant and received honoraria from Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk and Sanofi and has received research operating funds from the Boehringer Ingelheim-Eli Lilly Diabetes Alliance, MSD, AstraZeneca and Novo Nordisk. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this article received funding from Novo Nordisk. The funder had the following involvement in the article: medical writing support. EDAT- 2021/07/27 06:00 MHDA- 2022/01/08 06:00 PMCR- 2021/01/01 CRDT- 2021/07/26 06:23 PHST- 2020/12/23 00:00 [received] PHST- 2021/04/19 00:00 [accepted] PHST- 2021/07/26 06:23 [entrez] PHST- 2021/07/27 06:00 [pubmed] PHST- 2022/01/08 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2021.645563 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2021 Jul 7;12:645563. doi: 10.3389/fendo.2021.645563. eCollection 2021. PMID- 34302978 OWN - NLM STAT- MEDLINE DCOM- 20220301 LR - 20250103 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 171 DP - 2021 Sep TI - Anti-diabetic drugs and weight loss in patients with type 2 diabetes. PG - 105782 LID - S1043-6618(21)00366-2 [pii] LID - 10.1016/j.phrs.2021.105782 [doi] AB - INTRODUCTION: Obesity is frequently a comorbidity of type 2 diabetes. Even modest weight loss can significantly improve glucose homeostasis and lessen cardiometabolic risk factors in patients with type 2 diabetes, but lifestyle-based weight loss strategies are not long-term effective. There is an increasing need to consider pharmacological approaches to assist weight loss in the so called diabesity syndrome. Aim of this review is to analyze the weight-loss effect of non-insulin glucose lowering drugs in patients with type 2 diabetes. MATERIAL AND METHODS: A systematic analysis of the literature on the effect of non-insulin glucose lowering drugs on weight loss in patients with type 2 diabetes was performed. For each class of drugs, the following parameters were analyzed: kilograms lost on average, effect on body mass index and body composition. RESULTS: Our results suggested that anti-diabetic drugs can be stratified into 3 groups based on their efficacy in weight loss: metformin, acarbose, empagliflozin and exenatide resulted in a in a mild weight loss (less than 3.2% of initial weight); canagliflozin, ertugliflozin, dapagliflozin and dulaglutide induces a moderate weight loss (between 3.2% and 5%); liraglutide, semaglutide and tirzepatide resulted in a strong weight loss (greater than 5%). CONCLUSIONS: This study shows that new anti-diabetic drugs, particularly GLP1-RA and Tirzepatide, are the most effective in inducing weight loss in patients with type 2 diabetes. Interestingly, exenatide appears to be the only GLP1-RA that induces a mild weight loss. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Lazzaroni, Elisa AU - Lazzaroni E AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Ben Nasr, Moufida AU - Ben Nasr M AD - International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita Degli Studi Milano, Milan, Italy; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. FAU - Loretelli, Cristian AU - Loretelli C AD - International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita Degli Studi Milano, Milan, Italy. FAU - Pastore, Ida AU - Pastore I AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Plebani, Laura AU - Plebani L AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Lunati, Maria Elena AU - Lunati ME AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Vallone, Luciana AU - Vallone L AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Bolla, Andrea Mario AU - Bolla AM AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Rossi, Antonio AU - Rossi A AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Montefusco, Laura AU - Montefusco L AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy. FAU - Ippolito, Elio AU - Ippolito E AD - International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita Degli Studi Milano, Milan, Italy. FAU - Berra, Cesare AU - Berra C AD - Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS Multimedica, Milan, Italy. FAU - D'Addio, Francesca AU - D'Addio F AD - International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita Degli Studi Milano, Milan, Italy. FAU - Zuccotti, Gian Vincenzo AU - Zuccotti GV AD - Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, Dept. Biomedical and Clinical Sciences "L. Sacco", Universita di Milano and Pediatric Department, Buzzi Children's Hospital, Milan, Italy. FAU - Fiorina, Paolo AU - Fiorina P AD - Division of Endocrinology, ASST Fatebenefratelli-Sacco, Milan, Italy; International Center for T1D, Pediatric Clinical Research Center Romeo ed Enrica Invernizzi, DIBIC, Universita Degli Studi Milano, Milan, Italy; Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: paolo.fiorina@childrens.harvard.edu. LA - eng PT - Journal Article PT - Systematic Review DEP - 20210722 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Gastric Inhibitory Polypeptide/metabolism MH - Glucagon-Like Peptide 1/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Obesity/*drug therapy/metabolism MH - Weight Loss/*drug effects MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Acarbose (PubChem CID: 41774) OT - Anti-diabetic drugs OT - Body composition OT - Canagliflozin (PubChem CID: 24812758) OT - Dapagliflozin (PubChem CID: 9887712) OT - Diabesity OT - Empagliflozin (PubChem CID: 11949646) OT - Ertugliflozin (PubChem CID: 44814423) OT - Exenatide (PubChem CID: 45588096) OT - Liraglutide (PubChem CID: 16134956) OT - Metformin (PubChem CID: 4091) OT - Semaglutide (PubChem CID: 56843331) OT - Type 2 diabetes OT - Weight loss EDAT- 2021/07/25 06:00 MHDA- 2022/03/03 06:00 CRDT- 2021/07/24 20:13 PHST- 2021/06/01 00:00 [received] PHST- 2021/07/17 00:00 [revised] PHST- 2021/07/20 00:00 [accepted] PHST- 2021/07/25 06:00 [pubmed] PHST- 2022/03/03 06:00 [medline] PHST- 2021/07/24 20:13 [entrez] AID - S1043-6618(21)00366-2 [pii] AID - 10.1016/j.phrs.2021.105782 [doi] PST - ppublish SO - Pharmacol Res. 2021 Sep;171:105782. doi: 10.1016/j.phrs.2021.105782. Epub 2021 Jul 22. PMID- 34296522 OWN - NLM STAT- MEDLINE DCOM- 20211125 LR - 20240831 IS - 1758-8111 (Electronic) IS - 1758-8103 (Print) IS - 1758-8103 (Linking) VI - 11 IP - 5 DP - 2021 Oct TI - Confirmatory psychometric evaluations of the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT). PG - e12477 LID - 10.1111/cob.12477 [doi] LID - e12477 AB - The Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) was developed to assess weight-related physical and psychosocial functioning in the context of clinical trials. Data from two pivotal trials of once-weekly subcutaneous semaglutide for the purpose of weight management (NCT03548935 and NCT03552757) were analysed to confirm the structure, reliability, validity, and responsiveness of the IWQOL-Lite-CT and evaluate the magnitude of meaningful within-patient change in patients with overweight or obesity, with and without type 2 diabetes. Factor analyses and inter-item correlations confirmed the IWQOL-Lite-CT structure and scoring algorithm. Each composite score (physical, physical function, psychosocial, and total) demonstrated excellent internal consistency (Cronbach's alphas >/= 0.82) and test-retest reliability (intraclass correlation coefficients >/= 0.85) in both trials. Patterns of cross-sectional and longitudinal construct validity correlations were generally consistent with hypotheses. Each of the IWQOL-Lite-CT composites was able to discriminate between known groups. Effect sizes and paired t tests comparing IWQOL-Lite-CT scores at baseline and Week 68 were statistically significant for all composites in both trials (P < 0.0001), providing strong support for the ability to detect change. Results of anchor-based analyses supported responder thresholds ranging from 13.5 to 16.6 across composite scores. The IWQOL-Lite-CT, a comprehensive assessment of weight-related functioning from the patient perspective, is appropriate for use in clinical trials evaluating the efficacy of new treatments for weight management. CI - (c) 2021 Novo Nordisk. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation. FAU - Kolotkin, Ronette L AU - Kolotkin RL AUID- ORCID: 0000-0002-1300-2131 AD - Quality of Life Consulting, Durham, North Carolina, USA. AD - Department of Family Medicine and Community Health, Duke University School of Medicine, Durham, North Carolina, USA. AD - Faculty of Health and Social Sciences, Western Norway University of Applied Sciences, Forde, Norway. AD - Centre of Health Research, Forde Hospital Trust, Forde, Norway. AD - Morbid Obesity Centre, Vestfold Hospital Trust, Tonsberg, Norway. FAU - Williams, Valerie S L AU - Williams VSL AD - Department of Patient Reported Outcomes, RTI Health Solutions, Research Triangle Park, North Carolina, USA. FAU - von Huth Smith, Lisa AU - von Huth Smith L AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Meincke, Henrik Hjorth AU - Meincke HH AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Qin, Shanshan AU - Qin S AD - Department of Patient Reported Outcomes, RTI Health Solutions, Research Triangle Park, North Carolina, USA. FAU - Williams, Nicole AU - Williams N AD - Department of Patient Reported Outcomes, RTI Health Solutions, Research Triangle Park, North Carolina, USA. FAU - Fehnel, Sheri E AU - Fehnel SE AD - Department of Patient Reported Outcomes, RTI Health Solutions, Research Triangle Park, North Carolina, USA. LA - eng GR - Novo Nordisk/ PT - Journal Article DEP - 20210722 PL - England TA - Clin Obes JT - Clinical obesity JID - 101560587 SB - IM MH - Body Mass Index MH - Cross-Sectional Studies MH - *Diabetes Mellitus, Type 2 MH - Humans MH - Psychometrics MH - *Quality of Life MH - Reproducibility of Results MH - Surveys and Questionnaires MH - Tomography, X-Ray Computed PMC - PMC9285468 OTO - NOTNLM OT - clinical trials OT - functioning OT - health-related quality of life OT - obesity OT - overweight OT - validation COIS- This study was conducted under a research contract between Novo Nordisk and RTI Health Solutions and was funded by Novo Nordisk. Ronette L. Kolotkin is a consultant for and shareholder of Novo Nordisk and a consultant for RTI Health Solutions and receives royalties from Duke University for the IWQOL-Lite-CT. Sheri E. Fehnel, Valerie S. L. Williams, Nicole Williams, and Shanshan Qin are salaried employees of RTI Health Solutions. Henrik Hjorth Meincke and Lisa von Huth Smith are salaried employees of Novo Nordisk. EDAT- 2021/07/24 06:00 MHDA- 2021/11/26 06:00 PMCR- 2022/07/15 CRDT- 2021/07/23 07:16 PHST- 2021/05/24 00:00 [revised] PHST- 2021/03/02 00:00 [received] PHST- 2021/06/20 00:00 [accepted] PHST- 2021/07/24 06:00 [pubmed] PHST- 2021/11/26 06:00 [medline] PHST- 2021/07/23 07:16 [entrez] PHST- 2022/07/15 00:00 [pmc-release] AID - COB12477 [pii] AID - 10.1111/cob.12477 [doi] PST - ppublish SO - Clin Obes. 2021 Oct;11(5):e12477. doi: 10.1111/cob.12477. Epub 2021 Jul 22. PMID- 34293304 OWN - NLM STAT- MEDLINE DCOM- 20210827 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 9 IP - 9 DP - 2021 Sep TI - Efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial. PG - 563-574 LID - S2213-8587(21)00174-1 [pii] LID - 10.1016/S2213-8587(21)00174-1 [doi] AB - BACKGROUND: Semaglutide is an effective treatment for type 2 diabetes; however, 20-30% of patients given semaglutide 1.0 mg do not reach glycaemic treatment goals. We aimed to investigate the efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in adults with inadequately controlled type 2 diabetes on a stable dose of metformin with or without a sulfonylurea. METHODS: We did a 40-week, randomised, active-controlled, parallel-group, double-blind, phase 3B trial (SUSTAIN FORTE) at 125 outpatient clinics in ten countries. Participants (>/=18 years) with inadequately controlled type 2 diabetes (HbA(1c) 8.0-10.0%) with metformin and with or without sulfonylurea were randomly assigned (1:1) by an interactive web-response system to 2.0 mg or 1.0 mg once-weekly semaglutide. Participants, site personnel, the clinical study group, and investigators were masked to the randomised treatment. Outcomes included change from baseline at week 40 in HbA(1c) (primary outcome) and bodyweight (secondary confirmatory outcome), evaluated through trial product estimand (no treatment discontinuation or without rescue medication) and treatment policy estimand (regardless of treatment discontinuation or rescue medication) strategies. This study is registered with ClinicalTrials.gov, NCT03989232; EudraCT, 2018-004529-96; and WHO, U1111-1224-5162. FINDINGS: Between June 19 and Nov 28, 2019, of 1515 adults assessed for eligibility, 961 participants (mean age 58.0 years [SD 10.0]; 398 [41%] women) were included. Participants were randomly assigned to once-weekly semaglutide 2.0 mg (n=480 [50%]) or 1.0 mg (n=481 [50%]); 462 (96%) patients in the semaglutide 2.0 mg group and 471 (98%) in the semaglutide 1.0 mg group completed the trial. Mean baseline HbA(1c) was 8.9% (SD 0.6; 73.3 mmol/mol [SD 6.9]) and BMI was 34.6 kg/m(2) (SD 7.0). Mean change in HbA(1c) from baseline at week 40 was -2.2 percentage points with semaglutide 2.0 mg and -1.9 percentage points with semaglutide 1.0 mg (estimated treatment difference [ETD] -0.23 percentage points [95% CI -0.36 to -0.11]; p=0.0003; trial product estimand) and -2.1 percentage points with semaglutide 2.0 mg and -1.9 percentage points with semaglutide 1.0 mg (ETD -0.18 percentage points [-0.31 to -0.04]; p=0.0098; treatment policy estimand). Mean change in bodyweight from baseline at week 40 was -6.9 kg with semaglutide 2.0 mg and -6.0 kg with semaglutide 1.0 mg (ETD -0.93 kg [95% CI -1.68 to -0.18]; p=0.015; trial product estimand) and -6.4 kg with semaglutide 2.0 mg and -5.6 kg with semaglutide 1.0 mg (ETD -0.77 kg [-1.55 to 0.01]; p=0.054; treatment policy estimand). Gastrointestinal disorders were the most commonly reported adverse events (163 [34%] in the 2.0 mg group and 148 [31%] in the 1.0 mg group). Serious adverse events were similar between treatment groups, reported for 21 (4%) participants given semaglutide 2.0 mg and 25 (5%) participants given semaglutide 1.0 mg. Three deaths were reported during the trial (one in the semaglutide 1.0 mg group and two in the semaglutide 2.0 mg group). INTERPRETATION: Semaglutide 2.0 mg was superior to 1.0 mg in reducing HbA(1c), with additional bodyweight loss and a similar safety profile. This higher dose provides a treatment intensification option for patients with type 2 diabetes treated with semaglutide in need of additional glycaemic control. FUNDING: Novo Nordisk. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Frias, Juan P AU - Frias JP AD - Clinical Research, National Research Institute, Los Angeles, CA, USA. Electronic address: juan.frias@nritrials.com. FAU - Auerbach, Pernille AU - Auerbach P AD - Novo Nordisk, Soborg, Denmark. FAU - Bajaj, Harpreet S AU - Bajaj HS AD - LMC Diabetes and Endocrinology, Brampton, ON, Canada. FAU - Fukushima, Yasushi AU - Fukushima Y AD - Fukuwa Clinic, Tokyo, Japan. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine/Endocrinology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA. FAU - Macura, Stanislava AU - Macura S AD - Novo Nordisk, Soborg, Denmark. FAU - Sondergaard, Anette L AU - Sondergaard AL AD - Novo Nordisk, Soborg, Denmark. FAU - Tankova, Tsvetalina I AU - Tankova TI AD - Department of Endocrinology, Medical University of Sofia, Sofia, Bulgaria. FAU - Tentolouris, Nikolaos AU - Tentolouris N AD - Diabetes Centre, First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Buse, John B AU - Buse JB AD - Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. LA - eng SI - ClinicalTrials.gov/NCT03989232 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210721 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sulfonylurea Compounds) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet Diabetes Endocrinol. 2021 Sep;9(9):546-548. doi: 10.1016/S2213-8587(21)00205-9. PMID: 34293305 MH - Diabetes Mellitus, Type 2/*drug therapy MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptides/*administration & dosage MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Male MH - Metformin/administration & dosage MH - Middle Aged MH - Sulfonylurea Compounds/administration & dosage MH - Treatment Outcome MH - Semaglutide COIS- Declarations of interest JPF reports grants and personal fees from Novo Nordisk; grants from AstraZeneca, BMS, Janssen, Novartis, Oramed, and Pfizer; and grants and personal fees from Boehringer Ingelheim, Eli Lilly, Merck KGaA, and Sanofi. HSB reports trial fees paid to his institution by Novo Nordisk; speaking honoraria from Eli Lilly and Novo Nordisk; and trial fees paid to his institution by Amgen, AstraZeneca, Boehringer Ingelheim, Ceapro, Eli Lilly, Gilead, Janssen, Kowa Pharmaceuticals, Madrigal Pharmaceuticals, Merck KGaA, Novo Nordisk, Pfizer, Sanofi, and Tricida. IL reports grants, personal fees, and non-financial support from Novo Nordisk; grants, personal fees, and non-financial support from Novo Nordisk and Sanofi; personal fees and non-financial support from Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, and Janssen; personal fees from Intercept, Intarcia, TARGETPharma, Mannkind, Valeritas, Bayer, and Zealand Pharma, grants; and non-financial support from Merck and Pfizer, and grants from Mylan. TIT reports lecture fees and advisory board membership for Boehringer Ingelheim, AstraZeneca, Novo Nordisk, Sanofi, Eli Lilly, Novartis, and MSD. NT reports consultation fees from MSD, clinical trial fees from AstraZeneca, Eli Lilly, Boehringer Ingelheim, Sanofi, and Novo Nordisk, and unrestricted grants from Eli Lilly, Boehringer Ingelheim, ELPEN, and TrigoCare. ALS, PA, and SM are full-time employees of Novo Nordisk and own shares in the company. JBB reports a grant and non-financial support from Novo Nordisk; contracted consulting fees and travel support paid to the University of North Carolina (contract between University of North Carolina and the companies) from Adocia, AstraZeneca, Eli Lilly, Fractyl, Intarcia Therapeutics, Lexicon, MannKind, Metavention, Novo Nordisk, Sanofi, Senseonics, vTv Therapeutics, and Zafgen; research contracts, largely for clinical trials, and travel support paid to the University of North Carolina (contract between University of North Carolina and the companies) from AstraZeneca, Eli Lilly, Intarcia Therapeutics, Johnson & Johnson, Lexicon, NovaTarg, Novo Nordisk, Sanofi, Theracos, Tolerion, and vTv Therapeutics; consulting fees from Cirius Therapeutics, Fortress Biotech, Moderna, Pendulum Therapeutics, and Zealand Pharma; stock or options in lieu of payments for consulting and travel support for consulting activities from Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego, and Stability Health; and grants and non-financial support from the National Institutes of Health, Juvenile Diabetes Research Foundation International, Patient Centered Outcomes Research Institute, and the American Diabetes Association. YF declares no competing interests. The authors have not been paid or received compensation for their authorship. EDAT- 2021/07/23 06:00 MHDA- 2021/08/28 06:00 CRDT- 2021/07/22 20:10 PHST- 2021/04/12 00:00 [received] PHST- 2021/06/11 00:00 [revised] PHST- 2021/06/14 00:00 [accepted] PHST- 2021/07/23 06:00 [pubmed] PHST- 2021/08/28 06:00 [medline] PHST- 2021/07/22 20:10 [entrez] AID - S2213-8587(21)00174-1 [pii] AID - 10.1016/S2213-8587(21)00174-1 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2021 Sep;9(9):563-574. doi: 10.1016/S2213-8587(21)00174-1. Epub 2021 Jul 21. PMID- 34291491 OWN - NLM STAT- MEDLINE DCOM- 20220324 LR - 20260127 IS - 1464-5491 (Electronic) IS - 0742-3071 (Linking) VI - 38 IP - 10 DP - 2021 Oct TI - Once-weekly subcutaneous semaglutide treatment for persons with type 2 diabetes: Real-world data from a diabetes out-patient clinic. PG - e14655 LID - 10.1111/dme.14655 [doi] AB - AIMS: The once-weekly administered glucagon-like peptide 1 (GLP-1) receptor agonist (GLP-1RA) semaglutide, has, in clinical trials, demonstrated significant reductions in glycated haemoglobin A(1c) (HbA(1c) ) and body weight in persons with type 2 diabetes. We evaluated the real-world clinical effects of semaglutide once weekly in a hospital-based diabetes out-patient clinic. METHODS: This retrospective observational cohort study included persons with type 2 diabetes (n = 119) on a broad range of antidiabetic medicine: GLP-1RA naive persons (n = 37) and GLP-1RA-experienced persons (n = 82). Person characteristics at inclusion: age [median (quartiles)]: 65 (57, 72) years; body weight 99 (86, 118) kg; body mass index (BMI) 33 (29, 38) kg/m(2); HbA(1c) 61 (54, 69) mmol/mol/(7.7 (7.1, 8.5) %). Data were collected at baseline and after 3, 6 and 12 months of semaglutide treatment. Data were analysed using a general linear mixed model for repeated measurements. RESULTS: After 12 months, the reductions in HbA(1c) were (mean [95% confidence interval]: GLP-1RA naive: -12.8 [-17.0, -8.5] mmol/mol/ -1.2 [-1.6, -0.8]% (p < 0.01) and GLP-1RA experienced: -6.4 [-9.0, -3.8] mmol/mol/ -0.6 [-0.8, -0.4]% (p < 0.01), respectively. Body weight reductions in GLP-1RA naive: -5 [-6.9, -3.1] kg (p < 0.01) and GLP-1RA experienced: -3.2 [-4.4, -2.0] kg (p < 0.01), respectively. Seventy-five percent received 1 mg QW semaglutide. CONCLUSION: We observed effects of semaglutide once weekly on HbA(1c) and body weight comparable with the effects observed in clinical studies with fewer persons in our cohort receiving maximum dose of semaglutide. CI - (c) 2021 Diabetes UK. FAU - Hansen, Katrine B AU - Hansen KB AUID- ORCID: 0000-0002-2587-5589 AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. FAU - Svendstrup, Mathilde AU - Svendstrup M AUID- ORCID: 0000-0002-9176-1707 AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. FAU - Lund, Asger AU - Lund A AUID- ORCID: 0000-0003-1212-3764 AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. FAU - Knop, Filip K AU - Knop FK AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AUID- ORCID: 0000-0002-0456-6787 AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. AD - Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Vestergaard, Henrik AU - Vestergaard H AUID- ORCID: 0000-0003-3090-269X AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark. AD - Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. AD - Department of Medicine, Bornholms Hospital, Ronne, Denmark. LA - eng PT - Journal Article PT - Observational Study DEP - 20210804 PL - England TA - Diabet Med JT - Diabetic medicine : a journal of the British Diabetic Association JID - 8500858 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Administration Schedule MH - Female MH - Glucagon-Like Peptide 1/agonists MH - Glucagon-Like Peptides/*administration & dosage/pharmacology MH - Glycated Hemoglobin/metabolism MH - Humans MH - Injections, Subcutaneous MH - Male MH - Middle Aged MH - Outpatients MH - Retrospective Studies MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonists OT - semaglutide once weekly OT - type 2 diabetes EDAT- 2021/07/23 06:00 MHDA- 2022/03/25 06:00 CRDT- 2021/07/22 06:52 PHST- 2021/07/08 00:00 [revised] PHST- 2021/03/08 00:00 [received] PHST- 2021/07/19 00:00 [accepted] PHST- 2021/07/23 06:00 [pubmed] PHST- 2022/03/25 06:00 [medline] PHST- 2021/07/22 06:52 [entrez] AID - 10.1111/dme.14655 [doi] PST - ppublish SO - Diabet Med. 2021 Oct;38(10):e14655. doi: 10.1111/dme.14655. Epub 2021 Aug 4. PMID- 34286894 OWN - NLM STAT- MEDLINE DCOM- 20211019 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 11 DP - 2021 Nov TI - An indirect treatment comparison of the efficacy of semaglutide 1.0 mg versus dulaglutide 3.0 and 4.5 mg. PG - 2513-2520 LID - 10.1111/dom.14497 [doi] AB - AIM: To compare the effects of semaglutide 1.0 mg versus dulaglutide 3.0 and 4.5 mg on HbA1c and body weight in patients with type 2 diabetes. MATERIALS AND METHODS: A Bucher indirect comparison was conducted to compare efficacy outcomes of semaglutide 1.0 mg versus dulaglutide 3.0 and 4.5 mg using published results from the SUSTAIN 7 and AWARD-11 trials. Sensitivity analyses using individual patient data from SUSTAIN 7 and aggregate data from AWARD-11 were conducted to explore the impact of adjustment for cross-trial imbalances in baseline characteristics. RESULTS: Semaglutide 1.0 mg significantly reduced HbA1c versus dulaglutide 3.0 mg, with an estimated treatment difference (ETD) of -0.24%-points (95% confidence interval [CI] -0.43, -0.05), with comparable reductions in HbA1c versus dulaglutide 4.5 mg with an ETD of -0.07%-points (95% CI -0.26, 0.12). Semaglutide 1.0 mg significantly reduced body weight versus dulaglutide 3.0 and 4.5 mg with an ETD of -2.65 kg (95% CI -3.57, -1.73) and -1.95 kg (95% CI -2.87, -1.03), respectively. Sensitivity analyses supported the primary analysis findings. CONCLUSIONS: This indirect comparison showed significantly greater reductions in HbA1c with semaglutide 1.0 mg versus dulaglutide 3.0 mg and comparable HbA1c reductions versus dulaglutide 4.5 mg. Semaglutide 1.0 mg significantly reduced body weight versus both dulaglutide 3.0 and 4.5 mg. With several glucagon-like peptide-1 receptor agonists available, information regarding their comparative efficacy can be valuable to clinicians. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Pratley, Richard E AU - Pratley RE AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology, Department of Clinical Sciences, UT Southwestern Medical Center, University of Texas, Dallas, Texas, USA. FAU - Viljoen, Adie AU - Viljoen A AD - Borthwick Diabetes Research Centre, Stevenage, UK. FAU - Paine, Abby AU - Paine A AUID- ORCID: 0000-0002-2332-1099 AD - Zedediah Consulting on behalf of DRG Abacus (part of Clarivate), Wokingham, UK. FAU - Lawson, Jack AU - Lawson J AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Chubb, Barrie AU - Chubb B AUID- ORCID: 0000-0001-7271-051X AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Gorst-Rasmussen, Anders AU - Gorst-Rasmussen A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Miresashvili, Nino AU - Miresashvili N AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210809 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins MH - Semaglutide PMC - PMC9291551 OTO - NOTNLM OT - GLP-1 receptor agonist OT - dulaglutide OT - indirect comparison OT - semaglutide OT - type 2 diabetes COIS- RP reports consulting fees from AstraZeneca; consulting fees from Glytec, LLC; grants from Hanmi Pharmaceutical Co.; grants and consulting fees from Janssen; consulting fees from Merck; grants from Metavention; consulting fees from Mundipharma; grants, speaker fees and consulting fees from Novo Nordisk; consulting fees from Pfizer; grants from Poxel SA; grants and consulting fees from Sanofi; consulting fees from Scohia Pharma Inc.; consulting fees from Sun Pharmaceutical Industries; and personal consulting fees from Sanofi US Services, Inc. Except for consulting fees in February 2018 and June 2018 from Sanofi US Services, Inc., RP's services were paid for directly to AdventHealth, a non-profit organization. AMC is an employee and shareholder of Novo Nordisk A/S. IL has received research funding, advisory/consulting fees and/or other support from Novo Nordisk, Eli Lilly, Sanofi, AstraZeneca, Boehringer Ingelheim, Janssen, Intercept, Intarcia, TARGETPharma, Merck, Pfizer, Novartis, GI Dynamics, Mylan, Mannkind, Valeritas, Bayer and Zealand Pharma. AV has conducted research studies funded by, served as advisor for, and received lecture honoraria from Amgen, AstraZeneca, Boehringer, Daiichi, Eli Lilly, Napp, Novartis, Novo Nordisk, MannKind, Pfizer, Regeneron, Sanofi, Takeda and Tosoh. AP received consultancy fees to develop a statistical analysis plan for the analyses presented in this manuscript; she has also received personal fees from Novo Nordisk, Sanofi and Ultragenyx. JL is an employee of Novo Nordisk A/S. BC is an employee and a shareholder of Novo Nordisk A/S. AGR is an employee and minor stakeholder in Novo Nordisk A/S. NM is an employee of Novo Nordisk A/S. EDAT- 2021/07/22 06:00 MHDA- 2021/10/21 06:00 PMCR- 2022/07/18 CRDT- 2021/07/21 09:20 PHST- 2021/07/06 00:00 [revised] PHST- 2021/04/30 00:00 [received] PHST- 2021/07/16 00:00 [accepted] PHST- 2021/07/22 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/07/21 09:20 [entrez] PHST- 2022/07/18 00:00 [pmc-release] AID - DOM14497 [pii] AID - 10.1111/dom.14497 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Nov;23(11):2513-2520. doi: 10.1111/dom.14497. Epub 2021 Aug 9. PMID- 34281590 OWN - NLM STAT- MEDLINE DCOM- 20210721 LR - 20260127 IS - 1745-6215 (Electronic) IS - 1745-6215 (Linking) VI - 22 IP - 1 DP - 2021 Jul 19 TI - Does intervention with GLP-1 receptor agonist semaglutide modulate perception of sweet taste in women with obesity: study protocol of a randomized, single-blinded, placebo-controlled clinical trial. PG - 464 LID - 10.1186/s13063-021-05442-y [doi] LID - 464 AB - BACKGROUND: Preclinical studies demonstrated that glucagon-like peptide 1 (GLP-1) is locally synthesized in taste bud cells and that GLP-1 receptor exists on the gustatory nerves in close proximity to GLP-1-containing taste bud cells. This local paracrine GLP-1 signalling seems to be specifically involved in the perception of sweets. However, the role of GLP-1 in taste perception remains largely unaddressed in clinical studies. Whether any weight-reducing effects of GLP-1 receptor agonists are mediated through the modulation of taste perception is currently unknown. METHODS AND ANALYSIS: This is an investigator-initiated, randomized single-blind, placebo-controlled clinical trial. We will enrol 30 women with obesity and polycystic ovary syndrome (PCOS). Participants will be randomized in a 1:1 ratio to either semaglutide 1.0 mg or placebo for 16 weeks. The primary endpoints are alteration of transcriptomic profile of tongue tissue as changes in expression level from baseline to follow-up after 16 weeks of treatment, measured by RNA sequencing, and change in taste sensitivity as detected by chemical gustometry. Secondary endpoints include change in neural response to visual food cues and to sweet-tasting substances as assessed by functional MRI, change in body weight, change in fat mass and change in eating behaviour and food intake. DISCUSSION: This is the first study to investigate the role of semaglutide on taste perception, along with a neural response to visual food cues in reward processing regions. The study may identify the tongue and the taste perception as a novel target for GLP-1 receptor agonists. ETHICS AND DISSEMINATIONS: The study has been approved by the Slovene National Medical Ethics Committee and will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Results will be submitted for publication in an international peer-reviewed scientific journal. TRIAL REGISTRATION: ClinicalTrials.gov NCT04263415 . Retrospectively registered on 10 February 2020. CI - (c) 2021. The Author(s). FAU - Jensterle, Mojca AU - Jensterle M AUID- ORCID: 0000-0002-8861-8803 AD - Department of Endocrinology, Diabetes and Metabolic Diseases, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloska cesta 7, SI-1000, Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000, Ljubljana, Slovenia. FAU - Ferjan, Simona AU - Ferjan S AD - Department of Endocrinology, Diabetes and Metabolic Diseases, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloska cesta 7, SI-1000, Ljubljana, Slovenia. AD - Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000, Ljubljana, Slovenia. FAU - Battelino, Tadej AU - Battelino T AD - Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000, Ljubljana, Slovenia. AD - Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Bohoriceva 20, SI-1000, Ljubljana, Slovenia. FAU - Kovac, Jernej AU - Kovac J AD - Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000, Ljubljana, Slovenia. AD - Department of Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Bohoriceva 20, SI-1000, Ljubljana, Slovenia. FAU - Battelino, Saba AU - Battelino S AD - Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000, Ljubljana, Slovenia. AD - Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Zaloska cesta 2, SI-1000, Ljubljana, Slovenia. FAU - Suput, Dusan AU - Suput D AD - Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000, Ljubljana, Slovenia. FAU - Vovk, Andrej AU - Vovk A AD - Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000, Ljubljana, Slovenia. FAU - Janez, Andrej AU - Janez A AUID- ORCID: 0000-0002-6594-5254 AD - Department of Endocrinology, Diabetes and Metabolic Diseases, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloska cesta 7, SI-1000, Ljubljana, Slovenia. andrej.janez@kclj.si. AD - Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000, Ljubljana, Slovenia. andrej.janez@kclj.si. LA - eng SI - ClinicalTrials.gov/NCT04263415 PT - Clinical Trial Protocol PT - Journal Article DEP - 20210719 PL - England TA - Trials JT - Trials JID - 101263253 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2 MH - Double-Blind Method MH - Female MH - *Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Obesity/diagnosis/drug therapy MH - Perception MH - Randomized Controlled Trials as Topic MH - Single-Blind Method MH - Taste MH - Semaglutide PMC - PMC8287101 OTO - NOTNLM OT - Gustatory coding OT - Obesity OT - PCOS OT - Semaglutide OT - Taste COIS- M.J., T.B., S.B., D.S. A.V. and J.K. declare that they have no competing interests in this work. S.F. received lecture fees from NovoNordisk. A.J. is a member of the Advisory Boards of Novo Nordisk on insulin. None of the authors has any significant competing financial, professional or personal interests that might have influenced the performance or presentation of the work described in this manuscript. EDAT- 2021/07/21 06:00 MHDA- 2021/07/22 06:00 PMCR- 2021/07/19 CRDT- 2021/07/20 05:37 PHST- 2021/04/02 00:00 [received] PHST- 2021/07/09 00:00 [accepted] PHST- 2021/07/20 05:37 [entrez] PHST- 2021/07/21 06:00 [pubmed] PHST- 2021/07/22 06:00 [medline] PHST- 2021/07/19 00:00 [pmc-release] AID - 10.1186/s13063-021-05442-y [pii] AID - 5442 [pii] AID - 10.1186/s13063-021-05442-y [doi] PST - epublish SO - Trials. 2021 Jul 19;22(1):464. doi: 10.1186/s13063-021-05442-y. PMID- 34277983 OWN - NLM STAT- MEDLINE DCOM- 20220314 LR - 20260127 IS - 2398-9238 (Electronic) IS - 2398-9238 (Linking) VI - 4 IP - 3 DP - 2021 Jul TI - A population-adjusted indirect comparison of cardiovascular benefits of once-weekly subcutaneous semaglutide and dulaglutide in the treatment of patients with type 2 diabetes, with or without established cardiovascular disease. PG - e00259 LID - 10.1002/edm2.259 [doi] LID - e00259 AB - INTRODUCTION: Cardiovascular (CV) effects of once-weekly subcutaneous (s.c.) semaglutide 0.5 and 1 mg and dulaglutide 1.5 mg are reported in their respective placebo-controlled cardiovascular outcome trials (CVOTs), SUSTAIN 6 and REWIND. There is no head-to-head CVOT comparing these treatments and heterogeneity between their CVOTs renders conventional indirect comparison inappropriate. Therefore, a matching-adjusted indirect comparison (MAIC) was performed to compare the effects of s.c. semaglutide and dulaglutide on major adverse cardiovascular events (MACE) in patients with and without established cardiovascular disease (CVD). METHODS: Individual patient data from SUSTAIN 6 were matched with aggregate data from REWIND, using a propensity score method to balance baseline effect-modifying patient characteristics. Hazard ratios (HRs) for three-point (3P) MACE (CV death, non-fatal myocardial infarction, non-fatal stroke), anchored via placebo, were then indirectly compared between balanced populations. Sensitivity analyses were performed to test the robustness of the main analysis. RESULTS: After matching, included effect modifiers were balanced. In the main analysis, s.c. semaglutide was associated with a statistically significant 35% reduction in 3P MACE versus placebo (HR, 0.65 [95% confidence interval [CI]; 0.48, 0.87]) and nonsignificantly greater reduction (26%) versus dulaglutide (HR, 0.74 [95% CI; 0.54, 1.01]). Results were supported by all sensitivity analyses. CONCLUSIONS: This study demonstrated a statistically significant lower risk of 3P MACE for s.c. semaglutide versus placebo, in a population with lower prevalence of pre-existing CVD than that in the pre-specified primary analysis in SUSTAIN 6. Reduction in 3P MACE with s.c. semaglutide was greater than with dulaglutide, although not statistically significant. CI - (c) 2021 Novo Nordish A/S. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd. FAU - Evans, Lyndon Marc AU - Evans LM AUID- ORCID: 0000-0003-0671-0778 AD - Cardiff and Vale University Cardiff UK. FAU - Mellbin, Linda AU - Mellbin L AD - Department of Medicine Solna Karolinska Institutet Stockholm Sweden. FAU - Johansen, Pierre AU - Johansen P AUID- ORCID: 0000-0002-6287-7508 AD - Novo Nordisk A/S Soborg Denmark. AD - Present address: Novo Nordisk North West Europe Pharmaceuticals A/S Copenhagen Denmark. FAU - Lawson, Jack AU - Lawson J AD - Novo Nordisk A/S Soborg Denmark. FAU - Paine, Abby AU - Paine A AUID- ORCID: 0000-0002-2332-1099 AD - Zedediah Consulting on behalf of DRG Abacus (part of Clarivate) Wokingham UK. FAU - Sandberg, Anna AU - Sandberg A AD - Novo Nordisk A/S Soborg Denmark. AD - Present address: Oncopeptides AB Luntmakargatan 46 Stockholm Sweden. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210515 PL - England TA - Endocrinol Diabetes Metab JT - Endocrinology, diabetes & metabolism JID - 101732442 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - *Cardiovascular Diseases/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Glucagon-Like Peptides/analogs & derivatives MH - Humans MH - Hypoglycemic Agents MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins MH - Semaglutide PMC - PMC8279621 OTO - NOTNLM OT - *GLP-1 receptor agonist OT - *cardiovascular risks OT - *type 2 diabetes COIS- J.L. is an employee of Novo Nordisk A/S. P.J. and A.S. were employees of Novo Nordisk A/S during development of the manuscript. A.P. received consultancy fees for the statistical analyses presented in this manuscript; she has also received personal fees from Novo Nordisk, Sanofi and Ultragenyx. L.M.E. has received lecture fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk and research support from AstraZeneca and Novo Nordisk. Linda Mellbin has received lecture fees from Amgen, AstraZeneca, Bayer AB, Boehringer Ingelheim, Merck Sharp & Dohme, Novo Nordisk and Sanofi Aventis. She has also received consulting fees from or been involved in clinical trials funded by AstraZeneca, Bayer AG, Boehringer Ingelheim, Novo Nordisk and Sanofi Aventis. EDAT- 2021/07/20 06:00 MHDA- 2022/03/15 06:00 PMCR- 2021/05/15 CRDT- 2021/07/19 06:03 PHST- 2021/02/25 00:00 [received] PHST- 2021/04/22 00:00 [revised] PHST- 2021/04/23 00:00 [accepted] PHST- 2021/07/19 06:03 [entrez] PHST- 2021/07/20 06:00 [pubmed] PHST- 2022/03/15 06:00 [medline] PHST- 2021/05/15 00:00 [pmc-release] AID - EDM2259 [pii] AID - 10.1002/edm2.259 [doi] PST - epublish SO - Endocrinol Diabetes Metab. 2021 May 15;4(3):e00259. doi: 10.1002/edm2.259. eCollection 2021 Jul. PMID- 34267725 OWN - NLM STAT- MEDLINE DCOM- 20220107 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 12 DP - 2021 TI - Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide. PG - 645507 LID - 10.3389/fendo.2021.645507 [doi] LID - 645507 AB - Early and effective glycemic control can prevent or delay the complications associated with type 2 diabetes (T2D). The benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly recognized and they now feature prominently in international T2D treatment recommendations and guidelines across the disease continuum. However, despite providing effective glycemic control, weight loss, and a low risk of hypoglycemia, GLP-1RAs are currently underutilized in clinical practice. The long-acting GLP-1RA, semaglutide, is available for once-weekly injection and in a new once-daily oral formulation. Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e.g., patients with hepatic impairment or renal impairment). The oral formulation represents a useful option to help improve acceptance and adherence compared with injectable formulations for patients with a preference for oral therapy, and may lead to earlier and broader use of GLP-1RAs in the T2D treatment trajectory. Oral semaglutide should be taken on an empty stomach, which may influence the choice of formulation. As with most GLP-1RAs, initial dose escalation of semaglutide is required for both formulations to mitigate gastrointestinal adverse events. There are also specific dose instructions to follow with oral semaglutide to ensure sufficient gastric absorption. The evidence base surrounding the clinical use of semaglutide is being further expanded with trials investigating effects on diabetic retinopathy, cardiovascular outcomes, and on the common T2D comorbidities of obesity, chronic kidney disease, and non-alcoholic steatohepatitis. These will provide further information about whether the benefits of semaglutide extend to these other indications. CI - Copyright (c) 2021 Gallwitz and Giorgino. FAU - Gallwitz, Baptist AU - Gallwitz B AD - Department of Medicine IV - Diabetes, Endocrinology, Nephrology, Tubingen University Hospital, Tubingen, Germany. FAU - Giorgino, Francesco AU - Giorgino F AD - Department of Emergency and Organ Transplantation, University of Bari Aldo Moro, Bari, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20210629 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hemoglobins) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Administration, Oral MH - Body Weight MH - Cardiovascular Diseases/therapy MH - Comorbidity MH - Decision Making MH - Diabetes Mellitus, Type 2/drug therapy/*physiopathology MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Glucagon-Like Peptides/*administration & dosage MH - Hemoglobins/analysis MH - Humans MH - Hypoglycemia/drug therapy MH - Hypoglycemic Agents/administration & dosage MH - Injections, Subcutaneous MH - Liver/drug effects MH - Metformin/therapeutic use MH - Obesity/drug therapy MH - Renal Insufficiency, Chronic/therapy MH - Research Design MH - Risk MH - Stomach/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor PMC - PMC8276717 OTO - NOTNLM OT - glucagon-like peptide-1 receptor agonist (GLP-1RA) OT - oral OT - semaglutide OT - subcutaneous OT - type 2 diabetes COIS- FG has received research support from Eli Lilly, Lifescan, and Takeda, and has provided advisory services to AstraZeneca, Boehringer Ingelheim, Eli Lilly, Lifescan, Merck Sharp & Dohme, Novo Nordisk, Roche Diabetes Care, and Sanofi. BG has provided advisory services to AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, and Novo Nordisk, and has received lecture honoraria from Bristol Myers Squibb and the above-mentioned companies. The authors declare that this article received funding from Novo Nordisk. The funder had the following involvement in the article: medical writing support. EDAT- 2021/07/17 06:00 MHDA- 2022/01/08 06:00 PMCR- 2021/01/01 CRDT- 2021/07/16 06:36 PHST- 2020/12/23 00:00 [received] PHST- 2021/06/03 00:00 [accepted] PHST- 2021/07/16 06:36 [entrez] PHST- 2021/07/17 06:00 [pubmed] PHST- 2022/01/08 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2021.645507 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2021 Jun 29;12:645507. doi: 10.3389/fendo.2021.645507. eCollection 2021. PMID- 34264618 OWN - NLM STAT- MEDLINE DCOM- 20220309 LR - 20260127 IS - 1532-0650 (Electronic) IS - 0002-838X (Linking) VI - 104 IP - 1 DP - 2021 Jul 1 TI - Once-Weekly Semaglutide Is an Effective Adjunct for Weight Loss in Adults without Diabetes Who Are Overweight or Obese. PG - 96-97 FAU - Slawson, David C AU - Slawson DC AD - UNC Chapel Hill, Charlotte, NC, USA. LA - eng PT - Journal Article PL - United States TA - Am Fam Physician JT - American family physician JID - 1272646 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Body Weight MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Drug Administration Schedule MH - Glucagon-Like Peptides/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Overweight/complications/*drug therapy MH - Weight Loss MH - Semaglutide EDAT- 2021/07/16 06:00 MHDA- 2022/03/11 06:00 CRDT- 2021/07/15 17:18 PHST- 2021/07/15 17:18 [entrez] PHST- 2021/07/16 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] AID - d16683 [pii] PST - ppublish SO - Am Fam Physician. 2021 Jul 1;104(1):96-97. PMID- 34248838 OWN - NLM STAT- MEDLINE DCOM- 20220107 LR - 20260127 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 12 DP - 2021 TI - Efficacy of Semaglutide in a Subcutaneous and an Oral Formulation. PG - 645617 LID - 10.3389/fendo.2021.645617 [doi] LID - 645617 AB - Despite the benefits of early and effective glycemic control in the management of type 2 diabetes (T2D), achieving glycated hemoglobin (HbA(1c)) targets is challenging in some patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide effective reductions in HbA(1c) and body weight. Semaglutide is the only GLP-1RA that is available in both an injectable and oral formulation. The efficacy of once-weekly subcutaneous semaglutide and once-daily oral semaglutide has been investigated in the global SUSTAIN and PIONEER phase III clinical trial programs in a range of clinical settings, including early T2D managed with diet and exercise only, more established T2D uncontrolled on one to three oral antidiabetic drugs, and advanced disease treated with insulin. Across the SUSTAIN program, once-weekly subcutaneous semaglutide 1.0 mg reduced HbA(1c) by 1.5-1.8% after 30-56 weeks, which was significantly more than sitagliptin, liraglutide, exenatide extended release, dulaglutide, canagliflozin, or insulin glargine. Across the PIONEER program, once-daily oral semaglutide 14 mg reduced HbA(1c) by 1.0-1.4%, significantly more than sitagliptin or empagliflozin, and to a similar extent as liraglutide after 26 weeks. In addition, subcutaneous semaglutide reduced body weight significantly more than all active comparators tested, while oral semaglutide reduced body weight more than sitagliptin and liraglutide, and to a similar extent as empagliflozin. Neither formulation of semaglutide has been associated with an increased risk of hypoglycemia and both improve various measures of health-related quality of life. Semaglutide offers the benefits of a highly effective GLP-1RA in both injectable and oral formulations. Selection of the most appropriate formulation can be made on an individual basis to best suit the patient's preferences and needs. CI - Copyright (c) 2021 Meier. FAU - Meier, Juris J AU - Meier JJ AD - Diabetes Center Bochum-Hattingen, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20210625 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - *Administration, Oral MH - Body Weight/drug effects MH - Clinical Trials, Phase III as Topic MH - Diabetes Mellitus, Type 2/*drug therapy MH - Diet MH - Exercise Therapy MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Glycated Hemoglobin/*biosynthesis MH - Humans MH - Hypoglycemic Agents/administration & dosage/adverse effects MH - *Injections, Subcutaneous MH - Insulin/administration & dosage/therapeutic use MH - Quality of Life MH - Research Design MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor PMC - PMC8269445 OTO - NOTNLM OT - body weight OT - efficacy OT - glucagon-like peptide-1 receptor agonist (GLP-1RA) OT - glycated hemoglobin (HbA1c) OT - oral OT - semaglutide OT - subcutaneous OT - type 2 diabetes COIS- JJM has received lecture honoraria and consulting fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme (MSD), Novartis, Novo Nordisk, and Sanofi; has received reimbursement of congress participation fees and travel expenses from MSD, Novo Nordisk, and Sanofi; and has initiated projects supported by Boehringer Ingelheim, MSD, Novo Nordisk, and Sanofi. The author declares that this article received funding from Novo Nordisk. The funder had the following involvement in the article: medical writing support. EDAT- 2021/07/13 06:00 MHDA- 2022/01/08 06:00 PMCR- 2021/01/01 CRDT- 2021/07/12 05:47 PHST- 2020/12/23 00:00 [received] PHST- 2021/03/08 00:00 [accepted] PHST- 2021/07/12 05:47 [entrez] PHST- 2021/07/13 06:00 [pubmed] PHST- 2022/01/08 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2021.645617 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2021 Jun 25;12:645617. doi: 10.3389/fendo.2021.645617. eCollection 2021. PMID- 34217773 OWN - NLM STAT- MEDLINE DCOM- 20211124 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 178 DP - 2021 Aug TI - Real-world use of once-weekly semaglutide in patients with type 2 diabetes: Results from the SURE Switzerland multicentre, prospective, observational study. PG - 108931 LID - S0168-8227(21)00291-6 [pii] LID - 10.1016/j.diabres.2021.108931 [doi] AB - AIMS: SURE Switzerland (NCT03631186) investigated real-world once-weekly (OW) semaglutide use in adults with type 2 diabetes (T2D). METHODS: This multicentre, prospective, observational study enrolled adults with T2D with >/= 1 documented HbA(1c) value /=1 documented HbA(1c) value /=5%. Reported adverse events were consistent with the known safety profile of semaglutide. CONCLUSIONS: In routine clinical practice in Denmark/Sweden, use of OW semaglutide was associated with glycaemic and weight-loss benefits in a wide range of adults with T2D, supporting real-world use. CLINICALTRIALS. GOV IDENTIFIER: NCT03648281. CI - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Rajamand Ekberg, Neda AU - Rajamand Ekberg N AD - Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Academic Specialist Centre, Centre for Diabetes, Stockholm, Sweden. Electronic address: Neda.ekberg@ki.se. FAU - Bodholdt, Ulrik AU - Bodholdt U AD - Kastrup Doctors, Kastrupvej 326, 1.tv., DK-277 Kastrup, Denmark. Electronic address: ulrik@bodholdt.dk. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Vandtarnsvej 108-110, DK-2860 Soborg, Denmark. Electronic address: aicg@novonordisk.com. FAU - Catrina, Sergiu-Bogdan AU - Catrina SB AD - Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Academic Specialist Centre, Centre for Diabetes, Stockholm, Sweden. Electronic address: Sergiu-bogdan.catrina@ki.se. FAU - Grau, Katrine AU - Grau K AD - Novo Nordisk A/S, Vandtarnsvej 108-110, DK-2860 Soborg, Denmark. Electronic address: kgau@novonordisk.com. FAU - Holmberg, Cecilia Nagorny AU - Holmberg CN AD - Novo Nordisk A/S, Vandtarnsvej 108-110, DK-2860 Soborg, Denmark. Electronic address: ccnh@novonordisk.com. FAU - Klanger, Boris AU - Klanger B AD - LakarGruppen, Kallgatan 10, 722 11 Vasteras, Sweden. Electronic address: boris.klanger@ptj.se. FAU - Knudsen, Soren Tang AU - Knudsen ST AD - Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital, Aarhus, Denmark. Electronic address: soerknud@rm.dk. LA - eng SI - ClinicalTrials.gov/NCT03648281 PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20210625 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Denmark MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Glucagon-Like Peptides/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Prospective Studies MH - Sweden MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - Body weight OT - Glucagon-like peptide-1 receptor agonist OT - HbA(1c) OT - Real-world evidence OT - SURE study OT - Semaglutide OT - Type 2 diabetes EDAT- 2021/06/30 06:00 MHDA- 2021/10/26 06:00 CRDT- 2021/06/29 05:50 PHST- 2021/03/26 00:00 [received] PHST- 2021/06/10 00:00 [revised] PHST- 2021/06/17 00:00 [accepted] PHST- 2021/06/30 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/06/29 05:50 [entrez] AID - S1751-9918(21)00112-1 [pii] AID - 10.1016/j.pcd.2021.06.008 [doi] PST - ppublish SO - Prim Care Diabetes. 2021 Oct;15(5):871-878. doi: 10.1016/j.pcd.2021.06.008. Epub 2021 Jun 25. PMID- 34181914 OWN - NLM STAT- MEDLINE DCOM- 20210827 LR - 20210827 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 9 IP - 8 DP - 2021 Aug TI - Treatment of type 2 diabetes: challenges, hopes, and anticipated successes. PG - 525-544 LID - S2213-8587(21)00113-3 [pii] LID - 10.1016/S2213-8587(21)00113-3 [doi] AB - Despite the successful development of new therapies for the treatment of type 2 diabetes, such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors, the search for novel treatment options that can provide better glycaemic control and at reduce complications is a continuous effort. The present Review aims to present an overview of novel targets and mechanisms and focuses on glucose-lowering effects guiding this search and developments. We discuss not only novel developments of insulin therapy (eg, so-called smart insulin preparation with a glucose-dependent mode of action), but also a group of drug classes for which extensive research efforts have not been rewarded with obvious clinical impact. We discuss the potential clinical use of the salutary adipokine adiponectin and the hepatokine fibroblast growth factor (FGF) 21, among others. A GLP-1 peptide receptor agonist (semaglutide) is now available for oral absorption, and small molecules activating GLP-1 receptors appear on the horizon. Bariatric surgery and its accompanying changes in the gut hormonal milieu offer a background for unimolecular peptides interacting with two or more receptors (for GLP-1, glucose-dependent insulinotropic polypeptide, glucagon, and peptide YY) and provide more substantial glycaemic control and bodyweight reduction compared with selective GLP-1 receptor agonists. These and additional approaches will help expand the toolbox of effective medications needed for optimising the treatment of well delineated subgroups of type 2 diabetes or help develop personalised approaches for glucose-lowering drugs based on individual characteristics of our patients. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes Division, Katholisches Klinikum Bochum, St Josef Hospital, Ruhr University Bochum, Bochum, Germany. Electronic address: michael.nauck@rub.de. FAU - Wefers, Jakob AU - Wefers J AD - Diabetes Division, Katholisches Klinikum Bochum, St Josef Hospital, Ruhr University Bochum, Bochum, Germany. FAU - Meier, Juris J AU - Meier JJ AD - Diabetes Division, Katholisches Klinikum Bochum, St Josef Hospital, Ruhr University Bochum, Bochum, Germany. LA - eng PT - Journal Article PT - Review DEP - 20210625 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 0 (Pharmaceutical Preparations) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism/pathology MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Pharmaceutical Preparations/*administration & dosage/analysis MH - Prognosis COIS- Declaration of interests MAN has been a member on advisory boards or has consulted with AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Menarini/Berlin Chemie, Merck, Sharp & Dohme, and NovoNordisk. He has received grant support from AstraZeneca, Eli Lilly, Menarini/Berlin-Chemie, Merck, Sharp & Dohme, and NovoNordisk. He has also served on the speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly, Menarini/Berlin Chemie, Merck, Sharp & Dohme, and NovoNordisk. JJM has received consulting and speaker honoraria from AstraZeneca, Eli Lilly, Merck, Sharp & Dohme, Novo Nordisk, Sanofi, and Servier. He has received research support from Boehringer Ingelheim, Eli Lilly, Merck, Sharp & Dohme, Novo Nordisk, and Sanofi. JW has declares no competing interests. EDAT- 2021/06/29 06:00 MHDA- 2021/08/28 06:00 CRDT- 2021/06/28 20:11 PHST- 2021/03/03 00:00 [received] PHST- 2021/04/06 00:00 [revised] PHST- 2021/04/07 00:00 [accepted] PHST- 2021/06/29 06:00 [pubmed] PHST- 2021/08/28 06:00 [medline] PHST- 2021/06/28 20:11 [entrez] AID - S2213-8587(21)00113-3 [pii] AID - 10.1016/S2213-8587(21)00113-3 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2021 Aug;9(8):525-544. doi: 10.1016/S2213-8587(21)00113-3. Epub 2021 Jun 25. PMID- 34170647 OWN - NLM STAT- MEDLINE DCOM- 20210820 LR - 20260518 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 385 IP - 6 DP - 2021 Aug 5 TI - Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. PG - 503-515 LID - 10.1056/NEJMoa2107519 [doi] AB - BACKGROUND: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown. METHODS: In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks. RESULTS: The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, -1.9 kg, -3.6 kg, and -5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide. CONCLUSIONS: In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks. (Funded by Eli Lilly; SURPASS-2 ClinicalTrials.gov number, NCT03987919.). CI - Copyright (c) 2021 Massachusetts Medical Society. FAU - Frias, Juan P AU - Frias JP AUID- ORCID: 0000-0001-9486-1255 AD - From the National Research Institute, Los Angeles (J.P.F.); the Diabetes Research Centre, University of Leicester, and the National Institute of Health Research Leicester Biomedical Research Centre - both in Leicester, United Kingdom (M.J.D.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); Centro de Investigaciones Metabolicas, Buenos Aires (F.C.P.M.); and Eli Lilly, Indianapolis (L.F.L., B.K.B., B.L., X.C., K.B.). FAU - Davies, Melanie J AU - Davies MJ AD - From the National Research Institute, Los Angeles (J.P.F.); the Diabetes Research Centre, University of Leicester, and the National Institute of Health Research Leicester Biomedical Research Centre - both in Leicester, United Kingdom (M.J.D.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); Centro de Investigaciones Metabolicas, Buenos Aires (F.C.P.M.); and Eli Lilly, Indianapolis (L.F.L., B.K.B., B.L., X.C., K.B.). FAU - Rosenstock, Julio AU - Rosenstock J AD - From the National Research Institute, Los Angeles (J.P.F.); the Diabetes Research Centre, University of Leicester, and the National Institute of Health Research Leicester Biomedical Research Centre - both in Leicester, United Kingdom (M.J.D.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); Centro de Investigaciones Metabolicas, Buenos Aires (F.C.P.M.); and Eli Lilly, Indianapolis (L.F.L., B.K.B., B.L., X.C., K.B.). FAU - Perez Manghi, Federico C AU - Perez Manghi FC AD - From the National Research Institute, Los Angeles (J.P.F.); the Diabetes Research Centre, University of Leicester, and the National Institute of Health Research Leicester Biomedical Research Centre - both in Leicester, United Kingdom (M.J.D.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); Centro de Investigaciones Metabolicas, Buenos Aires (F.C.P.M.); and Eli Lilly, Indianapolis (L.F.L., B.K.B., B.L., X.C., K.B.). FAU - Fernandez Lando, Laura AU - Fernandez Lando L AD - From the National Research Institute, Los Angeles (J.P.F.); the Diabetes Research Centre, University of Leicester, and the National Institute of Health Research Leicester Biomedical Research Centre - both in Leicester, United Kingdom (M.J.D.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); Centro de Investigaciones Metabolicas, Buenos Aires (F.C.P.M.); and Eli Lilly, Indianapolis (L.F.L., B.K.B., B.L., X.C., K.B.). FAU - Bergman, Brandon K AU - Bergman BK AD - From the National Research Institute, Los Angeles (J.P.F.); the Diabetes Research Centre, University of Leicester, and the National Institute of Health Research Leicester Biomedical Research Centre - both in Leicester, United Kingdom (M.J.D.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); Centro de Investigaciones Metabolicas, Buenos Aires (F.C.P.M.); and Eli Lilly, Indianapolis (L.F.L., B.K.B., B.L., X.C., K.B.). FAU - Liu, Bing AU - Liu B AD - From the National Research Institute, Los Angeles (J.P.F.); the Diabetes Research Centre, University of Leicester, and the National Institute of Health Research Leicester Biomedical Research Centre - both in Leicester, United Kingdom (M.J.D.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); Centro de Investigaciones Metabolicas, Buenos Aires (F.C.P.M.); and Eli Lilly, Indianapolis (L.F.L., B.K.B., B.L., X.C., K.B.). FAU - Cui, Xuewei AU - Cui X AD - From the National Research Institute, Los Angeles (J.P.F.); the Diabetes Research Centre, University of Leicester, and the National Institute of Health Research Leicester Biomedical Research Centre - both in Leicester, United Kingdom (M.J.D.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); Centro de Investigaciones Metabolicas, Buenos Aires (F.C.P.M.); and Eli Lilly, Indianapolis (L.F.L., B.K.B., B.L., X.C., K.B.). FAU - Brown, Katelyn AU - Brown K AD - From the National Research Institute, Los Angeles (J.P.F.); the Diabetes Research Centre, University of Leicester, and the National Institute of Health Research Leicester Biomedical Research Centre - both in Leicester, United Kingdom (M.J.D.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); Centro de Investigaciones Metabolicas, Buenos Aires (F.C.P.M.); and Eli Lilly, Indianapolis (L.F.L., B.K.B., B.L., X.C., K.B.). CN - SURPASS-2 Investigators LA - eng SI - ClinicalTrials.gov/NCT03987919 PT - Clinical Trial, Phase III PT - Comparative Study PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210625 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Blood Glucose) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 9100L32L2N (Metformin) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - N Engl J Med. 2021 Aug 5;385(6):560-561. doi: 10.1056/NEJMe2109957. PMID: 34170646 CIN - Nat Rev Endocrinol. 2021 Sep;17(9):513. doi: 10.1038/s41574-021-00540-y. PMID: 34272516 CIN - Ann Intern Med. 2021 Nov;174(11):JC127. doi: 10.7326/ACPJ202111160-127. PMID: 34724396 CIN - N Engl J Med. 2022 Feb 17;386(7):e17. doi: 10.1056/NEJMc2114590. PMID: 35172065 CIN - N Engl J Med. 2022 Feb 17;386(7):e17. doi: 10.1056/NEJMc2114590. PMID: 35172066 MH - Blood Glucose/analysis MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Female MH - Gastric Inhibitory Polypeptide/*administration & dosage/adverse effects MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects/therapeutic use MH - Incretins/therapeutic use MH - Injections, Subcutaneous MH - Male MH - Metformin/therapeutic use MH - Middle Aged MH - Nausea/chemically induced MH - Weight Loss/drug effects MH - Tirzepatide MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide FIR - Rosenstock, Julio IR - Rosenstock J FIR - Welch, Michelle IR - Welch M FIR - Connery, Lisa IR - Connery L FIR - Gardner, Donald F IR - Gardner DF FIR - Meisner, Carl R IR - Meisner CR FIR - Rosen, Jeffrey B IR - Rosen JB FIR - Nunez, Lazaro D IR - Nunez LD FIR - Kutner, Mark E IR - Kutner ME FIR - Block, Bradley M IR - Block BM FIR - Busch, Robert S IR - Busch RS FIR - Chow, Christopher IR - Chow C FIR - Frias, Juan P IR - Frias JP FIR - Hsia, Stanley H IR - Hsia SH FIR - Kessler, Evan IR - Kessler E FIR - Layle, Stacey IR - Layle S FIR - Mehra, Purvi K IR - Mehra PK FIR - Mohseni, Rizwana H IR - Mohseni RH FIR - Oliver, Michael J IR - Oliver MJ FIR - Rohlf, Jane L IR - Rohlf JL FIR - Van, Joanna T IR - Van JT FIR - Martin, Earl E IR - Martin EE FIR - McCartney, Michael J IR - McCartney MJ FIR - Sorial, Ehab IR - Sorial E FIR - Soufer, Joseph IR - Soufer J FIR - Jenders, Robert A IR - Jenders RA FIR - Klein, Eric J IR - Klein EJ FIR - Nadar, Venkatesh IR - Nadar V FIR - Lavery, Sarah IR - Lavery S FIR - Condren, Stacey IR - Condren S FIR - Rosenfeld, Jack C IR - Rosenfeld JC FIR - Jabbour, Serge IR - Jabbour S FIR - Vaughn, Jordan IR - Vaughn J FIR - Gomez-Cuellar, Martha IR - Gomez-Cuellar M FIR - Sosa-Padilla, Miguel A IR - Sosa-Padilla MA FIR - Purighalla, Raman S IR - Purighalla RS FIR - Recknor, Chris IR - Recknor C FIR - Karr, Aaron W IR - Karr AW FIR - Mansilla-Letelier, Paola IR - Mansilla-Letelier P FIR - Cox, Michael IR - Cox M FIR - Lillestol, Michael J IR - Lillestol MJ FIR - Robinson, Jennifer G IR - Robinson JG FIR - True, David G IR - True DG FIR - Wynne, Alan G IR - Wynne AG FIR - Vazquez-Tanus, Jose B IR - Vazquez-Tanus JB FIR - Lucas, Kathryn J IR - Lucas KJ FIR - Murray, Alexander V IR - Murray AV FIR - Parker, John C IR - Parker JC FIR - Loy, Juan IR - Loy J FIR - Patel, Minesh A IR - Patel MA FIR - Soucie, Gary W IR - Soucie GW FIR - Blake, Dwight IR - Blake D FIR - Huling, Randall T IR - Huling RT FIR - Brockmyre, Andrew P IR - Brockmyre AP FIR - Blaze, Kenneth IR - Blaze K FIR - Gabra, Nashwa IR - Gabra N FIR - Arora, Samir IR - Arora S FIR - Gupta, Anil K IR - Gupta AK FIR - O'Mahony, John IR - O'Mahony J FIR - Lasko, Ben IR - Lasko B FIR - Blouin, Francois IR - Blouin F FIR - Dzongowski, Peter IR - Dzongowski P FIR - Numair, Huma N IR - Numair HN FIR - Patel, Mehulkumar IR - Patel M FIR - Matin, Roozbeh IR - Matin R FIR - Ali, Amar IR - Ali A FIR - Beltran Martinez, Adrian IR - Beltran Martinez A FIR - Hall, Timothy IR - Hall T FIR - Toms, Graham R IR - Toms GR FIR - Viljoen, Adie IR - Viljoen A FIR - Johnson, Timothy IR - Johnson T FIR - Gaunt, Richard IR - Gaunt R FIR - Gunstone, Anthony IR - Gunstone A FIR - Marrett, Paula-Jane IR - Marrett PJ FIR - Barnes, Lawrence IR - Barnes L FIR - Capehorn, Matthew IR - Capehorn M FIR - Cummings, Michael IR - Cummings M FIR - Davies, Melanie IR - Davies M FIR - Randeva, Harpal S IR - Randeva HS FIR - Alpizar-Salazar, Melchor IR - Alpizar-Salazar M FIR - Banda Elizondo, Ramiro G IR - Banda Elizondo RG FIR - Calvo Vargas, Cesar G IR - Calvo Vargas CG FIR - Nevarez Ruiz, Luis A IR - Nevarez Ruiz LA FIR - Violante Ortiz, Rafael M IR - Violante Ortiz RM FIR - Garcia Hernandez, Pedro A IR - Garcia Hernandez PA FIR - Gonzalez Galvez, Guillermo IR - Gonzalez Galvez G FIR - Vidrio Velazquez, Maricela IR - Vidrio Velazquez M FIR - Augusto, Gustavo A IR - Augusto GA FIR - Canani, Luis Henrique S IR - Canani LHS FIR - Alves, Breno B IR - Alves BB FIR - Franco, Denise R IR - Franco DR FIR - Pereira, Marcio A IR - Pereira MA FIR - Calil Salim, Camila P IR - Calil Salim CP FIR - de Souza, Filipe D IR - de Souza FD FIR - Aizenberg, Diego IR - Aizenberg D FIR - Calella, Pedro Rosario Fabian IR - Calella PRF FIR - Orio, Silvia I IR - Orio SI FIR - Fretes, Jose O IR - Fretes JO FIR - Gelersztein, Elizabeth IR - Gelersztein E FIR - MacKinnon, Ignacio IR - MacKinnon I FIR - Salzberg, Susana IR - Salzberg S FIR - Zaidman, Cesar J IR - Zaidman CJ FIR - Coronel, Maria J IR - Coronel MJ FIR - Chertkoff, Alejandro IR - Chertkoff A FIR - Nardone, Lucrecia IR - Nardone L FIR - Perez Manghi, Federico C IR - Perez Manghi FC FIR - Abalos, Franklin H IR - Abalos FH FIR - McCarthy, Shannon IR - McCarthy S FIR - Kim, Joshua IR - Kim J FIR - Gilfillan, Christopher IR - Gilfillan C FIR - Colquhoun, David M IR - Colquhoun DM FIR - Purnell, Peter W IR - Purnell PW FIR - Bloch, Mark T IR - Bloch MT FIR - D'Emden, Michael C IR - D'Emden MC FIR - Fiore, David Di IR - Fiore DD FIR - Shakib, Sepehr IR - Shakib S FIR - Zhou, Nathan D IR - Zhou ND FIR - Mosenzon Ninio, Ofri IR - Mosenzon Ninio O FIR - Goldhaber, Adiv IR - Goldhaber A FIR - Sabbah, Muhammad IR - Sabbah M FIR - Shehadeh, Naim IR - Shehadeh N FIR - Tirosh, Amir IR - Tirosh A FIR - Vishlitzky, Victor IR - Vishlitzky V FIR - Darawsha, Mahmud IR - Darawsha M FIR - Sack, Jessica IR - Sack J FIR - Wainstein, Julio IR - Wainstein J EDAT- 2021/06/26 06:00 MHDA- 2021/08/21 06:00 CRDT- 2021/06/25 12:33 PHST- 2021/06/26 06:00 [pubmed] PHST- 2021/08/21 06:00 [medline] PHST- 2021/06/25 12:33 [entrez] AID - 10.1056/NEJMoa2107519 [doi] PST - ppublish SO - N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25. PMID- 34169640 OWN - NLM STAT- MEDLINE DCOM- 20211018 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 23 IP - 10 DP - 2021 Oct TI - Response to Dahl et al.: Oral semaglutide improves postprandial glucose and lipid metabolism, and delays gastric emptying, in subjects with type 2 diabetes. PG - 2411-2413 LID - 10.1111/dom.14473 [doi] FAU - Horowitz, Michael AU - Horowitz M AUID- ORCID: 0000-0002-0942-0306 AD - Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. FAU - Rayner, Christopher K AU - Rayner CK AUID- ORCID: 0000-0002-5527-256X AD - Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia. AD - Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia. FAU - Marathe, Chinmay S AU - Marathe CS AUID- ORCID: 0000-0002-8086-2449 AD - Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. FAU - Wu, Tongzhi AU - Wu T AUID- ORCID: 0000-0003-1656-9210 AD - Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. FAU - Umapathysivam, Mahesh AU - Umapathysivam M AUID- ORCID: 0000-0001-8959-5239 AD - Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. FAU - Jones, Karen L AU - Jones KL AUID- ORCID: 0000-0002-1155-5816 AD - Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia. AD - Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. LA - eng PT - Comment PT - Letter PT - Research Support, Non-U.S. Gov't DEP - 20210716 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - IY9XDZ35W2 (Glucose) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - Diabetes Obes Metab. 2021 Jul;23(7):1594-1603. doi: 10.1111/dom.14373. PMID: 33710717 CIN - Diabetes Obes Metab. 2021 Oct;23(10):2414-2416. doi: 10.1111/dom.14485. PMID: 34212484 MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Gastric Emptying MH - Glucagon-Like Peptides MH - Glucose MH - Humans MH - Lipid Metabolism MH - Postprandial Period MH - Semaglutide EDAT- 2021/06/26 06:00 MHDA- 2021/10/21 06:00 CRDT- 2021/06/25 07:15 PHST- 2021/06/16 00:00 [revised] PHST- 2021/05/26 00:00 [received] PHST- 2021/06/17 00:00 [accepted] PHST- 2021/06/26 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/06/25 07:15 [entrez] AID - 10.1111/dom.14473 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Oct;23(10):2411-2413. doi: 10.1111/dom.14473. Epub 2021 Jul 16. PMID- 34157885 OWN - NLM STAT- MEDLINE DCOM- 20220107 LR - 20260127 IS - 1542-6270 (Electronic) IS - 1060-0280 (Linking) VI - 56 IP - 2 DP - 2022 Feb TI - Semaglutide for Weight Loss. PG - 224-226 LID - 10.1177/10600280211027204 [doi] FAU - Carris, Nicholas W AU - Carris NW AUID- ORCID: 0000-0001-8904-5034 FAU - Dietrich, Eric A AU - Dietrich EA AUID- ORCID: 0000-0002-6084-6329 LA - eng PT - Letter DEP - 20210622 PL - United States TA - Ann Pharmacother JT - The Annals of pharmacotherapy JID - 9203131 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2 MH - *Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Weight Loss MH - Semaglutide EDAT- 2021/06/24 06:00 MHDA- 2022/01/08 06:00 CRDT- 2021/06/23 05:37 PHST- 2021/06/24 06:00 [pubmed] PHST- 2022/01/08 06:00 [medline] PHST- 2021/06/23 05:37 [entrez] AID - 10.1177/10600280211027204 [doi] PST - ppublish SO - Ann Pharmacother. 2022 Feb;56(2):224-226. doi: 10.1177/10600280211027204. Epub 2021 Jun 22. PMID- 34142429 OWN - NLM STAT- MEDLINE DCOM- 20211018 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 10 DP - 2021 Oct TI - Use of once-weekly semaglutide in patients with type 2 diabetes in routine clinical practice: Results from the SURE Canada multicentre, prospective, observational study. PG - 2269-2278 LID - 10.1111/dom.14468 [doi] AB - AIM: To investigate once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D) in routine clinical practice. METHODS: The SURE Canada study was a multicenter, prospective, observational study. Adults with T2D and one or more documented HbA1c values 12 weeks or less before semaglutide initiation were enrolled. The primary endpoint was change in HbA1c from baseline to end of study (EOS; ~30 weeks). Secondary endpoints included change in body weight (BW), waist circumference and patient-reported outcomes (PROs) and the proportion of patients achieving HbA1c of less than 7.0%, weight loss (WL) of 5% or higher, and a composite of HbA1c reduction of 1% or higher and WL of 3% or higher at EOS. Data were analysed and presented for patients on semaglutide at EOS overall and for the following baseline medication subgroups: oral antihyperglycaemic drugs (OADs) only; GLP-1RA experienced; insulin +/- OADs without GLP-1RA. RESULTS: In total, 452 patients initiated semaglutide and 356 completed the study on treatment. For the 452 patients, mean baseline HbA1c was 8.1%; 86 (19.0%) patients had HbA1c of less than 7.0%. Mean dose of semaglutide at EOS was 0.76 +/- 0.31 mg. Mean HbA1c was reduced by 0.9%-point (95% confidence interval [CI]: 0.97; 0.78). Mean BW was reduced by 4.3 kg (95% CI: 4.79; 3.76). At EOS, 46.9% of patients achieved HbA1c of less than 7.0%, 40.9% achieved WL of 5% or higher and 24.1% achieved the composite endpoint. PROs improved from baseline to EOS. No new safety concerns were reported. CONCLUSIONS: In SURE Canada, patients treated with OW semaglutide in routine clinical practice experienced clinically significant improvements in HbA1c, BW and other outcomes, supporting semaglutide use in routine clinical practice. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Yale, Jean-Francois AU - Yale JF AUID- ORCID: 0000-0002-7833-9050 AD - McGill University Health Centre, Montreal, Quebec, Canada. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Grau, Katrine AU - Grau K AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Harris, Stewart AU - Harris S AD - Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. FAU - Klimek-Abercrombie, Agnieszka AU - Klimek-Abercrombie A AD - Novo Nordisk Canada Inc., Mississauga, Ontario, Canada. FAU - Rabasa-Lhoret, Remi AU - Rabasa-Lhoret R AUID- ORCID: 0000-0003-4706-5170 AD - Lotus Health Clinic, Halifax, Nova Scotia, Canada. FAU - Reardon, Laura AU - Reardon L AD - Montreal Clinical Research Institute, Montreal, Quebec, Canada. FAU - Woo, Vincent AU - Woo V AD - St Boniface Hospital, Winnipeg, Manitoba, Canada. FAU - Liutkus, Joanne AU - Liutkus J AD - Joanne F. Liutkus Medicine Professional Corporation, Cambridge, Ontario, Canada. LA - eng PT - Journal Article PT - Multicenter Study PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20210815 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Prospective Studies MH - Semaglutide PMC - PMC9291287 OTO - NOTNLM OT - GLP-1RA OT - SURE study OT - body weight OT - glycaemic control OT - routine clinical practice OT - semaglutide OT - type 2 diabetes COIS- JFY reports receiving grants from Novo Nordisk during the conduct of the study; and grants and personal fees from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Merck, Janssen and AstraZeneca, all outside the submitted work. AMC, KG and AK-A are employees of Novo Nordisk and own stock in the company. SH reports receiving grants from Novo Nordisk during the conduct of the study; grants, personal and other fees from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen and Sanofi; grants and other fees from Applied Therapeutics; personal and other fees from Bayer Inc. and Novo Nordisk; grants from Health Canada/First Nations and Inuit Health Branch, Canadian Institutes for Health Research, Juvenile Diabetes Research Foundation and The Lawson Foundation; and personal fees from HLS Therapeutics, all outside the submitted work. RR-L reports receiving grants from Diabetes Canada, Cystic Fibrosis Canada, CIHR, NIH, JDRF, Prometic and SFD; grants and personal fees from AstraZeneca, Janssen, Merck, Novo Nordisk, Sanofi Avantis and Vertex Pharmaceutical; grants, personal fees and non-financial support from Eli Lilly; personal fees from Abbott, Amgen, Boehringer Ingelheim, CPD Network, Dexcom, HSL therapeutics, Insulet, Neomed and Roche; personal fees and non-financial support from Medtronic; and non-financial support from Animas, all outside the submitted work. LR reports receiving consulting fees and serving on the advisory board for Novo Nordisk and Bioscript Solutions; speakers bureau and honoraria from Bausch and Novo Nordisk; and grants and research support from Novo Nordisk, all outside the submitted work. VW reports receiving personal fees from Novo Nordisk outside the submitted work. JL reports receiving personal fees, grants and non-financial support from Novo Nordisk, outside the submitted work. EDAT- 2021/06/19 06:00 MHDA- 2021/10/21 06:00 PMCR- 2022/07/18 CRDT- 2021/06/18 07:07 PHST- 2021/06/02 00:00 [revised] PHST- 2021/03/17 00:00 [received] PHST- 2021/06/14 00:00 [accepted] PHST- 2021/06/19 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2021/06/18 07:07 [entrez] PHST- 2022/07/18 00:00 [pmc-release] AID - DOM14468 [pii] AID - 10.1111/dom.14468 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Oct;23(10):2269-2278. doi: 10.1111/dom.14468. Epub 2021 Aug 15. PMID- 34128734 OWN - NLM STAT- MEDLINE DCOM- 20211021 LR - 20220531 IS - 1744-7593 (Electronic) IS - 1742-5247 (Linking) VI - 18 IP - 10 DP - 2021 Oct TI - Transient Permeation Enhancer(R) (TPE(R)) technology for oral delivery of octreotide: a technological evaluation. PG - 1501-1512 LID - 10.1080/17425247.2021.1942838 [doi] AB - INTRODUCTION: The FDA approval of oral semaglutide for type 2 diabetes (2019) and oral octreotide for acromegaly (2020) is evidence that selected niche peptides can be administered orally if formulated with selected intestinal permeation enhancers. AREAS COVERED: We evaluated the oral octreotide formulation, MYCAPSSA(R) (Chiasma Pharmaceuticals, Needham, MA, USA). An outline of the current standard of care in acromegaly and the benefits of oral octreotide versus depot injections is provided. We discuss the Transient Permeation Enhancer (TPE(R)) technology used and detail the safety and efficacy data from animal models and clinical trials. EXPERT OPINION: TPE(R) is an oily suspension of octreotide that includes a number of excipients that can transiently alter epithelial barrier integrity by opening of intestinal epithelial tight junctions arising from transcellular perturbation. Phase I studies using 20 mg octreotide capsules yielded a relative oral bioavailability of ~0.7% and primary endpoints were achieved in two Phase III studies. The oral octreotide dose required to achieve these endpoints was over 200 times that of the 0.1 mg immediate-release subcutaneous injection, a reminder of the difficulty in achieving oral absorption of macromolecules. Many acromegaly patients will prefer a convenient twice-daily oral formulation of octreotide compared to monthly depot injections. FAU - Brayden, David J AU - Brayden DJ AD - University College Dublin (UCD) School of Veterinary Medicine, UCD, Belfield, Dublin 4, Ireland. AD - UCD Conway Institute of Biotechnology, UCD, Belfield, Dublin 4, Ireland. AD - CURAM, the SFI Research Centre for Medical Devices, UCD, Belfield, Dublin 4, Ireland. FAU - Maher, Sam AU - Maher S AD - School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin 2, Ireland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210628 PL - England TA - Expert Opin Drug Deliv JT - Expert opinion on drug delivery JID - 101228421 RN - RWM8CCW8GP (Octreotide) SB - IM MH - *Acromegaly MH - Animals MH - Biological Availability MH - Clinical Trials, Phase I as Topic MH - Clinical Trials, Phase III as Topic MH - *Diabetes Mellitus, Type 2 MH - Humans MH - Octreotide MH - Technology OTO - NOTNLM OT - Oral peptide delivery OT - acromegaly OT - intestinal epithelia OT - octreotide OT - permeation enhancers OT - tight junctions OT - tpe(R) EDAT- 2021/06/16 06:00 MHDA- 2021/10/26 06:00 CRDT- 2021/06/15 13:16 PHST- 2021/06/16 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/06/15 13:16 [entrez] AID - 10.1080/17425247.2021.1942838 [doi] PST - ppublish SO - Expert Opin Drug Deliv. 2021 Oct;18(10):1501-1512. doi: 10.1080/17425247.2021.1942838. Epub 2021 Jun 28. PMID- 34102249 OWN - NLM STAT- MEDLINE DCOM- 20211015 LR - 20250418 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 177 DP - 2021 Jul TI - Comparative efficacy and safety of 8 GLP-1RAs in patients with type 2 diabetes: A network meta-analysis. PG - 108904 LID - S0168-8227(21)00264-3 [pii] LID - 10.1016/j.diabres.2021.108904 [doi] AB - AIMS: To inform clinical practice by comparing and ranking the lowing blood glucose and weight-loss abilities of 8 glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with type 2 diabetes (T2D). METHODS: We searched PubMed, EMBASE, and CENTRAL from database inception to April 13, 2021. The outcomes were Delta HbA(1c), Delta weight, adverse events [AE] withdrawals, and incidence of hypoglycemia. We estimated standardized mean differences [SMD] and summary odds ratios (ORs) using frequentist network meta-analysis with random effects. RESULTS: Retrieved trials included 11,126 patients, the overall mean age was 56.7 +/- 10.36 years old. In terms of efficacy, all GLP-1RAs were more effective than the placebo except albiglutide-30 mg QW (Delta weight: SMD -0.26 kg [95 %CI: -1.10, 0.59 kg). When it came to safety, oral semaglutide-14mgQD, semaglutide-1mgQW, Liraglutide-1.8mgQD, and Exenatide-2ugBID were associated with an increased risk of AE withdrawals. And GLP-1RAs were associated with a higher incidence of hypoglycemia than placebo except albiglutide-30mgQW and orally administered semaglutide-14mgQD. CONCLUSION: Overall GLP-1RAs were more efficacious than placebo in patients with T2D on efficacy. Unfortunately, differences between GLP1-RAs regarding safety were mostly not significant. We may realize the individualized GLP-1RAs administration based on blood glucose level and obesity degree. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Xia, Lin AU - Xia L AD - Department of Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China; Department of Pharmacy, Peking University People's Hospital, Beijing, China. FAU - Shen, Tiantian AU - Shen T AD - Department of Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China; Department of Pharmacy, Peking University People's Hospital, Beijing, China. FAU - Dong, Wenliang AU - Dong W AD - Department of Pharmacy, Peking University People's Hospital, Beijing, China; Department of Pharmacy Administration and Clinical Pharmacy, Peking University School of Pharmaceutical Sciences, Beijing, China. FAU - Su, Feng AU - Su F AD - Department of Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China; Department of Pharmacy, Peking University People's Hospital, Beijing, China. FAU - Wang, Jiaxue AU - Wang J AD - Department of Pharmacy, Peking University People's Hospital, Beijing, China; Department of Pharmacy Administration and Clinical Pharmacy, Peking University School of Pharmaceutical Sciences, Beijing, China. FAU - Wang, Qian AU - Wang Q AD - Nursing Department,Peking University People's Hospital, Beijing, China. FAU - Niu, Suping AU - Niu S AD - Clinical Trial institution, Scientific Research Department, Peking University People's Hospital, Beijing, China. FAU - Fang, Yi AU - Fang Y AD - Department of Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China; Department of Pharmacy, Peking University People's Hospital, Beijing, China. Electronic address: phaseistudy@163.com. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Review DEP - 20210606 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) SB - IM MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Liraglutide MH - Middle Aged OTO - NOTNLM OT - A network meta-analysis OT - Efficacy OT - GLP-1RAs OT - Safety OT - Type 2 diabetes COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2021/06/09 06:00 MHDA- 2021/10/16 06:00 CRDT- 2021/06/08 20:19 PHST- 2020/08/15 00:00 [received] PHST- 2021/05/14 00:00 [revised] PHST- 2021/06/03 00:00 [accepted] PHST- 2021/06/09 06:00 [pubmed] PHST- 2021/10/16 06:00 [medline] PHST- 2021/06/08 20:19 [entrez] AID - S0168-8227(21)00264-3 [pii] AID - 10.1016/j.diabres.2021.108904 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2021 Jul;177:108904. doi: 10.1016/j.diabres.2021.108904. Epub 2021 Jun 6. PMID- 34060209 OWN - NLM STAT- MEDLINE DCOM- 20210811 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 9 DP - 2021 Sep TI - Insights into the early use of oral semaglutide in routine clinical practice: The IGNITE study. PG - 2177-2182 LID - 10.1111/dom.14453 [doi] AB - Oral semaglutide is the first oral glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and showed significant benefits in glycaemic control and weight reduction versus active comparators in the PIONEER phase 3a randomized controlled trial programme. In this retrospective study, we present early data on the use of oral semaglutide in clinical practice, from the US IBM Explorys electronic health record database. In 782 patients prescribed oral semaglutide, 54.5% were women, and the mean age (SD) was 57.8 years (11.3); 66.0% of patients received their prescription from a primary care practitioner. Although prescribing information recommends increasing the dose to 7 mg after 30 days, 37.0% of patients received a prescription only for the initial 3 mg dose. Mean body mass index was 36.2 kg/m(2) (7.6); mean HbA1c was 8.4% (1.8%). Mean HbA1c change from baseline to approximately 6 months after oral semaglutide initiation was -0.9% (95% CI: -1.1%; -0.6%), with greater reductions in patients with higher baseline HbA1c. These data indicate prevalent early adoption of oral semaglutide in primary care, show real-world improvements in glycaemic control, and identify potential treatment gaps. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Faurby, Mads AU - Faurby M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lophaven, Soren AU - Lophaven S AD - Omicron ApS, Roskilde, Denmark. FAU - Noone, Josh AU - Noone J AD - Novo Nordisk, Plainsboro Township, New Jersey, USA. FAU - Wolden, Michael Lyng AU - Wolden ML AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. AD - Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210616 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Middle Aged MH - Retrospective Studies MH - Semaglutide PMC - PMC8453868 OTO - NOTNLM OT - GLP-1 OT - antidiabetic drug OT - database research OT - glycaemic control OT - observational study OT - type 2 diabetes COIS- V.R.A. has performed consultancy for Applied Therapeutics, Duke, Novo Nordisk, Pfizer and Sanofi, and has received research support via institutional contracts from Applied Therapeutics/Medpace, Eli Lilly, Premier/Fractyl, Novo Nordisk and Sanofi/Medpace. Her spouse has been employed at Janssen and Merck. M.F. is an employee and shareholder of Novo Nordisk A/S. S.L. is employed as a consultant by Novo Nordisk A/S. J.N. is an employee of Novo Nordisk. M.L.W. is an employee and shareholder of Novo Nordisk A/S. I.L. has received research funding, advisory/consulting fees and/or other support from AstraZeneca, Bayer, Boehringer Ingelheim, Duke CRI, Eli Lilly, GI Dynamics, Intercept, Intarcia, Janssen, Mannkind, Merck, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, TARGETPharma, Valeritas and Zealand Pharma. EDAT- 2021/06/02 06:00 MHDA- 2021/08/12 06:00 PMCR- 2021/09/21 CRDT- 2021/06/01 06:56 PHST- 2021/05/19 00:00 [revised] PHST- 2021/04/19 00:00 [received] PHST- 2021/05/25 00:00 [accepted] PHST- 2021/06/02 06:00 [pubmed] PHST- 2021/08/12 06:00 [medline] PHST- 2021/06/01 06:56 [entrez] PHST- 2021/09/21 00:00 [pmc-release] AID - DOM14453 [pii] AID - 10.1111/dom.14453 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Sep;23(9):2177-2182. doi: 10.1111/dom.14453. Epub 2021 Jun 16. PMID- 34047443 OWN - NLM STAT- MEDLINE DCOM- 20210811 LR - 20250623 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 23 IP - 9 DP - 2021 Sep TI - Comparative efficacy of glucose-lowering medications on body weight and blood pressure in patients with type 2 diabetes: A systematic review and network meta-analysis. PG - 2116-2124 LID - 10.1111/dom.14451 [doi] AB - AIM: To compare the effects of glucose-lowering drugs on body weight and blood pressure in adults with type 2 diabetes. METHODS: We searched Medline, Embase, the Cochrane Library, and grey literature sources until 29 September 2020 for randomized controlled trials of at least 24 weeks' duration assessing the effects of glucose-lowering drugs on body weight and blood pressure in adults with type 2 diabetes. We performed frequentist network meta-analyses and calculated weighted mean differences and 95% confidence intervals combining trial arms of different approved doses of a given intervention into a single group. We evaluated the confidence in pooled estimates using the CINeMA (Confidence In Network Meta-Analysis) framework. RESULTS: In total, 424 trials (276 336 patients) assessing 21 antidiabetic medications from nine drug classes were included. Subcutaneous semaglutide was the most efficacious in reducing body weight followed by oral semaglutide, exenatide twice-daily, liraglutide, and the sodium-glucose co-transporter-2 (SGLT-2) inhibitors empagliflozin, canagliflozin, dapagliflozin and ertugliflozin. The same agents also conferred the greatest reductions in systolic blood pressure. Metformin had a modest effect in reducing body weight and systolic blood pressure. Diastolic blood pressure was reduced with the SGLT-2 inhibitors pioglitazone, exenatide twice-daily and semaglutide. In subgroup analyses of trials with over 52 weeks' duration, semaglutide and SGLT-2 inhibitors reduced both body weight and systolic blood pressure. CONCLUSIONS: Semaglutide and SGLT-2 inhibitors conferred reductions both in body weight and blood pressure that were sustainable for over 1 year of treatment. These agents may be preferable treatment options for patients with type 2 diabetes who are overweight/obese and/or hypertensive. CI - (c) 2021 John Wiley & Sons Ltd. FAU - Tsapas, Apostolos AU - Tsapas A AUID- ORCID: 0000-0003-0221-4072 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. AD - Diabetes Centre, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. AD - Harris Manchester College, University of Oxford, Oxford, UK. FAU - Karagiannis, Thomas AU - Karagiannis T AUID- ORCID: 0000-0001-5242-0574 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Kakotrichi, Panagiota AU - Kakotrichi P AUID- ORCID: 0000-0003-2544-9819 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Avgerinos, Ioannis AU - Avgerinos I AUID- ORCID: 0000-0003-2232-1342 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Mantsiou, Chrysanthi AU - Mantsiou C AUID- ORCID: 0000-0002-1439-7374 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Tousinas, Georgios AU - Tousinas G AUID- ORCID: 0000-0003-2272-6403 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Manolopoulos, Apostolos AU - Manolopoulos A AUID- ORCID: 0000-0003-1055-0324 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Liakos, Aris AU - Liakos A AUID- ORCID: 0000-0003-3261-2979 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Malandris, Konstantinos AU - Malandris K AUID- ORCID: 0000-0002-5134-2401 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Matthews, David R AU - Matthews DR AUID- ORCID: 0000-0001-6504-0036 AD - Harris Manchester College, University of Oxford, Oxford, UK. AD - Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK. FAU - Bekiari, Eleni AU - Bekiari E AUID- ORCID: 0000-0001-9975-3835 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. AD - Diabetes Centre, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. LA - eng GR - European Foundation for the Study of Diabetes: PACT Programme supported by an unrestricted educational grant from AstraZeneca/ PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20210615 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Adult MH - Blood Pressure MH - Body Weight MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucose MH - Humans MH - Hypoglycemic Agents/therapeutic use OTO - NOTNLM OT - antidiabetic drug OT - network meta-analysis OT - systematic review OT - type 2 diabetes OT - weight control EDAT- 2021/05/29 06:00 MHDA- 2021/08/12 06:00 CRDT- 2021/05/28 09:09 PHST- 2021/05/19 00:00 [revised] PHST- 2021/02/07 00:00 [received] PHST- 2021/05/23 00:00 [accepted] PHST- 2021/05/29 06:00 [pubmed] PHST- 2021/08/12 06:00 [medline] PHST- 2021/05/28 09:09 [entrez] AID - 10.1111/dom.14451 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Sep;23(9):2116-2124. doi: 10.1111/dom.14451. Epub 2021 Jun 15. PMID- 34024887 OWN - NLM STAT- MEDLINE DCOM- 20211206 LR - 20260127 IS - 1348-4540 (Electronic) IS - 0918-8959 (Linking) VI - 68 IP - 6 DP - 2021 Jun 28 TI - Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials. PG - 739-742 LID - 10.1507/endocrj.EJ21-0129 [doi] AB - The PIONEER and SUSTAIN serial trials are designed to assess the efficacy outcomes with semaglutide in patients with type 2 diabetes, but are not powered to assess various safety outcomes. We sought to assess the risk of semaglutide in leading to various serious adverse events (SAEs) in patients with type 2 diabetes. Studies eligible for inclusion were the PIONEER and SUSTAIN trials of semaglutide. We conducted meta-analysis to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using both random-effects and fixed-effects model to evaluate the robustness of pooled results. We implemented subgroup analysis according to drug dosages and routes of administration and type of comparators. Twenty-one trials were included. Semaglutide versus control significantly reduced total SAEs (RR 0.92, 95% CI 0.87-0.97; I(2) = 0) and atrial fibrillation (RR 0.69, 95% CI 0.50-0.95; I(2) = 0), but significantly increased deep vein thrombosis (RR 3.66, 95% CI 1.09-12.25; I(2) = 0) and diarrhoea (RR 2.66, 95% CI 1.19-5.95; I(2) = 0). Semaglutide had no significant effects on 248 other kinds of SAEs. No statistically significant subgroup effects were observed. Semaglutide has a good safety profile in general and reduces atrial fibrillation by 31%, but increases diarrhoea by 166% and deep vein thrombosis by 266%. These findings may guide that semaglutide should be preferred or avoided in T2D patients with specific susceptibility factors. FAU - Yin, Dao-Gen AU - Yin DG AD - Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen 518110, China. FAU - Ding, Liang-Liang AU - Ding LL AUID- ORCID: 0000-0003-0374-2539 AD - Department of Endocrinology, First Affiliated Hospital of Yangtze University, Jingzhou 434000, China. FAU - Zhou, Hai-Rong AU - Zhou HR AD - Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen 518110, China. FAU - Qiu, Mei AU - Qiu M AUID- ORCID: 0000-0001-5013-657X AD - Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen 518110, China. FAU - Duan, Xue-Yan AU - Duan XY AD - Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen 518110, China. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20210522 PL - Japan TA - Endocr J JT - Endocrine journal JID - 9313485 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/*adverse effects/therapeutic use MH - Humans MH - Hypoglycemic Agents/*adverse effects/therapeutic use MH - Semaglutide OTO - NOTNLM OT - PIONEER OT - SUSTAIN OT - Safety OT - Semaglutide OT - Type 2 diabetes EDAT- 2021/05/25 06:00 MHDA- 2021/12/15 06:00 CRDT- 2021/05/24 07:55 PHST- 2021/05/25 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/05/24 07:55 [entrez] AID - 10.1507/endocrj.EJ21-0129 [doi] PST - ppublish SO - Endocr J. 2021 Jun 28;68(6):739-742. doi: 10.1507/endocrj.EJ21-0129. Epub 2021 May 22. PMID- 34024013 OWN - NLM STAT- MEDLINE DCOM- 20220407 LR - 20261012 IS - 2190-3948 (Electronic) IS - 2190-393X (Linking) VI - 12 IP - 1 DP - 2022 Jan TI - Development and approval of rybelsus (oral semaglutide): ushering in a new era in peptide delivery. PG - 1-6 LID - 10.1007/s13346-021-01000-w [doi] AB - Achieving efficacious systemic levels of orally administered peptides is incredibly challenging due to the significant barriers to their bioavailability-their stability in the gastrointestinal tract and challenge of transepithelial transit, and variable pharmacokinetics. Even so, as the generally preferred route of administration, significant research effort in academic and industrial settings has focused on enabling the systemic absorption of orally delivered peptides. Despite several decades of research, few have ever reached the market. The recent approval of Rybelsus(R) (oral semaglutide) by the FDA [1], the EMA [2], and the Pmda [3] represents a significant landmark in the delivery of therapeutic peptides and is the culmination of more than 30 years research and development of the drug delivery technology enabling the product-Emisphere's Eligen technology-and an outstanding commitment to scientific, technical, and clinical innovation by Novo Nordisk. Following years of fundamental and applied research, an innovative clinical strategy led to the aptly named PIONEER clinical programme. This included ten Phase 3 clinical trials that demonstrated the tablet formulation to be as effective as the already approved injectable form of the drug, and more effective than competitor products in terms of its blood glucose lowering effects and weight loss. Not only is this a potentially life changing medicine for diabetic patients, it holds tremendous commercial potential for Novo Nordisk, with some analysts predicting the product to reach $5 billion in peak revenues [3]. In this "Inspirational Note," we summarize some of the public domain work that led to the achievement of this significant milestone and provide commentary on its potential future impact. CI - (c) 2021. Controlled Release Society. FAU - Lewis, Andrew L AU - Lewis AL AD - Quotient Sciences, Mere Way Ruddington, Nottingham, NG11 6JS, UK. Andrew.Lewis@quotientsciences.com. FAU - McEntee, Nicholas AU - McEntee N AD - Quotient Sciences, Mere Way Ruddington, Nottingham, NG11 6JS, UK. FAU - Holland, Justin AU - Holland J AD - Quotient Sciences, Mere Way Ruddington, Nottingham, NG11 6JS, UK. FAU - Patel, Asma AU - Patel A AD - Quotient Sciences, Mere Way Ruddington, Nottingham, NG11 6JS, UK. LA - eng PT - Journal Article DEP - 20210522 PL - United States TA - Drug Deliv Transl Res JT - Drug delivery and translational research JID - 101540061 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/pharmacokinetics/therapeutic use MH - Humans MH - Hypoglycemic Agents MH - Peptides MH - Semaglutide EDAT- 2021/05/24 06:00 MHDA- 2022/04/08 06:00 CRDT- 2021/05/23 21:04 PHST- 2021/04/30 00:00 [accepted] PHST- 2021/05/24 06:00 [pubmed] PHST- 2022/04/08 06:00 [medline] PHST- 2021/05/23 21:04 [entrez] AID - 10.1007/s13346-021-01000-w [pii] AID - 10.1007/s13346-021-01000-w [doi] PST - ppublish SO - Drug Deliv Transl Res. 2022 Jan;12(1):1-6. doi: 10.1007/s13346-021-01000-w. Epub 2021 May 22. PMID- 34009708 OWN - NLM STAT- MEDLINE DCOM- 20210811 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 9 DP - 2021 Sep TI - Potential kidney protection with liraglutide and semaglutide: Exploratory mediation analysis. PG - 2058-2066 LID - 10.1111/dom.14443 [doi] AB - AIMS: To investigate whether effects on chronic kidney disease risk factors could explain the apparent reduction in kidney outcomes (composite of macroalbuminuria, doubling of serum creatinine, renal replacement therapy, or renal death), primarily driven by changes in albuminuria, after treatment with the glucagon-like peptide-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide in patients with type 2 diabetes in the LEADER and SUSTAIN 6 trials. MATERIALS AND METHODS: We evaluated the mediation effect of glycated haemoglobin (HbA1c), systolic blood pressure (BP), and body weight on the kidney effects of GLP-1RAs. Diastolic BP, haemoglobin, heart rate, low-density lipoprotein and total cholesterol, and white blood cell count were also investigated. The mediation effect was estimated by the novel Vansteelandt statistical method. Subgroups with estimated glomerular filtration rate (eGFR) <60 and >/=60 mL/min/1.73 m(2) were examined in LEADER. RESULTS: We observed that HbA1c mediated 25% (95% confidence interval [CI] -7.1; 67.3) and 26% (95% CI noncalculable), and systolic BP 9% (95% CI 2.8; 22.7) and 22% (95% CI noncalculable) of kidney effects of GLP-1RAs in LEADER and SUSTAIN 6, respectively. Small or no mediation was observed for the other parameters; for example, body weight mediated 9% (95% CI -7.9; 35.5) in the former and did not mediate effects in the latter study. Mediation by HbA1c was greater in patients with eGFR >/=60 mL/min/1.73 m(2) (57%) versus those with eGFR <60 mL/min/1.73 m(2) (no mediation). CONCLUSIONS: Our results suggest that HbA1c and systolic BP may moderately mediate kidney benefits of liraglutide and semaglutide, with all other variables having a small to no effect. Potential kidney benefits may be driven by other mediators or potentially by direct mechanisms. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Mann, Johannes F E AU - Mann JFE AUID- ORCID: 0000-0002-3154-5332 AD - Department of Nephrology, Friedrich Alexander University of Erlangen, Erlangen, Germany. AD - KfH Kidney Centre, Munich, Germany. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Leiter, Lawrence A AU - Leiter LA AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AD - Steno Diabetes Centre Copenhagen, Gentofte, Denmark. AD - Gentofte Hospital, Hellerup, Denmark. AD - University of Copenhagen, Copenhagen, Denmark. FAU - Wolthers, Benjamin AU - Wolthers B AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Perkovic, Vlado AU - Perkovic V AD - The George Institute, UNSW, Sydney, New South Wales, Australia. LA - eng GR - UL1 TR002489/TR/NCATS NIH HHS/United States GR - P30 DK124723/DK/NIDDK NIH HHS/United States GR - CIHR/Canada PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20210601 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Kidney MH - *Liraglutide/therapeutic use MH - Mediation Analysis MH - Semaglutide PMC - PMC8453827 OTO - NOTNLM OT - chronic kidney disease OT - glucagon-like peptide-1 receptor agonist OT - kidney mediation OT - liraglutide OT - semaglutide OT - type 2 diabetes COIS- J.F.E.M. has received speaker honoraria from Astra, Boehringer Ingelheim, Eli Lilly & Co, Medice, Novo Nordisk, Roche, and Vifor Pharma, research support from the European Union, Canadian Institutes of Health Research, Astra, Boehringer Ingelheim, Novo Nordisk, Roche and Sandoz, and consultation fees from Astra, Bayer, Novo Nordisk and Vifor Pharma. J.B.B.'s contracted consulting fees and travel support for contracted activities are paid to the University of North Carolina by Adocia, AstraZeneca, Dance Biopharm, Eli Lilly, Fortress Biotech, MannKind, NovaTarg, Novo Nordisk, Sanofi, Senseonics, vTv Therapeutics and Zafgen, as well as grant support from NovaTarg, Novo Nordisk, Sanofi, Tolerion and vTv Therapeutics. J.B.B. is also a consultant to Cirius Therapeutics Inc, CSL Behring, Fortress Biotech, Mellitus Health, Neurimmune AG, Pendulum Therapeutics, Stability Health and Zealand Pharma, holds stock/options in Mellitus Health, Pendulum Therapeutics, PhaseBio and Stability Health, and is supported by grants from the National Institutes of Health in part for this effort (UL1TR002489, P30DK124723). T.I. is an employee of Novo Nordisk and a significant stockholder. L.A.L. has received honoraria for advisory board participation from, and has provided continuing medical education on behalf of, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi and Servier, and has received research grants from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Lexicon, Novo Nordisk and Sanofi. R.E.P. has received research grants from Gilead Sciences, Lexicon Pharmaceuticals, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Sanofi-Aventis US LLC, and Takeda, has acted as a speaker for AstraZeneca, Novo Nordisk and Takeda, and as a consultant for AstraZeneca, Boehringer Ingelheim, Eisai, Inc., GlaxoSmithKline, Janssen Scientific Affairs LLC, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Pfizer and Takeda. All payments are made directly to his employer (AdventHealth). S.R. is a Novo Nordisk employee and stockholder. T.V. has served on scientific advisory panels, been part of speaker's bureaus for, served as a consultant to, and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Mundipharma, MSD/Merck, Novo Nordisk, Sanofi and Sun Pharmaceuticals. B.W. is a Novo Nordisk employee and stockholder. V.P. has participated in steering committees, advisory boards, and/or received honoraria and consultation fees from Amgen, Janssen, GlaxoSmithKline, Astellas, Boehringer Ingelheim, Baxter, Mitsubishi Tanabe, Mundipharma, Retrophin, Merck, Abbvie, Novo Nordisk, AstraZeneca, Gilead, Durect, Servier, Tricida, Novartis, Eli Lilly, Relypsa, Pharmalink, Bayer and Bristol-Myers Squibb. EDAT- 2021/05/20 06:00 MHDA- 2021/08/12 06:00 PMCR- 2021/09/21 CRDT- 2021/05/19 12:59 PHST- 2021/05/04 00:00 [revised] PHST- 2021/01/08 00:00 [received] PHST- 2021/05/16 00:00 [accepted] PHST- 2021/05/20 06:00 [pubmed] PHST- 2021/08/12 06:00 [medline] PHST- 2021/05/19 12:59 [entrez] PHST- 2021/09/21 00:00 [pmc-release] AID - DOM14443 [pii] AID - 10.1111/dom.14443 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Sep;23(9):2058-2066. doi: 10.1111/dom.14443. Epub 2021 Jun 1. PMID- 33977495 OWN - NLM STAT- MEDLINE DCOM- 20210622 LR - 20240415 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 38 IP - 6 DP - 2021 Jun TI - Weight Loss and Maintenance Related to the Mechanism of Action of Glucagon-Like Peptide 1 Receptor Agonists. PG - 2821-2839 LID - 10.1007/s12325-021-01710-0 [doi] AB - Obesity is a chronic disease associated with many complications. Weight loss of 5-15% can improve many obesity-related complications. Despite the benefits of weight reduction, there are many challenges in losing weight and maintaining long-term weight loss. Pharmacotherapy can help people with obesity achieve and maintain their target weight loss, thereby reducing the risk of obesity-related complications. The prevalence of obesity in the USA has been increasing over the past few decades, and despite the availability of approved anti-obesity medications (AOMs), people with obesity may not be accessing or receiving treatment at levels consistent with the disease prevalence. Reasons for low levels of initiation and long-term use of AOMs may include reluctance of public health and medical organizations to recognize obesity as a disease, lack of reimbursement, provider inexperience, and misperceptions about the efficacy and safety of available treatments. This article aims to inform primary care providers about the mechanism of action of one class of AOMs, glucagon-like peptide 1 receptor agonists (GLP-1RAs), in weight loss and longer-term maintenance of weight loss, and the efficacy and safety of this treatment class. GLP-1RA therapy was initially developed to treat type 2 diabetes. Owing to their effectiveness in reducing body weight, once-daily subcutaneous administration of liraglutide 3.0 mg has been approved, and once-weekly subcutaneous administration of semaglutide 2.4 mg is being investigated in phase III trials, for obesity management. Considerations regarding adverse effects and contraindications for different drug classes are provided to help guide treatment decision-making when considering pharmacotherapy for weight management in patients with obesity. FAU - Ard, Jamy AU - Ard J AUID- ORCID: 0000-0002-1643-6795 AD - Division of Public Health Sciences, Department of Epidemiology and Prevention, Wake Forest University School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC, 27157, USA. jard@wakehealth.edu. FAU - Fitch, Angela AU - Fitch A AD - MGH Weight Center, Massachusetts General Hospital, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. AD - Endocrine Unit, Division of Endocrinology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA. FAU - Fruh, Sharon AU - Fruh S AD - College of Nursing, University of South Alabama, Mobile, AL, USA. FAU - Herman, Lawrence AU - Herman L AD - Doctor of Medical Science Program, University of Lynchburg, Lynchburg, VA, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20210511 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Pharmaceutical Preparations) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - *Pharmaceutical Preparations MH - Weight Loss PMC - PMC8189979 OAB - Obesity is a growing public health issue that increases the risk of developing heart disease, type 2 diabetes, and osteoarthritis. Weight loss can reduce the risk of developing these health problems but, despite this, levels of obesity remain high. Achieving and maintaining weight loss is challenging for many individuals. There is therefore a need for some patients to take medications to help them lose weight and prevent weight regain. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are a type of medication originally developed to treat type 2 diabetes, but are now being used for the treatment of obesity because they are effective at helping people to lose weight. One GLP-1RA, liraglutide, has been approved to treat obesity, and another, semaglutide, is in clinical trials. GLP-1RAs work by reducing the appetite and feelings of hunger, slowing the release of food from the stomach, and increasing feelings of fullness after eating. Most people can tolerate GLP-1RAs well. The most common side effects (nausea, vomiting, and diarrhea) are usually mild and occur in the first few weeks of treatment, reducing over time. Because of the difficulties many people face in maintaining weight loss, lifelong treatment may be needed. In clinical trials, GLP-1RAs were well tolerated and effective at helping people prevent weight regain, and may be a good option for long-term weight control and lowering patients' chances of serious health problems. OABL- eng OTO - NOTNLM OT - Antiobesity medication OT - Glucagon-like peptide 1 receptor agonist OT - Obesity OT - Pharmacotherapy OT - Weight loss EDAT- 2021/05/13 06:00 MHDA- 2021/06/23 06:00 PMCR- 2021/05/11 CRDT- 2021/05/12 07:14 PHST- 2021/02/04 00:00 [received] PHST- 2021/03/12 00:00 [accepted] PHST- 2021/05/13 06:00 [pubmed] PHST- 2021/06/23 06:00 [medline] PHST- 2021/05/12 07:14 [entrez] PHST- 2021/05/11 00:00 [pmc-release] AID - 10.1007/s12325-021-01710-0 [pii] AID - 1710 [pii] AID - 10.1007/s12325-021-01710-0 [doi] PST - ppublish SO - Adv Ther. 2021 Jun;38(6):2821-2839. doi: 10.1007/s12325-021-01710-0. Epub 2021 May 11. PMID- 33969456 OWN - NLM STAT- MEDLINE DCOM- 20211028 LR - 20260127 IS - 1179-1926 (Electronic) IS - 0312-5963 (Print) IS - 0312-5963 (Linking) VI - 60 IP - 10 DP - 2021 Oct TI - Clinical Pharmacokinetics of Oral Semaglutide: Analyses of Data from Clinical Pharmacology Trials. PG - 1335-1348 LID - 10.1007/s40262-021-01025-x [doi] AB - OBJECTIVE: The absorption, distribution and elimination of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist for treating type 2 diabetes, was investigated using a population pharmacokinetic model based on data from clinical pharmacology trials. METHODS: A previously developed, two-compartment pharmacokinetic model, based on subcutaneous and intravenous semaglutide, was extended to include data from six oral semaglutide trials conducted in either healthy volunteers or subjects with renal or hepatic impairment. Five trials employed multiple doses of oral semaglutide (5-10 mg) and one was a single-dose (10 mg) trial. In a separate analysis, the model was re-estimated using data from a trial in subjects with type 2 diabetes. RESULTS: The model accurately described concentration profiles across trials. Post-dose fasting time, co-ingestion of a large water volume, and body weight were the most important covariates affecting semaglutide exposure. Bioavailability was 0.8% when oral semaglutide was dosed using the recommended dosing conditions (30 min post-dose fasting time, administered with 9% (75 mmol/mol). FINDINGS: A total of 1888 patients were identified in the overall ITT group. The mean change in the overall ITT group between preindex and postindex A(1c) values was -0.9% percentage points (-9.8 mmol/mol) (mean preindex A(1c), 8.2% [66.1 mmol/mol]) and -1.1 percentage points (-12.0 mmol/mol) (mean preindex A(1c), 8.2% [66.1 mmol/mol]) in the PP subgroup (all P < 0.001). Among the subgroup of patients with a baseline A(1c) value >9% (75 mmol/mol), percentage point changes in A(1c) were -2.2 (-24.0 mmol/mol) and -2.4 (-26.2 mmol/mol) (all P < 0.001). When accounting for prior GLP-1RA use, the GLP-1RA-naive stratum had double the mean reduction in A(1c) compared with the GLP-1RA-experienced stratum (-1.2 [-13.1 mmol/mol] vs -0.6 [-6.6 mmol/mol] percentage points). IMPLICATIONS: Semaglutide OW is associated with clinically and statistically significant A(1C) reduction and increases in reaching A(1) targets using real-world data, even in GLP-1RA-experienced patients, despite more frequent use of insulin or sodium glucose transport protein 2 inhibitors in this group. Target A(1c) attainment significantly increased overall and within all subgroups and strata, with approximately half of all patients attaining an A(1c) value <7% (53 mmol/mol) and three-quarters attaining an A(1c) value <8% (64 mmol/mol). CI - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Visaria, Jay AU - Visaria J AD - HealthCore Inc, Wilmington, Delaware. FAU - Uzoigwe, Chioma AU - Uzoigwe C AD - Novo Nordisk Inc, Plainsboro Township, New Jersey. FAU - Swift, Caroline AU - Swift C AD - Novo Nordisk Inc, Plainsboro Township, New Jersey. FAU - Dang-Tan, Tam AU - Dang-Tan T AD - Novo Nordisk Inc, Plainsboro Township, New Jersey. FAU - Paprocki, Yurek AU - Paprocki Y AD - Novo Nordisk Inc, Plainsboro Township, New Jersey. FAU - Willey, Vincent J AU - Willey VJ AD - HealthCore Inc, Wilmington, Delaware. Electronic address: vwilley@healthcore.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210328 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Cohort Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - *Medicare Part C MH - Retrospective Studies MH - United States MH - Semaglutide OTO - NOTNLM OT - GLP-1RA OT - T2DM OT - glucose control OT - hemoglobin A(1c) OT - real-world OT - semaglutide OT - type 2 diabetes mellitus COIS- Disclosures Chioma Uzoigwe, Caroline Swift, Tam Dang-Tan, and Yurek Paprocki report being employees of Novo Nordisk during the conduct of this study. In addition, Chioma Uzoigwe and Yurek Paprocki report being stockholders with Novo Nordisk. Jay Visaria and Vincent Willey report being employees of HealthCore, Inc during the conduct of this study. Authors from NovoNordisk contributed to the study by participating in study design, data analysis and interpretation, manuscript writing and revisions, and approval for publication. HealthCore Inc receives funding from numerous external entities to perform research projects. The authors have indicated that they have no other conflicts of interest regarding the content of this article. EDAT- 2021/04/01 06:00 MHDA- 2021/11/25 06:00 CRDT- 2021/03/31 05:48 PHST- 2020/11/16 00:00 [received] PHST- 2021/03/04 00:00 [revised] PHST- 2021/03/05 00:00 [accepted] PHST- 2021/04/01 06:00 [pubmed] PHST- 2021/11/25 06:00 [medline] PHST- 2021/03/31 05:48 [entrez] AID - S0149-2918(21)00111-9 [pii] AID - 10.1016/j.clinthera.2021.03.003 [doi] PST - ppublish SO - Clin Ther. 2021 May;43(5):808-821. doi: 10.1016/j.clinthera.2021.03.003. Epub 2021 Mar 28. PMID- 33772451 OWN - NLM STAT- MEDLINE DCOM- 20211025 LR - 20260127 IS - 1179-6901 (Electronic) IS - 1174-5886 (Print) IS - 1174-5886 (Linking) VI - 21 IP - 2 DP - 2021 Jun TI - A Review on the Efficacy and Safety of Oral Semaglutide. PG - 133-148 LID - 10.1007/s40268-021-00341-8 [doi] AB - There are numerous treatment options currently available for patients with type 2 diabetes mellitus; however, a multitude of patients continue to have inadequately controlled glycemic levels with their current antihyperglycemic regimen. Furthermore, the American Diabetes Association guidelines increasingly highlight the importance of multifactorial management and optimizing medication regimens that include cardiovascular, renal, and/or weight benefits in patients with type 2 diabetes mellitus. Glucagon-like peptide-1 receptor agonists belong to a novel class of type 2 diabetes mellitus agents that are becoming increasingly prevalent owing to their ability to improve glycemic status without the risk of hypoglycemia. Currently, there are three US Food and Drug Administration-approved glucagon-like peptide-1 receptor agonists, subcutaneous semaglutide, dulaglutide, and liraglutide, that also have an indication for reducing major adverse cardiovascular events in patients with type 2 diabetes mellitus and established cardiovascular disease. However, these agents are not often the first options because of their subcutaneous administration. Nevertheless, co-formulation of oral semaglutide with an absorption enhancer has shown to increase its bioavailability and has made its oral absorption possible. In the PIONEER trials, oral semaglutide effectively lowered blood glucose levels, and showed benefits on weight and cardiovascular outcomes; however, there is no Food and Drug Administration indication approved yet as the SOUL trial is still ongoing. Such characteristics of oral semaglutide may improve and increase its use compared to subcutaneous agents and possibly lead to earlier cardiovascular protection in addition to achieving glycemic control. FAU - Niman, Stephanie AU - Niman S AD - East Coast Institute for Research, LLC, 3550 University Blvd. South, Suite 101, Jacksonville, FL, 32216, USA. FAU - Hardy, Jennifer AU - Hardy J AD - East Coast Institute for Research, LLC, 3550 University Blvd. South, Suite 101, Jacksonville, FL, 32216, USA. FAU - Goldfaden, Rebecca F AU - Goldfaden RF AUID- ORCID: 0000-0002-6401-4888 AD - East Coast Institute for Research, LLC, 3550 University Blvd. South, Suite 101, Jacksonville, FL, 32216, USA. Rebecca.Goldfaden@ecirmed.com. FAU - Reid, Jessica AU - Reid J AD - East Coast Institute for Research, LLC, 3550 University Blvd. South, Suite 101, Jacksonville, FL, 32216, USA. AD - College of Pharmacy, University of Florida, Jacksonville, FL, USA. FAU - Sheikh-Ali, Mae AU - Sheikh-Ali M AD - Northeast Florida Endocrine and Diabetes Associates, Jacksonville, FL, USA. FAU - Sutton, David AU - Sutton D AD - Northeast Florida Endocrine and Diabetes Associates, Jacksonville, FL, USA. FAU - Choksi, Rushab AU - Choksi R AD - East Coast Institute for Research, LLC, 3550 University Blvd. South, Suite 101, Jacksonville, FL, 32216, USA. LA - eng PT - Journal Article PT - Review DEP - 20210326 PL - New Zealand TA - Drugs R D JT - Drugs in R&D JID - 100883647 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Semaglutide PMC - PMC8206300 COIS- Mae Sheikh-Ali has received a speaker honorarium from Novo Nordisk, Eli Lilly, AstraZeneca, Janssen, and Merck. David Sutton has received a speaker honorarium from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Zealand Pharma, AbbVie, Abbot, and Amarin. Stephanie Niman, Jennifer Hardy, Rebecca F. Goldfaden, Jessica Reid, and Rushab Choksi have no conflicts of interest that are directly relevant to the content of this article. EDAT- 2021/03/28 06:00 MHDA- 2021/10/26 06:00 PMCR- 2021/03/26 CRDT- 2021/03/27 06:28 PHST- 2021/03/10 00:00 [accepted] PHST- 2021/03/28 06:00 [pubmed] PHST- 2021/10/26 06:00 [medline] PHST- 2021/03/27 06:28 [entrez] PHST- 2021/03/26 00:00 [pmc-release] AID - 10.1007/s40268-021-00341-8 [pii] AID - 341 [pii] AID - 10.1007/s40268-021-00341-8 [doi] PST - ppublish SO - Drugs R D. 2021 Jun;21(2):133-148. doi: 10.1007/s40268-021-00341-8. Epub 2021 Mar 26. PMID- 33769850 OWN - NLM STAT- MEDLINE DCOM- 20210920 LR - 20260127 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 27 IP - 4 DP - 2021 Apr TI - Cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for type 2 diabetes. PG - 455-468 LID - 10.18553/jmcp.2021.27.4.455 AB - BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM). While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide. OBJECTIVE: To estimate the incremental value of oral semaglutide added to existing antihyperglycemic treatment for people with T2DM with additional risk for cardiovascular disease. METHODS: We estimated the lifetime cost-effectiveness of oral semaglutide added to current antihyperglycemic treatment for T2DM using a microsimulation model based primarily on the UK Prospective Diabetes Study (UKPDS) Outcomes Model 2 (OM2) equations. Oral semaglutide added to current antihyperglycemic treatment was separately compared with (a) ongoing background antihyperglycemic treatment, (b) sitagliptin, (c) empagliflozin, and (d) liraglutide. Comparators sitagliptin, empagliflozin, and liraglutide were added to ongoing antihyperglycemic treatment. We applied hazard ratios derived from a network meta-analysis for cardiovascular and renal outcomes to the UKPDS OM2 estimated baseline rates. Health state utilities and costs were derived from the published literature. We estimated total costs, life-years (LYs), quality-adjusted life-years (QALYs), clinical events, and cost per major adverse cardiovascular event (MACE) avoided, over a lifetime time horizon using discount rates of 3% for costs and outcomes. RESULTS: The lifetime total cost for people treated with oral semaglutide was $311,300, with costs for the other comparators ranging from $262,800 (background treatment alone) to $287,800 (liraglutide). Oral semaglutide resulted in the fewest MACE, including the fewest cardiovascular deaths. Among the 5 modeled treatment strategies, oral semaglutide had the highest LYs gained (8.43 vs. 7.76 [background treatment alone] to 8.29 [empagliflozin and liraglutide]) and the highest QALYs gained (4.11 vs. 3.70 [background treatment alone] to 4.03 [empagliflozin]). Oral semaglutide would likely be considered cost-effective compared with liraglutide (incremental cost-effectiveness ratio [ICER] = $40,100), and moderately cost-effective versus background treatment alone ([ICER] = $117,500/QALY) and sitagliptin (ICER = $145,200/QALY). The ICER for oral semaglutide compared with empagliflozin was approximately $458,400 per QALY. CONCLUSIONS: As modeled, oral semaglutide as an add-on therapy to background antihyperglycemic treatment produced incremental benefits in MACE avoided, along with greater QALYs compared with background antihyperglycemic treatment alone. Oral semaglutide use resulted in better outcomes than background treatment alone or sitagliptin, and similar outcomes to liraglutide or empagliflozin with overlapping 95% confidence ranges for QALYs. Oral semaglutide was estimated to be cost-effective compared with liraglutide and to have incremental cost-effectiveness ratios between $100,000 and $150,000 per QALY versus sitagliptin and background therapy alone, but it did not meet these thresholds compared with empagliflozin. DISCLOSURES: Funding for this study was provided by the Institute for Clinical and Economic Review, an independent organization that evaluates the evidence on the value of health care interventions. ICER reports grants from Laura and John Arnold Foundation, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Rind, Fazioli, Chapman, and Pearson are employed by ICER. Guzauskas and Hansen have nothing to disclose. Study results were presented at the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), November 14, 2019, at Brown University, Providence, RI. FAU - Guzauskas, Gregory F AU - Guzauskas GF AD - The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, Department of Pharmacy, University of Washington, Seattle. FAU - Rind, David M AU - Rind DM AD - Institute for Clinical and Economic Review (ICER), Boston, MA. FAU - Fazioli, Katherine AU - Fazioli K AD - Institute for Clinical and Economic Review (ICER), Boston, MA. FAU - Chapman, Richard H AU - Chapman RH AD - Institute for Clinical and Economic Review (ICER), Boston, MA. FAU - Pearson, Steven D AU - Pearson SD AD - Institute for Clinical and Economic Review (ICER), Boston, MA. FAU - Hansen, Ryan N AU - Hansen RN AD - The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, Department of Pharmacy, University of Washington, Seattle. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - J Manag Care Spec Pharm. 2021 Aug;27(8):1140-1141. doi: 10.18553/jmcp.2021.27.8.1140. PMID: 34337999 MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptides/administration & dosage/economics/*therapeutic use MH - Humans MH - Hypoglycemic Agents/administration & dosage/economics/*therapeutic use MH - Male MH - Middle Aged MH - Models, Economic MH - Quality-Adjusted Life Years MH - United States MH - Young Adult MH - Semaglutide PMC - PMC10390985 COIS- Funding for this study was provided by the Institute for Clinical and Economic Review, an independent organization that evaluates the evidence on the value of health care interventions. ICER reports grants from Laura and John Arnold Foundation, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan. ICER's annual policy summit is supported by dues from AbbVie, Aetna, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, uniQure, and United Healthcare. Rind, Fazioli, Chapman, and Pearson are employed by ICER. Guzauskas and Hansen have nothing to disclose. Study results were presented at the New England Comparative Effectiveness Public Advisory Council (New England CEPAC), November 14, 2019, at Brown University, Providence, RI. EDAT- 2021/03/27 06:00 MHDA- 2021/09/21 06:00 PMCR- 2021/04/01 CRDT- 2021/03/26 17:14 PHST- 2021/03/26 17:14 [entrez] PHST- 2021/03/27 06:00 [pubmed] PHST- 2021/09/21 06:00 [medline] PHST- 2021/04/01 00:00 [pmc-release] AID - 10.18553/jmcp.2021.27.4.455 [pii] AID - 10.18553/jmcp.2021.27.4.455 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2021 Apr;27(4):455-468. doi: 10.18553/jmcp.2021.27.4.455. PMID- 33744377 OWN - NLM STAT- MEDLINE DCOM- 20210716 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 175 DP - 2021 May TI - The long-term cost-effectiveness of oral semaglutide in the Netherlands based on the PIONEER 2, 3 and 4 randomized controlled trials. PG - 108759 LID - S0168-8227(21)00112-1 [pii] LID - 10.1016/j.diabres.2021.108759 [doi] AB - AIMS: To assess the long-term cost-effectiveness of novel glucagon-like peptide-1 (GLP-1) analog oral semaglutide versus sodium-glucose cotransporter-2 inhibitor empagliflozin, dipeptidyl peptidase-4 inhibitor sitagliptin and injectable GLP-1 analog liraglutide in the Netherlands, based on the results of the PIONEER clinical trials. METHODS: Outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Clinical data were derived from PIONEER 2, 3 and 4. Patients were assumed to receive initial treatments until glycated hemoglobin exceeded 7.5%, then treatment-intensified to basal insulin therapy. Costs were accounted from a societal perspective in 2019 euros (EUR). RESULTS: Oral semaglutide 14 mg was associated with improvements in quality-adjusted life expectancy of 0.15, 0.22 and 0.09quality-adjusted life years (QALYs) versus empagliflozin 25 mg, sitagliptin 100 mg and liraglutide 1.8 mg, respectively, with combined costs EUR1,032 higher, EUR115 higher and EUR1,267 lower. Oral semaglutide was therefore associated with incremental cost-effectiveness ratios of EUR7,061 and EUR516 per QALY gained versus empagliflozin and sitagliptin, respectively. CONCLUSIONS: Based on long-term projections, oral semaglutide 14 mg was considered cost-effective versus empagliflozin 25 mg and sitagliptin 100 mg and dominant versus liraglutide 1.8 mg for the treatment of type 2 diabetes in the Netherlands. CI - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Malkin, Samuel J P AU - Malkin SJP AD - Ossian Health Economics and Communications, Basel, Switzerland. Electronic address: malkin@ossianconsulting.com. FAU - Hunt, Barnaby AU - Hunt B AD - Ossian Health Economics and Communications, Basel, Switzerland. FAU - Huisman, Eline L AU - Huisman EL AD - Novo Nordisk BV, Alphen aan den Rijn, Netherlands. FAU - Grand, Tobias S AU - Grand TS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Chubb, Barrie AU - Chubb B AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng PT - Journal Article DEP - 20210317 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2/*drug therapy MH - Female MH - Glucagon-Like Peptides/*economics/pharmacology/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*economics/pharmacology/*therapeutic use MH - Male MH - Middle Aged MH - Netherlands MH - Randomized Controlled Trials as Topic MH - Semaglutide OTO - NOTNLM OT - Cost OT - Cost-effectiveness OT - Diabetes mellitus OT - Glucagon-like peptide-1 receptor agonist OT - Netherlands OT - Oral semaglutide COIS- Declaration of Competing Interest Samuel Malkin and Barnaby Hunt are employees of Ossian Health Economics and Communications GmbH. Ossian received consulting fees from Novo Nordisk A/S to support preparation of the analysis. Eline Huisman is an employee of Novo Nordisk BV. Tobias Grand and Barrie Chubb are employees of Novo Nordisk A/S, and Barrie Chubb owns Novo Nordisk stock. EDAT- 2021/03/22 06:00 MHDA- 2021/07/17 06:00 CRDT- 2021/03/21 20:56 PHST- 2020/12/22 00:00 [received] PHST- 2021/03/05 00:00 [revised] PHST- 2021/03/09 00:00 [accepted] PHST- 2021/03/22 06:00 [pubmed] PHST- 2021/07/17 06:00 [medline] PHST- 2021/03/21 20:56 [entrez] AID - S0168-8227(21)00112-1 [pii] AID - 10.1016/j.diabres.2021.108759 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2021 May;175:108759. doi: 10.1016/j.diabres.2021.108759. Epub 2021 Mar 17. PMID- 33710717 OWN - NLM STAT- MEDLINE DCOM- 20210630 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 7 DP - 2021 Jul TI - Oral semaglutide improves postprandial glucose and lipid metabolism, and delays gastric emptying, in subjects with type 2 diabetes. PG - 1594-1603 LID - 10.1111/dom.14373 [doi] AB - AIM: To assess the effects of oral semaglutide on postprandial glucose and lipid metabolism, and gastric emptying, in subjects with type 2 diabetes (T2D). MATERIALS AND METHODS: In this randomized, double-blind, single-centre, crossover trial, subjects with T2D received once-daily oral semaglutide (escalated to 14 mg) followed by placebo, or vice versa, over two consecutive 12-week periods. Glucose and lipid metabolism, and gastric emptying (paracetamol absorption) were assessed before and after two types of standardized meals (standard and/or fat-rich) at the end of each treatment period. The primary endpoint was area under the glucose 0-5-h curve (AUC(0-5h) ) after the standard breakfast. RESULTS: Fifteen subjects were enrolled (mean age 58.2 years, HbA1c 6.9%, body weight 93.9 kg, diabetes duration 3.1 years; 13 [86.7%] males). Fasting concentrations of glucose were significantly lower, and C-peptide significantly greater, with oral semaglutide versus placebo. Postprandial glucose (AUC(0-5h) ) was significantly lower with oral semaglutide versus placebo (estimated treatment ratio, 0.71; 95% CI, 0.63, 0.81; p < .0001); glucose incremental AUC (iAUC(0-5h/5h) ) and glucagon AUC(0-5h) were also significantly reduced, with similar results after the fat-rich breakfast. Fasting concentrations of triglycerides, very low-density lipoprotein (VLDL) and apolipoprotein B48 (ApoB48) were significantly lower with oral semaglutide versus placebo. AUC(0-8h) for triglycerides, VLDL and ApoB48, and triglycerides iAUC(0-8h/8h) , were significantly reduced after oral semaglutide versus placebo. During the first postprandial hour, gastric emptying was delayed (a 31% decrease in paracetamol AUC(0-1h) ) with oral semaglutide versus placebo. One serious adverse event (acute myocardial infarction) occurred during oral semaglutide treatment. CONCLUSION: Oral semaglutide significantly improved fasting and postprandial glucose and lipid metabolism, and delayed gastric emptying. CI - (c) 2021 Novo Nordisk A/S. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Dahl, Kirsten AU - Dahl K AUID- ORCID: 0000-0001-5063-1554 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Brooks, Ashley AU - Brooks A AD - Covance Clinical Research Unit Ltd, Leeds, UK. FAU - Almazedi, Firas AU - Almazedi F AD - Covance Clinical Research Unit Ltd, Leeds, UK. FAU - Hoff, Soren Tetens AU - Hoff ST AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Boschini, Cristina AU - Boschini C AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Baekdal, Tine A AU - Baekdal TA AUID- ORCID: 0000-0002-1348-0352 AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210329 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - IY9XDZ35W2 (Glucose) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Diabetes Obes Metab. 2021 Oct;23(10):2411-2413. doi: 10.1111/dom.14473. PMID: 34169640 CIN - Diabetes Obes Metab. 2021 Oct;23(10):2414-2416. doi: 10.1111/dom.14485. PMID: 34212484 MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - Gastric Emptying MH - Glucagon-Like Peptides MH - Glucose MH - Humans MH - Hypoglycemic Agents MH - Lipid Metabolism MH - Male MH - Middle Aged MH - Postprandial Period MH - Semaglutide PMC - PMC8251575 OTO - NOTNLM OT - GLP-1 analogue OT - dyslipidaemia OT - glycaemic control OT - incretin therapy OT - pharmacodynamics OT - type 2 diabetes COIS- KD, STH, CB and TAB are employees, and KD, STH and TAB shareholders, of Novo Nordisk A/S, the sponsor of this trial. FA and AB are employees of Covance Clinical Research Unit Ltd, the site where the trial was conducted; they did not receive any direct funding, nor have financial affiliations with the trial sponsor. EDAT- 2021/03/13 06:00 MHDA- 2021/07/01 06:00 PMCR- 2021/07/02 CRDT- 2021/03/12 12:59 PHST- 2021/03/05 00:00 [revised] PHST- 2020/08/11 00:00 [received] PHST- 2021/03/05 00:00 [accepted] PHST- 2021/03/13 06:00 [pubmed] PHST- 2021/07/01 06:00 [medline] PHST- 2021/03/12 12:59 [entrez] PHST- 2021/07/02 00:00 [pmc-release] AID - DOM14373 [pii] AID - 10.1111/dom.14373 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Jul;23(7):1594-1603. doi: 10.1111/dom.14373. Epub 2021 Mar 29. PMID- 33677922 OWN - NLM STAT- MEDLINE DCOM- 20220314 LR - 20250103 IS - 2093-5978 (Electronic) IS - 2093-596X (Print) IS - 2093-596X (Linking) VI - 36 IP - 1 DP - 2021 Feb TI - Peptidyl and Non-Peptidyl Oral Glucagon-Like Peptide-1 Receptor Agonists. PG - 22-29 LID - 10.3803/EnM.2021.102 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists are efficacious glucose-lowering medications with salient benefits for body weight and cardiovascular events. This class of medications is now recommended as the top priority for patients with established cardiovascular disease or indicators of high risk. Until the advent of oral semaglutide, however, GLP-1 receptor agonists were available only in the form of subcutaneous injections. Aversion to needles, discomfort with self-injection, or skin problems at the injection site are commonly voiced problems in people with diabetes, and thus, attempts for non-invasive delivery strategies have continued. Herein, we review the evolution of GLP-1 therapy from its discovery and the development of currently approved drugs to the unprecedented endeavor to administer GLP-1 receptor agonists via the oral route. We focus on the pharmacokinetic and pharmacodynamic properties of the recently approved oral GLP-1 receptor agonist, oral semaglutide. Small molecule oral GLP-1 receptor agonists are currently in development, and we introduce how these chemicals have addressed the challenge posed by interactions with the large extracellular ligand binding domain of the GLP-1 receptor. We specifically discuss the structure and pharmacological properties of TT-OAD2, LY3502970, and PF-06882961, and envision an era where more patients could benefit from oral GLP-1 receptor agonist therapy. FAU - Choe, Hun Jee AU - Choe HJ AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. FAU - Cho, Young Min AU - Cho YM AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. LA - eng PT - Journal Article PT - Review DEP - 20210224 PL - Korea (South) TA - Endocrinol Metab (Seoul) JT - Endocrinology and metabolism (Seoul, Korea) JID - 101554139 RN - 0 (Hypoglycemic Agents) RN - 0 (Isoquinolines) RN - 0 (Pyridines) RN - 0 (TT-OAD2) RN - 47E5O17Y3R (Phenylalanine) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Isoquinolines MH - Phenylalanine/analogs & derivatives MH - Pyridines/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC7937847 OTO - NOTNLM OT - Administration, oral OT - Drug development OT - Glucagon-like peptide 1 OT - Receptors, G-protein-coupled OT - Semaglutide COIS- CONFLICTS OF INTEREST Young Min Cho reports a grant from Sanofi and consultation fees from LG Chemical. Hun Jee Choe has nothing to declare. EDAT- 2021/03/09 06:00 MHDA- 2022/03/15 06:00 PMCR- 2021/02/01 CRDT- 2021/03/08 00:33 PHST- 2021/01/15 00:00 [received] PHST- 2021/01/29 00:00 [accepted] PHST- 2021/03/08 00:33 [entrez] PHST- 2021/03/09 06:00 [pubmed] PHST- 2022/03/15 06:00 [medline] PHST- 2021/02/01 00:00 [pmc-release] AID - EnM.2021.102 [pii] AID - enm-2021-102 [pii] AID - 10.3803/EnM.2021.102 [doi] PST - ppublish SO - Endocrinol Metab (Seoul). 2021 Feb;36(1):22-29. doi: 10.3803/EnM.2021.102. Epub 2021 Feb 24. PMID- 33667417 OWN - NLM STAT- MEDLINE DCOM- 20211111 LR - 20260202 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 397 IP - 10278 DP - 2021 Mar 13 TI - Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. PG - 971-984 LID - S0140-6736(21)00213-0 [pii] LID - 10.1016/S0140-6736(21)00213-0 [doi] AB - BACKGROUND: This trial assessed the efficacy and safety of the GLP-1 analogue once a week subcutaneous semaglutide 2.4 mg versus semaglutide 1.0 mg (the dose approved for diabetes treatment) and placebo for weight management in adults with overweight or obesity, and type 2 diabetes. METHODS: This double-blind, double-dummy, phase 3, superiority study enrolled adults with a body-mass index of at least 27 kg/m(2) and glycated haemoglobin 7-10% (53-86 mmol/mol) who had been diagnosed with type 2 diabetes at least 180 days before screening. Patients were recruited from 149 outpatient clinics in 12 countries across Europe, North America, South America, the Middle East, South Africa, and Asia. Patients were randomly allocated (1:1:1) via an interactive web-response system and stratified by background glucose-lowering medication and glycated haemoglobin, to subcutaneous injection of semaglutide 2.4 mg, or semaglutide 1.0 mg, or visually matching placebo, once a week for 68 weeks, plus a lifestyle intervention. Patients, investigators, and those assessing outcomes were masked to group assignment. Coprimary endpoints were percentage change in bodyweight and achievement of weight reduction of at least 5% at 68 weeks for semaglutide 2.4 mg versus placebo, assessed by intention to treat. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03552757 and is closed to new participants. FINDINGS: From June 4 to Nov 14, 2018, 1595 patients were screened, of whom 1210 were randomly assigned to semaglutide 2.4 mg (n=404), semaglutide 1.0 mg (n=403), or placebo (n=403) and included in the intention-to-treat analysis. Estimated change in mean bodyweight from baseline to week 68 was -9.6% (SE 0.4) with semaglutide 2.4 mg vs -3.4% (0.4) with placebo. Estimated treatment difference for semaglutide 2.4 mg versus placebo was -6.2 percentage points (95% CI -7.3 to -5.2; p<0.0001). At week 68, more patients on semaglutide 2.4 mg than on placebo achieved weight reductions of at least 5% (267 [68.8%] of 388 vs 107 [28.5%] of 376; odds ratio 4.88, 95% CI 3.58 to 6.64; p<0.0001). Adverse events were more frequent with semaglutide 2.4 mg (in 353 [87.6%] of 403 patients) and 1.0 mg (329 [81.8%] of 402) than with placebo (309 [76.9%] of 402). Gastrointestinal adverse events, which were mostly mild to moderate, were reported in 256 (63.5%) of 403 patients with semaglutide 2.4 mg, 231 (57.5%) of 402 with semaglutide 1.0 mg, and 138 (34.3%) of 402 with placebo. INTERPRETATION: In adults with overweight or obesity, and type 2 diabetes, semaglutide 2.4 mg once a week achieved a superior and clinically meaningful decrease in bodyweight compared with placebo. FUNDING: Novo Nordisk. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Davies, Melanie AU - Davies M AD - Diabetes Research Centre, University of Leicester, Leicester, UK; NIHR Leicester Biomedical Research Centre, Leicester, UK. FAU - Faerch, Louise AU - Faerch L AD - Novo Nordisk, Soborg, Denmark. FAU - Jeppesen, Ole K AU - Jeppesen OK AD - Novo Nordisk, Soborg, Denmark. FAU - Pakseresht, Arash AU - Pakseresht A AD - Novo Nordisk, Soborg, Denmark. FAU - Pedersen, Sue D AU - Pedersen SD AD - C-ENDO Diabetes and Endocrinology Clinic Calgary, Calgary, AB, Canada. FAU - Perreault, Leigh AU - Perreault L AD - University of Colorado Anschutz Medical Campus, Aurora, CO, USA. FAU - Rosenstock, Julio AU - Rosenstock J AD - Dallas Diabetes Research Center at Medical City, Dallas, TX, USA. FAU - Shimomura, Iichiro AU - Shimomura I AD - Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. FAU - Viljoen, Adie AU - Viljoen A AD - Borthwick Diabetes Research Unit, Lister Hospital, Stevenage, UK. FAU - Wadden, Thomas A AU - Wadden TA AD - Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. FAU - Lingvay, Ildiko AU - Lingvay I AD - University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: ildiko.lingvay@utsouthwestern.edu. CN - STEP 2 Study Group LA - eng SI - ClinicalTrials.gov/NCT03552757 PT - Clinical Trial, Phase III PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210302 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet. 2021 Mar 13;397(10278):942-943. doi: 10.1016/S0140-6736(21)00377-9. PMID: 33667415 MH - Adult MH - Aged MH - Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptides/administration & dosage/adverse effects/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use MH - Injections, Subcutaneous MH - Male MH - Middle Aged MH - Obesity/*drug therapy MH - Overweight/drug therapy MH - Treatment Outcome MH - Weight Loss/*drug effects MH - Semaglutide EDAT- 2021/03/06 06:00 MHDA- 2021/11/12 06:00 CRDT- 2021/03/05 20:10 PHST- 2020/11/27 00:00 [received] PHST- 2020/12/23 00:00 [revised] PHST- 2021/01/08 00:00 [accepted] PHST- 2021/03/06 06:00 [pubmed] PHST- 2021/11/12 06:00 [medline] PHST- 2021/03/05 20:10 [entrez] AID - S0140-6736(21)00213-0 [pii] AID - 10.1016/S0140-6736(21)00213-0 [doi] PST - ppublish SO - Lancet. 2021 Mar 13;397(10278):971-984. doi: 10.1016/S0140-6736(21)00213-0. Epub 2021 Mar 2. PMID- 33667415 OWN - NLM STAT- MEDLINE DCOM- 20210623 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 397 IP - 10278 DP - 2021 Mar 13 TI - Semaglutide and effective weight control. PG - 942-943 LID - S0140-6736(21)00377-9 [pii] LID - 10.1016/S0140-6736(21)00377-9 [doi] FAU - Latini, Roberto AU - Latini R AD - Department of Cardiovascular Medicine, Mario Negri Institute of Pharmacological Research IRCCS, 20156 Milan, Italy. Electronic address: roberto.latini@marionegri.it. FAU - Staszewsky, Lidia AU - Staszewsky L AD - Department of Cardiovascular Medicine, Mario Negri Institute of Pharmacological Research IRCCS, 20156 Milan, Italy. LA - eng PT - Comment PT - Journal Article DEP - 20210302 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - Lancet. 2021 Mar 13;397(10278):971-984. doi: 10.1016/S0140-6736(21)00213-0. PMID: 33667417 MH - Adult MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - Glucagon-Like Peptides MH - Humans MH - Obesity/drug therapy/prevention & control MH - Overweight MH - Semaglutide EDAT- 2021/03/06 06:00 MHDA- 2021/06/24 06:00 CRDT- 2021/03/05 20:10 PHST- 2021/01/20 00:00 [received] PHST- 2021/02/08 00:00 [accepted] PHST- 2021/03/06 06:00 [pubmed] PHST- 2021/06/24 06:00 [medline] PHST- 2021/03/05 20:10 [entrez] AID - S0140-6736(21)00377-9 [pii] AID - 10.1016/S0140-6736(21)00377-9 [doi] PST - ppublish SO - Lancet. 2021 Mar 13;397(10278):942-943. doi: 10.1016/S0140-6736(21)00377-9. Epub 2021 Mar 2. PMID- 33606902 OWN - NLM STAT- MEDLINE DCOM- 20210630 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 7 DP - 2021 Jul TI - Applying REWIND cardiovascular disease criteria to SUSTAIN 6 and PIONEER 6: An exploratory analysis of cardiovascular outcomes with semaglutide. PG - 1677-1680 LID - 10.1111/dom.14360 [doi] AB - In the REWIND trial, dulaglutide reduced cardiovascular (CV) risk versus placebo in patients with type 2 diabetes in both the "established CV disease" (CVD) and "CV risk factor" subgroups. The SUSTAIN 6 and PIONEER 6 trials of semaglutide used different criteria for established CVD from those used in REWIND. The present post hoc analysis assessed the effect of semaglutide on major adverse CV events (MACE) in a pooled population of SUSTAIN 6 and PIONEER 6 patients, re-categorized into CV risk subgroups using the REWIND CVD criteria. In the pooled analysis (n = 6480), a lower percentage of patients were in the established CVD subgroup, when using the REWIND CVD criteria, compared with the original trial CVD criteria (66.5% vs. 83.8%, respectively). After re-categorization, the risk of MACE was significantly lower with semaglutide versus placebo in the established CVD subgroup (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.59, 0.92) and nonsignificantly lower in the CV risk factor subgroup (HR 0.84, 95% CI 0.55, 1.28) (P-interaction = 0.60). These results suggest that the CV effects of semaglutide may extend to patients with type 2 diabetes across the CV risk continuum. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Verma, Subodh AU - Verma S AUID- ORCID: 0000-0002-4018-8533 AD - St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Fainberg, Udi AU - Fainberg U AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Husain, Mansoor AU - Husain M AUID- ORCID: 0000-0002-3740-6739 AD - Department of Medicine, Ted Rogers Centre for Heart Research, Toronto General Hospital Research Institute, University of Toronto, Toronto, Ontario, Canada. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ryden, Lars AU - Ryden L AD - Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden. FAU - Ripa, Maria Sejersten AU - Ripa MS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. LA - eng SI - ClinicalTrials.gov/NCT01720446 SI - ClinicalTrials.gov/NCT02692716 GR - P30 DK124723/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210318 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - *Cardiovascular System MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Semaglutide PMC - PMC8251906 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - cardiovascular disease OT - incretin therapy COIS- S.V. has received research grants and/or speaking honoraria from Boehringer Ingelheim/Eli Lilly, AstraZeneca, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, Valeant and Amgen. U.F., S.R. and M.S.R. are full-time employees of Novo Nordisk A/S. S.R. also holds stocks in Novo Nordisk A/S. M.H. has received personal fees from Boehringer Ingelheim and Janssen Inc. for advisory panel consultancy and speaker honoraria, grants and personal fees from AstraZeneca and Merck & Co for advisory panel consultancy and investigator-initiated clinical trial grants, personal fees from Roche for advisory panel consultancy, and grants and personal fees from Novo Nordisk for advisory panel consultancy, speaker honoraria and investigator-initiated preclinical study grants. L.R. reports grants from the Swedish Heart Lung Foundation, Stockholm County Council and Boehringer Ingelheim, and fees for consulting and speaking from Boehringer Ingelheim, Novo Nordisk, Eli Lilly, Merck and Bayer. J.B.B.'s contracted consulting fees and travel support for contracted activities are paid to the University of North Carolina by Adocia, AstraZeneca, Dance Biopharm, Dexcom, Eli Lilly, Fractyl, GI Dynamics, Intarcia Therapeutics, Lexicon, MannKind, Metavention, NovaTarg, Novo Nordisk, Orexigen, PhaseBio, Sanofi, Senseonics, vTv Therapeutics and Zafgen. J.B.B. also reports grant support from AstraZeneca, Eli Lilly, Intarcia Therapeutics, Johnson & Johnson, Lexicon, Medtronic, NovaTarg, Novo Nordisk, Sanofi, Theracos, Tolerion and vTv Therapeutics, is a consultant to Cirius Therapeutics Inc, CSL Behring, Fortress Biotech, Mellitus Health, Neurimmune AG, Pendulum Therapeutics, Stability Health and Zealand Pharma, holds stock/options in Mellitus Health, Pendulum Therapeutics, PhaseBio and Stability Health, and his effort here is also supported by grants from the National Institutes of Health (UL1TR002489, P30DK124723). EDAT- 2021/02/20 06:00 MHDA- 2021/07/01 06:00 PMCR- 2021/07/02 CRDT- 2021/02/19 17:13 PHST- 2021/02/04 00:00 [revised] PHST- 2020/11/19 00:00 [received] PHST- 2021/02/16 00:00 [accepted] PHST- 2021/02/20 06:00 [pubmed] PHST- 2021/07/01 06:00 [medline] PHST- 2021/02/19 17:13 [entrez] PHST- 2021/07/02 00:00 [pmc-release] AID - DOM14360 [pii] AID - 10.1111/dom.14360 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Jul;23(7):1677-1680. doi: 10.1111/dom.14360. Epub 2021 Mar 18. PMID- 33591618 OWN - NLM STAT- MEDLINE DCOM- 20210709 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 6 DP - 2021 Jun TI - Comparison of the injection-site experience of the starting doses with semaglutide and dulaglutide: A randomized, double-blind trial in healthy subjects. PG - 1415-1419 LID - 10.1111/dom.14349 [doi] AB - This double-blind, randomized, single-site, crossover trial compared the injection-site experience with the starting doses of semaglutide and dulaglutide. Healthy subjects (aged 18-75 years; body mass index >/= 25 kg/m(2) ; n = 104) were randomized 1:1, using a pregenerated list, to semaglutide 0.25 mg as the first injection and dulaglutide 0.75 mg as the second injection or vice versa; each was administered using their proprietary pen-injectors, according to instructions for use. The primary endpoint was intensity of injection-site pain, measured using a visual analogue scale (VAS; 0 mm = no pain, 100 mm = unbearable pain). Exploratory endpoints included intensity category, duration and quality of injection-site pain, and comparative assessment of injection-site pain with the two injections. The point estimate of the VAS score for injection-site pain intensity was 11.5 mm with dulaglutide versus 5.6 mm with semaglutide; mean (95% confidence interval) estimated treatment difference 5.9 (3.6; 8.2) mm; p < .0001. Other endpoints corroborated a less painful injection experience with semaglutide versus dulaglutide. Safety was consistent with reported data for the drugs. In conclusion, the injection-site experience with semaglutide was rated as less painful than that with dulaglutide. CI - (c) 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Snitker, Soren AU - Snitker S AUID- ORCID: 0000-0001-8313-6701 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Andersen, Andreas AU - Andersen A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Berg, Birgitte AU - Berg B AD - Novo Nordisk A/S, Soborg, Denmark. FAU - van Marle, Sjoerd AU - van Marle S AD - PRA Health Sciences, Groningen, the Netherlands. FAU - Sparre, Thomas AU - Sparre T AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng GR - This trial was funded by Novo Nordisk A/S/ PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210318 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - *Diabetes Mellitus, Type 2 MH - Double-Blind Method MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Healthy Volunteers MH - Humans MH - *Hypoglycemic Agents/adverse effects MH - Immunoglobulin Fc Fragments MH - Recombinant Fusion Proteins MH - Semaglutide PMC - PMC8251561 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - clinical trial COIS- SS, AA, BB and TS are employees of Novo Nordisk A/S; BB and TS own Novo Nordisk A/S stock. SvM is an employee of PRA Health Sciences, which was funded by Novo Nordisk A/S to conduct this trial. EDAT- 2021/02/17 06:00 MHDA- 2021/07/10 06:00 PMCR- 2021/07/02 CRDT- 2021/02/16 12:15 PHST- 2021/01/27 00:00 [revised] PHST- 2020/11/06 00:00 [received] PHST- 2021/02/09 00:00 [accepted] PHST- 2021/02/17 06:00 [pubmed] PHST- 2021/07/10 06:00 [medline] PHST- 2021/02/16 12:15 [entrez] PHST- 2021/07/02 00:00 [pmc-release] AID - DOM14349 [pii] AID - 10.1111/dom.14349 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Jun;23(6):1415-1419. doi: 10.1111/dom.14349. Epub 2021 Mar 18. PMID- 33545249 OWN - NLM STAT- MEDLINE DCOM- 20220421 LR - 20260127 IS - 0210-5705 (Print) IS - 0210-5705 (Linking) VI - 45 Suppl 1 DP - 2022 Apr TI - Acute gastric dilation associated with the use of semaglutide, a GLP-1 analogue. PG - 125-126 LID - S0210-5705(21)00010-8 [pii] LID - 10.1016/j.gastrohep.2020.11.021 [doi] FAU - Sanz Segura, Patricia AU - Sanz Segura P AD - Servicio de Aparato Digestivo, Hospital Royo Villanova, Zaragoza, Espana. Electronic address: patricia.sanz.segura@gmail.com. FAU - Arguedas Lazaro, Yolanda AU - Arguedas Lazaro Y AD - Servicio de Aparato Digestivo, Hospital Royo Villanova, Zaragoza, Espana. FAU - Mostacero Tapia, Sonia AU - Mostacero Tapia S AD - Servicio de Aparato Digestivo, Hospital Royo Villanova, Zaragoza, Espana. FAU - Nerin de la Puerta, Juan Manuel AU - Nerin de la Puerta JM AD - Servicio de Aparato Digestivo, Hospital Royo Villanova, Zaragoza, Espana. FAU - Sebastian Domingo, Juan Jose AU - Sebastian Domingo JJ AD - Servicio de Aparato Digestivo, Hospital Royo Villanova, Zaragoza, Espana. LA - eng LA - spa PT - Case Reports PT - Journal Article TT - Dilatacion gastrica aguda asociada al empleo de semaglutida, un analogo de GLP-1. DEP - 20210202 PL - Spain TA - Gastroenterol Hepatol JT - Gastroenterologia y hepatologia JID - 8406671 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Gastric Dilatation/chemically induced/complications MH - Glucagon-Like Peptide 1/adverse effects MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Semaglutide EDAT- 2021/02/06 06:00 MHDA- 2022/04/22 06:00 CRDT- 2021/02/05 20:10 PHST- 2020/09/18 00:00 [received] PHST- 2020/11/16 00:00 [revised] PHST- 2020/11/26 00:00 [accepted] PHST- 2021/02/06 06:00 [pubmed] PHST- 2022/04/22 06:00 [medline] PHST- 2021/02/05 20:10 [entrez] AID - S0210-5705(21)00010-8 [pii] AID - 10.1016/j.gastrohep.2020.11.021 [doi] PST - ppublish SO - Gastroenterol Hepatol. 2022 Apr;45 Suppl 1:125-126. doi: 10.1016/j.gastrohep.2020.11.021. Epub 2021 Feb 2. PMID- 33492219 OWN - NLM STAT- MEDLINE DCOM- 20211027 LR - 20260127 IS - 1958-5381 (Electronic) IS - 0767-0974 (Linking) VI - 37 IP - 1 DP - 2021 Jan TI - [An orally administered glucagon-like peptide 1 (GLP1) analogue: A landmark in the treatment of type 2 diabetes]. PG - 53-58 LID - 10.1051/medsci/2020261 [doi] AB - Semaglutide is the first peptide to receive European marketing authorization for oral administration in the treatment of type 2 diabetes. The active molecule is the same as the one marketed for weekly subcutaneous administration. It is associated with a new excipient, which protects it from degradation by gastric pepsin and allows its absorption in the stomach. This article presents the pharmacological characteristics of this drug, as well as a critical analysis of the results of the main phase III clinical trials. CI - (c) 2020 medecine/sciences - Inserm. FAU - Larger, Etienne AU - Larger E AD - Universite de Paris et Service de diabetologie et immunologie clinique, Hopital Cochin, APHP centre-universite de Paris, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. LA - fre PT - Journal Article PT - Review TT - Un analogue du glucagon-like peptide 1 (GLP1) administre par voie orale - Une nouveaute dans le traitement du diabete de type 2. DEP - 20210125 PL - France TA - Med Sci (Paris) JT - Medecine sciences : M/S JID - 8710980 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Clinical Trials, Phase III as Topic MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Therapy, Combination/methods/trends MH - Glucagon-Like Peptide 1/*analogs & derivatives MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Glycated Hemoglobin/drug effects/metabolism MH - Humans MH - Hypoglycemic Agents/administration & dosage/adverse effects MH - Semaglutide EDAT- 2021/01/26 06:00 MHDA- 2021/10/28 06:00 CRDT- 2021/01/25 12:12 PHST- 2021/01/25 12:12 [entrez] PHST- 2021/01/26 06:00 [pubmed] PHST- 2021/10/28 06:00 [medline] AID - msc200331 [pii] AID - 10.1051/medsci/2020261 [doi] PST - ppublish SO - Med Sci (Paris). 2021 Jan;37(1):53-58. doi: 10.1051/medsci/2020261. Epub 2021 Jan 25. PMID- 33439584 OWN - NLM STAT- MEDLINE DCOM- 20210924 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 26 IP - 16 Suppl DP - 2020 Dec TI - The importance of patient-reported outcomes in type 2 diabetes: insight from the PIONEER program with oral semaglutide. PG - S356-S367 LID - 10.37765/ajmc.2020.88556 [doi] AB - Patient-reported outcomes (PROs), including treatment satisfaction, patient well-being, and quality of life, are becoming increasingly important contributors to treatment decisions in clinical practice and the evaluation of health care services. PROs have been included in a number of clinical trials in patients with type 2 diabetes (T2D), including those investigating glucagon-like peptide-1 receptor agonists (GLP-1RAs). The first oral GLP-1RA, oral semaglutide, was approved in the United States in 2019. Four PROs were included in the PIONEER clinical study program that evaluated oral semaglutide in patients with T2D across the full diabetes disease spectrum. PRO findings in the PIONEER studies were generally similar for oral semaglutide and comparators, with some exceptions. Improvements in a number of the 36-item Short Form Survey domains were observed for oral semaglutide versus placebo, including general health, bodily pain, physical component summary, social functioning, and mental health. For general health and social functioning, differences significantly favored oral semaglutide versus empagliflozin, whereas role-physical and the physical component summary significantly favored empagliflozin compared with oral semaglutide. The Diabetes Treatment Satisfaction Questionnaire findings indicated that oral semaglutide improved feelings of unacceptably high blood sugars versus placebo (in PIONEER 4, 5, and 8) and sitagliptin (in PIONEER 7). Significant improvements in craving control and craving for savory were observed with oral semaglutide versus empagliflozin in the Control of Eating Questionnaire (in PIONEER 2). These data provide valuable information that can facilitate a patient-centered approach and guide decision-making in managed care to optimize each patient's treatment experience. FAU - Schneider, Doron AU - Schneider D AD - Tandigm Health, 300 Four Falls Corporate Center, 300 Conshohocken State Rd, Suite 260, Conshohocken, PA 19428. Email: dsch2699@gmail.com. FAU - Taddei-Allen, Patty AU - Taddei-Allen P FAU - Dougherty, Tanya AU - Dougherty T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Patient Reported Outcome Measures MH - Quality of Life MH - Semaglutide EDAT- 2021/01/14 06:00 MHDA- 2021/09/25 06:00 CRDT- 2021/01/13 12:53 PHST- 2021/01/13 12:53 [entrez] PHST- 2021/01/14 06:00 [pubmed] PHST- 2021/09/25 06:00 [medline] AID - 88556 [pii] AID - 10.37765/ajmc.2020.88556 [doi] PST - ppublish SO - Am J Manag Care. 2020 Dec;26(16 Suppl):S356-S367. doi: 10.37765/ajmc.2020.88556. PMID- 33439583 OWN - NLM STAT- MEDLINE DCOM- 20210924 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 26 IP - 16 Suppl DP - 2020 Dec TI - Cardiovascular outcomes, safety, and tolerability with oral semaglutide: insights for managed care. PG - S344-S355 LID - 10.37765/ajmc.2020.88555 [doi] AB - It is important to consider the safety profile of new medications in type 2 diabetes (T2D) when selecting the most appropriate treatment option for each patient. This can help ensure that patients achieve optimal response, that those experiencing adverse events are appropriately managed, and that treatment is tailored for those with pre-existing conditions such as cardiovascular disease (CVD), which is the leading cause of death in patients with T2D. The American Diabetes Association and American Association of Clinical Endocrinologists/American College of Endocrinology recommend a glucagon-like peptide-1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter 2 inhibitor with proven cardiovascular (CV) benefit in patients with established CVD or those at high risk of CVD. Injectable semaglutide is approved by the FDA for reducing the risk of major CV events in adults with T2D and established CVD. In PIONEER 6, the CV safety of the first GLP-1RA tablet, oral semaglutide, was noninferior to placebo, and a longer-term study (SOUL; NCT03914326) powered to assess a potential CV benefit is ongoing. The safety and tolerability profile of oral semaglutide across the PIONEER clinical trial program was consistent with the GLP-1RA class. The most common adverse events were gastrointestinal (GI) (eg, nausea, diarrhea, and vomiting), which were typically mild to moderate and transient. In clinical practice, oral semaglutide expands the treatment options available to patients with T2D and can be considered in patient populations suitable for injectable GLP-1RAs. FAU - Lingvay, Ildiko AU - Lingvay I AD - University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390. Email: Ildiko.Lingvay@utsouthwestern.edu. FAU - Taddei-Allen, Patty AU - Taddei-Allen P FAU - Dougherty, Tanya AU - Dougherty T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Managed Care Programs MH - Semaglutide EDAT- 2021/01/14 06:00 MHDA- 2021/09/25 06:00 CRDT- 2021/01/13 12:53 PHST- 2021/01/13 12:53 [entrez] PHST- 2021/01/14 06:00 [pubmed] PHST- 2021/09/25 06:00 [medline] AID - 88555 [pii] AID - 10.37765/ajmc.2020.88555 [doi] PST - ppublish SO - Am J Manag Care. 2020 Dec;26(16 Suppl):S344-S355. doi: 10.37765/ajmc.2020.88555. PMID- 33439582 OWN - NLM STAT- MEDLINE DCOM- 20210924 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 26 IP - 16 Suppl DP - 2020 Dec TI - Efficacy of oral semaglutide: overview of the PIONEER clinical trial program and implications for managed care. PG - S335-S343 LID - 10.37765/ajmc.2020.88554 [doi] AB - The first tablet formulation of a glucagon-like peptide-1 receptor agonist(GLP-1RA), oral semaglutide, was approved in September 2019 for the treatment of adults with type 2 diabetes (T2D). This article reviews data from the PIONEER phase 3a clinical trial program, which assessed the efficacy and safety of oral semaglutide in more than 9500 patients at different stages on the disease trajectory (mean diabetes duration,3.5-15 years) and on a range of background treatment regimens(monotherapy, added to 1 or 2 oral glucose-lowering agents, or added to insulin). The studies compared oral semaglutide (doses of 3 mg, 7 mg, or14 mg) with placebo, and selected commonly used glucose-lowering agents (empagliflozin 25 mg, sitagliptin 100 mg, or liraglutide 1.8mg). Across the studies, oral semaglutide provided greater glycated hemoglobin (A1C) reductions than placebo, empagliflozin, or sitagliptinat 26 weeks, and similar A1C reductions as liraglutide. The proportion of patients achieving the A1C level recommended by the American Diabetes Association of less than 7.0% (53 mmol/mol) was greater with oral semaglutide (7 mg, 42%-69%; 14 mg, 55%-77%) than placebo (7%-31%)and active comparators (25%-62%), with durable target achievement. Oral semaglutide was associated with similar reductions in body weight as empagliflozin and greater reductions than placebo, sitagliptin, or liraglutide. Oral semaglutide was also efficacious in patients with T2D and moderate renal impairment. These findings indicate that oral semaglutide presents a valuable option for treating patients with T2D in a managed care setting, with the potential to expand the number of patients benefiting from GLP‑1RAs. FAU - Rodbard, Helena W AU - Rodbard HW AD - Endocrine and Metabolic Consultants, 3200 Tower Oaks Blvd, Suite 250, Rockville, MD 20852. Email: hrodbard@comcast.net. FAU - Dougherty, Tanya AU - Dougherty T FAU - Taddei-Allen, Patty AU - Taddei-Allen P LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Managed Care Programs MH - Semaglutide EDAT- 2021/01/14 06:00 MHDA- 2021/09/25 06:00 CRDT- 2021/01/13 12:53 PHST- 2021/01/13 12:53 [entrez] PHST- 2021/01/14 06:00 [pubmed] PHST- 2021/09/25 06:00 [medline] AID - 88554 [pii] AID - 10.37765/ajmc.2020.88554 [doi] PST - ppublish SO - Am J Manag Care. 2020 Dec;26(16 Suppl):S335-S343. doi: 10.37765/ajmc.2020.88554. PMID- 33439581 OWN - NLM STAT- MEDLINE DCOM- 20210924 LR - 20210924 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 26 IP - 16 Suppl DP - 2020 Dec TI - Type 2 diabetes in the US managed care setting: the burden of disease and rationale for an oral glucagon-like peptide-1 receptor agonist. PG - S325-S334 LID - 10.37765/ajmc.2020.88552 [doi] AB - Diabetes affects an estimated 34 million US adults, with type 2 diabetes (T2D) accounting for 90% to 95% of cases. The downstream consequences of uncontrolled T2D are substantial, including an increased risk of microvascular complications (eg, renal impairment, retinopathy, and peripheral neuropathy), cardiovascular disease, impaired quality of life, and death. Overall, diabetes places a significant strain on the US health care system, with 7.8 million hospitalizations annually among patients with diabetes, and $237 billion in direct medical costs. Injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been available for T2D for over a decade, and are recommended, in particular, for patients with a compelling need to minimize hypoglycemia risk, curtail weight gain, or promote weight loss, and for patients with established cardiovascular disease. Despite being associated with high glucose-lowering efficacy, weight loss, and a low risk of hypoglycemia, injectable GLP-1RAs are relatively underutilized, and are associated with suboptimal adherence and persistence. These challenges may relate in part to the injectable route of administration, given that injection-related concerns have been linked with a failure to intensify T2D therapy in a timely manner (ie, therapeutic inertia), and are cited by patients as a barrier to initiating and persisting with injectable treatments. The approval of the first tablet formulation of a GLP-1RA for T2D, oral semaglutide, has the potential to address these challenges. In this context, we review the burden of T2D in the United States, the role of GLP-1RAs, the challenges of therapeutic inertia and poor adherence, and the rationale for an oral GLP-1RA, focusing on considerations for managed care. FAU - Dougherty, Tanya AU - Dougherty T FAU - Heile, Michael AU - Heile M AD - TriHealth Physician Partners, 6331 Glenway Ave, Cincinnati, OH 45211. Email: Michael_Heile@trihealth.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) MH - Cost of Illness MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Managed Care Programs MH - Quality of Life EDAT- 2021/01/14 06:00 MHDA- 2021/09/25 06:00 CRDT- 2021/01/13 12:53 PHST- 2021/01/13 12:53 [entrez] PHST- 2021/01/14 06:00 [pubmed] PHST- 2021/09/25 06:00 [medline] AID - 88552 [pii] AID - 10.37765/ajmc.2020.88552 [doi] PST - ppublish SO - Am J Manag Care. 2020 Dec;26(16 Suppl):S325-S334. doi: 10.37765/ajmc.2020.88552. PMID- 33439580 OWN - NLM STAT- MEDLINE DCOM- 20210924 LR - 20260127 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 26 IP - 16 Suppl DP - 2020 Dec TI - The evidence for oral semaglutide in type 2 diabetes from a managed care perspective. PG - S323-S324 LID - 10.37765/ajmc.2020.88553 [doi] FAU - Heile, Michael AU - Heile M AD - TriHealth Physician Partners, 6331 Glenway Ave, Cincinnati, OH 45211. Email: Michael_Heile@trihealth.com. FAU - Taddei-Allen, Patty AU - Taddei-Allen P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Managed Care Programs MH - Semaglutide EDAT- 2021/01/14 06:00 MHDA- 2021/09/25 06:00 CRDT- 2021/01/13 12:53 PHST- 2021/01/13 12:53 [entrez] PHST- 2021/01/14 06:00 [pubmed] PHST- 2021/09/25 06:00 [medline] AID - 88553 [pii] AID - 10.37765/ajmc.2020.88553 [doi] PST - ppublish SO - Am J Manag Care. 2020 Dec;26(16 Suppl):S323-S324. doi: 10.37765/ajmc.2020.88553. PMID- 33434602 OWN - NLM STAT- MEDLINE DCOM- 20210419 LR - 20260127 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 172 DP - 2021 Feb TI - Efficacy and safety of the glucagon-like peptide-1 receptor agonist oral semaglutide in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. PG - 108656 LID - S0168-8227(21)00009-7 [pii] LID - 10.1016/j.diabres.2021.108656 [doi] AB - OBJECTIVES: To evaluate the efficacy and safety of the glucagon-like peptide-1 (GLP-1) receptor agonist (RA) oral semaglutide in the treatment of type 2 diabetes mellitus (T2DM) patients. METHODS: Randomized controlled trials comparing oral semaglutide with placebo or other antihyperglycemic agents in T2DM patients were identified by searching PubMed, Embase, Cochrane Library and ClinicalTrials.gov. Risk ratios and mean differences with 95% confidence intervals were used to synthesize the results. RESULTS: Ten relevant studies involving 8,536 patients were finally included. Compared with placebo, oral semaglutide significantly reduced hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, self-measured plasma glucose (SMPG), serious adverse events and all-cause death and significantly increased the number of participants who achieved HbA1c < 7.0%. Compared with active comparators, oral semaglutide significantly reduced the level of HbA1c, body weight, and SMPG and significantly increased the number of participants who achieved HbA1c < 7.0%. Compared with placebo or active comparators, oral semaglutide did not increase the incidence of adverse events, hypoglycemia (severe or blood glucose-confirmed symptomatic), myocardial infarction, heart failure requiring hospitalization, stroke or acute pancreatitis but did increase the incidence of nausea, diarrhea and vomiting. CONCLUSIONS: Oral semaglutide has favorable efficacy and safety in the treatment of T2DM patients. Oral semaglutide may be superior to liraglutide, dulaglutide, empagliflozin and sitagliptin for T2DM patients who have obesity or poor adherence to injectable GLP-1 RAs. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Li, Jingxin AU - Li J AD - Department of Chinese Pharmacy, Hebei Maternity Hospital, 27 Shifeng Road, Qiaoxi District, Shijiazhuang 050051, Hebei Province, China. FAU - He, Ke AU - He K AD - Department of Pharmacy, The Fourth Hospital of Shijiazhuang/Shijiazhuang Obstetrics and Gynecology Hospital, 206 Zhongshan East Road, Changan District, Shijiazhuang 050017, Hebei Province, China. Electronic address: hkwkc77@163.com. FAU - Ge, Jun AU - Ge J AD - Department of Pharmacy, The Fourth Hospital of Shijiazhuang/Shijiazhuang Obstetrics and Gynecology Hospital, 206 Zhongshan East Road, Changan District, Shijiazhuang 050017, Hebei Province, China. FAU - Li, Caixia AU - Li C AD - Department of Pharmacy, The Fourth Hospital of Shijiazhuang/Shijiazhuang Obstetrics and Gynecology Hospital, 206 Zhongshan East Road, Changan District, Shijiazhuang 050017, Hebei Province, China. FAU - Jing, Zeng AU - Jing Z AD - Department of Pharmacy, The Fourth Hospital of Shijiazhuang/Shijiazhuang Obstetrics and Gynecology Hospital, 206 Zhongshan East Road, Changan District, Shijiazhuang 050017, Hebei Province, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20210109 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/pharmacology/*therapeutic use MH - Humans MH - Hypoglycemic Agents/pharmacology/*therapeutic use MH - Middle Aged MH - Semaglutide OTO - NOTNLM OT - Meta-analysis OT - Oral semaglutide OT - Randomized controlled trials OT - Type 2 diabetes mellitus COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2021/01/13 06:00 MHDA- 2021/04/20 06:00 CRDT- 2021/01/12 20:08 PHST- 2020/09/11 00:00 [received] PHST- 2020/12/25 00:00 [revised] PHST- 2021/01/06 00:00 [accepted] PHST- 2021/01/13 06:00 [pubmed] PHST- 2021/04/20 06:00 [medline] PHST- 2021/01/12 20:08 [entrez] AID - S0168-8227(21)00009-7 [pii] AID - 10.1016/j.diabres.2021.108656 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2021 Feb;172:108656. doi: 10.1016/j.diabres.2021.108656. Epub 2021 Jan 9. PMID- 33419635 OWN - NLM STAT- MEDLINE DCOM- 20220112 LR - 20260127 IS - 1873-460X (Electronic) IS - 1056-8727 (Linking) VI - 35 IP - 3 DP - 2021 Mar TI - Prevalence of normal coronary arteries by coronary computed tomography angiography (CCTA) in patients with type 2 diabetes mellitus from Semaglutide Treatment on Coronary Plaque Progression (STOP) trial. PG - 107840 LID - S1056-8727(20)30641-3 [pii] LID - 10.1016/j.jdiacomp.2020.107840 [doi] AB - INTRODUCTION: Coronary artery disease (CAD) is leading cause of morbidity and mortality among type 2 diabetics (T2DM). METHODS: 140 T2DM will be enrolled in randomized, double blind, placebo controlled Semaglutide Treatment On Coronary Plaque Progression (STOP) trial to determine effect of weekly subcutaneous semaglutide on coronary plaque progression. All participants will undergo Coronary Artery Calcium (CAC) Scoring and Coronary Computed Tomography Angiography (CCTA) at our center. A Fisher test, ANOVA and Kruskal Wallis were used. RESULTS: As of May 2020, 87 patients (81%) randomized (mean age 56.4 +/- 8.4 yrs. and 62% male) with documented CAD by CCTA. Approximately 20% of screened study population were screen failed due to normal coronaries (n= 14) or HbA1C<7 (n=7). Of interest, 14 persons with diabetes with normal coronaries (no calcification) were significantly more likely to be females (21% vs 62%), have higher glomerular filtration rate (106.5 +/- 19.4 vs 89.9 +/- 22.6 mL/min/1.73m(2); p= 0.006), and younger (53.4 +/- 9.0 vs 56.4 +/- 8.4 yrs.; p=0.02) than those who were randomized. CONCLUSION: Among T2DM, there is a significant portion who have normal coronary arteries and may have a better prognosis. Excluding these participants from cardiovascular studies may improve power and decrease sample size. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Birudaraju, Divya AU - Birudaraju D AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Cherukuri, Lavanya AU - Cherukuri L AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Kinninger, April AU - Kinninger A AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Dahal, Suraj AU - Dahal S AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Lakshmanan, Suvasini AU - Lakshmanan S AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Rezvanizadeh, Vahid AU - Rezvanizadeh V AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Ghanem, Ahmed K AU - Ghanem AK AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Flores, Ferdinand AU - Flores F AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Hamal, Sajad AU - Hamal S AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Pozon, Ryan G AU - Pozon RG AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Adudodla, Nishitha AU - Adudodla N AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Tayek, John A AU - Tayek JA AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Roy, Sion K AU - Roy SK AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. FAU - Budoff, Matthew J AU - Budoff MJ AD - Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, CA, USA. Electronic address: mbudoff@labiomed.org. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20201231 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Computed Tomography Angiography MH - Coronary Angiography MH - *Coronary Artery Disease/diagnosis/diagnostic imaging MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Female MH - Glucagon-Like Peptides/*therapeutic use MH - Humans MH - Male MH - Middle Aged MH - *Plaque, Atherosclerotic/complications/epidemiology MH - Predictive Value of Tests MH - Prevalence MH - Semaglutide OTO - NOTNLM OT - Coronary artery disease OT - Normal coronaries OT - Type 2 diabetes mellitus COIS- Declaration of competing interest Matthew J. Budoff, M.D., FACC discloses work for the National Institutes of Health and General Electric Healthcare; All other authors have no conflicts of interest. EDAT- 2021/01/10 06:00 MHDA- 2022/01/13 06:00 CRDT- 2021/01/09 05:29 PHST- 2020/10/01 00:00 [received] PHST- 2020/11/30 00:00 [revised] PHST- 2020/11/30 00:00 [accepted] PHST- 2021/01/10 06:00 [pubmed] PHST- 2022/01/13 06:00 [medline] PHST- 2021/01/09 05:29 [entrez] AID - S1056-8727(20)30641-3 [pii] AID - 10.1016/j.jdiacomp.2020.107840 [doi] PST - ppublish SO - J Diabetes Complications. 2021 Mar;35(3):107840. doi: 10.1016/j.jdiacomp.2020.107840. Epub 2020 Dec 31. PMID- 33354706 OWN - NLM STAT- MEDLINE DCOM- 20210929 LR - 20260127 IS - 1535-2900 (Electronic) IS - 1079-2082 (Print) IS - 1079-2082 (Linking) VI - 78 IP - 7 DP - 2021 Mar 18 TI - Management of type 2 diabetes with oral semaglutide: Practical guidance for pharmacists. PG - 556-567 LID - 10.1093/ajhp/zxaa413 [doi] AB - PURPOSE: To provide pharmacists with information on counseling patients with type 2 diabetes (T2D) receiving oral semaglutide. SUMMARY: Oral semaglutide, the first oral glucagon-like peptide 1 (GLP-1) receptor agonist (GLP-1RA), was approved for the treatment of adults with T2D by the US Food and Drug Administration in September 2019. Semaglutide has been coformulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate to improve bioavailability of semaglutide following oral administration. Oral semaglutide has been shown to have efficacy and safety profiles similar to those of other GLP-1RAs. Many patients with T2D have a complex oral medication regimen to manage their T2D and concomitant chronic comorbid conditions. Therefore, it is important that patients follow the dose administration instructions closely: oral semaglutide should be taken on an empty stomach upon waking with a sip (/= 7.0% receiving oral antiglycaemic medication (with no experience of injectable antiglycaemic medication). Therapy profiles were created using Japanese head-to-head trial data for orally administered semaglutide (7 mg and 14 mg), injectable dulaglutide (0.75 mg), and injectable liraglutide (0.9 mg). Profiles were not labelled. Choice tasks tested preference between hypothetical profiles, preference between profiles with actual trial data, and willingness to initiate treatment. Relative importance of attributes was determined using conditional logit regression. RESULTS: A total of 500 respondents were analysed: mean age 61.2 years; 93.8% male; mean HbA(1c) 7.6%; 78.2% with HbA(1c) >/= 7.0 to < 8%; 89% with HbA(1c) above personal target. Mean BMI was 25.4 kg/m(2); 49% had obesity (>/= 25 kg/m(2)). The treatment attribute with greatest importance was mode and frequency of administration (49.1%), followed by nausea risk (30.8%), weight change (11.3%), and HbA(1c) change (8.8%). Oral semaglutide 7 and 14 mg-like profiles were both preferred: the 7 mg-like profile was preferred over dulaglutide (by 91.0% of respondents) and liraglutide (by 89.4%); the 14 mg-like profile was preferred over dulaglutide (by 88.2%) and liraglutide (by 94.4%). Willingness to initiate treatment was also higher for orally administered semaglutide-like profiles: 62.4% with 7 mg and 64.0% with 14 mg, versus 13.6% and 11.0% with injectable GLP-1 RA-like profiles. Subgroup results were generally consistent with the overall sample. CONCLUSION: Japanese patients with T2D appear to prefer oral GLP-1 RA profiles over injectable GLP-1 RA profiles, and administration appears to be the most important factor in this decision. This highlights the unmet need for an effective and orally administered GLP-1 RA for the treatment of T2D in Japan. FAU - Igarashi, Ataru AU - Igarashi A AD - Unit of Public Health and Preventive Medicine, Yokohama City University School of Medicine, Kanagawa, Japan. AD - Department of Health Economics and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. FAU - Bekker Hansen, Brian AU - Bekker Hansen B AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Langer, Jakob AU - Langer J AD - Novo Nordisk Pharma Ltd., Tokyo, Japan. jklg@novonordisk.com. FAU - Tavella, Francesca AU - Tavella F AD - Adelphi Values PROVE, Cheshire, UK. FAU - Collings, Hannah AU - Collings H AD - Adelphi Values PROVE, Cheshire, UK. FAU - Davies, Neil AU - Davies N AD - Adelphi Values PROVE, Cheshire, UK. FAU - Wyn, Robin AU - Wyn R AD - Adelphi Values PROVE, Cheshire, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201127 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Japan MH - Male MH - Middle Aged PMC - PMC7854394 OTO - NOTNLM OT - Discrete choice experiment OT - GLP-1 receptor agonist OT - Patient preference OT - Type 2 diabetes (T2D) EDAT- 2020/11/28 06:00 MHDA- 2021/04/15 06:00 PMCR- 2020/11/27 CRDT- 2020/11/27 12:08 PHST- 2020/08/14 00:00 [received] PHST- 2020/11/04 00:00 [accepted] PHST- 2020/11/28 06:00 [pubmed] PHST- 2021/04/15 06:00 [medline] PHST- 2020/11/27 12:08 [entrez] PHST- 2020/11/27 00:00 [pmc-release] AID - 10.1007/s12325-020-01561-1 [pii] AID - 1561 [pii] AID - 10.1007/s12325-020-01561-1 [doi] PST - ppublish SO - Adv Ther. 2021 Jan;38(1):721-738. doi: 10.1007/s12325-020-01561-1. Epub 2020 Nov 27. PMID- 33238857 OWN - NLM STAT- MEDLINE DCOM- 20211209 LR - 20211214 IS - 1875-6506 (Electronic) IS - 1573-4021 (Linking) VI - 17 IP - 2 DP - 2021 TI - GLP-1RA and SGLT2i: Cardiovascular Impact on Diabetic Patients. PG - 149-158 LID - 10.2174/1573402116999201124123549 [doi] AB - BACKGROUND: Diabetes is a chronic disease with high complexity that demands strategic medical care with a multifactorial risk-reduction approach. Over the past decade, the treatment of type 2 diabetes mellitus (T2DM) has entirely changed. One of the paradigm changes has been the arrival of new drugs that reduce cardiovascular risk beyond the reduction of A1C. OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are two groups of antidiabetics drugs, which have demonstrated superiority compared to placebo for major cardiovascular events (MACE). METHODS: We update and discuss their impact on MACE expressed as relative risk (HR hazard ratio) and as the number needed to treat (NNT) to avoid one cardiovascular event in 5 years. We include the publications of the last 10 years. RESULTS: Empagliflozin, Canagliflozin and Dapagliflozin present an HR for MACE of 0.86, 0.86, 0.86 and an NNT of 38, 44, and 33, respectively (Dapagliflozin in secondary prevention). Regarding HHF (Hospitalization for Heart Failure), the HR was 0.65, 0.67, 0.73 and NNT was 44, 62, and 98, respectively. Lixisenatide, Exenatide, Liragutide, Semaglutide, Albiglutide and Dulaglutide presented for MACE an HR of 1.02, 0.91, 0.87, 0.74, 0.78, 0.88, respectively. There was no increase in the risk of HHF, but there was no benefit either. CONCLUSION: Cardiovascular benefits of the GLP-1RA and the SGLT2i are clinically significant. A number needed to treat under 50 is required to avoid one MACE in five years. These benefits have led to important changes in the Clinical Practice Guidelines and in the care of our patients with T2DM. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Pablo, Aschner AU - Pablo A AD - Department of Endocrinology, Javeriana University School of Medicine and San Ignacio University Hospital, Bogota, Colombia. FAU - Evelyn, Blanc AU - Evelyn B AD - Diabetes and Metabolism Department, Favaloro Foundation, University Hospital, Buenos Aires, Argentina. FAU - Claudia, Folino AU - Claudia F AD - Diabetes and Metabolism Department, Favaloro Foundation, University Hospital, Buenos Aires, Argentina. FAU - Yanina, Morosan A AU - Yanina MA AD - Diabetes and Metabolism Department, Favaloro Foundation, University Hospital, Buenos Aires, Argentina. LA - eng PT - Journal Article PL - United Arab Emirates TA - Curr Hypertens Rev JT - Current hypertension reviews JID - 101239891 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Pharmaceutical Preparations) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) SB - IM MH - *Cardiovascular Diseases/diagnosis/drug therapy/prevention & control MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/adverse effects MH - *Pharmaceutical Preparations MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects OTO - NOTNLM OT - Cardiovascular outcomes OT - GLP1 agonist OT - SGLT2i OT - cardiovascular mechanisms OT - cardiovascular disease. OT - glucose lowering medications OT - type 2 diabetes mellitus EDAT- 2020/11/27 06:00 MHDA- 2021/12/15 06:00 CRDT- 2020/11/26 05:29 PHST- 2020/03/28 00:00 [received] PHST- 2020/09/28 00:00 [revised] PHST- 2020/10/01 00:00 [accepted] PHST- 2020/11/27 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2020/11/26 05:29 [entrez] AID - CHYR-EPUB-111765 [pii] AID - 10.2174/1573402116999201124123549 [doi] PST - ppublish SO - Curr Hypertens Rev. 2021;17(2):149-158. doi: 10.2174/1573402116999201124123549. PMID- 33213122 OWN - NLM STAT- MEDLINE DCOM- 20211028 LR - 20211210 IS - 2724-6116 (Electronic) IS - 2724-6116 (Linking) VI - 46 IP - 2 DP - 2021 Jun TI - Obesity and GLP-1. PG - 168-176 LID - 10.23736/S2724-6507.20.03369-6 [doi] AB - Obesity is an important public health issue that has been on the rise over the last decades. It calls for effective prevention and treatment. Bariatric surgery is the most effective medical therapy for weight loss in morbid obesity, but we are in need for less aggressive treatments. Glucagon-like-peptide-1 receptor agonists are a group of incretin-based drugs that have proven to be productive for obesity treatment. Through activation of the GLP-1 receptor they not only have an important role stimulating insulin secretion after meals, but with their extrapancreatic actions, both peripheral and central, they also help reduce body weight by promoting satiety and delaying gastric emptying. Liraglutide in a dose of 3 mg is currently the only drug of this group that is approved by the FDA to treat obesity, with weight losses up to 8.5 kg in relatively short periods of time. Here we review the data so far collected of GLP-1 use for obesity with and without diabetes, including the recent data of oral semaglutide. FAU - Perez-Montes DE Oca, Alejandra AU - Perez-Montes DE Oca A AD - Department of Endocrinology and Nutrition, Germans Trias i Pujol University Hospital and Research Institute, Autonomous University of Barcelona, Badalona, Spain. FAU - Pellitero, Silvia AU - Pellitero S AD - Department of Endocrinology and Nutrition, Germans Trias i Pujol University Hospital and Research Institute, Autonomous University of Barcelona, Badalona, Spain - spellitero.germanstrias@gencat.cat. FAU - Puig-Domingo, Manel AU - Puig-Domingo M AD - Department of Endocrinology and Nutrition, Germans Trias i Pujol University Hospital and Research Institute, Autonomous University of Barcelona, Badalona, Spain. LA - eng PT - Journal Article PT - Review DEP - 20201119 PL - Italy TA - Minerva Endocrinol (Torino) JT - Minerva endocrinology JID - 101777342 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Incretins) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide 1 MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Incretins MH - Obesity/drug therapy EDAT- 2020/11/21 06:00 MHDA- 2021/10/29 06:00 CRDT- 2020/11/20 03:00 PHST- 2020/11/21 06:00 [pubmed] PHST- 2021/10/29 06:00 [medline] PHST- 2020/11/20 03:00 [entrez] AID - S0391-1977.20.03369-6 [pii] AID - 10.23736/S2724-6507.20.03369-6 [doi] PST - ppublish SO - Minerva Endocrinol (Torino). 2021 Jun;46(2):168-176. doi: 10.23736/S2724-6507.20.03369-6. Epub 2020 Nov 19. PMID- 33199417 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20260127 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 10 IP - 11 DP - 2020 Nov 16 TI - Impact of patient characteristics on efficacy and safety of once-weekly semaglutide versus dulaglutide: SUSTAIN 7 post hoc analyses. PG - e037883 LID - 10.1136/bmjopen-2020-037883 [doi] LID - e037883 AB - OBJECTIVE: In SUSTAIN 7, once-weekly semaglutide demonstrated superior glycated haemoglobin (HbA(1c)) and body weight (BW) reductions versus once-weekly dulaglutide in subjects with type 2 diabetes (T2D). This post hoc analysis investigated the impact of clinically relevant subject characteristics on treatment effects of semaglutide versus dulaglutide. DESIGN: Analyses by baseline age (<65, >/=65 years), sex (male, female), diabetes duration (5-10, >10 years), HbA(1c) (7.5-8.5, >8.5% (58-69, >69 mmol/mol)) and body mass index (BMI) (<30, 30-<35, >/=35 kg/m(2)). SETTING: 194 sites; 16 countries. PARTICIPANTS: Subjects with T2D (n=1199) exposed to treatment. INTERVENTIONS: Semaglutide 0.5 mg versus dulaglutide 0.75 mg (low-dose comparison); semaglutide 1.0 mg versus dulaglutide 1.5 mg (high-dose comparison), all subcutaneously once weekly. PRIMARY AND SECONDARY OUTCOME MEASURES: Change in HbA(1c) (primary endpoint) and BW (confirmatory secondary endpoint) from baseline to week 40; proportion of subjects achieving HbA(1c) targets (<7%, /=5%, >/=10%) at week 40; and safety. RESULTS: HbA(1c) and BW reductions (estimated treatment difference ranges: -0.22 to -0.70%-point; -1.76 to -3.84 kg) and proportion of subjects achieving HbA(1c) targets and weight-loss responses were statistically significantly greater for the majority of comparisons of semaglutide versus dulaglutide within each subgroup category and, excepting glycaemic control within the low-dose comparison in HbA(1c) subgroups, this was irrespective of subgroup or dose comparison. Gastrointestinal adverse events, the most common with both treatments, were reported by more women than men and, with semaglutide, decreased with increasing BMI. CONCLUSIONS: Consistently greater improvements in HbA(1c) and BW with semaglutide versus dulaglutide, regardless of age, sex, diabetes duration, glycaemic control and BMI, support the efficacy of semaglutide across the continuum of care in a heterogeneous population with T2D. TRIAL REGISTRATION NUMBER: NCT02648204. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Pratley, Richard E AU - Pratley RE AUID- ORCID: 0000-0002-2912-1389 AD - Translational Research Institute, AdventHealth, Orlando, Florida, USA Richard.Pratley.MD@AdventHealth.com. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Division of Endocrinology, Diabetes & Hypertension, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Medical and Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine/Endocrinology and Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA. FAU - Ludemann, Jorg AU - Ludemann J AD - Diabetes-Falkensee, Diabetes Centre and Centre for Clinical Studies, Falkensee, Germany. FAU - Yildirim, Emre AU - Yildirim E AD - Global Medical Affairs, Novo Nordisk A/S, Soborg, Denmark. FAU - Viljoen, Adie AU - Viljoen A AD - Borthwick Diabetes Research Centre, Lister Hospital, Stevenage, UK. LA - eng SI - ClinicalTrials.gov/NCT02648204 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201116 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Aged MH - *Diabetes Mellitus, Type 2/drug therapy MH - Female MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Immunoglobulin Fc Fragments MH - Male MH - Recombinant Fusion Proteins MH - Semaglutide PMC - PMC7670946 OTO - NOTNLM OT - clinical trials OT - diabetes & endocrinology OT - general diabetes COIS- Competing interests: The authors received no grants or funding for the writing of this article. In relation to the submitted work, RP reports grants from Novo Nordisk to his institution, AdventHealth, a nonprofit organisation, and VA also reports grants from Novo Nordisk to her institution.Outside of this work, RP reports speaker and consulting fees from AstraZeneca; consulting fees from Boehringer Ingelheim; consulting fees from Eisai, Inc.; consulting fees from GlaxoSmithKline; consulting fees from Glytec, LLC; consulting fees from Janssen; grants from Lexicon Pharmaceuticals; grants and consulting fees from Ligand Pharmaceuticals, Inc;, grants and consulting fees from Lilly; grants and consulting fees from Merck; consulting fees from Mundipharma; grants, speaker fees and consulting fees from Novo Nordisk; consulting fees from Pfizer; grants and consulting fees from Sanofi; grants, speaker fees and consulting fees from Takeda; and personal consulting fees from Sanofi US Services, Inc. Except for consulting fees in February 2018 and June 2018 from Sanofi US Services, Inc., RP's services were paid for directly to AdventHealth. VA has received consulting fees (to her institution) from Adocia; grants (to her institution) and consulting fees (to her institution) from AstraZeneca/BMS; consulting fees from Becton-Dickinson; grants (to her institution) from Boehringer Ingelheim; grants (to her institution) from Calibra; consulting fees from Duke University; grants (to her institution) from Eisai; grants (to her institution) from Fractyl; grants (to her institution) from Janssen; grants (to her institution) and consulting fees from Novo Nordisk; grants (to her institution) and consulting fees from Sanofi; grants (to her institution) from Theracos; and consulting fees from Zafgen, all outside of the submitted work; and is the spouse of an employee of Merck Research Laboratories. AMC is an employee ofNovo Nordisk. In relation to the submitted work, IL reports grants to her institution from Novo Nordisk. Outside of the submitted work, IL has received consulting fees from AstraZeneca; consulting fees from Boehringer Ingelheim; grants from GI Dynamics; consulting fees from Intarcia; consulting fees from Janssen; consulting fees from Lilly; consulting fees from Mannkind; grants from Merck; grants from Mylan; grants from Novartis; grants and consulting fees from Novo Nordisk; grants from Pfizer; consulting fees from Sanofi; consultant fees from TARGETPharma; and consulting fees from Valeritas, all outside of the submitted work. JL reports being an investigator in clinical studies for Eli Lilly and Novo Nordisk outside of the submitted work. EY was, at the time of writing the manuscript, an employee and minor shareholder of Novo Nordisk. AV has received lecture/other fees and non-financial (clinical research) support from AstraZeneca; non-financial (clinical research) support from Amgen; lecture/other fees from Boehringer Ingelheim; lecture/other fees and non-financial (clinical research) support from Eli Lilly; lecture/other fees fromMerck Sharp & Dohme; lecture/other fees from Napp, lecture/other fees and non-financial (clinical research) support from Novo Nordisk; non-financial (clinical research) support from Novartis; and lecture/other fees and non-financial (clinical research) support from Sanofi, all outside of the submitted work. EDAT- 2020/11/18 06:00 MHDA- 2021/05/15 06:00 PMCR- 2020/11/16 CRDT- 2020/11/17 06:12 PHST- 2020/11/17 06:12 [entrez] PHST- 2020/11/18 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2020/11/16 00:00 [pmc-release] AID - bmjopen-2020-037883 [pii] AID - 10.1136/bmjopen-2020-037883 [doi] PST - epublish SO - BMJ Open. 2020 Nov 16;10(11):e037883. doi: 10.1136/bmjopen-2020-037883. PMID- 33185364 OWN - NLM STAT- MEDLINE DCOM- 20210407 LR - 20260518 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 384 IP - 12 DP - 2021 Mar 25 TI - A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. PG - 1113-1124 LID - 10.1056/NEJMoa2028395 [doi] AB - BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known. METHODS: We conducted a 72-week, double-blind phase 2 trial involving patients with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end point was an improvement of at least one fibrosis stage with no worsening of NASH. The analyses of these end points were performed only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients. RESULTS: In total, 320 patients (of whom 230 had stage F2 or F3 fibrosis) were randomly assigned to receive semaglutide at a dose of 0.1 mg (80 patients), 0.2 mg (78 patients), or 0.4 mg (82 patients) or to receive placebo (80 patients). The percentage of patients in whom NASH resolution was achieved with no worsening of fibrosis was 40% in the 0.1-mg group, 36% in the 0.2-mg group, 59% in the 0.4-mg group, and 17% in the placebo group (P<0.001 for semaglutide 0.4 mg vs. placebo). An improvement in fibrosis stage occurred in 43% of the patients in the 0.4-mg group and in 33% of the patients in the placebo group (P = 0.48). The mean percent weight loss was 13% in the 0.4-mg group and 1% in the placebo group. The incidence of nausea, constipation, and vomiting was higher in the 0.4-mg group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%). Malignant neoplasms were reported in 3 patients who received semaglutide (1%) and in no patients who received placebo. Overall, neoplasms (benign, malignant, or unspecified) were reported in 15% of the patients in the semaglutide groups and in 8% in the placebo group; no pattern of occurrence in specific organs was observed. CONCLUSIONS: This phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution than placebo. However, the trial did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT02970942.). CI - Copyright (c) 2020 Massachusetts Medical Society. FAU - Newsome, Philip N AU - Newsome PN AD - From the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Soborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Universite, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, INSERM Unite Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.). FAU - Buchholtz, Kristine AU - Buchholtz K AD - From the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Soborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Universite, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, INSERM Unite Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.). FAU - Cusi, Kenneth AU - Cusi K AD - From the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Soborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Universite, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, INSERM Unite Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.). FAU - Linder, Martin AU - Linder M AD - From the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Soborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Universite, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, INSERM Unite Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.). FAU - Okanoue, Takeshi AU - Okanoue T AD - From the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Soborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Universite, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, INSERM Unite Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.). FAU - Ratziu, Vlad AU - Ratziu V AD - From the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Soborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Universite, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, INSERM Unite Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.). FAU - Sanyal, Arun J AU - Sanyal AJ AD - From the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Soborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Universite, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, INSERM Unite Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.). FAU - Sejling, Anne-Sophie AU - Sejling AS AD - From the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Soborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Universite, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, INSERM Unite Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.). FAU - Harrison, Stephen A AU - Harrison SA AD - From the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Soborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Universite, Hopital Pitie-Salpetriere, Assistance Publique-Hopitaux de Paris, INSERM Unite Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.). CN - NN9931-4296 Investigators LA - eng SI - ClinicalTrials.gov/NCT02970942 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20201113 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - EC 3.2.1.- (Amylases) RN - 62340-29-8 (Glucagon-Like Peptides) RN - EC 3.1.1.3 (Lipase) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Nat Rev Gastroenterol Hepatol. 2021 Jan;18(1):6. doi: 10.1038/s41575-020-00396-z. PMID: 33257834 CIN - N Engl J Med. 2021 Jul 8;385(2):e6. doi: 10.1056/NEJMc2106921. PMID: 34233104 CIN - N Engl J Med. 2021 Jul 8;385(2):e6. doi: 10.1056/NEJMc2106921. PMID: 34233105 CIN - Hepatobiliary Surg Nutr. 2021 Aug;10(4):518-521. doi: 10.21037/hbsn-2021-13. PMID: 34430533 CIN - Hepatobiliary Surg Nutr. 2021 Aug;10(4):541-544. doi: 10.21037/hbsn-21-231. PMID: 34430539 CIN - Natl Med J India. 2022 Jul-Aug;34(4):225-227. doi: 10.25259/NMJI_103_21. PMID: 35112549 MH - Adolescent MH - Adult MH - Aged MH - Amylases/blood MH - Biopsy MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Humans MH - Injections, Subcutaneous MH - Lipase/blood MH - Liver/pathology MH - Liver Cirrhosis/drug therapy/etiology/pathology MH - Male MH - Middle Aged MH - Non-alcoholic Fatty Liver Disease/blood/complications/*drug therapy/pathology MH - Young Adult MH - Semaglutide FIR - George, Jacob IR - George J FIR - Weltman, Martin IR - Weltman M FIR - Ryan, Marno IR - Ryan M FIR - Nicoll, Amanda IR - Nicoll A FIR - Toplak, Hermann IR - Toplak H FIR - Ludvik, Bernhard IR - Ludvik B FIR - Aigner, Elmar IR - Aigner E FIR - Francque, Sven IR - Francque S FIR - Geerts, Anja IR - Geerts A FIR - Horsmans, Yves IR - Horsmans Y FIR - Moreno, Christophe IR - Moreno C FIR - Balabanska, Rozalina IR - Balabanska R FIR - Mateva Vladimirova, Lyudmila IR - Mateva Vladimirova L FIR - Borman, Meredith IR - Borman M FIR - Jayakumar, Saumya IR - Jayakumar S FIR - McLeod, Magnus IR - McLeod M FIR - Minuk, Gerald IR - Minuk G FIR - Puglia, Marco IR - Puglia M FIR - Sebastiani, Giada IR - Sebastiani G FIR - Ghali, Peter IR - Ghali P FIR - Fung, Scott IR - Fung S FIR - Elkhashab, Mady IR - Elkhashab M FIR - Joy, Tisha IR - Joy T FIR - Aggarwal, Naresh IR - Aggarwal N FIR - Gronbaek, Henning IR - Gronbaek H FIR - Gluud, Lise Lotte IR - Gluud LL FIR - Yki-Jarvinen, Hannele IR - Yki-Jarvinen H FIR - Anty, Rodolphe IR - Anty R FIR - Bourliere, Marc IR - Bourliere M FIR - Larrey, Dominique IR - Larrey D FIR - Maynard-Muet, Marianne IR - Maynard-Muet M FIR - Wander, Lionel IR - Wander L FIR - Ratziu, Vlad IR - Ratziu V FIR - de Ledinghen, Victor IR - de Ledinghen V FIR - Guillaume, Maeva IR - Guillaume M FIR - Bureau, Christophe IR - Bureau C FIR - Papatheodoridis, George IR - Papatheodoridis G FIR - Germanidis, Georgios IR - Germanidis G FIR - Dalekos, George IR - Dalekos G FIR - Sinakos, Emmanouil IR - Sinakos E FIR - Dourakis, Spryridon IR - Dourakis S FIR - Notsumata, Kazuo IR - Notsumata K FIR - Mori, Kojiro IR - Mori K FIR - Itoh, Yoshito IR - Itoh Y FIR - Shima, Toshihide IR - Shima T FIR - Horimoto, Masayoshi IR - Horimoto M FIR - Anzai, Keizo IR - Anzai K FIR - Fujiyama, Shigetoshi IR - Fujiyama S FIR - Takaguchi, Koichi IR - Takaguchi K FIR - Yoneda, Masashi IR - Yoneda M FIR - Fujii, Hideki IR - Fujii H FIR - Enomoto, Hirayuki IR - Enomoto H FIR - Yamashita, Satoyoshi IR - Yamashita S FIR - Takami, Shiro IR - Takami S FIR - Vinnitskaya, Elena IR - Vinnitskaya E FIR - Bakulin, Igor G IR - Bakulin IG FIR - Pasechnikov, Viktor D IR - Pasechnikov VD FIR - Milovanova, Tatiana A IR - Milovanova TA FIR - Osipenko, Marina F IR - Osipenko MF FIR - Kargina, Lubov V IR - Kargina LV FIR - Sergeeva-Kondrachenko, Marina Y IR - Sergeeva-Kondrachenko MY FIR - Lysenko, Tatyana A IR - Lysenko TA FIR - Volkova, Anna R IR - Volkova AR FIR - Voychik, Emma A IR - Voychik EA FIR - Rogova, Larisa A IR - Rogova LA FIR - Zharkov, Alexey P IR - Zharkov AP FIR - Stepanova, Tatiana V IR - Stepanova TV FIR - Frolova, Elena V IR - Frolova EV FIR - Pasechnikov, Dmitriy V IR - Pasechnikov DV FIR - Trofimova, Olga V IR - Trofimova OV FIR - Peskov, Andrey B IR - Peskov AB FIR - Kunitsyna, Marina A IR - Kunitsyna MA FIR - Belkovets, Anna V IR - Belkovets AV FIR - Matsievich, Maria V IR - Matsievich MV FIR - Poteshkin, Yuriy Y IR - Poteshkin YY FIR - Mishchenko, Olga I IR - Mishchenko OI FIR - Belousova, Lidia V IR - Belousova LV FIR - Gaysina, Leylya R IR - Gaysina LR FIR - Alpenidze, Diana N IR - Alpenidze DN FIR - Antonova, Elizaveta IR - Antonova E FIR - Romero Gomez, M IR - Romero Gomez M FIR - Calleja, J IR - Calleja J FIR - Benlloch, S IR - Benlloch S FIR - Crespo Garcia, J IR - Crespo Garcia J FIR - Albillos Martinez, A IR - Albillos Martinez A FIR - Tome, S IR - Tome S FIR - Stal, Per IR - Stal P FIR - Hemmingsson, Joanna Udden IR - Hemmingsson JU FIR - Farngren, Johan IR - Farngren J FIR - Drenth, J P H IR - Drenth JPH FIR - Koek, G H IR - Koek GH FIR - Schreuder, T C M A IR - Schreuder TCMA FIR - Blokzijl, H IR - Blokzijl H FIR - Tushuizen, M E IR - Tushuizen ME FIR - Klemt-Kropp, M IR - Klemt-Kropp M FIR - Nieuwdorp, M IR - Nieuwdorp M FIR - Newsome, Philip IR - Newsome P FIR - Oben, Jude IR - Oben J FIR - Allison, Michael IR - Allison M FIR - Corless, Lynsey IR - Corless L FIR - Forrest, Ewan IR - Forrest E FIR - Hayes, Peter IR - Hayes P FIR - Miller, Michael IR - Miller M FIR - Bhalme, Mahesh IR - Bhalme M FIR - Aithal, Guru IR - Aithal G FIR - Claridge, Lee IR - Claridge L FIR - Austin, Andrew IR - Austin A FIR - Tsochatzis, Emmanuel IR - Tsochatzis E FIR - King, Andrew IR - King A FIR - Agarwal, Kosh IR - Agarwal K FIR - Ch'ng, Chin Lye IR - Ch'ng CL FIR - Cusi, Kenneth IR - Cusi K FIR - Schiff, Eugene IR - Schiff E FIR - Garvey, William Timothy IR - Garvey WT FIR - Hassanein, Tarek I IR - Hassanein TI FIR - Still, Christopher D IR - Still CD FIR - Overcash, Scott IR - Overcash S FIR - Landis, Charles IR - Landis C FIR - Bonabi, Gholamreza IR - Bonabi G FIR - Beshay, Isaac IR - Beshay I FIR - Ankoma-Sey, Victor IR - Ankoma-Sey V FIR - Kabler, Heidi A IR - Kabler HA FIR - Sholeff, Gregory T IR - Sholeff GT FIR - Bui, Hoa-Tuyet Thi Ami IR - Bui HTA FIR - Shin, Elliot E IR - Shin EE FIR - Bernstein, David E IR - Bernstein DE FIR - Ortiz Lasanta, Grisell IR - Ortiz Lasanta G FIR - Frias, Juan Pablo IR - Frias JP FIR - Rosenstock, Julio IR - Rosenstock J FIR - Pouzar, Joseph E IR - Pouzar JE FIR - Harrison, Stephen IR - Harrison S FIR - Lingvay, Ildiko IR - Lingvay I FIR - Desouza, Cyrus IR - Desouza C FIR - Kayali, Zeid IR - Kayali Z FIR - Shaw, Stephanie IR - Shaw S FIR - Jafri, Syed-Mohammed IR - Jafri SM FIR - Maheshwari, Anurag IR - Maheshwari A FIR - Malespin, Miguel IR - Malespin M FIR - Bhandari, Bal Raj IR - Bhandari BR FIR - Moussa, Sam E IR - Moussa SE FIR - Rabinovitz, Mordechai IR - Rabinovitz M FIR - Baum, Seth J IR - Baum SJ FIR - Gunn, Nadege T IR - Gunn NT FIR - Finnegan, Kevin R IR - Finnegan KR FIR - Moore, Ann IR - Moore A FIR - Khazanchi, Arun IR - Khazanchi A FIR - Jenders, Robert Allen IR - Jenders RA FIR - Bowman, William Kelly IR - Bowman WK FIR - Lasseter, Kenneth C IR - Lasseter KC EDAT- 2020/11/14 06:00 MHDA- 2021/04/10 06:00 CRDT- 2020/11/13 08:38 PHST- 2020/11/14 06:00 [pubmed] PHST- 2021/04/10 06:00 [medline] PHST- 2020/11/13 08:38 [entrez] AID - 10.1056/NEJMoa2028395 [doi] PST - ppublish SO - N Engl J Med. 2021 Mar 25;384(12):1113-1124. doi: 10.1056/NEJMoa2028395. Epub 2020 Nov 13. PMID- 33184979 OWN - NLM STAT- MEDLINE DCOM- 20210705 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 2 DP - 2021 Feb TI - Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes. PG - 581-588 LID - 10.1111/dom.14255 [doi] AB - AIM: To evaluate the effect of oral semaglutide on energy intake and appetite in subjects with type 2 diabetes (T2D). MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, two-period cross-over trial, 15 subjects with T2D received 12 weeks of treatment with once-daily oral semaglutide (4-week dose escalation from 3 to 7 to 14 mg) followed by placebo, or vice versa. Energy intake was measured during an ad libitum lunch, evening meal and snack box after a standard breakfast. Appetite ratings were measured using a visual analogue scale after standard and fat-rich breakfasts. Other assessments included eating and craving control (using the Control of Eating Questionnaire), and changes in body weight and composition. RESULTS: Following a standard breakfast, total daily ad libitum energy intake was significantly lower (38.9%) with oral semaglutide versus placebo in 13 evaluable subjects (estimated treatment difference, -5096.0 kJ; 95% CI -7000.0, -3192.1; P = .0001). After a fat-rich breakfast, there were significant differences in favour of oral semaglutide versus placebo for measures of satiety, hunger and for overall appetite score, with no significant differences following a standard breakfast. Fewer food cravings and better eating control were seen with oral semaglutide versus placebo. Overall, mean body weight decreased by 2.7 kg with oral semaglutide and 0.1 kg with placebo, mostly attributable to body fat mass loss. CONCLUSION: After 12 weeks of treatment, ad libitum energy intake was lower with oral semaglutide versus placebo, resulting in reduced body fat mass, and was associated with increased satiety and fullness after a fat-rich breakfast, and improved eating control. TRIAL REGISTRATION NUMBER: NCT02773381. CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Gibbons, Catherine AU - Gibbons C AD - Department of Psychology, University of Leeds, Leeds, UK. FAU - Blundell, John AU - Blundell J AUID- ORCID: 0000-0002-7085-9596 AD - Department of Psychology, University of Leeds, Leeds, UK. FAU - Tetens Hoff, Soren AU - Tetens Hoff S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Dahl, Kirsten AU - Dahl K AUID- ORCID: 0000-0001-5063-1554 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bauer, Robert AU - Bauer R AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Baekdal, Tine AU - Baekdal T AUID- ORCID: 0000-0002-1348-0352 AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT02773381 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20201127 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Appetite MH - Body Weight MH - Breakfast MH - Cross-Over Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Eating MH - Energy Intake MH - Food Preferences MH - Glucagon-Like Peptides MH - Humans MH - Semaglutide PMC - PMC7839771 OTO - NOTNLM OT - GLP-1 analogue OT - appetite control OT - body composition OT - energy regulation OT - incretin therapy OT - type 2 diabetes COIS- JB and CG received research grants from Novo Nordisk for the current study. JB served on a Novo Nordisk Obesity Advisory Board and received personal fees from Novo Nordisk, outside the submitted work. STH, KD, RB and TB are employees, and KD, STH and TB shareholders, of Novo Nordisk A/S, the sponsor of this trial. EDAT- 2020/11/14 06:00 MHDA- 2021/07/06 06:00 PMCR- 2021/01/27 CRDT- 2020/11/13 05:56 PHST- 2020/08/11 00:00 [received] PHST- 2020/10/30 00:00 [revised] PHST- 2020/11/06 00:00 [accepted] PHST- 2020/11/14 06:00 [pubmed] PHST- 2021/07/06 06:00 [medline] PHST- 2020/11/13 05:56 [entrez] PHST- 2021/01/27 00:00 [pmc-release] AID - DOM14255 [pii] AID - 10.1111/dom.14255 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Feb;23(2):581-588. doi: 10.1111/dom.14255. Epub 2020 Nov 27. PMID- 33179892 OWN - NLM STAT- MEDLINE DCOM- 20210104 LR - 20260127 IS - 1532-0650 (Electronic) IS - 0002-838X (Linking) VI - 102 IP - 10 DP - 2020 Nov 15 TI - Oral Semaglutide (Rybelsus) for the Treatment of Type 2 Diabetes Mellitus. PG - 627-628 FAU - Semenya, Afi Mansa AU - Semenya AM AD - Boston University/Boston Medical Center, Boston, MA, USA. FAU - Wilson, Stephen A AU - Wilson SA AD - Boston University/Boston Medical Center, Boston, MA, USA. LA - eng PT - Journal Article PL - United States TA - Am Fam Physician JT - American family physician JID - 1272646 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - Thyroid cancer, medullary SB - IM MH - Acute Kidney Injury/chemically induced MH - Administration, Oral MH - Carcinoma, Neuroendocrine/chemically induced MH - Constipation/chemically induced MH - Diabetes Mellitus, Type 2/*drug therapy MH - Diabetic Retinopathy MH - Diarrhea/chemically induced MH - Dyspepsia/chemically induced MH - Glucagon-Like Peptides/economics/*therapeutic use MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/economics/*therapeutic use MH - Nausea/chemically induced MH - Pancreatitis/chemically induced MH - Thyroid Neoplasms/chemically induced MH - Vomiting/chemically induced MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2020/11/13 06:00 MHDA- 2021/01/05 06:00 CRDT- 2020/11/12 12:09 PHST- 2020/11/12 12:09 [entrez] PHST- 2020/11/13 06:00 [pubmed] PHST- 2021/01/05 06:00 [medline] AID - d15290 [pii] PST - ppublish SO - Am Fam Physician. 2020 Nov 15;102(10):627-628. PMID- 33159658 OWN - NLM STAT- MEDLINE DCOM- 20210414 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 38 IP - 1 DP - 2021 Jan TI - Pharmacokinetics, Safety and Tolerability of Once-Weekly Subcutaneous Semaglutide in Healthy Chinese Subjects: A Double-Blind, Phase 1, Randomized Controlled Trial. PG - 550-561 LID - 10.1007/s12325-020-01548-y [doi] AB - INTRODUCTION: Once-weekly (OW) subcutaneous (s.c.) semaglutide is an injectable glucagon-like peptide-1 (GLP-1) analogue approved for the treatment of type 2 diabetes. This trial was designed to assess the pharmacokinetics, safety and tolerability of OW s.c. semaglutide in healthy Chinese subjects. METHODS: In this single-centre, randomised, double-blind, placebo-controlled trial, 36 healthy subjects were randomised to OW s.c. semaglutide 0.5 mg (n = 12), 1.0 mg (n = 12), or placebo (n = 12). Treatment (semaglutide or placebo) was blinded for the subjects, investigators and sponsor. The primary endpoint was steady-state semaglutide exposure, defined as the area under the curve over a dosing interval at steady state (AUC(0-168 h,SS)). RESULTS: In total, 34 subjects completed the trial. The steady-state exposure of semaglutide was higher for subjects treated with 1.0 mg semaglutide (AUC(0-168 h,ss): 7961 nmol h/l and C(max,ss): 55.9 nmol/l) compared to 0.5 mg semaglutide (AUC(0-168 h,ss): 4000 nmol h/l and C(max,ss): 28.8 nmol/l). The total exposure of semaglutide increased in a dose-proportional manner in healthy Chinese subjects; the treatment ratio (1.0 mg/0.5 mg) [95% confidence interval] for AUC(0-168 h,SS) was 1.99 [1.78; 2.23]. Treatment with OW s.c. semaglutide was well tolerated in healthy Chinese subjects. As expected for the GLP-1 receptor agonist class, the most common adverse events were gastrointestinal, and no new safety signals were identified. CONCLUSION: The pharmacokinetics, safety and tolerability of OW s.c. semaglutide in healthy Chinese subjects were consistent with previous clinical pharmacology trials of OW s.c. semaglutide in other populations. The results suggest that no dose adjustment is necessary for semaglutide in Chinese patients with T2D. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03288740. FAU - Shi, Aixin AU - Shi A AUID- ORCID: 0000-0002-9106-7643 AD - Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. aixins0302@126.com. FAU - Xie, Panpan AU - Xie P AD - Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. FAU - Nielsen, Lasse Lykke AU - Nielsen LL AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Skjoth, Trine Vang AU - Skjoth TV AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - He, Xuemei AU - He X AD - Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. FAU - Haugaard, Sine Pfeiffer AU - Haugaard SP AD - Novo Nordisk A/S, Bagsvaerd, Denmark. LA - eng SI - ClinicalTrials.gov/NCT03288740 PT - Clinical Trial, Phase I PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20201107 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) MH - China MH - *Diabetes Mellitus, Type 2 MH - Double-Blind Method MH - Glucagon-Like Peptides/adverse effects MH - Healthy Volunteers MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Semaglutide PMC - PMC7854449 OTO - NOTNLM OT - Diabetes OT - Glucagon-like peptide-1 receptor agonist OT - Pharmacokinetics OT - Randomised controlled trial OT - Semaglutide OT - Steady state exposure EDAT- 2020/11/08 06:00 MHDA- 2021/04/15 06:00 PMCR- 2020/11/07 CRDT- 2020/11/07 12:06 PHST- 2020/06/26 00:00 [received] PHST- 2020/10/23 00:00 [accepted] PHST- 2020/11/08 06:00 [pubmed] PHST- 2021/04/15 06:00 [medline] PHST- 2020/11/07 12:06 [entrez] PHST- 2020/11/07 00:00 [pmc-release] AID - 10.1007/s12325-020-01548-y [pii] AID - 1548 [pii] AID - 10.1007/s12325-020-01548-y [doi] PST - ppublish SO - Adv Ther. 2021 Jan;38(1):550-561. doi: 10.1007/s12325-020-01548-y. Epub 2020 Nov 7. PMID- 33150566 OWN - NLM STAT- MEDLINE DCOM- 20210917 LR - 20260127 IS - 1179-2027 (Electronic) IS - 1170-7690 (Print) IS - 1170-7690 (Linking) VI - 39 IP - 3 DP - 2021 Mar TI - Budget Impact of Oral Semaglutide Intensification versus Sitagliptin among US Patients with Type 2 Diabetes Mellitus Uncontrolled with Metformin. PG - 317-330 LID - 10.1007/s40273-020-00967-7 [doi] AB - BACKGROUND: Oral semaglutide was approved in 2019 for blood glucose control in patients with type 2 diabetes mellitus (T2DM) and was the first oral glucagon-like peptide 1 receptor agonist (GLP-1 RA). T2DM is associated with substantial healthcare expenditures in the US, so the cost of a new intervention should be weighed against clinical benefits. OBJECTIVE: This study evaluated the budget impact of a treatment pathway with oral semaglutide 14 mg daily versus oral sitagliptin 100 mg daily among patients not achieving target glycated hemoglobin (HbA1c) level despite treatment with metformin. METHODS: This study used the validated IQVIA CORE Diabetes Model to simulate the treatment impact of oral semaglutide 14 mg and sitagliptin 100 mg over a 5-year time horizon from a US healthcare sector (payer) perspective. Trial data (PIONEER 3) informed cohort characteristics and treatment effects, and literature sources informed event costs. Population and market share data were from the literature and data on file. The analysis evaluated the estimated budget impact of oral semaglutide 14 mg use for patients currently using sitagliptin 100 mg considering both direct medical and treatment costs to understand the impact on total cost of care, given underlying treatment performance and impact on avoidable events. RESULTS: In a hypothetical plan of 1 million lives, an estimated 1993 patients were treated with sitagliptin 100 mg in the target population. Following these patients over 5 years, the incremental direct medical and treatment costs of a patient using oral semaglutide 14 mg versus sitagliptin 100 mg was $US16,562, a 70.7% increase (year 2019 values). A hypothetical payer would spend an additional $US3,300,143 (7.1%) over 5 years for every 10% of market share that oral semaglutide 14 mg takes away from sitagliptin 100 mg. Univariate and scenario analyses with alternate inputs and assumptions demonstrated consistent results. CONCLUSIONS: Use of oral semaglutide 14 mg in patients currently receiving sitagliptin 100 mg substantially increases the budget impact for patients with T2DM whose blood glucose level is not controlled with metformin over a 5-year time horizon for US healthcare payers. FAU - Wehler, Elizabeth AU - Wehler E AD - IQVIA, 1 IMS Drive, Plymouth Meeting, PA, 19462, USA. beth.wehler@iqvia.com. FAU - Lautsch, Dominik AU - Lautsch D AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Kowal, Stacey AU - Kowal S AD - IQVIA, 1 IMS Drive, Plymouth Meeting, PA, 19462, USA. FAU - Davies, Glenn AU - Davies G AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Briggs, Andrew AU - Briggs A AD - London School of Hygiene & Tropical Medicine, London, UK. FAU - Li, Qianyi AU - Li Q AD - IQVIA, 1 IMS Drive, Plymouth Meeting, PA, 19462, USA. FAU - Rajpathak, Swapnil AU - Rajpathak S AD - Merck & Co., Inc., Kenilworth, NJ, USA. FAU - Alsumali, Adnan AU - Alsumali A AD - Merck & Co., Inc., Kenilworth, NJ, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201105 PL - New Zealand TA - Pharmacoeconomics JT - PharmacoEconomics JID - 9212404 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 53AXN4NNHX (Semaglutide) MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - *Metformin MH - Sitagliptin Phosphate MH - Semaglutide PMC - PMC7882575 OAB - Patients with type 2 diabetes mellitus (T2DM) have many treatment options. Choices depend on factors such as cost, preference, and patient characteristics. Oral semaglutide was recently approved for the treatment of T2DM as the first oral therapy of its class. This study estimated the cost for patients treated with sitagliptin 100 mg, a commonly used T2DM treatment, versus oral semaglutide 14 mg for patients whose disease is not well controlled with metformin. Costs and effects were estimated over 5 years for each treatment strategy using predictive model equations and clinical trial data for the two treatments. These costs were considered for both a hypothetical healthcare plan of 1 million lives and the full US population. A patient treated with oral semaglutide 14 mg would expect to see 70.7% higher costs than a patient treated with sitagliptin 100 mg over 5 years. For every 10% of patients who would switch from sitagliptin 100 mg to oral semaglutide 14 mg, costs would increase by 7.1%. Changing the cost of oral semaglutide 14 mg had the greatest impact on model results. The findings from the analysis were consistent across a range of alternate model inputs. Oral semaglutide 14 mg is more costly than sitagliptin 100 mg over 5 years. OABL- eng COIS- Adnan Alsumali, Dominik Lautsch, and Swapnil Rajpathak are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Glenn Davies was an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, at the time of the study. Andrew Briggs is a director and shareholder of Avalon Health Economics and received compensation from Merck & Co., Inc. as a consultant for this work. He has also been contracted by Bayer, Eisai, Janssen, Novartis, Sword Health, Amgen, and Daichii Sankyo and received compensation outside of the submitted work. Elizabeth Wehler is an employee of IQVIA, a consulting company that received funding from Merck & Co., Inc. to conduct the study as well as from other companies. Qianyi Li and Stacey Kowal were employees of IQVIA at the time of the study. EDAT- 2020/11/06 06:00 MHDA- 2021/09/18 06:00 PMCR- 2020/11/05 CRDT- 2020/11/05 06:11 PHST- 2020/09/19 00:00 [accepted] PHST- 2020/11/06 06:00 [pubmed] PHST- 2021/09/18 06:00 [medline] PHST- 2020/11/05 06:11 [entrez] PHST- 2020/11/05 00:00 [pmc-release] AID - 10.1007/s40273-020-00967-7 [pii] AID - 967 [pii] AID - 10.1007/s40273-020-00967-7 [doi] PST - ppublish SO - Pharmacoeconomics. 2021 Mar;39(3):317-330. doi: 10.1007/s40273-020-00967-7. Epub 2020 Nov 5. PMID- 33140575 OWN - NLM STAT- MEDLINE DCOM- 20210705 LR - 20210705 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 2 DP - 2021 Feb TI - Patients' preferences for once-daily oral versus once-weekly injectable diabetes medications: The REVISE study. PG - 508-519 LID - 10.1111/dom.14244 [doi] AB - AIMS: To understand patient preferences for once-daily oral versus once-weekly injectable type 2 diabetes mellitus (T2DM) medication administration profiles, and reasons for their preferences. MATERIALS AND METHODS: The REVISE study, a cross-sectional online survey of 600 participants with T2DM (United Kingdom, n = 300; United States, n = 300), elicited general preferences for once-daily oral versus once-weekly injectable diabetes medications, and reasons for the preference. Participants then viewed two videos describing the administration procedures for injectable dulaglutide and oral semaglutide, based on the product instructions for use. Thereafter, participants indicated their preference for a once-weekly injectable or a once-daily oral medication based on the video descriptions. Participants who switched preferences were asked to identify the reasons influencing their decision. RESULTS: The participants were predominantly male (n = 349; 58.2%), with a mean (SD) age of 64 (11.3) years. Nearly all (n = 557; 92.8%) were taking an oral T2DM medication, and 158 (26.3%) were using an injectable. Initially, 76.5% (n = 459; 95% confidence interval [CI] 73.1-79.9) preferred a once-daily oral and 23.5% a once-weekly injectable (n = 141; 95% CI 20.1-26.9; P < 0.0001). After viewing the videos describing the product-specific administration, the proportions of participants preferring each option were not statistically different (oral semaglutide administration description (n = 315; 52.5%; 95% CI 48.5-56.5; dulaglutide administration description (n = 285; 47.5%; 95% CI 43.5-51.5; NS, P = 0.2207). The most common reason for switching preferences was the timing and steps of administration. CONCLUSION: Several treatment-related characteristics, including route, frequency and complexity of the treatment, play a role in patients' preferences for T2DM treatments and should be considered during treatment selection. CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Boye, Kristina AU - Boye K AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Ross, Melissa AU - Ross M AUID- ORCID: 0000-0001-7317-9273 AD - Evidera Inc, Bethesda, Maryland, USA. FAU - Mody, Reema AU - Mody R AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Konig, Manige AU - Konig M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Gelhorn, Heather AU - Gelhorn H AUID- ORCID: 0000-0003-3566-1004 AD - Evidera Inc, Bethesda, Maryland, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201213 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) SB - IM MH - Cross-Sectional Studies MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Male MH - Middle Aged MH - *Patient Preference MH - United Kingdom/epidemiology PMC - PMC7839441 OTO - NOTNLM OT - United Kingdom OT - United States OT - daily oral OT - preferences OT - type 2 diabetes OT - weekly injectable COIS- Melissa Ross and Heather Gelhorn - nothing to disclose. Reema Mody, Manige Konig, and Kristina Boye are minor shareholders and employees of Eli Lilly and Company. EDAT- 2020/11/04 06:00 MHDA- 2021/07/06 06:00 PMCR- 2021/01/27 CRDT- 2020/11/03 05:52 PHST- 2020/07/07 00:00 [received] PHST- 2020/10/22 00:00 [revised] PHST- 2020/10/25 00:00 [accepted] PHST- 2020/11/04 06:00 [pubmed] PHST- 2021/07/06 06:00 [medline] PHST- 2020/11/03 05:52 [entrez] PHST- 2021/01/27 00:00 [pmc-release] AID - DOM14244 [pii] AID - 10.1111/dom.14244 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Feb;23(2):508-519. doi: 10.1111/dom.14244. Epub 2020 Dec 13. PMID- 33136765 OWN - NLM STAT- MEDLINE DCOM- 20210714 LR - 20260127 IS - 1533-4023 (Electronic) IS - 0160-2446 (Linking) VI - 77 IP - 1 DP - 2021 Jan 1 TI - Comparative Efficacy of Glucagon-like Peptide 1 Receptor Agonists and Sodium Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular Events in Type 2 Diabetes: A Network Meta-analysis. PG - 34-37 LID - 10.1097/FJC.0000000000000916 [doi] AB - The comparative efficacy of different glucagon-like peptide 1 receptor agonists and sodium glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular events (MACE) in type 2 diabetes with or without cardiorenal disease is undefined. PubMed and Embase were searched for relevant randomized trials. We conducted network meta-analysis within the Bayesian framework. Effect sizes were measured using hazard ratio (HR) and 95% confidence interval (CI). We calculated surface under the cumulative ranking curve (SUCRA) values to rank drug interventions for different type 2 diabetic subgroups. Albiglutide (HR 0.76, 95% CI 0.63-0.93) and subcutaneous semaglutide (HR 0.71, 95% CI 0.52-0.95), with the maximum SUCRA values, significantly reduced MACE versus lixisenatide in people with diabetes with cardiovascular disease; albiglutide (HRs: 0.69 and 0.72), with the maximum SUCRA value, significantly reduced MACE versus dapagliflozin and exenatide in people with diabetes with heart failure; and canagliflozin (HRs: 0.72 and 0.72) and liraglutide (HRs: 0.68 and 0.68), with the maximum SUCRA values, significantly reduced MACE versus exenatide and lixisenatide in people with diabetes with chronic kidney disease. In preventing MACE in type 2 diabetes, subcutaneous semaglutide and albiglutide are most effective for diabetes with cardiovascular disease, albiglutide is most effective for diabetes with heart failure, and canagliflozin and liraglutide are most effective for diabetes with chronic kidney disease. CI - Copyright (c) 2020 Wolters Kluwer Health, Inc. All rights reserved. FAU - Qiu, Mei AU - Qiu M AD - Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China. FAU - Ding, Liang-Liang AU - Ding LL AD - Department of Endocrinology, First Affiliated Hospital of Yangtze University, Jingzhou, China ; and. FAU - Wei, Xu-Bin AU - Wei XB AD - Departments of Cardiology, and. FAU - Liu, Shu-Yan AU - Liu SY AD - Endocrinology, the Second Affiliated Hospital of Kunming Medical University, Kunming, China . FAU - Zhou, Hai-Rong AU - Zhou HR AD - Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen, China. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Review PL - United States TA - J Cardiovasc Pharmacol JT - Journal of cardiovascular pharmacology JID - 7902492 RN - 0 (Incretins) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Cardiovascular Diseases/diagnosis/epidemiology/*prevention & control MH - Diabetes Mellitus, Type 2/diagnosis/*drug therapy/epidemiology MH - Humans MH - Incretins/adverse effects/*therapeutic use MH - Randomized Controlled Trials as Topic MH - Risk Assessment MH - Risk Factors MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/*therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor COIS- The authors report no conflicts of interest. EDAT- 2020/11/03 06:00 MHDA- 2021/07/15 06:00 CRDT- 2020/11/02 17:12 PHST- 2020/05/28 00:00 [received] PHST- 2020/08/31 00:00 [accepted] PHST- 2020/11/03 06:00 [pubmed] PHST- 2021/07/15 06:00 [medline] PHST- 2020/11/02 17:12 [entrez] AID - 00005344-202101000-00006 [pii] AID - 10.1097/FJC.0000000000000916 [doi] PST - ppublish SO - J Cardiovasc Pharmacol. 2021 Jan 1;77(1):34-37. doi: 10.1097/FJC.0000000000000916. PMID- 33131483 OWN - NLM STAT- MEDLINE DCOM- 20201103 LR - 20260127 IS - 0022-9040 (Print) IS - 0022-9040 (Linking) VI - 60 IP - 9 DP - 2020 Oct 14 TI - [Semaglutide for the Management of type 2 Diabetes: Clinical Evidence, Cardioprotective Effects, and Guidelines]. PG - 122-133 LID - 10.18087/cardio.2020.9.n1274 [doi] AB - Cardiovascular diseases remain a leading cause for unfavorable outcomes, including death, in patients with type 2 diabetes mellitus (DM2). In the recent decade, novel drugs, including glucagon-like peptide-1 receptor agonists (GPP-1-RA) and sodium-glucose cotransporter-2 inhibitors, have convincingly demonstrated their ability to reduce risk of cardiovascular complications in patients with DM2. This review discusses one of GPP-1-RA, semaglutide, with a special focus on the evidence-based data on its use, cardioprotective properties, and algorithms of administration consistent with current clinical recommendations. FAU - Kobalava, Zh D AU - Kobalava ZD AD - Peoples' Friendship University of Russia (RUDN University), Moscow. FAU - Kokhan, E V AU - Kokhan EV AD - Peoples' Friendship University of Russia (RUDN University), Moscow. LA - rus PT - Journal Article PT - Review DEP - 20201014 PL - Russia (Federation) TA - Kardiologiia JT - Kardiologiia JID - 0376351 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Cardiovascular Diseases/etiology/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - *Sodium-Glucose Transporter 2 Inhibitors MH - Semaglutide EDAT- 2020/11/03 06:00 MHDA- 2020/11/04 06:00 CRDT- 2020/11/02 05:32 PHST- 2020/07/14 00:00 [received] PHST- 2020/07/29 00:00 [accepted] PHST- 2020/11/02 05:32 [entrez] PHST- 2020/11/03 06:00 [pubmed] PHST- 2020/11/04 06:00 [medline] AID - 10.18087/cardio.2020.9.n1274 [doi] PST - epublish SO - Kardiologiia. 2020 Oct 14;60(9):122-133. doi: 10.18087/cardio.2020.9.n1274. PMID- 33115821 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20260127 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 8 IP - 2 DP - 2020 Oct TI - Superior weight loss with once-weekly semaglutide versus other glucagon-like peptide-1 receptor agonists is independent of gastrointestinal adverse events. LID - 10.1136/bmjdrc-2020-001706 [doi] LID - e001706 AB - INTRODUCTION: Gastrointestinal (GI) adverse events (AEs) are the most common AEs with glucagon-like peptide-1 receptor agonists (GLP-1RAs). Weight loss (WL) is slightly greater in people who experience GI AEs than those who do not. A previous mediation analysis of the SUSTAIN 1-5 trials indicated minor contribution of nausea/vomiting to the greater WL with once-weekly semaglutide versus comparators. Semaglutide demonstrated superior glycated hemoglobin and body weight (BW) reductions versus other GLP-1RAs in SUSTAIN 3 (versus exenatide extended release 2.0 mg), SUSTAIN 7 (versus dulaglutide) and SUSTAIN 10 (liraglutide 1.2 mg). The objective of this analysis was to assess if significantly greater WL with semaglutide versus other GLP-1RAs is mediated by nausea/vomiting and other GI AEs (diarrhea, constipation, dyspepsia) during dose escalation (baseline to week 12, when GI AEs are generally most prevalent) and from baseline to end of treatment (EOT: week 56 (SUSTAIN 3), 40 (SUSTAIN 7) or 30 (SUSTAIN 10)). RESEARCH DESIGN AND METHODS: Subjects within trials were subdivided into those who reported (yes/no) nausea/vomiting or any other GI AE. Change from baseline in BW was assessed within each trial and subgroup. A mediation analysis separated WL into direct or indirect (mediated by GI AEs) effects. RESULTS: From baseline to week 12 or EOT, the nausea/vomiting-mediated difference in WL was, respectively: 0.05 or 0.09 kg of 3.78 kg at EOT (SUSTAIN 3); 0.06 or 0.03 kg of 2.26 kg at EOT (low-dose comparison) and 0.08 or 0.04 kg of 3.55 kg at EOT (high-dose comparison) (SUSTAIN 7) and 0.05 or 0.09 kg of 3.82 kg at EOT (SUSTAIN 10). CONCLUSIONS: In SUSTAIN 3, 7 and 10, nausea/vomiting by week 12 (end of dose escalation) or throughout treatment contributed minimally (<0.1 kg) to the superior WL with semaglutide versus GLP-1RA comparators at EOT. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Department of Internal Medicine/Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas, USA Ildiko.Lingvay@UTSouthwestern.edu. FAU - Hansen, Thomas AU - Hansen T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Macura, Stanislava AU - Macura S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Marre, Michel AU - Marre M AD - Clinique Ambroise Pare, Neuilly sur Seine, France. AD - UMRS 1138, Metabolic Inflammation in Diabetes and its Complications Cordeliers Research Centre, Paris, France. FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes Division, Katholisches Klinikum Bochum, St Josef Hospital, Bochum, Germany. FAU - de la Rosa, Raymond AU - de la Rosa R AD - Endocrinology, Millennium Physician Group, Englewood, Florida, USA. FAU - Woo, Vincent AU - Woo V AD - Endocrinology and Metabolism, University of Manitoba, Winnipeg, Manitoba, Canada. FAU - Yildirim, Emre AU - Yildirim E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wilding, John AU - Wilding J AUID- ORCID: 0000-0003-2839-8404 AD - Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2 MH - *Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Weight Loss MH - Semaglutide PMC - PMC7594204 OTO - NOTNLM OT - body weight OT - diabetes mellitus OT - gastrointestinal tract OT - glucagon-like peptide 1 OT - type 2 COIS- Competing interests: IL reports receiving grants, personal fees and non-financial support from Novo Nordisk, both for and outside the submitted work; grants from Merck and Mylan; personal fees from Valeritas, TARGET Pharma, Intarcia and Mannkind; personal fees and non-financial support from Boehringer Ingelheim, Astra Zeneca, Janssen and Eli Lilly & Co; grants and non-financial support from Pfizer; grant, personal fees and non-financial support from Sanofi; all outside the submitted work. TH and SM do not have any conflicts of interest. MM reports receiving payment from Novo Nordisk for the submitted work; serving as consultant and on the advisory board of Novo Nordisk and Servier; consultant for Eli Lilly & Co and serving on the advisory board of Merck Sharp & Dohme. MAN has received fees for serving on advisory boards or lecturing for Astra Zeneca, Berlin-Chemie/Menarini, Boehringer Ingelheim, Eli Lilly & Co, Genentech, GlaxoSmithKline, Medscape, Merck Sharp&Dohme, Novo Nordisk, Sanofi-Aventis, Sun Pharma, Takeda and grant support for clinical studies from Astra Zeneca, Eli Lilly & Co, Glaxo Smith Kline, Merck Sharp & Dohme, Novo Nordisk and travel support for the above-mentioned activities. RdlR reports receiving speaker bureau honoraria from Novo Nordisk, Sanofi-Aventis and Boehringer Ingelheim. VW reports receiving grants, personal fees and other affiliations (ie, advisory boards) from Janssen, Boehringer Ingelheim, Astra Zeneca, Lilly, Novo Nordisk and Merck. EY reports being a full-time employee and minor stockholder of Novo Nordisk. JW reports grants, personal fees and fees paid into his institution from Astra Zeneca and Novo Nordisk; fees paid into his institution from Astellas, Janssen, Lilly and Rhythm Pharmaceuticals; personal fees and fees paid into his institution from Boehringer Ingelheim, Napp, Mundipharma International; grants and personal fees from Takeda. EDAT- 2020/10/30 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/10/28 CRDT- 2020/10/29 05:41 PHST- 2020/06/19 00:00 [received] PHST- 2020/09/08 00:00 [revised] PHST- 2020/09/08 00:00 [accepted] PHST- 2020/10/29 05:41 [entrez] PHST- 2020/10/30 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/10/28 00:00 [pmc-release] AID - 8/2/e001706 [pii] AID - bmjdrc-2020-001706 [pii] AID - 10.1136/bmjdrc-2020-001706 [doi] PST - ppublish SO - BMJ Open Diabetes Res Care. 2020 Oct;8(2):e001706. doi: 10.1136/bmjdrc-2020-001706. PMID- 33108617 OWN - NLM STAT- MEDLINE DCOM- 20210930 LR - 20261010 IS - 1179-1926 (Electronic) IS - 0312-5963 (Linking) VI - 60 IP - 2 DP - 2021 Feb TI - Pharmacokinetics and Clinical Implications of Oral Semaglutide for Type 2 Diabetes Mellitus. PG - 153-163 LID - 10.1007/s40262-020-00951-6 [doi] AB - Since the approval of subcutaneous glucagon-like peptide-1 receptor agonists, this therapeutic class has become a preferred choice for the management of type 2 diabetes due to A1C reduction, minimal risk of hypoglycemia, weight loss, and cardiovascular benefit. An oral option, with gastrointestinal absorption, would overcome any potential fear of injection among patients. Oral semaglutide has been studied in randomized controlled trials within the PIONEER program. From a robust pool of literature with a global patient population, oral semaglutide has been an effective option as monotherapy and combination therapy to improve clinical outcomes, such as A1C and body weight from baseline to week 78, depending on the randomized controlled trial. In addition, a noninferiority result was observed with oral semaglutide versus placebo in a cardiovascular outcomes trial in patients with type 2 diabetes with established cardiovascular disease or risk factors. Similar to injectable glucagon-like peptide 1 receptor agonists, transient nausea and vomiting was seen with oral semaglutide. Overall, this new oral option may be a choice for patients with barriers to injectable therapy. This review evaluates and summarizes the pharmacokinetics, pharmacodynamics, and clinical application of oral semaglutide in patients with type 2 diabetes. FAU - Clements, Jennifer N AU - Clements JN AUID- ORCID: 0000-0003-2431-6651 AD - Department of Nursing Administration, Spartanburg Regional Healthcare System, Spartanburg, SC, 29303, USA. Jclements1027@outlook.com. FAU - Isaacs, Diana AU - Isaacs D AD - Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic Diabetes Center, Cleveland, OH, 44195, USA. FAU - Hartman, Rachel E AU - Hartman RE AD - The University of Findlay College of Pharmacy, Findlay, OH, 45840, USA. FAU - Gambill, Kennedy AU - Gambill K AD - Department of Pharmacy, Spartanburg Medical Center, Spartanburg, SC, 29303, USA. AD - Department of Pharmacy Practice, East Tennessee State University, Johnson City, TN, 37601, USA. LA - eng PT - Journal Article PT - Review DEP - 20201027 PL - Switzerland TA - Clin Pharmacokinet JT - Clinical pharmacokinetics JID - 7606849 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor MH - *Glucagon-Like Peptides/administration & dosage/pharmacokinetics MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/pharmacokinetics MH - Randomized Controlled Trials as Topic MH - Semaglutide EDAT- 2020/10/28 06:00 MHDA- 2021/10/01 06:00 CRDT- 2020/10/27 17:39 PHST- 2020/10/04 00:00 [accepted] PHST- 2020/10/28 06:00 [pubmed] PHST- 2021/10/01 06:00 [medline] PHST- 2020/10/27 17:39 [entrez] AID - 10.1007/s40262-020-00951-6 [pii] AID - 10.1007/s40262-020-00951-6 [doi] PST - ppublish SO - Clin Pharmacokinet. 2021 Feb;60(2):153-163. doi: 10.1007/s40262-020-00951-6. Epub 2020 Oct 27. PMID- 33074557 OWN - NLM STAT- MEDLINE DCOM- 20210705 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 2 DP - 2021 Feb TI - Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as add-on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30-week, double-blind, phase 3a, randomized trial. PG - 404-414 LID - 10.1111/dom.14232 [doi] AB - AIM: To evaluate the efficacy and safety of once-weekly subcutaneous semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, versus once-daily sitagliptin as add-on to metformin in patients with type 2 diabetes (T2D) in a multiregional clinical trial. MATERIALS AND METHODS: In the 30-week, randomized, double-blind, double-dummy, active comparator SUSTAIN China trial, 868 adults with T2D inadequately controlled on metformin (HbA1c 7.0%-10.5%) were randomized to receive once-weekly semaglutide 0.5 mg (n = 288), semaglutide 1.0 mg (n = 290) or once-daily sitagliptin 100 mg (n = 290). The primary and confirmatory secondary endpoints were change from baseline to week 30 in HbA(1c) and body weight, respectively. RESULTS: The trial enrolled ~70% (605/868) of the patients in China, and the remaining patients from four other countries, including the Republic of Korea. Both doses of semaglutide were superior to sitagliptin in reducing HbA(1c) and body weight after 30 weeks of treatment. The odds of achieving target HbA(1c) of less than 7.0% (53 mmol/mol), weight loss of 5% or higher, or 10% or higher, and the composite endpoint of HbA(1c) less than 7.0% (53 mmol/mol) without severe or blood glucose-confirmed symptomatic hypoglycaemia no weight gain, were all significantly higher with both semaglutide doses compared with sitagliptin. The safety profile for semaglutide was consistent with the known class effects of GLP-1 receptor agonists (RAs). Consistent efficacy and safety findings were seen in the Chinese subpopulation. CONCLUSIONS: Once-weekly semaglutide was superior to sitagliptin in improving glycaemic control and reducing body weight in patients with T2D inadequately controlled on metformin. The safety and tolerability profiles were consistent with those of semaglutide and other GLP-1 RAs. Semaglutide is an effective once-weekly treatment option for the Chinese population. CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0003-1305-1598 AD - Peking University People's Hospital No. 11, Beijing, China. FAU - Dong, Xiaolin AU - Dong X AD - Jinan Central Hospital, Affiliated to Shandong University No. 105, Jinan, China. FAU - Li, Yiming AU - Li Y AD - Shanghai Huashan Hospital, Affiliated to Fudan University No. 12, Shanghai, China. FAU - Li, Yufeng AU - Li Y AD - Beijing Pinggu Hospital No. 59, Beijing, China. FAU - Lim, Soo AU - Lim S AUID- ORCID: 0000-0002-4137-1671 AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. FAU - Liu, Ming AU - Liu M AD - General Hospital of Tianjin Medical University No. 154, Tianjin, China. FAU - Ning, Zu AU - Ning Z AD - Novo Nordisk (China) Pharmaceuticals Co., Ltd, Beijing, China. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Skjoth, Trine Vang AU - Skjoth TV AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Yuan, Guoyue AU - Yuan G AD - The Affiliated Hospital of Jiangsu University No. 438, Zhenjiang, China. FAU - Eliaschewitz, Freddy G AU - Eliaschewitz FG AD - CPClin/DASA Centro de Pesquisas Clinicas, Sao Paulo, Brazil. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210103 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - China MH - *Diabetes Mellitus, Type 2/drug therapy MH - Double-Blind Method MH - Drug Therapy, Combination MH - Glucagon-Like Peptides/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - *Metformin/adverse effects MH - Republic of Korea MH - Sitagliptin Phosphate/adverse effects MH - Treatment Outcome MH - Semaglutide PMC - PMC7839591 OTO - NOTNLM OT - GLP-1 analogue, glycaemic control, incretin therapy, phase III study, randomized trial, type 2 diabetes COIS- LJ reports receiving personal fees from Novo Nordisk during the conduct of this study. ZN is an employee of Novo Nordisk. SR is an employee of and stockholder at Novo Nordisk. TVS is an employee of and shareholder at Novo Nordisk. XD, YiL, YuL, SL, ML and GY have nothing to disclose. FGE reports receiving grants from Novo Nordisk outside the submitted work. EDAT- 2020/10/20 06:00 MHDA- 2021/07/06 06:00 PMCR- 2021/01/27 CRDT- 2020/10/19 12:25 PHST- 2020/06/01 00:00 [received] PHST- 2020/10/05 00:00 [revised] PHST- 2020/10/13 00:00 [accepted] PHST- 2020/10/20 06:00 [pubmed] PHST- 2021/07/06 06:00 [medline] PHST- 2020/10/19 12:25 [entrez] PHST- 2021/01/27 00:00 [pmc-release] AID - DOM14232 [pii] AID - 10.1111/dom.14232 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Feb;23(2):404-414. doi: 10.1111/dom.14232. Epub 2021 Jan 3. PMID- 33068776 OWN - NLM STAT- MEDLINE DCOM- 20211119 LR - 20260127 IS - 2212-8778 (Electronic) IS - 2212-8778 (Linking) VI - 46 DP - 2021 Apr TI - GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. PG - 101102 LID - S2212-8778(20)30176-9 [pii] LID - 10.1016/j.molmet.2020.101102 [doi] LID - 101102 AB - BACKGROUND: GLP-1 receptor agonists (GLP-1 RAs) with exenatide b.i.d. first approved to treat type 2 diabetes in 2005 have been further developed to yield effective compounds/preparations that have overcome the original problem of rapid elimination (short half-life), initially necessitating short intervals between injections (twice daily for exenatide b.i.d.). SCOPE OF REVIEW: To summarize current knowledge about GLP-1 receptor agonist. MAJOR CONCLUSIONS: At present, GLP-1 RAs are injected twice daily (exenatide b.i.d.), once daily (lixisenatide and liraglutide), or once weekly (exenatide once weekly, dulaglutide, albiglutide, and semaglutide). A daily oral preparation of semaglutide, which has demonstrated clinical effectiveness close to the once-weekly subcutaneous preparation, was recently approved. All GLP-1 RAs share common mechanisms of action: augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion at hyper- or euglycemia, deceleration of gastric emptying preventing large post-meal glycemic increments, and a reduction in calorie intake and body weight. Short-acting agents (exenatide b.i.d., lixisenatide) have reduced effectiveness on overnight and fasting plasma glucose, but maintain their effect on gastric emptying during long-term treatment. Long-acting GLP-1 RAs (liraglutide, once-weekly exenatide, dulaglutide, albiglutide, and semaglutide) have more profound effects on overnight and fasting plasma glucose and HbA(1c), both on a background of oral glucose-lowering agents and in combination with basal insulin. Effects on gastric emptying decrease over time (tachyphylaxis). Given a similar, if not superior, effectiveness for HbA(1c) reduction with additional weight reduction and no intrinsic risk of hypoglycemic episodes, GLP-1RAs are recommended as the preferred first injectable glucose-lowering therapy for type 2 diabetes, even before insulin treatment. However, GLP-1 RAs can be combined with (basal) insulin in either free- or fixed-dose preparations. More recently developed agents, in particular semaglutide, are characterized by greater efficacy with respect to lowering plasma glucose as well as body weight. Since 2016, several cardiovascular (CV) outcome studies have shown that GLP-1 RAs can effectively prevent CV events such as acute myocardial infarction or stroke and associated mortality. Therefore, guidelines particularly recommend treatment with GLP-1 RAs in patients with pre-existing atherosclerotic vascular disease (for example, previous CV events). The evidence of similar effects in lower-risk subjects is not quite as strong. Since sodium/glucose cotransporter-2 (SGLT-2) inhibitor treatment reduces CV events as well (with the effect mainly driven by a reduction in heart failure complications), the individual risk of ischemic or heart failure complications should guide the choice of treatment. GLP-1 RAs may also help prevent renal complications of type 2 diabetes. Other active research areas in the field of GLP-1 RAs are the definition of subgroups within the type 2 diabetes population who particularly benefit from treatment with GLP-1 RAs. These include pharmacogenomic approaches and the characterization of non-responders. Novel indications for GLP-1 RAs outside type 2 diabetes, such as type 1 diabetes, neurodegenerative diseases, and psoriasis, are being explored. Thus, within 15 years of their initial introduction, GLP-1 RAs have become a well-established class of glucose-lowering agents that has the potential for further development and growing impact for treating type 2 diabetes and potentially other diseases. CI - Copyright (c) 2020 The Authors. Published by Elsevier GmbH.. All rights reserved. FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes Division, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany. Electronic address: michael.nauck@rub.de. FAU - Quast, Daniel R AU - Quast DR AD - Diabetes Division, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany. FAU - Wefers, Jakob AU - Wefers J AD - Diabetes Division, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany. FAU - Meier, Juris J AU - Meier JJ AD - Diabetes Division, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany. LA - eng PT - Journal Article PT - Review DEP - 20201014 PL - Germany TA - Mol Metab JT - Molecular metabolism JID - 101605730 RN - 0 (Blood Glucose) RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Insulin) RN - 839I73S42A (Liraglutide) RN - 0 (Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 5E7U48495E (rGLP-1 protein) RN - 74O62BB01U (lixisenatide) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Animals MH - Blood Glucose MH - Body Weight MH - Cardiovascular System/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy MH - Exenatide/pharmacology MH - Glucagon-Like Peptide 1/analogs & derivatives MH - Glucagon-Like Peptide-1 Receptor/*metabolism MH - Glucagon-Like Peptides/analogs & derivatives/pharmacology MH - Humans MH - Hypoglycemia MH - Immunoglobulin Fc Fragments MH - Insulin/pharmacology MH - Liraglutide/pharmacology MH - Neurodegenerative Diseases MH - Peptides/pharmacology MH - Psoriasis MH - Recombinant Fusion Proteins MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-2 Receptor PMC - PMC8085572 OTO - NOTNLM OT - Albiglutide OT - Body weight OT - Cardiovascular disease OT - Dulaglutide OT - Exenatide OT - Glucagon-like peptide-1 receptor agonists OT - Liraglutide OT - Lixisenatide OT - Semaglutide OT - Type 2 diabetes EDAT- 2020/10/18 06:00 MHDA- 2021/11/20 06:00 PMCR- 2020/10/14 CRDT- 2020/10/17 20:08 PHST- 2020/08/25 00:00 [received] PHST- 2020/10/09 00:00 [revised] PHST- 2020/10/12 00:00 [accepted] PHST- 2020/10/18 06:00 [pubmed] PHST- 2021/11/20 06:00 [medline] PHST- 2020/10/17 20:08 [entrez] PHST- 2020/10/14 00:00 [pmc-release] AID - S2212-8778(20)30176-9 [pii] AID - 101102 [pii] AID - 10.1016/j.molmet.2020.101102 [doi] PST - ppublish SO - Mol Metab. 2021 Apr;46:101102. doi: 10.1016/j.molmet.2020.101102. Epub 2020 Oct 14. PMID- 33058727 OWN - NLM STAT- MEDLINE DCOM- 20210831 LR - 20260127 IS - 2156-8944 (Electronic) IS - 2156-8944 (Linking) VI - 22 IP - 12 DP - 2020 Dec 14 TI - Total Synthesis of Semaglutide Based on a Soluble Hydrophobic-Support-Assisted Liquid-Phase Synthetic Method. PG - 821-825 LID - 10.1021/acscombsci.0c00134 [doi] AB - Considering the high cost of the production of semaglutide, which is currently the most promising antidiabetic drug especially for the treatment of type 2 diabetes mellitus, a new synthetic route of semaglutide production that possesses excellent yield and high purity is of vital importance. Herein, we reported a newly developed synthetic route of semaglutide that is simple and efficient, based on a soluble hydrophobic-support-assisted liquid-phase synthetic method by applying Alloc-chemistry to the synthesis of the main chain peptide and side chain peptide of semaglutide. With careful optimization of the reaction conditions and innovative strategy of post-synthetic treatments, the total yield and purity of the crude semaglutide was improved satisfactorily. FAU - Liu, Xingbang AU - Liu X AD - Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China. FAU - Zhang, Na AU - Zhang N AD - Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China. FAU - Gu, Xiaotong AU - Gu X AD - Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China. FAU - Qin, Yinhui AU - Qin Y AD - Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China. FAU - Song, Di AU - Song D AD - Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China. FAU - Zhang, Long AU - Zhang L AD - Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China. FAU - Ma, Shutao AU - Ma S AUID- ORCID: 0000-0003-1206-2375 AD - Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Wenhua Road, Jinan 250012, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201015 PL - United States TA - ACS Comb Sci JT - ACS combinatorial science JID - 101540531 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Lipids) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/*chemical synthesis/chemistry/therapeutic use MH - Humans MH - Hydrophobic and Hydrophilic Interactions MH - Hypoglycemic Agents/*chemical synthesis/chemistry/therapeutic use MH - Lipids/*chemistry MH - Molecular Structure MH - Solubility MH - Semaglutide OTO - NOTNLM OT - Alloc-chemistry OT - diatomite OT - peptide synthesis OT - post-synthetic treatment OT - semaglutide EDAT- 2020/10/16 06:00 MHDA- 2021/09/01 06:00 CRDT- 2020/10/15 20:08 PHST- 2020/10/16 06:00 [pubmed] PHST- 2021/09/01 06:00 [medline] PHST- 2020/10/15 20:08 [entrez] AID - 10.1021/acscombsci.0c00134 [doi] PST - ppublish SO - ACS Comb Sci. 2020 Dec 14;22(12):821-825. doi: 10.1021/acscombsci.0c00134. Epub 2020 Oct 15. PMID- 33039693 OWN - NLM STAT- MEDLINE DCOM- 20210920 LR - 20260127 IS - 1559-2030 (Electronic) IS - 1551-7144 (Linking) VI - 97 DP - 2020 Oct TI - Semaglutide for the treatment of non-alcoholic steatohepatitis: Trial design and comparison of non-invasive biomarkers. PG - 106174 LID - S1551-7144(20)30252-4 [pii] LID - 10.1016/j.cct.2020.106174 [doi] AB - Non-alcoholic steatohepatitis (NASH) is a chronic liver disease. There is a clear need to develop pharmacological treatment for patients with NASH as well as biomarkers that can diagnose the disease. We describe a trial of semaglutide treatment for NASH, identify key patient characteristics and compare the relationship of patient characteristics and non-invasive biomarkers/scores. NCT02970942 is a randomised, double-blind, placebo-controlled, multi-national Phase 2 trial of daily subcutaneous semaglutide (0.1 mg, 0.2 mg, 0.4 mg) in patients with biopsy-confirmed NASH, F1-F3 fibrosis, NAFLD Activity Score >/= 4, and body mass index (BMI) > 25 kg/m(2). Exploratory analyses were performed to evaluate correlations between baseline parameters and biomarkers in NASH. Mean (standard deviation [SD]) age of 320 randomised patients was 55 (11) years, mean BMI was 36 (6) kg/m(2), and 199 (62%) had type 2 diabetes. Of the total patients, 28% had F1 fibrosis, 23% had F2 fibrosis and 49% had F3 fibrosis. The highest area under the receiver operating characteristic curve (0.69) for accuracy in classifying fibrosis stage, F2-3 versus F1, was observed for Fib-4 and Enhanced Liver Fibrosis (ELF). No substantial correlation between BMI or other clinical or biochemical parameters and fibrosis stage was observed. In this large Phase 2 trial of semaglutide treatment for NASH, the clinical profile of enrolled patients was typical for patients with NASH. Of the investigated biomarkers/scores, ELF and Fib-4 showed the most apparent correlation in classifying fibrosis stage, but had only moderate predictive value. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Harrison, Stephen A AU - Harrison SA AD - Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK. Electronic address: stephenharrison87@gmail.com. FAU - Calanna, Salvatore AU - Calanna S AD - Novo Nordisk A/S, 2860 Soborg, Denmark. Electronic address: sca@novonordisk.com. FAU - Cusi, Kenneth AU - Cusi K AD - Division of Endocrinology, Diabetes & Metabolism, University of Florida, Gainesville, FL 32608, USA; Endocrinology, Diabetes and Metabolism, Malcom Randall VA Medical Center, Gainesville, FL 32608, USA. Electronic address: Kenneth.Cusi@medicine.ufl.edu. FAU - Linder, Martin AU - Linder M AD - Novo Nordisk A/S, 2860 Soborg, Denmark. Electronic address: MLIX@novonordisk.com. FAU - Okanoue, Takeshi AU - Okanoue T AD - Department of Gastroenterology & Hepatology, Saiseikai Suita Hospital, Suita, Japan. Electronic address: okanoue@suita.saiseikai.or.jp. FAU - Ratziu, Vlad AU - Ratziu V AD - Sorbonne University, ICAN - Institute for Cardiometabolism and Nutrition, Hopital Pitie Salpetriere, 75013 Paris, France. Electronic address: vlad.ratziu@inserm.fr. FAU - Sanyal, Arun AU - Sanyal A AD - Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23284, USA. Electronic address: arun.sanyal@vcuhealth.org. FAU - Sejling, Anne-Sophie AU - Sejling AS AD - Novo Nordisk A/S, 2860 Soborg, Denmark. Electronic address: asji@novonordisk.com. FAU - Newsome, Philip N AU - Newsome PN AD - National Institute for Health Research Birmingham Biomedical Research Centre and Liver Unit at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK. Electronic address: P.N.Newsome@bham.ac.uk. LA - eng SI - ClinicalTrials.gov/NCT02970942 GR - DH_/Department of Health/United Kingdom PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201008 PL - United States TA - Contemp Clin Trials JT - Contemporary clinical trials JID - 101242342 RN - 0 (Biomarkers) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Biomarkers MH - Biopsy MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides MH - Humans MH - *Liver Cirrhosis/drug therapy MH - Middle Aged MH - *Non-alcoholic Fatty Liver Disease/diagnosis/drug therapy MH - Randomized Controlled Trials as Topic MH - Semaglutide OTO - NOTNLM OT - Biomarkers OT - Clinical trial protocol OT - General diabetes OT - Hepatology OT - Non-alcoholic fatty liver disease OT - Semaglutide EDAT- 2020/10/12 06:00 MHDA- 2021/09/21 06:00 CRDT- 2020/10/11 20:25 PHST- 2020/05/29 00:00 [received] PHST- 2020/10/06 00:00 [revised] PHST- 2020/10/06 00:00 [accepted] PHST- 2020/10/12 06:00 [pubmed] PHST- 2021/09/21 06:00 [medline] PHST- 2020/10/11 20:25 [entrez] AID - S1551-7144(20)30252-4 [pii] AID - 10.1016/j.cct.2020.106174 [doi] PST - ppublish SO - Contemp Clin Trials. 2020 Oct;97:106174. doi: 10.1016/j.cct.2020.106174. Epub 2020 Oct 8. PMID- 33034163 OWN - NLM STAT- MEDLINE DCOM- 20211109 LR - 20260127 IS - 2040-1124 (Electronic) IS - 2040-1116 (Print) IS - 2040-1116 (Linking) VI - 12 IP - 6 DP - 2021 Jun TI - Evaluating the usability and safety of the semaglutide single-dose pen-injectors through summative (human factors) usability testing. PG - 978-987 LID - 10.1111/jdi.13429 [doi] AB - AIMS/INTRODUCTION: A single-dose, shield-activated pen-injector for each of the three approved dose variants (0.25, 0.5 and 1 mg) of once-weekly subcutaneous semaglutide has been developed to improve usability. This analysis presents findings from the summative usability testing process for the single-dose semaglutide pen-injectors, including the pen-injector four-pack cartons and instructions for use. MATERIALS AND METHODS: A total of 60 adults representing four user groups were included: patients with/without pen-injector experience, non-pharmacist healthcare professionals and pharmacists (each n = 15). Participants carried out four tasks: (i) pen-injector carton retrieval; (ii) first simulated injection; (iii) pen-injector retrieval; and (iv) second simulated injection. All participants carried out task 1, and patients and non-pharmacist healthcare professionals took part in tasks 2-4 (n = 45). The number and types of use errors, close calls and operational difficulties were evaluated, and participants subjectively rated the ease of each task on a scale of 1 (difficult) to 7 (easy). RESULTS: No potentially serious use errors and only one non-serious use error were reported. Eight participants committed use errors with no potential for harm, one participant committed an unclassified use error, one participant encountered a close call with no potential for harm and one participant experienced an operational difficulty. Mean ease-of-use ratings were 6.7 (task 1), 5.9 (task 2), 6.6 (task 3) and 6.9 (task 4). CONCLUSIONS: All three dose variants of the semaglutide single-dose pen-injector were considered easy to use (subjective feedback scores near 7) and not associated with any serious use errors, even when participants received no training before study participation. CI - (c) 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd. FAU - Klonoff, David C AU - Klonoff DC AD - Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, California, USA. FAU - Bassock, Stephanie AU - Bassock S AD - Emergo by UL, Chicago, Illinois, USA. FAU - Dwyer, Andrea AU - Dwyer A AD - Emergo by UL, Concord, Massachusetts, USA. FAU - Engels, Ella AU - Engels E AD - Emergo by UL, Concord, Massachusetts, USA. FAU - Qvist, Marianne AU - Qvist M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sparre, Thomas AU - Sparre T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Snitker, Soren AU - Snitker S AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng GR - Novo Nordisk A/S/ PT - Evaluation Study PT - Journal Article DEP - 20201118 PL - Japan TA - J Diabetes Investig JT - Journal of diabetes investigation JID - 101520702 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Diabetes Mellitus, Type 2/*drug therapy MH - Female MH - Glucagon-Like Peptides/*administration & dosage MH - Humans MH - Injections, Subcutaneous/*instrumentation MH - Male MH - Middle Aged MH - Patient Acceptance of Health Care/statistics & numerical data MH - *Syringes MH - *User-Centered Design MH - Semaglutide PMC - PMC8169358 OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Human factors engineering OT - Pen-injector COIS- DCK has acted as a consultant for Dexcom, EOFlow, Fractyl Laboratories Inc., Lifecare Inc., Novo Nordisk, Roche Diagnostics and Thirdwayv. Emergo by UL (SB, AD, EE) received funding for this study from Novo Nordisk, as well as funding for other studies by Novo Nordisk. MQ, TS and SS are employees of Novo Nordisk A/S; MQ and TS own stock in the company. EDAT- 2020/10/10 06:00 MHDA- 2021/11/10 06:00 PMCR- 2021/06/01 CRDT- 2020/10/09 05:43 PHST- 2020/08/19 00:00 [received] PHST- 2020/10/01 00:00 [accepted] PHST- 2020/10/10 06:00 [pubmed] PHST- 2021/11/10 06:00 [medline] PHST- 2020/10/09 05:43 [entrez] PHST- 2021/06/01 00:00 [pmc-release] AID - JDI13429 [pii] AID - 10.1111/jdi.13429 [doi] PST - ppublish SO - J Diabetes Investig. 2021 Jun;12(6):978-987. doi: 10.1111/jdi.13429. Epub 2020 Nov 18. PMID- 32998732 OWN - NLM STAT- MEDLINE DCOM- 20210517 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 19 IP - 1 DP - 2020 Sep 30 TI - Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. PG - 156 LID - 10.1186/s12933-020-01106-4 [doi] LID - 156 AB - BACKGROUND: Semaglutide is a glucagon-like peptide-1 (GLP-1) analog treatment for type 2 diabetes (T2D) available in subcutaneous (s.c.) and oral formulations. Two cardiovascular (CV) outcomes trials showed that in subjects with T2D at high risk of CV events there were fewer major adverse CV events (MACE; defined as CV death, non-fatal stroke, non-fatal myocardial infarction) with semaglutide than with placebo (hazard ratio [95% CI]: 0.74 [0.58;0.95] for once-weekly s.c. semaglutide and 0.79 [0.57;1.11] for once-daily oral semaglutide). However, there is little evidence for an effect of semaglutide on MACE in subjects not at high risk of CV events. This post hoc analysis examined CV effects of semaglutide in subjects across a continuum of baseline CV risk. METHODS: Data from the s.c. (SUSTAIN) and oral (PIONEER) semaglutide phase 3a clinical trial programs were combined according to randomized treatment (semaglutide or comparators) and analyzed to assess time to first MACE and its individual components. A CV risk model was developed with independent data from the LEADER trial (liraglutide vs placebo), considering baseline variables common to all datasets. Semaglutide data were analyzed to assess effects of treatment as a function of CV risk predicted using the CV risk prediction model. RESULTS: The CV risk prediction model performed satisfactorily when applied to the semaglutide data set (area under the curve: 0.77). There was a reduced relative and absolute risk of MACE for semaglutide vs comparators across the entire continuum of CV risk. While the relative risk reduction tended to be largest with low CV risk score, the largest absolute risk reduction was for intermediate to high CV risk score. Similar results were seen for relative risk reduction of the individual MACE components and also when only placebo comparator data were included. CONCLUSION: Semaglutide reduced the risk of MACE vs comparators across the continuum of baseline CV risk in a broad T2D population. Trial registrations ClinicalTrials.gov identifiers: NCT02054897, NCT01930188, NCT01885208, NCT02128932, NCT02305381, NCT01720446, NCT02207374, NCT02254291, NCT02906930, NCT02863328, NCT02607865, NCT02863419, NCT02827708, NCT02692716, NCT02849080, NCT03021187, NCT03018028, NCT03015220. FAU - Husain, Mansoor AU - Husain M AUID- ORCID: 0000-0002-3740-6739 AD - Ted Rogers Centre for Heart Research, Department of Medicine, University of Toronto, Toronto, ON, Canada. mansoor.husain@uhn.ca. FAU - Bain, Stephen C AU - Bain SC AD - Swansea University Medical School, Swansea, UK. FAU - Holst, Anders Gaarsdal AU - Holst AG AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mark, Thomas AU - Mark T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AD - University of Texas Southwestern Medical Center, Dallas, TX, USA. LA - eng SI - ClinicalTrials.gov/NCT01930188 SI - ClinicalTrials.gov/NCT02128932 SI - ClinicalTrials.gov/NCT02305381 SI - ClinicalTrials.gov/NCT02054897 SI - ClinicalTrials.gov/NCT03018028 SI - ClinicalTrials.gov/NCT03015220 SI - ClinicalTrials.gov/NCT03021187 SI - ClinicalTrials.gov/NCT01885208 SI - ClinicalTrials.gov/NCT01720446 SI - ClinicalTrials.gov/NCT02849080 SI - ClinicalTrials.gov/NCT02207374 SI - ClinicalTrials.gov/NCT02254291 SI - ClinicalTrials.gov/NCT02906930 SI - ClinicalTrials.gov/NCT02607865 SI - ClinicalTrials.gov/NCT02827708 SI - ClinicalTrials.gov/NCT02692716 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200930 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Biomarkers/blood MH - Blood Glucose/*drug effects/metabolism MH - Cardiovascular Diseases/mortality/*prevention & control MH - Clinical Trials, Phase III as Topic MH - Diabetes Mellitus, Type 2/blood/*drug therapy/mortality MH - Female MH - Glucagon-Like Peptides/adverse effects/*therapeutic use MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Randomized Controlled Trials as Topic MH - Risk Assessment MH - Risk Factors MH - Time Factors MH - Treatment Outcome MH - Semaglutide PMC - PMC7526237 OTO - NOTNLM OT - Cardiovascular OT - MACE OT - Oral semaglutide OT - PIONEER OT - Risk prediction model OT - SUSTAIN OT - Subcutaneous semaglutide OT - Type 2 diabetes COIS- MH received advisory board fees from AstraZeneca, Boehringer Ingelheim, Janssen, Merck, Novo Nordisk and Roche; research grants from AstraZeneca, Merck and Novo Nordisk; and speaker fees from Boehringer Ingelheim, Janssen and Novo Nordisk. SCB received honoraria fees, teaching and research grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk and Sanofi; funding for development of educational programs from Elsevier and Medscape; he also provided expert advice from All-Wales Medicines Strategy Group and National Institute for Health and Care Excellence (NICE) UK; and is a shareholder of Glycosmedia. AGH was a full-time employee of Novo Nordisk for the majority of manuscript development, and is a Novo Nordisk shareholder. TM was a full-time employee of Novo Nordisk for the majority of manuscript development, and is a Novo Nordisk shareholder. SM is an employee of Novo Nordisk and owns stock in the company. IL received grant support from Merck, Mylan, Novo Nordisk, Pfizer and Sanofi, personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Intarcia, Janssen, Mannkind, Novo Nordisk, Sanofi, TARGETPharma and Valeritas; and non-financial support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Jannsen, Novo Nordisk, Pfizer and Sanofi. EDAT- 2020/10/02 06:00 MHDA- 2021/05/18 06:00 PMCR- 2020/09/30 CRDT- 2020/10/01 05:26 PHST- 2020/06/19 00:00 [received] PHST- 2020/08/24 00:00 [accepted] PHST- 2020/10/01 05:26 [entrez] PHST- 2020/10/02 06:00 [pubmed] PHST- 2021/05/18 06:00 [medline] PHST- 2020/09/30 00:00 [pmc-release] AID - 10.1186/s12933-020-01106-4 [pii] AID - 1106 [pii] AID - 10.1186/s12933-020-01106-4 [doi] PST - epublish SO - Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4. PMID- 32991041 OWN - NLM STAT- MEDLINE DCOM- 20210705 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 1 DP - 2021 Jan TI - Gastrointestinal adverse events with insulin glargine/lixisenatide fixed-ratio combination versus glucagon-like peptide-1 receptor agonists in people with type 2 diabetes mellitus: A network meta-analysis. PG - 136-146 LID - 10.1111/dom.14202 [doi] AB - AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the recommended first injectable therapy in type 2 diabetes. However, long-term persistence is suboptimal and partly attributable to gastrointestinal tolerability, particularly during initiation/escalation. Gradual titration of fixed-ratio combination GLP-1 RA/insulin therapies may improve GLP-1 RA gastrointestinal tolerability. We compared gastrointestinal adverse event (AE) rates for iGlarLixi versus GLP-1 RAs during the first 12 weeks of therapy, including a sensitivity analysis with IDegLira. MATERIALS AND METHODS: The PICO framework was used to identify studies from MEDLINE, EMBASE and CENTRAL searches using a proprietary, web-based, standardized tool with single data extraction. Gastrointestinal AEs were modelled using a Bayesian network meta-analysis (NMA), using fixed and random effects for each recommended dose (treatment-specific NMA) and class (drug-class NMA). RESULTS: Treatment-specific NMA included 17 trials (n = 9030; 3665 event-weeks). Nausea rates were significantly lower with iGlarLixi versus exenatide 10 mug twice daily (rate ratio: 0.32; 95% credible interval: 0.15, 0.66), once-daily lixisenatide 20 mug (0.35; 0.24, 0.50) and liraglutide 1.8 mg once daily (0.48; 0.23, 0.98). Rates were numerically, but not statistically, lower versus once-weekly semaglutide 1 mg (0.60; 0.30, 1.23) and dulaglutide 1.5 mg (0.60; 0.29, 1.26), and numerically, but not statistically, higher versus once-weekly exenatide (1.91; 0.91, 4.03). Sensitivity analysis results were similar. In a naive, pooled analysis, vomiting was lower with iGlarLixi versus other GLP-1 RAs. CONCLUSIONS: During the first 12 weeks of treatment, iGlarLixi was generally associated with less nausea and vomiting than single-agent GLP-1 RAs. Enhanced gastrointestinal tolerability with fixed-ratio combinations may favour treatment persistence. CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Rayner, Christopher K AU - Rayner CK AUID- ORCID: 0000-0002-5527-256X AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia. FAU - Wu, Tongzhi AU - Wu T AUID- ORCID: 0000-0003-1656-9210 AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Whittington, Craig AU - Whittington C AD - Doctor Evidence, Santa Monica, California, USA. FAU - Kanters, Steve AU - Kanters S AD - Doctor Evidence, Santa Monica, California, USA. FAU - Guyot, Patricia AU - Guyot P AD - Sanofi, Paris, France. FAU - Shaunik, Alka AU - Shaunik A AD - Sanofi, Bridgewater, New Jersey, USA. FAU - Horowitz, Michael AU - Horowitz M AD - Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20201022 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Peptides) RN - 74O62BB01U (lixisenatide) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Bayes Theorem MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Insulin Glargine/adverse effects MH - Peptides MH - Glucagon-Like Peptide-2 Receptor PMC - PMC7756611 COIS- C.K.R. has received research funding from AstraZeneca, Merck Sharp & Dohme, Eli Lilly and Company, Novartis and Sanofi, and has participated in advisory boards for Allergan (now AbbVie). T.W. has received travel support from Novartis and Sanofi, and research funding from AstraZeneca and Novartis. V.R.A. has served as a consultant for Adocia, Applied Therapeutics, AstraZeneca, BD, Duke, Novo Nordisk, Sanofi and Zafgen, and has received research support from Applied Therapeutics, AstraZeneca/BMS, Boehringer Ingelheim, Calibra, Eisai, Premier/Fractyl, Janssen, Novo Nordisk, Sanofi and Theracos. C.W. was employed by Doctor Evidence at the time of the study. S.K. is an employee of Doctor Evidence, which has received funding from Sanofi, Merck Sharp & Dohme, Novartis and Novo Nordisk. C.W. and P.G. are employees and stockholders of Sanofi. A.S. was an employee and stockholder of Sanofi at the time of study conduct. M.H. has participated in advisory boards and/or symposia for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme, Novartis and Novo Nordisk. EDAT- 2020/09/30 06:00 MHDA- 2021/07/06 06:00 PMCR- 2020/12/23 CRDT- 2020/09/29 12:40 PHST- 2020/06/16 00:00 [received] PHST- 2020/09/08 00:00 [revised] PHST- 2020/09/23 00:00 [accepted] PHST- 2020/09/30 06:00 [pubmed] PHST- 2021/07/06 06:00 [medline] PHST- 2020/09/29 12:40 [entrez] PHST- 2020/12/23 00:00 [pmc-release] AID - DOM14202 [pii] AID - 10.1111/dom.14202 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Jan;23(1):136-146. doi: 10.1111/dom.14202. Epub 2020 Oct 22. PMID- 32987188 OWN - NLM STAT- MEDLINE DCOM- 20211119 LR - 20260127 IS - 2212-8778 (Electronic) IS - 2212-8778 (Linking) VI - 46 DP - 2021 Apr TI - Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease. PG - 101090 LID - S2212-8778(20)30164-2 [pii] LID - 10.1016/j.molmet.2020.101090 [doi] LID - 101090 AB - BACKGROUND: Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved to treat type 2 diabetes and obesity. They elicit robust improvements in glycemic control and weight loss, combined with cardioprotection in individuals at risk of or with pre-existing cardiovascular disease. These attributes make GLP-1 a preferred partner for next-generation therapies exhibiting improved efficacy yet retaining safety to treat diabetes, obesity, non-alcoholic steatohepatitis, and related cardiometabolic disorders. The available clinical data demonstrate that the best GLP-1R agonists are not yet competitive with bariatric surgery, emphasizing the need to further improve the efficacy of current medical therapy. SCOPE OF REVIEW: In this article, we discuss data highlighting the physiological and pharmacological attributes of potential peptide and non-peptide partners, exemplified by amylin, glucose-dependent insulinotropic polypeptide (GIP), and steroid hormones. We review the progress, limitations, and future considerations for translating findings from preclinical experiments to competitive efficacy and safety in humans with type 2 diabetes and obesity. MAJOR CONCLUSIONS: Multiple co-agonist combinations exhibit promising clinical efficacy, notably tirzepatide and investigational amylin combinations. Simultaneously, increasing doses of GLP-1R agonists such as semaglutide produces substantial weight loss, raising the bar for the development of new unimolecular co-agonists. Collectively, the available data suggest that new co-agonists with robust efficacy should prove superior to GLP-1R agonists alone to treat metabolic disorders. CI - Copyright (c) 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved. FAU - Baggio, Laurie L AU - Baggio LL AD - Lunenfeld-Tanenbaum Research Institute, Department of Medicine, Mt. Sinai Hospital, Toronto, Ontario, M5G 1X5 Canada. FAU - Drucker, Daniel J AU - Drucker DJ AD - Lunenfeld-Tanenbaum Research Institute, Department of Medicine, Mt. Sinai Hospital, Toronto, Ontario, M5G 1X5 Canada. Electronic address: drucker@lunenfeld.ca. LA - eng GR - 154321/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20200925 PL - Germany TA - Mol Metab JT - Molecular metabolism JID - 101605730 RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Receptors, Gastrointestinal Hormone) RN - OYN3CCI6QE (Tirzepatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - D6H00MV7K8 (gastric inhibitory polypeptide receptor) SB - IM MH - Adipose Tissue MH - Animals MH - Cardiovascular Diseases MH - Diabetes Mellitus, Type 2/metabolism MH - Fatty Liver MH - Gastric Inhibitory Polypeptide/pharmacology/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/genetics/*metabolism MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Metabolic Diseases/*drug therapy MH - Obesity/metabolism MH - Receptors, Gastrointestinal Hormone/drug effects MH - Weight Loss MH - Tirzepatide MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC8085566 OTO - NOTNLM OT - Adipose tissue OT - Cardiovascular disease OT - Diabetes OT - Obesity OT - Peptide OT - Receptor EDAT- 2020/09/29 06:00 MHDA- 2021/11/20 06:00 PMCR- 2020/09/25 CRDT- 2020/09/28 20:09 PHST- 2020/08/28 00:00 [received] PHST- 2020/09/13 00:00 [revised] PHST- 2020/09/17 00:00 [accepted] PHST- 2020/09/29 06:00 [pubmed] PHST- 2021/11/20 06:00 [medline] PHST- 2020/09/28 20:09 [entrez] PHST- 2020/09/25 00:00 [pmc-release] AID - S2212-8778(20)30164-2 [pii] AID - 101090 [pii] AID - 10.1016/j.molmet.2020.101090 [doi] PST - ppublish SO - Mol Metab. 2021 Apr;46:101090. doi: 10.1016/j.molmet.2020.101090. Epub 2020 Sep 25. PMID- 32975890 OWN - NLM STAT- MEDLINE DCOM- 20210427 LR - 20260304 IS - 1742-1241 (Electronic) IS - 1368-5031 (Print) IS - 1368-5031 (Linking) VI - 75 IP - 2 DP - 2021 Feb TI - Switching between GLP-1 receptor agonists in clinical practice: Expert consensus and practical guidance. PG - e13731 LID - 10.1111/ijcp.13731 [doi] LID - e13731 AB - BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an established treatment for patients with type 2 diabetes (T2D). Differences between GLP-1RAs in pharmacokinetics, dosing regimens and clinical effects, including cardiovascular (CV) outcomes, mean there may be benefits to switching from one to another. However, clinical guidance on switching is lacking and data from clinical trials are limited. This article provides a clinical perspective and consensus on the benefits of switching between GLP-1RAs, the triggers for switching and how best to manage this in clinical practice. Once weekly (OW) semaglutide is used as an example to illustrate how the authors might switch to a different GLP-1RA in clinical practice. METHODS: Literature was searched and perspectives from 10 healthcare professionals with experience in switching patients with T2D to OW semaglutide from another GLP-1RA were collated. RESULTS: Medical triggers for switching to another GLP-1RA included HbA(1c) targets not being met, a desire for additional weight loss, poor adherence, patients moving to increased CV risk status and adverse effects with the current GLP-1RA. Non-medical triggers for switching included patient preference, cost, formulary changes and insurance mandates. Once the decision to switch is made, an individualised approach is recommended, based on considerations that include reimbursement requirements, treatment duration with (and dose of) previous GLP-1RA, the patient's experience initiating the prior GLP-1RA, any concomitant treatment and clinical characteristics. When switching, it is important to emphasise that treatment burden will not increase and that if gastrointestinal adverse effects occur, they are typically transient. Any transient gastrointestinal adverse effects that may occur (or recur) when switching to another GLP-1RA can be reduced by slow up-titration and advising patients to reduce food portion sizes and fat intake. CONCLUSION: Switching from one GLP-1RA to another, such as OW semaglutide, can provide clinical benefits and may delay the need for treatment intensification. CI - (c) 2020 The Authors. International Journal of Clinical Practice published by John Wiley & Sons Ltd. FAU - Jain, Akshay B AU - Jain AB AUID- ORCID: 0000-0001-8515-5359 AD - University of British Columbia, Surrey, BC, Canada. FAU - Ali, Amar AU - Ali A AD - Oakenhurst Medical Practice, Blackburn, UK. FAU - Gorgojo Martinez, Juan J AU - Gorgojo Martinez JJ AUID- ORCID: 0000-0002-8679-0968 AD - Department of Endocrinology and Nutrition, Hospital Universitario Fundacion Alcorcon, Alcorcon, Spain. FAU - Hramiak, Irene AU - Hramiak I AD - Western University, London, ON, Canada. FAU - Kavia, Ketan AU - Kavia K AD - Manor Park Medical Practice, Leicester, UK. FAU - Madsbad, Sten AU - Madsbad S AUID- ORCID: 0000-0002-5017-1815 AD - Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark. FAU - Potier, Louis AU - Potier L AD - Bichat Hospital, APHP, Universite de Paris, Paris, France. FAU - Prohaska, Ben D AU - Prohaska BD AD - Northern Nevada Endocrinology, Reno, NV, USA. FAU - Strong, Jodi L AU - Strong JL AD - Ascension Medical Group, Stevens Point, WI, USA. FAU - Vilsboll, Tina AU - Vilsboll T AD - Steno Diabetes Center Copenhagen, Copenhagen, Denmark. LA - eng GR - Novo Nordisk/ PT - Consensus Statement PT - Journal Article DEP - 20201103 PL - United States TA - Int J Clin Pract JT - International journal of clinical practice JID - 9712381 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Weight Loss PMC - PMC7900946 COIS- ABJ has received honoraria for speaking from Abbott, AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Janssen, Merck, Novo Nordisk and Sanofi, and has been involved in advisory boards for Abbott, AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly, Novo Nordisk and Sanofi. AA has received research funding from Amgen, Eli Lilly, Merck, Pfizer and Sanofi and has received personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, NAPP, Novo Nordisk, Sanofi and Takeda. JJGM has received personal fees from Abbott, AbbVie Inc, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Esteve, Janssen, MSD, Mundipharma, Novo Nordisk, Pfizer, Roche and Sanofi. IH has received grants from AstraZeneca/Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lexicon Pharmaceuticals, Medtronic, Merck & Co., Novo Nordisk, the Population Health Research Institute and Sanofi. She has received personal fees from AstraZeneca/Bristol Myers Squibb, Bausch Health, Boehringer Ingelheim/Eli Lilly, Dexcom, Eli Lilly, GlaxoSmithKline, Insulet Crop., Janssen, Medtronic, Merck & Co., Novo Nordisk and Sanofi. IH has received non-financial support from AstraZeneca/Bristol Myers Squibb, Dexcom, GlaxoSmithKline, Insulet Corp., Janssen, Lexicon Pharmaceuticals, Medtronic, Merck & Co., Novo Nordisk, the Population Health Research Institute and Sanofi. KK has received personal fees for delivering educational talks from Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo UK, GlaxoSmithKline, Novo Nordisk and Pfizer, and has received personal fees for attending advisory boards from Amgen, Bristol Myers Squibb, Daiichi Sankyo UK and Pfizer. SM has received grants from Boehringer Ingelheim and Novo Nordisk, personal fees for advisory boards from Aventis, Boehringer Ingelheim, MSD and Novo Nordisk, and personal fees for lectures from Novo Nordisk. LP has received grants from Eli Lilly and Sanofi, personal fees from Eli Lilly, MSD, Novo Nordisk and Sanofi, and non-financial support from Eli Lilly, Novo Nordisk and Sanofi. BDP has no conflicts of interest to disclose. JLS has been on the Speaker Bureau of Abbott, AstraZeneca, Boehringer Ingelheim/Eli Lilly, Janssen, Merck, Novo Nordisk, Salix and Sanofi, has been a Board Member/Advisory Panel for Ascensia Diabetes, Novo Nordisk, and Sanofi. She has acted as a consultant for the American Diabetes Association, Novo Nordisk and Sanofi, and has received editorial support from Novo Nordisk and Sanofi. TV has received grants from Boehringer Ingelheim, Eli Lilly and Novo Nordisk, has received personal fees for consulting from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Mundipharma, Sanofi, Sun Pharma and Novo Nordisk, and has received personal fees for attending advisory boards from Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sun Pharma. EDAT- 2020/09/26 06:00 MHDA- 2021/04/28 06:00 PMCR- 2021/02/23 CRDT- 2020/09/25 12:18 PHST- 2020/06/24 00:00 [received] PHST- 2020/09/18 00:00 [accepted] PHST- 2020/09/26 06:00 [pubmed] PHST- 2021/04/28 06:00 [medline] PHST- 2020/09/25 12:18 [entrez] PHST- 2021/02/23 00:00 [pmc-release] AID - IJCP13731 [pii] AID - 10.1111/ijcp.13731 [doi] PST - ppublish SO - Int J Clin Pract. 2021 Feb;75(2):e13731. doi: 10.1111/ijcp.13731. Epub 2020 Nov 3. PMID- 32971040 OWN - NLM STAT- MEDLINE DCOM- 20201103 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 8 IP - 11 DP - 2020 Nov TI - Effects of once-weekly subcutaneous semaglutide on kidney function and safety in patients with type 2 diabetes: a post-hoc analysis of the SUSTAIN 1-7 randomised controlled trials. PG - 880-893 LID - S2213-8587(20)30313-2 [pii] LID - 10.1016/S2213-8587(20)30313-2 [doi] AB - BACKGROUND: Patients with type 2 diabetes have a high risk of developing chronic kidney disease. We examined the effects of semaglutide on kidney function and safety in a large, broad type 2 diabetes population. METHODS: We did a post-hoc analysis of 8416 patients with type 2 diabetes enrolled in the SUSTAIN 1-5 and SUSTAIN 7 randomised controlled trials, and the SUSTAIN 6 cardiovascular outcomes trial, to examine the effects of once-weekly subcutaneous semaglutide 0.5 mg and 1.0 mg versus comparators (active treatments or placebo) on estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and kidney adverse events. Data from SUSTAIN 1-5 and SUSTAIN 7 were pooled. eGFR and UACR were also analysed by kidney function and albuminuria status. FINDINGS: In SUSTAIN 1-5 and SUSTAIN 7, eGFR decreased from baseline to week 12 with all active treatments; estimated treatment differences (ETDs) versus placebo were -2.15 (95% CI -3.47 to -0.83) mL/min per 1.73 m(2) with semaglutide 0.5 mg and -3.00 (-4.31 to -1.68) mL/min per 1.73 m(2) with semaglutide 1.0 mg; after week 12, eGFR plateaued. In SUSTAIN 1-5 and SUSTAIN 7, from baseline to end of treatment the decline in eGFR was greater with semaglutide than with placebo (ETD -1.58 [95% CI -2.92 to -0.25] mL/min per 1.73 m(2) with semaglutide 0.5 mg and -2.02 [-3.35 to -0.68] mL/min per 1.73 m(2) with semaglutide 1.0 mg). In SUSTAIN 6, the decline in eGFR was greater with semaglutide than with placebo from baseline to week 16 (ETD -1.29 [95% CI -2.07 to -0.51] mL/min per 1.73 m(2) with semaglutide 0.5 mg and -1.56 [-2.33 to -0.78] mL/min per 1.73 m(2) with semaglutide 1.0 mg), but not from week 16 to week 104 (1.29 [0.30 to 2.28] mL/min per 1.73 m(2) with semaglutide 0.5 mg and 2.44 [1.45 to 3.44] mL/min per 1.73 m(2) with semaglutide 1.0 mg). Overall (ie, from baseline to week 104), the eGFR decline in SUSTAIN 6 was similar between semaglutide and placebo (ETD 0.07 [95% CI -0.92 to 1.07] mL/min per 1.73 m(2) with semaglutide 0.5 mg and 0.97 [-0.03 to 1.97] mL/min per 1.73 m(2) with semaglutide 1.0 mg). In SUSTAIN 1-5, UACR ratios at end of treatment to baseline were 0.917 with semaglutide 0.5 mg, 0.836 with semaglutide 1.0 mg, and 1.239 with placebo; at end of treatment, greater reductions in UACR were observed with semaglutide versus placebo (estimated treatment ratios 0.74 [95% CI 0.64 to 0.85] for semaglutide 0.5 mg and 0.68 [0.59 to 0.78] for semaglutide 1.0 mg). In SUSTAIN 6, UACR ratios at end of treatment (week 104) to baseline were 0.973 with semaglutide 0.5 mg, 0.858 with semaglutide 1.0 mg, and 1.302 with placebo; at week 104, greater reductions in UACR were observed with semaglutide versus placebo (estimated treatment ratios 0.75 [95% CI 0.66 to 0.85] for semaglutide 0.5 mg and 0.66 [0.58 to 0.75] for semaglutide 1.0 mg). In SUSTAIN 1-7, eGFR initially declined in patients with normal kidney function (and in those with mild kidney impairment with semaglutide 1.0 mg in SUSTAIN 6), but overall (ie, by week 30 for SUSTAIN 1-5 and SUSTAIN 7, and week 104 for SUSTAIN 6), eGFR did not differ between semaglutide and placebo. In SUSTAIN 1-6, UACR decreased in patients with pre-existing microalbuminuria or macroalbuminuria at baseline; it did not change or increased in those with normoalbuminuria at baseline. Kidney adverse events were balanced between treatment groups. INTERPRETATION: Across the SUSTAIN 1-7 trials, semaglutide was associated with initial reductions in eGFR that plateaued, and marked reductions in UACR. This post-hoc analysis suggests no increase in the risk of kidney adverse events with semaglutide versus the active comparators used across SUSTAIN 1-7. FUNDING: Novo Nordisk. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Mann, Johannes F E AU - Mann JFE AD - KfH Kidney Center, Munich, Germany; Friedrich Alexander University of Erlangen-Nurnberg, Erlangen, Germany. Electronic address: johannes.mann@kms.mhn.de. FAU - Hansen, Thomas AU - Hansen T AD - Novo Nordisk, Soborg, Denmark. FAU - Idorn, Thomas AU - Idorn T AD - Novo Nordisk, Soborg, Denmark. FAU - Leiter, Lawrence A AU - Leiter LA AD - Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada. FAU - Marso, Steven P AU - Marso SP AD - HCA Midwest Heart and Vascular Institute, Overland Park, Overland Park, KS, USA. FAU - Rossing, Peter AU - Rossing P AD - Steno Diabetes Center Copenhagen, Gentofte, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. FAU - Seufert, Jochen AU - Seufert J AD - Division of Endocrinology and Diabetology, Department of Medicine II, Medical Center -Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Tadayon, Sayeh AU - Tadayon S AD - Novo Nordisk, Soborg, Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Hellerup, Denmark. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200921 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet Diabetes Endocrinol. 2020 Nov;8(11):870-871. doi: 10.1016/S2213-8587(20)30301-6. PMID: 32971039 MH - Adult MH - Aged MH - Diabetes Mellitus, Type 2/*drug therapy/urine MH - Drug Administration Schedule MH - Female MH - Glomerular Filtration Rate/*drug effects/physiology MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Humans MH - Injections, Subcutaneous MH - Kidney/*drug effects/physiology MH - Male MH - Middle Aged MH - Treatment Outcome MH - Semaglutide EDAT- 2020/09/25 06:00 MHDA- 2020/11/04 06:00 CRDT- 2020/09/24 20:09 PHST- 2020/04/24 00:00 [received] PHST- 2020/07/16 00:00 [revised] PHST- 2020/07/20 00:00 [accepted] PHST- 2020/09/25 06:00 [pubmed] PHST- 2020/11/04 06:00 [medline] PHST- 2020/09/24 20:09 [entrez] AID - S2213-8587(20)30313-2 [pii] AID - 10.1016/S2213-8587(20)30313-2 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2020 Nov;8(11):880-893. doi: 10.1016/S2213-8587(20)30313-2. Epub 2020 Sep 21. PMID- 32945083 OWN - NLM STAT- MEDLINE DCOM- 20210705 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 23 IP - 1 DP - 2021 Jan TI - Adherence and persistence among patients with type 2 diabetes initiating dulaglutide compared with semaglutide and exenatide BCise: 6-month follow-up from US real-world data. PG - 106-115 LID - 10.1111/dom.14195 [doi] AB - AIM: To compare 6-month adherence, persistence and treatment patterns among patients initiating once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs), dulaglutide versus semaglutide, and dulaglutide versus exenatide BCise, using claims from the HealthCore Integrated Research Database. MATERIALS AND METHODS: Patients aged >/=18 years, with type 2 diabetes, >/=1 claim for dulaglutide, semaglutide or exenatide BCise during the index period February 2018 to December 2018 (index date = earliest GLP-1RA fill date), no claim for GLP-1RAs in the 6-month pre-index period, and continuous enrolment 6 months pre- and post-index were included. Dulaglutide users were propensity-matched 1:1 to semaglutide users (3852 pairs) or exenatide BCise users (1879 pairs). The proportions of adherent (proportion of days covered >/=80%) patients were compared using chi-squared tests. Persistence, measured as days to discontinuation, was analysed using a Cox regression model. RESULTS: Matched cohorts (dulaglutide:semaglutide and dulagutide:exenatide BCise) were balanced in baseline characteristics and the mean age was 54 and 55 years, respectively, with approximately 51% and 49% women, respectively. At 6 months, significantly more dulaglutide users were adherent than semaglutide (59.7% vs. 42.7%; P <0.0001) or exenatide BCise users (58.1% vs. 40.3%; P <0.0001). Cox regression showed that dulaglutide users were less likely to discontinue therapy than semaglutide (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.66, 0.76) or exenatide BCise users (HR 0.59, 95% CI 0.53, 0.65; P <0.0001, both). CONCLUSION: At 6-month follow-up, a higher proportion of patients initiating dulaglutide were adherent to and persistent with their treatment, compared to matched patients initiating either semaglutide or exenatide BCise. CI - (c) 2020 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Mody, Reema AU - Mody R AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Yu, Maria AU - Yu M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Nepal, Bal AU - Nepal B AD - HealthCore, Inc., Wilmington, Delaware, USA. FAU - Konig, Manige AU - Konig M AD - Eli Lilly and Company, Indianapolis, Indiana, USA. FAU - Grabner, Michael AU - Grabner M AD - HealthCore, Inc., Wilmington, Delaware, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201011 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Drug Administration Schedule MH - Exenatide/therapeutic use MH - Female MH - Follow-Up Studies MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Male MH - Middle Aged MH - Recombinant Fusion Proteins/therapeutic use MH - Semaglutide PMC - PMC7756843 OTO - NOTNLM OT - GLP-1 OT - dulaglutide OT - exenatide OT - type 2 diabetes COIS- R.M., M.Y. and M.K. are employees and stockholders of Eli Lilly and Company. B.N. and M.G. are employees of HealthCore Inc., a wholly owned subsidiary of Anthem Inc. HealthCore, Inc. was under contract with Eli Lilly and Company for the conduct of the study. EDAT- 2020/09/19 06:00 MHDA- 2021/07/06 06:00 PMCR- 2020/12/23 CRDT- 2020/09/18 05:56 PHST- 2020/07/14 00:00 [received] PHST- 2020/08/29 00:00 [revised] PHST- 2020/09/12 00:00 [accepted] PHST- 2020/09/19 06:00 [pubmed] PHST- 2021/07/06 06:00 [medline] PHST- 2020/09/18 05:56 [entrez] PHST- 2020/12/23 00:00 [pmc-release] AID - DOM14195 [pii] AID - 10.1111/dom.14195 [doi] PST - ppublish SO - Diabetes Obes Metab. 2021 Jan;23(1):106-115. doi: 10.1111/dom.14195. Epub 2020 Oct 11. PMID- 32912710 OWN - NLM STAT- MEDLINE DCOM- 20211015 LR - 20250418 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 15 IP - 2 DP - 2021 Apr TI - Comparison of the effects of 10 GLP-1 RA and SGLT2 inhibitor interventions on cardiovascular, mortality, and kidney outcomes in type 2 diabetes: A network meta-analysis of large randomized trials. PG - 208-211 LID - S1751-9918(20)30253-9 [pii] LID - 10.1016/j.pcd.2020.08.017 [doi] AB - The relative efficacy of different sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in reducing cardiorenal events in type 2 diabetic adults is unclear. We searched PubMed and Embase. Three primary endpoints were major adverse cardiovascular events (MACE), hospitalization for heart failure (HHF), and kidney function progression (KFP). Bayesian network meta-analysis was conducted to synthesize hazard ratio (HR) and 95% confidence interval (CI). We calculated surface under the cumulative ranking curve (SUCRA) to rank drug treatments. Subcutaneous semaglutide (HR 0.73, 95% CI 0.55-0.96) and albiglutide (HR 0.76, 95% CI 0.63-0.93) significantly reduced MACE versus lixisenatide. Canagliflozin (HRs: 0.69, 0.68, 0.67 and 0.58) and empagliflozin (HRs: 0.70, 0.69, 0.68 and 0.59) significantly reduced HHF versus dulaglutide, exenatide, lixisenatide and subcutaneous semaglutide. Dapagliflozin (HRs: 0.62, 0.60, 0.68 and 0.63) and empagliflozin (HRs: 0.64, 0.61, 0.69 and 0.64) significantly reduced KFP versus dulaglutide, exenatide, liraglutide and lixisenatide. Different drug treatments had the maximum SUCRA values as for preventing different cardiorenal endpoints. Different GLP-1 RAs and SGLT2 inhibitors have different efficacy in preventing cardiorenal endpoints in type 2 diabetes, and the most efficacious drugs are different as for preventing different cardiorenal endpoints. CI - Copyright (c) 2020 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved. FAU - Wei, Xu-Bin AU - Wei XB AD - Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. FAU - Wei, Wei AU - Wei W AD - Department of Pharmacy, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. FAU - Ding, Liang-Liang AU - Ding LL AD - Department of Cardiology, First Affiliated Hospital of Yangtze University, Jingzhou, China. FAU - Liu, Shu-Yan AU - Liu SY AD - Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address: 778091950@qq.com. LA - eng PT - Journal Article PT - Network Meta-Analysis DEP - 20200908 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Pharmaceutical Preparations) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Bayes Theorem MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Kidney MH - *Pharmaceutical Preparations MH - Randomized Controlled Trials as Topic MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects OTO - NOTNLM OT - Cardiorenal events OT - GLP-1 RAs OT - Network meta-analysis OT - SGLT2 inhibitors OT - Type 2 diabetes EDAT- 2020/09/12 06:00 MHDA- 2021/10/16 06:00 CRDT- 2020/09/11 05:37 PHST- 2020/05/28 00:00 [received] PHST- 2020/08/06 00:00 [revised] PHST- 2020/08/27 00:00 [accepted] PHST- 2020/09/12 06:00 [pubmed] PHST- 2021/10/16 06:00 [medline] PHST- 2020/09/11 05:37 [entrez] AID - S1751-9918(20)30253-9 [pii] AID - 10.1016/j.pcd.2020.08.017 [doi] PST - ppublish SO - Prim Care Diabetes. 2021 Apr;15(2):208-211. doi: 10.1016/j.pcd.2020.08.017. Epub 2020 Sep 8. PMID- 32912116 OWN - NLM STAT- MEDLINE DCOM- 20210527 LR - 20210527 IS - 1873-4286 (Electronic) IS - 1381-6128 (Linking) VI - 27 IP - 8 DP - 2021 TI - Effects of Glucagon-like Peptide-1 Receptor Agonists and Sodium-glucose Cotransporter 2 Inhibitors on Cardiorenal and Metabolic Outcomes in People Without Diabetes. PG - 1035-1042 LID - 10.2174/1381612826666200909142126 [doi] AB - During the last decade, the results of large-scale, randomized, clinical trials on newer antidiabetic agents, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium glucose cotransporter type 2 (SGLT2) inhibitor, have been published showing promising findings on cardiovascular and renal outcomes. Besides improving glycemic control, GLP-1 receptor agonists have been shown to modify cardiovascular risk factors, such as insulin resistance, body weight, blood pressure (BP), and lipid profile. Additionally, SGLT2 inhibitors except for glycemic control have been shown to induce weight loss and decrease BP. However, there are limited data regarding their effect on patients without diabetes. Therefore, the aim of the present review is to summarize the existing literature data regarding the effects of newer antidiabetic therapies on patients without diabetes. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Papazafiropoulou, Athanasia K AU - Papazafiropoulou AK AD - 1st Department of Internal Medicine and Diabetes Center, Tzaneio General Hospital of Piraeus, Greece. FAU - Melidonis, Andreas AU - Melidonis A AD - Diabetes and Cardiometabolic Center, Muetropolitan Hospital, Piraeus, Piraeus, Greece. FAU - Antonopoulos, Stavros AU - Antonopoulos S AD - 1st Department of Internal Medicine and Diabetes Center, Tzaneio General Hospital of Piraeus, Greece. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United Arab Emirates TA - Curr Pharm Des JT - Current pharmaceutical design JID - 9602487 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 9NEZ333N27 (Sodium) RN - IY9XDZ35W2 (Glucose) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Glucagon-Like Peptide-1 Receptor MH - Glucose MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Sodium OTO - NOTNLM OT - GLP-1 receptor agonists OT - Non-diabetic OT - SGLT2 inhibitors OT - canagliflozin OT - dapagliflozin OT - dulaglutide OT - empagliflozin OT - exenatide OT - liraglutide OT - semaglutide EDAT- 2020/09/12 06:00 MHDA- 2021/05/28 06:00 CRDT- 2020/09/11 05:30 PHST- 2020/07/07 00:00 [received] PHST- 2020/08/19 00:00 [accepted] PHST- 2020/09/12 06:00 [pubmed] PHST- 2021/05/28 06:00 [medline] PHST- 2020/09/11 05:30 [entrez] AID - CPD-EPUB-109828 [pii] AID - 10.2174/1381612826666200909142126 [doi] PST - ppublish SO - Curr Pharm Des. 2021;27(8):1035-1042. doi: 10.2174/1381612826666200909142126. PMID- 32910492 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20260127 IS - 1365-2710 (Electronic) IS - 0269-4727 (Print) IS - 0269-4727 (Linking) VI - 45 Suppl 1 IP - Suppl 1 DP - 2020 Sep TI - Cardiovascular safety outcomes of once-weekly GLP-1 receptor agonists in people with type 2 diabetes. PG - 61-72 LID - 10.1111/jcpt.13226 [doi] AB - WHAT IS KNOWN AND OBJECTIVE: People with type 2 diabetes (T2D) are at increased risk of cardiovascular disease (CVD), which in turn is associated with increased morbidity and mortality. The impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on cardiovascular (CV) outcomes has been investigated in CV outcomes trials (CVOTs). This review aims to help pharmacists and other healthcare professionals (HCPs) gain a better understanding of such CVOTs in T2D with a primary focus on the once-weekly (QW) GLP-1 RAs. METHODS: This narrative review mainly focuses on the evaluation of the similarities and differences in the design and results of CVOTs involving currently approved and marketed QW GLP-1 RAs-semaglutide subcutaneous, exenatide extended-release (ER) and dulaglutide. Results from CVOTs of dipeptidyl peptidase-4 inhibitors (DPP4is) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are also included. RESULTS AND DISCUSSION: Three CVOTs of QW GLP-1 RAs were identified for inclusion in this review: SUSTAIN 6 (semaglutide), EXSCEL (exenatide ER) and REWIND (dulaglutide), all of which varied in terms of trial design, patient demographics and other baseline characteristics. Results from these CVOTs demonstrated the CV safety of QW GLP-1 RAs compared with standard of care. Additionally, CV and renal benefits were demonstrated for semaglutide and dulaglutide, but not for exenatide ER. The CV safety of four DPP4is and three SGLT2is was demonstrated. None of the DPP4is had a CV or renal benefit, whereas all three SGLT2is were associated with CV and renal benefits. WHAT IS NEW AND CONCLUSION: This article provides an overview of the results from QW GLP-1 RA CVOTs, including the recently published results for dulaglutide, and places them within the broader T2D treatment landscape to help HCPs make informed decisions in daily practice. The QW GLP-1 RAs with benefits reaching beyond glycaemic control can provide a comprehensive treatment option for people with T2D at high risk of CVD, with CVD or chronic kidney disease. CI - (c) 2020 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd. FAU - Goldman, Jennifer D AU - Goldman JD AUID- ORCID: 0000-0002-9617-3998 AD - MCPHS University, Boston, MA, USA. LA - eng GR - Novo Nordisk Inc./ PT - Journal Article PT - Review PL - England TA - J Clin Pharm Ther JT - Journal of clinical pharmacy and therapeutics JID - 8704308 RN - 0 (Delayed-Action Preparations) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Cardiovascular Diseases/etiology/prevention & control MH - Delayed-Action Preparations MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Drug Administration Schedule MH - Exenatide/administration & dosage/adverse effects/pharmacology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/administration & dosage/adverse effects/analogs & derivatives/pharmacology MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacology MH - Immunoglobulin Fc Fragments/administration & dosage/pharmacology MH - Recombinant Fusion Proteins/administration & dosage/pharmacology MH - Research Design MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC7540076 OTO - NOTNLM OT - cardiovascular disease OT - cardiovascular outcomes trials OT - glucagon-like peptide-1 receptor agonist OT - safety OT - type 2 diabetes COIS- JD Goldman reports serving on speaker's bureau for Novo Nordisk and Sanofi and as a consultant for Becton Dickinson. EDAT- 2020/09/11 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/10/07 CRDT- 2020/09/10 12:28 PHST- 2020/02/05 00:00 [received] PHST- 2020/05/07 00:00 [revised] PHST- 2020/05/13 00:00 [accepted] PHST- 2020/09/10 12:28 [entrez] PHST- 2020/09/11 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/10/07 00:00 [pmc-release] AID - JCPT13226 [pii] AID - 10.1111/jcpt.13226 [doi] PST - ppublish SO - J Clin Pharm Ther. 2020 Sep;45 Suppl 1(Suppl 1):61-72. doi: 10.1111/jcpt.13226. PMID- 32910490 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20250103 IS - 1365-2710 (Electronic) IS - 0269-4727 (Print) IS - 0269-4727 (Linking) VI - 45 Suppl 1 IP - Suppl 1 DP - 2020 Sep TI - A review of GLP-1 receptor agonists in type 2 diabetes: A focus on the mechanism of action of once-weekly agents. PG - 17-27 LID - 10.1111/jcpt.13230 [doi] AB - WHAT IS KNOWN AND OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are one of the preferred approved treatment options for people with type 2 diabetes (T2D) and inadequate glycaemic control. The objective of this review is to provide a general clinical overview of the similarities and differences in the mechanisms of action (MoA) of the once-weekly GLP-1 RA class of medications, highlighting the role of pharmacists in providing optimal medication management, education and care for people with diabetes. METHODS: This is a narrative review of the published literature regarding the MoA of the currently available once-weekly GLP-1 RAs in T2D. RESULTS AND DISCUSSION: GLP-1 RAs have an established efficacy and safety profile. Their benefits derive from their blood glucose-lowering effects, which include pancreatic beta-cell-mediated glucose-dependent insulin secretion and suppressed glucagon release, and their ability to slow gastric emptying and promote satiety. GLP-1 RAs may also exert beneficial effects on multiple organ systems in which GLP-1 receptors are present, including the cardiovascular and renal systems. Differences between individual GLP-1 RAs with regard to their molecular size, structure and duration of action (short or longer acting) have led to differing pharmacodynamics and clinical effects such as degree of glycaemic control, weight loss abilities, cardiovascular effects and tolerability profiles. WHAT IS NEW AND CONCLUSION: From the literature, this appears to be the first review of the evidence base supporting the MoA of once-weekly GLP-1 RAs in T2D aimed at pharmacists, with a particular emphasis on the expanding role of pharmacists in team-based diabetes management. As a class, GLP-1 RAs are an effective treatment option for people with T2D, shown to achieve multi-factorial clinical benefits. The results suggest that when selecting or advising about treatments, pharmacists should consider how the different once-weekly GLP-1 RAs and their MoA affect clinical outcomes in order to ensure optimal treatment for individuals. CI - (c) 2020 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd. FAU - Cornell, Susan AU - Cornell S AUID- ORCID: 0000-0002-9934-035X AD - Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA. LA - eng GR - Novo Nordisk Inc./ PT - Journal Article PT - Review PL - England TA - J Clin Pharm Ther JT - Journal of clinical pharmacy and therapeutics JID - 8704308 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Blood Glucose/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - Drug Administration Schedule MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glycemic Control/methods MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacology MH - Patient Care Team/organization & administration MH - Pharmacists/organization & administration MH - Professional Role MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC7540167 OTO - NOTNLM OT - Type 2 diabetes OT - cardiovascular diseases OT - diabetes mellitus OT - dulaglutide OT - exenatide OT - glucagon-like peptide-1 receptor agonist OT - glycaemic control OT - mechanism of action OT - semaglutide COIS- S Cornell serves on the advanced practitioner advisory board for Novo Nordisk and Becton Dickinson. EDAT- 2020/09/11 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/10/07 CRDT- 2020/09/10 12:28 PHST- 2020/02/05 00:00 [received] PHST- 2020/04/24 00:00 [revised] PHST- 2020/05/10 00:00 [accepted] PHST- 2020/09/10 12:28 [entrez] PHST- 2020/09/11 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/10/07 00:00 [pmc-release] AID - JCPT13230 [pii] AID - 10.1111/jcpt.13230 [doi] PST - ppublish SO - J Clin Pharm Ther. 2020 Sep;45 Suppl 1(Suppl 1):17-27. doi: 10.1111/jcpt.13230. PMID- 32910489 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20260127 IS - 1365-2710 (Electronic) IS - 0269-4727 (Print) IS - 0269-4727 (Linking) VI - 45 Suppl 1 IP - Suppl 1 DP - 2020 Sep TI - Glycaemic and non-glycaemic efficacy of once-weekly GLP-1 receptor agonists in people with type 2 diabetes. PG - 28-42 LID - 10.1111/jcpt.13224 [doi] AB - WHAT IS KNOWN AND OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may confer a range of benefits for people with type 2 diabetes (T2D), which is reflected through their position within diabetes treatment guidelines. The objective of this narrative review is to explore the efficacy data of once-weekly (QW) GLP-1 RAs in terms of glycaemic control, body weight reduction, cardiovascular (CV) outcomes and potential renal protective effects to assist pharmacists and other healthcare professionals (HCPs) in treatment discussions with patients. METHODS: This a narrative review focused on 31 clinical trials involving the Phase 3 clinical programmes of the QW GLP-1 RAs dulaglutide, exenatide extended-release (ER) and semaglutide subcutaneous (s.c.). RESULTS AND DISCUSSION: The clinical trials were divided by their comparator arms and examined for trends. All QW GLP-1 RAs were superior to placebo for reductions in glycated haemoglobin (HbA(1c) ) and body weight. Data regarding QW GLP-1 RAs versus metformin were limited, likely due to metformin's use as the first-line pharmacologic for T2D. In the robust head-to-head trials of QW versus QW GLP-1 RAs, semaglutide s.c. was superior to both dulaglutide and exenatide ER regarding HbA(1c) and body weight; however, QW versus once-daily GLP-1 RA trials had mixed results depending on the comparators. Finally, in QW GLP-1 RA versus insulin trials, all QW GLP-1 RAs were as effective as insulin, particularly when hypoglycaemia and body weight were also considered. CV outcome trials demonstrated benefits in major adverse CV events and renal outcomes for semaglutide and dulaglutide. WHAT IS NEW AND CONCLUSION: This review collates recently published data and previously published Phase 3 results to allow pharmacists and other HCPs to understand all of the efficacy data available and the corresponding impact on treatment guidelines. QW GLP-1 RAs are emerging as important therapeutic options for people with T2D as they offer a spectrum of benefits extending beyond glycaemic control, but it is important to be aware of their efficacy differences when prescribing and discussing them with patients. CI - (c) 2020 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd. FAU - Patel, Dhiren AU - Patel D AUID- ORCID: 0000-0001-6450-8557 AD - VA Boston Healthcare System, Boston, MA, USA. LA - eng GR - Novo Nordisk Inc./ PT - Journal Article PT - Review PL - England TA - J Clin Pharm Ther JT - Journal of clinical pharmacy and therapeutics JID - 8704308 RN - 0 (Blood Glucose) RN - 0 (Delayed-Action Preparations) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Blood Glucose/drug effects MH - Delayed-Action Preparations MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - Drug Administration Schedule MH - Exenatide/administration & dosage/pharmacology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/administration & dosage/analogs & derivatives/pharmacology MH - Humans MH - Hypoglycemic Agents/*administration & dosage/pharmacology MH - Immunoglobulin Fc Fragments/administration & dosage/pharmacology MH - Recombinant Fusion Proteins/administration & dosage/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC7540306 OTO - NOTNLM OT - efficacy OT - glucagon-like peptide-1 receptor agonist OT - glycaemic control OT - type 2 diabetes OT - weight loss COIS- D Patel is an advisory board member and/or consultant for AstraZeneca, Becton Dickinson, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk and Sanofi; and is on the speakers' bureau for AstraZeneca, Boehringer Ingelheim, Merck, Novo Nordisk and Valeritas. EDAT- 2020/09/11 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/10/07 CRDT- 2020/09/10 12:28 PHST- 2020/02/07 00:00 [received] PHST- 2020/05/10 00:00 [accepted] PHST- 2020/09/10 12:28 [entrez] PHST- 2020/09/11 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/10/07 00:00 [pmc-release] AID - JCPT13224 [pii] AID - 10.1111/jcpt.13224 [doi] PST - ppublish SO - J Clin Pharm Ther. 2020 Sep;45 Suppl 1(Suppl 1):28-42. doi: 10.1111/jcpt.13224. PMID- 32910488 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20260127 IS - 1365-2710 (Electronic) IS - 0269-4727 (Print) IS - 0269-4727 (Linking) VI - 45 Suppl 1 IP - Suppl 1 DP - 2020 Sep TI - Managing the multifaceted nature of type 2 diabetes using once-weekly injectable GLP-1 receptor agonist therapy. PG - 7-16 LID - 10.1111/jcpt.13229 [doi] AB - WHAT IS KNOWN AND OBJECTIVE: As a highly prevalent chronic condition associated with complications and high mortality rates, it is important for pharmacists to have a comprehensive understanding of the impact of type 2 diabetes (T2D) and available treatment options. The use of injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is recommended as an effective and convenient treatment regimen for improving glycaemic control in individuals with T2D, with a good safety profile; however, the wider extent of its potential benefits often are unknown to clinical pharmacists. The objective of this article is to provide an overview of the impact of T2D on individuals and to discuss the multifaceted role of once-weekly (QW) GLP-1 RAs in addressing these challenges. METHODS: This is a narrative review of the published literature regarding the use of injectable GLP-1 RAs in managing health complications in people with T2D. RESULTS AND DISCUSSION: Recent findings reveal additional benefits of GLP-1 RAs in managing T2D complications, including atherosclerotic cardiovascular (CV) disease, retinopathy, neuropathy, and nephropathy. Dulaglutide and semaglutide have been shown to provide additional CV benefit in patients at high risk of CV events compared with standard of care/placebo and may offer renal protection in patients with chronic kidney disease. Cost-effectiveness studies, taking into consideration these different complications, have shown that QW GLP-1 RAs were cost-effective compared with other therapies. GLP-1 RAs may also help to improve overall health-related quality of life, reducing the risk of depression and 'diabetes distress', and limiting the risk of hypoglycaemia. WHAT IS NEW AND CONCLUSION: From the literature, this appears to be the first review of the evidence supporting the multifaceted role of QW GLP-1 RAs in T2D, with particular emphasis on their use in comorbid conditions, as well as associated potential financial and well-being benefits. The results suggest that QW GLP-1 RAs may be an attractive treatment option for improving glycaemic control in T2D, especially in individuals with (or at risk of) additional comorbidities or health complications. CI - (c) 2020 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd. FAU - Bzowyckyj, Andrew AU - Bzowyckyj A AUID- ORCID: 0000-0002-9007-5852 AD - Pacific University Oregon School of Pharmacy, Hillsboro, OR, USA. LA - eng GR - Novo Nordisk Inc./ PT - Journal Article PT - Review PL - England TA - J Clin Pharm Ther JT - Journal of clinical pharmacy and therapeutics JID - 8704308 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Drug Administration Schedule MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/administration & dosage/analogs & derivatives/pharmacology MH - Glycemic Control/methods MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacology MH - Immunoglobulin Fc Fragments/administration & dosage/pharmacology MH - Quality of Life MH - Recombinant Fusion Proteins/administration & dosage/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC7540468 OTO - NOTNLM OT - comorbidities OT - dulaglutide OT - economic impact OT - exenatide OT - glucagon-like peptide-1 receptor agonist OT - glycaemic control OT - management OT - semaglutide OT - treatment burden OT - type 2 diabetes mellitus COIS- A Bzowyckyj has no relevant conflicts of interest to declare. EDAT- 2020/09/11 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/10/07 CRDT- 2020/09/10 12:28 PHST- 2020/02/06 00:00 [received] PHST- 2020/04/24 00:00 [revised] PHST- 2020/05/10 00:00 [accepted] PHST- 2020/09/10 12:28 [entrez] PHST- 2020/09/11 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/10/07 00:00 [pmc-release] AID - JCPT13229 [pii] AID - 10.1111/jcpt.13229 [doi] PST - ppublish SO - J Clin Pharm Ther. 2020 Sep;45 Suppl 1(Suppl 1):7-16. doi: 10.1111/jcpt.13229. PMID- 32910487 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20260127 IS - 1365-2710 (Electronic) IS - 0269-4727 (Print) IS - 0269-4727 (Linking) VI - 45 Suppl 1 IP - Suppl 1 DP - 2020 Sep TI - Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes. PG - 43-60 LID - 10.1111/jcpt.13225 [doi] AB - WHAT IS KNOWN AND OBJECTIVE: In recent years, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) including once-weekly (QW) formulations have been incorporated into type 2 diabetes (T2D) clinical guidelines, making it essential that pharmacists and healthcare professionals (HCPs) have a clear understanding of their safety profiles. Currently, three QW GLP-1 RAs are approved and marketed in the United States for the treatment of T2D: dulaglutide, exenatide extended-release and semaglutide. This review provides pharmacists and HCPs with collated data related to potential safety and tolerability issues when patients use QW GLP-1 RAs, enabling patient education and treatment optimization. METHODS: This is a narrative review comparing the safety and tolerability of the three QW GLP-1 RAs, using data from Phase 3 clinical trials. Extracted safety data included gastrointestinal (GI) adverse events (AEs), hypoglycaemia, injection-site reactions, pancreatitis, neoplasms, gallbladder events, and diabetic retinopathy (DR) and/or its complications (DRCs). RESULTS AND DISCUSSION: A total of 30 trials were identified for inclusion; eight were head-to-head trials involving another GLP-1 RA; of these, six compared GLP-1 RAs with different dosing regimens (QW vs once-daily or twice-daily), and two were direct QW vs QW GLP-1 RA comparisons. The most commonly reported AEs were GI events (notably nausea, vomiting and diarrhoea), but there was variation between the three QW drugs. These were generally mild-to-moderate in severity and transient. Risk of hypoglycaemia, injection-site reactions, pancreatitis, neoplasms and gallbladder events was generally low across the GLP-1 RAs investigated. Overall rates of DR or DRC were low across the trials. Only in one trial (SUSTAIN 6) there were significantly more DRC events reported in patients treated with QW semaglutide (3.0%) compared with placebo (1.8%). This was likely due to the rapid improvement in glucose control in patients with pre-existing DR enrolled within that trial. WHAT IS NEW AND CONCLUSION: This review puts the latest clinical data from the marketed QW GLP-1 RAs into context with results from older Phase 3 trials, to enable pharmacists and HCPs to make informed treatment decisions. Each of the three QW GLP-1 RAs has their own safety profile, which should be considered when choosing the optimal treatment for patients. CI - (c) 2020 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd. FAU - Trujillo, Jennifer AU - Trujillo J AUID- ORCID: 0000-0001-7898-8029 AD - Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA. LA - eng GR - Novo Nordisk Inc./ PT - Journal Article PT - Review PL - England TA - J Clin Pharm Ther JT - Journal of clinical pharmacy and therapeutics JID - 8704308 RN - 0 (Blood Glucose) RN - 0 (Delayed-Action Preparations) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Blood Glucose/drug effects MH - Delayed-Action Preparations MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - Drug Administration Schedule MH - Exenatide/administration & dosage/adverse effects/pharmacology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/administration & dosage/adverse effects/analogs & derivatives/pharmacology MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacology MH - Immunoglobulin Fc Fragments/administration & dosage/adverse effects/pharmacology MH - Recombinant Fusion Proteins/administration & dosage/adverse effects/pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC7540535 OTO - NOTNLM OT - GLP-1 RA OT - dulaglutide OT - exenatide OT - safety OT - semaglutide OT - tolerability OT - type 2 diabetes COIS- J Trujillo has acted as a consultant and advisory board member for Novo Nordisk, Sanofi and BD Pharmaceuticals. EDAT- 2020/09/11 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/10/07 CRDT- 2020/09/10 12:28 PHST- 2020/02/05 00:00 [received] PHST- 2020/04/30 00:00 [revised] PHST- 2020/05/13 00:00 [accepted] PHST- 2020/09/10 12:28 [entrez] PHST- 2020/09/11 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/10/07 00:00 [pmc-release] AID - JCPT13225 [pii] AID - 10.1111/jcpt.13225 [doi] PST - ppublish SO - J Clin Pharm Ther. 2020 Sep;45 Suppl 1(Suppl 1):43-60. doi: 10.1111/jcpt.13225. PMID- 32900588 OWN - NLM STAT- MEDLINE DCOM- 20201204 LR - 20250103 IS - 1873-460X (Electronic) IS - 1056-8727 (Print) IS - 1056-8727 (Linking) VI - 34 IP - 12 DP - 2020 Dec TI - Anti-inflammatory properties of antidiabetic drugs: A "promised land" in the COVID-19 era? PG - 107723 LID - S1056-8727(20)30498-0 [pii] LID - 10.1016/j.jdiacomp.2020.107723 [doi] AB - Inflammation is implicated in the development and severity of the coronavirus disease 2019 (COVID-19), as well as in the pathophysiology of diabetes. Diabetes, especially when uncontrolled, is also recognized as an important risk factor for COVID-19 morbidity and mortality. Furthermore, certain inflammatory markers [i.e. C-reactive protein (CRP), interleukin-6 (IL-6) and ferritin] were reported as strong predictors of worse outcomes in COVID-19 positive patients. The same biomarkers have been associated with poor glycemic control. Therefore, achieving euglycemia in patients with diabetes is even more important in the era of the COVID-19 pandemic. Based on the above, it is clinically interesting to elucidate whether antidiabetic drugs may reduce inflammation, thus possibly minimizing the risk for COVID-19 development and severity. The present narrative review discusses the potential anti-inflammatory properties of certain antidiabetic drugs (i.e. metformin, pioglitazone, sitagliptin, linagliptin, vildagliptin, alogliptin, saxagliptin, liraglutide, dulaglutide, exenatide, lixisenatide, semaglutide, empagliflozin, dapagliflozin, canagliflozin), with a focus on CRP, IL-6 and ferritin. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Katsiki, Niki AU - Katsiki N AD - First Department of Internal Medicine, Diabetes Center, Division of Endocrinology and Metabolism, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece. FAU - Ferrannini, Ele AU - Ferrannini E AD - C.N.R. Institute of Clinical Physiology, Pisa, Italy. Electronic address: ferranni@ifc.cnr.it. LA - eng PT - Journal Article PT - Review DEP - 20200826 PL - United States TA - J Diabetes Complications JT - Journal of diabetes and its complications JID - 9204583 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 9100L32L2N (Metformin) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - X4OV71U42S (Pioglitazone) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Anti-Inflammatory Agents MH - COVID-19/*epidemiology/physiopathology/prevention & control MH - Comorbidity MH - Diabetes Mellitus, Type 2/*drug therapy/*epidemiology/physiopathology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Inflammation/*prevention & control MH - Metformin/therapeutic use MH - Pioglitazone/therapeutic use MH - Risk Factors MH - *SARS-CoV-2 MH - Sitagliptin Phosphate/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC7448766 OTO - NOTNLM OT - C-reactive protein OT - Dipeptidyl peptidase 4 inhibitors OT - Ferritin OT - Glucagon-like peptide-1 receptor agonists OT - Interleukin 6 OT - Metformin OT - Pioglitazone OT - Sodium-glucose co-transporter-2 inhibitors COIS- Declaration of competing interest NK has given talks, attended conferences and participated in trials sponsored by Astra Zeneca, Bausch Health, Boehringer Ingelheim, Elpen, Mylan, NovoNordisk, Sanofi and Servier. EF has received research support by Boehringher Ingelheim/Lilly&Co., AstraZeneca and Janssen and speaker's honoraria by Boehringer Ingelheim/Lilly&Co., Sanofi and AstraZeneca. EDAT- 2020/09/10 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/08/26 CRDT- 2020/09/09 05:24 PHST- 2020/06/10 00:00 [received] PHST- 2020/08/21 00:00 [revised] PHST- 2020/08/21 00:00 [accepted] PHST- 2020/09/10 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/09/09 05:24 [entrez] PHST- 2020/08/26 00:00 [pmc-release] AID - S1056-8727(20)30498-0 [pii] AID - 107723 [pii] AID - 10.1016/j.jdiacomp.2020.107723 [doi] PST - ppublish SO - J Diabetes Complications. 2020 Dec;34(12):107723. doi: 10.1016/j.jdiacomp.2020.107723. Epub 2020 Aug 26. PMID- 32897887 OWN - NLM STAT- MEDLINE DCOM- 20211130 LR - 20260127 IS - 1538-4683 (Electronic) IS - 1061-5377 (Linking) VI - 29 IP - 2 DP - 2021 Mar-Apr 01 TI - Semaglutide: A Novel Oral Glucagon-Like Peptide Receptor Agonist for the Treatment of Type 2 Diabetes Mellitus. PG - 100-108 LID - 10.1097/CRD.0000000000000351 [doi] AB - Diabetes mellitus (DM) is a complex and chronic condition that requires continuous medical care. Uncontrolled hyperglycemia can lead to serious microvascular and macrovascular complications, such as coronary artery disease, peripheral arterial disease, and stroke. Type 2 DM occurs when the pancreas is unable to produce adequate insulin to regulate glucose levels and when there is a decrease in sensitivity to insulin in the body. Insufficient glucagon-like peptide (GLP-1), a normal body hormone, plays an important role in the pathophysiology of DM. The introduction of the GLP-1 receptor agonists expanded therapeutic options in achieving glycemic control in adult patients. In 2005, the US Food and Drug Administration approved exenatide as the first injectable formulation, which led to the advancement of other injectable formulations within the class of GLP-1 receptor agonists. In 2019, semaglutide was approved as the first oral GLP-1 receptor agonist addressing the unmet needs in patients who benefit from therapy with this therapeutic class yet are unwilling to use an injectable drug. This article will provide an overview of the GLP-1 receptor agonists, including the pharmacology of semaglutide, its clinical evidence and role in therapy in type 2 DM. CI - Copyright (c) 2020 Wolters Kluwer Health, Inc. All rights reserved. FAU - Chan, Mabel AU - Chan M AD - From the Department of Pharmacy, NYU Winthrop Hospital, Mineola, NY. FAU - Dimitriou, Alexis AU - Dimitriou A AD - From the Department of Pharmacy, NYU Winthrop Hospital, Mineola, NY. FAU - Lam, Sum AU - Lam S AD - Department of Clinical Health Professions, College of Pharmacy and Health Sciences, St John's University, Queens, NY; and. AD - Divisions of Geriatric Medicine & Pharmacy, NYU Winthrop Hospital, Mineola, NY. LA - eng PT - Journal Article PL - United States TA - Cardiol Rev JT - Cardiology in review JID - 9304686 RN - 0 (Glucagon-Like Peptide Receptors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide Receptors MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Insulin MH - Semaglutide COIS- Disclosure: The authors declare no conflict of interest. EDAT- 2020/09/09 06:00 MHDA- 2021/12/01 06:00 CRDT- 2020/09/08 17:11 PHST- 2020/09/09 06:00 [pubmed] PHST- 2021/12/01 06:00 [medline] PHST- 2020/09/08 17:11 [entrez] AID - 00045415-202103000-00009 [pii] AID - 10.1097/CRD.0000000000000351 [doi] PST - ppublish SO - Cardiol Rev. 2021 Mar-Apr 01;29(2):100-108. doi: 10.1097/CRD.0000000000000351. PMID- 32897147 OWN - NLM STAT- MEDLINE DCOM- 20211222 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 132 IP - sup2 DP - 2020 Nov TI - Introducing a novel therapy for type 2 diabetes to primary care. PG - 1-2 LID - 10.1080/00325481.2020.1798686 [doi] FAU - Brunton, Stephen A AU - Brunton SA AD - Touro University California , Vallejo, CA, USA. LA - eng PT - Journal Article DEP - 20200908 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Lipids) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Blood Pressure MH - Diabetes Mellitus, Type 2/*drug therapy/therapy MH - Glycated Hemoglobin MH - Humans MH - Hypoglycemic Agents/administration & dosage/adverse effects/*therapeutic use MH - Lipids/blood MH - Practice Guidelines as Topic MH - Primary Health Care/*organization & administration/standards MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Type 2 diabetes OT - glucagon-like peptide-1 receptor agonist OT - oral semaglutide OT - primary care EDAT- 2020/09/09 06:00 MHDA- 2021/12/24 06:00 CRDT- 2020/09/08 12:12 PHST- 2020/09/09 06:00 [pubmed] PHST- 2021/12/24 06:00 [medline] PHST- 2020/09/08 12:12 [entrez] AID - 10.1080/00325481.2020.1798686 [doi] PST - ppublish SO - Postgrad Med. 2020 Nov;132(sup2):1-2. doi: 10.1080/00325481.2020.1798686. Epub 2020 Sep 8. PMID- 32893459 OWN - NLM STAT- MEDLINE DCOM- 20210903 LR - 20250103 IS - 1467-789X (Electronic) IS - 1467-7881 (Linking) VI - 22 IP - 1 DP - 2021 Jan TI - Cardiovascular outcome trials in obesity: A review. PG - e13112 LID - 10.1111/obr.13112 [doi] AB - Obesity is a global epidemic associated with over 200 health complications and a significant risk of developing cardiovascular disease (CVD), partly by increasing classical risk factors such as lipid and glucose levels and blood pressure. Weight loss through lifestyle interventions, pharmacotherapy and/or bariatric surgery improves CV risk factors. Cardiovascular outcome trials (CVOTs) of anti-obesity medications aim to evaluate the CV safety and benefits of pharmacotherapy. Many CVOTs in obesity have either failed to demonstrate a CV benefit or have been terminated prematurely because of safety issues, prompting regulatory agencies to define new requirements (based on those for CVOTs in type 2 diabetes [T2D]). CVOTs of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in T2D have demonstrated that some GLP-1RAs reduce CV risk and may help inform future CVOTs in obesity, given the approval of liraglutide 3.0 mg for obesity. In this review, the evidence for the link between obesity and CVD is considered in the context of studies showing that weight loss improves markers of CV risk and risk of adverse CV events. The review also examines the CVOTs in obesity that have been conducted to date and those under way, such as the SELECT trial with subcutaneous semaglutide of 2.4 mg. CI - (c) 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation. FAU - Wilding, John P H AU - Wilding JPH AUID- ORCID: 0000-0003-2839-8404 AD - Department of Cardiovascular and Metabolic Medicine, Institute of Lifecourse and Medical Sciences, University of Liverpool, Liverpool, UK. FAU - Jacob, Stephan AU - Jacob S AUID- ORCID: 0000-0002-4954-1145 AD - Department of Internal Medicine, Division of Endocrinology/Diabetology, Cardiometabolic Institute, Villingen-Schwenningen, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20200907 PL - England TA - Obes Rev JT - Obesity reviews : an official journal of the International Association for the Study of Obesity JID - 100897395 RN - 0 (Anti-Obesity Agents) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Anti-Obesity Agents/therapeutic use MH - *Cardiovascular Diseases/prevention & control MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - *Obesity/complications MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - anti-obesity medications OT - cardiovascular OT - obesity OT - outcome trial EDAT- 2020/09/08 06:00 MHDA- 2021/09/04 06:00 CRDT- 2020/09/07 06:02 PHST- 2020/05/11 00:00 [received] PHST- 2020/07/03 00:00 [revised] PHST- 2020/07/09 00:00 [accepted] PHST- 2020/09/08 06:00 [pubmed] PHST- 2021/09/04 06:00 [medline] PHST- 2020/09/07 06:02 [entrez] AID - 10.1111/obr.13112 [doi] PST - ppublish SO - Obes Rev. 2021 Jan;22(1):e13112. doi: 10.1111/obr.13112. Epub 2020 Sep 7. PMID- 32890462 OWN - NLM STAT- MEDLINE DCOM- 20210409 LR - 20260127 IS - 1751-486X (Electronic) IS - 1751-4851 (Linking) VI - 24 IP - 5 DP - 2020 Oct TI - Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. PG - 370-376 LID - S1751-4851(20)30140-9 [pii] LID - 10.1016/j.nwh.2020.07.005 [doi] AB - Semaglutide is an oral glucagon-like peptide receptor agonist approved in 2019 by the U.S. Food and Drug Administration. It is marketed under the brand name Rybelsus and was approved to be used in conjunction with lifestyle modifications to treat individuals with type 2 diabetes. It is the first in its drug class to be administered in a once-daily oral form. Through its actions on glucose control and body weight, this once-daily oral medication could contribute to better glycemic control and healthier lives for many women with type 2 diabetes. CI - Copyright (c) 2020 AWHONN. Published by Elsevier Inc. All rights reserved. FAU - Blakely, Kala K AU - Blakely KK FAU - Weaver, Kendra AU - Weaver K LA - eng PT - Journal Article DEP - 20200902 PL - United States TA - Nurs Womens Health JT - Nursing for women's health JID - 101304602 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) MH - Administration, Oral MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy MH - Female MH - Glucagon-Like Peptides/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - Rybelsus OT - diabetes OT - glucagon-like peptide-1 OT - oral OT - receptor agonist OT - semaglutide OT - type 2 diabetes EDAT- 2020/09/06 06:00 MHDA- 2021/04/10 06:00 CRDT- 2020/09/05 20:06 PHST- 2019/12/10 00:00 [received] PHST- 2020/03/07 00:00 [revised] PHST- 2020/07/01 00:00 [accepted] PHST- 2020/09/06 06:00 [pubmed] PHST- 2021/04/10 06:00 [medline] PHST- 2020/09/05 20:06 [entrez] AID - S1751-4851(20)30140-9 [pii] AID - 10.1016/j.nwh.2020.07.005 [doi] PST - ppublish SO - Nurs Womens Health. 2020 Oct;24(5):370-376. doi: 10.1016/j.nwh.2020.07.005. Epub 2020 Sep 2. PMID- 32886267 OWN - NLM STAT- MEDLINE DCOM- 20210414 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Linking) VI - 37 IP - 10 DP - 2020 Oct TI - Oral Semaglutide, A New Option in the Management of Type 2 Diabetes Mellitus: A Narrative Review. PG - 4165-4174 LID - 10.1007/s12325-020-01478-9 [doi] AB - According to current guidelines, glucagon-like peptide-1 (GLP-1) receptor agonists are the antidiabetic agent of choice in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD) and are also the preferable antidiabetic agent in patients with T2DM without CVD but with indicators of high cardiovascular risk. A limitation in the use of GLP-1 receptor agonists is that they are delivered by subcutaneous injections. In this context, the development of an orally administered formulation of semaglutide offers an additional option in the management of patients with T2DM. In the present review, we discuss the findings of the main trials that evaluated the safety and efficacy of oral semaglutide. Oral semaglutide appears to be more effective in reducing HbA(1c) levels and body weight than other antidiabetic agents and similarly effective to other GLP-1 receptor agonists. The safety profile of oral semaglutide is also comparable with other members of its class. Even though oral semaglutide did not reduce the incidence of the composite primary endpoint in a randomized controlled trial, a reduction in cardiovascular and all-cause mortality was observed. Therefore, oral semaglutide appears to represent a useful tool in the management of patients with TD2M, particularly those with established CVD or high cardiovascular risk and unwilling to receive injectable GLP-1 receptor agonists. FAU - Sofogianni, Areti AU - Sofogianni A AD - First Propedeutic Department of Internal Medicine, Medical School, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Tziomalos, Konstantinos AU - Tziomalos K AUID- ORCID: 0000-0002-3172-1594 AD - First Propedeutic Department of Internal Medicine, Medical School, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. ktziomalos@yahoo.com. LA - eng PT - Journal Article PT - Review DEP - 20200904 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) MH - Humans MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - *Glucagon-Like Peptides/administration & dosage MH - Hypoglycemic Agents/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists/administration & dosage MH - Administration, Oral MH - Semaglutide OTO - NOTNLM OT - Cardiovascular disease OT - Glucagon-like peptide-1 receptor agonists OT - Oral semaglutide OT - Type 2 diabetes mellitus OT - Weight EDAT- 2020/09/05 06:00 MHDA- 2021/04/15 06:00 CRDT- 2020/09/05 06:00 PHST- 2020/07/01 00:00 [received] PHST- 2020/09/05 06:00 [pubmed] PHST- 2021/04/15 06:00 [medline] PHST- 2020/09/05 06:00 [entrez] AID - 10.1007/s12325-020-01478-9 [pii] AID - 10.1007/s12325-020-01478-9 [doi] PST - ppublish SO - Adv Ther. 2020 Oct;37(10):4165-4174. doi: 10.1007/s12325-020-01478-9. Epub 2020 Sep 4. PMID- 32873415 OWN - NLM STAT- MEDLINE DCOM- 20210524 LR - 20260127 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 42 IP - 10 DP - 2020 Oct TI - Oral Semaglutide: The First-available Noninjectable Glucagon-like Peptide 1 Receptor Agonist. PG - 2100-2116 LID - S0149-2918(20)30351-9 [pii] LID - 10.1016/j.clinthera.2020.07.017 [doi] AB - PURPOSE: There are roughly 30 million Americans diagnosed with diabetes mellitus (DM), with nearly 95% of these cases being type 2 (T2)-DM. The American Diabetes Association continues to recommend metformin as the first-line initial treatment of T2DM, in combination with lifestyle modifications; yet, many require multiple therapies to achieve adequate glycemic control. In patients with atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, adding a glucagon-like peptide 1 receptor agonist is a preferred treatment option; however, many patients are apprehensive about injecting medications. Semaglutide is the first oral option in this life-saving medication class. The purpose of this article was to review the pharmacology, clinical trials, safety profile, along with recommended dosing and costs, of oral semaglutide used for managing patients with T2DM. METHODS: A search through the PubMed, MEDLINE and Cochrane libraries was conducted for literature published from January 2017 through December 2020, using the key word semaglutide. Articles were selected if they were related to the approval of oral semaglutide or provided novel clinical information regarding this drug entity in its oral dosage formulation. FINDINGS: Three Phase II studies of the pharmacokinetic properties and Phase III trials from the PIONEER series were ultimately selected, as these trials were thought to provide pivotal information to the US Food and Drug Administration for the approval of oral semaglutide. IMPLICATIONS: On review of the literature, it appeared that semaglutide is a viable option in treating T2DM. The use of this medication has been associated with glycosylated hemoglobin lowering similar to that with the injectable medication in its same class. Semaglutide was also showed some potential in preventing cardiovascular events as well as increasing weight loss. CI - Published by Elsevier Inc. FAU - Powell, Jason AU - Powell J AD - College of Medicine, University of Florida, Gainesville, FL, USA; College of Pharmacy, University of Florida, Gainesville, FL, USA. Electronic address: jpowell@cop.ufl.edu. FAU - Piszczatoski, Chris AU - Piszczatoski C AD - College of Medicine, University of Florida, Gainesville, FL, USA; College of Pharmacy, University of Florida, Gainesville, FL, USA. FAU - Taylor, James R AU - Taylor JR AD - College of Pharmacy, University of Florida, Gainesville, FL, USA. LA - eng PT - Journal Article PT - Review DEP - 20200829 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/*administration & dosage MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Metformin/therapeutic use MH - Renal Insufficiency, Chronic/complications MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonists OT - diabetes OT - oral antidiabetics OT - semaglutide EDAT- 2020/09/03 06:00 MHDA- 2021/05/25 06:00 CRDT- 2020/09/03 06:00 PHST- 2020/05/04 00:00 [received] PHST- 2020/07/27 00:00 [revised] PHST- 2020/07/28 00:00 [accepted] PHST- 2020/09/03 06:00 [pubmed] PHST- 2021/05/25 06:00 [medline] PHST- 2020/09/03 06:00 [entrez] AID - S0149-2918(20)30351-9 [pii] AID - 10.1016/j.clinthera.2020.07.017 [doi] PST - ppublish SO - Clin Ther. 2020 Oct;42(10):2100-2116. doi: 10.1016/j.clinthera.2020.07.017. Epub 2020 Aug 29. PMID- 32870471 OWN - NLM STAT- MEDLINE DCOM- 20210414 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Linking) VI - 37 IP - 10 DP - 2020 Oct TI - Lower Drug Cost of Successfully Treating Patients with Type 2 Diabetes to Targets with Once-Weekly Semaglutide versus Once-weekly Dulaglutide in Japan: A Short-Term Cost-Effectiveness Analysis. PG - 4446-4457 LID - 10.1007/s12325-020-01476-x [doi] AB - INTRODUCTION: In the head-to-head trial (SUSTAIN 7), the novel, injectable, once-weekly GLP-1 analogue semaglutide showed superiority in both glycemic outcomes and body weight reduction, compared with once-weekly dulaglutide in the treatment of type 2 diabetes (T2D). However, no economic evaluation using these data has yet been conducted in the Japanese setting. The objective of this analysis was to assess the short-term cost-effectiveness in Japan of once-weekly semaglutide 0.5 mg (the approved maintenance dose in Japan) compared with once-weekly dulaglutide 0.75 mg (the only licensed dose in Japan) over a 1-year period using Japanese cost data. METHODS: Responder endpoints were obtained from the SUSTAIN 7 trial to assess the cost of successfully treating patients to these targets ("cost of control"). Responder endpoint definitions consisted of single, dual, and triple composite endpoints related to glycemic control, body weight, and hypoglycemia outcomes. The cost of treatment was accounted from a healthcare payer perspective, capturing drug costs only. RESULTS: Treatment with once-weekly semaglutide 0.5 mg was associated with a lower cost and a lower cost per patient treated to target for all endpoints, compared with once-weekly dulaglutide 0.75 mg. For each JPY 1 spent on bringing patients to target with once-weekly semaglutide 0.5 mg, JPY 1.58, JPY 1.44, JPY 1.60, JPY 2.10, and JPY 2.33 would need to be spent on once-weekly dulaglutide 0.75 mg to achieve an equivalent outcome for endpoints of HbA1c /= 5%, and >/= 1.0% HbA1c reduction and >/= 3.0% weight loss, respectively. CONCLUSIONS: These findings suggest that once-weekly semaglutide is a cost-effective treatment option compared with once-weekly dulaglutide for patients with T2D in Japan. In the future, this finding should be extrapolated to traditional long-term cost-effectiveness analysis, using common outcomes such as quality-adjusted life years. FAU - Igarashi, Ataru AU - Igarashi A AD - Unit of Public Health and Preventive Medicine, Yokohama City University School of Medicine, Yokohama, Japan. AD - Department of Health Economics and Outcomes Research, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. FAU - Hunt, Barnaby AU - Hunt B AUID- ORCID: 0000-0001-5420-279X AD - Ossian Health Economics and Communications GmbH, Basel, Switzerland. hunt@ossianconsulting.com. FAU - Wilkinson, Lars AU - Wilkinson L AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Langer, Jakob AU - Langer J AD - Novo Nordisk Pharma Ltd., Tokyo, Japan. FAU - Pollock, Richard F AU - Pollock RF AD - Ossian Health Economics and Communications GmbH, Basel, Switzerland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200901 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) MH - Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - Drug Costs MH - Glucagon-Like Peptides/analogs & derivatives MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Immunoglobulin Fc Fragments MH - Japan MH - Recombinant Fusion Proteins MH - Semaglutide OTO - NOTNLM OT - Costs and cost analysis OT - Cost-benefit OT - Diabetes mellitus OT - Glucagon-like peptides OT - Japan OT - Semaglutide OT - Type 2 EDAT- 2020/09/02 06:00 MHDA- 2021/04/15 06:00 CRDT- 2020/09/02 06:00 PHST- 2020/07/22 00:00 [received] PHST- 2020/09/02 06:00 [pubmed] PHST- 2021/04/15 06:00 [medline] PHST- 2020/09/02 06:00 [entrez] AID - 10.1007/s12325-020-01476-x [pii] AID - 10.1007/s12325-020-01476-x [doi] PST - ppublish SO - Adv Ther. 2020 Oct;37(10):4446-4457. doi: 10.1007/s12325-020-01476-x. Epub 2020 Sep 1. PMID- 32862365 OWN - NLM STAT- MEDLINE DCOM- 20210414 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Linking) VI - 37 IP - 10 DP - 2020 Oct TI - Evaluation of the Long-Term Cost-Effectiveness of Once-Weekly Semaglutide Versus Dulaglutide and Sitagliptin in the Spanish Setting. PG - 4427-4445 LID - 10.1007/s12325-020-01464-1 [doi] AB - INTRODUCTION: Healthcare systems aim to maximize the health of the population, but must work within constrained budgets. Therefore, choosing therapies that are both effective and cost-effective is paramount. The present analysis assessed the cost-effectiveness of once-weekly semaglutide 0.5 mg and 1 mg versus once-weekly dulaglutide 1.5 mg and versus once daily sitagliptin 100 mg for the treatment of patients with type 2 diabetes with inadequate glycemic control on oral anti-hyperglycemic medications over patient lifetimes from a healthcare payer perspective in the Spanish setting. METHODS: Cost and clinical outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline cohort characteristics and treatment effects on initiation of semaglutide 0.5 mg and 1 mg, dulaglutide 1.5 mg and sitagliptin 100 mg were based on the once-weekly semaglutide clinical trial program (SUSTAIN 7 and 2). Captured costs included treatment costs and costs of diabetes-related complications. Projected outcomes were discounted at 3.0% annually. RESULTS: Projections of long-term clinical outcomes indicated that once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted life expectancy of 0.02 and 0.11 years, respectively, and discounted quality-adjusted life expectancy of 0.03 and 0.11 quality-adjusted life years (QALYs), respectively, versus dulaglutide 1.5 mg. Compared with sitagliptin, once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in discounted life expectancy of 0.17 and 0.24 years, respectively and discounted quality-adjusted life expectancy of 0.16 and 0.23 QALYs. The increased duration and quality of life with once-weekly semaglutide 0.5 mg and 1 mg resulted from a reduced cumulative incidence and delayed time to onset of diabetes-related complications. Avoided complications resulted in once-weekly semaglutide 0.5 mg and 1 mg being cost-saving versus dulaglutide 1.5 mg and versus sitagliptin 100 mg from a healthcare payer perspective. CONCLUSIONS: Once-weekly semaglutide 0.5 mg and 1 mg were considered dominant (more effective and less costly) versus sitagliptin 100 mg and dulaglutide 1.5 mg for the treatment of patients with type 2 diabetes with inadequate glycemic control on oral anti-hyperglycemic medications and are likely to be a good use of healthcare resources in the Spanish setting. FAU - Martin, Virginia AU - Martin V AD - Novo Nordisk Pharma SA, Madrid, Spain. FAU - Vidal, Josep AU - Vidal J AD - Endocrinology and Nutrition Department, Hospital Clinic, Barcelona, Spain. AD - Centro de Investigacion Biomedica en Red en Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Barcelona, Spain. FAU - Malkin, Samuel J P AU - Malkin SJP AD - Ossian Health Economics and Communications, Basel, Switzerland. FAU - Hallen, Nino AU - Hallen N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hunt, Barnaby AU - Hunt B AUID- ORCID: 0000-0001-5420-279X AD - Ossian Health Economics and Communications, Basel, Switzerland. hunt@ossianconsulting.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200829 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) MH - Cost-Benefit Analysis MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/analogs & derivatives MH - Humans MH - Hypoglycemic Agents MH - Immunoglobulin Fc Fragments MH - Quality of Life MH - Recombinant Fusion Proteins MH - *Sitagliptin Phosphate MH - Semaglutide OAB - Since healthcare systems aim to maximize the health of the population but must work within constrained budgets, choosing therapies that are both effective and cost-effective is paramount. We assessed the cost-effectiveness, from a Spanish healthcare payer perspective, of the newly marketed once-weekly semaglutide 0.5 mg and 1 mg versus two established therapies (dulaglutide 1.5 mg and sitagliptin 100 mg) for the treatment of patients with type 2 diabetes with inadequate glycemic control on oral anti-hyperglycemic medications over patient lifetimes.Outcomes were projected using a computer simulation model, based on two trials conducted as part of the once-weekly semaglutide clinical trial program (SUSTAIN 2 and SUSTAIN 7). Captured costs included treatment costs and costs of diabetes-related complications.Projections of long-term clinical outcomes indicated that once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.03 and 0.11 quality-adjusted life years (QALYs), respectively, versus dulaglutide 1.5 mg, and 0.16 and 0.23 QALYs, respectively, versus sitagliptin 100 mg. The increased duration and quality of life with once-weekly semaglutide 0.5 mg and 1 mg resulted from a reduced cumulative incidence and delayed time to onset of diabetes-related complications. Avoided complications resulted in once-weekly semaglutide 0.5 mg and 1 mg being cost-saving versus dulaglutide 1.5 mg and versus sitagliptin 100 mg.Once-weekly semaglutide 0.5 mg and 1 mg were more effective and less costly and therefore were considered dominant in both comparisons, and are likely to be a good use of healthcare resources in the Spanish setting. OABL- eng OTO - NOTNLM OT - Cost OT - Cost-effectiveness OT - Diabetes mellitus OT - Dulaglutide OT - GLP-1 receptor agonist OT - Semaglutide OT - Sitagliptin OT - Spain EDAT- 2020/08/31 06:00 MHDA- 2021/04/15 06:00 CRDT- 2020/08/31 06:00 PHST- 2020/06/16 00:00 [received] PHST- 2020/08/31 06:00 [pubmed] PHST- 2021/04/15 06:00 [medline] PHST- 2020/08/31 06:00 [entrez] AID - 10.1007/s12325-020-01464-1 [pii] AID - 10.1007/s12325-020-01464-1 [doi] PST - ppublish SO - Adv Ther. 2020 Oct;37(10):4427-4445. doi: 10.1007/s12325-020-01464-1. Epub 2020 Aug 29. PMID- 32857658 OWN - NLM STAT- MEDLINE DCOM- 20210609 LR - 20260127 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 26 IP - 9 DP - 2020 Sep TI - The Effectiveness and Value of Oral Semaglutide for Type 2 Diabetes Mellitus. PG - 1072-1076 LID - 10.18553/jmcp.2020.26.9.1072 [doi] AB - Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Fazioli, Rind, and Pearson are employed by ICER. Gazauskas and Hansen have nothing to disclose. FAU - Fazioli, Katherine T AU - Fazioli KT AD - Institute for Clinical and Economic Review, Boston, Massachusetts. FAU - Rind, David M AU - Rind DM AD - Institute for Clinical and Economic Review, Boston, Massachusetts. FAU - Guzauskas, Gregory F AU - Guzauskas GF AD - The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, Department of Pharmacy, University of Washington, Seattle. FAU - Hansen, Ryan N AU - Hansen RN AD - The Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute, Department of Pharmacy, University of Washington, Seattle. FAU - Pearson, Steven D AU - Pearson SD AD - Institute for Clinical and Economic Review, Boston, Massachusetts. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2/*drug therapy/economics MH - Glucagon-Like Peptides/*administration & dosage/economics MH - Humans MH - Hypoglycemic Agents/*administration & dosage/economics MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC10391231 COIS- Funding for this summary was contributed by Arnold Ventures, California Health Care Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Fazioli, Rind, and Pearson are employed by ICER. Gazauskas and Hansen have nothing to disclose. EDAT- 2020/08/29 06:00 MHDA- 2021/06/10 06:00 PMCR- 2020/09/01 CRDT- 2020/08/29 06:00 PHST- 2020/08/29 06:00 [entrez] PHST- 2020/08/29 06:00 [pubmed] PHST- 2021/06/10 06:00 [medline] PHST- 2020/09/01 00:00 [pmc-release] AID - 10.18553/jmcp.2020.26.9.1072 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2020 Sep;26(9):1072-1076. doi: 10.18553/jmcp.2020.26.9.1072. PMID- 32857647 OWN - NLM STAT- MEDLINE DCOM- 20210609 LR - 20260127 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 26 IP - 9 DP - 2020 Sep TI - Oral Semaglutide: Balancing Promising Therapeutics with Adverse Effects and Access Barriers. PG - 1077-1079 LID - 10.18553/jmcp.2020.26.9.1077 [doi] AB - No funding was received for this commentary. The author has nothing to disclose. FAU - Gunning, Karen AU - Gunning K AD - Professor, Department of Pharmacotherapy, PGY 2 Ambulatory Care Pharmacy Residency Director, and Associate Dean of Community Engagement, University of Utah College of Pharmacy; Adjunct Professor of Family & Preventive Medicine, University of Utah School of Medicine; and Clinical Pharmacist, University of Utah Sugarhouse Family Medicine Clinic, University of Utah Health. LA - eng PT - Journal Article PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC10391108 COIS- No funding was received for this commentary. The author has nothing to disclose. EDAT- 2020/08/29 06:00 MHDA- 2021/06/10 06:00 PMCR- 2020/09/01 CRDT- 2020/08/29 06:00 PHST- 2020/08/29 06:00 [entrez] PHST- 2020/08/29 06:00 [pubmed] PHST- 2021/06/10 06:00 [medline] PHST- 2020/09/01 00:00 [pmc-release] AID - 10.18553/jmcp.2020.26.9.1077 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2020 Sep;26(9):1077-1079. doi: 10.18553/jmcp.2020.26.9.1077. PMID- 32827435 OWN - NLM STAT- MEDLINE DCOM- 20210216 LR - 20260127 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 105 IP - 12 DP - 2020 Dec 1 TI - Efficacy of Once-Weekly Semaglutide vs Empagliflozin Added to Metformin in Type 2 Diabetes: Patient-Level Meta-analysis. PG - e4593-604 LID - dgaa577 [pii] LID - 10.1210/clinem/dgaa577 [doi] AB - CONTEXT: No head-to-head trials have directly compared once-weekly (OW) semaglutide, a human glucagon-like peptide-1 analog, with empagliflozin, a sodium-glucose co-transporter-2 inhibitor, in type 2 diabetes (T2D). OBJECTIVE: We indirectly compared the efficacy of OW semaglutide 1 mg vs once-daily (OD) empagliflozin 25 mg in patients with T2D inadequately controlled on metformin monotherapy, using individual patient data (IPD) and meta-regression methodology. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: IPD for patients with T2D receiving metformin monotherapy and randomized to OW semaglutide 1 mg (SUSTAIN 2, 3, 8 trials), or to OD empagliflozin 25 mg (PIONEER 2 trial) were included. Meta-regression analyses were adjusted for potential prognostic factors and effect modifiers. MAIN OUTCOME MEASURES: The primary efficacy outcomes were change from baseline to end-of-treatment (~1 year) in HbA1c (%-point) and body weight (kg). Responder outcomes and other clinically relevant efficacy measures were analyzed. RESULTS: Baseline characteristics were similar between OW semaglutide (n = 995) and empagliflozin (n = 410). Our analyses showed that OW semaglutide significantly reduced mean HbA1c and body weight vs empagliflozin (estimated treatment difference: -0.61%-point [95% confidence interval (CI): -0.72; -0.49] and -1.65 kg [95% CI: -2.22; -1.08], respectively; both P < 0.0001). Complementary analyses supported the robustness of these results. A significantly greater proportion of patients on OW semaglutide vs empagliflozin also achieved HbA1c targets and weight-loss responses. CONCLUSIONS: This indirect comparison suggests that OW semaglutide 1 mg provides superior reductions in HbA1c and body weight vs OD empagliflozin 25 mg in patients with T2D when added to metformin monotherapy. CI - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. FAU - Lingvay, Ildiko AU - Lingvay I AD - University of Texas Southwestern Medical Center at Dallas, Harry Hines Boulevard, Dallas, Texas. FAU - Capehorn, Matthew S AU - Capehorn MS AD - Rotherham Institute for Obesity, Clifton Medical Centre, Doncaster Gate, Rotherham, UK. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk, Vandtarnsvej, Soborg, Denmark. FAU - Johansen, Pierre AU - Johansen P AD - Novo Nordisk, Vandtarnsvej, Soborg, Denmark. FAU - Lawson, Jack AU - Lawson J AD - Novo Nordisk, Vandtarnsvej, Soborg, Denmark. FAU - Sandberg, Anna AU - Sandberg A AD - Novo Nordisk, Vandtarnsvej, Soborg, Denmark. FAU - Shaw, Robert AU - Shaw R AD - Novo Nordisk, Vandtarnsvej, Soborg, Denmark. FAU - Paine, Abby AU - Paine A LA - eng SI - ClinicalTrials.gov/NCT01930188 SI - ClinicalTrials.gov/NCT01885208 SI - ClinicalTrials.gov/NCT03136484 SI - ClinicalTrials.gov/NCT02863328 PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Benzhydryl Compounds/*administration & dosage MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptides/*administration & dosage MH - Glucosides/*administration & dosage MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Male MH - Metformin/*administration & dosage MH - Middle Aged MH - Treatment Outcome MH - Semaglutide PMC - PMC7549924 OTO - NOTNLM OT - GLP-1 receptor agonist OT - SGLT-2 inhibitor OT - indirect comparison OT - individual patient data OT - type 2 diabetes EDAT- 2020/08/23 06:00 MHDA- 2021/02/17 06:00 PMCR- 2020/08/22 CRDT- 2020/08/23 06:00 PHST- 2020/06/29 00:00 [received] PHST- 2020/08/19 00:00 [accepted] PHST- 2020/08/23 06:00 [pubmed] PHST- 2021/02/17 06:00 [medline] PHST- 2020/08/23 06:00 [entrez] PHST- 2020/08/22 00:00 [pmc-release] AID - 5896001 [pii] AID - dgaa577 [pii] AID - 10.1210/clinem/dgaa577 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4593-604. doi: 10.1210/clinem/dgaa577. PMID- 32826189 OWN - NLM STAT- MEDLINE DCOM- 20211015 LR - 20260127 IS - 1878-0210 (Electronic) IS - 1878-0210 (Linking) VI - 15 IP - 1 DP - 2021 Feb TI - Will oral semaglutide be a game-changer in the management of type 2 diabetes in primary care? PG - 59-68 LID - S1751-9918(20)30233-3 [pii] LID - 10.1016/j.pcd.2020.07.011 [doi] AB - GLP-1 receptor agonists (GLP-1RAs) are recommended for patients with type 2 diabetes (T2D), particularly those at high cardiovascular risk. Oral semaglutide is the first oral GLP-1RA. In clinical trials, oral semaglutide 14 mg reduced mean HbA(1c) by approximately 1.1-1.5% and reduced body weight by up to 5 kg. These changes were significantly greater compared with empagliflozin, sitagliptin and liraglutide (p < 0.05 for estimated treatment differences at 52 weeks in patients on treatment without rescue medication use). The most common side effects were gastrointestinal, mainly mild-to-moderate and transient nausea. Oral semaglutide may change the paradigm of T2D treatment in primary care. CI - Copyright (c) 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved. FAU - Seidu, Samuel AU - Seidu S AD - Leicester Diabetes Centre, University of Leicester, Leicester, UK. Electronic address: sis11@le.ac.uk. FAU - Mellbin, Linda AU - Mellbin L AD - Department of Medicine, Karolinska Instiutet Solna, Stockholm, Sweden. FAU - Kaiser, Marcel AU - Kaiser M AD - Practice for Internal Medicine and Diabetology, Frankfurt, Germany. FAU - Khunti, Kamlesh AU - Khunti K AD - Leicester Diabetes Centre, University of Leicester, Leicester, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20200819 PL - England TA - Prim Care Diabetes JT - Primary care diabetes JID - 101463825 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/diagnosis/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Primary Health Care MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - Glucose-lowering therapy OT - Oral semaglutide OT - Type 2 diabetes EDAT- 2020/08/23 06:00 MHDA- 2021/10/16 06:00 CRDT- 2020/08/23 06:00 PHST- 2020/03/06 00:00 [received] PHST- 2020/07/20 00:00 [revised] PHST- 2020/07/24 00:00 [accepted] PHST- 2020/08/23 06:00 [pubmed] PHST- 2021/10/16 06:00 [medline] PHST- 2020/08/23 06:00 [entrez] AID - S1751-9918(20)30233-3 [pii] AID - 10.1016/j.pcd.2020.07.011 [doi] PST - ppublish SO - Prim Care Diabetes. 2021 Feb;15(1):59-68. doi: 10.1016/j.pcd.2020.07.011. Epub 2020 Aug 19. PMID- 32815454 OWN - NLM STAT- MEDLINE DCOM- 20201109 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 132 IP - sup2 DP - 2020 Nov TI - GLP-1 receptor agonists in the treatment of type 2 diabetes: role and clinical experience to date. PG - 3-14 LID - 10.1080/00325481.2020.1798099 [doi] AB - Glucagon-like peptide-1 (GLP-1) is a hormone of the incretin system responsible for a variety of glucoregulatory effects, including glucose-dependent secretion of insulin and inhibition of glucagon release, the effects of which are impaired in people with type 2 diabetes (T2D). Targeting this deficiency using GLP-1 receptor agonists (GLP-1RAs) is a well-established approach in T2D, with over a decade of clinical experience now accrued. This article reviews the evidence for subcutaneous GLP-1RAs and their role in T2D treatment, and explores the rationale for an oral GLP-1RA from a primary care perspective. Clinical trials and real-world studies with subcutaneous GLP-1RAs indicate that these agents have good glycated hemoglobin (HbA(1) (c))-lowering efficacy, an inherently low potential for hypoglycemia, and reduce body weight. Cardiovascular outcomes trials have established cardiovascular safety, and three GLP-1RAs have been proven to reduce the risk of major adverse cardiovascular events (MACE) in patients with established cardiovascular disease or at high cardiovascular risk. The most common adverse events associated with GLP-1RAs are gastrointestinal effects, which tend to occur soon after initiation and decline over time. T2D treatment guidelines recommend GLP-1RAs as a therapeutic option in various settings, including in those patients: i) not achieving HbA(1) (c) targets after first-line metformin and lifestyle modifications; ii) at high risk of/with established atherosclerotic cardiovascular disease (regardless of HbA(1c); GLP-1RAs of proven benefit); iii) not achieving HbA(1) (c) targets on basal insulin if not already receiving a GLP-1RA. Despite the known benefits of GLP-1RAs, adherence and persistence rates are suboptimal, potentially due in part to injection-related concerns. With some patients having a preference for oral medications, the development of an oral GLP-1RA is a logical approach to improving treatment options for patients with T2D. Co-formulation of semaglutide with an absorption enhancer has enabled the development and recent approval of the first oral GLP-1RA, oral semaglutide, which has the potential to expand use of GLP-1RAs in clinical practice. FAU - Brunton, Stephen A AU - Brunton SA AD - Touro University California , Vallejo, CA, USA. FAU - Wysham, Carol H AU - Wysham CH AD - MultiCare Rockwood Clinic , Spokane, WA, USA. LA - eng PT - Journal Article PT - Review PT - Video-Audio Media DEP - 20200908 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - *Primary Health Care MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Type 2 diabetes OT - glucagon-like peptide-1 receptor agonist OT - oral semaglutide OT - primary care EDAT- 2020/08/21 06:00 MHDA- 2020/11/11 06:00 CRDT- 2020/08/21 06:00 PHST- 2020/08/21 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2020/08/21 06:00 [entrez] AID - 10.1080/00325481.2020.1798099 [doi] PST - ppublish SO - Postgrad Med. 2020 Nov;132(sup2):3-14. doi: 10.1080/00325481.2020.1798099. Epub 2020 Sep 8. PMID- 32815453 OWN - NLM STAT- MEDLINE DCOM- 20201109 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 132 IP - sup2 DP - 2020 Nov TI - Integrating oral semaglutide into clinical practice in primary care: for whom, when, and how? PG - 48-60 LID - 10.1080/00325481.2020.1798162 [doi] AB - Oral semaglutide is the first US Food and Drug Administration-approved oral glucagon-like peptide-1 receptor agonist (GLP-1RA) for the treatment of type 2 diabetes (T2D). Prior articles within this supplement reviewed the PIONEER trial program, which demonstrated that oral semaglutide reduced glycated hemoglobin and body weight when given to patients with uncontrolled T2D on various background therapies, and had a safety profile consistent with subcutaneous GLP-1RAs. This article provides guidance on integrating oral semaglutide into clinical practice in primary care. Patient populations with T2D who may gain benefit from oral semaglutide include those with inadequate glycemic control taking one or more oral glucose-lowering medication (e.g. after metformin), patients for whom weight loss would be beneficial, patients at risk of hypoglycemia, those who would historically have been considered for treatment with a subcutaneous GLP-1RA, and those receiving basal insulin who require treatment intensification. Like other GLP-1RAs, oral semaglutide is contraindicated in those with personal/family history of medullary thyroid carcinoma, and in those with multiple endocrine neoplasia syndrome type 2, as noted in a boxed warning in the prescribing information. Oral semaglutide has not been studied in those with a history of pancreatitis, is not recommended in patients with suspected/confirmed pancreatitis, and is not indicated in type 1 diabetes. When initiating oral semaglutide, gradual dose escalation is recommended to minimize the risk of gastrointestinal adverse events. As food and excess liquid reduce oral semaglutide absorption, patients should swallow the tablet with up to 4 fl oz/120 mL of water on an empty stomach upon waking, and should wait at least 30 minutes before eating, drinking, or taking other oral medications. Those managing patients should be aware of the potential impact of these dosing conditions on concomitant medications. When counseling patients, it is important to discuss these administration instructions, realistic therapeutic expectations, and strategies for mitigation of gastrointestinal events. Oral semaglutide provides a new option for add-on to initial T2D therapy (or later in the treatment paradigm), with the potential to enable more patients to benefit from the improvements in glycemic control, reductions in body weight, and low risk of hypoglycemia afforded by GLP-1RAs. FAU - Brunton, Stephen A AU - Brunton SA AD - Touro University California , Vallejo, CA, USA. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel. AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center , Jerusalem, Israel. FAU - Wright, Eugene E Jr AU - Wright EE Jr AUID- ORCID: 0000-0003-0796-0496 AD - Charlotte Area Health Education Center , Charlotte, NC, USA. LA - eng PT - Journal Article PT - Review PT - Video-Audio Media DEP - 20200908 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/*administration & dosage MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - *Primary Health Care MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Oral semaglutide OT - clinical practice OT - glucagon-like peptide-1 receptor agonist OT - guidelines OT - primary care OT - type 2 diabetes EDAT- 2020/08/21 06:00 MHDA- 2020/11/11 06:00 CRDT- 2020/08/21 06:00 PHST- 2020/08/21 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2020/08/21 06:00 [entrez] AID - 10.1080/00325481.2020.1798162 [doi] PST - ppublish SO - Postgrad Med. 2020 Nov;132(sup2):48-60. doi: 10.1080/00325481.2020.1798162. Epub 2020 Sep 8. PMID- 32815439 OWN - NLM STAT- MEDLINE DCOM- 20201109 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 132 IP - sup2 DP - 2020 Nov TI - Oral semaglutide in patients with type 2 diabetes and cardiovascular disease, renal impairment, or other comorbidities, and in older patients. PG - 37-47 LID - 10.1080/00325481.2020.1800286 [doi] AB - Patients with type 2 diabetes (T2D) often have comorbidities, such as cardiovascular disease or chronic kidney disease, and a large and growing proportion of the T2D patient population is over 65 years. There are many therapies for the treatment of T2D but not all are suitable for patients with comorbidities. Oral semaglutide is a tablet formulation of a glucagon-like peptide-1 receptor agonist (GLP-1RA) and was recently approved for the treatment of T2D, representing an oral alternative to injectable GLP-1RAs. This article reviews data from: PIONEER 6, a phase 3a cardiovascular outcomes trial in patients at high cardiovascular risk; PIONEER 5, a phase 3a trial in patients with moderate renal impairment; a post-hoc analysis of PIONEER data by age; and pharmacokinetic trials investigating the effects of renal impairment, gastrointestinal disease, and hepatic impairment on the exposure of oral semaglutide. PIONEER 6 demonstrated the cardiovascular safety of oral semaglutide compared with placebo (hazard ratio: 0.79; 95% confidence interval [CI]: 0.57, 1.11; p < 0.001 for noninferiority), ruling out excess cardiovascular risk. In PIONEER 5, oral semaglutide was superior to placebo in decreasing glycated hemoglobin over 26 weeks (estimated treatment difference [ETD]: -0.8%; 95% CI: -1.0, -0.6; p < 0.0001) and body weight (ETD: -2.5 kg; 95% CI: -3.2, -1.8; p < 0.0001), and renal function was unchanged in both treatment groups. There was no effect of age on glycemic efficacy of oral semaglutide and the presence of upper gastrointestinal disease or hepatic impairment did not affect the pharmacokinetics of semaglutide. Across the trials, the safety profile of oral semaglutide was as expected for a GLP-1RA, with gastrointestinal adverse events most commonly reported. As such, oral semaglutide provides an effective oral GLP-1RA treatment option in older patients and/or those with comorbidities, with no requirements for dose adjustment. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Faculty of Medicine, Hebrew University of Jerusalem , Jerusalem, Israel. AD - Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Centre , Jerusalem, Israel. FAU - Miller, Eden M AU - Miller EM AD - Diabetes Nation , Bend, OR, USA. FAU - Warren, Mark L AU - Warren ML AD - Physicians East , Greenville, NC, USA. LA - eng PT - Journal Article PT - Review PT - Video-Audio Media DEP - 20200908 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Age Factors MH - Aged MH - Cardiovascular Diseases/complications MH - Comorbidity MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Glucagon-Like Peptides/*administration & dosage MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Kidney Failure, Chronic/complications MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Oral semaglutide OT - cardiovascular disease OT - chronic kidney disease OT - hepatic impairment OT - older OT - renal impairment OT - type 2 diabetes EDAT- 2020/08/21 06:00 MHDA- 2020/11/11 06:00 CRDT- 2020/08/21 06:00 PHST- 2020/08/21 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2020/08/21 06:00 [entrez] AID - 10.1080/00325481.2020.1800286 [doi] PST - ppublish SO - Postgrad Med. 2020 Nov;132(sup2):37-47. doi: 10.1080/00325481.2020.1800286. Epub 2020 Sep 8. PMID- 32815436 OWN - NLM STAT- MEDLINE DCOM- 20201109 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 132 IP - sup2 DP - 2020 Nov TI - Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes compared with other oral antihyperglycemic agents and placebo. PG - 15-25 LID - 10.1080/00325481.2020.1798638 [doi] AB - Oral semaglutide is a tablet formulation of a glucagon-like peptide-1 receptor agonist (GLP-1RA), recently approved in the USA and other countries. This paper reviews data from clinical trials (PIONEER 1, 2, 3, and 7) comparing oral semaglutide (once-daily doses of 3, 7, or 14 mg) with either once-daily placebo, empagliflozin 25 mg, or sitagliptin 100 mg. After 26 weeks in PIONEER 1, patients randomized to 3, 7, or 14 mg doses of oral semaglutide monotherapy had statistically significant reductions in glycated hemoglobin (HbA(1) (c)) of 0.9%, 1.2%, and 1.4%, respectively, versus 0.3% with placebo. In the active-comparator studies, oral semaglutide 14 mg provided better glycemic control than empagliflozin or sitagliptin after 26 weeks, with durable effects. Body weight reductions were significantly greater with oral semaglutide than with placebo and sitagliptin. However, body weight reductions with oral semaglutide 14 mg versus empagliflozin 25 mg were not significantly different. Gastrointestinal adverse events (AEs) with oral semaglutide were mostly mild-to-moderate, occurred early in the course of treatment, and abated over time. Across these trials, 5-13% and 15-20% of patients experienced nausea with oral semaglutide 7 and 14 mg, respectively, and 2.3-3.4% and 5.1-8.0%, respectively, discontinued treatment due to gastrointestinal AEs. Severe or blood glucose-confirmed symptomatic hypoglycemia occurred infrequently with oral semaglutide and was seen most often in patients taking concomitant sulfonylureas. Findings from these trials indicate that the addition of oral semaglutide reduces HbA(1) (c) and body weight and is associated with a low risk of hypoglycemia. Oral semaglutide represents an additional option for treating people with type 2 diabetes in primary care, with the potential to expand the numbers of patients benefiting from GLP-1RAs beyond that currently seen with injectable formulations. FAU - Lavernia, Frank AU - Lavernia F AD - North Broward Diabetes Center , Pompano Beach, FL, USA. FAU - Blonde, Lawrence AU - Blonde L AUID- ORCID: 0000-0003-0492-6698 AD - Department of Endocrinology, Ochsner Medical Center , New Orleans, LA, USA. LA - eng PT - Journal Article PT - Review PT - Video-Audio Media DEP - 20200908 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Administration, Oral MH - Benzhydryl Compounds/administration & dosage MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/*administration & dosage MH - Glucosides/administration & dosage MH - Glycated Hemoglobin/drug effects MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Primary Health Care MH - Sitagliptin Phosphate/administration & dosage MH - Semaglutide OTO - NOTNLM OT - Oral semaglutide OT - comparative studies OT - empagliflozin OT - sitagliptin OT - treatment intensification OT - type 2 diabetes EDAT- 2020/08/21 06:00 MHDA- 2020/11/11 06:00 CRDT- 2020/08/21 06:00 PHST- 2020/08/21 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2020/08/21 06:00 [entrez] AID - 10.1080/00325481.2020.1798638 [doi] PST - ppublish SO - Postgrad Med. 2020 Nov;132(sup2):15-25. doi: 10.1080/00325481.2020.1798638. Epub 2020 Sep 8. PMID- 32815423 OWN - NLM STAT- MEDLINE DCOM- 20201109 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 132 IP - sup2 DP - 2020 Nov TI - Clinical review of the efficacy and safety of oral semaglutide in patients with type 2 diabetes considered for injectable GLP-1 receptor agonist therapy or currently on insulin therapy. PG - 26-36 LID - 10.1080/00325481.2020.1798127 [doi] AB - Injectable therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and insulin are high-efficacy options for people with type 2 diabetes (T2D) who require treatment intensification. In addition to high glycemic efficacy, GLP-1RAs offer weight loss benefits, and some agents have been shown to reduce cardiovascular risk. This article summarizes data from two clinical studies with the first oral GLP-1RA, oral semaglutide, in situations where injectable therapy is often considered, and provides guidance on use in primary care. PIONEER 4 compared oral semaglutide 14 mg with an injectable GLP-1RA, liraglutide 1.8 mg, or placebo in patients uncontrolled on oral glucose-lowering therapies. PIONEER 8 compared oral semaglutide with placebo in patients with T2D already on insulin therapy. Treatment with oral semaglutide gave similar reductions in glycated hemoglobin (HbA(1) (c)) compared with liraglutide at 26 weeks, and significantly greater reductions at 52 weeks. Changes in body weight with oral semaglutide were significantly greater compared with liraglutide after 26 and 52 weeks. Adding oral semaglutide 7 or 14 mg to insulin resulted in significant reductions in HbA(1) (c) and body weight at both 26 and 52 weeks compared with placebo, and facilitated a decrease in total daily insulin dosage. Oral semaglutide was associated with low proportions of patients experiencing severe or blood glucose-confirmed symptomatic hypoglycemia when added to oral glucose-lowering therapies, and did not increase the incidence of such events when added to insulin. The tolerability profile of oral semaglutide was consistent with that seen for injectable GLP-1RAs, with gastrointestinal side effects seen most frequently; most were transient and tended to occur during dose escalation. For patients requiring treatment intensification after oral therapy or as add-on to insulin, oral semaglutide provides effective glucose lowering and body weight loss, with low risk of hypoglycemia, thus broadening the range of therapeutic options for treatment of T2D in primary care. FAU - Wright, Eugene E Jr AU - Wright EE Jr AUID- ORCID: 0000-0003-0796-0496 AD - Charlotte Area Health Education Center , Charlotte, NC, USA. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Brigham and Women's Hospital; Harvard Medical School , Boston, MA, USA. LA - eng PT - Journal Article PT - Review PT - Video-Audio Media DEP - 20200908 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Placebos) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/*administration & dosage MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Insulin/therapeutic use MH - Placebos MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Oral semaglutide OT - comparative studies OT - glucagon-like peptide-1 receptor agonist OT - injectable therapy OT - insulin OT - treatment escalation OT - type 2 diabetes EDAT- 2020/08/21 06:00 MHDA- 2020/11/11 06:00 CRDT- 2020/08/21 06:00 PHST- 2020/08/21 06:00 [pubmed] PHST- 2020/11/11 06:00 [medline] PHST- 2020/08/21 06:00 [entrez] AID - 10.1080/00325481.2020.1798127 [doi] PST - ppublish SO - Postgrad Med. 2020 Nov;132(sup2):26-36. doi: 10.1080/00325481.2020.1798127. Epub 2020 Sep 8. PMID- 32799379 OWN - NLM STAT- MEDLINE DCOM- 20211230 LR - 20250103 IS - 1464-5491 (Electronic) IS - 0742-3071 (Linking) VI - 38 IP - 1 DP - 2021 Jan TI - Glucagon-like peptide-1 (GLP-1) receptor agonists in type 2 diabetes and long-term complications: FOCUS on retinopathy. PG - e14390 LID - 10.1111/dme.14390 [doi] FAU - Marchand, L AU - Marchand L AUID- ORCID: 0000-0001-9101-5002 AD - Department of Endocrinology and Diabetes, Centre Hospitalier Saint Joseph Saint Luc, Lyon. FAU - Luyton, C AU - Luyton C AD - Department of Endocrinology and Diabetes, Centre Hospitalier Saint Joseph Saint Luc, Lyon. FAU - Bernard, A AU - Bernard A AD - Department of Ophthalmology, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Benite. AD - Department of Ophthalmology, Centre Hospitalier Saint Joseph Saint Luc, Lyon, France. LA - eng PT - Journal Article DEP - 20200927 PL - England TA - Diabet Med JT - Diabetic medicine : a journal of the British Diabetic Association JID - 8500858 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Diabetes Mellitus, Type 2/*complications/*drug therapy MH - Diabetic Retinopathy/*epidemiology MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - ACCORD OT - ADVANCE OT - Diabetic Retinopathy OT - ELIXA OT - EXSCEL OT - Eye events OT - FOCUS OT - GLP-1 OT - Glucagon-like peptide-1 receptor agonists OT - HARMONY Outcomes OT - LEADER OT - Liraglutide OT - Lixisenatide OT - Long-term complications OT - Microvascular complications OT - PIONEER-6 OT - REWIND OT - SUSTAIN-6 OT - Semaglutide OT - Type 2 Diabetes OT - UKPDS OT - VADT OT - albiglutide OT - dulaglutide OT - exenatide OT - oral semaglutide EDAT- 2020/08/18 06:00 MHDA- 2021/12/31 06:00 CRDT- 2020/08/18 06:00 PHST- 2020/05/26 00:00 [received] PHST- 2020/07/16 00:00 [revised] PHST- 2020/08/12 00:00 [accepted] PHST- 2020/08/18 06:00 [pubmed] PHST- 2021/12/31 06:00 [medline] PHST- 2020/08/18 06:00 [entrez] AID - 10.1111/dme.14390 [doi] PST - ppublish SO - Diabet Med. 2021 Jan;38(1):e14390. doi: 10.1111/dme.14390. Epub 2020 Sep 27. PMID- 32781867 OWN - NLM STAT- MEDLINE DCOM- 20210407 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 132 IP - 8 DP - 2020 Nov TI - Oral glucagon-like peptide-receptor agonists (GLP1RA) counseling: comparison with insulin counseling. PG - 663-666 LID - 10.1080/00325481.2020.1809906 [doi] FAU - Kalra, Sanjay AU - Kalra S AD - Department of Endocrinology, Bharti Hospital Karnal , Karnal, India. FAU - Kalhan, Atul AU - Kalhan A AD - Endocrinology, Royal Glamorgan Hospital , Cardiff, United Kingdom of Great Britain and Northern Ireland. FAU - Berard, Lori AU - Berard L AD - Diabetes Management and Clinical Trial Operations - Nurse Consultant , Winnipeg, Manitoba, Canada. LA - eng PT - Editorial DEP - 20201019 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) SB - IM MH - Administration, Oral MH - Counseling MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptide-1 Receptor/*therapeutic use MH - Glucagon-Like Peptides/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Insulin/*therapeutic use MH - Practice Guidelines as Topic MH - Semaglutide OTO - NOTNLM OT - Counseling OT - GLP-1 RA OT - diabetes OT - insulin OT - oral GLP1 RA OT - semaglutide EDAT- 2020/08/13 06:00 MHDA- 2021/04/10 06:00 CRDT- 2020/08/13 06:00 PHST- 2020/08/13 06:00 [pubmed] PHST- 2021/04/10 06:00 [medline] PHST- 2020/08/13 06:00 [entrez] AID - 10.1080/00325481.2020.1809906 [doi] PST - ppublish SO - Postgrad Med. 2020 Nov;132(8):663-666. doi: 10.1080/00325481.2020.1809906. Epub 2020 Oct 19. PMID- 32780784 OWN - NLM STAT- MEDLINE DCOM- 20210623 LR - 20260127 IS - 1744-6848 (Electronic) IS - 1744-683X (Linking) VI - 16 IP - 44 DP - 2020 Nov 18 TI - A spectroscopic and molecular dynamics study on the aggregation process of a long-acting lipidated therapeutic peptide: the case of semaglutide. PG - 10122-10131 LID - 10.1039/d0sm01011a [doi] AB - The aggregation properties of semaglutide, a lipidated peptide drug agonist of the Glucagon-like peptide 1 receptor recently approved for the treatment of type 2 diabetes, have been investigated by spectroscopic techniques (UV-Vis absorption, steady-state and time-resolved fluorescence, and electronic circular dichroism) and molecular dynamics simulations. We show that in the micromolar concentration region, in aqueous solution, semaglutide is present as monomeric and dimeric species, with a characteristic monomer-to-dimer transition occurring at around 20 muM. The lipid chain stabilizes a globular morphology of the monomer and dimer species, giving rise to a locally well-defined polar outer surface where the lipid and peptide portions are packed to each other. At very long times, these peptide clusters nucleate the growth of larger aggregates characterized by blue luminescence and a beta-sheet arrangement of the peptide chains. The understanding of the oligomerization and aggregation potential of peptide candidates is key for the development of long acting and stable drugs. FAU - Venanzi, M AU - Venanzi M AD - Dept. of Chemical Science and Technologies, University of Rome Tor Vergata, Via Ricerca Scientifica, 1, 00133 Rome, Italy. venanzi@uniroma2.it. FAU - Savioli, M AU - Savioli M FAU - Cimino, R AU - Cimino R FAU - Gatto, E AU - Gatto E FAU - Palleschi, A AU - Palleschi A FAU - Ripani, G AU - Ripani G FAU - Cicero, D AU - Cicero D FAU - Placidi, E AU - Placidi E FAU - Orvieto, F AU - Orvieto F FAU - Bianchi, E AU - Bianchi E LA - eng PT - Journal Article PL - England TA - Soft Matter JT - Soft matter JID - 101295070 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides MH - Humans MH - *Molecular Dynamics Simulation MH - Peptides MH - Semaglutide EDAT- 2020/08/12 06:00 MHDA- 2021/06/24 06:00 CRDT- 2020/08/12 06:00 PHST- 2020/08/12 06:00 [pubmed] PHST- 2021/06/24 06:00 [medline] PHST- 2020/08/12 06:00 [entrez] AID - 10.1039/d0sm01011a [doi] PST - ppublish SO - Soft Matter. 2020 Nov 18;16(44):10122-10131. doi: 10.1039/d0sm01011a. PMID- 32770420 OWN - NLM STAT- MEDLINE DCOM- 20210423 LR - 20261010 IS - 1534-3170 (Electronic) IS - 1523-3782 (Linking) VI - 22 IP - 10 DP - 2020 Aug 8 TI - Cardiovascular Effects of Dipeptidyl Peptidase-4 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists: a Review for the General Cardiologist. PG - 105 LID - 10.1007/s11886-020-01355-5 [doi] AB - PURPOSE OF REVIEW: Results from cardiovascular (CV) outcome trials have revealed important insights into the CV safety and efficacy of glucose-lowering agents, including dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). RECENT FINDINGS: Among patients with T2DM, DPP-4i have no significant effect on risk of major adverse CV events (MACE: CV death, myocardial infarction, or stroke) with mixed results regarding risk for heart failure (HF). While sitagliptin and linagliptin have neutral effects on HF risk, saxagliptin significantly increases the risk of HF. The CV safety of the GLP-1RA class of medications has been clearly demonstrated, and select agents, such as liraglutide, semaglutide, albiglutide, and dulaglutide, reduce the risk of MACE in patients with T2DM and established CV disease. CV outcome trials have demonstrated CV safety but not incremental efficacy for DPP-4i in most cases. Select GLP-1RA have proven efficacy for MACE and should be considered by cardiologists for CV risk mitigation in the care of patients with T2DM and established CV disease. FAU - Patel, Kershaw V AU - Patel KV AD - Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8830, USA. FAU - Sarraju, Ashish AU - Sarraju A AD - Division of Cardiovascular Medicine and Cardiovascular Institute, Stanford University, Stanford, CA, USA. FAU - Neeland, Ian J AU - Neeland IJ AD - Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8830, USA. FAU - McGuire, Darren K AU - McGuire DK AUID- ORCID: 0000-0002-6412-7989 AD - Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8830, USA. Darren.McGuire@UTSouthwestern.edu. LA - eng GR - K23 DK106520/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review DEP - 20200808 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases) SB - IM MH - *Cardiologists MH - *Cardiovascular Diseases/chemically induced/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Dipeptidyl-Peptidase IV Inhibitors/adverse effects MH - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/adverse effects OTO - NOTNLM OT - Atherosclerotic cardiovascular disease OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonists OT - Heart failure OT - Type 2 diabetes mellitus EDAT- 2020/08/10 06:00 MHDA- 2021/04/24 06:00 CRDT- 2020/08/10 06:00 PHST- 2020/08/10 06:00 [entrez] PHST- 2020/08/10 06:00 [pubmed] PHST- 2021/04/24 06:00 [medline] AID - 10.1007/s11886-020-01355-5 [pii] AID - 10.1007/s11886-020-01355-5 [doi] PST - epublish SO - Curr Cardiol Rep. 2020 Aug 8;22(10):105. doi: 10.1007/s11886-020-01355-5. PMID- 32756221 OWN - NLM STAT- MEDLINE DCOM- 20210201 LR - 20260127 IS - 1547-1896 (Print) IS - 0893-7400 (Linking) VI - 33 IP - S8 Suppl 1 DP - 2020 Aug TI - Long-acting GLP-1 receptor agonists: Findings and implications of cardiovascular outcomes trials. PG - 19-30 LID - 10.1097/01.JAA.0000669452.63883.45 [doi] AB - Cardiovascular disease (CVD) is a common and serious comorbidity of type 2 diabetes mellitus (T2DM), and cardiovascular (CV) risk assessment has become an important aspect of evaluating new therapies for T2DM before approval by the FDA. Since 2008, in order to establish safety, new therapies for T2DM have been required to demonstrate that they will not result in an unacceptable increase in CV risk. Studies performed for this purpose are termed CV outcome trials, or CVOTs. This article reviews CVOTs completed to date for the class of long-acting glucagon-like peptide-1 receptor agonists (GLP-1RAs; liraglutide, exenatide extended-release, albiglutide, dulaglutide, semaglutide injectable, semaglutide oral) and implications for clinical management of T2DM. All CVOTs have confirmed long-acting GLP-1RAs to be noninferior to (not worse than) placebo with regard to first occurrence of a primary outcome of three-point major adverse cardiovascular events (MACE; composite outcome of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke). Further, a number of the studies demonstrated a statistically significant reduction in primary outcomes of three-point MACE with GLP-1RA treatment compared with placebo. As a result, the product labeling for liraglutide, semaglutide injectable, and dulaglutide has been updated with an indication for reducing the risk of MACE in adults with T2DM and established CVD (all) or multiple CV risk factors (dulaglutide only). These findings have brought about an exciting paradigm shift from concern about not inflicting CV harm to the exciting prospect of reducing risks of CV outcomes. Major diabetes care guidelines now encourage early consideration of GLP-1RA use in patients with atherosclerotic CVD. FAU - Urquhart, Scott AU - Urquhart S AD - Scott Urquhart practices at Diabetes and Thyroid Associates in Fredericksburg, Va., is chair of the Metabolic and Endocrine Disease Summit, an adjunct clinical professor in the PA program at James Madison University in Harrisonburg, Va., and a clinical instructor in the PA program at George Washington University in Washington, D.C. Stephen Willis practices at the Multicare-Rockwood Clinic in Spokane, Wash., and is department chair of the Endocrinology and Advanced Diabetes Center. Mr. Urquhart discloses that he has served on advisory boards for Astra Zeneca, Dexcom, and Sanofi; on speakers' bureaus for Astra Zeneca, Dexcom, and Novo Nordisk Inc; and as a consultant for Novo Nordisk Inc. Stephen Willis has served on an advisory board for Eli Lilly. This manuscript was funded by Novo Nordisk Inc. The authors have disclosed no other potential conflicts of interest, financial or otherwise. FAU - Willis, Stephen AU - Willis S LA - eng PT - Journal Article PT - Review PL - United States TA - JAAPA JT - JAAPA : official journal of the American Academy of Physician Assistants JID - 9513102 RN - 0 (Delayed-Action Preparations) RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 5E7U48495E (rGLP-1 protein) RN - WTT295HSY5 (dulaglutide) MH - Cardiovascular Diseases/epidemiology/etiology/prevention & control MH - Delayed-Action Preparations MH - Diabetes Mellitus, Type 2/complications/*drug therapy/epidemiology MH - Exenatide MH - Glucagon-Like Peptide 1/analogs & derivatives MH - Glucagon-Like Peptides/analogs & derivatives MH - *Heart Disease Risk Factors MH - Humans MH - Immunoglobulin Fc Fragments MH - Liraglutide MH - Recombinant Fusion Proteins MH - United States/epidemiology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2020/08/07 06:00 MHDA- 2021/02/02 06:00 CRDT- 2020/08/07 06:00 PHST- 2020/08/07 06:00 [entrez] PHST- 2020/08/07 06:00 [pubmed] PHST- 2021/02/02 06:00 [medline] AID - 01720610-202008001-00002 [pii] AID - 10.1097/01.JAA.0000669452.63883.45 [doi] PST - ppublish SO - JAAPA. 2020 Aug;33(S8 Suppl 1):19-30. doi: 10.1097/01.JAA.0000669452.63883.45. PMID- 32756220 OWN - NLM STAT- MEDLINE DCOM- 20210201 LR - 20260127 IS - 1547-1896 (Print) IS - 0893-7400 (Linking) VI - 33 IP - S8 Suppl 1 DP - 2020 Aug TI - Long-acting GLP-1RAs: An overview of efficacy, safety, and their role in type 2 diabetes management. PG - 3-18 LID - 10.1097/01.JAA.0000669456.13763.bd [doi] AB - Over recent decades, an improved understanding of the pathophysiology of type 2 diabetes mellitus (T2DM) and glucose regulation has led to innovative research and new treatment paradigms. The discovery of the gut peptide glucagon-like peptide-1 (GLP-1) and its role in glucose regulation paved the way for the class of GLP-1 receptor agonist compounds, or GLP-1RAs. The long-acting GLP-1RAs (dulaglutide, exenatide extended-release, liraglutide, semaglutide [injectable and oral]) are classified as such based on a minimum 24-hour duration of clinically relevant effects after administration. In phase 3 clinical trial programs of long-acting GLP-1RAs, A1C typically was reduced in the range of 1% to 1.5%, with reductions close to 2% in some studies. GLP-1RAs when used alone (without sulfonylureas or insulin) have a low risk of hypoglycemia because, like endogenous GLP-1, their insulinotropic effects are glucose-dependent. In addition to local actions in the gastrointestinal (GI) tract, GLP-1RAs stimulate receptors in the central nervous system to increase satiety, resulting in weight loss. All long-acting GLP-1RAs have, at minimum, been shown to be safe and not increase cardiovascular (CV) risk and most (liraglutide, semaglutide injectable, dulaglutide, albiglutide) have been shown in CV outcomes trials (CVOTs) to significantly reduce the risk of major cardiac adverse events. The class has good tolerability overall, with generally transient GI adverse events being most common. The weekly injectable agents offer scheduling convenience and may promote treatment adherence. One long-acting GLP-1RA is available as an oral daily tablet, which may be preferable for some patients and providers. FAU - Chun, Ji Hyun AU - Chun JH AD - Ji Hyun Chun practices endocrinology at OptumCare Medical Group in Orange County, Calif.; is a medical science liaison at Corcept Therapeutics in Menlo Park, Calif.; and is immediate past president of the American Society of Endocrine Physician Assistants. Amy Butts practices endocrinology at Wheeling (W. Va.) Hospital. Mr. Chun has no conflicts to disclose beyond his employment at Corcept Therapeutics. Ms. Butts has served on speakers' bureaus and advisory boards for Novo Nordisk Inc., on speakers' bureaus for Janssen Pharmaceuticals and Xeris Pharmaceuticals, and on advisory boards for Merck. This manuscript was funded by Novo Nordisk Inc. The authors have disclosed no other potential conflicts of interest, financial or otherwise. FAU - Butts, Amy AU - Butts A LA - eng PT - Journal Article PT - Review PL - United States TA - JAAPA JT - JAAPA : official journal of the American Academy of Physician Assistants JID - 9513102 RN - 0 (Delayed-Action Preparations) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - WTT295HSY5 (dulaglutide) MH - Administration, Oral MH - Delayed-Action Preparations MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Glucagon-Like Peptide 1/pharmacology/physiology/*therapeutic use MH - Glucagon-Like Peptides/administration & dosage/*analogs & derivatives/pharmacology/therapeutic use MH - Glucose/metabolism MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/administration & dosage/pharmacology/*therapeutic use MH - Immunoglobulin Fc Fragments/administration & dosage/pharmacology/*therapeutic use MH - Liraglutide/administration & dosage/pharmacology/*therapeutic use MH - Recombinant Fusion Proteins/administration & dosage/pharmacology/*therapeutic use MH - Safety MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2020/08/07 06:00 MHDA- 2021/02/02 06:00 CRDT- 2020/08/07 06:00 PHST- 2020/08/07 06:00 [entrez] PHST- 2020/08/07 06:00 [pubmed] PHST- 2021/02/02 06:00 [medline] AID - 01720610-202008001-00001 [pii] AID - 10.1097/01.JAA.0000669456.13763.bd [doi] PST - ppublish SO - JAAPA. 2020 Aug;33(S8 Suppl 1):3-18. doi: 10.1097/01.JAA.0000669456.13763.bd. PMID- 32744418 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 22 IP - 12 DP - 2020 Dec TI - Effects of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across body mass index categories in type 2 diabetes: Results of the LEADER and SUSTAIN 6 trials. PG - 2487-2492 LID - 10.1111/dom.14160 [doi] AB - Associations between body mass index (BMI) and the cardiovascular (CV) and kidney efficacy of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) are uncertain; therefore, data analysed separately from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN 6) were examined. These international, randomized, placebo-controlled trials investigated liraglutide and semaglutide (both subcutaneous) in patients with T2D and at high risk of CV events. In post hoc analyses, patients were categorized by baseline BMI (<25, >/=25-<30, >/=30-<35 and >/=35 kg/m(2) ), and CV and kidney outcomes with GLP-1 RA versus placebo were analysed. All baseline BMI data from LEADER (n = 9331) and SUSTAIN 6 (n = 3290) were included (91% and 92% of patients with overweight or obesity, respectively). In SUSTAIN 6, nominally significant heterogeneity of semaglutide efficacy by baseline BMI was observed for CV death/myocardial infarction/stroke (major adverse CV events, primary outcome of both; P(interaction) = .02); otherwise, there was no statistical heterogeneity for either GLP-1 RA versus placebo across BMI categories for key CV and kidney outcomes. The lack of statistical heterogeneity from these cardiorenal outcomes implies that liraglutide and semaglutide may be beneficial for many patients and is probable not to depend on their baseline BMI, but further study is needed. CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Verma, Subodh AU - Verma S AUID- ORCID: 0000-0002-4018-8533 AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. FAU - McGuire, Darren K AU - McGuire DK AD - Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Institute of Life Science, Swansea University, Swansea, UK. FAU - Bhatt, Deepak L AU - Bhatt DL AD - Brigham and Women's Hospital Heart and Vascular Center & Harvard Medical School, Boston, Massachusetts, USA. FAU - Leiter, Lawrence A AU - Leiter LA AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. FAU - Mazer, C David AU - Mazer CD AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. FAU - Monk Fries, Tea AU - Monk Fries T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Vrazic, Hrvoje AU - Vrazic H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Zinman, Bernard AU - Zinman B AUID- ORCID: 0000-0002-0041-1876 AD - Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. LA - eng SI - ClinicalTrials.gov/NCT01179048 SI - ClinicalTrials.gov/NCT01720446 GR - UC4 DK108612/DK/NIDDK NIH HHS/United States GR - UL1 TR002489/TR/NCATS NIH HHS/United States GR - U54 DK118612/DK/NIDDK NIH HHS/United States GR - U01 DK098246/DK/NIDDK NIH HHS/United States GR - P30 DK124723/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200904 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Body Mass Index MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Kidney MH - Liraglutide/therapeutic use MH - Semaglutide PMC - PMC7754406 OTO - NOTNLM OT - body mass index, cardiovascular, liraglutide, major adverse cardiovascular events, semaglutide COIS- SV reports personal fees and other from Boehringer Ingelheim, Eli Lilly, AstraZeneca, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, Valeant, Amgen, Sun Pharma and HLS Therapeutics. DKM reports consultancy fees for clinical trial leadership from AstraZeneca, Sanofi Aventis, Janssen, Boehringer Ingelheim, Merck & Co, Pfizer, Lilly US, Novo Nordisk, Lexicon, Eisai, GlaxoSmithKline and Esperion; consultancy fees from AstraZeneca, Sanofi Aventis, Lilly US, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Applied Therapeutics, Afimmune and Metavant. SCB reports personal fees and other from Abbott, AstraZeneca, Boehringer Ingelheim, BMS, Cellnovo, Diartis, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, Servier and Takeda; other from Cardiff University, Doctors.net, Elsevier, Onmedica, Omnia-Med, Medscape, All-Wales Medicines Strategy Group, National Institute for Health and Care Excellence (NICE) UK and Glycosmedia. DLB discloses the following relationships: advisory board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma, Regado Biosciences; board of directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; chair: American Heart Association Quality Oversight Committee; data monitoring committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Level Ex, MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); research funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); site co-investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; trustee: American College of Cardiology; unfunded research: FlowCo, Merck, Novo Nordisk, Takeda. LAL reports consultant and speaker fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi and Servier; research grant or support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Novo Nordisk and Sanofi. CDM reports research grants to institution and/or consulting honoraria from Amgen, Boehringer Ingelheim, CSL Behring, OctaPharma and Quark Pharmaceuticals. TMF and SR are employees of and shareholders in Novo Nordisk. HV was an employee of Novo Nordisk during the development of this manuscript. REP reports research grants from Gilead Sciences, Lexicon Pharmaceuticals, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Sanofi-Aventis US LLC and Takeda; speaker for AstraZeneca, Novo Nordisk and Takeda; consultant for AstraZeneca, Boehringer Ingelheim, Eisai, Inc., GlaxoSmithKline, Janssen Scientific Affairs LLC, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Pfizer and Takeda. All payments made directly to his employer (Florida Hospital/AdventHealth). BZ reports personal fees from Merck, Sanofi-Aventis, Eli Lilly, AstraZeneca and Janssen; personal fees and other from Novo Nordisk and Boehringer Ingelheim. JBB's contracted consulting fees are paid to the University of North Carolina by Adocia, AstraZeneca, Dance Biopharm, Dexcom, Eli Lilly, Fractyl, GI Dynamics, Intarcia Therapeutics, Lexicon, MannKind, Metavention, NovaTarg, Novo Nordisk, Orexigen, PhaseBio, Sanofi, Senseonics, vTv Therapeutics and Zafgen; he reports grant support from AstraZeneca, Eli Lilly, Intarcia Therapeutics, Johnson & Johnson, Lexicon, Medtronic, Novo Nordisk, Sanofi, Theracos, Tolerion and vTv Therapeutics; he is a consultant to Cirius Therapeutics Inc, CSL Behring, Mellitus Health, Neurimmune AG, Pendulum Therapeutics and Stability Health; he holds stock/options in Mellitus Health, Pendulum Therapeutics, PhaseBio and Stability Health; and he is supported by grants from the National Institutes of Health (UL1TR002489, U01DK098246, UC4DK108612, U54DK118612), PCORI and ADA. EDAT- 2020/08/04 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/12/22 CRDT- 2020/08/04 06:00 PHST- 2020/04/02 00:00 [received] PHST- 2020/07/24 00:00 [revised] PHST- 2020/07/29 00:00 [accepted] PHST- 2020/08/04 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/08/04 06:00 [entrez] PHST- 2020/12/22 00:00 [pmc-release] AID - DOM14160 [pii] AID - 10.1111/dom.14160 [doi] PST - ppublish SO - Diabetes Obes Metab. 2020 Dec;22(12):2487-2492. doi: 10.1111/dom.14160. Epub 2020 Sep 4. PMID- 32740122 OWN - NLM STAT- MEDLINE DCOM- 20210210 LR - 20260127 IS - 1547-1896 (Print) IS - 0893-7400 (Linking) VI - 33 IP - 8 DP - 2020 Aug TI - Long-acting GLP-1 receptor agonists: Findings and implications of cardiovascular outcomes trials. PG - 19-30 LID - 10.1097/01.JAA.0000669452.63883.45 [doi] AB - Cardiovascular disease (CVD) is a common and serious comorbidity of type 2 diabetes mellitus (T2DM), and cardiovascular (CV) risk assessment has become an important aspect of evaluating new therapies for T2DM before approval by the FDA. Since 2008, in order to establish safety, new therapies for T2DM have been required to demonstrate that they will not result in an unacceptable increase in CV risk. Studies performed for this purpose are termed CV outcome trials, or CVOTs. This article reviews CVOTs completed to date for the class of long-acting glucagon-like peptide-1 receptor agonists (GLP-1RAs; liraglutide, exenatide extended-release, albiglutide, dulaglutide, semaglutide injectable, semaglutide oral) and implications for clinical management of T2DM. All CVOTs have confirmed long-acting GLP-1RAs to be noninferior to (not worse than) placebo with regard to first occurrence of a primary outcome of three-point major adverse cardiovascular events (MACE; composite outcome of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke). Further, a number of the studies demonstrated a statistically significant reduction in primary outcomes of three-point MACE with GLP-1RA treatment compared with placebo. As a result, the product labeling for liraglutide, semaglutide injectable, and dulaglutide has been updated with an indication for reducing the risk of MACE in adults with T2DM and established CVD (all) or multiple CV risk factors (dulaglutide only). These findings have brought about an exciting paradigm shift from concern about not inflicting CV harm to the exciting prospect of reducing risks of CV outcomes. Major diabetes care guidelines now encourage early consideration of GLP-1RA use in patients with atherosclerotic CVD. FAU - Urquhart, Scott AU - Urquhart S AD - Scott Urquhart practices at Diabetes and Thyroid Associates in Fredericksburg, Va., is chair of the Metabolic and Endocrine Disease Summit, an adjunct clinical professor in the PA program at James Madison University in Harrisonburg, Va., and a clinical instructor in the PA program at George Washington University in Washington, D.C. Stephen Willis practices at the Multicare-Rockwood Clinic in Spokane, Wash., and is department chair of the Endocrinology and Advanced Diabetes Center. Mr. Urquhart discloses that he has served on advisory boards for Astra Zeneca, Dexcom, and Sanofi; on speakers' bureaus for Astra Zeneca, Dexcom, and Novo Nordisk Inc; and as a consultant for Novo Nordisk Inc. Stephen Willis has served on an advisory board for Eli Lilly. This manuscript was funded by Novo Nordisk Inc. The authors have disclosed no other potential conflicts of interest, financial or otherwise. FAU - Willis, Stephen AU - Willis S LA - eng PT - Journal Article PT - Review PL - United States TA - JAAPA JT - JAAPA : official journal of the American Academy of Physician Assistants JID - 9513102 RN - 0 (Delayed-Action Preparations) RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 5E7U48495E (rGLP-1 protein) RN - WTT295HSY5 (dulaglutide) MH - Administration, Oral MH - Cardiovascular Diseases/*etiology/*prevention & control MH - Delayed-Action Preparations MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Exenatide/administration & dosage MH - Glucagon-Like Peptide 1/administration & dosage/analogs & derivatives MH - Glucagon-Like Peptides/administration & dosage/*analogs & derivatives MH - Heart Disease Risk Factors MH - Humans MH - Immunoglobulin Fc Fragments/*administration & dosage MH - Injections MH - Liraglutide/*administration & dosage MH - Practice Guidelines as Topic MH - Recombinant Fusion Proteins/*administration & dosage MH - Treatment Outcome MH - United States MH - United States Food and Drug Administration MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2020/08/03 06:00 MHDA- 2021/02/11 06:00 CRDT- 2020/08/03 06:00 PHST- 2020/08/03 06:00 [entrez] PHST- 2020/08/03 06:00 [pubmed] PHST- 2021/02/11 06:00 [medline] AID - 01720610-202008000-00017 [pii] AID - 10.1097/01.JAA.0000669452.63883.45 [doi] PST - ppublish SO - JAAPA. 2020 Aug;33(8):19-30. doi: 10.1097/01.JAA.0000669452.63883.45. PMID- 32740121 OWN - NLM STAT- MEDLINE DCOM- 20210210 LR - 20260127 IS - 1547-1896 (Print) IS - 0893-7400 (Linking) VI - 33 IP - 8 DP - 2020 Aug TI - Long-acting GLP-1RAs: An overview of efficacy, safety, and their role in type 2 diabetes management. PG - 3-18 LID - 10.1097/01.JAA.0000669456.13763.bd [doi] AB - Over recent decades, an improved understanding of the pathophysiology of type 2 diabetes mellitus (T2DM) and glucose regulation has led to innovative research and new treatment paradigms. The discovery of the gut peptide glucagon-like peptide-1 (GLP-1) and its role in glucose regulation paved the way for the class of GLP-1 receptor agonist compounds, or GLP-1RAs. The long-acting GLP-1RAs (dulaglutide, exenatide extended-release, liraglutide, semaglutide [injectable and oral]) are classified as such based on a minimum 24-hour duration of clinically relevant effects after administration. In phase 3 clinical trial programs of long-acting GLP-1RAs, A1C typically was reduced in the range of 1% to 1.5%, with reductions close to 2% in some studies. GLP-1RAs when used alone (without sulfonylureas or insulin) have a low risk of hypoglycemia because, like endogenous GLP-1, their insulinotropic effects are glucose-dependent. In addition to local actions in the gastrointestinal (GI) tract, GLP-1RAs stimulate receptors in the central nervous system to increase satiety, resulting in weight loss. All long-acting GLP-1RAs have, at minimum, been shown to be safe and not increase cardiovascular (CV) risk and most (liraglutide, semaglutide injectable, dulaglutide, albiglutide) have been shown in CV outcomes trials (CVOTs) to significantly reduce the risk of major cardiac adverse events. The class has good tolerability overall, with generally transient GI adverse events being most common. The weekly injectable agents offer scheduling convenience and may promote treatment adherence. One long-acting GLP-1RA is available as an oral daily tablet, which may be preferable for some patients and providers. FAU - Chun, Ji Hyun AU - Chun JH AD - Ji Hyun Chun practices endocrinology at OptumCare Medical Group in Orange County, Calif.; is a medical science liaison at Corcept Therapeutics in Menlo Park, Calif.; and is immediate past president of the American Society of Endocrine Physician Assistants. Amy Butts practices endocrinology at Wheeling (W. Va.) Hospital. Mr. Chun has no conflicts to disclose beyond his employment at Corcept Therapeutics. Ms. Butts has served on speakers' bureaus and advisory boards for Novo Nordisk Inc., on speakers' bureaus for Janssen Pharmaceuticals and Xeris Pharmaceuticals, and on advisory boards for Merck. This manuscript was funded by Novo Nordisk Inc. The authors have disclosed no other potential conflicts of interest, financial or otherwise. FAU - Butts, Amy AU - Butts A LA - eng PT - Journal Article PT - Review PL - United States TA - JAAPA JT - JAAPA : official journal of the American Academy of Physician Assistants JID - 9513102 RN - 0 (Delayed-Action Preparations) RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) MH - Administration, Oral MH - Delayed-Action Preparations MH - Diabetes Mellitus, Type 2/*drug therapy MH - Exenatide/*administration & dosage/pharmacology MH - Glucagon-Like Peptide 1/physiology MH - Glucagon-Like Peptides/administration & dosage/*analogs & derivatives/pharmacology MH - Heart Disease Risk Factors MH - Humans MH - Immunoglobulin Fc Fragments/*administration & dosage/pharmacology MH - Injections MH - Liraglutide/*administration & dosage/pharmacology MH - Recombinant Fusion Proteins/*administration & dosage/pharmacology MH - Satiety Response/drug effects MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2020/08/03 06:00 MHDA- 2021/02/11 06:00 CRDT- 2020/08/03 06:00 PHST- 2020/08/03 06:00 [entrez] PHST- 2020/08/03 06:00 [pubmed] PHST- 2021/02/11 06:00 [medline] AID - 01720610-202008000-00016 [pii] AID - 10.1097/01.JAA.0000669456.13763.bd [doi] PST - ppublish SO - JAAPA. 2020 Aug;33(8):3-18. doi: 10.1097/01.JAA.0000669456.13763.bd. PMID- 32720500 OWN - NLM STAT- MEDLINE DCOM- 20230517 LR - 20250103 IS - 2724-6116 (Electronic) IS - 2724-6116 (Linking) VI - 48 IP - 2 DP - 2023 Jun TI - Pancreatitis and pancreatic cancer in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists: an updated meta-analysis of randomized controlled trials. PG - 206-213 LID - 10.23736/S2724-6507.20.03219-8 [doi] AB - INTRODUCTION: An association between glucagon-like peptide-1 receptor agonists (GLP1-RA) and risk of pancreatitis and pancreatic cancer has been suggested. Since its first description, several new trials (including three cardiovascular outcome trials) have been published, substantially increasing the available data set. This suggests the need for an update of the previous meta-analysis. EVIDENCE ACQUISITION: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials, with duration >/=52 weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug. The endpoints were pancreatitis, pancreatic cancer reported as serious adverse events. Mantel-Haenszel Odds Ratio (MH-OR) with 95% confidence interval (95% CI) was calculated for all outcomes defined above, on an intention-to-treat basis. EVIDENCE SYNTHESIS: A total of 43 trials fulfilling inclusion criteria (all reporting data on pancreatitis and pancreatic cancer) was identified. GLP-1 RA showed no association with pancreatitis (MH-OR 1.24 [0.94, 1.64]; P=0.13) and pancreatic cancer (MH-OR 1.28 [0.87, 1.89]; P=0.20). CONCLUSIONS: No clear evidence of risk for pancreatitis was observed, whereas data on pancreatic cancer are too scarce to draw any conclusion. FAU - Nreu, Besmir AU - Nreu B AD - Department of Diabetology, Careggi University Hospital, Florence, Italy. FAU - Dicembrini, Ilaria AU - Dicembrini I AD - Department of Diabetology, Careggi University Hospital, Florence, Italy. FAU - Tinti, Federico AU - Tinti F AD - Department of Diabetology, Careggi University Hospital, Florence, Italy. FAU - Mannucci, Edoardo AU - Mannucci E AD - Department of Diabetology, Careggi University Hospital, Florence, Italy. FAU - Monami, Matteo AU - Monami M AD - Department of Diabetology, Careggi University Hospital, Florence, Italy - matteo.monami@unifi.it. LA - eng PT - Journal Article DEP - 20200723 PL - Italy TA - Minerva Endocrinol (Torino) JT - Minerva endocrinology JID - 101777342 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Humans MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Hypoglycemic Agents/adverse effects MH - Glucagon-Like Peptide-1 Receptor/therapeutic use MH - Randomized Controlled Trials as Topic MH - *Pancreatitis/chemically induced/epidemiology/complications MH - *Pancreatic Neoplasms/drug therapy/chemically induced/complications MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2020/07/29 06:00 MHDA- 2023/05/17 06:42 CRDT- 2020/07/29 06:00 PHST- 2023/05/17 06:42 [medline] PHST- 2020/07/29 06:00 [pubmed] PHST- 2020/07/29 06:00 [entrez] AID - S0391-1977.20.03219-8 [pii] AID - 10.23736/S2724-6507.20.03219-8 [doi] PST - ppublish SO - Minerva Endocrinol (Torino). 2023 Jun;48(2):206-213. doi: 10.23736/S2724-6507.20.03219-8. Epub 2020 Jul 23. PMID- 32643857 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20240615 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 22 IP - 11 DP - 2020 Nov TI - Impact of microvascular disease on cardiovascular outcomes in type 2 diabetes: Results from the LEADER and SUSTAIN 6 clinical trials. PG - 2193-2198 LID - 10.1111/dom.14140 [doi] AB - The randomized, double-blind, cardiovascular outcomes trials LEADER (NCT01179048) and SUSTAIN 6 (NCT01720446) showed cardiovascular risk reduction in patients with type 2 diabetes treated with liraglutide and semaglutide, respectively, compared with placebo. This post hoc analysis examined the impact of microvascular disease at baseline on cardiovascular outcomes in these trials, and the efficacy of liraglutide (1.8 mg) and once-weekly semaglutide (0.5-1.0 mg) in patients with and without microvascular disease. In total, 9340 patients from LEADER and 3297 patients from SUSTAIN 6 were included in this analysis; of these, 5761 and 2356 had a history of microvascular disease at baseline and 3835 and 1640 had a history of both microvascular and macrovascular disease, respectively. Patients with microvascular disease were shown to have an increased risk of major adverse cardiovascular events compared with patients without microvascular disease (hazard ratio [95% confidence interval] in LEADER: 1.15 [1.03; 1.29], P = .0136; SUSTAIN 6: 1.56 [1.14; 2.17], P = .0064). Liraglutide and semaglutide consistently reduced cardiovascular risk in patients with and without microvascular disease. CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Verma, Subodh AU - Verma S AUID- ORCID: 0000-0002-4018-8533 AD - St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Swansea University Medical School, Swansea, UK. FAU - Honore, Julie Broe AU - Honore JB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - F E Mann, Johannes AU - F E Mann J AD - KfH Kidney Center, Munich, and Department of Nephrology, Friedrich Alexander University of Erlangen, Erlangen, Germany. FAU - A Nauck, Michael AU - A Nauck M AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes Center Bochum-Hattingen, St Josef Hospital (Ruhr-Universitat Bochum), Bochum, Germany. FAU - E Pratley, Richard AU - E Pratley R AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sejersten Ripa, Maria AU - Sejersten Ripa M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Zinman, Bernard AU - Zinman B AUID- ORCID: 0000-0002-0041-1876 AD - Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. LA - eng SI - ClinicalTrials.gov/NCT01179048 SI - ClinicalTrials.gov/NCT01720446 GR - P30 DK124723/DK/NIDDK NIH HHS/United States GR - UL1 TR002489/TR/NCATS NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200812 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) SB - IM MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Double-Blind Method MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Liraglutide/therapeutic use MH - Proportional Hazards Models PMC - PMC7689837 OTO - NOTNLM OT - cardiovascular disease OT - diabetic nephropathy OT - diabetic neuropathy OT - diabetic retinopathy OT - macrovascular disease OT - type 2 diabetes COIS- SV has received research grants and/or speaking honoraria from Boehringer Ingelheim/Eli Lilly, AstraZeneca, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, Valeant and Amgen. SCB has received research grants (includes principal investigator, collaborator or consultant and pending grants/grants already received) from Healthcare and Research Wales (Welsh Government) and Novo Nordisk. He has received other research support from Healthcare and Research Wales (Welsh Government), honoraria from Novo Nordisk, Sanofi, Lilly, Boehringer Ingelheim and Merck, and has ownership interest in Glycosmedia (diabetes online news service). JBH, SR and MSR are full-time employees of Novo Nordisk A/S. SR also holds stocks in Novo Nordisk A/S. JFEM has received speaker honoraria from Amgen, Astra, Boehringer Ingelheim, Braun, Fresenius, Gambro, Eli Lilly & Co, Medice, Novo Nordisk, Relypsa and Roche; research support from the European Union, Canadian Institutes of Health Research, Boehringer Ingelheim, Celgene, Novo Nordisk, Roche and Sandoz; and consulting fees from Astra, Bayer, Celgene, Fresenius, Eli Lilly & Co, Lanthio Pharma, Novo Nordisk, Relypsa, Sanifit and Vifor Pharma. MAN has served on advisory boards or consulted for AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Fractyl, GlaxoSmithKline, Servier, Menarini/Berlin Chemie, Merck, Sharp & Dohme and Novo Nordisk. His institution has received grant support from AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Intarcia, Menarini/Berlin-Chemie, Merck, Sharp & Dohme, Novartis Pharma and Novo Nordisk A/S. He has served on speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Menarini/Berlin Chemie, Sun Pharma, Merck, Sharp & Dohme and Novo Nordisk A/S. REP has received research grants from Gilead Sciences, Lexicon Pharmaceuticals, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Sanofi-Aventis US LLC and Takeda; has acted as a speaker for AstraZeneca, Novo Nordisk and Takeda; and as a consultant for AstraZeneca, Boehringer Ingelheim, Eisai Inc., GlaxoSmithKline, Janssen Scientific Affairs LLC, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Pfizer and Takeda. All payments are made directly to his employer (AdventHealth). BZ has received consulting fees from Merck, Novo Nordisk, Sanofi-Aventis, Eli Lilly, AstraZeneca, Janssen and Boehringer Ingelheim. JBB has been an advisor (all fees paid to the University of North Carolina) for Adocia, AstraZeneca, Dance Biopharm, Eli Lilly, MannKind, NovaTarg, Novo Nordisk, Senseonics, vTv Therapeutics and Zafgen; and received grant support from Novo Nordisk, Sanofi and vTv Therapeutics. He is a consultant to Cirius Therapeutics, CSL Behring, Mellitus Health, Neurimmune AG, Pendulum Therapeutics and Stability Health, and holds stock options in Mellitus Health, Pendulum Therapeutics, PhaseBio and Stability Health. He is supported by a grant from the National Institutes of Health (UL1TR002489). EDAT- 2020/07/10 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/11/26 CRDT- 2020/07/10 06:00 PHST- 2020/03/26 00:00 [received] PHST- 2020/07/03 00:00 [revised] PHST- 2020/07/05 00:00 [accepted] PHST- 2020/07/10 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/07/10 06:00 [entrez] PHST- 2020/11/26 00:00 [pmc-release] AID - DOM14140 [pii] AID - 10.1111/dom.14140 [doi] PST - ppublish SO - Diabetes Obes Metab. 2020 Nov;22(11):2193-2198. doi: 10.1111/dom.14140. Epub 2020 Aug 12. PMID- 32643514 OWN - NLM STAT- MEDLINE DCOM- 20201221 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 132 IP - 8 DP - 2020 Nov TI - Practical guidance for use of oral semaglutide in primary care: a narrative review. PG - 687-696 LID - 10.1080/00325481.2020.1788340 [doi] AB - As the cornerstone of type 2 diabetes (T2D) management within the community, primary care providers are now faced with the challenge of not only managing diabetes itself, but also preventing hypoglycemia and weight gain associated with intensive disease management, and reducing cardiovascular risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are well established as efficacious treatments for T2D, and the safety/tolerability profile of this drug class is well defined. However, despite their beneficial effects, GLP-1RAs are under-utilized, highlighting the need for novel approaches to increase their use in primary care. Oral semaglutide is the first oral GLP-1RA approved for the treatment of T2D, offering glucose lowering and body weight loss, a low risk of hypoglycemia, and no increase in cardiovascular risk. Oral semaglutide represents an additional treatment option for patients not achieving their glycemic goal despite treatment with metformin, either alone or with other hypoglycemic agents. Oral semaglutide has the potential to increase usage of GLP-1RAs in the primary care setting by addressing clinician and patient concerns about injections, and may facilitate earlier initiation of GLP-1RA therapy in T2D. Due to the formulation of oral semaglutide, clinicians need to be aware of specific considerations in order to ensure optimal use. Such considerations include dosing conditions and use of concomitant medications. This article provides practical guidance on the use of oral semaglutide in the primary care setting, based on evidence from clinical studies, including the phase 3a PIONEER program, and the authors' clinical experience. FAU - Morales, Javier AU - Morales J AUID- ORCID: 0000-0003-1005-0311 AD - Department of Medicine, Donald and Barbara Zucker School of Medicine, Hofstra/Northwell University , New York, NY, USA. FAU - Shubrook, Jay H AU - Shubrook JH AUID- ORCID: 0000-0001-5173-2656 AD - Primary Care Department, College of Osteopathic Medicine, Touro University California , Vallejo, CA, USA. FAU - Skolnik, Neil AU - Skolnik N AD - Abington Family Medicine , Jenkintown, PA, USA. LA - eng PT - Journal Article PT - Systematic Review DEP - 20200709 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - IX503L9WN0 (ganirelix) SB - IM MH - Blood Glucose MH - Cardiovascular Diseases/epidemiology MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/adverse effects/*therapeutic use MH - Gonadotropin-Releasing Hormone/analogs & derivatives MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Practice Guidelines as Topic MH - Randomized Controlled Trials as Topic MH - Weight Loss MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - incretins OT - oral semaglutide OT - primary care OT - type 2 diabetes EDAT- 2020/07/10 06:00 MHDA- 2020/12/22 06:00 CRDT- 2020/07/10 06:00 PHST- 2020/07/10 06:00 [pubmed] PHST- 2020/12/22 06:00 [medline] PHST- 2020/07/10 06:00 [entrez] AID - 10.1080/00325481.2020.1788340 [doi] PST - ppublish SO - Postgrad Med. 2020 Nov;132(8):687-696. doi: 10.1080/00325481.2020.1788340. Epub 2020 Jul 9. PMID- 32628589 OWN - NLM STAT- MEDLINE DCOM- 20210325 LR - 20250919 IS - 1875-6417 (Electronic) IS - 1573-3998 (Linking) VI - 17 IP - 3 DP - 2021 TI - Effects of Antidiabetic Drugs on Muscle Mass in Type 2 Diabetes Mellitus. PG - 293-303 LID - 10.2174/1573399816666200705210006 [doi] AB - BACKGROUND: When considering the administration of glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 (SGLT2) inhibitors, or metformin, it is important to understand their weight loss effect as well as the degree of muscle loss caused by each drug in clinical practice. OBJECTIVE: To comparatively examine the effects of GLP-1RAs and oral antidiabetic drugs, including SGLT2 inhibitors and metformin, on muscle mass and body weight in patients with type 2 diabetes via a network meta-analysis of randomized controlled trials. METHODS: We included randomized controlled trials evaluating the effects of antidiabetic drugs on muscle mass and body weight. Mean difference (MD) and 95% confidence intervals (CIs) were calculated using a random-effects network meta-analysis. RESULTS: Of the studies identified, 18 randomized controlled trials (1, 363 subjects) satisfied the eligibility criteria. In all studies, the effects of these drugs on fat-free mass (FFM) were evaluated. Therefore, FFM, which is used as an alternative index of muscle mass, was included in the study. Semaglutide (MD: -1.68, 95% CI: -2.84 to -0.52), dapagliflozin (-0.53, -0.93 to -0.13), and canagliflozin (-0.90, -1.73 to -0.07) showed a significant decrease in FFM compared with the placebo. Metformin did not show a significant decrease in FFM compared with the placebo. When compared with the placebo, semaglutide, dapagliflozin, ipragliflozin, and canagliflozin showed a significant weight loss. CONCLUSION: Although semaglutide, dapaglifrozin, and canagliflozin have a large weight loss effect, it is important to pay attention to muscle loss because a decrease in FFM was observed. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Ida, Satoshi AU - Ida S AD - Department of Diabetes and Metabolism, Ise Red Cross Hospital, Mie, Japan. FAU - Kaneko, Ryutaro AU - Kaneko R AD - Department of Diabetes and Metabolism, Ise Red Cross Hospital, Mie, Japan. FAU - Imataka, Kanako AU - Imataka K AD - Department of Diabetes and Metabolism, Ise Red Cross Hospital, Mie, Japan. FAU - Okubo, Kaoru AU - Okubo K AD - Department of Diabetes and Metabolism, Ise Red Cross Hospital, Mie, Japan. FAU - Shirakura, Yoshitaka AU - Shirakura Y AD - Department of Diabetes and Metabolism, Ise Red Cross Hospital, Mie, Japan. FAU - Azuma, Kentaro AU - Azuma K AD - Department of Diabetes and Metabolism, Ise Red Cross Hospital, Mie, Japan. FAU - Fujiwara, Ryoko AU - Fujiwara R AD - Department of Diabetes and Metabolism, Ise Red Cross Hospital, Mie, Japan. FAU - Murata, Kazuya AU - Murata K AD - Department of Diabetes and Metabolism, Ise Red Cross Hospital, Mie, Japan. LA - eng PT - Journal Article PT - Network Meta-Analysis PL - United Arab Emirates TA - Curr Diabetes Rev JT - Current diabetes reviews JID - 101253260 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0SAC974Z85 (Canagliflozin) SB - IM MH - Canagliflozin MH - *Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - Hypoglycemic Agents MH - Muscles MH - *Sodium-Glucose Transporter 2 Inhibitors MH - Treatment Outcome OTO - NOTNLM OT - Antidiabetic drugs OT - body weight OT - glucagon-like peptide-1 receptor agonists OT - muscle mass OT - network meta-analysis OT - type 2 diabetes mellitus EDAT- 2020/07/07 06:00 MHDA- 2021/03/26 06:00 CRDT- 2020/07/07 06:00 PHST- 2020/04/14 00:00 [received] PHST- 2020/06/16 00:00 [revised] PHST- 2020/06/21 00:00 [accepted] PHST- 2020/07/07 06:00 [pubmed] PHST- 2021/03/26 06:00 [medline] PHST- 2020/07/07 06:00 [entrez] AID - CDR-EPUB-107909 [pii] AID - 10.2174/1573399816666200705210006 [doi] PST - ppublish SO - Curr Diabetes Rev. 2021;17(3):293-303. doi: 10.2174/1573399816666200705210006. PMID- 32598218 OWN - NLM STAT- MEDLINE DCOM- 20201214 LR - 20260127 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 173 IP - 4 DP - 2020 Aug 18 TI - Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis. PG - 278-286 LID - 10.7326/M20-0864 [doi] AB - BACKGROUND: Several pharmacologic options for type 2 diabetes are available. PURPOSE: To compare benefits and harms of glucose-lowering drugs in adults with type 2 diabetes. DATA SOURCES: Several databases from inception through 18 December 2019 and ClinicalTrials.gov on 10 April 2020. STUDY SELECTION: English-language randomized trials that had at least 24 weeks of intervention and assessed the effects of glucose-lowering drugs on mortality, glycemic, and vascular outcomes. DATA EXTRACTION: Pairs of reviewers extracted data and appraised risk of bias. DATA SYNTHESIS: 453 trials assessing 21 antidiabetic interventions from 9 drug classes were included. Interventions included monotherapies (134 trials), add-on to metformin-based therapies (296 trials), and monotherapies versus add-on to metformin therapies (23 trials). There were no differences between treatments in drug-naive patients at low cardiovascular risk. Insulin regimens and specific glucagon-like peptide-1 receptor agonists (GLP-1 RAs) added to metformin-based background therapy produced the greatest reductions in hemoglobin A(1c) level. In patients at low cardiovascular risk receiving metformin-based background treatment (298 trials), there were no clinically meaningful differences between treatments for mortality and vascular outcomes. In patients at increased cardiovascular risk receiving metformin-based background treatment (21 trials), oral semaglutide, empagliflozin, liraglutide, extended-release exenatide, and dapagliflozin reduced all-cause mortality. Oral semaglutide, empagliflozin, and liraglutide also reduced cardiovascular death. Odds of stroke were lower with subcutaneous semaglutide and dulaglutide. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduced heart failure hospitalization and end-stage renal disease. Subcutaneous semaglutide and canagliflozin increased diabetic retinopathy and amputation, respectively. LIMITATION: Inconsistent definitions of cardiovascular risk and low-level confidence in some estimates for patients at low cardiovascular risk. CONCLUSION: In diabetic patients at low cardiovascular risk, no treatment differs from placebo for vascular outcomes. In patients at increased cardiovascular risk receiving metformin-based background therapy, specific GLP-1 RAs and SGLT-2 inhibitors have a favorable effect on certain cardiovascular outcomes. PRIMARY FUNDING SOURCE: European Foundation for the Study of Diabetes, supported by an unrestricted educational grant from AstraZeneca. (PROSPERO: CRD42019122043). FAU - Tsapas, Apostolos AU - Tsapas A AD - Clinical Research and Evidence-Based Medicine Unit and Diabetes Centre, Aristotle University of Thessaloniki, Thessaloniki, Greece, and Harris Manchester College, University of Oxford, Oxford, United Kingdom (A.T.). FAU - Avgerinos, Ioannis AU - Avgerinos I AUID- ORCID: 0000-0003-2232-1342 AD - Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece (I.A., T.K., K.M., A.M., A.L.). FAU - Karagiannis, Thomas AU - Karagiannis T AUID- ORCID: 0000-0001-5242-0574 AD - Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece (I.A., T.K., K.M., A.M., A.L.). FAU - Malandris, Konstantinos AU - Malandris K AD - Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece (I.A., T.K., K.M., A.M., A.L.). FAU - Manolopoulos, Apostolos AU - Manolopoulos A AUID- ORCID: 0000-0003-1055-0324 AD - Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece (I.A., T.K., K.M., A.M., A.L.). FAU - Andreadis, Panagiotis AU - Andreadis P AD - Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece, and North West Anglia NHS Foundation Trust, Peterborough City Hospital, Peterborough, United Kingdom (P.A.). FAU - Liakos, Aris AU - Liakos A AUID- ORCID: 0000-0003-3261-2979 AD - Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece (I.A., T.K., K.M., A.M., A.L.). FAU - Matthews, David R AU - Matthews DR AUID- ORCID: 0000-0001-6504-0036 AD - Harris Manchester College, University of Oxford, and Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, United Kingdom (D.R.M.). FAU - Bekiari, Eleni AU - Bekiari E AD - Clinical Research and Evidence-Based Medicine Unit and Diabetes Centre, Aristotle University of Thessaloniki, Thessaloniki, Greece (E.B.). LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20200630 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) SB - IM CIN - Ann Intern Med. 2020 Aug 18;173(4):311-312. doi: 10.7326/M20-4266. PMID: 32598225 CIN - Ann Intern Med. 2020 Nov 17;173(10):JC53. doi: 10.7326/ACPJ202011170-053. PMID: 33197350 CIN - Ann Intern Med. 2021 Jan;174(1):141. doi: 10.7326/L20-1278. PMID: 33460545 CIN - Ann Intern Med. 2021 Jan;174(1):140. doi: 10.7326/L20-1277. PMID: 33460546 MH - Blood Glucose/analysis MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Treatment Outcome EDAT- 2020/07/01 06:00 MHDA- 2020/12/15 06:00 CRDT- 2020/06/30 06:00 PHST- 2020/07/01 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/06/30 06:00 [entrez] AID - 10.7326/M20-0864 [doi] PST - ppublish SO - Ann Intern Med. 2020 Aug 18;173(4):278-286. doi: 10.7326/M20-0864. Epub 2020 Jun 30. PMID- 32584928 OWN - NLM STAT- MEDLINE DCOM- 20220105 LR - 20250103 IS - 2380-6591 (Electronic) IS - 2380-6583 (Print) VI - 5 IP - 10 DP - 2020 Oct 1 TI - Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review. PG - 1182-1190 LID - 10.1001/jamacardio.2020.1966 [doi] AB - IMPORTANCE: Recent randomized clinical trials have demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce cardiovascular events in at-risk individuals with type 2 diabetes. Despite these findings, GLP-1RAs are underused in eligible patients, particularly by cardiologists. OBSERVATIONS: To date, randomized clinical trials of albiglutide, dulaglutide, liraglutide, and injectable semaglutide have reported favorable cardiovascular outcomes. Most recently approved for clinical use, oral semaglutide has a favorable safety profile and is currently undergoing regulatory evaluation and further study for cardiovascular outcomes. Professional society guidelines now recommend GLP-1RA therapy for cardiovascular risk mitigation in patients with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD) or multiple ASCVD risk factors, independent of glucose control or background antihyperglycemic therapy (other diabetes medications being used). Additional conditions suitable for GLP-1RA therapy include obesity and advanced chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2), for which cardiovascular risk-reducing options are limited. Out-of-pocket costs and secondary advantages (eg, weight loss) may inform shared decision-making discussions regarding potential therapies. GLP-1RA therapy has a favorable safety profile. Its most common adverse effect is gastrointestinal upset, which typically wanes during the early weeks of therapy and may be mitigated by starting at the lowest dose and escalating as tolerated. Depending on baseline glycemic control, sulfonylureas and insulin may need to be decreased before GLP-1RA initiation; without concurrent use of insulin or sulfonylureas, GLP-1RAs are not associated with hypoglycemia. Multidisciplinary follow-up and collaborative care with primary care physicians and/or endocrinologists are important. CONCLUSIONS AND RELEVANCE: Findings from this review suggest that GLP-1RAs are safe, are well tolerated, and improve cardiovascular outcomes, largely independent of their antihyperglycemic properties, but they remain underused by cardiologists. This review provides a practical resource for cardiologists for initiating GLP-1RAs and managing the therapy in patients with type 2 diabetes and established ASCVD or high risk for ASCVD. FAU - Honigberg, Michael C AU - Honigberg MC AD - Cardiology Division, Massachusetts General Hospital, Boston. FAU - Chang, Lee-Shing AU - Chang LS AD - Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts. FAU - McGuire, Darren K AU - McGuire DK AD - Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas. FAU - Plutzky, Jorge AU - Plutzky J AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts. FAU - Aroda, Vanita R AU - Aroda VR AD - Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Boston, Massachusetts. FAU - Vaduganathan, Muthiah AU - Vaduganathan M AD - Division of Cardiovascular Medicine, Brigham and Women's Hospital Heart and Vascular Center, Boston, Massachusetts. LA - eng GR - T32 HL094301/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Review PL - United States TA - JAMA Cardiol JT - JAMA cardiology JID - 101676033 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cardiovascular Diseases/*complications MH - Contraindications, Drug MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Heart Failure/complications MH - Humans MH - Hypoglycemic Agents/economics/*therapeutic use MH - Obesity/complications MH - Overweight/complications MH - Renal Insufficiency, Chronic/complications MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC7744318 MID - NIHMS1633953 EDAT- 2020/06/26 06:00 MHDA- 2022/01/06 06:00 PMCR- 2021/05/05 CRDT- 2020/06/26 06:00 PHST- 2020/06/26 06:00 [pubmed] PHST- 2022/01/06 06:00 [medline] PHST- 2020/06/26 06:00 [entrez] PHST- 2021/05/05 00:00 [pmc-release] AID - 2766892 [pii] AID - 10.1001/jamacardio.2020.1966 [doi] PST - ppublish SO - JAMA Cardiol. 2020 Oct 1;5(10):1182-1190. doi: 10.1001/jamacardio.2020.1966. PMID- 32571416 OWN - NLM STAT- MEDLINE DCOM- 20201026 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 19 IP - 1 DP - 2020 Jun 22 TI - Indirect comparison of glucagon like peptide-1 receptor agonists regarding cardiovascular safety and mortality in patients with type 2 diabetes mellitus: network meta-analysis. PG - 96 LID - 10.1186/s12933-020-01070-z [doi] LID - 96 AB - BACKGROUND: The cardiovascular outcome trials (CVOTs) have shown that glucagon like peptide-1 receptor agonists (GLP1RAs) have varying degrees of cardiovascular (CV) safety in patients with type 2 diabetes mellitus (T2DM.) The lack of any head-to-head comparative trials among GLP1RAs urged the need for an indirect comparison of these agents. Therefore, this study was conducted to indirectly compare the CV safety and mortality effects among different GLP1RAs in patients with T2DM using network meta-analysis (NMA). METHODS: Medline was searched to identify GLP1RA CVOTs to date. The outcomes of interest were CV death, myocardial infarction (IM), stroke, and death from any cause. An NMA with binomial likelihood logit link model was used for the binary outcomes. We conducted both fixed effects and random effects models for each outcome, and selected the best model based on the deviance information and the average posterior residual deviance. This NMA was reported in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA-NMA). RESULTS: A total of seven GLP1RA CVOTs were included having 56,004 patients. The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21-0.99), dulaglutide (OR 0.46, 95% CI 0.20-0.97), albiglutide (OR 0.45, 95% CI 0.19-0.97), lixisenatide (OR 0.43, 95% CI 0.19-0.92) in reducing CV death events. No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events. The ranking results showed that oral semaglutide had the highest probability to be ranked first (> 90%) in reducing CV death and death from any cause. Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events. CONCLUSION: The GLP1RAs have shown significant benefits in terms of CV safety. The indirect comparison and ranking probability results have shown that one weekly semaglutide and oral semaglutide seems to be the preferred option in patients with T2DM and established or at high risk of CVD. This result can aid health care providers, pharmacy and therapeutics committees in hospitals, and insurance companies when deciding which GLP1RA to start or add to their formulary. FAU - Alfayez, Osamah M AU - Alfayez OM AD - Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia. FAU - Almohammed, Omar A AU - Almohammed OA AUID- ORCID: 0000-0002-3792-4106 AD - Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. oalmohammed@ksu.edu.sa. FAU - Alkhezi, Omar S AU - Alkhezi OS AD - Department of Pharmacy Practice, College of Pharmacy, Qassim University, Qassim, Saudi Arabia. FAU - Almutairi, Abdulaali R AU - Almutairi AR AD - Saudi Food and Drug Authority, Riyadh, Saudi Arabia. FAU - Al Yami, Majed S AU - Al Yami MS AD - Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20200622 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Aged MH - Biomarkers/blood MH - Blood Glucose/*drug effects/metabolism MH - Cardiovascular Diseases/diagnosis/mortality/*prevention & control MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/mortality MH - Female MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Incretins/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Protective Factors MH - Risk Assessment MH - Risk Factors MH - Time Factors MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor PMC - PMC7310317 OTO - NOTNLM OT - Cardiovascular disease OT - Diabetes mellitus OT - Heart failure OT - Meta-analysis OT - Myocardial infarction OT - Stroke OT - Type 2 COIS- The authors declare that they have no competing interests. EDAT- 2020/06/24 06:00 MHDA- 2020/10/27 06:00 PMCR- 2020/06/22 CRDT- 2020/06/24 06:00 PHST- 2020/02/09 00:00 [received] PHST- 2020/06/16 00:00 [accepted] PHST- 2020/06/24 06:00 [entrez] PHST- 2020/06/24 06:00 [pubmed] PHST- 2020/10/27 06:00 [medline] PHST- 2020/06/22 00:00 [pmc-release] AID - 10.1186/s12933-020-01070-z [pii] AID - 1070 [pii] AID - 10.1186/s12933-020-01070-z [doi] PST - epublish SO - Cardiovasc Diabetol. 2020 Jun 22;19(1):96. doi: 10.1186/s12933-020-01070-z. PMID- 32538541 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 22 IP - 11 DP - 2020 Nov TI - Semaglutide once weekly in people with type 2 diabetes: Real-world analysis of the Canadian LMC diabetes registry (SPARE study). PG - 2013-2020 LID - 10.1111/dom.14117 [doi] AB - AIMS: To investigate real-world short-term clinical outcomes in adults with type 2 diabetes (T2D) who initiated semaglutide in a specialist endocrinology practice in Canada. MATERIALS AND METHODS: This study was a retrospective observational study using data from the Canadian LMC Diabetes Registry. Adults with T2D who were naive to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy, initiated semaglutide therapy as usual standard of care between February 2018 and February 2019, and maintained semaglutide therapy during follow-up, were eligible for analysis. The primary outcome was mean change in glycated haemoglobin (HbA1c) at 3- to 6-month follow-up. RESULTS: In the final analytical cohort (n = 937), there was a statistically significant mean +/- SD reduction in HbA1c of -1.03 +/- 1.24% (11.3 +/- 13.6 mmol/mol, P < 0.001) and weight of -3.9 +/- 4.0 kg (P < 0.001), with no significant change in self-reported incidence of hypoglycaemia. There was a significant reduction in HbA1c and weight regardless of number of co-therapies or semaglutide dose. However, adults using the 1.0-mg dose had a significantly greater reduction in HbA1c compared to adults using the 0.25- to 0.5-mg dose (between-group difference - 0.24 +/- 0.06%, 2.6 +/- 0.7 mmol/mol; P < 0.001). Adults using basal-bolus therapy required a significantly lower median total daily dose of insulin after adding semaglutide (0.82 vs. 0.93 U/kg; P < 0.001). CONCLUSIONS: This retrospective observational study demonstrated that GLP-1RA-naive adults with T2D initiating semaglutide in a real-world clinical practice had a statistically and clinically significant reduction in HbA1c and body weight after 3 to 6 months, regardless of semaglutide dose or order of semaglutide therapy, with no significant change in reported incidence of hypoglycaemia. CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Brown, Ruth E AU - Brown RE AD - LMC Diabetes and Endocrinology, Toronto, Ontario, Canada. FAU - Bech, Peter G AU - Bech PG AD - Novo Nordisk Canada Inc, Mississauga, Ontario, Canada. FAU - Aronson, Ronnie AU - Aronson R AUID- ORCID: 0000-0002-8976-2321 AD - LMC Diabetes and Endocrinology, Toronto, Ontario, Canada. LA - eng GR - This study was funded by Novo Nordisk./International PT - Journal Article PT - Observational Study PT - Research Support, Non-U.S. Gov't DEP - 20200713 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Canada/epidemiology MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Registries MH - Semaglutide PMC - PMC7689820 OTO - NOTNLM OT - glycaemic control OT - hypoglycaemia OT - type 2 diabetes COIS- R.E.B. has no conflicts of interest to declare. P.G.B. is an employee of, and shareholder of, Novo Nordisk. R.A. reports research grants from Sanofi, Novo Nordisk, Janssen, AstraZeneca, Becton Dickinson Technologies, Boehringer Ingelheim, Eli Lilly, Zealand, Xeris, Medpace, Kowa, Insulet, Dexcom, Bausch Health, Tandem Diabetes and Bayer, and consultancies/personal fees from Sanofi, Novo Nordisk, Janssen, AstraZeneca, Becton Dickinson Technologies, Boehringer Ingelheim, Eli Lilly, HTL Strefa, Gilead and Merck. EDAT- 2020/06/17 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/11/26 CRDT- 2020/06/16 06:00 PHST- 2020/04/23 00:00 [received] PHST- 2020/06/08 00:00 [revised] PHST- 2020/06/11 00:00 [accepted] PHST- 2020/06/17 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/06/16 06:00 [entrez] PHST- 2020/11/26 00:00 [pmc-release] AID - DOM14117 [pii] AID - 10.1111/dom.14117 [doi] PST - ppublish SO - Diabetes Obes Metab. 2020 Nov;22(11):2013-2020. doi: 10.1111/dom.14117. Epub 2020 Jul 13. PMID- 32519795 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20250103 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 22 IP - 10 DP - 2020 Oct TI - The novel dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long-acting GLP-1 receptor agonists. PG - 1886-1891 LID - 10.1111/dom.14110 [doi] AB - The effect of dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide on gastric emptying (GE) was compared to that of GLP-1RAs in non-clinical and clinical studies. GE was assessed following acute and chronic treatment with tirzepatide in diet-induced obese mice versus semaglutide or long-acting GIP analogue alone. Participants [with and without type 2 diabetes (T2DM)] from a phase 1, 4-week multiple dose study received tirzepatide, dulaglutide or placebo. GE was assessed by acetaminophen absorption. In mice, tirzepatide delayed GE to a similar degree to that achieved with semaglutide; however, these acute inhibitory effects were abolished after 2 weeks of treatment. GIP analogue alone had no effect on GE or on GLP-1's effect on GE. In participants with and without T2DM, once-weekly tirzepatide (>/=5 and >/=4.5 mg, respectively) delayed GE after a single dose. This effect diminished after multiple doses of tirzepatide or dulaglutide in healthy participants. In participants with T2DM treated with an escalation schedule of tirzepatide 5/5/10/10 or 5/5/10/15 mg, a residual GE delay was still observed after multiple doses. These data suggest that tirzepatide's activity on GE is comparable to that of selective GLP-1RAs. CI - (c) 2020 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Urva, Shweta AU - Urva S AUID- ORCID: 0000-0002-3681-479X AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. FAU - Coskun, Tamer AU - Coskun T AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. FAU - Loghin, Corina AU - Loghin C AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. FAU - Cui, Xuewei AU - Cui X AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. FAU - Beebe, Emily AU - Beebe E AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. FAU - O'Farrell, Libbey AU - O'Farrell L AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. FAU - Briere, Daniel A AU - Briere DA AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. FAU - Benson, Charles AU - Benson C AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes Division, Katholisches Klinikum Bochum, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany. FAU - Haupt, Axel AU - Haupt A AUID- ORCID: 0000-0003-4502-0470 AD - Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. LA - eng GR - Funding was provided by Eli Lilly and Company/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200713 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - IY9XDZ35W2 (Glucose) RN - OYN3CCI6QE (Tirzepatide) SB - IM MH - Animals MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy MH - Gastric Emptying MH - Gastric Inhibitory Polypeptide MH - Glucagon-Like Peptide 1 MH - *Glucagon-Like Peptide-1 Receptor MH - Glucose MH - Mice MH - Tirzepatide PMC - PMC7539915 OTO - NOTNLM OT - GIP OT - GLP-1 analogue OT - antidiabetic drug OT - incretin therapy OT - type 2 diabetes COIS- S.U., T.C., L.O., E.B., D.B., X.C., A.H., C.B. and C.L. are employees and shareholders of Eli Lilly and Company. M.A.N. has been a member of advisory boards or consulted for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Fractyl, GlaxoSmithKline, Intarcia, Menarini/Berlin Chemie, Merck, Sharp & Dohme and NovoNordisk. His institution has received grant support from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline, Intarcia, Menarini/Berlin-Chemie, Merck, Sharp & Dohme, Novartis Pharma and Novo Nordisk A/S. He has served on the speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline, Menarini/Berlin Chemie, Merck, Sharp & Dohme and Novo Nordisk A/S. EDAT- 2020/06/11 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/10/07 CRDT- 2020/06/11 06:00 PHST- 2020/04/10 00:00 [received] PHST- 2020/05/27 00:00 [revised] PHST- 2020/06/04 00:00 [accepted] PHST- 2020/06/11 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/06/11 06:00 [entrez] PHST- 2020/10/07 00:00 [pmc-release] AID - DOM14110 [pii] AID - 10.1111/dom.14110 [doi] PST - ppublish SO - Diabetes Obes Metab. 2020 Oct;22(10):1886-1891. doi: 10.1111/dom.14110. Epub 2020 Jul 13. PMID- 32476529 OWN - NLM STAT- MEDLINE DCOM- 20210128 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 13 IP - 7 DP - 2020 Jul TI - Semaglutide injection for the treatment of adults with type 2 diabetes. PG - 675-684 LID - 10.1080/17512433.2020.1776108 [doi] AB - INTRODUCTION: Current estimates suggest that approximately 10% of the global adult population have type 2 diabetes. In recent years there has been a significant increase in the therapeutic options available for its treatment. This article examines the use of injectable semaglutide in the treatment of type 2 diabetes. AREAS COVERED: We will describe the global problem posed by type 2 diabetes followed by consideration of the glucagon-like peptide 1 receptor agonist class of glucose lowering therapies. The focus is then shifted to semaglutide and a description of the large phase 3 pre-approval trial programme known as SUSTAIN. There is consideration of glucose control, the primary end-point of the phase 3 programme, as well as secondary end-points such as weight and blood pressure. There follows a precis of the cardiovascular outcomes trial for subcutaneous semaglutide (SUSTAIN 6) and the post-approval publications. As well as the SUSTAIN trial programme we used PubMed to identify relevant publications. EXPERT OPINION: This section discusses the position of semaglutide and the risks and benefits versus other once weekly GLP-1RAs and finally the development of an oral version of semaglutide, which has recently been approved in the United States. FAU - Chudleigh, Richard A AU - Chudleigh RA AUID- ORCID: 0000-0003-4784-7746 AD - Singleton Hospital, Swansea Bay University Health Board. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Singleton Hospital, Swansea Bay University Health Board. AD - Diabetes Research Unit, Swansea University Medical School , UK. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20200707 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Blood Glucose/drug effects MH - Blood Pressure/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - Glucagon-Like Peptides/*administration & dosage/adverse effects/pharmacology MH - Humans MH - Hypoglycemic Agents/*administration & dosage/pharmacology MH - Injections MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - CVOT OT - T2DM OT - glp-1RA OT - glucagon-like peptide-1 OT - semaglutide OT - sustain OT - type 2 diabetes EDAT- 2020/06/02 06:00 MHDA- 2021/01/29 06:00 CRDT- 2020/06/02 06:00 PHST- 2020/06/02 06:00 [pubmed] PHST- 2021/01/29 06:00 [medline] PHST- 2020/06/02 06:00 [entrez] AID - 10.1080/17512433.2020.1776108 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2020 Jul;13(7):675-684. doi: 10.1080/17512433.2020.1776108. Epub 2020 Jul 7. PMID- 32448716 OWN - NLM STAT- MEDLINE DCOM- 20201013 LR - 20260127 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 30 IP - 7 DP - 2020 Jun 25 TI - Major cardiovascular events, heart failure, and atrial fibrillation in patients treated with glucagon-like peptide-1 receptor agonists: An updated meta-analysis of randomized controlled trials. PG - 1106-1114 LID - S0939-4753(20)30095-8 [pii] LID - 10.1016/j.numecd.2020.03.013 [doi] AB - BACKGROUND AND AIMS: Glucagon-like Peptide 1 Receptor Agonists (GLP1-RA) has been associated with a reduction of major cardiovascular events (MACE) and mortality on the basis of the results of cardiovascular outcome trials (CVOT). Several meta-analyses on this issue have been recently published; however, they were all restricted to CVOT, with the exclusion of all studies designed for other endpoints; moreover, other cardiovascular endpoints, such as atrial fibrillation and heart failure have not been fully explored. METHODS AND RESULTS: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration >/=52 weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug. We included 43 trials, enrolling 63,134 patients. A significant reduction of MACE (MH-OR 0.87 [0.83, 0.92]), all-cause mortality (MH-OR 0.89 [0.83, 0.96]), and a nonstatistical trend toward reduction of heart failure (MH-OR 0.93 [0.85, 1.01]) was observed - GLP1-RA did not increase the risk of atrial fibrillation (MH-OR 0.94 [0.84, 1.04]). CONCLUSION: The present meta-analysis confirms the favorable effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events, cardiovascular and all-cause mortality, stroke, and possibly myocardial infarction. Conversely, the effects on heart failure remain uncertain. Available data on atrial fibrillation seems to exclude any major safety issues in this respect. REGISTRATION NUMBER (PROSPERO): CRD42018115577. CI - Copyright (c) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved. FAU - Nreu, Besmir AU - Nreu B AD - Diabetology, Careggi Hospital and University of Florence, Italy. FAU - Dicembrini, Ilaria AU - Dicembrini I AD - Diabetology, Careggi Hospital and University of Florence, Italy. FAU - Tinti, Federico AU - Tinti F AD - Diabetology, Careggi Hospital and University of Florence, Italy. FAU - Sesti, Giorgio AU - Sesti G AD - Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology of the Sapienza University of Rome, Rome, Italy. FAU - Mannucci, Edoardo AU - Mannucci E AD - Diabetology, Careggi Hospital and University of Florence, Italy. FAU - Monami, Matteo AU - Monami M AD - Diabetology, Careggi Hospital and University of Florence, Italy. Electronic address: matteo.monami@unifi.it. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20200325 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Aged MH - Atrial Fibrillation/diagnosis/mortality/physiopathology/*prevention & control MH - Cause of Death MH - Diabetes Mellitus, Type 2/diagnosis/*drug therapy/mortality MH - Female MH - Heart Failure/diagnosis/mortality/physiopathology/*prevention & control MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Incidence MH - Incretins/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Myocardial Infarction/mortality/physiopathology/prevention & control MH - Protective Factors MH - Randomized Controlled Trials as Topic MH - Risk Assessment MH - Risk Factors MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - All-cause mortality OT - Atrial fibrillation OT - Glucagon-like peptide-1 receptor agonists OT - Heart failure OT - Major amputations OT - Major cardiovascular events OT - Meta-analysis COIS- Declaration of Competing Interest BN is presently employee of Novo Nordisk; ID has received speaking fees from Novonordisk; FT has no conflicts of interest to declare; EM has received consultancy fees from Merck and Novartis speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis and research grants from Merck, Novartis, and Takeda. GS has received speaking fees from Novo Nordisk, Merck Sharp & Dohme, Sanofi, Boehringer Ingelheim, Eli Lilly, Astra Zeneca, L-Nutra, Theras, Sanofi, Mundipharma, Omikron, and Novartis, and consultancy fees from Servier, Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Astra Zeneca, Merck Sharp & Dohme, Sanofi, Amgem and GlaxoSmithKline; MM has received speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis and research grants from Bristol Myers Squibb. All the authors approved the final version of this manuscript. Dr. Matteo Monami is the person who takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript. EDAT- 2020/05/26 06:00 MHDA- 2020/10/21 06:00 CRDT- 2020/05/26 06:00 PHST- 2020/01/21 00:00 [received] PHST- 2020/03/13 00:00 [revised] PHST- 2020/03/14 00:00 [accepted] PHST- 2020/05/26 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2020/05/26 06:00 [entrez] AID - S0939-4753(20)30095-8 [pii] AID - 10.1016/j.numecd.2020.03.013 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2020 Jun 25;30(7):1106-1114. doi: 10.1016/j.numecd.2020.03.013. Epub 2020 Mar 25. PMID- 32441473 OWN - NLM STAT- MEDLINE DCOM- 20200915 LR - 20260127 IS - 1930-739X (Electronic) IS - 1930-7381 (Print) IS - 1930-7381 (Linking) VI - 28 IP - 6 DP - 2020 Jun TI - Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. PG - 1050-1061 LID - 10.1002/oby.22794 [doi] AB - OBJECTIVE: The obesity epidemic is a public health concern, warranting further research into pharmacological treatments for weight management (WM) as an adjunct to lifestyle interventions. The Semaglutide Treatment Effect in People with obesity (STEP) program aims to investigate the effect of semaglutide versus placebo on weight loss, safety, and tolerability in adults with obesity or overweight. METHODS: Across five phase 3 trials (NCT03548935, WM; NCT03552757, WM in type 2 diabetes; NCT03611582, WM with intensive behavioral therapy; NCT03548987, sustained WM; and NCT03693430, long-term WM), ~5,000 participants are being randomly assigned to receive semaglutide 2.4 mg once weekly subcutaneously versus placebo. Results will be available in 2020/2021. For all trials, the primary end point is change from baseline to end of treatment in body weight. RESULTS: Participants have a mean age of 46.2 to 55.3 years, are mostly female (mean: 74.1%-81.0%), and have a mean BMI of 35.7 to 38.5 kg/m(2) and a mean waist circumference of 113.0 to 115.7 cm. CONCLUSIONS: The STEP program evaluates the efficacy and safety of semaglutide 2.4 mg subcutaneously once weekly in a broad population. The trials will provide insights on WM in people with obesity with and without type 2 diabetes and on long-term follow-up. CI - (c) 2020 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS). FAU - Kushner, Robert F AU - Kushner RF AUID- ORCID: 0000-0002-1380-3705 AD - Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. FAU - Calanna, Salvatore AU - Calanna S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Davies, Melanie AU - Davies M AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - National Institute for Health Research Leicester Biomedical Research Centre, Leicester, UK. AD - National Institute for Health Research Leicester Clinical Research Facility, Leicester, UK. FAU - Dicker, Dror AU - Dicker D AD - Department of Internal Medicine, Hasharon Hospital Rabin Medical Center, Petah Tikva, Israel. AD - Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Garvey, W Timothy AU - Garvey WT AUID- ORCID: 0000-0003-0822-0860 AD - Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA. AD - Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA. FAU - Goldman, Bryan AU - Goldman B AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine/Endocrinology, UT Southwestern Medical Center, Dallas, Texas, USA. AD - Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas, USA. FAU - Thomsen, Mette AU - Thomsen M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wadden, Thomas A AU - Wadden TA AD - Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Wharton, Sean AU - Wharton S AUID- ORCID: 0000-0003-0111-1530 AD - York University and Wharton Weight Management Clinic, Toronto, Ontario, Canada. FAU - Wilding, John P H AU - Wilding JPH AD - Obesity and Endocrinology Research, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK. FAU - Rubino, Domenica AU - Rubino D AD - Washington Center for Weight Management and Research, Arlington, Virginia, USA. LA - eng GR - P30 DK056336/DK/NIDDK NIH HHS/United States GR - P30 DK079626/DK/NIDDK NIH HHS/United States GR - Novo Nordisk/International PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Obesity (Silver Spring) JT - Obesity (Silver Spring, Md.) JID - 101264860 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptides/pharmacology/*therapeutic use MH - Humans MH - Hypoglycemic Agents/pharmacology/*therapeutic use MH - Male MH - Middle Aged MH - Obesity/*drug therapy MH - Treatment Outcome MH - Semaglutide PMC - PMC7318657 COIS- RFK has served on advisory boards for Novo Nordisk, received grant support during the conduct of these trials, and received fees for participating in educational films from Novo Nordisk. SC is an employee of and holds stock in Novo Nordisk. MD has received grant support from Novo Nordisk, Sanofi, Eli Lilly, Boehringer Ingelheim, and Janssen; has served on advisory boards and received consulting and speaker fees from AstraZeneca and Janssen; and has served on advisory boards for Servier and received speaker fees from Mitsubishi Tanabe Pharma Corporation and Takeda. DD has received grant support from Novo Nordisk and Boehringer Ingelheim and has served on advisory boards for and received consulting and speaker fees from AstraZeneca, Novo Nordisk, Boehringer Ingelheim, Teva, and Sanofi. WTG has served on advisory boards for Novo Nordisk, Sanofi, BOYDSense, Amgen, Gilead, and Boehringer Ingelheim and has received support for institutionally sponsored research from Sanofi, Pfizer, and Novo Nordisk. BG is an employee of and holds stock in Novo Nordisk. IL has received grant support from Novo Nordisk, Novartis, Pfizer, Merck, Mylan, and GI Dynamics; grant support for institutionally sponsored research from Novo Nordisk; and consulting fees from Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Sanofi, MannKind, Valeritas, Intarcia, and Janssen. MT is an employee of and holds stock in Novo Nordisk. TAW has served on advisory boards for Novo Nordisk and Weight Watchers and has received grant support, on behalf of the University of Pennsylvania, from Novo Nordisk. SW has received grant support and honoraria from and served on advisory boards for Novo Nordisk, Bausch Health, Eli Lilly, and Janssen and received nonfinancial support during the conduct of these trials. JPHW has received grant support from AstraZeneca, Novo Nordisk, and Takeda; has received personal fees from Boehringer Ingelheim, Napp, Novo Nordisk, Eli Lilly, Mundipharma, Sanofi, Janssen, and Takeda; and has served as a consultant for Astellas, AstraZeneca, Boehringer Ingelheim, Napp, Novo Nordisk, Eli Lilly, Mundipharma, Rhythm Pharmaceuticals, Sanofi, Janssen, and Wilmington Healthcare. DR has served on advisory boards for Arena, Eisai, Zafgen, and Novo Nordisk; has served as a clinical trials investigator for Bristol-Myers Squibb, Merck, Nutrisource, Arena, Eisai, Vivus, Orexigen, Sanofi, AstraZenca, Novo Nordisk, and Weight Watchers; and has participated on a speaker's bureau for Novo Nordisk and received grant support from Obeseinov SARL. EDAT- 2020/05/23 06:00 MHDA- 2020/09/17 06:00 PMCR- 2020/06/26 CRDT- 2020/05/23 06:00 PHST- 2019/12/20 00:00 [received] PHST- 2020/02/17 00:00 [revised] PHST- 2020/03/02 00:00 [accepted] PHST- 2020/05/23 06:00 [entrez] PHST- 2020/05/23 06:00 [pubmed] PHST- 2020/09/17 06:00 [medline] PHST- 2020/06/26 00:00 [pmc-release] AID - OBY22794 [pii] AID - 10.1002/oby.22794 [doi] PST - ppublish SO - Obesity (Silver Spring). 2020 Jun;28(6):1050-1061. doi: 10.1002/oby.22794. PMID- 32428416 OWN - NLM STAT- MEDLINE DCOM- 20210127 LR - 20260127 IS - 1744-764X (Electronic) IS - 1474-0338 (Linking) VI - 19 IP - 7 DP - 2020 Jul TI - Safety of injectable semaglutide for type 2 diabetes. PG - 785-798 LID - 10.1080/14740338.2020.1772230 [doi] AB - INTRODUCTION: Semaglutide is the most recently approved injectable glucagon-like peptide-1 receptor agonist (GLP-1RA) for people with type 2 diabetes (T2DM). It is one of the three currently marketed GLP-1RAs that can be administered once weekly. AREAS COVERED: This review focusses on the safety of injectable semaglutide. Semaglutide has been assessed in the SUSTAIN phase 3 clinical trial programme, which included patients across the disease spectrum, i.e. treatment-naive to those receiving insulin. The authors have looked at all published literature on safety considerations of once weekly GLP-1RA with particular reference to semaglutide. EXPERT OPINION: Semaglutide is the most powerful injectable GLP-1RA. The cardiovascular (CV) outcome trial (SUSTAIN 6) showed CV superiority and its adverse event profile is as expected for the GLP-1RA class with predominantly gastrointestinal side-effects. Concerns about the thyroid and pancreatic safety have not been substantiated. There is no indication of renal or liver harm for semaglutide. Data consistent with reno-protection and benefit in liver disease is presented. There is a modest signal for increased gall bladder adverse events. An increase in diabetic retinopathy (DR) events in the SUSTAIN 6 trial is the most concerning safety signal. Caution regarding DR is needed when initiating semaglutide and recommendations are suggested. FAU - Peter, Rajesh AU - Peter R AD - Department of Diabetes and Endocrinology, Neath Port Talbot Hospital, Swansea Bay University Health Board , Swansea, UK. AD - Department of Diabetes and Endocrinology, Singleton Hospital, Swansea Bay University Health Board , Swansea, UK. FAU - Bain, Steve C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Department of Diabetes and Endocrinology, Singleton Hospital, Swansea Bay University Health Board , Swansea, UK. AD - Diabetes Research Group, Swansea University Medical School , Swansea, UK. LA - eng PT - Journal Article PT - Review DEP - 20200604 PL - England TA - Expert Opin Drug Saf JT - Expert opinion on drug safety JID - 101163027 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/*administration & dosage/adverse effects/pharmacology MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacology MH - Injections MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - CVOT OT - DR OT - GLP-1RA OT - SUSTAIN OT - T2DM OT - diabetic retinopathy OT - glucagon-like peptide-1 OT - semaglutide OT - type 2 diabetes EDAT- 2020/05/20 06:00 MHDA- 2021/01/28 06:00 CRDT- 2020/05/20 06:00 PHST- 2020/05/20 06:00 [pubmed] PHST- 2021/01/28 06:00 [medline] PHST- 2020/05/20 06:00 [entrez] AID - 10.1080/14740338.2020.1772230 [doi] PST - ppublish SO - Expert Opin Drug Saf. 2020 Jul;19(7):785-798. doi: 10.1080/14740338.2020.1772230. Epub 2020 Jun 4. PMID- 32388115 OWN - NLM STAT- MEDLINE DCOM- 20210126 LR - 20260127 IS - 1768-3254 (Electronic) IS - 0223-5234 (Linking) VI - 198 DP - 2020 Jul 15 TI - Rational design and biological evaluation of gemfibrozil modified Xenopus GLP-1 derivatives as long-acting hypoglycemic agents. PG - 112389 LID - S0223-5234(20)30359-7 [pii] LID - 10.1016/j.ejmech.2020.112389 [doi] AB - Novel methods for peptides structural modification and bioactivity optimization are highly needed in peptide-based drug discovery. Herein, we explored the use gemfibrozil (GFZ) as an albumin binder to enhance the stability and improve the bioactivity of peptides. Short-acting Xenopus glucagon-like peptide-1 (xGLP-1) analogues with anti-diabetic activity were selected as the starting point. Mono-GFZ conjugation, peptide sequence hybridization, and dimeric-GFZ derivatization were successively used to generate novel GFZ-xGLP-1 conjugates, biologically screened by various in vitro and in vivo models. Dimeric-GFZ modified conjugate 3b was finally identified as a promising anti-diabetic candidate with high albumin binding affinity, enhanced in vivo stability in SD rats, and long-acting hypoglycemic activity in db/db mice. Moreover, GFZ endowed 3b with strong lipid-regulating ability in DIO and db/db mice. In a twelve-week study, chronic administration of 3b in db/db mice resulted in sustained glycemic control, to a greater extent than liraglutide and semaglutide. In addition, 3b showed comparable therapeutic efficacies to liraglutide and semaglutide on HbA1c and pancreas islets protection. Our studies reveal 3b as a potential candidate for the treatment of metabolic diseases and indicate dimeric-GFZ modification as a novel method for peptide optimization. CI - Copyright (c) 2020 Elsevier Masson SAS. All rights reserved. FAU - Han, Jing AU - Han J AD - Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China; School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, PR China. FAU - Fu, Junjie AU - Fu J AD - Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China. FAU - Yang, Qimeng AU - Yang Q AD - School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, PR China. FAU - Zhou, Feng AU - Zhou F AD - School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, PR China. FAU - Chen, Xinyu AU - Chen X AD - School of Chemistry and Materials Science, Jiangsu Normal University, Xuzhou, 221116, PR China. FAU - Li, Chenglin AU - Li C AD - Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, PR China. FAU - Yin, Jian AU - Yin J AD - Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China. Electronic address: jianyin@jiangnan.edu.cn. LA - eng PT - Journal Article DEP - 20200504 PL - France TA - Eur J Med Chem JT - European journal of medicinal chemistry JID - 0420510 RN - 0 (Albumins) RN - 0 (Blood Glucose) RN - Q8X02027X3 (Gemfibrozil) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Albumins/metabolism MH - Animals MH - Blood Glucose/drug effects MH - Diabetes Mellitus, Experimental MH - Diabetes Mellitus, Type 2/*drug therapy MH - Dose-Response Relationship, Drug MH - Drug Development MH - Gemfibrozil/administration & dosage/*chemistry/pharmacokinetics MH - Glucagon-Like Peptide 1/*chemistry MH - Glucagon-Like Peptides/pharmacology MH - Glucose Tolerance Test MH - HEK293 Cells MH - Humans MH - Hypoglycemic Agents/administration & dosage/*chemistry/pharmacokinetics MH - Liraglutide/pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Inbred ICR MH - Rats, Sprague-Dawley MH - Xenopus laevis MH - Semaglutide OTO - NOTNLM OT - Diabetes OT - Peptide drug discovery OT - Small molecule conjugation OT - Xenopus glucagon-like peptide-1 COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/05/11 06:00 MHDA- 2021/01/27 06:00 CRDT- 2020/05/11 06:00 PHST- 2020/01/28 00:00 [received] PHST- 2020/04/11 00:00 [revised] PHST- 2020/04/24 00:00 [accepted] PHST- 2020/05/11 06:00 [pubmed] PHST- 2021/01/27 06:00 [medline] PHST- 2020/05/11 06:00 [entrez] AID - S0223-5234(20)30359-7 [pii] AID - 10.1016/j.ejmech.2020.112389 [doi] PST - ppublish SO - Eur J Med Chem. 2020 Jul 15;198:112389. doi: 10.1016/j.ejmech.2020.112389. Epub 2020 May 4. PMID- 32372454 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 22 IP - 9 DP - 2020 Sep TI - The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials. PG - 1690-1695 LID - 10.1111/dom.14079 [doi] AB - It is unknown if the cardioprotective and renal effects of glucagon-like peptide-1 receptor agonists are consistent across blood pressure (BP) categories in patients with type 2 diabetes and at high risk of cardiovascular events. Using data from the LEADER (9340 patients) and SUSTAIN 6 (3297 patients) trials, we evaluated post hoc the cardiorenal effect of liraglutide and semaglutide on major adverse cardiovascular events (MACE) and nephropathy by baseline BP categories using a Cox proportional hazards model (treatment and subgroup as factors; adjusted for cardiorenal risk factors). Data from the two trials were analysed separately. In the LEADER and SUSTAIN 6 trials, the prevalence of stage 1 hypertension was 30% and 31%, respectively, and of stage 2 hypertension 41% and 43%, respectively. There was no statistical heterogeneity across the BP categories for the effects of liraglutide (P = .06 for MACE; P = .14 for nephropathy) or semaglutide (P = .40 for MACE; P = .27 for nephropathy) versus placebo. This implies that liraglutide and semaglutide may be beneficial for patients with type 2 diabetes, irrespective of their baseline BP. CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Leiter, Lawrence A AU - Leiter LA AUID- ORCID: 0000-0002-1040-6229 AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Institute of Life Science, Swansea University, Swansea, UK. FAU - Bhatt, Deepak L AU - Bhatt DL AD - Brigham and Women's Hospital Heart and Vascular Center & Harvard Medical School, Boston, Massachusetts, USA. FAU - Buse, John B AU - Buse JB AD - University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA. FAU - Mazer, C David AU - Mazer CD AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. FAU - Pratley, Richard E AU - Pratley RE AD - AdventHealth Hospital Translational Research Institute, Orlando, Florida, USA. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ripa, Maria Sejersten AU - Ripa MS AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Vrazic, Hrvoje AU - Vrazic H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Verma, Subodh AU - Verma S AUID- ORCID: 0000-0002-4018-8533 AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. LA - eng SI - ClinicalTrials.gov/NCT01179048 SI - ClinicalTrials.gov/NCT01720446 GR - P30 DK124723/DK/NIDDK NIH HHS/United States GR - LEADER and SUSTAIN 6 were sponsored by Novo Nordisk and are registered with ClinicalTrials.gov (NCT01179048 and NCT01720446, respectively)./International PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200603 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Pressure MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Liraglutide/therapeutic use MH - Semaglutide PMC - PMC7496251 OTO - NOTNLM OT - MACE OT - blood pressure OT - cardiovascular OT - liraglutide OT - semaglutide COIS- LAL reports consultant and speaker fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi and Servier; and research grant or support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Novo Nordisk and Sanofi. SCB reports personal fees and other from Abbott, AstraZeneca, Boehringer Ingelheim, BMS, Cellnovo, Diartis, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi-aventis, Schering-Plough, Servier and Takeda; and other from Cardiff University, Doctors.net, Elsevier, Onmedica, Omnia-Med, Medscape, All-Wales Medicines Strategy Group, National Institute for Health and Care Excellence (NICE) UK and Glycosmedia. DLB discloses the following relationships: Advisory Board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma and Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care and TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), and Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Level Ex, MJH Life Sciences, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today's Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); research funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, Medtronic, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi Aventis, Synaptic, and The Medicines Company; royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald's Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), and Svelte; Trustee: American College of Cardiology; and unfunded research: FlowCo, Merck, Novo Nordisk, and Takeda. JBB's contracted consulting fees are paid to the University of North Carolina by Adocia, AstraZeneca, Dance Biopharm, Dexcom, Eli Lilly, Fractyl, GI Dynamics, Intarcia Therapeutics, Lexicon, MannKind, Metavention, NovaTarg, Novo Nordisk, Orexigen, PhaseBio, Sanofi, Senseonics, vTv Therapeutics, and Zafgen; he reports grant support from AstraZeneca, Eli Lilly, Intarcia Therapeutics, Johnson & Johnson, Lexicon, Medtronic, Novo Nordisk, Sanofi, Theracos, Tolerion, and vTv Therapeutics; he is a consultant to Cirius Therapeutics Inc, CSL Behring, Mellitus Health, Neurimmune AG, Pendulum Therapeutics, and Stability Health; he holds stock/options in Mellitus Health, Pendulum Therapeutics, PhaseBio, and Stability Health; and he is supported by grants from the National Institutes of Health (UL1TR002489, U01DK098246, UC4DK108612 and U54DK118612), PCORI and ADA. CDM reports research grants to institution and/or consulting honoraria from Amgen, Boehringer Ingelheim, CSL Behring, OctaPharma and Quark Pharmaceuticals. REP reports research grants from Gilead Sciences, Lexicon Pharmaceuticals, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Sanofi-Aventis US LLC and Takeda; is a speaker for AstraZeneca, Novo Nordisk and Takeda; and a consultant for AstraZeneca, Boehringer Ingelheim, Eisai, Inc., GlaxoSmithKline, Janssen Scientific Affairs LLC, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Pfizer and Takeda; all payments are made directly to his employer (Florida Hospital/AdventHealth). SR is an employee of and shareholder in Novo Nordisk. MSR is an employee of Novo Nordisk. HV was an employee of Novo Nordisk at the time of manuscript development. SV reports consultant and speaker fees from Boehringer Ingelheim, Eli Lilly, AstraZeneca, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, Valeant, Amgen, HLS Therapeutics and Sun Pharma; and research support from Boehringer Ingelheim, Eli Lilly and Amgen. EDAT- 2020/05/07 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/09/17 CRDT- 2020/05/07 06:00 PHST- 2020/03/25 00:00 [received] PHST- 2020/04/29 00:00 [revised] PHST- 2020/05/01 00:00 [accepted] PHST- 2020/05/07 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/05/07 06:00 [entrez] PHST- 2020/09/17 00:00 [pmc-release] AID - DOM14079 [pii] AID - 10.1111/dom.14079 [doi] PST - ppublish SO - Diabetes Obes Metab. 2020 Sep;22(9):1690-1695. doi: 10.1111/dom.14079. Epub 2020 Jun 3. PMID- 32356231 OWN - NLM STAT- MEDLINE DCOM- 20210818 LR - 20240329 IS - 1724-6059 (Electronic) IS - 1121-8428 (Print) IS - 1121-8428 (Linking) VI - 33 IP - 5 DP - 2020 Oct TI - Nephroprotective effects of GLP-1 receptor agonists: where do we stand? PG - 965-975 LID - 10.1007/s40620-020-00738-9 [doi] AB - Glucagon-like peptide (GLP)-1 receptor agonists are the cornerstone in the treatment of hyperglycemia in many people suffering from type 2 diabetes (T2D). These drugs have potent glucose-lowering actions and, additionally, lower body weight through satiety induction while reducing blood pressure and dyslipidemia. Partly through these actions, GLP-1 receptor agonism was shown to reduce cardiovascular disease (CVD) in people with T2D with previous CVD or at high-risk thereof. In these cardiovascular safety trials, in secondary or exploratory analyses, GLP-1 receptor agonists were also shown to reduce macro-albuminuria, an accepted surrogate marker for diabetic kidney disease (DKD), a condition that still represents a major unmet medical need. In this review we will discuss the evidence which suggests renoprotection induced by GLP-1 receptor agonists and the potential mechanisms that may be involved. These include mitigation of hyperglycemia, overweight and insulin resistance, systemic and glomerular hypertension, dyslipidemia, sodium retention, inflammation and renal hypoxia. The recently initiated large-sized FLOW trial investigating the effects of semaglutide on hard renal outcomes in patients with DKD will provide clarity whether GLP-1 receptor agonists may reduce the burden of DKD in addition to their other beneficial metabolic and cardiovascular effects. FAU - Mosterd, Charlotte M AU - Mosterd CM AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, Location VUMC, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. FAU - Bjornstad, Petter AU - Bjornstad P AD - Section of Endocrinology, Department of Pediatrics and Division of Nephrology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA. FAU - van Raalte, Daniel H AU - van Raalte DH AD - Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, Location VUMC, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. d.vanraalte@amsterdamumc.nl. LA - eng PT - Journal Article PT - Review DEP - 20200430 PL - England TA - J Nephrol JT - Journal of nephrology JID - 9012268 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Pharmaceutical Preparations) SB - IM MH - *Cardiovascular Diseases/drug therapy/prevention & control MH - *Diabetes Mellitus, Type 2/complications/diagnosis/drug therapy MH - *Diabetic Nephropathies/drug therapy/prevention & control MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/adverse effects MH - *Pharmaceutical Preparations PMC - PMC7560915 OTO - NOTNLM OT - Albuminuria OT - Blood pressure OT - Diabetic kidney disease OT - GLP-1 receptor agonists OT - Incretin-based therapies COIS- Charlotte M. Mosterd has no conflict of interest. Petter Bjornstad has acted as a consultant for Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Sanofi, Novo Nordisk and Horizon Pharma. Petter Bjornstad also serves on the advisory board of XORTX. Daniel H. van Raalte. has acted as a consultant and received honoraria from Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk and Sanofi and has received research operating funds from the Boehringer Ingelheim-Eli Lilly Diabetes Alliance, MSD, AstraZeneca and Novo Nordisk. EDAT- 2020/05/02 06:00 MHDA- 2021/08/19 06:00 PMCR- 2020/04/30 CRDT- 2020/05/02 06:00 PHST- 2019/12/05 00:00 [received] PHST- 2020/04/11 00:00 [accepted] PHST- 2020/05/02 06:00 [pubmed] PHST- 2021/08/19 06:00 [medline] PHST- 2020/05/02 06:00 [entrez] PHST- 2020/04/30 00:00 [pmc-release] AID - 10.1007/s40620-020-00738-9 [pii] AID - 738 [pii] AID - 10.1007/s40620-020-00738-9 [doi] PST - ppublish SO - J Nephrol. 2020 Oct;33(5):965-975. doi: 10.1007/s40620-020-00738-9. Epub 2020 Apr 30. PMID- 32333876 OWN - NLM STAT- MEDLINE DCOM- 20200717 LR - 20260518 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 8 IP - 5 DP - 2020 May TI - Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. PG - 392-406 LID - S2213-8587(20)30074-7 [pii] LID - 10.1016/S2213-8587(20)30074-7 [doi] AB - BACKGROUND: New glucose-lowering medications need to be investigated in east Asian populations, as the clinical characteristics of type 2 diabetes differ between western and east Asian patients. The PIONEER 10 study aimed to evaluate the safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes. METHODS: PIONEER 10 was an open-label, randomised, active-controlled, phase 3a trial done at 36 sites (clinics and university hospitals) in Japan. Patients aged 20 years and older with uncontrolled type 2 diabetes were randomly assigned (2:2:2:1) to receive once-daily oral semaglutide 3 mg, 7 mg, or 14 mg, or once-weekly subcutaneous dulaglutide 0.75 mg for 52 weeks, as an add-on to their background medication. The primary endpoint was the number of treatment-emergent adverse events over 57 weeks. Supportive secondary endpoints (not controlled for multiplicity) included mean change from baseline in HbA(1c) and bodyweight at 52 weeks. This trial is registered with ClinicalTrials.gov, NCT03015220. FINDINGS: Between Jan 10, and May 30, 2017, 492 patients were screened and 458 were randomly assigned to oral semaglutide 3 mg (n=131), 7 mg (n=132), or 14 mg (n=130), or dulaglutide 0.75 mg (n=65). 448 (98%) patients completed the trial. Adverse events occurred in 101 (77%) of 131 patients with oral semaglutide 3 mg, 106 (80%) of 132 with oral semaglutide 7 mg, 111 (85%) of 130 with oral semaglutide 14 mg, and 53 (82%) of 65 with dulaglutide. The most common adverse events were infections and gastrointestinal events. Gastrointestinal adverse events (mostly mild and transient constipation and nausea) occurred in a dose-dependent manner with oral semaglutide. Adverse events led to premature treatment discontinuation in four (3%) of 131 patients receiving oral semaglutide 3 mg, eight (6%) of 132 receiving oral semaglutide 7 mg, eight (6%) of 130 receiving oral semaglutide 14 mg, and two (3%) of 65 receiving dulaglutide. No deaths or severe hypoglycaemic events were reported. Based on the treatment policy estimand (ie, regardless of study drug discontinuation or rescue medication use), estimated mean reductions in HbA(1c) from baseline (8.3%) to week 52 were -0.9 percentage points (SE 0.1) with oral semaglutide 3 mg, -1.4 percentage points (0.1) with oral semaglutide 7 mg, -1.7 percentage points (0.1) with oral semaglutide 14 mg, and -1.4 percentage points (0.1) with dulaglutide (estimated treatment difference -0.3% [95% CI -0.6 to -0.1] for oral semaglutide 14 mg vs dulaglutide; p=0.0170). Estimated mean changes in bodyweight from baseline (72.1 kg) to week 52 were 0.0 kg (SE 0.3) with oral semaglutide 3 mg, -0.9 kg (0.3) with oral semaglutide 7 mg, -1.6 kg (0.3) with oral semaglutide 14 mg, and 1.0 kg (0.4) with dulaglutide (estimated treatment difference -2.6 kg [95% CI -3.5 to -1.6] for oral semaglutide 14 mg vs dulaglutide; p<0.0001). INTERPRETATION: Oral semaglutide was well tolerated in Japanese patients with type 2 diabetes. Once-daily oral semaglutide significantly reduced HbA(1c) (14 mg dose) and bodyweight (7 mg and 14 mg doses) versus weekly subcutaneous dulaglutide 0.75 mg by week 52. FUNDING: Novo Nordisk. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Yabe, Daisuke AU - Yabe D AD - Department of Diabetes and Endocrinology, Gifu University Graduate School of Medicine, Gifu, Japan. Electronic address: ydaisuke-kyoto@umin.ac.jp. FAU - Nakamura, Jiro AU - Nakamura J AD - Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Aichi, Japan. FAU - Kaneto, Hideaki AU - Kaneto H AD - Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan. FAU - Deenadayalan, Srikanth AU - Deenadayalan S AD - Novo Nordisk, Soborg, Denmark. FAU - Navarria, Andrea AU - Navarria A AD - Novo Nordisk, Soborg, Denmark. FAU - Gislum, Mette AU - Gislum M AD - Novo Nordisk, Soborg, Denmark. FAU - Inagaki, Nobuya AU - Inagaki N AD - Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan. CN - PIONEER 10 Investigators LA - eng SI - ClinicalTrials.gov/NCT03015220 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Administration, Oral MH - Adult MH - Aged MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Female MH - Glucagon-Like Peptides/adverse effects/*analogs & derivatives/therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Immunoglobulin Fc Fragments/adverse effects/*therapeutic use MH - Male MH - Middle Aged MH - Recombinant Fusion Proteins/adverse effects/*therapeutic use MH - Semaglutide FIR - Arisaka, T IR - Arisaka T FIR - Asakura, T IR - Asakura T FIR - Azuma, N IR - Azuma N FIR - Fukuda, S IR - Fukuda S FIR - Fukushima, Y IR - Fukushima Y FIR - Harada, N IR - Harada N FIR - Inoue, S IR - Inoue S FIR - Ishida, H IR - Ishida H FIR - Ishii, H IR - Ishii H FIR - Ishikawa, S IR - Ishikawa S FIR - Jinnouchi, H IR - Jinnouchi H FIR - Kaneko, S IR - Kaneko S FIR - Kanno, K IR - Kanno K FIR - Kato, M IR - Kato M FIR - Kato, Y IR - Kato Y FIR - Kawada, T IR - Kawada T FIR - Kim, H IR - Kim H FIR - Kiyosue, A IR - Kiyosue A FIR - Matsuoka, O IR - Matsuoka O FIR - Miho, O IR - Miho O FIR - Nakamoto, S IR - Nakamoto S FIR - Nakamura, S IR - Nakamura S FIR - Nakanishi, S IR - Nakanishi S FIR - Nishimura, H IR - Nishimura H FIR - Numata, A IR - Numata A FIR - Ohama, T IR - Ohama T FIR - Okabe, T IR - Okabe T FIR - Okuguchi, F IR - Okuguchi F FIR - Osonoi, T IR - Osonoi T FIR - Sasaki, T IR - Sasaki T FIR - Seino, H IR - Seino H FIR - Shin, K IR - Shin K FIR - Shiraiwa, T IR - Shiraiwa T FIR - Sugiura, T IR - Sugiura T FIR - Wada, S IR - Wada S FIR - Yamauchi, A IR - Yamauchi A EDAT- 2020/04/26 06:00 MHDA- 2020/07/18 06:00 CRDT- 2020/04/26 06:00 PHST- 2019/11/26 00:00 [received] PHST- 2020/02/19 00:00 [revised] PHST- 2020/02/25 00:00 [accepted] PHST- 2020/04/26 06:00 [pubmed] PHST- 2020/07/18 06:00 [medline] PHST- 2020/04/26 06:00 [entrez] AID - S2213-8587(20)30074-7 [pii] AID - 10.1016/S2213-8587(20)30074-7 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2020 May;8(5):392-406. doi: 10.1016/S2213-8587(20)30074-7. PMID- 32333875 OWN - NLM STAT- MEDLINE DCOM- 20200717 LR - 20260518 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 8 IP - 5 DP - 2020 May TI - Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial. PG - 377-391 LID - S2213-8587(20)30075-9 [pii] LID - 10.1016/S2213-8587(20)30075-9 [doi] AB - BACKGROUND: Given the unique phenotype of type 2 diabetes in Japanese patients, novel therapies such as oral semaglutide require evaluation in this population. PIONEER 9 aimed to assess the dose-response of oral semaglutide and to compare the efficacy and safety of oral semaglutide with placebo and a subcutaneous GLP-1 receptor agonist in a Japanese population. METHODS: PIONEER 9 was a 52-week, phase 2/3a, randomised, controlled trial done at 16 sites (clinics and university hospitals) in Japan. Japanese patients aged 20 years or older with uncontrolled type 2 diabetes managed by diet or exercise or with oral glucose-lowering drug monotherapy (washed out) were randomly assigned (1:1:1:1:1) to receive double-blind once-daily oral semaglutide (3 mg, 7 mg, or 14 mg) or placebo, or open-label subcutaneous once-daily liraglutide 0.9 mg. The primary endpoint was change in HbA(1c) from baseline to week 26 with the trial product (primary) estimand (which assumes all patients remained on trial product without rescue medication use) in all randomly assigned patients. This trial is registered with ClinicalTrials.gov, NCT03018028. FINDINGS: Between Jan 10, and July 11, 2017, 243 patients were randomly assigned to oral semaglutide 3 mg (n=49), 7 mg (n=49), or 14 mg (n=48), or placebo (n=49), or to liraglutide 0.9 mg (n=48). Changes in HbA(1c) from baseline (mean 8.2%) to week 26 were dose-dependent with oral semaglutide (mean change -1.1% [SE 0.1] for oral semaglutide 3 mg, -1.5% [0.1] for 7 mg, and -1.7% [0.1] for 14 mg), -0.1% (0.1) with placebo, and -1.4% (0.1) with liraglutide 0.9 mg. Estimated treatment differences for change in HbA(1c) compared with placebo were -1.1 percentage points (95% CI -1.4 to -0.8; p<0.0001) for oral semaglutide 3 mg, -1.5 percentage points (-1.7 to -1.2; p<0.0001) for oral semaglutide 7 mg, and -1.7 percentage points (-2.0 to -1.4; p<0.0001) for oral semaglutide 14 mg. Estimated treatment differences for change in HbA(1c) compared with liraglutide 0.9 mg were 0.3 percentage points (95% CI -0.0 to 0.6; p=0.0799) for oral semaglutide 3 mg, -0.1 percentage points (-0.4 to 0.2; p=0.3942) for oral semaglutide 7 mg, and -0.3 percentage points (-0.6 to -0.0; p=0.0272) for oral semaglutide 14 mg. Gastrointestinal events, predominantly of mild or moderate severity, were the most frequently reported class of adverse event with oral semaglutide: constipation was most common, occurring in five to six (10-13%) patients with oral semaglutide, three (6%) with placebo, and nine (19%) with liraglutide 0.9 mg. INTERPRETATION: This study showed that oral semaglutide provides significant reductions in HbA(1c) compared with placebo in a dose-dependent manner in Japanese patients with type 2 diabetes, and has a safety profile consistent with that of GLP-1 receptor agonists. FUNDING: Novo Nordisk. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Yamada, Yuichiro AU - Yamada Y AD - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University Graduate School of Medicine, Akita, Japan. Electronic address: yamada@gipc.akita-u.ac.jp. FAU - Katagiri, Hideki AU - Katagiri H AD - Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan. FAU - Hamamoto, Yoshiyuki AU - Hamamoto Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. FAU - Deenadayalan, Srikanth AU - Deenadayalan S AD - Novo Nordisk, Soborg, Denmark. FAU - Navarria, Andrea AU - Navarria A AD - Novo Nordisk, Soborg, Denmark. FAU - Nishijima, Keiji AU - Nishijima K AD - Novo Nordisk Pharma, Tokyo, Japan. FAU - Seino, Yutaka AU - Seino Y AD - Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan. CN - PIONEER 9 investigators LA - eng SI - ClinicalTrials.gov/NCT03018028 PT - Clinical Trial, Phase II PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Administration, Oral MH - Adult MH - Aged MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Dose-Response Relationship, Drug MH - Female MH - Glucagon-Like Peptides/adverse effects/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Middle Aged MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide FIR - Fukushima, Y IR - Fukushima Y FIR - Hamamoto, Y IR - Hamamoto Y FIR - Hisatomi, A IR - Hisatomi A FIR - Ide, Y IR - Ide Y FIR - Inoue, S IR - Inoue S FIR - Kawada, T IR - Kawada T FIR - Kim, H IR - Kim H FIR - Kiyosue, A IR - Kiyosue A FIR - Matoba, K IR - Matoba K FIR - Matsuoka, O IR - Matsuoka O FIR - Nishimura, H IR - Nishimura H FIR - Noguchi, M IR - Noguchi M FIR - Osonoi, T IR - Osonoi T FIR - Sawada, S IR - Sawada S FIR - Shibasaki, Y IR - Shibasaki Y FIR - Shin, K IR - Shin K FIR - Yamada, Y IR - Yamada Y EDAT- 2020/04/26 06:00 MHDA- 2020/07/18 06:00 CRDT- 2020/04/26 06:00 PHST- 2019/12/10 00:00 [received] PHST- 2020/02/11 00:00 [revised] PHST- 2020/02/25 00:00 [accepted] PHST- 2020/04/26 06:00 [pubmed] PHST- 2020/07/18 06:00 [medline] PHST- 2020/04/26 06:00 [entrez] AID - S2213-8587(20)30075-9 [pii] AID - 10.1016/S2213-8587(20)30075-9 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2020 May;8(5):377-391. doi: 10.1016/S2213-8587(20)30075-9. PMID- 32333865 OWN - NLM STAT- MEDLINE DCOM- 20200717 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 8 IP - 5 DP - 2020 May TI - Oral semaglutide in Japanese versus non-Japanese patients with type 2 diabetes. PG - 350-352 LID - S2213-8587(20)30079-6 [pii] LID - 10.1016/S2213-8587(20)30079-6 [doi] FAU - Scheen, Andre J AU - Scheen AJ AD - Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liege, B-4000 Liege, Belgium; Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM), Liege University, B-4000 Liege, Belgium. Electronic address: andre.scheen@chuliege.be. LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Administration, Oral MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Glucagon-Like Peptides/adverse effects/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2020/04/26 06:00 MHDA- 2020/07/18 06:00 CRDT- 2020/04/26 06:00 PHST- 2020/02/28 00:00 [received] PHST- 2020/02/28 00:00 [accepted] PHST- 2020/04/26 06:00 [pubmed] PHST- 2020/07/18 06:00 [medline] PHST- 2020/04/26 06:00 [entrez] AID - S2213-8587(20)30079-6 [pii] AID - 10.1016/S2213-8587(20)30079-6 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2020 May;8(5):350-352. doi: 10.1016/S2213-8587(20)30079-6. PMID- 32306244 OWN - NLM STAT- MEDLINE DCOM- 20201210 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 37 IP - 5 DP - 2020 May TI - Evaluating the Long-Term Cost-Effectiveness of Once-Weekly Semaglutide Versus Once-Daily Liraglutide for the Treatment of Type 2 Diabetes in the UK. PG - 2427-2441 LID - 10.1007/s12325-020-01337-7 [doi] AB - INTRODUCTION: Once-weekly semaglutide 1 mg is a novel glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of type 2 diabetes that has demonstrated significantly greater reductions in glycated haemoglobin (HbA1c) and body weight than the GLP-1 RA once-daily liraglutide 1.2 mg in the SUSTAIN 10 trial. The present analysis aimed to evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus once-daily liraglutide 1.2 mg from a UK healthcare payer perspective. METHODS: Long-term outcomes were projected using the IQVIA CORE Diabetes Model (version 9.0), with baseline characteristics and treatment effects sourced from SUSTAIN 10. Patients were assumed to initiate treatment with GLP-1 RAs and continue treatment until HbA1c exceeded 7.5%, at which point GLP-1 RAs were discontinued and basal insulin was initiated. Pharmacy costs and costs of complications were measured in 2018 pounds sterling (GBP), with future costs and outcomes discounted at 3.5% per annum. Utilities were taken from published sources. RESULTS: In the base-case analysis, once-weekly semaglutide 1 mg was associated with an increase in discounted life expectancy of 0.21 years and discounted quality-adjusted life expectancy of 0.30 quality-adjusted life-years, compared with once-daily liraglutide 1.2 mg. Clinical benefits were achieved at reduced costs, with lifetime cost savings of GBP 140 per patient with semaglutide versus liraglutide, owing to a reduction in diabetes-related complications, in particular cardiovascular disease (mean cost saving of GBP 279 per patient). Therefore, once-weekly semaglutide 1 mg was dominant compared with once-daily liraglutide 1.2 mg. The results of the sensitivity analyses were similar, demonstrating the robustness of the base-case analysis. CONCLUSIONS: Once-weekly semaglutide 1 mg is a cost-effective treatment option versus once-daily liraglutide 1.2 mg, based on the SUSTAIN 10 trial, from a UK healthcare payer perspective. FAU - Johansen, Pierre AU - Johansen P AUID- ORCID: 0000-0002-6287-7508 AD - Novo Nordisk A/S, Soborg, Denmark. pirj@novonordisk.com. FAU - Chubb, Barrie AU - Chubb B AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hunt, Barnaby AU - Hunt B AD - Ossian Health Economics and Communications GmbH, Basel, Switzerland. FAU - Malkin, Samuel J P AU - Malkin SJP AD - Ossian Health Economics and Communications GmbH, Basel, Switzerland. FAU - Sandberg, Anna AU - Sandberg A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Capehorn, Matthew AU - Capehorn M AD - Rotherham Institute for Obesity, Rotherham, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200418 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) MH - Aged MH - Body Weight MH - Cost-Benefit Analysis MH - Diabetes Complications/economics/prevention & control MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drug Administration Schedule MH - Female MH - Glucagon-Like Peptides/administration & dosage/economics/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/administration & dosage/economics/*therapeutic use MH - Liraglutide/administration & dosage/economics/*therapeutic use MH - Male MH - Middle Aged MH - Models, Econometric MH - Quality-Adjusted Life Years MH - United Kingdom MH - Semaglutide PMC - PMC7467468 OTO - NOTNLM OT - Cost-effectiveness OT - Diabetes OT - Economic evaluation OT - Glucagon-like peptide-1 receptor agonists OT - Liraglutide OT - Semaglutide OT - Type 2 diabetes EDAT- 2020/04/20 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/04/18 CRDT- 2020/04/20 06:00 PHST- 2020/02/20 00:00 [received] PHST- 2020/04/20 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/04/20 06:00 [entrez] PHST- 2020/04/18 00:00 [pmc-release] AID - 10.1007/s12325-020-01337-7 [pii] AID - 1337 [pii] AID - 10.1007/s12325-020-01337-7 [doi] PST - ppublish SO - Adv Ther. 2020 May;37(5):2427-2441. doi: 10.1007/s12325-020-01337-7. Epub 2020 Apr 18. PMID- 32271261 OWN - NLM STAT- MEDLINE DCOM- 20210628 LR - 20260127 IS - 1473-5830 (Electronic) IS - 0954-6928 (Linking) VI - 31 IP - 3 DP - 2020 May TI - Effect of semaglutide on coronary atherosclerosis progression in patients with type II diabetes: rationale and design of the semaglutide treatment on coronary progression trial. PG - 306-314 LID - 10.1097/MCA.0000000000000830 [doi] AB - BACKGROUND: Cardiovascular morbidity and mortality are a major burden in patients with type 2 diabetic mellitus. In a landmark study, semaglutide (an injectable glucagon like peptide-1 receptor agonist) has been shown to significantly reduce cardiovascular events, however, the mechanism of benefit is still unknown. The primary hypothesis of our current study is to assess the effect of semaglutide to reduce progression of noncalcified coronary atherosclerotic plaque volume as measured by serial coronary CTA as compared to placebo in persons with diabetes over 1 year. METHODS: One hundred forty patients will be enrolled after signing informed consent and followed up for 12 months and with a phone call 30 days after medical discontinuation. All the participants will undergo coronary artery calcium scoring and coronary computed tomography angiography at our center at baseline and 12 months. Eligible participants will be randomly assigned to semaglutide 2 mg/1.5 ml (1.34 mg/ml) prefilled pen for subcutaneous (SC) injection or placebo 1.5 ml, pen-injector for SC injection in a 1:1 fashion as add-on to their standard of care. RESULTS: As of July 2019, the study was approximately 30% enrolled with an estimated enrollment completion by first quarter of 2020 and end of study by first quarter 2021. Thirty patients were enrolled as of 23 July 2019. Preliminary data of demographics and clinical characteristics were summarized. CONCLUSION: Our current study will provide important imaging-derived data that may add relevance to the clinically derived outcomes from liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results and semaglutide and cardiovascular outcomes in patients with type 2 diabetic mellitus 6 trials. FAU - Hamal, Sajad AU - Hamal S AD - Department of Cardiology, Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center, Torrance, California, USA. FAU - Cherukuri, Lavanya AU - Cherukuri L FAU - Shaikh, Kashif AU - Shaikh K FAU - Kinninger, April AU - Kinninger A FAU - Doshi, Jay AU - Doshi J FAU - Birudaraju, Divya AU - Birudaraju D FAU - Budoff, Matthew J AU - Budoff MJ LA - eng PT - Clinical Trial Protocol PT - Journal Article PL - England TA - Coron Artery Dis JT - Coronary artery disease JID - 9011445 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Computed Tomography Angiography MH - Coronary Angiography MH - Coronary Artery Disease/complications/*diagnostic imaging MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Disease Progression MH - Glucagon-Like Peptides/*therapeutic use MH - Humans MH - Incretins/*therapeutic use MH - Plaque, Atherosclerotic/complications/*diagnostic imaging MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Vascular Calcification/complications/*diagnostic imaging MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2020/04/10 06:00 MHDA- 2021/06/29 06:00 CRDT- 2020/04/10 06:00 PHST- 2020/04/10 06:00 [entrez] PHST- 2020/04/10 06:00 [pubmed] PHST- 2021/06/29 06:00 [medline] AID - 00019501-202005000-00019 [pii] AID - 10.1097/MCA.0000000000000830 [doi] PST - ppublish SO - Coron Artery Dis. 2020 May;31(3):306-314. doi: 10.1097/MCA.0000000000000830. PMID- 32267058 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 22 IP - 8 DP - 2020 Aug TI - Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme. PG - 1263-1277 LID - 10.1111/dom.14054 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended for glycaemic management in patients with type 2 diabetes (T2D). Oral semaglutide, the first oral GLP-1RA, has recently been approved for clinical use, based on the results of the randomized, Phase 3a Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) clinical trials. The PIONEER programme tested oral semaglutide in patients with T2D of duration ranging from 3.5 to 15 years, from monotherapy through to insulin add-on, in global populations and two trials dedicated to Japanese patients. Outcomes (glycated haemoglobin [HbA1c] and body weight reduction, plus other relevant efficacy and safety endpoints) were tested against both placebo and active standard-of-care medications. A separate trial evaluated the cardiovascular safety of oral semaglutide in patients with T2D at high cardiovascular risk. Over periods of treatment up to 78 weeks, oral semaglutide 7 and 14 mg once daily reduced HbA1c and body weight across the spectrum of T2D, and improved other diabetes-related endpoints, such as fasting plasma glucose. Oral semaglutide provided significantly better efficacy than placebo and commonly used glucose-lowering medications from the dipeptidyl peptidase-4 inhibitor (sitagliptin) and sodium-glucose co-transporter-2 inhibitor (empagliflozin) classes, as well as the subcutaneous GLP-1RAs liraglutide and dulaglutide. Oral semaglutide was well tolerated in line with the known safety profile of GLP-1RAs, with transient gastrointestinal events being the most common side effects reported. Cardiovascular safety was demonstrated for oral semaglutide in patients with cardiovascular disease or high cardiovascular risk. The results of the PIONEER programme suggest that oral semaglutide is efficacious and well tolerated for glycaemic control of T2D. The availability of oral semaglutide may help to broaden treatment choice and facilitate adoption of earlier GLP-1RA treatment in the paradigm of T2D management. CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Thethi, Tina K AU - Thethi TK AUID- ORCID: 0000-0001-6140-906X AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. FAU - Pratley, Richard AU - Pratley R AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. FAU - Meier, Juris J AU - Meier JJ AUID- ORCID: 0000-0002-5835-8019 AD - Diabetes Centre Bochum-Hattingen, St Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. LA - eng SI - ClinicalTrials.gov/NCT02906930 SI - ClinicalTrials.gov/NCT02863328 SI - ClinicalTrials.gov/NCT02607865 SI - ClinicalTrials.gov/NCT02863419 SI - ClinicalTrials.gov/NCT02827708 SI - ClinicalTrials.gov/NCT02692716 SI - ClinicalTrials.gov/NCT02849080 SI - ClinicalTrials.gov/NCT03021187 SI - ClinicalTrials.gov/NCT03018028 SI - ClinicalTrials.gov/NCT03015220 GR - Novo Nordisk/International PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20200513 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Liraglutide MH - Semaglutide PMC - PMC7384149 OTO - NOTNLM OT - GLP-1 analogue OT - Phase 3 study OT - cardiovascular disease OT - clinical trial OT - type 2 diabetes COIS- T.K.T. is on the speaker's bureau for Novo Nordisk and is one of the US national leads for the Semaglutide Cardiovascular Outcomes Trial in Patients With Type 2 Diabetes (SOUL) trial (NCT03914326). R.P. has received lecture and consulting fees from AstraZeneca; consulting fees from Boehringer Ingelheim, Eisai, GlaxoSmithKline and Mundipharma; grants and lecture/consulting fees from Glytec, Janssen, Novo Nordisk, Pfizer and Takeda; grants from Lexicon Pharmaceuticals; and grants and consulting fees from Ligand Pharmaceuticals, Lilly, Merck and Sanofi-Aventis US. Except for consulting fees in February 2018 and June 2018 received from Sanofi US Services, all fees for services were paid directly to AdventHealth, a non-profit organization. J.J.M. has received lecture honoraria and consulting fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme (MSD), Novo Nordisk, Novartis and Sanofi; has received reimbursement of congress participation fees and travel expenses from MSD, Novo Nordisk and Sanofi; and has initiated projects supported by Boehringer Ingelheim, MSD, Novo Nordisk and Sanofi. EDAT- 2020/04/09 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/07/27 CRDT- 2020/04/09 06:00 PHST- 2019/12/19 00:00 [received] PHST- 2020/03/27 00:00 [revised] PHST- 2020/04/05 00:00 [accepted] PHST- 2020/04/09 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/04/09 06:00 [entrez] PHST- 2020/07/27 00:00 [pmc-release] AID - DOM14054 [pii] AID - 10.1111/dom.14054 [doi] PST - ppublish SO - Diabetes Obes Metab. 2020 Aug;22(8):1263-1277. doi: 10.1111/dom.14054. Epub 2020 May 13. PMID- 32227613 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 22 IP - 8 DP - 2020 Aug TI - Semaglutide improves health-related quality of life versus placebo when added to standard of care in patients with type 2 diabetes at high cardiovascular risk (SUSTAIN 6). PG - 1339-1347 LID - 10.1111/dom.14039 [doi] AB - AIM: To assess what drives change in health-related quality of life (HRQoL) in type 2 diabetes in the SUSTAIN 6 trial and identify potential mediators of the treatment effect of semaglutide on HRQoL scores. MATERIALS AND METHODS: The Short Form (SF)-36v2(R) questionnaire [comprising physical component summary (PCS) and mental component summary (MCS)] was used to assess changes in HRQoL from baseline to week 104, by treatment, in a prespecified analysis. This post-hoc analysis assessed change in PCS and MCS using the following factors as parameter/covariate, using descriptive statistics and linear regressions: major adverse cardiac events, hypoglycaemia, gastrointestinal adverse events, at least one episode of nausea, vomiting or diarrhoea, and change in glycated haemoglobin (HbA1c), body weight, blood pressure, heart rate and estimated glomerular filtration rate. RESULTS: Mean change in overall PCS score was +1.0 with semaglutide versus +0.4 with placebo, and +0.5 versus -0.2 for MCS. The treatment effect of semaglutide versus placebo (unadjusted estimate) was 0.7 [(95% confidence interval 0.1, 1.2); P = 0.018] on PCS and this was reduced when adjusted for change in HbA1c [0.4 (-0.2, 1.0), P = .167] and body weight [0.3 (-0.3, 0.9), P = .314]. The unadjusted treatment effect on MCS [0.7 (-0.0, 1.5), P = .054] was only reduced when adjusted for change in HbA1c [0.3 (-0.4, 1.1), P = .397]. When adjusting for all other parameters separately, the estimated effect of semaglutide on PCS and MCS qualitatively did not change. CONCLUSIONS: Semaglutide improved HRQoL versus placebo; greater improvements with semaglutide versus placebo were possibly mediated, in part, by change in HbA1c and body weight. Clinicaltrials.gov: NCT01720446 (SUSTAIN 6). CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Jodar, Esteban AU - Jodar E AUID- ORCID: 0000-0002-1234-8560 AD - Faculty of Medicine, Universidad Europea de Madrid, Madrid, Spain. AD - Department of Endocrinology and Nutrition Service, Hospital Universitario QuironSalud Madrid, Madrid, Spain. FAU - Michelsen, Marie AU - Michelsen M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Polonsky, William AU - Polonsky W AD - Behavioral Diabetes Institute, San Diego, California. AD - Department of Psychiatry, University of California San Diego, La Jolla, California. FAU - Rea, Rosangela AU - Rea R AD - Department of Clinical Medicine, SEMPR, Universidade Federal do Parana, Curitiba, Brazil. FAU - Sandberg, Anna AU - Sandberg A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AUID- ORCID: 0000-0002-0456-6787 AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Hellerup, Denmark. FAU - Warren, Mark AU - Warren M AUID- ORCID: 0000-0001-6693-9860 AD - Department of Endocrinology, Physicians East, Greenville, North Carolina. FAU - Harring, Signe AU - Harring S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ziegler, Uwe AU - Ziegler U AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bain, Stephen AU - Bain S AUID- ORCID: 0000-0001-8519-4964 AD - Diabetes Research Unit Cymru, Swansea University Medical School, Swansea, UK. LA - eng SI - ClinicalTrials.gov/NCT01720446 GR - Novo Nordisk/International PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200427 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy/epidemiology MH - Glucagon-Like Peptides/therapeutic use MH - Heart Disease Risk Factors MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Quality of Life MH - Risk Factors MH - Standard of Care MH - Treatment Outcome MH - Semaglutide PMC - PMC7383680 OTO - NOTNLM OT - GLP-1 analogue OT - cardiovascular disease OT - hypoglycaemia OT - incretin therapy OT - type 2 diabetes OT - weight control COIS- E.J. reports receiving grants and personal fees from Novo Nordisk for the work for publication; grants and personal fees from Novo Nordisk, MSD, Lilly, Janssen, Pfizer, AstraZeneca, Sanofi, UCB, Amgen, grants from FAES and Shire, personal fees from Mundipharma and Novartis, all outside the submitted work. W.H.P. reports serving as a consultant for Novo Nordisk outside the submitted work; R.R. reports serving on the advisory panel and speaker's bureau of Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Eli Lilly and Sanofi and serving on the speaker's bureau of Takeda. T.V. reports serving as a consultant on the advisory panel of Amgen, Boehringer Ingelheim, Eli Lilly, AstraZeneca, MSD and Sun Pharmaceuticals and receiving grants from Boehringer Ingelheim and Eli Lilly; all outside the submitted work. M.W. reports receiving non-financial support from Novo Nordisk for the work for publication; receiving grants and personal fees from Novo Nordisk, Eli Lilly and Sanofi Aventis, grants from Gan and Lee and personal fees from AstraZeneca, all outside the submitted work. S.C.B. reports receiving honoraria, teaching and research sponsorship/grants from Abbott, AstraZeneca, Boehringer Ingelheim, Cellnovo, Eli Lilly, MSD, Novo Nordisk and Sanofi-Aventis; receiving funding for the development of educational programmes from Cardiff University, Doctors.net, Elsevier, Onmedica, Omnia-Med and Medscape; providing expert advice for the All-Wales Medicines Strategy Group and NICE UK; owning a share in Glycosmedia; all outside the submitted work. All other authors: nothing to disclose. EDAT- 2020/04/01 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/07/27 CRDT- 2020/04/01 06:00 PHST- 2019/12/23 00:00 [received] PHST- 2020/03/18 00:00 [revised] PHST- 2020/03/26 00:00 [accepted] PHST- 2020/04/01 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/04/01 06:00 [entrez] PHST- 2020/07/27 00:00 [pmc-release] AID - DOM14039 [pii] AID - 10.1111/dom.14039 [doi] PST - ppublish SO - Diabetes Obes Metab. 2020 Aug;22(8):1339-1347. doi: 10.1111/dom.14039. Epub 2020 Apr 27. PMID- 32077218 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20250630 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 22 IP - 7 DP - 2020 Jul TI - Efficacy and tolerability of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: A systematic review and network meta-analysis. PG - 1035-1046 LID - 10.1111/dom.14008 [doi] AB - AIM: To compare the efficacy and tolerability of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adults with type 2 diabetes. MATERIALS AND METHODS: Electronic databases were searched from inception to 24 April 2019 for randomized controlled trials reporting change in glycated haemoglobin (HbA1c) at approximately 24 and/or 52 weeks for SGLT-2is and/or GLP-1RAs (classified as short- and long-acting). Bayesian network meta-analyses were conducted to compare within and between SGLT-2i and GLP-1RA classes for cardiometabolic efficacy and adverse events (PROSPERO registration number: CRD42018091306). RESULTS: Sixty-four trials (53 trials of 24 weeks; seven trials of 52 weeks; four trials of both 24 and 52 weeks), comprising 31 384 participants were identified. Compared with placebo, all treatments improved HbA1c. Long-acting GLP-1RAs reduced HbA1c compared with short-acting GLP-1RAs and SGLT-2is, with semaglutide showing greater reduction compared with placebo [24 weeks: -1.49% (95% credible interval: -1.76, -1.22); 52 weeks: -1.38% (-2.05, -0.71)] and all other treatments. Long-acting GLP-1RAs showed benefits in body weight and waist circumference reduction, while SGLT-2is reduced blood pressure. SGLT-2is showed increased risk of genital infection in comparison with long-acting GLP-1RAs [odds ratio (95% credible interval): 5.26 (1.45, 25.00)], while GLP-1RAs showed increased risk of diarrhoea in comparison with SGLT-2is [short-acting GLP-1RAs: 1.65 (1.09, 2.49); long-acting GLP-1RAs: 2.23 (1.51, 3.28)]. No other differences were found between SGLT-2is and GLP-1RAs in adverse events. CONCLUSION: Long-acting GLP-1RAs showed superiority in reducing HbA1c levels, body weight and waist circumference. SGLT-2is showed reductions in blood pressure levels. This review provides essential evidence to guide treatment recommendations in the management of type 2 diabetes. CI - (c) 2020 John Wiley & Sons Ltd. FAU - Hussein, Humaira AU - Hussein H AUID- ORCID: 0000-0003-4308-9423 AD - Department of Health Sciences, University of Leicester, Leicester, UK. AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Zaccardi, Francesco AU - Zaccardi F AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Khunti, Kamlesh AU - Khunti K AUID- ORCID: 0000-0003-2343-7099 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AUID- ORCID: 0000-0002-9987-9371 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Patsko, Emily AU - Patsko E AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Dhalwani, Nafeesa N AU - Dhalwani NN AD - Real World Evidence, London, UK. FAU - Kloecker, David E AU - Kloecker DE AUID- ORCID: 0000-0002-8910-2091 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Ioannidou, Ekaterini AU - Ioannidou E AD - Diabetes Research Centre, University of Leicester, Leicester, UK. FAU - Gray, Laura J AU - Gray LJ AD - Department of Health Sciences, University of Leicester, Leicester, UK. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20200318 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Symporters) RN - 9NEZ333N27 (Sodium) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Bayes Theorem MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - Glucose MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Sodium MH - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - *Symporters OTO - NOTNLM OT - GLP-1 analogue OT - SGLT2 inhibitor OT - meta-analysis OT - network meta-analysis OT - type 2 diabetes EDAT- 2020/02/23 06:00 MHDA- 2021/06/25 06:00 CRDT- 2020/02/21 06:00 PHST- 2019/12/03 00:00 [received] PHST- 2020/02/07 00:00 [revised] PHST- 2020/02/17 00:00 [accepted] PHST- 2020/02/23 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/02/21 06:00 [entrez] AID - 10.1111/dom.14008 [doi] PST - ppublish SO - Diabetes Obes Metab. 2020 Jul;22(7):1035-1046. doi: 10.1111/dom.14008. Epub 2020 Mar 18. PMID- 32077010 OWN - NLM STAT- MEDLINE DCOM- 20210119 LR - 20210119 IS - 0065-2598 (Print) IS - 0065-2598 (Linking) VI - 1307 DP - 2021 TI - Effects of GLP-1 and Its Analogs on Gastric Physiology in Diabetes Mellitus and Obesity. PG - 171-192 LID - 10.1007/5584_2020_496 [doi] AB - The processing of proglucagon in intestinal L cells results in the formation of glucagon, GLP-1, and GLP-2. The GLP-1 molecule becomes active through the effect of proconvertase 1, and it is inactivated by dipeptidyl peptidase IV (DPP-IV), so that the half-life of endogenous GLP-1 is 2-3 min. GLP-1 stimulates insulin secretion from beta cells in the islets of Langerhans. Human studies show that infusion of GLP-1 results in slowing of gastric emptying and increased fasting and postprandial gastric volumes. Retardation of gastric emptying reduces postprandial glycemia. Exendin-4 is a peptide agonist of the GLP-1 receptor that promotes insulin secretion. Chemical modifications of exendin-4 and GLP-1 molecules have been accomplished to prolong the half-life of GLP-1 agonists or analogs. This chapter reviews the effects of GLP-1-related drugs used in treatment of diabetes or obesity on gastric motor functions, chiefly gastric emptying. The literature shows that diverse methods have been used to measure effects of the GLP-1-related drugs on gastric emptying, with most studies using the acetaminophen absorption test which essentially measures gastric emptying of liquids during the first hour and capacity to absorb the drug over 4-6 h, expressed as AUC. The most valid measurements by scintigraphy (solids or liquids) and acetaminophen absorption at 30 or 60 min show that GLP-1-related drugs used in diabetes or obesity retard gastric emptying, and this is associated with reduced glycemia and variable effects on food intake and appetite. GLP-1 agonists and analogs are integral to the management of patients with type 2 diabetes mellitus and obesity. The effects on gastric emptying are reduced with long-acting preparations or long-term use of short-acting preparations as a result of tachyphylaxis. The dual agonists targeting GLP-1 and another receptor (GIP) do not retard gastric emptying, based on reports to date. In summary, GLP-1 agonists and analogs are integral to the management of patients with type 2 diabetes mellitus and obesity, and their effects are mediated, at least in part, by retardation of gastric emptying. FAU - Maselli, Daniel B AU - Maselli DB AD - Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. FAU - Camilleri, Michael AU - Camilleri M AD - Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. camilleri.michael@mayo.edu. LA - eng PT - Journal Article PT - Review PL - United States TA - Adv Exp Med Biol JT - Advances in experimental medicine and biology JID - 0121103 RN - 0 (Blood Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy MH - *Gastric Emptying MH - *Glucagon-Like Peptide 1/agonists/analogs & derivatives MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents MH - *Obesity/drug therapy OTO - NOTNLM OT - Accommodation OT - Albiglutide OT - Appetite OT - Dulaglutide OT - Emptying OT - Exenatide OT - Liraglutide OT - Lixisenatide OT - Semaglutide EDAT- 2020/02/23 06:00 MHDA- 2021/01/20 06:00 CRDT- 2020/02/21 06:00 PHST- 2020/02/23 06:00 [pubmed] PHST- 2021/01/20 06:00 [medline] PHST- 2020/02/21 06:00 [entrez] AID - 10.1007/5584_2020_496 [doi] PST - ppublish SO - Adv Exp Med Biol. 2021;1307:171-192. doi: 10.1007/5584_2020_496. PMID- 32048148 OWN - NLM STAT- MEDLINE DCOM- 20201015 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 37 IP - 3 DP - 2020 Mar TI - A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release, Dulaglutide and Liraglutide in the UK. PG - 1248-1259 LID - 10.1007/s12325-020-01242-z [doi] AB - INTRODUCTION: Once-weekly semaglutide 1 mg is a novel glucagon-like peptide 1 receptor agonist (GLP-1 RA) that, in the SUSTAIN clinical trials, has demonstrated greater reductions in glycated haemoglobin (HbA1c) and body weight than the other GLP-1 RAs exenatide extended-release (ER) 2 mg, dulaglutide 1.5 mg and liraglutide 1.2 mg. The aim of this analysis was to evaluate the relative cost of control of achieving treatment goals in people with type 2 diabetes (T2D) treated with once-weekly semaglutide versus exenatide ER, dulaglutide and liraglutide from a UK perspective. METHODS: Proportions of patients reaching HbA1c targets (< 7.0% and < 7.5%), weight loss targets (>/= 5% reduction in body weight) and composite endpoints (HbA1c < 7.0% without weight gain or hypoglycaemia; reduction in HbA1c of >/= 1% and weight loss of >/= 5%) were obtained from the SUSTAIN clinical trials. Annual per patient treatment costs were based on wholesale acquisition costs from July 2019 in the UK. Cost of control was calculated by plotting relative treatment costs against relative efficacy. RESULTS: The annual per patient cost was similar for all GLP-1 RAs. Once-weekly semaglutide was superior to exenatide ER, dulaglutide and liraglutide in bringing patients to HbA1c and weight loss targets, and to composite endpoints. When looking at the composite endpoint of HbA1c < 7.0% without weight gain or hypoglycaemia, exenatide ER, dulaglutide and liraglutide were 50.0%, 21.6% and 51.3% less efficacious in achieving this, respectively, than once-weekly semaglutide. Consequently, the efficacy-to-cost ratios for once-weekly semaglutide were superior to all comparators in bringing patients to all endpoints. CONCLUSIONS: The present study showed that once-weekly semaglutide offers superior cost of control versus exenatide ER, dulaglutide and liraglutide in terms of achieving clinically relevant, single and composite endpoints. Once-weekly semaglutide 1 mg would therefore represent good value for money in the UK setting. FAU - Johansen, Pierre AU - Johansen P AUID- ORCID: 0000-0002-6287-7508 AD - Novo Nordisk A/S, Soborg, Denmark. pirj@novonordisk.com. FAU - Sandberg, Anna AU - Sandberg A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Capehorn, Matthew AU - Capehorn M AD - Rotherham Institute for Obesity, Rotherham, UK. LA - eng SI - figshare/10.6084/m9.figshare.11637510 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200211 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) MH - Body Weight MH - Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drug Administration Schedule MH - Exenatide/economics/therapeutic use MH - Female MH - Glucagon-Like Peptides/administration & dosage/analogs & derivatives/*economics/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/administration & dosage/*economics/*therapeutic use MH - Immunoglobulin Fc Fragments/economics/therapeutic use MH - Liraglutide/economics/therapeutic use MH - Male MH - Middle Aged MH - Recombinant Fusion Proteins/economics/therapeutic use MH - United Kingdom MH - Weight Gain MH - Semaglutide PMC - PMC7089718 OTO - NOTNLM OT - Cost of control analysis OT - Cost-effectiveness OT - Diabetes OT - Economic evaluation OT - Glucagon-like peptide 1 receptor agonists OT - Semaglutide OT - Type 2 diabetes EDAT- 2020/02/13 06:00 MHDA- 2020/10/21 06:00 PMCR- 2020/02/11 CRDT- 2020/02/13 06:00 PHST- 2019/12/10 00:00 [received] PHST- 2020/02/13 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] PHST- 2020/02/13 06:00 [entrez] PHST- 2020/02/11 00:00 [pmc-release] AID - 10.1007/s12325-020-01242-z [pii] AID - 1242 [pii] AID - 10.1007/s12325-020-01242-z [doi] PST - ppublish SO - Adv Ther. 2020 Mar;37(3):1248-1259. doi: 10.1007/s12325-020-01242-z. Epub 2020 Feb 11. PMID- 32005073 OWN - NLM STAT- MEDLINE DCOM- 20201222 LR - 20260202 IS - 1744-7682 (Electronic) IS - 1471-2598 (Linking) VI - 20 IP - 5 DP - 2020 May TI - Will oral semaglutide be used to reduce cardiovascular risk in subjects with type 2 diabetes instead of subcutaneous semaglutide? PG - 489-492 LID - 10.1080/14712598.2020.1724952 [doi] AB - Introduction: The 'glutides,' which stimulate the glucagon-like peptide 1 (GLP-1) receptor to stimulate insulin secretion, are used in the treatment of type 2 diabetes. Semaglutide is the first glutide to be developed in an oral form. The PIONEER series of clinical trials (Peptide Innovation for Early Diabetes Treatment) were undertaken to establish a clinical role for oral semaglutide.Areas covered: This evaluation is of PIONEER 6 in a non-inferiority phase 3a trial. In PIONEER 6, the primary outcome was the time from randomization to first occurrence of a major adverse cardiovascular event and this was non-inferior with oral semaglutide, compared to placebo.Expert opinion: In my opinion, there are several reasons why once-daily oral semaglutide may not replace once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes. Most importantly, subcutaneous semaglutide has already been shown to be superior to placebo in reducing cardiovascular risk, whereas the study of this with oral semaglutide will not be completed until 2024. Secondly, it is debatable whether subjects will find the daily protocol for taking oral semaglutide more convenient than that for the weekly subcutaneous formulation. FAU - Doggrell, Sheila A AU - Doggrell SA AD - Faculty of Health, Queensland University of Technology, Brisbane, Australia. LA - eng PT - Clinical Trial, Phase III PT - Equivalence Trial PT - Journal Article PT - Randomized Controlled Trial DEP - 20200205 PL - England TA - Expert Opin Biol Ther JT - Expert opinion on biological therapy JID - 101125414 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Aged MH - Cardiovascular Diseases/*etiology MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Female MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Heart Disease Risk Factors MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Male MH - Middle Aged MH - Placebo Effect MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Clinical trial OT - oral semaglutide OT - pioneer OT - subcutaneous semaglutide OT - type 2 diabetes EDAT- 2020/02/02 06:00 MHDA- 2020/12/23 06:00 CRDT- 2020/02/02 06:00 PHST- 2020/02/02 06:00 [pubmed] PHST- 2020/12/23 06:00 [medline] PHST- 2020/02/02 06:00 [entrez] AID - 10.1080/14712598.2020.1724952 [doi] PST - ppublish SO - Expert Opin Biol Ther. 2020 May;20(5):489-492. doi: 10.1080/14712598.2020.1724952. Epub 2020 Feb 5. PMID- 31990244 OWN - NLM STAT- MEDLINE DCOM- 20210402 LR - 20260127 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 23 IP - 6 DP - 2020 Jun TI - Oral semaglutide versus injectable glucagon-like peptide-1 receptor agonists: a cost of control analysis. PG - 650-658 LID - 10.1080/13696998.2020.1722678 [doi] AB - Aims: The efficacy and safety of oral semaglutide, the first glucagon-like peptide-1 (GLP-1) receptor agonist developed for oral administration for the treatment of type 2 diabetes, was evaluated in the PIONEER clinical trial program, and a recently published network meta-analysis allowed comparison with further injectable GLP-1 receptor agonists. The present study aimed to assess the short-term cost- effectiveness of oral semaglutide 14 mg versus subcutaneous once-weekly dulaglutide 1.5 mg, once-weekly exenatide 2 mg, twice-daily exenatide 10 microg, once-daily liraglutide 1.8 mg, once-daily lixisenatide 20 microg, and once-weekly semaglutide 1 mg, in terms of the cost per patient achieving glycated hemoglobin (HbA1c) targets (cost of control).Materials and methods: Cost of control was calculated by dividing the annual treatment costs associated with an intervention by the proportion of patients achieving the treatment target with an intervention, with outcomes calculated for targets of HbA1c 0.05, except for HF (0.046). In the combined glycaemic efficacy trials, the HR for effect of semaglutide versus comparators on MACE was 0.85 (95% CI 0.55, 1.33). CONCLUSIONS: In SUSTAIN and PIONEER combined, glucagon-like peptide-1 analogue semaglutide showed consistent effects on MACE versus comparators across varying CV risk. No effect of semaglutide on MACE was observed in subjects with prior HF. CI - (c) 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Husain, Mansoor AU - Husain M AUID- ORCID: 0000-0002-3740-6739 AD - Ted Rogers Centre for Heart Research, Toronto General Hospital Research Institute, Toronto, Canada. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Swansea University Medical School, Diabetes Research Unit Cymru, Swansea, UK. FAU - Jeppesen, Ole K AU - Jeppesen OK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - UT Southwestern Medical Center, Internal Medicine and Population and Data Sciences, Dallas, Texas. FAU - Sorrig, Rasmus AU - Sorrig R AUID- ORCID: 0000-0002-0059-1555 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Treppendahl, Marianne B AU - Treppendahl MB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AUID- ORCID: 0000-0002-0456-6787 AD - Steno Diabetes Center Copenhagen, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. LA - eng SI - ClinicalTrials.gov/NCT02054897 SI - ClinicalTrials.gov/NCT01930188 SI - ClinicalTrials.gov/NCT01885208 SI - ClinicalTrials.gov/NCT02128932 SI - ClinicalTrials.gov/NCT02305381 SI - ClinicalTrials.gov/NCT01720446 SI - ClinicalTrials.gov/NCT02906930 SI - ClinicalTrials.gov/NCT02863328 SI - ClinicalTrials.gov/NCT02607865 SI - ClinicalTrials.gov/NCT02863419 SI - ClinicalTrials.gov/NCT02827708 SI - ClinicalTrials.gov/NCT02692716 SI - ClinicalTrials.gov/NCT02849080 SI - ClinicalTrials.gov/NCT03021187 SI - ClinicalTrials.gov/NCT03018028 SI - ClinicalTrials.gov/NCT03015220 SI - EudraCT/2013-000632-94 SI - EudraCT/2012-004827-19 SI - EudraCT/2012-004826-92 SI - EudraCT/2013-004392-12 SI - EudraCT/2013-004502-26 SI - EudraCT/2012-002839-28 SI - EudraCT/2015-005622-19 SI - EudraCT/2015-005209-36 SI - EudraCT/2015-001351-71 SI - EudraCT/2015-005210-30 SI - EudraCT/2015-005326-19 SI - EudraCT/2015-003563-10 SI - EudraCT/2015-005593-38 SI - EudraCT/2016-000988-16 GR - Novo Nordisk A/S, Denmark/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200205 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Cardiovascular Diseases/epidemiology/prevention & control MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Heart Disease Risk Factors MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Risk Factors MH - Semaglutide PMC - PMC7064975 OTO - NOTNLM OT - cardiovascular disease OT - clinical trial OT - glucagon-like peptide-1 analogue OT - phase III study OT - type 2 diabetes COIS- M.H. discloses personal fees for advisory panel consultancy and speaker honoraria from Boehringer Ingelheim and Janssen Inc.; grants for investigator-initiated research studies and personal fees for advisory panel consultancy from AstraZeneca and Merck & Co; personal fees for advisory panel consultancy from Roche; and grants for investigator-initiated preclinical research and personal fees for advisory panel consultancy and speaker honoraria from Novo Nordisk. S.C.B. discloses grants, personal fees and other potential conflicts of interest from Novo Nordisk, and personal fees and other potential conflicts of interest from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme and Sanofi-Aventis, all for honoraria, teaching and research sponsorship or grants; also discloses other potential conflicts of interest from Elsevier and Medscape for development of educational programmes, and nonfinancial potential conflicts of interest from the All-Wales Medicines Strategy Group, and the National Institute for Health and Care Excellence UK for providing expert advice; and discloses a potential conflict of interest for owning shares in Glycosmedia. O.K.J., R.S. and M.B.T. are full-time employees of Novo Nordisk; O.K.J. and M.B.T. also report potential conflicts of interest for owning shares in Novo Nordisk. I.L. discloses institutional grant payments from Novo Nordisk, Novartis, Pfizer, Merck, Mylan and GI Dynamics; and personal fees from AstraZeneca, Eli Lilly, TARGETPharma, Novo Nordisk, Boehringer Ingelheim, Jenssen, Mannkind, Valeritas, Intarcia and Sanofi for consultancy. T.V. discloses personal fees from Amgen, AstraZeneca, Eli Lilly, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Novo Nordisk and Sun Pharma for advisory panels and consultancy. EDAT- 2020/01/07 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/03/11 CRDT- 2020/01/07 06:00 PHST- 2019/09/30 00:00 [received] PHST- 2019/12/23 00:00 [revised] PHST- 2019/12/27 00:00 [accepted] PHST- 2020/01/07 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2020/01/07 06:00 [entrez] PHST- 2020/03/11 00:00 [pmc-release] AID - DOM13955 [pii] AID - 10.1111/dom.13955 [doi] PST - ppublish SO - Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5. PMID- 31897524 OWN - NLM STAT- MEDLINE DCOM- 20210401 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 63 IP - 3 DP - 2020 Mar TI - Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial. PG - 473-485 LID - 10.1007/s00125-019-05065-8 [doi] AB - AIMS/HYPOTHESIS: Intra-abdominal or visceral obesity is associated with insulin resistance and an increased risk for cardiovascular disease. This study aimed to compare the effects of semaglutide 1.0 mg and canagliflozin 300 mg on body composition in a subset of participants from the SUSTAIN 8 Phase IIIB, randomised double-blind trial who underwent whole-body dual-energy x-ray absorptiometry (DXA) scanning. METHODS: Adults (age >/=18 years) with type 2 diabetes, HbA(1c) 53-91 mmol/mol (7.0-10.5%), on a stable daily dose of metformin (>/=1500 mg or maximum tolerated dose) and with an eGFR >/=60 ml min(-1) [1.73 m](-2) were randomised 1:1 to semaglutide 1.0 mg once weekly and canagliflozin placebo once daily, or canagliflozin 300 mg once daily and semaglutide placebo once weekly. Body composition was assessed using whole-body DXA scans. The study participants and investigator remained blinded throughout the trial, and quality of DXA scans was evaluated in a blinded manner. Change from baseline to week 52 in total fat mass (kg) was the confirmatory efficacy endpoint. RESULTS: A subset of 178 participants (semaglutide, n = 88; canagliflozin, n = 90) underwent DXA scanning at screening and were randomised into the substudy. Of these, 114 (semaglutide, n = 53; canagliflozin, n = 61) participants had observed end-of-treatment data included in the confirmatory efficacy analysis. Of the 178 participants in the substudy, numerical improvements in body composition (including fat mass, lean mass and visceral fat mass) were observed after 52 weeks with both treatments. Total fat mass (baseline 33.2 kg) was reduced by 3.4 kg and 2.6 kg with semaglutide and canagliflozin, respectively (estimated treatment difference: -0.79 [95% CI -2.10, 0.51]). Although total lean mass (baseline 51.3 kg) was also reduced by 2.3 kg and 1.5 kg with semaglutide and canagliflozin, respectively (estimated treatment difference: -0.78 [-1.61, 0.04]), the proportion of lean mass (baseline 59.4%) increased by 1.2%- and 1.1%-point, respectively (estimated treatment difference 0.14 [-0.89, 1.17]). Changes in visceral fat mass and overall changes in body composition (assessed by the fat to lean mass ratio) were comparable between the two treatment groups. CONCLUSIONS/INTERPRETATION: In individuals with uncontrolled type 2 diabetes on stable-dose metformin therapy, the changes in body composition with semaglutide and canagliflozin were not significantly different. Although numerical improvements in body composition were observed following treatment in both treatment arms, the specific impact of both treatments on body composition in the absence of a placebo arm is speculative at this stage. TRIAL REGISTRATION: ClinicalTrials.gov NCT03136484. FUNDING: This trial was supported by Novo Nordisk A/S, Denmark. FAU - McCrimmon, Rory J AU - McCrimmon RJ AD - School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. r.mccrimmon@dundee.ac.uk. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk A/S, Vandtarnsvej, Soborg, Denmark. FAU - Frias, Juan P AU - Frias JP AD - National Research Institute, Los Angeles, CA, USA. FAU - Lausvig, Nanna L AU - Lausvig NL AD - Novo Nordisk A/S, Vandtarnsvej, Soborg, Denmark. FAU - le Roux, Carel W AU - le Roux CW AD - Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland. FAU - Thielke, Desiree AU - Thielke D AD - Novo Nordisk A/S, Vandtarnsvej, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA. LA - eng SI - ClinicalTrials.gov/NCT03136484 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200102 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Blood Glucose) RN - 0SAC974Z85 (Canagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Blood Glucose/drug effects/metabolism MH - Body Composition/*drug effects MH - Canagliflozin/*administration & dosage/adverse effects MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Double-Blind Method MH - Drug Administration Routes MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Glycated Hemoglobin/drug effects/metabolism MH - Humans MH - Male MH - Metformin/administration & dosage/adverse effects MH - Middle Aged MH - Treatment Outcome MH - Semaglutide PMC - PMC6997246 OTO - NOTNLM OT - Body composition OT - Canagliflozin OT - Fat mass OT - Glucagon-like peptide receptor agonists OT - Randomised controlled trial OT - Semaglutide OT - Type 2 diabetes OT - Weight EDAT- 2020/01/04 06:00 MHDA- 2021/04/02 06:00 PMCR- 2020/01/02 CRDT- 2020/01/04 06:00 PHST- 2019/09/05 00:00 [received] PHST- 2019/11/06 00:00 [accepted] PHST- 2020/01/04 06:00 [pubmed] PHST- 2021/04/02 06:00 [medline] PHST- 2020/01/04 06:00 [entrez] PHST- 2020/01/02 00:00 [pmc-release] AID - 10.1007/s00125-019-05065-8 [pii] AID - 5065 [pii] AID - 10.1007/s00125-019-05065-8 [doi] PST - ppublish SO - Diabetologia. 2020 Mar;63(3):473-485. doi: 10.1007/s00125-019-05065-8. Epub 2020 Jan 2. PMID- 31848464 OWN - NLM STAT- MEDLINE DCOM- 20200409 LR - 20261010 IS - 1474-1784 (Electronic) IS - 1474-1776 (Linking) VI - 19 IP - 4 DP - 2020 Apr TI - Advances in oral peptide therapeutics. PG - 277-289 LID - 10.1038/s41573-019-0053-0 [doi] AB - Protein and peptide therapeutics require parenteral administration, which can be a deterrent to medication adherence. For this reason, there have been extensive efforts to develop alternative delivery strategies, particularly for peptides such as insulin that are used to treat endocrine disorders. Oral delivery is especially desirable, but it faces substantial barriers related to the structural organization and physiological function of the gastrointestinal tract. This article highlights strategies designed to overcome these barriers, including permeation enhancers, inhibitors of gut enzymes, and mucus-penetrating and cell-penetrating peptides. It then focuses on the experience with oral peptides that have reached clinical trials, including insulin, calcitonin, parathyroid hormone and vasopressin, with an emphasis on the advances that have recently led to the landmark approval of an oral formulation of the glucagon-like peptide 1 receptor agonist semaglutide for the treatment of type 2 diabetes. FAU - Drucker, Daniel J AU - Drucker DJ AUID- ORCID: 0000-0001-6688-8127 AD - Department of Medicine and Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada. drucker@lunenfeld.ca. LA - eng GR - 154321/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20191217 PL - England TA - Nat Rev Drug Discov JT - Nature reviews. Drug discovery JID - 101124171 RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Peptides) RN - 0 (Proteins) SB - IM MH - Administration, Oral MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Insulin/metabolism MH - Peptides/*pharmacology/*therapeutic use MH - Proteins/pharmacology/therapeutic use EDAT- 2019/12/19 06:00 MHDA- 2020/04/10 06:00 CRDT- 2019/12/19 06:00 PHST- 2019/11/07 00:00 [accepted] PHST- 2019/12/19 06:00 [pubmed] PHST- 2020/04/10 06:00 [medline] PHST- 2019/12/19 06:00 [entrez] AID - 10.1038/s41573-019-0053-0 [pii] AID - 10.1038/s41573-019-0053-0 [doi] PST - ppublish SO - Nat Rev Drug Discov. 2020 Apr;19(4):277-289. doi: 10.1038/s41573-019-0053-0. Epub 2019 Dec 17. PMID- 31801807 OWN - NLM STAT- MEDLINE DCOM- 20201214 LR - 20250103 IS - 1469-0756 (Electronic) IS - 0032-5473 (Print) IS - 0032-5473 (Linking) VI - 96 IP - 1133 DP - 2020 Mar TI - An overview of GLP-1 agonists and recent cardiovascular outcomes trials. PG - 156-161 LID - 10.1136/postgradmedj-2019-137186 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are emerging as an important therapy to consider for patients with type 2 diabetes (T2D) given this class of treatment's ability to reduce glycated haemoglobin and their associated weight loss and low risk for hypoglycaemia. Additionally, seven cardiovascular outcomes trials (CVOTs) have been performed in the past 4 years using lixisenatide, liraglutide, semaglutide, exenatide, albiglutide, dulaglutide and oral semaglutide. All have found non-inferiority for cardiovascular outcomes, with many finding superiority of these drugs. These findings have transformed our guidelines on pharmacological treatment of T2D. This review article will discuss GLP-1 RA therapy, review the seven CVOTs reported to date and discuss the implications on current guidelines and therapies going forward. CI - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Sheahan, Kelsey H AU - Sheahan KH AUID- ORCID: 0000-0001-7223-0911 AD - Endocrinology, University of Vermont Medical Center, Burlington, Vermont, USA kelsey.sheahan@uvmhealth.org. FAU - Wahlberg, Elizabeth A AU - Wahlberg EA AD - Internal Medicine, University of Vermont Medical Center, Burlington, Vermont, USA. FAU - Gilbert, Matthew P AU - Gilbert MP AD - Endocrinology, University of Vermont Medical Center, Burlington, Vermont, USA. LA - eng PT - Journal Article PT - Review DEP - 20191204 PL - England TA - Postgrad Med J JT - Postgraduate medical journal JID - 0234135 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Cardiovascular Diseases/drug therapy/metabolism MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Humans MH - Hypoglycemic Agents/*pharmacology MH - Medication Therapy Management/trends MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC7042958 OTO - NOTNLM OT - adult cardiology OT - clinical pharmacology OT - coronary heart disease OT - general diabetes COIS- Competing interests: MPG has worked as a consultant for Novo Nordisk and Sanofi, USA. KHS and EAW declare that there are no conflicts of interest regarding the publication of this article. EDAT- 2019/12/06 06:00 MHDA- 2020/12/15 06:00 PMCR- 2020/02/26 CRDT- 2019/12/06 06:00 PHST- 2019/10/03 00:00 [received] PHST- 2019/11/18 00:00 [revised] PHST- 2019/11/24 00:00 [accepted] PHST- 2019/12/06 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2019/12/06 06:00 [entrez] PHST- 2020/02/26 00:00 [pmc-release] AID - postgradmedj-2019-137186 [pii] AID - 10.1136/postgradmedj-2019-137186 [doi] PST - ppublish SO - Postgrad Med J. 2020 Mar;96(1133):156-161. doi: 10.1136/postgradmedj-2019-137186. Epub 2019 Dec 4. PMID- 31790314 OWN - NLM STAT- MEDLINE DCOM- 20200203 LR - 20260127 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 21 IP - 3 DP - 2020 Feb TI - An evaluation of liraglutide including its efficacy and safety for the treatment of obesity. PG - 275-285 LID - 10.1080/14656566.2019.1695779 [doi] AB - Introduction: The prevalence of obesity is increasing worldwide and associated conditions, particularly type 2 diabetes mellitus (T2DM), also show increasing prevalence. Lifestyle intervention should be the first line of management for obesity but additional pharmacotherapy is often required and bariatric surgery is appropriate in more severe cases. Drugs acting as glucagon-like peptide-1 receptor agonists (GLP-1RAs) developed for the management of T2DM reduce body weight and liraglutide is the first GLP-1RA to be approved for the treatment of obesity in patients with and without T2DM.Areas covered: In this review of relevant published material, the authors summarize the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of liraglutide for the treatment of obesity.Expert opinion: Liraglutide effectively reduces body weight and body fat through mechanisms involving reduced appetite and lowered energy intake, independent of its glucose-lowering effects. Like most of the other medications currently available for obesity, liraglutide has some common adverse effects, although generally not serious ones. Liraglutide has additional benefits in reducing cardiovascular events in patients with T2DM but the cost and the need for daily injections may limit its use in obesity. Newer GLP-1RAs, such as semaglutide, or other drugs in development for obesity may have advantages over liraglutide. FAU - Lin, Chen-Hsiu AU - Lin CH AD - Division of Cardiology, Department of Internal Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Shao, Li AU - Shao L AD - The VIP Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Zhang, Yu-Mei AU - Zhang YM AD - The VIP Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Tu, Yu-Ju AU - Tu YJ AD - The VIP Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. FAU - Zhang, Yuzhen AU - Zhang Y AUID- ORCID: 0000-0002-9570-1269 AD - Research Center for Translational Medicine, Shanghai East Hospital Affiliated to Tongji University School of Medicine, Shanghai, China. FAU - Tomlinson, Brian AU - Tomlinson B AUID- ORCID: 0000-0001-6717-5444 AD - Research Center for Translational Medicine, Shanghai East Hospital Affiliated to Tongji University School of Medicine, Shanghai, China. AD - Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau. FAU - Chan, Paul AU - Chan P AD - Division of Cardiology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei City, Taiwan. FAU - Liu, Zhongmin AU - Liu Z AD - Department of Cardiac Surgery, Shanghai East Hospital, Tongji University, Shanghai, China. LA - eng PT - Journal Article PT - Review DEP - 20191202 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Liraglutide/*therapeutic use MH - Obesity/*drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 receptor agonist OT - liraglutide OT - obesity OT - semaglutide OT - type 2 diabetes mellitus EDAT- 2019/12/04 06:00 MHDA- 2020/02/06 06:00 CRDT- 2019/12/03 06:00 PHST- 2019/12/04 06:00 [pubmed] PHST- 2020/02/06 06:00 [medline] PHST- 2019/12/03 06:00 [entrez] AID - 10.1080/14656566.2019.1695779 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2020 Feb;21(3):275-285. doi: 10.1080/14656566.2019.1695779. Epub 2019 Dec 2. PMID- 31770362 OWN - NLM STAT- MEDLINE DCOM- 20191219 LR - 20250103 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 61 IP - 1584 DP - 2019 Nov 4 TI - Drugs for type 2 diabetes. PG - 169-178 LA - eng PT - Journal Article PT - Review PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Thiazolidinediones) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/therapeutic use MH - Drug Compounding MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Insulin/adverse effects/therapeutic use MH - Metformin/adverse effects/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/therapeutic use MH - Sulfonylurea Compounds/adverse effects/therapeutic use MH - Thiazolidinediones/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Actoplus OT - Actos OT - Adlyxin OT - Alpha-Glucosidase Inhibitors OT - Amaryl OT - Avandia OT - Bydureon OT - Byetta OT - Cycloset OT - DPP-4 inhibitors OT - DiaBeta OT - Diamicrone OT - Duetact OT - Farxiga OT - Forxiga OT - GLP-1 receptor agonists OT - GlucoNorm OT - Glucobay OT - Glucophage OT - Glucotrol OT - Glumetza OT - Glynase OT - Glyset OT - Glyxambi OT - Invokamet OT - Invokana OT - Janumet OT - Januvia OT - Jardiance OT - Jentadueto OT - Kazano OT - Kombiglyze OT - Komboglyze OT - Lodalis OT - Meglitinides OT - Nesina OT - Onglyza OT - Oseni OT - Ozempic OT - Precose OT - Qtern OT - Qternmet OT - Riomet OT - Rybelsus OT - SGLT2 inhibitors OT - Segluromet OT - Soliqua OT - Steglatro OT - Steglujan OT - Sulfonylureas OT - Symlin OT - Synjardy OT - TZD OT - Thiazolidinediones OT - Tradjenta OT - Trajenta OT - Trulicity OT - Victoza OT - Welchol OT - Xigduo OT - Xultophy OT - acarbose OT - adverse effects OT - alogliptin OT - alogliptin/metformin OT - alogliptin/pioglitazone OT - bromocriptine OT - canagliflozin OT - canagliflozin/metformin OT - colesevelam OT - dapagliflozin OT - dapagliflozin/metformin OT - degludec OT - dosage OT - dulaglutide OT - efficacy OT - empagliflozin OT - ertugliflozin OT - exenatide OT - glargine OT - gliclazide OT - glimepiride OT - glipizide OT - glyburide OT - insulin OT - linagliptin OT - linagliptin/metformin OT - liraglutide OT - lixisenatide OT - metformin OT - miglitol OT - nateglinide OT - pioglitazone OT - pramlintide OT - pregnancy OT - repaglinide OT - rosiglitazone OT - safety OT - saxagliptin OT - saxagliptin/metformin OT - semaglutide OT - sitagliptin OT - sitagliptin/metformin OT - type 2 diabetes EDAT- 2019/11/27 06:00 MHDA- 2019/12/20 06:00 CRDT- 2019/11/27 06:00 PHST- 2019/11/27 06:00 [entrez] PHST- 2019/11/27 06:00 [pubmed] PHST- 2019/12/20 06:00 [medline] PST - ppublish SO - Med Lett Drugs Ther. 2019 Nov 4;61(1584):169-178. PMID- 31770356 OWN - NLM STAT- MEDLINE DCOM- 20191219 LR - 20260127 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 61 IP - 1583 DP - 2019 Oct 21 TI - Oral semaglutide (Rybelsus) for type 2 diabetes. PG - 166-168 LA - eng PT - Journal Article PT - Review PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Animals MH - Diabetes Mellitus, Type 2/*drug therapy MH - Female MH - Glucagon-Like Peptide-1 Receptor/antagonists & inhibitors MH - Glucagon-Like Peptides/adverse effects/pharmacology/*therapeutic use MH - Humans MH - Hypoglycemic Agents/adverse effects/pharmacology/*therapeutic use MH - Pregnancy MH - Randomized Controlled Trials as Topic MH - Semaglutide OTO - NOTNLM OT - Adlyxine OT - Bydureon OT - Byetta OT - Glucophage OT - Ozempic OT - Rybelsus OT - Trulicity OT - adverse effects OT - dosage OT - drug interactions OT - dulaglutide OT - efficacy OT - exenatide OT - lactation OT - liraglutide OT - lixisenatide OT - metformin OT - pregnancy OT - safety OT - semaglutide OT - type 2 diabetes EDAT- 2019/11/27 06:00 MHDA- 2019/12/20 06:00 CRDT- 2019/11/27 06:00 PHST- 2019/11/27 06:00 [entrez] PHST- 2019/11/27 06:00 [pubmed] PHST- 2019/12/20 06:00 [medline] PST - ppublish SO - Med Lett Drugs Ther. 2019 Oct 21;61(1583):166-168. PMID- 31769496 OWN - NLM STAT- MEDLINE DCOM- 20200924 LR - 20260127 IS - 1945-7197 (Electronic) IS - 0021-972X (Linking) VI - 105 IP - 2 DP - 2020 Feb 1 TI - Efficacy and Safety of Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials. LID - dgz072 [pii] LID - 10.1210/clinem/dgz072 [doi] AB - CONTEXT: Variations in the prevalence and etiology of type 2 diabetes (T2D) across race and ethnicity may affect treatment responses. Semaglutide is a glucagon-like peptide-1 analog approved for once-weekly, subcutaneous treatment of T2D. OBJECTIVE: To compare semaglutide efficacy and safety in race and ethnicity subgroups across the SUSTAIN trials. DESIGN: Post hoc analysis of data from phase 3 randomized SUSTAIN 1-5 and 7 (pooled), and SUSTAIN 6 trials. PARTICIPANTS: 3074 subjects (SUSTAIN 1-5 and 7) and 1648 subjects (SUSTAIN 6). INTERVENTIONS: Semaglutide 0.5 or 1.0 mg, placebo, or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine 100IU/ml and dulaglutide 0.75 or 1.5 mg). MAIN OUTCOME MEASURES: Change in hemoglobin A1C (HbA1c) and body weight from baseline to weeks 30, 40 and 104, and other efficacy and safety endpoints. RESULTS: HbA1c was reduced from baseline by 1.0 to 1.5 percentage points and 1.3 to 2.0 percentage points, and body weight was reduced by 2.3 to 4.7 kg and 3.6 to 6.1 kg with semaglutide 0.5 and 1.0 mg, respectively, across race and ethnicity subgroups. Minor changes in blood pressure and lipid profiles were observed. Adverse events (AEs) were reported in similar proportions of subjects across trials. More Asian versus other race subgroups discontinued treatment prematurely due to AEs. The most commonly reported AEs were gastrointestinal disorders. CONCLUSIONS: In this SUSTAIN trials post hoc analysis, semaglutide was associated with consistent and clinically relevant reductions in HbA1c and body weight in subjects with T2D, with minor variations in efficacy and safety outcomes associated with race or ethnicity. CI - (c) Published by Oxford University Press on behalf of the Endocrine Society 2019. FAU - DeSouza, Cyrus AU - DeSouza C AD - University of Nebraska Medical Center, Omaha, NE, US. FAU - Cariou, Bertrand AU - Cariou B AD - L'Institut du Thorax, Department of Endocrinology, CHU Nantes, Nantes, France. FAU - Garg, Satish AU - Garg S AD - Barbara Davis Center for Diabetes, University of Colorado Denver, Denver, CO, US. FAU - Lausvig, Nanna AU - Lausvig N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Navarria, Andrea AU - Navarria A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Fonseca, Vivian AU - Fonseca V AD - Tulane University Health Sciences Center, New Orleans, LA, US. LA - eng SI - ClinicalTrials.gov/NCT02054897 SI - ClinicalTrials.gov/NCT01930188 SI - ClinicalTrials.gov/NCT01885208 SI - ClinicalTrials.gov/NCT02128932 SI - ClinicalTrials.gov/NCT02305381 SI - ClinicalTrials.gov/NCT01720446 SI - ClinicalTrials.gov/NCT02648204 PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 2ZM8CX04RZ (Insulin Glargine) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Adult MH - Blood Glucose/drug effects MH - Body Weight/drug effects/ethnology MH - Diabetes Mellitus, Type 2/blood/*drug therapy/ethnology MH - Ethnicity/*statistics & numerical data MH - Female MH - Glucagon-Like Peptides/*administration & dosage/analogs & derivatives MH - Glycated Hemoglobin/drug effects MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Immunoglobulin Fc Fragments/administration & dosage MH - Insulin Glargine/administration & dosage MH - Male MH - Middle Aged MH - Racial Groups/*statistics & numerical data MH - Recombinant Fusion Proteins/administration & dosage MH - Treatment Outcome MH - Semaglutide EDAT- 2019/11/27 06:00 MHDA- 2020/09/25 06:00 CRDT- 2019/11/27 06:00 PHST- 2019/06/05 00:00 [received] PHST- 2019/10/01 00:00 [accepted] PHST- 2019/11/27 06:00 [pubmed] PHST- 2020/09/25 06:00 [medline] PHST- 2019/11/27 06:00 [entrez] AID - 5643670 [pii] AID - 10.1210/clinem/dgz072 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2020 Feb 1;105(2):dgz072. doi: 10.1210/clinem/dgz072. PMID- 31747740 OWN - NLM STAT- MEDLINE DCOM- 20191125 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 381 IP - 21 DP - 2019 Nov 21 TI - Oral Semaglutide and Cardiovascular Outcomes in Type 2 Diabetes. Reply. PG - 2076-2077 LID - 10.1056/NEJMc1913157#sa2 [pii] LID - 10.1056/NEJMc1913157 [doi] FAU - Husain, Mansoor AU - Husain M AD - Ted Rogers Centre for Heart Research, Toronto, ON, Canada. FAU - Donsmark, Morten AU - Donsmark M AD - Novo Nordisk, Soborg, Denmark. FAU - Bain, Stephen C AU - Bain SC AD - Swansea University Medical School, Swansea, United Kingdom. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2019 Nov 21;381(21):2075-2076. doi: 10.1056/NEJMc1913157. PMID: 31747739 MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Semaglutide EDAT- 2019/11/21 06:00 MHDA- 2019/11/26 06:00 CRDT- 2019/11/21 06:00 PHST- 2019/11/21 06:00 [entrez] PHST- 2019/11/21 06:00 [pubmed] PHST- 2019/11/26 06:00 [medline] AID - 10.1056/NEJMc1913157#sa2 [pii] AID - 10.1056/NEJMc1913157 [doi] PST - ppublish SO - N Engl J Med. 2019 Nov 21;381(21):2076-2077. doi: 10.1056/NEJMc1913157. PMID- 31747739 OWN - NLM STAT- MEDLINE DCOM- 20191125 LR - 20260127 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 381 IP - 21 DP - 2019 Nov 21 TI - Oral Semaglutide and Cardiovascular Outcomes in Type 2 Diabetes. PG - 2075-2076 LID - 10.1056/NEJMc1913157#sa1 [pii] LID - 10.1056/NEJMc1913157 [doi] FAU - Zweck, Elric AU - Zweck E AD - Heinrich Heine University, Dusseldorf, Germany. FAU - Westenfeld, Ralf AU - Westenfeld R AD - Heinrich Heine University, Dusseldorf, Germany. FAU - Szendroedi, Julia AU - Szendroedi J AD - German Diabetes Center, Dusseldorf, Germany. LA - eng PT - Comment PT - Letter PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2019 Aug 29;381(9):841-851. doi: 10.1056/NEJMoa1901118. PMID: 31185157 CIN - N Engl J Med. 2019 Nov 21;381(21):2076-2077. doi: 10.1056/NEJMc1913157. PMID: 31747740 MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Semaglutide EDAT- 2019/11/21 06:00 MHDA- 2019/11/26 06:00 CRDT- 2019/11/21 06:00 PHST- 2019/11/21 06:00 [entrez] PHST- 2019/11/21 06:00 [pubmed] PHST- 2019/11/26 06:00 [medline] AID - 10.1056/NEJMc1913157#sa1 [pii] AID - 10.1056/NEJMc1913157 [doi] PST - ppublish SO - N Engl J Med. 2019 Nov 21;381(21):2075-2076. doi: 10.1056/NEJMc1913157. PMID- 31744308 OWN - NLM STAT- MEDLINE DCOM- 20200907 LR - 20260127 IS - 1542-6270 (Electronic) IS - 1060-0280 (Linking) VI - 54 IP - 5 DP - 2020 May TI - Oral Semaglutide: First-in-Class Oral GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes Mellitus. PG - 478-485 LID - 10.1177/1060028019889064 [doi] AB - Objective:The purpose of this article is to review the pharmacological characteristics and clinical evidence of oral semaglutide for the treatment of type 2 diabetes mellitus (T2DM). Data Sources: A MEDLINE/PubMed search was conducted between January 1, 2005, and September 30, 2019. Search terms included semaglutide, glucagon-like peptide 1 receptor agonist, GLP-1 receptor agonist, and type 2 diabetes. Study Selection and Data Extraction Quantification: The following study designs were included in the analysis: systematic review and/or meta-analyses, clinical trial, or observational study design. Narrative reviews were excluded. Articles were included only if they were published in the English language or evaluated oral semaglutide with regard to pharmacology, pharmacokinetics, safety, and efficacy in humans. Data Synthesis: Oral semaglutide has been Food and Drug Administration approved for the treatment of T2DM as an adjunct to diet and exercise. Oral semaglutide has been shown to result in an absolute hemoglobin A(1C) reduction between -0.5% and -1.5% and weight reductions between -1 and -4.7 kg. Oral semaglutide has been shown to be noninferior to placebo for cardiovascular (CV) safety although additional CV outcomes trials are ongoing. Adverse effects appear to be similar to those of other glucagon-like peptide-1 receptor agonists and are gastrointestinal in nature. Relevance to Patient Care and Clinical Practice: Oral semaglutide may be appropriate as second- or third-line add-on therapy for patients with T2DM who are not meeting treatment goals on metformin and are overweight and reluctant to use an injectable drug. Conclusions: Oral semaglutide appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2DM. FAU - Cowart, Kevin AU - Cowart K AUID- ORCID: 0000-0002-6880-1600 AD - University of South Florida, Tampa, FL, USA. LA - eng PT - Journal Article PT - Review DEP - 20191119 PL - United States TA - Ann Pharmacother JT - The Annals of pharmacotherapy JID - 9203131 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/administration & dosage/adverse effects/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/administration & dosage/adverse effects/*therapeutic use MH - Metformin/therapeutic use MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - ambulatory care OT - antihyperglycemics OT - endocrinology OT - family medicine OT - type 2 diabetes EDAT- 2019/11/21 06:00 MHDA- 2020/09/08 06:00 CRDT- 2019/11/21 06:00 PHST- 2019/11/21 06:00 [pubmed] PHST- 2020/09/08 06:00 [medline] PHST- 2019/11/21 06:00 [entrez] AID - 10.1177/1060028019889064 [doi] PST - ppublish SO - Ann Pharmacother. 2020 May;54(5):478-485. doi: 10.1177/1060028019889064. Epub 2019 Nov 19. PMID- 31686781 OWN - NLM STAT- MEDLINE DCOM- 20200423 LR - 20260127 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 13 DP - 2019 TI - The development of an oral GLP-1 receptor agonist for the management of type 2 diabetes: evidence to date. PG - 2985-2996 LID - 10.2147/DDDT.S166765 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP1-RA) are prominent agents in the therapeutics of type 2 diabetes mellitus due to their exemplary efficacy in both preprandial and postprandial glycemia, their safety, low risk of hypoglycemia, their multilevel pathophysiological superiority, weight loss and importantly the observed benefits in cardiovascular disease reduction. Their major drawback is the subcutaneous route of administration, constituting a barrier to adoption and reason for treatment discontinuation. Thus, the development of an oral GLP1-RA agent would promote medication adherence and quality of life, further consolidating its beneficial effects in real-life clinical practice. However, this task is hampered by suboptimal gastrointestinal protein absorption. Yet, the introduction of oral semaglutide, a modified form of semaglutide with the addition of a carrier sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, may have provided a safe and effective way to reach systemic circulation while other molecules are in development. Whether this molecule still has the impressive cardiovascular effects demonstrated with the use of its precursor remains to be explored. However, to date, its efficacy and safety have already been showcased in a randomized trial. More research is warranted in order to further consolidate these findings across different type 2 diabetes mellitus (T2DM) subpopulations, and adequately powered studies with a longer follow-up that would allow the exploration of microvascular and macrovascular complications are needed. Finally, studies comparing oral semaglutide and similar molecules with other currently established antidiabetic agents to evaluate the relative efficacy, the cost-effectiveness and further understand its place in T2DM therapeutic algorithm are needed. This review focuses on the development of oral GLP1-RA agents and summarizes the challenges, milestones and expected benefits associated with a successful introduction. CI - (c) 2019 Antza et al. FAU - Antza, Christina AU - Antza C AD - 3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University, Thessaloniki, Greece. FAU - Nirantharakumar, Krishnarajah AU - Nirantharakumar K AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. FAU - Doundoulakis, Ioannis AU - Doundoulakis I AD - Department of Endocrinology and Diabetes, 424 General Military Hospital, Thessaloniki, Greece. FAU - Tahrani, Abd A AU - Tahrani AA AD - Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK. AD - Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK. AD - Department of Diabetes and Endocrinology, Birmingham Heartlands Hospital, Birmingham, UK. FAU - Toulis, Konstantinos A AU - Toulis KA AD - Institute of Applied Health Research, University of Birmingham, Birmingham, UK. AD - Department of Endocrinology and Diabetes, 424 General Military Hospital, Thessaloniki, Greece. LA - eng PT - Journal Article PT - Review DEP - 20190822 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/administration & dosage/chemistry/*pharmacology MH - Humans MH - Hypoglycemic Agents/administration & dosage/chemistry/*pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC6709822 OTO - NOTNLM OT - glucagon-like peptide OT - pharmacokinetics OT - therapeutics COIS- Dr Doundoulakis, Dr Antza, and Dr Toulis report no conflicts of interest in this work. Dr Nirantharakumar reports grants from National Institute for Health Research, MRC Medical Research Council, Diabetes UK, Vifor, and AstraZeneca, and personal fees from Merck Sharp & Dohme, Sanofi, and Boehringer Ingelheim, outside of and unrelated to the submitted work. Dr Tahrani reports grants, personal fees, and non-financial support from NovoNordisk, personal fees and non-financial support from Eli Lilly, Boehringer Ingelheim and AstraZeneca, and personal fees from Janssen, during the conduct of the study. The authors report no other conflicts of interest in this work. EDAT- 2019/11/07 06:00 MHDA- 2020/04/24 06:00 PMCR- 2019/08/22 CRDT- 2019/11/06 06:00 PHST- 2018/10/31 00:00 [received] PHST- 2019/06/27 00:00 [accepted] PHST- 2019/11/06 06:00 [entrez] PHST- 2019/11/07 06:00 [pubmed] PHST- 2020/04/24 06:00 [medline] PHST- 2019/08/22 00:00 [pmc-release] AID - 166765 [pii] AID - 10.2147/DDDT.S166765 [doi] PST - epublish SO - Drug Des Devel Ther. 2019 Aug 22;13:2985-2996. doi: 10.2147/DDDT.S166765. eCollection 2019. PMID- 31650514 OWN - NLM STAT- MEDLINE DCOM- 20200630 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 36 IP - 12 DP - 2019 Dec TI - Evaluation of the Cost Per Patient Achieving Treatment Targets with Oral Semaglutide: A Short-Term Cost-Effectiveness Analysis in the United States. PG - 3483-3493 LID - 10.1007/s12325-019-01125-y [doi] AB - INTRODUCTION: Oral semaglutide is the first orally administered glucagon-like peptide-1 receptor agonist for the treatment of type 2 diabetes, and has been evaluated in the PIONEER clinical trial program. These trials assessed the proportions of patients achieving single and composite endpoints, encompassing glycemic control [defined in terms of glycated hemoglobin (HbA1c)], weight loss, and hypoglycemia. The present study assessed the cost of control with oral semaglutide versus empagliflozin, sitagliptin, and liraglutide in the US. METHODS: Four endpoints were evaluated: (1) HbA1c /= 1.0%-point HbA1c reduction and weight loss >/= 3.0%; and (4) HbA1c < 7.0% without hypoglycemia and without weight gain. The proportions of patients achieving each endpoint were sourced from the PIONEER 2, 3 and 4 trials. Treatment costs were accounted over an annual time-period in 2019 US dollars (USD), based on wholesale acquisition cost. Cost of control was calculated by dividing treatment costs by the proportion of patients achieving each target. RESULTS: Oral semaglutide was consistently associated with the lowest cost of control for all four endpoints. For the targets of HbA1c 7.5%-8.0%, >8.0%-8.5%, >8.5%-9.0% and > 9.0%), background medications, diabetes duration and pancreatic beta-cell function. RESULTS: Mean HbA1c (% point) reductions increased from lowest to highest HbA1c subgroups (-0.9%, -1.2%,-1.5%, -1.7% and -2.3% [effect of subgroup within treatment: P = 0.247] for semaglutide 0.5 mg, and -1.1%, -1.4%, -1.9%, -2.1% and -2.7% [P = 0.045] for semaglutide 1.0 mg), with mean HbA1c ranges at week 30 of 6.3%-7.3% and 6.1%-6.9%, respectively. The corresponding BW reductions generally decreased with increasing baseline HbA1c (-4.4, -3.9, -3.9, -3.3 and -2.9 kg [P = 0.004], and -6.4, -5.9, -5.2, -4.5 and -4.8 kg [P < 0.001], respectively). HbA1c and BW reductions were consistently greater for semaglutide 1.0 mg versus 0.5 mg across background medication, diabetes duration and pancreatic beta-cell function subgroups. Adverse events with semaglutide were consistent with the glucagon-like peptide-1 receptor agonist class, with gastrointestinal events the most common. CONCLUSIONS: Semaglutide was consistently efficacious across the continuum of diabetes care in a broad spectrum of patient subgroups with a range of clinical characteristics. CI - (c) 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Brigham and Women's Hospital, Boston, Massachusetts. FAU - Capehorn, Matthew S AU - Capehorn MS AD - Rotherham Institute for Obesity, Clifton Medical Centre, Rotherham, UK. FAU - Chaykin, Louis AU - Chaykin L AD - Meridien Research, Bradenton, Florida. FAU - Frias, Juan P AU - Frias JP AUID- ORCID: 0000-0001-9486-1255 AD - National Research Institute, Los Angeles, California. FAU - Lausvig, Nanna L AU - Lausvig NL AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Macura, Stanislava AU - Macura S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ludemann, Jorg AU - Ludemann J AD - Diabetes-Falkensee, Diabetes-Centre and Centre for Clinical Studies, Falkensee, Germany. FAU - Madsbad, Sten AU - Madsbad S AD - Hvidovre Hospital, Hvidovre, Denmark. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Dallas Diabetes Research Center at Medical City, Dallas, Texas. FAU - Tabak, Omur AU - Tabak O AD - Istanbul Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey. FAU - Tadayon, Sayeh AU - Tadayon S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Diabetes Research Unit Cymru, Swansea University Medical School, Swansea, UK. LA - eng GR - Novo Nordisk/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191114 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptides/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/adverse effects MH - Semaglutide PMC - PMC7065219 OTO - NOTNLM OT - antidiabetic drug OT - glucagon-like peptide-1 OT - glucagon-like peptide-1 analogue OT - glycaemic control OT - type 2 diabetes OT - weight control COIS- VRA received consultant fees from Adocia, AstraZeneca/Bristol Myers-Squibb, Boehringer Ingelheim, Novo Nordisk, Sanofi and Zafgen, and grants from AstraZeneca/Bristol Myers-Squibb, Calibra, Eisai, Fractyl, Janssen, Novo Nordisk, Sanofi and Theracos, and is a partner of an employee of Merck. MSC received honoraria from Novo Nordisk, Boehringer Ingelheim, Eli Lilly, Janssen and Merck Sharp & Dohme, and grants from Novo Nordisk, Novartis, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Leo, and Abbott, and served as an expert advisor to the National Institute for Health and Care Excellence (NICE), an unpaid board member of the Association for the Study of Obesity (ASO) and the Primary Care Academy of Diabetes Specialists (PCADS), a part-time Medical Director at LighterLife (a commercial weight-loss company), a partner at Clifton Medical Centre, and a director at RIO Weight Management, Ltd. JPF received honoraria from Eli Lilly, Merck, Novo Nordisk, Sanofi and grants from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, Pfizer and Theracos. S Madsbad received honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk and Sanofi and grants from Boehringer Ingelheim and Novo Nordisk. JL served as a consultant for Eli Lilly and Novo Nordisk. JR received honoraria from Boehringer Ingelheim, Intarcia, Janssen, Novo Nordisk and Sanofi, and grants from Allergan, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Enanta, Genentech, GlaxoSmithKline, Intarcia, Janssen, Lexicon, Melior, Merck, Novo Nordisk, Oramed, PegBio, Pfizer and Sanofi. SCB received honoraria from Abbott, AstraZeneca, Boehringer Ingelheim, Cellnovo, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, Sanofi, received funding for the development of educational programmes from Cardiff University, http://doctors.net, Elsevier, Onmedica, Omnia-Med, Medscape, provided expert advice for All-Wales Medicines Strategy Group and NICE, UK, and is a shareholder of Glycosmedia. NLL, S Macura, and ST are employees of Novo Nordisk. LC and OT have no conflicts of interest to declare. EDAT- 2019/10/15 06:00 MHDA- 2021/06/25 06:00 PMCR- 2020/03/11 CRDT- 2019/10/15 06:00 PHST- 2019/07/08 00:00 [received] PHST- 2019/10/01 00:00 [revised] PHST- 2019/10/08 00:00 [accepted] PHST- 2019/10/15 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2019/10/15 06:00 [entrez] PHST- 2020/03/11 00:00 [pmc-release] AID - DOM13896 [pii] AID - 10.1111/dom.13896 [doi] PST - ppublish SO - Diabetes Obes Metab. 2020 Mar;22(3):303-314. doi: 10.1111/dom.13896. Epub 2019 Nov 14. PMID- 31606525 OWN - NLM STAT- MEDLINE DCOM- 20210127 LR - 20260127 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 46 IP - 6 DP - 2020 Nov TI - Efficacy of semaglutide versus liraglutide in clinical practice. PG - 515-517 LID - S1262-3636(19)30155-7 [pii] LID - 10.1016/j.diabet.2019.10.001 [doi] FAU - Goncalves, E AU - Goncalves E AD - Diabetes and Thyroid Associates, 2022 Brookwood Baptist Medical Center Drive, Suite #408, Birmingham, AL 35209, United States. Electronic address: goncalves.edison@gmail.com. FAU - Bell, D S AU - Bell DS AD - Southside endocrinology, 1900 Crestwood Blvd, suite 201, Irondale, AL 35210, United States. Electronic address: dshbell@yahoo.com. LA - eng PT - Comment PT - Letter DEP - 20191011 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - Diabetes Metab. 2020 Apr;46(2):100-109. doi: 10.1016/j.diabet.2019.101117. PMID: 31539622 MH - *Diabetes Mellitus, Type 2/drug therapy/epidemiology MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - *Liraglutide/therapeutic use MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 OT - Glycaemic control OT - Liraglutide OT - Receptor agonist OT - Semaglutide OT - Type 2 diabetes EDAT- 2019/10/14 06:00 MHDA- 2021/01/28 06:00 CRDT- 2019/10/14 06:00 PHST- 2019/09/27 00:00 [received] PHST- 2019/10/02 00:00 [accepted] PHST- 2019/10/14 06:00 [pubmed] PHST- 2021/01/28 06:00 [medline] PHST- 2019/10/14 06:00 [entrez] AID - S1262-3636(19)30155-7 [pii] AID - 10.1016/j.diabet.2019.10.001 [doi] PST - ppublish SO - Diabetes Metab. 2020 Nov;46(6):515-517. doi: 10.1016/j.diabet.2019.10.001. Epub 2019 Oct 11. PMID- 31600725 OWN - NLM STAT- MEDLINE DCOM- 20200316 LR - 20260127 IS - 1479-683X (Electronic) IS - 0804-4643 (Linking) VI - 181 IP - 6 DP - 2019 Dec TI - MANAGEMENT OF ENDOCRINE DISEASE: Are all GLP-1 agonists equal in the treatment of type 2 diabetes? PG - R211-R234 LID - 10.1530/EJE-19-0566 [doi] AB - GLP-1, a peptide hormone secreted from the gut, stimulating insulin and suppressing glucagon secretion was identified as a parent compound for novel treatments of diabetes, but was degraded (dipeptidyl peptidase-4) and eliminated (mainly by kidneys) too fast (half-life 1-2 min) to be useful as a therapeutic agent. GLP-1 receptor agonist has been used to treat patients with type 2 diabetes since 2007, when exenatide (twice daily) was approved in 2007. Compounds with longer duration of action (once daily, once weekly) and with increasingly better efficacy with respect to glycaemic control and body weight reduction have been developed, and in a recent ADA/EASD consensus statement, were recommended as the first injectable diabetes therapy after failure of oral glucose-lowering medications. Most GLP-1 receptor agonists (lixisenatide q.d., liraglutide q.d., exenatide q.w., dulaglutide q.w., albiglutide q.w., semaglutide q.w., all for s.c. injection, and the first oral preparation, oral semaglutide) have been examined in cardiovascular outcomes studies. Beyond proving their safety in vulnerable patients, most of whom had pre-existing heart disease, liraglutide, semaglutide, albiglutide, and dulaglutide reduced the time to first major adverse cardiovascular events (non-fatal myocardial infarction and stroke, cardiovascular death). Liraglutide, in addition, reduced cardiovascular and all-cause mortality. It is the purpose of the present review to describe clinically important differences, regarding pharmacokinetic behaviour, glucose-lowering potency, effectiveness of reducing body weight and controlling other cardiovascular risk factors, and of the influence of GLP-1 receptor agonist treatment on cardiovascular outcomes in patients either presenting with or without pre-existing cardiovascular disease (atherosclerotic, ischemic or congestive heart failure). FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes Division, St. Josef-Hospital, Ruhr-University of Bochum, Bochum, Germany. FAU - Meier, Juris J AU - Meier JJ AD - Diabetes Division, St. Josef-Hospital, Ruhr-University of Bochum, Bochum, Germany. LA - eng PT - Journal Article PT - Review PL - England TA - Eur J Endocrinol JT - European journal of endocrinology JID - 9423848 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 74O62BB01U (lixisenatide) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Animals MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Liraglutide/therapeutic use MH - Peptides/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-2 Receptor EDAT- 2019/10/11 06:00 MHDA- 2020/03/17 06:00 CRDT- 2019/10/11 06:00 PHST- 2019/07/22 00:00 [received] PHST- 2019/10/09 00:00 [accepted] PHST- 2019/10/11 06:00 [pubmed] PHST- 2020/03/17 06:00 [medline] PHST- 2019/10/11 06:00 [entrez] AID - EJE-19-0566.R1 [pii] AID - 10.1530/EJE-19-0566 [doi] PST - ppublish SO - Eur J Endocrinol. 2019 Dec;181(6):R211-R234. doi: 10.1530/EJE-19-0566. PMID- 31540867 OWN - NLM STAT- MEDLINE DCOM- 20200526 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 7 IP - 11 DP - 2019 Nov TI - Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial. PG - 834-844 LID - S2213-8587(19)30311-0 [pii] LID - 10.1016/S2213-8587(19)30311-0 [doi] AB - BACKGROUND: Existing guidelines for management of type 2 diabetes recommend a patient-centred approach to guide the choice of pharmacological agents. Although glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors are increasingly used as second-line agents, direct comparisons between these treatments are insufficient. In the SUSTAIN 8 trial, we compared the efficacy and safety of semaglutide (a GLP-1 receptor agonist) with canagliflozin (an SGLT2 inhibitor) in patients with type 2 diabetes. METHODS: This was a double-blind, parallel-group, phase 3b, randomised controlled trial done at 111 centres in 11 countries. Eligible patients were at least 18 years old and had uncontrolled type 2 diabetes (HbA(1c) 7.0-10.5% [53-91 mmol/mol]) on stable daily metformin therapy. Patients were randomly assigned (1:1) by use of an interactive web response system to subcutaneous semaglutide 1.0 mg once weekly or oral canagliflozin 300 mg once daily. The primary endpoint was change from baseline in HbA(1c), and the confirmatory secondary endpoint was change from baseline in bodyweight, both at week 52. The primary analysis population included all randomly assigned patients, using on-treatment data collected before initiation of rescue medication. The safety analysis was done on a population that included all patients exposed to at least one dose of trial product. The trial was powered for HbA(1c) and bodyweight superiority under reasonable assumptions. This trial is registered with ClinicalTrials.gov, NCT03136484. FINDINGS: Between March 15, 2017, and Nov 16, 2018, 788 patients were randomly assigned to semaglutide 1.0 mg (394 patients) or canagliflozin 300 mg (394 patients). 739 patients completed the trial (367 in the semaglutide group and 372 in the canagliflozin group). From overall baseline mean, patients receiving semaglutide had significantly greater reductions in HbA(1c) and bodyweight than those receiving canagliflozin (HbA(1c) estimated treatment difference [ETD] -0.49 percentage points, 95% CI -0.65 to -0.33; -5.34 mmol/mol, 95% CI -7.10 to -3.57; p<0.0001; and bodyweight ETD -1.06 kg, 95% CI -1.76 to -0.36; p=0.0029). Gastrointestinal disorders, most commonly nausea, were the most frequently reported adverse events with semaglutide, occurring in 184 (47%) of 392 patients; whereas infections and infestations (defined using the Medical Dictionary for Regulatory Activities, version 21.0), most commonly urinary tract infections, occurred more frequently with canagliflozin, in 136 (35%) of 394 patients. Premature treatment discontinuation because of adverse events occurred in 38 (10%) of 392 patients with semaglutide and in 20 (5%) of 394 patients with canagliflozin. One fatal adverse event confirmed unlikely to be caused by treatment occurred in the semaglutide group. INTERPRETATION: Once-weekly semaglutide 1.0 mg was superior to daily canagliflozin 300 mg in reducing HbA(1c) and bodyweight in patients with type 2 diabetes uncontrolled on metformin therapy. These outcomes might guide treatment intensification choices. FUNDING: Novo Nordisk. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine/Endocrinology, Department of Clinical Sciences, UT Southwestern Medical Center, University of Texas, Dallas, TX, USA. Electronic address: ildiko.lingvay@UTSouthwestern.edu. FAU - Catarig, Andrei-Mircea AU - Catarig AM AD - Novo Nordisk, Soborg, Denmark. FAU - Frias, Juan P AU - Frias JP AD - National Research Institute, Los Angeles, CA, USA. FAU - Kumar, Harish AU - Kumar H AD - Centre for Endocrinology and Diabetes, Amrita Hospital, Kochi, India. FAU - Lausvig, Nanna L AU - Lausvig NL AD - Novo Nordisk, Soborg, Denmark. FAU - le Roux, Carel W AU - le Roux CW AD - Diabetes Complications Research Centre, University College Dublin, Dublin, Ireland. FAU - Thielke, Desiree AU - Thielke D AD - Novo Nordisk, Soborg, Denmark. FAU - Viljoen, Adie AU - Viljoen A AD - Borthwick Diabetes Research Centre, Stevenage, UK. FAU - McCrimmon, Rory J AU - McCrimmon RJ AD - School of Medicine, University of Dundee, Dundee, UK. LA - eng SI - ClinicalTrials.gov/NCT03136484 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190917 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0SAC974Z85 (Canagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet Diabetes Endocrinol. 2019 Nov;7(11):818-820. doi: 10.1016/S2213-8587(19)30310-9. PMID: 31540866 MH - Adult MH - Aged MH - Body Weight MH - Canagliflozin/administration & dosage/adverse effects/*therapeutic use MH - Diabetes Mellitus, Type 2/*drug therapy MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptides/administration & dosage/adverse effects/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/administration & dosage/adverse effects/*therapeutic use MH - Male MH - Metformin/adverse effects/*therapeutic use MH - Middle Aged MH - Sodium-Glucose Transporter 2 Inhibitors MH - Treatment Outcome MH - Semaglutide EDAT- 2019/09/22 06:00 MHDA- 2020/05/27 06:00 CRDT- 2019/09/22 06:00 PHST- 2019/07/26 00:00 [received] PHST- 2019/08/23 00:00 [revised] PHST- 2019/09/02 00:00 [accepted] PHST- 2019/09/22 06:00 [pubmed] PHST- 2020/05/27 06:00 [medline] PHST- 2019/09/22 06:00 [entrez] AID - S2213-8587(19)30311-0 [pii] AID - 10.1016/S2213-8587(19)30311-0 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2019 Nov;7(11):834-844. doi: 10.1016/S2213-8587(19)30311-0. Epub 2019 Sep 17. PMID- 31539622 OWN - NLM STAT- MEDLINE DCOM- 20210707 LR - 20260127 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 46 IP - 2 DP - 2020 Apr TI - Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10). PG - 100-109 LID - S1262-3636(19)30132-6 [pii] LID - 10.1016/j.diabet.2019.101117 [doi] AB - AIMS: SUSTAIN 10 compared the efficacy and safety of the anticipated most frequent semaglutide dose (1.0mg) with the current most frequently prescribed liraglutide dose in Europe (1.2mg), reflecting clinical practice. METHODS: In this phase 3b, open-label trial, 577 adults with type 2 diabetes (HbA(1c) 7.0-11.0%) on 1-3 oral antidiabetic drugs were randomized 1:1 to subcutaneous once-weekly semaglutide 1.0mg or subcutaneous once-daily liraglutide 1.2mg. Primary and confirmatory secondary endpoints were changes in HbA(1c) and body weight from baseline to week 30, respectively. RESULTS: Mean HbA(1c) (baseline 8.2%) decreased by 1.7% with semaglutide and 1.0% with liraglutide (estimated treatment difference [ETD] -0.69%; 95% confidence interval [CI] -0.82 to -0.56, P<0.0001). Mean body weight (baseline 96.9kg) decreased by 5.8kg with semaglutide and 1.9kg with liraglutide (ETD -3.83kg; 95% CI -4.57 to -3.09, P<0.0001). The proportions of subjects achieving glycaemic targets of<7.0% and=6.5%, weight loss of=5% and=10%, and a composite endpoint of HbA(1c)<7.0% without severe or blood glucose-confirmed symptomatic hypoglycaemia and no weight gain were greater with semaglutide vs liraglutide (all P<0.0001). Both treatments had similar safety profiles, except for more frequent gastrointestinal disorders (the most common adverse events [AEs]) and AEs leading to premature treatment discontinuation with semaglutide vs liraglutide (43.9% vs 38.3% and 11.4% vs 6.6%, respectively). CONCLUSION: Semaglutide was superior to liraglutide in reducing HbA(1c) and body weight. Safety profiles were generally similar, except for higher rates of gastrointestinal AEs with semaglutide vs liraglutide. CI - Copyright (c) 2019 Elsevier Masson SAS. All rights reserved. FAU - Capehorn, M S AU - Capehorn MS AD - Rotherham Institute for Obesity, Clifton Medical Centre, S65 1DA Rotherham, South Yorkshire, UK. Electronic address: mcapehorn@yahoo.co.uk. FAU - Catarig, A-M AU - Catarig AM AD - Novo Nordisk A/S, DK-2860 Soborg, Denmark. FAU - Furberg, J K AU - Furberg JK AD - Novo Nordisk A/S, DK-2860 Soborg, Denmark. FAU - Janez, A AU - Janez A AD - Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia. FAU - Price, H C AU - Price HC AD - West Hampshire Community Diabetes Service, SO43 7NG Lyndhurst, UK. FAU - Tadayon, S AU - Tadayon S AD - Novo Nordisk A/S, DK-2860 Soborg, Denmark. FAU - Verges, B AU - Verges B AD - CHU, 21000 Dijon, France. FAU - Marre, M AU - Marre M AD - Clinique Ambroise Pare, 27, boulevard Victor-Hugo, 92200 Neuilly-sur-Seine, France. LA - eng PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190917 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 9100L32L2N (Metformin) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Diabetes Metab. 2020 Nov;46(6):515-517. doi: 10.1016/j.diabet.2019.10.001. PMID: 31606525 MH - Administration, Oral MH - Aged MH - Blood Glucose MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptides/administration & dosage/adverse effects/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/administration & dosage/adverse effects/*therapeutic use MH - Injections, Subcutaneous MH - Liraglutide/administration & dosage/adverse effects/*therapeutic use MH - Male MH - Metformin/therapeutic use MH - Middle Aged MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonist OT - Glycaemic control OT - Liraglutide OT - SUSTAIN OT - Semaglutide OT - Type 2 diabetes EDAT- 2019/09/21 06:00 MHDA- 2021/07/08 06:00 CRDT- 2019/09/21 06:00 PHST- 2019/06/14 00:00 [received] PHST- 2019/08/28 00:00 [revised] PHST- 2019/09/01 00:00 [accepted] PHST- 2019/09/21 06:00 [pubmed] PHST- 2021/07/08 06:00 [medline] PHST- 2019/09/21 06:00 [entrez] AID - S1262-3636(19)30132-6 [pii] AID - 10.1016/j.diabet.2019.101117 [doi] PST - ppublish SO - Diabetes Metab. 2020 Apr;46(2):100-109. doi: 10.1016/j.diabet.2019.101117. Epub 2019 Sep 17. PMID- 31530667 OWN - NLM STAT- MEDLINE DCOM- 20200727 LR - 20260518 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 42 IP - 12 DP - 2019 Dec TI - Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. PG - 2262-2271 LID - 10.2337/dc19-0898 [doi] AB - OBJECTIVE: To investigate the efficacy, safety, and tolerability of oral semaglutide added to insulin with or without metformin. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes uncontrolled on insulin with or without metformin were randomized to oral semaglutide 3 mg (N = 184), 7 mg (N = 182), or 14 mg (N = 181) or to placebo (N = 184) in a 52-week, double-blind trial. End points were change from baseline to week 26 in HbA(1c) (primary) and body weight (confirmatory secondary). Two estimands were defined: treatment policy (effect regardless of trial product discontinuation or rescue medication) and trial product (effect assuming trial product continuation without rescue medication) in randomized patients. RESULTS: Oral semaglutide was superior to placebo in reducing HbA(1c) (estimated treatment difference [ETD] -0.5% [95% CI -0.7, -0.3], -0.9% [-1.1, -0.7], and -1.2% [-1.4, -1.0] for 3, 7, and 14 mg, respectively; P < 0.001) and body weight (ETD -0.9 kg [95% CI -1.8, -0.0], -2.0 kg [-3.0, -1.0], and -3.3 kg [-4.2, -2.3]; P = 0.0392 for 3 mg, P /= 50 years with type 2 diabetes and CV disease or risk factors, oral semaglutide did not increase CV events. PG - JC28 LID - 10.7326/ACPJ201909170-028 [doi] FAU - Lipscombe, Lorraine L AU - Lipscombe LL LA - eng PT - Comment PT - Journal Article PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2019 Aug 29;381(9):841-851. doi: 10.1056/NEJMoa1901118. PMID: 31185157 MH - *Cardiovascular Diseases MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides MH - Humans MH - Hypoglycemic Agents MH - Risk Factors MH - Semaglutide EDAT- 2019/09/17 06:00 MHDA- 2020/03/21 06:00 CRDT- 2019/09/17 06:00 PHST- 2019/09/17 06:00 [entrez] PHST- 2019/09/17 06:00 [pubmed] PHST- 2020/03/21 06:00 [medline] AID - 2751443 [pii] AID - 10.7326/ACPJ201909170-028 [doi] PST - ppublish SO - Ann Intern Med. 2019 Sep 17;171(6):JC28. doi: 10.7326/ACPJ201909170-028. PMID- 31486321 OWN - NLM STAT- MEDLINE DCOM- 20191105 LR - 20260127 IS - 0370-629X (Print) IS - 0370-629X (Linking) VI - 74 IP - 9 DP - 2019 Sep TI - [Semaglutide, once weekly GLP-1 receptor agonist (Ozempic(R))]. PG - 488-494 AB - Semaglutide (Ozempic(R)) is a new once-weekly agonist of glucagon-like peptide-1 receptors (GLP-1 AR) indicated in the treatment of type 2 diabetes (T2D). Phase III clinical trials of the SUSTAIN programme demonstrated both the efficacy and safety of semaglutide in patients with T2D treated by diet and exercise, oral antidiabetic agents or even insulin. Direct and indirect comparative clinical trials showed that semaglutide (subcutaneous 0.5 or 1.0 mg once weekly) exerts a better glucose-lowering activity and a greater weight loss than other GLP-1 AR. Presented as prefilled pens for subcutaneous injection, semaglutide is currently reimbursed in Belgium after failure of antidiabetic therapy including metformin (HbA1c superior to 7,5 % or 58 mmol/mol) in T2D patients with body mass index ? 30 kg/m(2). FAU - Scheen, A J AU - Scheen AJ AD - Service de Diabetologie, Nutrition et Maladies metaboliques et Unite de Pharmacologie clinique, CHU Liege. LA - fre PT - Journal Article TT - Le medicament du mois. Le semaglutide, agoniste des recepteurs du GLP-1 en injection sous-cutanee hebdomadaire (Ozempic(R)). PL - Belgium TA - Rev Med Liege JT - Revue medicale de Liege JID - 0404317 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Belgium MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide-1 Receptor MH - *Glucagon-Like Peptides/therapeutic use MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - Semaglutide OTO - NOTNLM OT - Obesity OT - Once weekly administration OT - Semaglutide OT - Type 2 diabetes OT - Glucagon like peptide1 EDAT- 2019/09/06 06:00 MHDA- 2019/11/07 06:00 CRDT- 2019/09/06 06:00 PHST- 2019/09/06 06:00 [entrez] PHST- 2019/09/06 06:00 [pubmed] PHST- 2019/11/07 06:00 [medline] PST - ppublish SO - Rev Med Liege. 2019 Sep;74(9):488-494. PMID- 31436480 OWN - NLM STAT- MEDLINE DCOM- 20201105 LR - 20260127 IS - 1557-8593 (Electronic) IS - 1520-9156 (Linking) VI - 22 IP - 1 DP - 2020 Jan TI - Oral Semaglutide: A Review of the First Oral Glucagon-Like Peptide 1 Receptor Agonist. PG - 10-18 LID - 10.1089/dia.2019.0185 [doi] AB - Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are highly effective at lowering hemoglobin A1c (HbA1c) and facilitating weight loss. Four agents in the GLP-1 RA class, albiglutide, liraglutide, dulaglutide, and semaglutide, also have cardioprotective effects. However, subcutaneous administration of these agents remains a major reason for their underutilization. A new coformulation of semaglutide with sodium N-[8-(2-hydroxybenzoyl) amino caprylate (SNAC) is the first oral GLP-1 RA reviewed by the U.S. Food and Drug Administration (FDA). The SNAC technology prevents destruction of semaglutide in the stomach and facilitates transcellular absorption through the gastric membrane enabling semaglutide to reach systemic circulation intact. The oral formulation of semaglutide was studied in the PIONEER trials, demonstrating similar efficacy to the presently available GLP-1 RAs with regard to HbA1c lowering and weight loss. Although the PIONEER 6 trial suggests positive effects on cardiovascular mortality with oral semaglutide, these benefits may not fully be appreciated until the completion of the SOUL trial. FAU - Bucheit, John D AU - Bucheit JD AD - Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia. FAU - Pamulapati, Lauren G AU - Pamulapati LG AD - Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia. FAU - Carter, Nicole AU - Carter N AD - Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia. FAU - Malloy, Kevin AU - Malloy K AD - Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia. FAU - Dixon, Dave L AU - Dixon DL AD - Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia. FAU - Sisson, Evan M AU - Sisson EM AD - Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20191001 PL - United States TA - Diabetes Technol Ther JT - Diabetes technology & therapeutics JID - 100889084 RN - 0 (Caprylates) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (N-(8-(2-hydroxybenzoyl)amino)caprylate) SB - IM MH - Administration, Oral MH - Caprylates/*pharmacokinetics MH - Cardiovascular Diseases/etiology/prevention & control MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Drug Delivery Systems MH - Glucagon-Like Peptides/*administration & dosage/pharmacokinetics MH - Humans MH - Hypoglycemic Agents/*administration & dosage/pharmacokinetics MH - Renal Insufficiency, Chronic/etiology/prevention & control MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - Oral GLP-1 receptor agonists OT - PIONEER trials OT - SNAC technology OT - Semaglutide EDAT- 2019/08/23 06:00 MHDA- 2020/11/06 06:00 CRDT- 2019/08/23 06:00 PHST- 2019/08/23 06:00 [pubmed] PHST- 2020/11/06 06:00 [medline] PHST- 2019/08/23 06:00 [entrez] AID - 10.1089/dia.2019.0185 [doi] PST - ppublish SO - Diabetes Technol Ther. 2020 Jan;22(1):10-18. doi: 10.1089/dia.2019.0185. Epub 2019 Oct 1. PMID- 31426059 OWN - NLM STAT- MEDLINE DCOM- 20200305 LR - 20260127 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 171 IP - 4 DP - 2019 Aug 20 TI - In uncontrolled type 2 diabetes, adjunctive semaglutide reduced HbA1c and body weight vs sitagliptin. PG - JC16 LID - 10.7326/ACPJ201908200-016 [doi] FAU - Lipscombe, Lorraine L AU - Lipscombe LL LA - eng PT - Comment PT - Journal Article PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 9100L32L2N (Metformin) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - JAMA. 2019 Apr 16;321(15):1466-1480. doi: 10.1001/jama.2019.2942. PMID: 30903796 MH - Adult MH - Body Weight MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - *Metformin MH - Sitagliptin Phosphate MH - Semaglutide EDAT- 2019/08/20 06:00 MHDA- 2020/03/07 06:00 CRDT- 2019/08/20 06:00 PHST- 2019/08/20 06:00 [entrez] PHST- 2019/08/20 06:00 [pubmed] PHST- 2020/03/07 06:00 [medline] AID - 2748526 [pii] AID - 10.7326/ACPJ201908200-016 [doi] PST - ppublish SO - Ann Intern Med. 2019 Aug 20;171(4):JC16. doi: 10.7326/ACPJ201908200-016. PMID- 31422062 OWN - NLM STAT- MEDLINE DCOM- 20200526 LR - 20250103 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 7 IP - 10 DP - 2019 Oct TI - Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. PG - 776-785 LID - S2213-8587(19)30249-9 [pii] LID - 10.1016/S2213-8587(19)30249-9 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists differ in their structure and duration of action and have been studied in trials of varying sizes and with different patient populations, with inconsistent effects on cardiovascular outcomes reported. We aimed to synthesise the available evidence by doing a systematic review and meta-analysis of cardiovascular outcome trials of these drugs. METHODS: We searched MEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials for eligible placebo-controlled trials reporting major adverse cardiovascular events (MACE; ie, cardiovascular death, stroke, or myocardial infarction) up to June 15, 2019. We did a meta-analysis using a random-effects model to estimate overall hazard ratios (HRs) for MACE, its components, death from any cause, hospital admission for heart failure, kidney outcomes, and key safety outcomes (severe hypoglycaemia, pancreatitis, and pancreatic cancer). We also examined MACE in several subgroups based on patient characteristics (history of cardiovascular disease, BMI, age, baseline HbA1c, and baseline estimated glomerular filtration rate), trial duration, treatment dosing interval, and structural homology. FINDINGS: Of 27 publications screened, seven trials, with a combined total of 56 004 participants, were included: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN-6 (semaglutide), EXSCEL (exenatide), Harmony Outcomes (albiglutide), REWIND (dulaglutide), and PIONEER 6 (oral semaglutide). Overall, GLP-1 receptor agonist treatment reduced MACE by 12% (HR 0.88, 95% CI 0.82-0.94; p<0.0001). There was no statistically significant heterogeneity across the subgroups examined. HRs were 0.88 (95% CI 0.81-0.96; p=0.003) for death from cardiovascular causes, 0.84 (0.76-0.93; p<0.0001) for fatal or non-fatal stroke, and 0.91 (0.84-1.00; p=0.043) for fatal or non-fatal myocardial infarction. GLP-1 receptor agonist treatment reduced all-cause mortality by 12% (0.88, 0.83-0.95; p=0.001), hospital admission for heart failure by 9% (0.91, 0.83-0.99; p=0.028), and a broad composite kidney outcome (development of new-onset macroalbuminuria, decline in estimated glomerular filtration rate [or increase in creatinine], progression to end-stage kidney disease, or death attributable to kidney causes) by 17% (0.83, 0.78-0.89; p<0.0001), mainly due to a reduction in urinary albumin excretion. There was no increase in risk of severe hypoglycaemia, pancreatitis, or pancreatic cancer. INTERPRETATION: Treatment with GLP-1 receptor agonists has beneficial effects on cardiovascular, mortality, and kidney outcomes in patients with type 2 diabetes. FUNDING: None. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Kristensen, Soren L AU - Kristensen SL AD - BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK; Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark. FAU - Rorth, Rasmus AU - Rorth R AD - BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK; Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark. FAU - Jhund, Pardeep S AU - Jhund PS AD - BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. FAU - Docherty, Kieran F AU - Docherty KF AD - BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. FAU - Sattar, Naveed AU - Sattar N AD - BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. FAU - Preiss, David AU - Preiss D AD - Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford UK. FAU - Kober, Lars AU - Kober L AD - Department of Cardiology, Rigshospitalet University Hospital, Copenhagen, Denmark. FAU - Petrie, Mark C AU - Petrie MC AD - BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. FAU - McMurray, John J V AU - McMurray JJV AD - BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. Electronic address: john.mcmurray@glasgow.ac.uk. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20190814 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Lancet Diabetes Endocrinol. 2019 Oct;7(10):741-743. doi: 10.1016/S2213-8587(19)30267-0. PMID: 31422061 EIN - Lancet Diabetes Endocrinol. 2020 Mar;8(3):e2. doi: 10.1016/S2213-8587(20)30037-1. PMID: 32085827 MH - Diabetes Mellitus, Type 2/*drug therapy/mortality/physiopathology MH - Diabetic Angiopathies/etiology/*mortality/physiopathology MH - Diabetic Nephropathies/etiology/*mortality/physiopathology MH - Humans MH - Hypoglycemic Agents/*adverse effects/therapeutic use MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2019/08/20 06:00 MHDA- 2020/05/27 06:00 CRDT- 2019/08/19 06:00 PHST- 2019/06/17 00:00 [received] PHST- 2019/07/15 00:00 [revised] PHST- 2019/07/15 00:00 [accepted] PHST- 2019/08/20 06:00 [pubmed] PHST- 2020/05/27 06:00 [medline] PHST- 2019/08/19 06:00 [entrez] AID - S2213-8587(19)30249-9 [pii] AID - 10.1016/S2213-8587(19)30249-9 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2019 Oct;7(10):776-785. doi: 10.1016/S2213-8587(19)30249-9. Epub 2019 Aug 14. PMID- 31396537 OWN - NLM STAT- MEDLINE DCOM- 20200122 LR - 20260127 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2019 DP - 2019 TI - Risk of Malignant Neoplasia with Glucagon-Like Peptide-1 Receptor Agonist Treatment in Patients with Type 2 Diabetes: A Meta-Analysis. PG - 1534365 LID - 10.1155/2019/1534365 [doi] LID - 1534365 AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs, but there is concern that they may increase the risk of malignant neoplasia. The present meta-analysis examined the safety of GLP-1 receptor agonists with regard to malignant neoplasia. METHODS: We analyzed data from randomized controlled trials with a minimum duration of 24 weeks that assessed the incidence of neoplasms in type 2 diabetes patients receiving GLP-1 receptor agonists compared with placebo or other hypoglycemic drugs. We searched the MEDLINE, Embase, and Cochrane databases with a language restriction of English through October 1, 2018, and carried out a meta-analysis of the available trial data using a fixed effects model to calculate odds ratios (ORs) for neoplasia. RESULTS: Thirty-four relevant articles, providing data for 50452 patients, were included in the meta-analysis. Compared with the incidence of malignant neoplasia with placebo or other interventions, no increase in malignant neoplasm formation was observed with the use of GLP-1 receptor agonists (OR 1.04, 95% confidence interval (CI) 0.94-1.15; p = 0.46), liraglutide (OR 1.08, 95% CI 0.91-1.27; p = 0.38), exenatide (OR 1.00, 95% CI 0.86-1.16; p = 1.00), semaglutide (OR 0.89, 95% CI 0.35-2.22; p = 0.80), or albiglutide (OR 1.07, 95% CI 0.23-4.88; p = 0.93). A subanalysis of trials lasting longer than 3 years also showed no increase in the neoplasia risk with GLP-1 receptor agonist use (OR 1.03, 95% CI 0.92-1.15; p = 0.60). Between-trial statistical heterogeneity was low for all comparisons. CONCLUSION: GLP-1 receptor agonists can be used without safety concerns related to malignant neoplasia in patients with type 2 diabetes. FAU - Liu, Yufang AU - Liu Y AUID- ORCID: 0000-0003-2099-3989 AD - Department of Endocrinology, Peking University International Hospital, Beijing 102206, China. FAU - Zhang, Xiaomei AU - Zhang X AD - Department of Endocrinology, Peking University International Hospital, Beijing 102206, China. FAU - Chai, Sanbao AU - Chai S AD - Department of Endocrinology, Peking University International Hospital, Beijing 102206, China. FAU - Zhao, Xin AU - Zhao X AD - Department of Endocrinology, Peking University International Hospital, Beijing 102206, China. FAU - Ji, Linong AU - Ji L AUID- ORCID: 0000-0002-3262-2168 AD - Department of Endocrinology, Peking University People's Hospital, Beijing 100044, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20190716 PL - United States TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 5E7U48495E (rGLP-1 protein) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy/*epidemiology MH - Exenatide/therapeutic use MH - Glucagon-Like Peptide 1/analogs & derivatives/therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Incidence MH - Liraglutide/therapeutic use MH - Neoplasms/chemically induced/*epidemiology MH - Risk Factors MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC6664552 COIS- All authors have no conflicts of interest. EDAT- 2019/08/10 06:00 MHDA- 2020/01/23 06:00 PMCR- 2019/07/16 CRDT- 2019/08/10 06:00 PHST- 2019/03/19 00:00 [received] PHST- 2019/07/02 00:00 [accepted] PHST- 2019/08/10 06:00 [entrez] PHST- 2019/08/10 06:00 [pubmed] PHST- 2020/01/23 06:00 [medline] PHST- 2019/07/16 00:00 [pmc-release] AID - 10.1155/2019/1534365 [doi] PST - epublish SO - J Diabetes Res. 2019 Jul 16;2019:1534365. doi: 10.1155/2019/1534365. eCollection 2019. PMID- 31373167 OWN - NLM STAT- MEDLINE DCOM- 20200928 LR - 20250103 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 21 IP - 11 DP - 2019 Nov TI - GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: An updated meta-analysis including the REWIND and PIONEER 6 trials. PG - 2576-2580 LID - 10.1111/dom.13847 [doi] AB - A meta-analysis of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) and placebo concerning cardiorenal outcomes in patients with type 2 diabetes (T2D) is presented. An electronic search without language restrictions up to June 15, 2019 was conducted to determine eligible trials. A meta-analysis of available trial data was undertaken, using a random-effects model to calculate overall hazard ratios (HRs) and 95% confidence intervals (CIs). Data from seven CVOTs, comprising 56 004 patients (68.9% with established cardiovascular disease) were included. GLP-1RA reduced major cardiovascular events (MACE) by 13% (HR, 0.87; 95% CI, 0.80-0.96; P = 0.011) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (CVD) (P = 0.220). GLP-1RA also reduced the risk of cardiovascular death by 12%, of non-fatal stroke by 16%, of hospitalization for heart failure by 9%, of all-cause mortality by 11%, and the broad composite kidney outcome by 17%; the latter appeared to be driven only by a reduction in macroalbuminuria (HR, 0.76 [0.68-0.86]; P = 0.003). GLP-1RAs have moderate benefits concerning MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also robustly reduce the incidence of macroalbuminuria, without affecting the progression of diabetic renal disease. CI - (c) 2019 John Wiley & Sons Ltd. FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Maiorino, Maria Ida AU - Maiorino MI AUID- ORCID: 0000-0003-4659-7546 AD - Diabetes Unit, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Bellastella, Giuseppe AU - Bellastella G AD - Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Longo, Miriam AU - Longo M AD - Diabetes Unit, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Chiodini, Paolo AU - Chiodini P AD - Medical Statistics Unit, University of Campania "Luigi Vanvitelli", Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AD - Diabetes Unit, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20190828 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Diabetic Cardiomyopathies/*prevention & control MH - Diabetic Nephropathies/*prevention & control MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1RA OT - albiglutide OT - cardiorenal outcomes OT - cardiovascular outcome trials OT - dulaglutide OT - exenatide OT - liraglutide OT - lixisenatide OT - oral semaglutide OT - semaglutide OT - type 2 diabetes EDAT- 2019/08/03 06:00 MHDA- 2020/09/29 06:00 CRDT- 2019/08/03 06:00 PHST- 2019/06/21 00:00 [received] PHST- 2019/07/30 00:00 [revised] PHST- 2019/07/30 00:00 [accepted] PHST- 2019/08/03 06:00 [pubmed] PHST- 2020/09/29 06:00 [medline] PHST- 2019/08/03 06:00 [entrez] AID - 10.1111/dom.13847 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 Nov;21(11):2576-2580. doi: 10.1111/dom.13847. Epub 2019 Aug 28. PMID- 31340953 OWN - NLM STAT- MEDLINE DCOM- 20200723 LR - 20260127 IS - 2044-6055 (Electronic) IS - 2044-6055 (Linking) VI - 9 IP - 7 DP - 2019 Jul 23 TI - Comparative efficacy of once-weekly semaglutide versus SGLT-2 inhibitors in patients inadequately controlled with one to two oral antidiabetic drugs: a systematic literature review and network meta-analysis. PG - e023458 LID - 10.1136/bmjopen-2018-023458 [doi] LID - e023458 AB - OBJECTIVE: To determine the comparative efficacy of once-weekly semaglutide relative to sodium-glucose cotransporter 2 inhibitors (SGLT-2is) licensed in Europe and North America among patients with type 2 diabetes (T2D) inadequately controlled with 1-2 oral antidiabetics (OADs), using a network meta-analysis (NMA). Design systematic review and network meta-analysis. Data Sources EMBASE, MEDLINE and CENTRAL were searched from January 1994 to August 2017. METHODS: Randomised controlled trials with >/=20 weeks of treatment evaluating once-weekly semaglutide or SGLT-2is. Primary outcomes included change from baseline in: HbA1c, weight, systolic blood pressure, postprandial blood glucose and fasting plasma glucose. Fixed-effect and random-effect Bayesian NMA were used to indirectly compare treatment effects at 26 (+/-4) weeks. Metaregression and sensitivity analyses were conducted. Model selection was performed using the deviance information criterion and consistency was assessed by comparing indirect (edge-splitting) to direct evidence. RESULTS: Forty-eight publications representing 21 trials were included. The mean differences (MD) in change from baseline in HbA1c of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from -0.56% for canagliflozin 300 mg (95% credible interval (CrI): -0.76 to -0.33%), to -0.95% for dapagliflozin 5 mg (95% CrI: -1.20 to -0.69%). The MD in change from baseline in weight of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from -1.35 kg for canagliflozin 300 mg to -2.48 kg for dapagliflozin 5 mg, while change from baseline in fasting plasma glucose ranged from -0.41 mmol/L for canagliflozin 300 mg to -1.37 mmol/L for dapagliflozin 5 mg. Once-weekly semaglutide was not statistically differentiable than all SGLT-2is in reducing systolic blood pressure. NMA was not feasible for postprandial blood glucose and safety outcomes. CONCLUSION: Once-weekly semaglutide demonstrated statistically significant and clinically meaningful reductions in HbA1c and body weight in T2D patients inadequately controlled with 1-2 OADs compared to all SGLT-2is licensed in Europe and North America. CI - (c) Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Kanters, Steve AU - Kanters S AD - Precision Xtract, Vancouver, British Columbia, Canada. FAU - Wilkinson, Lars AU - Wilkinson L AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Vrazic, Hrvoje AU - Vrazic H AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sharma, Rohini AU - Sharma R AD - Precision Xtract, Vancouver, British Columbia, Canada. FAU - Lopes, Sandra AU - Lopes S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Popoff, Evan AU - Popoff E AD - Precision Xtract, Vancouver, British Columbia, Canada. FAU - Druyts, Eric AU - Druyts E AD - Precision Xtract, Vancouver, British Columbia, Canada. LA - eng PT - Comparative Study PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20190723 PL - England TA - BMJ Open JT - BMJ open JID - 101552874 RN - 0 (Benzhydryl Compounds) RN - 0SAC974Z85 (Canagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) RN - 1ULL0QJ8UC (dapagliflozin) SB - IM MH - Benzhydryl Compounds MH - Canagliflozin MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/*administration & dosage/therapeutic use MH - Glucosides MH - Humans MH - Hypoglycemic Agents/*administration & dosage/therapeutic use MH - Metformin MH - Randomized Controlled Trials as Topic MH - Sodium-Glucose Transporter 2 Inhibitors/*administration & dosage/therapeutic use MH - Treatment Outcome MH - Semaglutide PMC - PMC6661926 OTO - NOTNLM OT - SGLT-2 inhibitors OT - glucagon-like peptide-1 analogue OT - once-weekly semaglutide OT - sustain clinical trial programme OT - type 2 diabetes COIS- Competing interests: LW, HV and SL are employees of Novo Nordisk. RS, EP, ED and SK report funding provided by Novo Nordisk to Precision Xtract, where they are employees. EDAT- 2019/07/26 06:00 MHDA- 2020/07/24 06:00 PMCR- 2019/07/23 CRDT- 2019/07/26 06:00 PHST- 2019/07/26 06:00 [entrez] PHST- 2019/07/26 06:00 [pubmed] PHST- 2020/07/24 06:00 [medline] PHST- 2019/07/23 00:00 [pmc-release] AID - bmjopen-2018-023458 [pii] AID - 10.1136/bmjopen-2018-023458 [doi] PST - epublish SO - BMJ Open. 2019 Jul 23;9(7):e023458. doi: 10.1136/bmjopen-2018-023458. PMID- 31317516 OWN - NLM STAT- MEDLINE DCOM- 20191028 LR - 20260127 IS - 1179-1918 (Electronic) IS - 1173-2563 (Print) IS - 1173-2563 (Linking) VI - 39 IP - 8 DP - 2019 Aug TI - Glucagon-Like Peptide-1 Receptor Analogues in Type 2 Diabetes: Their Use and Differential Features. PG - 805-819 LID - 10.1007/s40261-019-00826-0 [doi] AB - Glucagon-like peptide-1 receptor analogues/agonists (GLP-1RAs) are well established as effective adjuncts to lifestyle modification in the treatment of type 2 diabetes (T2D) as monotherapy or in combination with oral glucose-lowering drugs +/- insulin. The six subcutaneous GLP-1RA formulations (i.e. twice-daily exenatide, once-daily liraglutide and lixisenatide, and once-weekly dulaglutide, exenatide and semaglutide) currently available in the EU and USA have many similarities, but also some unique features and properties. By stimulating GLP-1 receptors, GLP-1RAs increase insulin secretion and suppress glucagon release in a glucose-dependent manner, thereby improving clinical and patient-reported outcomes related to glycaemic control and weight. They also have been shown to reduce, or at least not increase, the risk of major cardiovascular outcomes. GLP-1RAs are generally well tolerated, with gastrointestinal and injection-site reactions being the most troublesome drug-related adverse events, and are associated with a very low intrinsic risk of hypoglycaemia. Treatment with GLP-1RAs should be customized to meet the clinical needs and personal preferences of the individual. FAU - Lyseng-Williamson, Katherine A AU - Lyseng-Williamson KA AUID- ORCID: 0000-0002-5104-1158 AD - Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. DEcorrespondence@springer.com. LA - eng PT - Journal Article PT - Review PL - New Zealand TA - Clin Drug Investig JT - Clinical drug investigation JID - 9504817 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM EIN - Clin Drug Investig. 2019 Sep;39(9):915-916. doi: 10.1007/s40261-019-00839-9. PMID: 31422551 EIN - Clin Drug Investig. 2019 Oct;39(10):1019. doi: 10.1007/s40261-019-00852-y. PMID: 31512163 EIN - Clin Drug Investig. 2020 Mar;40(3):291. doi: 10.1007/s40261-020-00892-9. PMID: 32040760 MH - Administration, Oral MH - Blood Glucose/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/administration & dosage/*therapeutic use MH - Injections, Subcutaneous MH - Insulin/*therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC6746674 COIS- K.A. Lyseng-Williamson is an employee of Adis International/Springer Nature, is responsible for the article content and declares no conflicts of interest. EDAT- 2019/07/19 06:00 MHDA- 2019/10/29 06:00 PMCR- 2019/07/18 CRDT- 2019/07/19 06:00 PHST- 2019/07/19 06:00 [pubmed] PHST- 2019/10/29 06:00 [medline] PHST- 2019/07/19 06:00 [entrez] PHST- 2019/07/18 00:00 [pmc-release] AID - 10.1007/s40261-019-00826-0 [pii] AID - 826 [pii] AID - 10.1007/s40261-019-00826-0 [doi] PST - ppublish SO - Clin Drug Investig. 2019 Aug;39(8):805-819. doi: 10.1007/s40261-019-00826-0. PMID- 31305048 OWN - NLM STAT- MEDLINE DCOM- 20200402 LR - 20260127 IS - 1532-0650 (Electronic) IS - 0002-838X (Linking) VI - 100 IP - 2 DP - 2019 Jul 15 TI - Semaglutide (Ozempic) for Type 2 Diabetes Mellitus. PG - 116-117 FAU - Chamberlin, Shaunta AU - Chamberlin S AD - University of Tennessee Graduate School of Medicine, Knoxville, TN, USA. FAU - Dabbs, William AU - Dabbs W AD - University of Tennessee Graduate School of Medicine, Knoxville, TN, USA. LA - eng PT - Journal Article PL - United States TA - Am Fam Physician JT - American family physician JID - 1272646 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/*pharmacology MH - Humans MH - Semaglutide EDAT- 2019/07/16 06:00 MHDA- 2020/04/03 06:00 CRDT- 2019/07/16 06:00 PHST- 2019/07/16 06:00 [entrez] PHST- 2019/07/16 06:00 [pubmed] PHST- 2020/04/03 06:00 [medline] AID - d14477 [pii] PST - ppublish SO - Am Fam Physician. 2019 Jul 15;100(2):116-117. PMID- 31246368 OWN - NLM STAT- MEDLINE DCOM- 20200420 LR - 20260127 IS - 1365-2036 (Electronic) IS - 0269-2813 (Print) IS - 0269-2813 (Linking) VI - 50 IP - 2 DP - 2019 Jul TI - Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and/or obesity. PG - 193-203 LID - 10.1111/apt.15316 [doi] AB - BACKGROUND: Obesity and type 2 diabetes are drivers of non-alcoholic fatty liver disease (NAFLD). Glucagon-like peptide-1 analogues effectively treat obesity and type 2 diabetes and may offer potential for NAFLD treatment. AIM: To evaluate the effect of the glucagon-like peptide-1 analogue, semaglutide, on alanine aminotransferase (ALT) and high-sensitivity C-reactive protein (hsCRP) in subjects at risk of NAFLD. METHODS: Data from a 104-week cardiovascular outcomes trial in type 2 diabetes (semaglutide 0.5 or 1.0 mg/week) and a 52-week weight management trial (semaglutide 0.05-0.4 mg/day) were analysed. Treatment ratios vs placebo were estimated for ALT (both trials) and hsCRP (weight management trial only) using a mixed model for repeated measurements, with or without adjustment for change in body weight. RESULTS: Elevated baseline ALT (men >30 IU/L; women >19 IU/L) was present in 52% (499/957) of weight management trial subjects. In this group with elevated ALT, end-of-treatment ALT reductions were 6%-21% (P<0.05 for doses>/=0.2 mg/day) and hsCRP reductions 25%-43% vs placebo (P < 0.05 for 0.2 and 0.4 mg/day). Normalisation of elevated baseline ALT occurred in 25%-46% of weight management trial subjects, vs 18% on placebo. Elevated baseline ALT was present in 41% (1325/3268) of cardiovascular outcomes trial subjects. In this group with elevated ALT, no significant ALT reduction was noted at end-of-treatment for 0.5 mg/week, while a 9% reduction vs placebo was seen for 1.0 mg/week (P = 0.0024). Treatment ratios for changes in ALT and hsCRP were not statistically significant after adjustment for weight change. CONCLUSIONS: Semaglutide significantly reduced ALT and hsCRP in clinical trials in subjects with obesity and/or type 2 diabetes. CI - (c) 2019 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. FAU - Newsome, Philip AU - Newsome P AUID- ORCID: 0000-0001-6085-3652 AD - National Institute for Health Research Birmingham Biomedical Research Centre and Liver Unit at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. AD - Centre for Liver & Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. FAU - Francque, Sven AU - Francque S AD - Department of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Antwerp, Belgium. FAU - Harrison, Stephen AU - Harrison S AD - Radcliffe Department of Medicine, University of Oxford, Oxford, UK. FAU - Ratziu, Vlad AU - Ratziu V AD - ICAN - Institute for Cardiometabolism and Nutrition, Hopital Pitie Salpetriere, Sorbonne University, Paris, France. FAU - Van Gaal, Luc AU - Van Gaal L AD - Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Edegem, Antwerp, Belgium. FAU - Calanna, Salvatore AU - Calanna S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hansen, Morten AU - Hansen M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Linder, Martin AU - Linder M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Sanyal, Arun AU - Sanyal A AUID- ORCID: 0000-0001-8682-5748 AD - Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia. LA - eng GR - UL1 TR002649/TR/NCATS NIH HHS/United States GR - Novo Nordisk/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190610 PL - England TA - Aliment Pharmacol Ther JT - Alimentary pharmacology & therapeutics JID - 8707234 RN - EC 2.6.1.2 (Alanine Transaminase) RN - 0 (Biomarkers) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Alanine Transaminase/metabolism MH - Biomarkers/*metabolism MH - Body Weight/drug effects MH - Cardiovascular Diseases/epidemiology/prevention & control MH - Clinical Trials, Phase II as Topic MH - Clinical Trials, Phase III as Topic MH - Diabetes Mellitus, Type 2/complications/*drug therapy/metabolism MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptide 1/analogs & derivatives MH - Glucagon-Like Peptides/*pharmacology/therapeutic use MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Inflammation/complications/drug therapy/*metabolism MH - Liver/*drug effects/enzymology/metabolism MH - Male MH - Middle Aged MH - Multicenter Studies as Topic/statistics & numerical data MH - Non-alcoholic Fatty Liver Disease/complications/metabolism/prevention & control MH - Obesity/complications/*drug therapy/metabolism MH - Randomized Controlled Trials as Topic/statistics & numerical data MH - Retrospective Studies MH - Weight Reduction Programs MH - Young Adult MH - Semaglutide PMC - PMC6617813 EDAT- 2019/06/28 06:00 MHDA- 2020/04/21 06:00 PMCR- 2019/07/10 CRDT- 2019/06/28 06:00 PHST- 2018/12/20 00:00 [received] PHST- 2019/01/19 00:00 [revised] PHST- 2019/05/01 00:00 [accepted] PHST- 2019/06/28 06:00 [entrez] PHST- 2019/06/28 06:00 [pubmed] PHST- 2020/04/21 06:00 [medline] PHST- 2019/07/10 00:00 [pmc-release] AID - APT15316 [pii] AID - 10.1111/apt.15316 [doi] PST - ppublish SO - Aliment Pharmacol Ther. 2019 Jul;50(2):193-203. doi: 10.1111/apt.15316. Epub 2019 Jun 10. PMID- 31227789 OWN - NLM STAT- MEDLINE DCOM- 20210330 LR - 20211022 IS - 1476-5454 (Electronic) IS - 0950-222X (Print) IS - 0950-222X (Linking) VI - 33 IP - 12 DP - 2019 Dec TI - New anti-hyperglycaemic agents for type 2 diabetes and their effects on diabetic retinopathy. PG - 1842-1851 LID - 10.1038/s41433-019-0494-z [doi] AB - There has been an increase in the range of non-insulin anti-hyperglycaemic agents used to treat type 2 diabetes. With the globally rising rates of type 2 diabetes and complications such as diabetic retinopathy, it is important for ophthalmologists to be aware of these new agents and their impacts on diabetic retinopathy and diabetic macular oedema. We conducted a review of the literature to determine if there were any beneficial or harmful effects of the currently used anti-hyperglycaemic agents on diabetic retinopathy or diabetic macular oedema. Our review of the current literature found that apart from thiazolidinediones, anti-hyperglycaemic agents have been reported to have beneficial or neutral effects on diabetic eye complications. Thiazolidinediones (pioglitazone is the only one currently available) have been linked to incident or worsening diabetic macular oedema, although the rate is believed to be low. Glucagon-like peptide 1 (GLP1) agonists (incretins) in general are beneficial except semaglutide which is associated with increased rates of diabetic retinopathy complications. These results have implications for selection of anti-hyperglycaemic agents for patients with diabetic retinopathy or macular oedema. Further studies need to be conducted to identify if reported beneficial effects are independent of the impact of glycaemic control. Early worsening of retinopathy with tight glycaemic control should also be noted in interpretation of future studies. FAU - Saw, Mercy AU - Saw M AD - Liverpool Diabetes Collaborative Research Unit, Ingham Institute for Applied Medical Research, University of New South Wales, Sydney, Australia. FAU - Wong, Vincent W AU - Wong VW AD - Liverpool Diabetes Collaborative Research Unit, Ingham Institute for Applied Medical Research, University of New South Wales, Sydney, Australia. FAU - Ho, I-Van AU - Ho IV AD - South West Retina, Retina Associates, Liverpool, Sydney, Australia. AD - Australian School of Advanced Medicine, Macquarie University, Sydney, Australia. FAU - Liew, Gerald AU - Liew G AD - South West Retina, Retina Associates, Liverpool, Sydney, Australia. gerald.liew@sydney.edu.au. AD - Centre for Vision Research, Westmead Millennium Institute of Medical Research, University of Sydney, Sydney, Australia. gerald.liew@sydney.edu.au. LA - eng PT - Journal Article PT - Review DEP - 20190621 PL - England TA - Eye (Lond) JT - Eye (London, England) JID - 8703986 RN - 0 (Hypoglycemic Agents) SB - IM CIN - Eye (Lond). 2021 Oct;35(10):2903-2904. doi: 10.1038/s41433-020-01209-y. PMID: 33005047 MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Diabetic Retinopathy/diagnosis/drug therapy/*etiology MH - Humans MH - Hypoglycemic Agents/*therapeutic use PMC - PMC7002655 COIS- The authors declare that they have no conflict of interest. EDAT- 2019/06/23 06:00 MHDA- 2021/03/31 06:00 PMCR- 2020/12/01 CRDT- 2019/06/23 06:00 PHST- 2019/02/04 00:00 [received] PHST- 2019/05/21 00:00 [accepted] PHST- 2019/04/19 00:00 [revised] PHST- 2019/06/23 06:00 [pubmed] PHST- 2021/03/31 06:00 [medline] PHST- 2019/06/23 06:00 [entrez] PHST- 2020/12/01 00:00 [pmc-release] AID - 10.1038/s41433-019-0494-z [pii] AID - 494 [pii] AID - 10.1038/s41433-019-0494-z [doi] PST - ppublish SO - Eye (Lond). 2019 Dec;33(12):1842-1851. doi: 10.1038/s41433-019-0494-z. Epub 2019 Jun 21. PMID- 31215727 OWN - NLM STAT- MEDLINE DCOM- 20200908 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 21 IP - 10 DP - 2019 Oct TI - Improved treatment satisfaction in patients with type 2 diabetes treated with once-weekly semaglutide in the SUSTAIN trials. PG - 2315-2326 LID - 10.1111/dom.13816 [doi] AB - AIM: To investigate treatment satisfaction with semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, versus placebo/active comparators in the SUSTAIN clinical trial programme. METHODS: In SUSTAIN 2-5 and 7, the Diabetes Treatment Satisfaction Questionnaire was used to evaluate patient-perceived treatment satisfaction, hyperglycaemia and hypoglycaemia. Post hoc subgroup analyses were conducted to explore the effects of gastrointestinal adverse events (GI AEs), weight loss (>/=5%) or achieving glycaemic (HbA1c < 7%) targets on treatment satisfaction. RESULTS: Overall treatment satisfaction increased from baseline to end of treatment with all treatments across trials. Improvements were significantly greater with semaglutide versus comparators/placebo in SUSTAIN 2-5 (all P < 0.05), and generally greater in patients who achieved versus did not achieve weight loss and glycaemic targets, often with greater improvements with semaglutide 1.0 mg versus comparator/placebo in both weight loss groups. In SUSTAIN 7, improvements in overall treatment satisfaction were generally similar between semaglutide and dulaglutide, irrespective of weight loss or glycaemic control. In SUSTAIN 7, changes in overall treatment satisfaction score were generally lower in patients with versus without GI AEs at week 16 (except dulaglutide 0.75 mg), but similar by week 40. Perceived hyperglycaemia was significantly reduced from baseline to end of treatment with semaglutide versus all comparators/placebo (all P < 0.05). No differences between treatments were observed for perceived hypoglycaemia. CONCLUSIONS: Semaglutide was associated with significantly greater (SUSTAIN 2-5) or similar (SUSTAIN 7) improvements in overall treatment satisfaction versus comparators/placebo. Improvements in overall treatment satisfaction were generally greater in patients achieving versus not achieving treatment targets. Clinicaltrials.gov: NCT01930188 (SUSTAIN 2), NCT01885208 (SUSTAIN 3), NCT02128932 (SUSTAIN 4), NCT02305381 (SUSTAIN 5) and NCT02648204 (SUSTAIN 7). EudraCT: 2012-004827-19 (SUSTAIN 2), 2012-004826-92 (SUSTAIN 3), 2013-004392-12 (SUSTAIN 4), 2013-004502-26 (SUSTAIN 5) and 2014-005375-91 (SUSTAIN 7). CI - (c) 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Jendle, Johan AU - Jendle J AUID- ORCID: 0000-0003-1025-1682 AD - Diabetes Endocrinology and Metabolism Research Center, School of Medical Sciences, Orebro University, Orebro, Sweden. FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AD - Department of Medicine III, Carl Gustav Carus University Hospital, Technische Universitat Dresden, Dresden, Germany. AD - Paul Langerhans Institute Dresden, Helmholtz Center Munich at Technische Universitat Dresden, Dresden, Germany. FAU - Polonsky, William H AU - Polonsky WH AD - Behavioral Diabetes Institute, University of California San Diego, San Diego, California. FAU - Silver, Robert AU - Silver R AD - Southern New Hampshire Diabetes and Endocrinology, Nashua, New Hampshire. FAU - Uusinarkaus, Kari AU - Uusinarkaus K AD - DaVita Medical Group, University of Colorado School of Medicine, Colorado Springs, Colorado. FAU - Hansen, Thomas AU - Hansen T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hakan-Bloch, Jonas AU - Hakan-Bloch J AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Tadayon, Sayeh AU - Tadayon S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Davies, Melanie J AU - Davies MJ AUID- ORCID: 0000-0002-9987-9371 AD - Diabetes Research Centre, University of Leicester, Leicester, UK. LA - eng SI - ClinicalTrials.gov/NCT01930188 SI - ClinicalTrials.gov/NCT01885208 SI - ClinicalTrials.gov/NCT02128932 SI - ClinicalTrials.gov/NCT02305381 SI - ClinicalTrials.gov/NCT02648204 SI - EudraCT/2012-004827-19 SI - EudraCT/2012-004826-92 SI - EudraCT/2013-004392-12 SI - EudraCT/2013-004502-26 SI - EudraCT/2014-005375-91 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190712 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose/*drug effects MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptide 1/analogs & derivatives MH - Glucagon-Like Peptides/administration & dosage/pharmacology/*therapeutic use MH - Humans MH - Hypoglycemic Agents/administration & dosage/pharmacology/*therapeutic use MH - Patient Satisfaction/*statistics & numerical data MH - Surveys and Questionnaires MH - Weight Loss/drug effects MH - Semaglutide PMC - PMC6771774 OTO - NOTNLM OT - glucagon-like peptide-1 analogue OT - hypoglycaemia OT - incretin therapy OT - type 2 diabetes OT - weight control COIS- J.J. reports consultant fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Medtronic and Sanofi; serving on speaker bureau for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Merck; all outside the submitted work. A.L.B. reports personal fees from Novo Nordisk during the conduct of the study. W.H.P. reports serving as a consultant for Novo Nordisk outside the submitted work. R.S. reports personal fees from Novo Nordisk, Eli Lilly and AstraZeneca outside the submitted work. K.U. reports other financial activities with Novo Nordisk and Astra Zeneca outside the submitted work. T.H. has nothing to disclose. J.H.-B. reports being previously employed by Novo Nordisk. S.T. has nothing to disclose. M.J.D. reports personal fees from Novo Nordisk, Sanofi-Aventis, Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, AstraZeneca, Janssen, Servier, Mitsubishi Tanabe Pharma Corporation and Takeda Pharmaceuticals International Inc., and grants from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim and Janssen, all outside the submitted work. EDAT- 2019/06/20 06:00 MHDA- 2020/09/09 06:00 PMCR- 2019/10/01 CRDT- 2019/06/20 06:00 PHST- 2019/03/25 00:00 [received] PHST- 2019/06/05 00:00 [revised] PHST- 2019/06/13 00:00 [accepted] PHST- 2019/06/20 06:00 [pubmed] PHST- 2020/09/09 06:00 [medline] PHST- 2019/06/20 06:00 [entrez] PHST- 2019/10/01 00:00 [pmc-release] AID - DOM13816 [pii] AID - 10.1111/dom.13816 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 Oct;21(10):2315-2326. doi: 10.1111/dom.13816. Epub 2019 Jul 12. PMID- 31189520 OWN - NLM STAT- MEDLINE DCOM- 20200522 LR - 20260518 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 7 IP - 7 DP - 2019 Jul TI - Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial. PG - 528-539 LID - S2213-8587(19)30194-9 [pii] LID - 10.1016/S2213-8587(19)30194-9 [doi] AB - BACKGROUND: Oral semaglutide is the first oral formulation of a glucagon-like peptide-1 (GLP-1) receptor agonist developed for the treatment of type 2 diabetes. We aimed to compare the efficacy and safety of flexible dose adjustments of oral semaglutide with sitagliptin 100 mg. METHODS: In this 52-week, multicentre, randomised, open-label, phase 3a trial, we recruited patients with type 2 diabetes from 81 sites in ten countries. Patients were eligible if they were aged 18 years or older (19 years or older in South Korea), had type 2 diabetes (diagnosed >/=90 days before screening), HbA(1c) of 7.5-9.5% (58-80 mmol/mol), and were inadequately controlled on stable daily doses of one or two oral glucose-lowering drugs (for 90 days or more before screening). Participants were randomly assigned (1:1) by use of an interactive web-response system, stratified by background glucose-lowering medication at screening, to oral semaglutide with flexible dose adjustments to 3, 7, or 14 mg once daily or sitagliptin 100 mg once daily. To approximate treatment individualisation in clinical practice, oral semaglutide dose could be adjusted on the basis of prespecified HbA(1c) and tolerability criteria. Two efficacy-related estimands were prespecified: treatment policy (regardless of treatment discontinuation or use of rescue medication) and trial product (on treatment and without use of rescue medication) for participants randomly assigned to treatment. The primary endpoint was achievement of HbA(1c) of less than 7% (53 mmol/mol) at week 52 and the confirmatory secondary efficacy endpoint was change in bodyweight from baseline to week 52. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT02849080, and European Clinical Trials Database, EudraCT number 2015-005593-38, and an open-label extension is ongoing. FINDINGS: Between Sept 20, 2016, and Feb 7, 2017, of 804 patients assessed for eligibility, 504 were eligible and randomly assigned to oral semaglutide (n=253) or sitagliptin (n=251). Most participants were male (285 [57%] of 504) with a mean age of 57.4 years (SD 9.9). All participants were given at least one dose of their allocated study drug except for one participant in the sitagliptin group. From a mean baseline HbA(1c) of 8.3% (SD 0.6%; 67 mmol/mol [SD 6.4]), a greater proportion of participants achieved an HbA(1c) of less than 7% with oral semaglutide than did with sitagliptin (treatment policy estimand: 58% [134 of 230] vs 25% [60 of 238]; and trial product estimand: 63% [123 of 196] vs 28% [52 of 184]). The odds of achieving an HbA(1c) of less than 7% was significantly better with oral semaglutide than sitagliptin (treatment policy estimand: odds ratio [OR] 4.40, 95% CI 2.89-6.70, p<0.0001; and trial product estimand: 5.54, 3.54-8.68, p<0.0001). The odds of decreasing mean bodyweight from baseline to week 52 were higher with oral semaglutide than with sitagliptin (estimated mean change in bodyweight, treatment policy estimand: -2.6 kg [SE 0.3] vs -0.7 kg [SE 0.2], estimated treatment difference [ETD] -1.9 kg, 95% CI -2.6 to -1.2; p<0.0001; and trial product estimand: -2.9 kg [SE 0.3] vs -0.8 kg [SE 0.3], ETD -2.2 kg, -2.9 to -1.5; p<0.0001). Adverse events occurred in 197 (78%) of 253 participants in the oral semaglutide group versus 172 (69%) of 250 in the sitagliptin group, and nausea was the most common adverse event with oral semaglutide (53 [21%]). Two deaths occurred in the sitagliptin group during the trial. INTERPRETATION: Oral semaglutide, with flexible dose adjustment, based on efficacy and tolerability, provided superior glycaemic control and weight loss compared with sitagliptin, and with a safety profile consistent with subcutaneous GLP-1 receptor agonists. FUNDING: Novo Nordisk A/S. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Pieber, Thomas R AU - Pieber TR AD - Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria. Electronic address: thomas.pieber@medunigraz.at. FAU - Bode, Bruce AU - Bode B AD - Atlanta Diabetes Associates, Atlanta, GA, USA. FAU - Mertens, Ann AU - Mertens A AD - Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Aging (CHROMETA), KU Leuven, Leuven, Belgium. FAU - Cho, Young Min AU - Cho YM AD - Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. FAU - Christiansen, Erik AU - Christiansen E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hertz, Christin L AU - Hertz CL AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wallenstein, Signe O R AU - Wallenstein SOR AD - Novo Nordisk A/S, Aalborg, Denmark. FAU - Buse, John B AU - Buse JB AD - Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. CN - PIONEER 7 investigators LA - eng SI - ClinicalTrials.gov/NCT02849080 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190609 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet Diabetes Endocrinol. 2019 Jul;7(7):500-502. doi: 10.1016/S2213-8587(19)30182-2. PMID: 31189516 EIN - Lancet Diabetes Endocrinol. 2019 Sep;7(9):e21. doi: 10.1016/S2213-8587(19)30247-5. PMID: 31320282 MH - Aged MH - Diabetes Mellitus, Type 2/*drug therapy MH - Female MH - Glucagon-Like Peptides/*administration & dosage/*adverse effects MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Middle Aged MH - Sitagliptin Phosphate/*therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide FIR - Akin, S IR - Akin S FIR - Aladag, N IR - Aladag N FIR - Arif, A A IR - Arif AA FIR - Aronne, L J IR - Aronne LJ FIR - Aronoff, S IR - Aronoff S FIR - Ataoglu, E IR - Ataoglu E FIR - Baik, S H IR - Baik SH FIR - Bays, H IR - Bays H FIR - Beckett, P L IR - Beckett PL FIR - Berker, D IR - Berker D FIR - Bilz, S IR - Bilz S FIR - Bode, B IR - Bode B FIR - Braun, E W IR - Braun EW FIR - Buse, J B IR - Buse JB FIR - Canani, L H S IR - Canani LHS FIR - Cho, Y M IR - Cho YM FIR - Chung, C H IR - Chung CH FIR - Colin, I IR - Colin I FIR - Condit, J IR - Condit J FIR - Cooper, J IR - Cooper J FIR - Delgado, B IR - Delgado B FIR - Eagerton, D C IR - Eagerton DC FIR - El Ebrashy, I N IR - El Ebrashy IN FIR - El Hefnawy, M H M F IR - El Hefnawy MHMF FIR - Eliaschewitz, F G IR - Eliaschewitz FG FIR - Finneran, M P IR - Finneran MP FIR - Fischli, S IR - Fischli S FIR - Fliesser-Gorzer, E IR - Fliesser-Gorzer E FIR - Geohas, J IR - Geohas J FIR - Godbole, N A IR - Godbole NA FIR - Golay, A IR - Golay A FIR - Gorban de Lapertosa, S IR - Gorban de Lapertosa S FIR - Gross, J L IR - Gross JL FIR - Gulseth, H L IR - Gulseth HL FIR - Helland, F IR - Helland F FIR - Hoivik, H O IR - Hoivik HO FIR - Issa, C IR - Issa C FIR - Kang, E S IR - Kang ES FIR - Keller, C IR - Keller C FIR - Khalil, S H A IR - Khalil SHA FIR - Kim, N H IR - Kim NH FIR - Kim, I J IR - Kim IJ FIR - Klaff, L J IR - Klaff LJ FIR - Laimer, M IR - Laimer M FIR - LaRocque, J C IR - LaRocque JC FIR - Lederman, S N IR - Lederman SN FIR - Lee, K-W IR - Lee KW FIR - Litchfield, W R IR - Litchfield WR FIR - Manning, M B IR - Manning MB FIR - Mertens, A IR - Mertens A FIR - Morawski, E J IR - Morawski EJ FIR - Murray, A V IR - Murray AV FIR - Nicol, P R IR - Nicol PR FIR - O'Connor, T M IR - O'Connor TM FIR - Oguz, A IR - Oguz A FIR - Ong, S IR - Ong S FIR - Ozdemir, A IR - Ozdemir A FIR - Palace, E M IR - Palace EM FIR - Palchick, B A IR - Palchick BA FIR - Pereles-Ortiz, J IR - Pereles-Ortiz J FIR - Pieber, T IR - Pieber T FIR - Prager, R IR - Prager R FIR - Preumont, V IR - Preumont V FIR - Riffer, E IR - Riffer E FIR - Rista, L IR - Rista L FIR - Rudofsky, G IR - Rudofsky G FIR - Sari, R IR - Sari R FIR - Scheen, A IR - Scheen A FIR - Schultes, B IR - Schultes B FIR - Seo, J A IR - Seo JA FIR - Shelbaya, S A IR - Shelbaya SA FIR - Sivalingam, K IR - Sivalingam K FIR - Sorli, C H IR - Sorli CH FIR - Stauble, S IR - Stauble S FIR - Streja, D A IR - Streja DA FIR - T'Sjoen, G IR - T'Sjoen G FIR - Tetiker, T IR - Tetiker T FIR - Van Gaal, L IR - Van Gaal L FIR - Vercammen, C IR - Vercammen C FIR - Warren, M L IR - Warren ML FIR - Weinstein, D L IR - Weinstein DL FIR - Weiss, D IR - Weiss D FIR - White, A IR - White A FIR - Winnie, M IR - Winnie M FIR - Wium, C IR - Wium C FIR - Yavuz, D IR - Yavuz D EDAT- 2019/06/14 06:00 MHDA- 2020/05/23 06:00 CRDT- 2019/06/14 06:00 PHST- 2019/04/09 00:00 [received] PHST- 2019/05/08 00:00 [revised] PHST- 2019/05/08 00:00 [accepted] PHST- 2019/06/14 06:00 [pubmed] PHST- 2020/05/23 06:00 [medline] PHST- 2019/06/14 06:00 [entrez] AID - S2213-8587(19)30194-9 [pii] AID - 10.1016/S2213-8587(19)30194-9 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2019 Jul;7(7):528-539. doi: 10.1016/S2213-8587(19)30194-9. Epub 2019 Jun 9. PMID- 31189517 OWN - NLM STAT- MEDLINE DCOM- 20200522 LR - 20260518 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 7 IP - 7 DP - 2019 Jul TI - Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. PG - 515-527 LID - S2213-8587(19)30192-5 [pii] LID - 10.1016/S2213-8587(19)30192-5 [doi] AB - BACKGROUND: Oral semaglutide is the first oral glucagon-like peptide-1 (GLP-1) receptor agonist for glycaemic control in patients with type 2 diabetes. Type 2 diabetes is commonly associated with renal impairment, restricting treatment options. We aimed to investigate the efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment. METHODS: This randomised, double-blind, phase 3a trial was undertaken at 88 sites in eight countries. Patients aged 18 years and older, with type 2 diabetes, an estimated glomerular filtration rate of 30-59 mL/min per 1.73 m(2), and who had been receiving a stable dose of metformin or sulfonylurea, or both, or basal insulin with or without metformin for the past 90 days were eligible. Participants were randomly assigned (1:1) by use of an interactive web-response system, with stratification by glucose-lowering medication and renal function, to receive oral semaglutide (dose escalated to 14 mg once daily) or matching placebo for 26 weeks, in addition to background medication. Participants and site staff were masked to assignment. Two efficacy-related estimands were defined: treatment policy (regardless of treatment discontinuation or rescue medication) and trial product (on treatment without rescue medication) in all participants randomly assigned. Endpoints were change from baseline to week 26 in HbA(1c) (primary endpoint) and bodyweight (confirmatory secondary endpoint), assessed in all participants with sufficient data. Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on ClinicalTrials.gov, number NCT02827708, and the European Clinical Trials Registry, number EudraCT 2015-005326-19, and is now complete. FINDINGS: Between Sept 20, 2016, and Sept 29, 2017, of 721 patients screened, 324 were eligible and randomly assigned to oral semaglutide (n=163) or placebo (n=161). Mean age at baseline was 70 years (SD 8), and 168 (52%) of participants were female. 133 (82%) participants in the oral semaglutide group and 141 (88%) in the placebo group completed 26 weeks on treatment. At 26 weeks, oral semaglutide was superior to placebo in decreasing HbA(1c) (estimated mean change of -1.0 percentage point (SE 0.1; -11 mmol/mol [SE 0.8]) vs -0.2 percentage points (SE 0.1; -2 mmol/mol [SE 0.8]); estimated treatment difference [ETD]: -0.8 percentage points, 95% CI -1.0 to -0.6; p<0.0001) and bodyweight (estimated mean change of -3.4 kg [SE 0.3] vs -0.9 kg [SE 0.3]; ETD, -2.5, 95% CI -3.2 to -1.8; p<0.0001) by the treatment policy estimand. Significant differences were seen for the trial product estimand: mean change in HbA(1c) -1.1 percentage points (SE 0.1; -12 mmol/mol [SE 0.8] versus -0.1 percentage points (SE 0.1; -1 mmol/mol [SE 0.8]; ETD -1.0 percentage points, 95% CI -1.2 to -0.8; p<0.0001); mean change in bodyweight -3.7 kg (SE 0.3) versus -1.1 kg (SE 0.3; ETD -2.7 kg, 95% CI -3.5 to -1.9; p<0.0001). More patients taking oral semaglutide than placebo had adverse events (120 [74%] of 163 vs 105 [65%] of 161), and discontinued treatment as a result (24 [15%] vs eight [5%]). Gastrointestinal events, mainly mild-to-moderate nausea, were more common with oral semaglutide than with placebo. Three deaths occurred during the treatment period that were not condsidered to be treatment related, one in the semaglutide group and two in the placebo group. INTERPRETATION: Oral semaglutide was effective in patients with type 2 diabetes and moderate renal impairment, potentially providing a new treatment option for this population. Safety, including renal safety, was consistent with the GLP-1 receptor agonist class. FUNDING: Novo Nordisk A/S. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel. Electronic address: ofrim@hadassah.org.il. FAU - Blicher, Thalia Marie AU - Blicher TM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Rosenlund, Signe AU - Rosenlund S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Eriksson, Jan W AU - Eriksson JW AD - Clinical Diabetology and Metabolism, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. FAU - Heller, Simon AU - Heller S AD - Academic Unit of Diabetes, Endocrinology and Metabolism, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK. FAU - Hels, Ole Holm AU - Hels OH AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Pratley, Richard AU - Pratley R AD - AdventHealth Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA. FAU - Sathyapalan, Thozhukat AU - Sathyapalan T AD - Academic Diabetes, Endocrinology and Metabolism Research Group, Hull York Medical School, University of Hull, Hull, UK. FAU - Desouza, Cyrus AU - Desouza C AD - Division of Diabetes, Endocrinology, and Metabolism, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA. CN - PIONEER 5 Investigators LA - eng SI - ClinicalTrials.gov/NCT02827708 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190609 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet Diabetes Endocrinol. 2019 Jul;7(7):500-502. doi: 10.1016/S2213-8587(19)30182-2. PMID: 31189516 CIN - Nat Rev Endocrinol. 2019 Sep;15(9):499. doi: 10.1038/s41574-019-0234-2. PMID: 31253858 EIN - Lancet Diabetes Endocrinol. 2019 Sep;7(9):e21. doi: 10.1016/S2213-8587(19)30246-3. PMID: 31320281 MH - Administration, Oral MH - Aged MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - *Diabetic Nephropathies MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptides/pharmacology/*therapeutic use MH - Humans MH - Male MH - Middle Aged MH - Renal Insufficiency/*complications MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide FIR - Abramof, R IR - Abramof R FIR - Alpenidze, D IR - Alpenidze D FIR - Aronoff, S IR - Aronoff S FIR - Astamirova, K IR - Astamirova K FIR - Barker, B IR - Barker B FIR - Bedel, G IR - Bedel G FIR - Belousova, L IR - Belousova L FIR - Benson, M IR - Benson M FIR - Beshay, I IR - Beshay I FIR - Biggs, W IR - Biggs W FIR - Blaze, K IR - Blaze K FIR - Bogdanski, P IR - Bogdanski P FIR - Busch, R IR - Busch R FIR - Chaidarun, S IR - Chaidarun S FIR - Chandran, S IR - Chandran S FIR - Chang, A IR - Chang A FIR - Chilka, S IR - Chilka S FIR - Cleland, A IR - Cleland A FIR - Connery, L IR - Connery L FIR - Cornett, G IR - Cornett G FIR - Delgado, B IR - Delgado B FIR - Desouza, C IR - Desouza C FIR - Donner, T IR - Donner T FIR - Eliasson, K IR - Eliasson K FIR - Eriksson, J IR - Eriksson J FIR - Folkerth, S IR - Folkerth S FIR - Forshaw, K IR - Forshaw K FIR - Frandsen, H A IR - Frandsen HA FIR - Frolova, E IR - Frolova E FIR - Gandy, W IR - Gandy W FIR - Gatipon, G IR - Gatipon G FIR - Golovach, A IR - Golovach A FIR - Gonzalez-Orozco, L IR - Gonzalez-Orozco L FIR - Gumprecht, J IR - Gumprecht J FIR - Haddad, E IR - Haddad E FIR - Hansen, T K IR - Hansen TK FIR - Hart, T IR - Hart T FIR - Hasan, S IR - Hasan S FIR - Hella, B IR - Hella B FIR - Heller, S IR - Heller S FIR - Hellgren, M IR - Hellgren M FIR - Hewitt, M IR - Hewitt M FIR - Hietaniemi, S IR - Hietaniemi S FIR - Hitz, M IR - Hitz M FIR - Houser, P IR - Houser P FIR - Huntley, R IR - Huntley R FIR - Jackson, R IR - Jackson R FIR - Jakobsen, P E IR - Jakobsen PE FIR - Kapoor, A IR - Kapoor A FIR - Kargina, L IR - Kargina L FIR - Kazakova, E IR - Kazakova E FIR - Khan, K IR - Khan K FIR - Klein, E IR - Klein E FIR - Knoble, H IR - Knoble H FIR - Krasnopeeva Kabachkova, N IR - Krasnopeeva Kabachkova N FIR - Krzeminski, A IR - Krzeminski A FIR - Kunitsyna, M IR - Kunitsyna M FIR - Lawhead, J IR - Lawhead J FIR - Levin, K IR - Levin K FIR - Levin, P IR - Levin P FIR - Lewy-Alterbaum, L IR - Lewy-Alterbaum L FIR - Lindmark, S IR - Lindmark S FIR - Lindsay, R IR - Lindsay R FIR - Luts, A IR - Luts A FIR - Lysenko, T IR - Lysenko T FIR - Madsbad, S IR - Madsbad S FIR - Maxwell, T IR - Maxwell T FIR - Mbogua, C IR - Mbogua C FIR - Mcknight, J IR - Mcknight J FIR - Metsarinne, K IR - Metsarinne K FIR - Milovanova, T IR - Milovanova T FIR - Morawski, E IR - Morawski E FIR - Mosenzon, O IR - Mosenzon O FIR - Nabriski, D IR - Nabriski D FIR - Nguyen, H IR - Nguyen H FIR - Nicol, P IR - Nicol P FIR - Nieminen, S IR - Nieminen S FIR - Nikkola, A IR - Nikkola A FIR - Norwood, P IR - Norwood P FIR - O'Donnell, P IR - O'Donnell P FIR - Odugbesan, A IR - Odugbesan A FIR - Parker, J IR - Parker J FIR - Pergaeva, Y IR - Pergaeva Y FIR - Peskov, A IR - Peskov A FIR - Plevin, S IR - Plevin S FIR - Pouzar, J IR - Pouzar J FIR - Pratley, R IR - Pratley R FIR - Reed, J IR - Reed J FIR - Rossing, P IR - Rossing P FIR - Sathyapalan, T IR - Sathyapalan T FIR - Sergeeva-Kondrachenko, M IR - Sergeeva-Kondrachenko M FIR - Shaikh, Z IR - Shaikh Z FIR - Shamkhalova, M IR - Shamkhalova M FIR - Shehadeh, N IR - Shehadeh N FIR - Shlesinger, Y IR - Shlesinger Y FIR - Silver, R IR - Silver R FIR - Snyder, B IR - Snyder B FIR - Soufer, J IR - Soufer J FIR - Strand, J IR - Strand J FIR - Sulosaari, S IR - Sulosaari S FIR - Tirosh, A IR - Tirosh A FIR - Traylor, H IR - Traylor H FIR - Uhlenius, N IR - Uhlenius N FIR - Vagapova, G IR - Vagapova G FIR - Yanovskaya, M IR - Yanovskaya M FIR - Zarutskaya, L IR - Zarutskaya L FIR - Zhdanova, E IR - Zhdanova E EDAT- 2019/06/14 06:00 MHDA- 2020/05/23 06:00 CRDT- 2019/06/14 06:00 PHST- 2019/03/19 00:00 [received] PHST- 2019/04/25 00:00 [revised] PHST- 2019/04/26 00:00 [accepted] PHST- 2019/06/14 06:00 [pubmed] PHST- 2020/05/23 06:00 [medline] PHST- 2019/06/14 06:00 [entrez] AID - S2213-8587(19)30192-5 [pii] AID - 10.1016/S2213-8587(19)30192-5 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2019 Jul;7(7):515-527. doi: 10.1016/S2213-8587(19)30192-5. Epub 2019 Jun 9. PMID- 31186300 OWN - NLM STAT- MEDLINE DCOM- 20200518 LR - 20260518 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 42 IP - 9 DP - 2019 Sep TI - PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. PG - 1724-1732 LID - 10.2337/dc19-0749 [doi] AB - OBJECTIVE: This trial compared the efficacy and safety of the first oral glucagon-like peptide 1 (GLP-1) receptor agonist, oral semaglutide, as monotherapy with placebo in patients with type 2 diabetes managed by diet and exercise alone. Two estimands addressed two efficacy-related questions: a treatment policy estimand (regardless of trial product discontinuation or rescue medication use) and a trial product estimand (on trial product without rescue medication use) in all randomized patients. RESEARCH DESIGN AND METHODS: This was a 26-week, phase 3a, randomized, double-blind, placebo-controlled, parallel-group trial conducted in 93 sites in nine countries. Adults with type 2 diabetes insufficiently controlled with diet and exercise were randomized (1:1:1:1) to once-daily oral semaglutide 3 mg, 7 mg, 14 mg, or placebo. The primary end point was change from baseline to week 26 in HbA(1c). The confirmatory secondary end point was change from baseline to week 26 in body weight. RESULTS: In the 703 patients randomized (mean age 55 years, 50.8% male, and mean baseline HbA(1c) 8.0% [64 mmol/mol]), oral semaglutide reduced HbA(1c) (placebo-adjusted treatment differences at week 26: treatment policy estimand, -0.6% [3 mg], -0.9% [7 mg], and -1.1% [14 mg]; trial product estimand, -0.7% [3 mg], -1.2% [7 mg], and -1.4% [14 mg]; P < 0.001 for all) and body weight (treatment policy, -0.1 kg [3 mg], -0.9 kg [7 mg], and -2.3 kg [14 mg, P < 0.001]; trial product, -0.2 kg [3 mg], -1.0 kg [7 mg, P = 0.01], and -2.6 kg [14 mg, P < 0.001]). Mild-to-moderate transient gastrointestinal events were the most common adverse events with oral semaglutide. Trial product discontinuations occurred in 2.3-7.4% with oral semaglutide and 2.2% with placebo. CONCLUSIONS: In patients with type 2 diabetes, oral semaglutide monotherapy demonstrated superior and clinically relevant improvements in HbA(1c) (all doses) and body weight loss (14 mg dose) versus placebo, with a safety profile consistent with other GLP-1 receptor agonists. CI - (c) 2019 by the American Diabetes Association. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Brigham and Women's Hospital, Harvard Medical School, Boston, MA varoda@bwh.harvard.edu. AD - MedStar Health Research Institute, Hyattsville, MD. FAU - Rosenstock, Julio AU - Rosenstock J AUID- ORCID: 0000-0001-8324-3275 AD - Dallas Diabetes Research Center at Medical City, Dallas, TX. FAU - Terauchi, Yasuo AU - Terauchi Y AUID- ORCID: 0000-0002-8872-3697 AD - Yokohama City University, Yokohama, Japan. FAU - Altuntas, Yuksel AU - Altuntas Y AD - Division of Endocrinology Metabolism Diabetes, Department of Internal Medicine, Sisli Hamidiye Etfal Teaching and Research Hospital, University of Health Sciences, Istanbul, Turkey. FAU - Lalic, Nebojsa M AU - Lalic NM AD - Clinic for Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. FAU - Morales Villegas, Enrique C AU - Morales Villegas EC AD - Cardiometabolic Research Center, Aguascalientes, Mexico. FAU - Jeppesen, Ole K AU - Jeppesen OK AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Christiansen, Erik AU - Christiansen E AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hertz, Christin L AU - Hertz CL AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Haluzik, Martin AU - Haluzik M AUID- ORCID: 0000-0002-0201-6888 CN - PIONEER 1 Investigators LA - eng SI - ClinicalTrials.gov/NCT02906930 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190611 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Administration, Oral MH - Adult MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Diet MH - Double-Blind Method MH - Exercise MH - Female MH - Glucagon-Like Peptides/*administration & dosage MH - Glycated Hemoglobin/drug effects MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Male MH - Middle Aged MH - Weight Loss/drug effects MH - Semaglutide FIR - Belkacem, Krim IR - Belkacem K FIR - Chiali, Nabil IR - Chiali N FIR - Bourezane, Samia IR - Bourezane S FIR - Guermaz, Rachida IR - Guermaz R FIR - Popivanov, Plamen IR - Popivanov P FIR - Lefterov, Ivaylo IR - Lefterov I FIR - Tankova, Tsvetalina IR - Tankova T FIR - Penchev, Ivan IR - Penchev I FIR - Koskova, Martina IR - Koskova M FIR - Hudcova, Miroslava IR - Hudcova M FIR - Vesela, Alica IR - Vesela A FIR - Rancova, Anna IR - Rancova A FIR - Haluzik, Martin IR - Haluzik M FIR - Kiyosue, Arihiro IR - Kiyosue A FIR - Matsuoka, Osamu IR - Matsuoka O FIR - Inoue, Satoshi IR - Inoue S FIR - Terauchi, Yasuo IR - Terauchi Y FIR - Fukushima, Yasushi IR - Fukushima Y FIR - Ide, Yumiko IR - Ide Y FIR - Violante Ortiz, Rafael Margarito IR - Violante Ortiz RM FIR - Morales Villegas, Enrique IR - Morales Villegas E FIR - Golovach, Albina IR - Golovach A FIR - Alpenidze, Diana IR - Alpenidze D FIR - Frolova, Elena IR - Frolova E FIR - Zhdanova, Elena IR - Zhdanova E FIR - Ruyatkina, Ludmila IR - Ruyatkina L FIR - Ershova, Olga IR - Ershova O FIR - Samoilova, Yulia IR - Samoilova Y FIR - Zyangirova, Svetlana IR - Zyangirova S FIR - Lalic, Katarina IR - Lalic K FIR - Lalic, Nebojsa IR - Lalic N FIR - Beljic Zivkovic, Teodora IR - Beljic Zivkovic T FIR - Ataoglu, Esra IR - Ataoglu E FIR - Bakiner, Okan IR - Bakiner O FIR - Dayan, Akin IR - Dayan A FIR - Sargin, Mehmet IR - Sargin M FIR - Mert, Meral IR - Mert M FIR - Adas, Mine IR - Adas M FIR - Tabak, Omur IR - Tabak O FIR - Altuntas, Yuksel IR - Altuntas Y FIR - Murray, Alexander IR - Murray A FIR - Iranmanesh, Ali IR - Iranmanesh A FIR - Schlau, Aron IR - Schlau A FIR - Wieskopf, Bram IR - Wieskopf B FIR - Snyder, Brian IR - Snyder B FIR - Griffin, Carl IR - Griffin C FIR - Fogarty, Charles IR - Fogarty C FIR - Lovell, Charles IR - Lovell C FIR - Allison, Dale IR - Allison D FIR - Fitz-Patrick, David IR - Fitz-Patrick D FIR - Grant, David IR - Grant D FIR - Klonoff, David IR - Klonoff D FIR - Williams, Dwayne IR - Williams D FIR - Armas, Eddie IR - Armas E FIR - Palace, Eileen IR - Palace E FIR - Ruoff, Gary IR - Ruoff G FIR - Martinez, Gilbert IR - Martinez G FIR - Perez, Gilberto IR - Perez G FIR - Bays, Harold IR - Bays H FIR - Tatu, Horia IR - Tatu H FIR - Maynard, James IR - Maynard J FIR - Cedeno, Jeanne-Elyse IR - Cedeno JE FIR - Aroda, Vanita IR - Aroda V FIR - Park, Jean IR - Park J FIR - Sutton, Jennefer IR - Sutton J FIR - Pouzar, Joe IR - Pouzar J FIR - Bertsch, John IR - Bertsch J FIR - Condit, Jonathan IR - Condit J FIR - Serje, Jorge IR - Serje J FIR - Cabaccan, Josel IR - Cabaccan J FIR - Risser, Joseph IR - Risser J FIR - Frias, Juan IR - Frias J FIR - Rosenstock, Julio IR - Rosenstock J FIR - Sivalingam, Kanagaratnam IR - Sivalingam K FIR - Maw, Kelli IR - Maw K FIR - Hanson, Lenita IR - Hanson L FIR - Billings, Liana IR - Billings L FIR - Connery, Lisa IR - Connery L FIR - Juarez, Mario IR - Juarez M FIR - Lillestol, Michael IR - Lillestol M FIR - Fraser, Neil IR - Fraser N FIR - Beckett, Paul IR - Beckett P FIR - Wade, Ralph IR - Wade R FIR - Gaona, Raul IR - Gaona R FIR - Jackson, Richard IR - Jackson R FIR - DeLuca, Robert IR - DeLuca R FIR - Alpizar, Sady IR - Alpizar S FIR - Herring, Sharon IR - Herring S FIR - Stringam, Stanley IR - Stringam S FIR - Bauer, Steven IR - Bauer S FIR - Gangi, Sumana IR - Gangi S FIR - Sligh, Teresa IR - Sligh T FIR - Jarrett, Wentworth IR - Jarrett W FIR - Fitzgibbons, William IR - Fitzgibbons W EDAT- 2019/06/13 06:00 MHDA- 2020/05/19 06:00 CRDT- 2019/06/13 06:00 PHST- 2019/04/15 00:00 [received] PHST- 2019/06/07 00:00 [accepted] PHST- 2019/06/13 06:00 [pubmed] PHST- 2020/05/19 06:00 [medline] PHST- 2019/06/13 06:00 [entrez] AID - dc19-0749 [pii] AID - 10.2337/dc19-0749 [doi] PST - ppublish SO - Diabetes Care. 2019 Sep;42(9):1724-1732. doi: 10.2337/dc19-0749. Epub 2019 Jun 11. PMID- 31186120 OWN - NLM STAT- MEDLINE DCOM- 20190719 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 394 IP - 10192 DP - 2019 Jul 6 TI - Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. PG - 39-50 LID - S0140-6736(19)31271-1 [pii] LID - 10.1016/S0140-6736(19)31271-1 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective treatments for type 2 diabetes, lowering glycated haemoglobin (HbA(1c)) and weight, but are currently only approved for use as subcutaneous injections. Oral semaglutide, a novel GLP-1 agonist, was compared with subcutaneous liraglutide and placebo in patients with type 2 diabetes. METHODS: In this randomised, double-blind, double-dummy, phase 3a trial, we recruited patients with type 2 diabetes from 100 sites in 12 countries. Eligible patients were aged 18 years or older, with HbA(1c) of 7.0-9.5% (53-80.3 mmol/mol), on a stable dose of metformin (>/=1500 mg or maximum tolerated) with or without a sodium-glucose co-transporter-2 inhibitor. Participants were randomly assigned (2:2:1) with an interactive web-response system and stratified by background glucose-lowering medication and country of origin, to once-daily oral semaglutide (dose escalated to 14 mg), once-daily subcutaneous liraglutide (dose escalated to 1.8 mg), or placebo for 52 weeks. Two estimands were defined: treatment policy (regardless of study drug discontinuation or rescue medication) and trial product (assumed all participants were on study drug without rescue medication) in all participants who were randomly assigned. The treatment policy estimand was the primary estimand. The primary endpoint was change from baseline to week 26 in HbA(1c) (oral semaglutide superiority vs placebo and non-inferiority [margin: 0.4%] and superiority vs subcutaneous liraglutide) and the confirmatory secondary endpoint was change from baseline to week 26 in bodyweight (oral semaglutide superiority vs placebo and liraglutide). Safety was assessed in all participants who received at least one dose of study drug. This trial is registered on Clinicaltrials.gov, number NCT02863419, and the European Clinical Trials registry, number EudraCT 2015-005210-30. FINDINGS: Between Aug 10, 2016, and Feb 7, 2017, 950 patients were screened, of whom 711 were eligible and randomly assigned to oral semaglutide (n=285), subcutaneous liraglutide (n=284), or placebo (n=142). 341 (48%) of 711 participants were female and the mean age was 56 years (SD 10). All participants were given at least one dose of study drug, and 277 (97%) participants in the oral semaglutide group, 274 (96%) in the liraglutide group, and 134 (94%) in the placebo group completed the 52-week trial period. Mean change from baseline in HbA(1c) at week 26 was -1.2% (SE 0.1) with oral semaglutide, -1.1% (SE 0.1) with subcutaneous liraglutide, and -0.2% (SE 0.1) with placebo. Oral semaglutide was non-inferior to subcutaneous liraglutide in decreasing HbA(1c) (estimated treatment difference [ETD] -0.1%, 95% CI -0.3 to 0.0; p<0.0001) and superior to placebo (ETD -1.1%, -1.2 to -0.9; p<0.0001) by use of the treatment policy estimand. By use of the trial product estimand, oral semaglutide had significantly greater decreases in HbA(1c) than both subcutaneous liraglutide (ETD -0.2%, 95% CI -0.3 to -0.1; p=0.0056) and placebo (ETD -1.2%, -1.4 to -1.0; p<0.0001) at week 26. Oral semaglutide resulted in superior weight loss (-4.4 kg [SE 0.2]) compared with liraglutide (-3.1 kg [SE 0.2]; ETD -1.2 kg, 95% CI -1.9 to -0.6; p=0.0003) and placebo (-0.5 kg [SE 0.3]; ETD -3.8 kg, -4.7 to -3.0; p<0.0001) at week 26 (treatment policy). By use of the trial product estimand, weight loss at week 26 was significantly greater with oral semaglutide than with subcutaneous liraglutide (-1.5 kg, 95% CI -2.2 to -0.9; p<0.0001) and placebo (ETD -4.0 kg, -4.8 to -3.2; p<0.0001). Adverse events were more frequent with oral semaglutide (n=229 [80%]) and subcutaneous liraglutide (n=211 [74%]) than with placebo (n=95 [67%]). INTERPRETATION: Oral semaglutide was non-inferior to subcutaneous liraglutide and superior to placebo in decreasing HbA(1c), and superior in decreasing bodyweight compared with both liraglutide and placebo at week 26. Safety and tolerability of oral semaglutide were similar to subcutaneous liraglutide. Use of oral semaglutide could potentially lead to earlier initiation of GLP-1 receptor agonist therapy in the diabetes treatment continuum of care. FUNDING: Novo Nordisk A/S. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Pratley, Richard AU - Pratley R AD - AdventHealth Translational Research Institute for Metabolism and Diabetes, Orlando, FL, USA. Electronic address: richard.pratley@flhosp.org. FAU - Amod, Aslam AU - Amod A AD - Life Chatsmed Garden Hospital and Nelson R Mandela School of Medicine, Durban, South Africa. FAU - Hoff, Soren Tetens AU - Hoff ST AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kadowaki, Takashi AU - Kadowaki T AD - Department of Diabetes and Metabolic Diseases and Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Metabolism and Nutrition, Mizonokuchi Hospital, Teikyo University, Kanagawa, Japan. FAU - Lingvay, Ildiko AU - Lingvay I AD - University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. FAU - Nauck, Michael AU - Nauck M AD - Diabetes Division, Department of Medicine I, St Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. FAU - Pedersen, Karen Boje AU - Pedersen KB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Saugstrup, Trine AU - Saugstrup T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Meier, Juris J AU - Meier JJ AD - Diabetes Division, Department of Medicine I, St Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. CN - PIONEER 4 investigators LA - eng SI - ClinicalTrials.gov/NCT02863419 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20190608 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 9100L32L2N (Metformin) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet. 2019 Jul 6;394(10192):4-6. doi: 10.1016/S0140-6736(19)31350-9. PMID: 31186119 EIN - Lancet. 2019 Jul 6;394(10192):e1. doi: 10.1016/S0140-6736(19)31519-3. PMID: 31282364 CIN - Ann Intern Med. 2019 Sep 17;171(6):JC29. doi: 10.7326/ACPJ201909170-029. PMID: 31525763 MH - Administration, Oral MH - Aged MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptides/*administration & dosage/therapeutic use MH - Humans MH - Injections, Subcutaneous MH - Liraglutide/*administration & dosage/therapeutic use MH - Male MH - Metformin/*administration & dosage/therapeutic use MH - Middle Aged MH - Treatment Outcome MH - Semaglutide EDAT- 2019/06/13 06:00 MHDA- 2019/07/20 06:00 CRDT- 2019/06/13 06:00 PHST- 2019/05/02 00:00 [received] PHST- 2019/05/20 00:00 [revised] PHST- 2019/05/21 00:00 [accepted] PHST- 2019/06/13 06:00 [pubmed] PHST- 2019/07/20 06:00 [medline] PHST- 2019/06/13 06:00 [entrez] AID - S0140-6736(19)31271-1 [pii] AID - 10.1016/S0140-6736(19)31271-1 [doi] PST - ppublish SO - Lancet. 2019 Jul 6;394(10192):39-50. doi: 10.1016/S0140-6736(19)31271-1. Epub 2019 Jun 8. PMID- 31185157 OWN - NLM STAT- MEDLINE DCOM- 20190903 LR - 20260518 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 381 IP - 9 DP - 2019 Aug 29 TI - Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. PG - 841-851 LID - 10.1056/NEJMoa1901118 [doi] AB - BACKGROUND: Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available for the subcutaneous form of the glucagon-like peptide-1 receptor agonist semaglutide but are needed for oral semaglutide. METHODS: We assessed cardiovascular outcomes of once-daily oral semaglutide in an event-driven, randomized, double-blind, placebo-controlled trial involving patients at high cardiovascular risk (age of >/=50 years with established cardiovascular or chronic kidney disease, or age of >/=60 years with cardiovascular risk factors only). The primary outcome in a time-to-event analysis was the first occurrence of a major adverse cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The trial was designed to rule out 80% excess cardiovascular risk as compared with placebo (noninferiority margin of 1.8 for the upper boundary of the 95% confidence interval for the hazard ratio for the primary outcome). RESULTS: A total of 3183 patients were randomly assigned to receive oral semaglutide or placebo. The mean age of the patients was 66 years; 2695 patients (84.7%) were 50 years of age or older and had cardiovascular or chronic kidney disease. The median time in the trial was 15.9 months. Major adverse cardiovascular events occurred in 61 of 1591 patients (3.8%) in the oral semaglutide group and 76 of 1592 (4.8%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.57 to 1.11; P<0.001 for noninferiority). Results for components of the primary outcome were as follows: death from cardiovascular causes, 15 of 1591 patients (0.9%) in the oral semaglutide group and 30 of 1592 (1.9%) in the placebo group (hazard ratio, 0.49; 95% CI, 0.27 to 0.92); nonfatal myocardial infarction, 37 of 1591 patients (2.3%) and 31 of 1592 (1.9%), respectively (hazard ratio, 1.18; 95% CI, 0.73 to 1.90); and nonfatal stroke, 12 of 1591 patients (0.8%) and 16 of 1592 (1.0%), respectively (hazard ratio, 0.74; 95% CI, 0.35 to 1.57). Death from any cause occurred in 23 of 1591 patients (1.4%) in the oral semaglutide group and 45 of 1592 (2.8%) in the placebo group (hazard ratio, 0.51; 95% CI, 0.31 to 0.84). Gastrointestinal adverse events leading to discontinuation of oral semaglutide or placebo were more common with oral semaglutide. CONCLUSIONS: In this trial involving patients with type 2 diabetes, the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo. (Funded by Novo Nordisk; PIONEER 6 ClinicalTrials.gov number, NCT02692716.). CI - Copyright (c) 2019 Massachusetts Medical Society. FAU - Husain, Mansoor AU - Husain M AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Donsmark, Morten AU - Donsmark M AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Dungan, Kathleen AU - Dungan K AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Eliaschewitz, Freddy G AU - Eliaschewitz FG AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Franco, Denise R AU - Franco DR AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Jeppesen, Ole K AU - Jeppesen OK AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Lingvay, Ildiko AU - Lingvay I AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Mosenzon, Ofri AU - Mosenzon O AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Pedersen, Sue D AU - Pedersen SD AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Tack, Cees J AU - Tack CJ AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Thomsen, Mette AU - Thomsen M AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Vilsboll, Tina AU - Vilsboll T AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Warren, Mark L AU - Warren ML AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). FAU - Bain, Stephen C AU - Bain SC AD - From the Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto (M.H.), and the C-endo Diabetes and Endocrinology Clinic, Calgary, AB (S.D.P.) - all in Canada; Medical Clinic III, Universitatsklinikum Carl Gustav Carus, Technische Universitat Dresden, and the Paul Langerhans Institute Dresden of Helmholtz Zentrum Munchen at Technische Universitat Dresden, German Center for Diabetes Research, Dresden, Germany (A.L.B.); the Division of Diabetes and Nutritional Sciences, Rayne Institute, King's College London, London (A.L.B.), and the Diabetes Research Unit Cymru, Swansea University Medical School, Swansea (S.C.B.) - both in the United Kingdom; Novo Nordisk, Soborg, Denmark (M.D., O.K.J., M.T.); the Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (K.D.); Centro de Pesquisas Clinicas/Diagnosticos da America Clinical Research Center, Sao Paulo (F.G.E., D.R.F.); the Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas (I.L.); the Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem (O.M.); the Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands (C.J.T); Clinical Metabolic Physiology, Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark (T.V.); and Physicians East, Greenville, NC (M.L.W.). CN - PIONEER 6 Investigators LA - eng SI - ClinicalTrials.gov/NCT02692716 PT - Clinical Trial, Phase III PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190611 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Ann Intern Med. 2019 Sep 17;171(6):JC28. doi: 10.7326/ACPJ201909170-028. PMID: 31525762 CIN - N Engl J Med. 2019 Nov 21;381(21):2075-2076. doi: 10.1056/NEJMc1913157. PMID: 31747739 MH - Administration, Oral MH - Aged MH - Cardiovascular Diseases/*chemically induced MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Male MH - Middle Aged MH - Risk MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide FIR - Bachaoui, Malika IR - Bachaoui M FIR - Hachelaf, Fatma Zohra IR - Hachelaf FZ FIR - Mansour, Abdellah Salah IR - Mansour AS FIR - Malek, Rachid IR - Malek R FIR - Aizenberg, Diego IR - Aizenberg D FIR - Baccaro, Claudia IR - Baccaro C FIR - Oviedo, Alejandra IR - Oviedo A FIR - Pozzi, Jose IR - Pozzi J FIR - Sanabria, Hugo IR - Sanabria H FIR - Visco, Virginia IR - Visco V FIR - Eliaschewitz, Freddy IR - Eliaschewitz F FIR - Aggarwal, Naresh IR - Aggarwal N FIR - Goldenberg, Ronald IR - Goldenberg R FIR - Gupta, Milan IR - Gupta M FIR - Husain, Mansoor IR - Husain M FIR - Li, Stephanie IR - Li S FIR - Pedersen, Sue IR - Pedersen S FIR - Tsoukas, George IR - Tsoukas G FIR - Gram, Jeppe IR - Gram J FIR - Gregersen, Soren IR - Gregersen S FIR - Hegedus, Laszlo IR - Hegedus L FIR - Madsbad, Sten IR - Madsbad S FIR - Vilsboll, Tina IR - Vilsboll T FIR - Birkenfeld, Andreas L IR - Birkenfeld AL FIR - Esser, Michael IR - Esser M FIR - Hagenow, Andreas IR - Hagenow A FIR - Kempe, Hans-Peter IR - Kempe HP FIR - Ludemann, Jorg IR - Ludemann J FIR - Nauck, Michael IR - Nauck M FIR - Schaum, Thomas IR - Schaum T FIR - Segner, Alexander IR - Segner A FIR - Wendisch, Ulrich IR - Wendisch U FIR - Wenzl-Bauer, Veronika IR - Wenzl-Bauer V FIR - Anjana, Ranjit Mohan IR - Anjana RM FIR - Bandgar, Tushar IR - Bandgar T FIR - Chaudhury, Tirthankar IR - Chaudhury T FIR - Desai, Ankush IR - Desai A FIR - Deshmukh, Vaishali IR - Deshmukh V FIR - Jacob, Jubbin IR - Jacob J FIR - Kumar, Harish IR - Kumar H FIR - Kudalkar, Harshada IR - Kudalkar H FIR - Marwah, Tiven IR - Marwah T FIR - Mukhopadhyay, Satinath IR - Mukhopadhyay S FIR - Mutha, Abhay IR - Mutha A FIR - Radhakrishnan, Chandni IR - Radhakrishnan C FIR - Prakash, Anupam IR - Prakash A FIR - Jabbar, Puthiyaveettil Khadar IR - Jabbar PK FIR - Sethi, Bipin IR - Sethi B FIR - Tandon, Nikhil IR - Tandon N FIR - Bashkin, Amir IR - Bashkin A FIR - Cohen, Josef IR - Cohen J FIR - Mosenzon, Ofri IR - Mosenzon O FIR - Sabbah, Muhammad IR - Sabbah M FIR - Shimon, Ilan IR - Shimon I FIR - Stern, Naftali IR - Stern N FIR - Wainstein, Julio IR - Wainstein J FIR - Buscemi, Silvio IR - Buscemi S FIR - Consoli, Agostino IR - Consoli A FIR - Lauro, Davide IR - Lauro D FIR - Maranghi, Marianna IR - Maranghi M FIR - Piatti, PierMarco IR - Piatti P FIR - Sesti, Giorgio IR - Sesti G FIR - Trevisan, Roberto IR - Trevisan R FIR - Hussein, Zanariah IR - Hussein Z FIR - Izani Wan Mohamed, Wan Mohd IR - Izani Wan Mohamed WM FIR - Ong, Tiong Kiam IR - Ong TK FIR - Ramanathan, Letchuman IR - Ramanathan L FIR - Rosman, Azhari IR - Rosman A FIR - Sothiratnam, Radhakrishna IR - Sothiratnam R FIR - Tan, Florence IR - Tan F FIR - Tan, Tong Boon IR - Tan TB FIR - Vijayasingham, Shalini IR - Vijayasingham S FIR - Yahaya, Norhayati IR - Yahaya N FIR - Arechavaleta-Granell, Maria IR - Arechavaleta-Granell M FIR - Rodriguez Briones, Ignacio IR - Rodriguez Briones I FIR - Gonzalez-Galvez, Guillermo IR - Gonzalez-Galvez G FIR - Garcia Hernandez, Pedro Alberto IR - Garcia Hernandez PA FIR - Jimenez-Ramos, Silvia IR - Jimenez-Ramos S FIR - Medina, Carlos IR - Medina C FIR - AlHakim, Mazin IR - AlHakim M FIR - Kooy, Adriaan IR - Kooy A FIR - Lieverse, Aloysius G IR - Lieverse AG FIR - Meesters, Eelco W IR - Meesters EW FIR - Tack, Cees J IR - Tack CJ FIR - Bogdanski, Pawel IR - Bogdanski P FIR - Czernecka, Ewa IR - Czernecka E FIR - Gajos, Grzegorz IR - Gajos G FIR - Stankiewicz, Andrzej IR - Stankiewicz A FIR - Szyprowska, Ewa IR - Szyprowska E FIR - Cif, Adriana IR - Cif A FIR - Guja, Cristian IR - Guja C FIR - Mindrescu, Nicoleta IR - Mindrescu N FIR - Mistodie, Cristina IR - Mistodie C FIR - Onaca, Adriana IR - Onaca A FIR - Vacaru, Georgeta IR - Vacaru G FIR - Vlaiculescu, Mihaela IR - Vlaiculescu M FIR - Zetu, Cornelia IR - Zetu C FIR - Badat, Aysha IR - Badat A FIR - Bonnici, Francois IR - Bonnici F FIR - Hoosen, Farzana IR - Hoosen F FIR - Lombaard, Johannes IR - Lombaard J FIR - Makan, Hemant IR - Makan H FIR - Moosa, Naeem IR - Moosa N FIR - Reddy, Jeevren IR - Reddy J FIR - Tayob, Mohammed IR - Tayob M FIR - Joshi, Pankaj IR - Joshi P FIR - Masmiquel Comas, Luis IR - Masmiquel Comas L FIR - de la Cuesta, Carment IR - de la Cuesta C FIR - Rivas Fernandez, Margarita IR - Rivas Fernandez M FIR - Ferrer Garcia, Juan Carlos IR - Ferrer Garcia JC FIR - Torres Jimenez, Rosa IR - Torres Jimenez R FIR - Tinahones Madueno, Francisco IR - Tinahones Madueno F FIR - Mauricio, Didac IR - Mauricio D FIR - Merino-Torres, Juan Francisco IR - Merino-Torres JF FIR - Zapatero, Antonio IR - Zapatero A FIR - Chen, Jung-Fu IR - Chen JF FIR - Chuang, Lee-Ming IR - Chuang LM FIR - Sheu, Wayne Huey-Herng IR - Sheu WH FIR - Tien, Kai-Jen IR - Tien KJ FIR - Boonyavarakul, Apussanee IR - Boonyavarakul A FIR - Deerochanawong, Chaicharn IR - Deerochanawong C FIR - Krittayaphong, Rungroj IR - Krittayaphong R FIR - Phornphutkul, Mattabhorn IR - Phornphutkul M FIR - Piyayotai, Dilok IR - Piyayotai D FIR - Suwanwalaikorn, Sompongse IR - Suwanwalaikorn S FIR - Tantiwong, Puntip IR - Tantiwong P FIR - Akturk, Mujde IR - Akturk M FIR - Altuntas, Yuksel IR - Altuntas Y FIR - Araz, Mustafa IR - Araz M FIR - Kemal Balci, Mustafa IR - Kemal Balci M FIR - Comlekci, Abdurrahman IR - Comlekci A FIR - Gullu, Sevim IR - Gullu S FIR - Ozgen, Ahmet IR - Ozgen A FIR - Tuna, Mazhar IR - Tuna M FIR - Unubol, Mustafa IR - Unubol M FIR - Bain, Stephen IR - Bain S FIR - Dhatariya, Ketan IR - Dhatariya K FIR - Galliford, Thomas IR - Galliford T FIR - Johnson, Andrew IR - Johnson A FIR - McCrimmon, Rory IR - McCrimmon R FIR - Mcknight, John IR - Mcknight J FIR - Philip, Sam IR - Philip S FIR - Russell-Jones, David IR - Russell-Jones D FIR - Vaidya, Bijay IR - Vaidya B FIR - Ackermann, Jeremy IR - Ackermann J FIR - Allison, Dale IR - Allison D FIR - Aronoff, Stephen IR - Aronoff S FIR - Baker, Claire IR - Baker C FIR - Bays, Harold IR - Bays H FIR - Bradley, Paul IR - Bradley P FIR - Brautigam, Donald IR - Brautigam D FIR - Brinson, Cynthia IR - Brinson C FIR - Busch, Robert IR - Busch R FIR - Cannon, Kevin IR - Cannon K FIR - Casaubon, Luis IR - Casaubon L FIR - Chang, Anna IR - Chang A FIR - Chaicha-Brom, Tira IR - Chaicha-Brom T FIR - Chilka, Sapna IR - Chilka S FIR - Chochinov, Ronald IR - Chochinov R FIR - Chu, James IR - Chu J FIR - Daboul, Nizar IR - Daboul N FIR - Desouza, Cyrus IR - Desouza C FIR - DiGiovanna, Michael IR - DiGiovanna M FIR - Dominguez, Michael IR - Dominguez M FIR - Dungan, Kathleen IR - Dungan K FIR - Eagerton, Donald IR - Eagerton D FIR - Everhart, Brian IR - Everhart B FIR - Farris, Neil IR - Farris N FIR - Fink, Raymond IR - Fink R FIR - Fitz-Patrick, David IR - Fitz-Patrick D FIR - Fogarty, Charles IR - Fogarty C FIR - Fraser, Neil IR - Fraser N FIR - Gilbert, Matthew IR - Gilbert M FIR - Hasan, Syed IR - Hasan S FIR - Huffman, David IR - Huffman D FIR - Jantzi, Curtis IR - Jantzi C FIR - Johnson, David IR - Johnson D FIR - Karounos, Dennis IR - Karounos D FIR - Lane, Wendy IR - Lane W FIR - Ledesma, Gilbert IR - Ledesma G FIR - Levenson, David IR - Levenson D FIR - Lillestol, Michael IR - Lillestol M FIR - Lingvay, Ildiko IR - Lingvay I FIR - Lovell, Charles IR - Lovell C FIR - Manning, Rickey IR - Manning R FIR - Marar, Isam IR - Marar I FIR - May, Michael IR - May M FIR - Meyers, Peter IR - Meyers P FIR - Nagelberg, Steven IR - Nagelberg S FIR - Nakhle, Samer IR - Nakhle S FIR - Ndukwu, Ikeadi IR - Ndukwu I FIR - O'Donnell, Philip IR - O'Donnell P FIR - Pantalone, Kevin IR - Pantalone K FIR - Philis-Tsimikas, Athena IR - Philis-Tsimikas A FIR - Rangaraj, Uma IR - Rangaraj U FIR - Reed, John IR - Reed J FIR - Reedy, Mark IR - Reedy M FIR - Reeves, Michael IR - Reeves M FIR - Risser, Joseph IR - Risser J FIR - Rosenblit, Paul IR - Rosenblit P FIR - Rosenstock, Julio IR - Rosenstock J FIR - Said, Sufyan IR - Said S FIR - Shaw, Stephanie IR - Shaw S FIR - Shlesinger, Yshay IR - Shlesinger Y FIR - Shneker, Ayham IR - Shneker A FIR - Silver, Robert IR - Silver R FIR - Sivalingam, Kanagaratnam IR - Sivalingam K FIR - Sofley, Carl IR - Sofley C FIR - Strzinek, Robert IR - Strzinek R FIR - Tandron, Ileana IR - Tandron I FIR - Thrasher, James IR - Thrasher J FIR - Warren, Mark IR - Warren M FIR - Wierum, Craig IR - Wierum C EDAT- 2019/06/12 06:00 MHDA- 2019/09/04 06:00 CRDT- 2019/06/12 06:00 PHST- 2019/06/12 06:00 [pubmed] PHST- 2019/09/04 06:00 [medline] PHST- 2019/06/12 06:00 [entrez] AID - 10.1056/NEJMoa1901118 [doi] PST - ppublish SO - N Engl J Med. 2019 Aug 29;381(9):841-851. doi: 10.1056/NEJMoa1901118. Epub 2019 Jun 11. PMID- 31168921 OWN - NLM STAT- MEDLINE DCOM- 20200908 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 21 IP - 10 DP - 2019 Oct TI - Incorporating and interpreting regulatory guidance on estimands in diabetes clinical trials: The PIONEER 1 randomized clinical trial as an example. PG - 2203-2210 LID - 10.1111/dom.13804 [doi] AB - Regulatory guidelines describe the use of estimands in designing and conducting clinical trials. Estimands ensure alignment of the objectives with the design, conduct and analysis of a trial. An estimand is defined by four inter-related attributes: the population of interest, the variable (endpoint) of interest, the way intercurrent events are handled and the population level summary. A trial may employ multiple estimands to evaluate treatment effects from different perspectives in order to address different scientific questions. As estimands may be an unfamiliar concept for many clinicians treating diabetes, this paper reviews the estimand concept and uses the PIONEER 1 phase 3a clinical trial, which investigated the efficacy and safety of oral semaglutide vs placebo, as an example of the way in which estimands can be implemented and interpreted. In the PIONEER 1 trial, two estimands were employed for each efficacy endpoint and were labelled as: (a) the treatment policy estimand, used to assess the treatment effect regardless of use of rescue medication or discontinuation of trial product, and provides a broad perspective of the treatment effect in the population of patients with type 2 diabetes in clinical practice; and (b) the trial product estimand, used to assess the treatment effect if all patients had continued to use trial product for the planned duration of the trial without rescue medication, thereby providing information on the anticipated treatment effect of the medication. Both approaches are complementary to understanding the effect of the studied treatments. CI - (c) 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Aroda, Vanita R AU - Aroda VR AUID- ORCID: 0000-0002-7706-4585 AD - Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Saugstrup, Trine AU - Saugstrup T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Buse, John B AU - Buse JB AD - Department of Medicine, Division of Endocrinology and Metabolism, Diabetes Care Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina. FAU - Donsmark, Morten AU - Donsmark M AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Zacho, Jeppe AU - Zacho J AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Davies, Melanie J AU - Davies MJ AUID- ORCID: 0000-0002-9987-9371 AD - Department of Health Sciences, Diabetes Research Centre, University of Leicester, Leicester, UK. LA - eng GR - UL1 TR001102/TR/NCATS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20190630 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - *Models, Statistical MH - *Randomized Controlled Trials as Topic/legislation & jurisprudence/standards MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC6771751 OTO - NOTNLM OT - Diabetes OT - GLP-1 receptor agonists OT - PIONEER OT - estimand OT - oral semaglutide OT - regulatory guidance COIS- V. R. A. has served as a consultant for Adocia, AstraZeneca, BD, Novo Nordisk, Sanofi and Zafgen; has received research grant support to her employing institution from AstraZeneca/BMS, Calibra, Eisai, Janssen, Novo Nordisk, Sanofi and Theracos; and declares that her spouse is an employee of Merck. J. B. has received contracted consulting fees that are paid to the University of North Carolina from Adocia, AstraZeneca, Dance Biopharm, Dexcom, Elcelyx Therapeutics, Eli Lilly, Fractyl, GI Dynamics, Intarcia Therapeutics, Lexicon, MannKind, Metavention, NovaTarg, Novo Nordisk, Orexigen, PhaseBio, Sanofi, Senseonics, Shenzhen HighTide, Takeda, vTv Therapeutics and Zafgen; has received grant support from AstraZeneca, Eli Lilly, GI Dynamics, GlaxoSmithKline, Intarcia Therapeutics, Johnson & Johnson, Lexicon, Medtronic, Novo Nordisk, Orexigen, Sanofi, Scion NeuroStim, Takeda, Theracos and vTv Therapeutics; has served as a consultant to Neurimmune AG; holds stock options in Mellitus Health, PhaseBio and Stability Health; and is supported by a grant from the National Institutes of Health (UL1TR002489). M. J. D. has served as a consultant, advisory board member and speaker for Novo Nordisk, Sanofi-Aventis and Lilly; has served as an advisory board member for Servier and Janssen; has served as a speaker for Boehringer Ingelheim and Takeda Pharmaceuticals International Inc; has received grants in support of the investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim and Janssen. T. S., M. D. and J. Z. are employees of Novo Nordisk A/S. T. S. and M. D. also hold shares in Novo Nordisk A/S. EDAT- 2019/06/07 06:00 MHDA- 2020/09/09 06:00 PMCR- 2019/10/01 CRDT- 2019/06/07 06:00 PHST- 2019/02/15 00:00 [received] PHST- 2019/05/30 00:00 [revised] PHST- 2019/06/02 00:00 [accepted] PHST- 2019/06/07 06:00 [pubmed] PHST- 2020/09/09 06:00 [medline] PHST- 2019/06/07 06:00 [entrez] PHST- 2019/10/01 00:00 [pmc-release] AID - DOM13804 [pii] AID - 10.1111/dom.13804 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 Oct;21(10):2203-2210. doi: 10.1111/dom.13804. Epub 2019 Jun 30. PMID- 31168765 OWN - NLM STAT- MEDLINE DCOM- 20200525 LR - 20200525 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 36 IP - 8 DP - 2019 Aug TI - The Management of Type 2 Diabetes with Once-Weekly Semaglutide Versus Dulaglutide: A Long-Term Cost-Effectiveness Analysis in Slovakia. PG - 2034-2051 LID - 10.1007/s12325-019-00965-y [doi] AB - INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists represent a class of treatments for type 2 diabetes that offer multifactorial benefits, including glycemic control, weight loss and low hypoglycemia risk. Once-weekly semaglutide is a novel GLP-1 analog that has been associated with improved glycemic control and reduced body mass index (BMI) versus once-weekly GLP-1 receptor agonist dulaglutide in SUSTAIN 7, which is reimbursed in patients with a BMI > 35 kg/m(2) in Slovakia. The aim of the present study was to evaluate the long-term cost-effectiveness of once-weekly semaglutide 0.5 mg and 1 mg versus dulaglutide 1.5 mg in Slovakia. METHODS: Clinical and cost outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline cohort characteristics and treatment effects were based on the sub-group of patients with a BMI > 35 kg/m(2) in SUSTAIN 7. Patients were modeled to receive once-weekly semaglutide or dulaglutide for 3 years, after which treatment was intensified to basal insulin. Treatment effects associated with once-weekly semaglutide and dulaglutide were maintained for the first 3 years before HbA1c increased to 7.0% and BMI reverted to baseline. Costs were accounted from a healthcare payer perspective in Slovakia and expressed in euros (EUR). Utilities relating to quality of life were taken from published sources. RESULTS: Once-weekly semaglutide 0.5 mg and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.04 and 0.07 quality-adjusted life years (QALYs), respectively, versus dulaglutide 1.5 mg. Lifetime medical costs were similar, with cost savings of EUR 20 and EUR 140 per patient with once-weekly semaglutide 0.5 mg and 1 mg, respectively, versus dulaglutide 1.5 mg. Both doses of once-weekly semaglutide were therefore considered dominant versus dulaglutide 1.5 mg. CONCLUSION: Both doses of once-weekly semaglutide represent cost-saving treatment options versus dulaglutide 1.5 mg for obese patients with type 2 diabetes in Slovakia. FUNDING: Novo Nordisk A/S. FAU - Malkin, Samuel J P AU - Malkin SJP AD - Ossian Health Economics and Communications, Basel, Switzerland. FAU - Russel-Szymczyk, Monika AU - Russel-Szymczyk M AD - Novo Nordisk Pharma Sp. z o.o, Warsaw, Poland. FAU - Psota, Marek AU - Psota M AD - Pharm-In spol. s.r.o, Bratislava, Slovakia. FAU - Hlavinkova, Lucia AU - Hlavinkova L AD - Novo Nordisk Slovakia s.r.o, Bratislava, Slovakia. FAU - Hunt, Barnaby AU - Hunt B AUID- ORCID: 0000-0001-5420-279X AD - Ossian Health Economics and Communications, Basel, Switzerland. hunt@ossianconsulting.com. LA - eng SI - figshare/10.6084/m9.figshare.8010869 PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190605 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 0 (Hypoglycemic Agents) RN - 62340-29-8 (Glucagon-Like Peptides) MH - Adult MH - Aged MH - Aged, 80 and over MH - Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2/*drug therapy/*economics/epidemiology MH - *Drug Administration Schedule MH - Female MH - Glucagon-Like Peptides/administration & dosage/*economics/*therapeutic use MH - Humans MH - Hypoglycemic Agents/administration & dosage/*economics/*therapeutic use MH - Male MH - Middle Aged MH - Slovakia/epidemiology PMC - PMC6822857 OTO - NOTNLM OT - Cost OT - Cost-effectiveness OT - Diabetes mellitus OT - Dulaglutide OT - GLP-1 analog OT - GLP-1 receptor agonist OT - Semaglutide OT - Slovakia EDAT- 2019/06/07 06:00 MHDA- 2020/05/26 06:00 PMCR- 2019/06/05 CRDT- 2019/06/07 06:00 PHST- 2019/03/05 00:00 [received] PHST- 2019/06/07 06:00 [pubmed] PHST- 2020/05/26 06:00 [medline] PHST- 2019/06/07 06:00 [entrez] PHST- 2019/06/05 00:00 [pmc-release] AID - 10.1007/s12325-019-00965-y [pii] AID - 965 [pii] AID - 10.1007/s12325-019-00965-y [doi] PST - ppublish SO - Adv Ther. 2019 Aug;36(8):2034-2051. doi: 10.1007/s12325-019-00965-y. Epub 2019 Jun 5. PMID- 31167654 OWN - NLM STAT- MEDLINE DCOM- 20200224 LR - 20260127 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 18 IP - 1 DP - 2019 Jun 6 TI - Cardiovascular risk reduction with once-weekly semaglutide in subjects with type 2 diabetes: a post hoc analysis of gender, age, and baseline CV risk profile in the SUSTAIN 6 trial. PG - 73 LID - 10.1186/s12933-019-0871-8 [doi] LID - 73 AB - BACKGROUND: The SUSTAIN 6 trial demonstrated that once-weekly semaglutide (0.5 and 1.0 mg) significantly reduced major adverse cardiovascular (CV) events (MACE) vs placebo in subjects with type 2 diabetes (T2D) and high CV risk. The effects of gender, age and baseline CV risk on outcomes are important considerations for further study. METHODS: Subjects were grouped according to gender, age (50-65 years and > 65 years), and CV risk profile at baseline (prior myocardial infarction [MI] or stroke vs no prior MI or stroke, and established CV disease [CVD] vs CV risk factors alone, including subjects with chronic kidney disease). Time to MACE and its individual components (CV death, nonfatal MI, nonfatal stroke), hospitalization for unstable angina or heart failure, and revascularization (coronary and peripheral) were analyzed for all subgroups. Additional analyses were performed for gender and age to investigate change from baseline in HbA(1c) and body weight, as well as tolerability. RESULTS: A total of 3297 subjects were included. The majority of subjects (60.7%) were male; 43% were > 65 years of age; 41.5% had a history of MI or stroke; and 76.8% had established CVD. Compared with placebo, semaglutide reduced the risk of the first occurrence of MACE and each MACE component consistently across all subgroups (gender, age, and baseline CV risk profile). Revascularizations, HbA(1c) and body weight were also reduced consistently across all subgroups compared with placebo. Gastrointestinal adverse events in all treatment groups were more common among women than men, but rates of premature treatment discontinuation were similar for both genders. CONCLUSIONS: In this post hoc analysis of SUSTAIN 6, once-weekly semaglutide vs placebo reduced the risk of MACE in all subjects included in the trial, regardless of gender, age, or baseline CV risk profile. Trial registry Clinicaltrials.gov, Identifying number: NCT01720446, Date of registration: October 29, 2012. FAU - Leiter, Lawrence A AU - Leiter LA AD - Division of Endocrinology and Metabolism, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 61 Queen St. East #6121, Toronto, ON, M5C 2T2, Canada. leiterl@smh.ca. FAU - Bain, Stephen C AU - Bain SC AD - Diabetes Research Unit Cymru, Swansea University Medical School, Swansea, Wales, UK. FAU - Hramiak, Irene AU - Hramiak I AD - University of Western Ontario, London, ON, Canada. FAU - Jodar, Esteban AU - Jodar E AD - Hospital Universitario Quironsalud, Madrid, Spain. FAU - Madsbad, Sten AU - Madsbad S AD - University of Copenhagen, Hvidovre, Denmark. FAU - Gondolf, Theis AU - Gondolf T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hansen, Thomas AU - Hansen T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Holst, Ingrid AU - Holst I AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AD - UT Southwestern Medical Center, Dallas, TX, USA. LA - eng SI - ClinicalTrials.gov/NCT01720446 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190606 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Age Factors MH - Aged MH - Cardiovascular Diseases/diagnosis/mortality/*prevention & control MH - Clinical Trials, Phase III as Topic MH - Diabetes Mellitus, Type 2/diagnosis/*drug therapy/mortality MH - Drug Administration Schedule MH - Female MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Incretins/*administration & dosage/adverse effects MH - Male MH - Middle Aged MH - Protective Factors MH - Randomized Controlled Trials as Topic MH - Risk Assessment MH - Risk Factors MH - Sex Factors MH - Time Factors MH - Treatment Outcome MH - Semaglutide PMC - PMC6551895 OTO - NOTNLM OT - Age OT - Baseline cardiovascular risk OT - Cardiovascular events OT - Cardiovascular outcome trial OT - Gender OT - SUSTAIN 6 OT - Semaglutide OT - Type 2 diabetes COIS- During the conduct of the study, L.A.L. received research grants to his institution from Novo Nordisk. Outside of the submitted work, he has received grants and/or personal fees for advisory panels, speakers' bureaus, and research support from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, Merck, Novo Nordisk, and Sanofi. He also reports research grants from GlaxoSmithKline and personal fees for advisory panels from Servier. Outside the submitted work, S.C.B. has received honoraria, teaching, and research sponsorship/grants from Abbott, AstraZeneca, Boehringer Ingelheim, Cellnovo, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, and Sanofi-aventis, Cardiff University, Doctors.net, Elsevier, Onmedica, Omnia-Med, Medscape, All-Wales Medicines Strategy Group, National Institute for Health and Care Excellence (NICE) UK, and Glycosmedia. Outside the submitted work, I.H. reports research grants and/or personal fees from AstraZeneca/Bristol-Myers Squibb, Boehringer Ingelheim, Dexcom, Eli Lilly, GlaxoSmithKline, Insulet Corp, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Medtronic, Merck & Co Inc, Population Health Research Institute, Roche Pharma, Sanofi, and Takeda. E.J. reports grants and personal fees from Novo Nordisk during the conduct of the study. He also reports grants and personal fees as a consultant and/or speaker from Amgen, AstraZeneca, Boehringer Ingelheim, Faes Farma, Fresenius, Janssen Pharmaceuticals, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Sanofi, Shire, and UCB. Outside of the submitted work, S.M. has received honoraria and/or lecture fees from AstraZeneca, Boehringer Ingelheim, Bristol-Meyers Squibb, Eli Lilly, Intarcia Therapeutics, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Novo Nordisk, and Sanofi Aventis. He has also received a research grant from Novo Nordisk and Boehringer Ingelheim. T.G., T.H., and I.H. report that they are full-time employees of Novo Nordisk A/S. I.L. received research grants to her institution and consulting fees from Novo Nordisk during the conduct of the study. Outside the submitted work, she has received grants and/or personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, GI Dynamics, Intarcia, Mannkind, Merck, Mylan, Novartis, NovoNordisk, Pfizer, Sanofi, TARGETPharma, and Valeritas. EDAT- 2019/06/07 06:00 MHDA- 2020/02/25 06:00 PMCR- 2019/06/06 CRDT- 2019/06/07 06:00 PHST- 2019/03/31 00:00 [received] PHST- 2019/05/17 00:00 [accepted] PHST- 2019/06/07 06:00 [entrez] PHST- 2019/06/07 06:00 [pubmed] PHST- 2020/02/25 06:00 [medline] PHST- 2019/06/06 00:00 [pmc-release] AID - 10.1186/s12933-019-0871-8 [pii] AID - 871 [pii] AID - 10.1186/s12933-019-0871-8 [doi] PST - epublish SO - Cardiovasc Diabetol. 2019 Jun 6;18(1):73. doi: 10.1186/s12933-019-0871-8. PMID- 31138195 OWN - NLM STAT- MEDLINE DCOM- 20191230 LR - 20200309 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 18 IP - 1 DP - 2019 May 28 TI - The CANVAS Program: implications of canagliflozin on reducing cardiovascular risk in patients with type 2 diabetes mellitus. PG - 64 LID - 10.1186/s12933-019-0869-2 [doi] LID - 64 AB - Canagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor that reduces blood glucose, as well as blood pressure, body weight, and albuminuria in patients with type 2 diabetes mellitus (T2DM). In the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, patients with T2DM and high cardiovascular risk treated with canagliflozin had a significantly lower risk of the composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke; hospitalization for heart failure; and renal outcomes, but also a greater risk of lower-limb amputation. Cardiovascular outcomes trials of some other T2DM agents (i.e., empagliflozin, dapagliflozin, liraglutide, semaglutide, albiglutide) have also shown potential cardiovascular and renal benefits. As a result, diabetes treatment guidelines have begun to incorporate consideration of cardiovascular and renal benefits into their treatment recommendations. Antihyperglycemic agents with proven beneficial cardiovascular effects represent a new opportunity for the diabetologist and cardiologist, in the setting of a multidisciplinary approach, to concomitantly improve glycemic control and reduce the risk of cardiovascular events in patients with T2DM. This review briefly discusses the pharmacology of canagliflozin, including clinical and preclinical data; it also describes the effects of canagliflozin on cardiovascular outcomes and side-effects, and compares these effects with other glucose-lowering agents with proven cardiovascular benefits. FAU - Carbone, Salvatore AU - Carbone S AD - Department of Internal Medicine, Pauley Heart Center, Virginia Commonwealth University, West Hospital, Room 529b, 1200 E Broad Street, Richmond, VA, 23298, USA. Salvatore.Carbone@vcuhealth.org. FAU - Dixon, Dave L AU - Dixon DL AD - Department of Pharmacotherapy and Outcome Sciences, School of Pharmacy, Virginia Commonwealth University, 410 N. 12th Street, Richmond, VA, 23298, USA. LA - eng PT - Journal Article PT - Review DEP - 20190528 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0SAC974Z85 (Canagliflozin) SB - IM MH - Biomarkers/blood MH - Blood Glucose/*drug effects/metabolism MH - Canagliflozin/adverse effects/*therapeutic use MH - Cardiovascular Diseases/diagnosis/mortality/physiopathology/*prevention & control MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/mortality MH - Evidence-Based Medicine MH - Humans MH - Protective Factors MH - Risk Assessment MH - Risk Factors MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/*therapeutic use MH - Time Factors MH - Treatment Outcome PMC - PMC6540565 OTO - NOTNLM OT - Canagliflozin OT - Diabetes mellitus OT - Major adverse cardiovascular event OT - Sodium glucose co-transporter 2 inhibitor COIS- The authors declare that they have no competing interests. EDAT- 2019/05/30 06:00 MHDA- 2019/12/31 06:00 PMCR- 2019/05/28 CRDT- 2019/05/30 06:00 PHST- 2019/03/22 00:00 [received] PHST- 2019/05/10 00:00 [accepted] PHST- 2019/05/30 06:00 [entrez] PHST- 2019/05/30 06:00 [pubmed] PHST- 2019/12/31 06:00 [medline] PHST- 2019/05/28 00:00 [pmc-release] AID - 10.1186/s12933-019-0869-2 [pii] AID - 869 [pii] AID - 10.1186/s12933-019-0869-2 [doi] PST - epublish SO - Cardiovasc Diabetol. 2019 May 28;18(1):64. doi: 10.1186/s12933-019-0869-2. PMID- 31099200 OWN - NLM STAT- MEDLINE DCOM- 20200406 LR - 20250103 IS - 2093-5978 (Electronic) IS - 2093-596X (Print) IS - 2093-596X (Linking) VI - 34 IP - 2 DP - 2019 Jun TI - The Role of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Reducing Cardiovascular Events in Patients with Type 2 Diabetes. PG - 106-116 LID - 10.3803/EnM.2019.34.2.106 [doi] AB - The prevalence of type 2 diabetes mellitus (T2DM), which is associated with cardiovascular morbidity and mortality, is increasing worldwide. Although there have been advances in diabetes treatments that reduce microvascular complications (nephropathy, neuropathy, retinopathy), many clinical studies have found that conventional oral hypoglycemic agents and glucose control alone failed to reduce cardiovascular disease. Thus, incretin-based therapies including glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2Is) represent a new area of research, and may serve as novel therapeutics for treating hyperglycemia and modifying other cardiovascular risk factors. Recently, it has been confirmed that several drugs in these classes, including canagliflozin, empagliflozin, semaglutide, and liraglutide, are safe and possess cardioprotective effects. We review the most recent cardiovascular outcome trials on GLP-1RAs and SGLT-2Is, and discuss their implications for treating patients with T2DM in terms of protective effects against cardiovascular disease. CI - Copyright (c) 2019 Korean Endocrine Society. FAU - Kim, Gwang Sil AU - Kim GS AD - Department of Internal Medicine, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea. AD - Cardiovascular and Metabolic Disease Center (CMDC), Inje University, Busan, Korea. FAU - Park, Joong Hyun AU - Park JH AD - Department of Neurology, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea. FAU - Won, Jong Chul AU - Won JC AUID- ORCID: 0000-0002-2219-4083 AD - Department of Internal Medicine, Inje University Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea. AD - Cardiovascular and Metabolic Disease Center (CMDC), Inje University, Busan, Korea. drwonjc@gmail.com. LA - eng GR - 2010-0020224/NRF/International PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20190509 PL - Korea (South) TA - Endocrinol Metab (Seoul) JT - Endocrinology and metabolism (Seoul, Korea) JID - 101554139 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cardiovascular Diseases/complications/*drug therapy MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*complications MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC6599901 OTO - NOTNLM OT - Diabetes mellitus OT - Heart failure OT - Hypoglycemic agents OT - Myocardial ischemia COIS- No potential conflict of interest relevant to this article was reported. EDAT- 2019/05/18 06:00 MHDA- 2020/04/09 06:00 PMCR- 2019/06/01 CRDT- 2019/05/18 06:00 PHST- 2019/01/15 00:00 [received] PHST- 2019/02/25 00:00 [revised] PHST- 2019/03/04 00:00 [accepted] PHST- 2019/05/18 06:00 [pubmed] PHST- 2020/04/09 06:00 [medline] PHST- 2019/05/18 06:00 [entrez] PHST- 2019/06/01 00:00 [pmc-release] AID - 34.e3 [pii] AID - 10.3803/EnM.2019.34.2.106 [doi] PST - ppublish SO - Endocrinol Metab (Seoul). 2019 Jun;34(2):106-116. doi: 10.3803/EnM.2019.34.2.106. Epub 2019 May 9. PMID- 31055989 OWN - NLM STAT- MEDLINE DCOM- 20190624 LR - 20260127 IS - 1744-8344 (Electronic) IS - 1477-9072 (Linking) VI - 17 IP - 5 DP - 2019 May TI - Liraglutide for the prevention of major adverse cardiovascular events in diabetic patients. PG - 377-387 LID - 10.1080/14779072.2019.1615444 [doi] AB - Introduction: The GLP-1 receptor agonist (GLP-1 RA) liraglutide has a half-life of approximately 13 h and is suitable for subcutaneous administration once daily. The use of liraglutide in people with type 2 diabetes has become popular because of the efficacy and durability in relation to glycemic control in combination with weight loss in most patients. Areas covered: PubMed searches were completed using the terms 'GLP-1 receptor agonist', 'Liraglutide', 'Liraglutide and CVD', 'Liraglutide and CVD risk factors'. The reference list of articles subsequently identified was searched and articles of interest were selected. Expert commentary: Liraglutide has been found superior to oral antidiabetic drugs and other GLP-1 RAs with greater reductions in both HbA1c and weight except when compared with semaglutide. Liraglutide has beneficial effects on blood pressure, weight, postprandial lipids, low-grade inflammation and on the myocardium. In the cardiovascular endpoint trial LEADER liraglutide reduced the composite endpoint of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke as well as cardiovascular and total mortality but had no effect on heart failure. Liraglutide reduces the progression of diabetic kidney disease. In the recent 2018 consensus report from EASD/ADA liraglutide is recommended to patients with established cardiovascular diseases after metformin. FAU - Madsbad, Sten AU - Madsbad S AD - a Department of Endocrinology , Hvidovre Hospital , Hvidovre , Denmark. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20190517 PL - England TA - Expert Rev Cardiovasc Ther JT - Expert review of cardiovascular therapy JID - 101182328 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Cardiovascular Diseases/etiology MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - Glucagon-Like Peptides/pharmacology MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Liraglutide/*therapeutic use MH - Risk Factors MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Cardiovascular risk factors OT - GLP-1 RA OT - LEADER OT - glycemic control OT - kidney disease OT - liraglutide OT - weigh loss EDAT- 2019/05/06 06:00 MHDA- 2019/06/25 06:00 CRDT- 2019/05/07 06:00 PHST- 2019/05/06 06:00 [pubmed] PHST- 2019/06/25 06:00 [medline] PHST- 2019/05/07 06:00 [entrez] AID - 10.1080/14779072.2019.1615444 [doi] PST - ppublish SO - Expert Rev Cardiovasc Ther. 2019 May;17(5):377-387. doi: 10.1080/14779072.2019.1615444. Epub 2019 May 17. PMID- 31044636 OWN - NLM STAT- MEDLINE DCOM- 20200220 LR - 20260127 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 22 IP - 10 DP - 2019 Oct TI - Cost-effectiveness of once-weekly semaglutide versus dulaglutide and lixisenatide in patients with type 2 diabetes with inadequate glycemic control in Sweden. PG - 997-1005 LID - 10.1080/13696998.2019.1614009 [doi] AB - Aims: This analysis evaluated the cost-effectiveness of once-weekly semaglutide vs glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes (T2D) uncontrolled on metformin or basal insulin in Sweden. Materials and methods: This cost-effectiveness analysis (CEA) was conducted using the Swedish Institute of Health Economics (IHE) Diabetes Cohort Model. Analyses were conducted from the Swedish societal perspective over a time horizon of 40 years. For patients uncontrolled on metformin, dulaglutide was the comparator, and data from the SUSTAIN 7 clinical trial was used. For patients uncontrolled on basal insulin, lixisenatide was chosen as the comparator and data was obtained from a network meta-analysis (NMA). Results: The results show that, in patients with inadequate control on metformin, semaglutide 1.0 mg dominated (i.e. provided greater clinical benefit, and was less costly) dulaglutide 1.5 mg. In patients with inadequate control on basal insulin, semaglutide 1.0 mg dominated lixisenatide. The reduction in costs is largely driven by the reduction in complications seen with once-weekly semaglutide. Limitations and conclusions: It is likely that this analysis is conservative in estimating the cardiovascular (CV) cost benefits associated with treatment with once-weekly semaglutide. In patients inadequately controlled on basal insulin, the analyses vs lixisenatide were based on results from an NMA, as no head-to-head clinical trial has been conducted for this comparison. These CEA results show that once-weekly semaglutide is a cost-effective GLP-1 RA therapy for the treatment of T2D in patients inadequately controlled on metformin or basal insulin, addressing many current clinician, patient, and payer unmet needs in Sweden. FAU - Ericsson, Asa AU - Ericsson A AD - Novo Nordisk Scandinavia AB , Malmo , Sweden. FAU - Fridhammar, Adam AU - Fridhammar A AD - The Swedish Institute for Health Economics , Lund , Sweden. LA - eng PT - Journal Article DEP - 20190523 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - 74O62BB01U (lixisenatide) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Blood Glucose/*drug effects MH - *Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2/*drug therapy MH - Female MH - Financing, Personal MH - Glucagon-Like Peptides/administration & dosage/*analogs & derivatives/economics MH - Humans MH - Hypoglycemic Agents/*administration & dosage/*economics MH - Immunoglobulin Fc Fragments/*administration & dosage/*economics MH - Male MH - Middle Aged MH - Peptides/*administration & dosage/*economics MH - Recombinant Fusion Proteins/*administration & dosage/*economics MH - Sweden MH - Semaglutide MH - Glucagon-Like Peptide-2 Receptor OTO - NOTNLM OT - Cost-effectiveness OT - GLP-1 OT - I10 OT - I18 OT - I19 OT - semaglutide OT - type 2 diabetes EDAT- 2019/05/03 06:00 MHDA- 2020/02/23 06:00 CRDT- 2019/05/03 06:00 PHST- 2019/05/03 06:00 [pubmed] PHST- 2020/02/23 06:00 [medline] PHST- 2019/05/03 06:00 [entrez] AID - 10.1080/13696998.2019.1614009 [doi] PST - ppublish SO - J Med Econ. 2019 Oct;22(10):997-1005. doi: 10.1080/13696998.2019.1614009. Epub 2019 May 23. PMID- 31034907 OWN - NLM STAT- MEDLINE DCOM- 20200821 LR - 20260127 IS - 1520-6017 (Electronic) IS - 0022-3549 (Print) IS - 0022-3549 (Linking) VI - 108 IP - 9 DP - 2019 Sep TI - Quantifying the Value of Orally Delivered Biologic Therapies: A Cost-Effectiveness Analysis of Oral Semaglutide. PG - 3138-3145 LID - S0022-3549(19)30255-2 [pii] LID - 10.1016/j.xphs.2019.04.022 [doi] AB - Oral semaglutide, which has undergone multiple phase 3 clinical trials, represents the first oral biologic medication for type 2 diabetes in the form of a daily capsule. It provides similar efficacy compared with its weekly injection counterpart, but it demands a dose on the order of 100 times as high and requires more frequent administration. We perform a cost effectiveness analysis using a first and second order Monte Carlo simulation to estimate quality-adjusted life expectancies associated with an oral daily capsule, oral weekly capsule, daily injection, and weekly injection of semaglutide. We conclude that the additional costs incurred to produce extra semaglutide for the oral formulation are cost effective, given the greater quality of life experienced when taking a capsule over a weekly injection. We also demonstrate that the potency of semaglutide allows the formulation to be cost effective, and less potent drugs will require increased oral bioavailability to make a cost effective oral formulation. CI - Copyright (c) 2019 American Pharmacists Association(R). Published by Elsevier Inc. All rights reserved. FAU - Abramson, Alex AU - Abramson A AD - Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139. FAU - Halperin, Florencia AU - Halperin F AD - Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115. FAU - Kim, Jane AU - Kim J AD - Harvard TH Chan School of Public Health, Department of Health Policy and Management, Center for Health Decision Science, Boston, Massachusetts 02115. FAU - Traverso, Giovanni AU - Traverso G AD - Department of Chemical Engineering and David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139. Electronic address: ctraverso@bwh.harvard.edu. LA - eng GR - R01 EB000244/EB/NIBIB NIH HHS/United States GR - R37 EB000244/EB/NIBIB NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20190426 PL - United States TA - J Pharm Sci JT - Journal of pharmaceutical sciences JID - 2985195R RN - 0 (Biological Products) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Administration, Oral MH - Biological Availability MH - Biological Products/*administration & dosage/economics MH - Blood Glucose/analysis/drug effects MH - *Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2/blood/*drug therapy/economics/epidemiology MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Drug Costs MH - Female MH - Glucagon-Like Peptides/*administration & dosage/economics/pharmacokinetics MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*administration & dosage/economics/pharmacokinetics MH - Injections, Subcutaneous/economics MH - Life Expectancy MH - Male MH - Middle Aged MH - Models, Economic MH - Monte Carlo Method MH - Quality-Adjusted Life Years MH - Time Factors MH - United States/epidemiology MH - Semaglutide PMC - PMC6708477 MID - NIHMS1527961 OTO - NOTNLM OT - GLP-1 receptor agonists OT - cost-effectiveness OT - diabetes OT - drug delivery OT - oral OT - quality of life COIS- Competing Interests: G.T. reports receiving consulting fees and research grants from Novo Nordisk. A.A. and G.T. are co-inventors on multiple patent applications describing oral biologic drug delivery. G.T. is a co-inventor on multiple patent applications describing systems enabling infrequent oral dosing and has a financial interest in Lyndra Therapeutics, Inc, a biotechnology company focused on addressing medication non-adherence through the application of gastric resident technologies. Complete details of all relationships for profit and not for profit for G.T. can found at the following link: https://www.dropbox.com/sh/szi7vnr4a2ajb56/AABs5N5i0q9AfT1IqIJAE-T5a?dl=0. EDAT- 2019/04/30 06:00 MHDA- 2020/08/22 06:00 PMCR- 2020/09/01 CRDT- 2019/04/30 06:00 PHST- 2019/03/24 00:00 [received] PHST- 2019/04/13 00:00 [revised] PHST- 2019/04/18 00:00 [accepted] PHST- 2019/04/30 06:00 [pubmed] PHST- 2020/08/22 06:00 [medline] PHST- 2019/04/30 06:00 [entrez] PHST- 2020/09/01 00:00 [pmc-release] AID - S0022-3549(19)30255-2 [pii] AID - 10.1016/j.xphs.2019.04.022 [doi] PST - ppublish SO - J Pharm Sci. 2019 Sep;108(9):3138-3145. doi: 10.1016/j.xphs.2019.04.022. Epub 2019 Apr 26. PMID- 31010349 OWN - NLM STAT- MEDLINE DCOM- 20200129 LR - 20260127 IS - 1941-837X (Electronic) IS - 1369-6998 (Linking) VI - 22 IP - 8 DP - 2019 Aug TI - Patient preferences and health state utilities associated with dulaglutide and semaglutide injection devices among patients with type 2 diabetes in Italy. PG - 806-813 LID - 10.1080/13696998.2019.1609482 [doi] AB - Aims: Several glucagon like peptide-1 (GLP-1) receptor agonists are available as weekly injections for treatment of type 2 diabetes. These medications vary in their injection devices, and these differences could impact quality-of-life and patient preference. The purpose of this study was to examine patient preferences and estimate health state utilities associated with injection devices for two weekly GLP-1 therapies. Materials and methods: Participants with type 2 diabetes in Italy (Milan, Rome) valued three health state vignettes in time trade-off interviews. The health states had identical descriptions of type 2 diabetes, but differed in description of the treatment process: (1) oral treatment regimen, (2) oral plus weekly dulaglutide injection, and (3) oral plus weekly semaglutide injection. Results: A total of 216 participants completed interviews (57.9% male; mean age = 60.5). Almost all patients (99.5%) preferred the oral health state over either injection health state. Comparing between the two injections, 88.4% preferred the dulaglutide health state, while 11.6% preferred the semaglutide state. Mean (SD) utilities were 0.907 (0.076) for oral, 0.894 (0.085) for dulaglutide, and 0.887 (0.087) for semaglutide. The mean (SD) utility difference between the injection device health states was 0.007 (0.019). Limitations: Although the health states were designed to match the injection device instructions for use as closely as possible, vignette-based methods are inherently limited because results are based on perceptions of the health states rather than actual patient experience with the devices. Conclusions: Results provide insight into patient preferences associated with injection devices for weekly GLP-1 receptor agonists. The majority of patients preferred the dulaglutide device over the semaglutide device, and for some patients, this difference had an impact on utility valuations. Patient preferences for injection devices could be an important factor to consider when selecting treatments for type 2 diabetes. FAU - Boye, Kristina S AU - Boye KS AD - a Eli Lilly and Company , Indianapolis , IN , USA. FAU - Matza, Louis S AU - Matza LS AD - b Evidera , Bethesda , MD , USA. FAU - Stewart, Katie D AU - Stewart KD AD - b Evidera , Bethesda , MD , USA. FAU - Jordan, Jessica AU - Jordan J AD - b Evidera , Bethesda , MD , USA. FAU - Biricolti, Giovanni AU - Biricolti G AD - c Eli Lilly Italia S.p.A , Sesto Fiorentino , Italy. FAU - Del Santo, Silvia AU - Del Santo S AD - c Eli Lilly Italia S.p.A , Sesto Fiorentino , Italy. FAU - Perez-Nieves, Magaly AU - Perez-Nieves M AD - a Eli Lilly and Company , Indianapolis , IN , USA. FAU - Federici, Marco O AU - Federici MO AD - c Eli Lilly Italia S.p.A , Sesto Fiorentino , Italy. FAU - Gentilella, Raffaella AU - Gentilella R AD - d Formerly with Eli Lilly Italia S.p.A , Sesto Fiorentino , Italy. FAU - Losi, Serena AU - Losi S AD - c Eli Lilly Italia S.p.A , Sesto Fiorentino , Italy. FAU - Norrbacka, Kirsi AU - Norrbacka K AD - e Eli Lilly Finland , Helsinki , Finland. LA - eng PT - Journal Article DEP - 20190517 PL - England TA - J Med Econ JT - Journal of medical economics JID - 9892255 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Administration, Oral MH - Aged MH - Blood Glucose/drug effects MH - Cost-Benefit Analysis MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptides/administration & dosage/*analogs & derivatives/therapeutic use MH - Glycated Hemoglobin/drug effects MH - Humans MH - Hypoglycemic Agents/administration & dosage/*therapeutic use MH - Immunoglobulin Fc Fragments/administration & dosage/*therapeutic use MH - Injections, Subcutaneous MH - Italy MH - Male MH - Middle Aged MH - *Patient Preference MH - Quality of Life MH - Recombinant Fusion Proteins/administration & dosage/*therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - I10 OT - I19 OT - Italy OT - Utility OT - dulaglutide OT - injection device OT - patient preference OT - semaglutide OT - time trade-off EDAT- 2019/04/24 06:00 MHDA- 2020/01/30 06:00 CRDT- 2019/04/24 06:00 PHST- 2019/04/24 06:00 [pubmed] PHST- 2020/01/30 06:00 [medline] PHST- 2019/04/24 06:00 [entrez] AID - 10.1080/13696998.2019.1609482 [doi] PST - ppublish SO - J Med Econ. 2019 Aug;22(8):806-813. doi: 10.1080/13696998.2019.1609482. Epub 2019 May 17. PMID- 30993527 OWN - NLM STAT- MEDLINE DCOM- 20191024 LR - 20260127 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 56 IP - 9 DP - 2019 Sep TI - Effects of exenatide long-acting release on cardiovascular events and mortality in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. PG - 1051-1060 LID - 10.1007/s00592-019-01347-0 [doi] AB - AIMS: Patients with type 2 diabetes (T2D) have an increased risk of cardiovascular disease. Recent cardiovascular outcome trials (CVOTs) with liraglutide, semaglutide, and albiglutide have shown significant reduction in major adverse cardiovascular events. Conversely, the CVOT with exenatide long-acting release (ELAR) confirmed cardiovascular safety of the drug, but did not reached superiority versus placebo. Herein, we systematically evaluated the effect of ELAR versus placebo or active comparators on cardiovascular events and mortality in patients with T2D. METHODS: We screened the literature for randomized controlled trials reporting cardiovascular events and deaths in patients receiving ELAR versus those receiving placebo or any other glucose-lowering medications. Event rates were pooled and compared using the random-effects model. RESULT: We retrieved 16 trials comparing the occurrence of cardiovascular events and mortality in patients treated with ELAR versus placebo or active comparators. The pooled rate ratio for cardiovascular events was similar in the two groups (0.99; 95% CI 0.92-1.06). The rate ratio for all-cause mortality was significantly lower in exenatide group than in comparators (0.87; 95% CI 0.77-0.97). When results of the EXSCEL trial were omitted, the pooled rate ratio for cardiovascular events and mortality was 0.80 (95% CI 0.40-1.63) and 0.75 (95% CI 0.30-1.84), respectively. CONCLUSIONS: Treatment with ELAR does not increase the risk of cardiovascular events and may reduce all-cause mortality. FAU - Bonora, B M AU - Bonora BM AD - Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy. FAU - Avogaro, A AU - Avogaro A AD - Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy. FAU - Fadini, G P AU - Fadini GP AUID- ORCID: 0000-0002-6510-2097 AD - Department of Medicine, University of Padova, Via Giustiniani 2, 35128, Padua, Italy. gianpaolo.fadini@unipd.it. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20190416 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Delayed-Action Preparations) RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Cardiovascular Diseases/epidemiology/etiology/mortality MH - Cardiovascular System/drug effects MH - Cause of Death MH - Delayed-Action Preparations/administration & dosage/*pharmacology MH - Diabetes Mellitus, Type 2/complications/*drug therapy/*epidemiology/mortality MH - Diabetic Angiopathies/drug therapy/*epidemiology/mortality MH - Exenatide/administration & dosage/*pharmacology MH - Female MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Incidence MH - Liraglutide/therapeutic use MH - Male MH - Middle Aged MH - Mortality MH - Randomized Controlled Trials as Topic/*statistics & numerical data MH - Semaglutide OTO - NOTNLM OT - Cardiovascular outcome trials OT - Pharmacology OT - Safety EDAT- 2019/04/18 06:00 MHDA- 2019/10/28 06:00 CRDT- 2019/04/18 06:00 PHST- 2019/01/22 00:00 [received] PHST- 2019/04/10 00:00 [accepted] PHST- 2019/04/18 06:00 [pubmed] PHST- 2019/10/28 06:00 [medline] PHST- 2019/04/18 06:00 [entrez] AID - 10.1007/s00592-019-01347-0 [pii] AID - 10.1007/s00592-019-01347-0 [doi] PST - ppublish SO - Acta Diabetol. 2019 Sep;56(9):1051-1060. doi: 10.1007/s00592-019-01347-0. Epub 2019 Apr 16. PMID- 30969018 OWN - NLM STAT- MEDLINE DCOM- 20200916 LR - 20250103 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 21 IP - 8 DP - 2019 Aug TI - Type 2 diabetes and the kidney: Insights from cardiovascular outcome trials. PG - 1790-1800 LID - 10.1111/dom.13743 [doi] AB - Diabetic kidney disease (DKD) still remains a progressive condition that is associated with higher risk of end-stage kidney disease and significant cardiovascular morbidity and mortality. Twelve cardiovascular outcome trials in type 2 diabetes (T2D) have been published to date. Most trials with dipeptidyl-peptidase inhibitors (SAVOR-TIMI 53 with saxagliptin, EXAMINE with alogliptin, TECOS with sitagliptin, and CARMELINA with linagliptin) and with glucagon-like peptide-1 receptor agonists (GLP-1RAs) (ELIXA with lixisenatide, LEADER with liraglutide, SUSTAIN-6 with semaglutide, EXCSEL with exenatide once-weekly, and HARMONY with albiglutide) pointed towards reduced albuminuria, which is a surrogate endpoint possibly heralding renal function preservation. The three trials with sodium-glucose co-transporter-2 inhibitors (SGLT-2is) (empagliflozin, canagliflozin and dapagliflozin) also showed a salutary effect on long-term estimated glomerular filtration rate, suggesting that SGLT-2is are more effective at mitigating loss of kidney function than incretin-based therapies; moreover, SGLT-2is also have the advantage of plausible haemodynamic mechanisms for improved renal outcomes. Despite some residual limitations linked to differences in study populations and patient characteristics, the cardiorenal protective actions of SGLT-2is, and to a lesser extent some GLP-1RAs, make them favourable medications for patients with T2D at increased cardiorenal risk. There is room for optimism that their use may change the paradigm of the ineluctable progression of DKD. CI - (c) 2019 John Wiley & Sons Ltd. FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy. FAU - De Nicola, Luca AU - De Nicola L AD - Division of Nephrology, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy. FAU - Maiorino, Maria Ida AU - Maiorino MI AUID- ORCID: 0000-0003-4659-7546 AD - Diabetes Division, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy. FAU - Bellastella, Giuseppe AU - Bellastella G AD - Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AD - Diabetes Division, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20190502 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/blood/complications/*drug therapy MH - Diabetic Angiopathies/etiology/*prevention & control MH - Diabetic Nephropathies/etiology/*prevention & control MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glomerular Filtration Rate/drug effects MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Incretins/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - albiglutide OT - alogliptin OT - canagliflozin OT - cardiovascular outcome trials OT - dapagliflozin OT - diabetic kidney disease OT - diabetic nephropathy OT - empagliflozin OT - exenatide OT - linagliptin OT - liraglutide OT - lixisenatide OT - saxagliptin OT - semaglutide OT - sitagliptin OT - type 2 diabetes EDAT- 2019/04/11 06:00 MHDA- 2020/09/17 06:00 CRDT- 2019/04/11 06:00 PHST- 2019/02/25 00:00 [received] PHST- 2019/03/25 00:00 [revised] PHST- 2019/04/07 00:00 [accepted] PHST- 2019/04/11 06:00 [pubmed] PHST- 2020/09/17 06:00 [medline] PHST- 2019/04/11 06:00 [entrez] AID - 10.1111/dom.13743 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 Aug;21(8):1790-1800. doi: 10.1111/dom.13743. Epub 2019 May 2. PMID- 30931886 OWN - NLM STAT- MEDLINE DCOM- 20200127 LR - 20260127 IS - 1603-6824 (Electronic) IS - 0041-5782 (Linking) VI - 181 IP - 12 DP - 2019 Mar 18 TI - [Glucagon-like peptide 1 receptor agonists for the treatment of Type 2 diabetes]. LID - V10180725 [pii] AB - Supraphysiological levels of the incretin hormone glucagon-like peptide 1 (GLP-1) have demonstrated a marked glucose-lowering effect in patients with Type 2 diabetes. Six GLP-1 receptor agonists are currently available for the treatment of Type 2 diabetes and have all proven to render significant reductions in both glycated haemoglobin level and body weight. However, of the clinical available compounds only liraglutide, dulaglutide and semaglutide have demonstrated reductions in the risk of cardiovascular disease. This review aims at providing an overview of the efficacy and safety of the GLP-1 receptor agonist class. FAU - Andersen, Andreas AU - Andersen A AD - tina.vilsboell.lauritsen.01@regionh.dk. FAU - Christensen, Alexander Sidelmann AU - Christensen AS FAU - Knop, Filip Krag AU - Knop FK FAU - Vilsboll, Tina AU - Vilsboll T LA - dan PT - Journal Article PT - Review PL - Denmark TA - Ugeskr Laeger JT - Ugeskrift for laeger JID - 0141730 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy MH - Glucagon-Like Peptide 1 MH - *Glucagon-Like Peptide-1 Receptor/antagonists & inhibitors MH - Glycated Hemoglobin MH - Humans MH - *Hypoglycemic Agents/therapeutic use MH - Liraglutide EDAT- 2019/04/02 06:00 MHDA- 2020/01/28 06:00 CRDT- 2019/04/02 06:00 PHST- 2019/04/02 06:00 [entrez] PHST- 2019/04/02 06:00 [pubmed] PHST- 2020/01/28 06:00 [medline] AID - V10180725 [pii] PST - ppublish SO - Ugeskr Laeger. 2019 Mar 18;181(12):V10180725. PMID- 30903796 OWN - NLM STAT- MEDLINE DCOM- 20190816 LR - 20260127 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 321 IP - 15 DP - 2019 Apr 16 TI - Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial. PG - 1466-1480 LID - 10.1001/jama.2019.2942 [doi] AB - IMPORTANCE: Phase 3 trials have not compared oral semaglutide, a glucagon-like peptide 1 receptor agonist, with other classes of glucose-lowering therapy. OBJECTIVE: To compare efficacy and assess long-term adverse event profiles of once-daily oral semaglutide vs sitagliptin, 100 mg added on to metformin with or without sulfonylurea, in patients with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, double-dummy, parallel-group, phase 3a trial conducted at 206 sites in 14 countries over 78 weeks from February 2016 to March 2018. Of 2463 patients screened, 1864 adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea were randomized. INTERVENTIONS: Patients were randomized to receive once-daily oral semaglutide, 3 mg (n = 466), 7 mg (n = 466), or 14 mg (n = 465), or sitagliptin, 100 mg (n = 467). Semaglutide was initiated at 3 mg/d and escalated every 4 weeks, first to 7 mg/d then to 14 mg/d, until the randomized dosage was achieved. MAIN OUTCOMES AND MEASURES: The primary end point was change in glycated hemoglobin (HbA1c), and the key secondary end point was change in body weight, both from baseline to week 26. Both were assessed at weeks 52 and 78 as additional secondary end points. End points were tested for noninferiority with respect to HbA1c (noninferiority margin, 0.3%) prior to testing for superiority of HbA1c and body weight. RESULTS: Among 1864 patients randomized (mean age, 58 [SD, 10] years; mean baseline HbA1c, 8.3% [SD, 0.9%]; mean body mass index, 32.5 [SD, 6.4]; n=879 [47.2%] women), 1758 (94.3%) completed the trial and 298 prematurely discontinued treatment (16.7% for semaglutide, 3 mg/d; 15.0% for semaglutide, 7 mg/d; 19.1% for semaglutide, 14 mg/d; and 13.1% for sitagliptin). Semaglutide, 7 and 14 mg/d, compared with sitagliptin, significantly reduced HbA1c (differences, -0.3% [95% CI, -0.4% to -0.1%] and -0.5% [95% CI, -0.6% to -0.4%], respectively; P < .001 for both) and body weight (differences, -1.6 kg [95% CI, -2.0 to -1.1 kg] and -2.5 kg [95% CI, -3.0 to -2.0 kg], respectively; P < .001 for both) from baseline to week 26. Noninferiority of semaglutide, 3 mg/d, with respect to HbA1c was not demonstrated. Week 78 reductions in both end points were statistically significantly greater with semaglutide, 14 mg/d, vs sitagliptin. CONCLUSIONS AND RELEVANCE: Among adults with type 2 diabetes uncontrolled with metformin with or without sulfonylurea, oral semaglutide, 7 mg/d and 14 mg/d, compared with sitagliptin, resulted in significantly greater reductions in HbA1c over 26 weeks, but there was no significant benefit with the 3-mg/d dosage. Further research is needed to assess effectiveness in a clinical setting. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02607865. FAU - Rosenstock, Julio AU - Rosenstock J AD - Dallas Diabetes Research Center at Medical City, Dallas, Texas. FAU - Allison, Dale AU - Allison D AD - Hillcrest Family Health Center, Waco, Texas. FAU - Birkenfeld, Andreas L AU - Birkenfeld AL AD - Department of Medicine III, Carl Gustav Carus University Hospital, Technische Universitat Dresden, Dresden, Germany. AD - Paul Langerhans Institute Dresden, Helmholtz Center Munich at Technische Universitat Dresden, Dresden, Germany. FAU - Blicher, Thalia Marie AU - Blicher TM AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Deenadayalan, Srikanth AU - Deenadayalan S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jacobsen, Jacob Bonde AU - Jacobsen JB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Serusclat, Pierre AU - Serusclat P AD - Endocrinology, Diabetology and Nutrition, Clinique Portes du Sud, Venissieux, France. FAU - Violante, Rafael AU - Violante R AD - Departamento Endocrinologia, Instituto Mexicano del Seguro Social, Ciudad Madero, Mexico. FAU - Watada, Hirotaka AU - Watada H AD - Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Davies, Melanie AU - Davies M AD - Diabetes Research Centre, University of Leicester, Leicester, England. CN - PIONEER 3 Investigators LA - eng SI - ClinicalTrials.gov/NCT02607865 PT - Clinical Trial, Phase III PT - Comparative Study PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Sulfonylurea Compounds) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - JAMA. 2019 Apr 16;321(15):1457-1458. doi: 10.1001/jama.2019.2941. PMID: 30903797 CIN - Ann Intern Med. 2019 Aug 20;171(4):JC16. doi: 10.7326/ACPJ201908200-016. PMID: 31426059 MH - Administration, Oral MH - Adult MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptide 1/*agonists MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Male MH - Metformin/therapeutic use MH - Middle Aged MH - Sitagliptin Phosphate/*administration & dosage/adverse effects MH - Sulfonylurea Compounds/therapeutic use MH - Semaglutide PMC - PMC6484814 COIS- Conflict of Interest Disclosures: Dr Rosenstock reported serving on scientific advisory boards and receiving honoraria or consulting fees from Eli Lilly, Novo Nordisk, Sanofi, Janssen, Boehringer Ingelheim, and Intarcia and receiving grants/research support from Merck, Pfizer, Sanofi, Novo Nordisk, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, AstraZeneca, Janssen, Genentech, Boehringer Ingelheim, Intarcia, and Lexicon. Dr Birkenfeld reported serving on advisory boards, participating in meetings, and acting as a research investigator for Novo Nordisk, Sanofi, Boehringer Ingelheim, and AstraZeneca. Drs Blicher and Deenadayalan and Mr Jacobsen reported that they are employees of Novo Nordisk. Dr Serusclat reported serving on advisory boards, participating in meetings, and acting as a research investigator for Novo Nordisk, Eli Lilly, Sanofi, Abbott, and Medtronic. Dr Violante reported acting as an advisory board member and speaker for Eli Lilly, AstraZeneca, Sanofi, Janssen, Novo Nordisk, Takeda Pharmaceuticals International Inc, and Boehringer Ingelheim and as a research investigator for Eli Lilly, AstraZeneca, Janssen, Novo Nordisk, Boehringer Ingelheim, and Merck Sharp & Dohme. Dr Watada reported acting as an advisory board member for Novo Nordisk and as a speaker for Astellas Pharma, Sanofi, Mitsubishi Tanabe Pharma, Novo Nordisk, Kowa Pharmaceutical, AstraZeneca, Takeda Pharmaceutical, Novartis, Nippon Boehringer Ingelheim, Merck Sharp & Dohme, Sumitomo Dainippon Pharma, Eli Lilly Japan, Sanwa Kagaku Kenkyusho, Ono Pharmaceutical, Kissei Pharmaceutical, and FUJIFILM Pharma and receiving grants from Astellas Pharma, Sanofi, Mitsubishi Tanabe Pharma, Novo Nordisk Pharma, AstraZeneca, Takeda Pharmaceutical, Novartis Pharma, Nippon Boehringer Ingelheim, Merck Sharp & Dohme, Sumitomo Dainippon Pharma, Eli Lilly Japan, Ono Pharmaceutical, Kyowa Hakko Kirin, Daiichi Sankyo, Terumo, Pfizer Japan, Mochida Pharmaceutical, Taisho Toyama Pharmaceutical, Johnson & Johnson, and Kowa. Dr Davies reported acting as a consultant, advisory board member, and speaker for Novo Nordisk, Sanofi-Aventis, and Lilly, as an advisory board member for Servier and Janssen, and as a speaker for Boehringer Ingelheim and Takeda Pharmaceuticals International Inc and receiving grants in support of investigator and investigator-initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, and Janssen. No other disclosures were reported. EDAT- 2019/03/25 06:00 MHDA- 2019/08/17 06:00 PMCR- 2019/09/23 CRDT- 2019/03/24 06:00 PHST- 2019/03/25 06:00 [pubmed] PHST- 2019/08/17 06:00 [medline] PHST- 2019/03/24 06:00 [entrez] PHST- 2019/09/23 00:00 [pmc-release] AID - 2729339 [pii] AID - joi190026 [pii] AID - 10.1001/jama.2019.2942 [doi] PST - ppublish SO - JAMA. 2019 Apr 16;321(15):1466-1480. doi: 10.1001/jama.2019.2942. PMID- 30887418 OWN - NLM STAT- MEDLINE DCOM- 20190617 LR - 20260127 IS - 1179-1918 (Electronic) IS - 1173-2563 (Linking) VI - 39 IP - 5 DP - 2019 May TI - Time-Matched Evaluation of Cardiovascular Risks Associated with Drugs for Type 2 Diabetes Mellitus. PG - 469-476 LID - 10.1007/s40261-019-00770-z [doi] AB - BACKGROUND AND OBJECTIVE: The results of large placebo-controlled clinical trials to evaluate cardiovascular risks associated with drugs for type 2 diabetes mellitus indicated different cardiovascular effects among these drugs, but the detailed design of each trial was not completely the same. The aim of this study was to perform time-matched evaluation of cardiovascular risks of drugs for type 2 diabetes. METHODS: We used the difference in restricted mean survival time (RMST) as a measure of cardiovascular risks. Regarding drugs for type 2 diabetes used currently, this study included all 10 clinical trials in patients with type 2 diabetes at high cardiovascular risk the results of which have been published as of 30 November 2018. Since the shortest study follow-up time was about 672 days in SUSTAIN-6, we chose 672 days as a common time point to estimate the RMSTs regarding each safety event. RESULTS: The differences of RMSTs (drugs for type 2 diabetes minus placebo: point estimate and 95% confidence interval) for major adverse cardiovascular events (MACE) were 8 days (1, 15) for semaglutide, 5 days (1, 9) for liraglutide, and 7 days (2, 13) for empagliflozin. Those for death from cardiovascular causes were 5 days (2, 8) for empagliflozin and 2 days (1, 4) for canagliflozin. Those for death from any cause were 4 days (1, 8) for empagliflozin. CONCLUSIONS: Through the evaluation up to 672 days, semaglutide, liraglutide, and empagliflozin decreased the risk of MACE. Concerning the risk of each cardiovascular event, risk reduction was seen with empagliflozin and canagliflozin. FAU - Kaneko, Masayuki AU - Kaneko M AD - Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. kanekom@pharm.kitasato-u.ac.jp. FAU - Narukawa, Mamoru AU - Narukawa M AD - Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. LA - eng PT - Journal Article PT - Review PL - New Zealand TA - Clin Drug Investig JT - Clinical drug investigation JID - 9504817 RN - 0 (Benzhydryl Compounds) RN - 0SAC974Z85 (Canagliflozin) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Benzhydryl Compounds/adverse effects/therapeutic use MH - Canagliflozin/adverse effects/therapeutic use MH - Cardiovascular Diseases/*chemically induced/diagnosis/*epidemiology MH - Clinical Trials as Topic/methods MH - Diabetes Mellitus, Type 2/*drug therapy/*epidemiology MH - Follow-Up Studies MH - Glucagon-Like Peptides/adverse effects/therapeutic use MH - Glucosides/adverse effects/therapeutic use MH - Humans MH - Hypoglycemic Agents/*adverse effects/therapeutic use MH - Liraglutide/adverse effects/therapeutic use MH - Risk Factors MH - Survival Rate/trends MH - Semaglutide EDAT- 2019/03/20 06:00 MHDA- 2019/06/18 06:00 CRDT- 2019/03/20 06:00 PHST- 2019/03/20 06:00 [pubmed] PHST- 2019/06/18 06:00 [medline] PHST- 2019/03/20 06:00 [entrez] AID - 10.1007/s40261-019-00770-z [pii] AID - 10.1007/s40261-019-00770-z [doi] PST - ppublish SO - Clin Drug Investig. 2019 May;39(5):469-476. doi: 10.1007/s40261-019-00770-z. PMID- 30875029 OWN - NLM STAT- MEDLINE DCOM- 20200506 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 36 IP - 5 DP - 2019 May TI - A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing Patients to HbA1c and Weight Loss Treatment Targets in the USA. PG - 1190-1199 LID - 10.1007/s12325-019-00915-8 [doi] AB - INTRODUCTION: The SUSTAIN 3 and 7 clinical trials compared the efficacy and safety of once-weekly semaglutide relative to exenatide extended-release (ER) and dulaglutide, respectively, in the treatment of patients with type 2 diabetes (T2D). The trials included a series of clinically relevant single and composite endpoints focused on improving glycemic control and reducing body weight, while avoiding hypoglycemia. The present study combined SUSTAIN 3 and 7 outcomes with short-term treatment costs to evaluate the relative cost of control of once-weekly semaglutide versus exenatide ER and dulaglutide. METHODS: Proportions of patients reaching three endpoints were taken from SUSTAIN 3 and 7 for comparisons with exenatide ER and dulaglutide, respectively. The endpoints investigated were HbA1c < 7.0%, HbA1c < 7.0% without hypoglycemia or weight gain, and a >/= 1.0% HbA1c reduction with >/= 5.0% weight loss. Annual per patient treatment costs were based on US wholesale acquisition costs from July 2018. Relative cost of control was calculated by plotting the ratio of the treatment costs and the ratio of the proportions of patients reaching each endpoint on the cost-efficacy plane. RESULTS: Once-weekly semaglutide 0.5 mg and 1.0 mg were most effective at bringing patients to each of the three endpoints across both SUSTAIN trials. The efficacy-to-cost ratios for once-weekly semaglutide 0.5 mg and 1.0 mg were also superior to all comparators when assessing both the single endpoint of HbA1c < 7.0% and the two composite endpoints including weight loss and hypoglycemia. CONCLUSIONS: The present study showed that once-weekly semaglutide 0.5 mg and 1.0 mg offer superior cost of control versus exenatide ER and dulaglutide in terms of achieving single and composite endpoints, based on an analysis of retrieved dropout data. Once-weekly semaglutide 0.5 mg and 1.0 mg would therefore represent good value for money in the USA, particularly in the attainment of multi-model T2D treatment goals. FUNDING: Novo Nordisk A/S. FAU - Johansen, Pierre AU - Johansen P AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hunt, Barnaby AU - Hunt B AUID- ORCID: 0000-0001-5420-279X AD - Ossian Health Economics and Communications GmbH, Basel, Switzerland. hunt@ossianconsulting.com. FAU - Iyer, Neeraj N AU - Iyer NN AD - Novo Nordisk Inc, Plainsboro, USA. FAU - Dang-Tan, Tam AU - Dang-Tan T AD - Novo Nordisk Inc, Plainsboro, USA. FAU - Pollock, Richard F AU - Pollock RF AD - Ossian Health Economics and Communications GmbH, Basel, Switzerland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190314 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) EIN - Adv Ther. 2019 May;36(5):1200. doi: 10.1007/s12325-019-00945-2. PMID: 30980280 MH - Body Weight MH - Diabetes Mellitus, Type 2/*drug therapy/economics/metabolism MH - Drug Administration Schedule MH - Exenatide/economics/*therapeutic use MH - Female MH - Glucagon-Like Peptides/*analogs & derivatives/economics/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/therapeutic use MH - Immunoglobulin Fc Fragments/economics/*therapeutic use MH - Male MH - Middle Aged MH - Recombinant Fusion Proteins/economics/*therapeutic use MH - Weight Loss MH - Semaglutide PMC - PMC6824375 OTO - NOTNLM OT - Costs and cost analysis OT - Diabetes mellitus OT - Glucagon-like peptides OT - Type 2 OT - United States EDAT- 2019/03/16 06:00 MHDA- 2020/05/07 06:00 PMCR- 2019/03/14 CRDT- 2019/03/16 06:00 PHST- 2018/11/27 00:00 [received] PHST- 2019/03/16 06:00 [pubmed] PHST- 2020/05/07 06:00 [medline] PHST- 2019/03/16 06:00 [entrez] PHST- 2019/03/14 00:00 [pmc-release] AID - 10.1007/s12325-019-00915-8 [pii] AID - 915 [pii] AID - 10.1007/s12325-019-00915-8 [doi] PST - ppublish SO - Adv Ther. 2019 May;36(5):1190-1199. doi: 10.1007/s12325-019-00915-8. Epub 2019 Mar 14. PMID- 30865526 OWN - NLM STAT- MEDLINE DCOM- 20190709 LR - 20260127 IS - 1530-891X (Print) IS - 1530-891X (Linking) VI - 25 IP - 6 DP - 2019 Jun TI - GREATER COMBINED REDUCTIONS IN HbA(1C) >/=1.0% AND WEIGHT >/=5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. PG - 589-597 LID - 10.4158/EP-2018-0444 [doi] AB - Objective: Semaglutide is a glucagon-like peptide 1 (GLP-1) analog for the once-weekly treatment of type 2 diabetes (T2D). In the global SUSTAIN clinical trial program, semaglutide demonstrated superior glycated hemoglobin (HbA(1c)) and body weight reductions versus comparators. This post hoc analysis compared the proportion of patients achieving combined reductions in glycemia and body weight versus comparators. Methods: A total of 5,119 subjects with T2D in the phase 3 SUSTAIN 1 through 5 and 7 trials, from 33 countries, were included in this post hoc analysis. Subjects received subcutaneous semaglutide 0.5 or 1.0 mg, placebo or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg, insulin glargine, dulaglutide 0.75 or 1.5 mg). The main endpoint was a composite of >/=1.0% HbA(1c) reduction and >/=5.0% weight loss at end of treatment. Results: Significantly greater proportions of subjects achieved the composite endpoint with semaglutide 0.5 (25 to 38%) and 1.0 mg (38 to 59%) versus comparators (2 to 23%). More subjects treated with semaglutide versus comparators achieved >/=1.0% HbA(1c) reductions (58 to 77% and 75 to 83% for semaglutide 0.5 and 1.0 mg versus 12 to 68%) and >/=5.0% weight loss (37 to 46%, 45 to 66% versus 4 to 30%). Proportions of subjects achieving targets were significantly higher with semaglutide 1.0 versus 0.5 mg in four of five trials. Semaglutide was well tolerated, with a safety profile similar to other GLP-1 receptor agonists. Conclusion: Significantly more subjects achieved both >/=1.0% HbA(1c) reduction and >/=5.0% weight loss with once-weekly subcutaneous semaglutide treatment versus comparators in the SUSTAIN trials. A dose-dependent effect was observed with semaglutide. Abbreviations: AE = adverse event; CV = cardiovascular; ER = extended release; GLP-1 = glucagon-like peptide 1; GLP-1 RA = glucagon-like peptide 1 receptor agonist; HbA(1c) = glycated hemoglobin; OAD = oral antidiabetic drug; sc = subcutaneous; T2D = type 2 diabetes. FAU - Rodbard, Helena W AU - Rodbard HW FAU - Bellary, Srikanth AU - Bellary S FAU - Hramiak, Irene AU - Hramiak I FAU - Seino, Yutaka AU - Seino Y FAU - Silver, Robert AU - Silver R FAU - Damgaard, Lars Holm AU - Damgaard LH FAU - Nayak, Gurudutt AU - Nayak G FAU - Zacho, Jeppe AU - Zacho J FAU - Aroda, Vanita R AU - Aroda VR LA - eng PT - Journal Article DEP - 20190313 PL - United States TA - Endocr Pract JT - Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists JID - 9607439 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Body Weight MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides MH - Glycated Hemoglobin MH - Humans MH - Hypoglycemic Agents MH - Semaglutide EDAT- 2019/03/14 06:00 MHDA- 2019/07/10 06:00 CRDT- 2019/03/14 06:00 PHST- 2019/03/14 06:00 [pubmed] PHST- 2019/07/10 06:00 [medline] PHST- 2019/03/14 06:00 [entrez] AID - S1530-891X(20)35970-X [pii] AID - 10.4158/EP-2018-0444 [doi] PST - ppublish SO - Endocr Pract. 2019 Jun;25(6):589-597. doi: 10.4158/EP-2018-0444. Epub 2019 Mar 13. PMID- 30863012 OWN - NLM STAT- MEDLINE DCOM- 20190731 LR - 20260127 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 13 DP - 2019 TI - Profile of semaglutide in the management of type 2 diabetes: design, development, and place in therapy. PG - 731-738 LID - 10.2147/DDDT.S165372 [doi] AB - Type 2 diabetes mellitus (T2DM) has become one of the leading causes of morbidity and mortality in developed countries. Low efficacy, weight gain, and hypoglycemia are the main pitfalls of previous treatments for T2DM. New therapies have been designed with the aim of improving the results in efficacy and quality of life. Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RA) increase glucose-dependent insulin secretion, decrease gastric emptying, and reduce postprandial glucagon secretion. The last GLP-1 RA approved by the US Food and Drug Administration and European Medicines Agency was semaglutide. This review describes its pharmacology, core clinical data coming from the randomized controlled trials included in the development program, proven cardiovascular benefits, safety issues, and precautions for the use of semaglutide in special populations. Additionally, an overview of the positioning of semaglutide in T2DM therapy and practical issues regarding semaglutide initiation are offered. FAU - Gomez-Peralta, Fernando AU - Gomez-Peralta F AD - Endocrinology and Nutrition Unit, Hospital General de Segovia, Segovia, Spain, fgomezperalta@gmail.com. FAU - Abreu, Cristina AU - Abreu C AD - Endocrinology and Nutrition Unit, Hospital General de Segovia, Segovia, Spain, fgomezperalta@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20190220 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/chemical synthesis/chemistry/*pharmacology MH - Humans MH - Hypoglycemic Agents/chemistry/*pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC6388990 OTO - NOTNLM OT - clinical practice OT - pharmacological treatment OT - safety OT - semaglutide OT - type 2 diabetes COIS- Disclosure Fernando Gomez-Peralta has received research support from Sanofi, Novo Nordisk, Boehringer Ingelheim, and Eli Lilly, has taken part in advisory boards for Sanofi, Novo Nordisk, and AstraZeneca Pharmaceuticals LP, and has acted as a speaker for Sanofi, Novo Nordisk, Boehringer Ingelheim, Novartis, Bristol-Myers Squibb Company, Eli Lilly, and AstraZeneca Pharmaceuticals LP. Cristina Abreu has received research support from Sanofi, Novo Nordisk, Boehringer Ingelheim Pharmaceuticals, and Lilly, and has acted as a speaker for Sanofi, Novo Nordisk, Boehringer Ingelheim Pharmaceuticals, AstraZeneca Pharmaceuticals LP, and Bristol-Myers Squibb Co. The authors report no other conflicts of interest in this work. EDAT- 2019/03/14 06:00 MHDA- 2019/08/01 06:00 PMCR- 2019/02/20 CRDT- 2019/03/14 06:00 PHST- 2019/03/14 06:00 [entrez] PHST- 2019/03/14 06:00 [pubmed] PHST- 2019/08/01 06:00 [medline] PHST- 2019/02/20 00:00 [pmc-release] AID - dddt-13-731 [pii] AID - 10.2147/DDDT.S165372 [doi] PST - epublish SO - Drug Des Devel Ther. 2019 Feb 20;13:731-738. doi: 10.2147/DDDT.S165372. eCollection 2019. PMID- 30851070 OWN - NLM STAT- MEDLINE DCOM- 20200710 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 21 IP - 7 DP - 2019 Jul TI - Duration of diabetes and cardiorenal efficacy of liraglutide and semaglutide: A post hoc analysis of the LEADER and SUSTAIN 6 clinical trials. PG - 1745-1751 LID - 10.1111/dom.13698 [doi] AB - Cardiovascular risk reduction with liraglutide and semaglutide in patients with type 2 diabetes was demonstrated in the LEADER (ClinicalTrials.gov: NCT01179048) and SUSTAIN 6 (ClinicalTrials.gov: NCT01720446) cardiovascular outcome trials. This post hoc analysis assessed the impact of diabetes duration (<5, 5 to <15, 15 to <25 and >/=25 years at baseline) on cardiorenal efficacy of these human glucagon-like peptide-1 analogues using a Cox proportional hazards model. Proportions of patients in the LEADER trial across diabetes duration strata were 15% (<5 years, n = 1377), 50% (5 to <15 years, n = 4692), 27% (15 to <25 years, n = 2504) and 8% (>/=25 years, n = 748); corresponding proportions in the SUSTAIN-6 trial were 13% (<5 years, n = 422), 48% (5 to <15 years, n = 1582), 30% (15 to <25 years, n = 977) and 10% (>/=25 years, n = 316). Overall, longer diabetes duration was associated with higher age; higher prevalence of females; history of ischaemic stroke, peripheral arterial disease and insulin use; and inferior renal function. There was an increased frequency of major adverse cardiovascular events (MACE), expanded MACE and nephropathy events with increasing diabetes duration. Liraglutide and semaglutide consistently reduced the risk of cardiorenal outcomes across categories of diabetes duration (P-interaction was not significant for all endpoints analysed). CI - (c) 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Verma, Subodh AU - Verma S AUID- ORCID: 0000-0002-4018-8533 AD - Department of Anesthesia, Division of Cardiac Surgery, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Institute of Life Science, Swansea University Medical School, Swansea, UK. FAU - Monk Fries, Tea AU - Monk Fries T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Mazer, C David AU - Mazer CD AD - Department of Anesthesia, Division of Cardiac Surgery, St. Michael's Hospital and University of Toronto, Toronto, Ontario, Canada. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes Center Bochum-Hattingen, St Josef Hospital (Ruhr-Universitat Bochum), Bochum, Germany. FAU - Pratley, Richard E AU - Pratley RE AUID- ORCID: 0000-0002-2912-1389 AD - Florida Hospital Translational Research Institute for Metabolism and Diabetes, Orlando, Florida. FAU - Rasmussen, Soren AU - Rasmussen S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Saevereid, Hans A AU - Saevereid HA AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Zinman, Bernard AU - Zinman B AUID- ORCID: 0000-0002-0041-1876 AD - Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Buse, John B AU - Buse JB AD - Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina. LA - eng SI - ClinicalTrials.gov/NCT01179048 SI - ClinicalTrials.gov/NCT01720446 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190402 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Aged MH - Cardiovascular Diseases/complications/epidemiology MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Female MH - *Glucagon-Like Peptides/adverse effects/therapeutic use MH - Humans MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Kidney Diseases/complications/epidemiology MH - *Liraglutide/adverse effects/therapeutic use MH - Male MH - Middle Aged MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - Semaglutide PMC - PMC6619033 OTO - NOTNLM OT - LEADER OT - SUSTAIN 6 OT - cardiorenal OT - cardiovascular OT - diabetes duration OT - efficacy OT - liraglutide OT - renal OT - semaglutide COIS- S. V. has received research grants and/or speaking honoraria from Boehringer Ingelheim/Eli Lilly, AstraZeneca, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, Valeant and Amgen. S. C. B. has received research grants as principal investigator, collaborator or consultant; has pending grants from Healthcare and Research Wales (Welsh Government) and Novo Nordisk; has received other research support from Healthcare and Research Wales (Welsh Government) and honoraria from Novo Nordisk, Sanofi, Lilly, Boehringer Ingelheim and Merck, and has an ownership interest in Gycosmedia (diabetes on-line news service). H. A. S., T. M. F. and S. R. are full-time employees of Novo Nordisk A/S. T. M. F. and S. R. hold stock in Novo Nordisk A/S. C. D. M. has received consulting fees from Amgen, Boehringer Ingelheim and OctaPharma. M. A. N. has served on advisory boards; has consulted for AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Fractyl, GlaxoSmithKline, Servier, Menarini/Berlin Chemie, Merck, Sharp & Dohme and Novo Nordisk; has served on speakers bureaus of AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Menarini/Berlin Chemie, Merck, Sharp & Dohme, Novo Nordisk A/S and Sun Pharma; and his institution has received grant support from AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Intarcia, Menarini/Berlin-Chemie, Merck, Sharp & Dohme, Novartis Pharma and Novo Nordisk A/S. R. E. P. has received research grants from Gilead Sciences, Lexicon Pharmaceuticals, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Sanofi-Aventis US LLC and Takeda; has acted as a speaker for AstraZeneca, Novo Nordisk and Takeda; and has acted as a consultant for AstraZeneca, Boehringer Ingelheim, Eisai, Inc., GlaxoSmithKline, Janssen Scientific Affairs LLC, Ligand Pharmaceuticals Inc., Lilly, Merck, Novo Nordisk, Pfizer and Takeda (all payments are made directly to his employer, Florida Hospital). B. Z. has received consulting fees from Merck, Novo Nordisk, Sanofi-Aventis, Eli Lilly, AstraZeneca, Jansse, and Boehringer Ingelheim. J. B. B. has been an advisor, with all fees paid to the University of North Carolina, to Adocia, AstraZeneca, Dance Biopharm, Eli Lilly, MannKind, NovaTarg, Novo Nordisk, Senseonics and vTv Therapeutics; has received grant support from Novo Nordisk, Sanofi and vTv Therapeutics; is a consultant to Neurimmune AG; is supported by a grant from the National Institutes of Health (UL1TR002489); and holds stock options in Mellitus Health, PhaseBio and Stability Health. AUTHOR CONTRIBUTIONS: Statistical analyses were performed by Soren Rasmussen, and Subodh Verma prepared the first draft. All authors were responsible for the content and editorial decisions, were involved at all stages of manuscript development and approved the final version. Patient level analysis data sets for the research presented in the publication are available from the corresponding author upon request. EDAT- 2019/03/10 06:00 MHDA- 2020/07/11 06:00 PMCR- 2019/07/10 CRDT- 2019/03/10 06:00 PHST- 2019/01/25 00:00 [received] PHST- 2019/03/04 00:00 [revised] PHST- 2019/03/06 00:00 [accepted] PHST- 2019/03/10 06:00 [pubmed] PHST- 2020/07/11 06:00 [medline] PHST- 2019/03/10 06:00 [entrez] PHST- 2019/07/10 00:00 [pmc-release] AID - DOM13698 [pii] AID - 10.1111/dom.13698 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 Jul;21(7):1745-1751. doi: 10.1111/dom.13698. Epub 2019 Apr 2. PMID- 30845101 OWN - NLM STAT- MEDLINE DCOM- 20190320 LR - 20250103 IS - 1523-2859 (Electronic) IS - 0025-732X (Linking) VI - 61 IP - 1566 DP - 2019 Feb 25 TI - Cardiovascular benefits of SGLT2 inhibitors and GLP-1 receptor agonists in Type 2 diabetes. PG - 26-28 LA - eng PT - Journal Article PL - United States TA - Med Lett Drugs Ther JT - The Medical letter on drugs and therapeutics JID - 2985240R RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CRI - JAMA. 2019 May 7;321(17):1720-1721. doi: 10.1001/jama.2019.2702. PMID: 31063571 MH - Cardiovascular Diseases/complications/*drug therapy MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Humans MH - Hypoglycemic Agents/adverse effects/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/*therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Adlyxin OT - Adlyxine OT - Bydureon OT - Farxiga OT - Forxiga OT - Glucophage OT - Invokana OT - Jardiance OT - Ozempic OT - Trulicity OT - Victoza OT - adverse effects OT - canagliflozin OT - dapagliflozin OT - dosage OT - dulaglutide OT - efficacy OT - empagliflozin OT - exenatide OT - liraglutide OT - lixisenatide OT - metformin OT - safety OT - semaglutide OT - type 2 diabetes EDAT- 2019/03/08 06:00 MHDA- 2019/03/21 06:00 CRDT- 2019/03/08 06:00 PHST- 2019/03/08 06:00 [entrez] PHST- 2019/03/08 06:00 [pubmed] PHST- 2019/03/21 06:00 [medline] PST - ppublish SO - Med Lett Drugs Ther. 2019 Feb 25;61(1566):26-28. PMID- 30833170 OWN - NLM STAT- MEDLINE DCOM- 20200525 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 7 IP - 5 DP - 2019 May TI - Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial. PG - 356-367 LID - S2213-8587(19)30066-X [pii] LID - 10.1016/S2213-8587(19)30066-X [doi] AB - BACKGROUND: Semaglutide is a once-weekly glucagon-like peptide-1 (GLP-1) analogue for type 2 diabetes. Few clinical trials have reported on the concomitant use of GLP-1 receptor agonists with sodium-glucose cotransporter-2 (SGLT-2) inhibitors. We aimed to investigate the efficacy and safety of semaglutide when added to SGLT-2 inhibitor therapy in patients with inadequately controlled type 2 diabetes. METHODS: The SUSTAIN 9 double-blind, parallel-group trial was done at 61 centres in six countries (Austria, Canada, Japan, Norway, Russia, and the USA). Adults with type 2 diabetes and HbA(1c) 7.0-10.0% (53-86 mmol/mol), despite at least 90 days of treatment with an SGLT-2 inhibitor, were randomly assigned (1:1) to receive subcutaneous semaglutide 1.0 mg or volume-matched placebo once weekly for 30 weeks, after a dose-escalation schedule of 4 weeks of 0.25 mg semaglutide or placebo and 4 weeks of 0.5 mg semaglutide or placebo. Existing antidiabetic medications, including SGLT-2 inhibitor treatment, were continued for the duration of the trial. Rescue medication, defined as intensification of background antidiabetic treatment or the initiation of new glucose-lowering medications, could be given to patients meeting specific criteria at the discretion of the investigator. The primary outcome was change in HbA(1c) from baseline at week 30, assessed in the full analysis set (all patients randomly allocated to treatment) using on-treatment data collected before rescue medication was started. The confirmatory secondary outcome was change in bodyweight from baseline to week 30. Safety was also assessed in the safety analysis set (all patients who received at least one dose of treatment). The trial was registered with ClinicalTrials.gov (NCT03086330). FINDINGS: Between March 15, and Dec 4, 2017, 302 patients were enrolled and randomly assigned to receive semaglutide 1.0 mg or placebo (full analysis set), of whom 301 received at least one dose of treatment (safety analysis set). One patient was assigned to semaglutide but was not treated (reason unknown). 294 (97.4%) patients completed the trial and 267 (88.4%) completed treatment. Baseline characteristics were generally comparable between groups. In addition to randomised medication and SGLT-2 inhibitor, 216 (71.5%) patients were taking metformin and 39 (12.9%) were taking sulphonylurea. Patients given semaglutide had greater reductions in HbA(1c) (estimated treatment difference -1.42% [95% CI -1.61 to -1.24]; -15.55 mmol/mol [-17.54 to -13.56]) and bodyweight (-3.81 kg [-4.70 to -2.93]) versus those randomised to placebo (both p<0.0001). 356 adverse events were reported by 104 (69.3%) patients in the semaglutide group, and 247 adverse events were reported by 91 (60.3%) patients in the placebo group. Gastrointestinal adverse events were most common and were reported in 56 (37.3%) patients in the semaglutide group and 20 (13.2%) in the placebo group. Serious adverse events occurred in seven (4.7%) patients in the semaglutide group and six (4.0%) in the placebo group. Severe or blood glucose-confirmed hypoglycaemic events were reported in four patients on semaglutide (2.7%). 16 patients stopped treatment early because of an adverse event, 13 of whom were in the semaglutide group. There were no deaths during the trial. INTERPRETATION: Adding semaglutide to SGLT-2 inhibitor therapy significantly improves glycaemic control and reduces bodyweight in patients with inadequately controlled type 2 diabetes, and is generally well tolerated. FUNDING: Novo Nordisk. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Zinman, Bernard AU - Zinman B AD - Mount Sinai Hospital, Toronto, ON, Canada. Electronic address: zinman@lunenfeld.ca. FAU - Bhosekar, Vaishali AU - Bhosekar V AD - Novo Nordisk, Bengaluru, India. FAU - Busch, Robert AU - Busch R AD - Albany Medical Center Division of Community Endocrinology, Albany, NY, USA. FAU - Holst, Ingrid AU - Holst I AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Ludvik, Bernhard AU - Ludvik B AD - 1st Medical Department and Karl Landsteiner Institute for Obesity and Metabolic Disorders, Rudolfstiftung Hospital, Vienna, Austria. FAU - Thielke, Desiree AU - Thielke D AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Thrasher, James AU - Thrasher J AD - Medical Investigations, Inc, Little Rock, AR, USA. FAU - Woo, Vincent AU - Woo V AD - University of Manitoba, Winnipeg, MB, Canada. FAU - Philis-Tsimikas, Athena AU - Philis-Tsimikas A AD - Scripps Whittier Diabetes Institute, San Diego, CA, USA. LA - eng SI - ClinicalTrials.gov/NCT03086330 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190301 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Placebos) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet Diabetes Endocrinol. 2019 May;7(5):328-329. doi: 10.1016/S2213-8587(19)30069-5. PMID: 30833171 EIN - Lancet Diabetes Endocrinol. 2019 May;7(5):e5. doi: 10.1016/S2213-8587(19)30109-3. PMID: 30872122 EIN - Lancet Diabetes Endocrinol. 2019 Aug;7(8):e20. doi: 10.1016/S2213-8587(19)30220-7. PMID: 31272930 EIN - Lancet Diabetes Endocrinol. 2019 Nov;7(11):e22. doi: 10.1016/S2213-8587(19)30323-7. PMID: 31621596 MH - Adult MH - Aged MH - Diabetes Mellitus, Type 2/blood/*drug therapy/epidemiology MH - Double-Blind Method MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Male MH - Middle Aged MH - Placebos MH - Sodium-Glucose Transporter 2 Inhibitors/*administration & dosage/adverse effects MH - Treatment Outcome MH - Semaglutide EDAT- 2019/03/06 06:00 MHDA- 2020/05/26 06:00 CRDT- 2019/03/06 06:00 PHST- 2019/01/10 00:00 [received] PHST- 2019/02/07 00:00 [revised] PHST- 2019/02/12 00:00 [accepted] PHST- 2019/03/06 06:00 [pubmed] PHST- 2020/05/26 06:00 [medline] PHST- 2019/03/06 06:00 [entrez] AID - S2213-8587(19)30066-X [pii] AID - 10.1016/S2213-8587(19)30066-X [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2019 May;7(5):356-367. doi: 10.1016/S2213-8587(19)30066-X. Epub 2019 Mar 1. PMID- 30793262 OWN - NLM STAT- MEDLINE DCOM- 20200226 LR - 20200226 IS - 1179-187X (Electronic) IS - 1175-3277 (Linking) VI - 19 IP - 5 DP - 2019 Oct TI - Evidence-Based Cardiovascular Risk Management in Diabetes. PG - 439-448 LID - 10.1007/s40256-019-00336-6 [doi] AB - Multipronged risk management in diabetes has contributed to the recent decline in cardiovascular mortality. Few antihyperglycemic drugs have been conclusively shown to have cardioprotective effects. These include metformin, liraglutide, semaglutide, dulaglutide, and sodium-glucose cotransporter-2 inhibitors. Statins are the cornerstone of treatment for people with established coronary artery disease (CAD) or at risk of CAD. In patients with persistent low-density lipoprotein cholesterol (LDL-C) levels > 70 mg/dL, the addition of ezetimibe or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors is recommended. In general, angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers should be included in the treatment regimen. The goal is to have blood pressure < 140/90 mmHg, whereas a lower goal of < 130/80 mmHg is recommended in patients with CAD or proteinuria (> 1 g/day). Aspirin antiplatelet therapy should be restricted for people with established CAD or those with multiple CAD risk factors. While antiobesity medications have a modest role in managing obesity, bariatric surgery in people with body mass index (BMI) >/= 40 or >/= 35 with comorbidities can substantially affect quality of life and may reduce cardiovascular risks. Prescribing therapeutic agents should take into consideration a variety of factors, including the patient's preferences and the drug's affordability, side effect profile, and proven cardiovascular benefit. FAU - Mooradian, Arshag D AU - Mooradian AD AD - Department of Medicine, University of Florida College of Medicine, 653-1 West 8th Street, 4th Floor-LRC, Jacksonville, FL, 32209, USA. arshag.mooradian@jax.ufl.edu. LA - eng PT - Journal Article PT - Review PL - New Zealand TA - Am J Cardiovasc Drugs JT - American journal of cardiovascular drugs : drugs, devices, and other interventions JID - 100967755 RN - 0 (Hypoglycemic Agents) SB - IM MH - Cardiovascular Diseases/*etiology MH - Diabetes Mellitus, Type 2/*drug therapy MH - Evidence-Based Medicine/methods MH - Humans MH - Hypoglycemic Agents/*adverse effects/*therapeutic use MH - Risk Factors MH - Risk Management EDAT- 2019/02/23 06:00 MHDA- 2020/02/27 06:00 CRDT- 2019/02/23 06:00 PHST- 2019/02/23 06:00 [pubmed] PHST- 2020/02/27 06:00 [medline] PHST- 2019/02/23 06:00 [entrez] AID - 10.1007/s40256-019-00336-6 [pii] AID - 10.1007/s40256-019-00336-6 [doi] PST - ppublish SO - Am J Cardiovasc Drugs. 2019 Oct;19(5):439-448. doi: 10.1007/s40256-019-00336-6. PMID- 30730773 OWN - NLM STAT- MEDLINE DCOM- 20190403 LR - 20260127 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 20 IP - 5 DP - 2019 Apr TI - The efficacy and safety of exenatide once weekly in patients with type 2 diabetes. PG - 501-510 LID - 10.1080/14656566.2019.1571040 [doi] AB - Exenatide once weekly (QW) is a glucagon-like peptide 1 receptor agonist (GLP-1RA) that was approved in 2012 in Europe and the U.S.A. for the treatment of type 2 diabetes (T2D). Areas covered: This review provides an overview of the safety and efficacy of exenatide QW for the treatment of T2D and evaluates the benefit-risk ratio compared to other available long-acting GLP-1RAs. In addition, the authors provide an outline of the novel formulations and delivery methods of exenatide. Expert opinion: Exenatide QW is an efficacious and safe treatment for T2D. However, head-to-head trials have demonstrated exenatide QW to be inferior to liraglutide and semaglutide with respect to effects on fasting plasma glucose, glycated hemoglobin A1c, and bodyweight. In addition, exenatide QW appears inferior to liraglutide and semaglutide in terms of cardiovascular risk reduction. Currently, the overall risk-benefit profiles for the range of GLP-1RAs point to liraglutide and semaglutide as first-choice for the management of T2D, which has been confirmed by a recently published consensus report on the treatment of T2D from the American Diabetes Association and the European Association for the Study of Diabetes. The pricing of exenatide QW will most likely be a key determinant for its place in the future management of T2D. FAU - Heimburger, Sebastian M AU - Heimburger SM AD - a Clinical Metabolic Physiology , Steno Diabetes Center Copenhagen , Gentofte , Denmark. FAU - Bronden, Andreas AU - Bronden A AD - a Clinical Metabolic Physiology , Steno Diabetes Center Copenhagen , Gentofte , Denmark. AD - b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark. FAU - Johansen, Nicklas J AU - Johansen NJ AD - a Clinical Metabolic Physiology , Steno Diabetes Center Copenhagen , Gentofte , Denmark. FAU - Dejgaard, Thomas F AU - Dejgaard TF AD - a Clinical Metabolic Physiology , Steno Diabetes Center Copenhagen , Gentofte , Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AD - a Clinical Metabolic Physiology , Steno Diabetes Center Copenhagen , Gentofte , Denmark. AD - b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark. FAU - Knop, Filip K AU - Knop FK AD - a Clinical Metabolic Physiology , Steno Diabetes Center Copenhagen , Gentofte , Denmark. AD - b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark. AD - c Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20190207 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - Body Weight MH - Diabetes Mellitus, Type 2/*drug therapy MH - Exenatide/*therapeutic use MH - Glucagon-Like Peptides/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Liraglutide/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Exenatide extended-release OT - cardiovascular adverse events OT - exenatide QW OT - glucagon-like peptide 1 OT - glucagon-like peptide 1 receptor agonist OT - glycaemic control OT - type 2 diabetes EDAT- 2019/02/08 06:00 MHDA- 2019/04/04 06:00 CRDT- 2019/02/08 06:00 PHST- 2019/02/08 06:00 [pubmed] PHST- 2019/04/04 06:00 [medline] PHST- 2019/02/08 06:00 [entrez] AID - 10.1080/14656566.2019.1571040 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2019 Apr;20(5):501-510. doi: 10.1080/14656566.2019.1571040. Epub 2019 Feb 7. PMID- 30718142 OWN - NLM STAT- MEDLINE DCOM- 20191211 LR - 20191217 IS - 1590-3729 (Electronic) IS - 0939-4753 (Linking) VI - 29 IP - 3 DP - 2019 Mar TI - Dypeptidylpeptidase-4 inhibitors and the cardiovascular system: How to manage the fil rouge. PG - 215-219 LID - S0939-4753(18)30365-X [pii] LID - 10.1016/j.numecd.2018.12.009 [doi] AB - Dypeptidylpeptidase-4 (DPP-4) inhibitors are a therapeutic option for improving glucose control in patients with type 2 diabetes. They can be prescribed at different stages of the natural history of the disease because of their low risk for hypoglycemia and associated weight gain. For all new drugs for diabetes, the US Food and Drug Administration requires the demonstration of the cardiovascular (CV) safety profile through pooled analyses of phase 3 studies or specifically designed trials. A significant superiority over placebo has been observed with a sodium-dependent glucose transporter-2 inhibitor, empagliflozin, and two glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, thus suggesting cardioprotective effects for some antidiabetic drugs. The neutral results of CV safety trials on DPP-4 inhibitors have been disappointing, appearing to contradict the data from pooled analyses and meta-analyses of early trials. The main aim of this review is to find a possible interpretation for the differences between the results of these early trials and the CV safety studies with DPP-4 inhibitors. We conclude that the hypothesis of additional beneficial effects by DPP-4 inhibitors (beyond the improvement of glucose control), on the CV system in low-risk patients in primary prevention, needs to be verified with specifically designed studies. CI - Copyright (c) 2018. Published by Elsevier B.V. FAU - Dicembrini, I AU - Dicembrini I AD - Diabetology, University of Florence, Italy. FAU - Monami, M AU - Monami M AD - Diabetology, University of Florence, Italy. FAU - Mannucci, E AU - Mannucci E AD - Diabetology, University of Florence, Italy. Electronic address: Edoardo.mannucci@unifi.it. LA - eng PT - Journal Article PT - Review DEP - 20190103 PL - Netherlands TA - Nutr Metab Cardiovasc Dis JT - Nutrition, metabolism, and cardiovascular diseases : NMCD JID - 9111474 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) SB - IM MH - Biomarkers/blood MH - Blood Glucose/*drug effects/metabolism MH - Cardiovascular Diseases/diagnosis/epidemiology/physiopathology/*prevention & control MH - Cardiovascular System/*drug effects/physiopathology MH - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/epidemiology MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/*therapeutic use MH - Humans MH - *Primary Prevention MH - Protective Factors MH - Risk Assessment MH - Risk Factors MH - Treatment Outcome OTO - NOTNLM OT - CV safety OT - Dypeptidylpeptidase-4 inhibitors OT - Type 2 diabetes EDAT- 2019/02/06 06:00 MHDA- 2019/12/18 06:00 CRDT- 2019/02/06 06:00 PHST- 2018/08/01 00:00 [received] PHST- 2018/12/18 00:00 [revised] PHST- 2018/12/27 00:00 [accepted] PHST- 2019/02/06 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/02/06 06:00 [entrez] AID - S0939-4753(18)30365-X [pii] AID - 10.1016/j.numecd.2018.12.009 [doi] PST - ppublish SO - Nutr Metab Cardiovasc Dis. 2019 Mar;29(3):215-219. doi: 10.1016/j.numecd.2018.12.009. Epub 2019 Jan 3. PMID- 30615985 OWN - NLM STAT- MEDLINE DCOM- 20200227 LR - 20260127 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 45 IP - 5 DP - 2019 Oct TI - Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. PG - 409-418 LID - S1262-3636(18)30222-2 [pii] LID - 10.1016/j.diabet.2018.12.001 [doi] AB - In individuals with type 2 diabetes, glycaemic control and cardiovascular risk factor management reduces the likelihood of late-stage diabetic complications. Guidelines recommend treatment goals targeting HbA(1c), body weight, blood pressure, and low-density lipoprotein cholesterol. Development of new treatments for type 2 diabetes requires an understanding of their mechanism and efficacy, as well as their relative effects compared to other treatment choices, plus demonstration of cardiovascular safety. Subcutaneous semaglutide is a glucagon-like peptide-1 receptor agonist currently approved in several countries for once-weekly treatment of type 2 diabetes. Semaglutide works via the incretin pathway, stimulating insulin and inhibiting glucagon secretion from the pancreatic islets, leading to lower blood glucose levels. Semaglutide also decreases energy intake by reducing appetite and food cravings, and lowering relative preference for fatty, energy-dense foods. Semaglutide was evaluated in the SUSTAIN clinical trial programme in over 8000 patients across the spectrum of type 2 diabetes. This review details the efficacy and safety profile of semaglutide in the SUSTAIN 1-5 and 7 trials, and its cardiovascular safety profile in the SUSTAIN 6 trial. Semaglutide consistently demonstrated superior and sustained glycemic control and weight loss vs. all comparators evaluated. In SUSTAIN 6, involving patients at high risk of cardiovascular disease, semaglutide significantly decreased the occurrence of cardiovascular events compared with placebo/standard of care (hazard ratio 0.74, P < 0.001 for non-inferiority). Through a comprehensive phase 3 clinical trial program, we have a detailed understanding of semaglutide's efficacy, safety, cardiovascular effects and comparative role in the treatment of type 2 diabetes. CI - Copyright (c) 2018. Published by Elsevier Masson SAS. FAU - Aroda, V R AU - Aroda VR AD - Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: varoda@bwh.harvard.edu. FAU - Ahmann, A AU - Ahmann A AD - Harold Schnitzer Diabetes Health Center at Oregon Health and Science University, Portland, OR, USA. Electronic address: ahmanna@ohsu.edu. FAU - Cariou, B AU - Cariou B AD - L'institut du thorax, CHU de Nantes, CIC 1413, Inserm, Nantes, France. Electronic address: bertrand.cariou@univ-nantes.fr. FAU - Chow, F AU - Chow F AD - Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong. Electronic address: b410773@mailserv.cuhk.edu.hk. FAU - Davies, M J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, UK. Electronic address: melanie.davies@uhl-tr.nhs.uk. FAU - Jodar, E AU - Jodar E AD - Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid, Spain. Electronic address: esteban.jodar@gmail.com. FAU - Mehta, R AU - Mehta R AD - Unidad de Investigacon en Enfermedades Metabolicas, Departamento de Endocrinologia y Metablismo, Instituto Nacional de Ciencias Medicas y Nutricion "Salvador Zubiran" Mexico City, Mexico. Electronic address: roopamehta@yahoo.com. FAU - Woo, V AU - Woo V AD - Section of Endocrinology and Metabolism, Health Sciences Centre, University of Manitoba, Winnipeg, MB, Canada. Electronic address: vwoo3@shaw.ca. FAU - Lingvay, I AU - Lingvay I AD - UT Southwestern Medical Center, Dallas, TX, USA. Electronic address: Ildiko.Lingvay@UTSouthwestern.edu. LA - eng PT - Journal Article PT - Review DEP - 20190104 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/adverse effects/*therapeutic use MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Incretins/adverse effects/*therapeutic use MH - Injections, Subcutaneous MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Cardiovascular OT - Efficacy OT - Glucagon-like peptide-1 receptor agonist OT - Semaglutide, SUSTAIN OT - Type 2 diabetes EDAT- 2019/01/08 06:00 MHDA- 2020/02/28 06:00 CRDT- 2019/01/08 06:00 PHST- 2018/09/27 00:00 [received] PHST- 2018/12/06 00:00 [revised] PHST- 2018/12/16 00:00 [accepted] PHST- 2019/01/08 06:00 [pubmed] PHST- 2020/02/28 06:00 [medline] PHST- 2019/01/08 06:00 [entrez] AID - S1262-3636(18)30222-2 [pii] AID - 10.1016/j.diabet.2018.12.001 [doi] PST - ppublish SO - Diabetes Metab. 2019 Oct;45(5):409-418. doi: 10.1016/j.diabet.2018.12.001. Epub 2019 Jan 4. PMID- 30609236 OWN - NLM STAT- MEDLINE DCOM- 20200330 LR - 20200330 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 21 IP - 5 DP - 2019 May TI - Heart failure and type 2 diabetes: From cardiovascular outcome trials, with hope. PG - 1081-1087 LID - 10.1111/dom.13629 [doi] AB - An excess risk of heart failure (HF) persists in patients with type 2 diabetes (T2D) despite optimal control of an array of conventional risk factors, including hyperglycaemia. Twelve cardiovascular outcome trials (CVOTs) have been published to date, although none, with the exception of the DECLARE trial with dapagliflozin, has included HF as a primary endpoint. The four trials with dipeptidyl-peptidase inhibitors (DPP-4i) (SAVOR-TIMI 53 with saxagliptin, EXAMINE with alogliptin, TECOS with sitagliptin and CARMELINA with linagliptin) failed to show any significant effect on HF risk in patients with T2D, with the notable exception of saxagliptin which was associated with a 27% increased risk. Five completed CVOTs with the GLP-1 RAs lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), exenatide once weekly (EXSCEL) and albiglutide (HARMONY) also failed to reveal any significant effect on HF risk. The three trials with sodium glucose co-transporter-2 inhibitors (SGLT-2i) (EMPA-REG OUTCOME with empagliflozin, CANVAS with canagliflozin and DECLARE with dapagliflozin) all revealed a robust and significant reduction in the hazard ratios of hospitalization for HF, from 27% to 35%, which remained consistent, significant and of similar magnitude regardless of the presence of a history of HF or established atherosclerotic cardiovascular disease. There is no association between reductions in HF risk and haemoglobin A1c (A1C) levels, while there is a significant association between reductions in HR for MACE and A1C levels (Spearman's correlation, r = 0.695; P = 0.013). All of the 12 CVOTs completed to date have provided reassurance of the overall cardiovascular safety of the newer anti-hyperglycaemic drugs. At present, the robust, consistent and reproducible reduction of approximately 30% in the risk of HF with SGLT-2i may be considered a class effect. The beneficial effect on MACE outcome observed with the use of some GLP-1RAs and SGLT-2i must be interpreted within the frame of the single trial. CI - (c) 2019 John Wiley & Sons Ltd. FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy. FAU - Meier, Juris J AU - Meier JJ AUID- ORCID: 0000-0002-5835-8019 AD - Diabetes Division, St Josef Hospital, Ruhr-University Bochum, Bochum, Germany. FAU - Esposito, Katherine AU - Esposito K AUID- ORCID: 0000-0002-3652-5154 AD - Diabetes Division, Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy. LA - eng PT - Journal Article PT - Review DEP - 20190214 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 SB - IM MH - Clinical Trials as Topic/statistics & numerical data MH - Diabetes Mellitus, Type 2/*complications/epidemiology/*therapy MH - Diabetic Angiopathies/*epidemiology/etiology MH - Heart Failure/epidemiology/*etiology/prevention & control MH - Humans MH - Risk Factors MH - Treatment Outcome OTO - NOTNLM OT - CVOTs OT - albiglutide OT - alogliptin OT - canagliflozin OT - dapagliflozin OT - empagliflozin OT - exenatide OT - heart failure OT - linagliptin OT - liraglutide OT - lixisenatide OT - major adverse cardiovascular events OT - saxagliptin OT - semaglutide OT - sitagliptin OT - type 2 diabetes EDAT- 2019/01/05 06:00 MHDA- 2020/03/31 06:00 CRDT- 2019/01/05 06:00 PHST- 2018/11/27 00:00 [received] PHST- 2018/12/21 00:00 [revised] PHST- 2019/01/02 00:00 [accepted] PHST- 2019/01/05 06:00 [pubmed] PHST- 2020/03/31 06:00 [medline] PHST- 2019/01/05 06:00 [entrez] AID - 10.1111/dom.13629 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 May;21(5):1081-1087. doi: 10.1111/dom.13629. Epub 2019 Feb 14. PMID- 30607467 OWN - NLM STAT- MEDLINE DCOM- 20190624 LR - 20200309 IS - 1432-0428 (Electronic) IS - 0012-186X (Linking) VI - 62 IP - 3 DP - 2019 Mar TI - Cardiovascular outcome trials of glucose-lowering medications: an update. PG - 357-369 LID - 10.1007/s00125-018-4801-1 [doi] AB - Three further cardiovascular (CV) outcome studies of glucose-lowering drugs (linagliptin, albiglutide and dapagliflozin) have recently been published, adding to the twelve earlier within-class studies. The linagliptin study (CARMELINA) recruited people with renal disease as well as prior CV events and confirms the overall CV safety (and other safety) of the dipeptidylpeptidase-4 (DPP4) inhibitors, with no heart failure risk associated with this agent. However, taken together with the findings from two previous studies of DPP4 inhibitors (sitagliptin and saxagliptin), the three DPP4 inhibitor CV outcome trials (CVOTs) have highlighted a safety signal regarding risk of pancreatitis. Like CARMELINA, the albiglutide study (Harmony Outcome) had a very high CV event rate. Despite being a short duration study, albiglutide showed strong superiority for reduction in the major adverse CV events (MACE) composite in people with extant cardiovascular disease (CVD), in line with the earlier studies on the GLP-1 receptor agonists (GLP-1RAs) liraglutide and semaglutide. Positive effects can be detected for all these medications from before 12 months and continue for the whole study duration. No new safety issues for albiglutide are identified and the lack of a pancreatitis or a pancreatic cancer signal for this class is now clear. For the sodium-glucose cotransporter-2 (SGLT2) inhibitor class, the DECLARE-TIMI 58 study (of dapagliflozin) clearly indicates strong protection for heart failure in those with CVD, and probably in those with no prior CVD. There is also strong protection against renal decline with dapagliflozin, with similar risk estimates in DECLARE as previously reported for empagliflozin and canagliflozin. However, findings for MACE outcomes with dapagliflozin are not concordant with the empagliflozin and canagliflozin studies, and are not convincingly superior across class and for the longer term. Care is required when prescribing the SGLT2 inhibitor class of medications to people with foot vascular issues or prior amputation, and to insulin users in regard of ketoacidosis. In summary, taking into account the findings from these new studies, it is suggested that a GLP-1RA should be offered to all people with CVD and type 2 diabetes, and SGLT2 inhibitors should be prescribed for those at high risk of heart failure or with progressive decline in eGFR. DPP4 inhibitors are a safe choice within the glucose-lowering stepped algorithm. FAU - Home, Philip AU - Home P AUID- ORCID: 0000-0001-5187-710X AD - Institute for Cellular Medicine - Diabetes, The Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. philip.home@newcastle.ac.uk. LA - eng PT - Journal Article PT - Review DEP - 20190103 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Blood Glucose) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Blood Glucose MH - Cardiovascular Diseases/*chemically induced MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/*adverse effects/therapeutic use MH - Humans MH - Hypoglycemic Agents/*adverse effects/therapeutic use OTO - NOTNLM OT - Cardiovascular outcomes OT - Glucose-lowering medications OT - Review OT - Type 2 diabetes mellitus EDAT- 2019/01/05 06:00 MHDA- 2019/06/25 06:00 CRDT- 2019/01/05 06:00 PHST- 2018/11/12 00:00 [received] PHST- 2018/12/04 00:00 [accepted] PHST- 2019/01/05 06:00 [pubmed] PHST- 2019/06/25 06:00 [medline] PHST- 2019/01/05 06:00 [entrez] AID - 10.1007/s00125-018-4801-1 [pii] AID - 10.1007/s00125-018-4801-1 [doi] PST - ppublish SO - Diabetologia. 2019 Mar;62(3):357-369. doi: 10.1007/s00125-018-4801-1. Epub 2019 Jan 3. PMID- 30604598 OWN - NLM STAT- MEDLINE DCOM- 20200527 LR - 20260127 IS - 2233-6079 (Print) IS - 2233-6087 (Electronic) IS - 2233-6079 (Linking) VI - 43 IP - 4 DP - 2019 Aug TI - Asian Subpopulations May Exhibit Greater Cardiovascular Benefit from Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Meta-Analysis of Cardiovascular Outcome Trials. PG - 410-421 LID - 10.4093/dmj.2018.0070 [doi] AB - BACKGROUND: Based on reported results of three large cardiovascular outcome trials (CVOTs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), we aimed to investigate the overall effect of GLP-1 RAs on major adverse cardiovascular events (MACEs) and to identify subpopulations exhibiting the greatest cardiovascular (CV) benefit. METHODS: Three CVOTs reporting effects of long-acting GLP-1 RAs were included: LEADER (liraglutide), SUSTAIN-6 (semaglutide), and EXSCEL (exenatide once weekly). In all studies, the primary endpoint was three-point MACE, comprising CV death, non-fatal myocardial infarction, and non-fatal stroke. Overall effect estimates were calculated as hazard ratios and 95% confidence intervals (CIs) using the random-effects model; subgroup analyses reported in the original studies were similarly analyzed. RESULTS: Overall, statistically significant risk reductions in MACE and CV death were observed. Subgroup analysis indicated a significant racial difference with respect to CV benefit (P for interaction <0.001), and more substantial risk reductions were observed in subjects of African origin (relative risk [RR], 0.78; 95% CI, 0.60 to 0.99) and in Asians (RR, 0.35; 95% CI, 0.09 to 1.32). However, post hoc analysis (Bonferroni method) revealed that only Asians exhibited a significantly greater CV benefit from treatment, compared with white subjects (P<0.0001). CONCLUSION: Long-acting GLP-1 RAs reduced risks of MACE and CV deaths in high-risk patients with type 2 diabetes mellitus. Our findings of a particularly effective reduction in CV events with GLP-1 RA in Asian populations merits further exploration and dedicated trials in specific populations. CI - Copyright (c) 2019 Korean Diabetes Association. FAU - Kang, Yu Mi AU - Kang YM AUID- ORCID: 0000-0002-6272-0666 AD - International Healthcare Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Cho, Yun Kyung AU - Cho YK AUID- ORCID: 0000-0002-4089-1376 AD - Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Lee, Jiwoo AU - Lee J AD - Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Lee, Seung Eun AU - Lee SE AD - Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Lee, Woo Je AU - Lee WJ AD - Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Park, Joong Yeol AU - Park JY AD - Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Kim, Ye Jee AU - Kim YJ AD - Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Jung, Chang Hee AU - Jung CH AUID- ORCID: 0000-0003-4043-2396 AD - Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. chjung0204@amc.seoul.kr. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes Center Bochum-Hattingen, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. Michael.nauck@rub.de. LA - eng PT - Journal Article PT - Meta-Analysis DEP - 20181227 PL - Korea (South) TA - Diabetes Metab J JT - Diabetes & metabolism journal JID - 101556588 RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) MH - Aged MH - *Asian People MH - Black People MH - Cardiovascular Diseases/*chemically induced/*ethnology/mortality MH - Diabetes Mellitus, Type 2/drug therapy MH - Exenatide/adverse effects/*pharmacology/therapeutic use MH - Female MH - Glucagon-Like Peptides/adverse effects/*pharmacology/therapeutic use MH - Humans MH - Hypoglycemic Agents/adverse effects/*pharmacology/therapeutic use MH - Liraglutide/adverse effects/*pharmacology/therapeutic use MH - Male MH - Middle Aged MH - Multicenter Studies as Topic MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - Treatment Outcome MH - White People MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor PMC - PMC6712219 OTO - NOTNLM OT - Agonist OT - Cardiovascular disease OT - Diabetes mellitus, type 2 OT - Glucagon-like peptide 1 OT - Incretins OT - Meta-analysis OT - Safety OT - Therapeutics COIS- Michael A. Nauck has been member on advisory boards or has consulted with AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Fractyl, GlaxoSmithKline, Menarini/Berlin Chemie, Merck, Sharp & Dohme, and NovoNordisk. He has received grant support from AstraZeneca, Eli Lilly & Co., Menarini/Berlin-Chemie, Merck, Sharp & Dohme, Novartis Pharma, and NovoNordisk. He has also served on the speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly % Co., Menarini/Berlin Chemie, Merck, Sharp % Dohme, and NovoNordisk. EDAT- 2019/01/04 06:00 MHDA- 2019/01/04 06:01 PMCR- 2019/08/01 CRDT- 2019/01/04 06:00 PHST- 2018/04/24 00:00 [received] PHST- 2018/11/29 00:00 [accepted] PHST- 2019/01/04 06:00 [pubmed] PHST- 2019/01/04 06:01 [medline] PHST- 2019/01/04 06:00 [entrez] PHST- 2019/08/01 00:00 [pmc-release] AID - 42.e51 [pii] AID - 10.4093/dmj.2018.0070 [doi] PST - ppublish SO - Diabetes Metab J. 2019 Aug;43(4):410-421. doi: 10.4093/dmj.2018.0070. Epub 2018 Dec 27. PMID- 30565096 OWN - NLM STAT- MEDLINE DCOM- 20200819 LR - 20260127 IS - 1179-1926 (Electronic) IS - 0312-5963 (Linking) VI - 58 IP - 6 DP - 2019 Jun TI - Safety and Pharmacokinetics of Single and Multiple Ascending Doses of the Novel Oral Human GLP-1 Analogue, Oral Semaglutide, in Healthy Subjects and Subjects with Type 2 Diabetes. PG - 781-791 LID - 10.1007/s40262-018-0728-4 [doi] AB - BACKGROUND: Oral semaglutide is a novel tablet containing the human glucagon-like peptide-1 (GLP‑1) analogue semaglutide, co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). The safety and pharmacokinetics of oral semaglutide were investigated in two randomised, double-blind, placebo-controlled trials. METHODS: In a single-dose, first-in-human trial, 135 healthy males received oral semaglutide (2-20 mg semaglutide co-formulated with 150-600 mg SNAC) or placebo with SNAC. In a 10-week, once-daily, multiple-dose trial, 84 healthy males received 20 or 40 mg oral semaglutide (with 300 mg SNAC), placebo, or placebo with SNAC, and 23 males with type 2 diabetes (T2D) received 40 mg oral semaglutide (with 300 mg SNAC), placebo, or placebo with SNAC. RESULTS: Oral semaglutide was safe and well-tolerated in both trials. The majority of adverse events (AEs) were mild, with the most common AEs being gastrointestinal disorders. In the single-dose trial, semaglutide exposure was highest when co-formulated with 300 mg SNAC. In the multiple-dose trial, semaglutide exposure was approximately twofold higher with 40 versus 20 mg oral semaglutide in healthy males, in accordance with dose proportionality, and was similar between healthy males and males with T2D. The half-life of semaglutide was approximately 1 week in all groups. CONCLUSION: The safety profile of oral semaglutide was as expected for the GLP-1 receptor agonist drug class. Oral semaglutide co-formulated with 300 mg SNAC was chosen for further clinical development. The pharmacokinetic results supported that oral semaglutide is suitable for once-daily dosing. CLINICALTRIALS. GOV IDENTIFIERS: NCT01037582, NCT01686945. FAU - Granhall, Charlotte AU - Granhall C AD - Novo Nordisk A/S, Vandtarnsvej 114, 2860, Soborg, Denmark. FAU - Donsmark, Morten AU - Donsmark M AD - Novo Nordisk A/S, Vandtarnsvej 114, 2860, Soborg, Denmark. FAU - Blicher, Thalia M AU - Blicher TM AD - Novo Nordisk A/S, Vandtarnsvej 114, 2860, Soborg, Denmark. FAU - Golor, Georg AU - Golor G AD - Early Phase Clinical Unit-Berlin, Parexel International GmbH, Klinikum Westend-Haus 18, Spandauer Damm 130, 14050, Berlin, Germany. FAU - Sondergaard, Flemming L AU - Sondergaard FL AD - Novo Nordisk A/S, Alfred Nobels Vej 27, 9220, Aalborg O, Denmark. FAU - Thomsen, Mette AU - Thomsen M AD - Novo Nordisk A/S, Vandtarnsvej 114, 2860, Soborg, Denmark. FAU - Baekdal, Tine A AU - Baekdal TA AD - Novo Nordisk A/S, Vandtarnsvej 114, 2860, Soborg, Denmark. tabq@novonordisk.com. LA - eng SI - ClinicalTrials.gov/NCT01037582 SI - ClinicalTrials.gov/NCT01686945 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Clin Pharmacokinet JT - Clinical pharmacokinetics JID - 7606849 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Adolescent MH - Adult MH - Area Under Curve MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Glucagon-Like Peptide 1/*analogs & derivatives MH - *Glucagon-Like Peptides/administration & dosage/adverse effects/blood MH - Healthy Volunteers MH - Humans MH - *Hypoglycemic Agents/administration & dosage/adverse effects/blood MH - Male MH - Metabolic Clearance Rate MH - Middle Aged MH - Young Adult MH - Semaglutide EDAT- 2018/12/20 06:00 MHDA- 2020/08/20 06:00 CRDT- 2018/12/20 06:00 PHST- 2018/12/20 06:00 [pubmed] PHST- 2020/08/20 06:00 [medline] PHST- 2018/12/20 06:00 [entrez] AID - 10.1007/s40262-018-0728-4 [pii] AID - 10.1007/s40262-018-0728-4 [doi] PST - ppublish SO - Clin Pharmacokinet. 2019 Jun;58(6):781-791. doi: 10.1007/s40262-018-0728-4. PMID- 30528435 OWN - NLM STAT- MEDLINE DCOM- 20200601 LR - 20260127 IS - 2241-5955 (Electronic) IS - 1109-9666 (Linking) VI - 60 IP - 6 DP - 2019 Nov-Dec TI - GLP-1 receptor agonists and cardiovascular outcome trials: An update. PG - 347-351 LID - S1109-9666(18)30408-1 [pii] LID - 10.1016/j.hjc.2018.11.008 [doi] AB - Major cardiovascular (CV) outcome trials with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are currently available. These agonists have proven their CV safety, in harmony with the US Food and Drug Administration (FDA) recommendation for antidiabetic drugs. The potential cardioprotective effect of incretin-based therapies is attributed to their multiple non-glycaemic actions in the CV system, including changes in insulin resistance, weight loss, reduction in blood pressure, improved lipid profile and direct effects on the heart and vascular endothelium. Liraglutide, semaglutide and albiglutide have been demonstrated to reduce the risk of major adverse cardiac events (MACE), whereas lixisenatide and extended-release exenatide had a neutral effect. Thus, it is conceivable that there are different drug-specific properties across the class of GLP-1 RAs. In this review, we discuss the results of the five recently published randomised CV outcome trials with GLP-1 RAs, along with the potential differences and the pleiotropic actions of these agents on the CV system. CI - Copyright (c) 2018 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved. FAU - Andrikou, Eirini AU - Andrikou E AD - First Cardiology Department, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece. FAU - Tsioufis, Costas AU - Tsioufis C AD - First Cardiology Department, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece. Electronic address: ktsioufis@hippocratio.gr. FAU - Andrikou, Ioannis AU - Andrikou I AD - First Cardiology Department, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece. FAU - Leontsinis, Ioannis AU - Leontsinis I AD - First Cardiology Department, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece. FAU - Tousoulis, Dimitrios AU - Tousoulis D AD - First Cardiology Department, Medical School, National and Kapodistrian University of Athens, Hippokration Hospital, Athens, Greece. FAU - Papanas, Nikolaos AU - Papanas N AD - Diabetes Centre, Second Department of Internal Medicine, Democritus University of Thrace, University Hospital of Alexandroupolis, Greece. LA - eng PT - Journal Article PT - Review DEP - 20181206 PL - Netherlands TA - Hellenic J Cardiol JT - Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese JID - 101257381 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 5E7U48495E (rGLP-1 protein) SB - IM MH - Aged MH - Blood Pressure/drug effects MH - Cardiovascular Diseases/epidemiology/*prevention & control MH - Cardiovascular System/*drug effects/physiopathology MH - Case-Control Studies MH - Diabetes Mellitus, Type 2/*drug therapy MH - Endothelium, Vascular/drug effects MH - Glucagon-Like Peptide 1/administration & dosage/analogs & derivatives/pharmacology/therapeutic use MH - Glucagon-Like Peptides/administration & dosage/pharmacology/therapeutic use MH - Humans MH - Hypoglycemic Agents/administration & dosage/pharmacology/therapeutic use MH - Insulin Resistance/physiology MH - Liraglutide/administration & dosage/pharmacology/therapeutic use MH - Middle Aged MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - United States/epidemiology MH - United States Food and Drug Administration MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Cardiovascular disease OT - Diabetes mellitus OT - Randomised controlled trials OT - Treatment EDAT- 2018/12/12 06:00 MHDA- 2020/06/02 06:00 CRDT- 2018/12/12 06:00 PHST- 2018/09/06 00:00 [received] PHST- 2018/11/09 00:00 [revised] PHST- 2018/11/14 00:00 [accepted] PHST- 2018/12/12 06:00 [pubmed] PHST- 2020/06/02 06:00 [medline] PHST- 2018/12/12 06:00 [entrez] AID - S1109-9666(18)30408-1 [pii] AID - 10.1016/j.hjc.2018.11.008 [doi] PST - ppublish SO - Hellenic J Cardiol. 2019 Nov-Dec;60(6):347-351. doi: 10.1016/j.hjc.2018.11.008. Epub 2018 Dec 6. PMID- 30499733 OWN - NLM STAT- MEDLINE DCOM- 20190318 LR - 20260127 IS - 1744-7666 (Electronic) IS - 1465-6566 (Linking) VI - 20 IP - 2 DP - 2019 Feb TI - Oral semaglutide for the treatment of type 2 diabetes. PG - 133-141 LID - 10.1080/14656566.2018.1552258 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists are highly potent antihyperglycemic drugs that impose low risk of hypoglycemia and also result in body weight reduction. Currently, all approved members of the class require administration by injection. Areas covered: This manuscript reviews oral semaglutide-an experimental GLP-1 receptor agonist in phase-3 clinical development. Available pharmacological and clinical data of the drug are reviewed, and important end-points described. Expert opinion: Oral peptide delivery has become possible with the discovery of absorption enhancers. The clinical development program of once-daily oral semaglutide has shown superiority in reducing glycosylated hemoglobin and body weight in comparison with placebo and active comparators (sitagliptin, liraglutide, and empagliflozin). Safety and tolerability of oral semaglutide is in line with injectable members of the class. Delayed gastric emptying, local increase in pH, and enhanced absorption do not seem to affect the exposure of a number of other oral drugs that have been tested (metformin, digoxin, oral contraceptive ethinylestradiol/levonorgestrel, lisinopril, warfarin, furosemide and rosuvastatin). Clinical questions for further investigation include the effectiveness and safety of oral semaglutide in cardiovascular indications. FAU - Hedrington, Maka S AU - Hedrington MS AD - a Department of Medicine , University of Maryland School of Medicine , Baltimore , MD , USA. FAU - Davis, Stephen N AU - Davis SN AD - a Department of Medicine , University of Maryland School of Medicine , Baltimore , MD , USA. LA - eng PT - Journal Article PT - Review DEP - 20181130 PL - England TA - Expert Opin Pharmacother JT - Expert opinion on pharmacotherapy JID - 100897346 RN - 0 (Benzhydryl Compounds) RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Benzhydryl Compounds/administration & dosage MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/*administration & dosage MH - Glucosides/administration & dosage MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/*administration & dosage/therapeutic use MH - Liraglutide/therapeutic use MH - Sitagliptin Phosphate/administration & dosage MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - Semaglutide OT - diabetes OT - glucose EDAT- 2018/12/01 06:00 MHDA- 2019/03/19 06:00 CRDT- 2018/12/01 06:00 PHST- 2018/12/01 06:00 [pubmed] PHST- 2019/03/19 06:00 [medline] PHST- 2018/12/01 06:00 [entrez] AID - 10.1080/14656566.2018.1552258 [doi] PST - ppublish SO - Expert Opin Pharmacother. 2019 Feb;20(2):133-141. doi: 10.1080/14656566.2018.1552258. Epub 2018 Nov 30. PMID- 30406850 OWN - NLM STAT- MEDLINE DCOM- 20190910 LR - 20191210 IS - 1539-0829 (Electronic) IS - 1534-4827 (Linking) VI - 18 IP - 12 DP - 2018 Nov 8 TI - The Evolving Role of the Cardiologist in the Management of Type 2 Diabetes. PG - 144 LID - 10.1007/s11892-018-1114-1 [doi] AB - PURPOSE OF REVIEW: To evaluate the treatment of type 2 diabetes from a cardiologist's view. RECENT FINDINGS: A new era in the treatment of type 2 diabetes began for the cardiologist in 2015 with the publication of the EMPA-REG outcome trial finding a significant reduction in CV death with empagliflozin (oral sodium-glucose co-transporter-2 [SGLT2] inhibitor) in patients with type 2 diabetes at increased cardiovascular risk. Shortly thereafter, the injectable glucagon-like peptide agonists (GLP-1) liraglutide and semaglutide found a significant reduction in composite major cardiovascular events (CV death, non-fatal MI, or stroke). Both classes have demonstrated significant renal protection when added to usual care. Moreover, there may be some exciting new benefits of SGLT2 inhibitors for patients with heart failure. These research studies are underway. These two new classes of cardiovascular drugs for type 2 diabetes usher in a new era for the cardiologist who sees greater than 50% of patients with diabetes. The off-target effect of these agents is different as with all new cardiovascular compounds. While safety profiles in these populations are consistent with the known effects of these classes, new off-target effects have been seen with some agents in this class. Ongoing collaboration between cardiologists and other care providers remains important in the implementation of the evidence and care of patients with type 2 diabetes. FAU - Chilton, Robert J AU - Chilton RJ AD - Division of Cardiology, UT Health San Antonio, 7703 Floyd Curl Drive, Mail Code 7872, San Antonio, TX, 78229, USA. chilton@uthscsa.edu. FAU - Gallegos, Kelly M AU - Gallegos KM AD - Division of Cardiology, UT Health San Antonio, 7703 Floyd Curl Drive, Mail Code 7872, San Antonio, TX, 78229, USA. FAU - Silva-Cardoso, Jose AU - Silva-Cardoso J AD - , Porto, Portugal. FAU - Oliveros, Rene AU - Oliveros R AD - Division of Cardiology, UT Health San Antonio, 7703 Floyd Curl Drive, Mail Code 7872, San Antonio, TX, 78229, USA. FAU - Pham, Son AU - Pham S AD - Division of Cardiology, UT Health San Antonio, 7703 Floyd Curl Drive, Mail Code 7872, San Antonio, TX, 78229, USA. LA - eng PT - Journal Article PT - Review DEP - 20181108 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 SB - IM MH - *Cardiologists MH - Cardiovascular Diseases/prevention & control MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*drug therapy MH - Humans MH - Outcome Assessment, Health Care MH - Risk Factors OTO - NOTNLM OT - Amputations OT - GLP-1 agonist OT - Heart failure OT - Kidney protection OT - Retinopathy OT - SGLT 2 inhibitors EDAT- 2018/11/09 06:00 MHDA- 2019/09/11 06:00 CRDT- 2018/11/09 06:00 PHST- 2018/11/09 06:00 [entrez] PHST- 2018/11/09 06:00 [pubmed] PHST- 2019/09/11 06:00 [medline] AID - 10.1007/s11892-018-1114-1 [pii] AID - 10.1007/s11892-018-1114-1 [doi] PST - epublish SO - Curr Diab Rep. 2018 Nov 8;18(12):144. doi: 10.1007/s11892-018-1114-1. PMID- 30372907 OWN - NLM STAT- MEDLINE DCOM- 20190301 LR - 20190301 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 108 DP - 2018 Dec TI - Recent updates on GLP-1 agonists: Current advancements & challenges. PG - 952-962 LID - S0753-3322(18)32753-7 [pii] LID - 10.1016/j.biopha.2018.08.088 [doi] AB - Glucagon-like peptide (GLP)-1 is an incretin hormone exhibiting several pharmacological actions such as neuroprotection, increased cognitive function, cardio-protection, decreased hypertension, suppression of acid secretion, increase in lyposis, and protection from inflammation. The most potent actions are glucose-dependent insulinotropic and glucagonostatic actions, stimulation of beta-cell proliferation, enhanced insulin secretion and reduced weight gain in patients with type-2 diabetes pertaining to blood glucose control. Despite all these actions, its short half-life (around 2 approximately min) and degradation by a dipeptidyl peptidase-4 enzyme (DPP-4) limits the therapeutic utility of GLP1. In this review, we have discussed DPP IV-resistant analogs of GLP-1 currently present in clinical trials such as Exenatide, Liraglutide, Semaglutide, Efpeglenatide, Exenatide ER, Ittca 650 (Intarcia), Dulaglutide, Albiglutide, and Lixisenatide. Moreover, we have also discussed in detail the pharmacology, signaling mechanisms, and pharmacokinetic properties (Cmax, Tmax, T(1/2,) Vd, and Bioavailability) of DPP IV-resistant analogs of (GLP-1). Interestingly, GLP-1 agonist drugs have shown better potential to treat type-2 diabetes mellitus (T2DM) as compared to currently used drugs in clinics without causing the side effects of hypoglycemia and weight gain. CI - Copyright (c) 2018 Elsevier Masson SAS. All rights reserved. FAU - Sharma, Dilip AU - Sharma D AD - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar 382355, Gujarat, India. FAU - Verma, Suril AU - Verma S AD - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar 382355, Gujarat, India. FAU - Vaidya, Shivani AU - Vaidya S AD - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar 382355, Gujarat, India. FAU - Kalia, Kiran AU - Kalia K AD - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar 382355, Gujarat, India. Electronic address: kirankalia@gmail.com. FAU - Tiwari, Vinod AU - Tiwari V AD - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar 382355, Gujarat, India. Electronic address: vinodtiwari1980@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20180927 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Animals MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism MH - Glucagon-Like Peptide 1/*agonists MH - Humans MH - Hypoglycemic Agents/*pharmacology/*therapeutic use MH - Signal Transduction/drug effects OTO - NOTNLM OT - DPP-4 inhibitors OT - GLP-1 agonists OT - Incretins OT - Type-2 diabetes mellitus EDAT- 2018/10/31 06:00 MHDA- 2019/03/02 06:00 CRDT- 2018/10/31 06:00 PHST- 2018/04/24 00:00 [received] PHST- 2018/08/04 00:00 [revised] PHST- 2018/08/15 00:00 [accepted] PHST- 2018/10/31 06:00 [pubmed] PHST- 2019/03/02 06:00 [medline] PHST- 2018/10/31 06:00 [entrez] AID - S0753-3322(18)32753-7 [pii] AID - 10.1016/j.biopha.2018.08.088 [doi] PST - ppublish SO - Biomed Pharmacother. 2018 Dec;108:952-962. doi: 10.1016/j.biopha.2018.08.088. Epub 2018 Sep 27. PMID- 30362224 OWN - NLM STAT- MEDLINE DCOM- 20200203 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 21 IP - 3 DP - 2019 Mar TI - Evaluation of the long-term cost-effectiveness of once-weekly semaglutide versus dulaglutide for treatment of type 2 diabetes mellitus in the UK. PG - 611-621 LID - 10.1111/dom.13564 [doi] AB - AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists are appealing as glucose-lowering therapy for individuals with type 2 diabetes mellitus (T2DM) as they also reduce body weight and are associated with low rates of hypoglycaemia. This analysis assessed the long-term cost-effectiveness of semaglutide 0.5 and 1 mg vs dulaglutide 1.5 mg (two once-weekly GLP-1 receptor agonists) from a UK healthcare payer perspective, based on the head-to-head SUSTAIN 7 trial, to inform healthcare decision making. MATERIALS AND METHODS: Long-term outcomes were projected using the IQVIA CORE Diabetes Model (version 9.0). Baseline cohort characteristics, changes in physiological parameters and adverse event rates were derived from the 40-week SUSTAIN 7 trial. Costs to a healthcare payer were assessed, and these captured pharmacy costs and costs of complications. Utilities were taken from published sources. RESULTS: Once-weekly semaglutide 0.5 and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.04 and 0.10 quality-adjusted life years, respectively, compared with dulaglutide 1.5 mg. Clinical benefits were achieved at reduced costs, with lifetime cost savings of GBP 35 with once-weekly semaglutide 0.5 mg and GBP 106 with the once-weekly semaglutide 1 mg, resulting from fewer diabetes-related complications due to better glycaemic control. Therefore, both doses of once-weekly semaglutide were considered dominant vs dulaglutide 1.5 mg (improving outcomes and reducing costs). CONCLUSIONS: Compared with treatment with dulaglutide, once-weekly semaglutide represents a cost-effective option for treating individuals in the UK with T2DM who are not achieving glycaemic control with metformin, projected to both improve clinical outcomes and reduce costs. CI - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Viljoen, Adie AU - Viljoen A AD - Borthwick Diabetes Research Centre, Lister Hospital (East and North Hertfordshire NHS Trust), Stevenage, UK. FAU - Hoxer, Christina S AU - Hoxer CS AD - Novo Nordisk Ltd, Gatwick, UK. FAU - Johansen, Pierre AU - Johansen P AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Malkin, Samuel AU - Malkin S AUID- ORCID: 0000-0003-1306-7784 AD - Ossian Health Economics and Communications, Basel, Switzerland. FAU - Hunt, Barnaby AU - Hunt B AUID- ORCID: 0000-0001-5420-279X AD - Ossian Health Economics and Communications, Basel, Switzerland. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Swansea University Medical School, Swansea, UK. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181128 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Clinical Trials as Topic/statistics & numerical data MH - Cost-Benefit Analysis MH - Diabetes Complications/economics/epidemiology MH - Diabetes Mellitus, Type 2/complications/*drug therapy/*economics/epidemiology MH - Drug Administration Schedule MH - Glucagon-Like Peptides/administration & dosage/*analogs & derivatives/economics MH - Health Care Costs/statistics & numerical data MH - Health Resources/economics/statistics & numerical data MH - Humans MH - Immunoglobulin Fc Fragments/*administration & dosage/economics MH - Models, Economic MH - Quality-Adjusted Life Years MH - Recombinant Fusion Proteins/*administration & dosage/economics MH - Time Factors MH - United Kingdom/epidemiology MH - Semaglutide PMC - PMC6587509 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - cost-effectiveness OT - incretin therapy COIS- A. V. has conducted clinical trials funded by and has received lecture and advisory board fees from Astra Zeneca, Boehringer-Ingelheim, Ely Lilly, Merck Sharpe Dohme, Napp, Novo Nordisk, Takeda and Sanofi. C. S. H. is an employee of Novo Nordisk Ltd and owns shares in Novo Nordisk A/S. P. J. is an employee of Novo Nordisk A/S. S. M. and B. H. are employees of Ossian Health Economics and Communications, which received consulting fees from Novo Nordisk A/S to support preparation of the analysis. S. C. B. has received honoraria, teaching and research sponsorship/grants from Astra-Zeneka, Boehringer Ingelheim, BMS, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novo Nordisk, Pfizer, Sanofi and Takeda. S. C. B. owns a share of Glycosmedia. AUTHOR CONTRIBUTIONS: The study was designed by all authors. B. H. and S. M. conducted the study. All authors contributed to analysis of the results. S. M. and B. H. drafted the manuscript and A. V., S. C. B., C. S. H and P. J. critically reviewed the manuscript and revised it for important intellectual content. All authors approved the final manuscript and agree to be accountable for all aspects of the work. EDAT- 2018/10/27 06:00 MHDA- 2020/02/06 06:00 PMCR- 2019/06/21 CRDT- 2018/10/27 06:00 PHST- 2018/07/27 00:00 [received] PHST- 2018/10/08 00:00 [revised] PHST- 2018/10/19 00:00 [accepted] PHST- 2018/10/27 06:00 [pubmed] PHST- 2020/02/06 06:00 [medline] PHST- 2018/10/27 06:00 [entrez] PHST- 2019/06/21 00:00 [pmc-release] AID - DOM13564 [pii] AID - 10.1111/dom.13564 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 Mar;21(3):611-621. doi: 10.1111/dom.13564. Epub 2018 Nov 28. PMID- 30296182 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20260127 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 11 IP - 11 DP - 2018 Nov TI - Semaglutide once-weekly: improved efficacy with a new safety warning. PG - 1061-1072 LID - 10.1080/17512433.2018.1534201 [doi] AB - Semaglutide once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) injection has been approved as an adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus (T2DM). Areas Covered: The safety and efficacy of the semaglutide once-weekly injection are reviewed using results from preliminary pharmacology studies and later-phase randomized control trials (RCTs) and meta-analyses. Semaglutide once-weekly is compared to placebo and active comparators for T2DM in the SUSTAIN clinical trial series, with outcomes of: glycemic control, weight loss, major adverse cardiovascular events, and adverse effects. Risk for diabetic retinopathy complications (DRCs) is reviewed in detail, due to significantly higher risk for DRCs seen in SUSTAIN 6. SUSTAIN 6 is the first instance of a GLP-1 RA demonstrating significantly increased risk for DRCs. Semaglutide's current regulatory approvals, practice considerations, and cost-effectiveness compared to similar therapies are also considered. Expert Commentary: Semaglutide demonstrates high glycemic efficacy and favorable safety profile, and reduces the risk for cardiovascular events. Mild to moderate gastrointestinal events and retinopathy complications were more common with semaglutide compared to placebo, though serious adverse events were similar to controls and infrequent. Improved clinical efficacy should be carefully weighed against the risk for GI and retinopathy complications. FAU - Coon, Scott A AU - Coon SA AUID- ORCID: 0000-0002-1534-6114 AD - a Department of Pharmacy Practice , St. Louis College of Pharmacy , St. Louis , MO , USA. FAU - Crannage, Erica F AU - Crannage EF AUID- ORCID: 0000-0001-8509-9609 AD - a Department of Pharmacy Practice , St. Louis College of Pharmacy , St. Louis , MO , USA. FAU - Kerwin, Lara C AU - Kerwin LC AD - a Department of Pharmacy Practice , St. Louis College of Pharmacy , St. Louis , MO , USA. FAU - Guyton, Justinne E AU - Guyton JE AD - a Department of Pharmacy Practice , St. Louis College of Pharmacy , St. Louis , MO , USA. LA - eng PT - Journal Article PT - Review DEP - 20181016 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose/drug effects MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Diabetic Retinopathy/epidemiology MH - Drug Administration Schedule MH - Glucagon-Like Peptides/*administration & dosage/adverse effects/pharmacology MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacology MH - Randomized Controlled Trials as Topic MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Type 2 diabetes mellitus OT - cardiovascular disease OT - glucagon-like peptide 1 OT - once weekly injection OT - retinopathy OT - semaglutide OT - weight loss EDAT- 2018/10/09 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/10/09 06:00 PHST- 2018/10/09 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/10/09 06:00 [entrez] AID - 10.1080/17512433.2018.1534201 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2018 Nov;11(11):1061-1072. doi: 10.1080/17512433.2018.1534201. Epub 2018 Oct 16. PMID- 30284349 OWN - NLM STAT- MEDLINE DCOM- 20200203 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 21 IP - 3 DP - 2019 Mar TI - Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial. PG - 499-508 LID - 10.1111/dom.13553 [doi] AB - AIMS: To assess the cardiovascular (CV) safety of oral semaglutide, the first tablet formulation of a glucagon-like peptide-1 receptor agonist. MATERIALS AND METHODS: PIONEER 6 is a multinational, randomized, placebo-controlled, double-blind trial in patients with type 2 diabetes at high risk of CV events (defined as being aged >/=50 years and having established CV disease [CVD] or moderate [stage 3] chronic kidney disease [CKD], or being aged >/=60 years with >/=1 other CV risk factor). Patients were randomized to once-daily oral semaglutide (up to 14 mg) or placebo added to standard of care. The primary composite endpoint is time to first occurrence of CV death or non-fatal myocardial infarction or non-fatal stroke. The primary hypothesis was to exclude an excess in CV risk with oral semaglutide by assessing non-inferiority versus placebo for the primary endpoint (non-inferiority margin of 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio). PIONEER 6 is event-driven, with follow-up continuing until accrual of at least 122 primary outcome events. There is no pre-defined minimal duration. RESULTS: Overall, 3183 patients have been enrolled (mean age 66.1 years, 31.6% females) in 214 sites across 21 countries. At baseline, the mean duration of diabetes was 14.9 years, mean glycated haemoglobin concentration was 66 mmol/mol (8.2%), and 84.6% of patients had established CVD/moderate CKD. CONCLUSIONS: PIONEER 6 will provide evidence regarding the CV safety of oral semaglutide in patients with type 2 diabetes and high CV risk. CI - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Bain, Stephen C AU - Bain SC AUID- ORCID: 0000-0001-8519-4964 AD - Diabetes Research Unit Cymru, Swansea University Medical School, Swansea, UK. FAU - Mosenzon, Ofri AU - Mosenzon O AD - Diabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel. FAU - Arechavaleta, Rosario AU - Arechavaleta R AD - Department of Endocrinology, Universidad Autonoma de Guadalajara, Jalisco, Mexico. FAU - Bogdanski, Pawel AU - Bogdanski P AD - Department of Education and Obesity Treatment and Metabolic Disorders, Poznan University of Medical Sciences, Poznan, Poland. FAU - Comlekci, Abdurrahman AU - Comlekci A AD - Department of Endocrinology, Dokuz Eylul University Faculty of Medicine, Balcova, Izmir, Turkey. FAU - Consoli, Agostino AU - Consoli A AD - Department of Medicine and Aging, and Center of Aging Science and Translational Medicine (CESI-Met), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy. FAU - Deerochanawong, Chaicharn AU - Deerochanawong C AD - Diabetes and Endocrinology Unit, Rajavithi Hospital, Rangsit Medical School, Bangkok, Thailand. FAU - Dungan, Kathleen AU - Dungan K AUID- ORCID: 0000-0003-1289-1595 AD - Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, Ohio. FAU - Faingold, Maria C AU - Faingold MC AD - Department of Endocrinology and Metabolism, Dr Cesar Milstein Hospital, Buenos Aires, Argentina. FAU - Farkouh, Michael E AU - Farkouh ME AD - Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, Ontario, Canada. FAU - Franco, Denise R AU - Franco DR AD - CPCLIN Clinical Research Center, Sao Paulo, Brazil. FAU - Gram, Jeppe AU - Gram J AD - Department of Endocrinology, Hospital of Southwest Denmark, Esbjerg, Denmark. FAU - Guja, Cristian AU - Guja C AUID- ORCID: 0000-0002-8703-0522 AD - Department of Diabetes, Nutrition and Metabolic Diseases, University of Medicine and Pharmacy 'Carol Davila', Bucharest, Romania. FAU - Joshi, Pankaj AU - Joshi P AD - Diabetes Care and Clinical Trials Centre, Pretoria, South Africa. FAU - Malek, Rachid AU - Malek R AD - Department of Internal Medicine, CHU Setif, Setif, Algeria. FAU - Merino-Torres, Juan F AU - Merino-Torres JF AD - Department of Endocrinology and Nutrition, University Hospital La Fe, Valencia, Spain. FAU - Nauck, Michael A AU - Nauck MA AUID- ORCID: 0000-0002-5749-6954 AD - Diabetes Center Bochum-Hattingen, Medical Department I, St Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. FAU - Pedersen, Sue D AU - Pedersen SD AD - C-ENDO Diabetes and Endocrinology Clinic, Calgary, Alberta, Canada. FAU - Sheu, Wayne H-H AU - Sheu WH AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan. AD - School of Medicine, National Yang-Ming University, Taipei, Taiwan. AD - School of Medicine, National Defense Medical Centre, Taipei, Taiwan. FAU - Silver, Robert J AU - Silver RJ AD - Southern New Hampshire Diabetes and Endocrinology, Nashua, New Hampshire. FAU - Tack, Cees J AU - Tack CJ AD - Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. FAU - Tandon, Nikhil AU - Tandon N AD - Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India. FAU - Jeppesen, Ole K AU - Jeppesen OK AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Strange, Mette AU - Strange M AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Thomsen, Mette AU - Thomsen M AD - Novo Nordisk A/S, Bagsvaerd, Denmark. FAU - Husain, Mansoor AU - Husain M AD - Peter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, Ontario, Canada. AD - Toronto General Hospital Research Institute, and the Ted Rogers Centre for Heart Research, Toronto, Canada. LA - eng PT - Clinical Trial Protocol PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181111 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Placebos) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Aged MH - Aged, 80 and over MH - Cardiovascular Diseases/epidemiology/*prevention & control MH - Cardiovascular System/*drug effects MH - Diabetes Mellitus, Type 2/complications/*drug therapy/epidemiology MH - Diabetic Angiopathies/epidemiology/prevention & control MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Humans MH - Hypoglycemic Agents/administration & dosage/adverse effects MH - Male MH - Metformin/administration & dosage/adverse effects MH - Middle Aged MH - Placebos MH - Renal Insufficiency, Chronic/complications/drug therapy/epidemiology MH - Multicenter Studies as Topic MH - Randomized Controlled Trials as Topic MH - Equivalence Trials as Topic MH - Semaglutide PMC - PMC6587508 OTO - NOTNLM OT - GLP-1 receptor agonist OT - cardiovascular disease OT - cardiovascular outcomes trial OT - oral semaglutide OT - type 2 diabetes COIS- S.C.B. has received honoraria, teaching and research sponsorship/grants from Abbott, AstraZeneca, Boehringer Ingelheim, BMS, Cellnovo, Diartis, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, Servier and Takeda, has received funding for educational programmes from Cardiff University, Doctors.net, Elsevier, Onmedica, Omnia-Med and Medscape, and has an ownership interest in Gycosmedia (a diabetes on-line news service). O.M. has received honoraria for advisory boards for Novo Nordisk, Eli Lilly, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, Jansen and Jansen, Novartis and AstraZeneca, is on Speaker's Bureau for AstraZeneca, Bristol-Myers Squibb, Novo Nordisk, Eli Lilly, Sanofi, Novartis, Merck Sharp & Dohme, Boehringer Ingelheim, has grants paid to her institution as study physician by AstraZeneca and Bristol-Myers Squibb, and has received research grant support through Hadassah Hebrew University Hospital from Novo Nordisk. R.A. has received honoraria for advisory boards for Novo Nordisk, Eli Lilly, Merck Sharp & Dohme, Sanofi, speaking fees from AstraZeneca, Novo Nordisk, Eli Lilly, Merck Sharpe & Dohme, Sanofi, and research support from AstraZeneca, Novo Nordisk, Eli Lilly, Merck Sharpe & Dohme, Sanofi. Ab.C. has served as an advisory panel/board member for Novo Nordisk, Sanofi, Eli Lilly, Merck Sharp & Dohme and AstraZeneca, has received research support from Novo Nordisk, AstraZeneca, Novartis, MSD and Boehringer Ingelheim, and has served on the Speaker's Bureau for Novo Nordisk, Sanofi, Eli Lilly, AstraZeneca and Merck Sharp & Dohme. Ag.C. has received lecture fees and fees for serving on advisory boards from Novo Nordisk, Eli Lilly, AstraZeneca, Sanofi Aventis, Merck Sharp & Dohme and Takeda, and grant support to his institution from AstraZeneca, Eli Lilly and Novo Nordisk. K.D. has received consulting fees from GlaxoSmithKline and Sanofi, research support from AstraZeneca, GlaxoSmithKline, Novo Nordisk, and Sanofi, and participated in CME-sponsored events funded by Novo Nordisk, Sanofi, Merck, Eli Lilly and AstraZeneca. M.C.F. has received consultancy fees from advisory boards for Novo Nordisk, Sanofi, AstraZeneca, Boehringer Ingelheim, Servier and Pfizer, and honoraria for speaking from Novo Nordisk, Sanofi, AstraZeneca, Boehringer Ingelheim and Servier. M.E.F. has received research support from Amgen and Novo Nordisk. D.R.F. has received honoraria from advisory boards for Sanofi, Eli Lilly, Abbott and Pfizer, and speaking engagements for Sanofi, Novo Nordisk, Eli Lilly, Merk Sharp & Dohme and Medtronic, and has received research grants from Novo Nordisk, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Sanofi, Novartis, Merck Sharp & Dohme, Boehringer Ingelheim, Amgen and OPKO. C.G. has participated in scientific advisory boards and received consulting/speaking fees from AstraZeneca, Bayer AG, Boehringer Ingelheim, Eli Lilly, Merck KGaA, Merck Sharp & Dohme, Novo Nordisk, and Sanofi. J.G. has received research funding from Merck Sharp & Dohme, Sanofi Aventis, Eli Lilly, and Novo Nordisk. P.J. has received consultancy fees from advisory boards for Novo Nordisk, Sanofi, AstraZeneca, Boehringer Ingelheim, Servier, Pfizer, Bayer, Eli Lilly, GlaxoSmithKline and Novartis, and honoraria for speaking from Novo Nordisk, Sanofi, Pfizer, Roche, Boehringer Ingelheim and Servier. R.M. has received speaker fees and advisory board honoraria from Novo Nordisk. J.F.M.-T. has participated in advisory panels for Merck, AstraZeneca and Novo Nordisk, has received research support from Merck, Novo Nordisk, Abbott, Nutricia and Vegenat, and is on the speakers' bureau for Merck, Novo Nordisk, Sanofi, AstraZeneca and Menarini. M.A.N. is a member of advisory boards or has consulted with AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Fractyl, GlaxoSmithKline, Intarcia, Menarini/Berlin Chemie, Merck, Sharp & Dohme and Novo Nordisk, has served on the speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Menarini/Berlin Chemie, Merck, Sharp & Dohme, and Novo Nordisk A/S, and his institution has received grant support from AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Intarcia, Menarini/Berlin-Chemie, Merck, Sharp & Dohme, Novartis and Novo Nordisk A/S. S.D.P has received consulting fees and honoraria for speaking from Novo Nordisk, AstraZeneca, Boehringer Ingelheim, Merck, Sanofi, Abbott, Eli Lilly, Valeant and Janssen. R.J.S. has received consultancy fees from Novo Nordisk and is on the Speaker's Bureau for AstraZeneca, Eli Lilly and Novo Nordisk. W.H.-H.S. has received advisor and/or speaker fees from AstraZeneca, Bayer HealthCare, Boehringer Ingelheim Pharmaceuticals, Daiichi-Sankyo, Eli Lilly and Company, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma Corporation, Novartis, Novo Nordisk, Pfizer, Sanofi-Aventis and Takeda Pharmaceutical Company. C.J.T. (or the institute with which he is associated) has received research grants, served as a consultant for, or gave lectures organised by Merck, AstraZeneca and Novo Nordisk. M.H. has received investigator-initiated research grants on projects related to GLP-1 biology from AstraZeneca, Merck, Novo Nordisk, has received consulting fees or honoraria from AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk and Roche, and is co-inventor of two provisional patents related to GLP-1. M.T., M.S. and O.K.J. are employees of Novo Nordisk A/S. P.B., C.D. and N.T. have no competing interests. AUTHOR CONTRIBUTIONS: S.C.B., O.M., R.A., P.B., Ab.C., Ag.C., C.D., K.D., M.C.F., M.E.F., D.R.F., J.G., C.G., P.J., J.F.M.-T., M.A.N., S.D.P., W.H.-H.S., R.S., C.J.T., N.T. and M.H. were principal study investigators (S.C.B. and M.H. were signatory investigators) involved in the conduct of the trial, interpreting the data and in writing, critically reviewing and approving the final manuscript. O.K.J. was the trial statistician and was involved in analysing the data and in writing, critically reviewing and approving the final manuscript. M.T. was involved in the design and conduct of the trial, interpreting the data, and in writing, critically reviewing and approving the final manuscript. M.S. was involved in the coordination and conduct of the trial, interpreting the data and in writing, critically reviewing and approving the final manuscript. EDAT- 2018/10/05 06:00 MHDA- 2020/02/06 06:00 PMCR- 2019/06/21 CRDT- 2018/10/05 06:00 PHST- 2018/06/20 00:00 [received] PHST- 2018/09/18 00:00 [revised] PHST- 2018/10/01 00:00 [accepted] PHST- 2018/10/05 06:00 [pubmed] PHST- 2020/02/06 06:00 [medline] PHST- 2018/10/05 06:00 [entrez] PHST- 2019/06/21 00:00 [pmc-release] AID - DOM13553 [pii] AID - 10.1111/dom.13553 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 Mar;21(3):499-508. doi: 10.1111/dom.13553. Epub 2018 Nov 11. PMID- 30269833 OWN - NLM STAT- MEDLINE DCOM- 20190606 LR - 20190606 IS - 1916-7075 (Electronic) IS - 0828-282X (Linking) VI - 34 IP - 10 DP - 2018 Oct TI - Diabetes Mellitus and Cardiovascular Disease: An Evidence-Based Review of Provincial Formulary Coverage. PG - 1362-1364 LID - S0828-282X(18)30514-2 [pii] LID - 10.1016/j.cjca.2018.07.011 [doi] AB - Cardiovascular mortality is the primary cause of death in patients with type 2 diabetes mellitus (T2DM). Recently, clinical trials of the sodium-glucose transport protein 2 (SGLT-2) inhibitors empagliflozin and canagliflozin and of the glucagon-like peptide-1 (GLP-1) agonists liraglutide and semaglutide demonstrated that the agents reduced cardiovascular events. Furthermore, empagliflozin and liraglutide reduced cardiovascular mortality. However, despite the proven cardiac benefits, many but not all provincial formularies have restrictive rules for payment and access for SGLT-2 inhibitors and GLP-1 agonists. These restrictions impede a practitioner's ability to provide optimal care for patients with T2DM and cardiovascular disease. The 2018 Diabetes Canada Guidelines recommend the use of a glucose-lowering agent with proven cardiovascular benefit (ie, empagliflozin, canagliflozin, liraglutide, or semaglutide) as second-line therapy after metformin, for patients with T2DM and cardiovascular disease who fail to achieve the glycemic target of A1C <7% with metformin. We recognize that provinces must allot resources especially when health care budgets are limited and not able to provide all available treatments. However, today we have glucose-lowering agents that reduce mortality in patients at very high cardiovascular risk. Furthermore, for empagliflozin, the cost effectiveness is highly favourable. Consequently, we urge provincial formularies to re-examine the access requirements for SGLT-2 inhibitors and to consider adding GLP-1 agonists use to reflect current evidence and clinical guideline recommendations. CI - Copyright (c) 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. FAU - Riar, Shivraj S AU - Riar SS AD - College of Medicine Regina, University of Saskatchewan, Saskatoon, Saskatchewan, Canada. FAU - Fitchett, David AU - Fitchett D AD - St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - FitzGerald, Jeremy AU - FitzGerald J AD - Department of Endocrinology, Regina University of Saskatchewan, Regina, Saskatchewan, Canada. FAU - Dehghani, Payam AU - Dehghani P AD - Prairie Vascular Research Network, Regina, Saskatchewan, Canada. Electronic address: payamde@gmail.com. LA - eng PT - Journal Article PT - Review DEP - 20180719 PL - England TA - Can J Cardiol JT - The Canadian journal of cardiology JID - 8510280 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) SB - IM MH - Blood Glucose/metabolism MH - Cardiovascular Diseases/*etiology/prevention & control MH - Diabetes Mellitus, Type 2/blood/*complications/drug therapy MH - *Evidence-Based Medicine MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - *Practice Guidelines as Topic EDAT- 2018/10/03 06:00 MHDA- 2019/06/07 06:00 CRDT- 2018/10/02 06:00 PHST- 2018/05/05 00:00 [received] PHST- 2018/07/14 00:00 [revised] PHST- 2018/07/15 00:00 [accepted] PHST- 2018/10/02 06:00 [entrez] PHST- 2018/10/03 06:00 [pubmed] PHST- 2019/06/07 06:00 [medline] AID - S0828-282X(18)30514-2 [pii] AID - 10.1016/j.cjca.2018.07.011 [doi] PST - ppublish SO - Can J Cardiol. 2018 Oct;34(10):1362-1364. doi: 10.1016/j.cjca.2018.07.011. Epub 2018 Jul 19. PMID- 30259238 OWN - NLM STAT- MEDLINE DCOM- 20191021 LR - 20250103 IS - 1534-3170 (Electronic) IS - 1523-3782 (Linking) VI - 20 IP - 11 DP - 2018 Sep 26 TI - Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Risk Reduction in Type 2 Diabetes Mellitus: Is It a Class Effect? PG - 113 LID - 10.1007/s11886-018-1051-2 [doi] AB - PURPOSE OF REVIEW: Mimetics and analogs that extend the half-life of native glucagon-like peptide-1 (GLP-1), i.e., glucagon-like peptide-1 receptor agonists (GLP-1 RAs), at therapeutic doses, are indicated as adjuncts to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). In patients with T2DM, GLP-1 RAs not only affect improvements in impaired beta cell and alpha cell function, suppress appetite, and induce weight loss but also possess multiple cardiovascular protective properties that potentially have a beneficial impact on atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality. RECENT FINDINGS: Required to demonstrate CV safety, compared to standard-of-care antidiabetic therapies, GLP-1 RAs have revealed statistically significant non-inferiority (p < 0.001), among CV outcome trials (CVOTs) thus far completed. Once-daily liraglutide and once-weekly semaglutide demonstrated significant superiority (p = 0.01 and p = 0.02, respectively), reducing 3-point composite major adverse cardiovascular events (MACE) in extreme risk secondary prevention adults with T2DM. Once-weekly exenatide demonstrated only a non-significant (p = 0.06) favorable trend for CV superiority, possibly due to in-trial mishaps, including placebo drop-ins with other CV protective medications. The short half-life lixisenatide was neutral (p = 0.81) in reducing MACE, most likely due to ineffective once-daily dosing. Structural differences among GLP-1 mimetics and analogs may explain potency differences in both A1C reduction and weight loss that may parallel important cardiovascular protective properties of the GLP-1 RA class. Significant superiority in reducing 3-point composite MACE in adults with T2DM with GLP-1 RAs has been limited to liraglutide and semaglutide. Careful attention to within-trial drop-in of cardioprotective antidiabetic agents assuring equipoise between placebo and investigational product groups might demonstrate significant MACE risk reduction with once-weekly exenatide. Maintenance of 24-h circulating levels, by an alternative administration method, may resurrect lixisenatide as a cardioprotective agent. Before a GLP-1 RA bioequivalence "class effect" claim for composite MACE risk reduction superiority can be fully discussed, we are obliged to wait for the pending results of CVOTs with other GLP-1 RAs, particularly albiglutide and dulaglutide, where steric hindrance may potentially inhibit full mimicry of pharmacologic GLP-1. FAU - Li, Yixing AU - Li Y AD - West Anaheim Medical Center, Department of Medicine, OPTI-West, 3033 West Orange Ave, Anaheim, CA, 92804, USA. FAU - Rosenblit, Paul D AU - Rosenblit PD AD - Dept. of Medicine, Div. Endocrinology, Diabetes & Metabolism, University California, Irvine, School of Medicine, Irvine, CA, USA. pdrosenblit@yahoo.com. AD - Diabetes Out-Patient Clinic, UCI Medical Center, Orange, CA, USA. pdrosenblit@yahoo.com. AD - Diabetes / Lipid Management & Research Center, 18821 Delaware St., Suite 202, Huntington Beach, CA, 92648, USA. pdrosenblit@yahoo.com. LA - eng PT - Journal Article PT - Review DEP - 20180926 PL - United States TA - Curr Cardiol Rep JT - Current cardiology reports JID - 100888969 RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cardiovascular Diseases/*drug therapy MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drug Administration Schedule MH - Glucagon-Like Peptide 1/*analogs & derivatives MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - Risk Reduction Behavior MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular disease OT - ELIXIR OT - EXSCEL OT - Glucagon-like peptide-1 OT - HARMONY OT - LEADER OT - REWIND OT - Receptor agonists (GLP-1 RAs) OT - SUSTAIN-6 OT - Type 2 diabetes mellitus (T2DM) EDAT- 2018/09/28 06:00 MHDA- 2019/10/23 06:00 CRDT- 2018/09/28 06:00 PHST- 2018/09/28 06:00 [entrez] PHST- 2018/09/28 06:00 [pubmed] PHST- 2019/10/23 06:00 [medline] AID - 10.1007/s11886-018-1051-2 [pii] AID - 10.1007/s11886-018-1051-2 [doi] PST - epublish SO - Curr Cardiol Rep. 2018 Sep 26;20(11):113. doi: 10.1007/s11886-018-1051-2. PMID- 30243806 OWN - NLM STAT- MEDLINE DCOM- 20191025 LR - 20260127 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 45 IP - 2 DP - 2019 Apr TI - Comparing once-weekly semaglutide to incretin-based therapies in patients with type 2 diabetes: a systematic review and meta-analysis. PG - 102-109 LID - S1262-3636(18)30173-3 [pii] LID - 10.1016/j.diabet.2018.09.002 [doi] AB - AIMS: Our aim was to compare once-weekly semaglutide to incretin-based therapies - defined as either dipeptidyl peptidase-4 inhibitors (DPP-4i) or other glucagon-like peptide-1 receptor agonist (GLP-1RA) - in patients with type 2 diabetes. METHODS: We searched for randomized trials comparing once-weekly semaglutide to other incretin-based therapies in patients with type 2 diabetes. We pooled trials that compared semaglutide to other GLP-1RA together, and those comparing semaglutide to DPP-4i together. The primary outcome was the change in haemoglobin A(1c) over time. RESULTS: Five trials met our inclusion criteria. There was a significantly greater reduction in haemoglobin A(1c) favouring semaglutide when compared to other GLP-1RA or DPP-4i [MD (95% CI) = -0.38% (-0.62, -0.15) and -1.14% (-1.53, -0.75) respectively]. There was a significantly greater weight loss favouring semaglutide when compared to other GLP-1RA or DPP-4i [MD (95% CI) = -2.50 kg (-3.91, -1.09) and -3.19 kg (-3.66, -2.72) respectively]. The proportion of patients achieving glycaemic goals and goal weight loss was greater in semaglutide-treated patients when compared to either other GLP-1RA or DPP-4i. However, semaglutide-treated patients had a significantly higher incidence of gastrointestinal side effects. CONCLUSIONS: While both once-weekly semaglutide and other incretin-based therapies can reduce haemoglobin A(1c), semaglutide causes a more potent haemoglobin A(1c) reduction and greater weight loss when compared to other incretin-based therapies. However, this potent effect of semaglutide was associated with a higher incidence of gastrointestinal side effects. Additional studies are needed to determine whether this marked reduction in both haemoglobin A(1c) and body weight may translate into improved cardiovascular outcomes. CI - Published by Elsevier Masson SAS. FAU - Mishriky, B M AU - Mishriky BM AD - Department of Internal Medicine, East Carolina University, Greenville, NC, USA. Electronic address: mishrikyb@ecu.edu. FAU - Cummings, D M AU - Cummings DM AD - Department of Family Medicine, East Carolina University, Greenville, NC, 27834 USA. Electronic address: cummingsd@ecu.edu. FAU - Powell, J R AU - Powell JR AD - Department of Internal Medicine, East Carolina University, Greenville, NC, 27834 USA. Electronic address: powellj@ecu.edu. FAU - Sewell, K A AU - Sewell KA AD - Laupus Health Sciences Library, East Carolina University, Greenville, NC, 27834 USA. Electronic address: browderk@ecu.edu. FAU - Tanenberg, R J AU - Tanenberg RJ AD - Division of Endocrinology, East Carolina University, Greenville, NC, 27834 USA. Electronic address: tanenbergr@ecu.edu. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20180920 PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Blood Glucose) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Blood Glucose/drug effects/metabolism MH - Diabetes Mellitus, Type 2/blood/*drug therapy/epidemiology MH - Dipeptidyl-Peptidase IV Inhibitors/administration & dosage/adverse effects MH - Drug Administration Schedule MH - Drug Therapy, Combination/adverse effects MH - Female MH - Glucagon-Like Peptide-1 Receptor/antagonists & inhibitors MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis/drug effects/metabolism MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Incretins/*administration & dosage/adverse effects MH - Male MH - Middle Aged MH - Randomized Controlled Trials as Topic/methods/statistics & numerical data MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonist OT - Meta-analysis OT - Semaglutide OT - Type 2 diabetes EDAT- 2018/09/24 06:00 MHDA- 2019/10/28 06:00 CRDT- 2018/09/24 06:00 PHST- 2018/05/25 00:00 [received] PHST- 2018/09/05 00:00 [revised] PHST- 2018/09/10 00:00 [accepted] PHST- 2018/09/24 06:00 [pubmed] PHST- 2019/10/28 06:00 [medline] PHST- 2018/09/24 06:00 [entrez] AID - S1262-3636(18)30173-3 [pii] AID - 10.1016/j.diabet.2018.09.002 [doi] PST - ppublish SO - Diabetes Metab. 2019 Apr;45(2):102-109. doi: 10.1016/j.diabet.2018.09.002. Epub 2018 Sep 20. PMID- 30227157 OWN - NLM STAT- MEDLINE DCOM- 20190809 LR - 20260127 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 111 DP - 2019 Jan TI - Glucagon-like peptide-1 receptor action in the vasculature. PG - 26-32 LID - S0196-9781(18)30165-7 [pii] LID - 10.1016/j.peptides.2018.09.002 [doi] AB - Glucagon-like peptide-1 receptor (GLP-1R) agonists augment insulin secretion and are thus used clinically to improve glycemia in subjects with type 2 diabetes (T2D). As recent data reveal marked improvements in cardiovascular outcomes in T2D subjects treated with the GLP-1R agonists liraglutide and semaglutide in the LEADER and SUSTAIN-6 clinical trials respectively, there is growing interest in delineating the mechanism(s) of action for GLP-1R agonist-induced cardioprotection. Of importance, negligible GLP-1R expression in ventricular cardiac myocytes suggests that cardiac-independent actions of GLP-1R agonists may account for the reduced death rates from cardiovascular causes in T2D subjects enrolled in the LEADER trial. Conversely, vascular smooth muscle cells (VSMCs) appear to express the canonical GLP-1R, and GLP-1/GLP-1R agonists exhibit a number of salutary actions on the vascular endothelium that could potentially contribute to GLP-1R agonists directly improving cardiovascular outcomes in subjects with T2D. We review herein the described actions of GLP-1/GLP-1R agonists on the vascular endothelium, which include antiproliferative actions on VSMCs and endothelial cells, reductions in oxidative stress, and increases in nitric oxide generation. GLP-1 also increases microvascular recruitment and microvascular blood flow. Taken together, such actions may explain the antihypertensive and/or antiatherosclerotic actions attributed to GLP-1/GLP-1R agonists in preclinical and clinical studies. Nonetheless, further mechanistic studies are still necessary to determine the relative importance of such actions in accounting for reductions in macrovascular cardiovascular disease in human subjects with T2D treated with GLP-1R agonists. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Almutairi, Malak AU - Almutairi M AD - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada. FAU - Al Batran, Rami AU - Al Batran R AD - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada. FAU - Ussher, John R AU - Ussher JR AD - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB Canada; Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB, Canada. Electronic address: jussher@ualberta.ca. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20180915 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) MH - Animals MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/blood/drug therapy MH - Endothelium, Vascular/drug effects/metabolism MH - Glucagon-Like Peptide 1/metabolism MH - Glucagon-Like Peptide-1 Receptor/*metabolism MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Liraglutide/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Blood flow OT - Cardioprotection OT - Endothelial function OT - Glucagon-like peptide-1 OT - Glucagon-like peptide-1 receptor OT - Vascular function EDAT- 2018/09/19 06:00 MHDA- 2019/08/10 06:00 CRDT- 2018/09/19 06:00 PHST- 2018/07/04 00:00 [received] PHST- 2018/09/10 00:00 [revised] PHST- 2018/09/11 00:00 [accepted] PHST- 2018/09/19 06:00 [pubmed] PHST- 2019/08/10 06:00 [medline] PHST- 2018/09/19 06:00 [entrez] AID - S0196-9781(18)30165-7 [pii] AID - 10.1016/j.peptides.2018.09.002 [doi] PST - ppublish SO - Peptides. 2019 Jan;111:26-32. doi: 10.1016/j.peptides.2018.09.002. Epub 2018 Sep 15. PMID- 30195966 OWN - NLM STAT- MEDLINE DCOM- 20190730 LR - 20260127 IS - 2352-3840 (Electronic) IS - 1499-2671 (Linking) VI - 43 IP - 2 DP - 2019 Mar TI - Semaglutide: Review and Place in Therapy for Adults With Type 2 Diabetes. PG - 136-145 LID - S1499-2671(18)30109-6 [pii] LID - 10.1016/j.jcjd.2018.05.008 [doi] AB - Guidelines increasingly highlight the importance of multifactorial management in type 2 diabetes, in contrast to the more traditional focus on glycemic control. Semaglutide, a recently approved glucagon-like peptide-1 receptor agonist, is indicated in Canada for adults with type 2 diabetes to improve glycemic control as monotherapy with diet and exercise when metformin is inappropriate or as an add-on to either metformin alone or metformin plus a sulfonylurea or basal insulin. The Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) clinical trial program for semaglutide comprises 6 pivotal global phase 3a trials (SUSTAIN 1 through 6) and 2 Japanese phase 3a trials. Phase 3b trials include SUSTAIN 7, and SUSTAIN 8 and 9 (both ongoing). Results from the completed trials support the superiority of semaglutide for reduction of glycated hemoglobin levels and weight loss vs. placebo as well as active comparators, including sitagliptin, exenatide extended-release, dulaglutide and insulin glargine. SUSTAIN 6 trial data confirmed cardiovascular safety and demonstrated significant reductions in major cardiovascular events with semaglutide vs. placebo, an outcome that confirmed the noninferiority of semaglutide. The robust and sustained effects of semaglutide on glycated hemoglobin levels and weight loss vs. comparators, as well as its safety and possible cardiovascular benefit, address an unmet need in the treatment of type 2 diabetes. This article overviews data from across the semaglutide clinical trial program, including efficacy and safety results and findings from post hoc analyses. The potential place of semaglutide in clinical practice is discussed. CI - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Goldenberg, Ronald M AU - Goldenberg RM AD - LMC Diabetes & Endocrinology, Thornhill, Ontario, Canada. Electronic address: ronaldgoldenberg@gmail.com. FAU - Steen, Oren AU - Steen O AD - LMC Diabetes & Endocrinology, Toronto, Ontario, Canada. LA - eng PT - Journal Article PT - Review DEP - 20180605 PL - Canada TA - Can J Diabetes JT - Canadian journal of diabetes JID - 101148810 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Canada MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/adverse effects/*therapeutic use MH - Glycated Hemoglobin/drug effects/metabolism MH - Humans MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - SUSTAIN trials OT - agoniste des recepteurs GLP-1 (glucagon-like peptide-1) OT - cardiovasculaire OT - cardiovascular OT - diabete de type 2 OT - glucagon-like peptide-1 (GLP-1) receptor agonist OT - perte de poids OT - semaglutide OT - type 2 diabetes OT - weight loss OT - etudes SUSTAIN EDAT- 2018/09/10 06:00 MHDA- 2019/07/31 06:00 CRDT- 2018/09/10 06:00 PHST- 2018/03/06 00:00 [received] PHST- 2018/05/31 00:00 [accepted] PHST- 2018/09/10 06:00 [pubmed] PHST- 2019/07/31 06:00 [medline] PHST- 2018/09/10 06:00 [entrez] AID - S1499-2671(18)30109-6 [pii] AID - 10.1016/j.jcjd.2018.05.008 [doi] PST - ppublish SO - Can J Diabetes. 2019 Mar;43(2):136-145. doi: 10.1016/j.jcjd.2018.05.008. Epub 2018 Jun 5. PMID- 30187176 OWN - NLM STAT- MEDLINE DCOM- 20190906 LR - 20260417 IS - 1539-0829 (Electronic) IS - 1534-4827 (Linking) VI - 18 IP - 10 DP - 2018 Sep 5 TI - Diabetes Treatment in the Elderly: Incorporating Geriatrics, Technology, and Functional Medicine. PG - 95 LID - 10.1007/s11892-018-1052-y [doi] AB - PURPOSE OF REVIEW: The current approach to diabetes in the elderly incorporates components from the comprehensive geriatric approach. The most updated guidelines from the American Diabetes Association reflect influence from the consensus made in 2012 with the American Geriatrics Society. Notably, the framework included the evaluation for geriatric syndromes (falls and urinary incontinence), functional and cognitive abilities. The goal for this review is to provide an updated summary of treatment strategies for community-dwelling older adults. We identified the need to expand our approach by addressing innovative approaches and scientific concepts from telemedicine, functional medicine, and geriatrics. RECENT FINDINGS: Findings on cardiovascular protection with sodium-glucose co-transporter 2 inhibitors (SGLT-2i) and some glucagon-like peptide 1 receptor agonists (GLP-1RA) support their use for older patients with diabetes. However, careful consideration for agent selection must incorporate the presence of geriatric issues, such as geriatric syndromes, or functional and cognitive decline, as they could increase the risk and impact adverse reactions. Telemedicine interventions can improve communication and connection between older patients and their providers, and improve glycemic control. Functional medicine concepts can offer additional adjuvant strategies to support the therapeutic interventions and management of diabetes in the elderly. A systematic review confirmed the efficacy and safety of metformin as first-line therapy of type 2 diabetes in the older adult, but multiple reports highlighted the risk for vitamin B12 deficiency. Randomized controlled trials showed the efficacy and safety of antihyperglycemic agents in the elderly, including some with longer duration and lesser risk for hypoglycemia. Randomized clinical trials showed cardiovascular protection with SGLT-2i (empagliflozin, canagliflozin) and GLP-1RA (liraglutide, semaglutide). The most current guidelines recommend addressing for geriatric syndromes, physical and cognitive function in the elderly, in order to individualize targets and therapeutic strategies. Clinicians managing diabetes in the elderly can play a major role for the early detection and evaluation of geriatric issues in their patients. Telemedicine interventions improve glycemic control, and certain functional medicine strategies could be adjuvant interventions to reduce inflammation and stress, but more studies focused on the elderly population are needed. FAU - Valencia, Willy Marcos AU - Valencia WM AD - Geriatric Research, Education and Clinical Center (GRECC), Miami VA Healthcare System, 1201 NW 16th St. (11 GRC), Miami, FL, 33125, USA. willy.valencia-rodrigo@va.gov. AD - Department of Humanities, Health and Society, Florida International University Herbert Wertheim College of Medicine, Miami, FL, USA. willy.valencia-rodrigo@va.gov. AD - Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA. willy.valencia-rodrigo@va.gov. FAU - Botros, Diana AU - Botros D AD - Jackson Memorial Hospital, University of Miami Miller School of Medicine, 1611 NW 12th Ave, Miami, FL, 33136, USA. FAU - Vera-Nunez, Maria AU - Vera-Nunez M AD - Institute for NeuroImmune Medicine (INIM), Nova Southeastern University College of Osteopathic Medicine, 3301 College Ave, CCR 4th Floor, Fort Lauderdale, FL, 33314, USA. FAU - Dang, Stuti AU - Dang S AD - Geriatric Research, Education and Clinical Center (GRECC), Miami VA Healthcare System, 1201 NW 16th St. (11 GRC), Miami, FL, 33125, USA. AD - Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. LA - eng PT - Journal Article PT - Systematic Review DEP - 20180905 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Hypoglycemic Agents) SB - IM MH - Aged MH - Cognition/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - *Geriatrics MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - Telemedicine MH - Treatment Outcome OTO - NOTNLM OT - Diabetes OT - Functional medicine OT - Geriatrics OT - Management OT - Older adult OT - Telemedicine EDAT- 2018/09/07 06:00 MHDA- 2019/09/07 06:00 CRDT- 2018/09/07 06:00 PHST- 2018/09/07 06:00 [entrez] PHST- 2018/09/07 06:00 [pubmed] PHST- 2019/09/07 06:00 [medline] AID - 10.1007/s11892-018-1052-y [pii] AID - 10.1007/s11892-018-1052-y [doi] PST - epublish SO - Curr Diab Rep. 2018 Sep 5;18(10):95. doi: 10.1007/s11892-018-1052-y. PMID- 30171481 OWN - NLM STAT- MEDLINE DCOM- 20190906 LR - 20250103 IS - 1539-0829 (Electronic) IS - 1534-4827 (Linking) VI - 18 IP - 10 DP - 2018 Aug 31 TI - Cardiovascular Effects of Different GLP-1 Receptor Agonists in Patients with Type 2 Diabetes. PG - 92 LID - 10.1007/s11892-018-1043-z [doi] AB - PURPOSE OF REVIEW: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have positive effects on weight loss, blood pressure, hyperlipidemia, and glycemic control. They exhibit a broad range of effects on the cardiovascular system that are independent of changes in blood glucose. Cardiovascular outcome trials have demonstrated safety of GLP-1 RAs but results for cardiovascular efficacy were varied. The aim of the present review is the assessment of the effects of GLP-1 RAs on cardiovascular risk factors, and major cardiovascular events. RECENT FINDINGS: Use of GLP-1 RAs was associated with relative risk reduction in cardiovascular mortality and all-cause mortality with no significant differences for the incidence of severe hypoglycemia, pancreatitis, pancreatic cancer, or medullary thyroid cancer when compared to placebo. Although there are differences between individual medications with respect to their effects on cardiovascular events, GLP-1 RAs offer a favorable risk-benefit profile. The present review confirms the cardiovascular safety and efficacy vs placebo of GLP-1 RAs in patients with type 2 diabetes at moderate-to-high atherosclerotic cardiovascular risk without significant side effects. Although professional guidelines recommend metformin as the sole first-line agent, GLP-1 RAs can be used as first-line therapy in individuals with type 2 diabetes who either are intolerant to metformin or have high cardiovascular risk factors. FAU - Bahtiyar, Gul AU - Bahtiyar G AD - Division of Endocrinology, State University of New York Health Science Center, Brooklyn, NY, USA. AD - Department of Medicine, Woodhull Medical & Mental Health Center, Brooklyn, NY, USA. AD - Department of Internal Medicine, Division of Endocrinology, Woodhull Medical & Mental Health Center, New York University School of Medicine, 760 Broadway, Brooklyn, NY, 11206, USA. FAU - Pujals-Kury, Jean AU - Pujals-Kury J AD - Division of Endocrinology, State University of New York Health Science Center, Brooklyn, NY, USA. FAU - Sacerdote, Alan AU - Sacerdote A AD - Division of Endocrinology, State University of New York Health Science Center, Brooklyn, NY, USA. Alan.Sacerdote@woodhullhc.nychhc.org. AD - Department of Medicine, Woodhull Medical & Mental Health Center, Brooklyn, NY, USA. Alan.Sacerdote@woodhullhc.nychhc.org. AD - Department of Internal Medicine, Division of Endocrinology, Woodhull Medical & Mental Health Center, New York University School of Medicine, 760 Broadway, Brooklyn, NY, 11206, USA. Alan.Sacerdote@woodhullhc.nychhc.org. LA - eng PT - Journal Article PT - Review DEP - 20180831 PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Biomarkers) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Biomarkers/metabolism MH - Blood Pressure MH - Cardiovascular System/*pathology MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Humans MH - Risk Factors MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Albiglutide OT - Cardiovascular outcomes OT - Cardiovascular risk factors OT - Dulaglutide OT - Exenatide OT - Glucagon-like peptide-1 receptor agonists OT - HbA1c OT - Liraglutide OT - Lixisenatide OT - Semaglutide OT - Type 2 diabetes EDAT- 2018/09/02 06:00 MHDA- 2019/09/07 06:00 CRDT- 2018/09/02 06:00 PHST- 2018/09/02 06:00 [entrez] PHST- 2018/09/02 06:00 [pubmed] PHST- 2019/09/07 06:00 [medline] AID - 10.1007/s11892-018-1043-z [pii] AID - 10.1007/s11892-018-1043-z [doi] PST - epublish SO - Curr Diab Rep. 2018 Aug 31;18(10):92. doi: 10.1007/s11892-018-1043-z. PMID- 30156747 OWN - NLM STAT- MEDLINE DCOM- 20190529 LR - 20250103 IS - 1520-7560 (Electronic) IS - 1520-7552 (Linking) VI - 35 IP - 1 DP - 2019 Jan TI - Glucagon-like peptide-1 receptor agonists in type 2 diabetes treatment: are they all the same? PG - e3070 LID - 10.1002/dmrr.3070 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are an important class of drugs with a well-established efficacy and safety profile in patients with type 2 diabetes mellitus. Agents in this class are derived from either exendin-4 (a compound present in Gila monster venom) or modifications of human GLP-1 active fragment. Differences among these drugs in duration of action (ie, short-acting vs long-acting), effects on glycaemic control and weight loss, immunogenicity, tolerability profiles, and administration routes offer physicians several options when selecting the most appropriate agent for individual patients. Patient preference is also an important consideration. The aim of this review is to discuss the differences between and similarities of GLP-1 RAs currently approved for clinical use, focusing particularly on the properties characterising the single short-acting and long-acting GLP-1 RAs rather than on their individual efficacy and safety profiles. The primary pharmacodynamic difference between short-acting (ie, exenatide twice daily and lixisenatide) and long-acting (ie, albiglutide, dulaglutide, exenatide once weekly, liraglutide, and semaglutide) GLP-1 RAs is that short-acting agents primarily delay gastric emptying (lowering postprandial glucose) and long-acting agents affect both fasting glucose (via enhanced glucose-dependent insulin secretion and reduced glucagon secretion in the fasting state) and postprandial glucose (via enhanced postprandial insulin secretion and inhibition of glucagon secretion). Other advantages of long-acting GLP-1 RAs include smaller fluctuations in plasma drug concentrations, improved gastrointestinal tolerability profiles, and simpler, more convenient administration schedules (once daily for liraglutide and once weekly for albiglutide, dulaglutide, the long-acting exenatide formulation, and semaglutide), which might improve treatment adherence and persistence. CI - (c) 2018 John Wiley & Sons, Ltd. FAU - Gentilella, Raffaella AU - Gentilella R AD - Eli Lilly Italia, Sesto Fiorentino, Italy. FAU - Pechtner, Valeria AU - Pechtner V AD - Lilly Diabetes, Eli Lilly and Company, Neuilly-sur-Seine, France. FAU - Corcos, Antonella AU - Corcos A AD - Eli Lilly Italia, Sesto Fiorentino, Italy. FAU - Consoli, Agostino AU - Consoli A AUID- ORCID: 0000-0002-1885-451X AD - Department of Medicine and Ageing Sciences and CeSI-Met, University D'Annunzio, Chieti, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20181004 PL - England TA - Diabetes Metab Res Rev JT - Diabetes/metabolism research and reviews JID - 100883450 RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 5E7U48495E (rGLP-1 protein) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9P1872D4OL (Exenatide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Exenatide/therapeutic use MH - Glucagon-Like Peptide 1/analogs & derivatives/therapeutic use MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - albiglutide OT - dulaglutide OT - exenatide OT - glucagon-like peptide-1 receptor agonist OT - liraglutide OT - lixisenatide OT - semaglutide EDAT- 2018/08/30 06:00 MHDA- 2019/05/30 06:00 CRDT- 2018/08/30 06:00 PHST- 2017/12/14 00:00 [received] PHST- 2018/07/30 00:00 [revised] PHST- 2018/08/18 00:00 [accepted] PHST- 2018/08/30 06:00 [pubmed] PHST- 2019/05/30 06:00 [medline] PHST- 2018/08/30 06:00 [entrez] AID - 10.1002/dmrr.3070 [doi] PST - ppublish SO - Diabetes Metab Res Rev. 2019 Jan;35(1):e3070. doi: 10.1002/dmrr.3070. Epub 2018 Oct 4. PMID- 30156447 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20250103 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 24 IP - 9-a Suppl DP - 2018 Sep TI - Health-Related Quality of Life Assessments with Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus. PG - S30-S41 LID - 10.18553/jmcp.2018.24.9-a.s30 [doi] AB - Type 2 diabetes (T2DM) is associated with significant impairment in health-related quality of life (HRQoL). A patient-centered collaborative approach is recommended to optimize clinical outcomes, including HRQoL, in this patient population. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) provide effective glycemic control and have demonstrated beneficial effects on HRQoL and treatment satisfaction. Available once-weekly GLP-1 RAs may offer enhanced convenience compared with daily GLP-1 RAs and include exenatide extended-release (ER), dulaglutide, and semaglutide. This article reviews the impact of once-weekly GLP-1 RAs on HRQoL and treatment satisfaction in patients with T2DM. Compared with oral antihyperglycemic drugs, insulin, and daily GLP-1 RAs, once-weekly GLP-1 RAs offer benefits with regard to HRQoL and treatment satisfaction. These benefits appear to be largely mediated by relative drug effects on glycemic control, weight, and hypoglycemia. While there was not an overall class benefit of once-weekly GLP-1 RAs compared with daily GLP-1 RAs on HRQoL and treatment satisfaction, results suggested that once-weekly GLP-1 RAs may enhance certain elements of treatment satisfaction and increase willingness to continue treatment. In 2 studies comparing once-weekly GLP-1 RAs with each other, semaglutide produced significantly greater improvement in overall treatment satisfaction compared with exenatide ER but not dulaglutide. Once-weekly GLP-1 RAs represent an effective and convenient treatment option that may potentially increase treatment satisfaction and enhance adherence, contributing to improved health outcomes. DISCLOSURES: This supplement was funded by Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Schneider reports advisory board fees from Intarcia, Lilly, and Novo Nordisk. Wyne has nothing to disclose. FAU - Billings, Liana K AU - Billings LK AD - 1 NorthShore University Health System, Skokie, Illinois. FAU - Handelsman, Yehuda AU - Handelsman Y AD - 2 Metabolic Institute of America, Tarzana, California. FAU - Heile, Michael AU - Heile M AD - 3 TriHealth, Cincinnati, Ohio. FAU - Schneider, Doron AU - Schneider D AD - 4 Jefferson Health at Abington Hospital, Abington, Pennsylvania. FAU - Wyne, Kathleen AU - Wyne K AD - 5 The Ohio State University Wexner Medical School, Columbus. LA - eng PT - Journal Article PT - Review PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Diabetes Mellitus, Type 2/blood/*drug therapy/psychology MH - Drug Administration Schedule MH - Glucagon-Like Peptide-1 Receptor/blood MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Insulin/blood MH - *Quality of Life/psychology MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10408424 COIS- This supplement was funded by Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Schneider reports advisory board fees from Intarcia, Lilly, and Novo Nordisk. Wyne has nothing to disclose. EDAT- 2018/08/30 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/09/01 CRDT- 2018/08/30 06:00 PHST- 2018/08/30 06:00 [entrez] PHST- 2018/08/30 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/09/01 00:00 [pmc-release] AID - 10.18553/jmcp.2018.24.9-a.s30 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2018 Sep;24(9-a Suppl):S30-S41. doi: 10.18553/jmcp.2018.24.9-a.s30. PMID- 30156446 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20250103 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 24 IP - 9-a Suppl DP - 2018 Sep TI - Cardiovascular Outcomes with Once-Weekly GLP-1 RAs: Clinical and Economic Implications. PG - S42-S52 LID - 10.18553/jmcp.2018.24.9-a.s42 [doi] AB - Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic cardiovascular (ASCVD) disease, which is the largest contributor to the economic burden of diabetes. Minimization of disease morbidity through comprehensive management of ASCVD risk factors, including but not limited to hyperglycemia, is a key goal of T2DM therapy. Emerging evidence with some glucagon-like peptide-1 receptor agonists (GLP-1 RAs) points to beneficial effects across a range of atherosclerotic risk factors and possible improvement of some cardiovascular outcomes independent of these effects. Given these benefits, there has been substantial interest in evaluating the cardiovascular safety of GLP-1 RAs as well as their potential to reduce the risk of major adverse cardiac events (MACE). Following the superior clinical outcome with the once-daily GLP-1 RA liraglutide (Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results [LEADER]), this review examines and summarizes the effects of once-weekly GLP-1 RAs, including exenatide extended release (ER), dulaglutide, and semaglutide, on reducing cardiovascular events in patients with T2DM. A phase 3 cardiovascular outcomes trial (EXSCEL) of exenatide ER found no significant difference between exenatide ER and placebo in reducing MACE in patients with T2DM. In a phase 3 premarketing trial in T2DM patients at high risk of cardiovascular disease (SUSTAIN-6), semaglutide significantly reduced the risks of MACE and non-fatal stroke compared with placebo. A phase 3 study (REWIND) is underway to evaluate the effects of dulaglutide on MACE. Considering the substantial costs of cardiovascular disease in patients with T2DM, it will be of interest to assess the impact of treatment with once-weekly GLP-1 RAs on cardiovascular disease-related costs among patients with T2DM. DISCLOSURES: This supplement was funded by Novo Nordisk. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Wyne has nothing to disclose. FAU - Heile, Michael AU - Heile M AD - 1 TriHealth, Cincinnati, Ohio. FAU - Wyne, Kathleen AU - Wyne K AD - 2 The Ohio State University Wexner Medical Center, Columbus. FAU - Billings, Liana K AU - Billings LK AD - 3 NorthShore University Health System, Skokie, Illinois. FAU - Cannon, Anthony AU - Cannon A AD - 4 Private Practice, Hamilton, New Jersey. FAU - Handelsman, Yehuda AU - Handelsman Y AD - 5 Metabolic Institute of America, Tarzana, California. FAU - Shannon, Michael AU - Shannon M AD - 6 Olympia Endocrinology, Lacey, Washington. LA - eng PT - Journal Article PT - Review PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cardiovascular Diseases/*drug therapy/*economics/epidemiology MH - Diabetes Mellitus, Type 2/*drug therapy/*economics/epidemiology MH - Drug Administration Schedule MH - Humans MH - Hypoglycemic Agents/administration & dosage/*economics MH - Randomized Controlled Trials as Topic/economics/methods MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC10408396 COIS- This supplement was funded by Novo Nordisk. Heile reports speaker fees from and has served as advisor to Novo Nordisk. Billings reports personal fees from Dexcom, Novo Nordisk, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Wyne has nothing to disclose. EDAT- 2018/08/30 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/09/01 CRDT- 2018/08/30 06:00 PHST- 2018/08/30 06:00 [entrez] PHST- 2018/08/30 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/09/01 00:00 [pmc-release] AID - 10.18553/jmcp.2018.24.9-a.s42 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2018 Sep;24(9-a Suppl):S42-S52. doi: 10.18553/jmcp.2018.24.9-a.s42. PMID- 30156445 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20260127 IS - 2376-1032 (Electronic) IS - 2376-0540 (Print) IS - 2376-0540 (Linking) VI - 24 IP - 9-a Suppl DP - 2018 Sep TI - Glycemic Efficacy, Weight Effects, and Safety of Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists. PG - S14-S29 LID - 10.18553/jmcp.2018.24.9-a.s14 [doi] AB - This article provides an overview of the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the treatment of type 2 diabetes mellitus (T2DM). GLP-1 RAs stimulate pancreatic GLP-1 receptors, which increases insulin secretion, delays gastric emptying, and increases satiety. As a class, GLP-1 RAs lower A1c levels and have been associated with reductions in weight and blood pressure and reduced fluctuations in glucose levels, and they have a low risk of hypoglycemia. Exenatide extended release (ER) and dulaglutide monotherapy have shown similar or superior reductions in A1c and weight compared with various oral antidiabetic drugs (OADs). Semaglutide has been shown to reduce both A1c and body weight compared with placebo and, in head-to-head studies versus both exenatide ER and dulaglutide, showed greater reductions in A1c and body weight. Once-weekly GLP-1 RAs have also been evaluated as add-on therapy in the continuum of care for the treatment of T2DM in combination with a variety of background medications, including 1 or more OADs (metformin, sulfonylureas, and/or thiazolidinediones), basal insulin, and prandial insulin. Gastrointestinal adverse events (e.g., nausea, vomiting, and diarrhea) are the most common side effects with once-weekly GLP-1 RAs. Rates of hypoglycemia, and especially major/severe hypoglycemia, are low with once-weekly GLP-1 RAs but, as expected, are higher when used in combination with sulfonylureas or insulin. These once-weekly GLP-1 RAs provide a safe and effective treatment option for patients with T2DM and may offer improved convenience and possibly greater adherence compared with daily GLP-1 RAs. DISCLOSURES: This supplement was funded by Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Schneider reports advisory board fees from Intarcia, Lilly, and Novo Nordisk. Wyne has nothing to disclose. FAU - Handelsman, Yehuda AU - Handelsman Y AD - 1 Metabolic Institute of America, Tarzana, California. FAU - Wyne, Kathleen AU - Wyne K AD - 2 The Ohio State University Wexner Medical Center, Columbus. FAU - Cannon, Anthony AU - Cannon A AD - 3 Private Practice, Hamilton, New Jersey. FAU - Shannon, Michael AU - Shannon M AD - 4 PMG Olympia Endocrinology, Lacey, Washington. FAU - Schneider, Doron AU - Schneider D AD - 5 Jefferson Health at Abington Hospital, Abington, Pennsylvania. LA - eng PT - Journal Article PT - Review PL - United States TA - J Manag Care Spec Pharm JT - Journal of managed care & specialty pharmacy JID - 101644425 RN - 0 (Blood Glucose) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM EIN - J Manag Care Spec Pharm. 2018 Nov;24(11):1196a. doi: 10.18553/jmcp.2018.24.11.1196a. PMID: 30806138 MH - Blood Glucose/*drug effects/metabolism MH - Body Weight/drug effects/*physiology MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Administration Schedule MH - Exenatide/administration & dosage MH - Glucagon-Like Peptide-1 Receptor/*physiology MH - Glucagon-Like Peptides/administration & dosage/analogs & derivatives MH - Glycemic Index/drug effects/physiology MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Immunoglobulin Fc Fragments/administration & dosage MH - Recombinant Fusion Proteins/administration & dosage MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC10408429 COIS- This supplement was funded by Novo Nordisk. Handelsman reports research grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Grifols, Janssen, Lexicon, Merck, Novo Nordisk, Regeneron, and Sanofi; speaker fees from Amarin, Amgen, AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, Regeneron, and Sanofi; and has served in advisory capacity to Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Eisai, Intarcia, Janssen, Lilly, Merck, Merck-Pfizer, Novo Nordisk, Regeneron, and Sanofi. Cannon reports speaker fees and owns stock in Novo Nordisk. Shannon reports consultant and speaker fees from Novo Nordisk and Boehringer Ingelheim-Lilly Alliance. Schneider reports advisory board fees from Intarcia, Lilly, and Novo Nordisk. Wyne has nothing to disclose. EDAT- 2018/08/30 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/09/01 CRDT- 2018/08/30 06:00 PHST- 2018/08/30 06:00 [entrez] PHST- 2018/08/30 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/09/01 00:00 [pmc-release] AID - 10.18553/jmcp.2018.24.9-a.s14 [doi] PST - ppublish SO - J Manag Care Spec Pharm. 2018 Sep;24(9-a Suppl):S14-S29. doi: 10.18553/jmcp.2018.24.9-a.s14. PMID- 30122306 OWN - NLM STAT- MEDLINE DCOM- 20180919 LR - 20260127 IS - 1474-547X (Electronic) IS - 0140-6736 (Linking) VI - 392 IP - 10148 DP - 2018 Aug 25 TI - Semaglutide and GLP-1 analogues as weight-loss agents. PG - 615-616 LID - S0140-6736(18)31826-9 [pii] LID - 10.1016/S0140-6736(18)31826-9 [doi] FAU - Kluger, Aaron Y AU - Kluger AY AD - Baylor Heart and Vascular Institute, Dallas, TX 75226, USA; Baylor Scott and White Research Institute, Dallas, TX, USA. FAU - McCullough, Peter A AU - McCullough PA AD - Baylor Heart and Vascular Institute, Dallas, TX 75226, USA; Baylor Scott and White Research Institute, Dallas, TX, USA; Baylor University Medical Center, Dallas, TX, USA; Baylor Jack and Jane Hamilton Heart and Vascular Hospital, Dallas, TX, USA. Electronic address: peteramccullough@gmail.com. LA - eng PT - Comment PT - Journal Article DEP - 20180816 PL - England TA - Lancet JT - Lancet (London, England) JID - 2985213R RN - 0 (Anti-Obesity Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2. PMID: 30122305 MH - *Anti-Obesity Agents MH - Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptide 1 MH - Glucagon-Like Peptides MH - *Hypoglycemic Agents MH - Semaglutide EDAT- 2018/08/21 06:00 MHDA- 2018/09/20 06:00 CRDT- 2018/08/21 06:00 PHST- 2018/07/29 00:00 [received] PHST- 2018/08/02 00:00 [accepted] PHST- 2018/08/21 06:00 [pubmed] PHST- 2018/09/20 06:00 [medline] PHST- 2018/08/21 06:00 [entrez] AID - S0140-6736(18)31826-9 [pii] AID - 10.1016/S0140-6736(18)31826-9 [doi] PST - ppublish SO - Lancet. 2018 Aug 25;392(10148):615-616. doi: 10.1016/S0140-6736(18)31826-9. Epub 2018 Aug 16. PMID- 30115742 OWN - NLM STAT- MEDLINE DCOM- 20190826 LR - 20260127 IS - 1470-8736 (Electronic) IS - 0143-5221 (Linking) VI - 132 IP - 15 DP - 2018 Aug 16 TI - Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: a comparative review. PG - 1699-1709 LID - 10.1042/CS20171299 [doi] AB - Type 2 diabetes (T2D) carries risks of both cardiovascular (CV) (myocardial infarction, stroke, and peripheral vascular disease) and microvascular (retinopathy/nephropathy/neuropathy) complications. Glucose-lowering is an effective strategy for preventing microvascular complications, but the extent to which it can reduce CV complications is less certain. Glucagon-like peptide-1 (GLP-1) agonists are potent glucose-lowering agents but also have potentially beneficial effects on other traditional (body weight, blood pressure (BP), and LDL cholesterol) and non-traditional risk factors (low grade inflammation and endothelial dysfunction). The results of four large CV outcome trials with GLP-1 agonists are now available. These have compared lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), and long-acting exenatide (EXSCEL) with placebo and standard of care over 2-4 years; four others (including with dulaglutide and albiglutide) are ongoing. LEADER and SUSTAIN-6 have demonstrated reductions in rates of major adverse CV events with active GLP-1 treatment but ELIXA and EXSCEL have not. In this review, we discuss the mechanisms by which GLP-1 receptor agonists act on the CV system and the design and conduct of these trials. Contrary to the assertions that (a) all GLP-1 agonists reduce CV disease in T2D but to different extents or (b) the magnitude of CV protection is predominantly related to glucose-lowering, we argue that CV benefit is specific to agents that provide longer acting agonism at the GLP-1 receptor. The mechanisms involve reduction in body weight and BP, and lowering of LDL-cholesterol and glucose, but pleiotropic effects-including suppression of low grade inflammation, vasodilation, and natriuresis-are also likely relevant. CI - (c) 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society. FAU - Boyle, James G AU - Boyle JG AD - Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, U.K. AD - School of Medicine, Wolfson Medical School Building, University Avenue, University of Glasgow, Glasgow G12 8TA, U.K. FAU - Livingstone, Rachel AU - Livingstone R AD - Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, U.K. FAU - Petrie, John R AU - Petrie JR AD - Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow G12 8TA, U.K. john.petrie@glasgow.ac.uk. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20180816 PL - England TA - Clin Sci (Lond) JT - Clinical science (London, England : 1979) JID - 7905731 RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 74O62BB01U (lixisenatide) RN - 0 (Glucagon-Like Peptide-2 Receptor) MH - Cardiovascular Diseases/blood/prevention & control MH - Cardiovascular System/*drug effects/metabolism MH - Diabetes Mellitus, Type 2/blood/*prevention & control MH - Exenatide/therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Liraglutide/therapeutic use MH - Peptides/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-2 Receptor OTO - NOTNLM OT - cardiovascular disease OT - clinical trials OT - glucagon-like peptide-1 OT - type 2 diabetes EDAT- 2018/08/18 06:00 MHDA- 2019/08/27 06:00 CRDT- 2018/08/18 06:00 PHST- 2018/06/26 00:00 [received] PHST- 2018/08/02 00:00 [revised] PHST- 2018/08/03 00:00 [accepted] PHST- 2018/08/18 06:00 [entrez] PHST- 2018/08/18 06:00 [pubmed] PHST- 2019/08/27 06:00 [medline] AID - CS20171299 [pii] AID - 10.1042/CS20171299 [doi] PST - epublish SO - Clin Sci (Lond). 2018 Aug 16;132(15):1699-1709. doi: 10.1042/CS20171299. Print 2018 Aug 16. PMID- 30101378 OWN - NLM STAT- MEDLINE DCOM- 20190411 LR - 20260127 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 62 IP - 3 DP - 2018 Dec TI - The safety and efficacy of once-weekly glucagon-like peptide-1 receptor agonist semaglutide in patients with type 2 diabetes mellitus: a systemic review and meta-analysis. PG - 535-545 LID - 10.1007/s12020-018-1708-z [doi] AB - OBJECTIVES: To investigate the safety and efficacy of once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide as monotherapy or add-on to other antihyperglycaemic agents (AHAs) in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, Embase, Cochrane library and ClinicalTrials.gov were searched from the inception to January 18, 2018. Randomised controlled trials (RCTs) comparing semaglutide with placebo or other AHAs in T2DM patients were included in our meta-analysis. Risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CI) were used to evaluate the outcomes. RESULTS: A total of 11 studies with 9519 patients were included in our meta-analysis. The results revealed that compared with placebo or other AHAs, semaglutide had further reduced the level of haemoglobin A1c (HbA1c) [MD 1.03%, 95% CI (0.85%, 1.22%), p < 0.00001], self-measured plasma glucose (SMPG) [MD 1.19 mmol/L, 95% CI (0.84 mmol/L, 1.53 mmol/L), p < 0.00001], fasting plasma glucose (FPG) [MD 1.33 mmol/L, 95% CI (0.97 mmol/L, 1.69 mmol/L), p < 0.00001] and weight [MD 3.61 kg, 95% CI (3.05 kg, 4.17 kg), p < 0.00001] and significantly increased participants who achieved HbA1c < 7.0% [RR 2.26, 95% CI (1.89, 2.70), p < 0.00001] in T2DM patients. Semaglutide had a significant increase in the incidence of adverse events (AEs) [RR 1.06, 95% CI (1.02, 1.11), p < 0.0001] and an analogous incidence in serious adverse events (SAEs) [RR 0.94, 95% CI (0.86, 1.02), p = 0.11] and hypoglycaemic events (severe or blood glucose (BG)-confirmed symptomatic) [RR 0.93, 95% CI (0.74, 1.16), p = 0.50] compared with the control group. CONCLUSIONS: This article revealed that semaglutide had a favourable efficacy and safety in treating T2DM patients. It maybe a superior choice for T2DM patients who have obesity or a poor adherence to daily AHAs. FAU - Li, Xuejing AU - Li X AD - Department of Pharmacy, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Qiaoxi District, 050051, Shijiazhuang, Hebei Province, China. FAU - Qie, Suhui AU - Qie S AD - Department of Pharmacy, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Qiaoxi District, 050051, Shijiazhuang, Hebei Province, China. FAU - Wang, Xianying AU - Wang X AD - Department of Pharmacy, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Qiaoxi District, 050051, Shijiazhuang, Hebei Province, China. FAU - Zheng, Yingying AU - Zheng Y AD - Department of Pharmacy, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Qiaoxi District, 050051, Shijiazhuang, Hebei Province, China. FAU - Liu, Yang AU - Liu Y AD - Department of Pharmacy, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Qiaoxi District, 050051, Shijiazhuang, Hebei Province, China. FAU - Liu, Guoqiang AU - Liu G AD - Department of Pharmacy, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Qiaoxi District, 050051, Shijiazhuang, Hebei Province, China. liugq1223@sohu.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20180812 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Glucagon-Like Peptides/*therapeutic use MH - Glycated Hemoglobin MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Efficacy OT - Meta-analysis OT - Safety OT - Semaglutide OT - Type 2 diabetes mellitus EDAT- 2018/08/14 06:00 MHDA- 2019/04/12 06:00 CRDT- 2018/08/14 06:00 PHST- 2018/04/19 00:00 [received] PHST- 2018/07/30 00:00 [accepted] PHST- 2018/08/14 06:00 [pubmed] PHST- 2019/04/12 06:00 [medline] PHST- 2018/08/14 06:00 [entrez] AID - 10.1007/s12020-018-1708-z [pii] AID - 10.1007/s12020-018-1708-z [doi] PST - ppublish SO - Endocrine. 2018 Dec;62(3):535-545. doi: 10.1007/s12020-018-1708-z. Epub 2018 Aug 12. PMID- 30091169 OWN - NLM STAT- MEDLINE DCOM- 20190819 LR - 20190819 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 21 IP - 1 DP - 2019 Jan TI - Cardiovascular protection in type 2 diabetes: Insights from recent outcome trials. PG - 3-14 LID - 10.1111/dom.13492 [doi] AB - This review examines recent randomized controlled cardiovascular (CV) outcome trials of glucose-lowering therapies in type 2 diabetes and their impact on the treatment of patients with type 2 diabetes. The trials were designed to comply with regulatory requirements to confirm that major adverse cardiac events (MACE) are not detrimentally affected by such therapies. Trials involving dipeptidyl peptidase-4 (DPP-4) inhibitors did not alter a composite MACE outcome comprising CV deaths, non-fatal myocardial infarction and non-fatal stroke; however, the possibility that some members of this class might incur a small increased risk or worsening of heart failure cannot be excluded. Some studies on glucagon-like peptide-1 receptor agonists (liraglutide: LEADER trial; semaglutide: SUSTAIN-6 trial) found significant benefits for MACE, while treatment with sodium-glucose co-transporter-2 inhibitors (empagliflozin: EMPA-REG OUTCOME trial; canagliflozin: CANVAS trial) also significantly reduced MACE and reduced hospitalization for heart failure. Comparisons among trials are complicated by variance in the populations recruited, particularly CV status at randomization, and differences in trial design, data collection and analyses. A large proportion of patients recruited into these trials have previously experienced adverse CV events; thus, the therapies are mostly assessing secondary prevention of a further event. This contrasts with the overall type 2 diabetes population receiving glucose-lowering therapies, of whom the majority will not have had MACE and will be regarded as primary prevention. Overall, the trials provide reassuring evidence that new glucose-lowering medications do not adversely affect CV events and some of these agents may offer CV protection. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Bailey, Clifford J AU - Bailey CJ AUID- ORCID: 0000-0002-6998-6811 AD - School of Life and Health Sciences, Aston University, Birmingham, UK. FAU - Marx, Nikolaus AU - Marx N AD - Department of Internal Medicine I, RWTH Aachen University, Aachen, Germany. LA - eng PT - Journal Article PT - Review DEP - 20180907 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Hypoglycemic Agents) MH - *Cardiovascular Diseases/complications/physiopathology MH - *Diabetes Mellitus, Type 2/complications/drug therapy/physiopathology MH - Humans MH - *Hypoglycemic Agents/adverse effects/therapeutic use MH - Randomized Controlled Trials as Topic OTO - NOTNLM OT - alogliptin OT - canagliflozin OT - cardiovascular outcomes OT - dapagliflozin OT - empagliflozin OT - exenatide OT - linagliptin OT - liraglutide OT - lixisenatide OT - metformin OT - saxagliptin OT - semaglutide OT - sitagliptin OT - type 2 diabetes EDAT- 2018/08/10 06:00 MHDA- 2019/08/20 06:00 CRDT- 2018/08/10 06:00 PHST- 2018/07/02 00:00 [received] PHST- 2018/07/29 00:00 [revised] PHST- 2018/08/04 00:00 [accepted] PHST- 2018/08/10 06:00 [pubmed] PHST- 2019/08/20 06:00 [medline] PHST- 2018/08/10 06:00 [entrez] AID - 10.1111/dom.13492 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 Jan;21(1):3-14. doi: 10.1111/dom.13492. Epub 2018 Sep 7. PMID- 30083774 OWN - NLM STAT- MEDLINE DCOM- 20190409 LR - 20250729 IS - 1433-2965 (Electronic) IS - 0937-941X (Linking) VI - 29 IP - 12 DP - 2018 Dec TI - Glucagon-like peptide-1 receptor agonists and fracture risk: a network meta-analysis of randomized clinical trials. PG - 2639-2644 LID - 10.1007/s00198-018-4649-8 [doi] AB - Our network meta-analysis analyzed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on fracture risk. By combining data from randomized controlled trials, we found that GLP-1 RAs were associated with a decreased bone fracture risk, and exenatide is the best option agent with regard to the risk of fracture. This study is registered with PROSPERO (CRD42018094433). INTRODUCTION: Data on the effects of GLP-1 RAs on fracture risk are conflicted. This study aimed to analyze the available evidence on the effects of GLP-1 RAs on fracture risk in type 2 diabetes mellitus patients. METHODS: Electronic databases were searched for relevant published articles, and unpublished studies presented at ClinicalTrials.gov were searched for relevant clinical data. All analyses were performed with STATA 12.0 and R software (Version 3.4.4). We estimated the risk ratio (RR) and 95% confidence interval (CI) by combining RRs for fracture effects of included trials. RESULTS: There were 54 eligible random control trials (RCTs) with 49,602 participants, including 28,353 patients treated with GLP-1 RAs. Relative to placebo, exenatide (RR, 0.17; 95% CI 0.03-0.67) was associated with lowest risk of fracture among other GLP-1 RAs. Exenatide had the highest probability to be the safest option with regard to the risk of fracture (0.07 per thousand), followed by dulaglutide (1.04%), liraglutide (1.39%), albiglutide (5.61%), lixisenatide (8.07%), and semaglutide (18.72%). A statistically significant inconsistency was observed in some comparisons. CONCLUSION: The Bayesian network meta-analysis suggests that GLP-1 RAs were associated with a decreased bone fracture risk compared to users of placebo or other anti-hyperglycemic drugs in type 2 diabetes mellitus patients, and exenatide is the best option agent with regard to the risk of fracture. FAU - Zhang, Y S AU - Zhang YS AD - Department of Pharmacy, Guangdong Medical University, No. 1, Xincheng Dadao, Songshan Lake Science and Technology Industry Park, Dongguan, 523808, China. FAU - Weng, W Y AU - Weng WY AD - Department of Pharmacy, Guangdong Medical University, No. 1, Xincheng Dadao, Songshan Lake Science and Technology Industry Park, Dongguan, 523808, China. FAU - Xie, B C AU - Xie BC AD - Department of Pharmacy, Guangdong Medical University, No. 1, Xincheng Dadao, Songshan Lake Science and Technology Industry Park, Dongguan, 523808, China. FAU - Meng, Y AU - Meng Y AD - Department of Pharmacy, Guangdong Medical University, No. 1, Xincheng Dadao, Songshan Lake Science and Technology Industry Park, Dongguan, 523808, China. FAU - Hao, Y H AU - Hao YH AD - Department of Pharmacy, Guangdong Medical University, No. 1, Xincheng Dadao, Songshan Lake Science and Technology Industry Park, Dongguan, 523808, China. FAU - Liang, Y M AU - Liang YM AD - Department of Pharmacy, Guangdong Medical University, No. 1, Xincheng Dadao, Songshan Lake Science and Technology Industry Park, Dongguan, 523808, China. FAU - Zhou, Z K AU - Zhou ZK AUID- ORCID: 0000-0001-9697-5897 AD - Department of Pharmacy, Guangdong Medical University, No. 1, Xincheng Dadao, Songshan Lake Science and Technology Industry Park, Dongguan, 523808, China. zhikunzhou@126.com. LA - eng GR - 81774344/National Natural Science Foundation of China (CN)/ PT - Journal Article PT - Network Meta-Analysis DEP - 20180806 PL - England TA - Osteoporos Int JT - Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA JID - 9100105 RN - 0 (Hypoglycemic Agents) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Osteoporos Int. 2019 Aug;30(8):1709-1710. doi: 10.1007/s00198-019-05013-7. PMID: 31119314 MH - Bayes Theorem MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Exenatide/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Osteoporotic Fractures/etiology/*prevention & control MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Fracture OT - Glucagon-like peptide-1 receptor agonists OT - Network meta-analysis OT - Type 2 diabetes mellitus EDAT- 2018/08/08 06:00 MHDA- 2019/04/10 06:00 CRDT- 2018/08/08 06:00 PHST- 2018/04/18 00:00 [received] PHST- 2018/07/19 00:00 [accepted] PHST- 2018/08/08 06:00 [pubmed] PHST- 2019/04/10 06:00 [medline] PHST- 2018/08/08 06:00 [entrez] AID - 10.1007/s00198-018-4649-8 [pii] AID - 10.1007/s00198-018-4649-8 [doi] PST - ppublish SO - Osteoporos Int. 2018 Dec;29(12):2639-2644. doi: 10.1007/s00198-018-4649-8. Epub 2018 Aug 6. PMID- 30047216 OWN - NLM STAT- MEDLINE DCOM- 20190819 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 21 IP - 1 DP - 2019 Jan TI - Impact on HbA1c and body weight of switching from other GLP-1 receptor agonists to semaglutide: A model-based approach. PG - 43-51 LID - 10.1111/dom.13479 [doi] AB - AIMS: Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue approved for the treatment of type 2 diabetes. The impact of switching treatment from another GLP-1 receptor agonist (GLP-1RA) to semaglutide was investigated by analyses of exposure-response models. METHODS: HbA1c and body weight time-course models were developed, using up to 30 weeks of observations from four trials in the semaglutide phase 3 programme. Given the recommended dosing for each GLP-1RA, pharmacokinetic profiles were simulated based on published population pharmacokinetic models and exposure was adjusted by the relative potencies to ensure that model predictions matched the effects observed in clinical trials. After 26 weeks of simulated treatment with liraglutide, dulaglutide or exenatide extended-release, simulated semaglutide treatment was initiated 1 day after the last once-daily dose of liraglutide and 1 week after the last once-weekly doses of dulaglutide or exenatide extended-release. RESULTS: The potency-adjusted total effective GLP-1RA concentration increased after switching from another GLP-1RA to semaglutide and was associated with reductions ranging from ~0.3% to ~0.8%-points for HbA1c and from ~2% to ~4% for body weight with semaglutide 1.0 mg. Temporary slight deteriorations in HbA1c were observed after switching to semaglutide 0.25 mg from liraglutide 1.2/1.8 mg or dulaglutide 1.5 mg. CONCLUSIONS: Exposure-response modelling suggests that switching to semaglutide from liraglutide, dulaglutide or exenatide extended-release results in further reductions in HbA1c and body weight. Initial slight deterioration in outcome values when switching to semaglutide 0.25 mg could be avoided by initiating semaglutide treatment at a higher dose. CI - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Overgaard, Rune V AU - Overgaard RV AUID- ORCID: 0000-0001-7095-4270 AD - Department of Quantitative Clinical Pharmacology, Novo Nordisk A/S, Soborg, Denmark. FAU - Lindberg, Soren O AU - Lindberg SO AD - Department of Medical and Science, Novo Nordisk A/S, Soborg, Denmark. FAU - Thielke, Desiree AU - Thielke D AD - Department of Global Medical Affairs, Novo Nordisk A/S, Soborg, Denmark. LA - eng PT - Clinical Trial, Phase II PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180823 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) MH - Adult MH - Aged MH - Body Weight/*drug effects MH - Diabetes Mellitus, Type 2/*drug therapy/epidemiology MH - Female MH - *Glucagon-Like Peptides/administration & dosage/pharmacology/therapeutic use MH - Glycated Hemoglobin/*analysis MH - Humans MH - *Hypoglycemic Agents/administration & dosage/pharmacology/therapeutic use MH - Male MH - Middle Aged MH - Models, Statistical MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC6585654 OTO - NOTNLM OT - GLP-1 OT - GLP-1 analogue OT - antidiabetic drug OT - population study OT - type 2 diabetes COIS- R. V. O., S. L. and D. T. are employed by and hold stock in Novo Nordisk. EDAT- 2018/07/27 06:00 MHDA- 2019/08/20 06:00 PMCR- 2019/06/20 CRDT- 2018/07/27 06:00 PHST- 2018/05/18 00:00 [received] PHST- 2018/07/09 00:00 [revised] PHST- 2018/07/21 00:00 [accepted] PHST- 2018/07/27 06:00 [pubmed] PHST- 2019/08/20 06:00 [medline] PHST- 2018/07/27 06:00 [entrez] PHST- 2019/06/20 00:00 [pmc-release] AID - DOM13479 [pii] AID - 10.1111/dom.13479 [doi] PST - ppublish SO - Diabetes Obes Metab. 2019 Jan;21(1):43-51. doi: 10.1111/dom.13479. Epub 2018 Aug 23. PMID- 30026333 OWN - NLM STAT- MEDLINE DCOM- 20181010 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 41 IP - 9 DP - 2018 Sep TI - A 26-Week Randomized Controlled Trial of Semaglutide Once Daily Versus Liraglutide and Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Diet and Exercise With or Without Metformin. PG - 1926-1937 LID - 10.2337/dc17-2381 [doi] AB - OBJECTIVE: To investigate the efficacy and safety of once-daily semaglutide in comparison with once-daily liraglutide and placebo in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This 26-week, multicenter, double-blind trial involved patients diagnosed with type 2 diabetes with HbA(1c) 7.0-10.0% (53-86 mmol/mol) and treated with diet and exercise with or without metformin. Patients were randomized 2:2:1 to once-daily semaglutide, liraglutide, or placebo in one of four volume-matched doses (semaglutide 0.05, 0.1, 0.2, or 0.3 mg and liraglutide 0.3, 0.6, 1.2, or 1.8 mg, with both compared within each volume-matched dose group). Primary end point was change in HbA(1c) from baseline to week 26. RESULTS: In total, 705 randomized patients were exposed to trial products. At week 26, a dose-dependent change in HbA(1c) was observed with semaglutide from -1.1% (0.05 mg) to -1.9% (0.3 mg) and with liraglutide from -0.5% (0.3 mg) to -1.3% (1.8 mg) (all P < 0.001 in favor of volume-matched semaglutide dose). Change with pooled placebo was -0.02% (P < 0.0001 vs. semaglutide). Gastrointestinal (GI) disorders were the most common adverse events (AEs) with semaglutide and liraglutide, occurring in 32.8-54.0% and 21.9-41.5% of patients, respectively. CONCLUSIONS: Once-daily semaglutide at doses up to 0.3 mg/day resulted in greater reductions in HbA(1c) compared with liraglutide or placebo but with a higher frequency of GI AEs. CI - (c) 2018 by the American Diabetes Association. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - University of Texas Southwestern Medical Center at Dallas, Dallas, TX. FAU - Desouza, Cyrus V AU - Desouza CV AD - University of Nebraska Medical Center, Omaha, NE. FAU - Lalic, Katarina S AU - Lalic KS AD - Faculty of Medicine, University of Belgrade, and Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Belgrade, Serbia. FAU - Rose, Ludger AU - Rose L AD - Institute for Diabetes Research in Munster, Munster, Germany. FAU - Hansen, Thomas AU - Hansen T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Zacho, Jeppe AU - Zacho J AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Pieber, Thomas R AU - Pieber TR AUID- ORCID: 0000-0003-3554-0405 AD - Medical University of Graz, Graz, Austria thomas.pieber@medunigraz.at. LA - eng SI - ClinicalTrials.gov/NCT02461589 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180719 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 839I73S42A (Liraglutide) RN - 9100L32L2N (Metformin) RN - 0 (Placebos) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Combined Modality Therapy MH - Diabetes Mellitus, Type 2/blood/*drug therapy/therapy MH - *Diet MH - Double-Blind Method MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Exercise/*physiology MH - Female MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Liraglutide/*administration & dosage/adverse effects MH - Male MH - Metformin/*administration & dosage/adverse effects MH - Middle Aged MH - Placebos MH - Treatment Outcome MH - Semaglutide EDAT- 2018/07/22 06:00 MHDA- 2018/10/12 06:00 CRDT- 2018/07/21 06:00 PHST- 2017/11/13 00:00 [received] PHST- 2018/06/18 00:00 [accepted] PHST- 2018/07/22 06:00 [pubmed] PHST- 2018/10/12 06:00 [medline] PHST- 2018/07/21 06:00 [entrez] AID - dc17-2381 [pii] AID - 10.2337/dc17-2381 [doi] PST - ppublish SO - Diabetes Care. 2018 Sep;41(9):1926-1937. doi: 10.2337/dc17-2381. Epub 2018 Jul 19. PMID- 29949126 OWN - NLM STAT- MEDLINE DCOM- 20190103 LR - 20260127 IS - 2520-8721 (Electronic) IS - 1109-3099 (Linking) VI - 17 IP - 3 DP - 2018 Sep TI - Clinical pharmacology of glucagon-like peptide-1 receptor agonists. PG - 333-350 LID - 10.1007/s42000-018-0038-0 [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are an important asset in the armamentarium for the treatment of type 2 diabetes mellitus (type 2 DM). Incretin failure is a critical etiopathogenetic feature of type 2 DM, which, if reversed, results in improved glycaemic control. GLP-1 RAs are injectable peptides that resemble the structure and function of endogenous incretin GLP-1, but as they are not deactivated by the dipeptidyl peptidase-4 (DPP-4), their half-life is prolonged compared with native GLP-1. Based on their ability to activate GLP-1 receptor, GLP-1 RAs are classified as short-acting (exenatide twice-daily and lixisenatide once-daily), and long-acting (liraglutide once-daily and the once-weekly formulations of exenatide extended-release, dulaglutide, and albiglutide). Semaglutide, another long-acting, once-weekly GLP-1 RA, was recently approved by the FDA and EMA. Although all of these agents potently reduce haemoglobin A1C (HbA1c), there are unique features and fundamental differences among them related to fasting and postprandial hyperglycaemia reduction, weight loss potency, cardiovascular protection efficacy, and adverse events profile. It is imperative that current evidence be integrated and applied in the context of an individualised patient-centred approach. This should include not only glucose management but also targeting as many as possible of the pathophysiologic mechanisms responsible for type 2 DM development and progression. FAU - Sfairopoulos, Dimitrios AU - Sfairopoulos D AD - Department of Internal Medicine, School of Medicine, University of Ioannina, Stavrou Niarchou Str, 45110, Ioannina, Greece. FAU - Liatis, Stavros AU - Liatis S AD - First Department of Propaedeutic and Internal Medicine, Medical School, Laiko General Hospital, National and Kapodistrian University of Athens, 10559, Athens, Greece. FAU - Tigas, Stelios AU - Tigas S AD - Department of Endocrinology, School of Medicine, University of Ioannina, 45110, Ioannina, Greece. FAU - Liberopoulos, Evangelos AU - Liberopoulos E AD - Department of Internal Medicine, School of Medicine, University of Ioannina, Stavrou Niarchou Str, 45110, Ioannina, Greece. vaglimp@yahoo.com. LA - eng PT - Journal Article PT - Review DEP - 20180612 PL - Switzerland TA - Hormones (Athens) JT - Hormones (Athens, Greece) JID - 101142469 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/administration & dosage/*analogs & derivatives/pharmacokinetics/pharmacology MH - Humans MH - Hypoglycemic Agents/administration & dosage/*pharmacology MH - Immunoglobulin Fc Fragments/administration & dosage/*pharmacology MH - Liraglutide/administration & dosage/*pharmacology MH - Recombinant Fusion Proteins/administration & dosage/*pharmacology MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Dulaglutide OT - Exenatide OT - GLP-1 receptor agonists OT - Liraglutide OT - Semaglutide OT - Type 2 diabetes EDAT- 2018/06/28 06:00 MHDA- 2019/01/04 06:00 CRDT- 2018/06/28 06:00 PHST- 2018/01/09 00:00 [received] PHST- 2018/05/14 00:00 [accepted] PHST- 2018/06/28 06:00 [pubmed] PHST- 2019/01/04 06:00 [medline] PHST- 2018/06/28 06:00 [entrez] AID - 10.1007/s42000-018-0038-0 [pii] AID - 10.1007/s42000-018-0038-0 [doi] PST - ppublish SO - Hormones (Athens). 2018 Sep;17(3):333-350. doi: 10.1007/s42000-018-0038-0. Epub 2018 Jun 12. PMID- 29944969 OWN - NLM STAT- MEDLINE DCOM- 20181105 LR - 20250103 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 143 DP - 2018 Sep TI - Cardiovascular outcome studies in type 2 diabetes: Comparison between SGLT2 inhibitors and GLP-1 receptor agonists. PG - 88-100 LID - S0168-8227(18)30599-0 [pii] LID - 10.1016/j.diabres.2018.06.008 [doi] AB - Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are two pharmacological classes that have proven their efficacy to reduce major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease in large prospective cardiovascular outcome trials (CVOTs): EMPA-REG OUTCOME (empagliflozin), CANVAS (canagliflozin), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). Some heterogeneity appears to exist between the various agents within the two pharmacological classes. Whether these positive results could be extrapolated to patients without cardiovascular disease is still unknown. The underlying mechanisms remain a matter of debate but appear to differ between SGLT2is and GLP-1RAs. One crucial question is which patient's characteristics should be taken into account to guide the choice between a SGLT2i or a GLP-1RA according to a personalized approach. Heart failure should encourage the use of a SGLT2i whereas moderate to severe chronic kidney disease should favour the prescription of a GLP-1RA. Despite the results of recent CVOTs, numerous patients who are good candidates for benefiting of these agents do not receive them in clinical practice. Currently, there is a paradigm shift in T2DM management, moving from a primary objective of glucose control to a cardiovascular and renal protection. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Scheen, Andre J AU - Scheen AJ AD - Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liege, University of Liege, Liege, Belgium; Clinical Pharmacology Unit, CHU Liege, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Liege, Belgium. Electronic address: andre.scheen@chu.ulg.ac.be. LA - eng PT - Journal Article PT - Review DEP - 20180623 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cardiovascular Diseases/*etiology/pathology MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Humans MH - Hypoglycemic Agents/pharmacology/*therapeutic use MH - *Sodium-Glucose Transporter 2 Inhibitors MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular disease OT - GLP-1 receptor agonists OT - Heart failure OT - Mortality OT - SGLT2 inhibitors OT - Type 2 diabetes EDAT- 2018/06/27 06:00 MHDA- 2018/11/06 06:00 CRDT- 2018/06/27 06:00 PHST- 2018/04/12 00:00 [received] PHST- 2018/05/14 00:00 [revised] PHST- 2018/06/13 00:00 [accepted] PHST- 2018/06/27 06:00 [pubmed] PHST- 2018/11/06 06:00 [medline] PHST- 2018/06/27 06:00 [entrez] AID - S0168-8227(18)30599-0 [pii] AID - 10.1016/j.diabres.2018.06.008 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2018 Sep;143:88-100. doi: 10.1016/j.diabres.2018.06.008. Epub 2018 Jun 23. PMID- 29932006 OWN - NLM STAT- MEDLINE DCOM- 20190923 LR - 20260127 IS - 1542-6270 (Electronic) IS - 1060-0280 (Linking) VI - 52 IP - 12 DP - 2018 Dec TI - Semaglutide: The Newest Once-Weekly GLP-1 RA for Type 2 Diabetes. PG - 1224-1232 LID - 10.1177/1060028018784583 [doi] AB - OBJECTIVE: To review efficacy and safety of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) semaglutide for type 2 diabetes (T2D). DATA SOURCES: A literature search of PubMed/MEDLINE and EMBASE using the term semaglutide was completed through April 2018. A search of clinicaltrials.gov was also conducted. STUDY SELECTION AND DATA EXTRACTION: English-language studies assessing the efficacy and/or safety of semaglutide were evaluated. DATA SYNTHESIS: Semaglutide is a newly approved GLP-1 RA for the treatment of T2D. Administered once weekly at a dose of 0.5 or 1 mg, it has been compared with placebo, sitagliptin, insulin glargine, a combination of oral antidiabetic therapies, and 2 GLP-1 RAs, exenatide ER and dulaglutide, and demonstrated greater efficacy compared with these therapies. Published data from studies ranging from 30 to 104 weeks duration demonstrate efficacy with decreases in hemoglobin A1C (A1C) ranging from 1.1% to 2.2%. Studies show reductions in weight from 1.4 to 6.5 kg. Semaglutide demonstrated a reduction in the composite outcome of cardiovascular (CV) death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo in patients at high risk of CV events (hazard ratio = 0.74; P = 0.02). Common adverse effects include nausea, vomiting, and diarrhea as seen with other GLP-1 RAs. Relevance to Patient Care and Clinical Practice: Semaglutide represents an attractive GLP-1 RA considering its A1C and weight reduction. It provides patient convenience and high patient satisfaction. CONCLUSIONS: Semaglutide is an appealing option for the treatment of T2D as a once-weekly GLP-1 RA with established glycemic, CV, and weight benefits. FAU - Tuchscherer, Rhianna M AU - Tuchscherer RM AUID- ORCID: 0000-0003-4355-8824 AD - 1 University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA. FAU - Thompson, Angela M AU - Thompson AM AD - 1 University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA. FAU - Trujillo, Jennifer M AU - Trujillo JM AD - 1 University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA. LA - eng PT - Journal Article PT - Review DEP - 20180622 PL - United States TA - Ann Pharmacother JT - The Annals of pharmacotherapy JID - 9203131 RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose/drug effects/metabolism MH - Body Weight/drug effects/physiology MH - Clinical Trials, Phase III as Topic/methods MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Administration Schedule MH - Glucagon-Like Peptide 1/*agonists MH - Glucagon-Like Peptides/*administration & dosage MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Weight Loss/drug effects/physiology MH - Semaglutide OTO - NOTNLM OT - antihyperglycemics OT - diabetes OT - drug information OT - medication safety OT - type 2 EDAT- 2018/06/23 06:00 MHDA- 2019/09/24 06:00 CRDT- 2018/06/23 06:00 PHST- 2018/06/23 06:00 [pubmed] PHST- 2019/09/24 06:00 [medline] PHST- 2018/06/23 06:00 [entrez] AID - 10.1177/1060028018784583 [doi] PST - ppublish SO - Ann Pharmacother. 2018 Dec;52(12):1224-1232. doi: 10.1177/1060028018784583. Epub 2018 Jun 22. PMID- 29915923 OWN - NLM STAT- MEDLINE DCOM- 20191031 LR - 20261012 IS - 1179-1926 (Electronic) IS - 0312-5963 (Linking) VI - 57 IP - 12 DP - 2018 Dec TI - Pharmacokinetics and Clinical Implications of Semaglutide: A New Glucagon-Like Peptide (GLP)-1 Receptor Agonist. PG - 1529-1538 LID - 10.1007/s40262-018-0668-z [doi] AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) came to market in the year 2005, as a new therapeutic classification, for clinical use in the management of type 2 diabetes mellitus (T2DM). Since 2005, there have been six approved products on the market, with the newest product being semaglutide (Novo Nordisk). Several studies have been conducted and completed evaluating its pharmacokinetics as a once-weekly subcutaneous injection. As a dose of 0.5 or 1 mg, semaglutide has a half-life of 7 days; therefore, it would reach steady state in 4-5 weeks. There are few drug interactions and dose adjustments are not necessary. However, similar to other GLP-1 RAs, semaglutide can delay gastric emptying and may impact the absorption of oral medications. Based on clinical trials, semaglutide has been compared with placebo, sitagliptin, exenatide extended release, and insulin glargine as monotherapy or add-on therapy. Semaglutide has resulted in a 1.5-1.9% glycosylated hemoglobin A(1c) reduction after 30-56 weeks. It also produced 5-10% weight reduction from baseline in clinical efficacy studies. Semaglutide can be another acceptable option for patients with T2DM, and it has a potential role among patients who require weight loss with a low risk of hypoglycemia. This article evaluates the pharmacokinetics of semaglutide and summarizes its application to clinical practice based on efficacy and safety data. FAU - Hall, Sylvie AU - Hall S AD - Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. FAU - Isaacs, Diana AU - Isaacs D AD - Cleveland Clinic, Endocrine and Metabolism Institute Diabetes Center, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. FAU - Clements, Jennifer N AU - Clements JN AD - Presbyterian College School of Pharmacy, 307 North Broad Street, Clinton, SC, 29325, USA. jclements@presby.edu. LA - eng PT - Journal Article PT - Review PL - Switzerland TA - Clin Pharmacokinet JT - Clinical pharmacokinetics JID - 7606849 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/drug therapy MH - Dose-Response Relationship, Drug MH - Glucagon-Like Peptides/*administration & dosage/adverse effects/pharmacokinetics MH - Glycated Hemoglobin/metabolism MH - Half-Life MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacokinetics MH - Injections, Subcutaneous MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide EDAT- 2018/06/20 06:00 MHDA- 2019/11/02 06:00 CRDT- 2018/06/20 06:00 PHST- 2018/06/20 06:00 [pubmed] PHST- 2019/11/02 06:00 [medline] PHST- 2018/06/20 06:00 [entrez] AID - 10.1007/s40262-018-0668-z [pii] AID - 10.1007/s40262-018-0668-z [doi] PST - ppublish SO - Clin Pharmacokinet. 2018 Dec;57(12):1529-1538. doi: 10.1007/s40262-018-0668-z. PMID- 29912998 OWN - NLM STAT- MEDLINE DCOM- 20190904 LR - 20260127 IS - 1533-7294 (Electronic) IS - 0094-3509 (Linking) VI - 67 IP - 6 suppl DP - 2018 Jun TI - Safety of Once-weekly Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes. PG - S25-S34 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been found efficacious in the treatment of type 2 diabetes (T2D), demonstrating the ability to lower HbA1c, and having the potential for inducing weight loss and reducing the risk of hypoglycemia, compared with other antihyperglycemic agents. Currently, 4 once-weekly (OW) GLP-1 RAs are approved: albiglutide, dulaglutide, exenatide ER, and recently, semaglutide. This review compares the relative safety of OW GLP-1 RAs, as well as their safety in comparison to other antihyperglycemic agents, using safety data reported in key sponsor-led phase 3 studies of the 4 OW GLP-1 RAs. The favorable safety profiles of OW GLP-1 RAs, added to their efficacy and the favorable weekly dosing regimen, make these agents appropriate options for patients with T2D. However, there are key differences within this class of drugs in macrovascular, microvascular, gastrointestinal and injection-site reaction adverse events, and these should be considered when healthcare providers are prescribing therapy. FAU - Frias, Juan P AU - Frias JP AD - National Research Institute, Los Angeles, California, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - J Fam Pract JT - The Journal of family practice JID - 7502590 RN - 0 (Blood Glucose) RN - 0 (Delayed-Action Preparations) RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - 5E7U48495E (rGLP-1 protein) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Blood Glucose/drug effects MH - Delayed-Action Preparations/administration & dosage MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drug Administration Schedule MH - Drug Monitoring/methods MH - Exenatide/adverse effects MH - Glucagon-Like Peptide 1/administration & dosage/adverse effects/*analogs & derivatives MH - Glucagon-Like Peptides/administration & dosage/adverse effects/*analogs & derivatives MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/administration & dosage/*adverse effects MH - Immunoglobulin Fc Fragments/administration & dosage/*adverse effects MH - Randomized Controlled Trials as Topic MH - Recombinant Fusion Proteins/administration & dosage/*adverse effects MH - Treatment Outcome MH - Semaglutide EDAT- 2018/06/19 06:00 MHDA- 2019/09/05 06:00 CRDT- 2018/06/19 06:00 PHST- 2018/06/19 06:00 [entrez] PHST- 2018/06/19 06:00 [pubmed] PHST- 2019/09/05 06:00 [medline] AID - jfp_6703r [pii] PST - ppublish SO - J Fam Pract. 2018 Jun;67(6 suppl):S25-S34. PMID- 29912997 OWN - NLM STAT- MEDLINE DCOM- 20190904 LR - 20260127 IS - 1533-7294 (Electronic) IS - 0094-3509 (Linking) VI - 67 IP - 6 suppl DP - 2018 Jun TI - Clinical Efficacy of Once-weekly Glucagonlike Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes. PG - S14-S24 AB - Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are indicated for restoring normoglycemia in patients with type 2 diabetes (T2D). This review analyzed and compared the efficacy results from 30 trials with the once-weekly (OW) GLP-1 RAs albiglutide, dulaglutide, exenatide extended-release (ER) and semaglutide. The 4 OW GLP-1 RAs showed a higher reduction in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG) and body weight, when compared to placebo. Semaglutide significantly reduced the HbA1c level (estimated treatment difference [ETD]: -0.62%; 95% confidence interval [CI], -0.79 to -0.44; P<0.0001), FPG (ETD: -15 mmol/L; 95% CI, -22 to -8.3; P<0.0001) and body weight (ETD: -3.73 kg; 95% CI, -4.53 to -2.93; P<0.0001) compared with exenatide ER. A direct comparison between OW, once-daily (OD), and twice-daily (BD) GLP-1 RAs indicated some trends in efficacy, for example, with OD liraglutide, providing a significant reduction in body weight vs albiglutide (ETD: 1.55 kg; 95% CI, 1.05-2.06; P<0.0001 for albiglutide), dulaglutide (ETD: 0.71 kg; 95% CI, 0.17 -1.26; P=0.011 for dulaglutide), and exenatide ER (ETD: 0.90 kg; 95% CI, 0.39- 1.40; P=0.0005 for exenatide ER). OW GLP-1 RAs also offered improved glycemic control when compared with the dipeptidyl peptidase-4 inhibitor sitagliptin. In conclusion, OW GLP-1 RAs offer a valid therapeutic option for T2D. FAU - Bailey, Timothy S AU - Bailey TS AD - AMCR Institute Inc., Escondido, CA, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - J Fam Pract JT - The Journal of family practice JID - 7502590 RN - 0 (Blood Glucose) RN - 0 (Delayed-Action Preparations) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - 5E7U48495E (rGLP-1 protein) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Blood Glucose/drug effects MH - Delayed-Action Preparations/administration & dosage MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drug Administration Schedule MH - Drug Monitoring/methods MH - Glucagon-Like Peptide 1/administration & dosage/*analogs & derivatives MH - Glucagon-Like Peptides/administration & dosage/analogs & derivatives MH - Humans MH - Hypoglycemia/*prevention & control MH - Hypoglycemic Agents/*administration & dosage MH - Immunoglobulin Fc Fragments/administration & dosage MH - Randomized Controlled Trials as Topic MH - Recombinant Fusion Proteins/administration & dosage MH - Treatment Outcome MH - Semaglutide EDAT- 2018/06/19 06:00 MHDA- 2019/09/05 06:00 CRDT- 2018/06/19 06:00 PHST- 2018/06/19 06:00 [entrez] PHST- 2018/06/19 06:00 [pubmed] PHST- 2019/09/05 06:00 [medline] AID - jfp_6703q [pii] PST - ppublish SO - J Fam Pract. 2018 Jun;67(6 suppl):S14-S24. PMID- 29912995 OWN - NLM STAT- MEDLINE DCOM- 20190904 LR - 20260127 IS - 1533-7294 (Electronic) IS - 0094-3509 (Linking) VI - 67 IP - 6 suppl DP - 2018 Jun TI - An Overview of the Burden of Illness and the Role of Once-Weekly Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Type 2 Diabetes. PG - S3-S7 AB - Type 2 diabetes (T2D) is a debilitating condition and more people are being diagnosed each year. T2D increases patients' risk of developing disabling micro- and macrovascular complications, significantly reduces patients' quality of life, and is a substantial global economic burden. The efficacy and safety of antihyperglycemic therapies have improved over the years and have increased the lifespan for these patients. Consequently, patients are living longer with the condition and the associated comorbidities, but with a lowered quality of life. Therefore, therapies should aim to provide both optimal glycemic control and improve quality of life. Glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy improves glycemic control, reduces body weight, and has a low risk for hypoglycemia. GLP-1 RAs are available as once-daily (OD), twice-daily (BD), or once-weekly (OW) injectable formulations; OW injections may increase patients' satisfaction and improve treatment adherence. In the last decade, concern has been raised about the cardiovascular (CV) safety of antihyperglycemic therapies. Clinical data have been limited on CV outcomes among OW GLP-1 RAs. However, a post hoc analysis of the SUSTAIN-6 trial suggested that semaglutide, the most recently US Food and Drug Administration (FDA)-approved OW GLP-1 RA therapy, may offer cardioprotection, addressing this previously unmet clinical need. FAU - Brunton, Stephen A AU - Brunton SA AD - Department of Pharmacy Practice, Roseman University of Health Sciences, Salt Lake City, Utah, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - J Fam Pract JT - The Journal of family practice JID - 7502590 RN - 0 (Delayed-Action Preparations) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Recombinant Fusion Proteins) RN - 53AXN4NNHX (Semaglutide) RN - WTT295HSY5 (dulaglutide) SB - IM MH - *Cost of Illness MH - Delayed-Action Preparations/administration & dosage MH - Diabetes Mellitus, Type 2/*drug therapy/psychology MH - Drug Administration Schedule MH - Glucagon-Like Peptides/administration & dosage/*analogs & derivatives MH - Humans MH - Hypoglycemia/prevention & control MH - Hypoglycemic Agents/*administration & dosage MH - Immunoglobulin Fc Fragments/*administration & dosage MH - Medication Adherence MH - Quality of Life/*psychology MH - Recombinant Fusion Proteins/*administration & dosage MH - Semaglutide EDAT- 2018/06/19 06:00 MHDA- 2019/09/05 06:00 CRDT- 2018/06/19 06:00 PHST- 2018/06/19 06:00 [entrez] PHST- 2018/06/19 06:00 [pubmed] PHST- 2019/09/05 06:00 [medline] AID - jfp_6703o [pii] PST - ppublish SO - J Fam Pract. 2018 Jun;67(6 suppl):S3-S7. PMID- 29893488 OWN - NLM STAT- MEDLINE DCOM- 20190415 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 11 DP - 2018 Nov TI - Effect of once-weekly semaglutide on the counterregulatory response to hypoglycaemia in people with type 2 diabetes: A randomized, placebo-controlled, double-blind, crossover trial. PG - 2565-2573 LID - 10.1111/dom.13422 [doi] AB - AIMS: To investigate the effects of semaglutide vs placebo on glucagon and other counterregulatory hormones during hypoglycaemia in type 2 diabetes (T2D). METHODS: In this double-blind, placebo-controlled, single-centre trial, we randomized 38 men and women (treated only with metformin) 1:1 to 2 12-week crossover periods of once-weekly subcutaneous semaglutide or placebo, each followed by a hypoglycaemic clamp procedure. The primary endpoint was change in glucagon concentration from target plasma glucose (PG) level 5.5 mmol/L to nadir (target 2.5 mmol/L). RESULTS: The mean (range) participant age was 54.2 (41-64) years, body mass index 29.4 (23.3-36.1) kg/m(2) , glycated haemoglobin 60.8 (44.3-83.6) mmol/mol (7.7 [6.2-9.8]%), and diabetes duration 4.5 (0.3-13.2) years. A total of 35 participants completed the trial and were included in the analyses. During the hypoglycaemic clamp from 5.5 mmol/L PG to nadir, the absolute change in mean glucagon concentration was similar for semaglutide vs placebo: 88.3 vs 83.1 pg/mL (estimated difference 5.2 pg/mL [95% confidence interval -7.7 to 18.1]). Concentrations of other counterregulatory hormones increased with both treatments, with a statistically significantly lower increase for noradrenaline and cortisol with semaglutide vs placebo. The glucose infusion rate to maintain constant clamp levels was similar for each treatment group, suggesting an overall similar counterregulatory response. The mean hypoglycaemic symptom score and proportion of participants recognizing hypoglycaemia during the study were lower for semaglutide vs placebo treatment at nadir, but cognitive function test results were similar. No new safety issues were observed for semaglutide. CONCLUSIONS: Semaglutide treatment did not compromise the counterregulatory glucagon response during experimental hypoglycaemia in people with T2D. CI - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Korsatko, Stefan AU - Korsatko S AD - Department of Internal Medicine, Medical University of Graz, Graz, Austria. FAU - Jensen, Lene AU - Jensen L AUID- ORCID: 0000-0002-7111-2486 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Brunner, Martina AU - Brunner M AD - Department of Internal Medicine, Medical University of Graz, Graz, Austria. FAU - Sach-Friedl, Stefanie AU - Sach-Friedl S AD - Department of Internal Medicine, Medical University of Graz, Graz, Austria. FAU - Tarp, Maja D AU - Tarp MD AD - Novo Nordisk A/S, Aalborg, Denmark. FAU - Holst, Anders G AU - Holst AG AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Heller, Simon R AU - Heller SR AUID- ORCID: 0000-0002-2425-9565 AD - University of Sheffield Medical School, Sheffield, UK. FAU - Pieber, Thomas R AU - Pieber TR AUID- ORCID: 0000-0003-3554-0405 AD - Department of Internal Medicine, Medical University of Graz, Graz, Austria. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180716 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Placebos) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Blood Glucose/drug effects/metabolism MH - Cross-Over Studies MH - Diabetes Mellitus, Type 2/*complications/*drug therapy/metabolism MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Glucagon-Like Peptides/*administration & dosage/pharmacology MH - Humans MH - Hypoglycemia/blood/chemically induced/epidemiology/*metabolism MH - Male MH - Middle Aged MH - Placebos MH - Semaglutide PMC - PMC6221089 OTO - NOTNLM OT - GLP-1 OT - GLP-1 analogue OT - hypoglycaemia OT - type 2 diabetes COIS- No potential conflicts of interest relevant to this article are reported by S.K., M.B. or S.S. S.R.H. has served on speaker panels for AstraZeneca, Eli Lilly, Novo Nordisk, Sanofi Aventis and Takeda, for which he has received personal remuneration. He has consulted for Boeringher Ingelheim, Eli Lilly, Novo Nordisk and Takeda, for which his institution has received remuneration. T.R.P. declares Board membership for Adocia, AstraZeneca, Eli Lilly, Novo Nordisk and Sanofi, and institutional grants from AstraZeneca and Novo Nordisk, and payment for lectures/speakers bureaus from Novo Nordisk. L.J., M.D.T. and A.G.H. are employed by and hold stock in Novo Nordisk. EDAT- 2018/06/13 06:00 MHDA- 2019/04/16 06:00 PMCR- 2018/11/07 CRDT- 2018/06/13 06:00 PHST- 2018/03/05 00:00 [received] PHST- 2018/06/08 00:00 [revised] PHST- 2018/06/09 00:00 [accepted] PHST- 2018/06/13 06:00 [pubmed] PHST- 2019/04/16 06:00 [medline] PHST- 2018/06/13 06:00 [entrez] PHST- 2018/11/07 00:00 [pmc-release] AID - DOM13422 [pii] AID - 10.1111/dom.13422 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Nov;20(11):2565-2573. doi: 10.1111/dom.13422. Epub 2018 Jul 16. PMID- 29870275 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20250103 IS - 1557-8593 (Electronic) IS - 1520-9156 (Linking) VI - 20 IP - S2 DP - 2018 Jun TI - The Clinical Impact of GLP-1 Receptor Agonists in Type 2 Diabetes: Focus on the Long-Acting Analogs. PG - S233-S241 LID - 10.1089/dia.2018.0103 [doi] AB - GLP-1 receptor agonists (GLP-1 RAs), introduced for clinical use in 2005, have excellent potency in reducing HbA(1c) and mean glucose, improving fasting plasma glucose, inducing weight loss or protecting against the weight gain associated with insulin therapy, reducing appetite, and delaying gastric emptying. Two of these medications, liraglutide and semaglutide, appear to have cardioprotective effects as reflected in cardiovascular outcomes studies. The GLP-1 RAs are associated with gastrointestinal side effects that tend to diminish over time. They have very low risk of hypoglycemia unless used in conjunction with insulin or insulin secretagogues. Two coformulations of GLP-1 RAs together with long-acting basal insulin are available for daily use. The original GLP-1 RA, exenatide, requires twice-daily injections; two short-acting analogs are given once daily. Three currently available long-acting GLP-1 RAs are injected once weekly, providing greater convenience and potentially improving patient adherence. Semaglutide appears to be the most effective in terms of HbA(1c) reduction and weight loss. GLP-1 RAs can be combined with all classes of antihyperglycemic agents except DPP-4 inhibitors. Current studies are exploring the use of an implantable osmotic pump for long-term administration of a rapid acting analog (exenatide), an oral preparation of semaglutide, benefits for management of obesity and nonalcoholic steatohepatitis, and mechanisms of cardioprotective effects. FAU - Rodbard, Helena W AU - Rodbard HW AD - Endocrine and Metabolic Consultants , Rockville, Maryland. LA - eng PT - Journal Article DEP - 20180605 PL - United States TA - Diabetes Technol Ther JT - Diabetes technology & therapeutics JID - 100889084 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin, Long-Acting) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9P1872D4OL (Exenatide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Blood Glucose MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Therapy, Combination MH - Exenatide/therapeutic use MH - Glucagon-Like Peptide 1/*analogs & derivatives MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Insulin, Long-Acting/therapeutic use MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular outcome trials OT - Clinical trials OT - GLP-1 receptor agonists OT - Pharmacotherapy. OT - Type 2 diabetes EDAT- 2018/06/06 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/06/06 06:00 PHST- 2018/06/06 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/06/06 06:00 [entrez] AID - 10.1089/dia.2018.0103 [doi] PST - ppublish SO - Diabetes Technol Ther. 2018 Jun;20(S2):S233-S241. doi: 10.1089/dia.2018.0103. Epub 2018 Jun 5. PMID- 29862621 OWN - NLM STAT- MEDLINE DCOM- 20190128 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 10 DP - 2018 Oct TI - Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. PG - 2426-2434 LID - 10.1111/dom.13396 [doi] AB - AIM: To evaluate the potential for semaglutide to help people with type 2 diabetes (T2D) achieve glycated haemoglobin (HbA1c) targets while avoiding unwanted outcomes, such as weight gain, hypoglycaemia and gastrointestinal (GI) side effects. MATERIALS AND METHODS: Data from the phase IIIa SUSTAIN 1 to 5 clinical trials were analysed. Participants had inadequately controlled T2D and were drug-naive (SUSTAIN 1) or on a range of background treatments (SUSTAIN 2 to 5). The main protocol-specified composite endpoint was the proportion of participants achieving HbA1c <53 mmol/mol (7.0%) at end of treatment (30 or 56 weeks) without weight gain and with no severe or blood glucose (BG)-confirmed symptomatic hypoglycaemia. A post hoc composite endpoint was the proportion of participants achieving the primary composite endpoint without moderate or severe GI adverse events (AEs). RESULTS: Across the SUSTAIN trials 1 to 5, 3918 participants with T2D were randomized to once-weekly subcutaneous semaglutide 0.5 mg, 1.0 mg, or comparators (placebo, sitagliptin 100 mg, exenatide extended release 2.0 mg or insulin glargine). The proportion of participants achieving HbA1c <53 mmol/mol (7.0%) with no weight gain and no severe/BG-confirmed symptomatic hypoglycaemia was 47% to 66% (semaglutide 0.5 mg) and 57% to 74% (semaglutide 1.0 mg) vs 7% to 19% (placebo) and 16% to 29% (active comparators; all P < .0001). More participants achieved the primary composite endpoint with no moderate or severe GI AEs with semaglutide vs comparators (all P < .0001). CONCLUSION: Semaglutide helped more people with T2D achieve HbA1c targets than did comparators in the SUSTAIN 1 to 5 trials, while avoiding unwanted outcomes such as weight gain, hypoglycaemia and GI side effects. CI - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - DeVries, J Hans AU - DeVries JH AD - Department of Endocrinology, Academic Medical Centre, Amsterdam, The Netherlands. AD - Profil Institute for Metabolic Research, Neuss, Germany. FAU - Desouza, Cyrus AU - Desouza C AD - Division of Diabetes Endocrinology & Metabolism, University of Nebraska Medical Center, Omaha, Nebraska. FAU - Bellary, Srikanth AU - Bellary S AD - School of Life and Health Sciences, Aston University, Birmingham, UK. FAU - Unger, Jeffrey AU - Unger J AD - Director, Metabolic Studies, Catalina Research Institute, Chino, California. FAU - Hansen, Oluf K H AU - Hansen OKH AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Zacho, Jeppe AU - Zacho J AD - Novo Nordisk Pharma Ltd., Tokyo, Japan. FAU - Woo, Vincent AU - Woo V AD - Section of Endocrinology and Metabolism, Health Sciences Centre, University of Manitoba, Winnipeg, Canada. LA - eng GR - Novo Nordisk A/S, Soborg, Denmark/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180709 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Blood Glucose/*drug effects/metabolism MH - Clinical Trials, Phase III as Topic/statistics & numerical data MH - Diabetes Mellitus, Type 2/*drug therapy/epidemiology MH - Female MH - Gastrointestinal Diseases/*chemically induced/epidemiology MH - Glucagon-Like Peptides/*therapeutic use MH - Glycated Hemoglobin/*drug effects/metabolism MH - Humans MH - Hypoglycemia/chemically induced MH - Male MH - Middle Aged MH - Multicenter Studies as Topic/statistics & numerical data MH - Randomized Controlled Trials as Topic/statistics & numerical data MH - Retrospective Studies MH - Weight Gain/*drug effects MH - Semaglutide PMC - PMC6175309 OTO - NOTNLM OT - GLP-1 OT - glycaemic control OT - hypoglycaemia OT - type 2 diabetes COIS- SB and VW received research grants from Novo Nordisk for the current study. CD received non-financial support from Novo Nordisk for the current study. Outside the submitted work, JHD received personal fees from Novo Nordisk; CD received grants and personal fees from Novo Nordisk and grants from the National Institutes of Health, Theracos, Sanofi and Janssen; SB received personal fees from Eli Lilly, MSD, AstraZeneca, Boehringer Ingelheim, Sanofi Aventis, Novo Nordisk, and Janssen; VW received grants and personal fees from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, AstraZeneca and Sanofi. JU participates at an advisory board for Novo Nordisk. OKHH and JZ are employees of Novo Nordisk. JZ is a shareholder of Novo Nordisk. EDAT- 2018/06/05 06:00 MHDA- 2019/01/29 06:00 PMCR- 2018/10/08 CRDT- 2018/06/05 06:00 PHST- 2018/02/02 00:00 [received] PHST- 2018/05/11 00:00 [revised] PHST- 2018/05/25 00:00 [accepted] PHST- 2018/06/05 06:00 [pubmed] PHST- 2019/01/29 06:00 [medline] PHST- 2018/06/05 06:00 [entrez] PHST- 2018/10/08 00:00 [pmc-release] AID - DOM13396 [pii] AID - 10.1111/dom.13396 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Oct;20(10):2426-2434. doi: 10.1111/dom.13396. Epub 2018 Jul 9. PMID- 29807374 OWN - NLM STAT- MEDLINE DCOM- 20180702 LR - 20180702 IS - 1439-4413 (Electronic) IS - 0012-0472 (Linking) VI - 143 IP - 11 DP - 2018 Jun TI - [Diabetes Mellitus Type 2: Recent Publications and New Drugs]. PG - 772-776 LID - 10.1055/s-0043-117490 [doi] AB - Since 2013 several placebo-controlled cardiovascular outcomes trails on new classes of glucose-lowering agents in addition to standard care have been reported. These trails were designed to demonstrate non-inferiority to placebo with regard to cardiovascular safety for patients with type 2 diabetes mellitus at high cardiovascular risk.For the glucagon-like peptide 1 (GLP-1)-receptor agonists liraglutide and semaglutide as well as for the sodium-glucose cotransporter-2 (SGLT-2) inhibitors empagliflozin and canagliflozin statistically significant reductions of the primary composite outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) were demonstrated. Cardiovascular outcomes trails for the dipeptidyl peptidase-4 (DPP-4) inhibitors saxagliptin, alogliptin, and sitagliptin did not show statistically significant differences for major cardiovascular events between treatment and placebo groups.Therefore, for patients with established cardiovascular disease who do not achieve sufficient blood glucose control on metformin monotherapy GLP-1-receptor agonists and SGLT-2 inhibitors should be favoured for diabetes therapy intensification. However, the use of DPP-4 inhibitors should be considered for patients who are in need of a well-tolerated and safe oral glucose-lowering therapy. CI - (c) Georg Thieme Verlag KG Stuttgart . New York. FAU - Elbelt, Ulf AU - Elbelt U AD - Medizinische Klinik m. S. Endokrinologie, Diabetes und Ernahrungsmedizin, Charite - Universitatsmedizin Berlin. LA - ger PT - Journal Article TT - Typ-2-Diabetes: Nach Metformin - Verandern neue Studien die Therapie? DEP - 20180528 PL - Germany TA - Dtsch Med Wochenschr JT - Deutsche medizinische Wochenschrift (1946) JID - 0006723 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Placebos) SB - IM MH - Blood Glucose/drug effects MH - Clinical Trials as Topic MH - *Diabetes Mellitus, Type 2/blood/drug therapy/metabolism MH - Humans MH - *Hypoglycemic Agents/pharmacology/therapeutic use MH - Placebos COIS- Ulf Elbelt hat innerhalb der letzten 3 Jahre Vortragshonorare von den Firmen Novo Nordisk Pharma GmbH, Berlin Chemie AG und Lilly Deutschland GmbH erhalten. EDAT- 2018/05/29 06:00 MHDA- 2018/07/03 06:00 CRDT- 2018/05/29 06:00 PHST- 2018/05/29 06:00 [entrez] PHST- 2018/05/29 06:00 [pubmed] PHST- 2018/07/03 06:00 [medline] AID - 10.1055/s-0043-117490 [doi] PST - ppublish SO - Dtsch Med Wochenschr. 2018 Jun;143(11):772-776. doi: 10.1055/s-0043-117490. Epub 2018 May 28. PMID- 29805980 OWN - NLM STAT- MEDLINE DCOM- 20181010 LR - 20250103 IS - 2314-6753 (Electronic) IS - 2314-6745 (Print) VI - 2018 DP - 2018 TI - GLP-1 Receptor Agonists and Cardiovascular Disease in Patients with Type 2 Diabetes. PG - 4020492 LID - 10.1155/2018/4020492 [doi] LID - 4020492 AB - Diabetes mellitus is a chronic disease prevalence of which is high and continually growing. Cardiovascular disease continues to be the leading cause of death in patients with T2DM. The prevention of cardiovascular complications and the cardiovascular safety of treatments should be a primary objective when selecting treatment. Among all the drugs available, the compounds known as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) appear to be not just innocuous in terms of CVD but indeed to be beneficial. GLP-1 RA actions not only translate on an improvement of well-known cardiovascular risk factors such as glycaemic control, dyslipidaemia, weight, or arterial hypertension but also might show benefits on endothelial function, coronary ischaemia, and heart failure. On the other hand, recent clinical trials aimed at studying cardiovascular episodes have been conducted with GLP-1 RAs. Only liraglutide and semaglutide have shown superiority in cardiovascular benefit compared with placebo. Although many of the mechanisms by which liraglutide and semaglutide produce a cardiovascular benefit are still unknown it would be desirable for these benefits to be incorporated into the therapeutic algorithms routinely used in clinical practice. The purpose of this review is to explore GLP-1 RA actions not only in cardiovascular risk factors (glucose, weight, and hypertension) but also the possible effects on established cardiovascular disease. FAU - Del Olmo-Garcia, Maria Isabel AU - Del Olmo-Garcia MI AUID- ORCID: 0000-0002-4278-2624 AD - Mixed Endocrinology, Nutrition and Dietetics Research Unit, University Hospital La Fe, Valencia, Spain. AD - Instituto de Investigacion Sanitaria La Fe, Valencia, Spain. AD - Spanish Clinical Research Network- (SCReN-) IIS La Fe, PT17/0017/0035, Valencia, Spain. FAU - Merino-Torres, Juan Francisco AU - Merino-Torres JF AD - Mixed Endocrinology, Nutrition and Dietetics Research Unit, University Hospital La Fe, Valencia, Spain. AD - Instituto de Investigacion Sanitaria La Fe, Valencia, Spain. AD - Spanish Clinical Research Network- (SCReN-) IIS La Fe, PT17/0017/0035, Valencia, Spain. LA - eng PT - Journal Article PT - Review DEP - 20180402 PL - United States TA - J Diabetes Res JT - Journal of diabetes research JID - 101605237 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Blood Glucose MH - Cardiovascular Diseases/*complications MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Incretins/*therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC5902002 EDAT- 2018/05/29 06:00 MHDA- 2018/10/12 06:00 PMCR- 2018/04/02 CRDT- 2018/05/29 06:00 PHST- 2017/11/09 00:00 [received] PHST- 2018/02/24 00:00 [revised] PHST- 2018/03/03 00:00 [accepted] PHST- 2018/05/29 06:00 [entrez] PHST- 2018/05/29 06:00 [pubmed] PHST- 2018/10/12 06:00 [medline] PHST- 2018/04/02 00:00 [pmc-release] AID - 10.1155/2018/4020492 [doi] PST - epublish SO - J Diabetes Res. 2018 Apr 2;2018:4020492. doi: 10.1155/2018/4020492. eCollection 2018. PMID- 29799205 OWN - NLM STAT- MEDLINE DCOM- 20190624 LR - 20260127 IS - 1543-8392 (Electronic) IS - 1543-8384 (Linking) VI - 15 IP - 7 DP - 2018 Jul 2 TI - Lithocholic Acid-Based Peptide Delivery System for an Enhanced Pharmacological and Pharmacokinetic Profile of Xenopus GLP-1 Analogs. PG - 2840-2856 LID - 10.1021/acs.molpharmaceut.8b00336 [doi] AB - GLP-1 analogs suffer from the main disadvantage of a short in vivo half-life. Lithocholic acid (LCA), one of the four main bile acids in the human body, possesses a high albumin binding rate. We therefore envisioned that a LCA-based peptide delivery system could extend the half-life of GLP-1 analogs by facilitating the noncovalent binding of peptides to human serum albumin. On the basis of our previously identified Xenopus GLP-1 analogs (1-3), a series of LCA-modified Xenopus GLP-1 conjugates were designed (4a-4r), and the bioactivity studies of these conjugates were performed to identify compounds with balanced in vitro receptor activation potency and plasma stability. 4c, 4i, and 4r were selected, and their LCA side chains were optimized to further increase their stability, affording 5a-5c. Compound 5b showed a more increased albumin affinity and prolonged in vitro stability than that of 4i and liraglutide. In db/ db mice, 5b exhibited comparable hypoglycemic and insulinotropic activity to liraglutide and semaglutide. Importantly, the enhanced albumin affinity of 5b resulted in a prolonged in vivo antidiabetic duration. Finally, chronic treatment investigations of 5b demonstrated the therapeutic effects of 5b on HbA1c, body weight, blood glucose, and pancreatic endocrine deficiencies on db/ db mice. Our studies revealed 5b as a promising antidiabetic candidate. Furthermore, our study suggests the derivatization of Xenopus GLP-1 analogs with LCA represents an effective strategy to develop potent long-acting GLP-1 receptor agonists for the treatment of type 2 diabetes. FAU - Han, Jing AU - Han J AUID- ORCID: 0000-0001-5605-1868 AD - School of Chemistry and Materials Science , Jiangsu Normal University , Xuzhou 221116 , PR China. FAU - Chen, Xinyu AU - Chen X AD - School of Chemistry and Materials Science , Jiangsu Normal University , Xuzhou 221116 , PR China. FAU - Zhao, Liming AU - Zhao L AUID- ORCID: 0000-0002-7917-8754 AD - School of Chemistry and Materials Science , Jiangsu Normal University , Xuzhou 221116 , PR China. FAU - Fu, Junjie AU - Fu J AUID- ORCID: 0000-0002-2741-7469 AD - Department of Medicinal Chemistry, School of Pharmacy , Nanjing Medical University , Nanjing 211166 , PR China. FAU - Sun, Lidan AU - Sun L AD - Department of Pharmaceutics, College of Medicine , Jiaxing University , Jiaxing 314001 , PR China. FAU - Zhang, Ying AU - Zhang Y AD - School of Chemistry and Materials Science , Jiangsu Normal University , Xuzhou 221116 , PR China. FAU - Zhou, Feng AU - Zhou F AD - School of Chemistry and Materials Science , Jiangsu Normal University , Xuzhou 221116 , PR China. FAU - Fei, Yingying AU - Fei Y AD - School of Chemistry and Materials Science , Jiangsu Normal University , Xuzhou 221116 , PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180604 PL - United States TA - Mol Pharm JT - Molecular pharmaceutics JID - 101197791 RN - 0 (Blood Glucose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 5QU0I8393U (Lithocholic Acid) RN - ZIF514RVZR (Serum Albumin, Human) RN - 0 (Xenopus Proteins) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Animals MH - Blood Glucose/drug effects MH - Diabetes Mellitus, Experimental/blood/*drug therapy MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Evaluation, Preclinical MH - Drug Stability MH - Glucagon-Like Peptide 1/analogs & derivatives/chemistry/*pharmacology MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - HEK293 Cells MH - Half-Life MH - Humans MH - Hypoglycemic Agents/chemistry/*pharmacology/therapeutic use MH - Liraglutide/pharmacology/therapeutic use MH - Lithocholic Acid/chemistry MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Rats MH - Rats, Sprague-Dawley MH - Serum Albumin, Human/metabolism MH - Treatment Outcome MH - Xenopus Proteins/chemistry/pharmacology MH - Semaglutide OTO - NOTNLM OT - glucagon-like peptide-1 OT - lithocholic acid OT - type 2 diabetes EDAT- 2018/05/26 06:00 MHDA- 2019/06/25 06:00 CRDT- 2018/05/26 06:00 PHST- 2018/05/26 06:00 [pubmed] PHST- 2019/06/25 06:00 [medline] PHST- 2018/05/26 06:00 [entrez] AID - 10.1021/acs.molpharmaceut.8b00336 [doi] PST - ppublish SO - Mol Pharm. 2018 Jul 2;15(7):2840-2856. doi: 10.1021/acs.molpharmaceut.8b00336. Epub 2018 Jun 4. PMID- 29766634 OWN - NLM STAT- MEDLINE DCOM- 20190205 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 9 DP - 2018 Sep TI - Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. PG - 2210-2219 LID - 10.1111/dom.13353 [doi] AB - AIMS: To assess the effect of baseline body mass index (BMI) and the occurrence of nausea and/or vomiting on weight loss induced by semalgutide, a once-weekly glucagon-like peptide 1 analogue for the treatment of type 2 diabetes. Semaglutide demonstrated superior reductions in HbA1c and superior weight loss (by 2.3-6.3 kg) versus different comparators across the SUSTAIN 1 to 5 trials; the contributing factors to weight loss are not established. MATERIALS AND METHODS: Subjects with inadequately controlled type 2 diabetes (drug-naive or on background treatment) were randomized to subcutaneous semaglutide 0.5 mg (excluding SUSTAIN 3), 1.0 mg (all trials), or comparator (placebo, sitagliptin, exenatide extended release or insulin glargine). Subjects were subdivided by baseline BMI and reporting (yes/no) of any nausea and/or vomiting. Change from baseline in body weight was assessed within each trial and subgroup. A mediation analysis separated weight loss into direct or indirect (mediated by nausea or vomiting) effects. RESULTS: Clinically relevant weight-loss differences were observed across all BMI subgroups, with a trend towards higher absolute weight loss with higher baseline BMI. Overall, 15.2% to 24.0% and 21.5% to 27.2% of subjects experienced nausea or vomiting with semaglutide 0.5 and 1.0 mg, respectively, versus 6.0% to 14.1% with comparators. Only 0.07 to 0.5 kg of the treatment difference between semaglutide and comparators was mediated by nausea or vomiting (indirect effects). CONCLUSIONS: In SUSTAIN 1 to 5, semaglutide-induced weight loss was consistently greater versus comparators, regardless of baseline BMI. The contribution of nausea or vomiting to this weight loss was minor. CI - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Ahren, Bo AU - Ahren B AUID- ORCID: 0000-0002-9804-5340 AD - Department of Clinical Sciences, Lund University, Lund, Sweden. FAU - Atkin, Stephen L AU - Atkin SL AUID- ORCID: 0000-0002-5887-7257 AD - Weill Cornell Medical College Qatar, Doha, Qatar. FAU - Charpentier, Guillaume AU - Charpentier G AD - Department of Diabetes and Endocrinology, Centre Hospitalier Regional Gilles de Corbeil, Evry, France. FAU - Warren, Mark L AU - Warren ML AUID- ORCID: 0000-0001-6693-9860 AD - Endocrinology and Metabolism, Physicians East, Greenville, North Carolina. FAU - Wilding, John P H AU - Wilding JPH AD - Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK. FAU - Birch, Sune AU - Birch S AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Holst, Anders Gaarsdal AU - Holst AG AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Leiter, Lawrence A AU - Leiter LA AUID- ORCID: 0000-0002-1040-6229 AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Canada. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180612 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 2ZM8CX04RZ (Insulin Glargine) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - *Body Mass Index MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Exenatide/therapeutic use MH - Female MH - Glucagon-Like Peptides/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Insulin Glargine/therapeutic use MH - Male MH - Middle Aged MH - Nausea/chemically induced MH - Sitagliptin Phosphate/therapeutic use MH - Treatment Outcome MH - Vomiting/chemically induced MH - Weight Loss/*drug effects MH - Semaglutide PMC - PMC6099440 OTO - NOTNLM OT - BMI OT - GLP-1 analogue OT - GLP-1 based therapy OT - gastrointestinal adverse events OT - nausea OT - type 2 OT - vomiting OT - weight control OT - weight loss COIS- B. A. has received speaking or consultancy fees from GSK, MSD, Novartis, Novo Nordisk and Sanofi. S. L. A. has received consultancy fees from Novo Nordisk. G. C. has received consultancy fees from AstraZeneca, Beckton Dickinson, Boehringer Ingelheim, Lilly, Novo Nordisk and Sanofi. M. L. W. has received speaking or consultancy fees from AstraZeneca, Lilly, Merck, Novo Nordisk and Sanofi; research funding for clinical trials (all paid to the institution) from AstraZeneca, Boehringer Ingelheim, Lilly, Mannkind Corporation, Medtronics, Mylan Pharmaceuticals, Novo Nordisk and Sanofi; and travel funding from AstraZeneca, Lilly, Novo Nordisk and Sanofi. J. P. H. W. has received consultancy fees (all paid into University funds) from GW Pharma, Janssen, Lilly, Merck, Novo Nordisk, Orexigen and Takeda; research grants for clinical trials from Janssen, Novo Nordisk, Sanofi and Takeda; and travel grants for conference attendance from Janssen and Novo Nordisk. S. B and A. G. H. are both full-time employees of Novo Nordisk. L. A. L. has received consultancy fees from AstraZeneca, Boehringer Ingelheim, Lilly, GSK, Janssen, Merck, Novo Nordisk, Sanofi and Servier; and grant funding for CME activity from AstraZeneca, Boehringer Ingelheim, Lilly, Janssen, Merck, Novo Nordisk and Sanofi. EDAT- 2018/05/17 06:00 MHDA- 2019/02/06 06:00 PMCR- 2018/08/20 CRDT- 2018/05/17 06:00 PHST- 2018/01/26 00:00 [received] PHST- 2018/04/27 00:00 [revised] PHST- 2018/05/06 00:00 [accepted] PHST- 2018/05/17 06:00 [pubmed] PHST- 2019/02/06 06:00 [medline] PHST- 2018/05/17 06:00 [entrez] PHST- 2018/08/20 00:00 [pmc-release] AID - DOM13353 [pii] AID - 10.1111/dom.13353 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Sep;20(9):2210-2219. doi: 10.1111/dom.13353. Epub 2018 Jun 12. PMID- 29764222 OWN - NLM STAT- MEDLINE DCOM- 20191004 LR - 20260127 IS - 1473-4877 (Electronic) IS - 0300-7995 (Linking) VI - 34 IP - 9 DP - 2018 Sep TI - Comparative efficacy of once-weekly semaglutide and SGLT-2 inhibitors in type 2 diabetic patients inadequately controlled with metformin monotherapy: a systematic literature review and network meta-analysis. PG - 1595-1603 LID - 10.1080/03007995.2018.1476332 [doi] AB - OBJECTIVE: Treatment intensification with additional anti-diabetic agents is recommended in type 2 diabetes (T2D) for patients inadequately controlled on metformin monotherapy. The present network meta-analysis (NMA) evaluated comparative efficacy and safety of once-weekly semaglutide and sodium-glucose co-transporter 2 inhibitors (SGLT-2is) in T2D patients inadequately controlled with metformin. METHODS: Randomized controlled trials with >/=20 weeks duration were searched in EMBASE, MEDLINE, and CENTRAL. Primary efficacy outcomes were: change from baseline in HbA(1c), weight, systolic blood pressure (SBP), post-prandial blood glucose (PPG), and fasting blood glucose (FPG). Treatment effects at 26 (+/-4) weeks were compared using Bayesian NMAs. Meta-regression and sensitivity analysis were used to address the trial heterogeneity. RESULTS: Eight trials were found eligible for this NMA. Statistically significant reductions in HbA1c were observed with both 1.0 mg and 0.5 mg doses of once-weekly semaglutide when compared to SGLT-2is. The mean differences in change from baseline in HbA(1c) for once-weekly semaglutide 1.0 mg vs SGLT-2is ranged from -0.66% for canagliflozin 300 mg (95% Credible Intervals [CrI]: -0.82, -0.50%) to -1.11% for dapagliflozin 5 mg (95% CrI: -1.37, -0.85%). Once-weekly semaglutide 1.0 mg performed significantly better than all SGLT-2is of interest in reducing weight and improving FPG levels: however, SBP reduction was not statistically differentiable. Results of sensitivity analysis and meta-regressions aligned with base-case results. NMAs were not possible for PPG and safety outcomes, due to lack of data. CONCLUSION: Once-weekly semaglutide treatment is significantly better compared to SGLT-2is in achieving adequate glycemic control in T2D patients inadequately controlled with metformin monotherapy. FAU - Sharma, Rohini AU - Sharma R AD - a Precision Xtract , Vancouver , BC , Canada. FAU - Wilkinson, Lars AU - Wilkinson L AD - b Novo Nordisk A/S , Soborg , Denmark. FAU - Vrazic, Hrvoje AU - Vrazic H AD - b Novo Nordisk A/S , Soborg , Denmark. FAU - Popoff, Evan AU - Popoff E AD - a Precision Xtract , Vancouver , BC , Canada. FAU - Lopes, Sandra AU - Lopes S AD - b Novo Nordisk A/S , Soborg , Denmark. FAU - Kanters, Steve AU - Kanters S AD - a Precision Xtract , Vancouver , BC , Canada. FAU - Druyts, Eric AU - Druyts E AD - c Precision Xtract , Boston , MA , USA. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20180529 PL - England TA - Curr Med Res Opin JT - Current medical research and opinion JID - 0351014 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Curr Med Res Opin. 2020 Feb;36(2):209-211. doi: 10.1080/03007995.2019.1678344. PMID: 31596638 MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/*pharmacology MH - Humans MH - Hypoglycemic Agents/pharmacology MH - Metformin/*pharmacology MH - Sodium-Glucose Transporter 2 Inhibitors/*pharmacology MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - Once-weekly semaglutide OT - SGLT-2 inhibitors OT - SUSTAIN 2 OT - SUSTAIN 7 OT - glucagon-like peptide-1 analog OT - type 2 diabetes EDAT- 2018/05/17 06:00 MHDA- 2019/10/08 06:00 CRDT- 2018/05/17 06:00 PHST- 2018/05/17 06:00 [pubmed] PHST- 2019/10/08 06:00 [medline] PHST- 2018/05/17 06:00 [entrez] AID - 10.1080/03007995.2018.1476332 [doi] PST - ppublish SO - Curr Med Res Opin. 2018 Sep;34(9):1595-1603. doi: 10.1080/03007995.2018.1476332. Epub 2018 May 29. PMID- 29756388 OWN - NLM STAT- MEDLINE DCOM- 20190205 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 20 IP - 9 DP - 2018 Sep TI - Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis. PG - 2255-2263 LID - 10.1111/dom.13361 [doi] AB - AIMS: To assess the efficacy and safety of semaglutide, a recently approved glucagon-like peptide 1 receptor agonist (GLP-1 RA) for type 2 diabetes. MATERIALS AND METHODS: We searched major electronic databases and grey literature sources for randomized controlled trials comparing semaglutide with placebo or other antidiabetic agents. Primary outcome was change from baseline in HbA1c. Secondary endpoints included change from baseline in body weight, blood pressure, heart rate and incidence of hypoglycaemia, gastrointestinal adverse effects, pancreatitis and diabetic retinopathy. RESULTS: A total of 6 placebo-controlled and 7 active-controlled studies with subcutaneous semaglutide were included. We identified only 1 trial with oral semaglutide. Compared with placebo, subcutaneous semaglutide 0.5 and 1 mg reduced HbA1c by 1.01% (95% CI, 0.56-1.47) and 1.38% (1.05-1.70), respectively. Both doses demonstrated superior glycaemic efficacy compared to other antidiabetic agents, including sitagliptin, exenatide, liraglutide, dulaglutide and insulin glargine. Semaglutide also had a beneficial effect on body weight (mean difference vs placebo -4.11 kg, 95% CI -4.85 to -3.37 for semaglutide 1 mg) and systolic blood pressure. We did not observe increased hypoglycaemia rates with semaglutide; nevertheless, we noted an increased incidence of nausea, vomiting and diarrhoea. Cases of pancreatitis were infrequent and the odds ratio for diabetic retinopathy compared with placebo was 1.32 (95% CI, 0.98-1.77). CONCLUSIONS: Semaglutide is a potent once-weekly GLP-1 RA, significantly reducing HbA1c, body weight and systolic blood pressure. However, it is associated with increased incidence of gastrointestinal adverse events. Results for pancreatitis and retinopathy require further assessment in post-approval pharmacovigilance studies. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Andreadis, Panagiotis AU - Andreadis P AUID- ORCID: 0000-0002-0968-1039 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Karagiannis, Thomas AU - Karagiannis T AUID- ORCID: 0000-0001-5242-0574 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Malandris, Konstantinos AU - Malandris K AUID- ORCID: 0000-0002-5134-2401 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Avgerinos, Ioannis AU - Avgerinos I AUID- ORCID: 0000-0003-2232-1342 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Liakos, Aris AU - Liakos A AUID- ORCID: 0000-0003-3261-2979 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Manolopoulos, Apostolos AU - Manolopoulos A AUID- ORCID: 0000-0003-1055-0324 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Bekiari, Eleni AU - Bekiari E AUID- ORCID: 0000-0001-9975-3835 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. FAU - Matthews, David R AU - Matthews DR AUID- ORCID: 0000-0001-9028-2328 AD - Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK. AD - Harris Manchester College, University of Oxford, Oxford, UK. FAU - Tsapas, Apostolos AU - Tsapas A AUID- ORCID: 0000-0003-0221-4072 AD - Clinical Research and Evidence-Based Medicine Unit, Second Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece. AD - Harris Manchester College, University of Oxford, Oxford, UK. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20180610 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Controlled Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Female MH - Glucagon-Like Peptides/*administration & dosage MH - Glycated Hemoglobin/drug effects MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/*administration & dosage MH - Male MH - Middle Aged MH - Treatment Outcome MH - Semaglutide OTO - NOTNLM OT - GLP-1 OT - meta-analysis OT - semaglutide OT - systematic review OT - type 2 diabetes EDAT- 2018/05/15 06:00 MHDA- 2019/02/06 06:00 CRDT- 2018/05/15 06:00 PHST- 2018/03/22 00:00 [received] PHST- 2018/04/30 00:00 [revised] PHST- 2018/05/09 00:00 [accepted] PHST- 2018/05/15 06:00 [pubmed] PHST- 2019/02/06 06:00 [medline] PHST- 2018/05/15 06:00 [entrez] AID - 10.1111/dom.13361 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Sep;20(9):2255-2263. doi: 10.1111/dom.13361. Epub 2018 Jun 10. PMID- 29748996 OWN - NLM STAT- MEDLINE DCOM- 20190205 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 9 DP - 2018 Sep TI - Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes. PG - 2238-2245 LID - 10.1111/dom.13358 [doi] AB - AIMS: To evaluate dose levels for semaglutide, a glucagon-like peptide-1 analogue approved for the treatment of type 2 diabetes, by examining the effects of demographic factors on efficacy and safety in an exposure-response analysis. METHODS: We analysed data from 1552 adults from four randomized phase III trials of 30 to 56 weeks' duration, investigating once-weekly semaglutide doses 0.5 and 1.0 mg. Exposure-response relationships were investigated using graphical and model-based techniques to assess the two dose levels and subgroups with the highest and lowest exposure and response. RESULTS: The population had the following demographic characteristics: baseline mean age between 53.2 and 58.4 years, glycated haemoglobin (HbA1c) between 64 and 67 mmol/mol (8.0% and 8.3%), body weight between 71.3 and 96.2 kg, and diabetes duration between 4.2 and 8.9 years. Exposure-response analysis showed a clear HbA1c and weight reduction across exposures after 30 weeks, irrespective of baseline values. The exposure-response for HbA1c was influenced by baseline HbA1c, and body weight exposure-response was influenced by sex, with limited impact of other factors. Analyses for relevant subgroups of baseline body weight, baseline HbA1c and sex indicated clinically relevant additional benefits with regard to HbA1c and weight with 1.0 vs 0.5 mg semaglutide. The proportion of participants reporting gastrointestinal (GI) side effects increased with increasing exposure, but was counteracted by tolerance development. CONCLUSIONS: The analysis showed that all subgroups obtained a clinically relevant benefit with semaglutide 0.5 mg and an additional benefit with semaglutide 1.0 mg. The increase in GI side effects with higher exposure was mitigated by gradually increasing the dose. CI - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Petri, Kristin C C AU - Petri KCC AUID- ORCID: 0000-0001-8417-8575 AD - Department of Quantitative Clinical Pharmacology, Novo Nordisk A/S, Soborg, Denmark. FAU - Ingwersen, Steen H AU - Ingwersen SH AD - Department of Quantitative Clinical Pharmacology, Novo Nordisk A/S, Soborg, Denmark. FAU - Flint, Anne AU - Flint A AD - Department of Clinical Pharmacology, Novo Nordisk A/S, Soborg, Denmark. FAU - Zacho, Jeppe AU - Zacho J AD - Department of Semaglutide Medical and Science, Global Development, Novo Nordisk A/S, Soborg, Denmark. FAU - Overgaard, Rune V AU - Overgaard RV AD - Department of Quantitative Clinical Pharmacology, Novo Nordisk A/S, Soborg, Denmark. LA - eng PT - Evaluation Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180615 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Blood Glucose/drug effects MH - Clinical Trials, Phase III as Topic MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Dose-Response Relationship, Drug MH - Female MH - Glucagon-Like Peptides/*administration & dosage MH - Glycated Hemoglobin/drug effects MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Male MH - Middle Aged MH - Randomized Controlled Trials as Topic MH - Treatment Outcome MH - Weight Loss/drug effects MH - Semaglutide PMC - PMC6099226 OTO - NOTNLM OT - GLP-1 OT - GLP-1 analogue OT - type 2 diabetes COIS- K.C.C.P., S.H.I., A.F., J.Z. and R.V.O. are employed by and hold stock in Novo Nordisk. EDAT- 2018/05/12 06:00 MHDA- 2019/02/06 06:00 PMCR- 2018/08/20 CRDT- 2018/05/12 06:00 PHST- 2018/02/19 00:00 [received] PHST- 2018/04/25 00:00 [revised] PHST- 2018/05/08 00:00 [accepted] PHST- 2018/05/12 06:00 [pubmed] PHST- 2019/02/06 06:00 [medline] PHST- 2018/05/12 06:00 [entrez] PHST- 2018/08/20 00:00 [pmc-release] AID - DOM13358 [pii] AID - 10.1111/dom.13358 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Sep;20(9):2238-2245. doi: 10.1111/dom.13358. Epub 2018 Jun 15. PMID- 29748368 OWN - NLM STAT- MEDLINE DCOM- 20190917 LR - 20250103 IS - 1524-4571 (Electronic) IS - 0009-7330 (Print) IS - 0009-7330 (Linking) VI - 122 IP - 10 DP - 2018 May 11 TI - Cardiovascular Effects of New Oral Glucose-Lowering Agents: DPP-4 and SGLT-2 Inhibitors. PG - 1439-1459 LID - 10.1161/CIRCRESAHA.117.311588 [doi] AB - Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents. DPP-4 inhibitors (gliptins) showed some positive cardiac and vascular effects in preliminary studies, and initial data from phase 2 to 3 clinical trials suggested a reduction in major cardiovascular events. However, subsequent CV outcome trials with alogliptin, saxagliptin, and sitagliptin showed noninferiority but failed to demonstrate any superiority compared with placebo in patients with type 2 diabetes mellitus and high CV risk. An unexpected higher risk of hospitalization for heart failure was reported with saxagliptin. SGLT-2 inhibitors (gliflozins) promote glucosuria, thus reducing glucose toxicity and body weight, and enhance natriuresis, thus lowering blood pressure. Two CV outcome trials in type 2 diabetes mellitus patients mainly in secondary prevention showed remarkable positive results. Empagliflozin in EMPA-REG-OUTCOME (EMPAgliflozin Cardiovascular OUTCOME Events in Type 2 Diabetes Mellitus Patients) reduced major cardiovascular events, CV mortality, all-cause mortality, and hospitalization for heart failure. In CANVAS (Canagliflozin Cardiovascular Assessment Study), the reduction in CV mortality with canagliflozin failed to reach statistical significance despite a similar reduction in major cardiovascular events. The underlying protective mechanisms of SGLT-2 inhibitors remain unknown and both hemodynamic and metabolic explanations have been proposed. CVD-REAL studies (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors; with the limitation of an observational approach) suggested that these favorable results may be considered as a class effect shared by all SGLT-2 inhibitors (including dapagliflozin) and be extrapolated to a larger population of patients with type 2 diabetes mellitus in primary prevention. Ongoing CV outcome trials with other DPP-4 (linagliptin) and SGLT-2 (dapagliflozin, ertugliflozin) inhibitors should provide additional information about CV effects of both pharmacological classes. CI - (c) 2018 The Authors. FAU - Scheen, Andre J AU - Scheen AJ AD - From the Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liege, Belgium (A.J.S.) andre.scheen@chu.ulg.ac.be. AD - Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Belgium (A.J.S.). LA - eng PT - Journal Article PT - Review PL - United States TA - Circ Res JT - Circulation research JID - 0047103 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Circ Res. 2018 Aug 3;123(4):e1-e2. doi: 10.1161/CIRCRESAHA.118.313466. PMID: 30355254 CIN - Circ Res. 2018 Aug 3;123(4):e3-e4. doi: 10.1161/CIRCRESAHA.118.313485. PMID: 30355255 MH - Cardiovascular Diseases/etiology/mortality/*prevention & control MH - Cardiovascular System/*drug effects MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Diabetic Cardiomyopathies/prevention & control MH - Diabetic Nephropathies/prevention & control MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/pharmacology/*therapeutic use MH - Hospitalization MH - Humans MH - Hypoglycemic Agents/adverse effects/pharmacology/*therapeutic use MH - Incretins/metabolism MH - Meta-Analysis as Topic MH - Multicenter Studies as Topic MH - Observational Studies as Topic MH - Risk MH - Sodium-Glucose Transporter 2 Inhibitors/pharmacology/*therapeutic use MH - Treatment Outcome MH - Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC5959222 OTO - NOTNLM OT - empagliflozin OT - heart failure OT - mortality OT - myocardial infarction OT - stroke EDAT- 2018/05/12 06:00 MHDA- 2019/09/19 06:00 PMCR- 2018/05/18 CRDT- 2018/05/12 06:00 PHST- 2018/05/12 06:00 [entrez] PHST- 2018/05/12 06:00 [pubmed] PHST- 2019/09/19 06:00 [medline] PHST- 2018/05/18 00:00 [pmc-release] AID - CIRCRESAHA.117.311588 [pii] AID - 10.1161/CIRCRESAHA.117.311588 [doi] PST - ppublish SO - Circ Res. 2018 May 11;122(10):1439-1459. doi: 10.1161/CIRCRESAHA.117.311588. PMID- 29707863 OWN - NLM STAT- MEDLINE DCOM- 20190205 LR - 20210109 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 9 DP - 2018 Sep TI - Glucagon-like peptide-1 receptor expression in the human eye. PG - 2304-2308 LID - 10.1111/dom.13339 [doi] AB - Semaglutide is a human glucagon-like peptide-1 (GLP-1) analogue that is in development for the treatment of type 2 diabetes. In the pre-approval cardiovascular outcomes trial SUSTAIN 6, semaglutide was associated with a significant increase in the risk of diabetic retinopathy (DR) complications vs placebo. GLP-1 receptor (GLP-1R) expression has previously been demonstrated in the retina in animals and humans; however, antibodies used to detect expression have been documented to be non-specific and fail to detect the GLP-1R using immunohistochemistry (IHC), a problem common for many G-protein coupled receptors. Using a validated GLP-1R antibody for IHC and in situ hybridization for GLP-1R mRNA in normal human eyes, GLP-1Rs were detected in a small fraction of neurons in the ganglion cell layer. In advanced stages of DR, GLP-1R expression was not detected at the protein or mRNA level. Specifically, no GLP-1R expression was found in the eyes of people with long-standing proliferative DR (PDR). In conclusion, GLP-1R expression is low in normal human eyes and was not detected in eyes exhibiting advanced stages of PDR. CI - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hebsgaard, Josephine B AU - Hebsgaard JB AD - Novo Nordisk A/S Global Research, Malov, Denmark. FAU - Pyke, Charles AU - Pyke C AD - Novo Nordisk A/S Global Research, Malov, Denmark. FAU - Yildirim, Emre AU - Yildirim E AD - Novo Nordisk A/S Global Medical Affairs, Malov, Denmark. FAU - Knudsen, Lotte B AU - Knudsen LB AUID- ORCID: 0000-0002-2439-7116 AD - Novo Nordisk A/S Global Research, Malov, Denmark. FAU - Heegaard, Steffen AU - Heegaard S AD - Department of Pathology, Rigshospitalet, Eye Pathology Section, University of Copenhagen, Copenhagen, Denmark. AD - Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Kvist, Peter H AU - Kvist PH AD - Novo Nordisk A/S Global Research, Malov, Denmark. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180524 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (RNA, Messenger) SB - IM CIN - Diabetes Obes Metab. 2019 Feb;21(2):446-447. doi: 10.1111/dom.13521. PMID: 30187661 MH - Adult MH - Aged MH - Diabetes Mellitus, Type 2/complications/*metabolism MH - Diabetic Retinopathy/etiology/*metabolism MH - Eye/*metabolism MH - Female MH - Glucagon-Like Peptide-1 Receptor/*metabolism MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization MH - Male MH - Middle Aged MH - RNA, Messenger/metabolism PMC - PMC6099507 OTO - NOTNLM OT - GLP-1 analogue OT - cardiovascular disease OT - diabetes complications OT - diabetic retinopathy COIS- S.H. declares no relevant conflict of interest. J.B.H. is a former employee of Novo Nordisk. C.P., E.Y., L.B.K. and P.H.K. are employees of Novo Nordisk. J.B.H., C.P., L.B.K. and P.H.K. are shareholders of Novo Nordisk. EDAT- 2018/05/01 06:00 MHDA- 2019/02/06 06:00 PMCR- 2018/08/20 CRDT- 2018/05/01 06:00 PHST- 2018/02/13 00:00 [received] PHST- 2018/04/13 00:00 [revised] PHST- 2018/04/23 00:00 [accepted] PHST- 2018/05/01 06:00 [pubmed] PHST- 2019/02/06 06:00 [medline] PHST- 2018/05/01 06:00 [entrez] PHST- 2018/08/20 00:00 [pmc-release] AID - DOM13339 [pii] AID - 10.1111/dom.13339 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Sep;20(9):2304-2308. doi: 10.1111/dom.13339. Epub 2018 May 24. PMID- 29693361 OWN - NLM STAT- MEDLINE DCOM- 20191125 LR - 20250103 IS - 1936-2692 (Electronic) IS - 1088-0224 (Linking) VI - 24 IP - 8 Suppl DP - 2018 Apr TI - Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials enrollment criteria to the US type 2 diabetes population. PG - S146-S155 AB - OBJECTIVES: Cardiovascular outcomes trials (CVOTs) for evaluating the safety of novel antidiabetic agents are required by the FDA. CVOTs vary in their design and inclusion criteria, making it difficult to evaluate their applicability to the general population. This study examined the proportion of adults eligible for 7 ongoing or completed glucagon-like peptide-1 receptor agonist (GLP-1 RA) CVOTs. STUDY DESIGN: This cross-sectional, retrospective, cohort study compared data from the National Health and Nutrition Examination Survey (NHANES) with published eligibility criteria from GLP-1 RA CVOTs. METHODS: Patient information on T2D status and other relevant characteristics were extracted from the 2009 to 2010 and the 2011 to 2012 NHANES. Weighted analyses of these data were used to calculate the numbers of adults with T2D in the US population who would have met eligibility criteria for enrollment in the following published or ongoing CVOTs: ELIXA (lixisenatide; NCT01147250), EXSCEL (Exenatide Study of Cardiovascular Event Lowering) (exenatide once weekly; NCT01144338), FREEDOM-CVO (exenatide via ITCA 650 miniature osmotic pump; NCT01455896), HARMONY Outcomes (albiglutide; NCT02465515), LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results) (liraglutide; NCT01179048), REWIND (Researching Cardiovascular Events With a Weekly INcretin in Diabetes) (dulaglutide; NCT01394952), and SUSTAIN-6 (semaglutide; NCT01720446). RESULTS: The proportion of adults with T2D eligible for enrollment varied substantially among CVOTs (6.4%-47.2%); EXSCEL, which had a pragmatic study design, had the most generalizable inclusion criteria. More than 60% of patients with T2D would have qualified for enrollment into at least 1 GLP-1 RA CVOT. CONCLUSIONS: Most adults with T2D in the United States would have qualified for enrollment into at least 1 of the GLP-1 RA CVOTs evaluated. EXSCEL had the most generalizable eligibility criteria of these trials and ELIXA the least. FAU - Wittbrodt, Eric T AU - Wittbrodt ET AD - AstraZeneca, Wilmington, DE. Email: eric.wittbrodt@astrazeneca.com. FAU - Eudicone, James M AU - Eudicone JM FAU - Bell, Kelly F AU - Bell KF FAU - Enhoffer, Devin M AU - Enhoffer DM FAU - Latham, Keith AU - Latham K FAU - Green, Jennifer B AU - Green JB LA - eng SI - ClinicalTrials.gov/NCT01147250 SI - ClinicalTrials.gov/NCT01144338 SI - ClinicalTrials.gov/NCT01455896 SI - ClinicalTrials.gov/NCT02465515 SI - ClinicalTrials.gov/NCT01179048 SI - ClinicalTrials.gov/NCT01394952 SI - ClinicalTrials.gov/NCT01720446 PT - Journal Article PL - United States TA - Am J Manag Care JT - The American journal of managed care JID - 9613960 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) CIN - Am J Manag Care. 2019 Apr;25(4):170-171. PMID: 30986012 CIN - Am J Manag Care. 2019 Apr;25(4):171-172. PMID: 30986013 MH - Cardiovascular Diseases/*drug therapy MH - Cohort Studies MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - Drug Administration Schedule MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Randomized Controlled Trials as Topic MH - Retrospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2018/04/26 06:00 MHDA- 2019/11/26 06:00 CRDT- 2018/04/26 06:00 PHST- 2018/04/26 06:00 [entrez] PHST- 2018/04/26 06:00 [pubmed] PHST- 2019/11/26 06:00 [medline] AID - 87534 [pii] PST - ppublish SO - Am J Manag Care. 2018 Apr;24(8 Suppl):S146-S155. PMID- 29688502 OWN - NLM STAT- MEDLINE DCOM- 20181231 LR - 20260202 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 103 IP - 6 DP - 2018 Jun 1 TI - Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial. PG - 2291-2301 LID - 10.1210/jc.2018-00070 [doi] AB - CONTEXT: Combination therapy with insulin and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is important for treating type 2 diabetes (T2D). This trial assesses the efficacy and safety of semaglutide, a GLP-1RA, as an add-on to basal insulin. OBJECTIVE: To demonstrate the superiority of semaglutide vs placebo on glycemic control as an add-on to basal insulin in patients with T2D. DESIGN: Phase 3a, double-blind, placebo-controlled, 30-week trial. SETTING: This study included 90 sites in five countries. PATIENTS: We studied 397 patients with uncontrolled T2D receiving stable therapy with basal insulin with or without metformin. INTERVENTIONS: Subcutaneous semaglutide 0.5 or 1.0 mg once weekly or volume-matched placebo. MAIN OUTCOME MEASURES: Primary endpoint was change in glycated Hb (HbA1c) from baseline to week 30. Confirmatory secondary endpoint was change in body weight from baseline to week 30. RESULTS: At week 30, mean HbA1c reductions [mean baseline value, 8.4% (67.9 mmol/mol)] with semaglutide 0.5 and 1.0 mg were 1.4% (15.8 mmol/mol) and 1.8% (20.2 mmol/mol) vs 0.1% (1.0 mmol/mol) with placebo [estimated treatment difference (ETD) vs placebo, -1.35 (14.8 mmol/mol); 95% CI, -1.61 to -1.10 and ETD, -1.75% (19.2 mmol/mol); 95% CI, -2.01 to -1.50; both P < 0.0001]. Severe or blood glucose-confirmed hypoglycemic episodes were reported in 11 patients (17 events) and 14 patients (25 events) with semaglutide 0.5 and 1.0 mg, respectively, vs seven patients (13 events) with placebo (estimated rate ratio vs placebo, 2.08; 95% CI, 0.67 to 6.51 and estimated rate ratio vs placebo, 2.41; 95% CI, 0.84 to 6.96 for 0.5 and 1.0 mg; both P = nonsignificant). Mean body weight decreased with semaglutide 0.5 and 1.0 mg vs placebo from baseline to end of treatment: 3.7, 6.4, and 1.4 kg (ETD, -2.31; 95% CI, -3.33 to -1.29 and ETD, -5.06; 95% CI, -6.08 to -4.04 kg; both P < 0.0001). Premature treatment discontinuation due to adverse events was higher for semaglutide 0.5 and 1.0 mg vs placebo (4.5%, 6.1%, and 0.8%), mainly due to gastrointestinal disorders. CONCLUSIONS: Semaglutide, added to basal insulin, significantly reduced HbA1c and body weight in patients with uncontrolled T2D vs placebo. FAU - Rodbard, Helena W AU - Rodbard HW AD - Endocrine and Metabolic Consultants, Rockville, Maryland. FAU - Lingvay, Ildiko AU - Lingvay I AD - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas. FAU - Reed, John AU - Reed J AD - Endocrine Research Solutions, Inc., Roswell, Georgia. FAU - de la Rosa, Raymond AU - de la Rosa R AD - Four Rivers Clinical Research, Paducah, Kentucky. FAU - Rose, Ludger AU - Rose L AD - Institute of Diabetes Research, Munster, Germany. FAU - Sugimoto, Danny AU - Sugimoto D AD - Cedar-Crosse Research Center, Chicago, Illinois. FAU - Araki, Eiichi AU - Araki E AD - Department of Metabolic Medicine, Kumamoto University, Kumamoto, Japan. FAU - Chu, Pei-Ling AU - Chu PL AD - Novo Nordisk Inc., Plainsboro, New Jersey. FAU - Wijayasinghe, Nelun AU - Wijayasinghe N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Norwood, Paul AU - Norwood P AD - University of California at San Francisco, Fresno, California. LA - eng SI - ClinicalTrials.gov/NCT02305381 PT - Clinical Trial, Phase III PT - Equivalence Trial PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Blood Glucose MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptides/*therapeutic use MH - Glycated Hemoglobin/*analysis MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Insulin/*therapeutic use MH - Male MH - Middle Aged MH - Treatment Outcome MH - Young Adult MH - Semaglutide PMC - PMC5991220 EDAT- 2018/04/25 06:00 MHDA- 2019/01/01 06:00 PMCR- 2018/04/23 CRDT- 2018/04/25 06:00 PHST- 2018/01/09 00:00 [received] PHST- 2018/04/17 00:00 [accepted] PHST- 2018/04/25 06:00 [pubmed] PHST- 2019/01/01 06:00 [medline] PHST- 2018/04/25 06:00 [entrez] PHST- 2018/04/23 00:00 [pmc-release] AID - 4981435 [pii] AID - jcem_201800070 [pii] AID - 10.1210/jc.2018-00070 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2018 Jun 1;103(6):2291-2301. doi: 10.1210/jc.2018-00070. PMID- 29687620 OWN - NLM STAT- MEDLINE DCOM- 20190205 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 9 DP - 2018 Sep TI - Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials. PG - 2291-2297 LID - 10.1111/dom.13331 [doi] AB - The efficacy and safety of semaglutide vs comparators in non-elderly (<65 years) and elderly (>/=65 years) patients with type 2 diabetes (T2D) across the SUSTAIN 1-5 trials were evaluated. Patients were randomized to once-weekly subcutaneous semaglutide (0.5 or 1.0 mg) vs placebo, sitagliptin, exenatide or insulin. The primary objective was change in HbA1c and secondary objectives were changes in body weight and safety. Mean HbA1c decreased from baseline by 1.2%-1.5% and 1.5%-1.9% vs 0%-0.9% (non-elderly, n = 3045) and by 1.3%-1.5% and 1.2%-1.8% vs 0.2%-1.0% (elderly, n = 854) with semaglutide 0.5 and 1.0 mg vs comparators. Similar reductions from baseline in mean body weight with semaglutide occurred in both age groups. Similar proportions of patients experienced adverse events; premature treatment discontinuations were higher in elderly vs non-elderly patients. No increased risk of severe or blood glucose-confirmed hypoglycaemia was seen with semaglutide vs comparators between age groups. Semaglutide had a comparable efficacy and safety profile in non-elderly and elderly patients across the SUSTAIN 1-5 trials, making it an effective treatment option for elderly patients with T2D. CI - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Warren, Mark AU - Warren M AUID- ORCID: 0000-0001-6693-9860 AD - Physicians East, Greenville, North Carolina. FAU - Chaykin, Louis AU - Chaykin L AD - Meridien Research, Bradenton, Florida. FAU - Trachtenbarg, David AU - Trachtenbarg D AD - University of Illinois College of Medicine at Peoria, Peoria, Illinois. FAU - Nayak, Gurudutt AU - Nayak G AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Wijayasinghe, Nelun AU - Wijayasinghe N AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Cariou, Bertrand AU - Cariou B AD - L'Institut du Thorax, Department of Endocrinology, CHU de Nantes, Nantes, France. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180607 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Exenatide/therapeutic use MH - Female MH - Glucagon-Like Peptides/*therapeutic use MH - Glycated Hemoglobin/drug effects MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/*therapeutic use MH - Insulin/therapeutic use MH - Male MH - Sitagliptin Phosphate/therapeutic use MH - Treatment Outcome MH - Semaglutide PMC - PMC6099273 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - glycaemic control OT - incretin therapy OT - type 2 diabetes COIS- M. W. has received research support from Novo Nordisk, Eli Lilly, Janssen, Shire, Pfizer, Mylan and Sanofi; is on the advisory panel of Novo Nordisk, Sanofi and Eli Lilly; and is on the speaker's bureau of Novo Nordisk, Eli Lilly, Janssen, AstraZeneca, Sanofi, Merck, Shire and Mannkind. L. C. is a consultant for Novo Nordisk and is on the advisory board of Intarcia Therapeutics. D. T. is on the advisory panel of Novo Nordisk and has received research support from Novo Nordisk, Sanofi Aventis and Sanofi. G. N. and N. W. are full-time employees of Novo Nordisk. B. C. is a consultant for Novo Nordisk; has received research support from Pfizer, Sanofi and Regeneron; and has received honoraria from Amgen, Pierre Fabre, Eli Lilly, MSD, Merck & Co, Novo Nordisk, Regeneron and Sanofi. EDAT- 2018/04/25 06:00 MHDA- 2019/02/06 06:00 PMCR- 2018/08/20 CRDT- 2018/04/25 06:00 PHST- 2018/01/24 00:00 [received] PHST- 2018/04/16 00:00 [revised] PHST- 2018/04/19 00:00 [accepted] PHST- 2018/04/25 06:00 [pubmed] PHST- 2019/02/06 06:00 [medline] PHST- 2018/04/25 06:00 [entrez] PHST- 2018/08/20 00:00 [pmc-release] AID - DOM13331 [pii] AID - 10.1111/dom.13331 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Sep;20(9):2291-2297. doi: 10.1111/dom.13331. Epub 2018 Jun 7. PMID- 29677253 OWN - NLM STAT- MEDLINE DCOM- 20190801 LR - 20260127 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 168 IP - 8 DP - 2018 Apr 17 TI - In type 2 diabetes, weekly semaglutide reduced HbA1c and increased weight loss more than weekly exenatide ER. PG - JC46 LID - 10.7326/ACPJC-2018-168-8-046 [doi] FAU - Bekiari, Eleni AU - Bekiari E FAU - Karagiannis, Thomas AU - Karagiannis T FAU - Tsapas, Apostolos AU - Tsapas A LA - eng PT - Comment PT - Journal Article PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) CON - Diabetes Care. 2018 Feb;41(2):258-266. doi: 10.2337/dc17-0417. PMID: 29246950 MH - *Diabetes Mellitus, Type 2 MH - Exenatide MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - Weight Loss MH - Semaglutide EDAT- 2018/04/21 06:00 MHDA- 2019/08/02 06:00 CRDT- 2018/04/21 06:00 PHST- 2018/04/21 06:00 [entrez] PHST- 2018/04/21 06:00 [pubmed] PHST- 2019/08/02 06:00 [medline] AID - 2678486 [pii] AID - 10.7326/ACPJC-2018-168-8-046 [doi] PST - ppublish SO - Ann Intern Med. 2018 Apr 17;168(8):JC46. doi: 10.7326/ACPJC-2018-168-8-046. PMID- 29668601 OWN - NLM STAT- MEDLINE DCOM- 20180424 LR - 20260127 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 97 IP - 16 DP - 2018 Apr TI - Efficacy and safety of once-weekly semaglutide for the treatment of type 2 diabetes: Protocol for a systematic review and meta-analysis. PG - e0420 LID - 10.1097/MD.0000000000010420 [doi] LID - e0420 AB - BACKGROUND: It is a great challenge for type 2 diabetes mellitus (T2DM) patients to maintain optimal glycemia, control body weight, blood pressure, and avoiding hypoglycemia. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs) can stimulate glucose-dependent insulin while inhibit glucagon secretion, delay gastric emptying, reduce appetite, and energy intake. Recently, a new once-weekly GLP-1 RAs, semaglutide, has been registered to treat patients with T2DM. METHODS: We will search Medline, Embase, Cochrane Library, and the ClinicalTrials.gov Website up to February 2018. Studies will be screened by title, abstract, and full text independently in duplicate. Phase III randomized controlled trials (RCTs) reports efficacy and safety data of semaglutide will be eligible for inclusion. Outcome variables will be assessed included glycemic control indexes (glycosylated hemoglobin [HbA1c]%, fasting plasma glucose [FPG], self-monitoring of blood glucose [SMPG], postprandial self-monitoring of blood glucose [PSMPG]), blood pressure indexes (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse rate), body weight control indexes (body weight, body mass index [BMI], and waist circumference), and any adverse events (including adverse events [AEs] varying degrees and AEs occurring in >/=5% patients by preferred term or other of clinical interest). Assessment of risk of bias and data synthesis will be performed using STATA software (version 12, Statacorp, College Station, Texas). Outcomes will report by weight mean difference (WMD) and risk ratios (RRs) and their 95% confidence intervals (95% CIs). Heterogeneity among studies will be evaluated using the I statistic. RESULTS: This review will evaluate glycemic, blood pressure, body weight control, and any adverse events of semaglutide as compared with other therapies. CONCLUSION: Our study will provide a comprehensive picture of semaglutide in T2DM. FAU - Shi, Fang-Hong AU - Shi FH AD - Department of Pharmacy, Renji Hospital Department of Pharmacy, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China. FAU - Li, Hao AU - Li H FAU - Cui, Min AU - Cui M FAU - Zhang, Zai-Li AU - Zhang ZL FAU - Gu, Zhi-Chun AU - Gu ZC FAU - Liu, Xiao-Yan AU - Liu XY LA - eng PT - Journal Article PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose/metabolism MH - Body Weight MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Administration Schedule MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Middle Aged MH - Systematic Reviews as Topic MH - Meta-Analysis as Topic MH - Semaglutide PMC - PMC5916683 COIS- The authors have no conflicts of interest to disclose. EDAT- 2018/04/19 06:00 MHDA- 2018/04/25 06:00 PMCR- 2018/04/20 CRDT- 2018/04/19 06:00 PHST- 2018/04/19 06:00 [entrez] PHST- 2018/04/19 06:00 [pubmed] PHST- 2018/04/25 06:00 [medline] PHST- 2018/04/20 00:00 [pmc-release] AID - 00005792-201804200-00027 [pii] AID - MD-D-18-01647 [pii] AID - 10.1097/MD.0000000000010420 [doi] PST - ppublish SO - Medicine (Baltimore). 2018 Apr;97(16):e0420. doi: 10.1097/MD.0000000000010420. PMID- 29667921 OWN - NLM STAT- MEDLINE DCOM- 20180611 LR - 20260127 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 130 IP - 4 DP - 2018 May TI - Glycemic control of type 2 diabetes mellitus across stages of renal impairment: information for primary care providers. PG - 381-393 LID - 10.1080/00325481.2018.1457397 [doi] AB - Chronic kidney disease (CKD) is a frequent complication of type 2 diabetes mellitus (T2DM) and elevates individuals' risk for cardiovascular disease, the leading cause of morbidity and mortality in T2DM. Achieving and maintaining tight glycemic control is key to preventing development or progression of CKD; however, improving glycemic control may be limited by effects of renal impairment on the efficacy and safety of T2DM treatments, necessitating dosing adjustments and careful evaluation of contraindications. Understanding the treatment considerations specific to each class of T2DM medication is important in individualizing therapy and improving glycemic, renal, and cardiovascular outcomes. Traditional glucose-lowering treatments include insulin, metformin, sulfonylureas, meglitinides, and thiazolidinediones. Each of these agents exhibits altered pharmacokinetics in patients with renal impairment except for the thiazolidinediones, which are metabolized by the liver and do not accumulate appreciably in patients with renal impairment. Newer glucose-lowering treatments include GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors. Of these, only the DPP-4 inhibitor linagliptin can be used across all stages of renal impairment without dosing restrictions or concerns regarding dose escalation, and all SGLT2 inhibitors are contraindicated when eGFR <45 mL/min/1.73m(2). Several of the newer treatments have also been investigated for effects on renal and cardiovascular outcomes, demonstrating potential benefits of the GLP-1 agonists liraglutide and semaglutide, as well as the SGLT2 inhibitors canagliflozin and empagliflozin, in reducing risk for some adverse renal and cardiovascular events. In addition, some DPP-4 inhibitors have been shown to reduce albuminuria, an indicator of glomerular dysfunction. Consideration of this information is useful in informing optimal management strategies for patients with T2DM and concomitant CKD. More clinical data from future and ongoing clinical trials, including data regarding potential renal and cardiovascular benefits, will be important in clarifying the safety and efficacy profiles of each of these agents in patients with CKD. FAU - Tong, Lili AU - Tong L AD - a Division of Nephrology and Hypertension , Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center , Torrance , CA , USA. FAU - Adler, Sharon AU - Adler S AD - a Division of Nephrology and Hypertension , Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center , Torrance , CA , USA. LA - eng PT - Journal Article PT - Review DEP - 20180418 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Benzamides) RN - 0 (Blood Glucose) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 9100L32L2N (Metformin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Thiazolidinediones) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (hemoglobin A1c protein, human) RN - 8V6OK1I088 (meglitinide) SB - IM MH - Benzamides/administration & dosage/therapeutic use MH - Blood Glucose/metabolism MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Diabetic Nephropathies/etiology/*metabolism MH - Dipeptidyl-Peptidase IV Inhibitors/administration & dosage/therapeutic use MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/*administration & dosage/therapeutic use MH - Insulin/administration & dosage/therapeutic use MH - Metformin/administration & dosage/therapeutic use MH - Patient Care Planning MH - Physicians, Primary Care MH - *Primary Health Care MH - Renal Insufficiency, Chronic/etiology/*metabolism MH - Sodium-Glucose Transporter 2 Inhibitors MH - Sulfonylurea Compounds/administration & dosage/therapeutic use MH - Thiazolidinediones/administration & dosage/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Type 2 diabetes mellitus OT - albuminuria OT - cardiovascular disease OT - contraindications OT - hyperglycemia OT - pharmacokinetics OT - renal insufficiency EDAT- 2018/04/19 06:00 MHDA- 2018/06/12 06:00 CRDT- 2018/04/19 06:00 PHST- 2018/04/19 06:00 [pubmed] PHST- 2018/06/12 06:00 [medline] PHST- 2018/04/19 06:00 [entrez] AID - 10.1080/00325481.2018.1457397 [doi] PST - ppublish SO - Postgrad Med. 2018 May;130(4):381-393. doi: 10.1080/00325481.2018.1457397. Epub 2018 Apr 18. PMID- 29580579 OWN - NLM STAT- MEDLINE DCOM- 20191004 LR - 20250103 IS - 1548-5609 (Electronic) IS - 1548-5595 (Linking) VI - 25 IP - 2 DP - 2018 Mar TI - New Glucose-Lowering Agents for Diabetic Kidney Disease. PG - 149-157 LID - S1548-5595(18)30002-8 [pii] LID - 10.1053/j.ackd.2018.01.002 [doi] AB - The prevalence of diabetes mellitus is increasing and is associated with a range of complications including nephropathy. New antidiabetic agents are sought which also have positive effects to diminish diabetic complications. Examples of promising new classes of such agents are glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter 2 inhibitors. In addition to cardiovascular protective effects such as weight loss and decreased blood pressure of some of these agents, there is evidence for renoprotective effects with these agents. This review elaborates on the main results of renoprotective effects of these 3 treatment classes. In conclusion, currently available trials have demonstrated renoprotective effects for certain glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, and the sodium-glucose cotransporter 2 inhibitors, empagliflozin and canagliflozin. Dipeptidyl peptidase-4 inhibitors did not show a significant renoprotective effect. Nevertheless, larger studies with respect to renoprotective effects of these 3 drug classes are currently being performed, and thus, no conclusions for all of these agents can yet be made. CI - Crown Copyright (c) 2018. Published by Elsevier Inc. All rights reserved. FAU - de Vos, Lisanne C AU - de Vos LC AD - Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia; and the Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Hettige, Thushan S AU - Hettige TS AD - Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia; and the Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Cooper, Mark E AU - Cooper ME AD - Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia; and the Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: mark.cooper@monash.edu. LA - eng PT - Journal Article PT - Review PL - United States TA - Adv Chronic Kidney Dis JT - Advances in chronic kidney disease JID - 101209214 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Drugs, Investigational) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - *Diabetic Nephropathies/etiology/prevention & control MH - Dipeptidyl-Peptidase IV Inhibitors/*pharmacology MH - Drugs, Investigational/pharmacology MH - Humans MH - *Hypoglycemic Agents/pharmacology MH - Sodium-Glucose Transporter 2 Inhibitors/*pharmacology MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Chronic kidney disease OT - DPP-4 inhibitors OT - Diabetes mellitus OT - GLP-1 receptor agonists OT - SGLT-2 inhibitors EDAT- 2018/03/28 06:00 MHDA- 2019/10/08 06:00 CRDT- 2018/03/28 06:00 PHST- 2017/05/01 00:00 [received] PHST- 2018/01/03 00:00 [revised] PHST- 2018/01/03 00:00 [accepted] PHST- 2018/03/28 06:00 [entrez] PHST- 2018/03/28 06:00 [pubmed] PHST- 2019/10/08 06:00 [medline] AID - S1548-5595(18)30002-8 [pii] AID - 10.1053/j.ackd.2018.01.002 [doi] PST - ppublish SO - Adv Chronic Kidney Dis. 2018 Mar;25(2):149-157. doi: 10.1053/j.ackd.2018.01.002. PMID- 29536338 OWN - NLM STAT- MEDLINE DCOM- 20190530 LR - 20260127 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 35 IP - 4 DP - 2018 Apr TI - A Randomized Trial Investigating the Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects. PG - 531-544 LID - 10.1007/s12325-018-0677-1 [doi] AB - INTRODUCTION: Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects. METHODS: In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC(0-168h))]. RESULTS: Steady-state exposure of semaglutide was similar for both populations: AUC(0-168h) estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C(max)) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC(0-168h) ERR 1.11; C(max) ERR 1.14). Dose-dependent increases in AUC(0-168h) and C(max) occurred in both populations. Accumulation was as expected, based on the half-life (t(1/2), ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p 80% achieved an HbA1c concentration <7.0% (Japanese Diabetes Society target). CONCLUSIONS: Semaglutide was well tolerated, with no new safety issues identified. Semaglutide treatment significantly reduced HbA1c and body weight vs additional OAD treatment in Japanese people with T2D. CI - (c) 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Kaku, Kohei AU - Kaku K AUID- ORCID: 0000-0003-1574-0565 AD - Department of General Internal Medicine 1, Kawasaki Medical School, Okayama, Japan. FAU - Yamada, Yuichiro AU - Yamada Y AD - Department of Endocrinology, Diabetes and Geriatric Medicine, Akita University Graduate School of Medicine, Akita, Japan. FAU - Watada, Hirotaka AU - Watada H AD - Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan. FAU - Abiko, Atsuko AU - Abiko A AD - Department of Internal Medicine, Asahikawa Medical University, Asahikawa, Japan. FAU - Nishida, Tomoyuki AU - Nishida T AD - Novo Nordisk Pharma Ltd., Tokyo, Japan. FAU - Zacho, Jeppe AU - Zacho J AD - Novo Nordisk Pharma Ltd., Tokyo, Japan. FAU - Kiyosue, Arihiro AU - Kiyosue A AD - Department of Internal Medicine, Tokyo-Eki Center-Building Clinic, Tokyo, Japan. LA - eng SI - ClinicalTrials.gov/NCT02207374 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180221 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Administration, Oral MH - Aged MH - Combined Modality Therapy/adverse effects MH - Diabetes Mellitus, Type 2/blood/*drug therapy/metabolism MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Drug Monitoring MH - Drug Resistance MH - Drug Therapy, Combination/adverse effects MH - Female MH - Follow-Up Studies MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/*administration & dosage/adverse effects/therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hyperglycemia/*prevention & control MH - Hypoglycemia/chemically induced/*prevention & control MH - Hypoglycemic Agents/*administration & dosage/adverse effects/therapeutic use MH - Injections, Subcutaneous MH - Japan MH - Male MH - Middle Aged MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC5969242 OTO - NOTNLM OT - GLP-1 analogue OT - glycaemic control OT - incretin therapy OT - phase III study OT - randomized trial OT - type 2 diabetes COIS- K.K. has received honoraria or consulting fees from Astellas Pharma, AstraZeneca KK, MSD KK, Ono Pharmaceutical, Kissei Pharmaceutical, Kowa Pharmaceutical, Sanofi KK, Sanwakagaku Kenkyusyo, Sumitomo Dainippon Pharma, Mitsubishi Tanabe Pharma, Novartis Pharma KK, Novo Nordisk, Nippon Boehringer Ingelheim, Taisho Toyama Pharmaceutical and Takeda, and research grants from Taisho Pharmaceutical, Mitsubishi Tanabe Pharma and Nippon Boehringer Ingelheim. Y.Y. has received honoraria or consulting fees from Novo Nordisk. H.W. has received honoraria for consulting from Boehringer Ingelheim, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eli Lilly, Kowa Pharmaceutical, Merck Sharp & Dohme, Novo Nordisk, Novartis, Ono Pharmaceutical, Sanofi, Sanwa Kagaku Kenkyusho, Takeda, Astellas Pharma, Mitsubishi Tanabe Pharma, AstraZeneca, Kyowa Hakko Kirin and Kissei Pharmaceutical, and grants from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eli Lilly, Kissei Pharma, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Novartis, Novo Nordisk, Pfizer, Sanofi, Sanwakagaku Kenkyusho, Takeda, Terumo Corp, Novartis, Astellas Pharma, Abbott Japan, Ono Pharmaceutical, Kyowa Hakko Kirin Co. Ltd, Kowa Pharmaceutical, Johnson & Johnson, Taisho Toyama Pharmaceutical, Nitto Boseki Company, Bayer, Bristol-Myers Squibb and Benefit one Health care. A.A. has received consulting and/or speaker fees from Novo Nordisk, Eli Lilly Japan, Nippon Boehringer Ingelheim, Kowa Pharmaceutical, Novartis International, Astellas Pharma, Mitsubishi Tanabe Pharma, Taisho Toyama Pharmaceutical, Kyowa Hakko Kirin, Sumitomo Dainippon Pharma, Sanofi, MSD, Takeda, AstraZeneca, Ono Pharmaceutical, Sanwa Kagaku Kenkyusho and Daiichi Sankyo, and research grants from Novo Nordisk. T.N. is an employee of Novo Nordisk and holds shares in the company. J.Z. is an employee of Novo Nordisk and holds shares in the company. A.K. has received honoraria and consultation fees from AstraZeneca. EDAT- 2018/01/13 06:00 MHDA- 2019/01/15 06:00 PMCR- 2018/05/25 CRDT- 2018/01/12 06:00 PHST- 2017/08/04 00:00 [received] PHST- 2017/12/29 00:00 [revised] PHST- 2018/01/08 00:00 [accepted] PHST- 2018/01/13 06:00 [pubmed] PHST- 2019/01/15 06:00 [medline] PHST- 2018/01/12 06:00 [entrez] PHST- 2018/05/25 00:00 [pmc-release] AID - DOM13218 [pii] AID - 10.1111/dom.13218 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 May;20(5):1202-1212. doi: 10.1111/dom.13218. Epub 2018 Feb 21. PMID- 29270818 OWN - NLM STAT- MEDLINE DCOM- 20190219 LR - 20190320 IS - 1573-7322 (Electronic) IS - 1382-4147 (Linking) VI - 23 IP - 3 DP - 2018 May TI - The influence of anti-hyperglycemic drug therapy on cardiovascular and heart failure outcomes in patients with type 2 diabetes mellitus. PG - 445-459 LID - 10.1007/s10741-017-9666-8 [doi] AB - Patients with type 2 diabetes mellitus (DM) are at a substantially increased risk of heart failure (HF) and HF mortality. Despite the lack of evidence that tight glycemic control reduces the incidence of cardiovascular (CV) events, a growing body of evidence suggests that the choice of glucose-lowering agents may influence outcomes including HF. Thiazolidinediones are associated with a significant risk of HF. For metformin, sulphonylureas and insulin, little data is available to indicate the impact on HF. The glucagon-like peptide-1 (GLP-1) agonists, liraglutide and semaglutide, have been shown to reduce major CV events, but did not affect rates of hospitalization for HF. Clinical trials have demonstrated diverse effects of Dipeptidyl peptidase-4 (DPP-4) inhibitors on HF; saxagliptin showed an increased risk of HF admissions, alogliptin was associated with higher rates of new HF admissions, while sitagliptin had a neutral effect. The sodium-glucose cotransporter 2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have been recently shown to reduce the incidence of HF and cardiovascular mortality in patients with and without a history of HF. This review will summarize key findings of the impact of glucose-lowering agents on CV safety and HF-associated outcomes, present available data on the underlying mechanisms for the benefits of the SGLT2 inhibitors on HF, and discuss strategies to improve outcomes in patients with DM and high CV risk. FAU - Asleh, Rabea AU - Asleh R AUID- ORCID: 0000-0002-0258-7402 AD - Department of Cardiovascular Diseases, Mayo Clinic, 200 First St. SW, Gonda 5 S, Rochester, MN, 55905, USA. asleh.rabea@mayo.edu. FAU - Sheikh-Ahmad, Mohammad AU - Sheikh-Ahmad M AD - Department of Endocrinology, Bnai-Zion Medical Center, Haifa, Israel. FAU - Briasoulis, Alexandros AU - Briasoulis A AD - Department of Cardiovascular Medicine, University of Iowa Hospitals and Clinics, Iowa City, IA, USA. FAU - Kushwaha, Sudhir S AU - Kushwaha SS AD - Department of Cardiovascular Diseases, Mayo Clinic, 200 First St. SW, Gonda 5 S, Rochester, MN, 55905, USA. LA - eng PT - Journal Article PT - Review PL - United States TA - Heart Fail Rev JT - Heart failure reviews JID - 9612481 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) SB - IM MH - Blood Glucose/drug effects/*metabolism MH - Diabetes Mellitus, Type 2/blood/complications/*drug therapy MH - Global Health MH - Heart Failure/epidemiology/etiology/*prevention & control MH - Humans MH - Hypoglycemic Agents/*pharmacology MH - Incidence MH - Prognosis OTO - NOTNLM OT - Diabetes mellitus OT - GLP-1 agonists OT - Glucose-lowering drugs OT - Heart failure OT - Outcome OT - SGLT2 inhibitors EDAT- 2017/12/23 06:00 MHDA- 2019/03/21 06:00 CRDT- 2017/12/23 06:00 PHST- 2017/12/23 06:00 [pubmed] PHST- 2019/03/21 06:00 [medline] PHST- 2017/12/23 06:00 [entrez] AID - 10.1007/s10741-017-9666-8 [pii] AID - 10.1007/s10741-017-9666-8 [doi] PST - ppublish SO - Heart Fail Rev. 2018 May;23(3):445-459. doi: 10.1007/s10741-017-9666-8. PMID- 29246950 OWN - NLM STAT- MEDLINE DCOM- 20180717 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 41 IP - 2 DP - 2018 Feb TI - Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial. PG - 258-266 LID - 10.2337/dc17-0417 [doi] AB - OBJECTIVE: To compare the efficacy and safety of once-weekly semaglutide 1.0 mg s.c. with exenatide extended release (ER) 2.0 mg s.c. in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this phase 3a, open-label, parallel-group, randomized controlled trial, 813 subjects with type 2 diabetes taking oral antidiabetic drugs were randomized (1:1) to semaglutide 1.0 mg or exenatide ER 2.0 mg for 56 weeks. The primary end point was change from baseline in HbA(1c) at week 56. RESULTS: Mean HbA(1c) (8.3% [67.7 mmol/mol] at baseline) was reduced by 1.5% (16.8 mmol/mol) with semaglutide and 0.9% (10.0 mmol/mol) with exenatide ER (estimated treatment difference vs. exenatide ER [ETD] -0.62% [95% CI -0.80, -0.44] [-6.78 mmol/mol (95% CI -8.70, -4.86)]; P < 0.0001 for noninferiority and superiority). Mean body weight (95.8 kg at baseline) was reduced by 5.6 kg with semaglutide and 1.9 kg with exenatide ER (ETD -3.78 kg [95% CI -4.58, -2.98]; P < 0.0001). Significantly more subjects treated with semaglutide (67%) achieved HbA(1c) <7.0% (<53 mmol/mol) versus those taking exenatide ER (40%). Both treatments had similar safety profiles, but gastrointestinal adverse events were more common in semaglutide-treated subjects (41.8%) than in exenatide ER-treated subjects (33.3%); injection-site reactions were more frequent with exenatide ER (22.0%) than with semaglutide (1.2%). CONCLUSIONS: Semaglutide 1.0 mg was superior to exenatide ER 2.0 mg in improving glycemic control and reducing body weight after 56 weeks of treatment; the drugs had comparable safety profiles. These results indicate that semaglutide treatment is highly effective for subjects with type 2 diabetes who are inadequately controlled on oral antidiabetic drugs. CI - (c) 2017 by the American Diabetes Association. FAU - Ahmann, Andrew J AU - Ahmann AJ AUID- ORCID: 0000-0002-4544-5404 AD - Harold Schnitzer Diabetes Health Center, Oregon Health & Science University, Portland, OR ahmanna@ohsu.edu. FAU - Capehorn, Matthew AU - Capehorn M AD - Rotherham Institute for Obesity, Clifton Medical Centre, Rotherham, U.K. FAU - Charpentier, Guillaume AU - Charpentier G AD - Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France. FAU - Dotta, Francesco AU - Dotta F AD - Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy. FAU - Henkel, Elena AU - Henkel E AD - Center for Clinical Studies, GWT-TU Dresden, Dresden, Germany. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - Departments of Internal Medicine and Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX. FAU - Holst, Anders G AU - Holst AG AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Annett, Miriam P AU - Annett MP AD - Novo Nordisk Inc., Plainsboro, NJ. FAU - Aroda, Vanita R AU - Aroda VR AD - MedStar Health Research Institute, Hyattsville, MD. LA - eng SI - ClinicalTrials.gov/NCT01885208 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20171215 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Blood Glucose) RN - 0 (Delayed-Action Preparations) RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 0 (Peptides) RN - 0 (Venoms) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM CIN - Ann Intern Med. 2018 Apr 17;168(8):JC46. doi: 10.7326/ACPJC-2018-168-8-046. PMID: 29677253 MH - Adult MH - Aged MH - Aged, 80 and over MH - Blood Glucose/drug effects/metabolism MH - Body Weight/drug effects MH - Delayed-Action Preparations/administration & dosage/adverse effects MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Administration Schedule MH - Exenatide MH - Female MH - Glucagon-Like Peptides/*administration & dosage/*adverse effects MH - Glycated Hemoglobin/drug effects MH - Humans MH - Hypoglycemic Agents/administration & dosage/adverse effects MH - Male MH - Metformin/administration & dosage MH - Middle Aged MH - Peptides/*administration & dosage/*adverse effects MH - Treatment Outcome MH - Venoms/*administration & dosage/*adverse effects MH - Young Adult MH - Semaglutide EDAT- 2017/12/17 06:00 MHDA- 2018/07/18 06:00 CRDT- 2017/12/17 06:00 PHST- 2017/02/28 00:00 [received] PHST- 2017/10/22 00:00 [accepted] PHST- 2017/12/17 06:00 [pubmed] PHST- 2018/07/18 06:00 [medline] PHST- 2017/12/17 06:00 [entrez] AID - dc17-0417 [pii] AID - 10.2337/dc17-0417 [doi] PST - ppublish SO - Diabetes Care. 2018 Feb;41(2):258-266. doi: 10.2337/dc17-0417. Epub 2017 Dec 15. PMID- 29236983 OWN - NLM STAT- MEDLINE DCOM- 20191212 LR - 20250103 IS - 1522-9645 (Electronic) IS - 0195-668X (Linking) VI - 39 IP - 25 DP - 2018 Jul 1 TI - Cardioprotective anti-hyperglycaemic medications: a review of clinical trials. PG - 2368-2375 LID - 10.1093/eurheartj/ehx668 [doi] AB - Despite extensive clinical efforts to achieve stricter glycaemic control over the past few decades, cardiovascular (CV) disease remains the leading cause of death among diabetic patients. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor (GLP-1-R) agonists have gained attention due to their apparent effects in reducing CV mortality. Four CV randomized controlled trials: EMPA-REG, CANVAS, LEADER, and SUSTAIN-6, found a decrease in CV events among patients with type 2 diabetes on empagliflozin, canagliflozin, liraglutide, and semaglutide, respectively. In light of this data, the US Food and Drug Administration has recently approved empagliflozin for CV mortality reduction in type 2 diabetic patients, making it the first diabetes medication approved for such an indication. The purpose of this review is to summarize the results of novel anti-hyperglycaemic medication trials, and shed light on their mode of action and cardioprotective pathways. FAU - Ahmed, Haitham M AU - Ahmed HM AD - Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Ave, Desk JB1 Cleveland, OH, USA. FAU - Khraishah, Haitham AU - Khraishah H AD - Beth Israel Deaconess Medical Center, 330 Brookline Ave Boston, MA, USA. FAU - Cho, Leslie AU - Cho L AD - Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Ave, Desk JB1 Cleveland, OH, USA. LA - eng PT - Journal Article PT - Review PL - England TA - Eur Heart J JT - European heart journal JID - 8006263 RN - 0 (Cardiotonic Agents) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cardiotonic Agents/*therapeutic use MH - Cardiovascular Diseases/*prevention & control MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*complications/*drug therapy MH - Diabetic Cardiomyopathies/*prevention & control MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2017/12/14 06:00 MHDA- 2019/12/18 06:00 CRDT- 2017/12/14 06:00 PHST- 2017/07/06 00:00 [received] PHST- 2017/11/20 00:00 [accepted] PHST- 2017/12/14 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2017/12/14 06:00 [entrez] AID - 4718126 [pii] AID - 10.1093/eurheartj/ehx668 [doi] PST - ppublish SO - Eur Heart J. 2018 Jul 1;39(25):2368-2375. doi: 10.1093/eurheartj/ehx668. PMID- 29221659 OWN - NLM STAT- MEDLINE DCOM- 20180919 LR - 20260305 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 6 IP - 2 DP - 2018 Feb TI - Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. PG - 105-113 LID - S2213-8587(17)30412-6 [pii] LID - 10.1016/S2213-8587(17)30412-6 [doi] AB - BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide. METHODS: In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. We searched PubMed and MEDLINE without language restrictions up to Sept 18, 2017, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) for cardiovascular efficacy outcomes and odds ratios for key safety outcomes. FINDINGS: Of 12 articles identified in our search and screened for eligibility, four trials of cardiovascular outcomes of GLP-1 receptor agonists were identified: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN 6 (semaglutide), and EXSCEL (extended-release exenatide). Compared with placebo, GLP-1 receptor agonist treatment showed a significant 10% relative risk reduction in the three-point major adverse cardiovascular event primary outcome (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke; HR 0.90, 95% CI 0.82-0.99; p=0.033), a 13% RRR in cardiovascular mortality (0.87, 0.79-0.96; p=0.007), and a 12% relative risk reduction in all-cause mortality (0.88, 0.81-0.95; p=0.002), with low-to-moderate between-trial statistical heterogeneity. No significant effect of GLP-1 receptor agonists was identified on fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospital admission for unstable angina, or hospital admission for heart failure. Overall, no significant differences were seen in severe hypoglycaemia, pancreatitis, pancreatic cancer, or medullary thyroid cancer reported between GLP-1 receptor agonist treatment and placebo. INTERPRETATION: Our findings show cardiovascular safety across all GLP-1 receptor agonist cardiovascular outcome trials and suggest that drugs in this class can reduce three-point major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality risk, albeit to varying degrees for individual drugs, without significant safety concerns. GLP-1 receptor agonists have a favourable risk-benefit balance overall, which should allow the choice of drug to be individualised to each patient's needs. FUNDING: Amylin Pharmaceuticals (AstraZeneca). CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Bethel, M Angelyn AU - Bethel MA AD - Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. Electronic address: angelyn.bethel@dtu.ox.ac.uk. FAU - Patel, Rishi A AU - Patel RA AD - Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. FAU - Merrill, Peter AU - Merrill P AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA. FAU - Lokhnygina, Yuliya AU - Lokhnygina Y AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA. FAU - Buse, John B AU - Buse JB AD - Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA. FAU - Mentz, Robert J AU - Mentz RJ AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA. FAU - Pagidipati, Neha J AU - Pagidipati NJ AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA. FAU - Chan, Juliana C AU - Chan JC AD - Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. FAU - Gustavson, Stephanie M AU - Gustavson SM AD - AstraZeneca Research and Development, Gaithersburg, MD, USA. FAU - Iqbal, Nayyar AU - Iqbal N AD - AstraZeneca Research and Development, Gaithersburg, MD, USA. FAU - Maggioni, Aldo P AU - Maggioni AP AD - Italian Association of Hospital Cardiologists (ANMCO) Research Center, Firenze, Italy. FAU - Ohman, Peter AU - Ohman P AD - AstraZeneca Research and Development, Gaithersburg, MD, USA. FAU - Poulter, Neil R AU - Poulter NR AD - International Centre for Circulatory Health, Imperial College London, London, UK. FAU - Ramachandran, Ambady AU - Ramachandran A AD - India Diabetes Research Foundation, Chennai, India; Dr A Ramachandran's Diabetes Hospitals, Chennai, India. FAU - Zinman, Bernard AU - Zinman B AD - Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Faculty of Medicine, University of Toronto, Toronto, ON, Canada. FAU - Hernandez, Adrian F AU - Hernandez AF AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA. FAU - Holman, Rury R AU - Holman RR AD - Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. CN - EXSCEL Study Group LA - eng GR - T32 HL069749/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20171206 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Lancet Diabetes Endocrinol. 2018 Feb;6(2):83-85. doi: 10.1016/S2213-8587(17)30413-8. PMID: 29221658 CIN - Diabetes Metab. 2018 Jun;44(3):193-196. doi: 10.1016/j.diabet.2017.12.009. PMID: 29551531 MH - Cardiovascular Diseases/*mortality/prevention & control MH - Cardiovascular System/*drug effects MH - Diabetes Mellitus, Type 2/*drug therapy MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Prognosis MH - Survival Rate MH - *Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2017/12/10 06:00 MHDA- 2018/09/20 06:00 CRDT- 2017/12/10 06:00 PHST- 2017/09/20 00:00 [received] PHST- 2017/10/27 00:00 [revised] PHST- 2017/10/27 00:00 [accepted] PHST- 2017/12/10 06:00 [pubmed] PHST- 2018/09/20 06:00 [medline] PHST- 2017/12/10 06:00 [entrez] AID - S2213-8587(17)30412-6 [pii] AID - 10.1016/S2213-8587(17)30412-6 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2018 Feb;6(2):105-113. doi: 10.1016/S2213-8587(17)30412-6. Epub 2017 Dec 6. PMID- 29205786 OWN - NLM STAT- MEDLINE DCOM- 20190111 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 4 DP - 2018 Apr TI - Pharmacokinetics and tolerability of semaglutide in people with hepatic impairment. PG - 998-1005 LID - 10.1111/dom.13186 [doi] AB - AIMS: To investigate whether the pharmacokinetic characteristics of semaglutide were altered in people with hepatic impairment, assessed using Child-Pugh criteria, vs those with normal hepatic function. METHODS: In this multicentre, open-label, parallel-group trial (sponsor Novo Nordisk, ClinicalTrials.gov ID NCT02210871), four groups of participants with normal hepatic function (n = 19) or mild (n = 8), moderate (n = 10) or severe (n = 7) hepatic impairment received a single, subcutaneous dose of 0.5 mg semaglutide. Semaglutide plasma concentrations were assessed frequently for 35 days after dosing. The primary endpoint was area under the semaglutide plasma concentration-time curve from time zero to infinity (AUC(0-infinity) ). No effect of hepatic impairment was declared if the 90% confidence interval (CI) for the between-group ratio (hepatic impairment/normal function) was within the interval 0.70 to 1.43. RESULTS: Semaglutide exposure was similar across all groups, with AUC(0-infinity) treatment ratios for mild impairment/normal function of 0.95 (90% CI 0.77, 1.16), moderate impairment/normal function 1.02 (90% CI 0.93, 1.12), and severe impairment/normal function 0.97 (90% CI 0.84, 1.12). The maximum plasma semaglutide concentration (C(max) ) did not appear to be influenced by hepatic function, with mild impairment/normal function treatment ratios of 0.99 (90% CI 0.80, 1.23), moderate impairment/normal function 1.02 (90% CI 0.88, 1.18) and severe impairment/normal function 1.15 (90% CI 0.89, 1.48; sensitivity analysis excluding one extreme semaglutide concentration: 1.05 [90% CI 0.88, 1.25]). In all, 10 participants reported 12 mild or moderate non-serious adverse events. No unexpected safety or tolerability issues were observed. CONCLUSIONS: Semaglutide exposure did not appear to be affected by hepatic impairment, suggesting that dose adjustment may not be necessary in patients with hepatic impairment. Semaglutide was well tolerated and there were no unexpected safety issues. CI - (c) 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Jensen, Lene AU - Jensen L AUID- ORCID: 0000-0002-7111-2486 AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kupcova, Viera AU - Kupcova V AD - 3rd Department of Internal Medicine, Derer's Hospital, Bratislava, Slovakia. FAU - Arold, Gerhard AU - Arold G AD - PRA Healthsciences, Berlin, Germany. FAU - Pettersson, Jonas AU - Pettersson J AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hjerpsted, Julie B AU - Hjerpsted JB AUID- ORCID: 0000-0002-6938-786X AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT02210871 PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20180117 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Diabetes Complications/*drug therapy/metabolism MH - Diabetes Mellitus, Type 2/complications/*drug therapy/metabolism MH - Female MH - Glucagon-Like Peptides/administration & dosage/*adverse effects/*pharmacokinetics MH - Humans MH - Liver/drug effects/physiopathology MH - Liver Diseases/complications/*drug therapy/metabolism MH - Male MH - Middle Aged MH - Semaglutide PMC - PMC5873441 OTO - NOTNLM OT - GLP-1 OT - GLP-1 analogue OT - liver OT - pharmacokinetics OT - type 2 diabetes EDAT- 2017/12/06 06:00 MHDA- 2019/01/12 06:00 PMCR- 2018/03/28 CRDT- 2017/12/06 06:00 PHST- 2017/07/10 00:00 [received] PHST- 2017/11/13 00:00 [revised] PHST- 2017/11/30 00:00 [accepted] PHST- 2017/12/06 06:00 [pubmed] PHST- 2019/01/12 06:00 [medline] PHST- 2017/12/06 06:00 [entrez] PHST- 2018/03/28 00:00 [pmc-release] AID - DOM13186 [pii] AID - 10.1111/dom.13186 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Apr;20(4):998-1005. doi: 10.1111/dom.13186. Epub 2018 Jan 17. PMID- 29178519 OWN - NLM STAT- MEDLINE DCOM- 20190111 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 4 DP - 2018 Apr TI - Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. PG - 889-897 LID - 10.1111/dom.13172 [doi] AB - AIMS: To evaluate diabetic retinopathy (DR) data from across the SUSTAIN clinical trial programme. MATERIALS AND METHODS: The SUSTAIN clinical trial programme evaluated the efficacy and safety of semaglutide, a glucagon-like peptide-1 analogue, for the treatment of type 2 diabetes (T2D). In SUSTAIN 6, a 2-year, pre-approval cardiovascular outcomes trial, semaglutide was associated with a significant increase in the risk of DR complications (DRC) vs placebo. DR data from across the SUSTAIN trials were evaluated, and post hoc analyses of the SUSTAIN 6 data were conducted. These included subgroup analyses to identify at-risk patients and a mediation analysis with initial change in glycated haemoglobin (HbA1c; percentage-points at week 16) as a covariate, to examine the role of the magnitude of reduction in HbA1c as an intermediate factor affecting risk of DRC. RESULTS: There was no imbalance in DR adverse events across the SUSTAIN 1 to 5 and Japanese trials. The majority of the effect with semaglutide vs placebo in SUSTAIN 6 may be attributed to the magnitude and rapidity of HbA1c reduction during the first 16 weeks of treatment in patients who had pre-existing DR and poor glycaemic control at baseline, and who were treated with insulin. CONCLUSIONS: Early worsening of DR is a known phenomenon associated with the rapidity and magnitude of improvement in glycaemic control with insulin; the DRC findings in SUSTAIN 6 are consistent with this. Guidance regarding the early worsening of DR is recommended with insulin. Similar recommendations may be appropriate for semaglutide. CI - (c) 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Vilsboll, Tina AU - Vilsboll T AUID- ORCID: 0000-0002-0456-6787 AD - Steno Diabetes Center Copenhagen, University of Copenhagen, Gentofte, Denmark. FAU - Bain, Stephen C AU - Bain SC AD - School of Medicine, Swansea University, Swansea, UK. FAU - Leiter, Lawrence A AU - Leiter LA AUID- ORCID: 0000-0002-1040-6229 AD - Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Ontario, Canada. FAU - Lingvay, Ildiko AU - Lingvay I AUID- ORCID: 0000-0001-7006-7401 AD - University of Texas Southwestern Medical Center, Dallas, Texas. FAU - Matthews, David AU - Matthews D AD - Oxford Centre for Diabetes, Endocrinology and Metabolism, and Harris Manchester College, University of Oxford, Oxford, UK. FAU - Simo, Rafael AU - Simo R AD - Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Barcelona and CIBERDEM (ISCIII), Madrid, Spain. FAU - Helmark, Ida Caroe AU - Helmark IC AD - Novo Nordisk, Soborg, Denmark. FAU - Wijayasinghe, Nelun AU - Wijayasinghe N AD - Novo Nordisk, Soborg, Denmark. FAU - Larsen, Michael AU - Larsen M AD - Department of Ophthalmology, Rigshospitalet and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20180108 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Aged MH - Blood Glucose/*drug effects/metabolism MH - Diabetes Mellitus, Type 2/blood/complications/*drug therapy/*epidemiology MH - Diabetic Retinopathy/blood/*epidemiology/etiology MH - Female MH - Glucagon-Like Peptides/adverse effects/*therapeutic use MH - Glycated Hemoglobin/*drug effects/metabolism MH - Humans MH - Japan/epidemiology MH - Male MH - Middle Aged MH - Risk Factors MH - Semaglutide PMC - PMC5888154 OTO - NOTNLM OT - GLP-1 analogue OT - antidiabetic drug OT - diabetic retinopathy COIS- T.V. declares personal fees from Amgen, Boehringer Ingelheim, Eli Lilly, AstraZeneca, Merck Sharp & Dohme, Sanofi, Novo Nordisk and Bristol-Myers Squibb, and grants (to her institution) from Eli Lilly and Novo Nordisk. S.B. has received grants (to his institution) and personal fees from Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Sanofi, Merck Sharp & Dohme, Janssen and Cellnovo. L.A.L. has received grants (to his institution) and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk and Sanofi, personal fees from Servier and grants (to his institution) from GlaxoSmithKline. I.L. has received grants (to her institution) and/or other fees from Novartis, GI dynamics, Pfizer, Merck and Novo Nordisk; personal fees from AstraZeneca, Sanofi and Lilly, and non-financial (editorial) support from AstraZeneca, Sanofi, Lilly, Novo Nordisk and Boehringer Ingelheim. D.M. has received grants (to his institution) from Novo Nordisk and Takeda and reports support from Janssen, Servier and Novartis; R.S. reports grants (to his institution) and personal fees from Novo Nordisk and OM Pharma, personal fees from Bayer, and non-financial support from Sanofi. I.C. and N.W. are full-time employees of Novo Nordisk. M.L. reports personal fees from Novo Nordisk. EDAT- 2017/11/28 06:00 MHDA- 2019/01/12 06:00 PMCR- 2018/04/06 CRDT- 2017/11/28 06:00 PHST- 2017/08/22 00:00 [received] PHST- 2017/11/02 00:00 [revised] PHST- 2017/11/21 00:00 [accepted] PHST- 2017/11/28 06:00 [pubmed] PHST- 2019/01/12 06:00 [medline] PHST- 2017/11/28 06:00 [entrez] PHST- 2018/04/06 00:00 [pmc-release] AID - DOM13172 [pii] AID - 10.1111/dom.13172 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Apr;20(4):889-897. doi: 10.1111/dom.13172. Epub 2018 Jan 8. PMID- 29049653 OWN - NLM STAT- MEDLINE DCOM- 20171023 LR - 20260127 IS - 1538-3598 (Electronic) IS - 0098-7484 (Print) IS - 0098-7484 (Linking) VI - 318 IP - 15 DP - 2017 Oct 17 TI - Effect of Oral Semaglutide Compared With Placebo and Subcutaneous Semaglutide on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial. PG - 1460-1470 LID - 10.1001/jama.2017.14752 [doi] AB - IMPORTANCE: Glucagon-like peptide-1 (GLP-1) receptor agonists are effective therapies for the treatment of type 2 diabetes and are all currently available as an injection. OBJECTIVES: To compare the effects of oral semaglutide with placebo (primary) and open-label subcutaneous semaglutide (secondary) on glycemic control in patients with type 2 diabetes. DESIGN, SETTING, AND PATIENTS: Phase 2, randomized, parallel-group, dosage-finding, 26-week trial with 5-week follow-up at 100 sites (hospital clinics, general practices, and clinical research centers) in 14 countries conducted between December 2013 and December 2014. Of 1106 participants assessed, 632 with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were randomized. Randomization was stratified by metformin use. INTERVENTIONS: Once-daily oral semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was change in hemoglobin A1c (HbA1c) from baseline to week 26. Secondary end points included change from baseline in body weight and adverse events. RESULTS: Baseline characteristics were comparable across treatment groups. Of the 632 randomized patients (mean age, 57.1 years [SD, 10.6]; men, 395 (62.7%); diabetes duration, 6.3 years [SD, 5.2]; body weight, 92.3 kg [SD, 16.8]; BMI, 31.7 [SD, 4.3]), 583 (92%) completed the trial. Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide (dosage-dependent range, -0.7% to -1.9%) and subcutaneous semaglutide (-1.9%) and placebo (-0.3%); oral semaglutide reductions were significant vs placebo (dosage-dependent estimated treatment difference [ETD] range for oral semaglutide vs placebo, -0.4% to -1.6%; P = .01 for 2.5 mg, <.001 for all other dosages). Reductions in body weight were greater with oral semaglutide (dosage-dependent range, -2.1 kg to -6.9 kg) and subcutaneous semaglutide (-6.4 kg) vs placebo (-1.2 kg), and significant for oral semaglutide dosages of 10 mg or more vs placebo (dosage-dependent ETD range, -0.9 to -5.7 kg; P < .001). Adverse events were reported by 63% to 86% (371 of 490 patients) in the oral semaglutide groups, 81% (56 of 69 patients) in the subcutaneous semaglutide group, and 68% (48 of 71 patients) in the placebo group; mild to moderate gastrointestinal events were most common. CONCLUSIONS AND RELEVANCE: Among patients with type 2 diabetes, oral semaglutide resulted in better glycemic control than placebo over 26 weeks. These findings support phase 3 studies to assess longer-term and clinical outcomes, as well as safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01923181. FAU - Davies, Melanie AU - Davies M AD - Diabetes Research Centre, University of Leicester, Leicester, United Kingdom. FAU - Pieber, Thomas R AU - Pieber TR AD - Medical University of Graz, Graz, Austria. FAU - Hartoft-Nielsen, Marie-Louise AU - Hartoft-Nielsen ML AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hansen, Oluf K H AU - Hansen OKH AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jabbour, Serge AU - Jabbour S AD - Thomas Jefferson University, Philadelphia, Pennsylvania. FAU - Rosenstock, Julio AU - Rosenstock J AD - Dallas Diabetes Research Center at Medical City, Dallas, Texas. LA - eng SI - ClinicalTrials.gov/NCT01923181 SI - ClinicalTrials.gov/NCT01923181 PT - Clinical Trial, Phase II PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - JAMA JT - JAMA JID - 7501160 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Administration, Oral MH - Blood Glucose/analysis/drug effects MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Dose-Response Relationship, Drug MH - Female MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Injections, Subcutaneous MH - Male MH - Middle Aged MH - Nausea/chemically induced MH - Semaglutide PMC - PMC5817971 COIS- Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Davies reported board membership and consultancy fees from Novo Nordisk; sanofi-aventis; Lilly; Merck, Sharp & Dohme; Boehringer Ingelheim; AstraZeneca; Servier; and Janssen; institutional grants from Novo Nordisk, sanofi-aventis, Lilly, Boehringer Ingelheim, and Janssen; and payment for lectures or speakers bureaus from Novo Nordisk; sanofi-aventis; Lilly; Merck, Sharp & Dohme; Boehringer Ingelheim; AstraZeneca; Janssen; Mitsubishi Tanabe Pharma; and Takeda Pharmaceuticals International. Dr Pieber reported board membership and consulting fees for AstraZeneca, Novo Nordisk, Roche Diabetes Care, and Eli Lilly; institutional grants from AstraZeneca and Novo Nordisk; and payment for lectures or speakers bureaus from Novo Nordisk. Dr Hartoft-Nielsen reported holding shares in Novo Nordisk. Mr Hansen reported holding shares in Novo Nordisk and a pending patent for semaglutide methods. Dr Jabbour reported board membership of the Endocrine Society; consultancy fees from AstraZeneca, Eli Lilly, and Janssen; institutional grants from AstraZeneca, Novo Nordisk, Eli Lilly, Merck, and Janssen; and payment for lectures or speakers bureaus from AstraZeneca, Eli Lilly, and Janssen. Dr Rosenstock reported research support from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Hanmi, Intarcia, Janssen, Lexicon, Merck, Novo Nordisk, Sanofi, and Pfizer; serving on advisory boards of and receiving consulting honoraria from Boehringer Ingelheim, Daiichi Sankyo, Intarcia, Janssen, Novo Nordisk, Sanofi, and Eli Lilly. EDAT- 2017/10/20 06:00 MHDA- 2017/10/24 06:00 PMCR- 2018/04/17 CRDT- 2017/10/20 06:00 PHST- 2017/10/20 06:00 [entrez] PHST- 2017/10/20 06:00 [pubmed] PHST- 2017/10/24 06:00 [medline] PHST- 2018/04/17 00:00 [pmc-release] AID - 2657376 [pii] AID - joi170116 [pii] AID - 10.1001/jama.2017.14752 [doi] PST - ppublish SO - JAMA. 2017 Oct 17;318(15):1460-1470. doi: 10.1001/jama.2017.14752. PMID- 29031006 OWN - NLM STAT- MEDLINE DCOM- 20180814 LR - 20180814 IS - 1753-0407 (Electronic) IS - 1753-0407 (Linking) VI - 10 IP - 2 DP - 2018 Feb TI - The kidney and cardiovascular outcome trials. PG - 88-89 LID - 10.1111/1753-0407.12616 [doi] AB - Chronic kidney disease (CKD) affects a substantial minority of people with type 2 diabetes (T2D). Analysis of US National Health and Nutrition Examination Survey (NHANES) datasets from 2007 through 2012 showed Stage 3 or worse disease (estimated glomerular filtration rate [eGFR] <60 mL/min per 1.73 m(2) ) in nearly one in five patients, with increasing age, blood pressure, obesity, and levels of glycemia all associated with higher likelihood of Stage 3 or worse CKD, comparable to findings from surveys from many other areas, which also show micro- or macroalbuminuria to be present in one-sixth to one-third of diabetic people. Improvement in albuminuria has been shown in clinical trials of glycemic interventions, including the Action to Control Cardiovascular Disease in Diabetes (ACCORD) trial, the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, in which the nephroprotective effect of blood pressure lowering was also demonstrated, and the UK Prospective Diabetes Study (UKPDS). However, over the past decade a host of cardiovascular outcome trials (CVOTs) have been performed with newer T2D therapeutic agents, and many of these have included intriguing information pertaining to renal disease and renal outcomes not necessarily related to changes in glycemia. It is of interest to review some of these findings. Glucagon-like peptide-1 (GLP-1) has been reported to increase glomerular filtration rate (GFR), renal blood flow, and the fractional excretion both of sodium and potassium, with renal GLP-1 receptors present in afferent arteriolar vascular smooth muscle cells, glomerular endothelial cells and macrophages, juxtaglomerular cells, and the proximal tubule, perhaps mediating the greater natriuresis seen after oral than intravenous sodium. In the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, the significant 13% reduction in the primary composite outcome of cardiovascular death, myocardial infarction, and stroke was found on subgroup analysis to particularly occur among participants with Stage 3 CKD, having eGFR 30-59 mL/min per 1.73 m(2) . No significant effect on eGFR was found with liraglutide, although both those receiving and not receiving the drug showed a decline in eGFR from approximately 75 to 65 mL/min per 1.73 m(2) over the 48-month period of observation. Liraglutide administration was associated with a significant reduction in albuminuria, with nearly a 25% lower likelihood of development of macroalbuminuria, and with the albumin: creatinine ratio (ACR) approximately 20% lower among treated people, regardless of the baseline level of eGFR. Similarly, in the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, a 34% increase in the urine ACR was reported among people receiving placebo, but the increase was 24% among those receiving lixisenatide, and in the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6), persistent macroalbuminuria developed among 2.7% of those receiving semaglutide, but among 4.9% of those receiving placebo. The enzyme dipeptidyl peptidase (DPP)-4 is, like the GLP-1 receptor, present in multiple renal membrane-bound locations, including afferent arteriolar vascular smooth muscle cells, mesangial cells, podocytes, and proximal tubular cells, and DPP-4 inhibitors appear to have salutary effects on albuminuria similar to those of the GLP-1 agents. In the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR)-Thrombolysis in Myocardial Infarction (TIMI) 53 trial, saxagliptin was associated with significantly less worsening and more improvement in microalbumin levels at 1 year, at 2 years, and by end-of-treatment. The reduction in microalbumin levels was similar in patients with and without renal impairment. Interestingly, there was no relationship between improvement in albuminuria and improvement in HbA1c. The other DPP4i CVOTs have not reported effects of these agents on renal function or albuminuria, but studies of sitagliptin and linagliptin suggest that these agents may also reduce albuminuria. Sodium-glucose cotransporter (SGLT) 2 inhibitors affect multiple sites, with the potential to affect renal function. The Canagliflozin Cardiovascular Assessment Study (CANVAS) showed a 27% reduction in progression of albuminuria, with a 40% reduction in eGFR, need for renal-replacement therapy, or death from renal causes associated with the use of canagliflozin. After a fall in mean eGFR with canagliflozin from 76 to 73 mL/min per 1.73 m(2) at 3 months, eGFR remained stable through 6 years while gradually declining during the period of observation with placebo. Evidence of dual effects of SGLT2 inhibition on both albuminuria and GFR was even more strongly shown in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME); in that CVOT, although there was an initial decline in eGFR with empagliflozin, from 94 mL/min per 1.73 m(2) through 192 weeks, eGFR was consistently higher with empagliflozin, although this was less clear in trial participants with baseline eGFR <60 mL/min per 1.73 m(2) . Empagliflozin also reduced the development of acute renal failure. Further analysis showed empagliflozin to be associated with a reduction in albuminuria, regardless of the baseline urine albumin level. The CVOTs have offered the possibility that diabetes treatment may move beyond surrogate endpoints to actual cardiovascular outcome benefits. It appears that these drugs will also lead to a reduction in adverse renal outcomes. We should look with optimism at this potential approach to a major complication of diabetes. CI - (c) 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd. FAU - Bloomgarden, Zachary AU - Bloomgarden Z AD - Icahn School of Medicine at Mount Sinai, New York, USA. LA - eng PT - Editorial PL - Australia TA - J Diabetes JT - Journal of diabetes JID - 101504326 SB - IM MH - Cardiovascular Diseases/*etiology MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*complications MH - Humans MH - Kidney Diseases/*etiology EDAT- 2017/10/17 06:00 MHDA- 2018/08/15 06:00 CRDT- 2017/10/15 06:00 PHST- 2017/10/17 06:00 [pubmed] PHST- 2018/08/15 06:00 [medline] PHST- 2017/10/15 06:00 [entrez] AID - 10.1111/1753-0407.12616 [doi] PST - ppublish SO - J Diabetes. 2018 Feb;10(2):88-89. doi: 10.1111/1753-0407.12616. PMID- 29020969 OWN - NLM STAT- MEDLINE DCOM- 20180613 LR - 20250103 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 16 IP - 1 DP - 2017 Oct 11 TI - Updates on cardiovascular outcome trials in diabetes. PG - 128 LID - 10.1186/s12933-017-0610-y [doi] LID - 128 AB - In 2008 the Food and Drug Administration introduced a guidance for industry that requires the investigation of cardiovascular outcomes of glucose-lowering medications. Since then, an increasing number of cardiovascular outcome trials have been completed in diabetes patients with high cardiovascular risk for members of the SGLT-2 and DPP4 inhibitors and GLP-1 receptor agonist classes. The trials confirmed cardiovascular safety for all tested anti-hyperglycaemic drugs and, in addition empagliflozin, semaglutide and liraglutide could even reduce cardiovascular risk. The present review summarizes the results of the DEVOTE, CANVAS, EXSCEL and ACE trials that tested cardiovascular safety of Insulin degludec, canagliflozin, once-weekly exenatide and acarbose and were published in 2017. We provide context on these results by comparing them with earlier trials of glucose-lowering drugs and give an outlook on what to expect in coming years. FAU - Schnell, Oliver AU - Schnell O AD - Forschergruppe Diabetes e. V., Ingolstaedter Landstrasse 1, Neuherberg, 85764, Munich, Germany. oliver.schnell@lrz.uni-muenchen.de. FAU - Ryden, Lars AU - Ryden L AD - Cardiology Unit, Department of Medicine K2, Karolinska Institute, 171 76, Stockholm, Sweden. FAU - Standl, Eberhard AU - Standl E AD - Forschergruppe Diabetes e. V., Ingolstaedter Landstrasse 1, Neuherberg, 85764, Munich, Germany. FAU - Ceriello, Antonio AU - Ceriello A AD - Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS) and Centro de Investigacion, Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Barcelona, Spain. AD - Department of Cardiovascular and Metabolic Diseases, IRCCS Multimedica Sesto San Giovanni, Via Milanese 300, 20099, Milan, Italy. CN - D&CVD EASD Study Group LA - eng PT - Journal Article PT - Review DEP - 20171011 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (SLC5A2 protein, human) RN - 0 (Sodium-Glucose Transporter 2) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM EIN - Cardiovasc Diabetol. 2017 Nov 15;16(1):150. doi: 10.1186/s12933-017-0633-4. PMID: 29141636 MH - Cardiovascular Diseases/blood/*drug therapy/epidemiology MH - Clinical Trials as Topic/*methods MH - Diabetes Mellitus, Type 2/blood/*drug therapy/epidemiology MH - Dipeptidyl-Peptidase IV Inhibitors/pharmacology/*therapeutic use MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Humans MH - Hypoglycemic Agents/pharmacology/*therapeutic use MH - Sodium-Glucose Transporter 2/metabolism MH - Sodium-Glucose Transporter 2 Inhibitors MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC5637292 OTO - NOTNLM OT - ACE OT - CANVAS program OT - CVOT OT - Cardiovascular risk OT - DEVOTE OT - Diabetes OT - EXSCEL OT - Heart EDAT- 2017/10/13 06:00 MHDA- 2018/06/14 06:00 PMCR- 2017/10/11 CRDT- 2017/10/13 06:00 PHST- 2017/09/26 00:00 [received] PHST- 2017/10/03 00:00 [accepted] PHST- 2017/10/13 06:00 [entrez] PHST- 2017/10/13 06:00 [pubmed] PHST- 2018/06/14 06:00 [medline] PHST- 2017/10/11 00:00 [pmc-release] AID - 10.1186/s12933-017-0610-y [pii] AID - 610 [pii] AID - 10.1186/s12933-017-0610-y [doi] PST - epublish SO - Cardiovasc Diabetol. 2017 Oct 11;16(1):128. doi: 10.1186/s12933-017-0610-y. PMID- 28991932 OWN - NLM STAT- MEDLINE DCOM- 20171013 LR - 20260127 IS - 1533-7294 (Electronic) IS - 0094-3509 (Linking) VI - 66 IP - 10 Suppl DP - 2017 Oct TI - Addressing Unmet Needs With Injectable Medications in Type 2 Diabetes Treatment: Glucagon-Like Peptide-1 Receptor Agonists. PG - S12-S16 AB - Since 2005, four new GLP-1RAs (liraglutide, albiglutide, dulaglutide, and lixisenatide) and a once-weekly formulation of exenatide were approved for the treatment of persons with T2DM. Another GLP-1RA, semaglutide, is under review by the FDA, as is exenatide administered via an osmotic mini-pump. FAU - Edelman, Steve V AU - Edelman SV AD - Professor of Medicine, University of California San Diego, Veterans Affairs Medical Center, San Diego, California, USA. LA - eng PT - Journal Article PL - United States TA - J Fam Pract JT - The Journal of family practice JID - 7502590 RN - 9P1872D4OL (Exenatide) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 839I73S42A (Liraglutide) RN - 0 (Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Venoms) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 74O62BB01U (lixisenatide) RN - 0 (Glucagon-Like Peptide-2 Receptor) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Exenatide MH - Glucagon-Like Peptides/analogs & derivatives/therapeutic use MH - Humans MH - Hypoglycemic Agents/pharmacology/*therapeutic use MH - Immunoglobulin Fc Fragments/therapeutic use MH - Liraglutide/therapeutic use MH - Peptides/therapeutic use MH - Recombinant Fusion Proteins/therapeutic use MH - Venoms/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-2 Receptor EDAT- 2017/10/11 06:00 MHDA- 2017/10/14 06:00 CRDT- 2017/10/10 06:00 PHST- 2017/10/10 06:00 [entrez] PHST- 2017/10/11 06:00 [pubmed] PHST- 2017/10/14 06:00 [medline] AID - jfp_6610n [pii] PST - ppublish SO - J Fam Pract. 2017 Oct;66(10 Suppl):S12-S16. PMID- 28942790 OWN - NLM STAT- MEDLINE DCOM- 20180814 LR - 20260127 IS - 2352-3840 (Electronic) IS - 1499-2671 (Linking) VI - 41 IP - 5 DP - 2017 Oct TI - Glucagon-like Peptide-1 Receptor Agonists: A Class Update for Treating Type 2 Diabetes. PG - 524-535 LID - S1499-2671(17)30672-X [pii] LID - 10.1016/j.jcjd.2017.08.242 [doi] AB - Current management options for treating type 2 diabetes are diverse. Many different classes of antidiabetes therapies are used in clinic, and several new candidates are in late-phase clinical trial. This therapeutic abundance is a windfall for patients because it facilitates individualized patient care. Evidence-based positioning of these agents is challenging, however, requiring comprehensive and balanced familiarity with each drug class. In this review, I provide a clinical update of glucagon-like peptide-1 receptor agonists (GLP-1RAs), a class of incretin-based, injectable antidiabetes therapies which improve fasting and postprandial blood glucose control through glucose-dependent pancreatic islet cell hormone secretion without significant risks for hypoglycemia. Chronic use of GLP-1RAs also promotes body weight loss through stimulation of GLP-1 receptors localized in hypothalamic satiety centres that regulate appetite, resulting in reduced caloric intake. Since 2005, when GLP-1RAs first received regulatory approval for type 2 diabetes, this class has expanded to include long-acting, once-weekly GLP-1RAs. Recent cardiovascular outcome trials demonstrate that long-term use of GLP-1RAs (liraglutide and semaglutide) reduce cardiovascular and renal complications of diabetes. Illustrating that GLP-1RAs are favourable in high-risk patients with type 2 diabetes. This review provides a clinical appraisal of the GLP-1RA class, highlighting intraclass similarities and differences, summarizing the clinical development of incretin-based diabetes therapies and focusing on currently approved GLP-1RAs. The review also discusses the implications of structural differences between GLP-1RA molecules and comments on the risks and benefits associated with GLP-1RAs and their positioning in treating type 2 diabetes. CI - Copyright (c) 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved. FAU - Lovshin, Julie A AU - Lovshin JA AD - Toronto General Hospital, Banting and Best Diabetes Centre, Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada. Electronic address: lovshin@lunenfeld.ca. LA - eng PT - Journal Article PT - Review PL - Canada TA - Can J Diabetes JT - Canadian journal of diabetes JID - 101148810 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Prognosis MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Glucagon-Like Peptide-1 Receptor OTO - NOTNLM OT - GLP-1R agonists OT - agonistes des recepteurs du GLP-1 OT - cardiovascular disease OT - diabetic nephropathy OT - diabete de type 2 OT - liraglutide OT - maladie cardiovasculaire OT - nephropathie diabetique OT - semaglutide OT - semaglutide OT - type 2 diabetes EDAT- 2017/09/26 06:00 MHDA- 2018/08/15 06:00 CRDT- 2017/09/26 06:00 PHST- 2016/09/06 00:00 [received] PHST- 2017/01/24 00:00 [revised] PHST- 2017/02/08 00:00 [accepted] PHST- 2017/09/26 06:00 [entrez] PHST- 2017/09/26 06:00 [pubmed] PHST- 2018/08/15 06:00 [medline] AID - S1499-2671(17)30672-X [pii] AID - 10.1016/j.jcjd.2017.08.242 [doi] PST - ppublish SO - Can J Diabetes. 2017 Oct;41(5):524-535. doi: 10.1016/j.jcjd.2017.08.242. PMID- 28941314 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 3 DP - 2018 Mar TI - Semaglutide improves postprandial glucose and lipid metabolism, and delays first-hour gastric emptying in subjects with obesity. PG - 610-619 LID - 10.1111/dom.13120 [doi] AB - AIM: To investigate the effects of semaglutide on fasting and postprandial glucose and lipid responses, and on gastric emptying. MATERIALS AND METHODS: This was a randomized, double-blind, placebo-controlled, 2-period, crossover trial. Subjects with obesity (N = 30) received once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, or placebo. After each 12-week treatment period, glucose and lipid metabolism were assessed before and after standardized meals. Gastric emptying (paracetamol absorption test) and peptide YY (PYY) response were also assessed. RESULTS: Semaglutide treatment significantly lowered fasting concentrations of glucose and glucagon, and increased insulin vs placebo (estimated treatment ratio: 0.95 [95% confidence interval: 0.91, 0.98]; 0.86 [0.75, 0.98]; 1.45 [1.20, 1.75], respectively). Postprandial glucose metabolism significantly improved with semaglutide vs placebo (incremental area under the curve 0 to 5 hours [iAUC(0-5h) ]; estimated treatment difference: glucose -1.34 mmol h/L [-2.42, -0.27]; insulin -921 pmol h/L [-1461, -381]; C-peptide -1.42 nmol h/L [-2.33, -0.51]). Fasting and postprandial lipid metabolism improved with semaglutide vs placebo. First-hour gastric emptying after the meal was delayed with semaglutide vs placebo (AUC(0-1h) ; estimated treatment ratio: 0.73 [0.61, 0.87]); this may have contributed to the lower postprandial glucose increase in semaglutide-treated subjects. Overall gastric emptying (AUC(0-5h) ) was not statistically different between treatments. Fasting and postprandial PYY responses were significantly lower with semaglutide vs placebo (P = .0397 and P = .0097, respectively). CONCLUSION: Semaglutide improved fasting and postprandial glucose and lipid metabolism. Overall gastric emptying was similar to that with placebo; however, the observed first-hour delay with semaglutide may contribute to a slower entry of glucose into the circulation. CI - (c) 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Hjerpsted, Julie B AU - Hjerpsted JB AUID- ORCID: 0000-0002-6938-786X AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Flint, Anne AU - Flint A AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Brooks, Ashley AU - Brooks A AD - Covance Clinical Research Unit Ltd, Leeds, UK. FAU - Axelsen, Mads B AU - Axelsen MB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Kvist, Trine AU - Kvist T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Blundell, John AU - Blundell J AUID- ORCID: 0000-0002-7085-9596 AD - Institute of Psychological Sciences, Faculty of Medicine and Health, University of Leeds, Leeds, UK. LA - eng PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20171027 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Blood Glucose/metabolism MH - Cross-Over Studies MH - Diabetes Mellitus, Type 2/complications/*drug therapy/physiopathology MH - Double-Blind Method MH - Drug Administration Schedule MH - Fasting/blood MH - Female MH - Gastric Emptying/*drug effects MH - Glucagon-Like Peptides/*administration & dosage MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Injections, Subcutaneous MH - Lipid Metabolism/drug effects MH - Male MH - Obesity/*complications/physiopathology MH - Postprandial Period MH - Semaglutide PMC - PMC5836914 OTO - NOTNLM OT - GLP-1 analogue OT - glucose metabolism OT - incretin therapy OT - insulin analogues OT - obesity therapy OT - phase I-II study COIS- M. B. A., A. F., J. B. H. and T. K. are full-time employees of, and hold shares in, Novo Nordisk A/S. A. B. has received research grants from Novo Nordisk. J. B. has received research, travel and accommodation grants within the submitted work from Novo Nordisk A/S, and advisory and speaker fees outside the submitted work from Novo Nordisk A/S. EDAT- 2017/09/25 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/03/05 CRDT- 2017/09/24 06:00 PHST- 2017/04/26 00:00 [received] PHST- 2017/09/06 00:00 [revised] PHST- 2017/09/08 00:00 [accepted] PHST- 2017/09/25 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2017/09/24 06:00 [entrez] PHST- 2018/03/05 00:00 [pmc-release] AID - DOM13120 [pii] AID - 10.1111/dom.13120 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Mar;20(3):610-619. doi: 10.1111/dom.13120. Epub 2017 Oct 27. PMID- 28939005 OWN - NLM STAT- MEDLINE DCOM- 20181018 LR - 20260127 IS - 1879-0828 (Electronic) IS - 0953-6205 (Linking) VI - 48 DP - 2018 Feb TI - Antidiabetic drugs and stroke risk. Current evidence. PG - 1-5 LID - S0953-6205(17)30368-0 [pii] LID - 10.1016/j.ejim.2017.09.019 [doi] AB - Cardiovascular disease (CVD) is the major cause of morbidity and mortality for individuals with type 2 diabetes (T2D). In particular, the risk for stroke is twice that of patients without diabetes, and diabetes may be responsible for >8% of first ischemic strokes. Therefore, the way to prevent stroke in these patients has become an important issue. Traditionally, glucose-lowering drugs had not been shown to protect against stroke. Moreover, several antidiabetic drugs (i.e., sulfonylureas, rosiglitazone) have been reported to be associated with increased risks of CVD and stroke. On the contrary, data on the CV risks and benefits associated with new antidiabetic treatment in patients with T2D are emerging - and look promising. Therefore, it could be of great value to find out if any type of these new antidiabetic agents has protective effect against stroke. We review the available evidence regarding the risk of stroke in individuals taking non-insulin antidiabetic agents. To date, several antidiabetic agents have shown to have a positive effect on stroke prevention. The accumulated evidence suggests that metformin, pioglitazone and semaglutide reduce stroke risk. These agents do not represent only a way of controlling blood glucose and but also offer the opportunity to reduce stroke risk. Surely, new data from ongoing and future studies will provide additional information to select the best treatment for decreasing stroke risk in T2D patients. CI - Copyright (c) 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. FAU - Castilla-Guerra, Luis AU - Castilla-Guerra L AD - Department of Internal Medicine, Hospital Virgen Macarena, University of Seville, Seville, Spain. Electronic address: lcastilla@us.es. FAU - Fernandez-Moreno, Maria Del Carmen AU - Fernandez-Moreno MDC AD - Department of Neurology, Hospital de Valme, University of Seville, Seville, Spain. FAU - Leon-Jimenez, David AU - Leon-Jimenez D AD - Department of Internal Medicine, Hospital Virgen Macarena, University of Seville, Seville, Spain. FAU - Carmona-Nimo, Eduardo AU - Carmona-Nimo E AD - Department of Internal Medicine, Hospital Virgen Macarena, University of Seville, Seville, Spain. LA - eng PT - Journal Article PT - Review DEP - 20170920 PL - Netherlands TA - Eur J Intern Med JT - European journal of internal medicine JID - 9003220 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - X4OV71U42S (Pioglitazone) RN - 0 (Thiazolidinediones) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose/drug effects MH - Diabetes Mellitus, Type 2/*complications/*drug therapy MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Metformin/therapeutic use MH - Pioglitazone MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - Stroke/epidemiology/*prevention & control MH - Thiazolidinediones/therapeutic use MH - Semaglutide OTO - NOTNLM OT - Antidiabetic agents OT - Diabetes OT - Glucose OT - Prevention OT - Stroke EDAT- 2017/09/25 06:00 MHDA- 2018/10/20 06:00 CRDT- 2017/09/24 06:00 PHST- 2017/07/04 00:00 [received] PHST- 2017/09/08 00:00 [revised] PHST- 2017/09/17 00:00 [accepted] PHST- 2017/09/25 06:00 [pubmed] PHST- 2018/10/20 06:00 [medline] PHST- 2017/09/24 06:00 [entrez] AID - S0953-6205(17)30368-0 [pii] AID - 10.1016/j.ejim.2017.09.019 [doi] PST - ppublish SO - Eur J Intern Med. 2018 Feb;48:1-5. doi: 10.1016/j.ejim.2017.09.019. Epub 2017 Sep 20. PMID- 28895030 OWN - NLM STAT- MEDLINE DCOM- 20181114 LR - 20261012 IS - 1559-0100 (Electronic) IS - 1355-008X (Linking) VI - 60 IP - 2 DP - 2018 May TI - Type 2 diabetes and cardiovascular prevention: the dogmas disputed. PG - 224-228 LID - 10.1007/s12020-017-1418-y [doi] AB - In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo. Other trials with newer diabetes drugs, including empagliflozin and canagliflozin (two sodium-glucose co-transporter-2 inhibitors), liraglutide and semaglutide (two GLP-1 receptor agonists) succeeded in demonstrating CV benefit in people with type 2 diabetes. In the last two decades, the equation "diabetes equals myocardial infarction" have contributed to the development of preventive therapy for risk factors in diabetes. In both primary and secondary prevention, the diabetic patients with high rates of statin and aspirin treatment have improved CV outcome, as compared with non-users. The drugs used to reduce glucose levels in patients with type 2 diabetes seem important for the ultimate cardiovascular outcome: the combination of intensive glycemic control, when safely attainable, with newer diabetes drugs (empagliflozin, canagliflozin, liraglutide, and semaglutide) may decrease the incidence of MACE, nephropathy and retinopathy. Moreover, depending on the drug used, CV mortality and heart failure may also be reduced. FAU - Giugliano, Dario AU - Giugliano D AUID- ORCID: 0000-0002-9377-873X AD - Section of Endocrinology and Diabetes, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, L. Vanvitelli University, Naples, Italy. dario.giugliano@unicampania.it. FAU - Maiorino, Maria Ida AU - Maiorino MI AD - Section of Endocrinology and Diabetes, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, L. Vanvitelli University, Naples, Italy. FAU - Bellastella, Giuseppe AU - Bellastella G AD - Section of Endocrinology and Diabetes, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, L. Vanvitelli University, Naples, Italy. FAU - Esposito, Katherine AU - Esposito K AD - Section of Endocrinology and Diabetes, Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, L. Vanvitelli University, Naples, Italy. LA - eng PT - Journal Article DEP - 20170911 PL - United States TA - Endocrine JT - Endocrine JID - 9434444 RN - 0 (Hypoglycemic Agents) SB - IM MH - Cardiovascular Diseases/etiology/*prevention & control MH - Diabetes Mellitus, Type 2/*complications/drug therapy MH - Humans MH - Hypoglycemic Agents/*therapeutic use OTO - NOTNLM OT - Cardiovascular prevention OT - Intensive glycemic control OT - Newer diabetes drugs OT - Type 2 diabetes EDAT- 2017/09/13 06:00 MHDA- 2018/11/15 06:00 CRDT- 2017/09/13 06:00 PHST- 2017/07/11 00:00 [received] PHST- 2017/08/31 00:00 [accepted] PHST- 2017/09/13 06:00 [pubmed] PHST- 2018/11/15 06:00 [medline] PHST- 2017/09/13 06:00 [entrez] AID - 10.1007/s12020-017-1418-y [pii] AID - 10.1007/s12020-017-1418-y [doi] PST - ppublish SO - Endocrine. 2018 May;60(2):224-228. doi: 10.1007/s12020-017-1418-y. Epub 2017 Sep 11. PMID- 28879786 OWN - NLM STAT- MEDLINE DCOM- 20171213 LR - 20171213 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 10 IP - 12 DP - 2017 Dec TI - Pharmacological management of type 2 diabetes: what's new in 2017? PG - 1383-1394 LID - 10.1080/17512433.2017.1376652 [doi] AB - Novelties in the management of type 2 diabetes are dominated by the commercialisation of new glucose-lowering agents, which offer alternatives to older antidiabetic medications, and by the publication of several prospective placebo-controlled outcome trials, which demonstrated not only cardiovascular safety but also cardiovascular and renal protection with some new medications. Areas covered: Updates regarding the use of glucose-lowering agents are discussed from a clinical point of view. Some new viewpoints concern older antidiabetic agents such as metformin, sulfonylureas and glitazones whose benefit-risk balance has been revisited, especially in high risk patients. The recent data regarding DPP-4 inhibitors (gliptins) focused on the safety profile of this pharmacological class, including in patients with impaired renal function. The highlight concerns the cardiovascular (and renal) protection by some GLP-1 receptor agonists (liraglutide, semaglutide) and SGLT2 inhibitors (empagliflozin, canagliflozin) in patients with high cardiovascular risk. Finally, efficacy and safety of new combinations and advances in insulin therapy will be briefly discussed. Expert commentary: The recent data from randomized controlled trials, meta-analyses and observational real-life studies should trigger a revision of the algorithm for the treatment of hyperglycemia in type 2 diabetes, especially in patients with high cardiovascular and/or renal risk. FAU - Scheen, Andre J AU - Scheen AJ AD - a Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine , CHU Liege , Liege , Belgium. AD - b Division of Clinical Pharmacology, Center for Interdisciplinary Research on Medicines (CIRM) , University of Liege , Liege , Belgium. LA - eng PT - Journal Article PT - Review DEP - 20170911 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) SB - IM MH - Animals MH - Blood Glucose/drug effects MH - Cardiovascular Diseases/prevention & control MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - *Drug Design MH - Drug Therapy, Combination MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects/pharmacology MH - Randomized Controlled Trials as Topic MH - Risk Factors OTO - NOTNLM OT - Cardiovascular OT - DPP-4 inhibitor OT - GLP-1 receptor agonist OT - SGLT2 inhibitor OT - kidney OT - metformin OT - new insulin EDAT- 2017/09/08 06:00 MHDA- 2017/12/14 06:00 CRDT- 2017/09/08 06:00 PHST- 2017/09/08 06:00 [pubmed] PHST- 2017/12/14 06:00 [medline] PHST- 2017/09/08 06:00 [entrez] AID - 10.1080/17512433.2017.1376652 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2017 Dec;10(12):1383-1394. doi: 10.1080/17512433.2017.1376652. Epub 2017 Sep 11. PMID- 28847797 OWN - NLM STAT- MEDLINE DCOM- 20170919 LR - 20250103 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 136 IP - 9 DP - 2017 Aug 29 TI - Cardiovascular Actions and Clinical Outcomes With Glucagon-Like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase-4 Inhibitors. PG - 849-870 LID - 10.1161/CIRCULATIONAHA.117.028136 [doi] AB - Potentiation of glucagon-like peptide-1 (GLP-1) action through selective GLP-1 receptor (GLP-1R) agonism or by prevention of enzymatic degradation by inhibition of dipeptidyl peptidase-4 (DPP-4) promotes glycemic reduction for the treatment of type 2 diabetes mellitus by glucose-dependent control of insulin and glucagon secretion. GLP-1R agonists also decelerate gastric emptying, reduce body weight by reduction of food intake and lower circulating lipoproteins, inflammation, and systolic blood pressure. Preclinical studies demonstrate that both GLP-1R agonists and DPP-4 inhibitors exhibit cardioprotective actions in animal models of myocardial ischemia and ventricular dysfunction through incompletely characterized mechanisms. The results of cardiovascular outcome trials in human subjects with type 2 diabetes mellitus and increased cardiovascular risk have demonstrated a cardiovascular benefit (significant reduction in time to first major adverse cardiovascular event) with the GLP-1R agonists liraglutide (LEADER trial [Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Ourcome Results], -13%) and semaglutide (SUSTAIN-6 trial [Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide], -24%). In contrast, cardiovascular outcome trials examining the safety of the shorter-acting GLP-1R agonist lixisenatide (ELIXA trial [Evaluation of Lixisenatide in Acute Coronary Syndrom]) and the DPP-4 inhibitors saxagliptin (SAVOR-TIMI 53 trial [Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53]), alogliptin (EXAMINE trial [Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome]), and sitagliptin (TECOS [Trial Evaluating Cardiovascular Outcomes With Sitagliptin]) found that these agents neither increased nor decreased cardiovascular events. Here we review the cardiovascular actions of GLP-1R agonists and DPP-4 inhibitors, with a focus on the translation of mechanisms derived from preclinical studies to complementary findings in clinical studies. We highlight areas of uncertainty requiring more careful scrutiny in ongoing basic science and clinical studies. As newer more potent GLP-1R agonists and coagonists are being developed for the treatment of type 2 diabetes mellitus, obesity, and nonalcoholic steatohepatitis, the delineation of the potential mechanisms that underlie the cardiovascular benefit and safety of these agents have immediate relevance for the prevention and treatment of cardiovascular disease. CI - (c) 2017 American Heart Association, Inc. FAU - Nauck, Michael A AU - Nauck MA AD - From Diabetes Center Bochum-Hattingen, St Josef-Hospital, Ruhr-University Bochum, Germany (M.A.N., J.J.M., M.A.E.A.); Department of Medicine, University of North Carolina, Chapel Hill (M.A.C.); and Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt Sinai Hospital, University of Toronto, Ontario, Canada (D.J.D.). michael.nauck@rub.de. FAU - Meier, Juris J AU - Meier JJ AD - From Diabetes Center Bochum-Hattingen, St Josef-Hospital, Ruhr-University Bochum, Germany (M.A.N., J.J.M., M.A.E.A.); Department of Medicine, University of North Carolina, Chapel Hill (M.A.C.); and Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt Sinai Hospital, University of Toronto, Ontario, Canada (D.J.D.). FAU - Cavender, Matthew A AU - Cavender MA AD - From Diabetes Center Bochum-Hattingen, St Josef-Hospital, Ruhr-University Bochum, Germany (M.A.N., J.J.M., M.A.E.A.); Department of Medicine, University of North Carolina, Chapel Hill (M.A.C.); and Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt Sinai Hospital, University of Toronto, Ontario, Canada (D.J.D.). FAU - Abd El Aziz, Mirna AU - Abd El Aziz M AD - From Diabetes Center Bochum-Hattingen, St Josef-Hospital, Ruhr-University Bochum, Germany (M.A.N., J.J.M., M.A.E.A.); Department of Medicine, University of North Carolina, Chapel Hill (M.A.C.); and Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt Sinai Hospital, University of Toronto, Ontario, Canada (D.J.D.). FAU - Drucker, Daniel J AU - Drucker DJ AD - From Diabetes Center Bochum-Hattingen, St Josef-Hospital, Ruhr-University Bochum, Germany (M.A.N., J.J.M., M.A.E.A.); Department of Medicine, University of North Carolina, Chapel Hill (M.A.C.); and Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt Sinai Hospital, University of Toronto, Ontario, Canada (D.J.D.). LA - eng PT - Journal Article PT - Review PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - Diabetes Mellitus, Type 2/drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use MH - Glucagon-Like Peptide 1/metabolism MH - Glucagon-Like Peptide-1 Receptor/*metabolism MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Myocardial Ischemia/prevention & control MH - Risk Factors MH - Ventricular Dysfunction/drug therapy MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - DPP-4Is OT - GLP-1 OT - GLP-1R agonists OT - acute myocardial infarction OT - cardiovascular events OT - cardiovascular outcomes trials OT - congestive heart failure OT - incretin OT - stroke EDAT- 2017/08/30 06:00 MHDA- 2017/09/20 06:00 CRDT- 2017/08/30 06:00 PHST- 2017/08/30 06:00 [entrez] PHST- 2017/08/30 06:00 [pubmed] PHST- 2017/09/20 06:00 [medline] AID - CIRCULATIONAHA.117.028136 [pii] AID - 10.1161/CIRCULATIONAHA.117.028136 [doi] PST - ppublish SO - Circulation. 2017 Aug 29;136(9):849-870. doi: 10.1161/CIRCULATIONAHA.117.028136. PMID- 28786547 OWN - NLM STAT- MEDLINE DCOM- 20181227 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 20 IP - 2 DP - 2018 Feb TI - Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy in Japanese people with type 2 diabetes. PG - 378-388 LID - 10.1111/dom.13082 [doi] AB - AIMS: To assess the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D). METHODS: In this phase IIIa randomized, open-label, parallel-group, active-controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0 mg) or once-daily oral sitagliptin 100 mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30 weeks. RESULTS: Overall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide- vs sitagliptin-treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin -1.13%, 95% confidence interval [CI] -1.32; -0.94, and -1.44%, 95% CI -1.63; -1.24; both P < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD -2.22 kg, 95% CI -3.02; -1.42 and -3.88 kg, 95% CI -4.70; -3.07; both P < .0001). CONCLUSIONS: In Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon-like peptide-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin. CI - (c) 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Seino, Yutaka AU - Seino Y AUID- ORCID: 0000-0002-1099-7989 AD - Kansai Electric Power Medical Research Institute, Kobe, Japan. AD - Kansai Electric Power Hospital, Osaka, Japan. FAU - Terauchi, Yasuo AU - Terauchi Y AD - Yokohama City University, Yokohama, Japan. FAU - Osonoi, Takeshi AU - Osonoi T AD - Naka Memorial Clinic, Ibaraki, Japan. FAU - Yabe, Daisuke AU - Yabe D AD - Kansai Electric Power Medical Research Institute, Kobe, Japan. AD - Kansai Electric Power Hospital, Osaka, Japan. AD - Kyoto University, Kyoto, Japan. FAU - Abe, Nobuyuki AU - Abe N AD - Abe Clinic, Oita, Japan. FAU - Nishida, Tomoyuki AU - Nishida T AD - Novo Nordisk Pharma Ltd, Tokyo, Japan. FAU - Zacho, Jeppe AU - Zacho J AD - Novo Nordisk Pharma Ltd, Tokyo, Japan. FAU - Kaneko, Shizuka AU - Kaneko S AD - Takatsuki Red Cross Hospital, Osaka, Japan. LA - eng SI - ClinicalTrials.gov/NCT02254291 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20171005 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Incretins) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Administration, Oral MH - Constipation/chemically induced/physiopathology/therapy MH - Diabetes Mellitus, Type 2/blood/*drug therapy/ethnology MH - Diarrhea/chemically induced/physiopathology/therapy MH - Dipeptidyl-Peptidase IV Inhibitors/administration & dosage/*adverse effects/therapeutic use MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Follow-Up Studies MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Glucagon-Like Peptides/administration & dosage/*adverse effects/therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hyperglycemia/*prevention & control MH - Hypoglycemia/chemically induced/prevention & control MH - Incretins/administration & dosage/*adverse effects/therapeutic use MH - Injections, Subcutaneous MH - Japan MH - Nausea/chemically induced/physiopathology/therapy MH - Patient Dropouts MH - Severity of Illness Index MH - Sitagliptin Phosphate/administration & dosage/*adverse effects/therapeutic use MH - Weight Loss/drug effects MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide PMC - PMC5813234 OTO - NOTNLM OT - GLP-1 OT - sitagliptin OT - type 2 diabetes COIS- Y.S. has received honoraria for consulting and/or speakers bureau from Kao; Kyowa Hakko Kirin; Taisho Pharmaceutical; Becton, Dickinson and Company; Novo Nordisk; MSD; Intarcia Therapeutics; Johnson & Johnson; GlaxoSmithKline; Takeda Pharmaceutical Company; Sanofi; Taisho Toyama Pharmaceutical; Eli Lilly & Company; Mitsubishi Tanabe Pharma; Ono Pharmaceutical; Kowa; Astellas Pharma; Boehringer Ingelheim; AstraZeneca; Sumitomo Dainippon Pharma; Daiichi Sankyo; Terumo; Arkray; and clinical commissioned/joint research grants from Arkray Marketing; Kowa; Hayashibara; Nippon Boehringer Ingelheim; Eli Lilly & Company; Terumo; Taisho Toyama Pharmaceutical; MSD K.K.; Ono Pharmaceutical; Novo Nordisk; Sumitomo Dainippon Pharma; Arklay. Y. T. has received honoraria for speakers bureau from Astellas Pharma; AstraZeneca K.K.; Bayer Yakuhin; Daiichi Sankyo; Sumitomo Dainippon Pharma; Eli Lilly Japan K.K.; Kowa; MSD K.K.; Mitsubishi Tanabe Pharma; Nippon Boehringer Ingelheim; Novo Nordisk; Ono Pharmaceutical; Sanwa Kagaku Kenkyusho; Sanofi K.K.; Shionogi & Company; Taisho Toyama Pharmaceutical; Takeda Pharmaceutical Company; and grants from Astellas Pharma; AstraZeneca K.K.; Bayer Yakuhin; Daiichi Sankyo; Sumitomo Dainippon Pharma; Eli Lilly Japan K.K.; Kowa; MSD K.K.; Mitsubishi Tanabe Pharma; Nippon Boehringer Ingelheim; Novo Nordisk; Ono Pharmaceutical; Pfizer Japan; Sanwa Kagaku Kenkyusho; Sanofi K.K., Shionogi & Company; Takeda Pharmaceutical Company. T. O. is a lecturer and clinical study investigator for Novo Nordisk. D. Y. has received consulting and/or speaker fees from MSD K.K.; Novo Nordisk; Takeda Pharmaceutical Company; Taisho Toyama Pharmaceutical; and clinical commissioned/joint research grants from Nippon Boehringer Ingelheim; Eli Lilly & Company; Taisho Toyama Pharmaceutical; MSD K.K.; Ono Pharmaceutical; Novo Nordisk; Arklay; Takeda Pharmaceutical Company. NA has no conflicts of interest. T.N. is an employee of Novo Nordisk and holds shares in the company. J. Z. is an employee of Novo Nordisk and holds shares in the company. S. K. has received honoraria for speakers bureau from Astellas Pharma; AstraZeneca K.K.; Daiichi Sankyo; Sumitomo Dainippon Pharma; Eli Lilly Japan K.K.; Kissei Pharmaceutical; Mitsubishi Tanabe Pharma; Novo Nordisk; Novartis Pharma K.K.; Ono Pharmaceutical; Sanofi K.K.; Taisho Toyama Pharmaceutical; Takeda Pharmaceutical Company; and grants from WebMD Global LLC. EDAT- 2017/08/09 06:00 MHDA- 2018/12/28 06:00 PMCR- 2018/02/15 CRDT- 2017/08/09 06:00 PHST- 2017/04/13 00:00 [received] PHST- 2017/08/03 00:00 [revised] PHST- 2017/08/04 00:00 [accepted] PHST- 2017/08/09 06:00 [pubmed] PHST- 2018/12/28 06:00 [medline] PHST- 2017/08/09 06:00 [entrez] PHST- 2018/02/15 00:00 [pmc-release] AID - DOM13082 [pii] AID - 10.1111/dom.13082 [doi] PST - ppublish SO - Diabetes Obes Metab. 2018 Feb;20(2):378-388. doi: 10.1111/dom.13082. Epub 2017 Oct 5. PMID- 28748377 OWN - NLM STAT- MEDLINE DCOM- 20180606 LR - 20250103 IS - 1432-5233 (Electronic) IS - 0940-5429 (Linking) VI - 54 IP - 10 DP - 2017 Oct TI - Microvascular effects of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized controlled trials. PG - 933-941 LID - 10.1007/s00592-017-1031-9 [doi] AB - AIMS: Results with GLP1-receptor agonists (GLP-1RA) on microvascular complications of diabetes are contrasting. In trials designed for cardiovascular outcomes, both liraglutide and semaglutide were associated with a relevant reduction in the incidence and progression of nephropathy. On the other hand, in the same trials, semaglutide was associated with an increased progression of retinopathy, and a similar trend was observed for liraglutide. This meta-analysis is aimed at assessing the effects of GLP-1RA on retinopathy and nephropathy. METHODS: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration >11 weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug. RESULTS: Of the 113 trials fulfilling the inclusion criteria, 78 and 62 did not report information on retinopathy and nephropathy, respectively. Treatment with GLP1-RA was not associated with a significant increase in the incidence of retinopathy (MH-OR [95% CI] 0.92 [0.74-1.16]. p = 0.49). In subgroup analyses, GLP1-RA were associated with a lower risk of retinopathy in comparison with sulfonylureas. Cases of macular edema were reported only in nine trials with no sign of increased risk. GLP1-RA reduced the incidence of nephropathy with respect to comparators (MH-OR [95% CI] 0.74 [0.60-0.92]. p = 0.005). This difference was significant versus placebo, but not versus any class of active comparators. CONCLUSIONS: GLP1-RA appear to reduce the incidence and/or progression of nephropathy and to have no specific effect on retinopathy-with the notable exception of semaglutide, which could have a negative impact on the retina. FAU - Dicembrini, Ilaria AU - Dicembrini I AD - Diabetology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Via delle Oblate 4, 50141, Florence, Italy. FAU - Nreu, Besmir AU - Nreu B AD - Diabetology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Via delle Oblate 4, 50141, Florence, Italy. FAU - Scatena, Alessia AU - Scatena A AD - Diabetology Unit, Ospedale San Donato Arezzo, Arezzo, Italy. FAU - Andreozzi, Francesco AU - Andreozzi F AD - Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy. FAU - Sesti, Giorgio AU - Sesti G AD - Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy. FAU - Mannucci, Edoardo AU - Mannucci E AD - Diabetology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Via delle Oblate 4, 50141, Florence, Italy. FAU - Monami, Matteo AU - Monami M AUID- ORCID: 0000-0001-9349-828X AD - Diabetology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Via delle Oblate 4, 50141, Florence, Italy. matteo.monami@unifi.it. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review DEP - 20170727 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM EIN - Acta Diabetol. 2017 Nov;54(11):1069-1071. doi: 10.1007/s00592-017-1049-z. PMID: 28924916 MH - Diabetes Mellitus, Type 2/complications/*drug therapy/metabolism/physiopathology MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Microvessels/*drug effects MH - Randomized Controlled Trials as Topic MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 receptor agonists OT - Meta-analysis OT - Nephropathy OT - Retinopathy EDAT- 2017/07/28 06:00 MHDA- 2018/06/07 06:00 CRDT- 2017/07/28 06:00 PHST- 2017/05/16 00:00 [received] PHST- 2017/07/16 00:00 [accepted] PHST- 2017/07/28 06:00 [pubmed] PHST- 2018/06/07 06:00 [medline] PHST- 2017/07/28 06:00 [entrez] AID - 10.1007/s00592-017-1031-9 [pii] AID - 10.1007/s00592-017-1031-9 [doi] PST - ppublish SO - Acta Diabetol. 2017 Oct;54(10):933-941. doi: 10.1007/s00592-017-1031-9. Epub 2017 Jul 27. PMID- 28741970 OWN - NLM STAT- MEDLINE DCOM- 20170904 LR - 20260127 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 26 IP - 9 DP - 2017 Sep TI - Efficacy and safety of once-weekly semaglutide for the treatment of type 2 diabetes. PG - 1083-1089 LID - 10.1080/13543784.2017.1360274 [doi] AB - Type 2 diabetes is a chronic metabolic disease characterized by persistent hyperglycemia resulting from progressive deficient of insulin in patients with a background of insulin resistance. Current treatment algorithms recommended by American Diabetes Association/The European Association for the Study of Diabetes promote a patient-centered approach that takes into account a comprehensive consideration of pharmacological properties of drugs, including glucose-lowering action, effects on body weight, correction on multiple pathophysiologic defects, tolerability, and long-term safety. Glucagon-likepeptide1 (GLP-1) receptor analogues are appealing due to the improved glycemic control in a glucose-dependent manner, modest weight loss and low risk of hypoglycemia. Areas covered: Semaglutide (Novo Nordisk), a once-weekly GLP-1 analogue, is currently in the phase III clinical trial for the treatment of type 2 diabetes. This article aims to review the pharmacological and clinical profiles of semaglutide based on the available clinical data. Expert opinion: Semaglutide achieved greater reduction from baseline in HbA(1c) in comparison to placebo. The greater proportion of patients in semaglutide group than that in placebo group achieved target HbA(1c) <7.0% and <6.5%, respectively. Semaglutide is the second GLP-1 analogue contributing to the reduced bodyweight and improving obesity related complications. More importantly, semaglutide is beneficial to diabetic patients with high cardiovascular risk according to the recently completed phase III trial. The incidence of gastrointestinal adverse effects increased with semaglutide dose. FAU - Tan, Xueying AU - Tan X AD - a College of Pharmacy , Zhejiang Pharmaceutical College , Ningbo , China. FAU - Cao, Xiaojing AU - Cao X AD - b Department of Pharmacy , The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou , China. FAU - Zhou, Minzhi AU - Zhou M AD - c School of Medicine , Zhejiang University City College , Hangzhou , China. FAU - Zou, Ping AU - Zou P AD - d Department of Pharmacy , The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China. FAU - Hu, Jingbo AU - Hu J AD - e College of Pharmaceutical Science , Zhejiang University , Hangzhou , China. LA - eng PT - Journal Article PT - Review DEP - 20170802 PL - England TA - Expert Opin Investig Drugs JT - Expert opinion on investigational drugs JID - 9434197 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Blood Glucose/drug effects MH - Cardiovascular Diseases/prevention & control MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - Glucagon-Like Peptides/adverse effects/pharmacology/*therapeutic use MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/adverse effects/pharmacology/*therapeutic use MH - Insulin Resistance MH - Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Semaglutide OT - cardiovascular protection OT - glucagon-like peptide 1 OT - once-weekly administration OT - type 2 diabetes OT - weight loss EDAT- 2017/07/26 06:00 MHDA- 2017/09/05 06:00 CRDT- 2017/07/26 06:00 PHST- 2017/07/26 06:00 [pubmed] PHST- 2017/09/05 06:00 [medline] PHST- 2017/07/26 06:00 [entrez] AID - 10.1080/13543784.2017.1360274 [doi] PST - ppublish SO - Expert Opin Investig Drugs. 2017 Sep;26(9):1083-1089. doi: 10.1080/13543784.2017.1360274. Epub 2017 Aug 2. PMID- 28726152 OWN - NLM STAT- MEDLINE DCOM- 20171127 LR - 20181202 IS - 1539-0829 (Electronic) IS - 1534-4827 (Linking) VI - 17 IP - 9 DP - 2017 Sep TI - Cardiovascular Outcome Trial Update in Diabetes: New Evidence, Remaining Questions. PG - 67 LID - 10.1007/s11892-017-0898-8 [doi] AB - PURPOSE OF REVIEW: Seven trials of new agents to treat type 2 diabetes (T2DM) have been performed to assess cardiovascular (CV) safety. A significant amount of information regarding the effects of drugs in three classes is available, with new data from multiple other trials expected shortly. This article provides a summary of recently completed trials. RECENT FINDINGS: The dipeptidyl peptidase-4 inhibitors studied thus far do not alter the risk of major adverse CV events (MACE). Glucagon like peptide-1 receptor agonists liraglutide and semaglutide, and the sodium glucose cotransporter-2 inhibitor empagliflozin, significantly reduced the risk of MACE. Empagliflozin also decreased the risk of hospitalization for heart failure. Agents demonstrating a CV outcome benefit also improved parameters of renal function. Several newer antihyperglycemic agents have been found to reduce the risk of important CV complications in high-risk patients with T2DM. Future trials are needed to assess the effects of additional drugs and the impact of therapy in lower risk patients and provide additional information regarding non-CV safety outcomes. FAU - Herbst, Rebecca AU - Herbst R AD - Department of Medicine, Division of Endocrinology, Duke University Medical Center, Durham, NC, USA. FAU - Bolton, Wilburn AU - Bolton W AD - Department of Medicine, Division of Endocrinology, Duke University Medical Center, Durham, NC, USA. FAU - Shariff, Afreen AU - Shariff A AD - Department of Medicine, Division of Endocrinology, Duke University Medical Center, Durham, NC, USA. FAU - Green, Jennifer B AU - Green JB AD - Department of Medicine, Division of Endocrinology, Duke University Medical Center, Durham, NC, USA. green094@mc.duke.edu. AD - Duke Clinical Research Institute, Durham, NC, USA. green094@mc.duke.edu. LA - eng PT - Journal Article PT - Review PL - United States TA - Curr Diab Rep JT - Current diabetes reports JID - 101093791 RN - 0 (Hypoglycemic Agents) SB - IM MH - Cardiovascular Diseases/*etiology MH - *Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*complications/drug therapy MH - Humans MH - Hyperglycemia/complications/drug therapy MH - Hypoglycemic Agents/therapeutic use MH - Risk Factors OTO - NOTNLM OT - Antihyperglycemic OT - Cardiovascular OT - Diabetes OT - Outcomes EDAT- 2017/07/21 06:00 MHDA- 2017/11/29 06:00 CRDT- 2017/07/21 06:00 PHST- 2017/07/21 06:00 [entrez] PHST- 2017/07/21 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] AID - 10.1007/s11892-017-0898-8 [pii] AID - 10.1007/s11892-017-0898-8 [doi] PST - ppublish SO - Curr Diab Rep. 2017 Sep;17(9):67. doi: 10.1007/s11892-017-0898-8. PMID- 28657399 OWN - NLM STAT- MEDLINE DCOM- 20170905 LR - 20250103 IS - 1941-9260 (Electronic) IS - 0032-5481 (Linking) VI - 129 IP - 7 DP - 2017 Sep TI - Combination SGLT2 inhibitor and GLP-1 receptor agonist therapy: a complementary approach to the treatment of type 2 diabetes. PG - 686-697 LID - 10.1080/00325481.2017.1342509 [doi] AB - Among persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment of diabetes-related complications and comorbidities beyond those related to hyperglycemia. use of glucose-lowering therapies with complementary activities that address multiple facets of the disease may improve long-term outcomes for patients with t2d. two recent drug classes developed for use in t2d, glucagon-like peptide-1 receptor agonists (glp-1ras) and sodium glucose cotransporter 2 (sglt2) inhibitors, have been shown in clinical trials to have beneficial effects on glycemic control, body weight, cardiovascular risk factors, and (for liraglutide, semaglutide, and empagliflozin) cardiovascular outcomes, while having an acceptable safety profile. between them, these drug classes directly or indirectly affect many of the organs and tissues involved in the pathogenesis of t2d, and their beneficial effects on glycemic- and cardiovascular-related parameters are likely to be complementary and potentially additive. in the largest clinical trial of a glp-1ra and an sglt2 inhibitor in combination (duration-8), patients with t2d (n = 685) who received exenatide plus dapagliflozin added to their treatment regimen for 28 weeks had significantly greater reductions from baseline in glycated hemoglobin, body weight, and systolic blood pressure compared with patients who received either drug as monotherapy. this review summarizes the complementary aspects of these drug classes and presents the available data among patients receiving dual therapy with a glp-1ra and an sglt2 inhibitor. FAU - Busch, Robert S AU - Busch RS AD - a Albany Medical Center Division of Community Endocrinology , Albany , NY , USA. FAU - Kane, Michael P AU - Kane MP AD - b Department of Pharmacy Practice , Albany College of Pharmacy and Health Sciences , Albany , NY , USA. LA - eng PT - Journal Article DEP - 20170628 PL - England TA - Postgrad Med JT - Postgraduate medicine JID - 0401147 RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transport Proteins) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Complementary Therapies MH - Diabetes Complications/*drug therapy/etiology MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Female MH - Glucagon-Like Peptide-1 Receptor/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Middle Aged MH - Sodium-Glucose Transport Proteins/*agonists/*therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Combination therapy OT - GLP-1 receptor agonists OT - SGLT2 inhibitors OT - complementary actions OT - dual therapy OT - type 2 diabetes EDAT- 2017/06/29 06:00 MHDA- 2017/09/07 06:00 CRDT- 2017/06/29 06:00 PHST- 2017/06/29 06:00 [pubmed] PHST- 2017/09/07 06:00 [medline] PHST- 2017/06/29 06:00 [entrez] AID - 10.1080/00325481.2017.1342509 [doi] PST - ppublish SO - Postgrad Med. 2017 Sep;129(7):686-697. doi: 10.1080/00325481.2017.1342509. Epub 2017 Jun 28. PMID- 28637887 OWN - NLM STAT- MEDLINE DCOM- 20171205 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 40 IP - 7 DP - 2017 Jul TI - Mitigating Cardiovascular Risk in Type 2 Diabetes With Antidiabetes Drugs: A Review of Principal Cardiovascular Outcome Results of EMPA-REG OUTCOME, LEADER, and SUSTAIN-6 Trials. PG - 821-831 LID - 10.2337/dc17-0291 [doi] AB - The U.S. Food and Drug Administration (FDA) issued a diabetes guidance in 2008 mandating that all new antidiabetes drugs rule out excess cardiovascular (CV) risk, defined as an upper bound of the two-sided 95% CI for major adverse CV events (MACE) of less than 1.80 preapproval and 1.30 postapproval. Over 25 large, prospective, randomized, controlled clinical trials involving nearly 195,000 subjects thus far have been completed or are ongoing in accordance with this guidance. The results of seven trials have been presented so far-three with dipeptidyl peptidase 4 inhibitors, one with a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and three with glucagon-like peptide 1 receptor agonists (GLP-1 RA). While all seven trials showed noninferiority in the rate of MACE with the use of these agents compared with placebo, three of them revealed CV benefits. Treatment with empagliflozin (an SGLT2 inhibitor) and treatment with liraglutide (a GLP-1 RA) both significantly reduced the risk of MACE, mortality from CV causes, and mortality from any cause when compared with placebo. Treatment with semaglutide, another GLP-1 RA, showed a significantly lower rate of MACE but not mortality from CV or any cause compared with placebo. In all of the trials, the effects of treatment on outcomes were out of proportion to the small differences in glycemic control levels, suggesting that the effects observed were likely unrelated to differences in the glucose-lowering efficacy. Overall, the results of these trials yield a favorable benefit-risk balance for these therapies in mitigating CV risk in patients with type 2 diabetes. More research is needed to elucidate the underlying mechanisms and confirm whether the CV benefits are a class effect or whether the benefits persist in patients without established CV disease or are evident even in patients without diabetes. CI - (c) 2017 by the American Diabetes Association. FAU - Kaul, Sanjay AU - Kaul S AUID- ORCID: 0000-0001-9640-4146 AD - Cedars-Sinai Medical Center, Los Angeles, CA sanjay.kaul@cshs.org. LA - eng PT - Journal Article PT - Review PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Benzhydryl Compounds) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM CIN - Diabetes Care. 2017 Dec;40(12):e174. doi: 10.2337/dc17-1527. PMID: 29162589 CIN - Diabetes Care. 2017 Dec;40(12):e175-e176. doi: 10.2337/dci17-0044. PMID: 29162590 EIN - Diabetes Care. 2018 Mar;41(3):640. doi: 10.2337/dc18-er03a. PMID: 29311153 MH - Animals MH - Benzhydryl Compounds/pharmacology/therapeutic use MH - Cardiovascular Diseases/etiology/*prevention & control MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - Glucosides/pharmacology/therapeutic use MH - Humans MH - Hypoglycemic Agents/pharmacology/*therapeutic use MH - Liraglutide/pharmacology/therapeutic use MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - Treatment Outcome MH - Semaglutide EDAT- 2017/06/24 06:00 MHDA- 2017/12/06 06:00 CRDT- 2017/06/23 06:00 PHST- 2017/02/07 00:00 [received] PHST- 2017/04/12 00:00 [accepted] PHST- 2017/06/23 06:00 [entrez] PHST- 2017/06/24 06:00 [pubmed] PHST- 2017/12/06 06:00 [medline] AID - 40/7/821 [pii] AID - 10.2337/dc17-0291 [doi] PST - ppublish SO - Diabetes Care. 2017 Jul;40(7):821-831. doi: 10.2337/dc17-0291. PMID- 28637886 OWN - NLM STAT- MEDLINE DCOM- 20171205 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Print) IS - 0149-5992 (Linking) VI - 40 IP - 7 DP - 2017 Jul TI - Cardiovascular Disease and Type 2 Diabetes: Has the Dawn of a New Era Arrived? PG - 813-820 LID - 10.2337/dc16-2736 [doi] AB - Hyperglycemia is the major risk factor for microvascular complications in patients with type 2 diabetes (T2D). However, cardiovascular disease (CVD) is the principal cause of death, and lowering HbA(1c) has only a modest effect on reducing CVD risk and mortality. The recently published LEADER and SUSTAIN-6 trials demonstrate that, in T2D patients with high CVD risk, the glucagon-like peptide 1 receptor agonists liraglutide and semaglutide reduce the primary major adverse cardiac events (MACE) end point (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke) by 13% and 24%, respectively. The EMPA-REG OUTCOME, IRIS (subjects without diabetes), and PROactive (second principal end point) studies also demonstrated a significant reduction in cardiovascular events in T2D patients treated with empagliflozin and pioglitazone. However, the benefit of these four antidiabetes agents (liraglutide, semaglutide, empagliflozin, and pioglitazone) on the three individual MACE end points differed, suggesting that different underlying mechanisms were responsible for the reduction in cardiovascular events. Since liraglutide, semaglutide, pioglitazone, and empagliflozin similarly lower the plasma glucose concentration but appear to reduce CVD risk by different mechanisms, there emerges the intriguing possibility that, if used in combination, the effects of these antidiabetes agents may be additive or even multiplicative with regard to cardiovascular benefit. CI - (c) 2017 by the American Diabetes Association. FAU - Abdul-Ghani, Muhammad AU - Abdul-Ghani M AUID- ORCID: 0000-0003-3839-1724 AD - Division of Diabetes, University of Texas Health Science Center at San Antonio, and South Texas Veterans Health Care System, San Antonio, TX albarado@uthscsa.edu. AD - Diabetes Clinical Research Center, Academic Health System, Hamad General Hospital, Doha, Qatar. FAU - DeFronzo, Ralph A AU - DeFronzo RA AUID- ORCID: 0000-0002-8581-6273 AD - Division of Diabetes, University of Texas Health Science Center at San Antonio, and South Texas Veterans Health Care System, San Antonio, TX. FAU - Del Prato, Stefano AU - Del Prato S AD - Department of Clinical and Experimental Medicine, University of Pisa School of Medicine, Pisa, Italy. FAU - Chilton, Robert AU - Chilton R AD - Division of Cardiology, University of Texas Health Science Center at San Antonio, and South Texas Veterans Health Care System, San Antonio, TX. FAU - Singh, Rajvir AU - Singh R AD - Diabetes Clinical Research Center, Academic Health System, Hamad General Hospital, Doha, Qatar. FAU - Ryder, Robert E J AU - Ryder REJ AD - Sandwell and West Birmingham Hospitals National Health Service Trust, Birmingham, U.K. LA - eng GR - R01 DK024092/DK/NIDDK NIH HHS/United States GR - R56 DK024092/DK/NIDDK NIH HHS/United States PT - Journal Article PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Benzhydryl Compounds) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - X4OV71U42S (Pioglitazone) RN - 0 (Thiazolidinediones) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM EIN - Diabetes Care. 2017 Nov;40(11):1606. doi: 10.2337/dc17-er11. PMID: 28887407 MH - Animals MH - Benzhydryl Compounds/pharmacology/therapeutic use MH - Cardiovascular Diseases/etiology/*prevention & control MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - Glucosides/pharmacology/therapeutic use MH - Humans MH - Hyperglycemia/complications/drug therapy MH - Hypoglycemic Agents/*therapeutic use MH - Liraglutide/pharmacology/therapeutic use MH - Pioglitazone MH - Randomized Controlled Trials as Topic MH - Risk Factors MH - Thiazolidinediones/pharmacology/therapeutic use MH - Treatment Outcome MH - Semaglutide PMC - PMC5481984 EDAT- 2017/06/24 06:00 MHDA- 2017/12/06 06:00 PMCR- 2018/07/01 CRDT- 2017/06/23 06:00 PHST- 2017/01/03 00:00 [received] PHST- 2017/04/05 00:00 [accepted] PHST- 2017/06/23 06:00 [entrez] PHST- 2017/06/24 06:00 [pubmed] PHST- 2017/12/06 06:00 [medline] PHST- 2018/07/01 00:00 [pmc-release] AID - 40/7/813 [pii] AID - 2736 [pii] AID - 10.2337/dc16-2736 [doi] PST - ppublish SO - Diabetes Care. 2017 Jul;40(7):813-820. doi: 10.2337/dc16-2736. PMID- 28606343 OWN - NLM STAT- MEDLINE DCOM- 20170803 LR - 20250103 IS - 1879-1913 (Electronic) IS - 0002-9149 (Linking) VI - 120 IP - 1S DP - 2017 Jul 1 TI - Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies. PG - S4-S16 LID - S0002-9149(17)30799-3 [pii] LID - 10.1016/j.amjcard.2017.05.009 [doi] AB - Choices for the treatment of type 2 diabetes mellitus (T2DM) have multiplied as our understanding of the underlying pathophysiologic defects has evolved. Treatment should target multiple defects in T2DM and follow a patient-centered approach that considers factors beyond glycemic control, including cardiovascular risk reduction. The American Association of Clinical Endocrinologists/American College of Endocrinology and the American Diabetes Association recommend an initial approach consisting of lifestyle changes and monotherapy, preferably with metformin. Therapy choices are guided by glycemic efficacy, safety profiles, particularly effects on weight and hypoglycemia risk, tolerability, patient comorbidities, route of administration, patient preference, and cost. Balancing management of hyperglycemia with the risk of hypoglycemia and consideration of the effects of pharmacotherapy on weight figure prominently in US-based T2DM recommendations, whereas less emphasis has been placed on the ability of specific medications to affect cardiovascular outcomes. This is likely because, until recently, specific glucose-lowering agents have not been shown to affect cardiorenal outcomes. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes 6 (SUSTAIN-6) recently showed a reduction in overall cardiovascular risk with empagliflozin, liraglutide, and semaglutide treatment, respectively. Moreover, empagliflozin has become the first glucose-lowering agent indicated to reduce the risk of cardiovascular death in adults with T2DM and established cardiovascular disease. Results from cardiovascular outcomes trials have prompted an update to the 2017 American Diabetes Association standards of care, which now recommend consideration of empagliflozin or liraglutide for patients with suboptimally controlled long-standing T2DM and established atherosclerotic cardiovascular disease because these agents have been shown to reduce cardiovascular and all-cause mortality when added to standard care. CI - Copyright (c) 2017 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Thrasher, James AU - Thrasher J AD - Medical Investigations, Inc, Little Rock, Ark. Electronic address: jthrashermd@yahoo.com. LA - eng PT - Journal Article PT - Review DEP - 20170530 PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Thiazolidinediones) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cardiovascular Diseases/prevention & control MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Diabetic Angiopathies/prevention & control MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Humans MH - Hyperglycemia/drug therapy/etiology MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Insulin/therapeutic use MH - Metformin/therapeutic use MH - Risk Factors MH - Sodium-Glucose Transporter 2 Inhibitors MH - Sulfonylurea Compounds/therapeutic use MH - Thiazolidinediones/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2017/06/14 06:00 MHDA- 2017/08/05 06:00 CRDT- 2017/06/14 06:00 PHST- 2017/06/14 06:00 [entrez] PHST- 2017/06/14 06:00 [pubmed] PHST- 2017/08/05 06:00 [medline] AID - S0002-9149(17)30799-3 [pii] AID - 10.1016/j.amjcard.2017.05.009 [doi] PST - ppublish SO - Am J Cardiol. 2017 Jul 1;120(1S):S4-S16. doi: 10.1016/j.amjcard.2017.05.009. Epub 2017 May 30. PMID- 28606340 OWN - NLM STAT- MEDLINE DCOM- 20170803 LR - 20250103 IS - 1879-1913 (Electronic) IS - 0002-9149 (Linking) VI - 120 IP - 1S DP - 2017 Jul 1 TI - Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes. PG - S17-S27 LID - S0002-9149(17)30807-X [pii] LID - 10.1016/j.amjcard.2017.05.015 [doi] AB - Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD)-namely myocardial infarction, heart failure, and stroke. Despite clear advances in the prevention and treatment of CVD, the impact of T2DM on CVD outcome remains high and continues to escalate. Available evidence indicates that the risk of macrovascular complications increases with the severity of hyperglycemia, thus suggesting that the relation between metabolic disturbances and vascular damage is approximately linear. Although current antidiabetic drugs are highly effective for the management of hyperglycemia, most T2DM patients remain exposed to a substantial and concrete risk of CVD. Over the last decade many glucose-lowering agents have been tested for their safety and efficacy in T2DM with CVD. Noteworthy, most of these studies failed to show a significant benefit in terms of CV morbidity and mortality, despite intensive glycemic control. The recent trials Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME); Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6); Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER); and Insulin Resistance Intervention After Stroke (IRIS) have shed some light on this important clinical issue, thus showing a convincing effect of empagliflozin, liraglutide, and pioglitazone on CVD outcomes. Here we provide a critical and updated overview of the main glucose-lowering agents and their risk/benefit ratio for the prevention of CVD in patients with T2DM. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Paneni, Francesco AU - Paneni F AD - University Heart Center, Cardiology, University Hospital Zurich, Switzerland; Center for Molecular Cardiology, University of Zurich, Switzerland. Electronic address: francesco.paneni@uzh.ch. FAU - Luscher, Thomas F AU - Luscher TF AD - University Heart Center, Cardiology, University Hospital Zurich, Switzerland; Center for Molecular Cardiology, University of Zurich, Switzerland. LA - eng PT - Journal Article PT - Review DEP - 20170530 PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Thiazolidinediones) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cardiovascular Diseases/*prevention & control MH - Diabetes Mellitus, Type 2/drug therapy MH - Diabetic Angiopathies/prevention & control MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Metformin/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors MH - Sulfonylurea Compounds/therapeutic use MH - Thiazolidinediones/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2017/06/14 06:00 MHDA- 2017/08/05 06:00 CRDT- 2017/06/14 06:00 PHST- 2017/06/14 06:00 [entrez] PHST- 2017/06/14 06:00 [pubmed] PHST- 2017/08/05 06:00 [medline] AID - S0002-9149(17)30807-X [pii] AID - 10.1016/j.amjcard.2017.05.015 [doi] PST - ppublish SO - Am J Cardiol. 2017 Jul 1;120(1S):S17-S27. doi: 10.1016/j.amjcard.2017.05.015. Epub 2017 May 30. PMID- 28554326 OWN - NLM STAT- MEDLINE DCOM- 20190207 LR - 20260127 IS - 1875-533X (Electronic) IS - 0929-8673 (Linking) VI - 25 IP - 13 DP - 2018 TI - Update on Cardiovascular Effects of Older and Newer Anti-diabetic Medications. PG - 1549-1566 LID - 10.2174/0929867324666170530075533 [doi] AB - It is known that Cardiovascular (CV) disease is the leading cause of morbidity and mortality in individuals with type 2 diabetes. Over the last years, one of the most discussed topics is the CV safety of anti-diabetic medications. Regarding CV safety of older antidiabetic agents the data are less clear and conclusions about their CV safety are mostly based on randomized controlled trials designed to assess their glucose lowering efficacy. In this review, we summarize the current knowledge about the CV safety of older and newer antidiabetic medications. According to the published literature metformin is the first line agent for the treatment of type 2 diabetes and seems to have cardio-protective effects. The choice of the second line agent when metformin monotherapy fails to achieve HbA1c targets is less clear. In the light of the findings of the EMPA-REG OUTCOME trial and the recently published LEADER and SUSTAIN 6 trials, empagliflozin, liraglutide and semaglutide seem reasonable options as second line agents for patients with CV disease. Sulfonylureas on the other hand, with the exception of gliclazide, should be avoided in those patients, although CV safety trials are still lacking. In individuals without CV disease any of the other classes of anti-diabetic medication can be selected on a patient-centered approach. Saxagliptin, alogliptin, sitagliptin and lixisenatide have been evaluated in CV safety trials and have neutral effects on CV outcomes, while pioglitazone may have some CV benefits. Saxagliptin and alogliptin, however, should be avoided in patients with heart failure, while pioglitazone is contraindicated in this population. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. FAU - Eleftheriadou, Ioanna AU - Eleftheriadou I AD - First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Grigoropoulou, Pinelopi AU - Grigoropoulou P AD - First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Liberopoulos, Evangelos AU - Liberopoulos E AD - Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece. FAU - Liatis, Stavros AU - Liatis S AD - First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Kokkinos, Alexandros AU - Kokkinos A AD - First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. FAU - Tentolouris, Nikolaos AU - Tentolouris N AD - First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Med Chem JT - Current medicinal chemistry JID - 9440157 RN - 0 (Benzhydryl Compounds) RN - 0 (Blood Glucose) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 839I73S42A (Liraglutide) RN - 9100L32L2N (Metformin) RN - X4OV71U42S (Pioglitazone) RN - 0 (Sodium-Glucose Transporter 2) RN - 53AXN4NNHX (Semaglutide) RN - HDC1R2M35U (empagliflozin) SB - IM MH - Benzhydryl Compounds/pharmacology/therapeutic use MH - Blood Glucose/metabolism MH - Cardiovascular Diseases/complications/*drug therapy MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/pharmacology/therapeutic use MH - Glucagon-Like Peptides/pharmacology/therapeutic use MH - Glucosides/pharmacology/therapeutic use MH - Humans MH - Hypoglycemic Agents/pharmacology/*therapeutic use MH - Insulin/pharmacology/therapeutic use MH - Liraglutide/pharmacology/therapeutic use MH - Metformin/pharmacology/therapeutic use MH - Pioglitazone/pharmacology/therapeutic use MH - Sodium-Glucose Transporter 2/metabolism MH - Semaglutide OTO - NOTNLM OT - Cardiovascular events OT - dipeptidyl peptidase-4 inhibitors OT - glucagon-like peptide-1 receptor agonists OT - insulin OT - metformin OT - pioglitazone OT - sodium-glucose co-transporters-2 inhibitors OT - sulfonylureas. EDAT- 2017/05/31 06:00 MHDA- 2019/02/08 06:00 CRDT- 2017/05/31 06:00 PHST- 2016/08/14 00:00 [received] PHST- 2017/05/15 00:00 [revised] PHST- 2017/05/15 00:00 [accepted] PHST- 2017/05/31 06:00 [pubmed] PHST- 2019/02/08 06:00 [medline] PHST- 2017/05/31 06:00 [entrez] AID - CMC-EPUB-83739 [pii] AID - 10.2174/0929867324666170530075533 [doi] PST - ppublish SO - Curr Med Chem. 2018;25(13):1549-1566. doi: 10.2174/0929867324666170530075533. PMID- 28550608 OWN - NLM STAT- MEDLINE DCOM- 20180717 LR - 20260127 IS - 1525-1497 (Electronic) IS - 0884-8734 (Print) IS - 0884-8734 (Linking) VI - 32 IP - 9 DP - 2017 Sep TI - Shifting Paradigms in the Medical Management of Type 2 Diabetes: Reflections on Recent Cardiovascular Outcome Trials. PG - 1044-1051 LID - 10.1007/s11606-017-4061-7 [doi] AB - An important challenge in the management of patients with type 2 diabetes is cardiovascular disease (CVD) prevention. While it is well established that intensive glycemic control prevents the onset and slows the progression of certain microvascular complications, such a strategy utilized in multiple clinical trials over the past few decades has failed to show a similar benefit with regard to cardiovascular events, including mortality. Despite this, a major hope has been the discovery of glucose-lowering medications that simultaneously improve cardiovascular outcomes. Over the past year and a half, four randomized clinical trials (involving empagliflozin, pioglitazone, liraglutide, and semaglutide) have reported important benefits in preventing adverse cardiovascular outcomes in patients with or at risk for type 2 diabetes and established CVD. On the basis of these landmark trials, we propose that a paradigm shift in the management of patients with type 2 diabetes, specifically in those with prior macrovascular disease. A transition from current algorithms based primarily on hemoglobin A1c values to a more comprehensive strategy additionally focused on CVD prevention seems warranted. FAU - Ismail-Beigi, Faramarz AU - Ismail-Beigi F AD - Division of Clinical and Molecular Endocrinology, Department of Medicine, Case Western Reserve University and VA Medical Center, 10900 Euclid Ave., Cleveland, OH, 44106-4951, USA. fxi2@case.edu. FAU - Moghissi, Etie AU - Moghissi E AD - Department of Medicine, UCLA, Geffen School of Medicine, Los Angeles, CA, USA. FAU - Kosiborod, Mikhail AU - Kosiborod M AD - Department of Cardiology, Saint Luke's Mid America Heart Institute, University of Missouri, Kansas City, MO, USA. FAU - Inzucchi, Silvio E AU - Inzucchi SE AD - Section of Endocrinology, Yale School of Medicine and Yale-New Haven Hospital, New Haven, CT, USA. LA - eng PT - Journal Article PT - Review DEP - 20170526 PL - United States TA - J Gen Intern Med JT - Journal of general internal medicine JID - 8605834 RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Aged MH - Cardiovascular Diseases/etiology/mortality/*prevention & control MH - Diabetes Mellitus, Type 2/complications/*drug therapy/economics MH - Female MH - Glycated Hemoglobin/drug effects MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Middle Aged MH - Randomized Controlled Trials as Topic PMC - PMC5570736 OTO - NOTNLM OT - MACE OT - The views expressed in this article do not represent any organization or entity OT - glycemic control OT - heart failure OT - hypoglycemia OT - individualization COIS- Dr. Ismail-Beigi has received grants from NIH and Novo Nordisk to conduct clinical trials. He has shares in Thermalin Diabetes, Inc., and serves as a consultant for Sanofi and COVANCE. Dr. Moghissi has served as a speaker/consultant for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Jansen, Merck, and Novo Nordisk. Dr. Kosiborod has research grants from AstraZeneca and Boehringer Ingelheim. He serves as a consultant/advisory board member for AstraZeneca, Amgen, Eli Lilly, Boehringer Ingelheim, GSK, Sanofi, Novo Nordisk, Merck (Diabetes), ZS Pharma, and Glytec, and is on the speakers bureau of Amgen. Dr. Inzucchi has served as a consultant to Merck, Janssen, Sanofi/Lexicon, and vTv Therapeutics. He has participated on clinical trial steering or publications committees for Boehringer Ingelheim, AstraZeneca, and Daiichi Sankyo. He has served as a member of data monitoring committees for Novo Nordisk and Intarcia. All remaining authors declare that they do not have a conflict of interest. EDAT- 2017/05/28 06:00 MHDA- 2018/07/18 06:00 PMCR- 2018/09/01 CRDT- 2017/05/28 06:00 PHST- 2017/03/03 00:00 [received] PHST- 2017/04/06 00:00 [accepted] PHST- 2017/03/29 00:00 [revised] PHST- 2017/05/28 06:00 [pubmed] PHST- 2018/07/18 06:00 [medline] PHST- 2017/05/28 06:00 [entrez] PHST- 2018/09/01 00:00 [pmc-release] AID - 10.1007/s11606-017-4061-7 [pii] AID - 4061 [pii] AID - 10.1007/s11606-017-4061-7 [doi] PST - ppublish SO - J Gen Intern Med. 2017 Sep;32(9):1044-1051. doi: 10.1007/s11606-017-4061-7. Epub 2017 May 26. PMID- 28545639 OWN - NLM STAT- MEDLINE DCOM- 20170809 LR - 20170809 IS - 1558-3597 (Electronic) IS - 0735-1097 (Linking) VI - 69 IP - 21 DP - 2017 May 30 TI - Novel Diabetes Drugs and the Cardiovascular Specialist. PG - 2646-2656 LID - S0735-1097(17)37026-2 [pii] LID - 10.1016/j.jacc.2017.04.014 [doi] AB - Recently, treatment with 2 newer classes of type 2 diabetes drugs were found to reduce events in patients with diabetes and cardiovascular (CV) disease, a group common in cardiology clinics. The sodium-glucose cotransporter 2 inhibitor, empagliflozin, markedly and rapidly reduced CV death and heart failure hospitalization, likely with hemodynamic/metabolic-driven mechanisms of action. More recently, the glucagon-like peptide-1 receptor agonists liraglutide and semaglutide also reduced CV death and/or major adverse CV events, but did so more slowly and did not influence heart failure risks, suggesting alternative mechanisms of benefit. We will discuss drug therapy for diabetes relative to CV risk, briefly summarize key findings of CV benefit from recent trials, discuss potential mechanisms for benefits of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 agonists, and suggest how such drugs might be embraced by CV specialists to reduce CV events and mortality in their patients. CI - Copyright (c) 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. FAU - Sattar, Naveed AU - Sattar N AD - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. FAU - Petrie, Mark C AU - Petrie MC AD - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. FAU - Zinman, Bernard AU - Zinman B AD - Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. FAU - Januzzi, James L Jr AU - Januzzi JL Jr AD - Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts; Baim Institute for Clinical Research, Boston, Massachusetts. Electronic address: jjanuzzi@partners.org. LA - eng PT - Journal Article PT - Review PL - United States TA - J Am Coll Cardiol JT - Journal of the American College of Cardiology JID - 8301365 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) SB - IM MH - Blood Glucose/metabolism MH - Cardiovascular Diseases/complications/mortality/*prevention & control MH - *Diabetes Mellitus, Type 2/blood/complications/drug therapy MH - Global Health MH - Humans MH - Hypoglycemic Agents/*pharmacology MH - Risk Factors MH - Survival Rate/trends OTO - NOTNLM OT - blood glucose OT - cardiovascular disease OT - heart failure OT - hypoglycemic agents OT - outcomes EDAT- 2017/05/27 06:00 MHDA- 2017/08/10 06:00 CRDT- 2017/05/27 06:00 PHST- 2016/12/21 00:00 [received] PHST- 2017/04/03 00:00 [revised] PHST- 2017/04/03 00:00 [accepted] PHST- 2017/05/27 06:00 [entrez] PHST- 2017/05/27 06:00 [pubmed] PHST- 2017/08/10 06:00 [medline] AID - S0735-1097(17)37026-2 [pii] AID - 10.1016/j.jacc.2017.04.014 [doi] PST - ppublish SO - J Am Coll Cardiol. 2017 May 30;69(21):2646-2656. doi: 10.1016/j.jacc.2017.04.014. PMID- 28533296 OWN - NLM STAT- MEDLINE DCOM- 20170822 LR - 20260127 IS - 1939-327X (Electronic) IS - 0012-1797 (Linking) VI - 66 IP - 6 DP - 2017 Jun TI - GLP-1R as a Target for the Treatment of Diabetic Retinopathy: Friend or Foe? PG - 1453-1460 LID - 10.2337/db16-1364 [doi] AB - Glucagon-like peptide 1 receptor (GLP-1R) agonists are increasingly being used as treatment for type 2 diabetes. Since the U.S. Food and Drug Administration published recommendations about the cardiovascular safety of new antidiabetes therapies for treating type 2 diabetes in 2008, the results of two outstanding clinical trials using GLP-1R agonists addressing this issue (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation [LEADER] and Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6]) have been published. Both studies found beneficial effects in terms of reducing the rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. However, their results regarding the progression of diabetic retinopathy (DR) were neutral with liraglutide (LEADER) or worse when compared with placebo in the case of semaglutide (SUSTAIN-6). These results are surprising because of the beneficial effects of GLP-1R analogs reported in experimental models of DR. In this Perspective, an overview of the mechanisms by which GLP-1R activation exerts its effects in preventing or arresting experimental DR is given. In addition, we consider the possible reasons for the negative results regarding the progression of DR in the SUSTAIN-6 study, as well as the gaps that still need to be covered to further clarify this important issue in the management of type 2 diabetes. CI - (c) 2017 by the American Diabetes Association. FAU - Simo, Rafael AU - Simo R AUID- ORCID: 0000-0003-0475-3096 AD - Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autonoma de Barcelona, Barcelona, Spain, and Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain rafael.simo@vhir.org cristina.hernandez@vhir.org. FAU - Hernandez, Cristina AU - Hernandez C AD - Diabetes and Metabolism Research Unit, Vall d'Hebron Research Institute, Universitat Autonoma de Barcelona, Barcelona, Spain, and Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain rafael.simo@vhir.org cristina.hernandez@vhir.org. LA - eng PT - Journal Article PT - Review PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) SB - IM MH - Animals MH - Cardiovascular Diseases/mortality MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Diabetic Retinopathy/*drug therapy/etiology MH - Disease Models, Animal MH - Disease Progression MH - Glucagon-Like Peptides/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Liraglutide/*therapeutic use MH - Molecular Targeted Therapy MH - Myocardial Infarction/epidemiology MH - Stroke/epidemiology MH - Treatment Outcome MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-1 Receptor EDAT- 2017/05/24 06:00 MHDA- 2017/08/23 06:00 CRDT- 2017/05/24 06:00 PHST- 2016/11/07 00:00 [received] PHST- 2017/03/19 00:00 [accepted] PHST- 2017/05/24 06:00 [entrez] PHST- 2017/05/24 06:00 [pubmed] PHST- 2017/08/23 06:00 [medline] AID - 66/6/1453 [pii] AID - 10.2337/db16-1364 [doi] PST - ppublish SO - Diabetes. 2017 Jun;66(6):1453-1460. doi: 10.2337/db16-1364. PMID- 28526920 OWN - NLM STAT- MEDLINE DCOM- 20180430 LR - 20260127 IS - 1432-0428 (Electronic) IS - 0012-186X (Print) IS - 0012-186X (Linking) VI - 60 IP - 8 DP - 2017 Aug TI - Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial. PG - 1390-1399 LID - 10.1007/s00125-017-4289-0 [doi] AB - AIMS/HYPOTHESIS: Semaglutide is a glucagon-like peptide-1 analogue in development for the treatment of type 2 diabetes. Its effects on first- and second-phase insulin secretion and other measures of beta cell function and glycaemic control were assessed. METHODS: In this single-centre, double-blind, placebo-controlled, parallel-group trial, conducted at the Profil Institut fur Stoffwechselforschung, Germany, 75 adult (aged 18-64 years) participants with type 2 diabetes (eligibility: HbA(1c) of 6.5-9.0% (47.5-74.9 mmol/mol); BMI 20.0-35.0 kg/m(2); and treatment with diet and exercise and/or metformin monotherapy with a dose unchanged in the 30 days prior to screening) were randomised (1:1) to once-weekly s.c. semaglutide 1.0 mg (0.25, 0.5, 1.0 mg escalated) or placebo for 12 weeks. Co-primary endpoints were changes from baseline to end of treatment in the first (AUC(0-10 min)) and second (AUC(10-120 min)) insulin secretion phases, as measured by the IVGTT. An arginine stimulation test (AST) and a 24 h meal stimulation test were also conducted. A graded glucose infusion test (GGIT) assessed insulin secretion rate (ISR) in treated participants and a group of untreated healthy participants. Safety endpoints were also assessed. RESULTS: In total, 37 participants received semaglutide and 38 received placebo. Following IVGTT, for insulin, both AUC(0-10min) and AUC(10-120min) were significantly increased with semaglutide (estimated treatment ratio [95% CI] 3.02 [2.53, 3.60] and 2.10 [1.86, 2.37], respectively; p < 0.0001). The 24 h meal test showed reduced fasting, postprandial and overall (AUC(0-24h)) glucose and glucagon responses with semaglutide (p < 0.0001). The AST showed that maximal insulin capacity increased following semaglutide treatment. During GGIT, semaglutide significantly increased ISR to levels similar to those in healthy participants. Semaglutide was well tolerated. CONCLUSIONS/INTERPRETATION: Twelve weeks of once-weekly treatment with semaglutide significantly improved beta cell function and glycaemic control in participants with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02212067 FUNDING: The study was funded by Novo Nordisk A/S. FAU - Kapitza, Christoph AU - Kapitza C AD - Profil Institut fur Stoffwechselforschung GmbH, Hellersbergstrasse 9, 41460, Neuss, Germany. christoph.kapitza@profil.com. FAU - Dahl, Kirsten AU - Dahl K AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jacobsen, Jacob B AU - Jacobsen JB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Axelsen, Mads B AU - Axelsen MB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Flint, Anne AU - Flint A AD - Novo Nordisk A/S, Soborg, Denmark. LA - eng SI - ClinicalTrials.gov/NCT02212067 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20170519 PL - Germany TA - Diabetologia JT - Diabetologia JID - 0006777 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adolescent MH - Adult MH - Blood Glucose/*drug effects MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptides/administration & dosage/*therapeutic use MH - Glycated Hemoglobin/metabolism MH - Humans MH - Hypoglycemic Agents/administration & dosage/therapeutic use MH - Insulin-Secreting Cells/*drug effects/*metabolism MH - Metformin/administration & dosage/therapeutic use MH - Middle Aged MH - Pregnancy MH - Young Adult MH - Semaglutide PMC - PMC5491562 OTO - NOTNLM OT - Beta cell function OT - Glycaemic control OT - Placebo-controlled trial OT - Semaglutide OT - Type 2 diabetes COIS- DATA AVAILABILITY: Researchers can be granted access to the anonymised data generated in this study. Access can be requested via www.novonordisk-trials.com/website/content/how-to-access-clinical-trial-datasets.aspx. The request for access will be reviewed and authorised by an independent review board. FUNDING: This study was funded by an unrestricted grant from Novo Nordisk A/S. DUALITY OF INTEREST: CK is an employee and co-owner of Profil, which has received research funds from Adocia, Astra Zeneca, Biocon, Boehringer Ingelheim, Dance Pharmaceuticals, Eli Lilly, Gulf Pharmaceutical Industries, Johnson & Johnson, Marvel Life Sciences Ltd., Medtronic, Medimmune, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi, Senseonics and Zealand Pharma. CK has received advisory and speaker fees from Sanofi, and travel grants from Novo Nordisk and Sanofi. MBA, KD, AF and JBJ are full-time employees of Novo Nordisk A/S. AUTHOR CONTRIBUTION: AF and CK designed the study. MBA, KD, AF, CK and JBJ participated in the conduct of the study, data collection, data analysis and interpretation, and writing and revision of the manuscript. All authors gave approval of the final version of the manuscript for publication. CK is the guarantor of this work. EDAT- 2017/05/21 06:00 MHDA- 2018/05/01 06:00 PMCR- 2017/05/19 CRDT- 2017/05/21 06:00 PHST- 2017/02/07 00:00 [received] PHST- 2017/03/31 00:00 [accepted] PHST- 2017/05/21 06:00 [pubmed] PHST- 2018/05/01 06:00 [medline] PHST- 2017/05/21 06:00 [entrez] PHST- 2017/05/19 00:00 [pmc-release] AID - 10.1007/s00125-017-4289-0 [pii] AID - 4289 [pii] AID - 10.1007/s00125-017-4289-0 [doi] PST - ppublish SO - Diabetologia. 2017 Aug;60(8):1390-1399. doi: 10.1007/s00125-017-4289-0. Epub 2017 May 19. PMID- 28526186 OWN - NLM STAT- MEDLINE DCOM- 20170703 LR - 20250103 IS - 1555-7162 (Electronic) IS - 0002-9343 (Linking) VI - 130 IP - 6S DP - 2017 Jun TI - Cardiovascular Protection in the Treatment of Type 2 Diabetes: A Review of Clinical Trial Results Across Drug Classes. PG - S18-S29 LID - S0002-9343(17)30467-9 [pii] LID - 10.1016/j.amjmed.2017.04.008 [doi] AB - Patients with type 2 diabetes (T2DM) have a significantly higher risk of developing cardiovascular disease (CVD)-namely myocardial infarction, heart failure, and stroke. Despite clear advances in the prevention and treatment of CVD, the impact of T2DM on CVD outcome remains high and continues to escalate. Available evidence indicates that the risk of macrovascular complications increases with the severity of hyperglycemia, thus suggesting that the relation between metabolic disturbances and vascular damage is approximately linear. Although current antidiabetic drugs are highly effective for the management of hyperglycemia, most T2DM patients remain exposed to a substantial and concrete risk of CVD. Over the last decade many glucose-lowering agents have been tested for their safety and efficacy in T2DM with CVD. Noteworthy, most of these studies failed to show a significant benefit in terms of CV morbidity and mortality, despite intensive glycemic control. The recent trials Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME); Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6); Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER); and Insulin Resistance Intervention After Stroke (IRIS) have shed some light on this important clinical issue, thus showing a convincing effect of empagliflozin, liraglutide, and pioglitazone on CVD outcomes. Here we provide a critical and updated overview of the main glucose-lowering agents and their risk/benefit ratio for the prevention of CVD in patients with T2DM. CI - Copyright (c) 2017. Published by Elsevier Inc. FAU - Paneni, Francesco AU - Paneni F AD - University Heart Center, Cardiology, University Hospital Zurich, Switzerland; Center for Molecular Cardiology, University of Zurich, Switzerland. Electronic address: francesco.paneni@uzh.ch. FAU - Luscher, Thomas F AU - Luscher TF AD - University Heart Center, Cardiology, University Hospital Zurich, Switzerland; Center for Molecular Cardiology, University of Zurich, Switzerland. LA - eng PT - Journal Article PT - Review PL - United States TA - Am J Med JT - The American journal of medicine JID - 0267200 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Thiazolidinediones) RN - 9100L32L2N (Metformin) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cardiovascular Diseases/prevention & control MH - Diabetes Mellitus, Type 2/*drug therapy MH - Diabetic Angiopathies/prevention & control MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Metformin/therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors MH - Sulfonylurea Compounds/therapeutic use MH - Thiazolidinediones/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiovascular disease OT - Glucose-lowering therapy OT - Type 2 diabetes treatment EDAT- 2017/05/21 06:00 MHDA- 2017/07/04 06:00 CRDT- 2017/05/21 06:00 PHST- 2017/05/21 06:00 [pubmed] PHST- 2017/07/04 06:00 [medline] PHST- 2017/05/21 06:00 [entrez] AID - S0002-9343(17)30467-9 [pii] AID - 10.1016/j.amjmed.2017.04.008 [doi] PST - ppublish SO - Am J Med. 2017 Jun;130(6S):S18-S29. doi: 10.1016/j.amjmed.2017.04.008. PMID- 28526182 OWN - NLM STAT- MEDLINE DCOM- 20170703 LR - 20250103 IS - 1555-7162 (Electronic) IS - 0002-9343 (Linking) VI - 130 IP - 6S DP - 2017 Jun TI - Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies. PG - S4-S17 LID - S0002-9343(17)30457-6 [pii] LID - 10.1016/j.amjmed.2017.04.004 [doi] AB - Choices for the treatment of type 2 diabetes mellitus (T2DM) have multiplied as our understanding of the underlying pathophysiologic defects has evolved. Treatment should target multiple defects in T2DM and follow a patient-centered approach that considers factors beyond glycemic control, including cardiovascular risk reduction. The American Association of Clinical Endocrinologists/American College of Endocrinology and the American Diabetes Association recommend an initial approach consisting of lifestyle changes and monotherapy, preferably with metformin. Therapy choices are guided by glycemic efficacy, safety profiles, particularly effects on weight and hypoglycemia risk, tolerability, patient comorbidities, route of administration, patient preference, and cost. Balancing management of hyperglycemia with the risk of hypoglycemia and consideration of the effects of pharmacotherapy on weight figure prominently in US-based T2DM recommendations, whereas less emphasis has been placed on the ability of specific medications to affect cardiovascular outcomes. This is likely because, until recently, specific glucose-lowering agents have not been shown to affect cardiorenal outcomes. The Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, and the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes 6 (SUSTAIN-6) recently showed a reduction in overall cardiovascular risk with empagliflozin, liraglutide, and semaglutide treatment, respectively. Moreover, empagliflozin has become the first glucose-lowering agent indicated to reduce the risk of cardiovascular death in adults with T2DM and established cardiovascular disease. Results from cardiovascular outcomes trials have prompted an update to the 2017 American Diabetes Association standards of care, which now recommend consideration of empagliflozin or liraglutide for patients with suboptimally controlled long-standing T2DM and established atherosclerotic cardiovascular disease because these agents have been shown to reduce cardiovascular and all-cause mortality when added to standard care. CI - Copyright (c) 2017 The Author. Published by Elsevier Inc. All rights reserved. FAU - Thrasher, James AU - Thrasher J AD - Medical Investigations, Inc, Little Rock, Ark. Electronic address: jthrashermd@yahoo.com. LA - eng PT - Journal Article PT - Review PL - United States TA - Am J Med JT - The American journal of medicine JID - 0267200 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Cardiovascular Diseases/prevention & control MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Diabetic Angiopathies/prevention & control MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Humans MH - Hyperglycemia/drug therapy/etiology MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Insulin/therapeutic use MH - Risk Factors MH - Sodium-Glucose Transporter 2 Inhibitors MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Dipeptidyl peptidase-4 inhibitors OT - Glucagon-like peptide-1 receptor agonist OT - Guidelines OT - Sodium glucose cotransporter 2 inhibitors OT - Treatment OT - Type 2 diabetes mellitus EDAT- 2017/05/21 06:00 MHDA- 2017/07/04 06:00 CRDT- 2017/05/21 06:00 PHST- 2017/05/21 06:00 [pubmed] PHST- 2017/07/04 06:00 [medline] PHST- 2017/05/21 06:00 [entrez] AID - S0002-9343(17)30457-6 [pii] AID - 10.1016/j.amjmed.2017.04.004 [doi] PST - ppublish SO - Am J Med. 2017 Jun;130(6S):S4-S17. doi: 10.1016/j.amjmed.2017.04.004. PMID- 28514822 OWN - NLM STAT- MEDLINE DCOM- 20170626 LR - 20170626 IS - 1439-4413 (Electronic) IS - 0012-0472 (Linking) VI - 142 IP - 10 DP - 2017 May TI - [Cardiovascular Effects of Antidiabetic Therapies]. PG - 737-745 LID - 10.1055/s-0043-100564 [doi] AB - Type 2- diabetes mellitus (T2DM) represents a major risk factor for cardiovascular complications and mortality. Strict glucose control in the early course of the disease prevents cardiovascular complications only in the long run. Non-medical therapies (diet, exercise, body weight reduction) bear little evidence for positive cardiovascular effects.Bariatric surgery is not number one choice in therapy of T2DM. Metformin seems to provide positive cardiovascular effects. Insulin seems to be cardiovascular neutral, as well as the DPP4-inhibitors Saxagliptin, Sitagliptin and Alogliptin. Concerning GLP-1-RAs, Lixisenatide has a neutral cardiovascular effect, whereas Liraglutide and Semaglutide reduce cardiovascular outcomes. The SGLT2-inhibitor Empagliflozin reduces cardiovascular mortality, total mortality and hospitalization by heart failure. CI - (c) Georg Thieme Verlag KG Stuttgart . New York. FAU - Laubner, Katharina AU - Laubner K FAU - Seufert, Jochen AU - Seufert J LA - ger PT - Journal Article TT - Kardiovaskulare Effekte antidiabetischer Therapie. DEP - 20170517 PL - Germany TA - Dtsch Med Wochenschr JT - Deutsche medizinische Wochenschrift (1946) JID - 0006723 RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) SB - IM MH - Cardiovascular Diseases/*complications MH - Diabetes Mellitus, Type 2/*complications/*drug therapy MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Metformin/therapeutic use EDAT- 2017/05/18 06:00 MHDA- 2017/06/27 06:00 CRDT- 2017/05/18 06:00 PHST- 2017/05/18 06:00 [entrez] PHST- 2017/05/18 06:00 [pubmed] PHST- 2017/06/27 06:00 [medline] AID - 10.1055/s-0043-100564 [doi] PST - ppublish SO - Dtsch Med Wochenschr. 2017 May;142(10):737-745. doi: 10.1055/s-0043-100564. Epub 2017 May 17. PMID- 28483748 OWN - NLM STAT- MEDLINE DCOM- 20190523 LR - 20190523 IS - 1535-2900 (Electronic) IS - 1079-2082 (Linking) VI - 74 IP - 13 DP - 2017 Jul 1 TI - Cardiovascular safety outcomes of new antidiabetic therapies. PG - 970-976 LID - 10.2146/ajhp160279 [doi] AB - PURPOSE: The cardiovascular safety outcomes of newer antidiabetic agents were reviewed. SUMMARY: Seven randomized, placebo-controlled trials involving patients with type 2 diabetes mellitus with or at risk for cardiovascular disease were reviewed. The trials examined the cardiovascular safety outcomes of the following agents: alogliptin, saxagliptin, and sitagliptin (dipeptidyl peptidase-4 [DPP-4] inhibitors); liraglutide, lixisenatide, and semaglutide (glucagon-like peptide-1 agonists); and empagliflozin (a sodium glucose cotransport-2 inhibitor). The DPP-4 inhibitor and lixisenatide trials showed a neutral effect on cardiovascular events (composite of cardiovascular death, myocardial infarction, or stroke, with or without unstable angina). Empagliflozin showed a significant reduction in cardiovascular events, cardiovascular death, all-cause death, and hospitalization due to heart failure (HF); liraglutide reduced cardiovascular events, cardiovascular death, and all-cause death, and semaglutide reduced cardiovascular events and nonfatal stroke. Most studies showed a neutral effect of the drug on hospitalization for HF; however, saxagliptin and alogliptin (in the subgroups of patients without a history of HF) showed a significant increase while empagliflozin showed a significant reduction in hospitalizations for HF. The data for empagliflozin, liraglutide, and semaglutide are compelling; however, further studies are necessary to confirm observed benefits and better characterize long-term safety and their use as a strategy to reduce cardiovascular events. CONCLUSION: A review of cardiovascular safety outcomes for new antidiabetic agents found that saxagliptin and alogliptin were associated with an increase in hospitalization for HF. The data for empagliflozin, liraglutide, and semaglutide showed a reduction in cardiovascular events and death or a neutral effect on cardiovascular endpoints. CI - Copyright (c) 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved. FAU - LeBras, Marlys H AU - LeBras MH AD - RxFiles Academic Detailing Program, Saskatoon Health Region, Saskatoon, Saskatchewan, Canada. FAU - Barry, Arden R AU - Barry AR AD - Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada arden.barry@ubc.ca. AD - Chilliwack General Hospital, Lower Mainland Pharmacy Services, Chilliwack, British Columbia, Canada. arden.barry@ubc.ca. FAU - Koshman, Sheri L AU - Koshman SL AD - Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada. LA - eng PT - Journal Article PT - Review DEP - 20170508 PL - England TA - Am J Health Syst Pharm JT - American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists JID - 9503023 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 89750-14-1 (Glucagon-Like Peptide 1) SB - IM MH - Animals MH - Cardiovascular Diseases/chemically induced/*diagnosis/epidemiology MH - Diabetes Mellitus, Type 2/diagnosis/drug therapy/epidemiology MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/*therapeutic use MH - Glucagon-Like Peptide 1/*agonists MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Randomized Controlled Trials as Topic/methods MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/*therapeutic use MH - Treatment Outcome OTO - NOTNLM OT - antidiabetic agent OT - cardiovascular disease OT - heart failure OT - pharmacotherapy OT - type 2 diabetes mellitus EDAT- 2017/05/10 06:00 MHDA- 2019/05/24 06:00 CRDT- 2017/05/10 06:00 PHST- 2017/05/10 06:00 [pubmed] PHST- 2019/05/24 06:00 [medline] PHST- 2017/05/10 06:00 [entrez] AID - ajhp160279 [pii] AID - 10.2146/ajhp160279 [doi] PST - ppublish SO - Am J Health Syst Pharm. 2017 Jul 1;74(13):970-976. doi: 10.2146/ajhp160279. Epub 2017 May 8. PMID- 28431666 OWN - NLM STAT- MEDLINE DCOM- 20180622 LR - 20250103 IS - 1878-1780 (Electronic) IS - 1262-3636 (Linking) VI - 43 Suppl 1 DP - 2017 Apr TI - GLP-1 receptor agonists and heart failure in diabetes. PG - 2S13-2S19 LID - S1262-3636(17)30068-X [pii] LID - 10.1016/S1262-3636(17)30068-X [doi] AB - The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI 53), whereas a markedly decreased risk was highlighted with the sodium - glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME. Yet, the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on myocardial function remain controversial. Whereas some promising observations have been reported in various animal models, the effects of GLP-1RAs on myocardial function in humans are more heterogeneous, while the positive effect on left ventricular ejection fraction (LVEF), if any, appears to be inconsistent and rather modest in most patients with HF. However, no increased risk of hospitalization for HF has been reported with GLP-1RAs in meta-analyses of phase-II/III trials (exenatide, albiglutide, dulaglutide, liraglutide), demonstrating the safety of this pharmacological class, and such findings have been confirmed by three large prospective cardiovascular outcome trials (ELIXA with lixisenatide, LEADER with liraglutide and SUSTAIN-6 with semaglutide). In particular, LEADER reported a trend towards a reduction in HF hospitalization (-13%, P = 0.14), together with a significant reduction in cardiovascular and all-cause mortality in patients with T2D at risk of cardiovascular disease. These results are reassuring in the face of the somewhat negative results of the FIGHT trial, which evaluated the effects of liraglutide in patients with advanced HF and low LVEF, such that further studies and caution are now required when using this agent to treat such patients in clinical practice. CI - (c) 2017 Elsevier Masson SAS. All rights reserved. FAU - Scheen, Andre J AU - Scheen AJ AD - Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Sart Tilman (B35), B-4000 Liege 1, Belgium; Clinical Pharmacology Unit, CHU Liege, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Liege, Belgium. Electronic address: andre.scheen@chu.ulg.ac.be. LA - eng PT - Journal Article PT - Review PL - France TA - Diabetes Metab JT - Diabetes & metabolism JID - 9607599 RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Heart Failure/etiology/*prevention & control MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Prospective Studies MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Cardiac function OT - Congestive heart failure OT - GLP-1 receptor agonist OT - LEADER OT - Liraglutide OT - Type 2 diabetes EDAT- 2017/04/23 06:00 MHDA- 2018/06/23 06:00 CRDT- 2017/04/23 06:00 PHST- 2017/04/23 06:00 [entrez] PHST- 2017/04/23 06:00 [pubmed] PHST- 2018/06/23 06:00 [medline] AID - S1262-3636(17)30068-X [pii] AID - 10.1016/S1262-3636(17)30068-X [doi] PST - ppublish SO - Diabetes Metab. 2017 Apr;43 Suppl 1:2S13-2S19. doi: 10.1016/S1262-3636(17)30068-X. PMID- 28413990 OWN - NLM STAT- MEDLINE DCOM- 20181010 LR - 20260127 IS - 1875-6417 (Electronic) IS - 1573-3998 (Linking) VI - 14 IP - 3 DP - 2018 TI - Effect of Glucagon-like Peptide-1 Receptor Agonists on All-cause Mortality and Cardiovascular Outcomes: A Meta-analysis. PG - 273-279 LID - 10.2174/1573399813666170414101450 [doi] AB - BACKGROUND: Cardiovascular disease is the leading cause of death in patients with type 2 diabetes. OBJECTIVE: To assess the impact of glucagon-like peptide-1 receptor agonist (GLP1RA) therapy, compared to placebo, on clinically relevant outcomes including all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalizations for heart failure, in patients with type 2 diabetes. METHODS: EMBASE, MEDLINE, and CENTRAL were searched (inception to September 2016) for randomized, double-blind, placebo-controlled trials of at least one year in duration that compared any GLP1RA to placebo in patients with type 2 diabetes. Both authors independently completed the literature search, data extraction, and risk of bias assessment. For each outcome, a Risk Ratio (RR) and 95% Confidence Interval (CI) were calculated using a Mantel-Haenszel random effects model. RESULTS: Eight trials (three albiglutide, two lixisenatide, two liraglutide, one semaglutide) consisting of 21,135 patients were included. Most patients had, or were at high risk for, cardiovascular disease. Follow- up ranged from 1-3.8 years. Trials contributing the majority of data were deemed to have a low risk of bias. The risk of all-cause mortality was lowered by 11% in patients receiving a GLP1RA (RR 0.89, 95% CI 0.81-0.99). There was no statistically significant difference between groups with respect to cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalizations for heart failure. CONCLUSION: GLP1RA therapy when compared to placebo reduced all-cause mortality in high cardiovascular risk patients with type 2 diabetes. They did not impact cardiovascular mortality, nonfatal MI, nonfatal stroke, or heart failure hospitalizations. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.org. FAU - Peterson, Shaylee C AU - Peterson SC AD - Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada. FAU - Barry, Arden R AU - Barry AR AD - Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PL - United Arab Emirates TA - Curr Diabetes Rev JT - Current diabetes reviews JID - 101253260 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Peptides) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) RN - 74O62BB01U (lixisenatide) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Cardiovascular Diseases/*mortality/*prevention & control MH - Diabetes Mellitus, Type 2/*complications/*drug therapy/*mortality MH - Diabetic Angiopathies/mortality/prevention & control MH - Double-Blind Method MH - Glucagon-Like Peptides/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Liraglutide/therapeutic use MH - Peptides/therapeutic use MH - Randomized Controlled Trials as Topic/statistics & numerical data MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide MH - Glucagon-Like Peptide-2 Receptor OTO - NOTNLM OT - Glucagon-like peptide-1 receptor agonists OT - cardiovascular diseases OT - hypoglycemic agents OT - incretins OT - liraglutide OT - type 2 diabetes mellitus. EDAT- 2017/04/18 06:00 MHDA- 2018/10/12 06:00 CRDT- 2017/04/18 06:00 PHST- 2017/02/13 00:00 [received] PHST- 2017/03/27 00:00 [revised] PHST- 2017/03/29 00:00 [accepted] PHST- 2017/04/18 06:00 [pubmed] PHST- 2018/10/12 06:00 [medline] PHST- 2017/04/18 06:00 [entrez] AID - CDR-EPUB-82816 [pii] AID - 10.2174/1573399813666170414101450 [doi] PST - ppublish SO - Curr Diabetes Rev. 2018;14(3):273-279. doi: 10.2174/1573399813666170414101450. PMID- 28402902 OWN - NLM STAT- MEDLINE DCOM- 20171205 LR - 20220321 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 127 DP - 2017 May TI - Cardiovascular outcome studies with incretin-based therapies: Comparison between DPP-4 inhibitors and GLP-1 receptor agonists. PG - 224-237 LID - S0168-8227(17)30390-X [pii] LID - 10.1016/j.diabres.2017.03.009 [doi] AB - Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes. Non-inferiority versus placebo was shown in large prospective cardiovascular outcome trials in patients with high cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP-4is were non confirmed as no cardiovascular protection could be evidenced. However, LEADER showed a significant reduction in major cardiovascular events, myocardial infarction, cardiovascular and all-cause mortality in patients treated by liraglutide compared to placebo. These positive results contrasted with the non-inferiority results with lixisenatide in ELIXA. They were partially confirmed with semaglutide in SUSTAIN 6 despite the absence of reduction in cardiovascular mortality. Hospitalisation for heart failure was not increased except with saxagliptin in SAVOR-TIMI 53. The reasons for different outcomes between trials remain largely unknown as well as the precise underlying mechanisms explaining the cardiovascular protection by liraglutide. The clinical relevance of results with DPP-4is and GLP-1RAs is discussed. Ongoing trials with linagliptin and several once-weekly GLP-1RAs should provide new insights into remaining fundamental questions. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Scheen, Andre J AU - Scheen AJ AD - Division of Diabetes, Nutrition and Metabolic Disorders, Department of Medicine, CHU Liege, University of Liege, Liege, Belgium; Clinical Pharmacology Unit, CHU Liege, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Liege, Belgium. Electronic address: andre.scheen@chu.ulg.ac.be. LA - eng PT - Journal Article PT - Review DEP - 20170325 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) SB - IM MH - Cardiovascular Diseases/*drug therapy MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use MH - Glucagon-Like Peptide-1 Receptor/administration & dosage/*therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Incretins/*therapeutic use MH - Outcome Assessment, Health Care MH - Prospective Studies MH - Risk Factors OTO - NOTNLM OT - Cardiovascular disease OT - Clinical trial OT - DPP-4 inhibitors OT - GLP-1 receptor agonists OT - Mortality OT - Type 2 diabetes EDAT- 2017/04/14 06:00 MHDA- 2017/12/06 06:00 CRDT- 2017/04/14 06:00 PHST- 2017/03/09 00:00 [received] PHST- 2017/03/13 00:00 [accepted] PHST- 2017/04/14 06:00 [pubmed] PHST- 2017/12/06 06:00 [medline] PHST- 2017/04/14 06:00 [entrez] AID - S0168-8227(17)30390-X [pii] AID - 10.1016/j.diabres.2017.03.009 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2017 May;127:224-237. doi: 10.1016/j.diabres.2017.03.009. Epub 2017 Mar 25. PMID- 28385659 OWN - NLM STAT- MEDLINE DCOM- 20180124 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 5 IP - 5 DP - 2017 May TI - Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. PG - 341-354 LID - S2213-8587(17)30092-X [pii] LID - 10.1016/S2213-8587(17)30092-X [doi] AB - BACKGROUND: Semaglutide is a novel glucagon-like peptide-1 (GLP-1) analogue, suitable for once-weekly subcutaneous administration, in development for treatment of type 2 diabetes. We assessed the efficacy and safety of semaglutide versus the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in patients with type 2 diabetes inadequately controlled on metformin, thiazolidinediones, or both. METHODS: We did a 56-week, phase 3a, randomised, double-blind, double-dummy, active-controlled, parallel-group, multinational, multicentre trial (SUSTAIN 2) at 128 sites in 18 countries. Eligible patients were aged at least 18 years (or at least 20 years in Japan) and diagnosed with type 2 diabetes, with insufficient glycaemic control (HbA(1c) 7.0-10.5% [53.0-91.0 mmol/mol]) despite stable treatment with metformin, thiazolidinediones, or both. We randomly assigned participants (2:2:1:1) using an interactive voice or web response system to 56 weeks of treatment with subcutaneous semaglutide 0.5 mg once weekly plus oral sitagliptin placebo once daily, subcutaneous semaglutide 1.0 mg once weekly plus oral sitagliptin placebo once daily, oral sitagliptin 100 mg once daily plus subcutaneous semaglutide placebo 0.5 mg once weekly, or oral sitagliptin 100 mg once daily plus subcutaneous semaglutide placebo 1.0 mg once weekly. The two oral sitagliptin 100 mg groups (with semaglutide placebo 0.5 mg and 1.0 mg) were pooled for the analyses. The primary endpoint was change in HbA(1c) from baseline to week 56, assessed in the modified intention-to-treat population (all randomly assigned participants who received at least one dose of study drug); change in bodyweight from baseline to week 56 was the confirmatory secondary endpoint. Safety endpoints included adverse events and hypoglycaemic episodes. This trial is registered with ClinicalTrials.gov, number NCT01930188. FINDINGS: Between Dec 2, 2013, and Aug 5, 2015, we randomly assigned 1231 participants; of the 1225 included in the modified intention-to-treat analysis, 409 received semaglutide 0.5 mg, 409 received semaglutide 1.0 mg, and 407 received sitagliptin 100 mg. Mean baseline HbA(1c) was 8.1% (SD 0.93); at week 56, HbA(1c) was reduced by 1.3% in the semaglutide 0.5 mg group, 1.6% in the semaglutide 1.0 mg group, and 0.5% with sitagliptin (estimated treatment difference vs sitagliptin -0.77% [95% CI -0.92 to -0.62] with semaglutide 0.5 mg and -1.06% [-1.21 to -0.91] with semaglutide 1.0 mg; p<0.0001 for non-inferiority and for superiority, for both semaglutide doses vs sitagliptin). Mean baseline bodyweight was 89.5 kg (SD 20.3); at week 56, bodyweight reduced by 4.3 kg with semaglutide 0.5 mg, 6.1 kg with semaglutide 1.0 mg, and 1.9 kg with sitagliptin (estimated treatment difference vs sitagliptin -2.35 kg [95% CI -3.06 to -1.63] with semaglutide 0.5 mg and -4.20 kg [-4.91 to -3.49] with semaglutide 1.0 mg; p<0.0001 for superiority, for both semaglutide doses vs sitagliptin). The proportion of patients who discontinued treatment because of adverse events was 33 (8%) for semaglutide 0.5 mg, 39 (10%) for semaglutide 1.0 mg, and 12 (3%) for sitagliptin. The most frequently reported adverse events in both semaglutide groups were gastrointestinal in nature: nausea was reported in 73 (18%) who received semaglutide 0.5 mg, 72 (18%) who received semaglutide 1.0 mg, and 30 (7%) who received placebo, and diarrhoea was reported in 54 (13%) who received semaglutide 0.5 mg, 53 (13%) who received semaglutide 1.0 mg, and 29 (7%) who received placebo. Seven (2%) patients in the semaglutide 0.5 mg group, two (<1%) in the semaglutide 1.0 mg group, and five (1%) in the sitagliptin group had blood-glucose confirmed hypoglycaemia. There were six fatal events (two in the semaglutide 0.5 mg group, one in the semaglutide 1.0 mg group, and three in the sitagliptin group); none were considered likely to be related to the trial drugs. INTERPRETATION: Once-weekly semaglutide was superior to sitagliptin at improving glycaemic control and reducing bodyweight in participants with type 2 diabetes on metformin, thiazolidinediones, or both, and had a similar safety profile to that of other GLP-1 receptor agonists. Semaglutide seems to be an effective add-on treatment option for this patient population. FUNDING: Novo Nordisk A/S. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Ahren, Bo AU - Ahren B AD - Department of Clinical Sciences, Division of Medicine, Lund University, Lund, Sweden. Electronic address: bo.ahren@med.lu.se. FAU - Masmiquel, Luis AU - Masmiquel L AD - Balearic Institute of Endocrinology and Nutrition (IBEN), Hospital Quironsalud Palmaplanas, Palma de Mallorca, Spain. FAU - Kumar, Harish AU - Kumar H AD - Amrita Viswa Vidyapeetham University, Kochi, Kerala, India. FAU - Sargin, Mehmet AU - Sargin M AD - Kartal Training and Research Hospital, Istanbul, Turkey. FAU - Karsbol, Julie Derving AU - Karsbol JD AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jacobsen, Sanja Hald AU - Jacobsen SH AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Chow, Francis AU - Chow F AD - Chinese University of Hong Kong, Hong Kong, China. LA - eng SI - ClinicalTrials.gov/NCT01930188 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20170403 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) RN - TS63EW8X6F (Sitagliptin Phosphate) RN - 0 (Thiazolidinediones) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Lancet Diabetes Endocrinol. 2017 May;5(5):315-317. doi: 10.1016/S2213-8587(17)30094-3. PMID: 28385658 MH - Aged MH - Diabetes Mellitus, Type 2/*drug therapy MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Glucagon-Like Peptides/*administration & dosage/adverse effects MH - Humans MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Male MH - Metformin/therapeutic use MH - Middle Aged MH - Sitagliptin Phosphate/*administration & dosage/adverse effects MH - Thiazolidinediones/therapeutic use MH - Semaglutide EDAT- 2017/04/08 06:00 MHDA- 2018/01/25 06:00 CRDT- 2017/04/08 06:00 PHST- 2017/01/15 00:00 [received] PHST- 2017/02/13 00:00 [revised] PHST- 2017/02/13 00:00 [accepted] PHST- 2017/04/08 06:00 [pubmed] PHST- 2018/01/25 06:00 [medline] PHST- 2017/04/08 06:00 [entrez] AID - S2213-8587(17)30092-X [pii] AID - 10.1016/S2213-8587(17)30092-X [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2017 May;5(5):341-354. doi: 10.1016/S2213-8587(17)30092-X. Epub 2017 Apr 3. PMID- 28385658 OWN - NLM STAT- MEDLINE DCOM- 20180423 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 5 IP - 5 DP - 2017 May TI - Glycaemic control and weight loss with semaglutide in type 2 diabetes. PG - 315-317 LID - S2213-8587(17)30094-3 [pii] LID - 10.1016/S2213-8587(17)30094-3 [doi] FAU - Madsbad, Sten AU - Madsbad S AD - Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, 2650 Hvidovre, Denmark; NNF Center for Basic Metabolic Research and Department of Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: sten.madsbad@regionh.dk. FAU - Holst, Jens J AU - Holst JJ AD - NNF Center for Basic Metabolic Research and Department of Medical Sciences, University of Copenhagen, Copenhagen, Denmark. LA - eng PT - Comment PT - Journal Article DEP - 20170403 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - Lancet Diabetes Endocrinol. 2017 May;5(5):355-366. doi: 10.1016/S2213-8587(17)30085-2. PMID: 28344112 CON - Lancet Diabetes Endocrinol. 2017 May;5(5):341-354. doi: 10.1016/S2213-8587(17)30092-X. PMID: 28385659 MH - Blood Glucose MH - *Diabetes Mellitus, Type 2 MH - Glucagon-Like Peptides MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents MH - *Weight Loss MH - Semaglutide EDAT- 2017/04/08 06:00 MHDA- 2018/04/24 06:00 CRDT- 2017/04/08 06:00 PHST- 2017/03/01 00:00 [received] PHST- 2017/03/01 00:00 [accepted] PHST- 2017/04/08 06:00 [pubmed] PHST- 2018/04/24 06:00 [medline] PHST- 2017/04/08 06:00 [entrez] AID - S2213-8587(17)30094-3 [pii] AID - 10.1016/S2213-8587(17)30094-3 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2017 May;5(5):315-317. doi: 10.1016/S2213-8587(17)30094-3. Epub 2017 Apr 3. PMID- 28349386 OWN - NLM STAT- MEDLINE DCOM- 20180531 LR - 20260127 IS - 1179-1926 (Electronic) IS - 0312-5963 (Print) IS - 0312-5963 (Linking) VI - 56 IP - 11 DP - 2017 Nov TI - Pharmacokinetics and Tolerability of a Single Dose of Semaglutide, a Human Glucagon-Like Peptide-1 Analog, in Subjects With and Without Renal Impairment. PG - 1381-1390 LID - 10.1007/s40262-017-0528-2 [doi] AB - BACKGROUND: The pharmacokinetics and tolerability of semaglutide, a once-weekly human glucagon-like peptide-1 analog in development for the treatment of type 2 diabetes mellitus, were investigated in subjects with/without renal impairment (RI). METHODS: Fifty-six subjects, categorized into renal function groups [normal, mild, moderate, severe, and end-stage renal disease (ESRD)], received a single subcutaneous dose of semaglutide 0.5 mg. Semaglutide plasma concentrations were assessed 11 weeks, enrolling patients with type 2 diabetes and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug. RESULTS: Of the 113 trials fulfilling inclusion criteria, 13 did not report information on pancreatitis, whereas 72 reported no events in all treatment groups. The incidence of pancreatitis and pancreatic cancer with GLP1-RA was not significantly different from that observed in comparator arms (MH-OR [95% CI] 0.93 [0.65-1.34], P = .71, and 0.94 [0.52-1.70], P = .84, respectively), whereas, a significantly increased risk of cholelithiasis (MH-OR [95% CI] 1.30 [1.01-1.68], P = .041) was detected. CONCLUSIONS: Presently available data confirm the safety of GLP-1 receptor agonists for pancreatitis. Conversely, therapy with those drugs is associated with an increased risk of cholelithiasis, which deserves further investigation. CI - (c) 2017 John Wiley & Sons Ltd. FAU - Monami, Matteo AU - Monami M AUID- ORCID: 0000-0001-9349-828X AD - Department of Diabetology, Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy. FAU - Nreu, Besmir AU - Nreu B AD - Department of Diabetology, Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy. FAU - Scatena, Alessia AU - Scatena A AD - Diabetology Unit, Osperdale San Donato Arezzo, Arezzo, Italy. FAU - Cresci, Barbara AU - Cresci B AD - Department of Diabetology, Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy. FAU - Andreozzi, Francesco AU - Andreozzi F AD - Diabetology Unit, Osperdale San Donato Arezzo, Arezzo, Italy. AD - Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy. FAU - Sesti, Giorgio AU - Sesti G AD - Diabetology Unit, Osperdale San Donato Arezzo, Arezzo, Italy. AD - Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy. FAU - Mannucci, Edoardo AU - Mannucci E AD - Department of Diabetology, Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20170620 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (GLP1R protein, human) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Biliary Tract/*drug effects MH - Cholelithiasis/*chemically induced/complications/epidemiology MH - Diabetes Mellitus, Type 2/complications/*drug therapy/metabolism MH - *Evidence-Based Medicine MH - Glucagon-Like Peptide-1 Receptor/metabolism MH - Humans MH - Hypoglycemic Agents/*adverse effects/therapeutic use MH - Incidence MH - Pancreas/*drug effects MH - Pancreatic Neoplasms/chemically induced/complications/epidemiology MH - Pancreatitis/chemically induced/complications/epidemiology MH - Randomized Controlled Trials as Topic MH - Reproducibility of Results MH - Risk MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 analogue OT - meta-analysis EDAT- 2017/03/01 06:00 MHDA- 2018/05/08 06:00 CRDT- 2017/03/01 06:00 PHST- 2017/01/14 00:00 [received] PHST- 2017/02/23 00:00 [revised] PHST- 2017/02/23 00:00 [accepted] PHST- 2017/03/01 06:00 [pubmed] PHST- 2018/05/08 06:00 [medline] PHST- 2017/03/01 06:00 [entrez] AID - 10.1111/dom.12926 [doi] PST - ppublish SO - Diabetes Obes Metab. 2017 Sep;19(9):1233-1241. doi: 10.1111/dom.12926. Epub 2017 Jun 20. PMID- 28197977 OWN - NLM STAT- MEDLINE DCOM- 20180227 LR - 20180227 IS - 1179-187X (Electronic) IS - 1175-3277 (Linking) VI - 17 IP - 3 DP - 2017 Jun TI - Interpreting Cardiovascular Endpoints in Trials of Antihyperglycemic Drugs. PG - 203-215 LID - 10.1007/s40256-017-0215-6 [doi] AB - In view of the significant cardiovascular (CV) morbidity and mortality in patients with type 2 diabetes mellitus, and concerns raised about the CV safety of some glucose-lowering drugs, the US Food and Drug Administration (FDA) issued guidance for the industry in 2008 to demonstrate CV safety for the approval of all new antihyperglycemic drugs. Seven randomized controlled trials involving around 60,000 participants have been completed so far and have demonstrated the CV safety of dipeptidyl peptidase 4 inhibitors (saxagliptin, alogliptin and sitagliptin), glucagon-like peptide-1 receptor agonists (lixisenatide, liraglutide and semaglutide) and a sodium-glucose co-transporter 2 inhibitor (empagliflozin) in patients with type 2 diabetes. Three of these trials have in fact reported superiority of the study drug over placebo in terms of CV outcomes. However, all these trials were primarily designed as non-inferiority trials to exclude an unacceptable risk of CV events with these drugs in the shortest possible time period. The potential long-term benefit or risks were not assessed effectively as the median follow-up in these studies was limited to 1.5-3 years. Also, these trials included patients with relatively long duration of diabetes, advanced atherosclerosis and higher CV risk. Thus, these trials were not intended to assess CV benefit and are best interpreted as evidence for CV safety of these antihyperglycemic medications. FAU - Chawla, Himika AU - Chawla H AD - Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, 110029, India. FAU - Tandon, Nikhil AU - Tandon N AD - Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, 110029, India. nikhil_tandon@hotmail.com. LA - eng PT - Journal Article PT - Review PL - New Zealand TA - Am J Cardiovasc Drugs JT - American journal of cardiovascular drugs : drugs, devices, and other interventions JID - 100967755 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Hypoglycemic Agents) SB - IM MH - Cardiovascular Diseases/*physiopathology MH - Cardiovascular System/*physiopathology MH - Diabetes Mellitus, Type 2/*drug therapy/*physiopathology MH - Dipeptidyl-Peptidase IV Inhibitors/therapeutic use MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Randomized Controlled Trials as Topic EDAT- 2017/02/16 06:00 MHDA- 2018/02/28 06:00 CRDT- 2017/02/16 06:00 PHST- 2017/02/16 06:00 [pubmed] PHST- 2018/02/28 06:00 [medline] PHST- 2017/02/16 06:00 [entrez] AID - 10.1007/s40256-017-0215-6 [pii] AID - 10.1007/s40256-017-0215-6 [doi] PST - ppublish SO - Am J Cardiovasc Drugs. 2017 Jun;17(3):203-215. doi: 10.1007/s40256-017-0215-6. PMID- 28151519 OWN - NLM STAT- MEDLINE DCOM- 20170829 LR - 20250103 IS - 1827-6806 (Print) IS - 1827-6806 (Linking) VI - 17 IP - 12 Suppl 2 DP - 2016 Dec TI - [Results of the LEADER study: current evidence and perspectives in research]. PG - 28S-31 LID - 10.1714/2616.26913 [doi] AB - The LEADER study is a trial performed to demonstrate the cardiovascular safety of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. The study was performed on patients with type 2 diabetes and high cardiovascular risk, mostly with prior cardiovascular events. Although the primary goal was the demonstration of non-inferiority versus placebo, the LEADER study revealed a significant reduction of the overall incidence of major cardiovascular events, as well as a reduction of all-cause and cardiovascular mortality. A trend toward a reduction, although not statistically significant, was also observed for the incidence of myocardial infarction, stroke, and hospitalization for heart failure. Even though it was designed for safety purposes, the LEADER study provided a demonstration that liraglutide treatment is associated with a relevant reduction of cardiovascular risk. These results support the use of the drug as one of the treatments of choice in patients with diabetes and prior cardiovascular events. Recently, similar results have been observed with another GLP-1 receptor agonist, semaglutide, whereas another component of the class, lixisenatide, failed to show any differences in comparison with placebo. Overall, these results raise interesting questions on similarities and differences across GLP-1 receptor agonists, as well as on potential mechanisms responsible for cardiovascular protection during liraglutide treatment. FAU - Mannucci, Edoardo AU - Mannucci E AD - SODc Diabetologia, Universita degli Studi, Azienda Ospedaliero-Universitaria Careggi, Firenze. LA - ita PT - Journal Article TT - I risultati dello studio LEADER: evidenze attuali e prospettive di ricerca. PL - Italy TA - G Ital Cardiol (Rome) JT - Giornale italiano di cardiologia (2006) JID - 101263411 RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Biomedical Research MH - Cardiovascular Diseases/etiology/*prevention & control MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Liraglutide/*therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2017/02/06 06:00 MHDA- 2017/08/30 06:00 CRDT- 2017/02/03 06:00 PHST- 2017/02/03 06:00 [entrez] PHST- 2017/02/06 06:00 [pubmed] PHST- 2017/08/30 06:00 [medline] AID - 10.1714/2616.26913 [doi] PST - ppublish SO - G Ital Cardiol (Rome). 2016 Dec;17(12 Suppl 2):28S-31. doi: 10.1714/2616.26913. PMID- 28151518 OWN - NLM STAT- MEDLINE DCOM- 20180910 LR - 20181202 IS - 1827-6806 (Print) IS - 1827-6806 (Linking) VI - 17 IP - 12 Suppl 2 DP - 2016 Dec TI - [Type 2 diabetes treatment and cardiovascular risk: what can we learn from trials?]. PG - 20S-27 LID - 10.1714/2616.26912 [doi] AB - Diabetes treatment should include drugs with absolutely no adverse effects toward cardiovascular risk. Indeed, it would be advisable to use drugs with intrinsic protective effect against the risk of cardiovascular events. Intervention trials aiming at demonstrating a protective cardiovascular effect of very tight glucose control have produced controversial results. It is commonly perceived, however, that early intervention with safe treatment strategies is likely to be beneficial. In regard to safety, in the attempt to firmly establish cardiovascular safety of new drugs for diabetes, Government Authorities have mandated that cardiovascular safety trials need to be performed for all new drugs registered for diabetes treatment. Several of such trials have already been performed and their results are available. These results support the cardiovascular safety of three dipeptidyl peptidase-4 inhibitors (sitagliptin, saxagliptin and alogliptin) and of a glucagon-like peptide-1 receptor agonist (GLP-1RA) (lixisenatide). These results, however, also document a plausible protective effect against cardiovascular risk associated with the use of a SGLT2 inhibitor (empagliflozin) and of two GLP-1RAs (liraglutide and semaglutide). Differences and similarities among the results of these cardiovascular safety trials as well as their potential implications will be discussed in this article. FAU - Consoli, Agostino AU - Consoli A AD - Dipartimento di Medicina Interna e Scienze dell'Invecchiamento e Centro Scienze dell'Invecchiamento e Medicina Traslazionale, Universita degli Studi "G. d'Annunzio", Chieti-Pescara. FAU - Febo, Fabrizio AU - Febo F AD - Dipartimento di Medicina Interna e Scienze dell'Invecchiamento e Centro Scienze dell'Invecchiamento e Medicina Traslazionale, Universita degli Studi "G. d'Annunzio", Chieti-Pescara. LA - ita PT - Journal Article TT - Trattamento farmacologico del diabete mellito di tipo 2 e rischio cardiovascolare: cosa e possibile capire dai trial? PL - Italy TA - G Ital Cardiol (Rome) JT - Giornale italiano di cardiologia (2006) JID - 101263411 RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) SB - IM MH - *Cardiovascular Diseases MH - Diabetes Mellitus, Type 2/*drug therapy MH - Dipeptidyl-Peptidase IV Inhibitors MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents MH - Risk Factors EDAT- 2017/02/06 06:00 MHDA- 2018/09/11 06:00 CRDT- 2017/02/03 06:00 PHST- 2017/02/03 06:00 [entrez] PHST- 2017/02/06 06:00 [pubmed] PHST- 2018/09/11 06:00 [medline] AID - 10.1714/2616.26912 [doi] PST - ppublish SO - G Ital Cardiol (Rome). 2016 Dec;17(12 Suppl 2):20S-27. doi: 10.1714/2616.26912. PMID- 28131656 OWN - NLM STAT- MEDLINE DCOM- 20180124 LR - 20180419 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 5 IP - 5 DP - 2017 May TI - Integration of recent evidence into management of patients with atherosclerotic cardiovascular disease and type 2 diabetes. PG - 391-402 LID - S2213-8587(17)30033-5 [pii] LID - 10.1016/S2213-8587(17)30033-5 [doi] AB - Cardiovascular outcome trials of antihyperglycaemic drugs and non-statin LDL-cholesterol-lowering drugs in patients with type 2 diabetes who have, or who are at high risk of, atherosclerotic cardiovascular disease have provided new evidence that has substantially affected the management of cardiovascular risk in these patients. On the basis of proven cardiovascular and renal benefit, the antihyperglycaemic drugs empagliflozin, liraglutide, and semaglutide-the latter being under review for approval by the US Food and Drug Administration and the European Medicines Agency-should be preferentially used as second-line treatments in these patient populations, typically in addition to metformin. Further treatment differentiation among the remainder of the antihyperglycaemic drugs should be made on the basis of evidence regarding cardiovascular safety, which is available for lixisenatide, alogliptin, saxagliptin, sitagliptin, and insulin glargine. The risk of heart failure, stroke, or retinopathy, or prevalent fasting versus postprandial hyperglycaemia, could also be considered in treatment decision making. Finally, emerging evidence of cardiovascular benefit for ezetimibe, alirocumab, and evolocumab positions these drugs as add-ons to maximally tolerated statin therapy or for those with statin intolerance. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Standl, Eberhard AU - Standl E AD - Munich Diabetes Research Group e.V. at Helmholtz Center, Neuherberg, Germany. Electronic address: eberhard.standl@lrz.uni-muenchen.de. FAU - Schnell, Oliver AU - Schnell O AD - Munich Diabetes Research Group e.V. at Helmholtz Center, Neuherberg, Germany. FAU - McGuire, Darren K AU - McGuire DK AD - University of Texas, Southwestern Medical Center, Dallas, TX, USA. FAU - Ceriello, Antonio AU - Ceriello A AD - Institut d'Investigacions Biomediques August Pi i Sunyer-IDIBAPS, Barcelona, Spain; Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Barcelona, Spain; IRCCS MultiMedica, Milan, Italy. FAU - Ryden, Lars AU - Ryden L AD - Cardiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. LA - eng PT - Journal Article PT - Review DEP - 20170126 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 0 (Anticholesteremic Agents) RN - 0 (Hypoglycemic Agents) SB - IM EIN - Lancet Diabetes Endocrinol. 2017 May;5(5):e3. doi: 10.1016/S2213-8587(17)30106-7. PMID: 28385660 MH - Anticholesteremic Agents/*therapeutic use MH - Atherosclerosis/*complications/drug therapy MH - Diabetes Mellitus, Type 2/*complications/drug therapy MH - Humans MH - Hypoglycemic Agents/*therapeutic use EDAT- 2017/01/31 06:00 MHDA- 2018/01/25 06:00 CRDT- 2017/01/30 06:00 PHST- 2016/08/05 00:00 [received] PHST- 2016/12/05 00:00 [revised] PHST- 2016/12/06 00:00 [accepted] PHST- 2017/01/31 06:00 [pubmed] PHST- 2018/01/25 06:00 [medline] PHST- 2017/01/30 06:00 [entrez] AID - S2213-8587(17)30033-5 [pii] AID - 10.1016/S2213-8587(17)30033-5 [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2017 May;5(5):391-402. doi: 10.1016/S2213-8587(17)30033-5. Epub 2017 Jan 26. PMID- 28121469 OWN - NLM STAT- MEDLINE DCOM- 20170329 LR - 20220408 IS - 1751-2441 (Electronic) IS - 1751-2433 (Linking) VI - 10 IP - 4 DP - 2017 Apr TI - SAVOR-TIMI to SUSTAIN-6: a critical comparison of cardiovascular outcome trials of antidiabetic drugs. PG - 429-442 LID - 10.1080/17512433.2017.1287562 [doi] AB - Since the inception of mandatory cardiovascular (CV) safety outcome trial (CVOT) promulgated by US FDA in 2008, seven trials have so far been published with three different classes of antidiabetic drugs in type 2 diabetes mellitus (T2DM). This mini-review aims to critically analyse these CVOTs in terms of different outcomes achieved. Areas covered: An electronic search pertaining to the subject was conducted till September 2016. The three CVOT conducted with saxagliptin, alogliptin and sitagliptin respectively, found them to be CV-neutral. However, both saxagliptin and alogliptin showed an increase in hospitalization due to heart failure (hHF), while sitagliptin had no such signal. The trial conducted with empagliflozin (EMPA-REG) found it to be superior in reducing major adverse cardiac events (MACE). The CVOT conducted with lixisenatide (ELIXA) was CV-neutral, but both liraglutide (LEADER) and semaglutide (SUSTAIN-6) demonstrated superiority in reducing MACE. Expert commentary: While EMPA-REG had robust reduction in the CV-death, all-cause death and hHF, there was a discordant non-significant increase in silent myocardial infarction (MI) (assessed in approximately 50% of patients) and non-fatal stroke. LEADER had concordant reduction in all CV endpoints. SUSTAIN-6 had most robust reduction in 3P-MACE, although no reduction in the CV-death, all-cause death and hHF were observed. FAU - Singh, Awadhesh Kumar AU - Singh AK AD - a Department of Endocrinology , G.D Hospital & Diabetes Institute , Kolkata , West Bengal , India. FAU - Singh, Ritu AU - Singh R AD - b Department of Gynecology , G.D Hospital & Diabetes Institute , Kolkata , West Bengal , India. LA - eng PT - Comparative Study PT - Journal Article PT - Review DEP - 20170206 PL - England TA - Expert Rev Clin Pharmacol JT - Expert review of clinical pharmacology JID - 101278296 RN - 0 (Hypoglycemic Agents) SB - IM MH - Cardiovascular Diseases/epidemiology/*etiology MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*drug therapy MH - Heart Failure/epidemiology/etiology MH - Humans MH - Hypoglycemic Agents/adverse effects/pharmacology/*therapeutic use MH - Myocardial Infarction/epidemiology/etiology MH - Stroke/epidemiology/etiology OTO - NOTNLM OT - Cardiovascular outcome trial OT - DPP-4 inhibitors OT - GLP-1 receptor agonists OT - SGLT-2 inhibitors OT - major adverse cardiovascular events EDAT- 2017/01/26 06:00 MHDA- 2017/03/31 06:00 CRDT- 2017/01/26 06:00 PHST- 2017/01/26 06:00 [pubmed] PHST- 2017/03/31 06:00 [medline] PHST- 2017/01/26 06:00 [entrez] AID - 10.1080/17512433.2017.1287562 [doi] PST - ppublish SO - Expert Rev Clin Pharmacol. 2017 Apr;10(4):429-442. doi: 10.1080/17512433.2017.1287562. Epub 2017 Feb 6. PMID- 28114464 OWN - NLM STAT- MEDLINE DCOM- 20171208 LR - 20260127 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 166 IP - 2 DP - 2017 Jan 17 TI - Semaglutide reduced a composite of CV events at 2 years in patients with type 2 diabetes and high CV risk. PG - JC8 LID - 10.7326/ACPJC-2017-166-2-008 [doi] FAU - Donato, Anthony A AU - Donato AA AD - Reading Health SystemReading, Pennsylvania, USA. LA - eng PT - Comment PT - Journal Article PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM CON - N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. PMID: 27633186 MH - Cardiovascular Diseases MH - *Diabetes Mellitus, Type 2 MH - Diabetic Angiopathies MH - *Glucagon-Like Peptides MH - Humans MH - Risk MH - Risk Factors MH - Semaglutide EDAT- 2017/01/24 06:00 MHDA- 2017/12/09 06:00 CRDT- 2017/01/24 06:00 PHST- 2017/01/24 06:00 [entrez] PHST- 2017/01/24 06:00 [pubmed] PHST- 2017/12/09 06:00 [medline] AID - 2598008 [pii] AID - 10.7326/ACPJC-2017-166-2-008 [doi] PST - ppublish SO - Ann Intern Med. 2017 Jan 17;166(2):JC8. doi: 10.7326/ACPJC-2017-166-2-008. PMID- 28110911 OWN - NLM STAT- MEDLINE DCOM- 20180910 LR - 20260127 IS - 2213-8595 (Electronic) IS - 2213-8587 (Linking) VI - 5 IP - 4 DP - 2017 Apr TI - Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. PG - 251-260 LID - S2213-8587(17)30013-X [pii] LID - 10.1016/S2213-8587(17)30013-X [doi] AB - BACKGROUND: Despite a broad range of pharmacological options for the treatment of type 2 diabetes, optimum glycaemic control remains challenging for many patients and new therapies are necessary. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue in phase 3 development for type 2 diabetes. We assessed the efficacy, safety, and tolerability of semaglutide monotherapy, compared with placebo, in treatment-naive patients with type 2 diabetes who had insufficient glycaemic control with diet and exercise alone. METHODS: We did a double-blind, randomised, parallel-group, international, placebo-controlled phase 3a trial (SUSTAIN 1) at 72 sites in Canada, Italy, Japan, Mexico, Russia, South Africa, UK, and USA (including hospitals, clinical research units, and private offices). Eligible participants were treatment-naive individuals aged 18 years or older with type 2 diabetes treated with only diet and exercise alone for at least 30 days before screening, with a baseline HbA(1c) of 7.0%-10.0% (53-86 mmol/mol). We randomly assigned participants (2:2:1:1) to either once-weekly subcutaneously injected semaglutide (0.5 mg or 1.0 mg), or volume-matched placebo (0.5 mg or 1.0 mg), for 30 weeks via prefilled PDS290 pen-injectors. Participants did their own injections and were encouraged to administer them on the same day of each week in the same area of their body; the time of day and proximity of meal times was not specified. We did the randomisation with an interactive voice or web response system. Investigators, participants, and the funder of the study remained masked throughout the trial. The primary endpoint was the change in mean HbA(1c) from baseline to week 30, and the confirmatory secondary endpoint was the change in mean bodyweight from baseline to week 30. We assessed efficacy and safety in the modified intention-to-treat population (ie, all participants who were exposed to at least one dose of study drug); both placebo groups were pooled for assessment. This trial was registered with ClinicalTrials.gov, number NCT02054897. FINDINGS: Between February 3, 2014, and August 21, 2014, we randomly assigned 388 participants to treatment; 387 received at least one dose of study medication (128 0.5 mg semaglutide, 130 1.0 mg semaglutide, 129 placebo). 17 (13%) of those assigned to 0.5 mg semaglutide, 16 (12%) assigned to 1.0 mg semaglutide, and 14 (11%) assigned to placebo discontinued treatment; the main reason for discontinuation was gastrointestinal adverse events such as nausea. Mean baseline HbA(1c) was 8.05% (SD 0.85); at week 30, HbA(1c) significantly decreased by 1.45% (95% CI -1.65 to -1.26) with 0.5 mg semaglutide (estimated treatment difference vs placebo -1.43%, 95% CI -1.71 to -1.15; p<0.0001), significantly decreased by 1.55% (-1.74 to -1.36) with 1.0 mg semaglutide (estimated treatment difference vs placebo -1.53%, -1.81 to -1.25; p<0.0001), and non-significantly decreased by 0.02% (-0.23 to 0.18) with placebo. Mean baseline bodyweight was 91.93 kg (SD 23.83); at week 30, bodyweight significantly decreased by 3.73 kg (95% CI -4.54 to -2.91) with 0.5 mg semaglutide (estimated treatment difference vs placebo -2.75 kg, 95% CI -3.92 to -1.58; p<0.0001), significantly decreased by 4.53 kg (-5.34 to -3.72) with 1.0 mg semaglutide (estimated treatment difference vs placebo -3.56 kg, -4.74 to -2.38; p<0.0001), and non-significantly decreased by 0.98 kg (-1.82 to -0.13) with placebo. No deaths were reported in any of the study groups and most reported adverse events were of mild or moderate severity. The most frequently reported adverse events in both semaglutide groups were gastrointestinal in nature: nausea was reported in 26 (20%) who received 0.5 mg semaglutide, 31 (24%) who received 1.0 mg semaglutide, and 10 (8%) who received placebo, and diarrhoea was reported in 16 (13%) who received 0.5 mg semaglutide, 14 (11%) who received 1.0 mg semaglutide, and three (2%) who received placebo. INTERPRETATION: Semaglutide significantly improved HbA(1c) and bodyweight in patients with type 2 diabetes compared with placebo, and showed a similar safety profile to currently available GLP-1 receptor agonists, representing a potential treatment option for such patients. FUNDING: Novo Nordisk A/S, Denmark. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Sorli, Christopher AU - Sorli C AD - Billings Clinic Research Center, Billings, MT, USA. Electronic address: chrissorli@gmail.com. FAU - Harashima, Shin-Ichi AU - Harashima SI AD - Graduate School of Medicine, Kyoto University, Kyoto, Japan. FAU - Tsoukas, George M AU - Tsoukas GM AD - Department of Medicine, McGill University, Montreal, QC, Canada. FAU - Unger, Jeffrey AU - Unger J AD - Catalina Research Institute, Chino, CA, USA. FAU - Karsbol, Julie Derving AU - Karsbol JD AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Hansen, Thomas AU - Hansen T AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Bain, Stephen C AU - Bain SC AD - School of Medicine, Swansea University, Swansea, Wales, UK. LA - eng SI - ClinicalTrials.gov/NCT02054897 PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20170117 PL - England TA - Lancet Diabetes Endocrinol JT - The lancet. Diabetes & endocrinology JID - 101618821 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 53AXN4NNHX (Semaglutide) RN - 0 (hemoglobin A1c protein, human) SB - IM CIN - Lancet Diabetes Endocrinol. 2017 Apr;5(4):236-238. doi: 10.1016/S2213-8587(17)30012-8. PMID: 28110912 CIN - Lancet Diabetes Endocrinol. 2017 May;5(5):329-330. doi: 10.1016/S2213-8587(17)30109-2. PMID: 28434490 CIN - Lancet Diabetes Endocrinol. 2017 May;5(5):330. doi: 10.1016/S2213-8587(17)30110-9. PMID: 28434491 CIN - Ann Transl Med. 2017 Dec;5(23):475. doi: 10.21037/atm.2017.10.09. PMID: 29285508 CIN - Ann Transl Med. 2017 Dec;5(24):505. doi: 10.21037/atm.2017.11.10. PMID: 29299466 MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy MH - Double-Blind Method MH - Female MH - Glucagon-Like Peptides/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Middle Aged MH - Placebo Effect MH - Treatment Outcome MH - Semaglutide EDAT- 2017/01/24 06:00 MHDA- 2018/09/11 06:00 CRDT- 2017/01/24 06:00 PHST- 2016/11/09 00:00 [received] PHST- 2016/12/07 00:00 [revised] PHST- 2016/12/08 00:00 [accepted] PHST- 2017/01/24 06:00 [pubmed] PHST- 2018/09/11 06:00 [medline] PHST- 2017/01/24 06:00 [entrez] AID - S2213-8587(17)30013-X [pii] AID - 10.1016/S2213-8587(17)30013-X [doi] PST - ppublish SO - Lancet Diabetes Endocrinol. 2017 Apr;5(4):251-260. doi: 10.1016/S2213-8587(17)30013-X. Epub 2017 Jan 17. PMID- 28102093 OWN - NLM STAT- MEDLINE DCOM- 20170310 LR - 20260127 IS - 1744-764X (Electronic) IS - 1474-0338 (Linking) VI - 16 IP - 3 DP - 2017 Mar TI - Cardiovascular safety and benefits of GLP-1 receptor agonists. PG - 351-363 LID - 10.1080/14740338.2017.1281246 [doi] AB - Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) constitute a class of drugs for the treatment of type 2 diabetes, and currently, six different GLP-1RAs are approved. Besides improving glycemic control, the GLP-1RAs have other beneficial effects such as weight loss and a low risk of hypoglycemia. Treatment with the GLP-1RA lixisenatide has been shown to be safe in patients with type 2 diabetes and recent acute coronary syndrome. Furthermore, liraglutide and semaglutide have been shown to reduce cardiovascular (CV) disease (CVD) risk in type 2 diabetes patients with established and/or high risk of CVD. The CV safety of the remaining GLP-1RAs in type 2 diabetes patients with established and/or high risk of CVD remains uncertain, but ongoing CV outcome trials (CVOTs) will elucidate this within a few years. Areas covered: The aim of this review is to provide an overview of the existing GLP-1RAs with a particular focus on their clinical effects on CV risk factors and their CV safety and benefits. Expert opinion: Data on the CV risks and benefits associated with GLP-1RA treatment in patients with type 2 diabetes and high risk of CVD are emerging - and look promising (especially for liraglutide and semaglutide). Data from ongoing CVOTs will be crucial for the positioning of the individual GLP-1RAs in the treatment of patients with type 2 diabetes and high risk of CVD. However, the long-term CV safety and the potential of GLP-1RAs to prevent CVD in type 2 diabetes patients with less risk of CVD (e.g. newly diagnosed patients) remain uncertain. FAU - Dalsgaard, Niels B AU - Dalsgaard NB AD - a Center for Diabetes Research, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark. FAU - Bronden, Andreas AU - Bronden A AD - a Center for Diabetes Research, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AD - a Center for Diabetes Research, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark. AD - b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark. FAU - Knop, Filip K AU - Knop FK AD - a Center for Diabetes Research, Gentofte Hospital , University of Copenhagen , Hellerup , Denmark. AD - b Department of Clinical Medicine, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark. AD - c The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark. LA - eng PT - Journal Article DEP - 20170119 PL - England TA - Expert Opin Drug Saf JT - Expert opinion on drug safety JID - 101163027 RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Cardiovascular Diseases/etiology/prevention & control MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucagon-Like Peptides/administration & dosage/pharmacology/therapeutic use MH - Humans MH - Hypoglycemic Agents/adverse effects/pharmacology/*therapeutic use MH - Liraglutide/adverse effects/pharmacology/therapeutic use MH - Risk Factors MH - *Glucagon-Like Peptide-1 Receptor Agonists MH - Semaglutide OTO - NOTNLM OT - Cardiovascular safety OT - glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) OT - type 2 diabetes EDAT- 2017/01/20 06:00 MHDA- 2017/03/11 06:00 CRDT- 2017/01/20 06:00 PHST- 2017/01/20 06:00 [pubmed] PHST- 2017/03/11 06:00 [medline] PHST- 2017/01/20 06:00 [entrez] AID - 10.1080/14740338.2017.1281246 [doi] PST - ppublish SO - Expert Opin Drug Saf. 2017 Mar;16(3):351-363. doi: 10.1080/14740338.2017.1281246. Epub 2017 Jan 19. PMID- 27981757 OWN - NLM STAT- MEDLINE DCOM- 20171102 LR - 20260127 IS - 1463-1326 (Electronic) IS - 1462-8902 (Linking) VI - 19 IP - 4 DP - 2017 Apr TI - Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: A systematic review and mixed-treatment comparison analysis. PG - 524-536 LID - 10.1111/dom.12849 [doi] AB - AIMS: To compare efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in people with type 2 diabetes. MATERIALS AND METHODS: We electronically searched, up to June 3, 2016, published randomized clinical trials lasting between 24 and 32 weeks that compared a GLP-1RA (albiglutide, dulaglutide, twice-daily exenatide and once-weekly exenatide, liraglutide, lixisenatide, semaglutide and taspoglutide) with placebo or another GLP-1RA. Data on cardiometabolic and safety outcomes were analysed using a mixed-treatment comparison meta-analysis. RESULTS: A total of 34 trials (14 464 participants) met the inclusion criteria; no published data for semaglutide were available. Compared with placebo, all GLP-1RAs reduced glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels (reductions ranged from -0.55% and -0.73 mmol/L, respectively, for lixisenatide to -1.21% and -1.97 mmol/L, respectively, for dulaglutide). There were no differences within short-acting (twice-daily exenatide and lixisenatide) or long-acting (albiglutide, dulaglutide, once-weekly exenatide, liraglutide and taspoglutide) groups. Compared with twice-daily exenatide, dulaglutide treatment was associated with the greatest HbA1c and FPG reduction (0.51% and 1.04 mmol/L, respectively), followed by liraglutide (0.45% and 0.93 mmol/L, respectively) and once-weekly exenatide (0.38% and 0.85 mmol/L, respectively); similar reductions were found when these 3 agents were compared with lixisenatide. Compared with placebo, all GLP-1RAs except albiglutide reduced weight and increased the risk of hypoglycaemia and gastrointestinal side effects, and all agents except dulaglutide and taspoglutide reduced systolic blood pressure. When all GLP-1RAs were compared with each other, no clinically meaningful differences were observed in weight loss, blood pressure reduction or hypoglycaemia risk. Albiglutide had the lowest risk of nausea and diarrhoea and once-weekly exenatide the lowest risk of vomiting. CONCLUSIONS: The RCTs in the present analysis show that all GLP-1RAs improve glycaemic control, reduce body weight and increase the risk of adverse gastrointestinal symptoms compared with placebo. Although there were no differences when short-acting agents were compared with each other or when long-acting agents were compared with each other, dulaglutide, liraglutide and once-weekly exenatide were superior to twice-daily exenatide and lixisenatide at lowering HbA1c and FPG levels. There were no differences in hypoglycaemia between these 3 agents, whilst once-weekly exenatide had the lowest risk of vomiting. These results, along with patient's preferences and individualized targets, should be considered when selecting a GLP-1RA. CI - (c) 2016 John Wiley & Sons Ltd. FAU - Htike, Zin Z AU - Htike ZZ AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK. FAU - Zaccardi, Francesco AU - Zaccardi F AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK. FAU - Papamargaritis, Dimitris AU - Papamargaritis D AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK. FAU - Webb, David R AU - Webb DR AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK. FAU - Khunti, Kamlesh AU - Khunti K AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK. FAU - Davies, Melanie J AU - Davies MJ AD - Diabetes Research Centre, University of Leicester, Leicester, UK. AD - Leicester Diabetes Centre, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK. LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Systematic Review DEP - 20170217 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 0 (Blood Glucose) RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Incretins) RN - 839I73S42A (Liraglutide) RN - 0 (Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Venoms) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) RN - 0 (hemoglobin A1c protein, human) RN - 2PHK27IP3B (taspoglutide) RN - 5E7U48495E (rGLP-1 protein) RN - WTT295HSY5 (dulaglutide) SB - IM MH - Blood Glucose/drug effects MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Administration Schedule MH - Exenatide MH - Female MH - Glucagon-Like Peptide 1/administration & dosage/adverse effects/analogs & derivatives MH - Glucagon-Like Peptides/administration & dosage/adverse effects/*analogs & derivatives MH - Glycated Hemoglobin/drug effects MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Immunoglobulin Fc Fragments/*administration & dosage/adverse effects MH - Incretins/*administration & dosage/adverse effects MH - Liraglutide/administration & dosage/adverse effects MH - Male MH - Middle Aged MH - Peptides/administration & dosage/adverse effects MH - Randomized Controlled Trials as Topic MH - Recombinant Fusion Proteins/*administration & dosage/adverse effects MH - Treatment Outcome MH - Venoms/administration & dosage/adverse effects MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP-1 analogue OT - network meta-analysis OT - systematic review OT - type 2 diabetes EDAT- 2016/12/17 06:00 MHDA- 2017/11/03 06:00 CRDT- 2016/12/17 06:00 PHST- 2016/10/06 00:00 [received] PHST- 2016/11/29 00:00 [revised] PHST- 2016/12/08 00:00 [accepted] PHST- 2016/12/17 06:00 [pubmed] PHST- 2017/11/03 06:00 [medline] PHST- 2016/12/17 06:00 [entrez] AID - 10.1111/dom.12849 [doi] PST - ppublish SO - Diabetes Obes Metab. 2017 Apr;19(4):524-536. doi: 10.1111/dom.12849. Epub 2017 Feb 17. PMID- 27921428 OWN - NLM STAT- MEDLINE DCOM- 20170619 LR - 20181202 IS - 0042-773X (Print) IS - 0042-773X (Linking) VI - 62 IP - 11 Suppl 4 DP - 2016 Fall TI - [Promising molecules for treatment of hyperglycemia in patients with type 2 diabetes]. PG - S67-71 AB - New antidiabetic drugs are being developed today that expand the range of pharmacological intervention, in particular for patients with type 2 diabetes (imeglimin, semaglutide, dulaglutide, FGF 21 analogue). At the same time innovations take place that "better" the well-proven molecules, they offer new application forms we have no experience of diabetology (osmotic pump for exenatide, faster acting insulin aspart). New properties are brought by just the change of concentration (insulin glargine in a concentration of 300 U/ml), unexpected positive results are also brought by new fixed-ratio combinations of antidiabetics (fixed-ratio combination of insulin degludec and liraglutide, fixed-ratio combination of insulin glargine and lixisenatide). Also results of clinical studies appear that concern molecules already in use which facilitate the formulation of new recommendations regarding treatment type 2 diabetes.Key words: type 2 diabetes mellitus - dulaglutide - FGF 21 - imeglimin - insulin aspart - insulin degludek - insulin glargine - ITCA 650 - liraglutide - national information diabetes system - semaglutide. FAU - Kvapil, Milan AU - Kvapil M LA - cze PT - Journal Article PT - Review TT - Perspektivni molekuly pro lecbu hyperglykemie u pacientu s diabetem 2. typu. PL - Czech Republic TA - Vnitr Lek JT - Vnitrni lekarstvi JID - 0413602 RN - 0 (Hypoglycemic Agents) SB - IM MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Humans MH - Hyperglycemia/*drug therapy/etiology MH - Hypoglycemic Agents/*therapeutic use EDAT- 2016/12/07 06:00 MHDA- 2017/06/20 06:00 CRDT- 2016/12/07 06:00 PHST- 2016/12/07 06:00 [entrez] PHST- 2016/12/07 06:00 [pubmed] PHST- 2017/06/20 06:00 [medline] AID - 59831 [pii] PST - ppublish SO - Vnitr Lek. 2016 Fall;62(11 Suppl 4):S67-71. PMID- 27863704 OWN - NLM STAT- MEDLINE DCOM- 20171108 LR - 20250103 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 39 IP - 5 DP - 2017 May TI - Cardiovascular Effects of Glucose-lowering Therapies for Type 2 Diabetes: New Drugs in Perspective. PG - 1012-1025 LID - S0149-2918(16)30793-7 [pii] LID - 10.1016/j.clinthera.2016.10.008 [doi] AB - PURPOSE: The purpose of this study was to review the results of clinical trials assessing the cardiovascular effects of drugs for type 2 diabetes and the cardiovascular effects of newer available drugs. METHODS: We performed a detailed search of PubMed-listed publications, reports from international meetings, and ongoing studies from clinical trials.gov. FINDINGS: Currently available drugs have neutral or, in some cases, negative effects on cardiovascular outcomes. Modern sulfonylureas appear to be safe, although the biguanide metformin has a slightly better cardiovascular safety profile than the sulfonylureas and is the first choice for monotherapy. The cardiovascular tolerability of thiazolidinediones (glitazones) remains controversial, with particularly adverse effects in patients with cardiac failure. The cardiovascular effects of insulin in type 2 diabetes appear neutral. Newer incretin-based therapies have been closely examined in a large number of clinical trials, some of which are still ongoing. The dipeptidyl peptidase-4 inhibitor (gliptins) trials to date have all found a neutral effect. Of the glucagon-like peptide-1 (GLP-1) agonists, lixisenatide had a neutral effect, whereas liraglutide and semaglutide had a benefit on outcomes. The results of the sodium-glucose transporter-2 (SGLT-2) inhibitor empaglifozin attracted interest when it was the first to report a strong benefit on cardiovascular mortality. Liraglutide and semaglutide had a neutral effect on cardiac failure admissions, whereas empaglifozin had a benefit. In each of the trials, there was not a clear effect on myocardial infarction and stroke. The mechanism of the cardiovascular benefit is debated, and further studies with other GLP-1 agonists and SGLT-2 inhibitors are awaited. IMPLICATIONS: After 2 decades of disappointment in attempting to control cardiovascular progression in type 2 diabetes with careful glycemic control, there is distinct hope that newer drugs, particularly the GLP-1 agonists and the SGLT-2 inhibitors, will have cardiovascular benefits independent of glycemic control. CI - Copyright (c) 2017 Elsevier HS Journals, Inc. All rights reserved. FAU - Thompson, Peter L AU - Thompson PL AD - Heart Research Institute, Sir Charles Gairdner Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Harry Perkins Institute of Medical Research, Perth, Australia. Electronic address: peter.thompson@health.wa.gov.au. FAU - Davis, Timothy M E AU - Davis TME AD - School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Fremantle Hospital, Perth, Australia. LA - eng PT - Journal Article PT - Review DEP - 20161115 PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Hypoglycemic Agents) RN - 0 (Incretins) RN - 0 (Insulin) RN - 0 (SLC5A2 protein, human) RN - 0 (Sodium-Glucose Transporter 2) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Sulfonylurea Compounds) RN - 0 (Thiazolidinediones) RN - 9100L32L2N (Metformin) RN - IY9XDZ35W2 (Glucose) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - *Cardiovascular Diseases/chemically induced/prevention & control MH - Diabetes Mellitus, Type 2/*drug therapy MH - Glucose/metabolism MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Incretins/therapeutic use MH - Insulin/therapeutic use MH - Metformin/therapeutic use MH - Sodium-Glucose Transporter 2 MH - Sodium-Glucose Transporter 2 Inhibitors MH - Sulfonylurea Compounds/therapeutic use MH - Thiazolidinediones/adverse effects/therapeutic use MH - Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - GLP agonists OT - SGLT-2 inhibitors OT - cardiovascular outcomes OT - glucose lowering drugs OT - type 2 diabetes EDAT- 2016/11/20 06:00 MHDA- 2017/11/09 06:00 CRDT- 2016/11/20 06:00 PHST- 2016/09/20 00:00 [received] PHST- 2016/10/15 00:00 [revised] PHST- 2016/10/17 00:00 [accepted] PHST- 2016/11/20 06:00 [pubmed] PHST- 2017/11/09 06:00 [medline] PHST- 2016/11/20 06:00 [entrez] AID - S0149-2918(16)30793-7 [pii] AID - 10.1016/j.clinthera.2016.10.008 [doi] PST - ppublish SO - Clin Ther. 2017 May;39(5):1012-1025. doi: 10.1016/j.clinthera.2016.10.008. Epub 2016 Nov 15. PMID- 27835045 OWN - NLM STAT- MEDLINE DCOM- 20171101 LR - 20171130 IS - 1557-8593 (Electronic) IS - 1520-9156 (Linking) VI - 18 IP - 12 DP - 2016 Dec TI - Cardiovascular Outcomes of New Medications for Type 2 Diabetes. PG - 749-758 AB - Cardiovascular (CV) disease remains the leading cause of death in people with diabetes, highlighting the importance of using treatment options that do not increase CV risk or possibly decrease CV outcomes. Since 2008, the Food and Drug Administration has required demonstration of CV safety for all new medications developed for the glycemic management of diabetes. Seven trials have been published that have established CV safety for three DPP-4 inhibitors (alogliptin, saxagliptin, and sitagliptin), three GLP-1 receptor agonists (liraglutide, lixisenatide, and semaglutide), and one sodium-glucose cotransporter-2 inhibitor (empagliflozin). Three of those studies also established superiority with liraglutide, empagliflozin, and semaglutide at reducing the composite primary endpoint of major CV events (CV death, nonfatal myocardial infarction, and nonfatal stroke). In addition, one trial found an increase in heart failure hospitalizations with saxagliptin. The findings of these trials must be compared and contrasted cautiously given the differences in patient populations and trial designs, but together they provide important information that can be used to shape our treatment guideline recommendations and patient-specific treatment decisions. FAU - Trujillo, Jennifer M AU - Trujillo JM AD - 1 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado , Aurora, Colorado. FAU - Wettergreen, Sara A AU - Wettergreen SA AD - 2 College of Pharmacy, University of North Texas System , Denton, Texas. FAU - Nuffer, Wesley A AU - Nuffer WA AD - 1 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado , Aurora, Colorado. FAU - Ellis, Samuel L AU - Ellis SL AD - 1 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado , Aurora, Colorado. FAU - McDermott, Michael T AU - McDermott MT AD - 1 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado , Aurora, Colorado. AD - 3 School of Medicine, University of Colorado , Aurora, Colorado. LA - eng PT - Journal Article PT - Review DEP - 20161111 PL - United States TA - Diabetes Technol Ther JT - Diabetes technology & therapeutics JID - 100889084 RN - 0 (Hypoglycemic Agents) SB - IM MH - Cardiovascular Diseases/chemically induced/*prevention & control MH - Diabetes Mellitus, Type 2/complications/*drug therapy MH - Humans MH - Hypoglycemic Agents/*adverse effects OTO - NOTNLM OT - Cardiovascular disease OT - Medications OT - Type 2 diabetes EDAT- 2016/11/12 06:00 MHDA- 2017/11/02 06:00 CRDT- 2016/11/12 06:00 PHST- 2016/11/12 06:00 [pubmed] PHST- 2017/11/02 06:00 [medline] PHST- 2016/11/12 06:00 [entrez] AID - 10.1089/dia.2016.0295 [doi] PST - ppublish SO - Diabetes Technol Ther. 2016 Dec;18(12):749-758. doi: 10.1089/dia.2016.0295. Epub 2016 Nov 11. PMID- 27817160 OWN - NLM STAT- MEDLINE DCOM- 20170822 LR - 20240603 IS - 1534-6242 (Electronic) IS - 1523-3804 (Print) IS - 1523-3804 (Linking) VI - 18 IP - 12 DP - 2016 Dec TI - Novel Anti-glycemic Drugs and Reduction of Cardiovascular Risk in Diabetes: Expectations Realized, Promises Unmet. PG - 79 AB - PURPOSE OF REVIEW: The purpose is to review evidence on cardiovascular risks and benefits of new treatments for type 2 diabetes mellitus. RECENT FINDINGS: In response to guidance issued by the Food and Drug Administration, thousands of patients have been enrolled in large randomized trials evaluating the cardiovascular effects of the three newest diabetes drug classes: glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose cotransporter 2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. Two studies of GLP-1 receptor agonists-one of liraglutide and one of semaglutide-have shown cardiovascular benefit relative to placebo, and one study of the SGLT-2 inhibitor empagliflozin has shown benefit. The other published cardiovascular outcome studies of the newest drug classes have generally supported safety, apart from an as-yet unresolved safety concern about increased rates of heart failure with DPP-4 inhibitors. Recent research suggests the thiazolidinedione pioglitazone may have beneficial effects on some cardiovascular outcomes as well, but these are counterbalanced by a known increase of the risk of heart failure with this drug. In general, more prospective randomized trial data is now available regarding the cardiovascular effects of the newer diabetes drugs than on the older drug classes. New evidence suggests that the newest diabetes drugs are safe from a cardiovascular perspective. Evidence on benefit from at least some members of the GLP-1 receptor agonist and SGLT-2 inhibitor classes is encouraging but not yet decisive. FAU - Flory, James H AU - Flory JH AD - Weill Cornell Medical College, 425 E 61st Street, Suite 301, New York, NY, 10065, USA. jaf9052@med.cornell.edu. FAU - Ukena, Jenny K AU - Ukena JK AD - Weill Cornell Medical College, 425 E 61st Street, Suite 301, New York, NY, 10065, USA. FAU - Floyd, James S AU - Floyd JS AD - Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA. AD - Department of Medicine, University of Washington, Seattle, WA, USA. LA - eng GR - K08 HL116640/HL/NHLBI NIH HHS/United States GR - K08 HS023898/HS/AHRQ HHS/United States PT - Journal Article PT - Review PL - United States TA - Curr Atheroscler Rep JT - Current atherosclerosis reports JID - 100897685 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) SB - IM MH - Animals MH - Blood Glucose MH - Cardiovascular Diseases/etiology/*prevention & control MH - Clinical Trials as Topic MH - Diabetes Mellitus, Type 2/*complications/drug therapy MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Risk Factors PMC - PMC5509052 MID - NIHMS871458 OTO - NOTNLM OT - Cardiovascular outcomes OT - Cardiovascular risk OT - Cardiovascular safety OT - Novel anti-glycemic drugs OT - Type 2 diabetes mellitus EDAT- 2016/11/07 06:00 MHDA- 2017/08/23 06:00 PMCR- 2017/12/01 CRDT- 2016/11/07 06:00 PHST- 2016/11/07 06:00 [entrez] PHST- 2016/11/07 06:00 [pubmed] PHST- 2017/08/23 06:00 [medline] PHST- 2017/12/01 00:00 [pmc-release] AID - 10.1007/s11883-016-0633-y [pii] AID - 10.1007/s11883-016-0633-y [doi] PST - ppublish SO - Curr Atheroscler Rep. 2016 Dec;18(12):79. doi: 10.1007/s11883-016-0633-y. PMID- 27708277 OWN - NLM STAT- MEDLINE DCOM- 20180815 LR - 20260127 IS - 1759-5010 (Electronic) IS - 1759-5002 (Linking) VI - 13 IP - 12 DP - 2016 Dec TI - Diabetes: Cardiovascular benefits of semaglutide. PG - 697 LID - 10.1038/nrcardio.2016.168 [doi] FAU - Lim, Gregory B AU - Lim GB LA - eng PT - Journal Article DEP - 20161006 PL - England TA - Nat Rev Cardiol JT - Nature reviews. Cardiology JID - 101500075 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Cardiovascular Diseases/*prevention & control MH - Diabetes Mellitus, Type 2/*complications/*drug therapy MH - Glucagon-Like Peptide 1/*analogs & derivatives MH - Glucagon-Like Peptides/adverse effects/*therapeutic use MH - Humans MH - Semaglutide EDAT- 2016/11/05 06:00 MHDA- 2018/08/16 06:00 CRDT- 2016/10/07 06:00 PHST- 2016/11/05 06:00 [pubmed] PHST- 2018/08/16 06:00 [medline] PHST- 2016/10/07 06:00 [entrez] AID - nrcardio.2016.168 [pii] AID - 10.1038/nrcardio.2016.168 [doi] PST - ppublish SO - Nat Rev Cardiol. 2016 Dec;13(12):697. doi: 10.1038/nrcardio.2016.168. Epub 2016 Oct 6. PMID- 27633186 OWN - NLM STAT- MEDLINE DCOM- 20161219 LR - 20260518 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 375 IP - 19 DP - 2016 Nov 10 TI - Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. PG - 1834-1844 AB - BACKGROUND: Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half-life of approximately 1 week, in type 2 diabetes are unknown. METHODS: We randomly assigned 3297 patients with type 2 diabetes who were on a standard-care regimen to receive once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. We hypothesized that semaglutide would be noninferior to placebo for the primary outcome. The noninferiority margin was 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio. RESULTS: At baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both. The primary outcome occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.58 to 0.95; P<0.001 for noninferiority). Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74; 95% CI, 0.51 to 1.08; P=0.12); nonfatal stroke occurred in 1.6% and 2.7%, respectively (hazard ratio, 0.61; 95% CI, 0.38 to 0.99; P=0.04). Rates of death from cardiovascular causes were similar in the two groups. Rates of new or worsening nephropathy were lower in the semaglutide group, but rates of retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation) were significantly higher (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P=0.02). Fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment because of adverse events, mainly gastrointestinal. CONCLUSIONS: In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide. (Funded by Novo Nordisk; SUSTAIN-6 ClinicalTrials.gov number, NCT01720446 .). FAU - Marso, Steven P AU - Marso SP AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Bain, Stephen C AU - Bain SC AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Consoli, Agostino AU - Consoli A AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Eliaschewitz, Freddy G AU - Eliaschewitz FG AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Jodar, Esteban AU - Jodar E AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Leiter, Lawrence A AU - Leiter LA AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Lingvay, Ildiko AU - Lingvay I AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Rosenstock, Julio AU - Rosenstock J AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Seufert, Jochen AU - Seufert J AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Warren, Mark L AU - Warren ML AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Woo, Vincent AU - Woo V AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Hansen, Oluf AU - Hansen O AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Holst, Anders G AU - Holst AG AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Pettersson, Jonas AU - Pettersson J AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. FAU - Vilsboll, Tina AU - Vilsboll T AD - From the Research Medical Center, Kansas City, MO (S.P.M.); School of Medicine, Swansea University, Swansea, United Kingdom (S.C.B.); Department of Medicine and Aging Science and Center of Excellence on Aging and Translational Medicine, G. d'Annunzio University, Chieti-Pescara, Italy (A.C.); CPClin Research Center/Hospital Israelita Albert Einstein, Sao Paulo (F.G.E.); Hospital Universitario Quiron Salud Madrid, Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid (E.J.); Li Ka Shing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto (L.A.L.), and the University of Manitoba, Winnipeg (V.W.) - both in Canada; University of Texas Southwestern Medical Center (I.L.) and Dallas Diabetes Research Center at Medical City (J.R.) - both in Dallas; University of Freiburg Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany (J.S.); Physicians East, Greenville, NC (M.L.W.); and Novo Nordisk, Soborg (O.H., A.G.H., J.P.), and the Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup (T.V.) - both in Denmark. CN - SUSTAIN-6 Investigators LA - eng SI - ClinicalTrials.gov/NCT01720446 PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20160915 PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 53AXN4NNHX (Semaglutide) SB - IM CIN - Ann Intern Med. 2017 Jan 17;166(2):JC8. doi: 10.7326/ACPJC-2017-166-2-008. PMID: 28114464 CIN - N Engl J Med. 2017 Mar 2;376(9):891. doi: 10.1056/NEJMc1615712. PMID: 28249136 CIN - N Engl J Med. ;376(9):890. doi: 10.1056/NEJMc1615712. PMID: 28252261 CIN - N Engl J Med. ;376(9):890-1. doi: 10.1056/NEJMc1615712. PMID: 28252263 CIN - Evid Based Med. 2017 Apr;22(2):57-58. doi: 10.1136/ebmed-2016-110652. PMID: 28270434 CIN - MMW Fortschr Med. 2023 Feb;165(2):66. doi: 10.1007/s15006-023-2301-9. PMID: 36703073 MH - Aged MH - Cardiovascular Diseases/mortality/*prevention & control MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Diabetic Nephropathies/epidemiology/prevention & control MH - Diabetic Retinopathy/epidemiology MH - Female MH - Gastrointestinal Diseases/chemically induced MH - Glucagon-Like Peptide 1/*analogs & derivatives MH - Glucagon-Like Peptides/adverse effects/*therapeutic use MH - Glycated Hemoglobin/analysis MH - Humans MH - Kaplan-Meier Estimate MH - Male MH - Middle Aged MH - Semaglutide FIR - Fitchett, David IR - Fitchett D FIR - Bebchuk, Judith D IR - Bebchuk JD FIR - Boon, Nicholas IR - Boon N FIR - Gardner, Timothy IR - Gardner T FIR - Inzucchi, Silvio IR - Inzucchi S FIR - Chaitman, Bernard R IR - Chaitman BR FIR - Bach, Richard IR - Bach R FIR - Gosselin, Gilbert IR - Gosselin G FIR - Laddu, Abhay A IR - Laddu AA FIR - Albert, Stewart G IR - Albert SG FIR - Gyawali, C Prakash IR - Gyawali CP FIR - Mullady, Daniel Kast IR - Mullady DK FIR - Block, Geoffrey IR - Block G FIR - Bushinsky, David IR - Bushinsky D FIR - Martin, Kevin IR - Martin K FIR - Alsheklhee, Amer IR - Alsheklhee A FIR - Cruz-Flores, Salvador IR - Cruz-Flores S FIR - Feen, Eli S IR - Feen ES FIR - Jacoby, Meagan A IR - Jacoby MA FIR - Picus, Joel IR - Picus J FIR - Schroeder, Mark A IR - Schroeder MA FIR - Akduman, Levent IR - Akduman L FIR - Dudney, B Wayne IR - Dudney BW FIR - Aberkane, Kahina IR - Aberkane K FIR - Bachaoui, Malika IR - Bachaoui M FIR - Benali, Leila Nadia IR - Benali LN FIR - Berra, Abdelaziz IR - Berra A FIR - Bouacha, Yachar IR - Bouacha Y FIR - Bouziani, Nadia IR - Bouziani N FIR - Charef, Takait Essalem IR - Charef TE FIR - Dahliz, Saadia IR - Dahliz S FIR - Far, Malika IR - Far M FIR - Griene, Samia IR - Griene S FIR - Guessas, Mahdi IR - Guessas M FIR - Guettaf, Nour El Houda IR - Guettaf NEH FIR - Hachelaf, Fatma Zohra IR - Hachelaf FZ FIR - Hannane, Souad Ibtissam IR - Hannane SI FIR - Lakabi, Zohra IR - Lakabi Z FIR - Salah Mansour, Abdellah IR - 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Kovaleva, Svetlana IR - Kovaleva S FIR - Kovalevskaia, Elena IR - Kovalevskaia E FIR - Krivosheeva, Inga IR - Krivosheeva I FIR - Kufelkina, Tatiana IR - Kufelkina T FIR - Kunitsyna, Marina IR - Kunitsyna M FIR - Kurbanova, Victoria IR - Kurbanova V FIR - Likhodey, Natalia IR - Likhodey N FIR - Lomova, Alena IR - Lomova A FIR - Lvova, Ludmila IR - Lvova L FIR - Lysenko, Tatyana IR - Lysenko T FIR - Malceva, Anna IR - Malceva A FIR - Martinovich, Alexey IR - Martinovich A FIR - Ogorodnikova, Evgeniya IR - Ogorodnikova E FIR - Osipova, Olga IR - Osipova O FIR - Ostrovskaya, Irina IR - Ostrovskaya I FIR - Postoeva, Anna IR - Postoeva A FIR - Prigoda, Natalya IR - Prigoda N FIR - Reshedko, Dmitry IR - Reshedko D FIR - Reshedko, Leonid IR - Reshedko L FIR - Reshedko, Galina IR - Reshedko G FIR - Rodionova, Tatyana IR - Rodionova T FIR - Ruyatkin, Dmitriy IR - Ruyatkin D FIR - Ruyatkina, Ludmila IR - Ruyatkina L FIR - Samylina, Irina IR - Samylina I FIR - Sardinov, Ruslan IR - Sardinov R FIR - Sergeeva-Kondrachenko, Marina IR - Sergeeva-Kondrachenko M FIR - Shabanova, Elena IR - Shabanova E FIR - Shatkovskaya, Natalia IR - Shatkovskaya N FIR - Shilina Kutuzova, Nadezhda IR - Shilina Kutuzova N FIR - Shimokhina, Olga IR - Shimokhina O FIR - Shuvaeva, Anna IR - Shuvaeva A FIR - Sorkina, Ekaterina IR - Sorkina E FIR - Sorokin, Maxim IR - Sorokin M FIR - Suvorova, Larisa IR - Suvorova L FIR - Sych, Yulia IR - Sych Y FIR - Talalaeva, Natalya IR - Talalaeva N FIR - Valeeva, Alfiya IR - Valeeva A FIR - Valeeva, Farida IR - Valeeva F FIR - Vinokurova, Valentina IR - Vinokurova V FIR - Yanovskaya, Elena IR - Yanovskaya E FIR - Yanovskaya, Maria IR - Yanovskaya M FIR - Zakharova, Tatiana IR - Zakharova T FIR - Zhukova, Elena IR - Zhukova E FIR - Zimina, Irina IR - Zimina I FIR - Zinenko, Anastasia IR - Zinenko A FIR - Znamenshchikova, Galina IR - Znamenshchikova G FIR - Arr Arroyo, Beatriz Perez IR - Arr Arroyo BP FIR - Beltran, Manuel IR - Beltran M FIR - Garcia Bidon, Hector IR - Garcia Bidon H FIR - Cepero, Daniel IR - Cepero D FIR - Sedeno Diaz, Jesus Maria IR - Sedeno Diaz JM FIR - Elvira, Javier IR - Elvira J FIR - Rivas Fernandez, Margarita IR - Rivas Fernandez M FIR - Obiols Fornells, Maria Angels IR - Obiols Fornells MA FIR - Garcia Ordonez, Miguel Angel IR - Garcia Ordonez MA FIR - Bascunana Quirell, Antonio IR - Bascunana Quirell A FIR - Mezquita Raya, Pedro IR - Mezquita Raya P FIR - Reyes, Rebeca IR - Reyes R FIR - Ruiz Serra, Antonio IR - Ruiz Serra A FIR - Serrarols Soldevila, Marta IR - Serrarols Soldevila M FIR - Lopez Suarez, Alejandro IR - Lopez Suarez A FIR - Terns, Manel IR - Terns M FIR - Chen, Jeng-Yeou IR - Chen JY FIR - Chou, Chien-Wen IR - Chou CW FIR - He, Chih-Tsueng IR - He CT FIR - Hsieh, Chang-Hsun IR - Hsieh CH FIR - Hsu, Brend Ray-Sea IR - Hsu BR FIR - Hua, Shih-Che IR - Hua SC FIR - Huang, Chung-Huei IR - Huang CH FIR - Huang, Yu-Yao IR - Huang YY FIR - Hung, Yi-Jen IR - Hung YJ FIR - Lee, Chien IR - Lee C FIR - Lin, Chen-Wei IR - Lin CW FIR - Lin, Chia-Hung IR - Lin CH FIR - Liou, Miaw-Jene IR - Liou MJ FIR - Lu, Wen-Tsung IR - Lu WT FIR - Lu, Chieh-Hsiang IR - Lu CH FIR - Sun, Jui-Hung IR - Sun JH FIR - Tai, Tsai-Sung IR - Tai TS FIR - Tien, Kai-Jen IR - Tien KJ FIR - Wang, Chih-Ching IR - Wang CC FIR - Wu, Ling-Yi IR - Wu LY FIR - Yang, Chwen-Yi IR - Yang CY FIR - Yen, Feng Chieh IR - Yen FC FIR - Yu, Hui-I IR - Yu HI FIR - Boonyasirinant, Thananya IR - Boonyasirinant T FIR - Boonyavarakul, Apussanee IR - Boonyavarakul A FIR - Deerochanawong, Chaicharn IR - Deerochanawong C FIR - Katekao, Wisuit IR - Katekao W FIR - Maneesai, Adisak IR - Maneesai A FIR - Naeowong, Witthawat IR - Naeowong W FIR - Pumprueg, Satchana IR - Pumprueg S FIR - Srichomkwun, Panudda IR - Srichomkwun P FIR - Sriratanasathavorn, Charn IR - Sriratanasathavorn C FIR - Sritara, Piyamitr IR - Sritara P FIR - Sunthornyothin, Sarat IR - Sunthornyothin S FIR - Tejavanija, Sirakarn IR - Tejavanija S FIR - Thirawuth, Varinsawat IR - Thirawuth V FIR - Wangpatharawanit, Phanthaboon IR - Wangpatharawanit P FIR - Wattanachanya, Lalita IR - Wattanachanya L FIR - Wongpraparut, Nattawut IR - Wongpraparut N FIR - Ahbab, Suleyman IR - Ahbab S FIR - Akin, Fulya IR - Akin F FIR - Akinci, Baris IR - Akinci B FIR - Akyay, Ozlem IR - Akyay O FIR - Altunbas, Hasan IR - Altunbas H FIR - Apaydin, Mahmut IR - Apaydin M FIR - Asik, Mehmet IR - Asik M FIR - Ataoglu, Esra IR - Ataoglu E FIR - Atasoy, Alp IR - Atasoy A FIR - Bahadir, Muzeyyen Arslan IR - Bahadir MA FIR - Beysel, Selvihan IR - Beysel S FIR - Cakal, Erman IR - Cakal E FIR - Calan, Mehmet IR - Calan M FIR - Caliskan, Mustafa IR - Caliskan M FIR - Cavdar, Umit IR - Cavdar U FIR - Comlekci, Abdurrahman IR - Comlekci A FIR - Delibasi, Tuncay IR - Delibasi T FIR - Demir, Tevfik IR - Demir T FIR - Demirci, Taner IR - Demirci T FIR - Dogan, Burcu IR - Dogan B FIR - Donmez, Halil IR - Donmez H FIR - Ergen, Abdul IR - Ergen A FIR - Eroglu, Mustafa IR - Eroglu M FIR - Erturk, Mehmet IR - Erturk M FIR - Guler, Serdar IR - Guler S FIR - Gumus, Tugba IR - Gumus T FIR - Gur, Savas IR - Gur S FIR - Imga, Narin IR - Imga N FIR - Kan, Seyfullah IR - Kan S FIR - Karakilic, Ersen IR - Karakilic E FIR - Karakose, Melia IR - Karakose M FIR - Kizilgul, Muhammed IR - Kizilgul M FIR - Mesci, Banu Alpaslan IR - Mesci BA FIR - Oguz, Aytekin IR - Oguz A FIR - Orbay, Ekrem IR - Orbay E FIR - Ozcelik, Ozgur IR - Ozcelik O FIR - Ozcelik, Sengul IR - Ozcelik S FIR - Ozisik, Secil IR - Ozisik S FIR - Saglam, Fatma IR - Saglam F FIR - Sagun, Hatice IR - Sagun H FIR - Samanci, Nilay IR - Samanci N FIR - Sari, Ramazan IR - Sari R FIR - Selek, Alev IR - Selek A FIR - Semerci, Aysun IR - Semerci A FIR - Tahmaz, Meryem IR - Tahmaz M FIR - Tarkun, Ilhan IR - Tarkun I FIR - Topaloglu, Oya IR - Topaloglu O FIR - Topsakal, Senay IR - Topsakal S FIR - Turker, Fatih IR - Turker F FIR - Tutal, Esra IR - Tutal E FIR - Ucan, Bekir IR - Ucan B FIR - Ukinc, Kubilay IR - Ukinc K FIR - Yaylali, Guzin IR - Yaylali G FIR - Yener, Serkan IR - Yener S FIR - Yenigun, Mustafa IR - Yenigun M FIR - Yerlikaya, Emrah IR - Yerlikaya E FIR - Abraham, Prakash IR - Abraham P FIR - Aftab, Saboor IR - Aftab S FIR - Bellary, Srikanth IR - Bellary S FIR - Cadzow, Ann IR - Cadzow A FIR - Chhokar, Balgit IR - Chhokar B FIR - Deshpande, M IR - Deshpande M FIR - Devany, Louise IR - Devany L FIR - Dokhe, Pratiksha IR - Dokhe P FIR - Elshashai, Ahmed IR - Elshashai A FIR - Febbraro, Salvatore IR - Febbraro S FIR - Inkster, Janet IR - Inkster J FIR - Jayia, Parminderjit IR - Jayia P FIR - Kurup, Uttura IR - Kurup U FIR - Lascar, Nadia IR - Lascar N FIR - MacKay, Judith IR - MacKay J FIR - Rajeev, Surya IR - Rajeev S FIR - Seetho, Ian IR - Seetho I FIR - Shiels, Hannah IR - Shiels H FIR - Shukla, Urmi IR - Shukla U FIR - Smith, Jamie IR - Smith J FIR - Stanciu, Daniela IR - Stanciu D FIR - Subramanian, Gowri IR - Subramanian G FIR - Taylor, Jonathan IR - Taylor J FIR - Weeraratne, Davinda IR - Weeraratne D FIR - Wilding, John IR - Wilding J FIR - Abreu, Marconi IR - Abreu M FIR - Agaiby, John IR - Agaiby J FIR - Agaiby, Eva IR - Agaiby E FIR - Aguillon, Ana IR - Aguillon A FIR - Ahmed, Syed IR - Ahmed S FIR - Alaoui, Rachid IR - Alaoui R FIR - Alarcon, Stephanie IR - Alarcon S FIR - Alexander, Lori IR - Alexander L FIR - Ali, Asim IR - Ali A FIR - Allen, Kay IR - Allen K FIR - Al-Maliky, Thouraya IR - Al-Maliky T FIR - Alvi, Madiha IR - Alvi M FIR - Andersen, James IR - Andersen J FIR - Anthony, Vincent IR - Anthony V FIR - Arcon-Rios, Sirlys IR - Arcon-Rios S FIR - Arkin, David IR - Arkin D FIR - Arodak, Bassam IR - Arodak B FIR - Arroyo, Sonia IR - Arroyo S FIR - Asmar, Imad IR - Asmar I FIR - Attel, Susan IR - Attel S FIR - Azar, Madona IR - Azar M FIR - Aziz, Ammara IR - Aziz A FIR - Azizad, Masoud IR - Azizad M FIR - Bachand, Trista IR - Bachand T FIR - Baier, Mara IR - Baier M FIR - Bajaj, Chris IR - Bajaj C FIR - Baker, Claire IR - Baker C FIR - Baker, Chelsea IR - Baker C FIR - Baker, Constance IR - Baker C FIR - Balentine, Tracy IR - Balentine T FIR - Ballard, Thomas IR - Ballard T FIR - Banarer, Salomon IR - Banarer S FIR - Banks, James IR - Banks J FIR - Barchini, George IR - Barchini G FIR - Barra, Joel IR - Barra J FIR - Barrett, John IR - Barrett J FIR - Bartilucci, Darlene IR - Bartilucci D FIR - Bauer, Nicole IR - Bauer N FIR - Baum, Howard IR - Baum H FIR - Baumann, Margaret IR - Baumann M FIR - Bax, Jessica IR - Bax J FIR - Bays, Harold IR - Bays H FIR - Becerra, Karen IR - Becerra K FIR - Bedel, Gary IR - Bedel G FIR - Behl, Noreen IR - Behl N FIR - Bell, Amy IR - Bell A FIR - Benavidez, Brenda IR - Benavidez B FIR - Bender, William IR - Bender W FIR - Bergamo, Katherine IR - Bergamo K FIR - Bernstein, Richard IR - Bernstein R FIR - Berry, Martha IR - Berry M FIR - Bestermann, William IR - Bestermann W FIR - Beyea, Matthew IR - Beyea M FIR - Bhambri, Rhajiv IR - Bhambri R FIR - Bice, C Robert IR - Bice CR FIR - Bilas, Alistaire IR - Bilas A FIR - Bishop, Keisha IR - Bishop K FIR - Bixler, Lacey IR - Bixler L FIR - Blair, Caitlin IR - Blair C FIR - Boncu, Otilia IR - Boncu O FIR - Bonner, Jo IR - Bonner J FIR - Borromeo, Azael IR - Borromeo A FIR - Botros, Emad IR - Botros E FIR - Boyd, Gary IR - Boyd G FIR - Bragg, Charlotte IR - Bragg C FIR - Brassfield, Amber IR - Brassfield A FIR - Breen, Jeanne IR - Breen J FIR - Brennan, Michael IR - Brennan M FIR - Brewington, Shannon IR - Brewington S FIR - Bricker, Charles IR - Bricker C FIR - Brickner, Charles IR - Brickner C FIR - Brown, Monica IR - Brown M FIR - Brown, April IR - Brown A FIR - Bryant, Danielle IR - Bryant D FIR - Buck, Genena IR - Buck G FIR - Buckley, Brandee IR - Buckley B FIR - Budzinski, Susan IR - Budzinski S FIR - Bukowski, Julie IR - Bukowski J FIR - Bunyard, Holly IR - Bunyard H FIR - Burdette, Tara IR - Burdette T FIR - Burgess-Blalock, Casey IR - Burgess-Blalock C FIR - Burton, Anna IR - Burton A FIR - Busch, Robert IR - Busch R FIR - Buse, John IR - Buse J FIR - Bushong, Denise IR - Bushong D FIR - Butler, Nancy IR - Butler N FIR - Byars, William IR - Byars W FIR - Bybee, Kevin IR - Bybee K FIR - Bye, Robin IR - Bye R FIR - Byers, Joyce IR - Byers J FIR - Caldwell, Ronald IR - Caldwell R FIR - Calvin, Krystle IR - Calvin K FIR - Camacho, Allison IR - Camacho A FIR - Cameron, John IR - Cameron J FIR - Cannon, Melanie IR - Cannon M FIR - Cannon, Daniel IR - Cannon D FIR - Cannon, Kevin IR - Cannon K FIR - Capuchino, Jonna IR - Capuchino J FIR - Cardella, Sally IR - Cardella S FIR - Carmolli-Cornette, Lisa IR - Carmolli-Cornette L FIR - Carpio, Gandahari IR - Carpio G FIR - Casagni, Kimberely IR - Casagni K FIR - Cassell, Bettina IR - Cassell B FIR - Castay, Cathleen IR - Castay C FIR - Catenacci, Victoria IR - Catenacci V FIR - Cerullo, Janis IR - Cerullo J FIR - Chaidarun, Sushela IR - Chaidarun S FIR - Chambers, Joseph IR - Chambers J FIR - Chaykin, Louis IR - Chaykin L FIR - Cherry, Amanda IR - Cherry A FIR - Cheyne, Theresa IR - Cheyne T FIR - Chochinov, Ronald IR - Chochinov R FIR - Choe, James IR - Choe J FIR - Chow, Christopher IR - Chow C FIR - Christina, Melanie IR - Christina M FIR - Christopher, Suzette IR - Christopher S FIR - Chu, James IR - Chu J FIR - Chuang, Ellie IR - Chuang E FIR - Church, Lara IR - Church L FIR - Ciampa, Anthony IR - Ciampa A FIR - Cohen, Erik IR - Cohen E FIR - Cohen, Neil IR - Cohen N FIR - Collins, Brittany IR - Collins B FIR - Combs, Judy IR - Combs J FIR - Comi, Richard IR - Comi R FIR - Conn, Brittany IR - Conn B FIR - Cook, Dorothy IR - Cook D FIR - Correll, Cheryl IR - Correll C FIR - Cortes, Guadelupe IR - Cortes G FIR - Cortez, Anita IR - Cortez A FIR - Covington, Damian IR - Covington D FIR - Critchson, Sharron IR - Critchson S FIR - Culmer, Dawn IR - Culmer D FIR - Cunningham, Linda IR - Cunningham L FIR - Curll, James IR - Curll J FIR - Daboul, Nizar IR - Daboul N FIR - Dagogo-Jack, Samuel IR - Dagogo-Jack S FIR - Daly-Barnes, Kristie IR - Daly-Barnes K FIR - Dang, Andy IR - Dang A FIR - Daniels, David IR - Daniels D FIR - Darlington, Haley IR - Darlington H FIR - Davis, Matthew IR - Davis M FIR - Daynes, Randall IR - Daynes R FIR - Dayton, Therese IR - Dayton T FIR - Dean, John IR - Dean J FIR - DeAtkine, David IR - DeAtkine D FIR - Delgado, Elizabeth IR - Delgado E FIR - DeMicco, Michael IR - DeMicco M FIR - DeSalle, Dina IR - DeSalle D FIR - Desouza, Cyrus IR - Desouza C FIR - Devlin, Deborah IR - Devlin D FIR - Dezube, Milana IR - Dezube M FIR - DiCerbo, Nancy IR - DiCerbo N FIR - DiDonato, Maureen IR - DiDonato M FIR - Diesburg-Stanwood, Amy IR - Diesburg-Stanwood A FIR - Dilembo, Jennifer IR - Dilembo J FIR - Diller, Philip IR - Diller P FIR - Diner, Jaime IR - Diner J FIR - Dluge-Aungst, Dawn IR - Dluge-Aungst D FIR - Dodis, Regina IR - Dodis R FIR - Donoho, Amanda IR - Donoho A FIR - Dor, Isaac IR - Dor I FIR - Doremus, Nathan IR - Doremus N FIR - Doriguzzi, David IR - Doriguzzi D FIR - Dostou, Jean IR - Dostou J FIR - Douglass, Sara IR - Douglass S FIR - Dowell, Michelle IR - Dowell M FIR - Draper, Brenda IR - Draper B FIR - Drincic, Andjela IR - Drincic A FIR - Du, Haiming IR - Du H FIR - Duckor, Steven IR - Duckor S FIR - Duclos, Michelle IR - Duclos M FIR - Duffy-Hidalgo, Bobbi IR - Duffy-Hidalgo B FIR - Duma, Carol IR - Duma C FIR - Duncan, Sheri IR - Duncan S FIR - Durant, Raegan IR - Durant R FIR - Durham, Nancy IR - Durham N FIR - Dusek, Jaclyn IR - Dusek J FIR - Eagerton, Donald IR - Eagerton D FIR - Ebeling, Kathleen IR - Ebeling K FIR - Ebenibo, Sotonte IR - Ebenibo S FIR - Edeoga, Chimaroke IR - Edeoga C FIR - Edgett, Robin IR - Edgett R FIR - Edwards, Gina IR - Edwards G FIR - Edwin, Jessica IR - Edwin J FIR - Egelhof, Richard IR - Egelhof R FIR - Ekwensi, James IR - Ekwensi J FIR - Elliott, Theresa Ohlson IR - Elliott TO FIR - Elmore, Miles IR - Elmore M FIR - Elson, Diane IR - Elson D FIR - Emmert, Laurie IR - Emmert L FIR - Entriken, Leslie IR - Entriken L FIR - Van Epps, Holly IR - Van Epps H FIR - Erie, Monica IR - Erie M FIR - Everhart, Brian IR - Everhart B FIR - Farmer, Mildred IR - Farmer M FIR - Farnesi, Darren IR - Farnesi D FIR - Fernandes, Leora IR - Fernandes L FIR - Ferrington, Beth IR - Ferrington B FIR - Fink, Vicky IR - Fink V FIR - Fishman, Norman IR - Fishman N FIR - Florida, Christine IR - Florida C FIR - Forker, Alan IR - Forker A FIR - Forward, John IR - Forward J FIR - Freudemann, Karen IR - Freudemann K FIR - Fuller, Gail IR - Fuller G FIR - Fuller, Gene IR - Fuller G FIR - Fusco, Frank IR - Fusco F FIR - Gagianas, Peter IR - Gagianas P FIR - Galagan, Robert IR - Galagan R FIR - Galloway, Allison IR - Galloway A FIR - Gansner, Elizabeth IR - Gansner E FIR - Gaona, Raul IR - Gaona R FIR - Garcia, Idolina IR - Garcia I FIR - Garcia, Gabriel IR - Garcia G FIR - Garvin, Maureen IR - Garvin M FIR - Gaudiani, Linda IR - Gaudiani L FIR - Gault, Jennifer IR - Gault J FIR - Gavazov, Miroslav IR - Gavazov M FIR - Gawad, Michael IR - Gawad M FIR - Gedbaw, Cassandra IR - Gedbaw C FIR - Gerace, Carmela IR - Gerace C FIR - Gilbert, Matthew IR - Gilbert M FIR - Godwin, Sarah IR - Godwin S FIR - Goebel, Tambra IR - Goebel T FIR - Goley, April IR - Goley A FIR - Golici, Laura IR - Golici L FIR - Gonzalez, M Antonieta IR - Gonzalez MA FIR - Goodhart, Charlene IR - Goodhart C FIR - Gosmanov, Aidar IR - Gosmanov A FIR - Goswami, Ketan IR - Goswami K FIR - Gray, Stephanie IR - Gray S FIR - Greco, Susan IR - Greco S FIR - Green, Carrie IR - Green C FIR - Greenberg, Craig IR - Greenberg C FIR - Griffen, Julie IR - Griffen J FIR - Gruenther, Peggy IR - Gruenther P FIR - Guadron-Hernandez, Liliana IR - Guadron-Hernandez L FIR - Guasp, Lisa IR - Guasp L FIR - Guice, Michael IR - Guice M FIR - Gunther, David IR - Gunther D FIR - Gustin, Harry IR - Gustin H FIR - Gutierrez, Haydee IR - Gutierrez H FIR - Haggag, Amina IR - Haggag A FIR - Haggar, Michelle IR - Haggar M FIR - Hammond, Judy IR - Hammond J FIR - Hanyok, April IR - Hanyok A FIR - Hardy, Chelsey IR - Hardy C FIR - Harper, Wayne IR - Harper W FIR - Harrell, Wendy IR - Harrell W FIR - Harris, Elizabeth IR - Harris E FIR - Harrison, Lindsay IR - Harrison L FIR - Hartsell, Rebecca IR - Hartsell R FIR - Haseeb, Myra IR - Haseeb M FIR - Hastings, Amber IR - Hastings A FIR - Hayes, Denise IR - Hayes D FIR - Hedrick, Carolyn IR - Hedrick C FIR - Helman, Laura IR - Helman L FIR - Helman, Max IR - Helman M FIR - Helton, Ashley IR - Helton A FIR - Hendrick, Mary IR - Hendrick M FIR - Hendrickson, Chase IR - Hendrickson C FIR - Hennekes, Gayle IR - Hennekes G FIR - Herbst, Ashley IR - Herbst A FIR - Hernandez, Graciela IR - Hernandez G FIR - Herring, Charles IR - Herring C FIR - Hess, Erika IR - Hess E FIR - Hilliard, Belinda IR - Hilliard B FIR - Hoagland, Emily IR - Hoagland E FIR - Hoberman, Eric IR - Hoberman E FIR - Hoffman, Lisa IR - Hoffman L FIR - Hoffmann, Amanda IR - Hoffmann A FIR - Hogan, Eileen IR - Hogan E FIR - Hook, Kristen IR - Hook K FIR - Van Hoornbeek, David IR - Van Hoornbeek D FIR - Hope, Morgan IR - Hope M FIR - Hopson, Barbara IR - Hopson B FIR - Horner, Joan IR - Horner J FIR - Horobetz, Catherine IR - Horobetz C FIR - Houser, Patricia IR - Houser P FIR - Htun, Wynn IR - Htun W FIR - Hudson, Tina IR - Hudson T FIR - Huerta, Bobbi IR - Huerta B FIR - Huizar, Sulmarur IR - Huizar S FIR - Hullett, Maggi IR - Hullett M FIR - Hummer, Kimberly IR - Hummer K FIR - Hwang, Seol Young IR - Hwang SY FIR - Ingram, William IR - Ingram W FIR - Ingram, Michelle IR - Ingram M FIR - Ismail-Beigi, Faramarz IR - Ismail-Beigi F FIR - Iverson, Leslie IR - Iverson L FIR - Jackson, Tamara IR - Jackson T FIR - Jackson, Timothy IR - Jackson T FIR - Jackson, Richard IR - Jackson R FIR - Jacqmein, Jeffrey IR - Jacqmein J FIR - Jantzi, Curtis IR - Jantzi C FIR - Joffrion, Isabelle IR - Joffrion I FIR - St John, Jennifer IR - St John J FIR - Johnson, Mandi IR - Johnson M FIR - Jones, Sheri IR - Jones S FIR - Juarez, Mario IR - Juarez M FIR - Juergens, Tricia IR - Juergens T FIR - Jutras, Sandra IR - Jutras S FIR - Kain, Angela IR - Kain A FIR - Kapogiannis, Christos IR - Kapogiannis C FIR - Kassem, Laure IR - Kassem L FIR - Kaster, Steven IR - Kaster S FIR - Katalenich, Bonnie IR - Katalenich B FIR - Kawa, Ashley IR - Kawa A FIR - Keiran, Sarah IR - Keiran S FIR - Ketchum, Michele IR - Ketchum M FIR - Keuchel, Janet IR - Keuchel J FIR - Khadka, Poonam IR - Khadka P FIR - Khamousia, Nidaa IR - Khamousia N FIR - Khan, Khaleda IR - Khan K FIR - Khan, Amna IR - Khan A FIR - Khan, Jaber IR - Khan J FIR - Kiester, Janet IR - Kiester J FIR - Kim, Grace IR - Kim G FIR - Kimmel, Murray IR - Kimmel M FIR - King, Kara IR - King K FIR - Kirkman, Marian Sue IR - Kirkman MS FIR - Kniffen, Wendy IR - Kniffen W FIR - Koehler, Timothy IR - Koehler T FIR - Konigsberg, Sarah IR - Konigsberg S FIR - Koren, Michael IR - Koren M FIR - Korngut, Irwin IR - Korngut I FIR - Krishnasamy, Sathya IR - Krishnasamy S FIR - Kuettel, Kevin IR - Kuettel K FIR - Kulow, Tanya IR - Kulow T FIR - Kumar, Mariananda IR - Kumar M FIR - Kumar, Swarooparani IR - Kumar S FIR - Kunst, Edward IR - Kunst E FIR - Kwan, Raymond IR - Kwan R FIR - Kwon, Elise IR - Kwon E FIR - LaBryer, Lauren IR - LaBryer L FIR - Laliberte, Alison IR - Laliberte A FIR - Lane, T IR - Lane T FIR - Lane, James IR - Lane J FIR - Lang, Jaqueline IR - Lang J FIR - Largay, Joseph IR - Largay J FIR - Larrabee, Patricia IR - Larrabee P FIR - Larsen, David IR - Larsen D FIR - Latif, Kashif IR - Latif K FIR - Lattinville, Brandi IR - Lattinville B FIR - Lawrence, Jereta IR - Lawrence J FIR - Leonard, Molly IR - Leonard M FIR - Leonard, Katie IR - Leonard K FIR - Lewis, Cora IR - Lewis C FIR - Lewis, Melissa IR - Lewis M FIR - Licklider, Deborah IR - Licklider D FIR - Lim, Jonea IR - Lim J FIR - Lipps, Janie IR - Lipps J FIR - Lisovskiy, Svetlana IR - Lisovskiy S FIR - Liu, Mon Hsia IR - Liu MH FIR - Livingston, Yolanda IR - Livingston Y FIR - Lloyd, Shannon IR - Lloyd S FIR - Loeck, Amanda IR - Loeck A FIR - Loesch, Ryan IR - Loesch R FIR - Lopez, Lina IR - Lopez L FIR - Loreto, Maria IR - Loreto M FIR - Lovre, Dragana IR - Lovre D FIR - Lu, Peter IR - Lu P FIR - Lucas, Kimberley IR - Lucas K FIR - Luevano, Gabriela IR - Luevano G FIR - Luna, Blanca IR - Luna B FIR - Lung, Janet IR - Lung J FIR - De La Luz, Mabel IR - De La Luz M FIR - Lynch, Michael IR - Lynch M FIR - Lyons, Timothy IR - Lyons T FIR - Mack, Debra IR - Mack D FIR - Madder, Robert IR - Madder R FIR - Magee, James IR - Magee J FIR - Mahakala, Aparna IR - Mahakala A FIR - Maheshwari, Hiralal IR - Maheshwari H FIR - Mallitz, Michelle IR - Mallitz M FIR - Maluchnik, Barabara IR - Maluchnik B FIR - Malyszko, Stacie IR - Malyszko S FIR - Manessis, Anastasios IR - Manessis A FIR - Mann, Kara IR - Mann K FIR - Marney, Annis IR - Marney A FIR - Marshall, Lisa IR - Marshall L FIR - Martin, Melissa IR - Martin M FIR - Maw, Kelli IR - Maw K FIR - May, Michael IR - May M FIR - Mayfield, Ronald IR - Mayfield R FIR - Mazhar, Ghazala IR - Mazhar G FIR - Mbogua, Caroline IR - Mbogua C FIR - McCartney, Michael IR - McCartney M FIR - McDuffie, Roberta IR - McDuffie R FIR - McKendall-Lewis, Chi IR - McKendall-Lewis C FIR - McKenzie, Leanna IR - McKenzie L FIR - McKibben, Kim IR - McKibben K FIR - McNair, Rebecca IR - McNair R FIR - Mehta, Praful IR - Mehta P FIR - Meisner, Carl IR - Meisner C FIR - Melchor, Nidia IR - Melchor N FIR - Mello, Curtis IR - Mello C FIR - Meredith, Melissa IR - Meredith M FIR - Michael, Donna IR - Michael D FIR - Micklewright, Gezina IR - Micklewright G FIR - Midyett, Catherine IR - Midyett C FIR - Miller, Jennifer IR - Miller J FIR - Miller, Alan IR - Miller A FIR - Miller, Todd IR - Miller T FIR - Miller, Neil IR - Miller N FIR - Miller, Kari IR - Miller K FIR - Minyon-Sarver, Dawnmarie IR - Minyon-Sarver D FIR - Mittadodla, Saritha IR - Mittadodla S FIR - Moeller, Jennifer IR - Moeller J FIR - Mohammadbhoy, Adrian IR - Mohammadbhoy A FIR - Mokshagundam, Sri IR - Mokshagundam S FIR - Moloughney, Morgan IR - Moloughney M FIR - Monaco, Susan IR - Monaco S FIR - Montgomery, Charles IR - Montgomery C FIR - Moody, Kelly IR - Moody K FIR - Mooney, Julie IR - Mooney J FIR - Moore, Melanie IR - Moore M FIR - Morawski, Emily IR - Morawski E FIR - Moreau, Cynthia IR - Moreau C FIR - Morekas, Demetra IR - Morekas D FIR - Morin, David IR - Morin D FIR - Mueller, Theresa IR - Mueller T FIR - Muir, Denise IR - Muir D FIR - Mullen, Julie IR - Mullen J FIR - Murak, Daniel IR - Murak D FIR - Naderi, Bahar IR - Naderi B FIR - Naidu, Jayaram IR - Naidu J FIR - Ndukwu, Ikeadi IR - Ndukwu I FIR - Nelson, Lauren IR - Nelson L FIR - Nelson, Laura IR - Nelson L FIR - Nelson, Claretha IR - Nelson C FIR - Neuberger, Cari IR - Neuberger C FIR - Neumeister, Amy IR - Neumeister A FIR - Nichols, Melissa IR - Nichols M FIR - Nickerson, Natalie IR - Nickerson N FIR - Nockerts, Nikki IR - Nockerts N FIR - O'Brien, Heather IR - O'Brien H FIR - Oden, Wendy IR - Oden W FIR - O'Donnell, Philip IR - O'Donnell P FIR - Odugbesan, Adeniyi IR - Odugbesan A FIR - Oiknine, Rachel IR - Oiknine R FIR - Olio, Tansy IR - Olio T FIR - Oliver, Michael IR - Oliver M FIR - Olmeda, Carly IR - Olmeda C FIR - Olsen, Sharon IR - Olsen S FIR - O'Neil, Christine IR - O'Neil C FIR - Ortega, Tania IR - Ortega T FIR - Ostrowski, Phillip IR - Ostrowski P FIR - Otah, Kenneth IR - Otah K FIR - Otero, Heydin IR - Otero H FIR - Packard, Kevin IR - Packard K FIR - Painter, Karolynn IR - Painter K FIR - Pangtay, Dennis IR - Pangtay D FIR - Pangtay, Sonia IR - Pangtay S FIR - Papacostea, Olivia IR - Papacostea O FIR - Papierniak, Nancy IR - Papierniak N FIR - Parker, Anna IR - Parker A FIR - Pascal, Aileen IR - Pascal A FIR - Pascal-Doriguzzi, Aileen IR - Pascal-Doriguzzi A FIR - Patel, Alpa IR - Patel A FIR - Patel, Christine IR - Patel C FIR - Patel, Minesh IR - Patel M FIR - Patel, Bhadresh IR - Patel B FIR - Patterson, Mark IR - Patterson M FIR - Paulus, Carolyn IR - Paulus C FIR - Peek, Michelle IR - Peek M FIR - Pegg, Ashley IR - Pegg A FIR - Phelps, Spencer IR - Phelps S FIR - Phillips, Bunny IR - Phillips B FIR - Piccola, Jeanne IR - Piccola J FIR - Pickett, Alicia IR - Pickett A FIR - Pinero, Gloria IR - Pinero G FIR - Pitts, Angella IR - Pitts A FIR - Platt, Jonathan IR - Platt J FIR - Poduri, Madhuri IR - Poduri M FIR - Poehls, Jennifer IR - Poehls J FIR - Ponte, Gaston IR - Ponte G FIR - Pop, Laurentiu IR - Pop L FIR - Power, Elisabeth IR - Power E FIR - Price, Evelyn IR - Price E FIR - Priest, Diane IR - Priest D FIR - Quadrel, Mark IR - Quadrel M FIR - Quinney, Rosylen IR - Quinney R FIR - Quyyumi, Shahed IR - Quyyumi S FIR - Rabalais, Muriel IR - Rabalais M FIR - Rabideau, Diane IR - Rabideau D FIR - Rahman, Jennifer IR - Rahman J FIR - Raidl, Christina IR - Raidl C FIR - Ramirez, Karina IR - Ramirez K FIR - Ramsey, Stacy IR - Ramsey S FIR - Rangaraj, Uma IR - Rangaraj U FIR - Rao, Veitla IR - Rao V FIR - Rasmussen, Brian IR - Rasmussen B FIR - Rasouli, Neda IR - Rasouli N FIR - Rauch, Ruth IR - Rauch R FIR - Ray, Shannon IR - Ray S FIR - Recker, Bridget IR - Recker B FIR - Redding, John IR - Redding J FIR - Redrick, Scott IR - Redrick S FIR - Reheis, Jordan IR - Reheis J FIR - Reiling, Joseph IR - Reiling J FIR - Reiling, Susan IR - Reiling S FIR - Rems, Lucy IR - Rems L FIR - Rettig, Kristin IR - Rettig K FIR - Reusch, Jane IR - Reusch J FIR - Reynolds, Michele IR - Reynolds M FIR - Ricci, Cassie IR - Ricci C FIR - Rice, Lucian IR - Rice L FIR - Rickard, Heather IR - Rickard H FIR - Rios-Santiago, Jessica IR - Rios-Santiago J FIR - Ritchey, Barbara IR - Ritchey B FIR - Rivera, Sylvia IR - Rivera S FIR - Rizos, Demetrius IR - Rizos D FIR - Rizvi, Syed Fahad IR - Rizvi SF FIR - Robbins, Robert IR - Robbins R FIR - Robison, Dawn IR - Robison D FIR - Rocco, Sheri IR - Rocco S FIR - Roche, Cathy IR - Roche C FIR - Rodes, Alfredo IR - Rodes A FIR - Perdomo Rodriguez, Juan Pablo IR - Perdomo Rodriguez JP FIR - Rodriguez, Maria IR - Rodriguez M FIR - Rojas, Martha IR - Rojas M FIR - Rokoff, Norma IR - Rokoff N FIR - Roney, Christopher IR - Roney C FIR - Rooker-Morris, Leslie IR - Rooker-Morris L FIR - Root, Connie IR - Root C FIR - Roozen, Cathy IR - Roozen C FIR - Ross, Irena IR - Ross I FIR - Roth, Marilynn IR - Roth M FIR - Roth, Eli IR - Roth E FIR - Rothman, Jeffrey IR - Rothman J FIR - Roura, Miguel IR - Roura M FIR - Russell, Kathleen IR - Russell K FIR - Russell, Emily IR - Russell E FIR - Rutherford, Cheryl IR - Rutherford C FIR - Salazar, Jennifer IR - Salazar J FIR - Salazar, Jorge IR - Salazar J FIR - Sanagorski, Rebecca IR - Sanagorski R FIR - Sandy, Amanda IR - Sandy A FIR - Santiago, Jose IR - Santiago J FIR - Saunders, Jacqueline IR - Saunders J FIR - Schmidt, Holli IR - Schmidt H FIR - Schneider, Christopher IR - Schneider C FIR - Schramm, Erich IR - Schramm E FIR - Schramm, Rashi IR - Schramm R FIR - Schultzaberger, Richard IR - Schultzaberger R FIR - Schweppe, Laurie IR - Schweppe L FIR - Scott, Robert IR - Scott R FIR - Scribner, Anita IR - Scribner A FIR - Seddon, Theresa IR - Seddon T FIR - Seekford, Jennifer IR - Seekford J FIR - Segel, Scott IR - Segel S FIR - Severance, Randall IR - Severance R FIR - Severson, Megan IR - Severson M FIR - Shah, Kayur IR - Shah K FIR - Shaw, Jessica IR - Shaw J FIR - Shay, Marc IR - Shay M FIR - Sheets, Michelle IR - Sheets M FIR - Shelton, Christina IR - Shelton C FIR - Shelton, Leslie IR - Shelton L FIR - Shelton, Sandra IR - Shelton S FIR - Shikany, James IR - Shikany J FIR - Shippey, Jeanette IR - Shippey J FIR - Shivaswamy, Vijay IR - Shivaswamy V FIR - Shlesinger, Yshay IR - Shlesinger Y FIR - Shlotzhauser, Tammi IR - Shlotzhauser T FIR - Shook, Mindy IR - Shook M FIR - Shore, David IR - Shore D FIR - Shvarts, Marina IR - Shvarts M FIR - Siddiqui, Muhammad IR - Siddiqui M FIR - Silver, Robert IR - Silver R FIR - Simon, Henry IR - Simon H FIR - Singh, Manmeet IR - Singh M FIR - Sites, Mary Jo IR - Sites MJ FIR - Sitton, Dee IR - Sitton D FIR - Sivalingam, Kanagaratnam IR - Sivalingam K FIR - Smith, Danielle IR - Smith D FIR - Smith, Kristy IR - Smith K FIR - Smith, Nina IR - Smith N FIR - Smith, Timothy IR - Smith T FIR - Smith, Jennifer IR - Smith J FIR - Snyder, Janice IR - Snyder J FIR - Snyder, Brian IR - Snyder B FIR - Sood, Ajay IR - Sood A FIR - Soon, Jennifer IR - Soon J FIR - Sorrentino, Lynn IR - Sorrentino L FIR - Sortor, Jennifer IR - Sortor J FIR - Sosnowchik, James IR - Sosnowchik J FIR - Soufer, Joseph IR - Soufer J FIR - Spears, Jeni IR - Spears J FIR - Spector, Linda IR - Spector L FIR - Speicher, Richard IR - Speicher R FIR - Stacey, Amy IR - Stacey A FIR - Stafford, Mollie IR - Stafford M FIR - Stanford, Jennifer IR - Stanford J FIR - Stayer, Martha IR - Stayer M FIR - Stell, Carol IR - Stell C FIR - Stenger, Elizabeth IR - Stenger E FIR - Stockhammer, Stanley IR - Stockhammer S FIR - Stoneman, Jill IR - Stoneman J FIR - Straatmann, Donna IR - Straatmann D FIR - Sugimoto, Danny IR - Sugimoto D FIR - Sugimoto, Michael IR - Sugimoto M FIR - Sultan, Farah IR - Sultan F FIR - Suryadevara, Sreenija IR - Suryadevara S FIR - Sutton, David IR - Sutton D FIR - Swan, Delores IR - Swan D FIR - Sy, Claude IR - Sy C FIR - Talley, Shellie IR - Talley S FIR - Talsania, Mitali IR - Talsania M FIR - Tan, Anjanette IR - Tan A FIR - Taylor, Peggy IR - Taylor P FIR - Thethi, Tina IR - Thethi T FIR - Thomas, Shannon IR - Thomas S FIR - Thompson, Casey IR - Thompson C FIR - Thottan, Anna IR - Thottan A FIR - Tiktin, Margaret IR - Tiktin M FIR - Tillson, Renee IR - Tillson R FIR - Timpe, Rebecca IR - Timpe R FIR - Tinney, Irene IR - Tinney I FIR - Tirado-Bernardini, Reinaldo IR - Tirado-Bernardini R FIR - Tobias, Cindy IR - Tobias C FIR - Tobin, Timothy IR - Tobin T FIR - Toe, Florence IR - Toe F FIR - Torello, Carole IR - Torello C FIR - Tousson, Amanda IR - Tousson A FIR - Tousson, Jennifer IR - Tousson J FIR - Toven, Julie IR - Toven J FIR - Tran, Carolyn IR - Tran C FIR - Trantow, Constance IR - Trantow C FIR - Travaglini, Stefano IR - Travaglini S FIR - Traylor, Henry IR - Traylor H FIR - Tripp, Dawn IR - Tripp D FIR - Tumyan, Anna IR - Tumyan A FIR - Turner, Juliana IR - Turner J FIR - Twine, Melissa IR - Twine M FIR - Tyson, Treva IR - Tyson T FIR - Underkofler, Chantal IR - Underkofler C FIR - Uzoaga, Enyibuaku IR - Uzoaga E FIR - Valdivia, Vanessa IR - Valdivia V FIR - Valencia, Patricia IR - Valencia P FIR - Valitutto, Michael IR - Valitutto M FIR - Vanderheiden, Anna IR - Vanderheiden A FIR - Varavenkataraman, Raghupathy IR - Varavenkataraman R FIR - Vickery, David IR - Vickery D FIR - Vincent, Shari IR - Vincent S FIR - Wadud, Khurram IR - Wadud K FIR - Wahl, Timothy IR - Wahl T FIR - Walker, Frank IR - Walker F FIR - Walsh, Kimberly IR - Walsh K FIR - Wang, Aileen IR - Wang A FIR - Wardell, Karla IR - Wardell K FIR - Weindorff, Kathleen IR - Weindorff K FIR - Weir, Maria IR - Weir M FIR - Weisbrot, Albert IR - Weisbrot A FIR - Weiss, Sarah IR - Weiss S FIR - Weiter, Kathleen IR - Weiter K FIR - Wenker, Matthew IR - Wenker M FIR - Wenocur, Howard IR - Wenocur H FIR - West, Mary IR - West M FIR - White, Elizabeth IR - White E FIR - White, Judith IR - White J FIR - Whitehead, Rebecca IR - Whitehead R FIR - Whittle, Jessica IR - Whittle J FIR - Wigley, Christine IR - Wigley C FIR - Wilkins, Francesca IR - Wilkins F FIR - Williams, Hayes IR - Williams H FIR - Williams, Megan IR - Williams M FIR - Williamson, Cathi IR - Williamson C FIR - Wilson, Lou Ellen IR - Wilson LE FIR - Windsor, Sheryl IR - Windsor S FIR - Wingo, Linder IR - Wingo L FIR - Winkle, Peter IR - Winkle P FIR - Wishard, Lisa IR - Wishard L FIR - Wisneski, Shanna IR - Wisneski S FIR - Witte, Melanie IR - Witte M FIR - Wolfman, Lindsay IR - Wolfman L FIR - Wollet, James IR - Wollet J FIR - Wood, Ruth IR - Wood R FIR - Wyatt, Holly IR - Wyatt H FIR - Yassini, Patrick IR - Yassini P FIR - Yeoman, Gary IR - Yeoman G FIR - York, Dayna IR - York D FIR - Young, Laura IR - Young L FIR - Young, Timothy IR - Young T FIR - Zaretzky, Joel IR - Zaretzky J FIR - Ziboh, Maureen IR - Ziboh M FIR - Zimmer, Erin IR - Zimmer E EDAT- 2016/09/17 06:00 MHDA- 2016/12/20 06:00 CRDT- 2016/09/17 06:00 PHST- 2016/09/17 06:00 [pubmed] PHST- 2016/12/20 06:00 [medline] PHST- 2016/09/17 06:00 [entrez] AID - 10.1056/NEJMoa1607141 [doi] PST - ppublish SO - N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15. PMID- 27563838 OWN - NLM STAT- MEDLINE DCOM- 20170310 LR - 20250103 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 25 IP - 10 DP - 2016 Oct TI - Investigational glucagon-like peptide-1 agonists for the treatment of obesity. PG - 1167-79 LID - 10.1080/13543784.2016.1221925 [doi] AB - INTRODUCTION: Obesity is a worldwide problem predisposing to type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease, cancer and other comorbidities. Lifestyle modification is the first line intervention but adjunctive pharmacotherapy is often required. The GLP-1 receptor agonists (GLP-1RAs) were developed primarily for T2DM and they also reduce body weight. Liraglutide was approved for the treatment of obesity and other GLP-1RAs are likely to be suitable for this indication. AREAS COVERED: This review describes the GLP-1RAs that have been approved for the treatment of T2DM as potential candidates for the treatment of obesity and the new agents currently under development which may have advantages in patient adherence. EXPERT OPINION: The GLP-1RAs offer a welcome addition to obesity pharmacotherapy. They appear to be free of serious adverse effects although uncertainty remains about possible risks of pancreatitis and neoplasms. However, they have frequent gastrointestinal side effects, particularly nausea, which limits their tolerability. Cardiovascular outcome studies in T2DM support their use and this is likely to increase in both T2DM and obesity. Other GLP-1RAs which can be given by subcutaneous injection once weekly or less frequently or by oral administration would have advantages especially if nausea is less frequent than with liraglutide. FAU - Tomlinson, Brian AU - Tomlinson B AD - a Research Center for Translational Medicine , Shanghai East Hospital Affiliated to Tongji University School of Medicine , Shanghai , China. AD - b Department of Medicine & Therapeutics , The Chinese University of Hong Kong , Shatin , Hong Kong. FAU - Hu, Miao AU - Hu M AD - b Department of Medicine & Therapeutics , The Chinese University of Hong Kong , Shatin , Hong Kong. FAU - Zhang, Yuzhen AU - Zhang Y AD - a Research Center for Translational Medicine , Shanghai East Hospital Affiliated to Tongji University School of Medicine , Shanghai , China. FAU - Chan, Paul AU - Chan P AD - c Division of Cardiology, Department of Internal Medicine, Wan Fang Hospital , Taipei Medical University , Taipei City , Taiwan. FAU - Liu, Zhong-Min AU - Liu ZM AD - d Department of Cardiac Surgery, Shanghai East Hospital , Tongji University , Shanghai , China. LA - eng PT - Journal Article PT - Review DEP - 20160826 PL - England TA - Expert Opin Investig Drugs JT - Expert opinion on investigational drugs JID - 9434197 RN - 0 (Anti-Obesity Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Animals MH - Anti-Obesity Agents/adverse effects/pharmacology/*therapeutic use MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/drug therapy/etiology MH - Drug Design MH - Humans MH - Liraglutide/adverse effects/pharmacology/therapeutic use MH - Obesity/complications/*drug therapy/physiopathology MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Efpeglenatide OT - GLP-1 receptor agonist OT - ITCA 650 OT - exenatide OT - liraglutide OT - obesity OT - semaglutide EDAT- 2016/08/27 06:00 MHDA- 2017/03/11 06:00 CRDT- 2016/08/27 06:00 PHST- 2016/08/27 06:00 [entrez] PHST- 2016/08/27 06:00 [pubmed] PHST- 2017/03/11 06:00 [medline] AID - 10.1080/13543784.2016.1221925 [doi] PST - ppublish SO - Expert Opin Investig Drugs. 2016 Oct;25(10):1167-79. doi: 10.1080/13543784.2016.1221925. Epub 2016 Aug 26. PMID- 27432074 OWN - NLM STAT- MEDLINE DCOM- 20170606 LR - 20181202 IS - 1878-1594 (Electronic) IS - 1521-690X (Linking) VI - 30 IP - 3 DP - 2016 Jun TI - Optimizing management of glycaemia. PG - 397-411 LID - S1521-690X(16)30019-7 [pii] LID - 10.1016/j.beem.2016.06.002 [doi] AB - The global epidemic of type 2 diabetes (T2DM) continues largely unabated due to an increasingly sedentary lifestyle and obesogenic environment. A cost-effective patient-centred approach, incorporating glucose-lowering therapy and modification of cardiovascular risk factors, could help prevent the inevitable development and progression of macrovascular and microvascular complications. Glycaemic optimization requires patient structured education, self-management and empowerment, and psychological support along with early and proactive use of glucose lowering therapies, which should be delivered in a system of care as shown by the Chronic Care Model. From diagnosis, intensive glycaemic control and individualised care is aimed at reducing complications. In older people, the goal is maintaining quality of life and minimizing morbidity, especially as overtreatment increases hypoglycaemia risk. Maintaining durable glycaemic control is challenging and complex to achieve without hypoglycaemia, weight gain and other significant adverse effects. Overcoming patient and physician barriers can help ensure adequate treatment initiation and intensification. Cardiovascular safety studies with newer glucose-lowering agents are now mandatory, with a sodium glucose co-transporter-2 inhibitor (empagliflozin), and two glucagon like peptide-1 receptor agonists (liraglutide and semaglutide) being the first to demonstrate superior CV outcomes compared with placebo. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Chatterjee, Sudesna AU - Chatterjee S AD - Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK; Diabetes Research Centre, College of Medicine, Biological Sciences & Psychology, University of Leicester, The Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. Electronic address: Sudesna.Chatterjee@uhl-tr.nhs.uk. FAU - Khunti, Kamlesh AU - Khunti K AD - Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK; Diabetes Research Centre, College of Medicine, Biological Sciences & Psychology, University of Leicester, The Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. FAU - Davies, Melanie J AU - Davies MJ AD - Leicester Diabetes Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK; Diabetes Research Centre, College of Medicine, Biological Sciences & Psychology, University of Leicester, The Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK. LA - eng PT - Journal Article PT - Review DEP - 20160613 PL - Netherlands TA - Best Pract Res Clin Endocrinol Metab JT - Best practice & research. Clinical endocrinology & metabolism JID - 101120682 RN - 0 (Hypoglycemic Agents) SB - IM MH - Cardiotoxicity MH - Diabetes Mellitus, Type 2/complications/*drug therapy/economics MH - *Disease Management MH - Humans MH - Hyperglycemia/complications/*drug therapy/economics MH - Hypoglycemic Agents/administration & dosage/adverse effects/therapeutic use OTO - NOTNLM OT - SGLT2 inhibitors OT - T2DM OT - glucose-lowering therapies OT - hypoglycaemia OT - incretin therapies OT - insulin EDAT- 2016/07/20 06:00 MHDA- 2017/06/07 06:00 CRDT- 2016/07/20 06:00 PHST- 2016/07/20 06:00 [entrez] PHST- 2016/07/20 06:00 [pubmed] PHST- 2017/06/07 06:00 [medline] AID - S1521-690X(16)30019-7 [pii] AID - 10.1016/j.beem.2016.06.002 [doi] PST - ppublish SO - Best Pract Res Clin Endocrinol Metab. 2016 Jun;30(3):397-411. doi: 10.1016/j.beem.2016.06.002. Epub 2016 Jun 13. PMID- 26694823 OWN - NLM STAT- MEDLINE DCOM- 20170303 LR - 20250103 IS - 1875-6417 (Electronic) IS - 1573-3998 (Print) IS - 1573-3998 (Linking) VI - 12 IP - 4 DP - 2016 TI - Glucagon-Like Peptide-1 Receptor Agonists for Type 2 Diabetes: A Clinical Update of Safety and Efficacy. PG - 403-413 AB - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly being used for the treatment of type 2 diabetes mellitus, but consideration of benefits and potential adverse events is required. This review examines the state of glycemic control, weight loss, blood pressure, and tolerability, as well as the current debate about the safety of GLP-1 RAs, including risk of pancreatitis, pancreatic cancer, and thyroid cancer. METHODS: A MEDLINE search (2010-2015) identified publications that discussed longer-acting GLP-1 RAs. Search terms included GLP-1 receptor agonists, liraglutide, exenatide, lixisenatide, semaglutide, dulaglutide, albiglutide, efficacy, safety, pancreatitis, pancreatic cancer, and thyroid cancer. Abstracts from the American Diabetes Association, European Association for the Study of Diabetes, and American Association of Clinical Endocrinologists from 2010 to 2015 were also searched. Efficacy and safety studies, pooled analyses, and meta-analyses were prioritized. RESULTS: Research has confirmed that GLP-1 RAs provide robust glycemic control, weight loss, and blood pressure re-duction. Current studies do not prove increased risk of pancreatitis, pancreatic cancer, or thyroid cancer but more trials are needed since publications that indicate safety or suggest increased risk have methodological flaws that prevent firm conclusions to be drawn about these rare, long-term events. CONCLUSION: GLP-1 RA therapy in the context of individualized, patient-centered care continues to be supported by current literature. GLP-1 RA therapy provides robust glycemic control, blood pressure reduction, and weight loss, but studies are still needed to address concerns about tolerability and safety, including pancreatitis and cancer. FAU - Drab, Scott R AU - Drab SR AD - University of Pittsburgh School of Pharmacy, 719 Salk Hall, Pittsburgh, PA 15261, USA. Drab@pitt.edu. LA - eng PT - Journal Article PT - Review PL - United Arab Emirates TA - Curr Diabetes Rev JT - Current diabetes reviews JID - 101253260 RN - 0 (Blood Glucose) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Venoms) RN - 5E7U48495E (rGLP-1 protein) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9P1872D4OL (Exenatide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Blood Glucose/drug effects/metabolism MH - Diabetes Mellitus, Type 2/*drug therapy MH - Exenatide MH - Glucagon-Like Peptide 1/adverse effects/analogs & derivatives/therapeutic use MH - Glucagon-Like Peptides/adverse effects/analogs & derivatives/therapeutic use MH - Humans MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Immunoglobulin Fc Fragments/adverse effects/therapeutic use MH - Peptides/adverse effects/therapeutic use MH - Recombinant Fusion Proteins/adverse effects/therapeutic use MH - Treatment Outcome MH - Venoms/adverse effects/therapeutic use MH - *Glucagon-Like Peptide-1 Receptor Agonists PMC - PMC5101635 EDAT- 2015/12/24 06:00 MHDA- 2017/03/04 06:00 PMCR- 2016/11/09 CRDT- 2015/12/24 06:00 PHST- 2015/09/22 00:00 [received] PHST- 2015/12/21 00:00 [revised] PHST- 2015/12/21 00:00 [accepted] PHST- 2015/12/24 06:00 [pubmed] PHST- 2017/03/04 06:00 [medline] PHST- 2015/12/24 06:00 [entrez] PHST- 2016/11/09 00:00 [pmc-release] AID - CDR-EPUB-72721 [pii] AID - CDR-12-403 [pii] AID - 10.2174/1573399812666151223093841 [doi] PST - ppublish SO - Curr Diabetes Rev. 2016;12(4):403-413. doi: 10.2174/1573399812666151223093841. PMID- 26642233 OWN - NLM STAT- MEDLINE DCOM- 20160525 LR - 20260127 IS - 1539-3704 (Electronic) IS - 0003-4819 (Linking) VI - 164 IP - 2 DP - 2016 Jan 19 TI - Benefits and Harms of Once-Weekly Glucagon-like Peptide-1 Receptor Agonist Treatments: A Systematic Review and Network Meta-analysis. PG - 102-13 LID - 10.7326/M15-1432 [doi] AB - BACKGROUND: Once-weekly glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of type 2 diabetes. PURPOSE: To summarize evidence for the cardiometabolic efficacy and adverse effects of once-weekly GLP-1RAs in adults with type 2 diabetes. DATA SOURCES: Electronic databases (PubMed, Web of Science, Cochrane Central Register of Controlled Trials, U.S. Food and Drug Administration, European Medicines Agency, ClinicalTrials.gov) and congress abstracts from inception through 26 September 2015. STUDY SELECTION: Randomized, controlled trials (>/= 24 weeks of follow-up) studying albiglutide, dulaglutide, once-weekly exenatide, semaglutide, and taspoglutide and reporting a cardiometabolic (primary outcome, hemoglobin A1c [HbA1c]) or safety outcome. DATA EXTRACTION: Extraction was done in duplicate, and risk of bias was assessed. No language restriction was applied. DATA SYNTHESIS: 34 trials (21,126 participants) were included. Compared with placebo, all once-weekly GLP-1RAs reduced HbA1c and fasting plasma glucose; taspoglutide, 20 mg, once-weekly exenatide, and dulaglutide, 1.5 mg, reduced body weight. Among once-weekly GLP-1RAs, the greatest differences were found between dulaglutide, 1.5 mg, and taspoglutide, 10 mg, for HbA1c (-0.4% [95% CI, -0.7% to -0.2%]), once-weekly exenatide and albiglutide for fasting plasma glucose (-0.7 mmol/L [CI, -1.1 to -0.2 mmol/L]; -12.6 mg/dL [CI, -19.8 to -3.6 mg/dL]), and taspoglutide, 20 mg, and dulaglutide, 0.75 mg, for body weight (-1.5 kg [CI, -2.2 to -0.8]). Clinically marginal or no differences were found for blood pressure, blood lipid levels, and C-reactive protein levels. Once-weekly exenatide increased heart rate compared with albiglutide and dulaglutide (1.4 to 3.2 beats/min). Among once-weekly GLP-1RAs, the risk for hypoglycemia was similar, whereas taspoglutide, 20 mg, had the greatest risk for nausea (odds ratios, 1.9 to 5.9). LIMITATION: Data were unavailable for semaglutide, definitions of outcomes were heterogeneous, the last-observation-carried-forward imputation method was used in 73% of trials, and publication bias is possible. CONCLUSION: Compared with other once-weekly GLP-1RAs, dulaglutide, 1.5 mg; once-weekly exenatide; and taspoglutide, 20 mg, showed a greater reduction of HbA1c, fasting plasma glucose, and body weight. Taspoglutide, 20 mg, had the highest risk for nausea; risk for hypoglycemia among once-weekly GLP-1RAs was similar. PRIMARY FUNDING SOURCE: Sanofi Aventis (grant to the University of Leicester). FAU - Zaccardi, Francesco AU - Zaccardi F FAU - Htike, Zin Zin AU - Htike ZZ FAU - Webb, David R AU - Webb DR FAU - Khunti, Kamlesh AU - Khunti K FAU - Davies, Melanie J AU - Davies MJ LA - eng PT - Journal Article PT - Network Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20151208 PL - United States TA - Ann Intern Med JT - Annals of internal medicine JID - 0372351 RN - 0 (Blood Glucose) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM CIN - Ann Intern Med. 2016 Jan 19;164(2):127-8. doi: 10.7326/M15-2610. PMID: 26641027 CIN - BMJ. 2015 Dec 09;351:h6702. doi: 10.1136/bmj.h6702. PMID: 26656272 MH - Blood Glucose/metabolism MH - Diabetes Mellitus, Type 2/blood/*drug therapy MH - Drug Administration Schedule MH - Glycated Hemoglobin/metabolism MH - Hemodynamics/drug effects MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/administration & dosage/*adverse effects/*therapeutic use MH - Nausea/chemically induced MH - Weight Loss MH - *Glucagon-Like Peptide-1 Receptor Agonists EDAT- 2015/12/08 06:00 MHDA- 2016/05/26 06:00 CRDT- 2015/12/08 06:00 PHST- 2015/12/08 06:00 [entrez] PHST- 2015/12/08 06:00 [pubmed] PHST- 2016/05/26 06:00 [medline] AID - 2474362 [pii] AID - 10.7326/M15-1432 [doi] PST - ppublish SO - Ann Intern Med. 2016 Jan 19;164(2):102-13. doi: 10.7326/M15-1432. Epub 2015 Dec 8. PMID- 26587691 OWN - NLM STAT- MEDLINE DCOM- 20160926 LR - 20250103 IS - 1744-7658 (Electronic) IS - 1354-3784 (Linking) VI - 25 IP - 2 DP - 2016 TI - An overview of new GLP-1 receptor agonists for type 2 diabetes. PG - 145-58 LID - 10.1517/13543784.2016.1123249 [doi] AB - INTRODUCTION: The increasing prevalence of type 2 diabetes mellitus (T2DM) and the eventual need for multiple medications in most patients stimulated the development of new drug classes to reduce plasma glucose levels. The GLP-1 receptor agonists (GLP-1RAs) are established as an option for treatment of T2DM after metformin. They are also effective in reducing body weight but current GLP-1RAs have to be given by subcutaneous injection daily or once weekly. AREAS COVERED: This review focuses on the new GLP-1RAs currently undergoing development, some of which require less frequent subcutaneous administration and others that are being developed in oral formulations that may favor patient adherence. EXPERT OPINION: The new GLP-1RAs may have the benefit of requiring less frequent subcutaneous dosing or being active by oral administration. However, cardiovascular outcome trials have shown that DPP4 inhibitors are neutral for cardiovascular events and the first cardiovascular outcome trial with lixisenatide reported similar results, whereas the trial with the SGLT2 inhibitor empagliflozin showed a reduction in cardiovascular events. These findings in patients with high cardiovascular risk may favor the use of SGLT2 inhibitors as a second line treatment after metformin but there should still be an important role for novel GLP-1RAs, especially when weight reduction is required. FAU - Tomlinson, Brian AU - Tomlinson B AD - a Research Center for Translational Medicine , Shanghai East Hospital Affiliated to Tongji University School of Medicine , Shanghai , China. AD - b Department of Medicine & Therapeutics , Prince of Wales Hospital, The Chinese University of Hong Kong , Shatin , Hong Kong. FAU - Hu, Miao AU - Hu M AD - b Department of Medicine & Therapeutics , Prince of Wales Hospital, The Chinese University of Hong Kong , Shatin , Hong Kong. FAU - Zhang, Yuzhen AU - Zhang Y AD - a Research Center for Translational Medicine , Shanghai East Hospital Affiliated to Tongji University School of Medicine , Shanghai , China. FAU - Chan, Paul AU - Chan P AD - c Division of Cardiology, Department of Internal Medicine , Wan Fang Hospital, Taipei Medical University , Taipei city , Taiwan. FAU - Liu, Zhong-Min AU - Liu ZM AD - d Department of Cardiac Surgery , Shanghai East Hospital, Tongji University , Shanghai , China. LA - eng PT - Journal Article PT - Review DEP - 20151217 PL - England TA - Expert Opin Investig Drugs JT - Expert opinion on investigational drugs JID - 9434197 RN - 0 (Hypoglycemic Agents) RN - 0 (SLC5A2 protein, human) RN - 0 (Sodium-Glucose Transporter 2) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Administration, Oral MH - Animals MH - Body Weight/drug effects MH - Diabetes Mellitus, Type 2/*drug therapy/physiopathology MH - Drug Design MH - Humans MH - Hypoglycemic Agents/administration & dosage/pharmacology/*therapeutic use MH - Injections, Subcutaneous MH - Medication Adherence MH - Sodium-Glucose Transporter 2 MH - Sodium-Glucose Transporter 2 Inhibitors MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Efpeglenatide OT - GLP-1 OT - GLP-1 receptor agonist OT - glymera OT - semaglutide OT - type 2 diabetes mellitus EDAT- 2015/11/21 06:00 MHDA- 2016/09/27 06:00 CRDT- 2015/11/21 06:00 PHST- 2015/11/21 06:00 [entrez] PHST- 2015/11/21 06:00 [pubmed] PHST- 2016/09/27 06:00 [medline] AID - 10.1517/13543784.2016.1123249 [doi] PST - ppublish SO - Expert Opin Investig Drugs. 2016;25(2):145-58. doi: 10.1517/13543784.2016.1123249. Epub 2015 Dec 17. PMID- 26358288 OWN - NLM STAT- MEDLINE DCOM- 20160726 LR - 20260127 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 39 IP - 2 DP - 2016 Feb TI - A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients With Type 2 Diabetes. PG - 231-41 LID - 10.2337/dc15-0165 [doi] AB - OBJECTIVE: To investigate the dose-response relationship of semaglutide versus placebo and open-label liraglutide in terms of glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a 12-week, randomized, double-blind phase 2 trial. Patients (n = 415) were randomized to receive a subcutaneous injection of semaglutide once weekly without dose escalation (0.1-0.8 mg) or with dose escalation (E) (0.4 mg steps to 0.8 or 1.6 mg E over 1-2 weeks), open-label liraglutide once daily (1.2 or 1.8 mg), or placebo. The primary end point was change in HbA1c level from baseline. Secondary end points included change in body weight, safety, and tolerability. RESULTS: Semaglutide dose-dependently reduced the level of HbA1c from baseline (8.1 +/- 0.8%) to week 12 by up to -1.7%, and body weight by up to -4.8 kg (1.6 mg E, P < 0.001 vs. placebo). Up to 81% of patients achieved an HbA1c level of <7%. HbA1c level and weight reductions with semaglutide 1.6 mg E were greater than those with liraglutide 1.2 and 1.8 mg (based on unadjusted CIs), but adverse events (AEs) and withdrawals occurred more frequently. The incidence of nausea, vomiting, and withdrawal due to gastrointestinal AEs increased with the semaglutide dose; most events were mild to moderate, transient, and ameliorated by dose escalation. There were no major episodes of hypoglycemia and few cases of injection site reactions. CONCLUSIONS: After 12 weeks, semaglutide dose-dependently reduced HbA1c level and weight in patients with type 2 diabetes. No unexpected safety or tolerability concerns were identified; gastrointestinal AEs typical of glucagon-like peptide 1 receptor agonists were mitigated by dose escalation. On this basis, weekly semaglutide doses of 0.5 and 1.0 mg with a 4-week dose escalation were selected for phase 3. CI - (c) 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. FAU - Nauck, Michael A AU - Nauck MA AD - Diabetes Centre, Bad Lauterberg, Harz, Germany michael.nauck@rub.de. FAU - Petrie, John R AU - Petrie JR AD - University of Glasgow, Glasgow, U.K. FAU - Sesti, Giorgio AU - Sesti G AD - University Magna Graecia, Catanzaro, Italy. FAU - Mannucci, Edoardo AU - Mannucci E AD - Careggi Teaching Hospital, Florence, Italy. FAU - Courreges, Jean-Pierre AU - Courreges JP AD - General Hospital, Narbonne, France. FAU - Lindegaard, Marie L AU - Lindegaard ML AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Jensen, Christine B AU - Jensen CB AD - Novo Nordisk A/S, Soborg, Denmark. FAU - Atkin, Stephen L AU - Atkin SL AD - Weill Cornell Medical College Qatar, Doha, Qatar. CN - Study 1821 Investigators LA - eng SI - ClinicalTrials.gov/NCT00696657 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150910 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Blood Glucose) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 0 (Glycated Hemoglobin) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 53AXN4NNHX (Semaglutide) SB - IM MH - Adult MH - Blood Glucose/drug effects MH - Body Weight MH - Diabetes Mellitus, Type 2/*drug therapy MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Drug Administration Schedule MH - Female MH - Glucagon-Like Peptides/*administration & dosage/adverse effects/analogs & derivatives MH - Glycated Hemoglobin/analysis/drug effects MH - Humans MH - Hypoglycemia/chemically induced MH - Hypoglycemic Agents/*administration & dosage/adverse effects MH - Injections, Subcutaneous MH - Liraglutide/*therapeutic use MH - Male MH - Middle Aged MH - Nausea/chemically induced MH - Treatment Outcome MH - Vomiting/chemically induced MH - Semaglutide EDAT- 2015/09/12 06:00 MHDA- 2016/07/28 06:00 CRDT- 2015/09/12 06:00 PHST- 2015/01/23 00:00 [received] PHST- 2015/08/04 00:00 [accepted] PHST- 2015/09/12 06:00 [entrez] PHST- 2015/09/12 06:00 [pubmed] PHST- 2016/07/28 06:00 [medline] AID - dc15-0165 [pii] AID - 10.2337/dc15-0165 [doi] PST - ppublish SO - Diabetes Care. 2016 Feb;39(2):231-41. doi: 10.2337/dc15-0165. Epub 2015 Sep 10. PMID- 26160096 OWN - NLM STAT- MEDLINE DCOM- 20151229 LR - 20250103 IS - 0030-9982 (Print) IS - 0030-9982 (Linking) VI - 65 IP - 7 DP - 2015 Jul TI - Once-weekly glucagon-like peptide 1 receptor agonists. PG - 796-8 AB - The once-weekly glucagon-like peptide 1 receptor agonists (QW GLP1RA) represent a major advancement in diabetes pharmaco-therapeutics. This review describes the basic, clinical, and comparative pharmacology of this novel class of drugs. It highlights the clinical placement and posology of these drugs. FAU - Kalra, Sanjay AU - Kalra S AD - Department of Endocrinology, Bharti Hospital & BRIDE, Karnal, India. FAU - Gupta, Yashdeep AU - Gupta Y AD - Department of Medicine, Government Medical College and Hospital, Chandigarh, India. LA - eng PT - Journal Article PT - Review PL - Pakistan TA - J Pak Med Assoc JT - JPMA. The Journal of the Pakistan Medical Association JID - 7501162 RN - 0 (Delayed-Action Preparations) RN - 0 (Hypoglycemic Agents) RN - 0 (Immunoglobulin Fc Fragments) RN - 0 (Incretins) RN - 0 (Peptides) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Venoms) RN - 5E7U48495E (rGLP-1 protein) RN - 62340-29-8 (Glucagon-Like Peptides) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9P1872D4OL (Exenatide) RN - WTT295HSY5 (dulaglutide) RN - 0 (Glucagon-Like Peptide-1 Receptor Agonists) SB - IM MH - Delayed-Action Preparations MH - Diabetes Mellitus, Type 2/*drug therapy MH - Drug Administration Schedule MH - Exenatide MH - Glucagon-Like Peptide 1/administration & dosage/analogs & derivatives MH - Glucagon-Like Peptides/administration & dosage/analogs & derivatives MH - Humans MH - Hypoglycemic Agents/*administration & dosage MH - Immunoglobulin Fc Fragments/administration & dosage MH - Incretins/*administration & dosage MH - Peptides/administration & dosage MH - Recombinant Fusion Proteins/administration & dosage MH - Venoms/administration & dosage MH - *Glucagon-Like Peptide-1 Receptor Agonists OTO - NOTNLM OT - Albiglutide, dulaglutide, exenatide QW, semaglutide. EDAT- 2015/07/15 06:00 MHDA- 2015/12/30 06:00 CRDT- 2015/07/11 06:00 PHST- 2015/07/11 06:00 [entrez] PHST- 2015/07/15 06:00 [pubmed] PHST- 2015/12/30 06:00 [medline] AID - 7416 [pii] PST - ppublish SO - J Pak Med Assoc. 2015 Jul;65(7):796-8. PMID- 24485345 OWN - NLM STAT- MEDLINE DCOM- 20141205 LR - 20260128 IS - 1872-8227 (Electronic) IS - 0168-8227 (Linking) VI - 103 IP - 2 DP - 2014 Feb TI - Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysis of randomized clinical trials. PG - 269-75 LID - S0168-8227(14)00025-4 [pii] LID - 10.1016/j.diabres.2014.01.010 [doi] AB - AIMS: Several randomized trials with metabolic outcomes have reported that glucagon like peptide-1 receptor agonists (GLP-1 RA) could be associated with an increased risk of pancreatitis. The present meta-analysis aimed to examine this hypothesis. METHODS: An extensive Medline, Embase, and Cochrane Database search for "exenatide", "liraglutide", "albiglutide", "taspoglutide", "dulaglutide", "lixisenatide", and "semaglutide" was performed up to March 31st, 2013. INCLUSION CRITERIA: (i) randomized trials, (ii) duration >/=12 weeks; (iii) on type 2 diabetes; and (iv) comparison of GLP-1RA with placebo or active drugs. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for pancreatitis. RESULTS: 80 eligible trials were identified. Of these, 39 had not disclosed their findings or did not report any information on pancreatitis. The remaining 41 trials enrolled 14,972 patients, with a total exposure of 14,333 patient x years (8353 and 5980 patient x years for GLP-1 receptor agonists and comparators, respectively). The overall risk of pancreatitis was not different between GLP-1RA and comparators (MH-OR: 1.01[0.37; 2.76]; p = 0.99). CONCLUSIONS: The present meta-analysis does not suggest any increase in the risk of pancreatitis with the use of GLP-1RA. However, it should be recognized that the number of observed cases of incident pancreatitis is very small and the confidence intervals of risk estimates are wide. CI - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved. FAU - Monami, Matteo AU - Monami M AD - Section of Geriatric Cardiology and Medicine, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy. FAU - Dicembrini, Ilaria AU - Dicembrini I AD - Obesity Agency, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy; Diabetes Agency, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy. FAU - Nardini, Camilla AU - Nardini C AD - Section of Geriatric Cardiology and Medicine, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy. FAU - Fiordelli, Irene AU - Fiordelli I AD - Section of Geriatric Cardiology and Medicine, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy. FAU - Mannucci, Edoardo AU - Mannucci E AD - Diabetes Agency, Careggi Teaching Hospital, Via delle Oblate 4, 50141 Florence, Italy. Electronic address: edoardo.mannucci@unifi.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20140114 PL - Ireland TA - Diabetes Res Clin Pract JT - Diabetes research and clinical practice JID - 8508335 RN - 9P1872D4OL (Exenatide) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) RN - 0 (Peptides) RN - 0 (Receptors, Glucagon) RN - 0 (Venoms) RN - 0 (GLP1R protein, human) RN - 2PHK27IP3B (taspoglutide) RN - 5E7U48495E (rGLP-1 protein) RN - 74O62BB01U (lixisenatide) RN - 0 (Glucagon-Like Peptide-2 Receptor) SB - IM MH - Diabetes Mellitus, Type 2/*drug therapy MH - Exenatide MH - Glucagon-Like Peptide 1/adverse effects/analogs & derivatives/therapeutic use MH - Glucagon-Like Peptide-1 Receptor MH - Humans MH - Hypoglycemic Agents/*adverse effects/therapeutic use MH - Liraglutide MH - Pancreatitis/*chemically induced MH - Peptides/adverse effects/therapeutic use MH - Randomized Controlled Trials as Topic MH - Receptors, Glucagon/*agonists MH - Venoms/adverse effects/therapeutic use MH - Glucagon-Like Peptide-2 Receptor OTO - NOTNLM OT - Glucagon like peptide-1 receptor agonists OT - Meta-analysis OT - Pancreatitis EDAT- 2014/02/04 06:00 MHDA- 2014/12/15 06:00 CRDT- 2014/02/04 06:00 PHST- 2013/05/02 00:00 [received] PHST- 2013/05/02 00:00 [revised] PHST- 2014/01/04 00:00 [accepted] PHST- 2014/02/04 06:00 [entrez] PHST- 2014/02/04 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] AID - S0168-8227(14)00025-4 [pii] AID - 10.1016/j.diabres.2014.01.010 [doi] PST - ppublish SO - Diabetes Res Clin Pract. 2014 Feb;103(2):269-75. doi: 10.1016/j.diabres.2014.01.010. Epub 2014 Jan 14.